DOI: 10.5958/j.2319-5886.3.1.001 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS nd Received: 2 Sep 2013 Revised: 8th Oct 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 3rd Nov 2013 A STUDY OF LUMBARISATION OF FIRST SACRAL VERTEBRA AMONG THE SOUTH INDIANS * Deepa TK1, Martin K John2 1,2 Assistant Professor, Department of Anatomy, MES medical college, Perinthalmanna, Kerala *Corresponding author e-mail:
[email protected] ABSTRACT Background: In the lumbosacral region, anatomical variations occur with changes in the number of sacral vertebra by deletion of first sacral vertebra or by the union of fifth lumbar or first coccyx with sacrum. The fifth lumbar vertebra may be fused with the sacrum in the case of sacralisation, or the first sacral vertebra may be fused with fifth lumbar vertebra in the case of lumbarisation. This may cause serious problems during spinal surgery if we may fail to recognise the lumbosacral transitional vertebra. Materials and methods: We studied 117 dry human sacra of South Indian population of known sex. Out of 117 sacra, 70 male and 47 female. The sacra with four vertebral segments were selected and studied its morphology. Its features were carefully examined and noted. Result: A typical sacrum consisting of five segments was observed in 103 (88.03%) specimen, while presence of lumbarisation was noted in 2 (1.70%) cases and sacralisation was noted in 12 (10.25%) cases. Sacrum with 3 pairs of sacral foramina is 1.70%. Among the 2 specimen, we got 1 male and 1 female respectively Conclusion: Present study shows that the lumbarisation of first sacral vertebra leads to the formation of three pairs of sacral foramina, which is 1.70% in South Indian population. This awareness of lumbosacral transitional vertebra (LSTV) will help to understand its importance during surgical procedures and also in reporting the radiographs such as X-rays, CT and MRI. Keywords: Anatomic variations, congenital anomaly, lumbarisation, sacral foramina INTRODUCTION The sacrum lies below the fifth lumbar vertebra and is formed by the fusion of five sacral vertebras. It is wedged between the two hip bones and takes part in forming the pelvis. It is triangular in shape. Its upper end or base which articulates with the fifth lumbar vertebra: a lower end or apex which articulate with the coccyx. It has four pairs of sacral foramina that communicate with sacral canal. At the cranial end of sacrum, when the fifth lumbar vertebra fuses with first sacral vertebra, known as the sacralisation of lumbar vertebra and when the first sacral vertebra fuses with the fifth lumbar vertebra, known as lumbarisation of first sacral vertebra.1 Normally, the sacrum is formed by the fusion of five rudimentary vertebrae. But anatomical variations of the sacrum have been reported like sacralisation of fifth lumbar vertebra and lumbarisation of first sacral vertebra. Sacralisation of fifth lumbar vertebra is the most common, whereas the lumbarisation of first sacral vertebra is less common.2 In the present study, the sacrum had four sacral vertebrae instead of five sacral vertebrae as in normal sacrum. There were three sacral foramina along the dorsal and pelvic sacral surface. This is due to non fusion of 1st and 2nd segments of the sacrum ie, the lumbarisation of the first sacral vertebra. S5 vertebra was normal and S2 vertebra was well developed as like S1. S1being completely separated from it, which may be due to developmental defect. 1 Deepa et al., Int J Med Res Health Sci. 2014;3(1):1-4 Bertolotti observed for the first time that, lumbarisation and sacralisation which comes under lumbosacral transitional vertebra are congenital anomalies of lumbosacral region.3 Defect in the segmentation of the lumbosacral spine during development is the main cause for this condition.3,4 Genetic factors and ossification defects are also the potential cause of variation for the lumbosacral transitional vertebra. In both case the morphology is the same. So it is difficult to differentiate between the two defects.5,6 In this study, we focused on the prevalence of sacrum with 3 pairs of sacral foramina among the South Indian population, that in turns help to find out the variations in patients during radiological investigations complaining low back pain. Knowledge of this variation is important to diagnose lower back pain; disc prolapsed and is helpful in procedures like lumbar puncture and spinal anaesthesia. male and the other one is female. Incidence of sacrum with 3 pairs of sacral foramina is 1.70%. Table 1: Frequency distribution of lumbarisation of 1st sacral vertebra & sacralisation of 5th lumbar vertebra Male Female Total Total number of sacra 70 47 117 Normal 61 42 103 Lumbarisation 1 1 2 Sacralisation 8 4 12 DSF-1 DSF-2 DSF-3 MATERIALS AND METHODS The present study includes 117 human sacra of known sex, were studied. All the sacra were of adult, but precise age was not known. Any change in the number of sacral vertebrae were selected and studied. The sacrum with four segments and three sacral foramina was noted. The specimen with lumbarisation were examined and recorded. Two fold subdivision of lumbarisation was used. (1) Unilateral complete lumbarisation (11) bilateral complete lumbarisation of first sacral vertebra. In this study, 2 sacrum with four sacral vertebrae and 3 pairs of sacral foramina showing bilateral complete lumbarisation of 1st sacral vertebra was selected. Incidence of sacrum with 3 pairs of sacral foramina is 1.70%. Among the 2 specimen, one is male and the other one is female respectively. RESULTS In the current study of 117 dry human sacra, 70 (60.5%) were male and 47 (39.5%) were female sacra. 14 cases (12.3%) of lumbosacral transitional vertebra and 103 (87.7%) normal vertebra are found. Among the 14 cases of lumbosacral transitional vertebras, we got 2sacra with four sacral vertebrae and three pairs of sacral foramina showing bilateral complete lumbarisation of 1st sacral vertebra. One is Fig 1. Dorsal surface of sacrum (DSF-1: First pair of dorsal sacral foramina, DSF-2: Second pair of dorsal sacral foramina, DSF-3:Third pair of dorsal sacral foramina) We came across the sacrum with only bilateral complete lumbarisation and not any unilateral complete lumbarisation in any specimen. Parameters in sacrum with bilateral complete lumbarisation were smaller than normal dimension. PSF-1 PSF-2 PSF-3 Fig 2: Pelvic surface of sacrum. (PSF1-first pair of pelvic sacral foramina, PSF2second pair of pelvic sacral foramina, PSF3- third pair of pelvic sacral foramina) 2 Deepa et al., Int J Med Res Health Sci. 2014;3(1):1-4 DISCUSSION Variations in vertebrae are affected by gender, developmental factors and race. An increased number of vertebrae occur more often in males and a reduced number occurs more frequently in females. Normally sacrum is formed by the fusion of five sacral vertebrae and it contains four pairs of sacral foramina. In the current study, we got sacrum with three pairs of sacral foramina showing bilateral complete lumbarisation of first sacral vertebra. In our study, the prevalence of sacrum with three pairs of sacral foramina is 1.70%. In the lumbosacral region, anatomical variations occur frequently, making the sacrum the most variable portion of spine. The variation may be attributed to the dependency of the final sacral morphology to the load related fusion of the bone structure.7 Failure to complete the ascending fusion may create a sixth lumbar vertebra, leaving a four piece or lumbarised sacrum. The occurrence of lumbosacral transitional vertebrae is linked to its embryological development and osteological defects. Vertebras are derived from the sclerotomes of the somites. Each sclerotome divides into three parts: cranial, middle and caudal. Embryologically, the vertebra receives contribution from caudal half of one sclerotome and from the cranial half of succeeding sclerotome. Thus lumbosacral transitional vertebras are caused by the border shifts. Sacralisation of fifth lumbar vertebra is due to cranial shift and the lumbarisation of first sacral segment is due to caudal shift.8 The vast majority of people are affected by this spinal abnormality are born with it ie, it is congenital. Less common reasons could be traumatic injury, extreme arthritic changes and purposeful spinal fusion surgery. Mutations in the HOX 10 and HOX 11 paralogous genes results in the normal pattering of lumbar and sacral vertebra as well as the changes in the axial pattern, such as lumbosacral transition vertebrae.6,9,10 A sacrum with three pairs of sacral foramina has clinical and medicolegal implications. In order to avoid surgery at an incorrect level, it is important to identify the lumbarisation of first sacral vertebra and the sacralisation of fifth lumbar vertebra. The condition of lumbarisation of 1st sacral vertebra deserves attention of clinical anatomist, radiologists, morphologists and forensic experts. Hence we are presenting such a variation which emphasize on its clinical relevance.11-13 Variation in segmental structure of vertebral column results in lumbarisation that demands more attention during anaesthetic and surgical intervention11. Knowledge of this variation is important to diagnose lower back pain, sciatica; disc prolapse and is helpful in procedures like spinal anesthesia and lumbar puncture.14 CONCLUSION The present study shows lumbarisation of first sacral vertebra with three pairs of sacral foramina instead of four pairs of sacral foramina. Sacrum is clinically important for caudal epidural block. So incorrect numbering can theorectically lead to problems with the administration of intradural or epidural anaesthetics.14 Surgical treatment of sacral lesions requires understanding of the underlying anatomy, a task made easier by understanding the developmental aspects and morphological changes that occur with growth. The knowledge of this kind of anomaly is important while reporting the CT, MRI films and Xrays for correct clinical and radiological assessment. Thus clinically the lumbarisation of 1st sacral vertebra is of paramount importance to surgeons, clinical anatomists, forensic experts and morphologists. REFERENCES 1. Bajami Singh. Sacrum with five pairs of sacral foramina. IJAV 2011;4:139-40 2. Frymoyer JW, Hadler NM, Kostuik JP, Weinsttein JN, Whitecloud TS. The adult spine: Principles and practice. New York: Raven press. 1991;2:2099 3. Delport EG, Cucuzzella TR, Marley J, Pruitt C, Delport AG. Lumbosacral transitional vertebrae; incidence in a consecutive patient series. Pain physician.2006;9(1); 53-56 4. Kim NH, Suk KS. The role of transitional vertebrae in spondylolysis and spondylolytic spondylolisthesis Bull, hosp. Jt.Dis.1997;56(3): 161-66 5. Tini PG, Wieser C, Zinn WM. The transitional vertebrae of lumbosacral spine: its radiological classification, incidence, prevalence and clinical significance. Rheumatology & rehabilitation. 1977;16(3) 180-85. 3 Deepa et al., Int J Med Res Health Sci. 2014;3(1):1-4 6. Wellik DM, Capecchi MR. Hox 10 and Hox 11 genes are required to globally pattern the mammalian skeleton. Science 2003; 301: 363-67. 7. Joseph S Cheng MD, John K Song MD. Anatomy of the Sacrum. Neurosurg Focus 2003; 15(2): 8. Sharma VA, Sharma DK, Shukla CK, Osteogenic study of lumbosacral transitional vertebra in central india region J.Anat Soc India.2011; 60(2) 212-17 9. Sadler TW. Langman’s medical embryology. Lippincott Williams & Wilkins, Philadelphia 2010: 11th edition :142 10. Carapuco M, Novoa A, Bobola N, Mallo M. Hox genes specify vertebral types in the presomatic mesoderm. Genes Dev 2003; 19; 2116-21 11. Bron LJ, Van Royan BJ and Wuisman P. The Clinical significance of lumbosacral transitional anomalies. Acta orthopaedica Belgica 2007;73(6) 687-95 12. Dharati MK, Shailesh kumar K , Chintan Lakhani, Srushti S Ruparelia, Shilpa patel, Padma Varlekar. A study of sacrum with three pairs of sacral foramina in Western India. IJMSPH 2012;1:12731. 13. Frazer JE. Anatomy of the human skeleton., edited by Breathnach ASJ and A. Churchill Livingstone London .1958; 5th ed: 33-38 14. Panjakash Samreen, Londhe shashikala and Kori Rohini. Lumbarisation of first sacral vertebra – a case report. IJBAMS 2012;2;154-57. 4 Deepa et al., Int J Med Res Health Sci. 2014;3(1):1-4 DOI: 10.5958/j.2319-5886.3.1.002 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Received: 2nd Sep 2013 Revised: 6th Oct 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 3rd Nov 2013 THE USE OF PERITONEAL DIALYSIS IN THE MANAGEMENT OF PATIENTS WITH RENAL FAILURE AT INSTITUTE OF KIDNEY DISEASES, PESHAWAR *Akhtar Sultan Z1, Saleem Nasir2, Hajira Bibi3 1 Professor and Head, Department of Nephrology, Institute of Kidney Diseases, Hayatabad Medical Complex, Peshawar 2 Training Medical Officer, Medical B Unit, Hayatabad Medical Complex, Peshawar. 3 Clinical Nutritionist, Institute of Kidney Diseases, Hayatabad Medical Complex, Peshawar. *Corresponding author email:
[email protected] ABSTRACT Peritoneal dialysis (PD) using an ordinary stylet cannula was studied in 253 patients (67% male and 33% female with age ranging from 3-67 years) suffering from renal failure. The study was conducted between January 2007 and December 2012. The procedure was well tolerated by the patients. The desired aims of dialysis including improvement in chemistry were achieved in all surviving (94.5%) cases. Mortality during PD was 5.5% and was related to the underlying causes of renal failure. Peritonitis seen in 30% cases was the commonest complication. Other complications in order of frequency were, hypokalemia (8%), severe hyperglycemia in diabetic patients (6%), and sever hypovolemia (5%), pericatheter leak (5%) and catheter blockage (2%). Perforation of the bowel, a serious complication occurring during insertion of the PD cannula was not seen in any of the cases. It is concluded from the study that PD is a simple and cost effective alternative to hemodialysis and have special advantages in the current set-up of the institute. The objective of our work was to study the results and complications of peritoneal dialysis in light of its efficacy as an alternative form of renal replacement therapy (RRT) to hemodialysis. Keywords: Peritoneal dialysis, peritonitis, hyperglycemia, hypovolemia INTRODUCTION Renal replacement therapy (RRT) in the form of dialysis (hemodialysis/ peritoneal dialysis) or transplantation remains the sole treatment for patients who sustain renal failure. The gold standard for renal failure (End stage renal disease-ESRD) is transplantation but unfortunately it is restricted by financial limitations in developing countries like Pakistan.1 Similarly the hemodialysis (HD) facilities are scarce due to the lack of necessary funds. At present there are only 175 dialysis centers throughout the country2 and few of them are available in remote areas. The dialysis treatment is in-fact expensive and at the same time lifesaving but due to meager facilities and poverty, the PD is a cheaper option in CKD patients with good residual renal function. Renal failure is becoming a public health problem with increasing incidence and prevalence, high cost and unfortunately poor outcome.3The total burden of ESRD continues to rise including patients with many advanced comorbidities.4The growing burden of this special population requires the use of alternative renal replacement therapy. Peritoneal dialysis (PD) is an alternative renal supportive therapy (RST) to HD which if use wisely can share some of the load. The utilization of peritoneal dialysis is low despite of equal patient survival on HD and PD, and fluctuates 5 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 only at around 15% of the ESRD population.5,6 Both PD and HD have their specific advantages and disadvantages and different factors influence the choice of RRT. PD is generally preferred to HD in very small children and those with severe cardiovascular instability.7,8 The better preservation of residual renal function, lower risk of infections with hepatitis B and C, better outcome after transplantation, preservation of vascular access and lower cost are arguments to promote PD as a good initial treatment. Hospital based PD may be the only option for elderly with significant morbidities making them unable to undergo HD. Despite a valuable and effective option with acceptable survival rates the use of PD is still low for special group of ESRD.6,9 There have been very few publications on the clinical experience of PD in our country; this study was therefore conducted with the aim to describe our experience and results of PD at our institute. MATERIAL AND METHODS Sample size and study location: This study was conducted at the department of Nephrology, Institute of Kidney Diseases, HMC, Peshawar between Jan 2007 and December 2012 after taking approval from the ethics committee of our institution. A total of 253 patients who presented with end stage renal disease (ESRD) / Acute Renal Failure (ARF) were recruited from January 2007 to December 2012 (6 years). Study subjects Inclusion criteria: Subjects from all age groups, including paediatric population (less than 8 years old), patients with poor cardiovascular status (blood pressure less than 100 systolic, evidence of previous myocardial infarction or cerebrovascular accident) and those with hepatitis B surface antigen were given PD instead of HD. Patents from far flung areas were given palliative PD if it was felt that their prospects of long term dialysis or transplant were extremely poor. Lack of HD slot or unavailability of consumables in the HD unit as well as refusal for HD by the patients or their relative were another reason for choosing PD. Verbal and written informed consent was obtained from the participants of the study. Exclusion criteria: Patients, who were hemodynamically stable, had prospects for long term maintenance hemodialysis and had prospects for renal transplantation. Those patients who had access and affordability for dialysis were excluded from the PD group. Age group more than 10 years with hemodynamic stability was also not included in the PD group. Peritoneal Dialysis Procedure: Following urinary catheterization, PD cannula insertion was performed as a bedside procedure in the ward using aseptic techniques and local anesthesia. In order to avoid perforation of the bowl and facilitate optimum positioning of the PD catheter, intraperitoneal infusion of about two liter dialysate using an ordinary intravenous cannula was usually carried out prior to insertion of the PD cannula. The cannula was secured and the entry point was closed by applying a pursestring suture. Hourly exchanges with 500 ml to 2000 ml standard PD solution (Braun or Otsuka) were carried out. Two hundred units of heparin were added to each liter of dialysate. Proper record of exchange with emphasis on accurate fluid balance was kept. Clinical and Biochemical assessment: Patients were assessed clinically and pre- and post-dialysis chemistry was measured to look at the efficacy of the dialysis. Statistical analysis: All the results were expressed as percentages and frequencies by using Microsoft Excel (version 2010). RESULTS Gender based distribution of patients with renal failure The data in table 1 show gender based distribution of patients with renal failure. It is clear from the table that among 253 patients 170 were male and 83 were female. The mean age of patients was 23 years ranged between 3 to 67 years. Table 1: Gender based distribution of patients with renal failure Gender Number Percentage Male 170 67 Female 83 33 Causes of chronic renal failure (CRF) The data in table 2 shows the various causes of chronic renal failure. Out of 253 cases 152 (60%) were suffering from chronic renal failure. Most of these patients had small echogenic kidneys (n=93) suggesting the underlying causes of glomerulonephritis in the majority followed by 6 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 diabetic nephropathy (n=18). The adult polycystic kidney disease was found in 16 cases followed by obstructive uropathy (n=14). Renal amyloidosis and cirrhosis was found in 6 and 5 cases, respectively. Table 2: Causes of chronic renal failure (CRF) (n=152) Causes of CRF Number % Small echogenic kidneys 93 61.18 (chronic glomerulonephritis) Diabetic nephropathy 18 11.84 Adult polycystic kidney 16 10.53 disease Obstructive uropathy 14 9.21 Renal amyloidosis 6 3.95 Cirrhosis 5 3.29 Causes of acute renal failure (ARF) 40% (101) of the patients had ARF. Table 3 shows the causes of ARF from various causes.. The commonest cause of ARF was post-diarrheal volume depletion (n=24) followed by hemolytic uremic syndrome (n=15), obstetrics (n=13) and septicemia (n=12). Other factors responsible included obstruction from calculi (n=11), acute glomerulonephritis (n=7), acute tublo-interstitial nephritis (n=5), acute pyelonephritis (n=5), hemolysis (n=3), post-operative (post-CABG) (n=3), and poisoning (n=3), respectively. Table 3: Causes of acute renal failure (n=101) Causes of ARF Number Post-diarrheal volume depletion 24 Hemolytic uremic syndrome 15 Obstetric 13 Septicemia 12 Obstruction from calculi 11 Acute glomerulonephritis 7 Acute tublo-interstitial nephritis 5 Acute Pyelonephritis 5 Hemolysis 3 Post-operative (post-CABG) 3 Poisoning 3 (ARF) % 23.76 14.85 12.87 11.88 10.89 6.93 4.95 4.95 2.97 2.97 2.97 Reasons for choosing peritoneal dialysis Reasons for choosing PD dialysis as an alternative to HD included; very small children (22.13%), HbsAg positive (11.86%), lack of HD slot (33.99%), palliative PD for CRF (33.99%) and cardiovascular instability (20.95%). Table 4: Reasons for choosing peritoneal dialysis Reasons for choosing PD Number Percentage Small children 56 22.13 HbsAg +ve 30 11.86 Lack of HD slot 86 33.99 Palliative care for CRF 86 33.99 Cardiovascular instability 53 20.95 Hepatitis B surface antigen status of the patients given peritoneal dialysis Thirteen patients in the ARF group and twenty patients in the CRF group had hepatitis B surface antigen positive (Table 5). Infection with hepatitis B may be associated with a variety of renal diseases i.e. membranous glomerulonephritis, membrane proliferative glomerulonephritis, IgA nephropathy, mesangial glomerulonephritis and amyloidosis etc.23,24 Table 5: Hepatitis B surface antigen of the patients given peritoneal dialysis HbsAg(+ve) HbsAg(-ve) Total 13 88 101 ARF 23 129 152 CRF 36 216 253 Total (ARF: Acute renal failure, CRF: Chronic renal failure) Effect of peritoneal dialysis on the blood chemistry of the patients There was an overall improvement in the blood chemistry of the patients. The peritoneal clearance of blood urea and serum creatinine before and after dialysis in both ARF and CRF patients is presented in table 6. Table.6 Effect of peritoneal dialysis chemistry of the patients Blood urea (mg/dl) 170-400 Pre-dialysis in ARF (mean 190) 50-110 Post-dialysis in ARF (mean 64) 280-324 Pre-dialysis in CRF (mean 300) 100-150 Post-dialysis in CRF (mean 120) on the blood S. Creatinine (mg/dl) 8-18 (mean 12) 1.2-3.5 (mean 1.4) 13-25 (mean 15) 4-6 (mean 5.0) (ARF: Acute renal failure, CRF: Chronic renal failure) 7 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 Complications during peritoneal dialysis Various complications during peritoneal dialysis were also experienced (Table 7). The most common complication was peritonitis which occurred in 76 (30%) cases, which responded to antibiotic therapy and removal of the PD cannula. Traumatic complications from insertion of the PD cannula were infrequent and were mainly minor intra-peritoneal bleed (n=15). None of the patient had perforation of the bowl. Other catheter related complications included pericatheter leak (n=13). Scrotal edema (n=10), pain on running fluid (n=8) and blockage of catheter (n=5), the later responding to repositioning of the catheter. Metabolic complications encountered were hypokalemia in 20 cases, severe hyperglycemia in 15 diabetic patients and severe hypovolemia requiring intravenous fluids in 13 cases. Table.7 Complications during peritoneal dialysis Complications Number % PD peritonitis 76 30.04 Blood stained effluent 15 5.93 Pericatheter leak 13 5.14 Scrotal edema 10 3.95 Pain on running fluid 8 3.16 Blockage of catheter 5 1.98 (catheter repositioned) Hypokalemia 20 7.91 Hyperglycemia 15 5.93 (in diabetes) Hypovolemia 13 5.14 Signs and symptoms of peritonitis Signs and symptoms of peritonitis in order of frequency were abdominal pain (98%), fever (77%), rigors (33%), diarrhea (17%), nausea and vomiting (13%) and constipation (10%). Table 8: Signs and symptoms of peritonitis (n=76) Symptoms and signs Number % Abdominal pain 75 98 Fever 59 77 Rigors 25 33 Diarrhea 13 17 Nausea and vomiting 10 13 Constipation 8 10 Abdominal tenderness 64 84 Leukocytosis 56 74 Cloudy fluid 76 100 Most patients with peritonitis had pyrexia (77%), abdominal tenderness (84%) and leukocytosis (74%). All (100%) patients suffering from peritonitis had cloudy fluid on return. Multiple other studies have also observed that more than 90% of the patients have cloudy fluid (100% of ours) and many have abdominal pain (98% of our patients).27,28 Frequency of organisms isolated from patients peritonitis Table 9 shows the incidence of different organisms responsible for peritonitis. Gram positive organisms were responsible for 44 cases of peritonitis and were either due to Staph aureus (28 cases) or Staph epidermis (16 cases). Peritonitis caused by Gram negative organisms was seen in 32 cases. These comprised Pseudomonas (19 cases), Enterobacter (10 cases) and E.coli (3 cases). Culture from 13 cases of peritonitis did not reveal any growth. Findings from other studies also revealed that gram-positive organisms are more responsible for causing most episodes of peritonitis (64.6%) than gram-negative organisms (20.5%).29 Table 9: Frequency of organisms isolated from patients peritonitis (n=76) Organisms Number % Staphylococcus aureus 28 36.84 Pseudomonas 19 25.00 Staphylococcus Epidemidis 16 21.05 Enterobacter 10 13.16 E.coli 3 3.95 DISUCUSSION The effectiveness of PD was evaluated in 253 subjects at the institute of Kidney Diseases, Peshawar. Kidney failure was more prevalent among male than in female. This was in agreement with the finding of Neugarten et al., (2000) that man experiences a more rapid decline in renal function and worse outcome than in female. The underlying mechanisms for this gender disparity are potentially related to differences between the sexes in glomerular structure, glomerular hemodynamics, diet, variations in the production and activity of local cytokines and hormones, and/or the direct effect of sex hormones on kidney cells.10,11 Further it is stated that men with chronic kidney disease (CKD) are 50% more likely to progress to renal failure.12 8 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 The causes of CRF findings suggested that a broader spectrum of CKD risk factors including both infectious and environmental factors as well as genetics predisposes to earlier onset and more rapid progression of CKD. Therefore a basic understanding of the vulnerabilities will help the treatment and prevention of CKD in this population. 13 On the other hand there is variably among the causes of ARF and differ from country to country and vary from center to center in a country. However, there has been an overall increase in the incidence of ARF with the changing etiology of ARF in the recent years. The incidence of obstetrical, surgical and diarrhea related ARF have decreased significantly, whereas those of ARF associated with malaria, sepsis, nephrotoxic drugs and liver diseases have increased. 14 The reason for using PD in our unit has gradually increased not only in ARF but also in CRF. 60% of our patients who had received PD had CRF. The usual form of PD given to CRF patients is CAPD using tencknoff catheter.15,16 Unfortunately, both the tenckoff catheter and the CAPD solution are imported items making the treatment costly and practically unaffordable for most of our patients. Hence we carry out IPD using stylet cannula and ordinary PD solution. In addition to financial restraints there are other reasons for our increasing use of PD. The majority of patients with CRF are usually illiterate with poor insight and hence generally non-compliant. Suffering from “denial syndrome” they often consult Hakims and visit shrines with the hope that their illness will be cured. Some of the patients belong to the far flung areas and are unable to attend frequently for maintenance HD. Commencing such patients on HD without ensuring HD its maintenance is of little benefit and may, in fact hazardous. For example, HD often causes loss of residual renal function and aggravates oliguria.17 Oliguria has been implicated as a poor prognostic factor in ARF and often lead to life threatening pulmonary edema in CRF.18,19 A few days of palliative PD rather than commencing on HD, in our experience stabilizes such patients and provides time for counseling and further planning such as establishing a permanent vascular access. Our patients with CRF often face delays in getting a successful arterio-venous fistula. Dialysis in the meantime is often provided via a temporary vascular catheter usually inserted into the subclavian vein, which often gets infected. This can lead to lifethreatening septicemia.20 It also causes stenosis or occlusion of the vein and may lead to failure of arteio-venous fistula on that side subsequently.21,22 By giving PD initially, we can prevent these complications. Provided certain precautions are taken, insertion of the style peritoneal cannula is usually a safe procedure. Perforation of the bowl is, however, a known complication which usually responds to conservative treatment.25,26 None of patients had either perforation of the bowel or severe hemorrhage. This was mainly due to our policy of introducing 2 to 3 liters of fluid into the peritoneal cavity before cannulation which minimizes the trauma. Minor bleeding occurred in five patients. Peritonitis curing in 76 patients was the commonest complication and was mainly due to lack of proper aseptic condition on part of patient’s relative. Dialysis was concluded when either the required aims were achieved or when peritonitis occurred. With removal of catheter and antibiotic therapy, peritonitis usually quickly settled. Pericatheter leak occurred in only five patients and responded to reduction in volume exchanges. Due to tremendous ultra-filtration, significant hypovolemia requiring the replacement fluid occurred in thirteen patients. Hypokalemia occurring in twenty of our cases was treated by the addition of potassium in the dialysate. Most our patients accepted PD well. The immediate aims of dialysis such as amelioration of uremic symptoms, correction of acidosis and improvement in azotemia were achieved in all patients. Fluid overload was also successfully treated with PD. Fluid removal facilitated the use of nutritional fluid. Some of the patients initially treated with PD due to lack of space in HD unit were later shifted to HD when space became available and further dialysis required. CONCLUSION From our experience, we conclude that PD is an excellent form of dialysis for the treatment of ARF, especially in children and elderly with cardiovascular-instability. In addition, it can be used as an initial treatment in those cases of CRF where the prospects of regular follow-up for long-term dialysis are extremely poor or when there is likelihood of delay in getting a permanent vascular access established. 9 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 ACKNOWLEDGMENT The authors sincerely thank the record keepers of our institution for maintaining and helping in retrieval of the relevant record. RECOMMENDATION There is a need for further studies including a larger sample size and long term follow up. REFRENCES 1. Siddiqa M, Azad M, Pervaiz MK, Ghias M, Shah GH and Hafeez U. Survival analysis of dialysis patients under parametric and non-parametric approaches. Electron. J. app. stat. anal. 2012;5(2); 271-88. 2. Pakistan Kidney Foundation (2008). Dialysis registry. http://www.kidneyfoundation.net.pk. 3. National Kidney Foundation. K/DOQI. Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am. J. Kidney Dis. 2002;39(2):S1-S66. 4. Guest S, Akonur A, Ghaffari A, Sloand J, and Leypoldt JK. Intermittent Peritoneal Dialysis: Urea Kinetic Modeling and Implications of Residual Kidney Function. Perit Dial Int. 2012;32(2): 142-48. 5. Gokal R, Mallick N. Peritoneal dialysis. Lancet. 1999;353(9155):823–28 6. Van Biesen W, Vanholder R and Lameire N. The role of peritoneal dialysis as the first-line renal replacement modality. Perit Dial Int. 2000;20 (4) 375-83. 7. Donalson MDC, Spargeon P, Haycock GB, Chantler C. Peritoneal dialysis in infants. Br MED J. 1983;286:759-60. 8. Pur G, Korzets A, Hochhauzer E, Eschar Y, Blum M, Avirum A. Cardiac arrhythmia during continuous ambulatory peritoneal dialysis. Nephron.1987; 45(3): 192-95. 9. Fourtounas C, Hardalias A, Dousdampanis P, Savidaki E and Vlachojannis JG. Intermittent peritoneal dialysis (IPD): an old but still effective modality for severely disabled ESRD patients. Nephrol. Dial. Transplant. 2009;24 (10): 321518. 10. Silbiger SR, Neugarten J. The role of gender in the progression of renal disease. Adv. Ren. Replace Ther. 2003;10(1):3-14. 11. Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J. Am. Soc. Nephrol. 2000;11:319–29. 12. National Chronic Kidney Disease Fact Sheet 2010. http://www.cdc.gov/diabetes/pubs/ factsheets/ kidney.htm 13. Martins D, Agodoa L, and Norris K.Chronic Kidney Disease in Disadvantaged Populations. Int. J Nephrol.2012; http://dx.doi.org/10.1155/ 2012/469265 14. Prakash J, Singh TB, Ghosh B, Malhotra V, Rathore SS, Vohra R, etal. Changing epidemiology of community-acquired acute kidney injury in developing countries: analysis of 2405 cases in 26 years from eastern India. Clin Kidney J. 2013;6(2): 150-55. 15. Nolph KD, Cutler SJ, Steinberg SM and Novak JW. Continuous ambulatory peritoneal dialysis in the United States: a three year study. Kidney Int. 1985;28:198-205. 16. Gokal R. Continuous ambulatory peritoneal dialysis- Ten years on. Q J Med. 1987;63(242): 465-72. 17. Ahmed M Alkhunaizi and Ribert. Management of Acute Renal Failure: New Prospectives. W Schrier. Am J Kidney Dis. 1996;28(3); 315-28. 18. Bullock ML, Umen AJ, Finkelstein M and Kean WF. The assessment of risk factots in 426 patients with ARF. Am J Kidney Dis. 1985;5 (2): 97-103 19. Anderson RJ, Linas SL, Bens AS, Henrich WL, Miller TR, Gabow PA etal., Nonoliguric acute renal failure. N Engl J med.1977;296 (20): 113438. 20. Derrick LR, Vance GF, Daniel JS, Ralph GC, Peter JC. Bacterial endocarditis in hemodialysis patients. Am J Kidney Dis. 1997;30 (4):521-24. 21. Shaheen FA, Sheikh IA, Badawi L, Al-Aqeil N, Reyati JM. Complication of subclavian vein cannulation in hemodialysis patietns. Saudi Kidney Diseases and transplantation Bulletin.1990 22. Schillinger F, Schillinger D, Montagnac R, Miller T. Postcatheterization vein stenosis on hemodialysis: comperative angiographic study of 50 subclaian and 50 internal jugular access. Nephrol Dial Transplant. 1991; 6 (10):722-24. 10 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 23. Johnson RJ, Couser WG. Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations. Kidney Int. 1990. ;37 (2):663-76. 24. Lai KN, Lai FM. Clinical features and the natural course of hepatitis B virus-related glomerulopathy in adults. Kidney Int Suppl. 1991;40(35);S24-S33. 25. Simkin EP, Wright FK. Perforating injuries of the bowl complicating peritoneal dialysis catheter.insertion. Lancet. 1968;291 (7533):6466. 26. Rubin J, Oreopoulos DG, Lio TT, Mathew’s r, Veber GA. Management of peritonitis and bowl perforation during chronic peritoneal dialysis. Nephron. 1976;16(3):220-25. 27. Tranaus A, Heimburger O, Lindholm B. Peritonitis on continuous ambulatory dialysis (CAPD); diagnostic findings, therapeutic outcomes and complications. Perit. Dial. Int. 1989;9: 179-190. 28. Fanigan MJ, Freeman RM, Lim VS. Cellular response to peritonitis among peritoneal dialysis patients. Am J Kidney Dis.1985;6 (4); 420-4. 29. Lartundo JAQ, Palomar R, Domingues-D A, Salas C, Ruiz-carado J, Rodrigo E, De-Francisco ALM and Aris M.. Microbial profile of peritoneal dialysis peritonitis and predictors of hospitalization. Adv. Perit. Dial. 2011;27 (1): 3842. 11 Akhtar et al., Int J Med Res Health Sci. 2014:3(1):5-11 DOI: 10.5958/j.2319-5886.3.1.003 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) th Received: 6 Sep 2013 Coden: IJMRHS Copyright @2013 th Revised: 9 Oct 2013 ISSN: 2319-5886 Accepted: 4th Nov 2013 Research article A STUDY ON CHANGES IN SERUM GGT AND MAGNESIUM LEVEL IN ALCOHOLIC LIVER DISEASE *Gandhi Paulin A1, Sendhav Sandip S2, Sanghani Hiren I2, Patel Arpita P3 1 Tutor, Departments of Biochemistry, G.C.S. Medical College, Ahmedabad, Gujarat, India Senior Resident, Departments of Biochemistry, B. J. Medical College & Civil Hospital, Ahmedabad, Gujarat 3 Junior Lecturer, Departments of Biochemistry, N.H.L. Medical College, Ahmedabad, Gujarat, India 2 *Corresponding author email:
[email protected] ABSRACT Aims: A study on changes in Serum GGT and Magnesium level in Alcoholic Liver Disease. Material and Methods: Serum GGT and Serum Mg++ were estimated with the help of commercially available kit in patients of Alcoholic Liver Disease (n=50) and Normal Individuals (n=50) on fully automated biochemistry analyzer Erba XL-640. Results: Serum GGT level was found significantly higher (P< 0.01) in Alcoholic patients as compared to healthy non-alcoholics. Moreover Serum Mg++ was found significantly lower (P< 0.01) in Alcoholic Liver Disease as compare to normal Individuals. In addition to that there is significant inverse correlation (r= - 0.553) between serum GGT and Mg++ in study group. Conclusions: None of the individual tests of conventional liver function tests are of much importance in diagnosis of liver disease; however when many of the liver function tests are abnormal at the same time, liver disease is the most probable diagnosis. Data of the present study clearly conclude that serum GGT activity along with serum Mg++ status can be useful marker for alcoholic liver disease. Keywords: Gamma Glutamyl Transferase, Magnesium, Alcoholic Liver Disease INTRODUCTION Excessive alcohol consumption and consequent medical disorders are considerable problems in our countries which causes a wide variety of medical and social problems1. It is estimated that only 20-50 % of patients with alcoholism are actually identified in health care and thus more reliable and accurate methods are urgently needed. There is no exact clinical finding or symptom clinical setting that can detect alcohol abuse in its early phase. So there are some biochemical substances in the body that can indicate the presence or progress of a condition or any genetic predisposition toward it, are called “Biomarkers” 2 which may detect excessive drinking and evaluate the extent of the resultant tissue damage. Gamma-glutamyl transferase (GGT) is a membranebound glycoprotein enzyme which catalyzes the transfer of the gamma-glutamyl moiety of glutathione to various peptide acceptors. Chronic ethanol consumption induces a rise in serum GGT, and it has therefore been widely used as an index of excessive ethanol intake 3-4. Its sensitivity varied from 15 to 85% in previous studies8-10. Recent work by comparing alcoholic group with normal control group which emphasis on important factor serum GGT activities which can increase in case of alcoholics 5-6. Magnesium (Mg++) a ubiquitous element, involve in membrane stabilization, ion transport, and Ca++ channel activity, cofactor for more than 300 enzymes 7 , may get depleted by several mechanisms associated with alcoholism like magnesium deficiency, including urinary Mg++ wastage, malnutrition, gastrointestinal losses, phosphate deficiency, acidosis/alkalosis, vitamin D deficiency etc. 12 Gandhi et al., Int J Med Res Health Sci. 2014;3(1):12-15 This work was aimed at investigating the diagnostic value of serum GGT level and Serum Mg++ level and correlation of serum GGT and Mg in the evaluation of chronic alcoholic liver disease. MATERIALS AND METHODS In the present cross-sectional study, 50 cases of Alcoholic liver disease and 50 normal individuals were selected from OPD and various clinical wards of B.J. Medical College and Civil Hospital, Ahmadabad, Gujarat during the period of April 2010 to December 2012. The study was approved by the BJ Medical college, Ahmadabad and inform consent form was obtained form the all participants. All patients were primarily evaluated by clinical examination and then confirmed by investigations for liver involvement due to alcoholism. In study group (n=50), we have included male patients between age of 20 – 60 years, BMI ≤ 30 kg/m 2, alcohol consumption for at least last 5 years with clinical evidence of alcoholic liver dysfunction. In control group (n=50), we have included normal healthy individuals having same age and sex. Exclusion criteria: Age < 20 or >60 years, Athletes, Clinical Evidence of current illness, Clinical evidence of any chronic infection, Smoking had not been allowed 1 hour prior to sampling, Protein energy malnutrition, Post operative patient, Patient taking anticonvulsant therapy (Benzodiazepines, 2 Phenobarbitone), BMI > 30 kg/m , Serum Bilirubin level > 20 mg/dL. Venous blood was collected in clot activator serum vacutte from all the participants. Serum was separated and analyzed for GGT, Mg on fully Auto Analyzer – Erba XL-640 at Biochemistry Section. Serum GGT was analyzed by carboxy substrate8 method and serum Mg was analyzed by calmagite method9 with commercially available ready to use reagent kits. Numerical variables are reported in terms of mean and standard deviation. Comparison between two groups is made with the Mann-Whitney test 10. Correlations were calculated with pearson product moment correlation coefficient by using graphpad prism version 3.03 statistical software. RESULTS Table 1: Comparison of Serum GGT and Magnesium in Alcoholic Liver Disease and Normal Individual GGT Magnesium Group-2 (Control Biological Group) Reference Interval n=50 Mean ± SD Mean ± SD 10-50 U/L 101.04 ± 52.2 42.02 ± 12.82 1.6 – 3.0 mg/dL 1.50 ± 0.49 2.03 ± 0.36 *P< 0.01: highly significant difference between two groups In this study we measured Serum activity of Gamma Glutamyl Transferase and Magnesium in both groups. There is highly significant difference observed in between study group and control group. Correlation between serum GGT and Magnesium level in alcoholic liver disease and normal individual during observation significant inverse correlation (r= - 0.533, P<0.01) was found in alcoholic patients whereas it was not significant in normal individual (r= 0.031, P>0.05). 3.5 Significance P value P<0.01* P<0.01* Graph 1: Study Group 3 Magnesium(mg/dL) Parameter Group-1(ALD Patients) n=50 2.5 2 1.5 1 0.5 0 0 100 200 300 GGT (U/L) Fig 1; Correlation of serum GGT with magnesium in Study group 13 Gandhi et al., Int J Med Res Health Sci. 2014;3(1):12-15 Graph 2: Control Group Magnesium (mg/dL) 3.5 3 2.5 2 1.5 1 0.5 0 0 20 40 60 80 100 GGT ( U/L) Fig 2: Correlation of serum GGT with magnesium in control group DISCUSSION Liver serves many important biological functions to sustain life, so early diagnosis of liver involvement is of utmost priority to prevent life threatening complications. Over past decade a large number of new laboratory markers have emerged for alcohol abuse. One of these is Gamma Glutamyl Transferase. In order to assess its usefulness, I have studied Serum GGT level and Serum Magnesium in 50 patients of alcoholic liver disease and 50 normal individual. I have tried to match control with the disease population as far as possible. Glutamyl transpeptidase (γGT) is an enzyme produced in the bile duct. It is induced by alcohol and its serum activity may be increased in heavy drinkers even in the absence of liver damage or inflammation. In this study the serum γGT levels were markedly increased in alcoholic patients (P<0.01). The GGT activity in serum increases after induction of the enzyme, and the possibility of parenchymal damage should always be considered. The elevation of γGT alone with no other liver function test abnormalities often results from induction by alcohol 11. The results of present study are correlate well with earlier studies by B. Usharani et al 2012 12, Turecky L et al. 2006 7, Subir kumar Das et al 2005 13 etc. Chronic alcohol abuse also causes primary malnutrition by insufficient dietary magnesium intake. Moreover, as the cause of secondary malnutrition chronic ethanol intake leads to functional and structural disorders in the gastrointestinal tract that result from its direct action on the gastrointestinal tract and damage to the liver and pancreas. In also affects the magnesium transport mechanisms in the plasma membrane, either directly (alcohol-related modification of the phospholipid environment or acetaldehyde-protein interaction) or indirectly (via the decrease in cellular ATP content).One of the major reasons for ethanolinduced hypomagnesaemia in alcohol abusers is increased urinary magnesium excretion due to damage to the renal proximal tubules and the Henle loop directly induced by ethanol 15-17. These study is also supported by data of previous studies Elisaf M. et al 1995 18 and Virginija Stasiukynienė et al 2002 19. It is concluded from the present study that the estimation of serum GGT can be useful and more cost-effective in diagnosing alcoholic liver diseases as it significantly rises in alcoholic liver disease. Moreover, serum Mg can also be used as a marker of chronic alcoholic liver disease along with serum GGT as they have significant correlation in alcoholic liver disease. CONCLUSION It is concluded from the present study that the estimation of serum GGT can be useful and more cost-effective in diagnosing alcoholic liver diseases as it significantly rises in alcoholic liver disease. Moreover, serum Mg can also be used as a marker of chronic alcoholic liver disease along with serum GGT as they have significant correlation in alcoholic liver disease. REFERENCES 1. Room R, Babor T, Rehm, J. Alcohol and public health. Lancet 2005; 365: 519–30. 2. Peterson K. Biomarkers for alcohol use and abuse: A summary. Alcohol Res Health 20042005; 28(1):30-37. 3. Zein M, Discombe G. Serum gamma-glutamyl transpeptidase as a diagnostic aid. The Lancet 1970; 296: 748–50. 4. Gogoi JB, Tyagi PK, Amit Singh. Study of serum gamma glutamyl transferase as a diagnostic marker in alcoholic hepatitis. IOSR Journal of Pharmacy (IOSRPHR) 2012; 2; 69-71. 5. Peters TJ, Cook CC. Obesity as a cause of ‘falsepositive’ alcohol misuse laboratory 14 Gandhi et al., Int J Med Res Health Sci. 2014;3(1):12-15 investigations. Addiction Biology 2002; 7:443– 46. 6. Katri Puukka. Gamma-glutamyl Transferase As a Marker of Alcohol Abuse: Effects of Moderate Drinking, Obesity & Increasing Age on Reference Intervals, University of Tampere, Medical School Seinajoki Central Hospital, Department of Laboratory Medicine and Medical Research Unit, Finland, 2007: pp 15. 7. Turecky L, Kupcova V, Szantova M. Serum magnesium levels in patients with alcoholic and non-alcoholic fatty liver. Bratisl Lek Listy. 2006; 107(3):58-61. chronic alcoholic patients during withdrawal. Medicina 2002; 38:892-95. alcohol 8. Bergmeyer H-U, Horder M, Rej R. IFCC methods for the measurement of catalytic concentrations of enzymes, J. Clin. Chem. Clin Biochem. 1986; 24: 497-510. 9. Gindler E. Colorimetric Determination With Bound "Calmagite" of. Magnesium in Human Blood Serum. Clin. Chem.1971; 17: 662. 10. Rosie Shier. Statistics:2.3 The Mann-Whitney U Test. Mathematics learning support center 2004:1-5. 11. Keeffe EB, Sunderland MC, Gabourel JD. Serum gamma-glutamyl transpeptidase activity in patients receiving chronic phenytoin therapy.Dig Dis Sci. 1986; 31(10): 1056-61. 12. Usharani B, Vennila R, Nalini N. Biochemical changes in Alcoholics: A case control study. International Journal of Research in Pharmaceutical and Biomedical Sciences 2012; 3: 201-05. 13. Subir Kumar Das, Prasunpriya Nayak, Vasudevan DM. Biochemical markers for alcohol consumption. IJCB 2005, 20(1): 35-42 14. Kocur J. Concentration of bioelements in alcohol dependent patients. Biul.Magnezol. 1997; 2: 239. 15. Elisaf M, Merkooropoulos M. Pathogenetic mechanisms of hypomagnesaemia in alcoholic patients. J. Trace Elem. Med. Biol. 1996; 9: 210. 16. Vormann J. Magnesium: nutrition and metabolism. Mol. Aspects Med.2003; 24: 27. 17. Elisaf M, Merkouropoulos M, Tsianos EV. Pathogenetic mechanisms of hypomagnesemia in alcoholic patients. J Trace Elem Med Biol 1995; 9: 210-14. 18. Virginija Stasiukynienė. Blood plasma potassium, sodium and magnesium levels in 15 Gandhi et al., Int J Med Res Health Sci. 2014;3(1):12-15 DOI: 10.5958/j.2319-5886.3.1.004 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 10 Sep 2013 Revised: 15th Oct 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 10th Nov 2013 EFFECT OF GONADAL HORMONES ON HYPOPHAGIC PROPERTY OF OPIOID ANTAGONIST NALOXONE Gargate Ashwini R1, Kulkarni Dushant V2 1 Associate Professor, 2M. Sc (Med Physiology) Student, Department of Physiology, Krishna Institute of Medical Sciences Deemed University, Karad, Maharashtra, India. *Corresponding author email:
[email protected] ABSTRACT Background: Studies have shown that hormonal fluctuations that occur over the estrous cycle in rats affect food intake. It is possible that estrogen affects food intake via Opioid system and other brain areas which are involved in regulation of food intake. Therefore it may affect the sensitivity of female rats to hypophagic effect of Opioid antagonist Naloxone. Testosterone in male rats also changes food intake. However, little is known about hoe these Gonadal hormones interact with Opioid receptors to modulate food intake. Objective: The aim of the study was to find out how Gonadal hormones affect hypophagic property of Naloxone. Methods: Basal food intake of 40 healthy adult females and 20 healthy adult male rats was recorded. Then they were injected intraperitoneally with Naloxone after fasting for 24 hrs. In female rats food intake was measured during different phases of the estrous cycle. All the rats were then subjected to gonadectomy. The food intake was measured after gonadectomy. The effect of Naloxone was also measured in deprivation paradigm after gonadectomy. Results: Female rats showed decreased food intake during proestrous and estrous phases. In female rats there was no hypophagia after Naloxone injection during these phases. Male rats showed hypophagia on Naloxone injection. Male rats showed increased food intake after gonadectomy. In female rats the increase in food intake was not significant when gonadectomy was done during metestrous and diestrous. However, Naloxone could induce hypophagia in all female rats after gonadectomy. Conclusion: Estrogen decreases food intake, it decreases sensitivity of female rats to hypophasic effects of Naloxone. Testosterone decreases food intake. Testosterone does not interfere with hypophagic effect of Naloxone. Keywords: Food intake, Gonadal hormones, Naloxone, Hypophagia. INTRODUCTION Appetite, energy balance and body weight gain are modulated by diverse neurochemical and neuroendocrine signals from different organs in the body and diverse regions in the brain. Alterations in the regulation of food intake and energy expenditure underlie the development, progression and recurrence of obesity.1,2 This has been the cause of obesity related complications like diabetes and hypertension etc. This energy balance and fuel utilization are significantly affected by gonadal hormones, estrogen in females and testosterone in males. Estrous cycle related effects on food intake have been linked to the effects of estrogen on central nervous system and peripheral tissues.3,4,5 Rodents typically cycle over 4-5 days and phases of estrous cycle are commonly classified by histological changes in vaginal cytology which is roughly divided into estrous, metestrous, 16 Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22 diestrous and proestrous.6 Food intake is generally increased during diestrous and decreased during estrous.7 So we confirmed these findings in our laboratory by conducting the present study. Previous studies suggest that estradiol acts on muopioid receptors to modulate the antinociception in rats.8 So estradiol may also modulate food intake by its action on mu-opioid receptors. Therefore it may affect the anorectic property of Opioid antagonist naloxone during different phases of estrous cycle in female rats. There are studies which show that in male rats testosterone reduces food intake. Other studies also show that opioid antagonist naloxone facilitates sexual behaviour9 and there is no satisfactory explanation to this. However, possible explanation could be the interaction between testosterone and Naloxone which can affect food intake as well. So the present study was undertaken to evaluate if Gonadal hormones alter food intake by acting on opioid receptors in the central nervous system in addition to their action on other parts of the CNS. MATERIALS AND METHODS The present study was approved Institutional Animal Ethics Committee of KIMS, Karad. 40 healthy adult female and 40 healthy adult male Wistar rats were used for the study. The average age was 3-4months old. Animals were weighed, marked and housed in separate polyvinyl cages in animal room having controlled room temp (25±20c). They were maintained on 12 hrs dark and 12 hrs light cycle with standard laboratory diet and water ad lib. First 8 days baseline food intake in all animals were recorded. In female rats food intake was recorded during different phases of estrous cycle. In deprivation paradigm, the animals were kept fasting for 24 hrs. Then saline 2ml was injected intraperitoneally at 9 am on the day of test. 30 mins after injection the food was weighed and introduced into the cage. Then the food intake was measured at an interval of ½ hr, 1hr, 2hrs and 24hrs. These values were considered as control. Same animals were used as control on 1st 24 hrs deprivation with saline injection and on 2nd 24 hrs deprivation they were injected with naloxone The animals were kept fasting for 24 hrs again on the next day. Then 2.5 mg/kg naloxone was injected intraperitoneally at 9 am on the day of test. 30 mins after injection the food was weighed and introduced Gargate AR et al., into the cage. Then the food intake was measured at an interval of ½ hr, 1hr, 2hrs and 24hrs. Every time the intake was measured by weighing food prior to and after each condition and adjusting for spillage that was collected in paper towel under wire mesh. Food intake in deprivation paradigm after saline and after naloxone injection in male and female rats was recorded. In addition to this the female rats’ food intake was recorded during different phases of estrous cycle after naloxone injection in deprivation paradigm. Vaginal cytology for stage of estrous cycle: Daily vaginal smears were obtained at 8.30am to assess the stage of estrous cycle. Smears were examined under light microscope. Stage of the cycle was assigned using the following criteria as previously described6 1) Proestrous when predominantly nucleated epithelial cells in the absence of leukocytes were present. 2) Estrous when sheets of nonnucleated squamus cornified cells in absence of leucocytes were present. 3) Metestrous (D1) when there was an equal distribution of leucocytes and cornified and nucleated epithelial cells. 4) Diestrous (D2) when a mixture of epithelial cells and leucocytes with predominance of leucocytes was present. Then both male and female rats were gonadectomised. Procedure for ovariectomy: The female rats were weighed and then injected with atropine sulphate in a dose of 0.25mg subcutaneously to minimise the respiratory discomfort. Intraperitoneal Sodium pentobarbitone in the dose of 35mg/kg body weight was injected for anaesthesia, whereas Ether inhalation was used to maintain a steady level of anaesthesia while doing gonadectomy. Anaesthetised rat was placed on a rat operating table with ventral surface facing towards operator. Animal was secured properly to the operation table. Midline incision was taken on lower abdomen extending for 2cms lengthwise. A snip was made through the fascia of abdominal rectus muscle. The points of forceps were forced through the snip and hole was extended opening the forceps. The ovary was found embedded in the fat lying just below the dorsal muscle mass. It was identified by fimbrial end. The ovary was drawn through the incision, uterus clamped in a haemostat and a ligature placed around the uterus just below fallopian tube and was tied tightly. The ovary was removed. Similarly other ovary was also removed. The muscle incision was closed with catgut 17 Int J Med Res Health Sci. 2014;3(1):16-22 and skin incision with thread. Powder Nebasulf was sprinkled over the sutures and Benzathin Penicillin, 3 lakh units was injected intramuscularly to prevent infection. Animal was allowed to recover from anaesthesia and then was transferred to respective cage. A period of 10 days was allowed for recovery from operative injury following which vaginal smears were examined for 1 week. Continuous diestrous was taken as an indication for successful gonadectomy. Procedure for Orchidectomy: The male rats were weighed and then injected with atropine sulphate in dose of 0.25mg subcutaneously to minimise the respiratory discomfort. Then they were anaesthetised as in female rats. Anaesthetised rat was kept on the rat operating table. Part to be operated was shaved properly. Under aseptic precautions ventral midline incision was made through the skin of the scrotum. The slight pressure was given on abdomen as rats are able to retract testes in abdominal cavity. They were freely movable within the scrotum. One testis was drawn through a skin incision. A slit was made through tunica and the testis was freed. The spermatic cord which was attached to the testis was doubly ligated and cord was cut between the ties. Other testis was removed similarly. Skin incision was closed with thread sutures. Powder Nebasulph was sprinkled on sutured skin and rat was injected with 3 lakh units of Benzathin Penicillin intramuscularly to prevent infection. 10 days were allowed for recovery from operative injury. After measuring 8 days basal food intake, all gonadectomised rats were injected with 2.5mg/kg intraperitoneally naloxone after keeping them fasting for 24 hrs. The food intake was measured as was done before gonadectomy. Food intake was measured in grams. Statistical analysis: For data analysis all the values were expressed in terms of mean ± standard error of mean. Differences between means were compared by applying paired‘t’ test. The effect was considered statistically significant if the probability of chance was less than 0.05 (p<0.005). RESULT Table 1: Food intake in female rats during different phases of estrous cycle Phase of estrous cycle Food intake (in gms.) at different time of the day 1hr 1.5hr 2.5hr Proestrous 0.6 ±0.44* 1.1±0.30* 2.0 ± 0.71* Estrous 1.35± 0.43 1.86±0.53 3.3±0.71 Metestrous 2.87±0.55* 4.16±0.98* 6.29 ±0.92* Diestrous 2.5 ± 0.15* 3.9 ±0.24* 5.3±0.23* *P< 0.05, data presented as Mean ± SEM 24hr 7.1 ± 0.24* 9.5 ±0.98 13.16 ±0.71* 13.82± 0.39 Table 2: Effect of different phases of estrous cycle on Naloxone induced hypophagia in deprivation paradigm in female rats. Phase of estrous cycle Food intake (in gms.) Proestrous 1hr 1.5hr 2.5hr 24hr. After saline injection 1.7 ±0.11 2.75 ± 0 4.2 ± 0.37 10.25 ±0.33 After Naloxone injection 1.2 ± 0.32 2.5 ± 0.16 3.9 ±0.24 19.0 ±0.39 Estrous After saline injection 1.33 + 0.40 1.98 ± 0.46 3.45 ±0.42 8.23 ± 0.77 After Naloxone injection 0.93 ±0.09 1.75 ±0.27 3.00 ±0.42 10.11 ± 0.29 Metestrous After saline injection 3.9 ±0.55 5.0 ±0.93 7.1 ±0.92 15.2±0.71 After Naloxone injection 1.2± 0.31* 1.98 ± 0.23* 3.56± 0.53* 14.7 ± 0.29 Diestrous After saline injection 3.1 ± 0.22 4.5 ±0.62 6.8 ±1.1 14.3±0.35 After Naloxone injection 1.5 ± 0.44* 2.25 ± 0.33* 4.25 ±0.53* 15.2 ± 0.75 *P< 0.05, data presented as Mean ± SEM Table 2 shows the effect of food deprivation on food intake in different phases of estrous cycle. After 24 hrs fasting in female rats during estrous phases there was no significant increase in food intake. 18 Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22 However, in metestrous, diestrous and proestrous phases the food intake was significantly increased after 24 hrs fasting. This table also shows effect of naloxone on food intake in different phases of estrous cycle. It was seen that Naloxone induced significant hypophagia in rats after 24hrs fasting in metestrous and diestrous. In proestrous and estrous phases naloxone could not induce hypophagia in deprivation paradigm. Table 3: Effect of gonadectomy on food intake and naloxone induced deprivation paradigm. Phase of estrous cycle Food intake (in gms) Proestrous 1hr 1.5hr saline injection before gonadectomy 1.7 ± 0.11 2.75 ± 0 saline injection after gonadectomy 4.8± 1.1* 5.89 ±0.76* Naloxone injection after gonadectomy 2.9 ±0.32* 4.2 ±0.16* Estrous saline injection before gonadectomy 1.33 ± 0.40 1.98± 0.46 saline injection after gonadectomy 3.16 ± 0.42* 3.6 ±0.53* Naloxone injection after gonadectomy 1.58 ± 0.29* 2.5± 0.15* Metestrous saline injection before gonadectomy 3.9 ± 0.55 5.0 ± 0.93 saline injection after gonadectomy 4.4 ±0.55 5.2 ±0.44 Naloxone injection after gonadectomy 2.12± 0.31* 3.75 ± 0.23* Diestrous saline injection before gonadectomy 3.1± 0.22 4.5 ± 0.62 saline injection after gonadectomy 4.9 ±0.33* 5.5 ± 0.9* Naloxone injection after gonadectomy 2.15 ± 0.65* 3.96 ± 1.07* *P< 0.05, data presented as Mean ± SEM Table 4: Food intake after orchidectomy and naloxone injection Before Gonadectomy Food intake (in gms.) 1hr 1.5hrs Basal food intake 2.2 ± 0.27 3.2 ± 0.46 After 24 hrs fasting After Saline injection 3.0 ± 0.36* 4.3 ± 0.55* After Naloxone injection 0.6 ± 0.24* 1.7 ± 0.28* After Gonadectomy Basal food intake 4.2 ± 0.48* 5.5 ± 0.45* After 24hrs fasting 1hr 1.5hrs After Saline injection 4.9 ± 0.57* 6.2 ± 0.42* After Naloxone injection 1.0 ± 0.19* 1.6 ± 0.42* *P< 0.05, data presented as Mean ± SEM Table 3 shows the effect of ovariectomy on food intake and hypophagia induced by Naloxone in female rats. It is seen that the food intake was significantly increased after ovariectomy in all female rats. However, the increase was not significant when ovariectomy was done during metestrous phase. hypophagia in female rats in 2.5hr 4.2 ± 0.37 6.7 ± 0.83* 5.3± 0.24* 24hr. 10.25 ± 0.33 14.6 ± 0.45* 13.9± 0.39 3.45± 0.42 5.06± 0.71* 3.75± 0.53* 8.23 ±0.77 13.66±0.98* 12.95 ±1.46 6.1 ± 0.92 6.7 ± 0.13 4.25± 0.53* 15.2 ± 0.71 15.6 ± 0.89 15.7 ± 0.29 6.8 ±1.1 7.7 ± 0.24* 5.43± 0.47* 14.3 ± 0.35 15.4 ± 0.56* 15.9 ± 0.98 2.5hrs 4.6 ± 0.80 24hrs 15.1± 0.82 5.7 ± 0.82* 3.0 ± 0.59* 15.6 ±0.82 11.8 ± 1.1 6.5 ± 0.60* 2.5hrs 7.2 ± 0.76* 3.0 ± 0.59* 17.0 ± 0.71* 24hrs 17.2 ±1.88 11.2 ±1.37 This increase was more pronounced in the female rats in which ovariectomy was done in estrous and proestrous phases. Naloxone induced significant hypophagia in all rats after ovariectomy in initial period after 24hrs food deprivation. Table 4 shows food intake in male rats. Food intake is significantly increased after orchidectomy. In 19 Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22 deprivation paradigm naloxone induced hypophagia in initial period of the day before and after orchidectomy. DISCUSSION The present study was designed to examine whether the gonadal hormones affect the hypophagic properties of naloxone upon food deprivation induced hyperphagia. It appears that naloxone induces hypophagia in food deprived male and female rats as compared to controls (saline). These concur with the earlier studies.10 It is known that after puberty male rats weigh and eat more than do female rats of same age. This sex difference is more pronounced with age. We also studied the role of sex hormones in regulation of food intake. We found that during the estrous phase the food intake of female rats was less and least in proestrous phase. The food intake was increased during diestrous but it was highest during metestrous. These findings are consistent with other workers.11-13 This could be because of wide variations in estrogen levels during the phases of estrous cycle. The sequence of phases in the cycle is proestrous, estrous, metestrous and diestrous. The estrogen levels start rising in diestrous reaching its peak in proestrous and start declining during estrous decreasing to lowest level during metestrous.14,15 Estrogen is known to affect food intake thorough central and peripheral mechanisms. Several lines of evidence indicate that the effects of estradiol on food intake are mediated by its actions on estrogen receptors within the brain. In the early 1970's, Wade and Zucker were the first to report that direct stimulation of the ventromedial hypothalamus (VMH) by estradiol influenced feeding behavior in female rats. They found that central implants of undiluted estradiol benzoate (EB) in the VMH decreased food intake in ovariectomized rats. 16 In this study we found that after gonadectomy in female rats there was a significant increase in food intake. This increase was more pronounced in female rats where gonadectomy was done during proestrous and estrous. Perhaps this explains the effect of withdrawal of high estrogen after gonadectomy. In our study we found that Naloxone which is an opioid receptor antagonist blocking mu- receptors, induces hypophagia in food deprived male and female rats (p<0.05) as compared to controls (saline). It appears that naloxone induces hypophagia in food deprived male and female rats as compared to controls (saline injection). These concur with the earlier studies.17,18 One of the main functions proposed for opioid peptides in the CNS is involvement in mediation of hunger component in the control of food intake. Changes in the beta endorphin content of pituitary or hypothalamus have been demonstrated under condition designed to reflect changes in the state of hunger or satiety in rats. In normal rats fasted for 23 days beta endorphin content of the whole hypothalamus is decreased.19 Several investigators have also reported that administration of beta endorphins in CNS increased food intake.20 Intake of palatable food containing sugar or high fat is selectively increased by mu-opioid agonist when injected into ventromedial striatum including nucleus accumbens.10 Other studies also show that agonists of mu, delta, kappa and ORL Opioid receptors increase food intake while Opioid receptor blockade decreases food intake.21 In female rats we studied the effect of estrous cycle phases on the hypophagic effect of Naloxone. It was observed that during proestrous and estrous phases the Naloxone failed to induce hypophagia in these rats. Our findings are consistent with earlier studies.22 It is seen from the previous studies that gonadal steroids modulate opioid peptides and receptors in the central nervous system.23- 25 Ovariectomy in rats results in an increased sensitivity to suppressive effects of Naloxone on food intake compared with estradioltreated ovariectomised rats.26-29 The probable explanation for this may be that estrogen acts on muopioid receptors in the brain to modulate the functions of Opioid peptides.8 When Naloxone is injected it fails to block the Opioid receptors which are already blocked competitively by estrogen. So Naloxone fails to induce hypophagia in the presence of high estrogen. In this study we found that after gonadectomy in all the female rats naloxone induced significant hypophagia when estrogen was no more there for competitive blockade of the receptors. In male rats also Naloxone induced hypophagia in deprivation paradigm. After gonadectomy the basal food intake of male rats was increased. After gonadectomy in these male rats food intake was significantly increased. In all these rats Naloxone induced significant hypophagia before and after gonadectomy. These findings suggest that testosterone in males interferes with the mechanisms on energy intake however unlike estrogen it does not interact 20 Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22 with opioid receptors to alter the hypophagic effect of Naloxone. Our findings concur with the other studies. Gonadectomised male rats treated with testosterone propionate showed decrease in food intake.21 7. CONCLUSION Amongst the Gonadal hormones estrogen in females and testosterone in males modulates food intake. However, estrogen interferes with the hypophagic effects of naloxone perhaps by competitive blockade while there is no such alteration caused by testosterone. How do these Gonadal hormones and Opioid receptors interact to modulate food intake needs to be further investigated. ACKNOWLEDGEMENT The authors are thankful to the vice chancellor and principle KIMS deemed university, Karad for providing us all the laboratory facilities for doing this work. We are also thankful to our laboratory technicians for assisting us during operative procedures. 8. 9. 10. 11. 12. Conflict of interest-None declared. REFERENCES 13. 1. Levin BE, Dunn-Meynell AA, Banks WA. Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signalling before obesity onset. Am J Physiol Regul Integr Comp Physiol. 2004; 286: 143–50. 2. MacLean PS, Higgins JA, Johnson GC. Metabolic adjustments with the development, treatment, and recurrence of obesity in obesity-prone rats. Am J Physiol Regul Integr Comp Physiol. 2004; 287:288–97. 3. Asarian L, Geary N. Modulation of appetite by gonadal steroid hormones. Philos Trans R Soc Lond B Biol Sci. 2006; 361: 1251–63. 4. Henry BA, Clarke IJ. Adipose tissue hormones and the regulation of food intake. J Neuroendocrinol. 2008; 20: 842–49. 5. Peter C. Butera. Estradiol and the control of food intake. Physiol. Behav. 2010; 9:99-175. 6. Schedin P, Mitrenga T, Kaeck M. Estrous cycle regulation of mammary epithelial cell proliferation, differentiation, and death in the Sprague-Dawley rat: a model for investigating the 14. role of estrous cycling in mammary carcinogenesis. J Mammary Gland Biol Neoplasia. 2000; 5: 211–25. Eckel LA, Houpt TA, Geary N. Spontaneous meal patterns in female rats with and without access to running wheels. Physiol Behav. 2000; 70: 397– 405. Erin C. Stoffel, Ulibarri CM, Folk JE. Gonadal hormone modulation of mu, kappa and delta Opioid nociception in male and female rats. J pain. 2005;6: 261-74. Cassidy Vuong, Stan H. M. Van Uum, Laura E. O'Dell. The Effects of Opioids and Opioid analogs on Animal and Human Endocrine Systems. Endocr Rev. 2010; 31: 98–132. Jones JG, Ritcher J A. The site of action of naloxone in suppressing food and water intake in rats. Life science 1981; 18:2055-64. Blaustein JD, Wade GN. Ovarian influences on meal patterns of female rats. Physiol Behav.1976;17: 201–08. Butcher RL, Collins WE, Fugo NW. Plasma concentrations of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4day estrous cycle of the rat. Endocrinology 1974; 94:1074–78. Ter Haar MB. Circadian and estrual rhythms in food intake in the rat. Horm Behav 1972;3: 213– 20. Ariel Garcia, Iman Allawzi, Kayla McGuire. The effects of progesterone and estrogen on vasoconstriction in rats. Biological Sciences Purdue University, W. Lafayette, IN,47907 1985: poster 11-16 15. Marcondes FK, Bianchi FJ, Tanno AP. Determination of the estrous cycle phases of rats: some helpful considerations. Brazilian Journal of Biology. 2002; 62: 609-614 16. Wade GN, Zucker I. Modulation of food intake and locomotor activity in female rats by diencephalic hormone implants. J Comp Physiol Psychol 1970; 72: 328–38. 17. Meli R, Pacilio M, Raso GM. Estrogen and raloxifene modulate leptin and its receptors in hypothalamus and adipose tissue from ovariectomized rats. Endocrinology. 2004; 145: 3115–21. 21 Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22 18. Gambert SR, Garthwaite JL, Pontzer CH, Hagen TC Fasting is associated with decrease in hypothalamic beta endorphin. Science 1981; 213: 1282-83 19. Temple DL, Leibiwitz SF. PVN implants: Effects on feeding pattern and micronutrient selection. Brain. Res. Bull. 1989; 23: 553-60. 20. Glass M J, Billinton CJ, Levin AS. Opioid and food intake: distribution of neural pathways. Neuropeptides 1999; 33: 360-68 21. DuPont A, Barden N, Cusan C. P-endorphin and met-enkephalin: Their distribution, modulation by estrogens and haloperidol, and role inneuroendocrine control. Fed Proc. 1980; 39: 2544. 22. Hahn EF, Fishman J. Changes in rat brain opiate receptor content upon castration and testosterone replacement. Biochem Biophys Res Commun. 1979; 90: 819-23. 23. Hong JS, Yoshikawa K, Lamartiniere CA. Sex related difference in the rat pituitary [Met”]enkephalin level-altered by gonadectomy. Brain Res. 1982; 251: 382-83. 24. Lee SA, Panerai E, Bellabara D, Friesen HG. Effect of endocrine modifications and pharmacological treatments on brain and pituitary concentrations of P-endorphin. Endocrinology. 1980; 107: 245-48. 25. Morley JE, Levine AS, M Grace, The effect of ova~ectomy, estradiol and progesterone on opioid modulation of feeding. Physiol Behav. 1984;33: 237-41. 26. Harishankar N, Giridharan N. Restoration of libido in male rats by administration of high dose testosterone propionate. Advanced Studies in Biology. 2012; 4: 557-71. 27. Witte MM, Resuehr D, Chandler AR. Female mice and rats exhibit species-specific metabolic and behavioral responses to ovariectomy. Gen Comp Endocrinol. 2010; 166: 520–28. 28. Rogers NH, Perfield JW, Strissel KJ. Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology. 2009; 150:2161–68. 29. Hans-Rudolf Berthoud. Multiple neural systems controlling food intake and body weight. Neuroscience and Biobehavioral Reviews. 2002; 26:393-28. 22 Gargate AR et al., Int J Med Res Health Sci. 2014;3(1):16-22 DOI: 10.5958/j.2319-5886.3.1.005 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS rd Received: 23 Sep 2013 Revised: 17th Oct 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 20th Nov 2013 HEMOGLOBIN A1C INDUCED DOWN-REGULATION OF CD36 OF PLASMODIUM FALCIPARUM PARASITIZED RED CELL Hassan Hijazi1, Atif Alagib2, *Hisham Waggiallah3 1 AL-Ghad International Colleges for Applied Health Science, Qassim, Saudia Arabia Tropical Medicine Research Institute, National Centre for research, Ministry of Science and Technology, P. O. 1304, Sudan. 3 Department of Medical Laboratory, Faculty of Medical Applied Science, Taibah University. P.O Box 3001, Almadinah Almonawarah, Saudia Arabia. 2 *Corresponding author email:
[email protected] ABSTRACT Objective: High values of glycosylated hemoglobin have been found to correlate with decreased deformability of erythrocyte. CD36 (Cluster of Differentiation 36) is an integral membrane protein found on the surface of many cell types of class B scavenger receptor family. Plasmodium falciparum and diabetes mellitus is associated many complications. Aim of this study to investigate the down-regulation of HbA1c to CD36 on P. falciparum parasitized red blood cells Diabetes mellitus patients. Methods: This is cross section study conducted among diabetic patients attending in Jabir Abo Eleiz diabetic center in Khartoum state. Venous blood samples were collected in heparin containers for Plasmodium falciparum culture, and random blood sugar. For HbA1c in 0.04 mg EDTA anticoagulant, 2-5 ml of blood was collected. Sample size was 45 samples and was collected from known diabetic patients with HbA1c more than 8%. All data were analyzed by using Statistical Package for Social Science (SPSS). Results: show the mean difference between CD36 negative control and CD36 positive control was found to be statistically significant increasing of CD36 presence at P. value =0.001 (P ≤0.001). The mean difference between CD36 positive control and diabetic patients with HbA1C more 8% was found to be statistically significant reduction of CD36 expression at p=0.001. Conclusion: Hyperglycemia (HbA1c) leads to decrease of CD36 expression and interfere with innate and active immunity. In this study HbA1c participates in increasing of P. falciparum malaria complications. Keywords: HbA1c, CD36, Plasmodium falciparum, Diabetes mellitus. INTRODUCTION Glycation of proteins is a frequent occurrence, but in the case of hemoglobin, a non-enzymatic reaction occurs between glucose and the N-end of the beta chain. Abnormal glycation, which can adversely affect hemoglobin and membrane proteins in erythrocytes, has been shown to correlate with reduced membrane fluidity1 separately, high values of glycosylated hemoglobin have been found to correlate with decreased deformability of erythrocyte.2 Hassan et al., CD36 is a multi-functional molecule. It has independent binding sites for different classes of ligands Such as modified phospholipids, thrombospondins, and free fatty acids. This enables CD36 responsible for several different cellular processes depending on the nature of the ligand and the type and location of the cell on which it is expressed. On phagocytes CD36 functions as a scavenger receptor helping in recognition and Int J Med Res Health Sci.2014;3(1):23-27 23 internalization of apoptotic cells3, falciparum malaria infected erythrocytes.4,5 CD36 also functions as an adhesion molecule, it has been identified CD36 as the receptor that helps in cytoadherence of Plasmodium Falciparum parasitized erythrocytes6, It has been reported that CD36 on platelet mediates clumping of P. falciparum infected erythrocytes is strongly associated with severe malaria.7 In contrast, CD36 on monocytes or macrophages can help phagocytosis of falciparum Infected erythrocytes. Thus the location of CD36 receptor can regulate the severity of malarial disease. Several studies have suggested an important role of CD36 in phagocytic clearance of apoptotic and Senescent cells.8 Malaria culture is the method to grow malaria parasite outside the body i.e. in an in vitro environment. P. falciparum is currently the only human malaria parasite that has been successfully cultured continuously in vitro. Although attempts for propagation of the parasites outside of humans or animal models.9 METHODOLOGY Ethical approval: Ethical clearance obtained from the Ethical Committee Board of the Tropical Medicine Research Institute. The consent was taken from patients and taken the permission from medical management of Jaber Abu Ezz Diabetes Center and selected individual after being informed with all objectives of the study and its health impact in the future. This is cross section study was conducted in Khartoum state among diabetic patients attending in Jabir Abo Eleiz diabetic Centre. In an aseptic conditions ml venous blood samples were collected in heparin containers for culture, Ox LDL, and Random Blood Sugar (RBS). For HbA1c in 0.04 mg EDTA anticoagulant, 2-5 ml of blood was collected. The samples were mixed well and tested within 6 hour. Samples were classified into three groups: Group I: 15 samples were collected from apparently health People free from any disease as negative control. Group II: 15 samples were cultured with Plasmodium falciparum as CD36 positive control. Culture technique as following: Erythrocytes were washed 3 times in Roswell Park Memorial Institute medium (RPMI) 1640 to remove citrate phosphate dextrose (CPD), serum, and leukocytes if present. Dilute to 5% hematocrit with cMCM in small flasks of 25cm2 (0.2 mL of packed cells to 4 mL of malaria culture media (MCM) or in 75-cm2 flasks (1.0 mL to 20 mL). Parasites were added to an appropriate parasitemia. Flask was put in a candle jar and loosens the screw cap. Produce low oxygen by burnt out candle and place the jar at 37 °C. MCM was replace every day (not necessary the day after sub cultivation). Subculture was cultured 2 times / week. Group III: 15 samples from known diabetic patients (HbA1c more than 8%) and were tested for CD36. CD36 was measured by Flow cytometer uses the principles of light scattering, light excitation, and emission of fluorochrome molecules to generate specific multi-parameter data from particles and cells in the size range of 0.5um to 40um diameter. Cells are hydro-dynamically focused in a sheath of phosphate buffer saline (PBS) before intercepting an optimally focused light source; Lasers are most often used as a light source in flow cytometer properties of single particles (e.g. cells, nuclei, chromosomes) during their passage within a narrow, precisely defined liquid stream. The hemolysate, where the labile fraction is eliminated hemoglobin’s are retained by a cationic exchange resin. Hemoglobin A1C (HbA1c) is specifically eluted after washing away the hemoglobin A1a+b fraction1 (HbA1a+b), and is quantified by direct photometric reading at 415 nm. Quality control: All reagents and test equipment were controlled according to the instructions in the procedures manual, manufacturing control and control sample were used in each test. Data analysis: Data were analyzed by using Statistical Package for Social Science (SPSS) version 21 and Microsoft Excel 2013. Results were obtained by using student T .test. RESULTS Table 1: Shows the mean difference of CD36 amount in negative control and positive control: Group N Mean ± SD DF T P Value CD36 negative control 15 0.3600 ± 0.12923 28 10.513 0.001** CD36 positive control 15 26.1000 ± 9.48194 P *≤ 0.05, P **≤ 0.01 Hassan et al., Int J Med Res Health Sci.2014;3(1):23-27 24 Table 2: Shows the mean difference of CD36 amount in negative control and diabetic patients with HbA1C ≥ 8% Group CD36 negative control CD36 in diabetic patient with HbA1C ≥ 8% N 15 15 Mean ± SD 0.3600 ± 0.12923 5.9460 ± 1.66648 DF 28 T 12.943 P Value 0.001** Table 3: Shows the mean difference of CD36 amount in positive control and diabetic patient with HbA1C ≥ 8% Group N Mean ± SD DF T Sign CD36 positive control 15 26.1000 ± 9.48194 28 8.108 0.001** CD36 in diabetic patient with HbA1C ≥ 8% 15 5.9460 ± 1.66648 Table 4: Shows mean difference of RBCs percentage containing (CD36); between CD36 negative control and positive control: Group N Mean ± SD DF T-value P-value CD36 negative control 15 1.7600 ± 0.64454 28 3.29 0.003** CD36 positive control 15 11.1800 ± 11.05740 Table 5: Shows mean difference of RBCs percentage containing (CD36) between CD36 positive control and diabetic patients with HbA1 C ≥ 8% Group N Mean ± SD DF T-value P-value CD36 positive control 15 11.1800 ± 11.05740 28 2.64 0.013* CD36 in diabetics patients with HbA1 C≥8% 15 3.6067 ± 1.11257 Forty five (45) individuals participated in the present study. In table: 1 the mean difference between CD36 negative control and CD36 positive control was found to be statistically significant at P. value =0.001 (P ≤0.001). The mean difference between CD36 negative control and CD36 in diabetic patients with HbA1C ≥ 8% was highly significant at P. value = 0.001 as shows in table 2. The mean difference between CD36 positive control and diabetic patient with HbA1C more 8% was found to be statistically significant at p=0.001 as shows in table 3. The mean difference percentage of RBCs containing (CD36) between CD36 negative control and CD36 positive control was found to be statistically significant at p = 0.003 as shown in table 4. The mean difference of percentage of RBCs containing (CD36) between CD36 Positive control and CD36 in diabetics patients with HbA1 C>8% was found to be statistically significant at p = 0.013 as shown in table 5. DISCUSSION HbA1c occurs when hemoglobin joins with glucose in the blood. Hemoglobin molecules make up the red Hassan et al., blood cells in the blood stream. When glucose sticks to these molecules it forms a glycosylated hemoglobin molecule, also known as A1c and HbA1c. The more glucose found in the blood the more glycated hemoglobin (HbA1c) will be present.10 CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a receptor for low density lipoprotein, and malaria infected erythrocytes. Despite an impressive increase in knowledge of CD36 functions, in depth understanding of the mechanistic aspects of this protein remains elusive. This study focuses on the impact of hemoglobin A1c on CD36 of Plasmodium falciparum infection in diabetic patients. In present study when data of red blood cells infected with P. falciparum (P.F) was compared with normal healthy RBCs there was significant (P < 0.001) expression of CD36 in the red blood cell in addition, comparison between the same groups also found significant (P < 0.003) increasing of RBCs percentage containing CD36 that means plasmodium falciparum could increases the expression of CD36 on the surface of the parasitized red cells. This agreed with Ho, M. and White, N.J. 1999,11 who were proposed CD36 a major receptor for P. falciparum-infected red blood Int J Med Res Health Sci.2014;3(1):23-27 25 cells (IRBCs). Moreover, comparison of the group that contains parasitized red blood cell (P. falciparum) with high concentration of glycosylated hemoglobin (HbA1c) more than 8% with normal healthy RBCs (negative control) there was significant (P < 0.001) expression of CD36, and the CD36 expression was expressed in the presence of HbA1c in small amount which indicates the P.F plays a role in IRBCs cell membrane leads to CD36 expression, this is has no conflict with previous study that represented .These abnormal circulatory properties of erythrocytes involve parasite-induced alterations in their biomechanical and adhesive properties and are important for survival and pathogenicity of P falciparum.12 Cytoadhesion is mediated by the antigenically variant P. falciparum erythrocyte membrane protein-1 (PfEMP1), which can bind to host receptors including CD36 and chondroitin sulfate A ˶CSA˵13 PfEMP1 is concentrated on electron-dense elevations of the membrane referred to as knobs.14,15 providing a platform for adherence under physiologic flow conditions.16 Increased erythrocyte rigidity and adhesiveness result in dramatically augmented hemodynamic resistance observed in microvasculature perfused with P falciparum–infected erythrocytes.17 However, the group that contains CD36 with high concentration of glycosylated hemoglobin (HbA1c) more than 8% has been compared with the group which contains CD36 in patient with P. falciparum malaria only (positive control) there was significant reduction of CD36 expression (P < 0.001), also this study agreed with Van Nieuwenhoven et al, 199818 was proposed that hyperglycemia might play an important role in the regulation of CD36 expression .The result in this study shows the significant effect of HbA1c on CD36 expression reduction. Thus, these results was agreed with the previous study shown that hyperglycemia is also associated with increased levels of reactive oxygen species in diabetic red blood cell and rise in the levels of the reactive carbonyl compounds that worsen their compromised functions, leading to diminished lifespan, accelerated nonenzymatic modification of proteins, and loss of protein function.19,20 A result of increased protein glycosylation could participate in the mechanism, whereby diabetic erythrocytes may acquire membrane abnormalities.21 Spectrin is a very important protein of erythrocyte membrane and a target for glycosylation and further oxidation, which might be responsible for increased number of poorly deformable erythrocytes Hassan et al., found among diabetic erythrocytes.22 Abnormal glycation, which can adversely affect hemoglobin and membrane proteins in erythrocytes, has been shown to correlate with reduced membrane fluidity1 separately, high values of glycosylated hemoglobin have been found to correlate with decreased deformability of erythrocyte.2 The reduction of CD36 expression may have remarkable in the development of severity P. falciparum malaria in diabetic patients. CONCLUSION We conclude that Plasmodium falciparum might increase the density and amount of CD36 in parasitized red blood cells. Hyperglycemia (HbA1c) leads to down-regulate of CD36 expression and interfere with innate and active immunity. In this study HbA1c participates in increasing of P. falciparum malaria complications. ACKNOWLEDGEMENT My sincere thanks extended to Hussain Higazi, and Sayed Alshamy for their strong helping and support. I am really indebted to the laboratories staff of Jaber Abu Ezz Diabetic center for their help and assistance. Conflict of Interest Statement: The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included. REFERENCES 1. Watala C, Zawodniak M, Bryszewska M, Nowak S. Nonenzymatic protein glycosylation. I. Lowered erythrocyte membrane fluidity in juvenile diabetes. Ann Clin Res. 1985; 17(6):327– 30. 2. 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CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Cell. 1989; 58: 95-101. McGilvray ID, Serghides L, Kapus A, Rotstein OD, Kain KC. Nonopsonic monocyte/macrophage phagocytosis of Plasmodium falciparum-parasitized erythrocytes: a role for CD36 in malarial clearance. Blood. 2000; 96:3231-40. Podrez, E. A., Febbraio, M., Sheibani, N., Schmitt, D., Silverstein, R. L., Hajjar, D. P., Cohen, P. A., Frazier, W. A., Hoff, H. F., and Hazen, S. L. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by Monocytegenerated reactive nitrogen species. J Clin Invest. 2000; 105:1095-108. Trager W, Jensen JB. "Continuous culture of Plasmodium falciparum: its impact on malaria research". Int J Parasitol. 1997; 27 (9): 989–1006. Pani LN, Korenda L, Meigs JB, Driver C, Chamany S, Fox CS etal., Relationship Between A1C and Glucose Levels in the General Dutch Population Diabetes Care. 2008; 10:1991-6. Ho M. and White NJ. Molecular mechanisms of cytoadherence in malaria. Am. J. Physiol. 1999; 276: C1231–C42. Cooke BM, Mohandas N, Coppel RL. Malaria and the red blood cell membrane. Semin Hematol. 2004; 41:173-188. Baruch DI, Rogerson SJ, Cooke BM. asexual blood stages of malaria antigens: cytoadherence. Chem Immunol. 2002; 80:144-162. Su XZ, Heatwole VM, Wertheimer SP. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell. 1995; 82:89-100. Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc. Natl. Acad. Sci. U.S.A. 1995; 92: 8264-68. Hassan et al., 16. Crabb BS, Cooke BM, Reeder JC, Waller JC, Caruana SR., Davern KM, et al., Targeted gene disruption shows that knobs enable malariainfected red cells to cytoadhere under physiological shear strees. Cell. 1997; 89:287-96. 17. Raventos SC, Kaul DK, Macaluso F, Nagel RL. Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum- infected erythrocytes. Proc Natl Acad Sci U S A. 1985; 82:3829-3833. 18. Van Nieuwenhoven FA, Luiken JJ, De Jong YF, Grimaldi PA, Van der Vusse GJ, Glatz JF Stable transfection of fatty acid translocase (CD36) in a rat heart muscle cell line (H9c2). J Lipid Res. 1998; 39:2039–47. 19. Constantin A, Constantinescu E, Dumitrescu M, Calin A, & Popov D. Effects of ageing on carbonyl stress and antioxidant defense in RBCs of obese Type 2 diabetic patients. Journal of Cellular and Molecular Medicine. 2005; 9: 683– 91 20. Schwartz RS, Madsen JW, Rybicki AC, Nagel RL. Oxidation of spectrin and deformability defects in diabetic erythrocytes. Diabetes. 1991; 40(6):70108. 21. Lux SE. Spectrin-actin membrane skeleton of normal and abnormal red blood cells. Seminars in Hematology. 1979; 16(1):21-51. 22. McMillan DE, Brooks SM. Erythrocyte spectrin glucosylation in diabetes. Diabetes. 1982; 31(3):64-69. Int J Med Res Health Sci.2014;3(1):23-27 27 DOI: 10.5958/j.2319-5886.3.1.006 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS rd Received: 23 Sep 2013 Revised: 19th Oct 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 12th Nov 2013 DERMATOGLYPHICS: A PREDICTOR TOOL TO ANALYZE THE OCCURRENCE OF BREAST CANCER Abilasha S1, *Harisudha R2, Janaki CS3 1 Tutor, Department of Anatomy, KSR Institute of Dental Science & Research, Tiruchengode, Namakkal, Tamil Nadu, India 2 Tutor, Department of Anatomy, Melmaruvathur Adhiparasakthi Institute of Medical Science and Research, Melmaruvathur, Kanchipuram, Tamil Nadu, India 3 Assistant Professor Department of Anatomy , Meenakshi Medical College and Research Institute, Enathur, Kanchipuram, Tamil Nadu, India *Corresponding author email:
[email protected] ABSTRACT Background: Dermatoglyphics is the branch of science that deals with the study of ridge patterns on finger tips, palm, sole and toes and when once formed, they remain unchanged throughout the except after severe injuries. These patterns can serve as a non-invasive, cost-effective tool which can be used for the prediction of cancer. This can also serve as a baseline guide to identify women with breast cancer. Objective: To study the digital dermatoglyphic patterns among women with breast cancer in comparison with normal individuals. Materials and methods: 50 female patients with breast cancer of age group between 30-70 years were compared with 50 control group of individuals with no history of cancer. The breast cancer patients and the control group were of the same age and sex. Digital dermatoglyphic patterns were taken among these individuals with the aid of a dermatoglyphic kit. Procedure involved was modified purvis smith method. Results: digital dermatoglyphic patterns were analyzed between the patients and control group of individuals which showed statistical difference. Conclusion: we conclude that there is a genetic influence on the dermatoglyphic patterns. With the aid of this, the occurrence of breast cancer can be predicted and this dermatoglyphics can serve as a non-invasive, anatomical marker and a predictor tool to determine the individuals with breast cancer. Keywords: Breast cancer, Dermatoglyphics, Ridge patterns, Genetic marker INTRODUCTION Dermatoglyphics is a branch of science that deals with the study of ridge patterns on finger tips, palm, sole and toes. Dermatoglyphics traits are epidermal ridges formed under genetic control early in development but may be affected by environmental factors during the first trimester of pregnancy. They however do not change significantly thereafter, thus maintaining stability not greatly affected by age. These epidermal ridges are closely related to volar pads and these ridge patterns form at the site of these pads. Harold and Cummins1coined the term dermatoglyphics in 1926, which they first used in a paper, the American journal of physical anthropology. A detailed description on ridge patterns was described in 17th century2. Widespread medical interest towards epidermal ridges developed only in the last few decades when it became an apparent factor that many patients with chromosomal aberrations had unusual ridge patterns. 28 Abilasha et al., Int J Med Res Health Sci. 2014;3(1):28-31 Inspection of these ridges therefore seems to provide a simple and cost effective means of information to determine whether the patients could have any underlying changes in genotype. 3 individuals and whorl was maximum in breast cancer patients which showed statistical significance.(p>0.05) MATERIALS AND METHODS The material for this present study consisted of fingerprints of patients selected from those attending outpatient and inpatient clinics in the department of Meenakshi Hospital, Kanchipuram and Jeevodhaya Cancer Hospital –Retteri, Chennai. Sample size: The study consisted of 100 subjects categorized into two groups including 50 patients with breast cancer and 50 control groups of individuals. Inclusion criteria: 1. 50 histopathologically conformed female breast cancer patients age between 30-65 years. 2. Age matched 50 female control group individuals with no history of cancer or any other genetic disorders. 3. Treated, untreated and operated patients were used for this study. Exclusion criteria: 1. Individuals who had deformities in their hands like burns or injury were excluded. 2. Genetic disorders other than breast cancer were also excluded. 3. Females under 30 years of age. Fig 1: Comparison of dermatoglyphics pattern between control and breast cancer (left hand) (A=Arch, UL= Ulnar Loop,RL= Radial Loop, W= Whorl, Tl-R= Twinned Loop Radial, Lp-U= Lateral Pocket Ulnar, Lp-R= Lateral Pocket Radial, Cp= Central Pocket Loop, Al= Accidental Loop.) In left hand ring finger, arch and ulnar loop were maximum in control group of individuals and whorls were maximum in breast cancer patients when compared to normal group. In left hand little finger ulnar loop was maximum in control group and arch, whorl was maximum in breast cancer patients which showed statistical significance. MATERIAL & METHODS Data collection: After obtaining permission from the Institutional Ethics Committee also inform consent form was taken from the patient. Total 100 patients (50 histopathologically conformed breast cancer and 50 normal age match control) were informed about the procedure in detail and data comprising of age, sex and address were taken. Method : In our study with the help of the modified Purvis smith method4 we have studied the fingerprint patterns of controls and breast cancer individuals by the arrangements of loop-ulnar loop, radial loop, whorl- plain whorl, central pocket loop whorl, archesplain arch, tented arch, radial twinned loop, ulnar twinned loop, accidental loop. The prints were analyzed with the help of the finger print analyst. RESULTS In left hand thumb, ulnar loop, twinned loop ulnar and twinned radial loop was maximum in control group of Fig 2: Comparison of dermatoglyphics pattern between control and breast cancer (right hand) (A=Arch, UL= Ulnar Loop,RL= Radial Loop, W= Whorl, Tl-R= Twinned Loop Radial, Lp-U= Lateral Pocket Ulnar, Lp-R= Lateral Pocket Radial, Cp= Central Pocket Loop, Al= Accidental Loop.) In right hand ring finger arch and whorl were maximum in breast cancer patients and arch was maximum in control group of individuals which showed statistical significance. (p>0.05) 29 Abilasha et al., Int J Med Res Health Sci. 2014;3(1):28-31 DISCUSSION Chintamani5, Bierman6, RJ Meier7, has identified a pattern of 6 or more digital whorls has been used to identify women with breast cancer and whorls were commonly observed in right ring finger and right little finger in breast cancer patients. Hence, the determination of dermatoglyphic pattern of the finger and palm is genetic, so it could serve as a suitable parameter for differentiating individuals. Our study also goes in accordance with the previous study that we identified a pattern of whorls in 6 out of 10 digits in 62% of the breast cancer patients whereas in a control group of individuals it was the ulnar loop pattern present in 6 out of digits. So this was a major difference observed in our study, and in our study too whorls were commonly seen in right ring finger and little finger among the breast cancer patients. Oladipo8 has observed a significant association with ulnar loop in 8 out of 10 digits in Nigerians and he has also concluded that these dermatoglyphic findings will serve as a baseline in the identification of women who are at increased risk of developing breast cancer and perhaps aid early treatment of the disease. He has also observed that ulnar loop had highest mean percentage frequency of the digital dermatoglyphic pattern followed by whorl, arch and radial loop i.e., ulnar loop and whorl was higher in right hand and radial loop and arch in left hand of breast cancer -patients. In our study, we identified a significant association with whorls and we have also observed that ulnar loop had highest mean percentage frequency followed by whorl, arch and radial loop. According to Natekar PE9, out of 1000 fingerprints, cancer patients had 33% whorls, 66.6% loops, 0.4% arches whereas the control group had 63.8% whorls, 35.5% loops and 0.7% arches. There was the presence of more than 6 loops in breast cancer patients. In our study, out of 2000 fingerprints, breast cancer patients had 47% loops, 44% whorls, 4% arches, 2% ulnar twinned loop, 0.8% radial twinned loop whereas the control group had 56% loops, 25% whorls, 8% arches, 7% ulnar twinned loop, 3% radial twinned loop. We have also observed there was the presence of 0.4% tented arch and 0.4% accidental loop among the breast cancer patients which was absent in a control group of individuals. There was presence of whorls in 6 out of 10 digits in 62% of the breast cancer patients. Sakineh Abbasi 10, with an ever increasing population it is important that methods be developed to identify individuals who are either at risk or already having illness in the most cost – efficient manner without sacrificing quality of care. The use of dermatoglyphics is a unique approach and cost effective for identification in such individuals. In his study of dermatoglyphic patterns, he has observed the significant difference in right hand middle finger, ring finger, left hand index finger, middle finger, ring finger, little finger where there was an increase in loop in all these digits and also observed whorls in 6 out of 10 digits in 48.7% of the breast cancer cases. In our study, we have observed the significant difference in the left hand thumb, ring finger, little finger, right hand ring finger. We have also observed that the whorls in <6 out of 10 digits in 62% of the breast cancer patients. CONCLUSION The present study concludes that as there is a genetic influence on the digital ridge patterns, these do not change throughout the life. Hence with the aid of this digital and dermatoglyphic pattern we can predict the occurrence of breast cancer and this dermatoglyphics can serve as a non-invasive, anatomical marker and a predictor tool to determine the individuals with breast cancer. We also conclude that with the help of this ability to predict the earliest changes associated with breast cancer it may allow to the introduction of more effective preventive strategies. ACKNOWLEDGEMENT I would like to thank Dr. Deenadayalan for his immense support to this work. REFERENCES 1. Cummins HH. Epidermal Ridge Configurations in Developmental Defects, with Particular References to the Ontogenetic Factors Which Condition Ridge Direction. American Journal of Anatomy.1926;38(1), 89-151. 2. Huang CM, Mi MP. Digital dermal patterns in breast cancer. Proc Natl Sci Counc Repub China B. 1987;11(2): 133-6 3. Book JA. A fingerprint method for genetical studies. Hereditas 1948;34:368 4. Purvis-Smith SG. Finger and palm printing technique for the children. Med J Austria 1969; 2:189. 5. Chintamani, Rohan khandelwal, Aliza mittal, Saijanani, Amita tuteja, Anju bansal etal., 30 Abilasha et al., Int J Med Res Health Sci. 2014;3(1):28-31 6. 7. 8. 9. 10. Qualitative and quantitative dermatoglyphic traits in patients with breast cancer. New Delhi, India. BMC Cancer 2007, 7:44 Bierman HR, Faith MR, Stewart ME. Digital dermatoglyphics in mammary cancer. Cancer Invest., 1988; 6(1): 15-27. Schaumann BA, Meier RJ. Trends in dermatoglyphic research. International Journal of Anthropology1989;4(4):247- 54 Oladipo GS, Paul CW, Bob-Manuel IF, Fawehinmi HB, Edibamode EI. Study of digital and palmar dermatoglyphic patterns of Nigerian women with malignant mammary neoplasm. J. Appl. Biosci.2009; 15: 829-34. Natekar PE, Desouza S, Motghare DD, Pandey AK. Digital dermal patterns in Carcinoma Breast. J. Anthropologist. 2006; 8: 251–254. Sakineh Abbasi, Nahid Einollahi, Nasrin Dashti, Vaez-zadeh F. Study of dermatoglyphic patterns of hands in women with breast cancer. Pak J Med Sci.2006,22(1): 18-22 31 Abilasha et al., Int J Med Res Health Sci. 2014;3(1):28-31 DOI: 10.5958/j.2319-5886.3.1.007 International Journal of Medical Research & Health Sciences www.ijmrhs.com Received: 1st Oct 2013 Research article Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Revised: 30th Oct 2013 Copyright @2013 ISSN: 2319-5886 Accepted: 13th Nov 2013 A PROFILE OF CARDIOVASCULAR DISEASES IN A TEACHING HOSPITAL IN KERALA *Celine TM1, Jimmy Antony2 1 Assistant Professor of Statistics, 2Assistant Professor of Health Education, Department of Community Medicine, MOSC Medical College, Kolenchery, Kerala, India *Corresponding author email:
[email protected] ABSTRACT Background and objective: cardiovascular diseases are increased in each year in India. Cardiovascular diseases more are occurred in the economically productive age group. This will affect their family and also the nation. Aim of the study is to find out the different types of heart diseases and the case fatality rate of cardiovascular disease from 1st April 2005 to 31st March 2010 in a teaching hospital. Materials and Methods: The retrospective study conducted on hospitalized patients admitted with cardiovascular diseases from 1st April 2005 to 31st March 2010. Medical records department follows the guide lines of International Classification of Diseases (ICD)-10 coding for entering the data, from that data were collected. Results: Of 10427 cases, 6324 (60.65%) were males and 4103(39.35%) females. Cardiovascular disease was more among males than females. It was more occurred in ≥60 years. Most of them were occurred due to cerebrovascular disease (33.7%). Ischemic heart disease was more among males than females. Total number of deaths due to cardiovascular disease was 797. Of them 525(65.87%) were males and 272(34.13%) females. Case fatality due to cardiovascular diseases was 7.64%. Case fatality among males (8.3%) were more than females (6.63%) (P=0.00). Conclusion: This study mentioned that most of the cases and deaths were occurred in 60 and above years. Second leading age group is 25-59 years. Accident in economically productive people was high. It will affect their family and also the nation. Hence it can be reduced by conducting health awareness programme. Key words: Case fatality, cardiovascular diseases, ischemic heart disease. INTRODUCTION Heart and blood vessel disease is called cardiovascular disease (CVD) or heart disease. It is the number one killer of women in worldwide, accounting for onethird of all deaths. Atherosclerosis is a term which describes any hardening of large arteries; it happened due to plaque. It causes the arteries narrow and this leads to the flow of blood through the arteries is difficult. Blood clots in anywhere in the narrow arteries then blood cannot flow it will lead to heart attack or stroke. An ischemic stroke occurred due to obstruction within the blood vessel supplying blood to brain. When the blood supply of that part of the brain Celine etal., is cutoff; it will cause the brain cell die. It will affect the smooth functioning of the body. A hemorrhagic stroke mostly happened due to the unrestrained hypertension; it leads to explosion of blood vessel in the brain. Heart failure, it occurs when the heart cannot supply sufficient blood for the functioning of the body. If it is not treated in time it becomes most terrible. A cross sectional study reported that the prevalence of coronary heart disease (CHD) in rural and urban areas of India was 3-4% and 8-10% respectively.1 The main objective of the study is to find out the different types of heart diseases and the case fatality rate of 32 Int J Med Res Health Sci. 2014;3(1): 32-36 cardiovascular disease during the period from 1st April 2005 to 31st March 2010 in a teaching hospital. METHOD Study design: The study was a retrospective study conducted on patients admitted with cardiovascular diseases in M.O.S.C Medical College, Kolenchery, Ernakulam, Kerala, India from 1st April 2005 to 31st March 2010. Selection of Description of patients: The study population consists of all patients admitted in the hospital due to cardiovascular diseases during the period from 1st April 2005 to 31st March 2010. The data were collected with the permission of Institutional Ethical Committee from the Medical Records department, follows the guide lines of International Classification of Diseases (ICD)-10 coding. 2 Statistics: Z test is applied for the comparison between proportions. Z test is used for comparing the sex wise difference between proportions of age, type of diseases. Critical ratio (Z) = sex wise difference between proportions age / standard error of difference between sex wise proportions. Formula for calculating Standard error of difference between sex wise proportions is √(p1q1 / n1) + (p2q2 / n2). P value is taken from the unit normal distribution table with the corresponding value of Z (critical ratio), its cut off value is 0.05. If it is less than or equal to 0.05 then there is significant difference between proportions otherwise there is no significant difference between proportions. Analyzing the data by using Microsoft excel. RESULT Table 1: Demographic distribution Age Male (%) Female Total (%) P Value (Yr) (%) 0-4 143(2.3) 97 (2.4) 240(2.3) 0.74 5-24 352 (5.6) 242(5.9) 594(5.7) 0.52 25-49 1096 (17.3) 534(13) 1630(15.6) 0.00 50-59 1309 (20.7) 610 (14.9) 1919(18.4) 0.00 60 & 3424(54.1) 2620(63.9) 6044(58.0) 0.00 above Total 6324 4103 10427 Out of 10427 cardiovascular cases 6324 (60.65%) were males and 4103(39.35%) were females. Cardiovascular disease was more in the age group of 60 and above years. In this age group, it was more in females than males. But it was more among males than females in the age group of 25-59, Shown in Table No.1. Table 2: Sex wise cardiovascular diseases of patients admitted with cardiovascular diseases P Diagnosis M F Total Value 18 14 32 Acute Rheumatic 1 fever(I00) 0.3% 0.3% 0.3% 65 99 164 Chronic rheumatic 0.00 heart diseases(I05-I09) 1.0% 2.4% 1.6% 1072 936 2008 Hypertension(I10-I15) 0.00 17.0% 22.8% 19.3% 2070 862 2932 Ischemic heart 0.00 disease(I20-I25) 32.7% 21.0% 28.1% Pulmonary heart 63 40 103 disease and diseases 1 of pulmonary 1.0% 1.0% 1.0% circulation(I26-I28) 691 1531 Other forms of heart 840 0.00 disease(I30-I52) 13.3% 16.8% 14.7% 2093 1417 3510 Cerebrovascular 0.14 diseases (I60-I69) 33.1% 34.5% 33.7% Diseases of arteries, 103 44 147 arterioles and 0.63 1.6% 1.1% 1.4% capilliaries(I70-I79) 6324 4103 10427 Total 100.0% 100.0% 100% Of the cardiovascular cases, most of them due to cerebrovascular disease and it occurred in both sex was same. Chronic rheumatic heart disease, hypertension and other forms of heart disease were more among females than males. But ischemic heart disease was more among males than females, shown in Table No.2. Of the ischemic heart disease, most of them were due to Chronic ischemic heart disease 1859(63.4%), 273 (9.3%) were due to Acute Myocardial infarction, 410(14.0%) were due to subsequent myocardial infarction and 390(13.3%) were due to other reasons. Of the cerebrovascular diseases, most of them were due to cerebral infarction1394(39.72%), 924(26.32%) were due to stroke, not specified as hemorrhage or infarction, 414(11.79%)were due to intracerebral hemorrhage, 193(5.5%) were due to subarachnoid hemorrhage and 585(16.67%) were due other reasons. 33 Celine etal., Int J Med Res Health Sci. 2014;3(1): 32-36 Fig 1: Sex wise Trend of Cardiovascular cases reported in a Teaching Hospital from 1st April 2005 to 31st March 2010 Highest number of cases reported during the year 1st April 2009 to 31st March 2010. Cardiovascular disease was more among males than females in each year, shown in Figure 1. Of the 10427 cases, 797 deaths were reported during the period from 1st April 2005 to 31st March 2010.Case fatality due to cardiovascular diseases was 7.64%. Of 797 deaths, 525(65.87%) were males and 272(34.13%) were females. Case fatality among male was 8.30% and among females 6.63%. Case fatality among males was more than females. (P=0.00) Table 3: Age wise case fatality of patients admitted with cardiovascular diseases from 1st April 2005 to 31st March 2010 Age No. of deaths Total P value cases 0-4 14 (5.8) 240 0.52 5-24 23(3.9) 594 0.4 25-49 78(4.8) 1630 Reference group 50-59 133(6.9) 1919 0.00 60 & above 549(9.1) 6044 0.00 Total 797(7.6) 10427 Within the column 2, represent the number of deaths and case fatality of each age group. Case fatality was more in the age group of 50 and above years compared to the age group 25-49 years. Case fatality was more in the age group of 60 and above years compared to the age group 50-59 years (P=0.00), shown in Table No. 3. Deaths due to cardiovascular diseases were more during 1st April 2007 to 31st March 2008. Male deaths were more than females in each year, shown in Fig 2. Fig 2: Sex wise trend of deaths due to cardiovascular diseases from 1st April 2005 to 31st March 2010 DISCUSSION In the developing countries most of the people have stimulated from their agrarian diets with physical activities to fast food with inactive habits. These types of changes lead to increase the possibility of developing cardiovascular diseases among people. It is a burden of disease over several decades in the developed countries. It is the leading cause of death in India.2 Several studies in India mentioned that prevalence of coronary heart disease in urban and rural areas was between 7-13 % and 2-7 % respectively.3,4 Dinesh C Sharma reported that the proportion of deaths due to heart disease is more in south India ,it was 25% and least in central region, it was 12 %. 5 A study reported that 25% of total mortality was due to cardiovascular diseases.6 Another study reported that cardiovascular disease in South India showed 10-15% increase occurred among young women. 7 A study mentioned that 50% of all deaths occurred in Kerala was due to cardiovascular diseases. (8) In the present study cardiovascular diseases was more among males (60.65%) than females (39.35%). It was more occurred in the age group of 60 and above years. It was more among females than males in the age group of 60 and above years. But it was more among males than females in the age group of 25-59. Hypertension was an important factor in the beginning of both cerebrovascular and ischemic heart disease. Thus 22 per cent of the cases of ischemic heart disease and 31.7 per cent of cases of myocardial infarction were hypertensive; 42.0 per cent of the cases of cerebral thrombosis were also hypertensive. The overall ratio of ischemic heart disease to cerebrovascular disease was 1.4:1; this ratio was same 34 Celine etal., Int J Med Res Health Sci. 2014;3(1): 32-36 for both sexes. A study mentioned that 8.72 million individuals go through hypertension and 3.48 million individuals go through diabetics in Kerala..8 Hypertension was the most powerful cause of vascular diseases among females than males. In the present study 19.3.3% hypertensive cases were reported. Hypertension was more among females than males. A study reported that the prevalence of Coronary Artery Diseases in the urban and rural areas of India was 12% and 7.5% respectively. 1 Raghavan’s study 9 mentioned that out of 4,335 autopsies, 13.1 per cent was due to cardiovascular diseases. Of the cardiovascular disease, 9.8% was due coronary artery disease. According to Wig’s study, the incidence of coronary artery disease was more in Amritsar and Calcutta.10, 11 Padmavati’s study report mentioned that 0.2 % of the medical admissions above 40 years of age was due to coronary artery diseases.12 In the present study mentioned that 1.4% of cardiovascular diseases were due to diseases of arteries, arterioles and capilliaries. According to Schroeder 13 the incidence of cerebrovascular and ischemic heart disease is different in different parts of the world. The prevalence of coronary artery disease in India is found to be less than other countries. Cerebrovascular disease was more occurred than ischemic heart disease in males. Among females cerebrovascular disease was occurred twice as that of ischemic heart disease. Chambers’s study pointed out that in India the consumption of less amount vitamin B-6 and folate content food and the increase fatty food consumption without physical exercise may increase the risk of ischemic heart disease.14 A study mentioned that mortality due ischemic heart disease among Indians living abroad was 40% more than that of Europeans. 15 According to Dhar’s study, 0.3% of all admission and 0.7% of all medical admission was due to ischemic heart disease. Myocardial infarction was 6.5 times more in males than females.16 In the present study ischemic heart disease was 28.1% of all cases. Ischemic heart disease was more among males than females. In the present study, of the ischemic heart disease, most of them were occurred due to Chronic ischemic heart disease 1859(63.4%), 273 (9.3%) were due to Acute Myocardial infarction, 410(14.0%) were due to subsequent myocardial infarction and 390(13.3%) were due to other reasons. Celine etal., Result of Dhar’s study mentioned that 0.44% of all admission and 1.1% of medical admission was due to cerebrovascular diseases. The incidence of crebrovascular disease is 0.44 per cent and 1.1 per cent of total and medical admissions, respectively.16 Muir’s study17 reported that incidence of cerebrovascular diseases was high in Indians and less among Chinese in Singapore. Another study also found the same result. 18 In the present study 33.7% of cardiovascular diseases was due to cerebrovascular disease. Of the cardiovascular cases most of the patients were admitted with Cerebrovascular disease. Proportion of Cerebrovascular disease in both sexes was same. In the present study, of the cerebrovascular cases, most of them were due to cerebral infarction 1394 (39.72%), 924(26.32%) were due to stroke, not specified as hemorrhage or infarction, 414(11.79%) were due to intracerebral hemorrhage, 193(5.5%) were due to subarachnoid hemorrhage and 585(16.67%) were due other reasons. Report of a study mentioned that about 25% of mortality occurred in the age group of 25- 69 years was due to heart diseases. Mortality occurred due to heart disease in the urban and rural areas was 32.8% and 22.9% respectively 5 In the present study case fatality was more in the age group of 60 and above years (9.1%) compared to the age group 50-59 years(6.9%).Case fatality occurred in the age group of 25-59 years was 5.9%. Padmavati’s study mentioned that 7.7% of total medical causes of death and 3% of total deaths was due to heart disease.12 A study report mentioned that in the western countries 50% of total deaths were due to heart disease.19,20 Another study mentioned that 19% of total deaths was due to heart disease and also mentioned that it is a leading cause of in both sexes.5 In the present study case fatality due to cardiovascular diseases was 7.64%. Case fatality among males (8.3%) was more than females (6.63%). CONCLUSION Cardiovascular disease was more among males than females. It was a no.1 killer disease. It will affect the smooth running of the affected people’s family. “Prevention is better than cure”. For reducing this with the help of implementing simple but effective prevention strategies, strengthening the health system and conduct quality improvement programmes. And also identify the reason for the onset of cardiovascular 35 Int J Med Res Health Sci. 2014;3(1): 32-36 disease in the younger age group and conduct awareness programmes. REFERENCES 1. Cardiological Society of India, Kerala Chapter. ACS Registry. http://www.csikerala.org/ acsregistry.php 2. Dorairaj Prabhakaran and Salim Yusuf, Guest Editors. Cardiovascular disease in India: Lessons learnt & challenges ahead. Indian Journal of Medical Research 2010;132(5): 529–530. 3. Xavier D, Pais P, Devereaux PJ, Xie C, Prabhakaran D, Reddy KS et al. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet 2008; 371 : 1435-42 4. Prabhakaran D, Yusuf S, Mehta S, Pogue J, Avezum A, Budai A, et al. Two-year outcomes in patients admitted with non-ST elevation acute coronary syndrome: results of the OASIS registry 1 and 2. Indian Heart J 2005; 57 : 217-25 5. Dinesh C. Sharma India's no.1 killer: Heart disease. India Today. 2010;April12 6. Mukherjee AK. India’s health: today and tomorrow. J Indian Med Assoc1995;93: 312–15. 7. The Times of India. Heart diseases rising among women. Hyderabad.2013; June 29. 8. Shyam PV. In Kerala, 110 die of heart disease daily Times of India. 2011;Sep 24 9. Raghavan, P. Etiological incidence of heart disease in Bombay. Analysis of 4335 autopsies. J. Indian M. A. 1941;10: 365, 10. Wig KL, Malhotra RP, Pathania NS. A study of clinical data of 500 cases of congestive heart failure. Indian Heart J.1953;5: 45 11. Gupta JC. A plea for concerted attack on atherosclerosis. Indian Heart J. 1957;9: 59 12. Padmavati S. The cardiac patient in underdeveloped countries. Am. Heart J. 1959;8: 418 13. Schroeder HA. Degenerative cardiovascular disease in the Orient. I. Atherosclerosis. Chron. Dis. 1958;8: 287 14. Chambers JC, Obeid OA, Refsum H. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asians and European men. Lancet 2000; 355: 523–27 15. Balarajan R. Ethnicity and variations in mortality from coronary heart disease. Health Trends1996;28:45–51 16. Dhar P. Thesis for M.D. (Medicine). Unpublished. 17. Muir CS. Coronary heart disease in seven racial groups in Singapore. Brit. Heart J.1960; 22:45 18. Danraj TJ, Acker MS, Danraj W, Ong WH, Yan TV. Ethnic group differences in coronary heart disease in Singapore. An analysis of necropsy records. Am. Heart J. 1959;58: 518 19. Wood PH. Diseases of the Heart and Circulation. Ed. 2. London, Eyre and Stottiswoode.1956. 20. White PD. Heart Disease. New York, The Macmillan Company, 1951,4th ed. 36 Celine etal., Int J Med Res Health Sci. 2014;3(1): 32-36 DOI: 10.5958/j.2319-5886.3.1.008 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS nd Received: 2 Oct 2013 Revised: 20th Nov 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 23rd Nov 2013 USE OF PROTON PUMP INHIBITORS IN GENERAL PRACTICE: IS IT RATIONALE? *Nousheen1, Tadvi NA2, Shareef SM3 1 IInd year MBBS student, Kamineni Institute of Medical Sciences, Narketpally, Andhra Pradesh, India 2 Department of Pharmacology, College of Medicine, Majmaah University, Kingdom of Saudia Arabia 3 Assistant Professor, Department of Pharmacology, Kamineni Institute of Medical Sciences, Narketpally *Corresponding author email:
[email protected] ABSTRACT Background: The incidence of improper use of PPIs varies from 40-70% in various studies. Initiation and the continuous use of these drugs without correct indications will result in significant cost to the patient. The present study was planned with the aim of finding out the rational use of PPIs in the in patients of a rural tertiary care hospital. Objectives: To assess indications of use of PPIs along with their dose, frequency, rationality of treatment, safety and efficacy. Methods: Prospective observational drug-utilization study of PPIs was conducted for two months in the inpatients of General Medicine and General Surgery wards. The sample size of study was (n=100). The case sheets of the patients were reviewed for PPIs prescription and relevant data was taken. A five point Likert scale with validated Reflux Disease Diagnostic Questionnaire (RDQ) having 12 items was used for evaluating symptoms score for assessing efficacy of PPIs. Results: A total of 46.72% inpatients were on proton pump inhibitors, in surgery(47.52% ) and medicine wards (46.01%). The indications for PPIs therapy were acute gastritis (4%) , Gastro Esophageal reflux disease (5%) , Duodenal ulcer(1%) , co-administration with Non Steroidal AntiInflammatory Drugs(32%). PPIs were prescribed irrationally in 58 % of patients without any valid indication. The incidence of polypharmacy was high, average number of drugs per prescription was 4.93. Antimicrobials were the most common drugs used in (71%). CONCLUSION: Proton pump inhibitors should be used more judiciously and awareness should be created among the clinicians in the hospital so that appropriate prescription of PPIs will improve the patient care at low cost. Keyword: Proton pump inhibitors, General practice, Rationale INTRODUCTION Proton pump inhibitors (PPIs) are a group of drugs that cause pronounced and long-lasting reduction of gastric acid production. They are most potent gastric acid suppressing drugs currently in clinical use.1 PPIs irreversibly inhibit the gastric H+-K+ ATPase pump also known as proton pump and reduce both basal and stimulated gastric output. Currently the PPIs available in India are omeprazole, esomeprazole, pantoprazole, rabeprazole and lansoprazole. PPIs are used therapeutically in active ulcers, Zollinger-Ellison syndrome, Gastro oesophageal Reflux Disease(GERD), GI bleeding, dyspepsia from NSAID’s and along with antibiotics for helicobacter pylori.2 PPIs are also given prophylactically along with NSAID’s or Steroids in patients with history of peptic ulcer / previous GI bleed / elderly patients.3 Proton pump inhibitors have been demonstrated to be safe and well tolerated drugs but short term adverse effects like headache, dizziness, diarrhoea, fatigue, rashes and abdominal pain have been reported in 5% of the patients taking proton pump inhibitors.4,5 Chronic therapy of PPIs carries an increased risk of bacterial enteritis due to decreased gastric acidity 37 Nousheen etal., Int J Med Res Health Sci. 2014;3(1):37-42 allowing colonization of ingested pathogens and also infection with clostridium difficile .6,7 long term use of PPIs have also been associated with increased risk of hip fractures, and community acquired pneumonia.8,9 In setting with low rate of such infections benefit of PPI therapy outweighs the risk developing it.10 Polypharmacy can also make the elderly patients more likely to confuse their use of medication schedule.11 Such risks are worth taking for life saving drugs that are clearly indicated, but prescribing PPIs that may not be clinically necessary can put patients at risk of complications. Inspite of the above mentioned concerns with PPIs, they have become one of the most commonly prescribed medicines worldwide. Some reports suggest that upto 60% of patients suffering from dyspepsia are on drugs like PPIs without proper indication. 12,13 . PPIs take longer time to provide symptom relief than H2 blockers or antacids. For sporadic dyspepsia, and immediate symptoms relief agents other than PPIs will provide greater patient satisfaction and better clinical outcomes.14 The prescriptions for the PPIs have increased consistently over the past years. Many drug utilization studies have reported widespread use of PPIs and that are outside the current prescribing guidelines.15,16 The incidence of improper use of PPIs varies from 40-70% in various studies. 17-19 Initiation and the continuous use of these drugs without correct indications will result in significant cost to the patient. The significance of rational use of drugs can be described by WHO definition which states that rational use of drugs require that, patients receive medications appropriate to their clinical needs in doses that meet their own individual requirement for an adequate period of time at lowest cost to them and their community. 17 Hence in this present scenario, where the use of PPIs is overwhelming, the present study is planned to know the rational use of PPIs in the in patients of General Surgery and General Medicine wards of a rural tertiary care hospital. Objectives To assess the indications of PPIs usage To find out percentage of irrational prescriptions with PPIs (Improper prescriptions without justified indication) To assess the frequency of usage of PPIs along with their dosage. To assess the safety, efficacy and cost effectiveness of PPIs. METHODOLOGY The study was conducted in the inpatient wards of General medicine and General surgery in Kamineni Institute of Medical Sciences (KIMS), Hospital in collaboration with the Department of pharmacology after taking permission from Institutional Ethics Committee. It was a prospective observational study conducted during the period of June 2013 to August 2013. Patients of either sex, admitted into the inpatient wards of General Medicine and General Surgery in KIMS hospital, Narketpally, between the age group of 20-70 yrs were included in the study. Informed consent was taken from all the patients. Patients not willing to give consent were excluded from the study. The sample size for the study was (n=100). The demographic data and the detailed history of patient regarding past, present, family, personal and drug history was taken. The other details like the present diagnosis, reason for the present admission, any investigations done to confirm the diagnosis, like endoscopy etc were also noted. The number of drugs, dosage form, frequency and duration of medications the patient is kept on were also taken. Patient were inquired regarding improvement in the symptoms or any adverse drug reactions during the present stay. A five point Likert scale with validated Reflux Disease Diagnostic Questionnaire (RDQ) 20having 12 items was used for evaluating symptoms score for assessing efficacy of PPIs. This questionnaire was filled by personal interview of the patient on inclusion in the study and on discharge of the patient from hospital. The questionnaire had maximum scoring of 40 and minimum of 12 depending on severity of symptoms like epigastric pain, bloating, vomiting, nausea, heart 21 burn, belching, anorexia etc. Inquiry regarding the adverse or untoward events occurring during the therapy with PPIs was also made from patients included in the study. The cost analysis of the PPIs was done by taking into consideration the available PPIs in the hospital and used in the study. Rationality of the prescription was assessed according to criteria mentioned in previous studies. 16,18,22-27 RESULTS Total 214 case sheets were reviewed, 101 from surgery department and 113 from medicine department over a 38 Nousheen etal., Int J Med Res Health Sci. 2014;3(1):37-42 period of two months. Out of these 214 cases 100 (46.72%) were on proton pump inhibitors. 47.52% inpatients of surgery wards and 46.01% of inpatients in medicine wards were on proton pump inhibitor therapy as shown in Table 1. Table1: Department wise distribution of patients on Proton pump inhibitors No. of No. of case patients Department patients sheets on PPIs on PPIs reviewed (%) 48 101 47.52 Surgery 52 113 46.01 Medicine 100 214 46.72 Total Z=0.442, Hence no significant difference in the prescription of PPIs between the Departments (test for difference between two proportions). Out of 100 patients on proton pump inhibitors majority of them 41% were middle aged between 41-60 years age group, and 61% were males and 39 % females shown in Table 2 and Table 3. Table 2: Age wise distribution of patients on proton pump inhibitors Age % of Patients 20-40 44 41-60 41 60 and above 15 Table 3: Gender Distribution of patients on proton pump inhibitors Gender % of patients Male 61 Female 39 Z= 4.5081, Hence significant difference in the prescription of PPIs between males and females Table 4: Indications for prescribing PPIs S.No Indication % of patients 1. Acute Gastritis 4 2. Duodenal ulcer 1 3. With NSAIDS 32 4. GERD 05 5. Others 58 4% of patients with acute gastritis , 5 % of patients for Gastro Esophageal Reflux Disease (GERD) , 1% Duodenal ulcer , 32 % of patients along with Non Steroidal Anti-Inflammatory Drug and 58 % of patients were prescribed PPIs for other reasons and were neither on NSAIDS nor were having any symptom related to GERD or acid peptic disease as shown in Table 4. Oral therapy with PPIs was prescribed in 70 % of patients and intravenous PPIs in 30% of patients. The intravenous PPI used in all these patients was Pantoprazole 40 mg given once daily early in the morning. Majority of the patients were prescribed PPIs once daily 97% only in 3% of the patients Twice daily therapy was administered. As shown in Table 5and Table 6. Table 5: Route of administration of PPI Route % of patients Oral 70 Intravenous 30 Table 6: frequency of administration of PPIs % of patients Frequency Once daily 97 Twice daily 03 Concomitant drugs The incidence of polypharmacy was high all the patients in the study were prescribed multiple drugs. Average number of drugs per prescription was 4.93. Antimicrobials were the most common drugs used in (71%) patients followed by non steroidal antiinflammatory drugs and multivitamin preparations in 32% patients as shown in Table 7. Table 7: Concomitant drugs used along with Proton pump inhibitors S.No 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. Drugs used Antimicrobials NSAIDs Multivitamin preparations Calcium and vitamin D Antihypertensives Vitamin C Antidiabetics Antiemetics Antiplatelets Purgatives /laxatives Corticosteroids Diuretics Antiepileptics Antacids Antimalarial Oral Iron therapy Hypolipidemics Tramadol patients % 71 32 32 07 09 10 03 13 03 02 01 03 01 03 04 05 03 22 39 Nousheen etal., Int J Med Res Health Sci. 2014;3(1):37-42 Majority of the patients 88% were having a low Likert score of < 20, prior to start of therapy only 12 % of the patients were having significant symptoms (Likert score above 21) related to Acid peptic disease or GERD as shown in Table 9. Table 8: Categorization based on likert scale Likert scale score 12 13-20 21-30 Above 30 % of patients at % of patients at onset of therapy discharge 47 41 07 05 73 22 05 00 DISCUSSION Table 9: Likert Score of patients at start of therapy with PPIs and at discharge (Mean ±SD) Likert score (Mean ±SD) At start of therapy 15.15 ± 5.28 At discharge 12.98 ± 1.90 Z Value= 3.86, Hence significant difference in the Likert score demonstrating efficacy of PPIs. Pantoprazole was most commonly prescribed PPI in 82% of patients followed by omeprazole in 11% and esomepraole in 7 % as shown in Table 10. Table 10: Proton pump inhibitors used in the study PPI Pantoprazole Omeprazole Esomeprazole % of patients 82 11 07 Table 11: Cost analysis of Proton pump inhibitors used in the study Drug Formu lation Dose Pantoprazole Oral 40 mg Pantoprazole IV 40 mg Omeprazole Oral 20 mg Esomeprazole Oral 20 mg OD= Once daily, Rs=Rupees Table 12: Common adverse effects during therapy with PPIs % of S.No Adverse effect patients 1. At least one adverse effect 14 2. Headache 5 3. Rash 3 4. Abdominal pain 3 5. Nausea 2 6. Constipation 2 7. Diarrhoea 1 8. Rhinitis 1 Freq uency Cost per day OD OD OD OD 6.5 Rs 60 RS 3 RS 3 RS Omeprazole and esomeprazole were cheaper in comparison to pantoprazole The prescriptions of proton pump inhibitors are increasing rapidly in India as well as worldwide and PPIs have become one of the most commonly prescribed drugs. The present study shows that total of 46.72 % of hospitalized patients were on proton pump inhibitors during the study period. This is in accordance with the previous study by Ramirez E et al28, who reported that the use of PPIs range from 28.65 % to 82.65% and Sandozi T17who reported use in 45 % of hospitalized patients. There was no significant difference in the prescription of proton pump inhibitor between the surgery and medicine departments (Z=0.442). The use of PPIs was significantly more in males in comparison to females Z= 4.5081. This is in accordance with the previous study by Mayet AY16. Only 42 % of the patients were prescribed PPIs according to the criteria of rationality. 58 % of the prescriptions of PPI were unjustifiable. This is in accordance to the study by Sandozi T17 (55 %) but more than the study by Mayet AY16 (43%). Study by Brandhagen DJ et al29 has reported 77.5% of unjustified prescriptions. Naunton M et al15 (39.6%). The frequency of administration of PPIs was once daily in 97% of cases, the doses of PPIs are recommended as once daily but can be given twice daily also for rapid action as steady state is achieved rapidly. The most common concomitant medications used with PPIs were Antimicrobials, this is a serious issue as 58% of the prescriptions of PPI were unjustified and it is well known fact that patients on proton pump inhibitors are also susceptible to colonization of pathogens which can lead to bacterial gastroenteritis and also their is higher risk of development of infection by Clostridium difficle (antibiotic associated diarrhoea). 32% of cases PPIs 40 Nousheen etal., Int J Med Res Health Sci. 2014;3(1):37-42 were given along with NSAIDS. This is in accordance with the studies by Kumar A et al30and Raghavendra B et al31 who have found high incidence of coprescription of PPIs with NSAIDs. The use of NSAIDs is an important predisposing factor for peptic ulcer disease in the community thus one of the important indications of PPIs is co-administration with NSAIDS to reduce the risk of gastrointestinal bleeding and peptic ulcers. In our study we used questionnaire based five point Likert assessment scale to evaluate the presence of GERD symptoms, dyspepsia and to assess the symptom severity and response to treatment.20 Though a number of symptom scales and Quality of life instruments have been used in clinical trials , not all have been fully validated. We used the Reflux Disease Diagnostic Questionnaire (RDQ) as it is specific for GERD and dyspepsia. The validity, reliability and responsiveness of this test have been well demonstrated. In our study 47 % of patients had RDQ score of 12 indicating that majority of the patients had no symptoms of GERD as this was the minimum possible score and only 12% patients had significant symptoms as demonstrated by RDQ score of more than 20. There was significant improvement in the RDQ score of the patients demonstrating the efficacy of PPIs (Z= 3.86). We cannot comment much on the efficacy as our study was non interventional and the duration of therapy with PPIs varied in the patients. The study design was not appropriate to evaluate our objective of efficacy with PPIs. Randomized prospective clinical trials are better in this regards. The most common proton pump inhibitor used was Pantoprazole in 82% of patients, followed by Omeprazole(11%) and Esomeprazole (7%). Atleast one adverse effect was seen in 14 % of the patients. Most common adverse effect was headache seen in 5 % of the patients. No serious or life threatening adverse effect was observed in patients receiving proton pump inhibitors. Cost analysis revealed that pantoprazole was twice more costly than omeprazole and esomeprazole formulations available in the hospital pharmacy. CONCLUSION Fifty eight percent of the patients in our study received Proton pump inhibitors improperly for unjustified indications. Increased awareness should be created among the clinicians in the hospital so that appropriate prescription of PPIs will improve the patient care at low cost. Although we found PPIs to be efficacious in our study, the study design was not suitable for evaluating efficacy. More drug utilization and pharmaco- economic studies should be conducted in future to compare the rationality of use of proton pump inhibitors and other anti secretory drugs like H2 blockers to know the exact scenario and plan the remedial measures. ACKNOWLEDGEMENT We thank Indian Council of Medical Research (ICMR) for funding this project through Short Term Studentship Programme. We also thank the Management and Principal, Kamineni Institute of Medical Sciences, Narketpally for cooperation during the conduct of study. REFERENCES 1. Blume H, Donath F, Warnke A, Schug BS. Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Safety. 2006;29(9): 769-84. 2. Hetzel D. Acid pump inhibitors. The treatment of gastroesophageal reflux. Australian Family Physician.1998;27(6):487-91. 3. Hawkins C, Hank GW. The gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs:A review of the literature. J Pain Symptom Manage 2000;20(2):140-51. 4. Katelaris PH. Proton pump inhibitors. Medical Journal of Australia.1998; 169(4):208-11. 5. Reilly JP. Safety profile of the proton-pump inhibitors. American Journal of Health-System Pharmacy.1999;56(23 Suppl 4):S11-7. 6. Lewis SJ, Franco S, Young G, O Keefe SJ. 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Magnitude and economic impact of inappropriate use of stress ulcer prophylaxis in non-ICU hospitalized patients. Am J Gastroenterol.2006;101(10):2200-5 28. Ramirez E, Lei S, Borobia A, Pinana E, Fudio S, Munoz R, et al. Overuse of PPIs in patients at admission, during treatment, and at discharge in a tertiary Spanish hospital, Current Clinical Pharmacology. 2010;5(4):288-97. 29. Brandhagen DJ, Phaley AM, Onstad GR, Freeman ML, Lurie N. Omeprazole use at an urban county teaching hospital. J Gen Intern Med. 1995;10(9):513-5. 30. Kumar A, Dalai CK, Ghosh AK, Ray M. Drug utilization study of co-administration of nonsteroidal anti-inflammatory drugs and gastroprotective agents in an orthopaedics outpatients department of a tertiary care hospital in West Bengal. IJBCP.2013;2(2):199-202. 31. Raghavendra B , Narendranath S, Ullal SD, Kamath R, Pai MR, Kamath S, et al. Trends in prescribing gastroprotective agents with non steroidal anti-inflammatory drugs in an Orthopaedic outpatient unit of a tertiary care hospital. Journal of Clinical and Diagnostic Research. 2009;3(3):1553-6. 42 Nousheen etal., Int J Med Res Health Sci. 2014;3(1):37-42 DOI: 10.5958/j.2319-5886.3.1.009 International Journal of Medical Research & Health Sciences www.ijmrhs.com Received: 5th Oct 2013 Research article Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Revised: 6th Nov 2013 Copyright @2013 ISSN: 2319-5886 Accepted: 16th Nov 2013 A STUDY ON SEXUAL DIMORPHISM OF THE HUMERUS IN TAMILNADU REGION *Anil Kumar Reddy Y1, Sheela Grace Jeevamani1, Indira Vijay Ingole2, Raghavendra1 1 Department of Anatomy, KFMS&R, Coimbatore, Tamilnadu, India Department of Anatomy, Dr. PDMMC, Amravati, Maharashtra, India 2 *Corresponding author email:
[email protected] ABSTRACT Sex determination from bones is of vital importance in anthropological studies and medico-legal cases. The present study focused on measurements of the Humerus and to evaluate the differences in sex present in the morphology through statistical analysis. Method: In our study, 120 dry adult humeri (56 right side & 64 left side) were studied of known sex. Damaged bones were excluded from the study. Each Humerus was measured for 11 parameters; measurements were taken by using a sliding caliper as described in the textbook of anthropology and previous studies. The osteometric data of the Humerus of present study is statistically analyzed and compared with other similar studies. Results: Statistical tests were applied to the metrical data obtained to assess whether the differences between the means of each parameter are statistically significant or not. Length of Humerus, the weight of the Humerus, Mid-shaft circumference, Transverse and Vertical diameter of superior articular surface, Bi-epicondylar width of the Humerus have been found to be more discriminatory parameters for the identification of sex from Humerus. Keywords: Sex determination, Humerus, Anthropology, Tamil Nadu INTRODUCTION Sex determination from bones is of vital importance in anthropological studies and medico-legal cases. The role of the skeleton is invaluable in estimating attributes such as age, sex, race, stature and presence of disease. If the whole skeleton is available, there should be no difficulty in arriving at an accurate diagnosis of sex, but when only a part of the skeleton is available, it poses increasing difficulty in assessment. Origin: L humerus, umerus, the shoulder, upper arm < IE *om(e)sos, the shoulder > Sans áṃsa-, Gr ōmos The humerus is the longest and largest bone of the upper extremity; it is divisible into a body and two extremities.1 Many workers have studied the morphometric data for the humerus in both sexes and statistical assessment of the value of this metrical study for sex determination of humerus. Present study Anil et al., focused on measurements of the humerus and to evaluate the differences in sex present in the morphology through statistical analysis. This study gives information regarding the role of human humerus in the determination of sex and to compare the present data with that of other workers. Many workers have studied the morphometric data for the humerus in both sexes and statistical assessment of the value of this metrical study for sexing humerus. Almost all bones of the human skeleton show some degree of sexual dimorphism. The accuracy of sex determination depends on the type and condition of the bone, age of the subject, the degree of fragmentation of the bones and biological variability. Obvious sex differences do not become apparent until after puberty, though specialized measurements on the pelvis can indicate sex even in fetal material. It is recognized that 43 Int J Med Res Health Sci. 2014;3(1):43-46 long bone cross-sectional area is greater in males as compared to females which reflects more rapid periosteal bone growth in boys.2 MATERIALS AND METHODS 9. Transverse diameter of the lower end or Biepicondylar width 10. Maximum length of the humerus 11. Weight of the humerus 120 dried adult humeri (56right side & 64 left side) were collected from the Anatomy Department of Karpagam Faculty of Medical Sciences & Research, Coimbatore. Damaged bones were excluded from the study. Measurements were taken by using a caliper as described in textbook of anthropology3 and previous studies. Metrical data of each humerus was collected using 11 Anthropometric parameters as described below. 1. Vertical diameter of the superior articular surface 2. Transverse diameter of superior articular surface 3. Circumference of the superior articular surface of humerus 4. Maximum width of the upper end or transverse diameter of the upper end 5. Circumference of the surgical neck 6. Mid-shaft circumference 7. Least shaft circumference 8. Transverse diameter of the lower articular surface Table 1: Measurements of Right Humerus (n=56) Mean Vertical diameter of the superior articular surface (cms) Transverse diameter of superior articular surface (cms) Circumference of the superior articular surface of humerus (cms) Maximum width of the upper end or transverse diameter of the upper end cms) Circumference of the surgical neck (cms) Mid-shaft circumference (cms) Least shaft circumference (cms) Transverse diameter of the lower articular surface (cms) Transverse diameter of the lower end or Biepicondylar width (cms) Maximum length of the humerus (cms) Weight of the humerus (cms) Fig 1: Measuring the maximum width of the upper end RESULT 120 dried adult humerus (56right side & 64 left sides) were studied in present study. Each humerus was measured for 11 parameters were already described as above. The measurements were tabulated and statistically analyzed. For each parameter we calculated Mean, Median, Mode, Standard deviation, T value and P Value. Range Standard Deviation M* 4.2 3.3-4.5 0.38 F* 3.8 3.2-4.1 0.55 M 3.96 3.5-4.1 0.26 F 3.7 3.2-4.3 0.38 M 12.8 11.5-14.3 0.88 F 12.1 10.8-14.5 1.10 M 4.63 4.2-5.2 0.28 F 4.4 3.9-5.2 0.36 M 8.6 6.7-10 1.11 F 7.2 5.6-9.4 1.13 M 6 5.1-5.2 0.67 F 5.5 5.2-6.6 0.56 M 5.6 5.2-6.4 0.58 F 5.4 5-6.4 0.52 M 5.1 3.5-6.2 0.99 F 4.6 4.5-5.9 0.74 M 5.2 4.2-6.4 0.89 F 4.5 3.3-6 1.2 M 31 26-32.7 6.64 F 26 28.5-33.6 9.68 M 99.3 60-126 24.9 F 84.8 60-120 19.2 P<0.05 considered as Significance; T value Degree of Freedom P value 2.37 54 <0.02 2.2 54 <0.02 2.9 54 <0.001 2.2 54 <0.02 2.7 54 <0.001 2.49 54 <0.01 1.24 54 >0.1 1.6 54 >0.1 2.5 54 <0.01 2.2 54 <0.02 2.1 54 <0.05 M-Male; F- Female 44 Anil et al., Int J Med Res Health Sci. 2014;3(1):43-46 Table 2: Measurements of Left Humerus (n=64) Vertical diameter of the superior articular surface (cms) Transverse diameter of superior articular surface (cms) Circumference of the superior articular surface of humerus (cms) Maximum width of the upper end or transverse diameter of the upper end (cms) Circumference of the surgical neck (cms) Mid-shaft circumference (cms) M* F* M F M F M F M F M F Least shaft circumference (cms) M F Transverse diameter of the lower M articular surface (cms) F Transverse diameter of the lower end or M Biepicondylar width (cms) F Maximum length of the humerus (cms) M F Weight of the humerus (cms) M F Mean Range 3.87 3.9 3.91 3.7 12.2 11.5 4.4 3.2-4.4 3.4-4 3.6-4.2 3.1-4.4 10.8-13.5 10.2-13.4 3.9-4.8 Standard Deviation 0.38 0.45 0.24 0.36 0.83 1.14 0.29 4.22 3.7-5.2 0.41 T value Degree of Freedom P value 2.79 62 <0.01 2.4 62 <0.01 2.73 62 <0.01 1.8 62 <0.05 6.85 6.6-9.3 1.47 2.06 62 <0.05 6.25 5.8-9.7 1.05 5.8 5.2-6.8 0.47 3.7 62 <0.001 5.69 5.2-6.4 0.53 5.54 5-6.6 0.48 1.6 62 >0.1 5.22 3.5-5.9 0.82 4.52 4.3-6.1 0.92 0.5 62 >0.3 4.39 4.2-6.1 0.88 4.9 3.8-6.4 0.97 2.5 62 <0.01 4.35 3.4-6.2 0.86 30.2 26.3-32.4 1.99 2.5 62 <0.01 29 27.8-32.5 1.77 97.2 70-140 22.84 2.3 62 <0.02 81.2 60-120 28.97 P<0.05 considered as Significance; *M- Male; F-Female DISCUSSION In the present study, there has been found a difference in the Vertical diameter, Transverse diameter and Circumference of the superior articular surface of right and left sides in the male and female humerus. These findings of our study are in conformity with the studies of Girish Patil (2011)4 study on south Indians and Derya Atamturk, M. Akif Akcal, Nucket mas 5 (2010) , but it is lower than the studies of Iscan MY et al (1998).6 The Maximum width of the upper end shown high differences between right and left sides in male and female humerus. Similar findings are reported by Derya Atamturk (2010).5 Significant range of differences observed in the measurements of Mid-shaft circumference and least shaft circumference. These findings of our study are in conformity with the studies of Singh S (1972)7, Kshirasagar et al (2001)8, Salles AD et al (2009)9, Derya Atamturk, (2010)5 and Iscan M.Y et al (1998)6, and Girish patil (2011)4, a study on south Indians. In the present study, there has been found a difference in the Bi-epicondylar width of right (table-17) and left sides (table-18) in male and female humerus and it is statistically highly significant. Results of our study are tallying with the results of studies by Singh S (1972)7, Singh et al (1974), Derya Atamturk, (2010)5, Girish patil (2011)4 study on south Indians, but not tallying with the findings of Iscan MY et al (1998).6 In the present study, the Maximum length of humerus is highly significant parameter there is a considerable amount value difference is found between males and females. Our findings are in conformity with the findings reported by Singh S (1972)7, Derya 5 Atamturk, (2010) and Iscan M.Y et al (1998)6, and Girish patil (2011)4 study on south Indians, show statistically significant sex differences between mean of Maximum length of right and left in males and females. 45 Anil et al., Int J Med Res Health Sci. 2014;3(1):43-46 In the present study, there has been found a difference in the Weight of the humerus of right and left sides in male and female humerus. Reports of similar study (same parameter) are not available for comparison. CONCLUSION To know the significant findings for identification of sex of humerus 120 (56right side & 64 left side) adult, fully ossified, dried humeri were studied. The measurements obtained from the humerus were compared to the values reported by previous workers. From the results it is cleared that based on no single parameter, sex of humeri cannot be decided. All the parameters have to be considered together for this purpose. Length of the humerus, Weight of the humerus, Midshaft circumference, Transverse and Vertical diameter of the superior articular surface, Bi-epicondylar width of humerus have been found to be more discriminating parameters for the identification of sex from humerus. However, the sex overlap is observed in all the parameters and indices. This may be due to genetic, nutritional and socio-economical difference in the individuals or may be due to hypo masculinity in female humerus and hyper masculinity in male humerus. 7. Singh S, Singh SP. Identification of sex from the humerus. Indian Journal of Medicine and Research. 1972, 60:1061-66. 8. Salles AD. Reconstruction of humeral length from measurements of its proximal and distal fragments. Braz. J. Morphol. Sci. 2009;26 (2): 5561 9. Kshirasagar SV, Chavan SK, Makhani CS, Kamkhedkar SG. Sexual Dimorphism of Humerus: A Study in Marathwada Region. Indian journal of Forensic Medicine and Pathology. 2001, 2(4): 10-45 10. A Tagaya, inter to pelation variation of sex disseresnces, an analesis of the extremity long bone measurements of Japonese, J.Anshroses, soe, Nippon 1987; 95: 45 –76 11. Robinson MS, Bldmos MA. The Skull and humerus in the determination of sex: reliability of discriminant function equations. Forensic Sci Int. 2009, 186(1-3): 86e1-5 12. Beck TJ, Ruff CB, Shaffer RA, Betsinger K, Trone DW, Brodine SK (2000) Stress fracture in military recruits: gender differences in muscle and bone susceptibility factors. 2000, 27(3):437-44 REFERENCES 1. Arnold F. Handbook of Functional Anatomy. Ester babnd Freiburg Im Breisgau. 1844. 1st Edition, p. 243. 2. Williams and Warwick Editors. Grays Anatomy Churchill Livingstone (1995), 38th Edition, p.626. 3. Krogman WM. The human skeleton in Forensic Medicine charise and Thomax springeld Illinosin, U.S.A. 1st Edition. 1962) 4. Girish patil, Sanjeev Kolagi, Umesh Ramadurg. Sexual dimorphism in the Humerus: South Indians. Journal of clinical and Diagnostic Research. 2011;5(3): 538-41. 5. Derya Atamturk, M. Akif Akcal, Izzet Duyar and Nuket Mas. Sex estimation from the radiographic measurements of the humerus. Eurasian J. Anthropol. 2010;1(2): 99-108. 6. Iscan MY. Forensic Anthropology around the world. For. Scl. Inter. 1998;74: 1-3. 46 Anil et al., Int J Med Res Health Sci. 2014;3(1):43-46 DOI: 10.5958/j.2319-5886.3.1.010 International Journal of Medical Research & Health Sciences www.ijmrhs.com Received: 8th Oct 2013 Research article Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Revised: 8th Nov 2013 Copyright @2013 ISSN: 2319-5886 Accepted: 20th Nov 2013 PROGNOSTIC INDICATORS AND PATTERNS OF RENAL RECOVERY IN PATIENTS REQUIRING HEMODIALYSIS FOR ACUTE KIDNEY INJURY * Vaddadi Suresh1, Usha Bhargavi E2, N.S.R.C Guptha3, Vinod L4, Vijay Kumar P 5, Ravinder P6. 1 Associate professor, 3Assistant professor, 4Post Graduate, 5Professor; Dept of Medicine, GSL General Hospital, Rajahmundry, Andhra Pradesh, India. 2 Assistant professor, Dept of Pathology, GSL General Hospital, Rajahmundry, Andhra Pradesh, India 6 Consultant Nephrologist, Apollo hospitals, Kakinada, Andhra Pradesh, India *Corresponding author email:
[email protected] ABSTRACT Background: The outcome of patients with acute kidney injury (AKI) is highly variable. Patients who receive renal replacement therapy (RRT) for similar diseases may recover differently. The factors that operate in each patient may alter the prognosis and outcome. Aims: Our study aims at identification of prognostic factors influencing recovery in patients who required hemodialysis for AKI. Material and Methods: Patients admitted in different ICUs with AKI who underwent hemodialysis in a tertiary care hospital over a three year period were included in the study. Time from day one of disease to first dialysis, hematological and biochemical parameters were noted. Patients were grouped based on the time taken for recovery of renal function following hemodialysis into group A (<2 weeks) and group B (>2 weeks). Studied parameters have been statistically analyzed to find any significant association with recovery time. Results: Out of 63 patients, 9 progressed to chronic kidney disease. In the remaining 54, Group A comprised 31 and group B 23. Out of all the factors studied, serum creatinine (7.0±1.3 vs 8.4±3.8; P=0.018), S. bicarbonate (21.7±2.8 vs 19.7±3.8; P=0.03), pH at admission (7.25±0.13 vs 7.1±0.19; P=0.048); number of hemodialysis sessions (3.5 ±1.5 vs 5±2.4; P=0.016) and time lag from day one of disease to first hemodialysis (8.6 ± 3.6 vs 11.5±5.9; P=0.007) showed significant association with recovery time. Conclusion: Recovery following AKI is influenced by factors liked delayed presentation, late initiation of hemodialysis, low pH and low bicarbonate which can predict delayed renal recovery following hemodialysis. Keywords: Acute Kidney Injury, Hemodialysis, Seurm creatinine. INTRODUCTION Acute kidney injury (AKI) is defined as a sudden loss of kidney function that results in the retention of urea and other nitrogenous waste products along with dysregulation of extracellular volume, electrolytes and acid base balance.1 It constitutes up to 20% of critically ill patients and is easily identified by a rise in the serum creatinine.2 The quantitative definition of AKI has long been a debate due to gross variations in various methods employed in measuring the glomerular filtration rate (GFR). In view of the need for a simple and uniform definition, RIFLE criteria was proposed and was later modified and presented as AKIN criteria.3,4 This, along with the recent change in the name of ARF to AKI will represent the entire spectrum of kidney disease and help in early detection of cases. These criteria rely on the baseline serum creatinine and the relative rise is used in the categorization into risk or injury or failure group. Even though serum creatinine is not an ideal marker of renal failure, it is 47 Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52 inexpensive and is readily available making it an invaluable investigation. Novel biomarkers of AKI like cystatin-C, Neutrophil gelatinase-associated lipocalin (NGAL), Kidney injury molecule 1(KIM 1) and many others are available, but their clinical utility is still under validation.5 The etiologies of AKI vary, most common being sepsis as reported from many studies globally. Infectious causes dominate the charts all over the world and severe malaria is an important addition to the list of AKI in India. It is known that patients with persistently high serum creatinine are at increased risk of developing chronic kidney disease due to tubular damage and interstitial scarring. The rates of renal recovery in different studies varied from 3699%, but these studies defined recovery by dialysis independence.6-8 Renal replacement therapy is life saving, especially in AKI and the decision to initiate, type and timing of RRT is the choice of the treating physician as per certain indications like anuria, uremic symptoms, refractory hyperkalemia, volume overload and metabolic acidosis. It is prudent to initiate “timely” rather than “early” hemodialysis as too early dialysis is as bad as delayed dialysis as it can result in increase in mortality.9 Intermittent hemodialysis is the most common method of RRT employed in India with varied outcomes. Renal transplantation is rarely if at all, needed for AKI patients. Following RRT, the decision to wean to conservative management is done based on the recovery of clinical, biochemical and metabolic parameters. These patients who are weaned from RRT generally recover; some early, some late and some may progress to ESRD, the factors operating are unclear.10 In India, non availability of RRT in many centers, financial constraints and patient unawareness regarding disease are major barriers for measuring the burden of renal disease in the community. The factors that determine the prognosis in these patients are believed to be multiple and our study aims at their identification. MATERIAL & METHOD This study was done in a tertiary hospital over a three year period from 2010 March to February 2013. Informed consent was taken from all the patients and Ethical clearance was obtained from Institutional Ethics Committee of the hospital. Inclusion criteria: 1) Patients both male and female aged between 20 to 70 years. 2) Patients admitted for various diseases in different intensive care units (ICU) including medical, surgical, cardiac, obstetric, Cardiothoracic and burns unit who developed AKI or admitted with AKI. 3) Patients who required hemodialysis in our hospital for severe renal disease. A total number of 63 patients formed the study population. Exclusion criteria: Patients with renal disease who did not receive hemodialysis, Patients with previous history of renal disease, obstructive uropathy or acute on chronic kidney disease and patients who already received hemodialysis outside before admission were excluded from the study. Their age, sex, place of living and occupation were noted. Physical examination was done and history regarding possible risk factors was taken. All patients have undergone hematological tests including Hb%, total and differential counts, and platelet counts. Their Serum creatinine, urea, random blood sugar, electrolytes and arterial blood gas analysis at admission were noted. Along with the treatment for primary condition, all patients underwent hemodialysis for different indications like uremic encephalopathy, Anuria/oliguria, refractory hyperkalemia, metabolic acidosis, volume overload etc. Standard bicarbonate hemodialysis protocol was given to all the patients which included two hours of dialysis at initiation and then increased to four hours during subsequent sessions. The number of sessions of dialysis required for the recovery of each patient was noted. The decision to wean from dialysis was made after the correction of primary metabolic abnormality or achievement of significant clinical improvement or adequate urine output. These patients were followed up thereafter starting from day one after weaning from dialysis. Serial measurements of S. Creatinine and urea were done after the 1st week, 2nd week, 3rd week and after 3 months. Falling patterns of Serum creatinine in patients who successfully completed the follow up was noted. Patients were classified based on the time taken for normalization of Serum creatinine (recovery) into two groups: Those who recovered within 2 weeks were placed in group A (N=31 ) and those who recovered after 2 weeks were kept under Group-B (N=23 ). Various parameters mentioned above were studied between the two groups to identify any significant 48 Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52 differences which are likely to influence the prognosis and outcome. RESULTS Out of 64 patients admitted for hemodialysis, 41(65%) were males and 22 (35%) were females. Most of the patients were agricultural laborers (65%). Out of 63 patients who completed three months of follow up, 9 (14.3%) met the definition of CKD at third month and hence these patients were not considered to have recovered. The remaining 54 Patients who recovered following hemodialysis, were grouped into group-A (n=31) and group-B. (n=23). The most common age group involved was between 41-50 years. Table 1: Patients age groups Age in years Group A (%) Group B (%) 20 or below 20 1 0 21-30 2 2 31-40 6 5 41-50 9 10 51-60 8 4 Above 60 5 2 Total 31 ( 57 %) 23 ( 43 %) Various hematological and biochemical parameters, risk factors, number of dialysis sessions were compared between the two groups to find any association with recovery time, as shown in Table-2 Table 2: showing comparison of various parameters between the two groups. Group-A (n=31) Group-B (n=23) Mean ± SD Mean ±SD P value Age in years 48.4 ± 12.9 45.5±10.6 0.38 Hb% 9.6±2.5 9.5±2.2 0.87 TLC (cells/mm3) 12890±5602 13626±5974 0.64 RBS (mg/dl) 146±68.6 156.7±123.7 0.68 S.Creatinine (mg/dl) 6.4±1.1 8.6±3.7 0.01* B.Urea (mg/dl) 183.3±58.9 210.8±76.1 0.14 Serum.Na+ (mEq/L) 142±7.94 137±9.8 0.06 + Serum.K (mEq/L) 4.98±1.12 5.39±1.34 0.22 H P 7.25±0.13 7.16±0.19 0.048* S.Bicarbonate (meq/L) 21.7±2.86 19.7±3.86 0.03* HDS 3.54±1.52 5.04±2.40 0.01* T.D (days) 8.6±3.6 11.5±5.9 0.04* Recovery duration(weeks) 1.83±0.37 3.57±1.2 ----HDS- number of hemodialysis sessions required, T.D- time delay between first symptom to hemodialysis. *Significance. Table 3: showing Gender, Habits and Other risk factors between two groups Group-A (n=31) Group-B (n=23) RISK FACTOR P value Sex Male 18 16 0.28 Female 13 7 0.27 Diabetes 5 10 0.028* Hypertenson 8 3 0.21 Smoking 11 9 0.5 Alcoholism 4 3 0.56 NSAID abuse 7 2 0.16 . Group A – Patients who recovered within two weeks; Group B – Patients who recovered after two weeks; (* represents statically significant ) 49 Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52 Table 4: showing different causes of AKI S.Creatinine in mg/dL Etiology of AKI Severe Malaria Sepsis Post Gastroenteritis Leptospirosis Acute glomerulonephritis Unknown Post cardiac or abdominal surgery Acute pyelonephritis Dengue Hemorrhagic fever Road traffic accident with Rhabdomyolysis Snakebite Contrast Nephropathy Acute Pancreatitis Total N=54 (%) 17 (27.2%) 9 (14.3%) 7 (11.1%) 6 (9.6%) 5 (8%). 7(11%) 5 (8%) 2 (3.2%) 1 (1.61%) 1 (1.61%) 1 (1.61%) 1 (1.61%) 1 (1.61%) 54 (100%) Followup creatinine between two groups 5 4 3 gr A 2 gr B 1 0 1 WEEK 2 WEEK 3WEEK 3MTH Fig 1: Shows fall of serum creatinine from day-1 after last session of hemodialysis (Note: The curves belonging to both the groups are steep during the first week) Statistics: All the statistical work was performed by using SPSS trail version 16 and Microsoft Excel 2007. Descriptive statistics were presented in the form of Mean ± Standard Deviation and Percentages. The independent samples T test is used to compare means and a p value < 0.05 is taken as statically significant. DISCUSSION Hemodialysis forms an important therapeutic option for severe AKI, but treatment of the primary condition is as important. In our study, all the patients fell into failure stage of RIFLE due to very high serum creatinine at presentation and stage 3 of AKIN criteria as all of them underwent hemodialysis. Males are commonly affected as they mostly work outside, getting exposed to infections, toxins and sustain dehydration.11 Patients over 40 years of age comprised 75% of the cases. This could be explained by gradually falling renal reserve with age. Our study highlighted the importance of recognizing severe malaria as important cause of AKI in India as it was the most common cause. Overall, infections comprised 75% of all causes of AKI. Nine patients (14.3%) met the definition of CKD after three months but their disease progression was not followed thereafter. Maximum recovery following weaning from hemodialysis was noticed in the immediate first week. There was a gradual fall of serum creatinine during subsequent three months. Comparison between patients with early (group-A) and late recovery (group-B) was done after the follow up period of three months. Age and hematological parameters showed no difference between the two 50 Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52 groups. Mean random blood sugar, blood urea, serum potassium are higher in group-B but showed no statical significance. Mean serum creatinine (6.4±1.1 vs 8.6±3.7; p <0.05), S. Bicarbonate (21.7±2.8 vs 19.7±3.8; p <0.05) and pH at admission ( 7.25±0.13 vs 7.1±0.19; p < 0.05), total number of hemodialysis sessions (3.5±1.5 vs 5±2.4; p <0.05 ), time delay between disease and treatment ( 8.6±3.6 vs 11.5±5.9; p <0.05), has shown statically significant association with the recovery time. Patients with high serum creatinine at admission (implying higher renal functional loss) took much longer to recover. Studies have shown that higher stages of AKI can result in prolonged hospital stay due to delayed renal recovery.12 patients with severe metabolic acidosis characterized by low bicarbonate and low pH took much longer time to recover. Metabolic acidosis results due to multiple factors apart from inability of the kidney to excrete metabolic acids. Hepatic involvement, which is commonly seen in Malaria, Leptospirosis, Dengue infections, Sepsis and as a component of multi organ dysfunction syndrome (MODS) along with starvation in these patients can contribute to significant metabolic acidosis. AKI patients who required more number of hemodialysis sessions had delayed recovery. This is because patients who had severe disease required more number of sessions and the recovery after weaning is also delayed owing to the severity. A very important outcome of this study is that delay in the initiation of hemodialysis in indicated patients resulted in delayed recovery following weaning. This is evidenced by the significantly higher time gap ( days ) between first symptoms and first hemodialysis in group B patients ( A vs B = 8.6 ± 3.6 vs 11.5 ± 5.9; p=0.04). The exact timing of dialysis, duration and withdrawal of dialysis sessions is Physician’s discretion, and is subjected to variations.13 Adding to delayed hospitalization, conservative approach is implemented by some, even when there is clear indication for RRT, which can actually worsen the metabolic complications and there by mitigating the chances of recovery even after subsequent RRT. The term “door to dialysis time” is suggested by some authors to emphasize the importance of timely hemodialysis. 14 In our study, patients with diabetes had delayed recovery. This could be because of underlying preexisting diabetic nephropathy in these patients. Contrast nephropathy is one condition where unequivocal evidence exists regarding renal damage and poor recovery following RRT in diabetes.15 whether or not, this can be extrapolated to other causes of AKI is not known. In our study, factors like gender, hypertension, smoking, alcoholism and even NSAID intake have not shown any association with recovery time. This is in contrast to earlier studies documenting NSAID use as a potential cause of renal damage as well as delayed renal recovery.16 However, we did not collect the data regarding the type, quantity and duration of use of NSAIDS in any patient included in the groups due to unreliability of patient history. The limitations of our study include small sample size, lack of application of Glomerular filtration rate, lack of long term follow up in recovered patients as some of them could have landed in worsening of renal function following apparent recovery, thus missing the true burden of AKI progressing into CKD. CONCLUSION AKI can have varied etiologies, and infections form the bulk of these cases. Along with the correction of primary cause, timely RRT can have significant impact on the recovery of patients. Patients presenting late, patients with high serum creatinine, low Ph and low serum bicarbonate at admission, patients who required more number of hemodialysis sessions and known diabetics irrespective of diabetes control, are prone for delayed recovery following weaning from hemodialysis. ACKNOWLEDGEMENTS We are thankful G.K Anand Kumar, dialysis technician and Ganapathi Swamy, statistician for their immense help in this project. REFERENCES 1. Fauci AS, Braunwald E, Kaspar DL, Hauser SL, Longo DL, Jameson JL. Acute renal failure. Harrison’s Principles of Internal Medicine.17th Ed.,McGraw‑Hill; 2008:1752‑61 2. Lameire N, Van Biesen W, Vanholder R. The changing epidemiology of Acute renal failure. Nat Clin Pract Nephrol 2006;2:364-77. 51 Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52 3. Bellomo R, Ronco C, Kellum JA Mehta RL, Palevsky P. Acute renal failure definition,outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8:204–12. 4. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, et al. Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11: R31. 5. Waring WS, Stephen AF. Earlier recognition of nephrotoxicity using novel biomarkers of acute kidney injury. Clinical Toxicology.2011;49: 720– 28. 6. Ishani A, Xue JL, Himmelfarb J, Eggers PW. Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol.2009; 20: 223– 228. 7. Coca SG, Yusuf B, Shlipak MG, Garg AX, Parikh CR. Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis.2009; 53: 961–73. 8. Wald R, Quinn RR, Luo J, Li P, Scales DC, Mamdani MM, et al. Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA .2009;302:1179–1185 9. Shiao CC, Ko WJ, Wu VC, Huang TM, Lai CF, Lin YF, et al. U-curve association between timing of renal replacement therapy initiation and inhospital mortality in postoperative acute kidney injury. PLoS One 2012;7:e42952 10. Steven GC, Swathi Singanamala. Chronic Kidney Disease after Acute Kidney Injury: A Systematic Review and Meta-analysis.kidney Intestinal.2012; 81(5): 442-48. 11. Kute VB, Shah PR. Outcome and prognostic factors of malaria-associated acute kidney injury requiring hemodialysis: A single center experience. Indian J nephrol. 2012; 22(1): 33-38. 12. Mehta P, Sinha A,Sami Hari P, Kalaivani M, Gulati A. Incidence of acute kidney injury in hospitalized children. Indian Pediatr.2012;49: 537–42 13. Gibney N, Hoste E, Burdmann EA, Bunchman T, Kher V, Viswanathan R et.al Timing of Initiation and Discontinuation of Renal Replacement Therapy in AKI: Unanswered Key Questions. Clin J Am Soc Nephrol. 2008;3(3):876-80 14. Andrade L, Cleto S, Seguro AC. Door-to-dialysis time and daily hemodialysis in patients with leptospirosis: Impact on mortality. Clin J Am Soc Nephrol. 2007; 2: 739 –44 15. Weisberg, Lawrence S., Peter B. Kurnik, and Brenda RC Kurnik. Risk of radiocontrast nephropathy in patients with and without diabetes mellitus. Kidney international. 1994;45(1): 25965. 16. Abraham PA, Keane WF. Glomerular and interstitial disease induced by nonsteroidal antiinflammatory drugs. American Journal of Nephrology. 1984;4(1): 1-6 52 Suresh et al., Int J Med Res Health Sci. 2014;3(1):47-52 DOI: 10.5958/j.2319-5886.3.1.011 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 27 Oct 2013 Revised: 18th Nov 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 28th Nov 2013 PSYCHOSOCIAL DETERMINANTS OF CONTRACEPTIVE REPRODUCTIVE AGE IN A RURAL AREA OF MAHARASHTRA USE AMONG WOMEN OF *Minhas S1, Sekhon H2 1 Reader, Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India. Psychiatrist & Chief Medical Officer, Composite Hospital, Central Reserve Police Force, Bantalab, Jammu, Jammu & Kashmir, India. 2 *Corresponding author email:
[email protected] ABSTRACT The World Health Organisation reports that an estimated 94 per cent of the population of the world lives in countries with policies that favour family planning. Despite this, five of every six couples of reproductive age do not use adequate measures of fertility regulation. Gender inequalities in patriarchal societies ensure that men play a critical role in the decisions on family matters. The present study was undertaken to study the nature of acceptance of contraceptive practices and the psychosocial determinants. Methods: This was a community based cross sectional descriptive study. The anticipated prevalence of contraceptive practices among the 206 women in the age group of 15-49 years was 50%. Considering a margin of error of 10%, with finite correction and 10% of nonresponse and 95% CI, the sample size was calculated. 90 married women in the reproductive age group of 15-49 years residing at the village were studied after drawing the sample with simple random sampling method. Results: There were 55 (61.11%) women who practised contraception. In case of 03 (3.33%) couples, husbands used condoms, while in case of remaining 52 (57.78%), wife had undergone tubectomy. Conclusion: From the present study, it was concluded that the most common method of contraception practiced in the study population was tubectomy and a range of psychosocial factors played an important role in decision making. Keywords: Women, Rural, Contraception, Psychosocial, Tubectomy. INTRODUCTION An expert Committee of the World Health Organisation (WHO) has defined family planning as “a way of thinking and living that is adopted voluntarily, upon the basis of knowledge, attitudes and responsible decisions by individuals and couples to attain certain objectives”.1 Even though the technology was available, only nine per cent of women in the developing countries had access to contraceptive services in 1965. The use increased to 50 per cent by 1990. Nonetheless, wide geographical variations still persisted.2 The world conference of the International Women’s Year 1975 declared “the right of the women to decide freely and responsibly on the number and spacing of their children and to have access to information and means to enable them to exercise that right”. The United Nations International Women’s Decade (1976-1985) helped to increase awareness about many issues concerning women’s health including excessive pregnancies, inappropriate timing and spacing of pregnancies and poor educational levels2. During the International Conference on Population Development programme of action, it was recognized that demographic goal-driven family planning programmes, may by their very nature violate basic human rights (ICPD 1994).3 The WHO reports that an estimated 94 per cent of population of the world lives in countries with policies that favour family planning. Despite these policies five of every 53 Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58 six couples of reproductive age do not use adequate measures of fertility regulation.4 Currently, over 97 percent of sterilisations are tubectomies.5 It has been deduced by research that family planning is the first and most important step for rural development.6 Family planning means better health for the mothers and their children and more opportunities for the family as a whole.7 A majority of women in most developing countries are aware of the health risks posed by frequent pregnancies, and thus the importance of birth spacing, but this awareness has not satisfactorily translated into action.2A study conducted on eligible rural women revealed that most of them were concerned about child survival and also that they viewed children as an important source of their support in old age. The size of family was usually decided by in-laws and partner support played a predominant role in the decision. Pressure from the inlaws to have more number of children was found to be significantly higher in families where the women were less educated or illiterate.8 Despite the decline in total fertility rate worldwide, there are still millions of women with unmet contraceptive needs in developing countries. There are more married women with an unmet contraceptive need (about 31 million) in India than any other country.9 The National Family Health Survey III (NFHS III), carried out in 29 states during 2005-06, shows that nearly 45 per cent of women in India were married off before they turned 18. It also shows that over 71 per cent of women who got married under 18 years had received no education. Early marriage impacts a woman's health and education. It shows that women who are getting married early are giving birth also at an early age. While 52.5 per cent of the under 18 marriages were in rural areas, it was 28.1 per cent in urban areas.10 But the Total Fertility Rate (TFR) has shown a decline over the years. In the state of Maharashtra itself, the TFR has shown a decline, from 2.9 (NFHS-I), to 2.5 (NFHS -II) and 2.1 (NFHS -III).11 Many studies have been conducted till now on this issue but still there are gaps in the information on the sporadic nature of acceptance of contraceptive practices, especially in this rural area of the state.12 In view of the same, this study was undertaken in a rural area of Maharashtra, India. Aim: This study aimed at conducting an epidemiological survey among the married women in the age group of 15-49 years, residing a rural area of Maharashtra, India to find out the current contraceptive practices. Objectives: 1. To determine the current contraceptive practices among married women in a village in Pune district of Mahrashtra. 2. To suggest promotional strategies for better utilisation of family planning services MATERIAL AND METHODS It was a community based cross sectional descriptive study. The reference population was women who were married and in the reproductive age group (aged 15-49 years) residing in the rural areas of Maharashtra. The exclusion criteria were all women who were divorced, separated, widowed, infertile, who had attained menopause, who had undergone hysterectomy and women who had migrated to the village but were not permanently residing there. The actual study population included all married women in the reproductive age group of 15 – 49 years residing in the village. Simple random sampling was done. The anticipated prevalence of contraceptive practices among the 206 married women, considering a margin of error of 10%, with finite correction and 10% of nonresponse and 95% CI, the sample size was calculated to be 90. For selection of subjects, a serial list of all the married women in the reproductive age group of 15 – 49 years was made. Using random number table generated random numbers and the women corresponding to these numbers from this population were included in the sample. House to house visits were carried out and the eligible women were interviewed using a pre-tested standardized questionnaire. Verbal consent of the respondents was taken before the questionnaire was administered. A pilot study was undertaken on 20 subjects (who were later excluded from the actual study) which helped to further standardize the questionnaire and make certain amendments in it. A brief introduction about the study was given by the principal worker to the subjects. The services of a medico-social worker were sought for interpretation and better communication with the subjects. Confidentiality of the identity of the respondent and the information provided was assured. RESULTS Out of the sample of 90, there were 55 (61.11%) who practiced contraception (table-1). 54 Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58 Table 1: Distribution of Respondents Based on Contraception Usage Contraceptive users (%) Non-users Total Tubectomy Condom (%) 52 (57.78) 03 (3.33) 35 (38.89) 90 In case of three (3.33%) couples, the husbands used condoms, while in the case of remaining 52 (57.78%), the wives had undergone tubectomy. No other mode of contraception was found in the subjects who were studied as a sample. For analysis purposes, the three (3.33%) couples using condoms were excluded. Subsequent analysis was done against tubectomy users and non-users of any contraceptive method. On studying the distribution of tubectomy status by age of respondent (table-2), a significant association was found between defined age groups and tubectomy status (p<0.01). Table 2: Distribution of Tubectomy Status by Age of Respondent Tubectomy (%) Age Total (%) User Non-User (Years) <25 06 (11.54) 19 (54.29) 25 (28.73) 25-34 24 (46.15) 12 (34.29) 36 (41.38) ≥35 22 (42.31) 04 (11.43) 26 (29.89) Total 52 (100.00) 35 (100.00) 87 (100.00) Chi square Statistic: 20.689 df = 2 p<0.01 Mean (SD): Users: 33.23 (6.94) Non-users: 25.31 (6.03), ‘t’ statistic=5.49, df=85, p<0.01 There was a significant difference in age of husbands between users and non-users (p<0.01) (table – 3). Table 3: Distribution of Tubectomy Status by Age of Husband Age Tubectomy (%) (Years) User Total (%) Non-User <30 04 (07.69) 19 (54.29) 23 (26.44) 30-40 31 (59.62) 14 (40.00) 45 (51.72) >40 17 (32.69) 02 (05.71) 19 (21.84) Total 52 (100.00) 35 (100.00) 87 (100.00) Chi square Statistic: 25.706 df = 2 p<0.01 Mean (SD): Users: 37.83 (6.75) Non-users: 29.23 (6.64), ‘t’ statistic=5.86, df=85, p<0.01 Two-third of users i.e. 39 (75.00%) users got married before the age of 18 years and only 13 (25.00%) users did so at or after attaining the age of 18 years (table 4). Table 4: Distribution of Tubectomy Status by Age of Respondent at Marriage Age Tubectomy (%) (Years) User Total (%) Non-User <18 39 (75.00) 14 (40.00) 53 (60.92) ≥18 13 (25.00) 21 (60.00) 34 (39.08) Total 52 (100.00) 35 (100.00) 87 (100.00) Chi square Statistic (Yates corrected): 9.344, p value: <0.01 Median age at marriage: Users:16, Non-users: 18 It was found that significantly higher percentage of users had age at marriage less than 18 years as compared to non-users (p<0.01). There were more users with three or more children than non-users (table-5). Table 5: Distribution of Tubectomy Status by Total Number of Children Number of Tubectomy(%) Children User Non-user Total (%) 1-2 18 (34.62) 24 (88.89) 42 (53.16) ≥3 34 (65.38) 03 (11.11) 37 (46.84) Total 52 (100.00) 27 (100.00) 79 (100.00) Note: Eight couples who do not have any children were excluded. Chi square Statistic (Yates corrected): 18.90, p value<0.01 The highest level of education was found to be graduation while the lowest was illiterate in the case of husbands, while it was high school and illiterate in the case of the respondents (table -6,7). Table 6: Distribution of Tubectomy Status by Educational Qualification of Husband Educational Tubectomy (%) Qualification User Total (%) Non-User <Middle 14 (26.92) 12 (34.29) 26 (29.89) ≥Middle 38 (73.08) 23 (65.71) 61 (70.11) Total 52 100.00) 35 (100.00) 87 (100.0) Chi square Statistic (Yates corrected): 0.246, p value = 0.6 Table 7: Distribution of Tubectomy Status by Educational Qualification of Respondent Educational Tubectomy (%) Qualification User Total (%) Non-User <Middle 22 (42.31) 17 (48.57) 39 (44.83) ≥Middle 30 (57.69) 18 (51.43) 48 (55.17) Total 52 35 87 55 Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58 Chi square Statistic (Yates corrected): 0.126, p value = 0.7 Level of education of the husband did not have a significant association with tubectomy (p>0.05). It was also observed that greater is the income, the more is the acceptance for tubectomy (table – 8). Table 8: Distribution of Tubectomy Status by Total Monthly Income Income Tubectomy (%) Total (%) User Non-User <2000 01 (01.92) 07 (20.00) 08 (09.19) 2000-2999 10 (19.23) 13 (37.14) 23 (26.44) 3000-3999 25 (48.08) 09 (25.71) 34 (27.59) ≥4000 16 (30.77) 06 (17.14) 22 (25.29) Total 52 (100.00) 35 (100.00) 87 (100.0) Chi square Statistic (Yates corrected): 10.30, p value <0.01 Logistic Regression A model for Logistic Regression Analysis was prepared, taking those predictor variables which had shown a significance of p≤0.1 in the univariate analysis. The multivariate analysis was done to assess the effect or association or impact of age of respondents, age of husband, age of respondent at marriage, age of respondent at birth of first child, total number of children, occupation of respondents, combined income of respondents and husband, on tubectomy status. Women with no child were excluded from this analysis, since they will not have information regarding age at birth of the first child and a number of children will be zero. In this analysis, only the combined income was found to have a significant association with tubectomy status, with p value less than the conventional i.e. p<0.05, Odds Ratio = 15.29 with 95% Confidence Interval: 2.44 – 95.69. It was observed that the odds of acceptance of tubectomy among those couples who had a combined income of ≥3000 rupees per month were 15.29 times more than the couples who had a combined monthly income less than this figure. DISCUSSION In the present study, the figures for contraceptive prevalence as well as female sterilization, both are above the corresponding national figures. The current level of contraceptive use i.e. contraceptive prevalence rate defined as percentage of currently married women aged 15-49 years who are currently using a method or whose husbands are using a contraceptive method, is one of the principal determinants of fertility. It is also an indicator of the success of family planning programmes.11 As per NFHS III, contraceptive prevalence rate for currently married women in India is 56 percent (four percent more than NFHS II). Female sterilization with a prevalence of 37 percent, accounts for 66 percent of all contraceptive use (NFHS II: 34.2 percent; NFHS I: 27.3 percent). In the state of Maharashtra, the prevalence of female sterilization is 44.2 percent.11 Sterilisation has been a widely used method of contraception in India. It has been found that unmet need decreases with age, from 27 percent for women aged 15-19 years, to two percent for women aged 45-49 years. The unmet need for family planning among currently married women is 13 percent, down from 16 percent in NFHS II.11 In the present study, it was revealed that the age of users was significantly higher than non-users, which is similar to findings of previous studies.13-15 A significant association was also found between tubectomy and the age of the respondent at marriage (p<0.01). The median age at marriage is 16 years and 18 years among users and non-users respectively. One in six women begins childbearing in the age group 15-19 years. The age at which women start bearing children is an important demographic determinant of fertility.11 Similar results were observed in the present study i.e., 46 (58.22%) of the respondents had given birth to their first child before they turned 20 years of age. Delayed childbearing may reduce maternal and infant health risks but in addition, also provide increased opportunities for women to acquire education, skills and great aspiration for herself and her family.15 The permanent method of contraception has been found to be accepted by 70.7% of the women with three or more children and only 29.3% accepted this method with one or two living children.16 In the present study, a significant association was observed between tubectomy and the total number of children (p<0.01). The mean number of children for currently married women was found to be 2.96 and 1.37 in case of users and non-users respectively. There were six respondents who had only female children and all of them were non-users. It appears that the family is considered complete only if male children are there, whether they are in addition to the female children or not; only then is tubectomy resorted to. It shows that the gender of the children is a determining factor for 56 Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58 undergoing tubectomy. The extent to which the status of women is related to awareness, knowledge, and practice of family planning in India shows a definite statistical relationship between women's status and women's ability to control fertility. It was found that a higher percentage of couples who have two or more surviving children, particularly if they are boys, practiced family planning.17, 18 Education as such has not been found to have any significant association with tubectomy although better is the educational qualification, more likely is the decision to resort to it.16,17,19-21 In NFHS III, overall, just over half i.e. 55 percent of women were found to be literate while 78 percent males were found to be so. In case of rural areas, 49.7 percent of women and 23.0 percent of men were found to be illiterate. In fact, besides income, the greatest difference in fertility was found to be due to education. The use of female sterilization is higher for females with less education.11 In a study conducted in a developed country, it was hypothesised that the current contraceptive use among the sexually active, fertile women was related to their attitude towards the different types of contraceptive methods available, social influences, the perceptions of ability to use a method correctly and also consistently, and communication with their respective partner. In the present study too, education has been observed to play an important role in partner support and the decision making process.22 Wealth has been found to have a positive effect on women’s contraceptive use. In NFHS III, contraceptive use was found to be 42 percent among the lowest quintile, while it increased to 68 percent in the highest quintile. It was observed in the present study that in the case of those couples who had both members earning, acceptance of tubectomy was more. Income has been found to influence the acceptance of family planning methods and an increasing trend of acceptance has been observed with the increase in income.16 From the present study it is evident that sterilization is fairly well accepted, however more knowledge is needed on reversible methods. Since the findings of the current study are comparable to other similar studies and the NFHS III data, it highlights that the results of the current study can be used as a background to conduct more such studies so as to add on to the information that already exists. It would help to generate community specific data in order to benefit for research, development and planning purposes. CONCLUSION This study brings out that knowledge about contraceptive is nearly universal and that education enhances the ability of individuals to achieve desired demographic goals.11 It reiterates the fact that education plays a major role in creating better awareness amongst people. The choice of contraceptive appears to be determined a lot more by a general like or dislike towards medical methods, rather than weighing merits of the individual available methods.22 Effective contraceptive practices have the potential, not only to improve the lives of the women, men and children involved, but also to benefit couples, families and communities.23 RECOMMENDATIONS Based on this study, it is recommended that what is required is the need to strengthen social marketing programmes for non-clinical family planning products and services in such areas. Greater effort needs to be made to involve men in the process of family planning and male sterilization requires to be given impetus. Awareness about methods other than female sterilization must be improved by village level campaigns. To help encourage adoption of family planning and reduce fertility, the government should emphasize education for women, enforce the legal minimum age at marriage, promote employment opportunities for women, improve women's role in decision making, and encourage inter-spousal communication in family affairs. Conflicts of interest; None identified. REFERENCES 1. Park K. Park’s Textbook of Preventive and Social Medicine. 22nd Edition. Banarsidas Bhanot, Jabalpur, India, 2007; 389, 392. 2. Sein T, Rafei UM. The history and development of public health in developing countries. In: Detels Roger, McEwen James, Beaglehole Robert and Tanaka Heizo editors. Oxford Textbook of Public Health. 4th Edition. Oxford Medical Publications, 2005; 44-45. 3. Gruskin S, Tarantola D. Health and human rights. In: Detels Roger, McEwen James, Beaglehole Robert and Tanaka Heizo editors. Oxford 57 Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Textbook of Public Health. 4th Edition. Oxford Textbook of Public Health. Oxford Medical Publications, 2005; 4th Edition 325. Tyler CW, Peterson BH. Family planning programmes and practices: An epidemiological viewpoint. In: Wallace B Robert editor. MaxcyRosenau-Last: Public Health and Preventive Medicine.. Appleton and Lange 1998; 14th Editionl: 1187. National Population Policy 2000. Operational Strategies: Meeting the unmet needs. Available at https://www. india.unfpa.org/drive/National Population-Policy2000.pdf. Accessed on 06-122013. Mokarapong T. Family planning is the first and most important step for rural development. J Thai Assoc Volunt Steriliz. 1983; 75-85. Gandhi I. India: the human factor in overcoming population problems. Asian Pac Popul Programme News. 1984;13 (1):15-6 Kartikeyan S, Chaturvedi RM. Family planning: views of female non-acceptors in rural India. J Postgrad Med. 1995 Apr-Jun; 41(2):37-9. Wang S, An L, Cochran SD. Women. In: Detels Roger, McEwen James, Beaglehole Robert and Tanaka Heizo editors. Oxford Textbook of Public Health.. Oxford Medical Publications, 2005; 4th Ed: 1591. Daily News and Analysis: NFHS III. February 23, 2007. www.dnaindia.com. International Institute for Population Sciences (IIPS) and Macro International. National Family Health Survey (NFHS-3), 2005–06: India: 2007;Volume I. Department of International Economic and Social Affairs. Population Division UN: Recent trends and conditions of fertility. United Nations. Popul Bull UN. 1983; (15):1-14. Sengupta R, Lhungdim H .Factors associated with Contraceptive Practices and Unmet Need among Young Currently Married Women in the Rural Areas of Empowered Action Group (EAG) States of India. IIPS Seminar Jul 2011. Available at: iipsindia.org/pdf/Vol.%2052%20No.%203%20& %204%20July-2011.pdf. Accessed on 06-12-2013. Susuman SA. Son Preference and Contraceptive Practice among Tribal Groups in Rural South India. Stud. Tribes Tribals, 2006;4(1): 31-40. 15. Khokhar A, Mehra M. Contraceptive Use in Women From a Resettlement Area in Delhi. Indian Journal of Community Medicine, 2005;30 Available at:http://www.indmedica.com/journals. php?journalid=7&issueid=28&articleid=302 &action=article. Accessed on 06-12-2013. 16. Mohanan P, Kamath A, Sajjan BS. Fertility pattern and family planning practices in a rural area in Dakshina Kannada. Indian Journal of Community Medicine, 2003;28 (1): 15-18 17. Vaidyanathan KE. Status of women and family planning: the Indian case. Asia Pac Popul J. 1989; 4 (2):3-18 18. (No authors cited) India: sterilization is common; women know little about other methods. Prog Hum Reprod Res. 1991;18:2-3. 19. Kaur G, Singh TR. Acceptance of family planning practice among rural women clientele. Indian J Public Health. 1982; 26 (3):194-9 20. Takkar N, Goel P, Saha PK, Dua D. Contraceptive practices and awareness of emergency contraception in educated working women. Indian J Med Sci 2005;59:143-9 21. Gupta VM, Jain R, Sen P. Study of interspouse communication and adoption of family planning and immunization services in a rural block of Varanasi District. Indian J Public Health. 2001;45 (4):110-5. 22. Oddens BJ. Determinants of contraceptive use among women of reproductive age in Great Britain and Germany. II: Psychological factors. J Biosoc Sci. 1997;29(4):437-70 23. TMM Maja. Factors impacting on contraceptive practices. Health Sa Gesondheid. 2007;12(1):3038. 58 Minhas et al., Int J Med Res Health Sci. 2014;3(1):53-58 DOI: 10.5958/j.2319-5886.3.1.012 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 30 Oct 2013 Revised: 3rd Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 12th Dec 2013 CLINICO-PATHOLOGICAL PROFILE IN THE INFANTS AND CHILDREN IN DENGUE 2012 EPIDEMIC, KOLKATA *Saha K Ashis1, Ghosh Shibendu2. 1 Assistant Professor, General Medicine, K P C Medical College & Hospital, Jadavpur, Kolkata, West Bengal Professor, General Medicine, Ramkrisna Mission Seba Pratisthan, Kolkata, West Bengal, India 2 *Corresponding author email:
[email protected] ABSTRACT Background: Dengue fever (DF) is responsible for cyclical and frequent epidemic in different parts of India in its varieties of presentations. In 1992 large number of children died of Dengue hemorrhagic fever (DHF). Aims and objective: In this study, we evaluated the demography and clinico-pathological profile in dengue affected infants and children in 2012 Kolkata epidemic. Materials and methods: Total 233 patients (between 1-18 years, with either Non structural protein 1 antigen or dengue Immunoglobulin positive) admitted in our hospital. After taking proper history and physical examination, blood were sent for different hematological and biochemical examinations on the day of admission and after 24-48 hours of admission. We differentiated the dengue patients into DF and DHF based on platelet count. Results: Male female ratio and DF to DHF ratio were 1: 0.86 and 1: 3.5 respectively. Mean age of DF and DHF were 10.31±5.41 years and 12.6±4.51 years respectively. Mean duration of fever in DF and DHF cases were 5.33±1.13 and 6.08±1.79 days respectively. Headache, backache, nausea/vomiting, rash, anorexia, loose motions were statistically significant in DF. In spite of significant positive tourniquet test in DHF patients (76.92%), only 13 patients showed evidence of bleeding. Hematocrit (Hct) values between 30-40 and below 30 were significant in DHF and DF patients respectively. Leucopenia and increased liver enzymes (SGOT and SGPT) were commonly observed in both DF and DHF patients. Hepatomegaly was observed in 13.72% of DF patients, whereas, isolated hepatomegaly, ascites, combined hepatomegaly with ascites and evidence of pleural effusion were observed in 4.94%, 1.64%, 3.29% and 7.14% of DHF patients respectively. Conclusion: In seropositive DHF patients, fever, headache, backache, loose motions were the predominant symptoms associated with hepatomegaly, elevated liver enzymes and evidence of plasma leakage. Keywords: Clinico-pathology, Dengue epidemic, Infants, Children, Kolkata INTRODUCTION Over several decades, Dengue, an Arbo virus infection, is responsible for cyclical and more frequent epidemic in rural as well as urban areas of India, showing a wide variety of presentations from subclinical or mild self limiting disease to severe form of disease, like, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS).1 DHF first crept into Kolkata in 1963-65, this was followed by the recurrent occurrence of outbreaks.2 In the 1992 epidemic, large number of affected children died of DHF/DSS. Dengue may be manifested by its typical clinical features, but its presentation may be variable making the doctor puzzled. Our present study was to evaluate the demography and clinic-pathological profile of 59 Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64 dengue fever in infants and children during the 2012 dengue epidemic in Kolkata. PATIENTS & METHODOLOGY Inclusion criteria: In 2012 epidemic, total 233 infants and children between the ages of 1 to 18 years, were admitted in our hospital on and from the month of 1st August to 31st October with either Non structural protein 1 antigen (NS1, antigen) positive or dengue Immunoglobulin M (IgM) positive. Exclusion criteria: Patient suffering from any infection, viral hepatitis during this period. Ethical clearance: This study was started after getting approval from Ethical Committee and informed consent form obtained from the patients’ parties. Methodology: Thorough history-taking and physical examination was performed in all these patients. Just after admission, 5 ml. of blood was collected aseptically from each patient. 1 ml of clotted blood was used for non structural protein 1 (NS1) antigen and immunoglobulin M (IgM) antibody by Mac ELISA manufactured by Panibo Diagnostics, remaining 4ml of Blood sample was used for examination of hematological and biochemical profile immediately. Between the interval of 24 and 48 hours after admission, 4 ml of blood sample was collected. 2 ml of blood was kept in EDTA vial and was sent for platelet count both by manual methods (light microscopy and Neubauer chamber) and Coulter counter method and hematocrit. Rest 2 ml of clotted blood was used for biochemical tests (SGPT, SGOT). Daily platelet count was advised for those patients having platelet count less than 100000/cc. Imaging studies like, Ultrasonography and chest x-ray were performed to detect Ascites and pleural effusion respectively. We differentiated the dengue patients into Dengue fever (DF) and DHF based on platelet count. (Since there was no DSS detected among in this group). These patients were treated with intravenous fluid, Paracetamol according to WHO protocol.3 No Table 1: Demographic distribution Features Mean age yrs Male sex Female sex *significant patient was treated with NSAID. When vital statistics of these patients came to normal; they were discharged from hospital. Statistics: Then, we compared the demographic data, symptoms, laboratory investigations between DF and DHF by Open stat and Statcalc statistical Calculators. P value of <0.05 was considered as statistical significance. RESULTS In our study, all our patients were either NS1 (79%) or IgM (21%) positive. Male female ratio was 1: 0.86, whereas ratio of DF to DHF ratio was 1: 3.5. Male to female ratio in DF was 1: 1 and in DHF, 1:1.16. Mean age of DF and DHF were 10.31±5.41 years and 12.6±4.51 years respectively [table 1]. All the patients were admitted with fever. Mean duration of fever in DF and DHF cases were 5.33±1.13 and 6.08±1.79 days respectively. Common symptoms were Headache (62.74%, 30.76%), backache (58.82%, 30.76%), nausea/vomiting (62.74%, 47.25%), rash (29.41%, 15.93%), anorexia (60.78%, 13.73%), loose motion (35.29%, 18.68%) in both DF and DHF respectively. In spite of significant positive tourniquet test in DHF patients (76.92%), severe bleeding was seen in only 13 patients. [Table 2]. Most of the patients were anemic. Hematocrit (Hct) between 30-40 was significant in DHF patients, whereas, Hct was observed below 30 in significant number of DF patients. Leucopenia and raised liver enzymes (SGOT and SGPT) were commonly observed in both DF and DHF patients without any statistical difference. But, the International normalized ratio (INR) was only elevated more than 1.5 in DHF patients [Table 3]. Sonographically, Isolated hepatomagaly observed in 13.72% and 4.94% DF and DHF patients respectively, whereas, ascites and ascites associated with hepatomagaly were observed in 1.64% and 3.29% of DHF patients respectively. Again, chest x-ray showed evidence of pleural effusion in DHF patients only [Table 4]. DF (51) 10.31 ±5.41 26 25 DHF (182) 12.6 ±4.51 98 84 P value 0.04* 0.35 0.35 60 Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64 Table 2: Common symptoms Symptoms DF (51) DHF (182) Fever (days) 5.33±1.13 6.08±1.79 Headache 32 (62.74 %) 56(30.76%) Backache 30 (58.82%) 56 (30.76%) Nausea/vomiting 32 (62.74%) 86 (47.25%) Rash 15 (29.41%) 29 (15.93%) Anorexia 31 (60.78%) 52 (13.73%) Loose motion 18 (35.29%) 34 (18.68%) Retro orbital pain 4 (7.8%) 6 (3.29%) Types of bleeding Positive tourniquet test 0 140 (76.92%) Epistaxis 0 3 (1.64%) Skin 0 4 (2.19%) Gum 0 3 (1.64%) Hematemesis/melena 0 3 (1.64%) *-- Significant, **-- Very significant, *** -- Extremely significant Table 3: Hematological, biochemical distribution: Parameter DF (51) DHF (182) Hematocrit (L/L) ≥40 (37) 2 (3.92%) 4 (2.19%) (30-40) 20 (39.21%) 120 (65.93%) (<30) 29 (56.86%) 58 (31.86%) Hemoglobin (gm/dl) 10.5±1.4 10.3±1.1 Total leukocyte count <1000-3000/cc 20 (39.21%) 60 (32.96%) >3000-4000/cc 19 ( 37.25%) 80 (43.95%) >4000/cc 12 (23.52%) 42 (23.07 %) Platelet count ≤20000/cc (8) 0 8 ( 4.39%) >20000 – 40000/cc 0 28 (15.38%) SGOT >3 times normal 15 (29.41%) 66 (36.26%) SGPT >100 – 200 IU/L 10 (19.60%) 31 (17.03%) SGPT >200 – 350 IU/L 5 (9.80%) 18 (9.89%) SGPT >350 IU/L 2 (3.92%) 14 (7.69%) INR >1.5 (21) 0 21 (11.53%) % Amongst total (233) 88 (37.76%) 86(36.90%) 136(58.36%) 44 (18.88%) 83(35.62%) 52 (22.31%) 10 (4.29%) P value 0.0001** 0.00001*** 0.0001** 0.02* 0.01* 0.00001*** 0.005** 0.07 140 (60.08%) 3(1.28%) 4(1.71%) 3(1.28%) 3 (1.28%) % amongst total (233) P value 6 (2.57%) 140 (60.08%) 37.33 - 2.46 0.0003** 0.0006** 80 (34.33%) 99(42.48%) 54(23.17%) 0.20 0.19 0.47 8(3.43%) 28(12.01%) 81(34.76%) 41(17.59%) 23 (9.87%) 16 (6.86%) 21 (9.01%) 0.18 0.33 0.49 0.17 - ** Very significant, SGOT: Serum aspartate aminotransferase, SGPT: Serum alanine aminotransferase; INR: International normalized ratio Table 4: Radiological distribution: Items Ascites Hepatomegaly USG Ascites & Hepatomegaly Hepatosplenomegaly Chest x-ray DF (51) 0 7 (13.72%) 0 0 0 DHF (182) 3 (1.64%) 9 (4.94%) 6 (3.29%) 0 13 (7.14%) % Amongst total patients (233) 1.28 6.86 2.57 0 5.57 61 Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64 DISCUSSION Age group affected by dengue fever as shown by Narayanan et al4 was 7 to 8 years of age, which was similar to the study done by Kabra SK et al5 and Banik GB et al.6 Though dengue fever is a well-known disease of child-age group, but since 1980’s there is slight inclination towards higher age group in case of DHF, as shown in various studies in Latin America and South-East Asia. Similarly, in our study, the mean age was 10.31 and 12.6 years in DF and DHF respectively. Though according to previous belief, DHF/DSS is due to either previous infection or passive transfer of antibody from the mother7, but in our study, DHF occurred at higher age group – so it may be due to antibodies, acquired by the patients at earlier ages. According to some author, it may be due to virulent virus rather than pre-infection antibody status.8 Few available hospital studies demoed male-female distribution in dengue fever. Kabra SK et al5 showed girl preponderance as also seen in the study done by Mittal H et al.9 Three independent studies in India and Singapore showed that males were twice more common than females.10 , 11 Hospital based study in Delhi showed male to female ratio 2.5:1.12 Similarly, in our study, there was slight edging of boys over girls. In study done by Mittal et al showed that fever (100%), headache (63%), abdominal pain (71%) and petechiae (35.5%) were more common.9 Fever, vomiting were most frequent symptoms as shown by Narayanan M et al.4 Similar pictures were observed in our study, but in addition, headache, anorexia was also frequently found. In our study, 76.92% DHF patients showed positive tourniquet test, which was much higher than that was observed in the study of Kabra et al.5 It may be due to thrombocytopenia and capillary fragility, either or both. Low proportion of positivity in tourniquet test in Indian population may be due to darker skin color or dengue strain difference in Indian subcontinent.13, 14. The tourniquet test will never correlate with overt bleeding manifestation as shown by Wali et al.15 It may be due to difference in pathogenesis, like, vascular permeability and/or capillary fragility. Since in our study, only 13 patients showed evidence of bleeding, amongst them, evidence of epistaxis, gum bleeding and hematemesis were observed in 1.64% of DHF patients, which was very low as compared to other studies 5. According to WHO’s protocol for management of DHF, 1-2 hourly documentation of Hematocrit (Hct) value is very essential for monitoring intravenous fluid therapy. But, if pretreatment Hct value is not known, it is very difficult to demonstrate the percentage of hemoconcentration in DHF. Hemoconcentration is very important factor that correlates platelet count with bleeding manifestations. This was shown in different studies.16, 17. In our study, Hct >40 was observed in 3.92% of DF and 2.19% of DHF patients, whereas, Hct >30-40 was observed in 65.93% of DHF patients. So according to our study, it may not be a good indicator of monitoring fluid therapy in infants and children in presence of moderate anemia which was near 10 gm% in our study population. In our study, leucopenia (<5000/cc) was observed in 76.81% of patients, whereas, Ratageri et al18 showed 21% of patients suffered from leucopenia and Benerjee19 et al demonstrated no evidence of leucopenia in their studies. So, leucopenia may be an indicator of virulent dengue strain in our epidemic. Our study showed 182 (78.11%) children suffered from thrombocytopenia, amongst them, 36 (19.77%) had platelet count <40000/cc. Similarly, 82% and 96%rombocytopenic patients were described in the studies of Ratageri et al18 and Banerjee et al19 respectively. This thrombocytopenia may be due to decreased production in bone marrow, temporary bone marrow suppression20, virus-antibody complex mediated immune destruction21 of platelet or increased consumption of platelet induced by secondary infection associated with release of high level of platelet activating factors or increased adhesiveness of platelet to the vascular endothelial cells.22 In DHF, there may be evidence of plasma leakage as evidenced by ascites and pleural effusion. In our study, 13 (7.14%) patients showed evidence of pleural effusion in the chest x-ray, 3 (1.64%) patients suffered from isolated ascites and 6 patients (3.29%) suffered from ascites associated with hepatomegaly. On the contrary, 70% and 54% of children demonstrated pleural effusion and ascites respectively in the study of Ratageri et al.18 According to some observations, massive T-cell activation producing cytokines (interferon γ, interleukin 2 and TNF α) and infected cell lysis by CD 4+ and CD8+ dengue specific lymphocytes are mainly responsible for plasma 62 Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64 leakage. Interaction between infected cells and immune cells induces release of cytokines directly by macrophages and monocytes. One important laboratory finding is elevation of liver enzymes, which was reported in various studies.23-.25. Similarly, in our study, the rise in SGPT >100 U/L was observed in 34.32% of patients. Evidence of vomiting, hepatomegaly and elevated liver enzymes may be a clue to the diagnosis of dengue in the background of the epidemic. CONCLUSION Dengue fever is more prevalent in Kolkata. Mean age of DF and DHF patients were 10.31 and 12.6 years respectively. Male to female ratio was 1.13:1. In seropositive DHF patients, fever, headache, backache, loose motions were the predominant symptoms associated with hepatomegaly, elevated liver enzymes and evidence of plasma leakage. Leucopenia may be due to a virulent strain of dengue virus. Key-massage: Evidence of fever, vomiting, backache with or without bleeding associated with hepatomegaly, elevated liver enzymes and thrombocytopenia may be a clue to the diagnosis of dengue hemorrhagic fever. Due to the high prevalence of anemia, rise in Hematocrit is not at all helpful to the diagnosis of DHF. Funding: Nil. Competing interests: Nil. REFERENCES 1. WHO. WHO report on global surveillance of epidemic prone infectious diseases. http:/www/who.int/emc. doctments/surveillance/docs/whocdscsrisr 2001.html. 2. Sarkar JK, Chatterjee SN, Chakrabarti SK. Virological and serological studies of cases of hemorrhagic fever in Calcutta. Indian J Med Ref 1964b, 52:684. 3. World Health Organization. Dengue hemorrhagic fever: Diagnosis, treatment and Control. Geneva, World Health Organization, 1995. whqlibdoc.who.int/publications/1997/9241545003 _eng_pdf. 4. Narayanan M, Arvind MA, Thilothammal N, Prema R, Sargunum CS, Rex, Ramamurty N. Dengue fever Epidemic in Chennai- A study of Clinical Profile and Outcome. Indian Pediatr 2002; 39:1027-33 5. Kabra SK, Jain Y, Pandey RM, Madhulika, Singhal T, Tripathi P, Broor S, Seth P, Seth V. Dengue hemorrhagic fever in children in the 1996 Delhi epidemic. Trans R Soc Trop Med Hyg. 1999; 93: 294-98. 6. Banik GB, Pal TK, Mandal A, Chakrabarty MS, Chakrabarti SK. Dengue hemorrhagic fever in Calcutta. Indian Pediatr 1994; 31:685-87 7. Halstead SB. Antibody, macrophage, dengue virus infection, shock and hemorrhage. A pathologic cascade. Rev Infect Dis 1989;11: 83036 8. Sumaro W, Jahja E, Gubler DJ, Suharyono W, Sorensen K. Clinical observations on virologically confirmed fatal dengue infections in Jakarta, Indonesia. Bull WHO 1983; 61: 920-29 9. Mittal H, Faridi MM, Arora SK, Patil R. Clinicohematological profile and platelet trends in children with dengue epidemic in North India. Indian J Pediatr 2012; 79:467-71 10. Agarwal R, Kapoor S, Nagar R, Mishra A, Tandon R, Mathur A et al. A clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at Lucknow, India. Southeast Asian J Trop Med Public Health 1999; 30:735-40 11. Goh KT, Ng SK, Chan YC, Lim SJ, Chua EC: Epidemiological aspects of an outbreak of dengue fever/dengue hemorrhagic fever in Singapore. Southeast Asian J Trop Med Public Health 1987; 18:295-302 12. Wali JP, Biswas A, Handa R, Aggarwal P, Wig N, Dwivedi SN. Dengue hemorrhagic fever in adults: a prospective study of 110 cases. Trop Doct 1999; 29:27-30 13. Srivastava VK, Suri S, Bhasin A, Srivastava A, Bharadwaj M. An epidemic of dengue hemorrhagic fever and dengue shock syndrome in Delhi: a clinical study. Ann Trop Pediatr 1990;10:329-34 14. Gomber S, Ramachandran VG, Kumar S, Agarwal KN, Gupta P, Gupta P et al. Hematological observations as diagnostic markers in dengue 63 Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. hemorrhagic fever- a reappraisal. Indian Pediatr 2001; 38:477-81 Wali JP, Biswas A, Handa R, Aggarwal P, Wig N, Handa R. Validity of tourniquet test in dengue hemorrhagic fever. J Assoc Physician India. 1999;47:203-04 Bethell DB, Gamble J, Loc PP, Dung NM, Chau TTH, Loan HT et al. Non-invasive measurement of microvasvascular leakage in patients with dengue hemorrhagic fever. Clin Infect Dis 2001; 32: 243-53. Tripathi BK, Gupta B, Sinha RS, Prasad S, Sharma DK. Experience in adult population in dengue outbreak in Delhi. J Assoc Physicians India 1998; 46:273-76 Ratageri H, Shepur TA, Wari PK, Chavan SC. Clinical profile and outcome of Dengue fever cases. Ind J of Pediatrics 2005; 72:705-06 Banerjee M, Chatterjee T, Chowdhury GS, Srinivas V, Kataria VK. Dengue: A Clinicohematological profile. MJAFI 2008; 64: 333-36 Halstead SB. Dengue. Lancet. 2007; 370:1644-52 Wang S, He R, Patarapotikul J, Innis BL, Anderson R. Antibody-enhanced binding of dengue-2 virus to human platelets. Virology 1995; 213:254-57 Yang KD, Wang CL, Shaio MF. Production of cytokines and platelet activating factor in secondary dengue virus infection. J Infect Dis 1995; 172:604 Kalayanarooj S, Vaughn DW, Nimmannitya S, Green S, Sutayakom S, Kunentrasai N et al. Early clinical and laboratory indicators of acute dengue illness. J Infect Dis 1997; 176:313-21 Pushpa V, Venkatadesikalu M, Mohan S, Cherian T, John TJ, Ponnuraj EM. An epidemic of dengue hemorrhagic fever/dengue shock syndrome in tropical India. Ann Trop Pediatr 1998; 18:289-93 Kuo Ch, Tai DI, Chang-Chien CS, Lan CK, Chiou SS, Liaw TF. Liver biochemical tests and dengue fever. Am J Trop Med Hyg. 1992; 47:265-70. 64 Saha et al., Int J Med Res Health Sci. 2014;3(1):59-64 DOI: 10.5958/j.2319-5886.3.1.013 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS st Received: 31 Oct 2013 Revised: 14th Nov 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 18th Nov 2013 EVALUATION OF MODIFIED HODGE TEST AS AN INDICATOR OF KLEBSIELLA PNEUMONIAE CARBAPENEMASE (KPC) PRODUCTION BY USING bla KPC GENE PCR *Priyadarshini Shanmugam, Nirupa Soundararajan, Jeya Meenakshisundaram Department of Microbiology, Chettinad Hospital and Research Institute, Tamilnadu, India *Corresponding author email:
[email protected] ABSTRACT Introduction: Carbapenems belong to the Beta Lactam group of antimicrobial agents. They are often used as “lastline agents” or “antibiotics of last resort” in critically ill patients. Carbapenem resistance in Enterobacteriaceae may be due to various reasons but Klebsiella pneumoniae Carbapenemase (KPC) enzyme production is the commonest. Phenotypic as well as genotypic methods can be used to detect Carbapenemases. Among the phenotypic tests, Modified Hodge Test (MHT) is relatively easy to perform. Aims and Objectives: This study aimed to determine the prevalence of carbapenem resistance among Enterobacteriaceae isolates and calculate the sensitivity of MHT as an indicator of KPC production. Materials and Methods: All Enterobacteriaceae isolates from clinical samples were included in this study and were screened for Carbapenem resistance. 45 randomly chosen Carbapenem Resistant Enterobacteriaceae isolates were subjected to MHT and blaKPC gene detection by PCR. Results: 2035 Enterobacteriaceae isolates were tested and 5.2% were found to be resistant to Imipenem, 22.9 % were resistant to Meropenem and 4.42 % were resistant to both Imipenem and Meropenem. The sensitivity of MHT was calculated to be 90% and specificity was calculated to be 60% Keywords: Carbapenemase, Modified Hodge Test, Enterobacteriaceae, bla KPC gene INTRODUCTION Bacteria belonging to the Enterobacteriaceae family are normally present as harmless human gut flora. These bacteria are the leading cause of a wide range of opportunistic infections.1 Carbapenems belongs to the Beta Lactam group of antimicrobial agents, which kill bacteria by inhibiting the bacterial cell wall synthesis.2 They possess the broadest spectrum of activity and greatest potency against Gram-positive and Gramnegative bacteria. 3 As a result, they are often used as “last-line agents” or “antibiotics of last resort” when patients with infections become gravely ill or are suspected of harboring resistant bacteria.3 Carbapenem resistance among Enterobacteriaceae members is of great concern as these bacteria are easily transmissible among patients, leading to hospital acquired infections Priyadarshini et al., (HAI), but can also spread into the community, resulting in community acquired cases.1 Carbapenem resistance in Enterobacteriaceae may be due to various reasons that include hyper production of the Amp C beta lactamase, loss of porins, production of metallo beta lactamases (MBL) and production of K pneumonia carbapenemases.1 Carbapenemases increasingly have been reported worldwide in Enterobacteriaceae in the past 10 years.4, 5 A large variety of carbapenemases has been identified in Enterobacteriaceae belonging to 3 classes of β-lactamases: the Ambler class A, B, and D βlactamases. 3 In addition, rare chromosome encoded cephalosporinases (Ambler class C) produced by Enterobacteriaceae may possess slight extended 65 Int J Med Res Health Sci.2014;3(1):65-70 activity toward carbapenems.4 Their identification is of primary importance since carbapenemase producers are resistant not only to most Beta-lactams but also to other main classes of antibiotics. 5 Carbapenemases can be detected by phenotypic as well as genotypic methods.6 Modified Hodge Test (MHT) is a phenotypic method which is relatively simple and easy to perform in a laboratory. 6 This cloverleaf technique, or Modified Hodge test, has been extensively used as a phenotypic technique for detecting carbapenemase activity. 5 Limitations of the MHT in terms of clinical performance are its lack of specificity and the delay in obtaining the results upto 24 or 48 hours after isolation of a bacterial colony.5 The molecular detection of blaKPC is the gold standard for diagnosis, but the majority of laboratories in our country does not have the resources necessary to perform this test. 7 The aim of this study was to determine the prevalence of Carbapenem resistance among Enterobacteriaceae and detect the bla KPC gene prevalence among randomly chosen Carbapenem resistant Enterobacteriaceae clinical isolates in our 750 bed hospital. The study also aimed to evaluate the performance of the Modified Hodge test and calculate the sensitivity of MHT as an indicator of Klebsiella Pneumoniae Carbapenemase (KPC) production. MATERIALS AND METHODS The isolates in this study were collected in a period of one year from July 2012 to June 2013. The study was conducted at Chettinad Hospital and Research Institute, Chennai. The institutional ethical committee approval was obtained prior to commencement of this study. All Enterobacteriaceae isolates from clinical samples like pus, wound swab, sputum, endotracheal aspirate, blood and urine were included in this study. The samples were collected after obtaining informed consent from the patients. For evaluation of Modified Hodge Test by PCR, 45 isolates which were resistant to both or either Imipenem or Meropenem were randomly selected. MHT and bla KPC PCR were performed on these 45 isolates These isolates were screened for Carbapenem resistance in addition to the routine antibiotic susceptibility testing, which was performed by the Kirby Bauer method, as per the CLSI guidelines 2012. 8 Antimicrobial discs used were Ampicillin (10μg), Gentamicin (10μg), Amikacin (30μg), Cefazolin (30 μg), Cefuroxime (30μg) Ceftazidime (30μg), Cefotaxime (30μg), Ceftriaxone (30μg), Cefepime (30μg), Ciprofloxacin (5μg), Cotrimoxazole (23.75/1.25μg), Piperacillin/ tazobactam (100/10μg), Imipenem (10μg), Meropenem (10 µg), Polymyxin B (300 units) and Colistin (10µg). Modified Hodge Test Phenotypic detection of Carbapenemase production was done by using the Modified Hodge test. This test was performed as per the CLSI guidelines 2012. 8 A 0.5 Mac Farland’s suspension of ATCC Escherichia coli 25922 was diluted 1:10 in sterile saline. This was inoculated on a Mueller Hinton agar plate, as for the routine disc diffusion testing. The plate was dried for 5 minutes and a disc of Imipenem 10 μg was placed in the centre of the agar plate. 3-5 colonies of the test organism were picked and inoculated in a straight line, from the edge of the disc, up to a distance of at least 20mm. The plates were incubated at 370C overnight and they were examined next day. They were checked for an enhanced growth around the test organism, at the intersection of the streak and for a zone of inhibition. The presence of an enhanced growth indicated Carbapenemase production, and the absence of an enhanced growth meant that the test isolate did not produce carbapenemase. 8 bla KPC gene detection The isolates which gave positive results for the modified Hodge test were submitted to molecular detection of the bla KPC gene by PCR. The PCR Kits were procured from Helini Biomolecules, Chennai. Isolates with negative test results were also randomly chosen for PCR. The Polymerase Chain Reaction was set up in a PCR vial, after adding the master mix, the forward and reverse primers and the extracted DNA from the isolates. The primers used for PCR amplification and the reaction conditions were Forward Primer: 5’-GCT CAG GCG CAA CTG TAA G-3’ Reverse Primer: 5’-AGC ACA GCG GCA GCA AGA AAG-3’. The PCR vial was placed in PCR machine (Corpect Research 96 wells, Australia) and it was subjected to initial denaturation at 94ºC for 3 min, followed by 30 cycles of denaturation at 94ºC for 1 minute, annealing at 60ºC for 1minute and extension at 72ºC for 1minute. A final extension procedure was carried out at 72º C for 5 min. Next the PCR products were subjected to electrophoresis on 2% agarose gel stained with ethidium bromide and visualized with UV 66 Priyadarshini et al., Int J Med Res Health Sci.2014;3(1):65-70 light The antibiogram for the Carbapenem Resistant Enterobacteriaceae was analyzed RESULTS 2035 non repetitive isolates of Enterobacteriaceae were obtained from clinical samples such as pus, urine, blood, sputum and endotracheal aspirates, over a period of 1 year. Of these, 1178 (57.88%) were Escherichia coli, 444 (21.81) were Klebsiella species, 178 (8.7%) Proteus species, 154 (7.56%) Citrobacter species and 81 (3.9%) were Enterobacter isolates Fig 1: Total number of Enterobacteriaceae isolates (Figure1). Figure 2 shows the number of carbapenem resistant isolates among the individual genera. The antibiogram of the Enterobacteriaceae isolates is tabulated in Table 1 and the antibiotic resistance pattern of the CRE are tabulated in Table 2. Of the total of 2035 isolates, 106 (5.2%) were resistant to Imipenem and 468 (22.9 %) were resistant to Meropenem and 90 (4.42 %) were resistant to both Imipenem and Meropenem. Fig 2: Carbapenem Resistance pattern of the Isolates Table 1: Antibiotic Resistance pattern of the Enterobacteriaceae (% of Resistance) ANTIBIOTIC Amikacin Ampicillin Cefazolin Cefuroxime Cefotaxime Cefepime Ciprofloxacin Cotirmox Colistin Genta Imipenem Meropenem Nitrofurantoin Norfloxacin Piperacillin Tazobactam Polymyxin B Tobramycin Ecoli 9.67 % 85.7 % 71.3% 64.9 % 61.1 % 53.2 % 63.1 % 55.2 % 0% 36.76 % 3.23 % 21.3 % 11.7 % 59.54 % 19.9 % 0% 39.47 % Klebsiella 16.64 % 100 % 66.67 % 59.46 % 53.38 % 42.79 % 47.07 % 50.9 % 0% 34.0 %1 9.68 % 20.95 % 31.15 % 31.15 % 21.78 % 0% 16.17 % Proteus 31.46 % 71.51% 82.58 % 66.83 % 49.43 % 39.32 % 58.99 % 68.02 % 100 % 46.07 % 6.82 % 50.15 % 87.87 % 49.2 % 15.47 % 100 % 48.14 % Citrobacter 16.88 % 88.42 % 72.73 % 58.44 % 51.3 % 37.66 % 40.26 % 46.75 % 2.6 % 34.42 % 5.84 % 16.23 % 33.78 % 36.49 % 21.52 % 0% 29.49 % Enterobacter 11.11 % 69.14 % 82.72 % 65.43 % 46.91 % 38.27 % 41.98 % 45.68 % 0% 32.1 % 4.94 % 13.58 % 43.48 % 30.43 % 13.58 % 1.23 % 34.78 % 67 Priyadarshini et al., Int J Med Res Health Sci.2014;3(1):65-70 Table 2: Antibiotic resistance pattern of the 45 Multi Drug Resistant Enterobacteriaceae Percentage of Resistance Klebsiella(n =22) Ecoli (n =20) Citrobacter (n =2 Proteus (n = 1) Amikacin 59 % 33% 100 % 100 % Ampicillin 100 % 100 % 100 % 100 % Cefazolin 100 % 100 % 100 % 100 % Cefuroxime 100 % 100 % 100 % 100 % Cefotaxime 100 % 100 % 100 % 100 % Cefipime 96% 100 % 100 % 100 % Ciprofloxacin 91 % 91% 100 % 100 % Cotrimoxazole 100 % 100 % 100 % 100 % Colistin 0% 5% 0% 100 % Gentamicin 73 % 67% 100 % 100 % Imipenem 77 % 67% 100 % 100 % Meropenem 96 % 95% 50 % 100 % Nitrofurantoin (urine) 100% 20% 100 % 100 % Piperacillin Tazobactam 100 % 100 % 100 % 100 % Polymyxin B 0% 0% 0% 100 % Tobramycin 94 % 73% 100 % 100 % For evaluation of Modified Hodge Test by bla KPC detection using PCR, 45 isolates which were resistant to both or either Imipenem or Meropenem had been selected. Of these, 22 were Klebsiella pneumoniae, 20 were Escherichia coli, 2 were Citrobacter species and 1 was Proteus mirabilis). Of the 45 isolates, 43 (95.5 %) were resistant to Meropenem, 34 (75.5%) were resistant to Imipenem and 29 (64.4%) were resistant to both Imipenem and Meropenem. Modified Hodge Test was positive in 37 (82.2%) out of 45 isolates and bla KPC gene was detected in 30 (66.7 %) isolates (Table 3). Of the 30 blaKPC gene positive isolates, MHT was positive in 27 and negative in 3 isolates. Of the 15 blaKPC gene negative isolates, MHT was positive in 10 (66.6%) and negative in 5 (33.3%) isolates. Considering PCR for bla KPC gene as the gold standard for the detection of Klebsiella pneumoniae Carbapenemase, the sensitivity and specificity of MHT was calculated using the formula: Sensitivity = a/a+b and Specificity = d/ c+d. [Where ‘a’ is True Positive (27), 'b' is False Negative (3), 'c' is False Positive (10) and’d’ is True Negative (15) ]. In the present study, the sensitivity of MHT was calculated to be 90 % and the specificity was 60%. The positive predictive value was 72.97% and the Negative predictive value was 83.33%. Figure 3 shows isolates with positive MHT, displaying the characteristic clover leaf like indentation and Figure 4 shows the visualization of the PCR products by gel electrophoresis. Fig 3: Positive Modified Hodge Test Fig4: bla KPC gene PCR : Gel Electrophoresis showing positive and negative isolates Table 3: Results of MHT and blaKPC gene PCR MHT & Total MHT Bla KPC bla KPC Isolates (+ve) gene(+ve) gene (+ve) 22 19 13 11 Klebsiella E coli 20 16 15 14 Citrobacter 2 1 1 1 Proteus 1 1 1 1 Total 45 37 30 27 68 Priyadarshini et al., Int J Med Res Health Sci.2014;3(1):65-70 DISCUSSION In our study, 5.2% of the isolates were resistant to Imipenem, 22.9 % were resistant to Meropenem and 4.42 % were resistant to both Imipenem and Meropenem. The highest percentage of resistance to Carbapenems was seen in Klebsiella species, 9.68% to Imipenem and 20.9% to Meropenem, followed by Escherichia coli, Proteus, Citrobacter and Enterobacter (Table 1). A study by Ramana et al 1 showed that, among the different Enterobacteriaceae members tested, Klebsiella spp. showed the highest percentage of carbapenem resistance at 30%, whereas Proteus spp. and Citrobacter spp revealed comparatively low carbapenem resistance of 17% and 12%, respectively. The prevalence of carbapenem resistance in our study was less than that of Ramana et al. Another study by Parveen et al 9 showed that 45 (43.6%) of K. pneumoniae from clinical specimens, were resistant to meropenem by the disk diffusion test. Among isolates reported to the National Healthcare Safety Network in 2006–2007 carbapenem resistance was reported in up to 4.0% of Escherichia coli and 10.8% of K. pneumoniae isolates that were associated with certain device-related infections. 10 In the present study, the sensitivity of Modified Hodge test was calculated to be 90%. A similar study by Anderson et al 11 which had also evaluated the modified Hodge test for detection of KPC-mediated resistance inferred that the test demonstrated 100% sensitivity and specificity for detection of KPC activity. Diana Doyle et al 12 in her study showed that MHT had a sensitivity of 98% for detecting KPC producers and 93% for OXA-48-like enzyme producers but was less than optimal for detecting MBLs. The sensitivity of MHT as inferred by our study was less than that of the sensitivity of the other 2 studies. This could necessitate changes in the MHT to make it more sensitive. A study was carried out by Pasteren et al 13 using an optimized MHT known as Pseudomonas aeruginosa MHT (PAE MHT) which demonstrated 100% sensitivity and 98% specificity for detection of KPC activity without any indeterminate result. Another study in Greece, showed that Modified Hodge test detected 98% KPC producers, keeping PCR as the gold standard [6] In contrast, another study by D. Girlich et al 5 showed that the overall sensitivity and specificity of the MHT was low (77.4% and 38.9%, respectively). In our study too, the specificity of MHT was low- only 60%. Hatipoglu et al 14 also state that the MHT has a low specificity. This could be because Modified Hodge Test detects other carbapenemase enzymes in addition to KPC. Of the 3 MHT negative isolates, one was positive for bla KPC gene. Adriane BC et al 15 have also reported such isolates carrying silent genes. 8 (17.7%) isolates were resistant to carbapenems, but were MHT negative. They may have developed a different resistance mechanism other than carbapenemase production. Prevalence of bla KPC gene was found to be 66.67% among the carbapenem resistant isolates. blaKPC gene was not detected in 10 MHT positive isolates. This could indicate the presence of a carbapenemase other than KP Carbapenemase. Resistance to both imipenem and meropenem is a strong indicator of carbapenemase production rather resistance to either one of the carbapenems, as this may imply a different resistance mechanism CONCLUSION Modified Hodge Test is a sensitive test for Klebsiella pneumoniae Carbapenemase production. It is recommended that all isolates showing intermediate sensitivity or resistance pattern to carbapenems be screened for the production of carbapenemases by Modified Hodge test, which will provide a costeffective and rapid approach for the detection of carbapenemases in Enterobacteriaceae. REFERENCES 1. Ramana KV, Rao R, Sharada V, Kareem MA, Reddy LR, Ratna Mani MS. Modified Hodge test: A useful and the low cost phenotypic method for detection of carbapenemase producers in Enterobacteriaceae members. Journal of Natural Science, Biology and Medicine. 2013;4(2):346-48 2. Nagaraj S, Chandran SP, Shamanna P, Macaden R. Carbapenem resistance among Escherichia coli and Klebsiella pneumoniae in a tertiary care hospital in south India, Indian Journal of Medical Microbiology. 2012; 30(1): 93-95. 3. Krisztina MP, Wallace, Endimiani A, Magdalena AT, Robert A B. Minireview Carbapenems: Past, Present, and Future. Antimicrobial Agents and Chemotherapy. 2011; 55(11): 4943–60. 4. Nordmann P, Naas T, and Poirel L. Global Spread of Carbapenemase producing Enterobacteriaceae. Emerging Infectious Diseases. 2011;17(10):1791 69 Priyadarshini et al., Int J Med Res Health Sci.2014;3(1):65-70 5. Girlich D, Poirel L, and Nordmann P. Value of the Modified Hodge Test for Detection of Emerging Carbapenemases in Enterobacteriaceae. Journal of Clinical Microbiology p. 2012; 50(2): 477–79. 6. Amjad A, Mirza IA, Abbasi SA, Farwa U, Malik N, Zia F. Modified Hodge test: A simple and effective test for detection of carbapenemase production. Iranian Journal of Microbiology. 2011;3(4): 189-93 7. Cury AP, Andreazzi D, Maffucci M, Hehl H C, Rossi F . The modified Hodge test is a useful tool for ruling out Klebsiella pneumoniae Carbapenemase. CLINICS 2012; 67(12):1427-31 8. The Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility testing, twenty second informational supplement, M100-S22, Clinical and Laboratory Standards Institute, 2012. 9. Parveen RM, Harish BN, Parija SC. Emerging Carbapenem Resistance Among Nosocomial Isolates of Klebsiella pneumoniae in South India. International Journal of Pharma And Bio Sciences. 2010;1(2): 10. Gupta N, Brandi M. Limbago M, Patel JB and Kallen AJ60 d Carbapenem-Resistant Enterobacteriaceae: Epidemiology and Prevention. CID 2011:53; 60-67 11. Anderson KF, Lonsway DR, Rasheed JK, Biddle J, Jensen B, McDougal LK, et al Evaluation of Methods to Identify the Klebsiella pneumoniae Carbapenemase in Enterobacteriaceae. Journal of Clinical Microbiology, 2007; 45(8): 2723–25. 12. Diana Doyle D, Peirano G, Lascols C, Lloyd T, Church DL. and Pitouta JDD. Laboratory Detection of Enterobacteriaceae That Produce Carbapenemases. Journal of Clinical Microbiology.2012 ;50 (12 ): 3877–80 13. Pasteran F, Veliz O, Rapoport M, Guerriero L, and Corso A. Sensitive and Specific Modified Hodge Test for KPC and Metallo-Beta- Lactamase Detection in Pseudomonas aeruginosa by Use of a Novel Indicator Strain, Klebsiella pneumoniae ATCC 700603. Journal of Clinical Microbiology. 2011;49 (12): 4301–03. 14. Hatipoglu M, Balta S, Cakar M, Demirkol S, Kurt O, Dinc M .Modified Hodge test as screening test for spreading Carbapenemase resistance has become more important. 2013 CLINICS, 1175. 15. Adriane BC, Rita de Cassia de Andrade Melo, Maria AVM, Ana CSL . Multidrug resistant gene, including bla KPC and bla CTX-M-2 among Klebsiella pneumoniae isolated in Recife, Brazil. Rev.da Sociedade Brasileira de Medicina Tropical. 2012; 45 (5): 572-78. 70 Priyadarshini et al., Int J Med Res Health Sci.2014;3(1):65-70 DOI: 10.5958/j.2319-5886.3.1.014 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 4 Nov 2013 Revised: 24th Nov 2013 Research article STUDY OF NEURAL INDIVIDUALS PLASTICITY IN BRAILLE Copyright @2013 ISSN: 2319-5886 Accepted: 10th Dec 2013 READING VISUALLY CHALLENGED *Nikhat Yasmeen1, Mohammed Muslaiuddin Khalid2, Abdul Raoof Omer siddique1, Madhuri Taranikanti1, Sanghamitra Panda1, D.Usha Rani3 1 Department of Physiology, Shadan Institute of Medical Sciences, Hyderabad, Andhrapradesh, India Department of Emergency Medicine, Care Hospital, Hyderabad, Andhra Pradesh, India 3 Department of Physiology, Apollo Institute of Medical Sciences & Research, Hyderabad,Andhra Pradesh, India 2 *Corresponding author mail:
[email protected] ABSTRACT Background: Neural plasticity includes a wide range of adaptive changes due to loss or absence of a particular sense. Cortical mapping or reorganization is evolutionary conserved mechanism which involves either an unmasking of previously silent connections and/or sprouting of new neural elements. Aims & Objectives -To compare the Somatosensory evoked potentials (SSEPs) wave form in normal and visually challenged individuals. Materials & Methods: 20 visually challenged males in the age group of 21 -31 yrs were included in the study along with 20 age & sex matched individuals. Subjects were screened for general physical health to rule out any medical disorder, tactile sensibility i.e., sensation of light touch, pressure, tactile localization & discrimination to rule out any delay in the peripheral conduction disorder. Somatosensory evoked potentials were recorded on Nicolet Viking select neuro diagnostic system version 10.0.The placement of electrodes & recording of potentials were done based on methodology in chiappa. Data was subjected to various statistical analyses using SPSS version 17.0 software. N20 & P25 latencies were shorter and amplitudes were larger in visually challenged individuals compared to age & sex matched individuals. Conclusions: In visually challenged individuals, decrease in latencies indicate greatly improved of information in the nervous system & increase in amplitudes indicate the extent and synchronization of neural network involved in processing of vision. Keywords: Neural plasticity, Somatosensory evoked potentials, Cortical mapping, Visually challenged INTRODUCTION In humans as well as in many animals, cortical area has enormous capacity for reorganization i.e plastic changes.1 The present study was undertaken to study the cross modal interactions of sensory modalities in visually challenged individuals for the exploration of neural plasticity using somatosensory evoked potentials. In our central nervous system perception is modulated due to the redundant informational inputs from more than one sensory organ. In blind individuals Occipital cortex that is deprived of its normal inputs is Nikhat et al., invaded by inputs from other modalities supporting the concept of cross-modal plasticity.2-5 Specific electrophysiological recordings & functional imaging studies of visually challenged individuals have depicted that touch modality is not only sharpened in these individuals but also plays a major role in their perception.Various animal models have been used to study the changes occur both at the cellular & synaptic level i.e activity based competition between the differential sensory inputs.6 71 Int J Med Res Health Sci. 2014;3(1): 71-75 The molecular mechanism underlying neural plasticity is probably due to unmasking of connections or the upregulation of synaptic efficacy.7 As we all know that the thalamus is considered as the gateway for the sensory information reaching the cortex, the reorganization can occur at this level or at the level of polymodal association areas.8 Specific somatosensory & auditory evoked potentials have demonstrated that cross-modal plasticity develops in visually challenged individuals due to their dependence on tactile & auditory information.9- 12 In blind Braille readers there was structural & functional cortical reorganization along with relevant changes in the behavior & perceptual capacities as demonstrated by imaging studies. METHODS 20 visually challenged individuals were recruited from Govt. hostel for blind boys, Dilsukhnagar area, Hyderabad & study was conducted at the Electrophysiology lab, Upgraded Department of Physiology, Osmania Medical College, Koti, Hyd., during Dec.2009 to Dec.2011. 20 Age & Sex matched controls were also included in the study. Subjects with history of nervous system disorders, usage of antidepressants, narcotic drugs, CNS stimulants were not included in the study. Subjects with late onset of blindness due to other medical reasons were excluded from the study. Subjects were screened for general physical health to rule out any medical disorder, tactile sensibility i.e sensation of light touch, pressure, tactile localization & discrimination to rule out any delay in the peripheral conduction disorder. Prior to study, ethical guidelines were followed; consent was taken, after the subjects were told about the aims & objectives of the study. Procedure : This study was conducted on patients using 3-channel with normal averaging technique.13 The procedure was explained to the patient and consent taken.Patient was asked to sit comfortably on a chair and instructed to gently close his/her eyes while relaxing all the head and neck muscles during the recording. Patient is asked to count the number of stimuli so as to get proper recordings. Electrodes of the 3 channels were placed on the patient at appropriate sites after it’s proper abrasion. Placement of electrodes & recording of potentials were done in accordance with the methodology in Chiappa.13 Surface EEG electrodes are used. Frontol electrode [Fz] is used as the reference in most montages. Active recording electrodes are placed as follows: 1. 1st channel: Over the contralateral C3’/C4’ scalp region (2cm posterior to C3 or C4) 2. 2nd channel: Over the C5/C2 cervical spinous process (referred to as C5S or C2S and located relative to the prominent C7 spinous process with the neck flexed. 3. 3rd channel: At Erb’s point (2-3 cm above clavicle in the angle between it and posterior border of the clavicular head of the Sternocleidomastoid muscle ipsilaterally. 4. Inactive recording electrodes of the 3 channels were placed on Fz position on the scalp. 5. Ground electrode: is placed between the stimulating and the recording electrodes relatively close to the former. We have used a band around the forearm. 6. Stimulation electrode: using surface disk electrodes placed between the tendons of palmaris longus and flexor carpi radialis, i.e., at the supinated wrist, median nerve was stimulated. Stimuli of 0.2-0.3 msec duration are given at 4-7 Hz. The intensity of the current was adjusted till a visible twitch was produced. Data-sheet was made using Microsoft word & excel sheets.Statistical analysis was done using PASW 18.0 (SPSS Inc.Chicago,USA) RESULTS This Comparative study consisted of 20 congenitally blind males (Group A) and 20 normal sighted individuals(Group B) The mean pattern of latency of SEP-N20 after wrist stimulation was found to be significant I.e P value = 0.000 (<0.0001) for right side & P-value = 0.001 (<0.005) for left wrist.The mean pattern of latency of SEP-P25 after wrist stimulation was found to be significant i.e. P value =0.000(<0.0001) & p=0.022(<0.05).The mean pattern of latencies of N9& N13, inter-peak latencies of SEP’s did not show significant difference (P > 0.05) between the two groups.(TABLE –I) 72 Nikhat et al., Int J Med Res Health Sci. 2014;3(1): 71-75 Table 1: Statistical analysis of mean pattern of latencies on wrist stimulation MEAN PATTERN OF LATENCIES N9 N13 N20 P25 N9-N13 N9-N20 N13-N20 WRIST RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT RIGHT LEFT GROUP A 9.25±0.62 9.17±0.69 12.54±0.39 12.54±0.43 17.5±0.58 17.8±0.53 20.63±0.53 21.03±1.08 3.41±0.62 3.58±0.84 8.07±0.22 8.69±0.81 5.31±0.52 5.19±0.25 GROUP B 9.48±0.68 8.89±0.64 12.68±0.78 12.49±0.53 18.49±0.7 18.54±0.79 21.69±1.08 21.81±1.0 3.47±1.06 3.22±0.77 8.20±0.19 8.88±0.72 5.33±0.39 5.28±0.34 Table 2: Statistical analysis of mean pattern of Amplitude on wrist stimulation MEAN PATTERN OF WRIST GROUP A GROUP B AMPLITUDE N9 RIGHT 2.12±2.44 1.9±1.73 LEFT 1.90±1.57 1.67±1.77 N13 RIGHT 0.87±0.55 0.91±0.66 LEFT 0.79±0.73 0.41±0.68 N20 RIGHT 4.82±1.36 2.74±0.95 LEFT 4.2±2.5 2.76±0.83 P25 RIGHT 1.24±0.68 0.77±0.52 LEFT 1.28±0.56 1.14±0.62 The mean pattern of amplitude of SEP-N20 after wrist stimulation was found to be significant i.e P- value = 0.000 (<0.0001) for right side & P-value = 0.004 (<0.005) for left wrist. The mean pattern of amplitude of SEP-P25 after wrist stimulation was found to be significant i.e. P value =0.021(<0.05) for right side .The mean pattern of amplitudes of N9& N13 SEP’s did not show significant difference (P > 0.05) between the two groups.(TABLE-II) DISCUSSION This study compares the latencies and amplitudes of SEP’s in normal and congenitally blind individuals thereby giving an insight into the sharpening of other sensory modalities in the absence of vision. The present study throws light on the efficiency and rapidity of neural processing of information in congenitally blind subjects. P-VALUE 0.274 0.270 0.463 0.725 0.000 0.001 0.000 0.022 0.83 0.168 0.105 0.438 0.894 0.406 P-VALUE 0.778 0.667 0.834 0.092 0.000 0.004 0.021 0.452 Following SEP parameters were recorded - N20, P25, N13, N9 latencies and amplitude; N9-N13, N9-N20, N13-N20 inter-peak latencies and N20-P25 amplitude in blind and was compared with that of age-matched normal controls using the independent sample‘t’ test. The congenitally blind individuals use more than one finger for Braille reading;index middle & ring finger. Hence the median nerve was stimulated in the wrist to get a cumulative record of the reading fingers. Somatosensory evoked potentials like other evoked potentials are path-specific electrical signals are produced in the areas of signal processing which correspond to the synaptic junctions of various neurons and they give good temporal resolution in milliseconds domain.N20 & P25 Latencies were decreased and N20 & p25 amplitudes increased in the congenitally blind when compared to same group in the congenitally blind individuals,there were highly 73 Nikhat et al., Int J Med Res Health Sci. 2014;3(1): 71-75 significant differences in N20 & P25 Latencies & amplitudes stimulation on right side than the left side. According to previous studies done by Alvaro et al & Dayanand G et al;there was increase in amplitude of N20 Potential & the increase was more on the right/dominant side14 In another comparative study SEPs were recorded in 10 blind & 15 control subjects & data revealed that there were significant increase in N20 & P22 SEP’S on right-sided stimulation suggesting activity dependant alteration in spatio-temporal components of signal processing15 In a PET study to decipher the cross-modal plasticity in the visually challenged individuals by electro-tactile stimulation of tongue,results have shown that the occipital area is part of a neural network for discriminating touch sensations along with posterior parietal cortex as there was increase in regional blod flow(rRBF) in the occipital cortex & that the increase was related to the performance of particular task16 In another functional magnetic resonance imaging study 12 congenitally and early-onset blind subjects were studied with fMRI reading & results reveal that there was activation of the primary sensory area along with polymodal association areas17 Studies in congenitally blind Braille readers have shown that there was reorganization of tactile & auditory tracts to the central retinal targets both at the sub-cortical & cortical levels.18-20 Another brain -imaging study demonstrated that there is difference in pattern of activation of visual cortex in late and congenitally blind subjects. Early blind subjects when compared to late blind have better tactile & auditory sensibility as demonstrated by event related potentials recorded over the posterior cortical areas.21-22 CONCLUSIONS In congenitally blind individuals, decrease in N20 & P25 latencies indicate greatly improved processing of information in the nervous system; increase in N20 & P25 amplitudes indicate the extent and synchronization of neural network involved in processing of information for a wider Neural network could be due to changes in the local connectivity as several local mechanisms have been proposed, including sprouting, unmasking of silent synapses and/or changes in the modulatory effects of lateral connections. In accordance with the principles of lateral inhibition; the tactile & auditory modalities also exert the modulatory effects on perception of visual modality both at the sub-cortical & cortical level. Thus it can be formulated that in the spatio-temporal framework the demarcation between uni-modal & polymodal association areas can undergo reorganization i.e plastic changes both at gross & at molecular level. ACKNOWLEDGEMENT I would like to express my heartfelt gratitude to Prof.& Hod Dr. B.Ram Reddy & all those who have helped me in completing my work REFERENCES 1. Norihiro S, Tomohisa O, Manabu H, Yoshiharu Y. Critical Period for Cross-Modal Plasticity in Blind Humans: A Functional MRI Study NeuroImage. 2002;16:389–400 2. Kato N. Plasticity in an aberrant geniculocortical pathway in neonatally lesioned cats. Neuroreport. 1993;4:915-18. 3. Florence SL, Taub HB, Kaas JH. Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys.Science. 1998; 282:1062 4. Frost DO, Metin C. Introduction of functional retinal projections to the somatosensory system Nature. 1985;317:162–64. 5. Sterr A, Muller MM, Elbert T, Rockstroh B, Pantev C, Taub E. Perceptual correlates of changes in cortical representation of fingers in blind multifinger Braille readers. J Neurosci; 1998; 18: 4417–23 6. Bavelier D, Neville HJ . Cross-modal plasticity: where and how? Nat Rev Neurosci.2002;3:443–52 7. Pascual-Leone A. Modulation of human cortical motor outputs during the acquisition of new fine motor skills. J. Neurophysiol.1995;74:1037–45 8. Buchel C, Price C, Frackowiak RS, Friston K. Different activation patterns in the visual cortex of late and congenitally blind subjects. Brain. 1998;121;409–19 9. Hamilton RH, Pascual-Leone A, Rodriguez D, Schlaug G. Increased prevalence of absolute pitch 74 Nikhat et al., Int J Med Res Health Sci. 2014;3(1): 71-75 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. in blind musicians; Abstr Soc Neurosci; 2000; 26: 739–13. Lessard N, Pare M, Lepore F, Lassonde M. Earlyblind human subjects localize sound sources better than sighted subjects. Nature 1998; 395:278–80. Thomas Elbert, Annette Sterr, BrigitteRockstroh, Christo Pantev, Matthias M, Muller et al; Expansion of the tonotopic area in the auditory cortex of blind; J Neurosci.2002;15(22): 9941–44. Yabe, Takao CA, Kaga, Kimitaka. Sound lateralization test in adolescent blind individuals. Neuroreport. 2005;16(9): 939–42. Chiappa KH. Evoked Potentials in Clinical Medicine. Raven Press, New York 1990, 2nd ed.371-473 Dayanand G, Roopkala MS, Srinivas R, Ranjeev Sharma. A Comparative study of median nevre somatosensory evoked potentials in the totally blind and normal subjects. Indian journal of physiology and pharmacology.2008 ; 52(2 ) 183188 Alvaro Pascual-Leone, Fernando Torres. Plasticity of the sensorimotor cortex representation of the reading finger in Braille readers Brain.1992;116:39-52 Ptito M, Moesgaard S, Gjedde A and Kupers R. Cross modal plasticity revealed by electro tactile stimulation in the congenitally blind. Brain. 12824. Norihiro Sadato, Tomohisa Okada, Manabu Honda, Yoshiharu Yonekura. Critical Period for Cross-Modal Plasticity in Blind Humans: A Functional MRI Ron Kupers, Arnaud Fumal, Alain Maertens, De Noordhout, Albert Gjedde, Jean Schoenen, etal., Maurice Ptito; Transcranial magnetic stimulation of the visual cortex induces somatotopically organized qualia in blind subjects. Proc Natl Acad Sci USA;2006;103(35):1325 rost DO. Boire, D, Gingras, G, Ptito M. Surgically created neural pathways mediate visual pattern discrimination. Proc. Natl. Acad. Sci. USA;2000; 97, 11068–73 Sur M. Garraghty PE. Roe AW. Experimentally induced projections into auditory thalamus and cortex. Science. 1988; 242, 1437–41 21. Neimeyer W, Starlinger I. Do the blind hear better? Investigations on auditory processing in congenital or early acquired blindness. II. Central functions. Audiology;1981; 20;510-15 22. Roder B, Teder-Salejarvi W, Sterr A, Rosier F,Hillyard SA, Neville HJ. Improved auditory spatial tuning in blind humans. Nature. 1999; 400(6740): 162–166 75 Nikhat et al., Int J Med Res Health Sci. 2014;3(1): 71-75 DOI: 10.5958/j.2319-5886.3.1.015 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 13 Nov 2013 Revised: 8th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 15th Dec 2013 NUTRITIONAL STATUS OF TRIBAL CHILDREN IN ANDHRA PRADESH *Gangam Sukhdas1, Sairam Challa1, Prakash Bhatia2, A.R. Rao3, Koteswara Rao.P4 1 Associate Professor, 2Principal and Professor, 3Assistant Professor, Department of Community Medicine, Apollo Institute of Medical Sciences and Research, Hyderabad, India 4 Health Officer, Urban Health Center (AIMSR), Shaikpet Nala, Hyderabad, India. * Corresponding author email:
[email protected] ABSTRACT Context: Tribes constitute separate socio-cultural groups, having distinct customs, traditions, marriage, kinship, and property inheritance systems. They live largely in agricultural and pre-agricultural level of technology. Their dependency on nature and impoverished economy bear effect on the nutritional status different compared to the general population. Aims: To study the prevalence of malnutrition in the under-five years age group tribal children in the three regions of Andhra Pradesh and compare the same with national statistics. Methods and Material: A cross sectional survey was carried out to assess the nutritional status of under-five age group children in three Integrated Tribal Development Agency (ITDA) blocks of Andhra Pradesh. Results & Conclusions: Based on the WHO Child Growth Standards, the prevalence of malnutrition was lower in the AP tribal blocks than the national averages among tribal populations, but higher than the overall national and state averages. Keywords: Nutrition, Scheduled Tribes, Wasting, Stunting, Underweight. INTRODUCTION The Tribal Population in India is 8.6 percent according to 2011 census.1 Tribes constituted separate sociocultural groups having distinct customs, traditions, marriage, kinship, property inheritance system and living largely in agricultural and pre-agricultural level of technology. Their dependency on nature and impoverished economy may affect the nutritional status as compared to their counterparts in the general population. Young children in India suffer from some of the highest levels of stunting, underweight, and wasting observed in any country in the world, and 7 out of every 10 young children are anaemic.2 The percentage of children under age five years who are underweight is almost 20 times as high in India as would be expected in a healthy, well-nourished population and is almost twice as high as the average percentage of underweight children in sub-Saharan African countries. Near about fifty percent of the children under the age of five years in India are moderately or severely malnourished. The prevalence of under nutrition is more in vulnerable groups like Tribal population. While Andhra Pradesh harbors nearly 9 percent of the Indian Tribal population, there are limited studies on the nutritional status of Tribal Children in Andhra Pradesh. Hence a study was contemplated to assess the nutritional status of Tribal children in Andhra Pradesh. Objectives 1. To study the prevalence of malnutrition in the Under-Five years age group tribal children in the three regions of Andhra Pradesh. 2. To compare the nutritional status of tribal children in Andhra Pradesh with that of national statistics. 76 Sukhdas et al., Int J Med Res Health Sci. 2014;3(1):76-79 METHODS AND MATERIAL Study Design: A large community based, cross sectional study was conducted in 2007 to assess various health indicators in tribal blocks of Andhra Pradesh. The current article is an extract from this study. The study was planned to cover three Integrated Tribal Development Agency (ITDA) blocks one each in Rayalseema, Telangana and Coastal area to cover all the three regions of the state of Andhra Pradesh. Three ITDA blocks were selected including, Srisailam ITDA project (21 villages; Rayalaseema region), Bhadrachalam ITDA project (25 villages; Telangana region), and Rampachodavaram ITDA (19 villages; Coastal region). In each of the selected ITDA blocks 1000 households were covered thereby a total of 3000 households were covered with 5% as attrition rate to accommodate the locked houses and also migrated population. The target was to cover over 10,000 populations. The villages were listed out in cumulative order as was provided by the tribal welfare department and among them villages were randomly selected to cover the 1000 households. Clearance from Institutional Ethics Committee was obtained. All children less than five completed years of age were included in the study with the informed consent of the mother. A pretested questionnaire was used to interview the mothers and record the Child’s anthropometric data. The questionnaire included variables of demography, gestational history, birth history, immunization status, feeding history and clinical findings apart from Height/Length, Weight and Mid Arm circumference. Standard procedures were followed to measure Weight and Height/Length of the child. WHO Child Growth Standards3,4 were used for assessment of nutritional status of the children. A stunted child4 has a height-for-age z-score that is at least 2 standard deviations (SD) below the median for the WHO Child Growth Standards. Chronic malnutrition is an indicator of linear growth retardation that results from failure to receive adequate nutrition over a long period and may be exacerbated by recurrent and chronic illness. A wasted child4 has a weight-for-height z-score that is at least 2 SD below the median for the WHO Child Growth Standards. Wasting represents a recent failure to receive adequate nutrition and may be affected by recent episodes of diarrhea and other acute illnesses. An underweight child4 has a weight-for-age z-score that is at least 2 SD below the median for the WHO Child Growth Standards. This condition can result from either chronic or acute malnutrition, or both. RESULTS AND DISCUSSION A total of 1,013 Tribal children under five years of age were surveyed. Of these 544 were boys and 469 girls. Among the 1,013 tribal children who were assessed for malnutrition, 489 (48.27 %) were stunted, 239 (23.59 %) wasted and 490 (48.37%) underweight as per WHO Growth Standards.4 The Prevalence of stunting was 49.50 percent in Bhadrachalam, 51.21 percent in Srisailam and 48.66 percent in Rampachodavaram. The prevalence of wasting was 23.08 percent in Bhadrachalam, 24.06 percent in Srisailam and 23.37 percent in Rampachodavaram. The prevalence of underweight was 48.16 percent in Bhadrachalam, 49.23 percent in Srisailam and 47.13 percent in Rampachodavaram (Table 1). The prevalence of stunting (height-for-age) in the tribal children of Andhra Pradesh (48.27 percent) as assessed by the current study is similar to that of the national average of 48 percent. But it is much lower than the national average of stunting among the scheduled tribes of 54 percent as found in National Family Health Survey (NFHS -3). 2 Whereas it is higher than the overall prevalence in Andhra Pradesh of 43 percent as found in NFHS-35 (Fig 1). The prevalence of wasting (weight-for-height) is 23.59 percent in the current study which is more than overall percent of India (20 percent) or Andhra Pradesh (12 percent). But lesser percent are wasted as compared to a national average of wasting among the scheduled tribes of 28 percent as found in NFHS-3. The prevalence of underweight (weight-for-age) in the current study was 48.37 percent which is higher than the overall average of the country (43 percent) and AP state (33 percent). But it is lower than the prevalence of underweight among the tribal children of India (55 percent). 77 Sukhdas et al., Int J Med Res Health Sci. 2014;3(1):76-79 Table 1 : Prevalence of Under Nutrition Among Under Five Age Group Children in Three ITDA Blocks Of Andhra Pradesh POPULATION Sample Stunted % N AP (TRIBAL) Boys 544 Girls 469 Pooled 1013 Bhadrachalam Boys 163 Girls 136 Pooled 299 Srisailam Boys 252 Girls 201 Pooled 453 Rampachodavaram Boys 129 Girls 132 Pooled 261 Wasted % N 260 229 489 47.79 48.83 48.27 129 110 239 23.71 23.45 23.59 263 227 490 48.35 48.40 48.37 80 68 148 49.08 50.00 49.50 38 31 69 23.31 22.79 23.08 78 66 144 47.85 48.53 48.16 130 102 232 51.59 50.75 51.21 61 48 109 24.21 23.88 24.06 124 99 223 49.21 49.25 49.23 62 65 127 48.06 49.24 48.66 30 31 61 23.26 23.48 23.37 61 62 123 47.29 46.97 47.13 60 50 55 54 48.27 48.37 48 43 43 40 30 Underweight N % 33 28 23.59 20 20 12 10 0 AP ITDA Stunted AP Wasted INDIA INDIA TRIBAL Underweight (All values in percentages) Fig1: Status of Under-Five Child Nutrition: Current Study & NFHS-3 CONCLUSION Malnutrition continues to be a persistent public health problem in India and more so among the Scheduled Tribes of the country. While the indicators of malnutrition among the under five tribal children in the current study done in Andhra Pradesh are better than the country figures, they are much higher than the national averages of tribal populations. With a wide cultural diversity among tribes, like in AP, efforts to identify food taboos and fads and addressing the same through ICDS support may help in the long run to bridge the gaps. 78 Sukhdas et al., Int J Med Res Health Sci. 2014;3(1):76-79 ACKNOWLEDGMENTS We are thankful to the Director, Tribal Cultural Research and Training Institute, Tribal welfare Department, Hyderabad, and also thankful to Project Officers of ITDA Bhadrachalam, Srisailam and Rampachodavaram for their support while conducting the study. REFERENCES 1. Primary Census Abstract for Total population, Scheduled Castes and Scheduled Tribes, 2011 Office of the Registrar General & Census Commissioner,India.http://www.censusindia.gov.i n/2011-Documents/SCST%20Presentation%202810-2013.ppt 2. Fred Arnold, Sulabha Parasuraman, P. Arokiasamy, and Monica Kothari. Nutrition in India. National Family Health Survey (NFHS-3), India, 2005-06. Mumbai: International Institute for Population Sciences; Calverton, Maryland, USA: ICF Macro. 2009 3. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl 2006;450:76 -85. 4. World Health Organization. Training Course on Child Growth Assessment. Geneva, WHO, 2008. 5. International Institute for Population Sciences (IIPS) and Macro International. 2008. National Family Health Survey (NFHS-3), India, 2005-06: Andhra Pradesh. Mumbai: IIPS. 79 Sukhdas et al., Int J Med Res Health Sci. 2014;3(1):76-79 DOI: 10.5958/j.2319-5886.3.1.016 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 13 Nov 2013 Revised: 11th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 17th Dec 2013 INCIDENCE AND LOCATION OF ZYGOMATICOFACIAL FORAMEN IN ADULT HUMAN SKULLS Senthil Kumar. S*, Kesavi D Department of Anatomy; Sri Ramachandra Medical College and Research Institute, Chennai – 600 116 *Corresponding author email:
[email protected] ABSTRACT This study was to investigate the morphology, topographic anatomy and variations of Zygomaticofacial foramen (ZFF). Frequency variations and Location/distance of ZFF from surrounding standard landmarks were evaluated in 100 adult human dry skulls. The frequency of ZFF was varied from being single to as many as four foramina and absence of ZFF, which was classified into Type I – V for single, double, triple, four foramina and absence of ZFF respectively. The frequency (%) of these types was Type I: 46 & 51, Type II: 31 & 26, Type III: 4 & 6, Type IV: 1 & 1 and Type V: 18 & 16 respectively on right & left sides of the skulls. The mean distance of Zygomaticofacial foramen from Zygomaticomaxillary suture, nearest part of Orbital margin, Frontozygomatic suture, Zygomaticotemporal suture and Zygomatic angle was 13.8 & 12.2mm, 6.8 & 6.9mm, 24.8 & 26.7mm, 20.8 & 21.5mm and 12.4 & 13.5mm respectively on right & left sides of skulls. Knowledge on these variables will be helpful for surgeons for various surgical procedures like Orbitozygomatic craniotomy, for nerve block and Malar reduction surgeries. Keywords: Zygomaticofacial foramen, Orbital margin, Zygomaticbone, Zygomaticofacial nerve INTRODUCTION Zygomaticofacial foramen (ZFF) usually situated on the Zygoma nearer to infraorbital margin.1 Zygomaticofacial nerves and vessels emerge out through this foremen.1, 2 It is more predominant on right side in male and left side in female population.3 The location and frequency of ZFF vary significantly among individuals and races due to the difference of anthropometry of human from region to region. Current understanding on ZFF is very limited in the Indian population. ZFF with its structures serves as an important landmark for locating inferior orbital fissure during Orbitozygomatic craniotomy,4 for nerve block, Malar reduction surgeries5, in management of infraorbital tumors, Plastic and Reconstructive surgeries. Hence this study has been aimed to evaluate the location and frequency variations of ZFF in adult human dry skulls. MATERIALS AND METHODS Study has been conducted in the Department of Anatomy, Sri Ramachandra Medical College and Research Institute, Chennai. A total of 100 adult dry skulls were collected from the dissection hall and observed for frequency variations of ZFF. Distance of Zygomaticofacial foramen from Zyomaticomaxillary suture, nearest part of Orbital margin, Frontozygomatic suture, Zygomaticotemporal suture and Zygomatic angle (fig: 1) has been measured with digital vernier caliper on both sides (Right and Left) of the skull and compared. Specimens with very small decalcified pits were excluded. 80 Senthil Kumar. S et al., Int J Med Res Health Sci. 2014;3(1):80-83 Fig 1: Showing the distance from ZFF (encircled) to Zygomaticomaxillary suture (a), nearest part of Orbital margin (b), Zygomaticofrontal suture (c), Zygomatic angle (d), Zygomaticotemporal suture (e) Observations: A total of 100 dry skulls were examined. The frequency of ZFF were varied from being absent to as many as four foramina. Based on it all the skulls were classified in to following types. Type I: Single Foramen (fig: 2) Type II: Double Foramina (fig: 3) Type III: Triple Foramina (fig: 4) Type IV: Four Foramina (fig: 5) Type V: Absence of ZFF (fig: 6) Fig 4: Type III: Triple Foramina Fig 5: Type IV: Four Foramina Fig 6: Type V: Absence of ZFF Fig 2: Type I: Single Foramen Table 1: Frequencies of Zygomaticofacial foramina SIDE Type I (%) Type II (%) different Type III (%) types of Type IV (%) Type V (%) RIGHT 46 31 4 2 18 LEFT 51 26 6 1 16 The mean distance of ZFF from Zyomaticomaxillary suture, nearest part of Orbital margin, Frontozygomatic suture, Zygomaticotemporal suture and Zygomatic angle was 13.8 & 12.2mm, 6.8 & 6.9mm, 24.8 & 26.7mm, 20.8 & 21.5mm and 12.4 & 13.5mm respectively on right & left sides of skulls. Fig 3: Type II: Double Foramina 81 Senthil Kumar. S et al., Int J Med Res Health Sci. 2014;3(1):80-83 DISCUSSION In the present study absence of ZFF (Type V) has been found in 18 & 16% of right & left sides of skulls. Aksu F et al6 stated absence of ZFF at 15.6% of cases which includes both right and left side skulls. Whereas Marios Loukas et al7 quoted absence of ZFF at 1% among 200 specimens. Cajeron DM et8 al found ZFF in 38 and 13% of right and left of the skulls which is lower than our study (right: 82 and left: 84%). In line with most of the studies frequency of ZFF was ranging from absent to as many as four but Aksu F et al6 found five foramina in 1.3% of skulls (5 of 160sides, i.e. 80 skulls). Based on the frequency of ZFF we classified them into Type I – V as mentioned earlier. Type I to IV were occurred in 46 & 51%, 31 & 26%, 4 & 6% and 1 & 1% of right & left sides of the 100 skulls. In the similar study with 100 sample conducted by Ongeti et al9 only three types i.e. from Type I, II and III of our study were reported in 42 & 45%, 35 & 31% and 23 & 17% of right and left side of skulls respectively. Among these types only Type I and II are similar to present study and Type III was with higher frequency than the present findings. Likewise, the current study is showing the wide variations from the existing studies in the frequency of ZFF (table 2). The mean distance of ZFF from Zygomaticomaxillary suture was 13.8mm (right) and 12.2mm (left) among 100 skulls whereas it was 18.8mm in the study by Aksu F et al6. The mean distance of ZFF from nearest part of Orbital margin was 6.8 & 6.9 mm (right & left) respectively in our study which is higher than Aksu F et al6 (5.94mm) and Hwang SH et al5 (7.61mm). ZFF situated in 24.8mm (right) & 26.7mm (left) distance from Frontozygomatic suture which is almost similar to the Martins C et al (25mm)4 and Aksu F et al6 (26.2mm). Likewise the mean distance of ZFF from Zygomaticotemporal suture was 20.8mm (right) & 21.5mm (left) and Zygomatic angle was 12.4mm (right) & 13.5mm (left) in the present study. The etiology behind the absence of ZFF and the path by which the neurovascular bundle emerges out in such cases has not reported in the existing literature and the same could not be evaluated in the present study because of the fact that present study has been conducted in the dry skulls, which holds the limitation of the study. Since the cone-beam computed tomography (CBCT) has an excellent accuracy in evaluating the ZFF10, further studies can be conducted using CBCT to evaluate the fate of neurovascular bundle in absence of ZFF along with the medical history of subjects. The present study is not similar to the most of the existing studies. The comparisons made in the discussion were with non Indian studies as there was very less/nil number of studies we encountered in literature search. The variant anthropometric measurements were probably due to difference of skull anthropometry in different regions of the World. Similar studies are suggested to be conducted in the India in order to standardize the foresaid findings which will be helpful for different surgical procedures like Orbitozygomatic craniotomy, for nerve block, Malar reduction surgeries and in management of infraorbital tumors. Table 2: Comparison of Present study findings with different existing studies AUTHOR Present study Ongeti et al9 Aksu Cajeron DM et Marios 6 TYPE etal al8 Loukas et al7 Right Left Right Left Righ Left (%) (%) (%) (%) (%) t (%) (%) (%) TYPE I 46 51 42 52 44 46 12 40 TYPE II 31 26 35 31 45 20 75 15 TYPE III 4 6 23 17 6.3 13 13 5 TYPE IV 1 1 --4.4 0.5 0.5 1 TYPE V Absent 1.3 Absent Hwang et al5 (%) SH 50.9 30 9 0.9 82 Senthil Kumar. S et al., Int J Med Res Health Sci. 2014;3(1):80-83 CONCLUSION Frequency of ZFF and its distance from surrounding standard landmarks were varying from existing studies and knowledge on them is helpful for surgeons for various surgical procedures. reliability in cone-beam computed tomography. Acta Odontol Scand. 2013; Posted online on 1 Jul 2013. (doi:10.3109/00016357.2013.814804) ACKNOWLEDGEMENT I would like to thank Sri Ramachandra University for giving the opportunity. REFERENCES 1. Susan Standring. Face and Scalp In Gray’s Anatomy – An Anatomical Basis of Clinical Practice. 5th ed. Elsevier. China. 467-497. 2. Dutta AK. The Skull In Essentials of Human Anatomy Current Books International.Kolkata.2012: 2(5th ed);3-65. 3. Kaur J, Choudhry R, Raheja S, Dhissa NC. Non metric traits of the skull and their role in anthropological studies. J. Morphol. Sci, 2012;29(4):189-94 4. Martins C, Li X, Rhoton Al Jr. role of the Zygomaticofacial foramen in the orbitozygomatic craniotomy: Anatomic report. Neurosurgery 2003 Jul; 53(1): 168 -73 5. Hwang SH, Jin S, Hwang K. Location of the Zygomaticofacial foramen related to malar reduction. J Craniofac Surg 2007; 18(4):872 – 74 6. Aksu F, Ceri NG, Arman C, Zeybek FG, Tetik S. Location and Incidence of the zygomaticofacial foramen: An anatomic study. Clin Anat. 2009; 22(5):559 – 62 7. Marios Loukas, Deyzi Gueorguieva Owens, Shane Tubbs, Georgi. Zygomaticofacial, Zygomaticoorbital and Zygomaticotemporal foramina: anatomical study. Anatomical Science International 2008; 83(2):77 - 82 8. Cajeron DM, Osses AO, Faig-leite H. Zygomaticofacialforamen’s anatomical stusy and its importance in the ondontology.2007. available from: http://ojs.fosjc.unesp.br/index.php/cob/ article/download/329/259 9. K. Ongeti, J. Hassanali, J. Ogeng’o, H. Saidi. Biometric features of facial foramina in adult Kenyan skulls. Eur J Anat 2008; 12(1):89-95 10. Del Neri NB, Araujo-Pires AC, Andreo JC, Rubira-Bullen IR, Ferreira Junior O. Zygomaticofacial foramen location accuracy and 83 Senthil Kumar. S et al., Int J Med Res Health Sci. 2014;3(1):80-83 DOI: 10.5958/j.2319-5886.3.1.017 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Received: 15th Nov 2013 Revised: 11th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 18th Dec 2013 ROLE OF MRI IN EVALUATION OF PAINFUL KNEE *Rajpal Yadav1, Sushil G Kachewar2 1 Chief Resident, 2Professor, Department of Radio-diagnosis, Rural Medical College, PIMS (DU), Loni, Maharashtra, India *Corresponding author email:
[email protected] ABSTRACT Introduction: Requests for knee Magnetic Resonance Imaging (MRI) are most often made when the patient presents with a painful knee. This pain might be due to trauma or infection or inflammation. Complete clinical examination is not possible in such situations as the patients cannot co-operate due to severe pain. There comes the role of noninvasive multiplanar imaging. Hence this study was undertaken to evaluate how MRI can evaluate painful knee. Methods: 50 consecutive patients who were referred for MRI evaluation of painful knee were included in this study. Specific findings that explained the cause of pain were compiled. Results: In this present study of 50 patients, and 17 were females (34%) and 33 were males (66%).The mean age was 36.70± 13.14 years. Traumatic causes outnumbered non traumatic etiologies of painful knee. Injury to the anterior cruciate ligament (ACL) was the commonest soft tissue abnormality encountered. Partial tears were more common than complete tears. Tibial attachment was commonly affected than femoral attachment. Injured posterior horn of the medial meniscus and medial collateral ligament, were the commonest associated findings. Conclusion: MRI evaluation in patients with painful knee is of vital importance, as MRI can demonstrate the exact nature and extent of bony as well as soft tissue abnormality. Multiplanar imaging capacity and noninvasive nature of MRI enable a satisfactory diagnosis in such patients in whom a complete clinical examination is almost impossible due to pain. Keywords: Painful Knee; MRI; Ligaments, Imaging. INTRODUCTION Painful knees can bring tears to our eyes. It may either be of traumatic origin or non traumatic origin like infection or inflammation. Examination by a surgeon or orthopedician is usually not conclusive to pinpoint the exact lesion causing pain.1, 2 Hence optimum treatment is hampered. Therefore non invasive imaging which can demonstrate the underlying pathology without any significant discomfort to the patient is needed.3 This study was therefore undertaken to analyze the utility of magnetic resonance imaging (MRI) in pinpointing the cause of painful knee. The aim was to find common imaging findings in our setup. MATERIALS AND METHODS Inclusion criteria: Patients of either sex from >20years, having acute or chronic painful knee were included in this study, history of painful knee was noted but as such patients cannot be accurately evaluated clinically due to their pain. Exclusion criteria: Patients who could not co-cooperate for MRI examination, patients have undergone prior surgical procedures and who had metallic implants or metallic clips in situ were also excluded as these are contraindications for MRI evaluation. Methodology: Philips Achieva 1.5Tesla High Gradient MRI Scanner was used for evaluating 50 consecutive patients having 84 Rajpal et al., Int J Med Res Health Sci. 2014;3(1):84- 87 painful knee as the presenting complaint. The present study was approved by the Institutional Ethical and Research Cell and informed consent from all the patients was obtained for this study. RESULTS Analysis of demographic characteristics shows that in this present study of 50 patients, 17 were females (34%) and 33 were males (66%). This is because males are generally more active than females and travel a lot. Hence their knees are exposed to more wear and tear. Also they are at more risk of injury. The following table shows the distribution of patients as per different age groups. The mean age of patients in this study was 36.70± 13.14. The maximum numbers of patients were seen in 40-50 years age group. Table 1: Distribution of patients according to age AGE (Years) No. of Patients % <20 08 16% 20-30 10 20% 30-40 10 20% 40-50 14 28% 50-60 07 14% >60 01 02% TOTAL 50 100% MEAN ± SD 36.70±13.14 MRI could satisfactorily identify the exact nature of injury in all cases. Anterior cruciate ligament (ACL) was the most commonly injured ligament. Right sided injuries were more common than the left side. Partial thickness tears were more common. Tibial attachment was more involved than the femoral attachment. Table 2: Distribution of MRI findings of ACL involvement Number of Findings % Patients Side Left 18 36% Right 32 64% ACL tear Compete 17 34% Partial 27 54% Location of ACL tear Midsubstance 14 28% Femoral attachment 8 16% Tibial attachment 27 54% Involvement of medial as well as lateral meniscus was also seen satisfactorily on MRI. The distribution of findings of meniscal involvement is summarized in Table 3. Overall medial meniscus was more commonly involved rather than the lateral meniscus. Posterior horn was more involved in either of the cases than the anterior horn. Table 3: Distribution of findings of meniscal involvement on MRI Findings Medial Meniscus Lateral Meniscus No. of patients (%) No. of patients (%) 8(16%) Anterior Horn 7(14%) 21(42%) Posterior Horn 35(70%) Involvement of posterior cruciate ligament (PCL) was also satisfactorily demonstrated by MRI. The distribution of findings of PCL involvement is summarized in Table 4. Table 4: Distribution of findings of meniscal involvement on MRI Findings Complete Tear Partial Tear BUCKLING No. of patients 04 02 21 (%) 08% 04% 42% DISCUSSION A plethora of pathologies can present as painful knee. Imaging is useful to identify and confirm the clinically suspected pathologies and also to assessing its extent and gravity.3-6 Clinical examination in such cases usually suggests internal derangement. So correct diagnosis is needed to perform or to avoid invasive procedures like Arthroscopy. A host of imaging modalities is available for evaluation of the knee joint. Plain radiographs demonstrate bone pathologies clearly. Soft tissue and cystic lesions may be missed. Only a focal bulge on overlying soft tissues may be noticed. Computerized tomography (CT scan) may show the lesions, but the exact tissue characterization may be limited. In experienced hands, musculoskeletal ultrasound can very well depict the soft tissue pathology. The biggest advantage of MRI is that it shows the entire lesion in multiple planes so that correct diagnosis and management strategy can be planned. The MRI 85 Rajpal et al., Int J Med Res Health Sci. 2014;3(1):84- 87 appearance of various soft tissue lesions has been studied and mentioned in literature. 4-16 On MRI ACL and PCL are seen as hypo intense bands on T1W, T2W as well as STIR (Short Tau Inversion Recovery) images. Any injury to them manifests as a hyperintense appearance on T2W and STIR images. This injury may result in partial or full thickness tear of these structures. Fig 1: STIR sagittal images showing pathologies of ACL and PCL Similarly, the meniscus of knee too is seen as a hypo intense structure on T1W, T2W as well as STIR images. Any injury to them manifests as a hyperintense appearance on T2W and STIR images. This injury may result in partial or full thickness tear of these structures. MRI is used to obtain the sections of these regions of interest in different planes. Standard planes are the axial, coronal and sagittal planes. Sometimes oblique images too may be required. The representative MRI appearance of soft tissue injury presenting as painful knee is shown in following image. It has been found that the disruption of a knee ligament is commonest pathology in patients having post traumatic knee pain. It is important to develop a mechanistic approach to associate the imaging findings with their anatomic relevance.17 Substantial pain and disability caused in Osteoarthritis of the knee shows a poor correlation with plain radiographs. Pain receptors have been found in joint capsule, ligaments, synovium as well as in the subchondral bone. It has now been understood that no definitive treatment modality can relieve the pain and knee surgery does not necessarily guarantee improvement. Hence a proper clinical assessment of knee and appropriate MRI examination can permit proper treatment.18 Not only adults, but children and adolescents too, commonly present with knee pain. Again the commonet performed a pediatric cross-sectional imaging study is the MRI of the knee. Differences between adult and pediatric knee imaging exist and in younger age group one has to remember normal developmental variants, injury and disease patterns unique to children and adolescents.19 MRI has revolutionized diagnostic imaging of the knee as this innovative technology allows superior soft tissue details with multiplanar imaging capability that provide accurate evaluation of the intra and extra articular structure of the knee which are demonstrated with other imaging modalities.MRI is accurate, non invasive technique for evaluating the structures of the knee, marrow space, synovium and periarticular soft tissue concerning the knee.20, 21 It has great capacity in diagnosing meniscal tear and classifying them into grade and type which would avoid unnecessary arthroscopic examination. It is a very good modality to diagnose a complete tear of the ACL. New discoveries in the field of computer science and telecommunications have reduced the cost of MRI knee studies. This too has increased the acceptance of MRI imaging by the orthopedic community with quote results almost same and satisfactory as a non invasive replacement for arthrography and non therapeutic Arthroscopy. 22 CONCLUSION Plethora of causes can cause painful knee. It is a common symptom in all age groups. Correct treatment necessitates accurate noninvasive diagnosis. Imaging of the knee joint by MRI can satisfactorily provide the correct diagnosis. This has led to the increase use as well as the increased acceptance of MRI in the imaging evaluation of painful knee. REFERENCES 1. Terry GC, Tagert BE, Young MJ. Reliability of the clinical assessment in predicting the cause of internal derangement of the knee. Arthroscopy. 1995;11(5):568-76 2. Yoon YS, Rah JH, Park HJ: A prospective study of the accuracy of clinical examination evaluated by arthroscopy of the knee. Int Orthop. 1997;21(4):223-27 86 Rajpal et al., Int J Med Res Health Sci. 2014;3(1):84- 87 3. McCarthy CL, McNally EG. The MRI appearance of cystic lesions around the knee. Skeletal Radiol. 2004;33:187–209 4. Trieshmann HW Jr, Mosure JC: The impact of magnetic resonance imaging of the knee on surgical decision making. Arthroscopy. 1996;12(5):550-55 5. Dorsey ML, Liu PT, Leslie KO, Beauchamp CP. Painful suprapatellar swelling: Diagnosis and discussion. Skeletal Radiol. 2008;37:937–38 6. Christian SR, Anderson MB, Workman R, Conway WF, Pope TL. Imaging of anterior knee pain. Clin Sports Med. 2006; 25(4):681-702 7. Janzen DL, Peterfy CG, Forbes JR, Tirman PF, Genant HK. Cystic lesions around the knee joint: MR imaging findings. AJR Am J Roentgenol. 1994;163:155–61. 8. Hirji Z, Hanjun JS, Choudur HN. Imaging of Bursae. J Clin Imaging Sci. 2011;1:22. 9. Burk DL, Dalinka MK, Kanal E. Meniscal and ganglion cysts of the knee: MR evaluation AJR Am J Roentgenol 1988; 150:331-336 10. Pouders C, De Maeseneer M, Van Roy P, Gielen J, Goossens A, Shahabpour M. Prevalence and MRI-anatomic correlation of bone cysts in osteoarthritic knees. Am J Roentgenol. 2008; 190:17–21. 11. Recht MP, Applegate G, Kaplan P. The MR appearance of cruciate ganglion cysts: A report of 16 cases. Skeletal Radiol. 1994;23:597-600 12. Fielding JR, Franklin PD, Kustan J . Popliteal cysts: a reassessment using magnetic resonance imaging. Skeletal Radiol. 1991;20:433-35 13. Miller TT, Staron RB, Koenigsberg T. MR imaging of Baker’s cyst: association with internal derangement, effusion and degenerative arthropathy. Radiology. 1996;201:247-50 14. Fritschy D, Fasel J, Imbert JC, Bianchi S, Verdonk R, Wirth CJ. The popliteal cyst. Knee Surg Sports Traumatol Arthrosc. 2006; 14:623–28 15. Dorsey ML, Liu PT, Leslie KO, Beauchamp CP. Painful suprapatellar swelling: Diagnosis and discussion. Skeletal Radiol. 2008; 37:937–38 16. Recht MP, Applegate G, Kaplan P. The MR appearance of cruciate ganglion cysts: A report of 16 cases. Skeletal Radiol. 1994; 23:597-600 17. Miller LS, Yu JS. Radiographic indicators of acute ligament injuries of the knee: a mechanistic approach. Emerg Radiol. 2010;17(6):435-44 18. Haviv B, Bronak S, Thein R. The complexity of pain around the knee in patients with osteoarthritis. Isr Med Assoc J. 2013;15(4):178-81 19. Orth RC. The pediatric knee. Pediatr Radiol. 2013;43:90-98 20. Kachewar SG, Kulkarni DS. Distant perijoint calcifications: sequel of non traumatic brain injury-a review and case report. Journal of Clinical and Diagnostic Research. 2013;7:2606-2609. 21. Kachewar SG, Singh H. Perigenicular Heterotopic Ossification: A rare sequelae of non traumatic brain injury. Nepal Journal of Neurosciences. 2010;1:21-23 22. Nikken JJ, Oei EHG, Ginai AZ. Acute peripheral joint injury: cost and effectiveness of low-fieldstrength MR imaging results of randomized controlled trail. Radiology. 2005;236: 958–67 87 Rajpal et al., Int J Med Res Health Sci. 2014;3(1):84- 87 DOI: 10.5958/j.2319-5886.3.1.018 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Received: 27th Nov 2013 Revised: 15th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 21st Dec 2013 A RETROSPECTIVE STUDY OF PRESCRIPTION PATTERN OF ANTIMICROBIALS IN AN URBAN HEALTH CENTRE RUN BY A MEDICAL COLLEGE *Bala Sharmin S, Chincholkar Aparna S, Wagh Ranjit J, Mutalik Madhav M. Department of Pharmacology, MIMER Medical College, Talegaon Dabhade, India * Corresponding author email:
[email protected] ABSTRACT Background: Antimicrobials are widely prescribed agents in clinical practice. Overuse of antimicrobials has led to emergence of drug resistance. Aims: The present study was aimed at knowing the choice of antimicrobial prescribing and to understand the rationality of antimicrobial usage. Materials and Methods: A retrospective prescription audit was done of all 655 prescriptions issued between 01/01/2012 and 31/12/2012 at the outpatient department of Urban Health Centre attached to a medical college. Demographic information, diagnosis, and medication details (dose, duration, frequency) were recorded and analyzed, and data was expressed as percentages. Results: Of the total number of prescriptions, 46% prescriptions were containing at least one or more than one antimicrobial agent. Average number of antimicrobials prescribed per prescription was 1.35. Cotrimoxazole was the most common antimicrobial agent prescribed. Of the total 307 items of prescribed antimicrobials, 57% were prescribed by proprietary name and 43% by nonproprietary name. Out of the antimicrobial items prescribed, 44% were available at the pharmacy of the Urban Health Centre. Fifty eight percent of antimicrobials prescribed were from WHO Essential Drug List. Conclusion: Among the various antimicrobials prescribed at the Urban Health Centre, cotrimoxazole was found to be the most commonly prescribed antimicrobial agent in the year 2012. More than half of the antimicrobials were prescribed by proprietary name. Less than half of the antimicrobials prescribed were available at the Urban Health Centre. Majority of the antimicrobials prescribed were from the WHO Essential Drug List. Keywords: Prescription pattern, Antimicrobials, retrospective study, Cotrimoxazole INTRODUCTION Antimicrobial agents are widely prescribed in health care set-ups for treatment of common ailments like coryza, cough, fever or pain in abdomen.1 Irrational and unnecessary use of antimicrobials remains common in developing countries.1,2 The overuse or inadvertent use of antimicrobials is known to lead to the emergence of drug resistance.3,4 Drug resistance is one of the major obstacles in medical management of diseases.1 Many physicians augment the drug therapy with a high dose of antimicrobials and prescribe various antimicrobial combinations. A study showed that polypharmacy is now-a-days a common practice.5 Also, many medications are available as ‘over the counter’ drugs. Many antimicrobials thus may be taken without knowing the appropriate dosage and frequency. Many times the antimicrobials are discontinued before completing the antimicrobial course of the specified days. This results in inadequate treatment, and also increases the possibility of emergence of drug resistance. Considering all these issues, the present study was undertaken. The objectives of the present study were: 1) To know the 88 Bala Sharmin et al., Int J Med Res Health Sci. 2014;3(1):88-91 prevalence of conditions associated with infections and to know what antimicrobial agents were prescribed, 2) To determine whether the drug prescribing was rationally in accordance with WHO guidelines for prescribing drugs, 3) To identify common errors in prescriptions, and propose interventions for improvement. MATERIALS AND METHODS This was a retrospective prescription audit. The study was approved by the Institutional Ethics Committee. All the prescriptions issued in the outpatient department of the Urban Health Centre of Bhausaheb Sardesai Rural Hospital attached to MIMER Medical College, Talegaon-Dabhade (located in Pune district of Maharashtra) were studied. The prescriptions issued from 01/01/2012 to 31/12/2012 were included in the study, and the total number of prescriptions were 655. It was not necessary to exclude any prescriptions on account of incompleteness or illegibility. Demographic information of the patients, diagnosis of the illnesses, the medication details (dose, duration, frequency, formulation, and whether prescribed from WHO Essential Drug List6 or not), and the follow-up details of the patients were recorded. All prescriptions were critically evaluated using guidelines of WHO as described in ‘How to investigate drug use in health facilities’.10 The common antimicrobial agents prescribed, the different types of antimicrobials prescribed, the number of antimicrobials prescribed per prescription, and the availability of antimicrobial agents at the Urban Health Centre were recorded. Further, whether the physicians prescribed the medications with proprietary or nonproprietary names was also noted. Indicators used for prescription pattern study: A. Prescribing Indicators: 1, 8 1. Average number of drugs per encounter was calculated by dividing the total number of drugs prescribed by the total number of prescriptions. 2. Average number of antimicrobials per prescription was calculated by dividing total number of antimicrobials prescribed by the total number of prescriptions. 3. Percentage of drugs prescribed from WHO Essential Drug List was determined by dividing the number of products prescribed from the WHO Essential Drug List by the total number of drugs prescribed, multiplied by 100. B) Facility indicators: 1, 8 a) Availability of copy of Essential Drug List by stating “Yes” or “No”. b) Availability of drugs was calculated by dividing the number of specified products actually in stock by the total number of drugs on the checklist of essential drugs multiplied by 100. Selection of Cases: All the prescriptions issued at the Urban Health Centre from 01/01/2012 to 31/12/2012 were included in the study. Statistical Analysis: It is a descriptive study and purposive sampling was done. Data was analyzed and expressed as a percentage. RESULTS Of the total 655 prescriptions, 46% prescriptions were containing at least one or more antimicrobial agents. Average number of antimicrobials prescribed per prescription was 1.35. Of the total 226 patients taking antimicrobials, 82 were males and 142 were females. There were 84 children. Upper respiratory tract infection was the most common diagnosis in all adults and children followed by diarrhea (Figure 1) (Table 1). There were 26 different antimicrobials prescribed, of which 4 were prescribed most commonly. Cotrimoxazole was the most common drug prescribed to both adults and children (36.2%) followed by metronidazole, norfloxacin, and amoxicillin (Figure 2). A single antimicrobial was prescribed in 81% of all prescriptions, whereas 17% prescriptions contained two antimicrobial agents. The prescriptions containing cephalosporins were 2%. Percentage of antimicrobial items prescribed by brand name (proprietary name) was 57% and those prescribed by non-proprietary name was 43%. The doses of the antimicrobial medications were prescribed according to standard regimens. Of the 226 patients, 63 came for follow-up and 22 of them received antimicrobials on follow-up. Antimicrobial agent was changed in 15% patients on follow-up. Out of all the antimicrobial items prescribed, 44% were available at the pharmacy of the Urban Health Centre. Most common antimicrobial prescribed from outside the Urban Health Centre was doxycycline. The WHO Essential Drug List was available at the Urban Health Centre. Fifty eight percent of antimicrobials prescribed were from WHO Essential Drug List. Of the antimicrobials prescribed from WHO Essential Drug checklist, 46% were available at the pharmacy of the Urban Health Centre. 89 Bala Sharmin et al., Int J Med Res Health Sci. 2014;3(1):88-91 Fluoroquinolones (norfloxacin, ciprofloxacin) were administered to 5 children, of which three had the diagnosis of diarrhea, and two were diagnosed with fever and chills. Table 1: Some common disease conditions and corresponding antimicrobial prescribed Most common diagnosis Most common antimicrobials prescribed Upper respiratory tract Cotrimoxazole infection (URTI) Loose Motion Metronidazole Urinary Tract Infection Norfloxacin (UTI) Injury Cotrimoxazole Folliculitis Cotrimoxazole 48.20% 14.60% URTI Loose motion 23.40% 9.60% UTI 4.20% Injury Others Fig 1: Diagnosis observed in percentage: URTI- Upper respiratory tract infection, UTI- Urinary tract infection 40.00% 36.20% 32.20% 30.00% 20.00% 15.70% 10.00% 11.20% 4.70% 0.00% Fig 2: Antimicrobials prescribed DISCUSSION There is a widespread use of antimicrobials all over the world. In a study from rural clinics in Western China, almost half of the prescriptions contained antimicrobial agents.9 This figure was 54.8% in Lagos, Nigeria, 67% in Hai Phong Province, Vietnam, 27.1% in a primary healthcare centre in Lebanon, 15.3% in United States, and 32% in Spain.9 In a study from India, 69% prescriptions contained one or more antimicrobial agents.4 In the present study, 46% prescriptions contained one or more antimicrobial agents. The difference is statistically significant. (Z=8.08, p<0.001). Upper respiratory tract infection was the most common diagnosis, and cotrimoxazole was the most commonly prescribed antimicrobial agent (36%) followed by metronidazole, norfloxacin, and amoxicillin. Two other studies also found cotrimoxazole as the most commonly prescribed antimicrobial agent (36% prescriptions).4, 7 The results are comparable with our study. In a study conducted in Kyrgyz Republic, penicillin G was the most common antimicrobial agent prescribed3. Now-a-days the cephalosporins are one of the most commonly prescribed antimicrobials in various countries. A study in South India reported cefixime to be the most commonly prescribed antimicrobial agent2. In the present study there were 26 different antimicrobials prescribed of which 4 were prescribed most commonly; however, the cephalosporins were infrequently prescribed. In a study conducted in China, there were 49 antimicrobials prescribed in total, 17 of them were prescribed frequently.9 In the present study, prescriptions with one antibiotic comprised 81% of all prescriptions, those with two antimicrobials represented 17%. In the study conducted in China, prescriptions with one antibiotic comprised 40.6% of all prescriptions, and those with two antibiotics represented 7.08%9. The frequency and proportion of prescribed antimicrobials in the present study are higher compared with the other studies. 9 The average number of medicines per encounter (2.8%) is higher than the range of 1.3–2.2 found in similar studies in other countries conducted at the district or regional levels, either in hospitals or health centers. 1 Though a significant number of antimicrobials were prescribed by the non-proprietary name, the physicians prescribed majority of the antimicrobials by brand (proprietary) name. It was found in the prescriptions that the doses of the antimicrobial medications were appropriate in context with the medical conditions and the patient factors. Almost one third of the patients taking antimicrobials returned for follow up. Less than half of the antimicrobials prescribed were available at the Urban Health Centre. Majority of the antimicrobials 90 Bala Sharmin et al., Int J Med Res Health Sci. 2014;3(1):88-91 were prescribed from the WHO Essential Drug List (58%). When this figure was compared with those from other studies, it was found that the percentage of antimicrobials prescribed from WHO Essential Drug List was higher in other studies, e.g. being 79% in a study done in Lesotho and with the WHO study showing that the adherence to the Essential Medicine List in Tanzania was 88% (Ofori-Adjei, 1992) and in Nepal 86%.1 It was suggested that improvements in the prescribing pattern can be made by prescribing the drugs to a larger extent by their non-proprietary name. More antimicrobial agents should be prescribed from the WHO Essential Drug List. We suggest that more drugs which are prescribed and included in the WHO Essential Drug List should be available in the Urban Health Centre pharmacy. In the present study, it was noticed that fluoroquinolones were administered to 5 patients less than 18 years of age. Fluoroquinolones may damage growing cartilage and cause arthropathy. Therefore these drugs are not routinely recommended for patients less than 18 years of age.11 3. 4. 5. 6. 7. CONCLUSION Prescription audit of prescriptions over a period of 1 year at the Urban Health Centre of a rural hospital showed that antimicrobials were widely prescribed. Cotrimoxazole was the most common antimicrobial prescribed. There were antimicrobial items found to be prescribed by the proprietary name in significant number of prescriptions. Suggestions and recommendations from this particular audit would be useful to improve the prescribing trends for the benefit of the recipients. 8. 9. ACKNOWLEDGEMENTS I sincerely thank the Urban Health Centre staff and the Department of Preventive and Social Medicine for extending help in providing all the necessary information of the patients visiting the Urban Health Centre. REFERENCES 1. Antibiotics prescribing pattern at 6 hospitals in Lesotho. Retrieved from apps.who.int/ medicinedocs/documents/s21028en/s21028en.pdf. (Accessed on November 15, 2013). 2. Khade A, Shakeel M, Bashir M, George S, Annaldesh S, Bansod K. Prescription pattern of antimicrobial agents in a teaching hospital of 10. 11. South India. Int J Basic Clin Pharmacol 2013; 2(5): 567-70. Baktygul K, Marat B, Ashirali Z, Rashid H, Sakamoto J. An assessment of antibiotics prescribed at the secondary health care level in the Kyrgyz Republic. Nagoya J. Med. Sci. 2011;73: 157-68. Indira K, Chandy S, L Jeyaseelan, Kumar R and Suresh S. Antimicrobial prescription patterns for common acute infections in some rural and urban health facilities of India. Indian J Med Res 2008;128:165-71. Kumari R, Idris M, Bhushan V, Khanna A, Agrawal M, Singh. S.K. Assessment of prescription pattern at the public health facilities of Lucknow district. Indian J Pharmacol. 2008;40(6):243-7. WHO Essential Drug List. Retrieved from: www.who.int/medicines/publications/essentialmed icines. (Accessed on February 24, 2013) Furones J A. Drug utilization Study related to Antibiotics in Primary Health Care; INABIS98. Retrieved from: www.mcmaster.ca/inabis98/ occupational/furones0821/index.html. (Accessed on November 15, 2013). Introduction to Drug Utilization and Research/ WHO International Working Group forDrug Statistics Methodology, Drug Utilization Research and Clinical Pharmacological Services. Retrieved from: http://apps.who.int/medicinedocs /en/d/Js4882e/8.4.html#Js4882e.8.4. (Accessed on February 25, 2013). Dong L, Yan H, Wang D. Antibiotic prescribing patterns in village health clinics across 10 provinces of Western China. J Antimicrob Chemother. 2008;62(2):410-15. WHO. How to investigate drug use in health facilities: selected drug use indicators, Geneva, World Health Organisation, 1993, WHO/DAP/93 1993;1:1-87. (Accessed on February 24, 2013) Deck DH, Pharm D, Lisa G, Winston, MD. Sulfonamides, trimethoprim, and quinolones. In: Katzung BG, Masters S, Trevor A. Basics and clinical pharmacology. Tata McGrawHill;2012;12th edition:836 91 Bala Sharmin et al., Int J Med Res Health Sci. 2014;3(1):88-91 DOI: 10.5958/j.2319-5886.3.1.019 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 29 Nov 2013 Revised: 18th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 23rd Dec 2013 PREVALENCE AND FUNGAL PROFILE OF PULMONARY ASPERGILLOSIS IN IMMUNOCOMPROMISED AND IMMUNOCOMPETENT PATIENTS OF A TERTIARY CARE HOSPITAL Prakash Ved1, *Mishra Prem P2, Verma Shashi K3, Sinha Shivani4, Sharma Mahendra5 1 Associate Professor, 2Assistant Professor, 4MD student Department of Microbiology, RMCH, Bareilly, UP, India 3 Professor, Department of Physiology, RMCH, Bareilly, UP, India 5 Statistician cum lecturer, Dept of community Medicine; RMCH, Bareilly, UP, India *Corresponding author email:
[email protected] ABSTRACT Background: Aspergillus is a fungus which may present an array of pulmonary manifestations, depending on the patient's immunological and physiological state. Although the incidence of pulmonary aspergillosis occurs primarily in immunocompromised patients but the incidence is also rising in immunocompetent individuals, especially in developing countries. Aim: The objective of the study was to determine the prevalence and predisposing factors of pulmonary aspergillosis along with species identification. Materials and Methods: One hundred and three patients admitted to the Department of Chest and Tuberculosis and in the Department of Medicine from Jan 2012 to Jan 2013 were included in this study. The patients were epitomized on the basis of clinical signs and symptoms, physical examination, chest radiography, CT scans, histopathological examination, bronchoscopy and fungal examination including potassium hydroxide mount, fungal culture of sputum and bronchoalveolar lavage. Species identification was done by colony characteristics, slide culture and Lactophenol Cotton blue mount. Results: Out of the 103 patients, (63 males and 40 females) Aspergillus species has been isolated from 17 (16.5%) males and 07 (6.79%) females. Various predisposing factors of pulmonary aspergillosis have been identified in which pulmonary tuberculosis, chronic smoking and environmental exposure to asbestos, cement its tops the list. Many of the patients had multiple predisposing factors. Aspergillus species were isolated in 24 (23.3%) cases. Aspergillus fumigatus was the predominant species isolated in 13 (54.16%) cases followed by Aspergillus flavus in 07 (29.16%) cases, Aspergillus niger in 03 (12.5 %) and Aspergillus terrus in 1 (4.16%) cases. Conclusion: It is concluded that the prevalence of pulmonary Aspergillosis is quite high in immunocompromised individuals and low in immunocompetent individuals. An adequate and efficient evaluation of the etiological agents has a crucial role in the management of such patients. Keywords: Aspergillus, Tuberculosis, Sputum, Immunocompromised. INTRODUCTION In recent years fungal infections are one of the important cause of pulmonary infections.1 Aspergillus primarily affects the lungs, causing a variety of manifestations, including allergic bronchopulmonary aspergillosis (ABPA), aspergilloma, and invasive Prakash et al., aspergillosis. Invasive pulmonary aspergillosis is an increasingly common fungal infection with high morbidity and mortality in immunocompromised patients. The incidence and clinical impact of these infections is on the rise in the developed countries, Int J Med Res Health Sci. 2014;3(1):92-97 92 which is possibly related to increased number of immunocompromised patients, owing to improved survival from AIDS, malignancies and more intensive cytotoxic therapy, organ transplantation and better treatment and prophylaxis for other fungal infections.2 Immunocompromised individuals are susceptible to pulmonary aspergillosis, but invasive aspergillosis is extremely uncommon in individual’s with intact immunity. Immunocompetent persons seldom develop this infection and do so only in the presence of other pulmonary and systemic abnormalities such as fibrotic lung disease,3 suppurative infection4 or treatment with corticosteroids.5 Pulmonary aspergillosis shows a variable inimitable pattern of lung disease that primarily depend on the patient's immune status. Preexisting lung diseases acts as a significant predisposing cause for pulmonary aspergillosis.6,7 Pulmonary aspergillosis is generally presented as a wide range of pulmonary manifestations, from aspergilloma with a comparatively benign course, to invasive pulmonary aspergillosis, which can be terminal. Pulmonary aspergillosis is one of the main causes of pulmonary infections and creates a complicated diagnostic challenge due to lack of pathognomonic clinical features. The diagnosis of aspergillosis is frequently missed as the diagnostic tests for their detection is not done in routine diagnostic laboratories and/or is not suspected by the physician. Therefore, the present study aims to a) detect the prevalence of pulmonary aspergillosis in immunocompromised and immunocompetent individuals. b) To study the various predisposing factors. c) Isolation and differentiation of Aspergillus species from clinical specimens of patients suffering from pulmonary infections. METHODS This study was conducted on 103 patients with different chronic pulmonary infections admitted in the wards of Department of Chest and Tuberculosis, and Department of Medicine between the period of January 2012 to January 2013. The cases are the patients with various chronic pulmonary infections of more than one year on whom bronchoscopy, radio imaging was done. This work has been approved by the Institutional Ethical Committee. Data were collected regarding age, sex, detailed medical history (immunosuppressive conditions like Prakash et al., pulmonary tuberculosis, Diabetes mellitus, AIDS etc, chronic smoking and environmental exposure to asbestos, cement etc smoking), physical examination (vital signs, cyanosis, pallor, clubbing etc), chest radiography, Computed Tomography (C.T) scan, bronchoscopy etc. A complete blood picture and histopathological examination were done. We have considered the infections/diseases as a prime risk factor in patients with multiple risk factors. The sputum and bronchoalveolar lavage was homogenized and direct microscopy was performed by using 10% KOH mount. It was inoculated on one set of Sabouraud's Dextrose Agar (SDA) [HIMEDIA, MUMBAI] plain and SDA with Chloramphenicol (0.05 mg/mL) [HIMEDIA, MUMBAI] and also on Czapek Dox agar [HIMEDIA, MUMBAI]. The inoculated SDA were incubated at 25˚C and at 37˚C. The colony morphology of obverse as well as reverse was studied.8 Tease Mount Preparation (TMP) of the mould isolated was prepared in Lacto Phenol Cotton Blue (LPCB) for identification detailed morphology including hyphae, phialides, vesicles and spores. The confirmation of fungal species was done by slide culture.9 Statistical analysis: The data were analyzed by using SPSS version 17. The descriptive analysis and chi square test were applied. The results obtained were presented by using appropriate tables and charts. RESULTS A total of 103 patients {63 (61.16%) males and 40 (38.83 %)} of various age groups with indications of chronic pulmonary infections were admitted in the wards of the Hospital during the study period as shown in Table 1 and Table 2. The chi square test is appropriate at 5% level which shows no significance among culture positive males and females while significant in age group > 40 years (Elderly). Aspergillus species have been isolated from 17 (16.5%) males and 07 (6.79%) females. The elderly patients (>40 years) had a higher incidence of pulmonary aspergillosis in males as well as females. There are 17 culture positive cases among immunocompromised and 07 cases among immunocompetent cases. Based on the data of the clinical history, the various risk factors like pulmonary tuberculosis, diabetes mellitus, HIV infection, chronic smoking, recurrent respiratory tract infections, Bronchial Asthma, Pleural effusion, environmental 93 Int J Med Res Health Sci. 2014;3(1):92-97 exposure to asbestos, cement and other chemicals are documented in Figure 1. Aspergillus fumigatus was the predominant species isolated from 13 (54.17%) cases significant by chi square test, followed by Aspergillus flavus which was isolated in 7 (29.17%) cases, 3 (12.5%) cases of Aspergillus Niger and 1 (4.7 %) case of Aspergillus terrus as depicted in Table 3 and figure 2. Table 1: Distribution of culture positive and culture negative patients on the basis of sex. SEX Culture Positive Patients Culture Negative Total P value Patients MALE 17 46 63 =1.231 FEMALE 07 33 40 P= 0.2671 TOTAL 24 79 103 Table 2: Age group of culture positive and culture negative patients. Age Group Culture Positive Culture Negative Total 0-20 YRS 21-40 YRS >40 YRS TOTAL 01 08 15 24 23 24 32 79 24 32 47 103 P value =6.92 P= 0.0314* *Significant Table 3: The incidence of Aspergillus species isolated among patients of chronic lung disease. SPECIES No. of Positive Cultures Percentage P value Aspergillus fumigatus Aspergillus flavus Aspergillus niger Aspergillus terrus 45 40 35 30 25 20 15 10 5 0 13 07 03 01 54.17% 29.17% 12.5% 4.7 % = 6.92 P= 0.0314* *Significant 42 33 31 24 22 21 15 9 3 6 3 0 1 4 1 4 2 1 total no of patients no of positive culture Fig 1: The various risk factors in the patients that may be associated with pulmonary aspergillosis Note: various patients had multiple risk factors. Prakash et al., Int J Med Res Health Sci. 2014;3(1):92-97 94 Aspergill Aspergill us terrus us niger 4% 13% Aspergill us flavus 29% Aspergill us fumigatu s 54% Fig 2: Percentage of Aspergillus species in culture positive patients. DISCUSSION Aspergillus species are common saprobic in the soil, and their vegetative spores are ever present. Generally, only immunocompromised patients or the individuals who suffer from other chronic lung conditions are susceptible. Recently, reports of invasive pulmonary aspergillosis in immunocompetent patients have increased in the clinical literature.10,11 Immunocompetent patients are generally asymptomatic and only incidentally they are found to have aspergillosis.12-14 Though, the rare cases of pulmonary aspergillosis in patients with intact immune system have been documented.11 In recent time, reports about invasive pulmonary aspergillosis in COPD patients and apparently non15-22 immunocompromized patients have been reported. In our study, the prevalence of pulmonary aspergillosis was 23.3%. The prevalence was higher than Henderson et al23 who reported an incidence of 11%, Pepy et al24 reporting 8% and Campbell and Clayton 8.2 % respectively.25 This might be due to the more exposure of the patients to the predisposing factors and environmental conditions favouring the growth of the fungus. Among the risk factors pulmonary tuberculosis, chronic smoking, bronchial Asthma, bronchogenic carcinoma was seen. Multiple risk factors were also found in patients admitted. Risk factors such as COPD, systemic corticosteroid therapy, nonhaematological malignancy, chronic renal disease, liver failure, diabetes mellitus, near-drowning, HIV infection, etc have been described in earlier studies.2629 The incidence of aspergillosis was more common in Prakash et al., males as compared to females, more in adults as compared to children which may be due to increased exposure to risk factors. Our study showed a higher incidence of Aspergillosis among immunocompromised individuals and low in immunocompetent individuals. More recently, reports have described patients with normal immunity and invasive or semiinvasive infections caused by Aspergillus species, most commonly Aspergillus fumigatus, involving the chest wall30, brain, middle ear31, and lung10,14. Methods of prompt diagnosis of pulmonary aspergillosis are based on isolation of Aspergillus in culture, serological methods and histopathological examination which is an invasive method, for which both clinicians and patients may be reluctant to undertake. The culture was positive in 24 (23.3%) samples. Aspergillus fumigatus was the predominant species isolated in 13 (54.17%) cases which is in line with the findings of Bordane et al and Shahid et al.32, 33 The other species isolated were Aspergillus flavus, Aspergillus niger and Aspergillus terrus in 7 (29.17%), 3 (12.5%), and 1 (4.7 %) cases respectively. CONCLUSION Finding of Aspergillus species in respiratory tract samples in the patients should not be routinely discarded as colonization, even if the patients are immunocompetent[27]. It is concluded from the present study that the prevalence of pulmonary Aspergillosis in immunocompromised as well as immunocompetent patients is rising in our country; hence, any patient of chronic lung infection not responding to regular antibiotic therapy should be investigated for infection by Aspergillus. Any indication of aspergillosis, by positive sputum culture, serological tests, should compel the physician to initiate anti-fungal treatment. ACKNOWLEDGMENT We would like to express our special thanks to our teachers who made us capable to do this wonderful project which also helped us to gain the knowledge from experience. Secondly, we would also like to thank Miss Vandana Thakur and other technicians who helped us to carry out our work smoothly. Thanks again to all who helped us. Disclaimer: None Int J Med Res Health Sci. 2014;3(1):92-97 95 REFERENCES 1. Randhava HS. Mycology Respiratory and systemic mycoses: an overview. Indian J Chest Dis Allied Sci. 2000; 42(4):207-19 2. Chander J. Superficial Cutaneous Mycosis. Textbook of Medical Mycology. 2nd ed. Mehta Publishers, New Delhi, India; 2009. p.p. 272-73 3. Roselle GA, Kaufmann CA. Invasive pulmonary aspergillosis in a non immunocompromised patient. Amer J Med Sci. 1978;276:357-61 4. Emmons RW, Able ME, Tenenberg DJ, Schachter J. Fatal pulmonary psittacosis and aspergillosis: case report of dual infection. Arch Int Med. 1980;140:697-98 5. Ng TT, Robson GD, Denning DW. Hydrocortisone-enhanced growth of Aspergillus spp: implications for pathogenesis. Microbiology. 1994;140:2475-79 6. Kampmeier RH, Block HA. Pulmonary aspergillosis in association with bronchial carcinoma. Amer Rev Tuberc. 1934; xxxv: 315 7. Villar TG, Cortez Pimental J, Freitas M, Costa E. The tumour like forms of Aspergillosis of the lung (Pulmonary Aspergilloma). Thorax. 1962;17:2238 8. Fisher F, cook N. Superficial mycosis and Dermatophytes in Fundaments of Diagnostic Mycology. W.B. Saunders company.1998; 330331 9. Procop GW, Roberts GD. Laboratory Methods in Basic Mycology. In: Bailey and Scott's Diagnostic Microbiology 10th edition, Belly A. Forbes, Daniel F. Sahm, Alice S. Weissfeld (eds) Mosby (1998) pp. 953. 10. Karam GH, Griffin FM, Jr. Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts. Rev Infect Dis.1986;8:357– 63 11. Clancy CJ, Nguyen MH. Acute communityacquired pneumonia due to Aspergillus in presumably immunocompetent hosts: clues for recognition of a rare but fatal disease. Chest. 1998;114:629–34 12. Aquino SL, Kee ST, Warmock ML, Gamsu G. Pulmonary aspergillosis: imaging findings with pathologic correlation. AJR Am J Roentgenol 1994;163:811-15 Prakash et al., 13. Miller WT. Aspergillosis: a disease with many faces. Semin Roentgenol 1996;31:52-66 14. Sobonya RE. Fungal diseases including allergic bronchopulmonary aspergillosis. In: Thurlbeck WM, Churg AM, editors. Pathology of the lung. 2nd ed. New York, NY: Thieme Medical Publishers; 1995:303-32 15. Blot SI, Vandewoude KH, Colardyn FA. Evaluation of outcome in critically ill patients with nosocomial enterobacter bacteremia: results of a matched cohort study. Chest. 2003;123:1208–13 16. Groeneveld AB, Tran DD, van der Meulen J, Nauta JJ, Thijs LG. Acute renal failure in the medical intensive care unit: predisposing, complicating factors and outcome. Nephron. 1991;59:602–10 17. Noble JS, MacKirdy FN, Donaldson SI, Howie JC. Renal and respiratory failure in Scottish ICUs. Anaesthesia. 2001;56:124–29 18. Fisher JR, Conway MJ, Takeshita RT, Sandoval MR. Necrotizing fasciitis. Importance of roentgenographic studies for soft-tissue gas. JAMA. 1979;241:803–06 19. Lewis M, Kallenbach J, Ruff P, Zaltzman M, Abramowitz J, Zwi S. Invasive pulmonary aspergillosis complicating influenza A pneumonia in a previously healthy patient. Chest. 1985;87:691–93 20. Pittet D, Huguenin T, Dharan S, Sztajzel-Boissard J, Ducel G, Thorens JB etal., Unusual cause of lethal pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1996;154:541–44 21. Bulpa PA, Dive AM, Garrino MG, Delos MA, Gonzalez MR, Evrard PA, Glupczynski Y, Installe EJ. Chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis: benefits of intensive care? Intensive Care Med. 2001;27:59–67 22. Karam GH, Griffin FM. Invasive pulmonary aspergillosis in nonimmunocompromised, nonneutropenic hosts. Rev Infect Dis. 1986;8:357– 63 23. Henderson AH, English MP, Veeht RJ. Pulmonary Aspergillosis: A survey of its occurrence in the patients with chronic lung diseases and a discussion of the significance of diagnostic tests. Thorax. 1968;23:513-21 Int J Med Res Health Sci. 2014;3(1):92-97 96 24. Pepys J, Riddel RW, Citron KM, Clayton YM, Short EL. Clinical and immunological significance of Aspergillus fumigatus in sputum. Am Rev Resp Dis. 1959;80:167-180. 25. Campbell MJ, Clayton YM. Bronchopulmonary aspergillosis. Am Rev Resp Dis. 1964; 89: 186 26. Vandewoude KH, Blot SI, Depuydt P, et al. Clinical relevance of Aspergillus isolation from respiratory tract samples in critically ill patients. Crit Care. 2006;10:R31 27. Dimopoulos G, Piagnerelli M, Berre J. Disseminated aspergillosis in intensive care unit patients: an autopsy study. J Chemother 2003;15:71–75 28. Vandewoude KH, Blot SI, Benoit D, et al. Invasive aspergillosis in critically ill patients: attributable mortality and excesses in length of ICU stay and ventilator dependence. J Hosp Infect 2004;56:269–276. 29. Meersseman W, Vandecasteele SJ, Wilmer A. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004;170:621–25 30. Fisher MS. Case report 750: aspergillosis of the chest wall in an apparently immunocompetent host. Skeletal Radiol. 1992;21:410–13 31. Kim DG, Hong SC, Kim HJ. Cerebral aspergillosis in immunologically competent patients. Surg Neurol 1993;40:326–31 32. Bordane EJ Jr. The clinical spectrum of Aspergillosis. Part II: Classification and description. Rc Crit Rev Clin Lab Sci. 1980;13:85 33. Shahid M, Malik A, Bhargava R. Prevalence of aspergillosis in chronic lung diseases. IJMM 2001; 19(4): 201-205. Prakash et al., Int J Med Res Health Sci. 2014;3(1):92-97 97 DOI: 10.5958/j.2319-5886.3.1.020 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Received: 7th Dec 2013 Research article Coden: IJMRHS Copyright @2013 ISSN: 2319-5886 th Revised: 19 Dec 2013 Accepted: 21st Dec 2013 SOCIODEMOGRAPHIC PROFILE OF SPEECH AND LANGUAGE DELAY UP TO SIX YEARS OF AGE IN INDIAN CHILDREN *Abraham Binu1, Raj Sunil1, Stephenson Baburaj2, Mohandas MK2 1 Assistant Professor, 2Professor, Department of Pediatrics, Dr SMCSI Medical College, Trivandrum, Kerala *Corresponding author email:
[email protected] ABSTRACT Background: Speech and language is the most important skill for the child’s development and scholastic performance. Awareness of the delay is important in the programs for early identification. Purpose: to assess the prevalence of speech and language delay in children from age group 0 to six years of age. Methodology: The speech and language development of children coming in the well baby clinic and daily pediatric clinic of age group from birth to 6 years were evaluated using Language Evaluation Scale Trivandrum (LEST). The prevalence of speech and language delay in each age group was calculated and also analyzed in the sociodemograhic profile. Results: A total of 102 children were studied in which 13.7% had language delay. 18% had questionable language delay and 15.7% had suspect language delay. Though among language delay mixed type was more, children had more difficulty in doing expressive items. Language delay was also found to be more prevalent in males, single child, first born child and children of working mothers. Parental age, education or socioeconomic status was not found to be related to language delay. Conclusion: The 13.7% prevalence of language delay in the children indicates the need of early identification and for it a simple screening tool like LEST is a must during the routine evaluation of young children in pediatric clinics. Health care givers and parents should ensure that babies grow up in a language rich, nurturing and stimulating environment right from birth onwards. Key words: LEST, Language delay, Speech delay, First born child INTRODUCTION Speech and language is the most useful and most widely used form of communication. Communication is integral to overall developmental progress in young children mainly in cognitive, social – emotional and adaptive development. Speech helps the children to get attention from others, to satisfy their needs, to influence the behavior of others, to develop social relations and as they grow, it plays an important role in their academic achievements.1 Language typically develops in a very predictable fashion, and assessment of language development should be a central part of every well-child visit. Pediatricians are in an excellent position to identify children's speech and language problems early and to make appropriate referrals for further evaluation and treatment services. The children who have communication problems may develop behavior problems and difficulty to read and write later in life.2 Children’s capacity to communicate and the vocabulary power when they enter preschool are important for good scholastic performance. Children with language problems in preschool are at risk of poor educational achievement in school age and are at increased risk to develop emotional and 98 Abraham et al., Int J Med Res Health Sci. 2014;3(1): 98-103 behavioral disorders.3 Early intervention may prevent or decrease the severity of language delays in school age and increase later academic success in school. To underline this fact, there is increasing number of evidences coming up that intervention given or started during infancy or preschool age has a greater positive effect than services provided at school age.4 The language development of a child may be a good marker of developmental delay. Delay in acquiring language development is often an early indicator of pervasive developmental problems and future learning disability. This indicates the need for assessment of all babies less than 2 years. This study is planned to evaluate the prevalence of language and speech delay in children from birth to 6 years of life as preschool years are the most ideal time for the early identification of communication delay which will help to start the early intervention. It will also be useful to evaluate the prevalence of expressive and receptive type of delay among the children which help to focus our attention to that part. This study also tries to evaluate the communication delay in the context of maternal and paternal education and occupational status. There is a scarcity of studies involving all these factors. So this study is aimed to involve all these factors which will help to know the multiple factors influencing the language and speech development. Aims and Objectives: The aim of the present study was to assess the speech and developmental outcomes in children from age group 0 to six years. The objectives were to find the prevalence of speech and language delay in children from age birth to six years of age and to find the sociodemographic characteristics associated with it. MATERIALS AND METHODS The Study was conducted by Department of Pediatrics after getting ethical clearance from the institutional ethical committee of Dr SMCSI Medical College, Trivandrum, Kerala, also taken informed consent from parents. Study design: A descriptive study of cross sectional design. Study population: The children attending well baby clinic and daily pediatric clinic of a tertiary care centre, Dr SMCSI Medical College, Karakonam of age group birth to six years. Considering the prevalence of developmental delay as 6.6%(p) as per the study done by Nair MKC et al5, margin of error at 5%(m), confidence level as 95%(t=1.96), the minimum sample size is estimated to be 102 using the formula t2xp(1-p)/m2 Selection of cases: The inclusion criteria consist of children in the age group 0-6 years coming in the outpatient and well baby clinic of Pediatric Department for routine checkups, minor illnesses and also for vaccination. Those children with severe sickness and those with developmental delay in other domains like gross motor, fine motor and social were excluded. Tools for the study The study is done by using a performa consisting of the socio demographic parameters like age, sex, family order, living with parents or not and sibling details. Details of paternal age, education and occupation are assessed. The socioeconomic class is assessed using Modified Kuppuswami Scale.6 Maternal details of age; education and occupational status as house wife or working mother were also assessed. The speech and language assessment is done using Language Evaluation Scale Trivandrum (LEST) which was developed by Child Development Centre, 7 Trivandrum . Other tests are Receptive Expressive Emergent Language Scale (REELS) and Early Language Milestone Scale (ELM Scale 2).7 But LEST is a culturally appropriate locally relevant simple language development screening tool which can be used both to professionals, those who are working in the field of child development and even with the mothers to pick up speech delay in the early years of life. The assessment of language delay was done by assessing if the child is able to do all items on the left side of their corresponding age in the LEST Chart. The interpretation is done in four ways as in Table1 Table1: Interpretation of LEST7 Normal – All items done Questionable – One item not done. language delay using Suspect – Two items not done Delay – Three or more items not done The distribution of children in different age groups are calculated in 0-1 year, 1-2 year, 2-3 year, 3-4 year, 4-5 year and 5-6 years and the speech and language developmental pattern was assessed in these age 99 Abraham et al., Int J Med Res Health Sci. 2014;3(1): 98-103 groups. The prevalence speech and language delay was calculated as normal, questionable, suspect and delay which were the outcome variables. Each item is compared in the sociodemographic schedule with different age groups. The type of delay was also assessed as expressive, receptive or mixed type. The delays were compared with different age groups. Statistical analysis: Mean, standard deviation and Student t tests were used for analysis of continuous variables and Chi Square test was used for categorical variables. A p value below or equal to 0.05 was considered to be statistically significant for a 95% Confidence Interval. The Statistical software SPSS 16.0 was used for the analysis of the data and Microsoft Excel was used to generate tables. RESULTS The study was conducted in children attending the well baby and pediatric clinics of Department of Pediatrics, Dr SMCSI Medical College Trivandrum, Kerala. A total of 102 children were assessed for the study in which 49(48%) were females and 53(52%) were males and the difference was not statistically significant (P value 0.73). Depending on the age of children they were divided into 6 groups 0-1 year, 1-2 year, 2-3 year, 3-4 year, 4-5 year and 5-6 years. Among the 102 children studied, the total percentage of children with language delay was 13.7%. 15.7% children were in the suspect and 18 % were in the questionable group. The prevalence of language delay in each age group is given in table 2 Among the total 14 of 102 children who had language delay, 10.8% children were having a mixed type of delay, 1% was having receptive and 2% were having an expressive type of delay. Regarding the type of items children could not do during assessment, 20% had difficulty in doing both items. Comparing expressive and receptive type of language items individually, 16% could not do expressive items only compared to 9.1% who could not do receptive items only. This shows that children had more difficulty in doing expressive items. The percentage of males having delay were found to be more compared with that of females (15.1% males with 12.2% females) and the difference was not found to be statistically significant (p value 0.67). The sub analysis of children with language delay according to delay, questionable and suspect group is given in table 3. Table 2: Language delay in each age group Age Group (yr) Normal (%) Questionable (%) Suspect (%) Delay (%) Total 0-1 14(70.0) 4(20.0) 1(50) 1(5) 20 1-2 11(52.4) 6(28.6) 3(14.3) 1(4.8) 21 2-3 7(46.7) 1(6.7) 3(20) 4(26.7) 15 3-4 6(40) 3(20) 3(20) 3(20) 15 4-5 7(43.8) 2(12.5) 4(25) 3(18.8) 16 5-6 9(60) 2(13.3) 2(13.3) 2(13.3) 15 Total 54(52.9) 18(17.6) 16(15.7) 14(13.7) 102 Table 3: Gender related variation in language delay Sex Normal (%) Questionable (%) Female 30(61.2) 6(12.2) Male 24(45.3) 12(22.6) Total 54(52.9) 18(17.6) The majority of the children were of the first order which was 67 (61.8%). Of the rest, 37 children (36.3%) were 2nd order. Language Delay was found to be more prevalent among the first born child in this present study. 17.5% delay was seen in the first child compared to 8.1% seen in the second born child. Language delay was found also to be more prevalent Suspect (%) 7(14.3) 9(17) 16(15.7) Delay (%) 6(12.2) 8(15.1) 14(13.7) Total 49 53 102 in the single child in the family. 17.3% of 52 single children were having delay compared to 10% of 50 children who were not single kids in the family and it was significant (p value -0.033) In the present study no association could be made with the parental age and language delay. Among the 14 children with language delay, fathers of half children 100 Abraham et al., Int J Med Res Health Sci. 2014;3(1): 98-103 had passed 10th class and other half were degree holders. Similarly of those 14 children, 5 mothers had passed 10th class and 9 mothers were degree holders. This shows that all the parents of children with language delay were educated. It has been found that among the children of house wife mothers’, 4 children (11.2%) had language delay. But among the children of working mothers’, 10 children (30.8%) had language delay. Among the 14 children who had language delay, 11 children were living with parents. For 2 children their fathers were not in the state and for one child, both parents were not in the state. No association could be made about the language delay in children not living with both their parents as the number of children in those groups was very less. The socioeconomic class grading was also done among the children studied using Modified Kuppuswami Grade and the socioeconomic class of the children with language delay was analyzed and shown in table 4. Table 4: Socioeconomic class and language delay Social No Delay Delay Total Class (%) Present (%) Class 1 1(100) 1 Class 2 19(86.4) 3(13.6) 22 Class 3 50(86.2) 8(13.8) 58 Class 4 17(85) 3(15) 20 Class 5 1(100) 1 Majority of children belonged to 2, 3 and 4 socioeconomic grades. No significant association was seen with lower or higher socioeconomic class and language delay. DISCUSSION A cross sectional study in 102 children was conducted using Language Evaluation Scale Trivandrum (LEST 0-6) from the age group birth to 6 years of age to find out the prevalence of language and speech delay. The total percentage of children with language delay was 13.7. In the study done by Nair MKC et al5, 6.6 % of language delay was observed for the age group 0-12 months using LEST against 4% prevalence for the same using Receptive Expressive Emergent Language Scale (REELS). In the present study it was 5% below 1 yr age was comparable. For the age group 13 to 24 months, the study done by Nair MKC et al5, prevalence of speech and language delay among at risk babies was 29.7% using LEST as Abraham et al., against 6.6% by using REELS and 5.7% using both tests. In the present study it was found to be 4.8%. The difference may be due to the factor that in the present study the babies coming to the well baby clinic were observed and at risk babies were not included in the study. In a study done by James et al in 1980 the speech and language delay in the age group 0 to 2 years was around 5%8. In the present study, it was 4.87% which was comparable. For the age group 2-3 years, the speech and/or language delay was 6.9% in the study done by Burdon et al, it was 6.9%9. The language delay was 2.6 % in the study done by Silva et al in 1983.10 But in the present study it was 26.7% which was significantly higher that the other studies. For the age group 3-4 years, in the study done by James et al the speech or / and language delay was 5%.6 In our study it was 20% which was higher. For the age group 5-6 years, in the study by Beitchman et al, the speech and/or language delay was 11.78%.11 In another study by Stevenson et al it was 6.8%.12 In the present study the speech delay was 13.3% which can be compared to the study done by Beithchman et al. In a study done by Nair MKC et al5 in children of age 13 to 24months, 24% had a language delay in the receptive area using LEST as against 5.1% using REELS. Similarly 42% had a language delay in expressive area by using LEST as against 7.4% using REELS. In the study done by James et al the mixed language delay was 2.14%8, expressive delay was 4.27% and receptive delay was 3.95%. In the present study the mixed language delay was found to be more. Among the items not done by children in our study, 16% could not do expressive items and 9.1% could not do receptive items. This showed that children have more difficulty in doing the expressive items. In the study done by Nair MKC et al5 in children of age 13 to 24months, 24% had delay in the receptive language and 42% had delay in expressive language by using Language Evaluation Scale Trivandrum (LEST). In the study done by Tomblin13 et al 87% of children with articulation disorders were boys and in the study done by Choudhary et al 70% of the children were males.14 In the present study though the number of males with language delay was more (57%), the difference was not significant. In the study done by Broookerhouser et al15 children born late in family birth order was a significant factor 101 Int J Med Res Health Sci. 2014;3(1): 98-103 for language delay. In another study by Nelson et al single child in the family was also found to be a factor.16 In the present study also first born children had a more language delay. Similarly a single child in the family was also found to be a significant factor. In the study done by Nelson et al, older parents and younger mother age was found to be a significant factor16. From the present study no such association could be made with parental age. The study done by Campell et al showed an association between lower maternal education and language delay.17 The systematic evidence review done by Nelson et al also showed similar picture.. Another study done by Tallal et al also showed an association between lower paternal education level and language delay.18 This study does not support that fact and all the parents of the children were educated. Children of house wife mothers had significantly less language delay than children of working mothers. Similarly those living with both the parents had less delay but the difference were not significant. In the study done by Tallal et al18 lower socioeconomic class was a risk factor for language delay. In our study there was no significant association between socioeconomic status and language delay. CONCLUSION The study showed that language delay was more prevalent in below 2 years of age, in first born child and single child in the family. This reveals the importance of early screening and the importance of the stimulation they get from the whole family. The language development does not depend on the age, educational or socioeconomic status of the parents but the quality time the care givers spend with the child. The prevalence of 13.7% speech and language delay in the normal children enlightens the need for early screening programs. Because communication is central to personal development, social interaction and learning ability of child, delay in the language and speech development should be identified as early as possible. Health workers should make sure that the babies are growing in a language rich environment and parents should be educated about it as well. ACKNOWLEDGEMENT The authors are very thankful to the Department and Management of Dr SMCSI Medical College for their generous support and encouragement during the period of study. The authors also acknowledge Mr Sanu Johnson for computer work and Mrs Deepa S Mony for her contribution in data collection. REFERENCES 1. Elizabeth B Hurlock. Child Development. 6th Edition, Tata McGraw Hill Publishers: 1942;13549 2. Backer l, Cantwell D. A prospective psychiatric follow up of children with speech/language disorder. Journal of the American Academy of child and Adoslescent psychiatry.1987; 26 :546-53 3. Prizant B. Communication disorders and emotional /behavioural disorders in children. Journal of Speech and Hearing Disorders.1990;55:179-92 4. Barnett W, Escobar C. Economic costs and benefits of early intervention, Hand book of early childhood Intervention,3rd Edn, In SJ Meisels & J P Shoukoff:1990; 560-82 5. Kavitha SR, Nair MKC. Validation of LEST (1-2 years) against REELS Language Evaluation Scale Trivandrum (1-2 Research Form 2006) Against Receptive Expressive Emergent Language Scale. Teens .2006; 1(2):29-31 6. Sushama Bai S. History taking. Clinical Evaluation of New borns, Infants and Children 2nd Edition. Jaypee Brothers Medical Publishers. 2009; Chapter 3:13 7. MKC Nair ,GS Harikumaran Nair, AO Mini, S Indulekha,S Letha and PS Russel.Development and Validation of Language Evaluation Scale Trivandrum for Children Aged 0-3 years - lest (03). Indian Pediatr. 2013;50:463-67 8. James Law, James Boyle. Francis Harris. Prevelance and natural history of primary and language delay: findings from a systematic review of literature. Int J Lang Comm Dis. 2000;35(2): 169-72 9. Burden V, Stott CM, Forge J, Goodyer I. The Cambridge Language and Speech Project (CLASP): I. Detection of language difficulties at 36 to 39 months. Dev Med Child Neurol. 1996;38:613–31 10. Silva PA, Williams SM, McGee R. A longitudinal study of children with developmental language delay at age three: later intelligence, reading and behaviour problems. Developmental Medicine and Child Neurology. 1987;29:630–40 102 Abraham et al., Int J Med Res Health Sci. 2014;3(1): 98-103 11. Beitchman JH, Nair R, Clegg M. Prevalence of psychiatric disorders in children with speech and language disorders. J Am Acad Child Adolesc Psychiatry 1986; 25: 528-35 12. Stevenson J. Developmental changes in the mechanisms linking language disabilities and behaviour disorders. In JH Beitchman, Cohen NJ, Konstantareas MM, Tannock R. Language, Learning and Behavior Disorders: Developmental, Biological and Clinical Perspectives Cambridge University Press;1996;5th edition:234-45 13. Tomblin JB, Smith E, Zhang X. Epidemiology of specific language impairment: prenatal and perinatal risk factors. Journal of Communication Disorders.1997;30:325–44 14. Choudhury N, Benasich AA. A family aggregation study: the influence of family history and other risk factors on language development. J Speech Lang Hear Res. 2003;46:261–72 15. Brookhouser PE, Hixson PK, Matkin ND. Early childhood language delay: the otolaryngologist’s perspective. Laryngoscope. 1979;89:1898–13 16. Nelson HD, Peggy Nygrien, Miranda Walker, Rita Panoscha. Screening for speech and language delay in preschool children: systematic evidence review for the US Preventive Services Task Force. Pediatrics. 2006;117(2):301-02 17. Campbell TF, Dollaghan CA, Rockette HE. Risk factors for speech delay of unknown origin in 3year-old children. Child Dev. 2003;74:346–57 18. Tallal P, Ross R, Curtiss S. Familial aggregation in specific language impairment. J Speech Hear Disord. 1989;54:167–73 103 Abraham et al., Int J Med Res Health Sci. 2014;3(1): 98-103 DOI: 10.5958/j.2319-5886.3.1.021 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 8 Dec 2013 Revised: 18th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 21st Dec 2013 URIC ACID AND HYPERTENSION: DOES URIC ACID LICK THE JOINTS AND BITES THE HEART? * Vittal BG1, Bhaskara K2, Naveenkumar GH3 1 Associate Professor of Biochemistry, 2 Associate Professor of Orthopaedics, 3 Assistant Professor of Community Medicine, Bidar Institute of Medical Sciences, Bidar, Karnataka, India * Corresponding author email:
[email protected] ABSTRACT Background: Uric acid a metabolic end product of purine degradation is implicated in gout as aetiology. Its increased levels have also been associated with hypertension, cardiovascular morbidity and mortality. Few studies have been conducted, especially in India to elucidate association of uric acid with prehypertension. Aims: This study intends to assess the association of serum uric acid levels with blood pressure in normotensive, prehypertensive and hypertensive population. It also intends to check whether there is an incremental rise of serum uric acid with increasing blood pressure. Material and methods: Two hundred outpatients who met inclusion and exclusion criteria and consented formed study population. Blood pressure of each participant was measured followed by venipuncture to collect venous blood for measurement of serum uric acid. Participants were categorised into 4 groups as Normal, Prehypertension, Hypertension –Stage 1, Hypertension Stage -2 as per Joint National Committee 7 classification. Data was analysed to know levels of serum uric acid among the four categories and to verify association of uric acid with blood pressure. Results and Conclusions: Stepwise increase in serum uric acid levels was observed along with increasing blood pressure. Strong positive linear correlation was observed between serum uric acid levels and mean blood pressure (Pearson’s correlation coefficient r = 0.74; p< 0.0001). Uric acid was associated (r = 0.442) with blood pressure in prehypertension population. Serum uric acid levels are associated with prehypertension and hypertension and are independent and strong predictors of cardiovascular mortality. Keywords: Blood pressure, Prehypertension, Uric acid. INTRODUCTION Uric acid is an end product of purine degradation in humans and is primarily excreted through urine. Serum uric acid levels are regulated by dietary purine intake, endogenous metabolism of purines, and its urinary excretion rate. In the process of evolution 15 million years ago, two mutations rendered uricase gene non-functional in humans and great apes. Consequently uric acid is not converted to readily water soluble and easily excreted product allantoin, thus resulting in higher serum uric acid levels in humans and great apes.1 Vittal et al., As early as in 1848 AD, Sir Alfred Garrod demonstrated that Gout, an inflammatory disease of joints was associated with Hyperuricemia i.e, increased levels of serum uric acid (>7mg/dl in males and >6mg/dl in females).2 Gout is a disease of joints characterised by the deposition of monosodium urate crystals in joint space causing inflammation and painful joints. A few years later, in 1874 AD, Frederick Mohamed postulated for the first time that “People with high blood pressure belong to gouty families” suggesting Int J Med Res Health Sci. 2014;3(1):104-109 104 the possible association of Hyperuricemia with high blood pressure. 3 Association of elevated serum uric acid with hypertension was further reported by many researchers. At the end of the 19th century many studies demonstrated that uric acid was also associated with cardiovascular morbidity. However, lack of possible mechanism by which hypertension and uric acid are associated led to conclusion that uric acid is not a true risk factor for cardiovascular disease. 4-9 Amidst contradicting reports, Mohamed’s hypothesis that uric acid has a causative role in hypertension remains controversial even after over 130 years. Recent animal studies and clinical observations indicate the possible direct causal role of uric acid in pathogenesis of hypertension by various 10 mechanisms. Of late, increasing evidence is being gathered suggestive of association and causal role of uric acid in hypertension and cardiovascular morbidity. 11 Hitherto studies conducted have not assessed the association of serum uric acid levels blood pressure in prehypertensives and its incremental rise with increasing blood pressure. So in this study we intend to assess the association of serum uric acid levels with blood pressure in normotensive, prehypertensive and hypertensive participants. We also intend to check whether there is an incremental rise of serum uric acid with increasing blood pressure. MATERIALS AND METHODS Our study was conducted at Regional Diagnostic Laboratory of District Hospital, Bidar, a teaching hospital affiliated to the Bidar Institute of Medical Sciences, Karnataka, India. Study spanned over a period of 3 months from August to October 2013. Institutional Ethical committee approval was taken before commencement of study and our procedures were in accordance with the Helsinki Declaration of 1975, as revised in 2000.12 The subjects for this prospective study were outpatients who visited regional diagnostic laboratory for routine investigations. Two hundred participants (103 men and 97 women) of age group 20 to 60 years formed the study population. Subjects who fulfilled below mentioned inclusion and exclusion criteria were informed and explained about the study and after their informed written consent were included in the study. Vittal et al., Inclusion and exclusion criteria: Paediatric and psychiatric patients, pregnant women, diagnosed cases of essential secondary hypertension, medications like uricosuric drugs and antihypertensive drugs were excluded in the study. Study participants were made to sit comfortably on a chair for five minutes. Systolic and diastolic blood pressures were measured twice by auscultatory method with a mercury sphygmomanometer (cuff size, 12.5 x 40 cm) on the right arm. The first and fifth phases of Korotkoff’s sounds were taken as the criteria for SBP and DBP respectively. The mean of two consecutive readings was recorded and used for analysis.13 Mean of systolic and diastolic blood pressure was calculated (SBP+DBP/2) and noted as mean blood pressure. As per Joint National Committee (JNC)7 classification of blood pressure, Participants were categorised as normal if systolic blood pressure (SBP) was <120mm of Hg and Diastolic blood pressure (DBP) was <80mm of Hg; prehypertensive if SBP/DBP is 120-139/or 8089 mm of Hg; Stage 1 Hypertensive if SBP/DBP is 140-159/or 90-99mm of Hg and were categorised as Stage 2 hypertensives if SBP/DBP is ≥160/or ≥100 mm of Hg.14 Under aseptic precautions, venipuncture was performed on median cubital vein and 2ml of blood was collected into a sterile evacuated plastic tube with red stopper with no additives. Blood samples were allowed to clot at room temperature for 30 minutes. Samples were centrifuged at 1500g for 15 minutes for serum separation.15 Serum uric acid levels were measured by modified Trinder’s method16, 17 using ERBA XL 300 fully automated analyser. To ensure quality, daily internal quality control samples were run and day to day coefficient of variance (CV) was <5%. The laboratory also had an external quality assurance programme in place. Statistical Analysis: Statistical analysis of participant data was performed using “IBM SPSS Statistics 20” software. The data was analysed to measure age-sex distribution of participants, to categorise participants as normal, prehypertension, Stage-1 hypertension and stage-2 hypertension along with their mean blood pressures and mean serum uric acid levels. Pearson’s correlation coefficient was calculated to elucidate the statistically significant association between serum uric acid levels and blood pressure.18 Int J Med Res Health Sci. 2014;3(1):104-109 105 RESULTS Characteristics of study population: The demographic characteristics of the study population are summarised in table 1. Study population comprised of 200 participants of whom 103 were men and 97 were women.. Table: 1. Age sex distribution of study population with mean blood pressure Age (years) Number of Males Number of females 20 - 30 35 44 31 - 40 14 14 41 - 50 17 15 51 - 60 37 24 * mean ± standard deviation Blood pressure* (mm of Hg) 98.08 ± 9.09 101.96 ± 13.13 107.21 ± 14.27 112.23 ± 12.69 Mean age of the study population was 40.06±13.8 years and mean age of males and females was 41.98 ± 13.48 years and 38.03 ± 13.91 years respectively. The mean blood pressure of study population showed an increasing trend with age The prevalence of undiagnosed hypertension in population was 22% (n = 44) and of undiagnosed prehypertension was 42% (n = 84), put together comprising nearly 65% of study population. A stepwise increase in serum uric acid levels was observed when study population was categorised into four groups namely, Normal, Prehypertension, Hypertension stage-1, Hypertension stage-2 based on the JNC 7 classification of blood pressure. Similar increasing trend in mean serum uric acid level was observed along with mean blood pressure of the study population. (Table-2) Table: 2. Serum uric acid and blood pressure in normotensives, prehypertensives and hypertensives JNC 7 BP classification14 Serum Uric acid* Blood Pressure* (mm Males Females (SBP/DBP mm of Hg) (mg/dl) of Hg) Normal 30 42 5.09 ± 0.65 92.95 ± 4.7 (<120/ and <80) Prehypertension 47 37 5.70 ± 0.73 104.08 ± 5.21 (120-139/ or 80-89) Hypertension Stage-1 18 14 6.81 ± 0.77 119 ± 6.94 (140-159/ or 90-99) Hypertension Stage-2 8 4 7.59 ± 0.57 136.41 ±6.86 (≥160/ or ≥ 100) * mean ± standard deviation Statistically highly significant (p<0.0001) difference in mean serum uric acid was observed between normal and prehypertension categories; and also between prehypertension and hypertension stage-1 JNC 7 categories. Similar but less profound, statistically significant difference (<0.01) was noted between Stage-1 and Stage-2 hypertension categories. A strong positive linear correlation was observed between serum uric acid levels and mean blood pressure (Pearson’s correlation coefficient r = 0.74). Correlation is highly significant at the 0.05 level (2tailed) and the P-value is < 0.0001. (Figure 1). Similar correlation was also noted between serum uric acid and systolic blood pressure (r = 0.746) and diastolic blood pressure (r = 0.609). Uric acid was associated strongly (r = 0.442) with blood pressure in the prehypertension population while a weak correlation (r = 0.113) was observed in normal population. Vittal et al., Fig 1: Scatter diagram showing correlation of serum uric acid levels with mean blood pressure. DISCUSSION Our prospective study consisting of 200 participants showed an association of serum uric acid with blood pressure in apparently healthy individuals, undiagnosed prehypertensive subjects and Int J Med Res Health Sci. 2014;3(1):104-109 106 hypertensive individuals. This is the first study conducted in India to elucidate the association of serum uric acid levels with blood pressure in prehypertensive population. Study population comprised of adult individuals from 20 years to 60 years. Mean age of the study population was 40.06±13.8 years comparable to other similar studies that had a mean age of 42.3±0.2 years19 and 41.6 years.20 Although known hypertensive patients were excluded from the study, 22% (n = 44) of participants were hypertensivses and 42% (n = 84) were prehypertensives. Similar prevalence of 21 prehypertension (39%) among adults in India and Unitesd states of America22 was reported by separate researchers. It is noteworthy that, a large percentage of the population who are at risk of developing hypertension (42%) and undiagnosed hypertensives (22%) who may develop cardiovascular morbidity go unnoticed. Serum uric acid levels were positively (r = 0.740) and significantly (p < 0.0001) associated with blood pressure in our study. A similar positive and statistically significant correlation was observed by other researchers. 19, 20, 22, 23 A stepwise incremental rise of serum uric acid was observed with increasing blood pressure when participants were categorised as per JNC7 classification as normal, prehypertension, hypertension stage-1, and hypertension stage-2. A similar incremental increase of uric acid was observed in a cross sectional study conducted in Japan. However this study categorised the participants based on Japanese society guidelines JSH-2009 rather than JNC 7 classification.19 A similar association (r = 0.15; p < 0.001) was demonstrated by a study on large prospective male cohort. They also demonstrated that serum uric acid was independently related to mortality from congestive heart failure and stroke. 20 Positive association (r = 0.32) of serum uric acid with prehypertension independent of smoking BMI and other confounding factors was observed in a study.22 A study demonstrated significant (p < 0.0001) correlation between uric acid and prehypertension in adults but the study also noted, unlike our study, that the association was not statistically significant in older individuals over 65 years of age. 23 Vittal et al., In a nine year follow-up study, association of serum uric acid with incident hypertension was observed and stronger association was noted among blacks. 24 PIUMA study, with a cohort of 1720 patients with follow-up of 12 years noted that, subjects with higher uric acid levels were at higher risk of developing cardiovascular events (relative risk 1.73; 95% confidence interval) than the subjects with lower uric acid levels. 25 A study on 125 children (age group 6-18 years) with primary hypertension demonstrated the association of serum uric acid with systolic blood pressure (r = 0.80) and diastolic blood pressure (r = 0.66). 26 Another study in paediatric age group also observed the association of serum uric acid levels with ambulatory diastolic blood pressure (r = 0.29; p = 0.0033). 27 Serum uric acid has long been associated with hypertension, the primary aetiology of cardiovascular morbidity. Several large cohort studies have demonstrated that serum uric acid was predictive of mortality due to ischaemic heart diseases in women. 28 Few studies demonstrated the independent and significant association of uric acid with risk of cardiovascular mortality29 and myocardial infarction. 30 It was observed in a study that serum uric acid level was a strong and independent predictor of cardiovascular mortality in middle aged men. 31 Increased serum uric acid levels have been associated with elevated blood pressure and cardiovascular morbidity and mortality. But the causal role of uric acid in hypertension and pathogenesis of cardiovascular events has not been clear. 5- 9 Recent studies have elucidated the plausible mechanisms that explain how elevated uric acid causes hypertension. Studies on animal models have shown that increased uric acid levels cause renal microvascular and tubular interstitial injury. Uric acid also increases juxtaglomerular renin production and decreases nitric oxide synthase expression in macula densa; collectively contributing to blood pressure elevation.10 CONCLUSION Serum uric acid levels are associated with hypertension and are independent and strong predictors of cardiovascular mortality, myocardial infarction and coronary artery diseases in both sexes of different ethnic groups. So it may not an exaggeration Int J Med Res Health Sci. 2014;3(1):104-109 107 to state that “Uric acid licks the joints and bites the heart” Limitations of the study: The study population was drawn from outpatients of a hospital that may not form a representative sample of the general population. Confounders like serum creatinine, serum uric acid, serum albumin, history of alcohol intake, and dietary protein and sodium consumption that alter serum uric acid and /or blood pressure were not taken into consideration. REFERENCES 1. Wu X, Muzny DM, Lee CC, Caskey CT. Two independent mutational events in the loss of urate oxidase during hominid evolution. J Mol Evol. 1992;34:78–84 2. Garrod A. Observations on the blood and urine of gout, rheumatism and Bright’s disease. Medical Chirurgical Transactions 1848; 31:83 3. Mohamed F. On chronic Bright’s disease, and its essential symptoms. Lancet 1879; 1:399–401. 4. Heinig M, Johnson RJ. Role of uric acid in hypertension, renal disease, and metabolic syndrome. Cleve Clin J Med. 2006; 73 (12): 105964 5. Kanbay M, Solak Y, Dogan E, Lanaspa MA, Covic A. Uric acid in hypertension and renal disease: the chicken or the egg? Blood Purif. 2010;30(4):288-95 6. Mazzali M, Kanbay M, Segal MS, Shafiu M, Jalal D, Feig DI, Johnson RJ. Uric acid and hypertension: cause or effect? Curr Rheumatol Rep. 2010;12 (2): 108-17 7. Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, etal., Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003; 41 (6): 1183-90. 8. Feig DI, Mazzali M, Kang DH, Nakagawa T, Price K, Kannelis J, Johnson RJ. Serum uric acid: a risk factor and a target for treatment? J Am Soc Nephrol. 2006; 17 (4 Suppl 2): S69-73. 9. Feig DI. The role of uric acid in the pathogenesis of hypertension in the young. J Clin Hypertens (Greenwich). 2012 Jun; 14 (6): 346-52. 10. Hwu CM, Lin KH. Uric acid and the development of hypertension. Med Sci Monit. 2010; 16 (10): RA224-30. Vittal et al., 11. Johnson RJ, Feig DI, Herrera-Acosta J, Kang DH. Resurrection of uric acid as a causal risk factor in essential hypertension. Hypertension. 2005; 45 (1): 18-20. 12. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects accessed from http://www.wma.net/en/30publications/10policies/ b3/ on 20.12.2013. 13. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN etal., Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation. 2005;111 (5): 697-716. 14. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (Internet) (updated 4 December 2013) available from http://www.nhlbi.nih.gov/guidelines/hypertension/ jnc7full.pdf 15. CLSI. Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays: Approved Guideline. 5th Ed. CLSI document H21-A5. Wayne, PA: Clinical and Laboratory Standards Institute; 2008. 16. Trinder P. Determination of blood glucose using 4-amino Phenazone as oxygen acceptor. J Clin Pathol. 1969 March; 22 (2): 246. 17. Trivedi RC, Rebar L, Berta E, Stong L. New enzymatic method for serum uric acid at 500 nm. Clin Chem. 1978; 24 (11): 1908-11. 18. Cohen J, Cohen P, West SG, Aiken LS. Applied Multiple Regression/Correlation Analysis for the Behavioural Sciences.2003;3rd ed Mahwah, NJ: Lawrence Earlbaum Associates. 19. Kansui Y, Ohtsubo T, Goto K, Sakata S, Ichishima K, Fukuhara M, Ohta Y, Matsumura K. Association of serum uric acid with blood pressure in Japanese men. Cross-sectional study in worksite group. Circ J. 2011;75(12):2827-32 20. Strasak A, Ruttmann E, Brant L, Kelleher C, Klenk J, Concin H, Diem G, Pfeiffer K, Ulmer H; Int J Med Res Health Sci. 2014;3(1):104-109 108 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. VHM&PP Study Group. Serum uric acid and risk of cardiovascular mortality: a prospective longterm study of 83,683 Austrian men. Clin Chem. 2008; 54 (2): 273-84. Gupta R, Deedwania PC, Achari V, Bhansali A, Gupta BK, Gupta A, Mahanta TG, Asirvatham AJ, Gupta S, Maheshwari A, Saboo B, Jali MV, Singh J, Guptha S, Sharma KK. Normotension, prehypertension, and hypertension in urban middle-class subjects in India: prevalence, awareness, treatment, and control. Am J Hypertens. 2013; 26 (1): 83-94. Syamala S, Li J, Shankar A. Association between serum uric acid and prehypertension among US adults. J Hypertens. 2007; 25 (8): 1583-9. Liang J, Xue Y, Zou C, Zhang T, Song H, Qi L. Serum uric acid and prehypertension among Chinese adults. J Hypertens. 2009; 27 (9): 1761-5. Mellen PB, Bleyer AJ, Erlinger TP, Evans GW, Nieto FJ, Wagenknecht LE etal., Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study. Hypertension. 2006 Dec; 48 (6): 1037-42. Verdecchia P, Schillaci G, Reboldi G, Santeusanio F, Porcellati C, Brunetti P. Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study. Hypertension. 2000; 36 (6): 1072-78 Feig DI, Johnson RJ. Hyperuricemia in childhood primary hypertension. Hypertension. 2003; 42 (3): 247-52. Jones DP, Richey PA, Alpert BS, Li R. Serum uric acid and ambulatory blood pressure in children with primary hypertension. Pediatr Res. 2008; 64 (5): 556-61. Freedman DS, Williamson DF, Gunter EW, Byers T. Relation of serum uric acid to mortality and ischaemic heart disease. The NHANES I Epidemiologic Follow-up Study. Am J Epidemiol 1995;141: 637–44 Fang J, Alderman MH. Serum uric acid and cardiovascular mortality: the NHANES I Epidemiologic Follow-up Study, 1971–1992. JAMA 2000; 283:2404 –10. Bos MJ, Koudstall PJ, Hofman A, Witteman JCM, Breteler MM. Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam Study. Stroke 2006;37:1503–7 Vittal et al., 31. Niskanen LK, Laaksonen DE, Nyyssonen K, Alfthan G, Lakka HM, Lakka TA, Salonen JT. Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med 2004;164: 1546–51. Int J Med Res Health Sci. 2014;3(1):104-109 109 DOI: 10.5958/j.2319-5886.3.1.022 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS nd Received: 2 Dec 2013 Revised: 18th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 22nd Dec 2013 STUDY OF PRESCRIBING PATTERN OF ANTIMICROBIAL AGENTS IN AN IPD OF A TERTIARY CARE HOSPITAL IN AHMEDNAGAR *Kapure NL, Nayak BB, Raul AR, Vijaykumar AN, Vijayprasad S, Vakade KP, Jadhav AR Department of Pharmacology, PDVVPF’S Medical College, Ahmednagar, Maharashtra *Corresponding author email:
[email protected] ABSTRACT Objectives: To evaluate the pattern of use of Antimicrobial drugs in IPD patients admitted for various illnesses. Materials and Methods: It is a retrospective and observational study, conducted during the period of January, 2011 to December, 2011. Prescription record of 252 patients admitted in IPD of Medicine & Surgery departments of the PDVVPFs Medical College & Hospital, Ahmednagar were studied. These data were obtained from Medical Record Departmeent (MRD) of the hospital. The study was conducted after obtaining permission from the Institutional Ethics Committee (IEC) of the college. Data were analyzed for- average number of antimicrobials prescribed per prescription, the relationship between patient age and sex, percentage usage of various antimicrobial groups and percentage use of individual antimicrobials. Results: It was observed that 75 % of patients were prescribed 1-2 antimicrobial agent and 25 % were prescribed 3 or more than 3 antimicrobials. Cephalosporins were the most preferred antimicrobials followed by quinolones and aminoglycosides. Fluconazole was found to be most commonly prescribed antifungal whereas Artesunate and Metronidazole were most preferred antimalarial and antiamoebic drugs. Conclusion: It can be concluded from the present study that physicians preferred to prescribe 2 or more than 2 antibacterial agents in a prescription. To treat various infections Cephalosporins and quinolones were observed to be most prescribed antibacterials. Fluconazole, Artesunate & Metronidazole were found to be commonly prescribed antifungal, antimalarial and antiamoebic agents. Uses of Macrolides, Tetracyclines & Vancomycin were very low. However, aminoglycosides were commonly prescribed to young males and Cepahalosporins to young female patients. Keywords: Drug utilization, Antimicrobial agent, Prescription INTRODUCTION As per data by All India Origin Chemists and Distributors-Advance Working, Action & Correction S y s t e m ( AIOCD-AWACS) m a r k e t research firm, antibiotics therapy rank as the 1st in all the super groups in pharmaceutical market with 14.8% growth in the month of February 2012. It occupies around 19 % in over 60,000 cr market. However they are the least studied drugs in terms of drug utilization studies.1 The principal aim of drug utilization research is to facilitate appropriate use of drugs in patient Kapure et al., populations, minimize the adverse event and drug interactions leading to better patient outcome. Drug utilization studies are powerful exploratory tools to ascertain the role of drugs in the society. They create a sound sociomedical and health economic basis for making health care decisions.2 Drug utilization is defined as marketing, distribution, prescription and the use of drugs in society, with special emphasis on the resultant medical, social and economic consequences.3 Often, drugs are not used, keeping in mind their safety Int J Med Res Health Sci. 2014;3(1):110-114 110 and efficacy.4 Rational drug prescribing is the use of the least number of drugs to obtain the best possible effect in the shortest period and at a reasonable cost .5 Irrational prescribing and disparity between the prescription and the consumption of medicines may offset the benefits which are demonstrated by randomized controlled trials on drug efficacy.6-9 The present study was planned to examine the patterns of drug prescription of Antimicrobials in the IPD of the internal medicine and surgery in the PDVVPF’s Medical C o l l e ge Hospital, Ahmednagar a tertiary care hospital. MATERIALS AND METHODS Study Design: A retrospective, observational study. Study Duration: 1 year from 01/01/2011 to 31/12/2011 Study Population: Medical Record (MR) data were obtained from MRD department; consisting of prescription records of 252 patients that admitted in the internal medicine and surgery in the PDVVPF’s Medical College Hospital, Ahmednagar a tertiary care hospital in Ahmednagar district. Procedure: The study was conducted after the permission from the Institutional Ethics Committee. Total 327 patients’ data were screened and analyzed as per the inclusion and exclusion criteria and 252 patients were selected for this study. Patient related information like age, gender, diagnosis, month of admission, drug related information like number of drugs prescribed were collected on a customized data collection sheet. Inclusion criteria: All patients who were admitted in the IPD of the Medicine and Surgery departments and were prescribed on the antibiotics for various infections. Exclusion criteria: Incomplete data. Parameters studied: Following parameters were taken in the study 1.Average number of antimicrobials prescribed per prescription. 2.Percentage usage of various antimicrobials 3.Percentage usage of drugs in each antimicrobial group 4.Frequency of systemic infection at different months 5.Relationship between patient d e mo gr aph i cs and prescription pattern Statistical analysis: The data were subjected to descriptive analysis using Microsoft Excel. Utilization Kapure et al., of different classes of drugs as well as individual drugs was analyzed and presented as a percentage. RESULT The total number of prescriptions analyzed was 252 .The numbers of drugs per prescription varied from one to more than four (Table-1) Table 1: Number of antimicrobials per prescriptions in number and percentage Number of antimicrobials per No of pts ( % ) prescriptions One 112(44.44) Two 80 (31.74) Three 36(14.28) Four or more than four 24( 9.52) Total no of prescriptions studied 252 Table 2: Percentage usage of antimicrobial group Drug class Drug Cefuroxime Cefotaxime Ceftriaxone Cefoperazone Cefixime Cefepime Ciprofloxacin Quinolones Ofloxacin Levofloxacin Norfloxacin Aminoglycosides Amikacin Gentamicin Streptomycin Amoxicillin Penicillins Penicillin - V Ampicillin Fluconazole Antifungals Itraconazole Ketoconazole Artesunate Antimalarials Chloroquine Primaquine Metronidazole Antiamoebics Tinidazole Ornidazole Macrolides Others Tetracyclines Vancomycin Cephalosporins drugs in each (%) of prescriptions 33.3 25.3 6.32 1.58 1.58 1.58 14.28 12.69 7.92 4.75 20.62 4.75 3.17 11.1 4.75 3.17 4 2.7 1.3 2 1.7 0.8 13.6 6.4 4 3.17 3.17 1.58 Int J Med Res Health Sci. 2014;3(1):110-114 111 PERCENTAGE Table 3: Frequency of systemic infection in different months System Highest Lowest Involved frequency frequency GIT Sep (70%) Feb (15%) CVS May (85%) Jan (10%) CNS Feb (50%) July (5%) RS Oct (70%) Jan (10%) OTHER Aug (60%) March (10%) 80 70 60 50 40 30 20 10 0 Fig 1: Prescribing frequency of antimicrobial group of drugs 76 80 70 0-15 60 16-30 31-60 >60 48 50 36 28 20 20 16 1412 12 40 30 16 20 4 10 4 0 0 0 1616 0 8 4 43 322 0 0 02 0 4 Fig 2: Age-wise prescribing frequency of antimicrobials in males 0 -15 1 6-30 3 1-60 >60 25 20 20 15 88 10 6 4 5 0 10 8 8 0 0 0 2 12 6 4 0 4 0 6 2 0 3 3 2 344 0 2 0 11 It was observed that 1, 2, 3 & 4 or >4 Antimicrobials were prescribed to 44.44%, 31.74%, 14.28% & 9.52% respectively (Table-1). Among the Antimicrobials Cephalosporins was found to be prescribed to the largest number (71.42%) of patients, followed by Quinolone (39.68%), Aminoglycoside (28.57%), Antiamoebic (24%), Penicillins (19.04%), Antifungal (8%), Antimalarial (4.5%) & others were 8% (Fig-1). Among the cephalosporin’s use of cefuroxime was highest (33.33%), followed by cefotaxime (25.39%), ceftriaxone (6.32%), Cefoperazone, Cefixime, Cefepime each were 1.58% respectively. Among the fluoroquinolones it was found Ciprofloxacin was mostly preferred (14.28%), followed Ofloxacin (12.69%), Levofloxacin (7.9%), Norfloxacin (4.79%). Amikacin among the Aminoglycosides was the most chosen drug (20.62%) followed by Gentamicin (4.75%), streptomycin (3.75%). Among Penicillins Amoxicillin was used to the extent of 11.1%, followed by Benzyl Penicillin 4.75% and Ampicillin 3.17%. Among the oral antifungal drugs Flucanazole was observed to be the most favoured to the extent of 4 % followed by Itraconazole 2.7% and Ketoconazole 1.3% . Artesunate was prescribed to 2 %. Chloroquine 1.7 % & Primaquine 0.8% as antimalarials. Among Antiamoebic drugs Metronidazole was used to the extent of 13.6% , followed by Tinidazole 6.4% & Ornidazole 4 % . Macrolides, Tetracyclines, Vancomycin were used in 3.1%, 3.1% & 1.5% respectively (Table-2) . Patients admitted due to CVS disease were observed highest among all the diseases (85%) in the month of May & lowest in the month of January (10%). Infections of the nervous system caused to the extent of 15 % in the February & 5 % in the July. Other infection were found 60% in August and the lowest occurrence was in March (10%) (Table3). In young male patients Aminoglycisides & Antimalarials were found to be highest & lowest prescribed drugs respectively whereas Cephalosporins & Quinolone were highly preferred for younger as well as older female patients .Younger age male patients were mostly admitted for the CVS & endocrine disorders. However in younger & adult female patients were commonly associated with CVS & GI disorders. (Fig 2 & 3) DISCUSSION Fig 3: Age-wise prescribing frequency of antimicrobial in females Kapure et al., The clinical setting in the medical ward w a r r a n t s the use of drugs from various drug classes. Rational prescription of drugs is essential for better patient 112 Int J Med Res Health Sci. 2014;3(1):110-114 care. The first step in any intervention programme to improve drug utilization is to assess the extent of existing problem in prescribing. The objective of our study was to evaluate the drug utilization patterns among patients admitted to the IPD of a tertiary care hospital. The demographic results of patients admitted to the IPD over a period of 12 months revealed a male preponderance with a mean age of around 50 years, 10 similar to a study carried out in Nepal in 2005. In contrast, Smythe et al (1993) showed an equal number of male and female patients admitted to the hospital 11 with a mean age of 65 years. Previous Indian studies also documented male predominance which suggests that more males are admitted in an Indian setting for 12 infections. The probable reasons for this finding could be the male to female ratio is higher in the state of Maharashtra and overall in the India. In the Indian scenario it is noticed that female populations are reluctant to utilize health care facilities even if they are critically ill and especially from lower socioeconomic strata. A wide spectrum of clinical diagnoses was observed including sepsis, renal failure, acute respiratory distress syndrome, multi organ dysfunction, head injury, cvs related disorder and diabetes complication. Debilitating condition of the patients due to underlying disease, invasive diagnostic and therapeutic procedures and prolonged utilization of life support equipment predisposes these patients to infections It was noticed that most of the antimicrobial agents were prescribed by brand name (60%) which requires revision of current prescribing practice. Extensive polypharmacy (> 90 %) that is more than five drugs were prescribed in all the patients. Polypharmacy is defined as concomitant use of five or more drugs and it could enhance drug interactions and drug related 13 problems. It is difficult to treat patients in the IPD with multiple co‐morbidities with less number of drugs as they require drugs for treatment of specific conditions as well as for prophylaxis, but it is also essential to keep a balance between the number of drugs and effective pharmacotherapy. High antimicrobial prescribing frequency was observed in our study inconsistent with earlier studies 14 from Nepal which documented 30%. More than one antimicrobial agent was prescribed among (69%) of the prescriptions. This could be expected since Diabetes, multi organ dysfunction, IHD, respiratory Kapure et al., tract infections was prevalent among the patients of the present study necessitating therapeutic as well as prophylactic utilization of antimicrobials. Antimicrobial protocol and guidelines; formulary based antimicrobial restrictions can be used to improve rational usage of antimicrobials. A multidisciplinary approach can be adopted in the ICU and IPD set up involving intensive care specialist; infectious disease control s p e c i a l i s t , pharmacists and microbiologists can work together for more rational antimicrobial pharmacotherapy. CONCLUSION It can be concluded from the present study that physicians preferred to prescribe 2 or more than 2 antibacterial agents in a prescription. To treat various infections Cephalosporins and quinolones were observed to be most prescribed antibacterials. Fluconazole, Artesunate & Metronidazole were found to be commonly prescribed antifungal, antimalarial and antiamoebic agents. Use of Macrolides, Tetracyclines & Vancomycin was very low. However, aminoglycosides were commonly prescribed to young males and Cepahalosporins to young female patients. In conclusion, a wide spectrum of clinical diagnosis and a variety of drugs were utilized for various drug classes. Overall, the scope for improving rational use of antimicrobial agents exists. Antibiotic resistance is increasing at an alarming rate leading to increasing morbidity, mortality and treatment cost. A key factor in the development of an antibiotic resistance is inappropriate use of antibiotics. The medical fraternity needs to understand that antibiotics are precious and finite resources, and unless conscious efforts are made to contain the problem of drug resistance, multidrug resistant organism untreatable by ever known antibiotic may emerge reversing the medical progress by ranking and returning as back to pre-antibiotic. Pharmacoeconomic studies in the hospital can encourage cost effective antimicrobial drug therapy. This will help in rationalizing prescribing practices based on the feedback from these studies and practices between institutions, regions and countries can be compared. REFERENCES 1. Mukherjee R. Antidiabetic drugs post highest growth in Feb. Times o f I n d i a . Mumbai edition. 5th April 2012: 36. Int J Med Res Health Sci. 2014;3(1):110-114 113 2. Bakssas I, Lunde PKM. National drug policies; the need for drug utilization studies. Trends Pharmacolo Sci 1986; 7: 331. 3. WHO, The selection of essential drugs. WHO technical report 1977; 615: 36. 4. Lunde PKM, Levy M. Drug utilization – geographical differences and clinical implications. Introductory remarks. In: Duchene-Marullaz, P, ED. Advances in pharmacology and therapeutics. Oxford, Pergamon Press 1978;6:7982. 5. Gross F . Drug utilization therapy a n d practice. The present situation in the Federal Republic of Germany. Eur J Clin Pharmacol 1981; 19:387-94. 6. Cochrane AL. Effectiveness and efficiency – Random reflections on health services. London, the Nuffield Provincial Hospitals Trust, 1982. 7. Stolley PD, Lasagna L. Prescribing patterns of physicians. Journal of chronic diseases 1969; 22:395-405. 8. Westerholm B. Therapeutic auditing at the national and international levels. Br J Clin Pharmacol, 1986;22:55S-9S. 9. Pullar T, Kumar S, Tindall H, Freely M. Time to stop counting the tablets? Clin Pharmacol Ther 1989;46:163-8 10. Srishyla MV, Krishnamurthy M, Nagarani MA. Prescription audit in an Indian hospital setting using the DDD (Defined Daily Dose) concept. Indian J Pharmacol 1994; 26:23‐8. 11. Smythe MA, Melendy S, Jahns B. An exploratory analysis of medication utilization in a medical intensive care unit. Crit Care MED 1993; 21 (9): 319‐23. 12. Biswal S, Mishra P, Malhotra S. Drug utilization pattern in the intensive care unit of a tertiary care hospital. J Clin Pharmacol 2006; 46:945‐51. 13. Viktil KK, Blix HS, Moger TA. Polypharmacy as commonly defined is an indicator value in the assessment of drug‐related problems. Br J Clin Pharmacol 2007; 63(2):187‐95. 14. Shankar PR, Partha P, Dubey AK. Intensive care unit drug utilization in a teaching hospital in Nepal. Kathmandu Univ Med J 2005; 3(10):130‐7. Kapure et al., Int J Med Res Health Sci. 2014;3(1):110-114 114 DOI: 10.5958/j.2319-5886.3.1.023 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 24 Nov 2013 Revised: 15th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 18th Dec 2013 MORPHOMETRIC STUDY OF THE SACRAL HIATUS IN NIGERIAN DRY HUMAN SACRAL BONES *Ukoha Ukoha U1, Okafor Joseph I2, Anyabolu Arthur E1, Ndukwe Godwin U3, Eteudo Albert N4, Okwudiba Nchedo J2 1 Department of Anatomy, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria. Department of Anatomy, Anambra State University, Uli, Nigeria. 3 Department of Anatomy, Ebonyi State University, Abakaliki, Nigeria. 4 Department of Anatomy, College of Medicine and Health Sciences, Abia State University, Uturu, Nigeria. 2 *Corresponding author email:
[email protected] ABSTRACT Background: The sacrum is a large triangular bone formed by the fusion of the five sacral vertebrae and forms the caudal region of the vertebral column. Aims: This was aimed at studying the morphometry of the sacral hiatus noting its anatomical variations that is useful in caudal epidural anaesthesia. Materials and Methods: Eighty three intact adult sacra of unknown sex were measured with vernier callipers and the various shapes of the sacral hiatus were also noted. Results: The findings revealed that inverted U (48.2%) was the most predominant shape; followed by inverted V (34.9%), dumbbell (4.8%), bifid (4.8%) and irregular (4.8%). The mean anteroposterior diameter at the apex was 5.52 ± 1.89mm. The mean length of the sacral hiatus was 20.05 ± 9.22mm and the transverse width at base of hiatus was 12.35 ± 3.12mm. There was complete spina bifida in 1.2% and absence of sacral hiatus in another 1.2%. Conclusion: The knowledge of anatomical variations of sacral hiatus is important in the administration of caudal epidural anaesthesia in the studied population and may help to reduce its failure rate. Keywords: Sacral hiatus, caudal epidural block (CEB), sacral vertebra. INTRODUCTION The sacrum is a large triangular bone formed by the fusion of five sacral vertebrae and it also forms the caudal region of the vertebral column. It forms the posterosuperior wall of the pelvic cavity, wedged between the innominate bones.1 Due to its great size, the sacrum is usually the last bone of a buried body to rot. The ancients may thus have believed the sacrum to be the focal point, around which the body could be reassembled in the after-life.1 The opening at the caudal end of the sacral canal is the sacral hiatus formed due to failure of fusion of laminae of the fifth (occasionally 4th) sacral vertebrae. The sacral hiatus is an inverted V-shaped space located at the distal part of the sacrum. This space is formed by incomplete midline fusion of the posterior elements of the distal portion of the fifth or sometimes, the fourth sacral vertebra. The sacral hiatus is covered posteriorly by the posterior aspect of the sacrococcygeal membrane and is an important landmark in caudal epidural block.2 Sacral approach to epidural space is used for giving analgesics and anaesthesia for a variety of operations. Caudal epidural block (CEB) has been widely used for the treatment of lumbar spinal disorders, management of chronic back pain, in obstetrics,3 and orthopaedic practice.4 The technique of CEB depends upon accurate localization of sacral hiatus through which access to sacral epidural space is gained. Some authors 115 Ukoha et al., Int J Med Res Health Sci. 2014;3(1):115-119 have reported that one of the anatomic reasons of caudal epidural anaesthesia failure is the absence of sacral hiatus. One of the important key factors for successful caudal epidural anaesthesia may be clear understanding of the normal anatomy of sacral hiatus and surrounding structures.4 Sacral hiatus exhibits variations in morphology which differ among populations and the reliability and success of epidural anaesthesia depend upon these anatomical variations. These variations have not been well documented in the Nigerian population, hence this study is meant to address this. The parameters studied were the following: i. Shapes of the sacral hiatus. ii. Level of apex with respect to the sacral vertebrae. iii. Level of base with respect to the sacral vertebrae. iv. The length of the sacral hiatus measured from the apex to the midpoint of the base. v. The anteroposterior diameter – at the apex. vi. The transverse width at the base measured between the inner aspects of the inferior limits of sacral cornua. Only sacra with complete sacral hiatus were used for the study and damaged, mutilated and deformed sacra were excluded. Data Analysis: Data were expressed as mean and standard deviation for continuous variables, and percentage for categorical variables. Comparative analysis was done using Analysis of variance (ANOVA). The statistical software used was SPSS Version 16.0. MATERIALS AND METHODS The study was conducted on 83 intact adult dry human sacra obtained from various Anatomy museums in the South-East and South-South zones of Nigeria. Bones of undetermined age and gender were used. They were preserved in dry conditions free from moisture, dust, insects or moths. Direct measurements were taken with vernier callipers (God Marc Tools, Japan; accurate to 0.02mm). RESULTS Table 1: Frequency distribution of the shape of sacral hiatus Shape of Sacral Hiatus Absent Bifid Complete spina bifida Dumbbell Inverted U Inverted V Irregular Total Frequency 1 4 1 4 40 29 4 83 Percentage 1.2 4.8 1.2 4.8 48.2 34.9 4.8 100 Table 2: Frequency distribution of the level of apex with respect to the sacral vertebrae. Level of apex with respect to the sacral vertebrae Frequency Percentage None S2 S3 S4 S5 Total 2 2 17 58 4 83 2.4 2.4 20.5 69.9 4.8 100 Table 3: Frequency distribution of the level of base with respect to the sacral vertebrae Level of base with respect to the sacral vertebrae Frequency Percentage None Coccyx S4 S5 2 6 2 73 2.4 7.2 2.4 88 116 Ukoha et al., Int J Med Res Health Sci. 2014;3(1):115-119 Total 83 100 Table 4: The length, transverse width and anteroposterior diameter of the sacral hiatus Variables Mean±SD Median Range Length (mm) 20.05 ± 9.22 20.50 6.10 – 57.0 Transverse Width (mm) 12.35 ± 3.12 13.00 5.0 – 20.50 Anteroposterior Diameter (mm) 5.52 ± 1.89 5.10 0.40 – 11.10 Table 5: Mean and standard deviation of the length, transverse width and anteroposterior diameter according to the shape of sacral hiatus Shape of Sacral Hiatus Length (mm) Transverse Width (mm) 11.03 ± 2.48 13.50 ± 1.08 12.45 ± 2.80 12.81 ± 3.52 8.20 ± 2.51 Bifid 11.03 ± 2.48 Dumbbell 13.50 ± 1.08 Inverted U 22.17 ± 8.42 Inverted V 20.91 ± 9.88 Irregular 8.20 ± 2.51 Data are expressed as means and standard deviations. Anteroposterior Diameter (mm) 4.60 ± 1.73 4.78 ± 0.52 5.26 ± 1.83 6.07 ± 2.06 5.80 ± 1.70 Table 6: Mean and standard deviation of the length, transverse width and anteroposterior diameter of sacral hiatus according to the level of apex with respect to the sacral vertebrae Level of apex with respect to sacral vertebrae S2 Length (mm) 49.55 ± 10.54 S3 26.59 ± 8.27 S4 17.81 ± 6.52 S5 10.0 ± 1.15 Data are expressed as means and standard deviations. Transverse Width (mm) 14.05 ± 1.34 Anteroposterior Diameter (mm) 8.60 ± 3.54 12.35 ± 2.55 11.99 ± 3.05 16.78 ± 4.25 5.43 ± 1.85 5.42 ± 1.82 5.78 ± 1.71 Table 7: Mean and standard deviation of the length, transverse width and anteroposterior diameter of the sacral hiatus according to the level of base with respect to the sacral vertebrae Level of base with respect to Length (mm) sacral vertebrae S4 28.0 ± 4.24 S5 19.48 ± 9.24 Coccyx 24.35 ± 8.64 Data are expressed as means and standard deviations. Transverse Width (mm) 15.0 ± 2.83 12.18 ± 3.14 13.57 ± 2.80 Anteroposterior Diameter (mm) 6.50 ± 2.12 5.44 ± 1.90 6.18 ± 1.82 DISCUSSION The detailed morphometric study of sacral hiatus is of great relevance, since this route is frequently utilized for caudal epidural anaesthesia in perineal surgery, and caudal analgesia for painless delivery. Edward and Hingson in 1942 for the first time took advantage of this natural gap in the lower end of the sacral canal for continuous caudal analgesia during labour.3 Since then, the sacral hiatus has been an important landmark in caudal epidural block. However, failures have often been encountered in caudal epidural block owing to anatomical variations in the sacral hiatus. In 1999, Tsui et al reported that the failure rate was about 25%.5 Shape Table 1 showed the frequencies of the various shapes of sacral hiatus in the study population. The inverted U shape (48.2%) was most dominant, followed by the inverted V shape (34.90%), both of which were considered normal. The results were similar to studies by Seema et al6 and Shewale et al.7 In a study by Vijisha and Baskaran,8 the inverted U and inverted V had equal frequencies of 35% each. The abnormal shapes constituted 15.6% and 1.2% were absent. Comparison with studies by other authors ( 117 Ukoha et al., Int J Med Res Health Sci. 2014;3(1):115-119 Table 8) showed similarities in the normal shapes, but the present study had lower frequencies in the abnormal shapes. Only the population under study presented with a bifid sacral hiatus. Level of Apex The level of apex of sacral hiatus in relation to sacral vertebrae in the study population is shown in Table 2. It was quite variable and extended between the middle of S2 and mid-S5. The S4 vertebra (69.9%) was the most dominant level. In 2.4%, the wall was open. The results of the present study in comparison (Table 9) agreed with studies by Ramamurthi and Anil9 and Seema et al6 as well as standard Anatomy textbooks.1 Level of Base In the study population, Table 3 showed the various levels of base with respect to the sacral vertebrae. The most dominant level was the S5 (88%) vertebra. In 2.4% of the sacra, the sacral hiatus was completely obliterated and the lower end of the canal was closed due to bony undergrowth. Comparison with other studies supported the fact that the level of base was at the S5 vertebra in most of the population (Table 10). Length, transverse width and anteroposterior diameter at apex The results are shown in Table 4. The mean length and mean transverse width were 20.05mm and 12.35mm respectively. The anteroposterior diameter at apex of sacral hiatus is important as it should be sufficiently large to admit a needle, and varying diameters could cause subcutaneous deposition of anaesthetic drug. In the present study, mean anteroposterior diameter was 5.52mm. Table 5 showed the mean length, transverse width and anteroposterior diameter of the sacral hiatus according to its shape. Analysis of variance (ANOVA) indicated significant variations in length (F = 4.32; P = 0.003) among the different shapes. On the other hand, no significant differences were observed in transverse width (F = 2.41; P = 0.057) and in the anteroposterior diameters (F = 1.22; P = 0.309) of the various shapes. The mean length, transverse width and anteroposterior diameter of sacral hiatus according to the level of apex is seen in Table 6. Analysis of variance (ANOVA) showed significant variations in length (F = 22.37; P = 0.000) and transverse width (F = 3.42; P = 0.021) among the different levels. No significant difference (F = 1.93; P = 0.132) was observed in the anteroposterior diameter of the various levels. In Table 7, the mean length, transverse width and anteroposterior diameter of the sacral hiatus according to the level of base is determined. Analysis of variance (ANOVA) indicated no significant variations in length (F = 1.56; P = 0.217), transverse width (F = 1.29; P = 0.280) and the anteroposterior diameter (F = 0.70; P = 0.498) among the different levels. Table 8: Incidence of various shapes of sacral hiatus in dry human sacral bones by various authors Shape Inverted U Inverted V Irregular Dumbbell Bifid Complete spina bifida Elongated Absent Seema et al (2013) 42.95% 27.52% 16.11% 13.42% - Shewale et al (2013) 40.69% 32.35% 9.31% 5.89% 0.98% Anil et al (2013) 31% 25.80% 20.60% 5% - Current Study (2013) 48.20% 34.90% 4.8% 4.8% 4.8% 1.2% - 9.31% 0.98% 17.20% - 1.2% Table 9: Incidence of level of apex of sacral hiatus in dry human sacral bones recorded by various authors Level S2 S3 S4 S5 Anil et al (2013) 7.76% 41.38% 50.86% - Seema et al (2013) 4.03% 35.57% 56.37% 4.03% Shewale et al (2013) 4% 15% 66.50% 14.50% Current Study (2013) 2.40% 20.50% 69.90% 4.80% Table 10: Incidence of level of base of sacral hiatus in dry human sacral bones reported by various authors Level S4 Anil et al (2013) 18.97% Seema et al (2013) 13.42% Shewale et al (2013) 2% Current Study (2013) 2.4% 118 Ukoha et al., Int J Med Res Health Sci. 2014;3(1):115-119 S5 72.41% Coccyx 8.62% CONCLUSION 70.47% 16.11% Information obtained from studies on anatomical variations of the sacral hiatus is important in caudal epidural block (CEB). In the present study, 83 dry human sacra were studied and the irregular, bifid and dumbbell shapes were 4.8% each. The sacral hiatus was completely absent in 1.2% and 1.2% had spina bifida, bringing the total rate of sacral hiatus abnormalities to 16.9%. The rate should be kept in mind when administering caudal epidural anaesthesia in the Nigerian population. 82% 16% 88% 7.2% 10. Ramamurthi KS, Anil KR. Anatomical study of sacral hiatus for successful caudal epidural block. Int J Med Res Health Sci, 2013; 2(3):496-500 REFERENCES 1. Williams PL (ed). Gray’s Anatomy, 38th edition, Churchill Livingstone, 2000; 592-31, 673-74. 2. http://www.MedicineNet.com. The Sacrum The Holy Bone, 2003. Accessed 15th June, 2013. 3. Senoglu N, Senoglu M, Oksuz H, Gumusalan Y, Yuksel KZ, Zencirci B et al. Landmarks of the hiatus for caudal epidural block: An anatomical study. British Journal of Anaesthesia. 2005; 95 (5):692- 695. 4. Edwards WB, Hingson RA. Continuous caudal anesthesia in obstetrics. American Journal of surgery. 1942; 57:459-464. 5. Sekiguchi M, Yabuki S, Satoh K, Kikuchi S. An Anatomic study of the sacral Hiatus: A Basis for successful caudal epidural Block. Clinical Journal of Pain. 2004; 20(1): 51-54. 6. Tsui BC, Tarkkila P, Gupta S, Kearney R. Confirmation of caudal needle placement using nerve stimulation. Anaesth Analg 1999; 91:374-8. 7. Seema, Singh M, Mahajan A. An anatomical study of variations of sacral hiatus in sacra of North Indian origin and its clinical significance. Int. J. Morphol., 2013; 31(1):110-114. 8. Shewale SN, Laeeque M, Kulkarni PR, Diwan CV. Morphological and Morphometrical Study of Sacral Hiatus. International Journal of Recent Trends in Science And Technology. 2013; 6(1):48-52. 9. Vijisha P, Baskaran S. Morphometrical analysis of sacral hiatus and its clinical significance. The Health Agenda, 2013; 1(1): 10-14. 119 Ukoha et al., Int J Med Res Health Sci. 2014;3(1):115-119 DOI: 10.5958/j.2319-5886.3.1.024 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 15 Dec 2013 Revised: 26th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 28th Dec 2013 COMPARISON OF HEMATOLOGICAL PARAMETERS BETWEEN PLASMODIUM FALCIPARUM, PLASMODIUM VIVAX AND CONTROL GROUP *Ashis Kumar Saha1, Somnath Maitra2, Subhas Chandra Hazra3 1 Assistant Professor, 2Senior Resident, 3Professor and Head, Department of General Medicine, K P C Medical College & Hospital, Kolkata, India *Corresponding author email:
[email protected] ABSTRACT Aims: Malaria, a morbid disease of Tropical countries, may harmful if it cannot be diagnosed at its early phase, by observing the changes in hematological parameters. Our aim was to compare the hematological parameters between Plasmodium falciparum and vivax in relation to control healthy group in West Bengal. Methods and materials: In total 238 slide or dual antigen positive patients (120= Plasmodium vivax, 118=plasmodium falciparum) clinical hematological, renal parameters were compared. Results: In Plasmodium vivax and falciparum, male to female ratio was 3:1 and 1.3:1 respectively. Significant elevation in erythrocyte sedimentation rate (ESR),differential lymphocyte count, creatinine and significant lowering of platelet count, fasting blood sugar (FBS) were observed in plasmodium vivax group, whereas, significant elevation of hemoglobin, differential monocyte count, mean corpuscular hemoglobin concentration were seen in plasmodium falciparum group. Haemoglobin and FBS were significantly lower, whereas, ESR, creatinine, differential monocyte count were high in vivax group, total white blood cell and platelet count, hematocrit were low in both Plasmodium infection and mean corpuscular hemoglobin, differential lymphocyte count were significantly low in falciparum group as compared to control group. Conclusion: Combination of low hemoglobin, fasting blood sugar and significantly raised ESR is highly significant in predicting severity of Plasmodium infection in patients of malaria endemic areas, which was evidenced in our present study. P. falciparum and vivax suffered from lymphopenia and thrombocytopenia respectively. Keywords: Hematological parameters, Plasmodium falciparum, Plasmodium vivax, West Bengal INTRODUCTION Malaria, a morbid disease of Tropical countries, like, India, Pakistan, Bangladesh, is now of global importance; because, it is responsible for 1.5 to 2 million of deaths yearly in the world1, and three fourth of cases were suffered in India amongst 2.48 million of malarial cases of South-East Asia.2 In Tropical countries, where malaria is endemic, it is very essential to differentiate malaria from other viral or bacterial infections by symptoms and signs3 to prevent future fatal complications, like, cerebral, renal, and gastrointestinal. Hence in these areas, unnecessary antimalarial treatment to treat the possible cases before diagnosis is one of the causes of drug resistance. 4 In India, Plasmodium falciparum (p. falciparum) and Plasmodium vivax (p. vivax) are responsible for malaria. This disease is transmitted by the bite of the anopheles mosquito. Incubation period in malaria is ten to fifteen days. After entry, the sporozoites in the circulation in the human body, attach to the hepatocytes through the receptors for thrombospondin and properdin.5 In the hepatocytes, sporozoites are transformed to schizonts. Each schizont produces a large number of merozoites in the hepatocyte. Most of 120 Ashis et al., Int J Med Res Health Sci. 2014;3(1): 120-127 the merozoites are released into circulation. In the circulation, each merozoite is entered in the red blood cell (RBC) and produces 24 to 32 merozoites during the asexual stage of the life cycle. As p. falciparum enters the RBC, following thing things may occur. Firstly, increased secretion of inflammatory cytokines (tumor necrosis factor α, interleukin 1, 10 and interferon γ), secondly, due to over expression of cell adhesion molecule, endothelial cell become activated, thirdly, coagulation cascade activation as a result of platelet activation and endothelial damage, fourthly, sequestration of parasitized RBC due to over expression of cell adhesion molecule, iNOS.6-10 As a result, there are changes in the morphology and number in different cell lines. Now-a-days, in case of p. vivax malaria, biochemical and hematological parameters occur. Hematological changes include hemoglobin, packed cell volume (Hct), total white blood cell count (WBC), platelet count, blood glucose, Creatinine. These changes may vary with the nutritional status, demographic factors, individual and environmental immunity.11 Our aim was to compare the hematological and renal parameters between p. falciparum and p. vivax affected patients in relation to healthy group in West Bengal. MATERIALS AND METHODS Inclusion criteria: Total 238 patients [120 plasmodium vivax (males 90 and females 30) and 118 plasmodium falciparum ( males 68 and females 50)] between the ages of 2 to 80 years who were admitted in our hospital from 2011 to 2013 years with symptoms and signs suggestive of malaria, like, fever with chill and rigor, headache, nausea with or without vomiting, arthralgia, diarrhea, weakness, drowsiness, confusion, stupor, anemia, jaundice, signs of dehydration, hepatomegaly, and slpenomegaly, whose blood were positive for malaria parasite in thick or thin blood film stained by Giemsa stain and/or dual antigen positive for plasmodium vivax or plasmodium falciparum. They were subdivided into 2 groups according their antigen positive type (Group A: Plasmodium vivax (N=120), Group B: Plasmodium falciparum (N=118) Exclusion criteria: We excluded the patients suffering from different infection producing sepsis, dengue infection, viral hepatitis, Leptospirosis during this period. Ethical clearance: This three years study was conducted only after getting permission from the ethics committee of our hospital and informed consent obtained from our patients’ parties. Detailed clinical history was taken from the patient, followed by, thorough clinical examination. Then blood was used for thick and thin blood film, stained with Gimsa stain, for detection of malaria parasite under microscope and for detection of malarial antigen of both p. falciparum and p. vivax. If at least, one asexual form of parasite was detected in 100 microscopic fields of thick blood film examined under microscope using oil immersion lens (100xmagnification) – it is considered as positive. After confirmation of the diagnosis, 5 ml. of blood was collected from each patient aseptically in a vial containing ethylene diamine tetra acetic acid (EDTA) and was promptly analyzed for routine hematological parameters, which included, the following, like, total WBC count, hemoglobin (Hb) estimation, hematocrit (Hct), Mean Corpuscular Hemoglobin (MCV), Mean Corpuscular Hemoglobin (MCH), mean corpuscular hemoglobin (MCHC), erythrocyte sedimentation rate (ESR), platelet count. Another 2 ml. of blood was collected in a vial and serum was separated and estimated Creatinine, blood sugar. Hemoglobin was estimated by the acid hematin method, PCV by Wintrobe’s method, blood sugar by enzymatic method, Creatinine by the alkaline picrate method. These are all conventional methods. Similarly, blood from 100 patients in the healthy group (Group C: n=100), which consist of patient’s party, lab technicians having no history of disease in the recent past or present were done of same parameters. Data were collected and analyzed statistically. Statistical analysis : The data were expressed in terms of means±SD (standard deviation). Then, all the means were compared between p. vivax and p. falciparum group and control group separately at 95% confidence interval using student ‘t’test and, ‘p’ value were extracted. ‘p’ value of less than 0.05 was considered as statistically significant. In statistics, a confidence interval (CI) is a type of interval estimate of a population parameter and is used to indicate the reliability of an estimate. It is an observed interval. In applied practice, confidence intervals are typically stated at the 95% confidence level. 121 Ashis et al., Int J Med Res Health Sci. 2014;3(1): 120-127 RESULTS Table:1 Comparison between p. vivax and p. falciparum affected patients as compared to control group Parameters P. vivax (Group A ) P. falciparum (Group B ) Age (years) 42.82±88.4 27.2±14.2 101.72±0.20 100.9±0.19 11.785±2.1 12.32±1.52 ESR mm/1st hour 75.18±6.42 68.78±7.79 MCV (fl) 82.74±8.41 83.14±7.85 MCH (pg) 27.72±8.21 28.94±6.45 MCHC (g/dl) 34.18±1.62 35.47±1.48 Hematocrit 34.88±4.346 33.179±3.136 6653.16±1999.0 6008.92±1393.5 42.14±12.42 36.39±15.45 10.10±2.17 13.59±6.80 42.67±21.02 46.39±18.18 3.01±4.19 4.12±4.79 1.45±2.12 1.72±1.64 1.61.±0.61 1.81.±0.91 Creatinine mg/dl 0.94±0.57 0.71±0.45 Fasting blood sugar mg/dl 93.8±18.67 100.35±10.89 Temperatures (oF) Hemoglobin (gm%) Total WBC count /cc Differential count lymphocyte (%) Monocyte (%) Neutrophil (%) Eosinophil (%) Basophil (%) Platelet Lack/ cc count count count count count count Control Group C(100) 32.49±4.15 98.1±0.31 12.51±0.45 15.75±5.56 84.62±8.56 32.64±4.52 35.10±1.98 41.45±5.2 8096.21±35.4 44.13±15.87 8.68±4.95 43.77±21.31 2.92±7.1 0.57±0.12 2.51.±0.81 0.71±0.25 98.25±11.92 95% CI$ -0.61 — 31.85 0.75 – 0.84 -1.008 – -0.07 4.57 – 8.22 -2.47 – 1.67 -3.10 – 0.66 -1.58 – -0.79 0.73— 2.669 203.50— 1084.98 2.17 – 9.32 -4.77 – -2.205 -8.74 – 1.302 -2.25 – 0.04 -0.75 – 0.21 -293.95— 39410.8 0.098— 0.361 -10.46— -2.63 P value$ 0.059 0.00** 0.02* 0.000*** 0.704 0.204 0.000*** 0.000*** 0.00** 0.00** 0.00** 0.145 0.58 0.27 0.053 0.00** 0.00** 95% CI@ -7.11 – 27.77 3.55 – 3.68 P value@ 0.24 0.00** 95% CI^ P value^ -8.18 -2.39 2.73 –2.86 0.00** -0.50 0.12 51.87— 55.54 -3.67 0.71 -5.21 – -2.18 -0.09 0.83 -9.39 – -7.14 -2362.13 -1812.44 0.22 – 0.00** -1.14-- -0.30 0.00** 43.01— 77.20 -4.14 – 0.38 0.00** -6.73 -- 3.10 -1.14 – 0.70 0.00** -7.84 -- 5.29 -1837.23 -1048.86 0.00** -5.75 – 1.77 0.29 -0.57 – 1.77 0.01* - 6.14 – 5.14 0.86 - 1.43 – 1.61 0.90 -0.39– 2.79 0.14 -0.01 – 1.07 0.055 0.82 – 1.47 0.00** -1.851241--70602.88 0.109—0.35 0.00** -93244 -- 46753.37 0.09-0.09 0.00** -8.70—-0.19 0.04* -0.94 5.14 0.17 0.10 0.64 0.00** 0.00** 0.00** – 0.18 0.00** – 0.11 0.00** -- - 11.93 – - 3.54 2.29 – 5.52 -2.65– 7.89 – 0.00** 0.000*** 0.00** 0.32 1.0 $= Comparison with P.Vivax vs P. Falciparum, @= Comparison with P. Vivax vs Control, ^= Comparison with P. Falciparum vs Control, *Significant, **Very significant, ***extremely significant A. Characteristics of the studied population –In case of p. vivax, affected male (n=90) to female (n=30) ration was 3:1, whereas, in case of falciparum (male=68, female=50), it was 1.36:1. Temperature in both p. vivax and p. falciparum groups were significantly raised as compared to control group. B. Comparison of hematological parameters between p. vivax (120) and p. falciparum (n=118) group – P. vivax showed a significant elevation in ESR (75.18±6.42 vs. 68.78±7.79 mm / 1st hour, p=0.00), differential lymphocyte count [(42.14±12.42) % vs. (36.39±15.45) %, p=0. 00], creatinine (0.94±0.57 vs. 0.71±0.45 mg/dl, p=0. 00) and significant lowering of platelet count (161792.45±61165.62 vs. 181350.87±91122.45/cc, p=0. 05) Fasting blood sugar level (93.8±18.67 vs. 100.35±10.89 mg/dl, p=0. 00) as compared to p. falciparum group. Whereas, p. falciparum group showed a significant elevation in hemoglobin (12.32±1.52 vs. 11.78±2.1 gm/dl, p=0.02), differential monocyte count [(13.59±6.80) % vs. (10.10±2.17) %], and MCHC (35.47±1.48 vs. 34.18±1.62 g/dl, p=0.00), and significant lowering of WBC count (6653.16±1999.01 vs. 6008.92±1393.56 /cc, p=0.00), as compared to p. vivax group. C. Comparison of hematological parameters between p. vivax group (n=120) and control group (n=100) – In p. vivax group, hemoglobin (11.78±2.1 vs. 12.51±0.45 gm/dl, p=00), MCH (27.72±8.21 vs. 122 Ashis et al., Int J Med Res Health Sci. 2014;3(1): 120-127 32.64± 4.52 pg, p=0.00), Hct (34.88±4.34 vs. 41.45±5.2, p=0.00), total WBC count (6653.16±1999.01 vs. 8096.21±35.41 /cc, p=0.00), total platelet count (161792.45±1165.62 vs. 251350.10±81315.62 / cc, p=0.00), fasting blood sugar level (93.8±18.67 vs. 98.25±11.92 gm/dl, p=0.04) were significantly low as compared to healthy control group. Whereas, in former group showed significantly raised ESR (75.18±6.42 vs. 15.75±5.56 mm / 1st hour, p=0.00), differential monocyte count [(10.10±2.17) % vs. (8.68±4.95) %, p=0.01] and serum creatinine (0.94±0.57 vs. 0.71±0.25 mg/dl, p=0.00) as compared to later group. D. Comparison of hematological parameters between p. falciparum group (n=118) and control group (n=100) -- MCH (28.94±6.45 vs. 32.64±4.52 pg), Hct (33.17±3.13 vs. 41.45±5.2, p=0.00), total WBC count (6008.92±1393.56 vs. 8096.21±1035.41), differential lymphocyte count [(36.39±15.45) % vs. (44.13±15.87) %, p=0.00] total platelet count (181350.87±91122.45 vs. 251350.10±81315.62 /cc, p=0.00) were reduced significantly in p. falciparum group, whereas, ESR (68.78±7.79 vs. 15.75±5.56 mm /1st hour), differential monocyte count[(13.59±6.80) % vs. (8.68±4.95) %, p=0.00], basophil count [(1.72±1.64) % vs. (0.57±0.12) %, p=0.00] were raised significantly as compared to control group. DISCUSSION After the development of the microscope by Antonie Van Leeuwenhoek in the 15th century, diagnosis of many parasitic diseases including malaria was possible. Moreover, in the last three decades, many more investigation methods have come into action, thus refine and modify our diagnosis. Due to huge cost for development Newer tests based on serology (Falkon assay screening test ELISA (FAST-ELISA, Rapid antigen detection systems (RDTs), real-time polymerase chain reaction, loop-mediated isothermal amplification (Lamp and Luminex), mass spectrometry12 to diagnose accurately the malaria infection at its earliest phase, direct microscopy and sociological methods and hematological parameters for supporting diagnosis are still the gold standard for the diagnosis of malaria infection. Ashis et al., In our present study, male to female ratio were 3:1, 1.36:1 in p. vivax and p. falciparum respectively. But, when we considered the total number of affected patients, the ratio was 1.97:1, whereas, in the study done by Muwonge H et al. The ratio was 2.5:1.13 In a study done by Hussain M M et al14. The ratios were 1.73:1 and 2:1 at p. vivax and p. falciparum respectively. Our study showed the extreme male preponderance over female in case of p. vivax infection than p. falciparum infection. Mean age of incidence of malaria in our study in p. vivax, p. falciparum and control group were 42.88±88.4 years, 27.2±14.2 years and 32.49±4.15 years respectively, which showed an age incidence in p. falciparum was close to the control group. But in a study done by Hussain M M et al14 age incidence were 29.25±1.9 years, 27.98±2.4 years and 29.48±2.6 years in p. vivax, P. falciparum and control group respectively, which showed an age incidence in the case of p. falciparum group was nearer to the our value (, 27.2±14.2 years), whereas, in the case of p. vivax group, age incidence was much higher in our study than the study of Hussain M M et al14 (42.88±88.4 years vs. 29.25±1.9 years). P. vivax, p. falciparum and control groups in our study showed mean axillary temperature of 101.7±0.01o F, 100.9±0.1o F and 98.1±0.31o F respectively, which was higher as compared to the study done by Hussain M M et al (99.65±0.1o F, 98.91±0.3o F and 97.68±0.1o F in p. vivax, p. falciparum and the control group respectively). 14 In malaria, anemia is multifactorial in origin—like, hemolysis of parasitized and non-parasitized RBC, depressed or ineffective erythropoiesis15, nutritional deficiency, especially in case of females, blood due to hook worm infestation (which is most common in West Bengal), decreased erythrocyte production. 16 Present study demoed significantly low hemoglobin in p. vivax group (11.785±2.1 gm/dl) as compared to the p. falciparum group (12.32±1.52 gm/dl, p=0.02) and control group (12.51±0.45 gm/dl, p=0.00). This observation is not consistent with previous reports of Plasmodium infection, in which, hemoglobin degradation resulting anemia had a good correlation with severity of infection due to p. falciparum.17 In present study, low hemoglobin may be due to nutritional deficiency or increased blood loss in association with hemolysis of parasitized or nonparasitized RBCs. 123 Int J Med Res Health Sci. 2014;3(1): 120-127 In our present study, ESR was significantly raised in p. vivax than in p. falciparum (75.18±6.42 mm/1st hour vs. 68.78±7.79 mm/1st hour) as shown in other study done by Hussain M M et al (82.19±5.1 mm/1st hour vs. 77.79±4.5 mm/1st hour).14 Again, combination of low hemoglobin and raised ESR, as shown in our study, was highly significant hematological parameters in predicting p. vivax malaria infection in endemic areas in patients who are symptomatic, but false smear negative or serologically negative due to very low parasitemia, as shown in other studies done by Erhart et al18 and Gerardin et al.19 Mean value of total WBC count was significantly low in p. falciparum group as compared to p. vivax group (6008.92±1393.56/cc vs. 6653.16±1999.01, p=0.00). Commonly, the total WBC count is within normal range20, 21, except, in a few studies, where there was evidence of leucopenia. 21, 22 In our present study, in p. falciparum group, there was also leucopenia, which was also consistent with other Indian study done in malaria endemic area, where there was also evidence of leucopenia.23 In Panama22 and Turkey24, also there were evidences of leucopenia in cases of p. vivax, p. falciparum and dual infection. In our present study, there was significant reduction differential lymphocyte count in p. falciparum ((36.39±15.45) %, p=0.00) as compared to p. vivax (42.14±12.42) % and control group (44.13±15.87) %. Usually, differential lymphocyte count in acute malaria, varies with the increase or decrease in differential WBC lines. Hence, in respect to differential lymphocyte count, varying reports (increase, decrease or normal) were observed in different studies in case of acute malaria infection21. According to recent literature, lymphopenia may occur in non-immune adult21, 25 and in children in endemic areas. 17, 21 In the present study, though, the differential lymphocyte count was within normal range, but, it was in the low range of normal in p. falciparum group. The factors responsible for transient lymphopenia are: firstly, tissue distribution of lymphocytes26 from freely flowing blood stream to the endothelial lining of the blood vessels to adhere27, secondly, lymphocyte destruction due to Fas-induced apoptosis. 28 Owing to the high rate of lymphocyte destruction in p. falciparum affected patients, both absolute and differential count will be low.29 This may explain why mean total lymphocyte counts was in lower range of normal in p. falciparum group. Ashis et al., Usually, phagocytes (Neutrophil and macrophages) and/or natural killer [NK] cells are the effector cells, been activated as a result of an immune response to blood borne pathogens. So, obviously, an early pathological hall-mark in acute malaria is reticuloendothelial cell hyperplasia involving macrophages.21 Monocytosis was the constant hematological finding in different studies of acute malaria17, 30-32 as well as, in our present study, where significant monocytosis were observed in both p. vivax and p. falciparum groups [(10.10±2.17)%, vs. (13.59±6.80)%,], as compared to control group[ (8.68±4.95)% p =0.01]. In our study, mean neutrophil count was within normal range as compared to control group [p. vivax= (42.67±21.02) %, p. falciparum= (46.39±18.18) %, control group = (43.77±21.31) %], which was consistent with the other study in India31, where 85% of patients had normal Neutrophil count, as well as, study done in Singapore.33 Though, few studies demonstrated neutropenia27, which may be the result of increased margination and sequestration of neutrophils due to increased expression of cell adhesion molecules [ICAM—1 and VCAM—1] occurred in acute malaria. Some earlier studies demonstrated neutrophilia also.17 Though our study showed no difference in eosinophil count in p. vivax and p. falciparum [(3.01±4.19) %, (4.12±4.79) % ] as compared to control (2.92±7.1) %, but few studies in the world34, showed evidence of eosinopenia, whose significance was not explained. But, during recovery, these patients showed rebound neutrophilia34, which was explained as the result of enhanced T-helper—2 cell response, which occurred during this period. Now-a-days, lots of work have been going on regarding the platelet hemostasis in acute malaria, because of the fact that, complexes of platelet and coagulation factors surround the flowing and sequestrated parasitized RBCs and enclose vascular endothelium.21 The different studies on acute malaria in the world17,23, 31, 35, 36 showed that the magnitude of thrombocytopenia varied according to species and severity of infection. It was also shown that p. vivax group was associated with severe thrombocytopenia than p. falciparum group. Similarly, our present study showed thrombocytopenia in p. vivax group was more severe than that in p. falciparum group (161792.45±61165.62 /cc. vs. 181350.87±91122.45/cc), though the count was within 124 Int J Med Res Health Sci. 2014;3(1): 120-127 normal limit, as compared to control group (251350.10±81315.62/cc). This thrombocytopenia stimulates bone marrow to produce an increased number of megakaryocytes, which ultimately produce megaplatelets and leave the bone marrow to enter the circulation; the stimulating factor being thrombopoietin, a key platelet growth factor, which was described in the study done by Cyril et al37. As a result of increased number of megaplatelets, mean platelet volume will be increased during acute malaria infection.17, 23. The pathophysiology of thrombocytopenia is multifactorial. Firstly, splenic sequestration of RBC, secondly, antibody mediated platelet dysfunction, thirdly, release of adenosine diphosphate (ADP) as a result of hemolysis of parasitized RBCs, fourthly, abnormal megakaryocytosis, fifthly, invasion of platelets by parasites, sixthly, phagocytosis of platelets, seventhly, oxidative stress.21, 38 In our present study, MCHC was significantly reduced in p. vivax group as compared to p. falciparum group (34.18±1.62 g/dl. Vs. 35.47±1.48 g/dl, p=0.00), but, only MCH were reduced in both groups as compared to control group (p. vivax = 27.72±8.21 pg., p. falciparum = 28.94±6.45 pg., control = 32.64±4.52 pg.). But, all the RBC indices were within normal limits, which may be due to the following factors: firstly, low production of cytokines, secondly, less endothelial cell activation; thirdly, milder changes in coagulation profile, fourthly, diminished sequestration, fifthly, decreased hemolysis in less severe malaria. Our present study demoed significantly raised serum creatinine level in p. vivax group as compared to p. falciparum (0.94±0.57 mg/dl, vs. 0.71±0.45 mg/dl., p=0.00) and control group (0.71±0.25 mg/dl.). This study was consistent with the study done by Ogdaboyl E O et al39 and Delanghe J et al40, in which, raised creatinine was seen in the Nigerian population. The elevated serum creatinine is probably due to ineffective filtration ability as a result of renal functional impairment. In our study, plasma glucose level was lower in p. vivax group (93.8±18.67 mg/dl) as compared to p. falciparum group (100.35±10.89 mg/dl) and control group (98.25±11.92 mg/dl). This low blood glucose levels as well as low hemoglobin level are the two most reliable indicators and hematological parameters in predicting the presence of p. vivax malaria as shown in other studies also18, 19. CONCLUSION Malaria infection was twice more common in males than females. Younger age group was the victim of plasmodium falciparum, whereas, plasmodium vivax affected higher age group. Plasmodium vivax affected patients were more anemic. The combination of low hemoglobin, low fasting blood sugar and significantly raised ESR is highly significant in predicting severity of Plasmodium infection in patients of malaria endemic areas, which was evidenced in our present study. Lymphopenia was observed in Plasmodium falciparum affected patients, whereas, thrombocytopenia in Plasmodium vivax affected patients, but, significant monocytosis was observed in both groups. Significantly reduced MCHC was observed in Plasmodium vivax groups, whereas, MCH was reduced in both groups. Conflict of interest: Nil. REFERENCES 1. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005;434: 214-17 2. Yadav D, Chandra J, Dutta AK. Benign tertian malaria: how benign is it today? Indian J. Pediatr. 2012;79(4): 525-27 3. Lathia TB, Joshi R. Can hematological parameters discriminate malaria from non malarious acute febrile illness in the tropics? Indian J. Med. Sci. 2004;58: 239-44 4. Barnish G, Bates I, Iboro J. Newer drug combinations for malaria. BMJ. 2004;328: 151112 5. Nadeem M, Ali N, Qamar MA. Hematological findings in acute malarial infection list of authors along with highest qualification and institute. Biomedica. 2002;18: 62-65 6. Costa E T M, Avril M, Nogueira A, Gysin J. Cytoadhesion of Plasmodium falciparum-infected erythrocytes and the infected placenta: a two-way pathway. Brazilian Journal of Medical and Biological Research. 2006;39(12): 1525-36 7. Francisschetti I M B. Does activation of blood coagulation cascade have a role in malaria pathogenesis? Trends in Parasitology. 2008;24(6): 258-63 125 Ashis et al., Int J Med Res Health Sci. 2014;3(1): 120-127 8. Ghosh K, Shetty S. Blood coagulation in falciparum malaria—a review. Parasitology Research. 2008;102(4): 571-76 9. Clark LA, Budd AC, Alleva LM, Cowden WB. Human malarial disease: a consequence of inflammatory cytokine release. Malaria Journal. 2006;5:85 10. Haldar K, Mohandas N. Malaria, eryrhrocytic infection, and anemia. Hematology/The Education Programme of the American Society of Hematology. 2009;10:87-93 11. Price R N, Simpson J A, Nosten F. Factors contributing to anemia after uncomplicated falciparum malaria. Am. J. Trop. Med. Hyg. 2001;65: 614-22. 12. Ndao M. Diagnosis of parasitic diseases: old and new approaches. Interdisciplinary Perspectives on Infectious Diseases. 2009; Article ID 278246. 13. Muwonge H, Kikomeko S, Sembajjwe LF, Seguya A, Namugwanya C. How reliable are Hematological Parameters in predicting Uncomplicated Plasmodium falciparum Malaria in an Endemic region? ISRN Tropical Medicine. 2013; Article ID 673798. 14. Hussian MM, Sohali M, Abhishek K, Raziuddin M. Investigation on Plasmodium vivax infection influencing the host factors in tribal dominant and malaria endemic population of Jharkhand. Saudi J Biol Sci. 2013;20(2): 195-203 15. Weatherall DJ, Miller LH, Baruch DI, Marsh K, Doumbo OK, Casals-Pascual C. et al. Malaria and the red cell. Hematology Am. Soc. Hematol. Educ. Program. 2002;35-57 16. Philips RE, Pasvol G. Anemia in Plasmodium falciparum malaria. Baillieres Clin. Hematol. 1992;5: 315-30. 17. Maina RN, Walsh D, Gaddy C, Nongo G, Waitumbi J, Otieno L. Impact of Plasmodium falciparum infection on hematological parameters in children living in Western Kenya. Malar. J. 2010;9(suppl 3):S4 18. Erhart LM, Yingyuen K, Chuanak N, Buathong N, Laoboonchai A, Miller RS. et al. Hematological and clinical indices of malaria in a semi-immune population of Western Thailand. Am. J. Trop. Med. Hyg. 2004;70: 8-14. 19. Gerardin P, Rogier C, Ka AS, Jouvencel P, Brousse V, Imbert P. Prognostic value of thrombocytopenia in African children with Ashis et al., 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. falciparum malaria. Am. J. Trop. Med. Hyg. 2002;66: 686-91 Haroon H, Fazel PA, Naeem A, Mobin A, Naqvi A, Makki K. Hide and seek hematological aspects of malaria—a developing country perspective. Journal of Infection in Developing Countries. 2013;7(3): 273-79 Abdalla S H, Pasvol G. malaria: A Hematological Perspective.2004; Imperial College Press, London. www.uptodate.com/contents/anemia-in-malaria Reiley C G, Barrett Jr O. Leukocyte response in acute malaria. Am. J. of the Med. Sciences. 1971;262(3): 153-58 Chandra S, Chandra H. Role of hematological parameters as an indicator of acute malarial infection in uttarakhand state of India. Mediterranean Journal of Hematology and infectious Diseases. 2013;5(1): Article ID e2013009. Koltas LS, DEmirhindi S, Hazar S, Ozcan K. Supportive presumptive diagnosis of plasmodium vivax malaria: thrombocytopenia and red cell distribution width. Saudi Medical Journal. 2007;28(4): 535-39 Richards M W, Behrens RH, Doherty JE. Short report: Hematological changes in acute, imported Plasmodium falciparum malaria. Am. J. of Trop. Med. And Hyg. 1998;59(6): 859 Hviid L, Kemp K, Kern P. What is the cause of lymphopenia in malaria? Infection and Immunity. 2000;68(10): 6087-89 Dale DC, Wolff SM. Studies of the Neutropenia of acute malaria. Blood. 1973;41(2): 197-206 Kern P, Dietrich M, Hemmer C, Wellinghausen N. Increased levels of soluble Fas ligand in serum in Plasmodium falciparum malaria. Infection and Immunity. 2000;68(5): 3061-63 Balde AT, Sarthou J, Roussilhon C. Acute Plasmodium falciparum infection is associated with increased percentage of apoptotic cells. Immunology Letters. 1995;46(1-2): 59-62 Abdalla SH. Peripheral blood and bone marrow leucocytes in Gambian children with malaria: numerical changes and evaluation of phagocytosis. Annals of Tropical Paediatrics. 1988;8(4):250-58 Akhtar S, Gumashta R, Mahore S, Maimoon S. Hematogical changes in malaria: a comparative study. Journal of Pharmacy and Biological Sciences. 2012;2(4):15-19 126 Int J Med Res Health Sci. 2014;3(1): 120-127 32. El-Shoura SM. Falciparum malaria in naturally infected human patients: IV-Ultra structural changes in peripheral white blood cells. Annales de Parasitologie Humaine et Comparee. 1993;68(4):169-75 33. Kueh YK, Yeo KL. Hematological alterations in acute malaria. Scandinavian Journal of Hematology. 1982;29(2):147-52 34. Davis TME, Ho M, Supanaranond W, Looareesuwan S, Pukrittayakamee S, White N J. Changes in the peripheral blood eosinophil count in falciparum maqlaria. Acta Tropica. 1991;48(3): 243-46 35. Taylor W RJ, Widjaja H, Basri H. Changes in the total leukocyte and platelet counts in Papuan and non Papuan adults from Northeast Papua infected with acute Plasmodium vivax or uncomplicated Plasmodium falciparum malaria. Malaria Journal; 2008;7: article 259. 36. Khan SJ, Abbas Y, Marwat MA. Thrombocytopenia as an indicator of malaria in adult population. Malaria research and treatment. 2012;Article ID 405981. 37. Kreil A, Wenisch G, Brittenham S, Looareesuwan S, Peck-Radosavljevic M. Thrombopoietin in Plasmodium falciparum malaria. British Journal of Haematology. 2000;109(3):534-36 38. Lacerda MVG, Maurao MPG, Coelho H C, Santos JB. Thrombocytopenia in malaria: who cares? Memorias do Instituto Oswaldo Cruz. 2011;106910: 52-63. 39. Ogdaboyl EO, Tsado RD. Renal and hepatic dysfunction in malaria patient in Minna, North Central Nigeria. Online J. Health Allied Sci. 2009; 8(3):8 40. Delanghe J, De Slypere JP, De Buyzere M, Robbrecht J, Wieme R, Vermeulen A. Normal reference values for creatine, creatinine and carnitine are lower in vegetarians. Clin. Chem. 1989;35(8):1802-03 127 Ashis et al., Int J Med Res Health Sci. 2014;3(1): 120-127 DOI: 10.5958/j.2319-5886.3.1.025 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th th Received: 12 Dec 2013 Revised: 25 Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 28th Dec 2013 NONLINEAR DYNAMIC ANALYSIS OF VOICE: A NORMATIVE STUDY IN THE INDIAN POPULATION Jacqueline B. Fernandes1, *Radish Kumar Balasubramanium2, Arivudai Nambi Pitchaimuthu2, Jayashree S. Bhat3 1 II MASLP, 2 Associate Professor, 3Professor & Head, Department of Audiology and Speech Language Pathology, Kasturba Medical college (Manipal University), Mangalore, India. *Corresponding author email:
[email protected] ABSTRACT Background: The aim of this study was to establish normative data for the Indian population using Nonlinear dynamic analysis. In this study, correlation dimension, a measure of nonlinear dynamic analysis was performed for normophonic young, middle aged and elderly voices. Materials and Methods: For this purpose, normophonic young, middle aged and elderly individuals were selected without a history of voice/respiratory problems and vocal abuse/ misuse. 60 participants were selected in each group. All of these individuals had a normal voice as evaluated through GRBAS scale. Sound Recorder, on a computer desktop was used for voice recording and “convert” code in MATLAB as well as D2.ini.writer software based on TISEAN package (Hegger, Kantz & Schreiber, 1999) was used for the calculation of Correlation dimension (D2). Correlation dimension measures were obtained for each participant, for both steady vowel phonations (/a/, /i/, /u/) as well as narration samples. Results: The correlation dimension measures across the group revealed a significant main effect of the groups indicating correlation dimension increases with increase in age. Conclusions: The application of nonlinear dynamic measures in the assessment of voice is a novel venture and thus this study provides normative data for correlation dimensions in the Indian population for future comparisons against the disordered voice samples. Further studies are warranted to investigate the same in the clinical population. Also other nonlinear dynamic analysis methods need to be investigated to obtain the normative data in the Indian population. Keywords: Nonlinear dynamic analysis, Correlation dimension, Normophonic voice, INTRODUCTION Acoustic analysis does not appraise completely the true nature of the underlying vocal fold function. Yet, acoustic analysis is still used in the voice assessment due to some level of correspondence between voice production and voice acoustics. Though not perfect, much can be inferred about the vocal physiology based on the acoustic analysis. A normal voice signal is said to be quasi periodic and must have very minimal cycle to cycle variability in frequency as well as amplitude. When the voice is periodic and/or nearly periodic, measures such as Jitter and Shimmer are reliable whereas they are unreliable in the case of severely perturbed voices due to the difficulty in identifying cycle boundaries. Due to this reason, traditional measures such as jitter, shimmer have lost their value in the assessment of aperiodic voices. Nonlinear dynamic analysis endeavor to recognize and explain the presence of ‘‘rules’’ underlying the random nature of a severely perturbed voices. This approach considers the severely perturbed voices as 128 Jacqueline et al., Int J Med Res Health Sci. 2014;3(1);128- 132 ‘‘chaotic’’ in nature. Chaos theory believes that erratic looking temporal behavior does not arise randomly, but is deterministic in nature i.e., initial condition(s) determines the end result based on some law/rule.1 A potential advantage of this method, when compared with traditional perturbation measures of the voice signal, is the possibility of objectively quantifying dysphonia severity without the requirement of cycle boundary detection. Also, non linear methods have the capability of analyzing all the types of voice signal (periodic as well as aperiodic voice). There are two most commonly used nonlinear methods which include phase space portraits and the subsequent computation of correlation dimension.2 Usually, voice waveform data are entrenched in phase space and then reconstructed using the method of lag variables or delay coordinates.3 A periodic signal will show a closed trajectory in phase space, with increasing perturbation resulting in irregular or chaotic trajectories.3-5 Though vocal fold vibration is graphically represented as a trajectory in phase space with time,2 further computation is required to objectively quantify the complexity of the signal in space. Correlation dimension (D2) is one such measure that quantifies the complexity of the signal by specifying the number of degrees of freedom (ie, dimensions) needed to describe a dynamic system like voice.5 If the dynamics of a system can be determined to be low dimensional, then a complex determinism may exist, which is responsible for the observed signal profile.6 Alternatively, more complex the system, greater the number of degrees of freedom are required to describe its dynamic state, and the higher the correlation dimension. These nonlinear dynamic methods have been analyzed in both pathological and non pathological voice samples5, 7-9 in several studies. In the modern clinical outlook, its popularity is limited. Also, there are no normative available in the Indian context. Hence, the present study is an attempt in this direction. Results of this study would guide the speech language pathologist in a more efficient assessment and management of voice disorders. Aim of the study: To obtain a normative data for voice using Non Linear Dynamic Analysis. METHOD This study followed a cross sectional normative study design, with Non Random Convenient Sampling. The institutional ethical approval was obtained prior to the conduct of the study. Participants were alienated into three different groups based on age10 which are as follows: Table 1: Age Range Classification10 AGE RANGE GROUP NAME 18 – 40 Years Young Adults 41- 60 Years Middle Aged Adults 61 Years & Above Older Adults Each group consisted of 60 individuals out of which 30 were females and 30 were males. All the participants were normal healthy individuals without any history of vocal abuse/misuse, smoking, neurological, organic and non organic vocal pathological conditions. All the participants had a normal voice as evaluated perceptually by three trained speech pathologists using the GRBAS (Grade Roughness Breathiness Asthenia Strain) scale.11 Prior to the study an informed consent was obtained from all the participants. Instrumentation: Sound Recorder, a computer device was used for recording of the voices. A dynamic microphone was used to record voice. Adobe Audition (version 3.0) was used for noise reduction from the samples. Correlation Dimension was o bt ai ned by means of M AT L A B (matrix laboratory) developed by Math Works and D2.ini.writer software based on TISEAN package.12 Procedure: During the voice sample recording, the participants were seated in a comfortable chair. All the voice samples were directly recorded in Sound Recorder using a dynamic microphone. The distance between the microphone and the participant’s mouth was constantly maintained at 10 cm. After a brief period of familiarization, the participants were instructed to phonate vowel /a/ at their habitual loudness and pitch as if the vowel was a word in a conversation, and were also instructed to avoid singing it. The task was demonstrated to each participant and instructions were repeated as and when required. The task was repeated if the experimenter felt that the voice produced did not sound like their habitual voice production. The recordings were carried out in a 129 Jacqueline et al., Int J Med Res Health Sci. 2014;3(1);128- 132 sound treated room in a single sitting for all the participants. Similarly, a narration sample was also recorded using the same set up. A common topic that was maintained for narration was “home”. Analysis: The pre recorded voice samples collected for each participant was individually analyzed by means of a code written using MATLAB. The recorded voice samples were stored in “.wav” format. The voice samples were then fed into MATLAB by means of a “convert” code in order to transform it into “.txt” file format. Once the “.txt” format was obtained the file was then fed into a D2.ini.writer based on the TISEAN package12 in order to obtain the embedding dimension values. (Correlation Dimension, D2). A total of 15 correlation dimension values were obtained for each sample. The mean values for every dimension were calculated in order to obtain a normative range across the three age groups as well as to compare the variation amongst the three age ranges. RESULTS The present study was carried out with an aim to obtain normative data for the acoustic analysis of voice using Non Linear Dynamic Analysis. Age related differences were analyzed using one way ANOVA with bonferronis post hoc test. Fig. 1: Mean dimension values for sustained vowel /across the three groups. The above figure depicts no significant change amongst the three groups until the 7th dimension at p>o.05. However, a gradual increase in the mean dimension values was observed in older adults beyond the 8th dimension at p<0.05. Young and middle aged adults displayed similar profiles in the mean correlation dimension values. Fig. 2: Mean dimension values for narration across the three groups. The above figure indicates differences in the correlation dimension values across the three groups. Older adults showed a higher dimension value in comparison to young adults at p<0.05. The middle aged adults depicted a comparatively reduced mean value when compared with younger and older adults at p<0.05. The results revealed significant differences for phonation of vowel /a/, and narration at p < 0.05. DISCUSSION With the development of nonlinear vocal fold models, studies have put forward the means of assessing nonlinearity in the voice signal through various methods. These methods provide quantifiable data by considering the chaotic components in a voice signal. Various nonlinear dynamic analysis methods have been described in the literature. These include the development of phase space portraits, attractors, and the use of correlation dimension, all of which have produced variable results. In the present study, correlation dimension was used to characterize the normal voice samples across adults and geriatric in Indian population. Results of one way ANOVA revealed that the correlation dimension measures across the group revealed a significant main effect of the groups i.e., as the age increases, correlation dimension values increases. This suggests that as the age increases, complexity in the laryngeal mechanism also increases thereby providing chaos in the vocal fold vibration. Sulica reported that the age related anatomical changes occurs in the laryngeal system such as degenerative changes to the lamina propria and the 130 Jacqueline et al., Int J Med Res Health Sci. 2014;3(1);128- 132 mucosal glands in the larynx, all of which results in reduced production of laryngeal mucus which further causes intermittent alteration in vocal fold vibratory patterns thereby inducing changes in pitch, loudness and quality as well.13 Thus, it can be stated that non linearity is inherent in the laryngeal mechanism with the presence of chaos in the voice production. Higher correlation dimension values were reported in systems that have more chaos or deterministic noise. They suggest that the anatomical alterations in the vocal mechanism that occur for any pathological conditions result in higher values of correlation dimension. Hence, we can opine that anatomical alterations in the vocal mechanism that are exhibited by aged individuals could be the underlying cause for obtaining higher correlation dimension measures in this study.14 Baken reported that the Fractal dimension values are representative of the vibratory function of the vocal folds.15 Baken considered vocal folds to be oscillators whose movements if affected by means of any change in the vocal mechanism be it due to aging or organic pathology results in irregularity or chaos in the regular oscillations of the vocal folds. This irregularity in oscillation caused an increase in the value of the fractal dimension.15 Alternatively, a study carried out by Nicollas et al16 in children aged 6-12 years using nonlinear dynamic analysis reported that correlation dimension measure decreased with increasing age in children. Their results were attributed to several factors. The main factor considered amongst them was the evolution of the pediatric larynx.14,17 In support of this view, Eckel et al17 reported that the subglottic airway rapidly increases during the first 2 years and then follows a linear mode. During the same period, fundamental frequency decreases from 450 to 300 Hz, while membranous vocal fold increase by 1 mm. Histologically, it is well known that the collagen distribution in the vocal folds varies with age, with large variations in collagen fiber type occurring during the period between 6 years and mutation, corresponding to the ‘‘pre mutation’’.18 These histological changes, though not measured in the present study would have contributed to increased correlation dimension values in the older adults. However, it is interesting to note that correlation dimension values were more for young adults in comparison to middle aged adults. The explanation for this was unclear. Thus, nonlinear dynamic analysis of voice provided a quantifiable data on the age related changes in the voice production. It was evident that as the age increases, complexity of dimensions also increases with the decreased predictability of geriatric voices. This effect was pronounced in both phonation as well as the narration samples. Thus, it can be considered as a useful tool in the assessment of voice. However, it cannot replace the existing voice analysis techniques available to the voice clinician. Yet, it may add to the battery of voice assessment procedures. CONCLUSION The application of nonlinear dynamic measures in the assessment of voice is a novel venture and thus, this study provides normative data for correlation dimension in the Indian population for future comparisons with disordered voice samples. The correlation dimension measures across the group revealed a significant main effect of the group indicating that, correlation dimension values increases with increase in age. Further studies are warranted to investigate the same in the clinical population. Moreover, another nonlinear dynamic analysis methods need to be investigated to obtain the normative data in the Indian population. ACKNOWLEDGMENT: We thank our Dean, Kasturba Medical College (Manipal University), Mangalore for permitting us to carry out the study. REFERENCES 1. Williams GP. Chaos theory tamed. Washington, DC: Joseph Henry Press; 1997. 2. Jiang JJ, Zhang Y, McGilligan C. Chaos in voice, from modeling to measurement. Journal of Voice. 2006; 20: 2-17 3. Herzel H, Berry D, Titze IR, Saleh, M. Analysis of voice disorders with methods from nonlinear dynamics. Journal of Speech and hearing Research. 1994; 37: 1008 –19 4. Giovanni A, Ouaknine M, Guelfucci B, Yu P, Zanaret M, Triglia JM. Nonlinear Behavior of Vocal Fold Vibrations: The Role of Coupling between the Vocal Folds. Journal of Voice. 1999: 13; 465 – 76 131 Jacqueline et al., Int J Med Res Health Sci. 2014;3(1);128- 132 5. Zhang Y, Jiang JJ, Wallace MS, Zhou L. Comparison of nonlinear dynamic methods and perturbation methods for voice analysis. Journal of Acoustical Society of America. 2005; 118: 2551 – 60 6. Behrman A, Baken RJ. Correlation Dimension of Electroglottographic data from healthy and pathologic subjects. Journal of Acoustical Society of America. 1997; 102:2371 – 79 7. Herzel H, Mende W, Wermke K. Bifurcation and chaos in newborn infant cries. Physics Letters A.1990;145:418–24. 8. Rahn DA, Chou M, Jiang JJ, Zhang Y. Phonatory impairment in Parkinson’s disease: evidence from nonlinear dynamic analysis and perturbation analysis. Journal of Voice. 2007;21:64–71. 9. Butte CJ, Zhang Y, Song HQ, Jiang JJ. Perturbation and nonlinear dynamic dnalysis of different singing styles. Journal of Voice. 2009;23(6):647–52 10. Cichero J, Murdoch BE. Acoustic signature of the normal swallow: characterization by age, gender, and bolus volume. Annals of Otology Rhinology and Laryngology. 2002;111: 623-32. 11. Hirano M. Clinical examination of voice. New York: Springer verlag; 1981. 12. Hegger R, Kantz H, Schreiber T. Practical Implementation of Nonlinear time series methods: The TISEAN package, CHAOS: An interdisciplinary Journal of Nonlinear Sciences. 1999: 9; 413 - 17. 13. Sulica L. Voice Medicine: The Ageing Voice. Voice and Aging Sciences. ; 2009 [cited]. Available from: http://www.voicemedicine.com/aging.htm. 14. Jiang JJ, Zhang Y, Stern J. Modeling of chaotic vibrations in symmetric vocal folds. Journal of Acoustical Society of America. 2001; 110: 212028 15. Baken RJ. Irregularity of Vocal Period and Amplitude: A first approach to Fractal Analysis of Voice. Journal of Voice. 1994; 4: 185 –97 16. Nicollas R, Garrel R, Ouaknine M, Giovanni A, Nazarian B, Triglia, MJ. Normal Voice in Children Between 6 and 12 Years of age: Database and Nonlinear Analysis. Journal of Voice. 2008; 22: 671-75 17. Eckel HE, Koebke J, Sittel C, Sprinzl GM, Pototschnig C, Stennert, E. Morphology of the human larynx during the first five years life studied on whole organ serial sections. Annals of Otology, Rhinology and Laryngology. 1999; 108: 232-38 18. Hacki T, Heitmuller S. Development of the Child’s Voice: Pre -mutation, Mutation. International Journal of Pediatric Otorhinolaryngology. 1999; 49: 141- 44 132 Jacqueline et al., Int J Med Res Health Sci. 2014;3(1);128- 132 DOI: 10.5958/j.2319-5886.3.1.026 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 14 Dec 2013 Revised: 26th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 28th Dec 2013 COMPARISON OF THE EFFECT OF MIME THERAPY VERSUS CONVENTIONAL THERAPY ON THE SUNNYBROOK FACIAL GRADING SYSTEM IN PATIENTS WITH ACUTE BELL’S PALSY *Mistry Gopi S1, Sheth Megha S2, Vyas Neeta J3 1 Post graduate student, 2Lecturer, 3Principal, SBB College of physiotherapy, Ahmedabad, Gujarat, India *Corresponding author email:
[email protected] ABSTRACT Background: Facial resting symmetry and expressions are determinants of facial attractiveness & being a marker of good health. Mime therapy is a combination of mime and physiotherapy and aims to promote symmetry of the face at rest and during movement. The objective of this study is to compare the effect of Mime therapy and conventional therapy on the facial functions in patients with acute Bell’s palsy. Method: The quasi-experimental study was conducted at SBB College of physiotherapy. A convenience sample was taken consisting of 30 participants, 10 in each group. Group A received Mime therapy. Group B, conventional therapy and Group C received home exercise program. Facial symmetry at rest and movement was assessed through Sunnybrook facial grading scale (FGS) after completion of 10 sessions to each group. At the end of treatment, response to treatment was assessed by the Patient’s global impression of change scale (PGIC). Level of significance was kept at 5%. Result: Analysis of variance was used to compare all outcomes. At the end of 10 sessions, scores on Sunnybrook FGS (p<0.001) and PGIC (p<0.001) shows significant difference within and between groups. Post hoc Bonferroni test was used for multiple comparisons. FGS shows significant differences between groups A&B (p<0.001) and groups A&C (p<0.001). But no significant difference was seen between groups B&C(p=1.00). PGIC scale shows significant differences between groups A&B (p<0.001) and A&C (p<0.001) but no significant difference was seen between groupsB&C (p=1. 00). Conclusion: Mime therapy improves facial symmetry and functions more than conventional therapy and home exercises in people with acute Bells’ Palsy. No difference was found between conventional therapy and home exercise program. Key words: Bell’s palsy, Mime therapy, Sunnybrook facial grading system, Patient’s Global Impression of change scale, electrical stimulation. INTRODUCTION The term Bells’ Palsy is defined as an idiopathic, acute and unilateral paresis or paralysis of the face which may be partial or complete occurring with equal frequencies on right and left sides of the face.1 The major cause of Bell’s Palsy is idiopathic, accounting for 50% of all cases. Other few suggested causes are exposure to cold, middle ear infections, dental and ENT surgeries and traumatic.2 The problems faced in acute phase of Bell’s palsy include difficulty in closing the affected side eye, facial deviation to the unaffected side, difficulty in drinking, eating and speaking along with psychological problems and facial appearance is the main concern in any phase of Bell’s palsy.2,4 Facial palsy is classified according to House and Brackmann score into 6 grades, where grade 1 is normal, grade 2 has slight dysfunction, grade 3 has moderate dysfunction, grade 4 has moderate to severe dysfunction, grade 5 has severe dysfunction and grade Gopi et al., Int J Med Res Health Sci. 2014;3(1):133-136 133 6 has total paralysis.3 Mime therapy consists of auto massage, stretching with facilitation exercises, relaxation, inhibition of synkinesis and coordination and emotional expression exercises.4 A Cochrane review done by Teixeira LJ et al in February 2011 has concluded that there is only very low quality evidence that facial exercise reduces sequel in acute cases.5 Facial symmetry is a determinant of facial attractiveness, it is a marker of good health and it influences interpersonal attraction.6, 7 Bell’s palsy can dramatically affect, patients general quality of life and expressions and interpersonal communications. Patient’s with bell’s palsy suffer not only the functional consequences of impaired facial motion but also the psychological appearance of skewed facial deviations.8 Less evidences are available for the effectiveness of mime therapy in improving facial symmetry in acute phase management in Bell’s palsy, so arises the need of the student. The objective of this study is to assess and compare the effect of Mime therapy and conventional therapy on the facial symmetry and functions in patients with Bell’s palsy in the early stage of paresis. METHODOLOGY A Quasi experimental study was conducted at SBB College of physiotherapy and convenience sampling was used. The study consisted of 30 participants, 10 in each group. The study was carried out from June 2013 to October 2013. Inclusion criteria: Males and females diagnosed with Bell’s palsy in the age group of 18-70 years with acute onset (1-3wks) and no other neurological deficit involving the face were included. Exclusion criteria: Subjects with a history of surgical intervention for the ear and facial nerve palsy, pain of any other origin and non co-operative patients were excluded. Materials used were powder, mirror, standard electrical stimulator with accessories and infra red lamp. Outcome measures used were 13-item Sunnybrook facial grading system (SBFGS) 8 and the Patients' Global Impression of Change (PGIC) scale. 9 SBFGS includes 3 components resting symmetry, symmetry of voluntary movement and synkinesis. Resting symmetry of 3 components are checked eye, cheek (naso labial fold) and mouth. In symmetry of voluntary movements there are 4 components for standard expressions and grades are given according to the symmetry during movements; in synkinesis again Gopi et al., there are 4 grades according to the amount of synkinesis. The study was reviewed & approved by the Institutional Ethics Committee, SBB College of Physiotherapy, V S General Hospital, Ahmedabad, Gujarat. Subjects were explained the procedure and purpose of the study & written informed consent was taken. After initial neurological examination the participants were assigned randomly into three groups, Group A: Mime therapy group, Group B: Conventional therapy group and Group C: Home exercise group. Then severity of the condition was measured by Sunnybrook Composite Score (SBC) pre treatment and post treatment. Group A was given 10 sessions of Mime therapy which included auto massage- effleurage and kneading for 10 to 15minutes on both the sides of the face, stretching exercises of the muscles of the affected side followed by facilitation, specific low intensity exercises to co-ordinate both the halves of the face, active assisted exercises for affected side of the face, exercises of mouth and eye with simultaneous inhibition of synkinesis if present. A mirror was used for biofeedback. Exercises to increase participants awareness of lip movements such as a,e,i, o etc. Group–B was given Electrotherapy (Conventional therapy) for 10 Sessions. It included Infrared radiations (up to 7 days from the date of onset) to affected side followed by electrical stimulation (Surged Faradic current) of affected muscles with 3 sets of 30 contractions for each nerve trunk. Exercise program to all facial muscles was given as below. Group –C was a control group. They were given 10 Sessions of home exercise program including, massage, facial muscle exercise program in front of mirror, 5-6 times in a day and home advices. Level of significance was kept at 5%. RESULTS Analysis of results was done with SPSS version 16.0. ANOVA (Post Hoc Bonferroni test) was used to analyze the difference in facial symmetry post intervention in 30 patients with acute Bell’s palsy. The mean age of the participants was 44.1 years in group A, 46.2 years in group B and 41.9 years in group C. There were 6 females and 4 males in groups A and B and 5 males and 5 females in group C. Int J Med Res Health Sci. 2014;3(1):133-136 134 Post hoc analysis of SBFGS showed that there was B (p<0.001) and group A & C (p<0.001) but no statistically significant difference between group A significant difference between group B & C (p=1.00). and B (p<0.001) and Group A and C (p<0.001) but no Table 1 show that differences in mean Sunnybrook significant difference between group B and C Composite (SBC) scores in all three groups is (p=1.00). Post hoc analysis of PGIC showed there was statistically significant. (p<0.001) statistically significant difference between group A & Table 1: Comparison of mean composite score of SBFGS (Mean ± SD) Variable Group A Group B Group C F value p value SBC(Pre) 38.5±14.5 33.6±15.79 38.5±12.31 SBC(Post) 86.2±6.81 53.8±12.79 60.9±19.5 SBC(Diff) 48.2±15.31 23.0±10.88 **- Very significance, SBC- Sunnybrook composite score Table 2: Comparison of total score of PGIC (Mean ± SD) Groups Mean±SD 23.4±13.06 A B C 6.60±0.699 3.70±0.675 4.00±1.15 11.935 F value p value 33.498 <0.001** <0.001** **-very significance DISCUSSION The present clinical trial was conducted to study the effect of Mime therapy on facial symmetry in patients with acute Bell’s palsy. The SBFGS used to evaluate severity of facial nerve paresis, included three components resting symmetry, voluntary movements and synkinesis.10 In the present study, asymmetry has reduced in all three groups but more in a Mime therapy group than others. This improvement may be because massage improves circulation and maintains muscle properties. Visual feedback has shown to control muscle activities in facial muscles.11 Also miming demands highly refined sense of body and muscle control. A study done by Ryan J, 2009 has concluded that massage done in mime therapy has shown to create new growth and increase production of collagen and connective tissue in facial muscles and restore facial muscle action.12 Study done on mime therapy efficacy in patients with long term facial nerve paresis shows that mime therapy improves facial symmetry13. In accordance with a study of Cronin and Steenerson (2003) biofeedback by surface electromyography results revealed improvement in facial symmetry.14 Ahmad SJ and Rather AH (2012) did a prospective study of physical therapy in facial nerve paralysis and found that physiotherapy in the form of electrotherapy Gopi et al., and facial exercises has an effective role in the early management of peripheral facial paralysis. 15 Because the effectiveness of therapeutic changes differs greatly among patients, it is essential that effectiveness of trials directly measure patient related improvement and satisfaction with treatment. 15 The PGIC is patient-reported, and asked the subject to “indicate how you feel now, compared to how you felt before receiving treatment in this study” on a 7-point scale. The cost of the treatment is low as along with therapy at physiotherapy center, home program is an integral part of the treatment. 9 So mime therapy is a good choice of treatment for people with bell’s palsy. Thus Mime therapy can be used in the treatment of people with acute Bell’s palsy to get improvement in facial asymmetry within a shorter period of time. Limitations of the study are that subjects were not followed up for a longer period of time. Randomization was not done. Home exercise protocol was not supervised. CONCLUSION Mime therapy improves facial symmetry and functions more than conventional therapy and home exercises in people with acute Bells’ Palsy. No difference was 135 Int J Med Res Health Sci. 2014;3(1):133-136 found between conventional therapy and home exercise program. Conflict of interest: Nil REFERENCES 1. Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell’s Palsy and herpes simplex virus: identification of viral DNA in and oneurial fluid and muscle. Ann Intern Med 2006; 124(1):27-30 2. Leo LJ. Effectiveness of Mime therapy to improve facial symmetry in acute Bell’s palsy patients- A Randomised controlled trial. American journal of physical therapy 2012;24(3):245-47. 3. Cederwall E, Olsen MF, Hanner P,Fogdestam I. Evaluation of physiotherapeutic treatment interventions in Bell’s Palsy. Physiother theory Pract. 2006;22:43-52 4. Buerskens CHG, Heymans PG. Mime therapy improves facial symmetry in patients with longterm facial nerve paresis. Australian Journal of Physiotherapy 2006; 52: 177-83 5. Teixeira LJ, Soares BG, Vieira VP, Prado GF. Physical therapy for Bell s palsy (idiopathic facial paralysis). Cochrane Database Syst Rev 2008; 3: CD006283. 6. Fink B and Penton-Voak. Evolutionary psychology of facial attractiveness. Current Directions of Psychological Science 2002;1:15458 7. Heymans PG. The impact of facial paresis: Psychological mechanism. In Buerskens CHG et al (Eds) The Facial Palsies, Utrecht: Australian Physiotherapy Association 2006;335-56. 8. John K Niparko, Lawrence R Lustig. Clinical neurology; Diagnosing and Managing Disorders of Hearing, Balance and the Facial Nerve. Informa Health Care. 2003;23:245-47 9. Turk DC, Dworkin RH, Allen RR. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain. 2003;106(3):337–45 10. Buerskens CHG, Heymans PG. Patients with facial nerve paresis: Description of outcomes. American Journal of Otolaryntology 2004;25:394400 Gopi et al., 11. Shafshak TF. The treatment of facial palsy from the point of view of physical and rehabilitation medicine. Eura Medicophys.2006; 42:41-47 12. Joyce Ryan, Microcurrent facial: An electrical current to restore facial muscles. April 17,2009. 13. Hu WL, Ross B, Nedzelski J. Reliability of the Sunnybrook Facial Grading System by novice users. J Otolaryngol 2001; 30:208-11. 14. Cronin GW, Steenerson RL. The effectiveness of neuromuscular facial retraining combined with electromyography in facial paralysis rehabilitation. otolaryngol Head Neck Surg 2003;128:534-38 15. Ahmad SJ and Rather AH. A Prospective Study of Physical Therapy in Facial Nerve Paralysis experience at a Multispecialty Hospital of Kashmir 2012;15(2):145-48 Int J Med Res Health Sci. 2014;3(1):133-136 136 DOI: 10.5958/j.2319-5886.3.1.027 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 26 Aug 2013 Revised: 13th Oct 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 26th Dec 2013 CARDIOVASCULAR RESPONSES DURING DEEP WATER RUNNING VERSUS SHALLOW WATER RUNNING IN SCHOOL CHILDREN Anerao Urja M 1, Shinde Nisha K2, Khatri S M3 1 Postgraduate student, 2Associate Professor, 3 Principal, Department of Cardio-respiratory Physiotherapy, College of Physiotherapy, Pravara Institute of Medical Sciences, Pravara Medical Trust, Loni. *Correspondence author email:
[email protected] ABSTRACT Overview: As the school going children especially the adolescents’ need workout routine; it is advisable that the routine is imbibed in the school’s class time table. In India as growing number of schools provide swimming as one of the recreational activities; school staff often fails to notice the boredom that is caused by the same activity. Deep as well as shallow water running can be one of the best alternatives to swimming. Hence the present study was conducted to find out the cardiovascular response in these individuals. Methods: This was a Prospective Cross-Sectional Comparative Study done in 72 healthy school going students (males) grouped into 2 according to the interventions (Deep water running and Shallow water running). Cardiovascular parameters such as Heart rate (HR), Saturation of oxygen (SpO2), Maximal oxygen consumption (VO2max) and Rate of Perceived Exertion (RPE) were assessed. Results: Significant improvements in cardiovascular parameters were seen in both the groups i.e. by both the interventions. Conclusion: Deep water running and Shallow water running can be used to improve cardiac function in terms of various outcome measures used in the study. Keywords: Deep water running, Shallow water running, cardiovascular responses. INTRODUCTION The importance of regular physical exercise, as part of therapy in everyday life, has a favorable influence on the important parameters of the cardiovascular system. A number of studies have also shown that regular physical exercise can decrease risk of the development of many cardiovascular diseases and also other health problems of both adults as well as children.1 People who are physically active live longer. Regular exercise reduces the risk of dying prematurely.2 Recommendations for appropriate amounts of physical activity for the young population, including school-age youth, have been developed by several organizations and agencies. Although recent reviews have summarized the benefits of regular physical activity on the health of youth and its potential for reducing the incidence of chronic diseases that are manifested in adulthood, a more systematic approach is indicated. 1-9 These reports present results of a systematic evaluation of evidence dealing with the effects of regular physical activity on several health and behavioral outcomes in school-age youth, with the goal of developing a recommendation for the amount 137 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 of physical activity deemed appropriate to yield beneficial health and behavioral outcomes. According to the current worldwide survey, childhood and adolescent health problems are one of the top five problems in the world in the year 2012. 3 They also identified that this health issue is important not only for the health care industry but also for the health of the children as they mature into adults. The health industry has recognized this problem and is beginning to mobilize with new programs aimed specifically at children. Numerous health risks have been associated with adolescent overweight, including hypertension, respiratory disease, several orthopedic disorders, diabetes mellitus and elevated serum lipid concentrations. 4, 5 Development of specialized physical activity programs are necessary as school systems face the reality of cutting programs, such as physical education and recess, to spend more time preparing for the standardized tests and examinations. Also; due to recent advances in technology; video games and gaming consoles have become more popular than outdoor sports activities thus; limiting the regular physical exercise. Current recommendations indicate that school-aged youth should participate daily in 60 minutes or more of moderate-to-vigorous physical activity that is appropriate and enjoyable; and involves a variety of activities including resistance training, aerobic activities such as swimming, bicycling, running and jogging. 1, 3, 10 Program developed should be such that it helps boys and girls develop competence and confidence in their abilities to engage in different types of physical activities. Fitness professionals who incorporate such training into kid-friendly classes and personal training sessions need to understand and appreciate the physical and psychosocial perspective of children and adolescents. 11 Therefore, program design considerations for developing successful programs should be such that regular participation in a training program has the potential to positively influence many health and fitness measures. As the school going children especially the adolescents’ need workout routine; it is advisable that the routine is imbibed in the school’s class time table. In India as a growing number of schools provide swimming as one of the recreational activities; school staff often fails to notice the boredom that is caused by the same activity. Deep as well as shallow water running can be one of the best alternatives to swimming. If the program is supervised and well taught it can be beneficial for both physical as well as psychological perspectives in the growth of the children. But; the change following the water running that would occur in terms cardiovascular parameters is still unidentified are not expressed. The evidence shows that there are many benefits of both deep water running and shallow water running. Since there were no prior studies performed to compare both the above groups; hence, it’s very important to study the changes in the cardiovascular responses and document them. Hence; the aim of the study was to compare cardiovascular responses after deep water running and shallow water running. Accordingly the hypotheses were formulated. METHODS There were 100 students who were screened for age, symptoms, and/or risk factors for any medical contraindications to exercise or any risk for disease. After finding their suitability as per inclusion and exclusion criteria were requested to participate in the study.8 students did not meet the inclusion criteria. The students were randomly selected for the study with the use of random table numbers. Thus, out of 92 students 72 were selected to participate in the study. These 72 students were explained about the study and intervention. A written informed consent form previously approved by the Institutional Ethical committee (IEC) was obtained and was signed by the School Principal and each student. The 72 students participated in the study. The demographic data for each student was filed. Pre treatment assessment of HR; SpO2, RPE, VO2max were done. In group A(N=35) students were receiving Deep Water Running. It takes place in water deep enough for students to be submersed to the neck. The use of flotation aids, such as a buoyancy belt was used to suspend the student so a lack of ground contact occurs during the exercise. In Group B (N=37) students were receiving Shallow Water Running. It was performed in shallow water typically below the xiphoid level, where students run/walk propelling themselves through the water. 12 Both the interventions were given for the duration of 6 weeks (3 times/ week) for 45minutes. At the end of 6 weeks post test measurements of the students were 138 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 taken. Data was collected and recorded. All the students completed the study. The data was recorded on the 1st day of the intervention and on the 18th day of intervention for each participant. subjected to statistical analysis. Various statistical measures such a mean, standard deviation (SD) and test of significance such as paired and unpaired ‘t’ test were utilized to analyze the data. The results were concluded to be statistically significant with p <0.05 and highly significant with p < 0.001 and not significant with p>0.05. Paired ‘t’ test was used to compare the differences of scores on pre-intervention and post-intervention within a single group. Unpaired ‘t’ test was used to compare differences between the two groups i.e. the control group (Group A) and the study group (Group B). RESULTS The results of the study were analyzed in terms of increase or decrease in Heart Rate, VO2max, RPE, SpO2 and comparison was made between the first and 18th day of the treatment. Statistical analysis was done by GraphPad InStat (Trial version) software. The data were entered into an excel spreadsheet, tabulated and Table 1: Table showing demographic data Demographics Group A Age (years) 16.51+ 1.269 Height (mts) 1.5+ 0.0943 Weight (kgs) 54.17+ 6.853 2 BMI(kg/m ) 22.12+1.773 100 98.14 Group B 16.40+ 1.116 1.57+ 0.064 52.10+ 4.408 21.02+ 1.323 98.37 98.54 80.1 79.37 98.64 74 73.25 80 58.46 56.51 60 40.1 39.77 SpO2 40 0 5.67 5.6 20 Group A Group B Heart rate 1.5 Group A Day1 RPE 1.45 VO2max Group B Day18 Fig.1.The following graph shows the mean of parameters of participants in group A and group B on 1st day & 18th day. Table.2: Showing mean difference of outcome measures in Group A and Group B and their Statistical inference Outcome Measure MEAN DIFFERENCE t df P Inference Heart Rate(b/m) SpO2 RPE VO2max(ml/kg/min) Group A 6.12±3.47 0.4±0.14 4.06±0.63 16.41±4.32 0.018 4.338 1.142 2.202 70 70 70 70 0.9851 <0.0001 0.2575 0.0310 Not Significant Highly Significant Not Significant Significant Group B 6.108±1.70 0.27±0.11 4.22±0.55 18.69±4.45 The difference between parametsers for DWR on day 1 and on day 18 were found to be extremely significant for HR (p= <0.0001) and RPE (p=<0.0001) and VO2max (p=<0.0001), very significant for SpO2 (p=0.0058). This indicates that the interventions in form of Deep water running in school children was effective in improving cardiovascular parameters in terms of Heart rate, SpO2, RPE, and VO2max. The difference between parameters for SWR on day 1 and on day 18 were found to be extremely significant 139 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 for HR (p= <0.0001) and RPE (p=<0.0001), VO2max (p=<0.0001), and SpO2 (p=0.0004). This indicates that the interventions in form of Shallow water running in school children was effective in improving cardiovascular parameters in terms of Heart rate, SpO2, RPE, and VO2max. The results between SWR and DWR on day 18 were not significant in improving VO2max (p=0.2032), RPE (p=0.5090), SpO2 (p=0.3224), HR (p=0.2253). This indicates that both the interventions in form of Deep water running and Shallow water running in school children were effective in improving cardiovascular parameters in terms of Heart rate, SpO2, RPE, and VO2max. The results of mean differences of the outcome measures indicate that both Deep Water running and Shallow water running improve Heart rate and RPE similarly. The VO2max is improved more in Deep Water running as compared to Shallow Water Running and SpO2 is best improved during Shallow Water Running as compared to Deep Water Running. DISCUSSION The study conducted in Loni; to compare Deep water running to Shallow water running. It is also believed to be the first study in India to compare the two water running techniques in hydrotherapy. This study titled cardiovascular responses in deep water running versus shallow water running in school children was performed in school boys aged between 15 to 19 years. This population was chosen to generalize the results for this age group. This study was conducted at Pravara swimming pool, Loni, was completed in the month of November 2012. The results of the study indicated that the intervention in the form of Deep water and shallow water running in school children was effective in improving cardiovascular parameters in terms of Heart rate, Spo2, RPE, and VO2max and were also comparable to other studies. In a study by Chu KS et al in 200213 measured maximal physiological responses to Deep-Water and Treadmill Running in Young and Older Women, they observed Lower HRmax values in DWR for both age groups (p < .05). Another study by Town GP and colleagues14 concluded that HRmax values for SWR and DWR were 88.6% and 86% of TMR, respectively. In a Comparative study the authors Michaud et al15 found that heart rate were significantly greater (p < 0.05) for treadmill running. These results when compared with the present study; the mean heart rate of participants during Shallow water running and deep water running at the end of the study were 73.25+2.201 and 74.13+3.66 respectively. Authors noted that heart rate has been reported to decrease during head-out water immersion exercise compared with air. 16-19 The mechanism responsible for the lower heart rate during immersion is the redistribution of blood volume from the periphery to the central region. The increased hydrostatic pressure of the water, concomitant with peripheral vasoconstriction to reduce heat loss forces peripheral blood into the thorax. This results in an enhanced venous return and a decreased stroke volume while maintaining cardiac output. 17 The possible explanation for reduction of heart rate in this present study was in accordance with an explanation given by Sophie Heywood.20 According to Sophie Heywood; the hydrostatic pressure which is depth dependent; there is increased stroke volume and cardiac output. The Cardiac output (CO) is the product of Stroke volume (SV) and Heart rate. Thus, during water immersion it is found that heart rate is reduced.20 The hydrostatic pressure causes an immediate increase in venous return, right atrium pressure and, hence, stroke volume. Increased stroke volume allows for the maintenance of cardiac output with lower HR as stated by Christie et al. in 1990. 18 A reflex response of the cardiovascular system to the cold receptors in the skin could also have contributed to the depressed HR in the water as the water temperature of 32.5 C is slightly lower than thermo-neutral for the resting condition.21 This study showed extremely significant difference between the SpO2 in SWR group at the start of the study and SPO2 on at the end of the study (p<0.0001). The mean SpO2 of participants in SWR at the end of the study was 98.54±0.5054. The difference between the SPO2 in DWR group at the start of the study and SpO2 on at the end of the study were very significant (p<0.0001). The mean SpO2 of participants in DWR on at the end of the study was 98.65 (SD= +0.4808). These results are comparable with other studies. Bishop et al.22 reported a higher O2 pulse during DWR compared with TMR. Results of O2 pulse during DWR was 4.34 and 3.81 during TMR (p<0.01). The higher O2 pulse during DWR was largely a result of lower VO2 not that of higher HR. 140 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 The rate of perceived exertion measured in this study was on the Borg’s (CR10) scale. In a study by authors Hall et al studied the cardio-respiratory responses to underwater treadmill walking in healthy females; found that the Borg scale of perceived exertion(6-20) showed that walking in water at 4.5 and 5.5 km/hr was significantly harder than on land (p<0.001). 23 It was also concluded that walking in chest-deep water yields higher energy costs than walking at similar speeds on land. 23 These responses were similar to the present study. The difference between the RPE on at the start of the study and RPE on at the end of the study were extremely significant (p<0.0001) for both the groups. The difference between the VO2max on at the start of the study and Vo2max on at the end of the study were extremely significant (p=<0.0001) for both the groups. These results where comparable with a study by Davidson K and McNaughton DK who examined the ability of deep water running training to improve cardiovascular fitness in a young sedentary population. 24 Ten untrained female subjects were allocated into a DWR and road running (RR) group. Subjects underwent pre-test VO2max testing which was repeated after each training program. Results indicated both methods produced a significant increase in VO2max compared with the pre-test without a significant difference between the two. Authors studied the intensity of exercise in deep-water running and found that VO2 during the last session of deep-water running (73% of maximum VO2) was not significantly different from that of the treadmill hard run (78%), but was significantly higher than that of the treadmill normal run (62%).25 In a comparative study it was found that peak oxygen consumption was significantly greater (p < 0.05) for treadmill running.15 Although at a similar relative exercise intensity treadmill running VO2, was significantly greater than deep-water running. Several studies have shown that maximal oxygen uptake (VO2max) attained during treadmill running is lowered during DWR. 16, 26-29 Town and Bradley in 1991 found that the highest values reached for VO2 and HR were 73.5 and 86% of VO2 max and HR max on land, respectively.28 A study found VO2 and HR during DWR to be 86 and 91% of those obtained on land. 27 These findings are similar to those reported in other studies. 27, 30 Responses to sub maximal exercise on the treadmill and when immersed to the neck have also been investigated. 30-32 A study reported lower HR during DWR than treadmill running at any given VO2.30 Implications for practice: In the participants of this study; it was found that both DWR and SWR serve as effective tool in improving cardiovascular responses. The above results point out that such form of exercise if given as a form aerobic training may improve cardiovascular indexes and so increases cardiorespiratory endurance and parameters. The results also indicate that both Deep Water running and Shallow water running improve Heart rate and RPE similarly. The VO2max is improved more in Deep Water running and SpO2 is best improved during Shallow Water Running so the intervention can be modified s per the requirements of the participant. In addition to benefits that physical activity has on physical health and fitness, physical activity also has a positive influence on academic performance and selfesteem. Because of the protective and health benefits of habitual physical activity, it is important that children are physically active and that they continue this behavior through adolescence into adulthood. Aquatic therapy is justifiably a rapidly expanding, beneficial form of rehabilitation. Understanding the theory of water techniques is essential in implementing an aquatic therapy program. The success of the program depends on the pleasure and benefits achieved by the patients. The environment should also be conductive to family and social interaction that ultimately encourages the compliance of long-term exercise programs. In the current study; all the boys who participated successfully completed the study without missing a single session with the same enthusiasm, eagerness, zeal and keenness throughout the study. The goals established at the initial and subsequent evaluations were met as quickly and as sensibly as possible. Limitations of the study: Certain limitations of the present study include small sample size, relatively short term intervention, little follow up and the present study has focused only on boys so the findings are applicable to patients within this category only. Suggestions for future research: Healthy school going boys who were between the age group of 15 to 19 years were included in this study. Since the study included regular participation for continuous 6 weeks girls were not included for the same. Therefore; further study can be conducted to generalize the results for 141 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 female population. Also; this study was the first to measure the cardiovascular parameters changes during water running. Since the study was conducted in a rural area, adequate instruments to measure VO2max; were not available. Hence, future authors who are interested in research can use a VO2max analyzer for their study. Moreover; as the above mentioned results cannot be generalized to all the types of age groups in both the genders; the same intervention must be studied in another age group to see the effect of this intervention in both the genders. CONCLUSION Thus accepting the alternate hypothesis and rejecting the null hypothesis, we conclude that 6 weeks of training given in terms of DWR and SWR is effective in improving cardiovascular responses when measured on PACER test, Borg’s Scale and Pulse oxymeter. REFERENCES 1. Rosengren A, Wilhelmsen L. Physical activity protects against coronary death and deaths from all causes in middle-aged men. Evidence from a 20year follow-up of the primary prevention study in Goteborg. Ann Epidemiol. 1997;7(1):69-75. 2. Leitzmann MF, Park Y, Blair A, Ballard-Barbash R, Mouw T, Hollenbeck AR, Schatzkin A. Physical activity recommendations and decreased risk of mortality. Arch Intern Med. 2007;167(22):2453-60. 3. Walter R. Thompson. Worldwide survey of fitness trends for. ACSM’s Health & Fitness journal 2012, 15(6):9-18. 4. Gortmaker SL, Dietz WH Jr, Cheung LW. Inactivity, diet and the fattening of America. J Am Diet Assoc 1990; 90:1247-55. 5. Ramesh K Goyal, Vitthaldas N Shah, Banshi D Saboo, Sanjiv pathak, Naveen Shah, Mukesh Gohel et al Prevalence of Overweight and Obesity in Indian Adolescent School Going Children: Its Relationship with Socioeconomic Status and Associated Lifestyle Factors. JAPI.2010; 58:15158. 6. Edu sports survey report 2012 view at http://articles.timesofindia.indiatimes.com/2012-09 08/health/33018852_1_vitamin-d-deficiencylifestyle-obesity; http://indiatoday.intoday.in/story/indian-kids-not- involving-in-outdoor activities/1/154945.html; http://www.dnaindia.com/academy/report_sportsno-more-mere-childs-play_1711275. 7. Kapil U, Singh P, Pathak P, Dwivedi S, Bhasin S. Prevalence of Obesity Amongst Affluent Adolescent School Children in Delhi. Indian Pediatrics 2002; 39:449-452. 8. Parekh A, Parekh M, Vadasmiya D. Prevalence of overweight and obesity in adolescents of urban and rural area of Surat,Gujrat. National Journal Of Medical Research. 2012;2:( 3) 325-29. 9. Sedentary Lifestyle 2012 view at http://articles.timesofindia.indiatimes.com/keywo rd/sedentary-lifestyle/recent/5. 10. American College of Sports Medicine. ACSM’s Guidelines for Exercise Testing and Prescription. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2006. 11. Strong, W., R. Malina, C. Blimkie, Stephen R. Danials, Rodney K. Dishman, Bernard Gutin et al. Evidence based physical activity for schoolage youth. Journal of Pediatrics 2005;146(6) 73237. 12. Gappmaier E., Lake W, Nelson AG, & Fisher AG. Aerobic exercise in water versus walking on land: Effects on indices of fat reduction and weight loss of obese women. The Journal of Sports Medicine and Physical Fitness. 2006, 46: 564-69. 13. Chu KS, Rhodes EC, Taunton JE. Maximal physiological responses to deep-water and treadmill running in young and older women. J Aging Phys Act 2002; 10: 306-13. 14. Town, G. P., S. S. Bradley. Maximal Metabolic Responses to Deep and Shallow Water Running in Trained Runners. Medicine and Science in Sports and Exercise. 1991, 23 (2): 238-241. 15. Michaud TJ, Rodriguez J, Andres FF, Flynn MG, Lambert CP. Comparative Exercise Response of Deep Water and Treadmill Running. Journal of Strength and Conditioning Research. 1995, 9(2): 104-109. 16. Dowzer CN, Reilly T, Cable NT, & Nevill A. Maximal physiological responses to deep and shallow water running. Ergonomics. 1999, 42: 275-81. 17. Avellini BA, Shapiro Y, Pandolf K.B. Cardiorespiratory physical training in water and on land, 142 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. European Journal of Applied Physiology 1983; 50: 255-63. Christie JL, Sheldahl LM, Tristani FE, Wann LS, Sagar KB, Levandoski SG, Ptacin MJ, Sobocinski KA, Morris RD. Cardiovascular regulation during head-out water immersion exercise, journal of applied physiology, 1990; 69: 657-64. Connelly TP, Sheldahl LM, Tristani FE, Levandoski SG, Kalkhoff RK, Hoffman MD, Kalbflei Sch JH. Effect of increased central blood volume with water immersion on plasma catecholamines during exercise, journal of applied physiology 1990; 69: 651 -56. Hinman RS, Heywood SE, & Day AR. Aquatic physical therapy for hip and knee osteoarthritis: Results of a single-blind randomized controlled trial. Physical Therapy. 2007;87: 32-43. Gleim GW, & Nicholas JA. Metabolic costs and heart rate responses to treadmill walking in water at different depths and temperatures. The American Journal of Sports Medicin. 1989;17, 248-252. Bishop PA, Frazier S, Smith J, Jacobs D. Physiological responses to treadmill and water running, physician and sportsmedicine, 1989; 17:87-94. Hall J, Macdonald IA, Maddiso PJ, O'Hare JP. Cardio-respiratory responses to underwater treadmill walking in healthy females. European Journal of Applied Physiology and Occupational Physiology. 1998;77:278-84. Davidson K and McNaughton DK. Deep water running training and road running improve VO2max in untrained women. Journal of Strength and Conditioning Research. 2000; 14:191-95. Ritchie SE, Hopkins WG. The Intensity of Exercise in Deep Water Running. International Journal of Sports Medicine 1991;12 (1): 27-29. Glass B, Wilson D, Blessing D, Miller E. A Physiological Comparison of Suspended Deep Water Running to Hard Surface Running. Journal of Strength and Conditioning Research. 1995;9(1): 17-21. Butts NK, Tucker M, Smith R. Maximal Responses to Treadmill and Deep Water Running in High School Female Cross Country Runners. Research Quarterly for Exercise and Sport. 1991, 62 (2): 236-39. 28. Town GP, Bradley SS. Maximal Metabolic Responses to Deep and Shallow Water Running in Trained Runners. Medicine and Science in Sports and Exercise. 1991;23 (2): 238-41. 29. Frangolias DD, Rhodes EC. Maximal and Ventilatory Threshold Responses to Treadmill and Water Immersion Running. Medicine and Science in Sport and Exercise 1995, 27 (7): 100713. 30. Svedenhag J, Seger J. Running on Land and in Water: Comparative Exercise Physiology. Medicine and Science in Sport and Exercise. 1992;24 (10): 1155-60. 31. D’Acquisto LJ, D’Acquisto DM, Renne D. Metabolic and cardiovascular responses in older women during shallow water exercise. J Strength Cond Res 2000; 15: 12-19. 32. Kimberley Meredith-Jones, Michael Legge, Lynnette M. Jones. Circuit based deep water running improves cardiovascular fitness, strength and abdominal obesity in older, overweight women. Medicina Sportiva . 2009,13 (1): 5-12. 143 Anerao et al., Int J Med Res Health Sci. 2014;3(1):137-143 DOI: 10.5958/j.2319-5886.3.1.028 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886 th th Received: 27 Nov 2013 Revised: 18 Dec 2013 Accepted: 28th Dec2013 Research article A CADAVERIC STUDY ON ANATOMICAL VARIATIONS OF THE SUPERFICIAL PALMAR ARCH Vidhya Ramakrishnan1, Anil kumar Reddy Y 2, Aruna. S3, Balaji Thotakura4, Suba Ananthi5 1,2 Department of Anatomy, KFMS&R, Coimbatore, Tamilnadu, India. Department of Anatomy, Indira Gandhi Institute of Medical Sciences, Pondycherry, India 4 Department of Anatomy, Chettinad Hospital and Research Institute, Padur, Chennai, India 3 *Corresponding author email:
[email protected] ABSTRACT Background: The Superficial Palmar arch (SPA) is an anastomosis between the ulnar and radial artery in the palm. Maximum contribution in the arch is by an ulnar artery and it is completed by superficial palmar branch of radial artery or arteria princeps pollicis or arteria radialis indicis or median artery. The SPA develops as a terminal plexus of axis artery which is later joined by median, ulnar and radial arteries as these arteries develop. Materials & Methods: Present study conducted in the Department of Anatomy, Chettinad Hospital and Research Institute on 50 (28 right and 22 left) formalin fixed hands were used. The variations observed were classified as per Coleman and Anson, 1961, classification of the superficial palmar arch. Results: As per Coleman and Anson classification, complete arch of type A was seen in 43 hands (86%) and of type B in 3 hands (6%). In this study incomplete arch was seen in 4 hands (8%, 1 right and 3 left), persistent median artery type H supplying the radial side of the palm and digits was seen in only one hand (2%). Conclusion: The data regarding the study on variations of SPA is helpful in crushing injury of hand, arterial grafting, and vascular trauma of the upper extremity. Keywords: Superficial Palmar arch, Radial artery, Ulnar artery, Median artery, Coronary artery bypass graft INTRODUCTION A hand or manus is a prehensile, multi fingered body part located at the end of upper limb or forelimb of primates and some other vibrates used for both gross and fine motor skills. In order to perform its various functions, it is richly supplied with blood vessels and nerves1. The radial and ulnar arteries provide most of the blood supply to the hands. Additional circulation may come from the median artery or the interosseous arterial system. The superficial palmar arch (SPA) is an anastomosis fed mainly by the ulnar artery. About a third of the SPA are formed by the ulnar artery alone, a further third are completed by the superficial palmar branch of the radial artery and a third by the arteria radialis indicis, a branch of either arteria princeps pollicis or the median artery2. The radial and ulnar arteries form 4 circuits in the hand; anterior and posterior carpal arches at the level of carpal bones, superficial and deep palmar arches at the mid of palmar level3. Among these the superficial and the deep palmar arches are the most important circuits because they provide the principal blood supply to all the structures in the hands. The SPA develops as a terminal plexus of axis artery which is later joined by median, ulnar and radial arteries as these arteries develop4. According to one of the extensive studies conducted on 1200 formalin fixed hands, by Coleman and Anson in 1961, the variations in the SPA were classified as Vidhya et al., Int J Med Res Health Sci. 2014;3(1):144-148 144 complete and incomplete arches which were further subdivided into various subtypes as follows3. GROUP I – Complete Arch : Type A: classical radio ulnar arch , Type B: Ulnar arch, Type C : medianoulnar arch ,Type D: radio-mediano-ulnar arch, Type E: ulnar artery & a branch from deep arch GROUP II – Incomplete Arch : Type F: radial and ulnar arteries without anastomosis, Type G; only ulnar artery without supply to thumb and index finger, Type H : ulnar and median arteries without anastomosis, Type I: Median, radial and ulnar arteries without anastomosis incomplete arches, 3 were of type F (6%) and 1 was of type H (2%) (Tab. 1) Table 1: Incidence percentage of variations in the current study Arch type No. of hands Percentage Complete arch 46 92 Type A 43 86 Type B 3 6 Incomplete arch 4 8 Type F 3 6 Type H 1 2 Most of the arches seen in the current study were of type A (Fig. 2), formed by the ulnar artery and completed on the radial side either by the superficial branch of the radial artery or princeps pollicis artery or radialis indicis artery, branches of radial artery. Only ulnar artery formed the arch (Fig. 3) in only 3 hands and ulnar & radial without anastomosis (Fig. 4) in 3 hands. Persistent median artery supplying the radial side of the palm and digits (Fig. 5) was seen in only one hand. Fig 1: Coleman and Anson classification Hence the frequent anatomic variations encountered in the formation of the SPA and increasing incidence of taking radial arterial grafts for coronary bypass attracted the interest in checking its incidence. MATERIALS AND METHODS For the current study 50 human cadaveric hands (28 right and 22 left) fixed in formalin (10%) solution, hands in the Department of Anatomy, Chettinad Hospital and Research Institute were used. Macroscopic dissection of the palm was done according Cunningham’s manual of practical anatomy and variations in the formation and branching pattern of the SPA were studied, variation were noted and compared with similar studies conducted previously. Fig. 2: Complete arch, Type A – Classical radio ulnar arch. (RA: Radial artery, UA: Ulnar artery) OBSERVATION Out of the 50 hands, complete arch was seen in 46 hands (24 right and 22 left) and incomplete arch in 4 hands. As per Coleman and Anson classification, complete arch of type A was seen in 43 hands (86%) and of type B in 3 hands (6%). Between the Vidhya et al., Fig. 3: Complete arch, Type B – Ulnar arch . (UA: Ulnar artery) Int J Med Res Health Sci. 2014;3(1):144-148 145 Fig. 4: Incomplete arch, Type F – Radial and ulnar arteries without anastomosis (UA: Ulnar artery, RA : Radial artery). Fig. 5: Incomplete arch, Type H – Mediano-ulnar arch (2%), MA – Median artery, UA – Ulnar artery. DISCUSSION Advanced methods in Microsurgical techniques for the reconstructing surgery of the hand and Upper extremity and the choice of using a radial artery graft during Coronary artery bypass grafting (CABG) have necessitated the understanding of vascular architecture in the palm. Developmental the anomalies of blood vessels may be due to: (i) The choice of unusual paths in the primitive vascular plexuses. (ii) The persistence of vessels normally obliterated. (iii) The disappearance of vessels normally retained. (iv) Incomplete development. The normal arterial blood supply to the human hand is well documented, although the vascular supply to the hand and digits via the SPA is known to be variable (Al-Turk & Metcalf, 1984; Iossifidis, 19954, Ikeda et al, 1988, Onderoglu et al, 19975). The systematic arterial patterns of the hand were first described by Jaschtschinski, 18976. Various anomalous patterns in the arterial arches have been studied and various Vidhya et al., classifications based on the contribution from the formative branches, mainly superficial branches of the radial artery and ulnar artery have been proposed by various authors. SPA was seen in all the 50 hands (100%) dissected (25 right, 25 left) unlike Brent et al7 (2010) who reported a case of unilateral absence of the SPA in one hand he observed. Complete arch was seen in 92% of the hands (46, 22 left and 24 right) in the current study. These results are similar to those reported by MariosLoukas et al (2005)8, who observed the presence of 90% complete arches in his study. Although complete arches seem to be more prevalent, as observed in the present study, in most of the studies done by Coleman and Anson, 1961 (78.5%), Suleyman et al, 2007 (75%) 9, Silvia et al, 2003 (60%) 10 , Nicolas et al, 2010 (58%) 11; some authors like Valeria et al, 2004 (47.5%) 12 and Elizabeth O’ Sullivan et al, 2002 (46.8%) 13 lesser incidence of complete arches was reported. The classical radio-ulnar arch formed by ulnar artery and the superficial branch of radial artery or princeps pollicis artery or radialis indicis artery (Coleman and Anson, 1961, Type A) was seen in 43 hands (86%, 21 left and 22 right) in the current study unlike other authors (Silvia et al, 2003, 67%; Suleyman et al, 2007, 40%; MariosLoukas et al, 2005, 40% and Coleman and Anson, 1961, 34%) who have reported a lesser incidence of the same type. The ulnar type of arch formed by the ulnar artery alone (Coleman and Anson, 1961, Type B) was seen in 3 hands (6%, 2right and 1 left) in the present study. In comparison such an arch was more prevalent in other studies such as Coleman and Anson, 1961, 37%; Suleyman et al, 2007, 35%; MariosLoukas et al, 2005, 35%; Silvia et al, 2003, 23%. In this study incomplete arch was seen in 4 hands (8%, 1 right and 3 left) in par with Marios Loukas et al, 2005, who reported it in 10% of his study and unlike other authors (Elizabeth O’ Sullivan et al, 2002, 53.2%; Valeria et al, 2004, 52.5%; Nicolas et al, 2010, 42%; Silvia et al, 2003, 40%; Suleyman et al, 2007, 25% and Coleman and Anson, 1961, 21.5%, who have reported increased occurrence of the same (Fig. 6). Int J Med Res Health Sci. 2014;3(1):144-148 146 60% 50% 40% 30% 20% 10% 0% 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Type Type Type Type Type Type Type Type Type A B C D E F G H I Coleman and Anson 1961 Fig. 6: Incomplete superficial Palmar arch Current study VsVarious authors The most consistent incomplete arch was ulnar and radial arteries without anastomosis (Coleman and Anson, 1961, Type F), seen in 3 hands in this study (6%, 2 left and 1 right hands). This type was seen in 3.2% of the hands by Coleman and Anson, 1961; in 20% of the hands by Suleyman et al, 2007 and in 33% of the hands by Silvia et al, 2003 (Fig. 7). 35.00% 30.00% 25.00% 20.00% 15.00% 10.00% 5.00% 0.00% Coleman & Suleyman Silvia et al Current Anson et al 2007 2003 study 1961 Fig. 7: Type F of incomplete superficial palmar arch - Current study Vs Various authors Only one of Coleman and Anson, Type H, in which median and ulnar arteries supplied the palm without anastomosis, was observed in the current study (2%, left hand). Whereas Coleman and Anson reported 3.8% of the same type and Silvia et al, 10 % ( Fig 8). The other types of arches described by Coleman and Anson (Types C, D, E, G and I) were not observed in the current study. Vidhya et al., Fig. 8: Various types of arches - Current study Vs Coleman & Anson’s CONCLUSION The superficial and deep palmar arches account for a rich anastomosis between arteries of the palm. Wounds of the palm bleed profusely but heal rapidly because of this anastomosis. An injury in the ulnar artery or the SPA may compromise the arterial supply of the fingers, particularly if there is an insufficient anastomosis between the superficial and deep palmar arches. The sound knowledge about the vascular patterns in the palm is crucial in microsurgical procedures of hand and in amputations and in the choice of using the radial artery for coronary bypass graft and in preventing possible complications during hand surgery. Identifying the presence of median artery and its participation in the arch completion is important in ligation of radial or ulnar artery in case of vascular trauma. In addition, the identification of any variation in the arterial pattern of the hand using Doppler ultrasonography, photoplethysomography and oximetric techniques acquires great importance in various surgical interventions in the hand.14 The present study gives necessary information to understand the vascular architecture and its common and rare variations in the hand. Int J Med Res Health Sci. 2014;3(1):144-148 147 REFERENCES 1. Al-Turk M, Metcalf WK. A study of the superficial palmar arteries using the Doppler Ultrasound Flowmeter. Journal of Anatomy. 1984; 138:27–32 2. Susan Standring. Williams and Warwick Editors – Grays Anatomy 38th Edition. 3. Coleman S, Anson J. Arterial pattern in handbased upon a study of 650 specimens. Surgery. Gynaecology. Obstetrics, 1961; 409-24 4. Iossifidis. Aneurysm of the superficial palmar arch. International Orthopaedics (SICOT). 1995; 19:403-404. 5. Onderoglu S, Basar R, Erbil KM, Cumhur M. Complex variation of the superficial palmar arch – case report. Surgical and Radiology Anatatomy.1997; 19:123–25 6. Jaschtschinski SN. Morphology and topography of the Arcusvolarissublimis and profundus of the person. Anatomy notebooks. 1897; 7:161-88. 7. Brent AC, Paula Ferrada, Roger Walcott. Demonstration of unilateral absence of the palmar arch without collateral circulation. British Journal of Surgery. 2006; 60: 652-55 8. Marios Loukas. Anatomical variations of the superficial land deep palmar arches. Folia Morphology.2005; 64( 2); 115-18 9. Süleyman Murat Tagil. Variations and clinical importance of the superficial palmar arch. S.D.Ü. TýpFak. Derg. 2007; 14(2):11-16. 10. Silvia. Morphologic variations of the superficialpalmar arc. Acta Cir Bras. 2003;18(3): 46-49 11. Nicolás Ernesto Ottone. Analysis and clinical importance of superficial arterial palmar irrigation and its variants over 86 Cases. International Journal of Morphology. 2010; 28(1):157-64 12. Valéria Paula, SassoliFazan. Superficial palmar arch: an arterial diameter study. J Anat. 2004;204(4): 307–11. 13. Elizabeth O’Sullivan, Barry S Mitchell. Association of the absence of palmaris longus tendon with an anomalous superficial palmar arch in the human hand. Journal of Anatomy. 2002; 202(2): 253. 14. Takkallapalli Anitha. Variations in the formation of superficial palmar arch and its clinical Vidhya et al., significance in hand surgery. Int J Biol Med Res. 2011; 2(2): 543-46 Int J Med Res Health Sci. 2014;3(1):144-148 148 DOI: 10.5958/j.2319-5886.3.1.029 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 12 Dec 2013 Revised: 26th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 29th Dec 2013 COMPARATIVE STUDY OF GONADOTROPIN LEVELS AND CLINICAL PRESENTATION IN SURGICAL AND NATURAL MENOPAUSE *Naik Raviraj R, Chandel Rittu S, Abichandani Leela G Department of Biochemistry, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India *Corresponding author email:
[email protected] ABSTRACT Introduction: Menopause means complete stoppage of menses for last one year due to failure of follicular activities of the ovaries. This can be determined by the various hormones secreted by ovary such as LH and FSH. As these hormones are responsible for normal maintenance of basic ovarian function in reproductive life; there occurs considerable alteration in their levels in menopause. Aims and Objectives :- 1] To study and compare ovarian function by determining levels of LH and FSH in Surgical and Natural menopause. 2] To study and compare ovarian function in Surgical and Natural menopause. Brief Methodology: - Case study: - 50 women with surgical menopause between 45 – 50 years of age. Control study: - 50 women with natural menopause between 45 – 50 years of age. Material & Methodolgy :- Fasting serum samples of all women with surgical and natural menopause were analysed for LH and FSH on Immulite 1000 chemiluminiscence based analyser in special investigation lab. Summary of the Results :- Mean levels of LH and FSH were higher in surgical menopausal women as compared to natural menopausal women. Women in surgical menopause suffered from more vasomotor symptoms and cognitive decline as compared to women in natural menopause group Keywords: Surgical menopause, Natural menopause, LH, FSH, Chemiluminiscence INTRODUCTION Follicle stimulating hormone (FSH) and Luteinizing Hormone (LH) is secreted by beta cells of the adenohypophysis. FSH controls the ripening of primordial follicles and in conjugation with LH activates secretion of estrogen. FSH is suppressed by estrogen secretion through a negative feedback mechanism. 1 In conjugation with FSH, LH activates secretion of estrogen, brings about the maturation of the ovum and causes ovulation. Following ovulation LH produces luteinization of granulosa and theca cells and initiate progesterone secretion. LH also stimulates the secretion of testosterone and androstenedione in ovarian stroma which diffuses into follicular fluid and are aromatized into estradiol.1 Menopause is defined as that point in time when permanent cessation of menstruation occurs following loss of ovarian activity.2 It takes 12 months of amenorrhoea to confirm menopause. Sixty million women in India are above the age of 55 years . It is therefore important to address all these menopause related impairment and apply prophylactic measures so that these women can have an enjoyable and healthy life.3 Menopause normally occurs between the ages of 45 and 55 years ; the average being 47 years3. Surgical menopause is the cessation of menses resulting 149 Naik Raviraj et al., Int J Med Res Health Sci. 2014;3(1):149- 154 from surgical removal of the uterus, leaving one or both ovaries, or the removal of both ovaries.4Women who have undergone hysterectomy with ovaries preserved will experience menopausal symptoms because of hypoestrogenism caused by depletion of oocytes. Hysterectomy is surgery to remove a woman’s uterus. In physiological or natural menopause, the ovaries gradually lose function, secreting less hormones over time. With surgical menopause, the loss of ovarian hormones happens instantly with no adaptation time. The onset of menopausal symptoms is therefore much quicker and symptoms are usually more severe. 6 Symptoms associated with surgical menopause are often more severe than with natural menopause, particularly the vasomotor symptoms of hot flushes and night sweats.6 Hot flushes are the most common symptom of the climacteric and occur in 75% of postmenopausal women in whom it is more common after Hysterectomy.7 Hot flushes tend to last longer and be more severe in women who have had a surgically induced menopause.8 It is recognized that hot flushes occur with the pulsatile release of LH.9 The symptoms are characteristic of a heat dissipation response , and consist of sweating on the face , neck and chest as well as peripheral vasodilation. 10 There is an acute rise in the skin temperature of several degrees centigrade,11 a transient increase in heart rate , fluctuations in the electrocardiographic baseline and a pronounced decrease in skin resistance.12 Tataryn IV et al13 conducted a study on LH , FSH and skin temperature during the menopausal hot flush and found positive correlation of simultaneous skin temperature and circulating LH levels. These data suggest that LH or the factors that trigger its pulsatile release are related to the mechanism responsible for the initiation of hot flushes. Depressed mood is more common after a hysterectomy, as it results in a greater frequency and severity of vasomotor symptoms.14 It could be a 'domino effect' of vasomotor symptoms, causing sleep disturbance and tiredness, which in turn precipitate depression.15 Cognitive decline is directly related to hot flushes in women who have undergone hysterectomy, but natural menopause itself does not necessarily result in significant cognitive dysfunction.16 During a hot flush , blood flow decreases in the hippocampus , possibly impairing Naik Raviraj et al., memory and cognition. 16 Such reductions in blood flow may contribute to the decreased mental clarity and short-term verbal memory problems experienced by postmenopausal women.16Symptoms of menopause are irritability, mood swings, sudden tears, anxiety, depression, memory lapses, headaches, vaginal tissue atrophy that can lead to more urinary tract or vaginal infections and urinary incontinence, loss of skin tone and osteoporosis. Other symptoms include heart palpitations, insomnia, loss of libido, vaginal dryness and painful intercourse, fatigue, weight changes and difficulty in losing weight, itchy skin and difficulty in concentrating.6 Aims & Objectives 1.To study and compare hormonal levels of LH , FSH in Surgical and Natural menopause. 2.To compare the symptoms like hot flushes and cognitive decline in Surgical and Natural menopause. MATERIAL AND METHODS Place of study: Special investigation laboratory of Department of Biochemistry, Grant Medical College & Sir JJ group of hospitals. Samples were collected from female patients and staff of the hospital. Study design: Prospective study. Institutional Ethical Committee clearance was taken. Study population: Present study includes 50 women (cases) belonging to surgical menopausal group and 50 women (controls) belonging to Natural menopausal group. Ethics: Institutional Ethical Committee approval, Informed consent were taken from all the women included in the study. Period of study: July 2011 – September 2013. Inclusion criteria: 1. Women aging between 44 to 50 years who have undergone Total Hysterectomy in past one to two years. 2. Women aging between 44 to 52 years who were experiencing natural menopause since past one to two years. Exclusion criteria - women with: 1. Hormonal intake in any form e.g.: Drugs, Soyaflavons. 2. Endocrine disorder. eg: Hyperpituitarism. 3. Ovarian Tumors. Blood Sample Collection- 5 ml blood sample was collected by venipuncture in plain tube. All blood 150 Int J Med Res Health Sci. 2014;3(1):149- 154 samples were centrifuged at 4500 revolutions per minute for 5 minutes to obtain clear serum. Serum samples are then stored between 2-80C before analyzing on Immulite 1000 chemiluminiscence machine. Biochemical Analysis: All the hormonal parameters (LH, FSH) were measured by Solid Phase Competitive Chemilumniscent Enzyme Immunoassay. The solid phase (bead) is coated with rabbit antihormonal polyclonal antibody. The reagent contains alkaline phosphatase conjugated to respective hormone. This hormone-enzyme conjugate competes with respective hormone in patients blood sample for limited antibody binding sites on bead. The excess sample and reagent are removed by centrifugal wash. Finally chemiluminiscent substrate is added to the bead and the signal is generated in proportion to the bound enzyme. Fully automated enzyme amplified chemiluminescent immunoassay based Immulite 1000 analyzers was used. Measurement of these blood hormonal parameters was done by using commercial kits from Siemens Medical Solutions Diagnostics, Los Angeles, CA, USA. Statistical analysis: Numerical variables were reported in terms of mean and standard deviation. An independent (unpaired) sample t-test was used to compare the difference of means for independent quantitative variables following normal distribution. Pearson chi-square test was used to test the significance of qualitative variables like symptoms. Variables showing P-value less than 0.05 were considered to be statistically significant and less than 0.01 as very significant. The SPSS software was used for data analysis. RESULTS The present study included 50 women with surgical menopause and 50 women with Natural menopause, thus a total of 100 subjects fulfilling the inclusion criteria were enrolled in this study. Age at Menopause: In this study the mean age at menopause in the study group was 46.76 years ± 1.43, while that in the control group was 50.9 ± 0.83 years. On applying independent (Unpaired) sample t – test, the difference in mean age at menopause between two groups was found significantly different at the 0.01 level of significance. Table:1. Mean Age statistics of surgical and natural menopausal. Menopause N Mean Age at menopause ± Standard Deviation (Years) Surgical 50 46.76 ±1.437 Natural 50 50.9 ±0.839 Mean Difference= -4.14 Years Table 2: Serum mean LH level of surgical and natural menopausal females Menopause LH[mIU/ml] FSH [mIU/ml] Surgical 37.32±2.924 104.62± 12.952 Natural 22.96±4.389 66.4±9.216 P Value < 0.001 < 0.001 Note: Reference values in Postmenopausal women LH: 11.3 – 39.8 mIU/ml, FSH 21.7 – 153 mIU/ml LH: In this study the mean level of Luteinizing hormone in study group was found to be 37.32±2.92 while that in control group was 22.96±4.38. On applying independent (Unpaired) sample t – test, the difference between mean LH levels in both the groups was found to be very significant with P value < 0.001. FSH: In this study the mean level of Follicle stimulating hormone in the study group was 104.62±12.95 while that in the control group was 66.4±9.21. On applying independent (Unpaired) sample t – test, the difference in mean FSH level in both the groups was found to be very significant with P value < 0.001. (Independent Sample t test:- t value 17, df-88.49, P value <0.001) Table 3: Clinical feature of surgical and Natural menopause Mood Swings Osteoporosis Hot Flushes Irritability headache Memory lapses anxiety depression Sudden tears Vaginal tissue atrophy Surgical menopause 32 (64%) 35 (70%) 44 (88%) 44 (88%) 30 (60%) 33 (66%) 34 (68%) 30 (60%) 31 (62%) 35 (70%) Natural menopause 20 (40%) 27 (54%) 28 (56%) 28 (56%) 18 (36%) 18 (36%) 20 (40%) 20 (40%) 15 (30%) 16 (32%) 151 Naik Raviraj et al., Int J Med Res Health Sci. 2014;3(1):149- 154 Hot flushes: In the present study 88% of the women in surgical menopausal group had hot flushes as compared to only 56% of women in natural menopausal group. On applying Pearson Chi-square test, the frequency of hot flushes in surgical menopause was significantly higher than that in natural menopause with P < 0.001. Mood Swings : In the present study 64% of the women in surgical menopausal group had mood swings as compared to only 40% of women in natural menopausal group. On applying Pearson Chisquare test, the frequency of mood swings in surgical menopause was significantly higher than that in natural menopause with P < 0.05. Women with hot flushes are more likely to experience disturbed sleep, depressive symptoms and significant reductions in quality of life. Women in surgical menopause suffer more from hot flushes thus are more affected by mood swings. LH and FSH levels were found to be significantly increased in surgical menopause as compared to natural menopause. Women belonging to surgical menopause group suffer more from hot flushes and mood swings as compared to women in the natural menopause group. DISCUSSION In the present study the mean age of the surgical menopausal group was significantly lesser than that of the natural menopausal group; which was well supported by another study done by Ozdemir S et al. 17 Ovarian function was indeed depressed in the natural menopausal women but was still preserved for 1 to 2 years after menopause. 18 In the present study, serum LH and FSH levels in the group of women within 2 years after surgical menopause were significantly higher than those in the group of natural menopausal women at a comparable period after menopause. Similar finding were suggested by Nobuaki Furuhashi et al18 who reported significantly increased levels of LH and FSH within 2 years after surgical menopause as compared to their levels in natural menopause. Similarly Edward.E et al19 also found a significant increase in LH and FSH levels in surgical menopause. Carina C.W. Chan et al20 found that women with hysterectomy had significantly elevated serum FSH level and lower stromal blood flow indices as compared to healthy natural menopausal women. S.Muttukrishna et al21 reported that ovarian inhibin A & B were cleared from circulation within short period of surgical menopause which was responsible for early rise of FSH in surgical menopause. The ovaries are the predominant source of Inhibin A and B22 which are characterized for their inhibitory effect on pituitary follicle-stimulating hormone (FSH) secretion23, by a negative feedback regulation24,25. It has been speculated that after surgical menopause and the fall in inhibins ; estradiol and progesterone stimulates increase in the synthesis as well as secretion of FSH and LH.21 It is well established fact that estradiol demonstrate a direct pituitary site of estrogen negative feedback on LH and FSH responsiveness to GnRH but the effect of estradiol on FSH responsiveness is greater than that on LH and this effect is attenuated with aging and menopause.26 This negative feedback is disrupted in surgical menopause because of abrupt deficiency of estradiol which may also contribute to more increase in levels of LH and FSH when compared with natural menopause.27 In the present study the percentage of surgical menopausal women experiencing hot flushes , mood swings was significantly higher than that of natural menopausal women. Pearce J et al28 and Bachmann GA et al29 reported similar significant difference in hot flushes percentage between two menopausal groups and concluded that hot flushes tends to last longer and be more severe in women who have had a surgically induced menopause. Nachtigall et al30 reported that 100% of surgically menopausal women had vasomotor symptoms, and 90% had severe symptoms which lasted an average of 8.5 years after menopause. Another study done by Tataryn IV et al13 found a positive correlation of simultaneous skin temperature and circulating LH levels. So it may suggest that LH or the factors that trigger its pulsatile release relate to the mechanism responsible for the initiation of hot flushes.13 Depressed mood is more common after surgical menopause, as it results in a greater frequency and severity of vasomotor symptoms. 31 So it could be a 'domino effect' of vasomotor symptoms, causing sleep disturbance and tiredness, which in turn precipitate depression. 15 152 Naik Raviraj et al., Int J Med Res Health Sci. 2014;3(1):149- 154 CONCLUSION LH and FSH levels were found to be significantly increased in surgical menopause as compared to natural menopause. Significant increases in the levels of these hormones are seen in surgical menopause due to sudden decline in the function of ovarian activity. These women suffer more from hot flushes, cognitive decline and mood swings as compared to women in the natural menopause group. ACKNOWLEDGMENT Technical help at special investigation laboratory, JJ Hospital Conflict of interest: Nil REFERENCES 1. Padubidri VG, Daftary SN. Shaws Textbook of Gynaecology. 14 ed. New Delhi: Elsevier India Pvt.Ltd ; 2008. Physiology . Chapter 3; p:36-41. 2. Marc A.Fritz and Leon Speroff. Clinical Gynaecologic Endocrinology and Infertility. 8th ed.New Delhi; Wolter Kluwer India Pvt.Ltd ;2008. Menopausal and Perimenopausal Transition. Chapter 17 ; p:681. 3. Padubidri VG, Daftary SN. Shaws Textbook of Gynaecology. 14 ed. New Delhi: Elsevier India Pvt.Ltd ; 2008. Perimenopause, Menopause, Premature Menopause and Postmenopausal bleeding. Chapter 5; p:52-55. 4. Kate MB. Can Hysterectomy Be Considered a Risk Factor for Cardiovascular Disease ; In the circulation Journal of American heart association. 2005 ; 111 : 1456 – 58. 5. Pratap Kumar, Narendre Malhotra. Jeffcoates principle of gynaecology. 7th ed. New Delhi : Jaypee Brothers Pvt.Ltd ; 2008. Menopause; Chapter 53; p:872-73. 6. Crystal Hannan. Surgical Menopause: Hysterectomy & Oophorectomy. [Internet].Available from : http://www.ndaccess.com/CrystalHannanND/For ms/Surgical%20Menopause.pdf.htm 1999 7. Pearce J, Hawton K, Blake F. Psychological and sexual symptoms associated with the menopause and the effects of hormone replacement therapy. Br J Psych 1995; 167: 163-73. 8. Bachmann GA. Vasomotor flushes in menopausal women. Am J Obstet Gynecol 1999; 180: S312– 16 9. Rebar RW & Spitzer IB. The physiology and measurement of hot flushes. Am J Obstet Gynecol 1987; 156: 1284–88. 10. Freedman RR. Physiology of hot flushes. Am J Hum Biol 2001; 13: 453–64. 11. Sturdee DW, Reece BL. Thermography of menopausal hot flushes. Maturitas 1979; 1: 201– 05 12. Sturdee DW, Wilson KA, Pipili E. Physiological aspects of the menopausal hot flush. BMJ 1978; 2: 79–80. 13. Tataryn IV, Meldrum DR, Lu KH, Frumar AM ; LH , FSH and skin temperature during the menopausal hot flush. Journal of Clinical Endocrinology and Metabolism 1979. ; 49(1): 152-54. 14. Avis NE, Brambilla D, McKinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women’s Health Study. Ann Epidemiol 1994; 4 : 214-20 15. Maoz B, Shiber A, Lazer S. The prevalence of psychological distress among postmenopausal women attending a menopausal cliic and the effect of hormone replacement therapy on their mental state. J Menopause. 1994; 1:137-41. 16. Shepherd JE. Effects of estrogen on congnition mood, and degenerative brain diseases. J Am Pharm Assoc . 2001; 41:221-28. 17. Ozdemir S, Celik C, Gorkemili H, Kiyici A, Kaya,B. Compared effects of surgical and natural menopause on climacteric symptoms, osteoporosis and metabolic syndrome. Int J Gynecol and Obst 2009; 106: 57-61. 18. Nobuaki Furuhashi, Tetsuro Abe, Masakuni Suzuki. Changes in Hypophysio-ovarian Endocrinological Function of Post-menopausal and Surgical menopausal women : In Tohoku J Med 1976 ; 120;19 -24 19. Edward E, Allen H, Decherney. David Russ episodic secretion of LH and FSH after surgical menopause : In International Journal of obstetrics and gynaecology .1973 ; 41(2): 227 33. 20. Carina CW, Chan Ernest HY, Pak-Chung Ho. Ovarian Changes After Abdominal Hysterectomy 153 Naik Raviraj et al., Int J Med Res Health Sci. 2014;3(1):149- 154 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. for Benign Conditions : In J Reproductive Sciences 2005 ;12(1):54 – 57. Muttukrishna S, Sharma S, Barlow DH, Ledger W. Serum inhibins, estradiol, progesterone and FSH in surgical menopause : a demonstration of ovarian pituitary feedback loop in women ; In Journal of Human reproduction 2002., 17(10) : 2535 – 39. Seifer DB, Scott RT, Bergh PA. Women with declining ovarian reserve may demonstrate a decrease in day 3 serum inhibin B before a rise in day 3 FSH.J Fertil. Steril ; (1999) ; 72 : 63–65. Vale W, Rivier C, Hsueh A, Campen C, Meunier H, Bicsak T, et al. Chemical and biochemical characterization of the inhibin family protein hormones. Recent Prog Horm Res 1988;44:1–34. Groome NP, Illingworth PJ, O’Brien M, Pai R, Rodger FE, Mather, J etal., Measurement of dimeric inhibin-B throughout the human menstrual cycle. J. Clin. Endocrinol. Metab. (1996) ; 81:1401–05. Klein NA, Illingworth PJ, Groome NP, McNeilly AS, Battaglia DE, Soules MR. Decreased inhibin B secretion is associated with the monotropic FSH rise in older, ovulatory women: a study of serum andfollicular fluid levels of dimeric inhibin A and B in spontaneous menstrualcycles. J. Clin. Endocrinol. Metab. (1996); 81: 2742–45 Shaw ND, Histed SN, Srouji SS. Estrogen Negative Feedback on GonadotropinSecretion: Evidence for a Direct Pituitary Effect in Women. J Clin Endocrinol Metab. 2010, 95(4):1955–61. Chakravarti S, Collins WP, Newton JR, Oram DH, Studd JW. Endocrine changes and symptomatology after oophorectomy in premenopausal women . In International Journal of obstetrics and gynaecology 1977; 84(10) : 769 – 75 Pearce J, Hawton K, Blake F. Psychological and sexual symptoms associated with the menopause and the effects of hormone replacement therapy. Br J Psych 1995; 167: 163-73. Bachmann GA. Vasomotor flushes in menopausal women. Am J Obstet Gynecol 1999; 180: S312– 16 Nachtigall LE. Pre-operative care and patient evaluation. Proceedings of the 1996 annual meeting of the American College of Obstetricians and Gynecologists; 1996 Apr 29-May 1; Denver. 31. Avis NE, Brambilla D, McKinlay SM, Vass K. A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women’s Health Study. Ann Epidemiology 1994; 4 : 214-20 154 Naik Raviraj et al., Int J Med Res Health Sci. 2014;3(1):149- 154 DOI: 10.5958/j.2319-5886.3.1.030 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 30 Oct 2013 Revised: 28th Nov 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 18th Dec 2013 EFFECT OF PACLITAXEL ALONG WITH DI ALLYL SULFIDE ON IMMUNO COMPETENT CELLS, IMMUNE COMPLEXES AND IMMUNOGLOBULINS CHANGES IN 7,12 DI METHYL BENZ(A) ANTHRACENE INDUCED SKIN CANCER IN WISTAR RATS. *Muninathan N1, Ursula Sampson2, Prashanth Talikoti3, Uma Maheshwari4, Archana5, Kumar6 Department of Biochemistry, Meenakshi Medical College and Research Institute, Enathur, Kanchipurm, Tamil Nadu, India *Corresponding author email:
[email protected] ABSTRACT Our recent studies have shown that naturally occurring dietary organo sulfure compounds such as di allyl sulfide and paclitaxel are capable of inhibiting polycyclic aromatic hydrocarbon (PAH) metabolism and subsequent PAHDNA adduct formation in Wistar rats. In this study these plant phenols were tested for their effects against PAHs and 7,12 Di Methyl Benz (A) Anthracene -induced skin tumorigenesis in rats. Each compounds was evaluated as a possible anticarcinogen in an initiation and promotion and a complete skin tumorigenesis protocol. In the two-stage tumor protocol in Wistar rats using 7,12-dimethylbenz(a)anthracene as the initiating agent followed by twice weekly applications of acetone as tumor promoter each plant compounds afforded significant protection against skin tumorigenicity. The protective effects were verified both by prolongation of latency period and by subsequent tumor development. Our results suggest that these plants compounds have substantial though variable potential for modifying the risk of skin tumorigenicity induced by a wide variety of chemicals and of these combinations of Paclitaxel and Di allyl sulfide was shown to have maximal chemo protective effects. Keywords: Paclitaxel, Di allyl sulfide, DMBA, Skin cancer. INTRODUCTION Skin cancer is the most common form of human cancer. It is estimated that over 1 million new cases occur annually.1,2 The annual rates of all forms of skin cancer are increasing each year, representing a growing public concern. It has also been estimated that nearly half of all Americans who live to age 65 will develop skin cancer at least once3. The most common warning sign of skin cancer is a change in the appearance of the skin, such as a new growth or a sore that will not heal. In India, skin cancers constitute about 1-2% of all diagnosed cancers. Basal cell carcinoma is the commonest form of skin cancer worldwide, but various studies from India have consistently reported SCC as the most prevalent skin malignancy4. Although complete data of incidence is not available, various cancer registries in India reported cumulative incidence of skin cancer varying from 0.5 to 2 per 100 000 population5. Although, the incidence of skin cancers in India is lower as compared to the Western world, because of a large population, absolute number of cases is estimated to be significant. Skin cancer patients have stage IV receive chemotherapy and /or hormonal therapy to suppress cancer cells and control the disease. The goal of chemotherapy is to destroy, shrink primary tumors, slow the tumor growth, and to kill cancer cells that 155 Muninathan et al., Int J Med Res Health Sci. 2014;3(1):155-160 may have spread (metastasized) to other parts of the body from the original tumor. Chemotherapeutic drugs elicit some toxicity towards normal cells also, that limits its usage. Paclitaxel is a naturally occurring antineoplastic agent has shown great promise in the therapeutic treatment of certain human solid tumors particularly in metastatic breast cancer, skin cancer, lung cancer and refractory ovarian cancer6. Paclitaxel's antitumor activity was discovered in1960’s during a large scale 35,000 plants-screening program sponsored by the National Cancer Institute (NCI), USA. Paclitaxel is a most effective drug in skin cancer, it has several important side affects particularly neutropenia, peripheral neuropathy and hypersensitivity reactions7. Myelo suppression or neutropenia is the principal dose limiting toxicity of paclitaxel on all administration schedules. It is undeniable that the need for new agents with both improved activity and acceptable safety profile is urgent. Nausea, vomiting, thrombocytopenia, mucositis, decreased appetite and diarrhea are the less common side effects of administration of paclitaxel. Ongoing clinical trials suggest that combining paclitaxel with other anticancer drugs may be an effective treatment for patients with skin cancer. Researchers are exploring ways to reduce the side effects of treatment improve the quality of patients' lives, and reduce pain. The chemotherapeutic and antitumor activity associated with garlic has been attributed to the presence of various organosulfide-based active compounds including Di Allyl sulfide6. A topical application of Di allyl sulfide is the most promising approach for treating skin tumors as it leads to a localized effect at the desired site with minimal side effects. Polycyclic aromatic hydrocarbons (PAHs) are commonly occurring environmental contaminants and are widely distributed in the environment as pollutants of air, water and soil8. Benzo (a) pyrene is the most toxic compound of PAHs.9 The purpose of the present study is to evaluate the combined effect of Paclitaxel and Di allyl sulfide against the DMBA induced skin carcinogenesis. MATERIALS AND METHODS Chemicals: 7,12 Dimethyl benz (a) anthracene and Di allyl sulfide were purchased from Sigma chemical company, USA. All the other chemicals used were of analytical grade. Animal care and housing: Male Wistar rats, 6-8 weeks of age and weighing 150-200g, were used. The animals were procured from Central Animal House Block, Meenakshi Medical College and Research institute, Kanchipuran, Tamil Nadu, India and maintained in a controlled environmental condition of temperature and humidity on alternatively 12 h light/dark cycles. All animals were fed standard pellet diet (Gold Mohor rat feed, Ms.Hindustan Lever Ltd., Mumbai) and water ad libitum. This research work on Wistar male rats was sanctioned and approved by the Institutional Animal Ethical Committee Experimental Design The animals were divided in to six groups of 6 animals each. Group I animals served as control, Group II as animals treated with DMBA (5 µg/kg of body weight) per animal in acetone (100 µL), three times a week for 28 weeks to induce skin cancer. After tumor induction: Group III animals were treated with Paclitaxel (33mg/kg b.wt) once in a week for 4 weeks in intra muscular. Group IV animals were treated with garlic extract of Di allyl sulfide (250µg/animal) for 30 days daily. Group V animals were treated with both Paclitaxel and Di allyl sulfide (as in group III and group IV) daily. After the experimental period of 32 weeks, the animals were sacrificed by cervical dislocation. Blood sample was collected via cardiac puncture, and add 2-3drops of EDTA anticoagulant. The following Biochemical analysis was done: 1. Estimation of total white blood cells: Enumerated by the method of John (1972)10 2. Differential Leucocyte count: By the method of John (1972) 10 3. Soluble immune complex was estimated by the method of Seth and Srinivas (1981) 11 4. Nitro blue tetrazolium (NBT) reduction test: was carried out by the method of gifford and malavista (1970) 12 5. Neutrophil function test: By the method of Wilkinson (1977) 13 6. Ig G was quantitatively measured: by Tenant et al (1979) 14 156 Muninathan et al., Int J Med Res Health Sci. 2014;3(1):155-160 7. Phagocytic index: by the method of Wilkinson (1977) 13. 8. Avidity index: by the method of Wilkinson (1977) 13. RESULTS Immunocompetent cells : Fig. 1 represents the effect of paclitaxel and Di allyl sulfide on the status of immunocompetent cells in various experimental groups. Group II cancer bearing animals show a significant (p<0.001) decrease in the cell counts when compared with group I control animals. Paclitaxel and Di allyl sulfide treatment caused a significant decrease in leucocytes (p<0.05), lymphocyte (p<0.01), neutrophils (p<0.01), absolute lymphocyte count (p<0.05) and absolute neutrophil count (p<0.05). Di Allyl Sulfide along with paclitaxel treated group V animals caused a considerable changes (p<0.001; p<0.01) in cell count. However the effect was more pronounced in the group VI animals treated with both paclitaxel and Di allyl sulfide when compared with group I control animals. Units - Total leucocyte count : cu mm x 102 ; Lymphocyte : % ; Neutrophils : %; Absolute lymphocyte count : mm3 x 102 Absolute neutrophil count : no/mm3 / 102 Fig 1: Effect of paclitaxel and Di allyl sulfide on the status of immunocompetent cells Immune complexes: Fig. 2 depicts the effect of paclitaxel and Di Allyl Sulfide on immune complexes like phagocytic index, avidity complex, NBT reduction and SIC in various experimental groups. Group II cancer bearing animals showed a significant (p<0.001) decrease in the immune complexes when compared with group I control animals. Paclitaxel treatment caused a significant (p<0.01; p<0.05) decrease in the levels of immune complexes. Upon paclitaxel and Di allyl sulfide treatment there found to be a significant (p<0.001; p<0.01) increase in the levels of immune complexes. Fig 2: Effect of paclitaxel and Di Allyl Sulfide on immune complexes 157 Muninathan et al., Int J Med Res Health Sci. 2014;3(1):155-160 Immunoglobulins Fig 3 display the levels of immunoglobulins like IgG, IgA, and Ig M in various experimental groups. IgG and IgM levels were decreased considerably (p<0.001) in cancer bearing group II animals with an increase (p<0.001) in IgA level when compared with group I control animals. Upon paclitaxel treatment the levels of IgG, IgM were significantly (p<0.05) decreased where as IgA level was increased (p<0.01) in group III animals. Di allyl sulfide along with paclitaxel treated group V animals showed considerable alterations in the levels of Immunoglobulins (p<0.001) when compared with group II cancer bearing animals. In group VI animals treated with both paclitaxel and Di allyl sulfide show no significant changes when compared with group I control animals. Fig 3: Levels of immunoglobulins like IgG, IgA, and Ig M in various experimental groups. DISCUSSION Immunomodulatory activities: Chemotherapy remains the major hope for the treatment of cancer and is always associated with some degree of haemopoietic tissue toxicity and immune suppression. Although cancer itself is immunosuppressive, cytotoxic antineoplatic therapy is the primary contributor to the clinical immunodeficiency observed in cancer patients. Severe leucopenia, thrombocytopenia alterations in circulating platelets, white and red blood cells are the main side effects of chemotherapy leading to the decrease of chemotherapy dose or discontinuation of treatment.15 The most common complication associated with cytotoxic antineoplatic therapy occurs with the onset of neutropenia.16 Though paclitaxel is a potent anticancer agent the major limiting side effect is myelosuppression. It induces troublesome neutropenia of grade 3-4 with decrease in WBC count in more than 50% of the patients. Abnormal content of immunoglobulin indicate the concised humoral immunity and reduction in immune response. Thompson et a.l17 have reported decreased levels of IgG and IgM in skin cancer conditions. The levels of IgG and IgM were also decreased in various other cancerous conditions.18-20 IgA content alone was Muninathan et al., found to be increased in the skin cancer bearing rats. Chandy et al21, have reported that the elevated serum IgA levels may be due to the failure of clearance mechanism by the damaged liver. This indicates the severity of liver damage which directly correlates with the progression of the disease. A significant alteration in the neutrophil functions has been observed in all our study. The killing ability of the neutroplil as indicated by the NBT reduction and phagocytic ability of the neutrophils as indicated by the phagocytic index and the avidity index has been significantly decreased in the cancer bearing animals which was further decreased upon treatment with paclitaxel. Soluble serum immune complexes serve as an indicator of immune responses either due to presence of excess antigens or antibodies. This may be due to decreased antibody production during cancer. Immunomodulation through natural or synthetic substances may be considered as an alternative for the prevention and cure of neoplastic diseases.22, 23 Flavanoids are polyphenol substances of plant origin, having biological and antioxidative properties.24 Several reports have demonstrated the beneficial effect 158 Int J Med Res Health Sci. 2014;3(1):155-160 of flavanoids in preventing toxicity of different agents.25-27 Flavanoids display a remarkable array of biochemical and pharmacologiocal actions some of which suggest that certain members of this group of compounds significantly affect the function of the immune system. They also affect the function of enzyme system critically involved in the immune system. Di allyl sulfide contains organo sulfur compounds that play a very important role in scavenging free radicals. In our study also Di allyl sulfide exhibited positive effect on the immune system which can be attributed to its flavanoid content. Ali et al. (2000) have reported that Di allyl sulfide stimulates immune response in rats. Mesbah Lahouel28 have reported the effect of Di allyl sulfide on haemotoxicity of chemotherapeutic drugs. Considering the possible mode of antitumor action of Di allyl sulfide it is likely that it could be mediated by immunomodulatory activity of Di allyl sulfide. The present study has given the hope that Di allyl sulfide can confer in the reduction of side effects due to chemotherapeutic agents and may be used in humans in future. CONCLUSION From the present study, the effect of Paclitaxel- DAS combination proved to be effective chemotherapeutic agent against DMBA induced skin cancer in wistar rats compared to that of paclitaxel or Di allyl sulfide confirmed analyzing the total white blood cells, Differential leukocyte count, Soluble immune complex, neutophil function tests, IgG, IgM, IgA levels and Phagocytic , Avidity indexs in blood samples REFERENCES 1. American Cancer Society. 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Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells. American cancer society.2007; 1083-95. 8. Peluso G, Nicolai R, Reda E, Benatti P, Barbarisi A and Calvani M. Cancer and anticancer therapyinduced modifications on metabolism medicated by carnitine system. J. Cell Physiol., 2000; 182: 339-50. 9. Balasenthil S, Rao KS and Nagini S. Garlic induces apoptosis during DMBA induced hamster buccal pouch carcinogenesis. Oral Oncology. 2002; 38 : 431-46. 10. John MB. Laboratory medicine hematology 4th edition, CV Mosby Co ST louis .1972. pp 11981204. 11. Seth P. and Srinivas RV. Circulating immune complexes in cervical cancer-simple method for detection and characterization. Indian J Med Res. 1981; 73: 926-929. 12. Gifford RH. and Malawista SE. A simple rapid micro method for detecting chronic granulomatus this of childhood. J Lab Clin Med .1970; 108: 18-21. 13. Wilkinson DC. 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Zh. Vopr. Neivorhir. 1985; 615-19. 19. Micksche M, Luger T, Michelica W. and Tatra G. Investigations on general immune reactivity in untreated cervical cancer patients. 1978;4:121-24 20. Robert JT, Janique Richoz, Anne Constable Kellie D. Curtis Karen H. Dingley and Kenneth W. Turteltaub. The Effect of coffee on enzymes involved in metabolism of the dietary carcinogen 2- amino – 1 – methyl – 6 – phenylimidazo [4, 5 – b] pyridine in rats. Chemico – Biological Interactions. 1975; 145 : 251 – 65. 21. Chandy KG, Huebscher SG, Elias E, Berg J. Khan, Khan M. and Burnett D. Dual role of the liver in regulating polymeric IgA in man: studies on patients with liver diseases. Clin. Exp. Immunol., 1983;52 : 207-18. 22. Basic I, Milas L, Gordina J and Withers HR. Invitro destruction of tumor cells by macrophage from mice treated with coryne-bacterium granulosum. Journal of the National cancer Institute. 1975; 55:589-96. 23. Sver L, Orsolic N, Tadic Z, Njari B, Valpotic I. and Basic I. A royal jelly as a new potential immunomodulator in rats and mice. Comparative Immunology, Microbiology and Infections Diseases. 1996; 19: 31-38. 24. Merghem, R. Origine biogenese des molecules d' origine naturelle, importances pour "industrie pharmaceutique. Seminaire national sur les substances bioactives d" origine vegetable. Jijel, Algerie, 2001;12:105-11. 25. Mesbah Lahowel and Jean Paul Fillastre. Role of flavonoids in the prevention of haemato toxicity due to chemotherapeutic agents. Haema. 2004; 7(3): 313-20. 26. Lopez - Lazaro M, Martin - Corderoc, Ayuso MK. Two new flavonol glycosides as DNA topoisomerase I poisons. Z. Naturforsch. 2000; 55: 898-02. 27. Siess MH, Le Bon AM. Canivene - Lavier MC. and Suschetet M. Mechanism involved in chemoprevention of flavonoids. Bio factors. 2000;12:93. 28. Harborne JB and Williams CA. Advances in flavanoid research since 1992. Phytochem. 2000; 55: 481-54. 160 Muninathan et al., Int J Med Res Health Sci. 2014;3(1):155-160 DOI: 10.5958/j.2319-5886.3.1.031 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 5 Nov 2013 Revised: 8th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 29th Dec 2013 A STUDY ON EARLY DETECTION OF CHANGES IN VISUAL PATHWAY DUE TO DIABETES MELLITUS BY VISUAL EVOKED POTENTIAL Rajesh Kumar1, Sundararajan D2, Rajvin Samuel Ponraj3, M Srinivasan4 1 Post graduate student, 2 Associate Professor, 3Post graduate student,4 Professor, Department of Ophthalmology, Meenakshi Medical College and Hospital, Kancheepuram, Tamil Nadu, India *Corresponding author email:
[email protected] ABSTRACT Electrical potentials have been recorded by surface Evoked Potentials namely the Somatosensory Evoked Potential, Auditory Brainstem Response and Visual Evoked Potential [VEP]. Visual conduction disturbance can be evaluated by these instruments. A mass response of cortical and possibly subcortical may be represented, visual areas to visual stimuli. Diabetic patients without a past history of cerebrovascular accidents diagnosed with Non- Proliferative Diabetic retinopathy[DR] with a best corrected visual acuity at least 6/9.This study was done to assess whether a delay in VEP latency observed in diagnosed type II DM patients could be ascribed to dysfunction of the retinal or post retinal structures or by both. It is to find out whether the VEP latencies are altered in diabetes or not, if altered and to correlate duration of the diabetes mellitus with visual evoked potential changes. Visual evoked potentials are useful as a non invasive investigatory method in establishing central nervous system neuropathy developing in diabetes. This study clearly shows that changes in VEP may be detected in diabetics before the onset of retinopathy. Future studies should be focused on evaluation of the time that elapses between the appearance of the first detectable pathologic electrophysiologic changes and the first ophthalmoscopically detectable retinal changes in patients with Diabetes Mellitus [DM]. Keywords: Pattern reversal, Photostress, electrodes. INTRODUCTION Electrical potentials that occur in the cortex after stimulation of a sense organ, which can be recorded by surface electrodes, are known as Evoked Potentials [EP]. e.g. Somatosensory Evoked Potential (SEP), Auditory Brainstem Response (ABR) and Visual Evoked Potential (VEP). A change has been observed over time with the clinical use of Electric potentials. There have been advances in imaging technology, especially in magnetic resonance imaging (MRI), have reduced the use of EP testing in clinical practice. MRI largely remains an imaging, structural, or anatomic test and therefore gives more accurate information about structural problems. EP testing assesses functionality and thus supplies information about the physiology of a certain anatomic pathway, providing much less spatial or localizing information than MRI does.1 These electric potentials are used in the detection of anterior visual conduction disturbance. A mass response of cortical and possibly subcortical may be represented, visual areas to visual stimuli.2,3 VEP affection is related to age of onset of diabetes and glycemic control. Any abnormalities in the visual pathway can be detected with the help of VEP much prior to appearance of visual symptoms or changes in fundus examination.4 161 Rajesh et al., Int J Med Res Health Sci. 2014;3(1): 161-164 These equipments permit one sectioning of structures which help in visual pathway neural conduction.5 Evaluation of bioelectric activity of the retinal layers is done with the help of electroretinographic signals with patterned stimuli (PERG)6. The aim of this study is to evaluate the visual pathway abnormalities in diabetic patients without retinopathy and with non-prolierative diabetic retinopathy (NPDR) and to determine abnormal frequency and to investigate the relationship between other variables such as duration of diabetes and degree of metabolic control. Fig 1: Visual evoked potential3 Aim & Objectives Aim: Aim of this work is to assess whether a delay in VEP latency observed in diagnosed type II DM patients could be ascribed to dysfunction of the retinal or post retinal structures or by both. Objectives: 1. To find whether the VEP-PR latencies are altered in diabetes or not. 2. To correlate duration of the diabetes mellitus with visual evoked potential changes. MATERIALS AND METHODS Experimental design: A cross sectional study. Subjects: Patients were selected from the outpatient of Ophthalmology Department of Meenakshi Medical College & Hospital, Kanchipuram . An informed consent and ethical committee clearance have been taken for this study. Inclusion criteria: 1. No past history of cerebrovascular accidents 2. Diabetic patients with duration of 1-10 years. 3. Non- Proliferative Diabetic retinopathy 4. Best corrected visual acuity at least 6/9 Exclusion criteria: 1. Cataract, 2. Glaucoma 3. Vitreous opacities or any evidence of optic atrophy 4. Peripheral nervous system disease 5. Proliferative diabetic retinopathy General examination and systemic examination: General examination was done in the Department of Ophthalmology and a detailed history of Cerebrovascular diseases, Cataract, Glaucoma, any Optic nerve pathology and TB was taken. Visual evoked potentials were recorded using pattern reversal stimulation Study Group: The study groups were divided into Group I, Group II and Group III. Group I: 40 normal age and sex matched subjects, were selected as control group. Group II: 40 subjects with DM Type II without retinopathy, with duration of diabetes varying from 1 year to 10 years Group III: We evaluated 40 subjects with DM type II with non-proliferatve retinopathy with duration of diabetes varying from 1 year to 10 years. In this study waveform pattern latencies which are P 100 and N 75 and amplitude of VEP were chosen as the parameters. Visual Evoked Potential used from the Diopsys Nova Company with the electrodes placement on the scalp as shown in Fig 2: The diffuse light flash stimulus is rarely used due to the high variability within and across subjects. The checkerboard patterns utilize alternate light and dark squares and stripes, respectively. These squares and stripes which are equal are then presented one at a time via a computer screen. Fig 2: Placement of Electrodes, Scalp electrodes was used: 1.Frontal (FP2), 2. Occipital (O2), 3. Grounding (C2) electrodes6 Statistical Analysis: Student‘t’ test (Independent sample t test") was used for comparison of VEP between control and diabetes group. One way analysis of variance (ANOVA) was used for comparing the VEP latencies and amplitude with duration of DM and different level of glycemic control 162 Rajesh et al., Int J Med Res Health Sci. 2014;3(1): 161-164 RESULTS Table 1: Tabulation comprising 40 patients studied over period of 10 years No. of Age Duration of DM Subjects Group I Group II Group III 40 40 40 49.13 ± 4.52 52.70 ± 3.87 4.00 1.76 53.33±4.39 5.47 ± 2.25 Table 2: Comparison of P100 latency, N75 latency of Visual Evoked Potential No. of Subjects P100 latency (ms) N75 latency (ms) 40 93.82 ± 2 67.46 ± 5.28 Group I 40 100.30 ± 4.91 70.76 ± 6.77 Group II 40 107.30 ± 4.54 73.81 ± 4.58 Group III * The mean difference is significant at the < 0.05 level P value < 0.0001* < 0.0001* < 0.0001* Table 3: Comparison of Amplitude of Visual Evoked Potential between the groups No. of Amplitude (v) p value Subjects 40 7.52 ± 1.18 Group I <0.0001* 40 3.61 ± 1.24 Group II 40 2.77 ± 1.56 Group III * The mean difference is significant at the < 0.05 level Table 4: Relationship of various glycemic levels of Diabetes Mellitus with Visual Evoked Potential Latency (P100). FBG No. of P100 latency Amplitude (v) p value (mg/dl) Subjects (ms) 25 97.81 ± 4.25 <126 4.35 2.04 20 126-145 > 0.0001* 103.60 3.07 2.92 1.39 108.40 3.70 3.28 1.90 * The mean difference is significant at the < 0.05 level >145 35 Table 5: Analysis of P100 Latency in regard with different durations of Diabetes Mellitus: Duration (yrs) No. of Subjects P100 latency (ms) Amplitude(ms) p value 28 <3 < 0.0001* 96.31 6.38 5.54 1.61 102.29 1.72 3.30 0.98 < 0.0001* 105.79 2.92 * The mean difference is significant at the < 0.05 level 1.83 0.45 < 0.0001* 3–7 7 – 10 28 24 Relationship between duration of diabetes and VEP latency and amplitude: Among the subjects, the duration of type II diabetes mellitus was found to be between 1 year and 10 years with a mean of 4.73 ± 1.42 years. The subjects were distributed into 3 groups based on the duration of diabetes - Subjects > 3 years, 3 – 7 years and < 7 years duration of diabetes mellitus. Amplitude of VEP and duration of diabetes: The mean P100 – N145 amplitude was significantly Rajesh et al., reduced with the increasing duration of diabetes. (p.value <0.05) DISCUSSION Peripheral and central neuropathy in diabetic patients can be determined by Electrophysiological investigations. Many patients who were clinically examined showed a decrease of nerve conduction velocity. 10 Int J Med Res Health Sci. 2014;3(1): 161-164 In our study it appears that pattern stimulated VEP (P100 and N75 latencies) in people with diabetes mellitus shows a distinct prolongation of the latency period which could be explained with findings of Karlica et al.3 In our study VEP latencies and amplitude was correlated with duration of diabetes and we found there was a significant changes in VEP. This could be explained from the basis of poor metabolic control, diabetes duration, dislipidemia and diabetic nephropathy and the probable physiological mechanism could be that VEP abnormalities for both eyes is associated with parasympathetic autonomic neuropathy and the hyposthetic form of lower-limb sensory neuropathy. The mean N75 latency, P100 latency and P100-N145 amplitude were prolonged in those with HbA1c >7% but the difference were not statistically significant. 2. 3. 4. 5. CONCLUSION Visual evoked potentials are useful as a non invasive investigatory method in establishing central nervous system neuropathy developing in diabetes. This study clearly shows that changes in VEP may be detected in diabetics before the onset of retinopathy. This study also shows that the VEP changes may be related to the poor control and long duration of the disease, both of which were associated with significant VEP latency prolongation and decreased amplitude. Thus VEP measurement is essential for the detection of pre retinopathy changes and has the potential to reduce DM complications. Furthermore, it can be performed whenever a patient with diabetes without retinopathy shows a worsening of metabolic control, to evaluate the impairment of visual pathways. It is important to emphasise that, when tight metabolic control is achieved, these abnormalities disappear, suggesting that VEP impairment is only functional and completely reversible. Future studies should be focused on evaluation of the time that elapses between the appearance of the first detectable pathologic electrophysiologic changes and the first ophthalmoscopically detectable retinal changes in patients with DM. 6. pathways function , Impaired saccadic eye movement in diabetic patients: Documenta Ophthalmologica 1999;99: 11-20 Andrew BE, Jane G Boggs. Clinical Utility of Evoked Potentials. Journal name. 2010;vol:pgnos Dobrila Karlica, Davor Galetovi, Milan Ivanisevi, Veselin Skrabi, Ljubo Znaor and Darija Juri. Visual Evoked Potential in the Detection of Prediabetic Form of Diabetic Retinopathy in Patients with Diabetes- Mellitus. Antropol. 2010;34(2): 525-29 Samahy RM, Matter AM, Nassef, Osman AF. VEP in children and adolescents with type l diabetes mellitus. Pediatric Diabetes, 2010,Suppl. 14: 35 Vincenzo Parisi, Luigi Uccioli, Giovanna Monticone, Leoluca Parisi, Gianluca Manni, Daniel Ippoliti, etal., Electrophysiological assessment of visual function in IDDM patients. Electroencephalography and clinical Neurophysiologjy. 1997;104, 171 -79 Vincenzo Parisil, Luigi Uccioli. Visual electrophysiological responses in persons with type l diabetes. Diabetes/Metabolism Research and Reviews, 2001; 17: 125:18 REFERENCES 1. Marco Alessandrini, Vincenzo Parisi, Ernesto Bruno, Pier Giorgio. The relationship with visual 164 Rajesh et al., Int J Med Res Health Sci. 2014;3(1): 161-164 DOI: 10.5958/j.2319-5886.3.1.032 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 12 Dec 2013 Revised: 26th Dec 2013 Research article Copyright @2013 ISSN: 2319-5886 Accepted: 29th Dec 2013 EFFECT OF 30°AND 60° HEAD UP TILT ON CARDIOVASCULAR RESPONSES IN NORMOTENSIVE AND HYPERTENSIVE INDIVIDUALS *Badwe AN1, Soodan KS2, Kulkarni NB3, Latti RG4 1 Associate Professor, 3Professor, 4Professor & HOD, Department of Physiology, Rural Medical College, Pravara Institute of Medical Sciences, Loni, Rahata, Ahmednagar, Maharashtra, India 2 Ex-Principal Rural Medical College, Pravara Institute of Medical Sciences, Loni, Rahata, Ahmednagar, Maharashtra, India *Corresponding author email:
[email protected], Mob: +91-9096035553 ABSTRACT Since 50 years, head up tilt table testing is being used by physiologists and physicians for different purposes. Many investigators have studied the effect of head up tilt at a specific angle on cardiovascular and autonomic functions in healthy individuals and reported usefulness of HUT in assessing the integrity of cardiovascular and autonomic functions. In present study effect of 30° and 60° head up tilt is studied on cardiovascular parameters (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial blood pressure (MAP), heart rate/min (HR), rate pressure product (RPP)) in normotensive and hypertensive individuals. METHODS: Effect of 30° and 60° head up tilt on cardiovascular parameters was studied in normotensive (n=50) and hypertensive individuals (n=50) aged 15-70 years. Blood pressure and heart rate were determined by using electronic blood pressure apparatus. RESULTS: 30° and 60° HUT produced decrease in SBP, PP, MAP and increase in DBP, HR, RPP in both groups. The results were significant at selected different time intervals. The changes produced by 60° HUT were more significant than 30° HUT. The changes produced in the hypertensive group were more prominent than normotensive group. In conclusion significant changes in HR and RPP in hypertensive individuals indicated more myocardial oxygen consumption and myocardial work at both angles of HUT. Keywords: Hypertensive, head up tilt, cardiovascular parameters INTRODUCTION Since 50 years, head up tilt table testing is being used by physiologists and physicians for different purposes. This includes effect of head up tilt (HUT) on heart rate and blood pressure changes in posture, for modeling responses to haemorrhage, as a technique for evaluating orthostatic hypotension, as a method to study haemodynamic and neuroendocrine responses in congestive autonomic dysfunction and hypertension, as well as tool of drug research.1-6 Many investigators have studied the effect of head up tilt at a specific angle on cardiovascular and autonomic functions in healthy individuals and reported Badwe AN et al., usefulness of HUT in assessing the integrity of cardiovascular and autonomic functions. 7,8 From literature survey conducted, it is found that, there are few studies conducted to study the effect of head up tilt on cardiovascular responses in hypertensive individuals. The studies conducted so far, have studied the effect of head up tilt mainly on cardiovascular parameters such as Systolic blood pressure (SBP), Diastolic blood pressure (DBP), heart rate variability (HR), Cardiac output (CO). 9-10 Hence in the present study we decided to study the following objectives in selected hypertensive patients from the 165 Int J Med Res Health Sci. 2014;3(1):165-170 Medicine department and the Family Medicine Department of Pravara Rural Hospital, Loni. Objectives:1. To study the effect of 30° and 60° head up tilt on cardiovascular parameters 2. Comparison of investigated parameters in normotensive group and hypertensive group MATERIALS AND MEHTODS It was a case control study conducted in the department of Physiology at Rural Medical College, Pravara Institute of Medical Sciences. The male subjects selected for the study were between the age group of 20-70 years (n=100) and were grouped in two groups as: 1. Normotensive (control group n=50) 2. Hypertensive (Study group n=50) Control group: Age matched normotensive healthy subjects were selected as control and were selected from clerical, teaching staff and students of our institute, who fulfilled following criteria, were included as control subjects in the study: No signs of cardiac, vascular or neurological involvement No history of diabetes mellitus, hypertension No history of drug treatment No history of systemic illness Their normal blood pressure status was considered according to guidelines of, Seventh Report of the Joint National Committee (JNC7) 11 on Prevention, Detection, Evaluation and Treatment of high blood pressure and Indian Hypertension Guidelines II, 2007 with optimal value as <120/<80 mm Hg and further variations in systolic blood pressure was considered in the range of 120-139 mmHg.Diastolic blood pressure variation was considered in the range of 80-89 mmHg. Study group (Hypertensive): Study group included the hypertensive patients attending to Medicine department and the Family Medicine Department of Rural Medical College on outpatient basis. Hypertensive subjects suffering from major illness such as severe diabetic condition, congestive heart failure, coronary artery disease, arrhythmias were excluded from the study. Same type of exclusion criteria was used for inclusion of normotensive subjects in the proposed study. The study protocol was approved by the Institutional Research Ethical Committee. In this group also patients were between the age group of 20-70 years with diagnosed hypertension (i.e., history of hypertension less than 1 year).Hypertensive subjects were considered as, having systolic blood pressure of 140-159 mmHg and diastolic blood pressure of 90-99 mm Hg (Grade I hypertension = According to Joint National committee VII and Indian Hypertension Guidelines II, 2007).11-14 These subjects were under treatment or on blood pressure lowering medication with controlled hypertension (target blood pressure value 140/90) at the time of study. Their hypertensive status was determined by consulting physician of Medicine department and Family Medicine department. METHODS All subjects were called by appointment in the laboratory, 2 hours after light brake fast in the morning (09.00am-12.00pm). Subjects were instructed not to consume caffeinated beverage and to avoid smoking before 12 hours of the test. Subjects were informed in detail about study protocol and written consent was obtained before the study. Before beginning of the test, anthropometric characteristics such as height (cm), weight (Kg), body mass index (BMI, Kg/m2), percent fat (%), fat mass (FM, kg), fat free mass (FFM, kg) were recorded in all subjects. Percent fat (%), fat mass (FM, kg), fat free mass (FFM, kg) parameters were determined by method of measurements of girth as described by McArdle et al.15 Subjects were made to lie comfortably on tilt table for 20 minutes in the supine position. Three straps were applied at the level of knee, waist and head. After 20 minutes of rest baseline cardiovascular parameters (SBP, DBP, PP, MAP, HR/MIN, RPP) were recorded at 1,5,10 minutes of interval by using digital blood pressure monitor (Digicheck, Japan). Thereafter subjects underwent gradual head up tilt at 30°, 60° angles of tilt with the speed of 5°/Sec. During head up tilt manoeuvre passive head up tilt protocol was followed only for 10 minutes. Tilt table with foot board was used in the study to support body weight. The following sequence of recording was followed. 1. Basal: 20 minutes of rest on tilt table in supine position 2. After 30° HUT 3. After 60° HUT Cardiac parameters were recorded immediately after 1,5,10 minutes of HUT. Between each HUT the 166 Badwe AN et al., Int J Med Res Health Sci. 2014;3(1):165-170 subject was tilted back to horizontal position and allowed to rest for 10 minutes. Statistical analysis: For each parameter of both groups-mean and standard deviation (SD) were calculated. To find any significant change the data was analyzed for the same group by applying Student t – test and between two groups by applying unpaired ttest. The P values less than 0.05 (P<0.05) were considered as statistically significant. RESULTS: Table:1. Anthropometric characteristics of subjects Parameter Normotensive Hypertensive Age(yrs) Height (cm) Body weight kg BMI (Kg/m2) % Fat Fat Mass (Kg) Fat Free Mass (Kg) 35.72±1.88 163.86±1.01 55.26±1.20 20.81±0.48 23.89±1.01 13.47±0.67 41.76±0.92 49.28±1.94 164.74±1.10 65.56±1.71 24.21±0.57 31.10±1.05 21.02±1.18 43.94±0.82 Values are Mean ± SE Higher values of anthropometric characteristics were recorded in hypertensive individuals as compared to control group, which were non significant (Table: 1). All results are presented graphically for better understanding of the effect produced by both angles of head up tilt in both study groups. Table: 2. Effect of 30°, 60°head up tilt on cardiovascular parameters in normotensive Basal 30°HUT 1 Min 5 Min 10 Min 1 Min SBP 121.4±1.66 117.44±1.80*‡‡‡ 118.42±2.03‡‡‡ 119.64±1.79‡‡‡ 116.94±2.13* DBP 76.26±1.30 77.04±1.30‡‡‡ 77.22±1.21‡‡‡ 78.1±1.57 78.8±1.43 PP 45.88±1.29 40.4±1.64*** 41.2±1.70* 41.7±1.71* 38.34±1.66*** MAP 91.51±1.60 90.43±1.79 89.53±1.82 90.24±1.80 91.49±1.51‡‡‡ HR/MIN 75.6±1.60 78.14±1.79*††† 80.52±1.82***††† 79.6±1.80*††† 89.24±2.01*** RRP 9.0±2.74 9.09±2.30 9.48±2.59* 9.72±1.16** 10.43±0.31***††† Parameter 60° HUT 5 Min 10 Min 121.84±1.78 117.66±2.14* 80.26±2.25 80.54±1.58* 40.24±1.90* 37.4±1.67*** 93.09±2.31‡‡‡ 92.88±1.62‡‡‡ 91.56±1.93*** 89.62±2.56*** 11.35±0.41***††† 10.64±0.33***††† Values are Mean ± SE. Pressure values are in mmHg. Basal values are before tilt. SBP: systolic blood pressure, DBP: diastolic blood pressure, PP: pulse Pressure, MAP: mean arterial blood pressure, HR/MIN: heart rate/min RPP: rate pressure. (Paired t –test:*P<0.05significant, **P<0.01 highly significant ***P<0.001 very highly significant, Comparison between 30° and 60° head up tilt: †P<0.05significant, ††P<0.01 highly significant †††P<0.001 very highly significant, Unpaired t test: ‡P<0.05 significant, ‡‡P<0.01 highly significant ‡‡‡<0.001 very highly significant) Normotensive: 30° HUT caused minimal and significant decrease in SBP after 1 min of HUT. After 1 minute of tilt, there was minimal decrease in SBP, which remained insignificantly lower than basal value for a total duration of 10 minutes of HUT. DBP showed a marginal increase than basal value after 1 minute of HUT and remained almost constant throughout the 10 minutes duration of HUT. PP registered very highly significant decrease (P<0.001) in its value than the basal value after 1 minute of tilt and showed a further significant decrease (P<0.05) at 5 and 10 minutes of HUT. MAP (=DBP+1/3 PP) showed insignificant decrease after 1 minute of HUT and the same pattern was continued for 5 and 10 minutes of HUT. HR also registered increase in its value, which was more than basal value. This change was significant after 1minute (P<0.05) and at 5 (P<0.001), 10 (P<0.05) minutes of HUT. RPP showed a marginal insignificant increase in its value after 1 minute of HUT, however after 5 (P<0.01) and 10 (P<0.001) minutes of HUT, RPP registered a significant increase in its value. 167 Badwe AN et al., Int J Med Res Health Sci. 2014;3(1):165-170 60° HUT: 60° HUT produced more significant changes in cardiovascular parameters as compared to 30° HUT. SBP decreased significantly (P<0.05) after 1 and 10 minutes (P<0.05) of HUT. Insignificant increase was observed at 5 minutes of HUT, than basal value. DBP registered a marginal insignificant increase at 1 and 5 minutes of HUT, however at 10 minutes of HUT significant (P<0.05) increase in DBP was recorded. PP registered significant decrease at 1(P<0.001), 5(P<0.05), 10(P<0.001), minutes of HUT. This decrease was lower than basal value. MAP showed insignificant decrease in its value after 1,5,10 minutes of HUT. HR registered very highly significant (P<0.001) increase as compared to basal values throughout the duration of 10 minutes of HUT. RPP also recorded very highly significant (P<0.001) increase in its value as compared to basal values throughout the duration of 10 minutes of HUT Table: 3 Effect of 30° and 60°head up tilt on cardiovascular parameters in hypertensive Basal 30°HUT 60° HUT 1 Min 5 Min 10 Min 1 Min 5 Min 140.4±3.59 141.72±2.48 142.48±2.70† 140.5±2.58† 137.4±3.04‡‡‡ 136.58±3.83†‡‡‡ SBP 93.84±1.99 93.92±2.54 96.36±1.99 96.48±1.84 95.58±1.74‡‡‡ 95.00±1.92‡‡‡ DBP 49.78±2.15 45.50±1.99 45.88±2.00* 43.9±2.56* 46.66±2.90 43.78±1.99** PP 109.33±2.16 111.25±1.81 111.65±2.02 111.03±1.73 100.60±3.18* 109.56±2.11‡‡‡ MAP 75.48±1.96 75.80±2.31 76.82±1.78†† 79.82±1.95** 84.26±1.74***†††‡ 83.72±1.85***†††‡ HR/MIN 10.7±0.36 10.98±0.38††† 10.82±0.39 10.84±0.38 11.74±0.43*** 11.58±0.40* RRP Parameter 10 Min 132.62±3.49†‡‡‡ 94.14±1.70 40.68±1.96*** 107.71±1.78‡‡‡ 84.80±2.33***††‡ 11.40±0.41* Values are Mean ± SE .Pressure values are in mmHg. Basal values are before tilt.SBP: systolic blood pressure, DBP: diastolic blood pressure, PP: Pulse pressure, MAP: mean arterial blood pressure, HR/MIN: heart rate/min, RPP: rate pressure product. (Paired t –test:*P<0.05significant, **P<0.01 highly significant ***P<0.001 very highly significant, Comparison between 300 and 600 head up tilt : †P<0.05significant, ††P<0.01 highly significant †††P<0.001 very highly significant, Unpaired t test: ‡P<0.05 significant, ‡‡P<0.01 highly significant ‡‡‡<0.001 very highly significant) Hypertensive: All cardiovascular parameters recorded in hypertensives registered increase its value, as compared with normotensives at 30°and 60° HUT at different time intervals. 30° HUT: SBP registered a marginal insignificant increase in its value than the basal value after 1and 5 minutes of HUT. After 10 minutes of HUT decline in SBP was observed and returned to baseline values. DBP also registered a marginal insignificant increase in its value than basal value after 1 minute of HUT and this insignificant increase was followed for 5 and 10 minutes of HUT. PP showed an insignificant increase after 1 minute of HUT and increase at 5 and 10 minutes of HUT, was found to be more significant (P<0.05) than basal value. MAP recorded insignificant increase in its value after 1,5,10 minutes of HUT HR recorded initially decrease in its value as compared to basal value, however at 10 minutes of HUT significant (P<0.01) increase in HR was observed. RPP recorded a marginal insignificant increase than basal value after 1,5,10 minutes of HUT. 60°HUT: HUT SBP decreased insignificantly and remained lower than basal value during 1, 5, 10 minutes of HUT. DBP recorded a marginal increase in its value than basal value at 1,5,10 minutes of HUT PP recorded insignificant decrease after 1 minute of HUT, however this decrease was significant at 1 minute (P<0.01) and 10 minutes (P<0.001) of HUT than initial basal value. MAP registered a significant increase in its value after 1minute (P<0.05) of HUT.MAP showed further a marginal decrease at 1 and 5 minutes of HUT, than basal value. HR recorded a highly significant increase (P<0.001) at 1,5,10 minutes of HUT. RPP also registered very highly significant (P<0.001) increase in its value after 1 minute of HUT and remained significant (P<0.05) increased at 5 and 10 minutes of HUT. DISCUSSION In the present study, we studied effect of 30° and 60° HUT on cardiovascular parameters in normotensive and hypertensive subjects. 168 Badwe AN et al., Int J Med Res Health Sci. 2014;3(1):165-170 Normotensive: SBP, PP and MAP parameters decreased, while DBP, HR/MIN, RPP increased gradually as the angle of HUT increased. At 30° HUT changes recorded in SBP, PP, HR/MIN, RPP were significant. Similarly same pattern of decrease in SBP, PP, and MAP was observed in normotensive at 60° HUT and significant pattern of increase in DBP, HR/MIN, and RPP was observed. Except decrease in MAP other findings of our study agree with the study conducted by Vijayalaxmi et al15.It is important to note that, autonomic functions vary with ageing 16 and parasympathetic 17 is also reduced, since our subjects were selected from different age group (20-70 yrs). In normotensive subjects, significant fluctuations were not observed, since, during the initial phase of HUT intact autonomic activity18 stabilized the cardiovascular parameters during the total duration of HUT. Hypertensive: In hypertensive individuals, SBP, PP, MAP showed decrease at 300 and 600 HUT. Similarly DBP, HR/MIN, RPP showed increase in their value at both angles of HUT. However, these changes were more significant at higher angle of 60° HUT, in both groups. MAP is dependent on heart rate (HR), stroke volume (SV) and total peripheral resistance (TPR), which can be correlated as MAP=HR X SVX TPR. During HUT, changes like pooling of blood in lower parts of the body and low carotid pressure in the carotid sinus occur.19 These gravity induced changes produced decreases in venous return, stroke volume, pulse pressure, mean arterial pressure which cause tachycardia and vasoconstriction, due to baroreceptor reflex20. In this upright posture increase in heart rate and peripheral resistance regulate blood pressure. This mechanism is more effective in younger individuals than older ones in maintaining blood pressure in upright posture. 21 This was the major factor to cause a decrease in SBP, PP and MAP during HUT. Increase in HR, as reported by other studies is tilt dependent, which remained elevated throughout the period of HUT. However, this increase in HR may be due to increase in sympathetic stimulation and withdrawal of vagal tone, which is the prominent finding in hypertensive.22 HUT 30° and 60° produced an increase in RPP in both groups, but this increase was more in the hypertensive group than normotensive group. HUT of 60° produced a more significant increase in its value throughout the duration of HUT. The increase in RPP was caused due to increase in SBP and HR.RPP (Robinson Index) was expressed as RPP= SBP X HR X10-3. 23RPP indicates myocardial oxygen consumption and cardiac work in normal subjects as well as patients with heart diseases.24 It also indicates onset of ischaemia in patients undergoing surgery or the onset of coronary pain during exercise.25,26 Higher values of RPP recorded in hypertensive than normotensive indicate more oxygen consumption, coronary blood flow and more myocardial work. CONCLUSION The results of this study indicate a significant effect of HUT on cardiovascular parameters in hypertensive group. It is worth noting that, significant changes in HR and RPP in hypertensive individuals indicated more myocardial oxygen consumption and myocardial work at both angles of HUT. These are more prominent at higher angles of HUT than the lower angle of HUT. REFERENCES 1. Severe K, Lefrandt, Nordby G, Os I. Autonomic function in hypertensive and normotensive subjects. 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Rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic 169 Badwe AN et al., Int J Med Res Health Sci. 2014;3(1):165-170 7. 8. 9. 10. 11. 12. 13. 14. 15. features of insulin resistance syndrome. Am J Hypertens 1998;11:523-31. Vaz M, Kulkarni RN, Rodrigues D, Shetty PS. Immediate heart rate responses to head up tilt in healthy human subjects: response characteristics and variability. Indain J Physiol Phramacol 1993:37(4):323-27. Jahan N, Deepak KK, Kaushal Navita, Paudel BH. Effect of graded head up tilt on parasympathetic reactivity. Indain J Physiol Phramacol 1996:40(4):309-17. James MA, Robinson G T, Potter JF. The effect of systemic blood pressure on cardiovascular reflexes in elderly subjects.Clinical Physiology 2008:21(1):67-76. Wahbha MMAE, Wilson , Hainsworth R. Cardiovascular response to upright tilting in hypertensive patients with and without renal impairment and before and following nisoldopine treatment. Br. J. Clin. Pharmac 1990;29:733-39. Guidelines sub committee. 1993 Guidelines for the management of mild hypertension:memorandum from a World Health Organization/ International Society of Hypertension meeting.J Hypertens 1993;11:905-918. Joint National Committee on prevention, detection and treatment of high blood pressure .The sixth report of the Joint Committee on prevention, detection and treatment of high blood pressure.(JNC VI). Arch Intern Med 1997;157: 2413-46. Chobanian AV, Bakris GL, Black AR. Joint Committee on prevention, detection and treatment of high blood pressure. National Heart, Lung and Blood Institute, National high blood pressure programme coordinating committee. Seventh report of the Joint Committee on prevention, detection and treatment of high blood pressure. Hypertension 2003;42:1206-52. Shah Siddharth, convenor. Practical guidelines for physicians: Indian hypertension guidelines 2007. Supported by unrestricted educational grant Pfizer, India. Website address McArdle W, Katch F, Katch V. Body composition assessment. In Exercise Physioloy: energy, Nutrition and Human Performance.5th Ed,Lippincott Williams and Wilkins, Baltimore:2001:772-776. 16. Collins KJ, AN Exton-Smith. Functional changes in autonomic responses with ageing. Age and Ageing 1980:9:17-24. 17. Vita GP, Calabro R, Toscano. Cardiovascular reflex test: Assessment of age adjusted normal range. J. Neural Sci 1986;75:263-74. 18. Guyton AC, Hall JE. Nervous regulation of the circulation and rapid control of arterial pressure. In T.B of Medical Physiology.11th Ed ,Saunders, Philadelphia. 2006:204-14. 19. Neto JAN, Gallo L, Manco JC. Mechanism of tachycardia on standing: Studies in normal individuals and in chronic changes in heart patients. Cardiovas Res. 1980;14:541-50. 20. Florica V, Kem DC. Plasma norepinephrine, blood pressure and heart rate response to graded change in body position. Aviat Space Environ Med 1985;56:1166-71. 21. Luutonen S, Antila K, Errko M. Haemodynamic response to head up tilt in elderly hypertensive and diabetic. Age and ageing 1995;24(4):315-20. 22. Langewitz W, Ruddel H, Schachinger H. Reduced parasympathetic cardiac control in patients with hypertension at rest and mental stress. Am Hear J 1994;127:199-204. 23. Pepper MG, Crawley BE.Technical note: Calculation and display of the rate/pressure product during anaesthesia using binary rate multipliers. Med and Bio. Eng and Comput.1985;23:187-89. 24. Globel FL, Nordstrom LA, Nelson RR. The rate pressure –product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation 1978;57:549-56 25. Cokkinos DV, Vorodis ES. Constancy of pressure product in pacing induced angina pectoris. British Heart Journal 1976;38:39-42. 26. Robinson BF. Relation heart rate and systolic blood pressure to the onset of pain in angina pectoris. Circulation 1967;35:1073-80. 170 Badwe AN et al., Int J Med Res Health Sci. 2014;3(1):165-170 DOI: 10.5958/j.2319-5886.3.1.033 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 10 Oct 2013 Revised: 18th Nov 2013 Letter to Editor Copyright @2013 ISSN: 2319-5886 Accepted: 10th Dec 2013 PEDAGOGY TO ANDRAGOGY Darshana Bennadi Senior Lecturer, Dept. of Public Health Dentistry, Sree Siddhartha Dental College and Hospital, Tumkur, India. Corresponding author email:
[email protected] Dear Sir, I would like to congratulate Muneshwar JN, Mirza Shiraz Baig, Zingade US, Khan ST for highlighting a very important issue regarding the teaching methods for health care professionals.1 Study has proved the Chinese proverb: “If I hear, I forget; if I see, I remember; if I do, I know”. Along with this I want to focus little on “podcast” as new teaching method. At present, education trend have changed from pedagogy to andragogy i.e. from a teacher-centered learning to a student-centered learning. These methods of education trends have identified many different learning styles as well. So, now it has become necessary for educators to train themselves to upcoming teaching methods. 2 Many new teaching methods are evolving in the current electronic world. In which Podcasts as a supplement to live lectures is one of the teaching method, which have been adopted by many universities. Podcasting is user friendly, where information is recorded, then uploaded to a website or published through programs like iTunes and made accessible to students. The file can then be played on a computer or digital player.3,4 Recently many studies have been conducted using podcast as a new aid and its effectiveness. Studies have shown that audio podcasts as an effective aid for review before exams, enhancing student performance; acceptability and perceived utility of podcasts was good among students. Introduction of podcasts in the beginning will offer the students a lot of flexibility in learning, with regard to place and time.4 Darshana Bennadi, Podcasts as a supplement to live lectures as teaching method has open up for future research to assess their utility on a long-term basis so as to pave the way for introducing podcasts as one of the teaching method. REFERENCES: 1. Muneshwar JN, Mirza Shiraz Baig, Zingade US, Khan ST. A questionnaire based evaluation of teaching methods amongst MBBS students. Int J Med Res Health Sci.2013;2(1):19-22 2. Poonam Kharb, Prajna Paramita Samanta, Manisha Jindal, Vishram Singh. The Learning Styles and the Preferred Teaching – Learning Strategies of First Year Medical Students. Journal of Clinical and Diagnostic Research. 2013;7(6): 1089-92 3. Burns TM. The forecast for podcasts: sunny skies but not necessarily with clear visibility. Neurology. 2007; 68(15):E19-20. 4. Kalludi SN, Punja D, Pai KM, Dhar M. Efficacy and perceived utility of podcasts as a supplementary teaching aid among first-year dental students. AMJ 2013; 6(9): 450-57 Int J Med Res Health Sci. 2014;3(1):171 171 DOI: 10.5958/j.2319-5886.3.1.034 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan - Mar) Coden: IJMRHS Received: 4th Dec 2013 Revised: 18th Dec 2013 Review article Copyright @2013 ISSN: 2319-5886 Accepted: 21st Dec 2013 EMERGING ROLE OF VITAMIN D IN HEALTH *Deepanjali Lomte Associate Professor, Department of Pharmacology, Dr.Vasantrao Pawar Medical College, Hospital & Research Centre, Nashik, Maharashtra, India. *Corresponding author email:
[email protected] ABSTRACT Vit. D is a steroid prohormone. It is synthesized in the skin under ultra –violet light exposure. Traditionally, Vit.D3, cholecalciferol and calcitriol were known to have a role only in calcium and bone mineral metabolism. This article takes an account of the current view on the impact of Vit D deficiency on human health. Research has now shown the indisputable role of Vit D in prevention/treatment of some cancers, osteoporosis, rheumatoid arthritis, multiple sclerosis, tuberculosis, hypertension, and diabetes mellitus. In addition lower maternal Vit. D levels are associated with Pregnancy Induced Hypertension (PIH), suggesting that Vit. D deficiency may be a modifiable risk factor for PIH. Greater awareness of the problem of a high prevalence of vitamin D inadequacy is required among researchers, clinicians, and patients. Special efforts on the medical and social fronts are necessary to combat this preventable epidemic of vitamin D deficiency. Keywords: Vitamin D, 25-Hydroxyvitamin D, PIH, Pregnancy, Hypervitaminosis D, Cholecalciferol, Calcitriol. INTRODUCTION Vitamin D is more important nutrient for health. Vitamin D is actually a hormone rather than a vitamin. Despite its discovery 100 years ago, Vit D has emerged as one of the most controversial nutrients and prohormones of the 21st century, and a lot of research has been in place on this molecule. Traditionally, Vitamin D was viewed as a permissive factor in calcium and bone mineral metabolism. It works with the Parathyroid hormone (PTH), acts on the kidneys, bone & intestine and influences gene expression. The research leads us to newer therapies with newer concepts.1 Research has now shown Vit D's indisputable role in both inherent and adaptive immunity. Vit D is a Steroid prohormone and it is synthesized in the skin under ultra-violet light exposure. 7Dehydrocholesterol present in the skin absorbs UV light over wavelengths of 290-300 nm [UVB] to synthesize Vit D3. Synthesis in the skin epidermis takes place over several days; the quantity (intensity) and quality (appropriate wavelength) of sunlight are both important this biosynthesis can be inadequate due to poor dietary intake, absorption, or poor exposure to sunlight [UVB]. The deficiency can occur because of fat malabsorption, anticonvulsant use, chronic kidney disease and obesity and is seen in high-risk groups like elderly women, dark-skinned people, people from areas with a thick layer of ozone, women using sunscreen lotions, and people from urban areas.2 In urban and polluted areas, the UV light of 290-300nm wave length gets filtered out; hence, skin may not get enough of this light. Therefore, there is a high rate of Vit D deficiency even among the urban population. Hence, foods and dietary supplements are necessary. Cod liver oil, salmon and sardines, fortified milk, egg, fortified yogurt, mushrooms, fortified soy products, oysters, and fortified cereals are rich sources of Vit D. Activation of Vitamin D: It takes place in the following manner: 1 Deepanjali, Int J Med Res Health Sci. 2014;3(1):172-175 172 Fig 1: Activation of Vitamin D Under situations of minimal exposure to sunlight, a specific recommendation of a daily supplement of 400 IU (10 µg) is retained for the Indian population. RDA for pregnant women is 200 IU per day and the maximum safe daily dose is 2,000 IU. Due to increased deficiency screening for vitamin D levels is important for most individuals. A serum concentration of 25 (OH) D is the best indicator of vitamin D. The Emerging Roles of Vit D: It is now considered important in cell differentiation, proliferation, and immune function. It is an important factor in prevention/treatment of some forms of cancer, osteoporosis, rheumatoid arthritis, multiple sclerosis, hypertension, cardiovascular disease, obesity, psoriasis, and psychiatric diseases. The role of vitamin D in pregnancy is also taking new dimensions. Vit. D and Pregnancy: Maternal Vit.D deficiency is common during pregnancy and throughout gestation. If a women is Vit. D deficiency, it leads to a number of serious health problems likes poor bone mineralization in infants, low birth weight baby and other adverse pregnancy outcomes.3-5 There are different deficiency levels. The risk of rickets increases significantly when the total circulating 25(OH)D falls below 10 ng/mL (25 nmol/L), whereas cathelicidin mRNA expression as a marker of immune function continues to be suppressed until 25(OH)D circulating levels reach at least 20 ng/mL (50 nmol/L).6 The recently revised Institute of Medicine's (IOM) 2010 criterion for Vit D deficiency of total circulating 25(OH) D is <20 ng/mL (50 nmol/L), Optimal serum concentrations of 25(OH) D3 are at or above 30 ng/mL (>75 nmol/L), and Vit D toxicity is present when levels are at or above 150 ng/mL (374 nmol/L).7 Rates of deficiency of Vit D are more with women who have darker pigmentation and women who have limited access to sunlight, through limited outdoor activity.8 Vit D deficiency exists in a higher percentage in obese women. Women including pregnant women, with a BMI >30, are at increased risk of Vit D deficiency.8 The adipose tissue serves as a repository for Vit D that does not get into the circulation. As per recent guidelines Recommended Daily Allowance (RDA) of Vit. D during pregnancy is 200400 IU/day and more than 2,000 IU/day has been toxic not just to the pregnant women but to the any one. As per recent research, higher dosages of Vit D are not just safe during pregnancy, but increased dosage may actually reduce the risk of complications. In a study, 500 women who were at least 12 weeks pregnant took 400, 2000, or 4000 IU of Vit D per day. The women who took 4,000 IU were less prone for preterm labour or infections during pregnancy. Vit D intoxication is extremely rare and easy to treat. Pregnant women who get too little Vit D are more likely to develop PIH (Pregnancy induced hypertension) and are also more likely to require a Cesarean section. They concluded that giving 4,000 IU a day to pregnant women may not only improve birth outcomes but also does not cause toxicity.9 Pregnant women with a serum level of 25-OH Vit D <75 nmol/L are considered to be Vit D3 deficient.10 Until recently, it was thought that Vit D deficiency was common only in high-risk women (women with dark skin and those with minimal exposed skin), but it is quite high even in low-risk women. All women therefore should be offered testing for Vit D status in early pregnancy and recommended supplementation if deficient.11 Women with a 25-OH Vit D3 <75 nmol/L are considered Vit D deficient and should have a dietary assessment for calcium intake. They should receive a higher dose up to 1000 IU. They should be offered retesting at 28 weeks of pregnancy. If the higher dose of Vit D does not improve the serum Vit D levels, then malabsorption syndrome (such as celiac disease) should be ruled out or else the patient may be noncompliant. Pregnant women should have enough Vit D at the time of delivery to insure sufficient Vit D levels in their baby for the first 4-6 months of life. The transplacental passage of maternal 25-OH Vit D3 is the sole source of Vit D in the developing fetus. 173 Deepanjali, Int J Med Res Health Sci. 2014;3(1):172-175 Therefore, infants are wholly dependent on their mother for their Vit D status. Infants born to Vit Ddeficient mothers will be Vit D deficient and hence will require supplementation in the form of cholecalciferol bolus (50,000 IU) dose orally. The obstetricians must understand the importance of vitamin D supplementation to pregnant and nursing mothers, which will go a long way in preventing rickets. Emerging Role of Vitamin D in Other Diseases: The role of Vit D in osteoporosis and muscle weakness is indisputable. But, there is a recent trend to give a higher dose of Vit D to prevent the osteoporotic fracture. In a placebo controlled study, oral Vit.D (700-800 IU/d) with or without calcium supplementation was given to elderly persons. The results show that there was statistically significant (23-43%) reduction in risk of a hip fracture and any non-vertebral fracture.12-15 Multiple sclerosis is an autoimmune disease which is more prevalent in temperate climates than the tropics and is also seen much more commonly in women. It is associated with lower serum vitamin D levels, and Vit D supplementation may have a preventive role in multiple sclerosis. The protective role of optimal Vit.D status and lower risk of cancer has been reported in many studies. Seven decades ago, Pellers and etal first time reported that sunlight exposure may reduce the risk of cancer.16 In another study it has been reported that when the concentration of 25 OH Vit.D > 32 ng/ml, there was 50% reduction in breast and colorectal cancer.17-18 The higher the Vit D level, the lower the risk of cancer. Vitamin D acts as an immunosuppressant in rheumatoid arthritis as well. Vit.D has a preventive role in development of diabetes mellitus. Pittas AG and et al studied on high dosage of calcium and Vit.D over 2-4 years in 83779 women with no history of diabetes. In this study for group one calcium >1200 mg/day and Vit. D >800 IU/day was given. For group two calcium <600 mg/day and Vit. D <400 IU/day was given. The results show that in group one there was 33% lower risk of type 2 diabetes as compared to group two.19 In another study in Finland over 31 years Vit. D in a dose of 2000 IU/day was administered to 10366 children during their first year of life and result show that the risk of type 1 diabetes reduce by 80%.20 Tuberculosis is associated with lower Vit D levels. Before the antikoch's treatment was available, high dosages of Vit D were given to patients. We see this disease in urban areas in women with a specific dressing style which prevents adequate sunlight exposure. Adverse Effects of Vit D Therapy: The primary toxicity associated with Calcitriol is to increase intestinal calcium and phosphate absorption, along with the potential to mobilize osseous calcium and phosphorus concentrations. Hypervitaminosis D is treated by immediate withdrawal of the vitamin, a low calcium diet, administration of glucocorticoids and vigorous fluid support. Forced saline diuresis with loop diuretics for hypercalcemia is useful. With this plasma Ca2+ concentration fall to normal and Ca2+ in soft tissue tends to mobilize. Conspicuous improvement in renal function occurs.1 Deepanjali, Int J Med Res Health Sci. 2014;3(1):172-175 CONCLUSION To summarize, Vit D deficiency is highly prevalent and contributes to women's health greatly. Getting too little vitamin D is worse than getting too much. Newer reports are changing our ideas about the optimal Vit D status and the role of Vit D in health, especially in relation to modern chronic diseases affecting women. It must be remembered that some populations are still very much under treated, and pregnancy-associated complications can be reduced with correction of the deficient state. In spite of the close relation of vitamin D to human health, vitamin D deficiency is not widely recognized as a problem by doctors and patients. Greater awareness of the problem of a high prevalence of vitamin D inadequacy is required among researchers, clinicians and patients. Women in the underprivileged sections, both in urban and rural India, are battling inadequate resources, multiparty, imposed customs of clothing, and social vulnerability of the fairer sex which coupled with the urban environmental decay will continue to pose the threat of Vit D deficiency. Special efforts on the medical and social fronts are necessary to combat this preventable epidemic of vitamin D deficiency. 174 REFERENCES 1. Peter A. Friedman, Agents affecting Mineral Ion. Homeostasis and Bone Turnover. Goodman and Gillman’s Pharmacological basis of Therapeutics. 12th Ed:1280-94 2. Adams JS, Chen H. Chun R. Substrate and enzyme trafficking as a means of regulating 1,25dihydroxyvitamin D synthesis and action: the human innate immune response. J Bone Miner Res. 2007;22:V20 3. Viljakainen HT. Saamio E, Hytinantti T. Maternal vitamin D status determines bone variables in the newborn. J Clin Endocrmol Metab. 2010;95:l74957 4. Mahon P, Harvey N, Crozier S, et al. Low maternal vitamin D status and fetal bone development: Cohort study. J Bone Mincr Res. 2009;25:l4-9. 5. Pasco JA, Wark JD, Carlin JB. Maternal vitamin D in pregnancy may influence nol only offspring bone mass but other aspects of musculoskeletal health and adiposity. Med Hypotheses. 2008;71:266-69 6. Walker V, Zhang X, Rastegar I. Cord blood vitamin D status impacts innate immune responses. J Clin Endocrinol Mctab. 2010;96:l835-43 7. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary reference intakes for vitamin D and calcium. Washington, DC: National Academy Press; 2010. www.ncbi.nlm.nih.gov. NCBI › Literature › Books helf 8. Johnson DD, Wagner CL, Hulsey TC. Vitamin D deficiency and insufficiency is common during pregnancy. Am J Pcrinatol. 2011:28:7-12 9. Hollis B, Johnson D, Hulsey T. Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 201l;26:2341-57 10. National Institute for Health and Clinical Excellence. Antenatal Care Routine care for the Healthy Pregnant Women. NICE Clinical Guideline 62, London. 2009 11. Southern Health. Vit D and calcium in pregnancy and breast feeding information sheet for women (to be developed) clinical protocols and guidelines, Maternity. 2009: http://www.monashhealth.org/ icms_docs/6643_Vitamin_D_in_pregnancy_a nd_the_term_newborn.pdf 12. BischoIT-Ferrari HA, Willett WC. Wong JB. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257-64 13. Chapuy MC, Arlot ME, Duboeuf F. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327:1637-42 14. Chapuy MC, ArJot ME, Delmas PD. et al. Effect of calcium and cholecalciferol treatment fot 3 years on hip fractures in elderly women. BMJ. 1994:308:1081-82 15. Lips P, Graafmans WC, Ooms ME. Vitamin D supplementation and fracture incidence in elderly persons: a randomized, placebo-controlled clinical trial. Ann Intern Mcd. 1996:124;400-06 16. Peller S, Stephenson CS. Skin irritation and cancer in the United States Navy. Am J Vied Sci. 1937; 194:326-33 17. Lappc JM. Travers-Gustafason D, Davies KM. Vitamin D and calcium supplemcnlation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007:85:1586-91 18. Dembrow M. High vitamin D: Rx for cancer prevention? Clin Advisor. 2007;10:54-57 19. Pittas AG, Dawson-Hughes B, Li T. Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care. 2006:29:650-56 20. Hypponen E, Laara E, Reunanen A.. Intake of vitamin D and risk of type 1 diabetes: a birthcohort study. Lancet. 2001;358: 1500-03 175 Deepanjali, Int J Med Res Health Sci. 2014;3(1):172-175 DOI: 10.5958/j.2319-5886.3.1.036 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 25 Sep 2013 Revised: 23rd Oct 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 18th Nov 2013 KIMURA’S DISEASE: A RARE CASE REPORT *Nagarekha Kulkarni Professor, Department of Pathology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India Corresponding author email:
[email protected] ABSTRACT Introduction: Kimura’s disease is of unknown etiology. Case report: This report describes an interesting case of Kimura’s disease in an 18 years old male manifesting as a unilateral left sided parotid swelling with multiple cervical lymphadenopathy. There was eosinophilia and increased levels of circulating IgE. Patient was treated with surgical excision and corticotherapy, cetrizine was prescribed. Histologically there were numerous follicles with prominent germinal centres. Interfollicular area was infiltrated with eosinophils and plasma cells. Conclusion: Any swelling in the head and neck region associated with eosinophilia should make one to suspect the Kimura’s disease. Keywords: eosinophilia, lymphadenopathy, angiolymphoid hyperplasia INTRODUCTION The history of Kimura’s disease dates back to 1937 when HT Kimm and C Szeto first described about it.1 Kimura et al in the year 1948 was the pioneer to describe the microscopic features of the disease. Hence, the disease is recognised by his name.1 This disease is seen in young Asian males and the cause of this rare entity is not known. Only 200 cases are reported since its histological description and sporadic in the rest of the world.2 Clinically the disease presents as swelling in the head and neck region characterised by eosinophilia in blood and tissue with marked elevated serum immunoglobulin E (IgE) levels.3 This report describes a rare case of Kimura’s disease in a 18 years old male who presented with parotid swelling CASE REPORT An 18 years old male presented to the ENT outpatient department with the swelling on the left side of the face below the left ear. It was sudden in onset and progressed gradually to attain the size of 12X10cms. There was no past history of prolonged fever, cough, loss of weight and loss of appetite. He was nonalcoholic and non-smoker. The family history was unremarkable. On palpation the swelling was diffuse, non-tender, firm, multiple over left parotid region The swelling was measuring 12x10cms, mobile, skin over the swelling was pinchable and hyperpigmented. Other groups of the lymph nodes were not enlarged. There was no hepatosplenomegaly. Bilateral ear and facial nerve examination were within normal limits. The vital signs and laboratory investigations were normal except there was eosinophilia and elevated IgE levels as shown in table-1. Neck ultrasonography revealed enlarged parotid gland with altered echotexture, multiple enlarged pre and post auricular lymphnodes. Fine needle aspiration biopsy revealed features of reactive lymphadenitis. After a course of antibiotics the swelling was excised and sent for the histopathological examination. He was treated with 179 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 levofloxacin, acclofenac, cetrizine and B- complex tablets. The specimen was received in the histopathology section. Macroscopic examination revealed a well circumscribed mass measuring 12X8X5cms. External surface was unremarkable and cut section showed grey white homogenous areas as shown in figure - 1. The specimen was processed routinely in the histopathological section and the sections were stained with haematoxylin and eosin stain (H/E). Microscopic examination revealed the architecture of the lymph nodes with numerous follicles showing hyperplastic feature with germinal centers. Many eosinophils and plasma cells were present in the interfollicular area. Also seen are perifollicular fibrosis, prominent blood vessels with endothelial proliferation and mild hyaline change as shown in figure 2. The diagnosis of Kimura’s disease was made. Table 1: Shows vital signs and laboratory findings Vital Signs: Pulse Rate: 86/minute, Blood Pressure: 130/80 mm of Hg, Respiratory Rate: 28/minute Temperature: 38.5oc Laboratory Investigations: Hb%: 11.8g/dl (normal:12.5-14.5g/dl) RBC Count: 3.8millions/cmm (normal:4.5-5.5millions/cmm) Haematocrit: 34% (normal: 35% to 45%) WBC Count: 9800 cells/cmm (normal: 4000 to 11,000/cmm) Differential Count: Neutrophils: 65%, Lymphocytes: 23%, Eosinophils: 10%, Monocytes: 02% Basophils: 00% Bleeding Time-3 minutes 30 seconds (Normal:2-6minutes) Clotting Time-4 minutes 30 seconds (Normal: 2-8minutes) Absolute eosinophil count: 600 cells/cmm (Normal:40-440cells/cmm) Serum IgE:4.4mg/dl (Normal: 0.01 – 0.04 mg/dl) Stool tests: negative for parasites Random Blood Sugar: 90mg/dl (normal: 80 to 110mg/dl) Blood Urea: 19mg/dl (normal: 5 to 25mg/dl) Serum Creatinine: 0.8mg/dl (normal: 0.8 to 1.2mg/dl) Serological Investigations: HIV-1 & 2:Negative , HBsAg : Negative Routine Urine Examination: Albumin: Nil, Sugar: Nil, Urine micro: 1-2 pus cells/HPF Table 2: Shows the difference between kimura’s disease and angiofollicular hyperplasia with eosinophilia1 Kimura’s disease Young man (2nd-3rd decade) Oriental Voluminous subcutaneous salivary gland involvement mass, adenopathy, Angiofollicular hyperplasia with eosinophilia Middle aged woman (3rd-5th decade) Westerner Subcutaneous or dermal cervical papules or nodules; overlying skin is erythematous or pigmented; rare adenopathies Same aspect. Histiocytoid vessels with particular endothelial cells (different sized nuclei and protrusion into the vessel lumen) Follicular hyperplasia, eosinophil infiltration of interfollicular and perivascular zones with abcess formation and lysis, postcapillary venule proliferation Elevated total IgE, hypereosinophilia, benign No increase in IgE, hypereosinophilia. Benign form of a pathology group of vascular proliferation diseases ranging from hemangioendothelioma to epitheloid angiosarcoma 180 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 Fig 1: Cut section of the specimen showing homogenous grey white areas. Fig 2: Showing the microscopic picture of Kimura's disease 40X(H/E). syndrome), benign and malignant lesions of the gland and cysts should be differentiated. However the following conditions like lymphoma, metastasis, ALHE, Langerhans cell histiocytosis, florid follicular hyperplasia, Castleman’s disease, drug reaction, dermatopathic lymphadenopathy, parasitic lymphadenitis and allergic granulomatosis of Chung and Strauss are to be considered in differential diagnosis.3 Laboratory analysis showed peripheral blood eosinophilia and increased serum total IgE concentration. There was no proteinuria. Regional lymphadenopathy, peripheral blood eosinophilia and increased IgE levels are commonly seen in Kimura’s disease, but not in ALHE. Renal involvement is found in half the patients of Kimura’s disease. Yuen et al 6 reported that renal involvement is about 60%. Table-2 reveals the differences and similarities between Kimura’s disease and ALHE.1 Surgical excision of the lesion is the first line therapy. Corticosteroids therapy is partly unsuccessful. Radiation and cytotoxic therapy has to be considered for the refractory lesions which do not respond to surgery. Cetrizine (histamine [H-1] receptor blockers) induced a complete remission in a corticosteroid dependent patient within 2 months of treatment. DISCUSSION CONCLUSION Kimura’s disease is a chronic inflammatory condition where in the etiology may not be established. Hence, there was a misconception between this disease and angiolymphoid hyperplasia with eosinophilia (ALHE). But later it was proved that they were two separate disorders. Autoimmune/allergic response was seen in Kimura’s disease as against benign vascular hyperplasia in ALHE.4 There is no age preponderance to this disease. However 2nd and 3rd decade have been reported in many literature, which also collaborates with the present case.5 Won Jun Choi et al reviewed 54 patients and found that the mean age of the patients was 33.1 years with head and neck region being more commonly involved5. Other areas to be involved are kidneys, orbit, ears, spermatic cord and median nerve.5 Clinical differential diagnosis should include chronic inflammatory disorder of the salivary glands, granulomatous gland disease (cat-scratch disease, sarcoidosis) and autoimmune disease (Sjogren’s This rare case report underlines the importance of taking into account Kimura’s disease when there is eosinophilia in the peripheral blood and swelling in the head and neck region. ACKNOWLEDGEMENT I thank the Director, Principal, Head of the Department & all staff members of the Department of Pathology & ENT, VIMS, Bellary for their support & encouragement to prepare this report. REFERENCES 1. Larroche C, Bletry O. Kimura’s disease. Orphanet encyclopedia. February 2005: http://www.orpha.net/data/patho/GB/ukkimura.pdf 2. Veerendra Kumar, Salini, Savida Haridas. Kimura’s disease: An uncommon cause of lymphadenopathy. Indian J Med Paediatr Oncol. 2010;31(3):89-90. 181 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 3. Savage NW, Vucicevic Boras V. Unilateral intraparotid swelling: a case report of Kimura’s disease and review of differential diagnosis. Case reports in Otolaryngology. 2013;3: http://dx.doi.org/10.1155/ 2013/ 795921. 4. Mariatos G, Gorgoulis VG, Laskaris G and Kittas C. Epitheloid hemangioma (angiolymphoid hyperplasis with eosinophilia) in the oral mucosa : a case report and review of the literature. Oral Oncology. 1999;35(4):435-38 5. Won Jun Choi, Jae Hur, Joo Yeon Ko, Kwang Yeoll Yeo, Joung Soo Kim, Hee Joon Yu. An unusual clinical presentation of Kimura’s disease occurring on the buttock of a five year old boy.Ann Dermatol. 2010;22(1):57-60. 6. Yuen HW, Goh YH, Low WK, Lim- Tan SK. Kimura’s disease: a diagnostic and therapeutic challenge. Singapore Med J. 2005;46:179-83. 182 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 DOI: 10.5958/j.2319-5886.3.1.036 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 25 Sep 2013 Revised: 23rd Oct 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 18th Nov 2013 KIMURA’S DISEASE: A RARE CASE REPORT *Nagarekha Kulkarni Professor, Department of Pathology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India Corresponding author email:
[email protected] ABSTRACT Introduction: Kimura’s disease is of unknown etiology. Case report: This report describes an interesting case of Kimura’s disease in an 18 years old male manifesting as a unilateral left sided parotid swelling with multiple cervical lymphadenopathy. There was eosinophilia and increased levels of circulating IgE. Patient was treated with surgical excision and corticotherapy, cetrizine was prescribed. Histologically there were numerous follicles with prominent germinal centres. Interfollicular area was infiltrated with eosinophils and plasma cells. Conclusion: Any swelling in the head and neck region associated with eosinophilia should make one to suspect the Kimura’s disease. Keywords: eosinophilia, lymphadenopathy, angiolymphoid hyperplasia INTRODUCTION The history of Kimura’s disease dates back to 1937 when HT Kimm and C Szeto first described about it.1 Kimura et al in the year 1948 was the pioneer to describe the microscopic features of the disease. Hence, the disease is recognised by his name.1 This disease is seen in young Asian males and the cause of this rare entity is not known. Only 200 cases are reported since its histological description and sporadic in the rest of the world.2 Clinically the disease presents as swelling in the head and neck region characterised by eosinophilia in blood and tissue with marked elevated serum immunoglobulin E (IgE) levels.3 This report describes a rare case of Kimura’s disease in a 18 years old male who presented with parotid swelling CASE REPORT An 18 years old male presented to the ENT outpatient department with the swelling on the left side of the face below the left ear. It was sudden in onset and progressed gradually to attain the size of 12X10cms. There was no past history of prolonged fever, cough, loss of weight and loss of appetite. He was nonalcoholic and non-smoker. The family history was unremarkable. On palpation the swelling was diffuse, non-tender, firm, multiple over left parotid region The swelling was measuring 12x10cms, mobile, skin over the swelling was pinchable and hyperpigmented. Other groups of the lymph nodes were not enlarged. There was no hepatosplenomegaly. Bilateral ear and facial nerve examination were within normal limits. The vital signs and laboratory investigations were normal except there was eosinophilia and elevated IgE levels as shown in table-1. Neck ultrasonography revealed enlarged parotid gland with altered echotexture, multiple enlarged pre and post auricular lymphnodes. Fine needle aspiration biopsy revealed features of reactive lymphadenitis. After a course of antibiotics the swelling was excised and sent for the histopathological examination. He was treated with 179 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 levofloxacin, acclofenac, cetrizine and B- complex tablets. The specimen was received in the histopathology section. Macroscopic examination revealed a well circumscribed mass measuring 12X8X5cms. External surface was unremarkable and cut section showed grey white homogenous areas as shown in figure - 1. The specimen was processed routinely in the histopathological section and the sections were stained with haematoxylin and eosin stain (H/E). Microscopic examination revealed the architecture of the lymph nodes with numerous follicles showing hyperplastic feature with germinal centers. Many eosinophils and plasma cells were present in the interfollicular area. Also seen are perifollicular fibrosis, prominent blood vessels with endothelial proliferation and mild hyaline change as shown in figure 2. The diagnosis of Kimura’s disease was made. Table 1: Shows vital signs and laboratory findings Vital Signs: Pulse Rate: 86/minute, Blood Pressure: 130/80 mm of Hg, Respiratory Rate: 28/minute Temperature: 38.5oc Laboratory Investigations: Hb%: 11.8g/dl (normal:12.5-14.5g/dl) RBC Count: 3.8millions/cmm (normal:4.5-5.5millions/cmm) Haematocrit: 34% (normal: 35% to 45%) WBC Count: 9800 cells/cmm (normal: 4000 to 11,000/cmm) Differential Count: Neutrophils: 65%, Lymphocytes: 23%, Eosinophils: 10%, Monocytes: 02% Basophils: 00% Bleeding Time-3 minutes 30 seconds (Normal:2-6minutes) Clotting Time-4 minutes 30 seconds (Normal: 2-8minutes) Absolute eosinophil count: 600 cells/cmm (Normal:40-440cells/cmm) Serum IgE:4.4mg/dl (Normal: 0.01 – 0.04 mg/dl) Stool tests: negative for parasites Random Blood Sugar: 90mg/dl (normal: 80 to 110mg/dl) Blood Urea: 19mg/dl (normal: 5 to 25mg/dl) Serum Creatinine: 0.8mg/dl (normal: 0.8 to 1.2mg/dl) Serological Investigations: HIV-1 & 2:Negative , HBsAg : Negative Routine Urine Examination: Albumin: Nil, Sugar: Nil, Urine micro: 1-2 pus cells/HPF Table 2: Shows the difference between kimura’s disease and angiofollicular hyperplasia with eosinophilia1 Kimura’s disease Young man (2nd-3rd decade) Oriental Voluminous subcutaneous salivary gland involvement mass, adenopathy, Angiofollicular hyperplasia with eosinophilia Middle aged woman (3rd-5th decade) Westerner Subcutaneous or dermal cervical papules or nodules; overlying skin is erythematous or pigmented; rare adenopathies Same aspect. Histiocytoid vessels with particular endothelial cells (different sized nuclei and protrusion into the vessel lumen) Follicular hyperplasia, eosinophil infiltration of interfollicular and perivascular zones with abcess formation and lysis, postcapillary venule proliferation Elevated total IgE, hypereosinophilia, benign No increase in IgE, hypereosinophilia. Benign form of a pathology group of vascular proliferation diseases ranging from hemangioendothelioma to epitheloid angiosarcoma 180 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 Fig 1: Cut section of the specimen showing homogenous grey white areas. Fig 2: Showing the microscopic picture of Kimura's disease 40X(H/E). syndrome), benign and malignant lesions of the gland and cysts should be differentiated. However the following conditions like lymphoma, metastasis, ALHE, Langerhans cell histiocytosis, florid follicular hyperplasia, Castleman’s disease, drug reaction, dermatopathic lymphadenopathy, parasitic lymphadenitis and allergic granulomatosis of Chung and Strauss are to be considered in differential diagnosis.3 Laboratory analysis showed peripheral blood eosinophilia and increased serum total IgE concentration. There was no proteinuria. Regional lymphadenopathy, peripheral blood eosinophilia and increased IgE levels are commonly seen in Kimura’s disease, but not in ALHE. Renal involvement is found in half the patients of Kimura’s disease. Yuen et al 6 reported that renal involvement is about 60%. Table-2 reveals the differences and similarities between Kimura’s disease and ALHE.1 Surgical excision of the lesion is the first line therapy. Corticosteroids therapy is partly unsuccessful. Radiation and cytotoxic therapy has to be considered for the refractory lesions which do not respond to surgery. Cetrizine (histamine [H-1] receptor blockers) induced a complete remission in a corticosteroid dependent patient within 2 months of treatment. DISCUSSION CONCLUSION Kimura’s disease is a chronic inflammatory condition where in the etiology may not be established. Hence, there was a misconception between this disease and angiolymphoid hyperplasia with eosinophilia (ALHE). But later it was proved that they were two separate disorders. Autoimmune/allergic response was seen in Kimura’s disease as against benign vascular hyperplasia in ALHE.4 There is no age preponderance to this disease. However 2nd and 3rd decade have been reported in many literature, which also collaborates with the present case.5 Won Jun Choi et al reviewed 54 patients and found that the mean age of the patients was 33.1 years with head and neck region being more commonly involved5. Other areas to be involved are kidneys, orbit, ears, spermatic cord and median nerve.5 Clinical differential diagnosis should include chronic inflammatory disorder of the salivary glands, granulomatous gland disease (cat-scratch disease, sarcoidosis) and autoimmune disease (Sjogren’s This rare case report underlines the importance of taking into account Kimura’s disease when there is eosinophilia in the peripheral blood and swelling in the head and neck region. ACKNOWLEDGEMENT I thank the Director, Principal, Head of the Department & all staff members of the Department of Pathology & ENT, VIMS, Bellary for their support & encouragement to prepare this report. REFERENCES 1. Larroche C, Bletry O. Kimura’s disease. Orphanet encyclopedia. February 2005: http://www.orpha.net/data/patho/GB/ukkimura.pdf 2. Veerendra Kumar, Salini, Savida Haridas. Kimura’s disease: An uncommon cause of lymphadenopathy. Indian J Med Paediatr Oncol. 2010;31(3):89-90. 181 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 3. Savage NW, Vucicevic Boras V. Unilateral intraparotid swelling: a case report of Kimura’s disease and review of differential diagnosis. Case reports in Otolaryngology. 2013;3: http://dx.doi.org/10.1155/ 2013/ 795921. 4. Mariatos G, Gorgoulis VG, Laskaris G and Kittas C. Epitheloid hemangioma (angiolymphoid hyperplasis with eosinophilia) in the oral mucosa : a case report and review of the literature. Oral Oncology. 1999;35(4):435-38 5. Won Jun Choi, Jae Hur, Joo Yeon Ko, Kwang Yeoll Yeo, Joung Soo Kim, Hee Joon Yu. An unusual clinical presentation of Kimura’s disease occurring on the buttock of a five year old boy.Ann Dermatol. 2010;22(1):57-60. 6. Yuen HW, Goh YH, Low WK, Lim- Tan SK. Kimura’s disease: a diagnostic and therapeutic challenge. Singapore Med J. 2005;46:179-83. 182 Nagarekha Int J Med Res Health Sci. 2014;3(1):179-182 DOI: 10.5958/j.2319-5886.3.1.037 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 29 Sep 2013 Revised: 28th Oct 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 13th Nov 2013 SCOLIOSIS CORRECTION IN CHILDREN-ANAESTHETIC CHALLENGE: A CASE REPORT * Amarjeet D Patil1, Sivashankar KR2, Arpan Sashankar3, Shikha A Malhotra4, Nitin Kapoor5, Charu Sudan6 1 Assistant Professor, 2Professor & Head, 3Assistant Professor, 4,5,6Resident, Department of Anaesthesiology, MGM Medical College and Hospital, Kamothe, Navi Mumbai, India * Corresponding author email:
[email protected] ABSTRACT Kyphoscoliosis is a challenging surgery to surgeons but even more challenging to anaesthesiologist to give anaesthesia and maintain it throughout the surgery and post operative pain relief and ventilation. Here we are describing the case of 3 years old male child weighing 9kg for surgical correction of spine deformity with instrumentation. Keywords: Scoliosis, Children and Anaesthesia INTRODUCTION Scoliosis is defined as a curvature in the vertebral column from side to side and kyphosis is a curvature from anterior to posterior.1 Kyphoscoliosis can be congenital, idiopathic or postural. Surgical correction is usually attempted from the age of 10. Advances in paediatric anaesthesia and expertise of the surgeons are allowing this correction to be attempted at the very early stage. Positioning of the infant for surgery, gross fluid shifts and manipulation of neural structures pose a challenge to the anaesthesiologist. Surgical correction with instrumentation in a boy of nine kilos is described in this paper.2,3 instrumentation with complete preaparedness for invasive monitoring and replacement of blood and blood products. CASE REPORT Nine kgs, 3 years, boy was admitted in our tertiary care hospital, MGM Medical College & Hospital, Navi Mumbai, for surgical correction of deformity of spine since one year. Clinical examination revealed no other congenital anamoly and cardiorespiratory system not deranged apart from the positional change. Radiological findings revealed the extent of angulation of the vertebral column in all directions. The child was planned for surgical correction with Amarjeet et al., Fig 1: Pre-operative X-ray of patient AP & Lateral views TECHNIQUE4 The infant was assessed, prepared, premedicated as per standard protocol.5 Intravenous induction, intubation with non depolarizing blocking agents was resorted to once the peripheral iv line was secured. Central line (Rt internal jugular canulation 4.5 fg) and Int J Med Res Health Sci. 2014;3(1):183-185 183 left radial artery canulated Positioning of the infant for surgery was supplemented by cotton bundles apart from standard bolsters. Proper eye padding given.6 Standard monitoring of oxygen saturation, end tidal carbon dioxide (EtCO2), invasive blood pressure (IBP), central venous pressure (CVP) and urine output was being done, neuromuscular monitoring was not possible because the instrument was defective on that day.7 Anaesthesia was maintained with intermittent neuromuscular blocking agents, inhalational anaesthetic and opiod analgesia. We took care to avoid hypothermia by warming mattress,warm fluids.8 Surgery was uneventful for 480 minutes.9 Elective postoperative mechanical ventilation was done for 24 hours.10 DISCUSSION Very few cases have been reported of infants below 10 kgs undergoing surgical correction and instrumentation of gross Kyphoscoliosis. Positioning of the child should be preferably with 9 poster frame.11 We had resorted to cotton bundles for the same, canulation of Internal jugular vein and radial artery in children needs experienced hands. Proper monitoring of effects of gross fluid shifts is mandatory along with correction of the same. Monitoring of spinal cord functions could not be done in this surgery. No complications were noticed in the form of brachial plexus injury and ocular changes or air embolism. CONCLUSION With clinical experience of the Anaesthesiolgist, expertise of the surgeon, surgical correction of kyphoscoliosis even in children is possible now-adays12-14. ACKNOWLEDGEMENT We would like to extend our heartfelt gratitude to the Department of Orthopedics, Department of Pediatrics, Radiology and Physiotherapy. Fig 2: Post operative X-ray AP view Fig 3: Post operative X-ray AP & Lateral view Amarjeet et al., REFERENCES 1. Weinstein SL, Dolan LA, Spratt KF, Peterson KK, SpoonamoreMJ, Ponseti IV. Health and function of patients with untreated idiopathic scoliosis. A 50 year natural history study. JAMA 2003; 289:559-67. 2. Michael AE, Davandra Patel. Contin Educ Anaesth. Crit Care Pain 2006;6 (1): 13-16. 3. Ogilvie JW, Winter RB, Bradford DS, Lonstein JE, Ogilvie JW, eds. Historical Aspects of Scoliosis. Moe’s Textbook of Scoliosis and other Spinal deformities 3rd Edition. WB Saunders Company. Philadelphia, USA, 1995; 1-4. 4. Salem MR, Klowden AJ, Gregory GA, ed. Pediatric Anesthesia. Anesthesia for Orthopedic Surgery Churchill Livingstone, New York, USA, 2002; 617-61. 5. Standards, Guidelines, Statements and Other Documents. www.asahq.org 6. Myers M, Hamilton SR, Bogosian A, Smith CH, Wagner TA. Visual loss as a complication of Int J Med Res Health Sci. 2014;3(1):183-185 184 7. 8. 9. 10. 11. 12. 13. 14. spine surgery: A review of 37 cases. Spine 1997; 22:1325-29. Ramirez N, Richards BS, Warren PD, Williams GR. Complications after posterior spinal fusion in Duchenne’s muscular dystrophy. J Pediatr Orthop 1997; 17:109-14. Sessler DI. Mild perioperative hypothermia. N Engl J Med 1997; 336:1730-37. Tsirikos AI, Chang W, Dabney KW, Miller F. Comparison of one stage versus two stage anteroposterior spinal fusion in pediatric patients with cerebral palsy and neuromuscular scoliosis. Spine 2003; 28:1300-05. Rawlins BA, Winter RB, Lonstein JE. Reconstructive spine surgery in pediatric patients with major loss in vital capacity. J Pediatr Orthop 1996; 16:284-292. Winter RB, Lonstein JR, Herkowitz H, Garfin SR, Balderstone RA, Eismont FJ, etal., Juvenile and Adolescent Scoliosis. Rothman-Simeone, The Spine 4th Edition. WB Saunders Company, Philadelphia, USA, 1999; 325-72. Wazeka AN, DiMaio MF, Boachie-Adjei O, Oheneba MD. Outcome of pediatric patients with severe restrictive lung disease following reconstructive spine surgery. Spine 2004; 29:528534 Merola A, Haher T, Brkaric M. A multicenter study of the outcomes of the surgical treatment of adolescent idiopathic scoliosis using the Scoliosis Research Society (SRS) outcome instrument. Spine 2002; 27:2046-2051. Shapiro G, Green DW, Fatica NS, Boachie-Adjei O. Medical complications in scoliosis surgery. Curr Opin Pediatr 2001; 13: 36-41. Amarjeet et al., Int J Med Res Health Sci. 2014;3(1):183-185 185 DOI: 10.5958/j.2319-5886.3.1.038 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 28 Sep 2013 Revised: 18th Oct 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 22nd Nov 2013 AGGRESSIVE ANGIOMYXOMA PRESENTING AS HUGE BROAD LIGAMENT TUMOR- A RARE CASE REPORT *Krishna Mandade1, Kashika singh1, Aptulkar2, Angarkar3, Bhavthankar DP4 1 Junior resident, Department of OBGY, 2Asso. Prof, Department of Surgery, 3Professor, Department of Pathology, Prof & Head, Department of OBGY, Pravara Rural hospital Loni, Maharashtra, India. 4 *Corresponding author email:
[email protected] ABSTRACT Aggressive angiomyxoma was first described in 1983 by Steeper and Rosai, and fewer than 150 cases have been reported in the world medical literature. Aggressive angiomyxoma is a rare mesenchymal tumor occurring predominantly in the pelvic-perineal region of females of age group 30 to 50 yrs. These tumors are benign and often reach too large dimensions before becoming clinically symptomatic. We report such a case presented as broad ligament tumor, a very unusual presentation. Patient underwent laprotomy and tumor was successfully excised. Keywords: Aggressive angiomyxoma, Pouch of Douglas. INRTODUCTION Aggressive angiomyxomas (AA) are rare, slow growing benign tumors which are, predominantly, located on the perineum of reproductive age women.1,2 These lesions are characterized as soft, non-encapsulated tumors with finger-like projections infiltrating the surrounding soft tissues. The tumour presents as a large multilobular or polypoid mass or swelling. It is important to diagnose this condition because a tumor is locally infiltrative and surgery is usually the first line of treatment, radical surgery with wide margins and long-term follow-up is advised.3 CASE 40 yrs female came to OPD with complain of pain in abdomen, difficulty in passing stools and urine and feeling of abdominal mass since 2 months in OPD of Pravara Rural Hospital, Loni. Dist. Ahmednagar in Maharashtra in India. Mass associated with pain and bowel complain was initially small and gradually progressed to present size. Krishna et al., There was no history of fever, cough, cold, nausea, vomiting, and bleeding per-vaginal, apparent weight loss. Last menstrual period was 10 days back. Past menstrual history was regular with cycle and flow and there were no clots and no dysmenorrhea. Patient was Para 2 Live 2. Both were full term normal deliveries & history of tubal ligation done 15 yrs back. Past, personal and family history was insignificant. On examination, general condition of the patient was good and vitals were stable. No peripheral lymphadenopathy and other signs of malignancy found. Per abdomen: Non tender abdominal mass felt corresponding to 24-26 weeks; oval, on Rt. side of lumbar spine, arising from pelvis, slightly mobile, firm in consistency, around 20*15cm. Rt. iliac fossa completely obliterated. Per vaginal examination: Uterus normal size, firm, mobile, separately felt from the mass which was felt in Rt. Adnexa. 186 Int J Med Res Health Sci. 2014;3(1):186-189 Rt. Adnexa was fixed; bogginess felt in Rt. fornix, Lt. Fornix was relatively free. Per Rectal examination: large firm mass felt anteriorly free from rectal mucosa, POD was obliterated & mass compressing rectal lumen. All hematological investigations were done and the investigation reports were within normal limits. USG suggestive of a large tumor of size 21*20*8cm arising from Rt. Adnexa. Ovaries seen separately from tumor on Transvaginal sonography examination. Uterus of normal size with normal ecotexture of ovaries. Tumor with some cystic and some hyper lucent areas in between. On Color Doppler vascularity set in. Fine needle aspiration cytology (FNAC): suggestive of Tumor cells cytologically bland and have a spindled, ovoid or stellate appearance with ovoid nuclei and evenly dispersed chromatin. CT scan and MRI evaluations could not be done due to no affordability. CA125 levels was 9IU. On the basis of the clinical picture and Ultrasound review patient diagnosed as large Rt. Sided Broad ligament tumor. Exploratory laprotomy under General anesthesia performed. Large whitish shiny tumor nearly of 20*20 cm drawn out of peritoneal cavity which was arising from Rt. Adnexa of the uterus and its extension as peduncle in POD and also in the ischiorectal fossa noted. With combined surgical approach Tumor excised completely by securing bowel, bladder and ureters. Along with the tumor uterus with bilateral ovaries which were observed to be normal removed by the conventional method of Hysterectomy. Haemostasis achieved completely with moderate intraoperative loss. No remnants of tumor left. Fig 2: External appearance with pedunculated extension of tumor. Post-op was uneventful. Repeat haemogram was 11gm%. Patient discharged on 10th Post operative day. Histopathology gross: Shiny white brown Tumor mass measuring 22*20*7cm arising from lateral Wall of body of uterus. Cut surface: Myxomatous & hemorrhagic areas. Tumor is extended as pedunculated globular 8.5*7*3cm attached to the lower side of uterus near Cervix. Another extended mass 9 *7*2. 5cm noted on the posterior aspect of the Uterus. Fig 3: Cut Surface of tumor. Section from tumor show sparsely cellular tumor composed of numerous haphazardly arranged small to large blood vessels set in myxoid stroma. Stroma shows collagen fibrils, scattered smooth muscle bundles. The Tumor cells cytologically bland and have a spindled, ovoid or stellate appearance with ovoid nuclei and evenly dispersed chromatin. Stroma is distinctly myxoid. Fig 1: Tumor attached to broad ligament seen. 187 Krishna et al., Int J Med Res Health Sci. 2014;3(1):186-189 Fig 4: Section from pelvic mass showing varying sized blood vessels surrounded by cells with ovoid to spindle nuclei & a myxoid stroma (H & E x 280). DISCUSSION Aggressive angiomyxoma is a rare tumor of mesenchymal origin first described in 1983 by Steeper and Rosai. The age distribution is wide, with the peak incidence at 31 to 35.4 Female to male ratio of slightly more than 6:1 . The size may vary from 1-60 cm.5 On gross examination it is rubbery and white or soft and gelatinous. The tumor presents as a large multilobular or polypoid mass or swelling.5 Locally infiltrative but non-metastasising; that may present as a vulval mass, vaginal polyp, bartholin or a vaginal cyst, ovarian cyst, etc. These lesions are characterized as soft, non-encapsulated tumours with finger-like projections infiltrating the surrounding soft tissues.6 The tumor grows slowly, and its benign nature is suggested by the histology and by the fact that it shows no tendency to metastasize. However it usually tends locally to recure.6 The rarity of this condition makes the preoperative diagnosis fairly difficult, It has been also related to hormonal activity which explains female dominance.7 The diagnosis can be made considering the clinical presentation aided by ultrasound, CT or MRI shows a hypodense mass with translevator extension, displacing rather than invading the pelvic organs. FNA reduces the diagnostic possibilities but histopathology alone gives the definite diagnosis.8 Differential diagnosis: Benign: myxolipoma, myxoid neurofibroma and myxoid leiomyoma to myxofibrosarcoma, myxoid variant of liposarcoma, leiomyosarcoma. Malignant: fibrous histiocytoma and botryoid rhabdomyosarcoma. The distinctively striking vascular component in aggressive angiomyxoma helps in ruling out most of the above mentioned neoplasms as differentials. The optimal treatment for AA is wide local excision with tumor free margin, as this tumor is locally invasive and tends to infiltrate deep into pelvic soft tissues.9 Pre-operative knowledge of tumor extent is important in determining surgical approach and MRI features of AA are characteristic.9 Recurrence is local and reported in 36-72%. This surgery is challenging because of the infiltration and the difficult dissection and value of extensive surgical resection to obtain clear margins has been questioned.10 In the past, most authors advocated wide excision even if genitourinary and digestive tract resections were necessary. Radiotherapy and chemotherapy may not have much role due to the low mitotic activity seen. GnRH agonist and tamoxifen have been used successfully in few patients.11 The response can be assessed by clinical assessment, patient's symptomatology and radiographic findings. Because of the abdominal and pelvic organ manipulation, hospital stays are generally longer, and patients are at higher risk of developing problems such as deep venous thrombosis and pulmonary embolism while they await the return of bowel function after the procedure. There are many unanswered questions about treatment and follow-up strategies for this rare disease; because this tumor is slow growing and is often symptomatic only when the tumor is large, radiographic follow-up is best. CONCLUSION Although a rare diagnosis, aggressive angiomyxoma can present with unusual features. Detailed radiological examination is helpful in suspecting the problem, but histology is the gold standard for diagnosis. It should be distinguished from benign myxoid tumors with low risk of local recurrence. Therefore, recurrence of tumor may be avoided by wide local excision which is curative and prognosis of such tumor is good. 188 Krishna et al., Int J Med Res Health Sci. 2014;3(1):186-189 REFERENCES 1. Steeper TA, Rosai J. Aggressive angiomyxoma of the pelvis and perineum: report of nine cases of a distinctive type ofgynaecologic soft tissue neoplasm. Am J Clin Pathol 1983; 7:453 2. Chan YM, Hon E, Ngai SW, Ng TY, Wong LC. Aggressive angiomyxoma in females: is radical resection the only option? Acta Obstet Gynecol Scand 2000;79(3): 216-20. 3. Wiser A, Korach J, Gotlieb WH, Fridman E. Importance of Accurate Preoperative Diagnosis in the Management of Aggressive Angiomyxoma: Report of Three Cases and Review of the Literature,” Abdominal Imaging. 2006;31(3):38386. 4. Gungor T, Zengeroglu S, Kaleli A, Kuzey GM. Aggressive angiomyxoma of the vulva and vagina. A common problem: misdiagnosis. Eur J Obstet Gynecol Reprod Biol 2004; 112: 114–16. 5. Fetsch JF, Laskin WB, Lefkowitz M, Kindblom L, Meis-Kindblom JM. Aggressive angiomyxoma. A clinicopathologic study of 29 female patients. Cancer 1996; 78: 79–90. 6. H. Adwan, P.D Kamel and G. Glazer, “ A Solitary Encapsulated Pelvic Aggressive Angiomyxoma,” Annals of The Royal college of Surgeons of England, vol. 86, No. 6, November 2004, pp. W1W3. 7. Htwe M, Deppisch LM, Saint-Julien JS. Hormonedependent, aggressive angiomyxoma of the vulva. Obstet Gynecol 1995; 86(4 Pt 2): 697-99. 8. Amezcua CA, Begley SJ, Mata N, Felix JC, Ballard CA. Aggressive angiomyxoma of the female genital tract: a clinicopathologic and immunohistochemical study of 12 cases. Int J Gynecol Cancer 2005; 15: 140-145. 9. Kaur A, Makhija PS, Vallikad E, Padmashree V, Indira HS. Multifocal aggressive angiomyxoma: a case report. J Clin Pathol 2000; 53: 798–99. 10. Siassi RM, Papadopoulos T, Matzel KE. Metastasizing aggressive angiomyxoma. N Engl J Med 1999;341:1772. 11. Behranwala KA, Thomas JM. 'Aggressive' angiomyxoma: a distinct clinical entity. Eur J Surg Oncol 2003; 29(7):559-63. 189 Krishna et al., Int J Med Res Health Sci. 2014;3(1):186-189 DOI: 10.5958/j.2319-5886.3.1.039 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 30 Sep 2013 Revised: 28th Oct 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 9th Nov 2013 ANGIOMYOLIPOMA OF A KIDNEY: A CASE REPORT *Manish Shah, Mrunal N. Ketkar, Sudhir J. Kothari, Shilpa S. Patankar, Ravi M. Swami Department of Surgery, Bharati Hospital and Research Centre, Pune Satara road, Dhankawdi, Pune, Maharashtra, India *Corresponding author email:
[email protected] ABSTRACT Angiomyolipoma is a rare benign tumour of the kidney. They are composed of abnormal vasculature, smooth muscle and adipose elements. They may be associated with Tuberous sclerosis. The unilateral presentation is uncommon. Angiomyolipoma is presented as an enlarge lump in the abdomen may mimic malignant lesion such as renal cell carcinoma, yet malignancy has to be ruled out. The diagnosis of this condition may not be straight forward with imaging alone. Excision is recommended for definite histopathological diagnosis (in symptomatic patients) and to prevent the potential risk of haemorrhage and malignancy. A case of benign giant Angiomyolipoma is presented here because of its uncommon occurrence. Keywords: Angiomyolipoma , Unilateral, Kidney INTRODUCTION Angiomyolipoma is a rare benign tumour of the kidney. It is found in approximately 45-80% of patients with tuberous sclerosis and are typically bilateral and asymptomatic. In patients without tuberous sclerosis, renal angiomyolipomas can be unilateral and tend to be larger.1Angiomyolipoma is a benign clonal neoplasm consisting of varying amounts of mature adipose tissue, smooth muscle, and thickwalled vessels. It is most likely derived from the perivascular epithelioid cells, and its growth may be hormone dependent. It shows female predominance and rarity before puberty.2 It may mimic renal cell carcinoma. Diagnosis is done with the help of ultrasonography, CT scan and histology. CASE REPORT A 75 yr. an old woman from rural area presented with lump in right side of the abdomen that the patient had noticed 1 year previously. (Bharati Hospital). The lump had gradually increased in size over a period of time. She had complaints of pain since 1 day. On examination, she was anaemic (8.3gm %) with large retroperitoneal lump that occupied right side of abdomen, the lump was firm in consistency and tender. She had no lymphedema or other palpable lymph node. Ultrasonography revealed a well defined echoic lesion noted of size 14.6 X 8.7 cm, associated with upper pole of the right kidney extending upto the epigastric region and midline on right side. CT scan revealed a large well defined mass lesion showing density with peripheral soft tissue component seen in right hypochondriac and right lumbar region measuring 13 X 11 X 10 cm. The mass is seen in medial to pancreas and (Inferior vena cava) displacing it superolaterally. Superiorly mass extending to liver and inferiorly to the right iliac fossa. The mass completely encasing right kidney and displacing it inferiorly, most likely liposarcoma. (figure 1) A malignant tumour was suspected based on the imaging and clinical features. In view of above finding and pain, malignancy needed to be ruled out. The patient underwent surgery and tumour was excised intact 190 Manish et al., Int J Med Res Health Sci. 2014;3(1):190-192 (figure 2). Its weight was 1800 grams. A nephrectomy was done due to inability to differentiate it from renal cell carcinoma. 4 units of blood were transfused preoperatively and in addition 3 units were given (blood group AB positive) She made an uneventful recovery. An angiomyolipoma was confirmed by histopathological assessment. Post operatively, a single large well circumscribed an encapsulated firm mass measuring 20 X 15 X 9 cm weight 1800grams. The cut section appears yellowish brown with areas of hemorrhage (figure 3). Microscopy- tumour showed mature adipocytes, separated by fibrohyalinisedseptae showing vascular proliferation and area of smooth muscle cell in bundles (figure 4). Fig 1: CT scan showing lesion Fig 2 : Intra operative photograph Angiomyolipoma Fig 3 : Specimen showing renal Angiomyolipoma. Blood vessel Fat Smooth Muscle Fig 4: Histopathology - Angiomyolipoma DISCUSSION Angiomyolipoma is a rare benign tumour of the kidney. It is found in approximately 45- 80% of patients with tuberous sclerosis and are typically bilateral and asymptomatic with F: M predominance of 2:I. The mean age of presentation is 30 years. In contrast, of the 60 -70% of patient with AML who do not have tuberous sclerosis present later in life, during 5th or 6th decade and this tumour can be unilateral and tend to be larger than those associated with tuberous sclerosis. Tuberous sclerosis is an autosomal dominant disorder comprising adenoma sebaceum, mental retardation and epilepsy .1 Angiomyolipoma consists of varying amount of mature adipose tissue, smooth muscle and thick walled vessels. It is mostly likely derived from perivascular epitheloidcell. Extrarenal occurrence have been reported in hilarlymphatics, retroperitoneum and liver and direct extension into the venous system. 2 On diagnostic imaging, it may mimic a malignancy. On ultrasonography, it gives a well circumscribed, highly echogenic often associated with shadowing. On CT scan, well defined mass is seen (confined by a value of -20 to-80 Hounsfield units). 2 Differential diagnosis for this are subtypes of sarcoma including fibrosarcoma, leiomyosarcoma, liposarcoma and renal cell carcinoma.3 Positive immunoreactivity for HMB-45 is characteristic for angiomyolipoma and can be used to differentiate it from sarcoma.4, 5 The patient with tumour with intermediate features or calcification should be managed proactively because the likely diagnosis in most such cases is renal cell carcinoma. Patients with isolated lesions less than 4 cm, can be followed up with a yearly CT scan or Ultrasonography to define the growth rate and clinical significance. Similarly, Patients with asymptomatic or mildly symptomatic lesions greater than 4 cm should 191 Manish et al., Int J Med Res Health Sci. 2014;3(1):190-192 be followed up with semiannual ultrasonography. Patients with lesions greater than 4 cm with moderate or severe symptoms (bleeding or pain) should undergo surgical intervention either in the form of tumour excision with or without nephrectomy, renal-sparing surgery or renal arterial embolization.2 Complications are as follows, Retroperitonal hemorrhage, hematuria, hypovolemic shock, hypertension, abscess formation. CONCLUSION Angiomyolipoma is a rare tumour of the kidney.5 They may be confused with malignant tumours especially when the presentation is unilateral. CT Scan and ultrasonography helps in diagnosis. Symptomatic patient requires surgical intervention. REFERENCES 1. Smith and Tanagho’s. General urology. McGrawHill & Lange. 18th ed. Chapter 22: 330-31,. 2. Campbell - Walsh Urology. Renal Tumours. WB. Saunders; Philadelphia, PA. 9th edition.Chapter47:1578-80 3. Steiner MS, Goldman SM, Fishman EK, Marshall FF. The natural history of renal angiomyolipoma. J Urol. 1993, 150:1782-86. 4. De la Cruz Ruiz M, Rivero M, Fernandez DL. Giant renal angiomyolipoma. Arch EspUrol 1999; 52: 381–5 5. Hostis HL, Deminiere C, Ferriere JM. Renal angiomyolipoma: a clinicopathologic, immunohistochemical, and follow-up study of 46 cases. Am J Pathol 1999; 23: 1011–20. 192 Manish et al., Int J Med Res Health Sci. 2014;3(1):190-192 DOI: 10.5958/j.2319-5886.3.1.040 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS nd Received: 2 Sep 2013 Revised: 8th Oct 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 13th Nov 2013 RIGHT SIDED CONGENITAL DIAPHRAGMATIC HERNIA: A RARE CASE REPORT *Amit Narkhede1, Shrikhande DY2, Prasant Nigwekar3, Santosh Yadav1, Haresh Kasodariya1 1 PG Student, 2Professor and Head, 3Asso. Professor, Department of pediatrics, Rural Medical College, Pravara Institute of Medical Sciences (DU), Loni, Maharashtra, India *Corresponding author email:
[email protected] ABSTRACT A diaphragmatic hernia is defined as a communication between abdominal and thoracic cavity with or without abdominal contents in the thorax. The true incidence of Congenital diaphragmatic hernia is 1 in 5000 live births while right side diaphragmatic hernia (15%) is rare comparing to left side diaphragmatic hernia (85%) because liver plugs the opening. Congenital diaphragmatic hernia typically refers to Bochdalek form, other forms are rarer. Despite advances in neonatal intensive care, congenital diaphragmatic hernia is associated with high mortality and morbidity. The posterolateral right congenital DH is a rare diaphragmatic defect. Females are twice affected than that of males. The symptoms are non characteristic and patients with this disease maybe without symptoms for a long period. The main tool for diagnosis of congenital DH is radiography. Surgical correction is required. Keywords: Right sided congental diaphragmatic hernia, Posterolateral, Liver plugs at right side INTRODUCTION A diaphragmatic hernia is defined as a communication between abdominal and thoracic cavity with or without abdominal contents in the thorax. Right side diaphragmatic hernia (15%) is rare comparing to left side diaphragmatic hernia (85%) because liver plugs the opening. Congenital diaphragmatic hernia typically refers to Bochdalek form, other forms are rare. The posterolateral right congenital DH is a rare diaphragmatic defect. Females are twice affected than that of males. The symptoms are non characteristic and patients with this disease maybe without symptoms for a long period.1 CASE REPORT age, preterm, appropriate for gestational age (birth weight 2300 gms, was brought to our hospital on 1 day of life with complaints of respiratory distress and noisy breathing. Patient had tachypnea, grunting, air entry absent over the right hemithorax along with Peristaltic sounds heard over right hemi thorax. Chest X ray shows Presence of bowel loops and liver in the right hemi-thorax. Left lung showed nearly complete expansion, Arterial Blood gas analysis showed features of respiratory acidosis, other investigations were within normal limits. The neonate was referred to neonatal surgical unit for surgical correction, after stabilization. A male neonate, born in a private hospital to nonconsanguineous parents 36th week of gestational Amit et al., 193 Int J Med Res Health Sci. 2014;3(1):193-194 early diagnosis is necessary in such situation; surgical correction is the treatment modality. Conflict of interest: Nil REFERENCES Fig 1: Chest X ray shows Presence of bowel loops and liver, in the right hemi-thorax. Left lung showed nearly complete expansion DISCUSSION A diaphragmatic hernia is defined as a communication between abdominal and thoracic cavity with or without abdominal contents in the thorax. The true incidence of Congenital diaphragmatic hernia is 1 in 5000 live births.1 Rightsided diaphragmatic hernia (15%) is rare, compared to left-sided diaphragmatic hernia (85%) because liver plugs the opening. Congenital diaphragmatic hernia typically refers to Bochdalek form, other forms are rarer.2 Malformation of diaphragm allows the abdominal organs to push into proper lung formation despite advances in neonatal intensive care; congenital diaphragmatic hernia is associated with high mortality and morbidity due to two complications namely pulmonary hypoplasia and pulmonary hypertension.2 The posterolateral right Congenital Diaphagmatic Hernia is a rare diaphragmatic defect. Females are twice affected than that of males.1 Newborns with CHD often have severe respiratory distress which can be life threatening unless diagnosed and treated early.3,4 The symptoms are non characteristic and patients with this disease maybe without symptoms for a long period. The main tool for diagnosis of congenital DH is radiography. Surgical correction is required. ECMO has been used as a part of treatment strategy in some hospitals.3 1. Akhil maheshwari and waldermar A carlo. Diaphragmatic hernia. Nelson textbook of pediatrics,19th edition,:594-96 2. George BM. Report of a Case Strangulated RightSided Diaphragmatic Hernia. AMA Arch Surg. 195,72(2):273-74. 3. Bryner BS, Kim AC, Khouri JS, Drongowski RA, Bruch SW, Hirschl RB et al., Right-sided congenital diaphragmatic hernia: high utilization of extracorporeal membrane oxygenation and high survival. J Pediatr Surg. 2009;44(5):883-7. 4. Christopher VVM, Canino JE, Jules RC, James JR. Congenital Right Diaphragmatic Hernia. Misericordia Hospital Philadelphia, Penna congenital right diaphragmatic hernia associated with Thorax. Thorax. 1950;5:133 CONCLUSION Diaphragmatic hernia is the congenital anomaly that manifests itself since birth in the form of severe respiratory distress. Suspicion of the condition and Amit et al., 194 Int J Med Res Health Sci. 2014;3(1):193-194 DOI: 10.5958/j.2319-5886.3.1.041 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS st Received: 21 Oct 2013 Revised: 18th Nov 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 10th Dec 2013 CAPILLARY HEMANGIOMA OF THE COLUMELLA OF NOSE *Muthubabu K, Sakthivel M, Srinivasan MK, Kalpana G, Twinkle Radhakrishnan, Ancy Anthony Dept. of ENT, Meenakshi Medical College and Research Institute, Kanchipuram, Tamilnadu, India *Corresponding author email:
[email protected] ABSTRACT Capillary hemangioma is a common condition but a capillary hemangioma arising from the columella of the nose is rare. Here we report a 24 year old man who presented with a pedunculated swelling in the nasal columella. This was excised. Histopathological examination showed features suggestive of capillary hemangioma, the case was presented here due to rare occurrence in the nasal columella. Patients present with epistaxis and cosmetic alterations. Wide excision and cauterization of the base gives excellent results. Keywords: Columella, capillary hemangioma. INTRODUCTION Capillary hemangioma arising from the columella of the nose is rare. Capillary haemangiomas can occur anywhere in the nasal cavity and has even been reported in the ethmoids.1 Congenital lesions of capillary haemangioma have been reported in children.2 Capillary haemangiomas can grow in size to produce nasal obstruction, hence earlier surgical intervention is advisable.3 Frequent nose picking with fingers has been cited as etiological factor. Cryo application is one modality of treatment.5 Wide excision and cautery is the treatment of choice. CASE REPORT A 24 year old person presented with complaints of swelling hanging from the nose of one month duration. He gave history of frequent nose picking with his fingers. To start with the swelling was small in size and has attained the present size (fig 1). He gave history of bleeding from the mass at times. It was not painful. He was also bothered about the cosmetic alteration. On examination a reddish pedunculated mass was seen arising from the columella of the nose on the right side. The stalk was narrow. The size of the mass was about 2 cms. It was nontender, bled on Muthubabu et al., touch, hanging and freely mobile. Anterior rhinoscopy was done. The septum, turbinates and nasal mucosa was found to be normal. Postnasal space was normal. Under Local anaesthesia, infiltration with 2% xylocaine in the columella of nose around the mass was done. The pedunculated mass was excised completely and the base was cauterized with bipolar cautery. A wide excision of the mass was done. The specimen was sent for histopathology which confirmed capillary hemangioma ( fig 2&fig 3). The wound was sutured with 3 – 0 chromic catgut. There was no recurrence on follow up. Fig 1: Capillary hemangioma arising from the nasal columella. 195 Int J Med Res Health Sci. 2014;3(1):195-196 argon laser has also been considered by some for the removal of this hemangiomas.10 CONCLUSION Capillary hemangiomas are a common tumour. But occurrence in the nasal columella is rare. Patients present with epistaxis and cosmetic alterations. Wide excision and cauterization of the base gives excellent results. REFERENCES Fig 2: Photomicrograph showing lobular arrangement of thinned out capillaries lined by plump endothelium and thinned out squamous epithelium. (10 X) Fig 3: Photomicrograph showing proliferation of thinned out capillaries lined by plump endothelial cells. (40 X) DISCUSSION Capillary hemangiomas are benign tumours arising from the vascular tissues of skin and mucosa. They are made up of small capillaries which are normal in size but more in number. These tumours may be either flat to the skin, raised or protrude out as a nodule. In our case the hemangioma protruded out as a nodule. They are usually typically bright red in colour. Large capillary hemangioma arising from the nasal columella has been rarely reported.6 Adult capillary hemangiomas have also been reported in the upper eyelid.7 In the nasal cavity, cases with capillary hemangioma involving the middle turbinate8 and in the nasal septum has also been identified.9 Previous nasal trauma and nose picking has been implicated as possible etiological factors.4 In our case the cause of the capillary hemangioma could be his persistant nose picking habit. Small tumours like the one reported here can be easily excised and the base cauterized. An Muthubabu et al., 1. Swapan K Gosh, Rajkumar Chathurvedi. Capillary haemangioma of the ethmoid. Indian Journal of Otolaryngology. 2004; 56(2): 148-49 2. Nedev P. Lobular capillary haemangioma of the nasal cavity in children. Trakia Journal of Sciences. 2008; 6(1): 63-67. 3. Milton Waner, Julie Kastenbaum, Kathrin Scherer. Haemangiomas of the nose – Surgical management using modified subunit approach. Arch Facial Plast Surg 2008; 10(5):329-334. 4. Puxeddu R, Berlucchi M, Ledda GP, Porado G, Farina D, Nicolai P. Lobular capillary hemangioma of nasal cavity. Ann J Rhinol. 206 ; 20 (4): 480 – 4. 5. Mohammed Maqbool, Suhail Maqbool. Tumours of the nose and paranasal sinuses. Textbook of ear nose and throat diseases 2013; Chapter 38, page 169. 6. Bora H, Bandyapadhyay SN, Sinha R, Bhuria R, Mukherjee S, Das KK,Mukherjee PB. Large capillary hemangioma arising from the nasal columella: A case report. Journal of Indian Medical Association 2001; 99(5):269 – 70. 7. Robert JP, Thomas I, Warner, Heather AD, Potter, Daniel M, Albert. Adult capillary hemangioma. Archives of ophthalmology 2012;130 (8):999 8. Kartaran H, Uraldi C, Arl N, Aktas D. Lobular capillary hemangioma of the middle turbinate . Acta otolaryngol 2006; 126: 442 – 444. 9. Ayotunde J Fasunla, Oluwatasin S Adebola, Clement A Okolo ,Adereni AA. Nasal septal lobular hemangioma in West Africa sub region ; A case report. Case journal 2009 ; 2 : 8952. 10. Lemarchand VF. Indications for laser in the treatment of capillary hemangioma. J.Mal.Vasc.1992:17(1) 41 – 3. 196 Int J Med Res Health Sci. 2014;3(1):195-196 DOI: 10.5958/j.2319-5886.3.1.042 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1(Jan- Mar) Coden: IJMRHS th Received: 29 Oct 2013 Revised: 24th Nov 2013 Case report DELTO-PECTORAL FLAPS FOR SECONDARY RECURRENT PAROTID TUMORS: CASE SERIES DEFECTS Copyright @2013 ISSN: 2319-5886 Accepted: 6th Dec 2013 FOLLOWING EXCISION OF *Adedeji Taiwo O1, Tobhi James E1, Olaosun Adedayo O1, Oseni Oyeniran G2, Idowu Julius A1, Olaitan Peter B2 1 Department of Ear Nose and Throat, Ladoke akintola University of Technology Teaching Hospital, Osogbo Department of Surgery, Ladoke akintola University of Technology Teaching Hospital, Osogbo 2 *Corresponding author email:
[email protected] ABSTRACT Background: Extensive infiltration of the skin by parotid gland tumors often lead to the surgeon seeking various options that will lead to good cosmetic appearance and reduced donor site morbidity. Materials and Methods: This is a report of two patients with extensively enlarged parotid tumors with associated skin loss and depth that was difficult to close. Consent/permission was obtained from the patients. The case notes of the patients were reviewed and it shows that apart from local tissues and skin grafts, delto-pectoral flaps could come handy. Outcome is reported in this report. Results: Two patients who had a deltopectoral flap cover of their defects following excision of huge parotid tumors involving the infiltration of the overlying skin are reported in this study. There was good aesthetic outcome with minimal and acceptable donor site morbidity. Conclusion: Delto-pectoral flaps should be considered an option in covering defects following parotid tumour excision. Keywords: Recurrent parotid tumours, Delto-pectoral flaps, Secondary defects, Cosmesis INTRODUCTION Parotid gland tumors are not common.1-3 Generally, salivary gland tumors represent about 1-3% of head and neck tumours.2 In our environment, it constitutes 1.7% of head and neck tumours3. Seventy eight to eighty percent of parotid tumours are benign.2, 3 Parotid tumours elicit considerable medical interest because of their multifaceted clinical presentation, varied histological appearances and the associated difficulties in predicting their prognosis.1,3 In most cases, therapy consists of parotidectomy and adjuvant therapy – mainly radiotherapy which is reserved for cases with malignancies.2 Surgical intervention varies from limited excision to extensive parotidectomy with facial nerve sacrifice with or without neck dissection2. Factors that influence surgical therapies include facial nerve invasion, tumour extension, histological characteristics and positive limits of the tumor.2 The recurrent parotid gland tumor is a challenge to both the patient and the surgeon. Factors responsible for tumor recurrence include histological grade, extent of the tumour, invasion of adjacent structures and poor surgical technique. Recurrence is more common in malignant tumors4 but in pleomorphic adenoma (a benign tumour), if the capsule ruptured during removal, tumour may implant and cause recurrence.4 Management of recurrent parotid tumour is challenging.4 There is a need for wide surgical excision4 and facial nerve as well as the surrounding soft tissues including skin sacrifices is inevitable. Wide defects are therefore produced necessitating a flap cover or a skin graft. The significant depression created by complete tumour excision is a source of concern for the patient about cosmesis and challenge to the doctor about its closure. 197 Adedeji et al., Int J Med Res Health Sci. 2014;3(1):197-201 Various options available for repairing the defect include fat grafts, sternocleidomastoid muscle rotation flaps, cellular dermal graft and free vascularized facial graft.4 The deltopectoral flap is a useful, reliable and versatile regional flap that can be used in selected circumstances for major head and neck 5 reconstruction. This article reports two cases of recurrent parotid gland tumours that were managed by the use of deltopectoral flaps in repairing the defects created following wide surgical excision. over to fill the defect. This was transferred under the skin of the lateral neck. The result was functionally and cosmetically accepted by the patient. CASE NO 1 A.I. was a 69yr old male Nigerian referred from a private hospital on account of left sided parotid swelling. Progressive left sided parotid swelling noticed about a year prior to presentation. No associated swelling in other parts of the body, no pain and no facial weakness. Examination at presentation showed left sided parotid swelling which measured 6cm x 8cm in its widest dimension. It was firm, non tender with no associated parapharyngeal / oropharyngeal extension and no facial nerve involvement. Full blood count, electrolyte and urea and chest radiograph were normal. An ultrasound revealed a cystic mass 4.5cm x 4.7cm in widest dimension. Fine needle aspiration for cytology suggested a benign lesion. Patient had superficial parotidectomy under general anesthesia. Findings at surgery were a cystic mass about 6x6cm which contained sero-sanguinous fluid. Patient was noticed to have developed House and Brachman grade II facial palsy. Histology of the tumour showed adenoid cystic carcinoma on account of which he was referred for radiotherapy and discharged to clinic but was lost to follow up. He however re-presented two years later on account of 2 months history of recurrent parotid swelling with associated pain and worsening of facial weakness. Examination revealed 8cm x8cm left parotid swelling, firm, non tender and no differential warmth. There was grade III facial palsy. Full blood count, electrolyte and urea, chest radiograph and clotting profile were normal. He had a total parotidectomy. Operative findings were tumour with a cystic cavity that had infiltrated the root of zygoma, facial nerve, posterior wall of external auditory canal and ramus of the mandible. There was a big cavity of about 6 cm depth created. A deltopectoral flap was then designed and raised and de-epithelialised and the distal part turned Fig 1: Huge left parotid tumour infiltrating the skin and ear lobule. Fig 2: Case 1 at surgery (filling the defect with delto-pectoral flap) Fig 3: Post operative appearance CASE NO 2 A 73yr old widow who presented on account of left sided progressive parotid swelling of five years duration. No associated swelling in other part of the body, no history of pain, trauma or facial weakness and no alteration in the size of the tumour during food intake. Examination revealed an elderly woman with 198 Adedeji et al., Int J Med Res Health Sci. 2014;3(1):197-201 12x 11cm left sided parotid mass, firm, non tender and no differential warmth. Full blood count, electrolyte and urea and chest radiograph were normal, electrocardiograph showed left ventricular hypertrophy, neck ultrasound revealed a non homogenous mass with multi-septated cystic masses measuring 10x20mm. Fine needle aspiration for cytology was suggestive of pleomorphic adenoma. She had superficial parotidectomy. Findings at surgery were multi-nodular cystic mass about 25x18cm in its widest dimension. Histology of the tumour showed adenoid cystic carcinoma on account of which she had 54 cGy of radiotherapy. Three years later, patient represented with 6 months history of recurrence. The recurrence was associated with pain, facial weakness, and ulceration and bleeding. Examination revealed an elderly woman with a left parotid mass about 16x8cm in widest dimension which had involved lobule of the ear with a central area of ulceration. Full blood count, electrolyte and urea, and chest radiograph were normal. She had total parotidectomy. Operative findings were multi-nodular masses which had invaded the lobule of the ear and infiltrated the branches of the facial nerve and associated facial weakness. (Fig 4). A wide defect of 10 x 12cm) was created. (Fig 5). Delto-pectoral flap of 24cm length and 8cm width was designed, raised and partly deepithelialised. It was transferred by tunneling subcutaneously into the defect. It covered the defect completely and healed perfectly. The result was functionally and aesthetically acceptable to the patient Fig 4: Extensive recurrent left parotid tumor infiltrating the skin and ear lobule Fig 5: Defect after excision Fig 6: Postoperative appearance of case 2. DISCUSSION The delto-pectoral flap remains a useful, reliable, and versatile regional flap that can be used alone or in combination with other flaps in selected circumstances for major head and neck reconstruction5. It has provided an excellent source of thin and pliable tissue that form appropriate source of donor tissue for reconstruction of limited defects of the pharynx, esophagus, and skin of the neck6. The flap has become the most commonly used pedicle regional flap for head and neck reconstruction while providing coverage for most defects of the head and neck from the scalp and skull base to the cervical region and hypopharynx7. It continues to play an important role in head and neck reconstruction, reflecting its versatility, reliability, and ease of harvest7. The current reports show the versatility of this flap in covering secondary defects from parotidectomy especially in our environment where patients present rather late with tumours that may leave a defect that may not close directly. While Microvascular procedure might have given a better result, facility for this is often not available in most developing countries. This flap therefore comes handy in managing this difficult and extensive defect 199 Adedeji et al., Int J Med Res Health Sci. 2014;3(1):197-201 especially with the attending cosmetic problem that might arise following the use of inappropriate tissue for the closure. Head and neck surgeries present unique challenges because of the variety of functions that head and neck are responsible for, including speech, swallowing, sensation, oral continence, airway protection and facial expression. Deformities of the head and neck region can have devastating effects on the appearance and function of the patient and are among the most disabling and socially isolating defects with significant impact on the patient’s quality of life. Reconstruction of such defects continues to be an extremely demanding challenge for surgeons who aim to restore form and function with minimal surgical morbidity. These reconstructive surgeries must always be performed in a way that preserves these functions as much as possible. The surgery may be done to restore function, improve cosmetic appearance, or a combination of both. In the cases presented here, both function and aesthesis were preserved with the flaps-one covering the wide defect smoothly and the other occluding a depth created by the excision of the tumors. Gardiner et al.8 reported three cases of recurrent head and neck carcinoma viewed as challenging reconstructive problems because of the extent of the extirpative surgery necessary and the substantial risk of complications that would be associated with previous treatment techniques. They showed that myocuteneous flaps were quite versatile and useful in head and neck reconstructive process8. Hurvitz et al.9 reported that although defects of the head and neck region present a challenge, successful cosmetic and functional results have been achieved with both local and free tissue flaps. In the first of the cases presented in this article, deltopectoral flap was designed, raised and deepithelialised. It was transferred by tunneling subcutaneously into the defect to fill the cavity created while in the second case, the flap with 24cm by 8cm was designed, raised and partly de-epithelialised. It covered the defect completely and healed perfectly. Both results were functionally and aesthetically acceptable to the patients. Delto- pectoral flap is therefore useful in the reconstruction of defects and restoration of cosmetic value to the patients following surgical excision of recurrent parotid tumours. While the flap functions effectively for aesthesis and function, the limitation of the flap is in the fact that it was bulky and needed to be divided secondarily to remove the bulkiness on the side of the neck in one of the patients. This was in a woman with thick subcutaneous fat. The second problem arose as a result of the fact that the secondary defect was closed directly and this led to about 2-3cm lift of the ipsilateral breast compared to the contralateral side. Although the 73 year old woman was satisfied and did not bother about the disparity in the breasts as a result of the flaps, caution is suggested in raising these flaps in women. Indeed, this problem of lift and the bulkiness that may need a second procedure must always be explained to the patients. Deltopectoral flaps are therefore part of the armamentaria that can be considered for parotidectomy defects. CONCLUSION Delto-pectoral flaps should be considered an option in covering defects following parotid tumour excision. It is useful in the reconstruction of defects, restoration of cosmetic value to the patients with minimal and acceptable donor site morbidity. REFERENCES 1. Somefun OA, Oyeneyin JO, Abdulkarrem FB, da Lilly- Tariah OB, Nimkur LT, Esan OO. Surgery of parotid gland tumours in Lagos: a 12 year review. Niger Postgrad Med J. 2007; 14(1): 72-75. 2. Mag A, Cotulbea S, Lupescu S et al. Parotid Gland Tumours. J Exp Med Surg Resear. 2010; 4: 259263. 3. Nzegwu MA, Ngozi NR, Ugochukwu AI et al. A Review of Salivary Gland Neoplasm in Eastern Nigeria for A Five- Year Period from January 1, 2000 to December 31st 2004. Adv in Bioresear 2011; 2(1): 28 – 32 4. Carrol WR, Morgan CE. Diseases of the Salivary Glands. In Ballenger’s Otorhinolaryngology Head and Neck Surgery, sixteenth edition (Snow JB, Ballenger JJ eds) BC Decker Inc. Hamilton, Ontario, 2003; 1441 – 1454. 5. Gilas T, Sako K, Razack MS et al. Major Head and neck reconstruction using deltopectoral flap. A 20 year experience. Am J Surg 1986; 152(4): 430 – 434. 6. Mortensen M, Genden EM, Role of the island deltopectoral flap in contemporary head and neck 200 Adedeji et al., Int J Med Res Health Sci. 2014;3(1):197-201 reconstruction. Ann Otol Rhinol Laryngol. 2006 ;115(5):361-364 7. Yang JY, Rosen MR, Keane WM. Flaps and Grafts in the Head and Neck. In Ballenger’s Otorhinolaryngology Head and Neck Surgery, sixteenth edition (Snow JB, Ballenger JJ eds) BC Decker Inc. Hamilton, Ontario, 2003; 972- 996. 8. Gardiner LJ, Ariyan S, Pillsbury HC. Myocuteneous flaps for challenging problems in head and neck reconstruction. Arch Otolaryngol. 1983; 109(6): 396- 399. 9. Hurvitz KA, Kobayashi M, Evans GR. Current options in head and neck reconstruction. Plast. Reconstr. Surg. 2006; 118(5):122e-133e. 201 Adedeji et al., Int J Med Res Health Sci. 2014;3(1):197-201 DOI: 10.5958/j.2319-5886.3.1.043 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 9 Nov 2013 Revised: 8th Dec 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 13th Dec 2013 RABIES: NEED FOR ACTIVE AND PASSIVE IMMUNISATION G N S Sangeetha Lakshmi Dept of General Medicine, Baptist Christian Hospital, Tezpur, Assam Corresponding author email:
[email protected] ABSTRACT Rabies is an acute highly fatal viral disease of the CNS caused by Lyssavirus Type-I. It has a long and variable incubation period. It is a communicable disease of man that is always fatal. The combined administration of a single dose of anti rabies serum with a course of vaccine, together with local treatment of the wound is the best specific prophylactic treatment after exposure of man to rabies. Here, we report a case of rabies, who developed the disease in spite of having taken three doses of anti rabies vaccine (Post exposure). Keywords: Rabies Immunoglobulin, Human Diploid Cell Vaccine, Post-exposure Prophylaxis, Intra-dermal Regimen. INTRODUCTION Rabies is a zoonotic disease of warm blooded carnivore animals. It is transmitted to man usually by bites or licks of rabid animals on broken skin and mucous membrane. Human Rabies is endemic in India. According to a recent WHO estimate, 55000 deaths occur annually due to human rabies globally 20,000 (36%) of which occur in India.1 CASE REPORT A female patient aged 55 years presented to the Casualty of a secondary care hospital in Assam with history of feeling feverish, headache, vomiting and increased irritation since the morning of 29.05.2012. She was admitted to the hospital with a provisional diagnosis of Acute Sinusitis / Headache for evaluation. At admission on physical examination vitals were stable, mild frontal sinus tenderness was seen, and rest of the systemic examination was normal. Complete blood count, Random Blood Sugar, Serum Creatinine, Serum Electrolytes, Liver Function Test, complete Urine examination were within normal limit. Tests for the peripheral smear of malaria and Rapid test for Scrub Typhus was Negative. Chest-X-Ray and ECG were within Normal limit. After admission, in the ward she was found to be reluctant to drink water. Further examination revealed agoraphobia, hydrophobia and a healed wound on the nasal bridge. On reviewing history, the patient’s attendant revealed that the patient had been bitten by a street dog on the nasal bridge 2 weeks ago. The patient was taken to a local physician and given HDC vaccine-Rabipur on ‘0’ day - 1st dose, 3rd day - 2nd dose, 7th day - 3rd dose ; post exposure. The 4th dose was not taken, as the patient developed symptoms of rabies two days prior to the 4th dose. The patient was however not RIG advised. The patient was well until 27.05.2012 (14 days after the dog bite) doing all household work. The neither relatives nor patient could tell about the fate of the dog. A clinical diagnosis of rabies was made. The 202 Sangeetha., Int J Med Res Health Sci. 2014;3(1):202-204 patient was discharged on request and advised to go to a higher Centre. DISCUSSION The prophylaxis of rabies is with an Anti rabies vaccine and rabies Immunoglobulin. The Post exposure Prophylaxis depend on the category of the wound.2 Approach to Post-exposure Prophylaxis (PEP): Management of animal bite wound: Wound Toilet: Rabies virus enters the human body through a bite or scratch. An efficient wound toilet can be done by prompt and gentle washing with soap and flushing the wound with running water for 10 minutes. Considering the importance of this step all clinics that are likely to encounter patients with dog bites should have wound washing facilities. Passive immunization – rabies Immunoglobulin (RIG): RIG should also be administered as passive immunisation for immediate protection before the development of immunity from the vaccine, It should be given at the same time as the first dose of vaccine and no later than 7 days after the first dose.2 Rabies vaccine and RIG should never be administered at the same site or in the same syringe. Two types of Rabies antibody preparations are available: Human rabies immunoglobulin (HRIG) and Equine rabies immunoglobulin (ERIG). The recommended dose of ERIG is 40 International units (IU) /Kg 3 up to a maximum of 3000 IU 2, ERIG may be occasionally associated with anaphylaxis. A skin test may be performed prior to the administration of ERIG but WHO does not advocate skin sensitivity test (SST) anymore.4 The recommended dose of HRIG is 20 IU/Kg3 up to a maximum of 1500IU.2 Adverse effect of HRIG includes local pain and low grade fever. The wounds should be infiltrated with RIG (if anatomically feasible) and the remainder of the dose should be given intramuscularly (IM) in the gluteal region. If the exposure involves a mucous membrane, the entire dose should be administered IM. With multiple or large wounds, the RIG may need to be diluted for adequate infiltration. Active Immunisation – Anti rabies Vaccine: HDC vaccines are mostly used as they are generally safe and highly potent. All age groups of animal bite victims of category II and III require the same number of injections and dose per injection. The category III exposures in addition require administration of rabies immunoglobulin. The vaccination schedule recommended for Post exposure Prophylaxis consist of 6 doses (1 ml each) on days 0, 3, 7, 14 and 28 and a booster dose on day 90. Injections are given intramuscularly (deltoid).2 Intra-dermal (ID) Regimens: The use of this route leads to considerable savings in terms of the total amount of vaccine needed for a full Post-exposure vaccination. A vaccine which has been approved by Drug Controller General of India (DGCI) for use by intra-dermal route have to be used [2] .The vaccines used are same; however route, dose and site of administration differ. The Regimen approved by DGCI has updated Thai Red Cross schedule (2-2-2-0-2).2 Approach to a patient requiring RIG when none is available: In circumstances when no immunoglobulin is available greater emphasis should be given to proper wound toileting followed by Essen schedule. 2 RIG is life saving biologic in patients with severe exposure to rabies, but scarce and expensive. Worldwide less than 3% of risk exposure cases receive RIG and it is often not injected into wounds.5,6 Fear of anaphylaxis with ERIG and the cost of HRIG are the main barrier. ERIG is indigenously produced, less expensive, more widely available. ERIG should be promoted as an ‘institutional product’7 and given by trained persons in all first referral unit (FRU) hospitals. The safety profile of ERIG is good in many studies.8 Post exposure prophylaxis applied adequately is highly effective in prevention of human disease but its use is low in India (2.1%).9 The compliance to vaccine in India is 40.5%.9 After recognition of a rabies exposure, when a patient approaches a local physician, exposure has to be assessed to see which category it falls into. The need for RIG and active immunisation has to be stressed and informed to the patient by the local physician. In our case, the patient should have been administered RIG along with the first dose of rabies vaccine or been informed of the need to enable the patient to approach a higher centre for the same. Rabies can be confirmed in patients early in the illness by antigen detection using immuno fluorescence of skin biopsy, and by virus isolation from saliva and other secretions. These tests are not available in our hospital, therefore they were not done. 203 Sangeetha., Int J Med Res Health Sci. 2014;3(1):202-204 CONCLUSION The approach to the management of rabies consists of wound toilet, active and passive Immunisation should be made available at the Primary Health Centres (PHC) across the country. As HRIG is expensive, ERIG can be used as it is less expensive and more widely available. WHO has recommended the use of intra-dermal (ID) route of administration of HDC vaccine which not only reduces the cost of Post-exposure Prophylaxis, but also allows wider coverage in available quantity of vaccine? This case shows the need for the combined administration of RIG and Anti rabies vaccine in every case of exposure of man to rabies. Every instance of human exposure should be treated as a medical emergency. REFERENCES 1. Haniv J, Gdalenich M, Mimouni D, Gross E, Shpilberg O. Successful post exposure rabies prophylaxis after erronous starting treatment. Prev Med 1999; 29(1): 28-31 2. National guidelines for rabies Prophylaxis and Intra-dermal Administration of Cell Culture rabies Vaccines – 2007. www.ncdc.gov.in/Rabies_Guidelines.pdf 3. World Health Organisation 2005: WHO expert consultation on rabies. First report (First Report Edition), Geneva, WHO, 2005. http://apps.who.int/iris/bitstream/10665/85346/1/9 789241209823_eng.pdf 4. Rabies Vaccines: WHO Position paper. Wkly Epidemiol Record 2010; 85:309-20. 5. David Anderson. WHO guidelines dealing with immunoglobulin use impede rabies prevention. Asian Biomed. 2007; 1:103-7. 6. Association for Prevention and Control of Rabies in India (APCRI), assessing the burden of rabies in India: WHO Sponsored National Multi Centric rabies Survey, 2004. http://rabies.org.in/rabiesjournal/rabies-06/SpecialArticle1.htm 7. Sudarshan MK, Ashwath Narayana DH, Ravish HS. Is skin sensitivity test required for administering equine rabies immunoglobulin ? The National Medical Journal of India. 2011;24(2):80-82 8. Chawan VS, Tripathi RK, Sankhel L, Feravdes AC, Dastary GV Safety of equine rabies 9. 10. 11. 12. immunoglobulin in Grade-III bites. Indian J Community Med 2007; 32:73-74 Sudarshan MK. Assessing the burden of rabies in India. WHO sponsored national multi-centric rabies survey 2003. Final report August 2003. Bangalore, Association for Prevention and control of Rabies in India (APCRI), 2003. Tapan Ranjan, Durga Madhab Sathapathy, Ashiwini Kumar Pradhan. Safety of Equine rabies Immunoglobulin into fingers and toes. Asian Bio medicine. 2012;6(3):429-32. Wilde H, Chutivongse S. Equine rabies immunoglobulin : a product with a underserved poor reputation. An J Trop Med Hyg. 1990;42(2):175-8. Sudarshan MK, Madhusudan SN, Mahendra BJ, Rao NS, Aswath Narayana DH Abdul Rahman S, Assessing the burden of human rabies in India. Results of a national multi-centre epidemiological survey. Int J Infect Dis 2007, 11:29-35. 204 Sangeetha., Int J Med Res Health Sci. 2014;3(1):202-204 DOI: 10.5958/j.2319-5886.3.1.044 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue (1 Jan- Mar) Coden: IJMRHS th Received: 11 Nov 2013 Revised: 8th Dec 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 13th Dec 2013 SPONTANEOUS NEPHROCUTANEOUS FISTULA IN TUBERCULOUS PYELONEPHRITIS: AN UNUSUAL OCCURRENCE Apoorv Sharma1, *Zeeshanuddin Ahmad1, Arpan choudhary1, Moolchand Songra2 1 MS Senior Resident, Department Of Surgery, GMC Bhopal, Madhya Pradesh, India HOD and Professor, Department Of Surgery, GMC Bhopal, Madhya Pradesh, India 2 *Corresponding author email:
[email protected] ABSTRACT Nephrocutaneous fistula has an uncommon incidence and occur usually as a complication of operative procedures on kidneys, renal injuries (penetrating or iatrogenic), renal uroliths, renal tumors and chronic UTI with resultant perirenal abscesses. The most common causes identified are renal calculi and chronic renal tuberculosis. We intend to highlight a case of a woman aged 35years, complaining of watery discharge through the skin in the right lumbar region for the past six months. A fistulogram was done which showed the passage of contrast dye in the collecting system. The patient underwent a simple nephrectomy on the concerned side and recuperated without any complication in the postoperative period. Keywords: Kidney, Fistula, Renal tuberculosis, Nephrocutaneous. INTRODUCTION Spontaneous nephrocutaneous fistula (NCF) is a rare condition. Majority develop secondary to postoperative, trauma, chronic urinary tract infection, renal stones1. Few cases as a complication of xanthogranulomatous pylonephritis has also been reported to the literature2, however occurrence of this condition due to renal tuberculosis is a rare phenomenon. The fistula may be internal (the fistulous communication between kidney and adjacent viscera like colon, duodenum, or jejunum) or external, like nephrocutaneous fistula.3We report a rare case of Spontaneous nephrocutaneous fistula due to renal tuberculosis. CASE REPORT Complaints - A 35 year old female presented with complaint of insidious onset watery discharge from her right flank for 6 months. There was no history of loin pain, back pain, lump in abdomen, fever, frequency of urination or burning micturition at any time during the course of illness. She never underwent any surgical intervention in the past. There was also no history of previous purulent discharge. Examination -The physical examination revealed a fistulous orifice in the skin on the right lumbar region with surrounding induration. Examination of chest, abdomen, spine and genitourinary systems was unremarkable. There was no lymphadenopathy. On examination watery discharge was of ammoniacal smell. Culture and sensitivity of the discharge and urine were sterile. X-ray chest, spine and KUB were normal. Routine blood tests including renal functions were normal and patient was not found diabetic. Investigation - A fistulogram was done which showed the passage of contrast dye in the right collecting system travelling down freely up to the ureter and bladder (Figure 1). Excretory urography revealed nonfunctioning right kidney with normal function 205 Apoorv et al., Int J Med Res Health Sci. 2014;3(1):205-207 opposite side. Ultrasound abdomen revealed small right kidney with significant cortical loss and fistula site biopsy was inconclusive. Treatment- In view of non functioning right kidney, nephrectomy was planned with excision of the fistula. Intraoperatively shrunken, atrophic kidney was found adhered to the surrounding tissue and perinephric fat with caseous material filled in (Putty kidney). After careful separation from surrounding tissue simple nephrectomy was performed by excision of the entire fistulous tract including skin and subcutaneous tissue. Histopathology - Histopathological examination of the specimen showed tuberculous pyelonephritis. The postoperative period was uneventful. Patient was started on antitubercular drugs and was discharged on the seventh post-operative day. Fig 1: Fistulogram showing passage of contrast agent to the right collecting system freely up to the bladder DISCUSSION Spontaneous nephrocutaneous fistula without previous surgical history is rare.4 Most of the cases reported in the literature was associated with chronic UTI, renal tumors, renal tuberculosis and nephrolithiasis. Patients often overlook minor complaints of backache and flank pain; such neglected cases often harbor an underlying perinephric abscess5 that may lead to the genesis of a spontaneous NCF. A review of literature suggests renal calculus being the most common cause followed by tubercular and xanthogranulomatous pyelonephritis and reflux disease. 6,7 However some reports favor open surgical procedure being commonest. 8 Tuberculous pyelonephritis usually starts in renal parenchyma and ureters and bladder are secondarily involved. The mode of spread is hematogenous. Three pathological stages have been described. At any stage, when there is significant fibrosis and outlet obstruction, the pus may find its way along the path of least resistance-forming renocutaneous, reno-colic or reno-pleural fistula. The case under discussion had total outlet obstruction in proximal ureter due to progressive fibrosis and obstruction causing atrophic, putty kidney and renocutaneous fistula. The clinical features related to renal tuberculosis are variable and range from simple fatigue, anorexia and weight loss, to the attacks of loin pain and haematuria. Other features depend upon the stage of disease and extent of involvement. Apart from routine investigations, culture and sensitivity of urine, abdominal ultrasound, fistulography, excretory urography and DTPA renal scintigraphy are important diagnostic tools. Early changes are best detected by excretory urography / pyelography while chronic changes are evaluated with the help of ultrasound or CT scan. Plain films are helpful in detecting lesions in the lungs and areas of calcification in kidneys, adrenals and adjacent lymph nodes. The standard treatment of nephrocutaneous fistula is nephroureterectomy with complete debridement of affected perirenal fat, muscles, and subcutaneous tissue. The surgery is followed by anti-TB regimen and long-term follow-up. Classification of TB Pyelonephritis I: Nondestructive (infiltrate) tuberculosis of kidney II: Initial destruction (papillitis or small, by diameter about 1 cm, single cavity); III: Marked destruction (caverns or policavernosial tuberculosis one of kidney segments); IV: Total or subtotal destruction (policavernose tuberculosis, tubercular pyonephrosis, calcification). They distinguish three forms of tuberculosis: tuberculoinfiltrative, ulcerous and scar. CONCLUSION We highlight here the rarity of spontaneous nephrocutaneous fistula and renal tuberculosis as an important differential diagnosis to be kept in mind in the Indian scenario. 206 Apoorv et al., Int J Med Res Health Sci. 2014;3(1):205-207 REFERENCES 1. Singer AJ. Spontaneous nephrocutaneous fistula. Urology 2002; 60(6): 1109–10. 2. Biyani CS, Torella F, comford PA, Brough SJ. Xanthogranulomatous pyelonephrins with bilateral Nephrocutaneous fistulae. Urol Int 1997: 59: 4647. 3. Ansari MS, Singh I, Dogra PN. Spontaneous nephrocutaneous fistula—2 unusual case reports with review of literature. Int Urol Nephrol. 2004;36:239–43. 4. Alberto A, Antunes, Adriano A, Calado, Evandro F. Spontaneous nephrocutaneous fistula. International Braz J Urol 2004; 30: 316-18. 5. Karfopoulos AS, Murray W, Stone FJ. Nephrocutaneous fistula. J Med Soc NY 1981; 78: 379. 6. Iseki T, Kawamura M. Spontaneous passage of renal calculi through nephrocutaneous fistula due to calculous pyelonephritis. Br J Urol 1987; 59(3): 285–86. 7. Lewi HJE, Scott R. Calculocutaneous sinus. Urology. 1986;28:232–34. 8. Das S, Ching V. Nephrocutaneous sinus: a case report. J Urol 1979; 122: 232. 9. Hargreave TB. The kidney and ureter. In: Cusheiri A, Giles GR, Moosa AR, (edi). Essential surgical practice, 3rd ed. Oxford. Butterworth- Heinemann; 1995:1487. 207 Apoorv et al., Int J Med Res Health Sci. 2014;3(1):205-207 DOI: 10.5958/j.2319-5886.3.1.045 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS nd Received: 21 Nov 2013 Revised:1 8th Dec 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 21th Dec 2013 CONGENITAL GIANT MELANOCYTIC NEVI – TIP OF THE ICEBERG *Veena G1, Sathish Selva Kumar2, Meenakshisundaram3, Rajalakshmi V4 1 Senior Resident, 2Assistant Professor, 3Associate Professor, 4Professor & HOD, Department of Pathology, ESIC Medical college & PGIMSR , K. K. Nagar, Chennai. *Corresponding author email:
[email protected] ABSTRACT Congenital Giant Melanocytic Nevus (CGMN), pigmented lesion present since birth, occurs in 1 % of infants worldwide. Fifteen percent of CGMN are localized in the head and neck region and it can also have a bathing trunk distribution. It grows proportionally to the size of the body as the child matures and grows with variation in colour and surface texture. A 29 years old female presented to the Gynecology Out Patient Department for infertility. She also had multiple large nevi of varying sizes present since birth. The lesion was distributed all over the body. She also complained of sudden appearance of swellings at the back which were later excised and the histopathological examination showed the presence of neural nevus involving the dermis and subcutaneous tissue. This case is being reported for its rarity, the higher risk for melanoma transformation, its association with meningeal melanosis and few benign / malignant tumors. Keywords: Congenital, Nevi, Melanoma INTRODUCTION Melanocytic nevus refers to any congenital/acquired lesion of melanocytes. They are common and they present with numerous clinical and histologic types. This variation in clinical and histologic presentations necessitates thorough knowledge to differentiate from malignant tumors. Congenital Giant Melanocytic Nevus, classified according to the size of the nevus,1-4 are present since birth.1 These pigmented lesions are to be followed up regularly because of their association with melanoma transformation, meningeal melanosis and few benign / malignant tumors. CASE REPORT A 29 years old female presented to Gynecology Department for infertility. Incidentally, she brought to the notice of the gynecologist about multiple blackish lesions of varying sizes all over the body Veena et al., since birth. She also complained of sudden appearance of multiple nodules on her back of three months duration. On examination multiple large pigmented lesions were seen in the upper part of chest, back and face. Few areas of the pigmented lesions showed hair. The pigmented areas of the back showed three nodules measuring 5x4cm, 7x5cm and 8x5cm each with wrinkled skin (Fig 1). All other laboratory parameters were within normal limits. The clinical differential diagnosis of the nodules was neurofibroma. One of the nodules was excised and sent for histopathological examination. Gross – Specimen of skin with soft tissue mass measuring 10x8x5 cm. The skin showed wrinkling and hyperpigmentation. The cut section showed many specs of black discoloration of less than 0.3 cm, involving the subcutis (Fig 2). Int J Med Res Health Sci. 2014;3(1):208-211 208 Microscopy -Sections showed structure of skin with dermis showing interlacing fascicles of spindle shaped cells with elongated nuclei interspersed with collagen fibers, melanophages containing melanin pigments (Fig 3). The skin appendages were also surrounded by similar cells. Melanin bleach was done and it confirmed that the pigments were melanin. Immunohistochemistry showed positivity for HMB 45 and S 100 (Fig 4). Final diagnosis of congenital giant melanocytic nevus was made. Fig 3 b): shows dermis with interlacing fascicles of spindle shaped cells interspersed with collagen fibres and theques of melanocytes (40 X) Fig 1: CGMN involving the back, is hair borne. Nodules are seen (arrow). Fig 4: Immunohistochemistry – a) Melanocytes showing positivity for HMB 45 (100 X) Fig 2: GROSS- Cut section shows multiple black pigmented specs extending upto the subcutis. Fig 4: IHC – b) Melanocytes showing positivity for S100 (100 X) DISCUSSION Fig 3: a) epidermis and underlying dermis showing melanocytes (100 X) Veena et al., Melanocytes are of neural crest origin and they migrate along nerves that emerge from the spinal cord and merge with the skin. As they reach the skin, they spread out evenly among the epidermal cells. These melanocytes produce pigments, which protect the skin from damage by the ultraviolet rays from the sunlight. Congenital Melanocytic Nevi (CMN) Int J Med Res Health Sci. 2014;3(1):208-211 209 reflects a failure of the normal process of migration of melanocytes into the skin. Instead of spreading out evenly into the skin, many cells collect at the same spot . Majority of the CMN are sporadic as our case, but few familial cases have also been reported. Congenital melanocytic nevi are present at birth in 1% to 2% of newborns.1-3 Large CGMN are rare occurring 1 in 20,000 to 1 in 500,000 newborns.1 CMN are classified according to their size, as smallless than 1.5cm , medium 1.5-19.9cm and large more than 20 cm.1,3,4 Zeal LH et al recommended defining CGMN as nevi covering 1% body surface area in the face and neck and 2% elsewhere in the body. . Hence our case according to this can be classified as CGMN. The size is significant as it determines the therapeutic options and risk for malignancies. CGMN can occur in both sexes4 with a slight female predilection5. Majority of Congenital melanocytic nevi, increase in size during first trimester of pregnancy.5,6 Clinically the CMN are tan to brown, small, uniformly pigmented, flat to elevated with well defined, round borders. Giant melanocytic nevus is darkly colored and well delineated from the normal skin. Giant CMN are often covered with hair or proliferative nodules.7 CGMN can occur at any site, may involve whole extremity, scalp or the trunk and may extend into the placenta. CGMN is associated with meningeal or cerebral melanosis. The majority of these patients lead normal life without any complications. CGMN is at an increased risk for the development of melanoma and is as high as 5-7 % by age 60 years, and Arif et al suggested the incidence as 2% to 31 % for melanoma transformation.5,8 In another study, 70% of melanomas occur in patients with giant CMN before puberty.5 Hence there is no age limitation for the risk of melanoma transformation. The risk of melanoma may be greater in those with giant congenital melanocytic nevi with larger diameter.1,9 Another study suggests multiple nevi alone or with associated posterior midline location of large congenital melanocytic nevi may be complicated by underlying cranial or spinal leptomeningeal melanocytosis.10 Crowe et al11, in their study of 223 patients with neurofibromatosis found that 3 patients had extensive CMN. Von Recklinghausen in his monograph Veena et al., described 1 of 28 patients as having giant CMN. Few benign conditions like diffuse lipomatosis, hamartomas, hemangiomas, lymphangiomas, mastocytomas, schwannomas, Von-Recklinghausen's disease, vitiligo, structural brain malformations, hypertrophy of skull bones, skeletal asymmetry, hydrocephalus are associated with CGMN. The explanation for these mixed neoplasms is that CMN precursor cell, at least in some cases, is pluripotent stem cell which has the capacity to give rise to multiple cell types.12 Similarly malignant conditions associated with CGMN are neuroectodermal tumors, malignant melanoma (6% to 12%), neurocutaneous melanosis, rarely rhabdomyosarcoma. One of the syndromes known as Epidermal Nevus syndrome, also known as Feuerstein syndrome/ Solomon's syndrome, consists of extensive congenital nevi with abnormalities of central nervous system (CNS), musculoskeletal system, cardiovascular, genitourinary and eyes.12 A study of 57 patients with CMN, suggests that somatic mosaicism for NRAS codon 61 mutations in a progenitor cell within the neuroectoderm cause multiple CMN and neuromelanosis (including nonmelanocytic CNS lesions).13 Treatment is usually to obtain an acceptable cosmetic result to decrease the psychosocial inconvenience to the patient and to minimize the risk of malignancy. Curettage is an alternative to surgical excision if performed in the first 2 weeks of life.14 Even after complete removal of the nevi, the risk of malignancy persists as the melanoma can occur at extracutaneous sites, especially in CNS.5, 15 CONCLUSION Long term follow up of the CGMN patients helps in early diagnosis of malignant melanoma and various benign/malignant tumors. Regular follow up of the patient with magnetic resonance imaging is essential for early detection of CNS complications. Anxious couples need to be counseled, as there is no risk associated with pregnancies. This case reported for its rarity and its associated complications. REFERENCES 1. Mary Wu Chang, Vourc’h-Jourdain M.The Risk for Melanoma in large, congenital melanocytic nevi, J Am Acad Dermatol 2012, Int J Med Res Health Sci. 2014;3(1):208-211 210 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. www.jwatch.org/./risk-melanoma-largecongenital-melanocytic-nevi. Alper JC, Holmes LB. The incidence and significance of birthmarks on a cohort of 4641 newborns, Pediatric Dermatology. 2012;1(1):5868 James WD, Berger TG. Andrews ’Diseases of the skin: clinical Dermatology, Saunders Elsevier. 2006; 10th edn ; Philadelphia, pg 678-79 Karthik Natarajan. Congenital Melanocytic Nevi : Catch Them Early!. J Cutan Aesthet Surg. 2013;6(1) :38-40. Bhagyalakshmi A. Giant Congenital Melanocytic Nevus of Scalp: a rare case. International Journal of Research in Medical Sciences. 2013;1(3):31719 Timothy McCalmont, Dirk M Elston. Melanocytic Nevi. Updated Jun 3, 2013, emedicine.medscape.com/article /1058445. Price HN, Schaffer JV. Congenital Melanocytic Nevi-when to worry and how to treat: Facts and controversies. Clinics in Dermatology. 2010;28(3):293-302 Arif Turkmen, Ebopras, DaghanIsik, Mehmet Bekerecioglu. Comparison of Classification Systems for Congenital Melanocytic Nevi. Dermatologic Surgery 2010;36:1554-62 Hale EK, Stein J, Ben- Porat L. Association of melanoma and neurocutaneous melanocytosis with large congenital melanocytic nevi- results from the NYU-LCMN registry. Br J Dermatol. 2005;152(3): 512-17 Lovett A, Maari C, Decarie JC. Large congenital melanocytic nevi and neurocutaneous melanocytosis: one pediatric center’s experience. J Am Acad Dermatol. 2009;61(5):766-74 Crowe FW. A Clinical,Pathological and Genetic study of multiple Neurofibromatosis. Springfield,IL,Charles C Thomas,1956,p 181. Fitzpatrick’s Dermatology in General Medicine. Klaus Wolff. Melanocytic tumors, Benign neoplasia and hyperplasia of melanocytes,1;7the ed: C1099-1101. Veronica A. Multiple Congenital Melanocytic Nevi and Neurocutaneous Melanosis Are Caused by Postzygotic Mutation in codon 61 of NRAS, Journal of Investigative Dermatology. 2013;133, 2229-36 Veena et al., 14. Linda E . De Raev. Curettage of Giant Congenital Melanocytic Nevi in Neonates. Arch Dermatol. 2002;138(7) 943-47 15. Marghoob AA, Schoenbach SP, Kopf AW. Large Congenital nevi and the risk for the development of malignant melanoma. Arch Dermatol 1996;132:170 Int J Med Res Health Sci. 2014;3(1):208-211 211 DOI: 10.5958/j.2319-5886.3.1.046 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Received: 28th Nov 2013 Case report Coden: IJMRHS Copyright @2013 ISSN: 2319-5886 th Revised: 18 Dec 2013 Accepted: 21st Dec 2013 PRIMARY UROTHELIAL CARCINOMA OF PROSTATE: A RARE CASE REPORT * Vandana Gangadharan1, Geetha Prakash2, Eswari V3, Indhu Kannan4 1 Assisstant Professor, 2Professor and HOD, 3Associate Professor, 4 Post Graduate, Department of Pathology, Meenakshi medical college, hospital and Research institute, Enathur, Tamilnadu, India *Corresponding author email:
[email protected] ABSTRACT Primary urothelial carcinoma of the prostate is a rare clinicopathological entity which as a rule bears an unfavourable prognosis. We report a case of a 75 year old male who presented with a history of voiding difficulty. With a provisional diagnosis of Benign Prostate Hyperplasia both clinically and by needle biopsy a Trans Urethral Resection was undertaken. Histopathology showed acini lined by malignant transitional epithelial cells with stromal invasion. No primary in the bladder was detected on the investigation. A CK 7/ CK 20 copositivity on Immunohistochemistry confirmed our diagnosis of Primary Urothelial Carcinoma of Prostate. Key words: Urothelial, carcinoma, prostate, primary INTRODUCTION Transitional cell carcinoma of prostate is carcinoma of urothelial origin. The reported incidence of prostatic transitional cell carcinoma ranges from 21.8 – 36.7% depending mainly on the manner of examination.1,2 Urothelial carcinoma of the prostate is rarely primary and usually represents synchronous or metachronous spread from carcinoma of bladder and urethra.3 The frequency of primary urothelial carcinoma, ranges from 1- 4% of all prostate tumours in adults.3,4 Most patients are older with a similar age distribution to urothelial carcinoma of the bladder i.e. 45 to 90 years.4 The primary prostatic transitional cell carcinoma involves the entire prostatic urethra particularly areas near the verumontanum, the large prostatic duct and nearby acini. They presumably arise from urothelium lining the prostatic urethra and the proximal portion of prostatic ducts. It has been postulated that these may develop through a hyperplasia – dysplasia sequence, possibly from reserve cells within the urothelium.5 Stephen et al 6 also suggests that tumour originating in the prostate may be the result of malignant Vandana et al., transformation of prostatic urothelium. On the other hand secondary prostatic transitional cell carcinoma mainly involves the bladder neck or posterior prostatic tissue and results from the direct pagetoid spread of urothelial carcinoma in situ or a direct pathologic invasion of bladder urothelial carcinoma. However whether primary or secondary transitional cell carcinoma of prostate is believed to have a poor prognosis.7 CASE REPORT A 75yr old male patient presented with a 3 month history of voiding difficulty, symptoms of nocturia and very few episodes of dysuria. This was not associated with significant anorexia or weight loss. No other positive history was elicited. Serum PSA done was within normal limits. Ultrasonography revealed prostatic enlargement without any nodules. Int J Med res Health Sci. 2014;3(1):212-215 212 Initial prostatic biopsy with a provisional diagnosis of Benign Prostatic Hyperplasia reported focal acini showing hyperplasia with low grade PIN changes. The patient was followed with Trans Urethral resection of prostate which revealed prostatic acini with adenomatous hyperplasia and a focus of ducts lined by malignant transitional epithelial cells with mitotic figures and areas of necrosis and stromal invasion. – suggesting Transitional cell carcinoma of prostate. Fig 1: Urothelial Carcinoma Prostate 40x Fig 2: High grade cytological features (40x) Fig 3: Cytokeratin 7 positivity (40x) The urinary bladder was evaluated with clinical and ultrasonography to rule out secondary TCC prostate Vandana et al., from a bladder primary carcinoma. This turned out to be negative. Immunohistochemisty with CytoKeratin 7 (CK 7) and Cytokeratin 20 (CK 20) was positive while Prostate Specific Antigen (PSA) was negative which confirmed our diagnosis. DISCUSSION Prostate cancer is one of the most common cancers in men. Prostatic cancer occurs microscopically in up to 50% men by the age of 50 and almost all men aged 80 years showed some microscopic evidence of prostate cancer. 8 Besides the garden variety of prostatic adenocarcinoma many variants and a wide histological spectrum have been described. These include mucinous carcinoma, neuroendocrine carcinoma, sarcomatoid carcinoma, squamous cell carcinoma, urothelial carcinoma etc.3 Primary urothelial carcinoma of prostate is rare with an incidence ranging from 1-4%3,4 and arises either from prostatic urethra or from the urothelial lining of the larger periurethral prostatic ducts.9 Patients usually present with symptoms of haematuria, urinary obstruction or prostatitis as was seen in our case.3,10 Wadhwa et al 11 describes an atypical case presenting as bleeding per rectum due to a rectal ulcer. Digital rectal examination is abnormal in the majority of cases but is rarely the presenting sign.10 Clinically urothelial carcinoma of prostate may be mistaken for nodular hyperplasia or prostatitis which was the provisional diagnosis in our case too.3 Serum prostate specific antigen (PSA) which is the cornerstone in the diagnosis of prostatic adenocarcinoma is not elevated in primary urothelial carcinoma of prostate (< 4 ng/dl).3 Radiological findings can overlap and play limited role in the diagnosis of unusual neoplasms of prostate including urothelial carcinomas.12 Most cases are diagnosed by TUR or less often by needle biopsy.13 TURP is preferred due to more false negative reports with needle biopsy as seen in our case as well. However, in all suspected cases of primary urothelial prostate cancer the possibility of secondary involvement from an apparent or occult bladder primary must be excluded. This may require random biopsies of urinary bladder mucosa.14 Histologically the diagnostic criteria for primary prostatic urothelial carcinoma are identical to those for urothelial cancer of the bladder; most cancers are moderately or poorly differentiated and usually associated with prominent chronic inflammation. 213 Int J Med res Health Sci. 2014;3(1):212-215 Squamous metaplasia is rare.3 They may be seen to spread by invasion of prostatic stroma initially. Local spread beyond prostate gland as well as metastasis may occur.10 Distinguishing urothelial carcinoma from prostatic adeno carcinoma is clinically important because of the oestrogen unresponsiveness of the former.3 Prostatic adenocarcinoma may respond to hormonal therapy and cystoprostatectomy may not be needed. Diagnosis also determines the stage for prognostication.15 Urothelial Carcinoma is usually distinguished from poorly-differentiated Prostatic AdenoCarcinoma by its histopathological characteristics (Fig 1) including the presence of solid nests of cells associated with dense or abundant cytoplasm and striking nuclear pleomorphism, with the absence or rarity of glandular lumina. The serum free PSA level is a main marker for prostate adenocarcinoma screening 15 .In difficult cases IHC may be mandatory. The sensitivity and specificity of PSA are high in prostate cancer, at 100% sensitivity. In poorly-differentiated prostate cancer and PAC, the expression levels of PSA may reach 85–95%. PSA is the oldest and most commonly used immunohistochemical marker to identify cancers of prostatic origin.16 CK7 and CK20 are also useful markers to distinguish PAC from UC. Bassily et al17 studied the expression of CK7 and CK20 in PAC and UC, and estimated their usefulness for distinguishing between the two tumors. In the prostatic and metastatic tumors, neither was positive for the markers. However, 61% of the UC cases were positive for CK7 and CK20. CONCLUSION Primary urothelial carcinoma is a rare type of prostatic carcinoma which as a rule bears an unfavourable prognosis. As a primary tumor it makes only 1-4 % of tumors of the prostate. It originates in the poorly differentiated reservoir cells of the prostatic periurethral ductus which explains why diagnosis is most often obtained in advanced stages thus limiting its management to radical surgery. Its distinction from prostatic adenocarcinoma is pertinent for both treatment and prognostication. Thus Transitional Cell Carcinoma should be considered as a differential diagnosis in cases with obstructive symptoms and normal PSA. Vandana et al., REFERENCES 1. Lerner SP, Shen S. Pathologic assessment and clinical significance of prostatic involvement by transitional cell carcinoma and prostate cancer. Urol Oncol. 2008; 26(5):481-85 2. Shen SS, Lerner SP, Muezzinoglu B, Truong LD, Amiel G, Wheeler TM. Prostatic involvement by transitional cell carcinoma in patients with bladder cancer and its prognostic significance. Hum Pathol Jun 2006; 37(6):726-34 3. Bostwick DG, Eble JN (eds): Urologic surgical pathology. St Louis Mosby, 2000 Pgno 4. Greene LF, O’Dea MF, Dockerty MB. Primary transitional cell carcinoma of prostate. J Urol 1976; 116:235-37 5. Karpas CM, Moumgis B. Primary transitional cell carcinoma of the prostate: possible pathogenesis and relationship to reserve cell hyperplasia of prostatic periurethral ducts. J Urol 1969;101:20105 6. Stephen W. Hardeman and Mark S Soloway. Transitional cell carcinoma of prostate : Diagnosis, staging and management. World J Urol. 1988;6:170-74 7. Varghese SL, Grossfeld GD. The prostatic gland : malignancies other than adenocarcinomas. Radiol Clin North America 2000; 38 : 179-202 8. Cho JY. Prostate In: Kim S H editor. Radiology Illustrated: Uroradiology. Philadelphia, P A:Saunders, 2003:571-606 9. Pickup M, VanTH, Der Kwast. My approach to intraductal lesions of the prostate gland. J clin Pathol 2007;60(8):856-65 10. David J Grignon. Unusual subtypes of prostate cancer. Modern Pathology. 2004;17:316-27 11. Wadhwa P, Mandal AK, Singh SK, Goswami AK, Sharma SC, Joshi K et al., Primary transitional cell carcinoma of the prostate presenting as a rectal ulcer. Urol Int. 2004; 72(2):176-77 12. Chang JM, Lee HJ, Lee SE, Byun SS, Choe GY, Kim Sh etal., Unusual tumours involving the prostate : radiological – pathological findings. British journal Of Radiology.2008;81: 907-15 13. Oliai BR, Kahane H, Epstein JI. A clinicopathologic analysis of urothelial carcinomas diagnosed on prostate needle biopsies. Am J surg pathol 2001;25:794-801 Int J Med res Health Sci. 2014;3(1):212-215 214 14. Young RH, Sringley JR, Amin MB. Variants of prostatic adenocarcinoma, other primary carcinomas of prostate and secondary carcinoma. In: Tumours of the prostate gland, seminal vesicles, male urethra and penis. Armed forces institute of pathology: Washington D C, 2000,21755 15. Xiaoqing Yang, Chen Xu, Jianing Guo, Chunrui Yang, Yuming Yang, and Ruifa Han. A novel subtype of primary prostatic adenocarcinoma : A case report. Oncol Lett. 2013; 6(5): 1303–06 16. Epstein JI., PSA, PAP as immunohistochemical markers in prostate cancer. Urol Clin North Am. 1993;20:757–70 17. Bassily NH, Vallorosi CJ, Akdas G, Montie JE, Rubin MA. Coordinate expression of cytokeratins 7 and 20 in prostate adenocarcinoma and bladder urothelial carcinoma. Am J Clin Pathol. 2000;113:383–88 Vandana et al., Int J Med res Health Sci. 2014;3(1):212-215 215 DOI: 10.5958/j.2319-5886.3.1.047 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Received: 28th Nov 2013 Case report Coden: IJMRHS Copyright @2013 ISSN: 2319-5886 th Revised: 18 Dec 2013 Accepted: 21st Dec 2013 EARLY OCULAR FINDINGS IN A PATIENT OF MAROTEAUX-LAMY SYNDROME *Haldipurkar Tanvi S1, Misra Somen2 1 Post graduate student, 2Professor, Department of Ophthalmology, Pravara Institute of Medical Sciences, Loni, Maharashtra, India *Corresponding author email:
[email protected] ABSTRACT The Maroteaux-Lamy disease or mucopolysaccharidosis type VI is an inherited severe metabolic disorder which is very rare. It is caused by a deficiency of the enzyme Arylsulfatase B and characterized by a heterogeneous clinical, radiological and genetic presentation. We report a case of Maroteaux-Lamy syndrome in a child aged 9 years whose diagnosis was suspected clinically by the combination of a dysmorphic syndrome, prominent ophthalmological signs, hepatomegaly and normal intelligence. Keywords: Maroteaux- Lamy, cloudy cornea, retinopathy INTRODUCTION The mucopolysaccharidoses (MPSs) are a group of disorders caused by inherited defects in lysosomal enzymes resulting in widespread intra- and extracellular accumulation of glycosaminoglycans (GAG). Mucopolysaccharidoses are caused by a reduction in the activity of specific lysosomal enzymes involved in the breakdown of GAG, which results in a wide spectrum of clinical manifestations. They may present as a mild type which is compatible with a normal lifespan or may be fatal in the first few months of life.1 They have been subdivided according to the enzyme defect and systemic manifestations. They include MPS IH (Hurler), MPS IS (Scheie), MPS IH/S (Hurler/Sheie), MPS II (Hunter), MPS III (Sanfilippo), MPS IV (Morquio), MPS VI (Maroteaux-Lamy), MPS VII (Sly) and MPS IX (Natowicz). The Mucopolysaccharidoses have a spectrum of systemic manifestations, including airway and respiratory distress, skeletal deformities, ophthalmological, intellectual and neurological impairment, cardiac abnormalities, and gastrointestinal problems1. Ocular findings are common in mucopolysaccharidosis and occasionally can manifest with significant visual Tanvi et al., impairment. Corneal opacification of varying severity is frequently seen which prompts the paediatrician to refer a patient to the ophthalmologist. Other ocular findings may include retinopathy, optic nerve swelling and optic atrophy, ocular hypertension, and glaucoma.2 CASE A 9 year old male child presented to our out-patient department (OPD) with complaints of diminution of vision in the eyes, stunted growth and coarse facial features (Fig 1). His father had noticed the stunted growth and coarse facial feature since two years. On inquiry, the child had mild bone aches, joint pain and restricted joint movements in the region of wrists and neck. He gave complaints of diminution of vision for the past two years for both distance and near. The patient’s father also noticed whitening of both corneas which prompted him to bring the child to the ophthalmology OPD. The parents of the boy had a second degree consanguineous marriage. He had an elder male sibling with no similar complaints and no positive family history suggestive of a metabolic Int J Med Res Health Sci. 2014;3(1):216-219 216 disorder. The boy had previously visited more than one general practitioner for stunted growth but was misdiagnosed as malnutrition. We did a complete ophthalmological and systemic examination of the child along with blood investigations which revealed the diagnosis of mucopolysaccharidosis type VI (Maroteaux-Lamy).3 On ophthalmological examination we found the vision to be 6/36 and 6/60 in the right and the left eye respectively. Best corrected vision was 6/9 in both eyes with a refractive error of +0.75/-1.00 X 55o, +1.00/-1.50 X 105o in right (RE) and left (LE) eye respectively. On external examination with slit lamp biomicroscopy, patient had bilateral diffuse epithelial haze (Fig 2) with reduced central convexity of the corneas. Corneal topography with Allegro Oculyzer (Wavelight AG, Germany) showed central corneal flattening (Fig. 3) with a keratometry values as follows: RE -K1: 39.6D K2: 40.2D, LE -K1: 39.3D K2: 40.4D. Intraocular pressure (IOP) with an applanation tonometer was 16 and 18mm Hg in the right and left eyes respectively. Central corneal thickness noted was 555µm and 520µm respectively. On electrophysiological testing, the electroretinogram (ERG) showed a bilateral reduced sensitivity of photoreceptors especially cones. Optical coherence tomography (OCT) of the retinal nerve fibre layer and macula was within normal level. On systemic evaluation the child showed the most signs of MPS, namely stunted growth, skeletal deformity with skeletal dystosis multiplex demonstrated on X-ray (Fig 4), and cardiac involvement with non-rheumatic affection of the cardiac valves which was confirmed by 2D echography. Urine was positive for mucopolysaccharidosis and a confirmatory diagnosis was done by assessing the arylsulphatase B enzyme levels in the blood3. Spectrophotometric assay using para nitro catchecol sulphate and flurimetric assay using 4-methyl umbelliferone showed a low level of aryl sulphatase B 12.6 nmol/hr/mg (normal-115-226). Fig 1: Stunted growth with coarse facial features (Photograph taken after consent from of the patient’s father) SUBEPITHELIAL DEPOSITS SEEN AS CLOUDING Fig 2: Subepithelial haze seen under slit lamp examination (cloudy cornea) Fig 3: Corneal topography showing central lattening Fig 4: X-ray showing skeletal dystosis multiplex with short, broad metacarpals and phalanges Tanvi et al., Int J Med Res Health Sci. 2014;3(1):216-219 217 DISCUSSION Maroteaux- Lamy syndrome (mucopolysaccharidosis type VI) is a disorder of lysosomal storage. It is characterised by a defect in the production of the enzyme arylsulphatase B. This causes abnormal deposition of the GAG, dermatan sulphate. The mucopolysaccharidoses are caused by a specific deficiency of lysosomal enzymes which lead to the deposition of glycosaminoglycans in various organs in the body. This may give rise to a wide spectrum of clinical phenotypes. The deposition of the GAG is seen in many organs and tissues in the body. Patients with the severe form of MPS I, MPS II and MPS VI present early to the clinician, as their respiratory, cardiac and skeletal deformities make the diagnosis straight forward. In case of mild forms of MPS I, MPS III, MPS IV, careful examination may reveal the corneal clouding and thereafter a paediatric reference is often made. The deposition of GAG within the layers of the cornea gives it a cloudy appearance.2 Detailed ophthalmological examination often becomes difficult owing to the corneal opacification, thickening and due to the physical and mental capabilities of most patients. MPS VI may present as a wide spectrum of clinical features, but all the affected children are intellectually normal. This was true in our case which prompted the child to complain about his poor vision. Individuals with Maroteaux- Lamy disease have short stature, coarse facial features, restrictive joint problems and hepatosplenomegaly. Some other features include middle ear disease, sensorineural deafness, upper airway problems and cardiomyopathy. Ocular findings in MPS VI are progressive increased corneal opacification and corneal thickening. Patients may however present with clear corneas. Raised IOP and both acute and chronic angle closure glaucoma have been reported in MPS VI.4 Optic nerve involvement in the form of swelling and optic atrophy has also been seen.5, 6 However among the various MPS syndromes, Maroteaux- Lamy disease has a less severe phenotype with mild skeletal deformities and a longer lifespan. Since the ocular findings are progressive in nature, the role of the ophthalmologist becomes paramount. The increased life span of these children due to the advent of the bone marrow transplant and the enzyme replacement therapy has widened the scope for their ocular treatment.7 Tanvi et al., Our case was unique due to isolated ophthalmological symptoms. On examination, we found the other signs suggestive of MPS VI and then further reference was made.8 The child had a normal intellect with coarse facial features and skeletal deformities. Cardiac involvement was seen however the respiratory system is unaffected at this time. Ocular involvement with corneal opacification with corneal flattening was seen. On investigation delayed cones response was seen on ERG testing suggesting a retinopathy.9 The child needs to be tested on a regular basis for any development of glaucoma4, worsening of the corneal clarity or other complications which may reduce his quality of life and require appropriate treatment. CONCLUSION Mucopolysaccharidoses are a complex group of diseases which are rare and difficult to diagnose as well as treat. The patient may present to any specialty of medicine due to its varied presentation. It becomes imperative on the clinicians part that a careful and meticulous examination is done which can help diagnose this disease. Ophthalmological involvement, although rare as an initial finding, should definitely be kept in mind when facing a case of mucopolysaccharidosis. REFERENCES 1. Muenzer J. The mucopolysaccharidoses: a heterogeneous group of disorders with variable pediatric presentations. J Pediatr 2004;144(5 Suppl): 27-34 2. Ashworth JL, Biswas S, Wraith E, Lloyd IC. The ocular features of the mucopolysaccharidoses. Eye.2006;20 :553–63 3. Lehman TJA, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology 2011;50 (Suppl 5):v41-v48 4. Cantor LB, Disseler JA, Wilson FM 2nd. . Glaucoma in the Maroteaux-Lamy syndrome. Am J Ophthalmol 1989;108:426-30 5. Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol.2006;51 :1–17 6. Summers CG, Ashworth JL. Ocular manifestations as key features for diagnosing mucopolysaccharidoses. Rheumatology 2011;50 (Suppl 5):v34-v40 Int J Med Res Health Sci. 2014;3(1):216-219 218 7. Giugliani R, Harmatz P, Wraith JE.. Management guidelines for mucopolysaccharidosis VI. Pediatrics.2007;120(2):405-18 8. Muenzer J. Overview of the mucopolysaccharidoses. Rheumatology 2011;50 (Suppl 5) :v4-v12 9. Suppiej A, Rampazzo A, Cappellari A, Traverso A, Tormene AP, Pinello L et al. The Role of Visual Electrophysiology in Mucopolysaccharidoses. J Child Neurol. 2013;28(10):1203-09 Tanvi et al., Int J Med Res Health Sci. 2014;3(1):216-219 219 DOI: 10.5958/j.2319-5886.3.1.048 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS Copyright @2013 ISSN: 2319-5886 th th Received: 9 Dec 2013 Revised: 23 Dec 2013 Accepted: 26th Dec 2013 Case report SYNCHRONOUS OCCULT METASTASISING DUODENAL CARCINOID AND OVARIAN MUCINOUS CYSTADENOCARCINOMA – MULTIPLE PRIMARY MALIGNANCIES IN THE SAME PATIENT *Devadass Clement W1, Sridhar Honnappa1, Aarathi R Rau1, Sharat Chandra2 1 Department of Pathology, M.S. Ramaiah Medical College, Bangalore, India Department of Surgical Oncology, M.S. Ramaiah Medical College, Bangalore, India 2 *Corresponding author email:
[email protected] ABSTRACT Gastrointestinal carcinoid tumors are uncommon neuroendocrine tumours that may be associated with synchronous or metachronous primary tumours of other histological type, most frequently colorectal adenocarcinomas. Primary ovarian mucinous adenocarcinomas have been reported to coincide with few other ovarian tumours and minority of these tumours may occur in association with Lynch syndrome. However association of duodenal carcinoid with ovarian mucinous adenocarcinoma is distinctly unusual and, to our knowledge, has not been previously described. We report a case of occult metastasising duodenal atypical carcinoid that was incidentally detected during surgical intervention performed for left ovarian mucinous cystadenocarcinoma in a middle aged female. The carcinoid tumour was Stage IIIB with regional nodal metastasis and the ovarian tumour was Stage IA with low grade histology. Key words: Duodenal carcinoid, multiple primary malignancies, synchronous tumours. INTRODUCTION Synchronous and metachronous “Multiple primary malignancies” (MPM) are relatively rare with an overall occurrence rate between 0.73% to 11.7%.1-3 About 20-29% of small intestinal carcinoid tumours (CT’s) are associated with synchronous or metachronous primary non-carcinoid tumours, with colorectal adenocarcinomas being the commonest.4, 5 Primary ovarian mucinous carcinoma have been reported in conjunction with other ovarian tumors like teratoma, Brenner tumour, and Sertoli-Leydig cell tumour and some occur in the setting of Lynch syndrome.6 However the simultaneous occurrence of duodenal CT, which is rare, and ovarian mucinous cystadenocarcinoma, which according to recent studies constitutes only 3% all ovarian cancers, in the same patient is unusual. We present a case of metastasising duodenal CT that was incidentally detected during Devadass et al., treatment of ovarian mucinous cystadenocarcinoma in middle aged female. CASE REPORT A 40 year old female presented with pain and mass per abdomen of one year duration. She also complained of progressively increasing intermittent episodes of respiratory distress, diarrhoea, palpitations and weight loss. She denied history of prolonged therapy with H2 blockers and family history of malignancies. Abdominal examination revealed firm lobulated central pelvic mass. Abdomino-pelvic computed tomography revealed a large complex cystic ovarian mass [Figure 1]. A complete digestive tract endoscopy, chest X-ray and gastric and colonic biopsies were normal. Laparotomy showed a left ovarian tumour, the frozen sections of which revealed mucinous Int J Med Res Health Sci. 2014;3(1):220-223 220 adenocarcinoma. In addition an area of intramural thickening was present in D1 duodenal segment with associated serosal puckering, omental adhesions and enlarged adherent sub-pyloric nodes suggestive of metastasis/implants. The paraaortic lymphnodes were also enlarged. A clinical FIGO Stage IIIC was assigned and total abdominal hysterectomy, bilateral salpingoophorectomy and pelvic lymphadenectomy, omentectomy, appendicectomy and sampling of duodenal serosal nodularity, sub-pyloric and paraaortic nodes was performed. Fig 1: Abdomino-pelvic computed tomography showing a large complex cystic ovarian mass. Pathological findings: Gross examination revealed a tensely cystic, bosselated left ovarian mass, measuring 23x18x10 cm with intact capsule and multilocular mucoid cut surface with mural ragged solid and nodulocystic areas exhibiting foci of necrosis and haemorrhage [Figure 2]. Microscopy revealed a well differentiated mucinous cystadenocarcinoma with expansile pattern of invasion, grade 1 (Universal grading system) [Figure 3]. 2: Multiloculated left ovarian mass with mural ragged solid and nodulocystic areas (O), enlarged subpyloric nodes (SP) with greater omental adhesions (GO) and unremarkable appendix (A). Fig Devadass et al., Fig 3: A- Ovarian mucinous adenocarcinoma with architecturally complex papillary cystic areas, BExpansile pattern of invasion; C- Glandular formations lined by disorderly epithelium exhibiting moderate nuclear atypia (x400 H&E). The pathological examination of the uterus, right ovary, bilateral fallopian tubes, bilateral pelvic and paraortic lymphnodes, appendix and peritoneal washings revealed no significant abnormality. The microscopy of the duodenal serosal nodularity revealed a histologically different tumour composed of organoid formations of relatively monotonous cuboidal cells exhibiting stippled chromatin and mitotically active nuclei (4-5/10HPF) consistent with Neuroendocrine tumour, grade II (Atypical carcinoid) [Figure 4]. This was further confirmed by immunohistochemistry which revealed positive staining of pan-cytokeratin and chromogranin in the tumour cells with a 40% Ki67 index [Figure 5]. The 3 subpyloric lymphnodes isolated revealed metastasis of the neuroendocrine tumour (pN1) Fig 4: A- Subpyloric lymph node (LN) with metastatic carcinoid tumour (CT); B- Duodenal serosal nodule showing Atypical carcinoid; C- Atypical carcinoid showing monotonous cells exhibiting stippled chromatin and mitotically active nuclei (arrows) (x400 H&E). Int J Med Res Health Sci. 2014;3(1):220-223 221 Fig 5: Duodenal tumour showing A- positivity for Pan Cytokeratin; B- positivity for Chromogranin; CNuclear positivity for Ki-67 [x400]. Further, extensive sampling of the ovarian tumour failed to reveal any teratomatous/ carcinoid component. A final diagnosis of Left ovarian mucinous cystadenocarcinoma, pT1aG1 pN0 pM0, TNM/FIGO Stage IA with synchronous duodenal Neuroendocrine tumour, grade II, TNM Stage IIIB was made. DISCUSSION CT’s are relatively uncommon slow growing neuroendocrine tumours, derived from enterochromaffin cells, that are capable of secreting vasoactive substances and 73-85% of these tumours occur in the gastrointestinal tract (GIT).7 Duodenal carcinoids are rare , accounting for < 2% of all GIT carcinoids, with an annual incidence of 0.07/100,000.5 About 91% have metastasis at time of detection presumably because they are difficult to diagnose and majority are asymptomatic and behave in an indolent form.5 Clinical features are varied and depend on the anatomic location, tumour size and metastasis and majority are incidentally detected. 8 They may present as carcinoid syndrome with cutaneous flushing, diarrhoea palpitations, abdominal pain and bronchospasm. G-cell tumours followed by D-cell tumours account for majority of duodenal CT’s, the former may occur with multiple endocrine neoplasia type 1 and the latter may occur with neurofibromatosis type 1. Unlike their midgut and hindgut counterparts, proximal duodenal CT are less well characterized and exhibit variable biological course necessitating individualised treatment strategy for each patient.9 Devadass et al., In the present case the patient had palpitations, diarrhoea and respiratory distress, all of which were attributed to the huge ovarian tumour. The duodenal CT was detected incidentally during the surgical treatment of the associated ovarian malignancy. CT’s may be associated with other synchronous primary malignant tumours. Berner M et al reported that out of 270 GIT CT’s analysed 7.8% had synchronous primary malignancy, two thirds of which were colorectal adenocarcinomas and 80% of which were detected during the treatment of the other associated malignancy. 10 Mullen et al reviewed 24 duodenal CT’s and found that 38% had synchronous or metachronous non-carcinoid malignancies, 77.8% of which were adenocarcinomas. 9 Associated ovarian malignancies were not detected in these studies. We describe the first case, to our knowledge, of a duodenal CT and a simultaneous ovarian mucinous cystadenocarcinoma. The mechanisms involved in the occurrence of MPM have not been fully explained. Genetic susceptibility, failure of immunological surveillance and exposure to carcinogens has been implicated.1, 2, 4 Some authors have hypothesised that CT’s produce growth factors which may determine neoplastic transformation or influence tumour growth at other sites.4 It has been reported that prognosis of patients with synchronous CT’s and non-carcinoid tumours is determined by the stage of the non-carcinoid tumour rather than the CT. 10 This probably is applicable for those cases wherein the CT component is nonmetastasising.4, 5 In the present case the ovarian malignancy was well differentiated and FIGO stage I, with an excellent prognosis and 5 year survival rate of 95%.6 The CT had regional node metastasis with Stage III B, and logically will determine the survival of this patient. The five year survival rate for CT’s with only local spread is 88% in contrast to 25% for those with metastasis.5 Combined curative resection is the treatment of choice for synchronous MPM.1, 2 However, in this case a second malignancy was not suspected pre-operatively. Pancreaticoduodenectomy is the subsequent treatment in the management, which will be done after she recovers from the first surgery. CONCLUSION The possibility of MPM should always be considered in the pre-operative evaluation. The association of Int J Med Res Health Sci. 2014;3(1):220-223 222 CT’s with colorectal adenocarcinomas and ovarian mucinous adenocarcinomas with other primary ovarian tumours and Lynch syndrome have been described. As the management may differ in the finding of a second primary, we should not limit ourselves to these known associations. The clinicians should be aware of this rare entity so that pre planned stage specific treatment may be delivered resulting in better outcome. REFERENCES 1. Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple Primary Malignancies- Epidemiological Analysis at a Single Tertiary Institution. J Gastrointestin Liver Dis 2010;19:69-73 2. Anania G, Santini M, Marzetti A, Scagliarini L, Vedana L, Resta G, et al. Synchronous primary malignant tumours of the breast, caecum and sigma. Case report. G Chir 2012;33:409-10 3. Demandante CG, Troyer DA, Miles TP. Multiple primary malignant neoplasms; case report and a comprehensive review of the literature. Am J Clin Oncol 2003;26:79-83 4. Gurzu S, Bara T Jr, Bara T, Jung I. Synchronous intestinal tumours: aggressive jejunal carcinoid and sigmoid malignant polyp. Rom J Morphol Embryol 2012;53:193-96 5. Gao L, Lipka S, Hurtado-Cordovi J, Avezbakiyev B, Zuretti A, Rizvon K, et al. Synchronous Duodenal Carcinoid and Adenocarcinoma of the Colon. World J Oncol 2012;3:239-42 6. Soslow RA. Mucinous Ovarian Carcinoma: Slippery business. Cancer 2011; 117:451-53 7. Babovic-Vuksanovic D, Constantinou CL, Rubin J, Rowland CM, Schaid DJ, Karnes PS. Familial Occurrence of Carcinoid Tumors and Asssociation with Other Malignant Neoplasms. Cancer Epidemiol Biomarkers Prev 1999;8:715-19 8. Erbil Y, Barbaros U, Kapran Y, Yanik BT, Bozbora A, Ozarmaoan S. Synchronous Carcinoid Tumour of the Small Intestine and Appendix in the Same Patient. West Indian Med J 2007;56:187-89 9. Mullen JT, Wang H, Yao JC, Lee JH, Perrier ND, Pisters PWT, et al. Carcinoid tumours of the duodenum. Surgery 2005;138:971-78 10. Berner M. Digestive carcinoids and synchronous malignant tumors. Helv Chir Acta. 1993;59:75766 Devadass et al., Int J Med Res Health Sci. 2014;3(1):220-223 223 DOI: 10.5958/j.2319-5886.3.1.049 International Journal of Medical Research & Health Sciences www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS th Received: 12 Dec 2013 Revised: 26th Dec 2013 Case report Copyright @2013 ISSN: 2319-5886 Accepted: 31st Dec 2013 SYNCHRONOUS POORLY DIFFERENTIATED GASTRIC ADENOCARCINOMA WITH GASTROINTESTINAL STROMAL TUMOR: A CASE REPORT Magdalene K. F. Professor in Pathology, Sree Narayana Institute of Medical Sciences, Chalaka, Kerala, India *Corresponding author email:
[email protected] ABSRACT Gastrointestinal stromal tumor (GIST) is categorized as a mesenchymal tumor. In the abdomen more than half occur in the stomach. Adenocarcinoma is the most common epithelial malignancy of stomach comprising over 90% of all gastric cancers. The simultaneous occurrence of both these tumors together is rare. This is an interesting case report of a 54 year old lady with synchronous occurrence of GIST and poorly differentiated adenocarcinoma of intestinal type. A brief review of literature is done regarding the reported cases and proposed hypothesis. Keywords: Poorly differentiated carcinoma, GIST, Synchronous INTRODUCTION The most common gastric tumors are epithelial tumors. Adenocarcinomas constitute the most common type of epithelial gastric tumors. Gastrointestinal stromal tumors (GIST) are non epithelial tumor which can occur in the stomach. In the gastrointestinal tract 1% of all malignancies1, 2 and 5.7% of sarcomas3 are accounted by GIST. GISTs and adenocarcinomas have two separate histogenesis. It is extremely rare for the co-existence of GIST and adenocarcinoma. GISTs have been reported in the literature to coexist with tumors of different histogenesis such as adenocarcinomas, carcinoids, MALT lymphomas and Burkitt’s lymphomas 4,5,6, as well as with different mesenchymal tumors.7-13 Here is a case report of a 54 year old lady with poorly differentiated adenocarcinoma and synchronous gastrointestinal stromal tumor which was incidentally detected. CASE REPORT A 54 year old lady was admitted with vomiting, following food intake, of 3weeks duration. There was associated abdominal discomfort and belching. She gave a history of loss of appetite and weight loss which was of 3 months duration. On general examination the patient was emaciated and pale. The systemic examination was unremarkable. Blood routine was normal except for the low hemoglobin level (5gm%). Urine routine was normal. Ultrasonograghy showed diffuse thickening of the gastric pyloric antral wall. Magdalene Oesophagogastroduodenoscopy showed multiple ulcerations with hypertrophied margins in the lesser curvature and antrum and the impression was gastric outlet obstruction. Endoscopic biopsy done showed microscopic features of a poorly differentiated carcinoma. A lower radical gastrectomy was done and the specimen was received in the histopathology lab. An ulcerating infiltrating neoplasm measuring 30x25mm was detected in the lesser curvature adjacent to which another nodular firm grey white mesenchymal neoplasm measuring 25x20mm was also Int J Med Res Health Sci. 2014;3(1):224-227 224 noted [Figure1]. The microscopy of the ulcerating tumor showed features of a poorly differentiated intestinal type adenocarcinoma [Figure 2]. The tumor was infiltrating the full thickness of the gastric wall and extended to the serosal fat of the lesser curvature. Four out of nine lymph nodes showed evidence of metastasis. Fig 3b: Microscopy of gastrointestinal stromal tumor showing the sheet- like and fascicular arrangement of spindle shaped cells (H&E X 40x) Fig 1: Ulcerating infiltrating gastric carcinoma in the lesser curvature of stomach (blue arrow) with adjacent nodular firm grey white gastrointestinal stromal tumor (red arrow) Fig 2: Microscopy of poorly differentiated intestinal type adenocarcinoma in the gastric wall (H&E X 10x) The adjacent nodular firm white neoplasm showed microscopic feature of a submucosal spindle cell mesenchymal neoplasm which was circumscribed. A fascicular and sheet like arrangement of plump spindle shaped cells were noted [Figure 3a,b]. Mitotic activity was less than 5/50 HPF. No areas of necrosis were found. Based on the mitotic count of less than 5/50 HPF and size of the tumor less than 5 cm, the histological diagnosis was GIST-low risk type. Immunohistochemical markers were advised for confirmation of GIST. Immunohistochemical markers were done for the identification of origin of the tumors. The mesenchymal neoplasm was CD 117 (c-kit protein) moderately to strongly positive demonstrating a combined membranous and diffuse cytoplasmic staining pattern. Additionally, CD 34 protein was observed to be membranous stain positive, whereas S100, desmin and SMA demonstrated negative or very weak reactivity. The poorly differentiated intestinal type adenocarcinoma was cytokeratin positive. A final report of synchronous poorly differentiated intestinal type adenocarcinoma and GIST (low risk type) was arrived. Since intestinal type adenocarcinomas could be due to Helicobacter pylori they were searched in the gastric mucosa but were not detected microscopically. The resected gastric margins and omentum were free of neoplasm. The postoperative course was uneventful. Following surgery the patient received adjuvant chemotherapy, but unfortunately died of progressive disease 16 months later. Fig 3a: Microscopy of circumscribed submucosal spindle cell gastrointestinal stromal tumor (H&E X 10x) Magdalene Int J Med Res Health Sci. 2014;3(1):224-227 225 DISCUSSION GIST was named in the earlier literature as leiomyomas, schwannomas, leiomyosarcomas and leiomyoblastomas. Electron microscopy and immunohistochemical stains recognized it as a distinct entity.14 Mazur and Clark15 introduced the term GIST in 1983. The synchronous occurrence of GIST and gastric carcinomas are rare. A few reports of simultaneous presence of poorly differentiated adenocarcinoma and GIST have been reported.7-13 Most of the adenocarcinomas were detected after endoscopic biopsies. GIST was diagnosed as an incidental finding. No high risk types of GIST have been reported in association with gastric carcinoma .The tumors were mostly less than 5cm.Recently Karahan N et al.16 have reported in a neurofibromatosis type-1 patient with development of simultaneous multiple GIST and signet ring cell carcinoma. The synchronous occurrence of these two tumors has excited many and it raises the question as to why they occur together. The reason for the simultaneous origin of GIST and adenocarcinoma may be due to coincidence. Gene mutations were another reason that was proposed. Recently Yan Y et al 17 conducted molecular analysis and clinicopathological profile of KIT/PDGFRA in both these tumors. No relationship was obvious according to this study. H. pylorus is another cause that may be considered. H. pylori can cause simultaneous development of gastric carcinoma and lymphoma 7. Such a relationship with GIST is not proved yet. In the present case study no H. pylori could be detected. Another hypothesis is the role of carcinogenic agent. It may act on neighboring tissues and may lead to the development of tumors in the same organ with different histogenesis.18, 19 CONCLUSIONS The synchronous occurrence of a GIST with gastric carcinoma is rare, and little is known about this association. Coexisting GISTs are in most cases small, asymptomatic tumors and are detected incidentally during surgery for gastric carcinomas. Hence specimens should be handled cautiously to detect associated lesions. Since most of the cases were poorly differentiated adenocarcinomas further studies are needed to know whether the associated GIST Magdalene influenced the differentiation of the tumor. Molecular studies are also further needed to explain the simultaneous development of tumors of different histogenesis. Disclosure of conflicts of interest: The author declares that there is no financial relationship with any organization in this case study and that there is no conflict of interest. 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