Publications by authors named "Muhammad Almas Hashmi"

14 Publications

  • Page 1 of 1

Emerging Antimicrobial Resistance in Neonatal Sepsis.

J Coll Physicians Surg Pak 2020 Dec;30(12):1312-1315

Department of Paediatrics, Fauji Foundation Hospital, Rawalpindi, Foundation University, Islamabad, Pakistan.

Objective: To determine the frequency and antimicrobial sensitivity pattern of microbial agents causing neonatal sepsis.

Study Design: Descriptive study.

Place And Duration Of Study: Neonatal ICU, Fauji Foundation Hospital, Rawalpindi; Foundation University, Islabambad, from May 2017 to April 2019.

Methodology: Data of all neonates admitted with sepsis during study period was retrieved from computer database. Age at admission, gender, duration of hospital stay and culture reports were recorded. Culture positive patients were further analysed regarding their antibiotic sensitivity.

Results: A total of 1,070 neonates, male:female = 1.36:1, mostly newborn, were included in the study. Total mortality was 182 (17%). Blood culture was positive in 79 (7.4%). Gram positive organisms were identified in 37 (46.8%) Staphylococci in 29 (36.7%), Enterococci 7 (8.9%), Corynebacterium species in 1 (1.3%). Gram negative were isolated in 42 (53.2%) Acinetobacter Baumanni in 14 (17.7%), Klebsiella in 12 (15.2%), Enterobacter spp. In 7 (8.8%), E.coli in 5 (6.3%), Pseudomonas in 2 (2.5%) and Proteus in 1 (1.3%) and Serratia in 1 (1.3%) each. Sensitivity pattern of Gram positive organisms was: vancomycin 30/37 (81.1%), ciprofloxacin 13/37 (35.1%) and Gentimicin 12/37 (32.4%). Gram negative organisms sensitivity pattern was: meropenem 12/42 (28.6%), chloramphenical 10/42 (23.8%), gentimicin 6/42 (14.3%), ciprofloxacin 5/42 (11.9%). Highly resistant strains of Klebsiella (13/14) and Acinitobacter (5/12) were sensitive to colomycin only.

Conclusion: Common organisms responsible for neonatal sepsis were Styphylococci, Acinitobacter, Klebsiella and E.Coli. Gram positive organisms showed sensitivity to vancomycin and gentamicin. Gram negative organisms were highly sensitive to colomycin. Key Words: Neonatolgy, Neonatal sepsis, Antimicrobial sensitivity, Neonatal mortality.
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http://dx.doi.org/10.29271/jcpsp.2020.12.1312DOI Listing
December 2020

ATP7B Mutation Analysis: Wilson Disease, A Difficult to Diagnose Case.

J Coll Physicians Surg Pak 2020 04;30(4):433-434

Department of Pediatrics, Foundation University, Islamabad, Pakistan.

Wilson's Disease (WD) is a common metabolic disorder predominantly involving liver, brain, and eyes. Pancreatic, renal, psychiatric, and cardiac involvement have also been described. No single investigation can be considered diagnostic of WD; therefore, diagnosis is based upon a series of tests best interpreted using Wilson disease diagnostic index (WDDI). We present a difficult-to-diagnose, 9-year girl of consanguineous parents, with chronic liver disease and portal hypertension. Initial workup was equivocal with significantly low serum ceruloplasmin, normal urinary copper excretion and absent Kaiyser-Fleischer (KF) rings. Diagnosis was established by ATP7B mutation analysis. The patient was found homozygous for c.3955C>T (p.Arg1319Ter) in exon 19, a rare mutation described in literature, which results in premature truncation of peptide chain. Key Words: ATP7B, Wilson disease, Copper, Mutations, Hepatolenticular degeneration.
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http://dx.doi.org/10.29271/jcpsp.2020.04.433DOI Listing
April 2020

Genetic testing of two Pakistani patients affected with rare autosomal recessive Fanconi-Bickel syndrome and identification of a novel SLC2A2 splice site variant.

J Pediatr Endocrinol Metab 2019 Nov;32(11):1229-1233

Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan.

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive carbohydrate metabolism disorder caused by mutations in SLC2A2 encoding the glucose transporter 2 (GLUT2) protein. The clinical manifestations include hepatomegaly, conditional hypo/hyperglycemia, rickets, short stature and proximal renal tubular dysfunction. GLUT2 regulates monosaccharide homeostasis through sugar sensing and transmembrane transportation during high/low glucose levels. In the current study, we present two siblings suffering from FBS. The patients presented with doll-like facies, failure to gain weight and height, abdominal distension and firm hepatomegaly. The family had a history of deaths of twin male siblings in the neonatal period and twin female siblings at ages 10 months and 2.5 years, respectively. Clinical presentation and biochemical investigations including a complete blood count, electrolytes, liver and renal function tests suggested FBS. Mutation screening of SLC2A2 confirmed the diagnosis with identification of a novel homozygous splice site variant predicting an in-frame deletion [p.(Gly166-S169del)] in the GLUT2 protein. The in-silico analysis predicted the variant to affect the three-dimensional conformation of the fourth transmembrane helix of the encoded protein, rendering the non-functionality of GLUT2 in both patients of the family under study.
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http://dx.doi.org/10.1515/jpem-2019-0235DOI Listing
November 2019

Spectrum of UGT1A1 variants in Pakistani children affected with inherited unconjugated hyperbilirubinemias.

Clin Biochem 2019 Jul 27;69:30-35. Epub 2019 May 27.

Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address:

Inherited unconjugated hyperbilirubinemias are a group of disorders characterized by increased levels of serum unconjugated bilirubin and arise because of the imbalance between its production and elimination from the body. It includes Crigler-Najjar syndrome and Gilbert syndrome. Crigler-Najjar syndrome type 1 represents the extreme severe end of the spectrum with complete absence of hepatic bilirubin uridine diphosphoglucuronate glucuronosyltransferase (UGT1A1). Crigler-Najjar syndrome type 2 patients have intermediate levels of bilirubin owing to incomplete deficiency of UGT1A1, and Gilbert syndrome lies at the extreme mild end of the spectrum with only slightly raised bilirubin level. Here, we present spectrum of UGT1A1 genetic variants in 25 Pakistani children from 23 unrelated families affected with persistent unconjugated hyperbilirubinemias. The promoter region, coding exons and splice junctions of the UGT1A1 were PCR amplified and subjected to Sanger sequencing. Eleven sequence variants were identified underlying disease phenotype including a novel c.582delC variant. Overall, c.622_625dupCAGC was the most frequent variant followed by c.1021C>T found in Crigler-Najjar syndrome type 1 patients. The evaluation of promoter polymorphism A(TA)TAA in the affected children and their families further supported the body of evidence that the A(TA)TAA allele could enhance the effect of other structural variants in Crigler-Najjar syndrome patients. To our knowledge, this is the first comprehensive study on molecular genetics of persistent unconjugated hyperbilirubinemias from Pakistan. This study expands the spectrum of UGT1A1 variants and should help in improved clinical diagnosis, genetic counseling and prenatal diagnosis of the affected families.
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http://dx.doi.org/10.1016/j.clinbiochem.2019.05.012DOI Listing
July 2019

Identification of a novel mutation in a consanguineous Pakistani family affected by rare infantile GM1 gangliosidosis.

J Genet 2018 Dec;97(5):1445-1449

Medical Genetics Research Laboratory, Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan.

Monosialotetrahexosylganglioside (GM1) is a rare lysosomal storage disorder caused by the deficiency of beta-galactosidase (β-Gal) encoded by galactose beta 1 (). It is clinically characterized by developmental delay attributed to multifold accumulation of GM1 gangliosides in nerve cells. In this study, we present a case of infantile GM1 gangliosidosis in a consanguineous Pakistani family. The child was presented with developmental delay, hepatosplenomegaly and recurrent chest infections at 7.5 months of age. Radiological and biochemical investigations including magnetic resonance imaging (MRI), bonemarrow biopsy and urine oligosaccharide analyses suggested lysosomal storage disorder. Significantly low levels of β-Gal enzyme confirmed the diagnosis of GM1 gangliosidosis. DNA sequencing of identified a homozygous 2-bp deletion c.881-882delAT (p.Tyr294Terfs) in exon 8. analysis supported the deleterious effect of the variant. This study extends mutation spectrum and should benefit genetic counselling and prenatal diagnosis of the affected family.
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December 2018

Effectiveness and Safety of Sofosbuvir in Treatment-NäiveChildren with Hepatitis C Infection.

J Coll Physicians Surg Pak 2017 Jul;27(7):423-426

Department of Paediatric Gastroenterology and Hepatology, The Children's Hospital and The Institute of Child Health, Lahore.

Objective: To determine the effectiveness and safety of Sofosbuvir and Ribavirin combination in treatment-näivechildren with HCV infection.

Study Design: An experimental study.

Place And Duration Of Study: Gastroentrology, Hepatology Department, The Children's Hospital and The Institute of Child Health, Lahore, from January to December 2016.

Methodology: HCV PCR positive treatment-näivepatients, 5 to 18 years of age, were enrolled by consecutive nonprobability sampling. Clinical features and investigations including complete blood count, bilirubin, ALT, PTand HCV genotyping were done. All patients were started on Sofosbuvir 400 mg once daily and Ribavirin 10-15 mg/kg/day. Patients were followed on 4-weekly basis. PCR was done after 4 weeks; if positive then again at 12 weeks. End of treatment and 12 weeks post treatment PCR was done in all patients. Total duration of therapy was 24 weeks. Computer program SPSS version 20 was used for data analysis.

Results: Atotal of 35 patients with mean age of 10.24 ±2.80 years, including 22 boys (62.86%), and 13 girls (37.14%) were included. The most common HCV genotype was genotype 3 encountered in 27 (77.15%), followed by genotype 1 in 6 (17.14%), while 2 (5.71%) patients were untypable. Thirty (85.71%) patients achieved rapid virological response while the rest 5 (14.28%) had early virological response. End-of-treatment PCR was negative in all patients. SVR was achieved by 34 (97.14%) patients. The treatment was well tolerated. Headache was observed in 8 (22.86%) patients, which improved spontaneously.

Conclusion: Sofosbuvir and Ribavirin combination is highly effective in HCV genotypes 1 and 3 with no major undesirable short-term side effects.
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http://dx.doi.org/2657DOI Listing
July 2017

Spontaneous Perforation Of Bile Duct, Clinical Presentation, Laboratory Work Up, Treatment And Outcome.

J Ayub Med Coll Abbottabad 2016 Jul-Sep;28(3):518-522

Department of Paediatric Gastroenterology Hepatology, The Children's Hospital & the Institute of Child Health, Lahore, Pakistan.

Background: Spontaneous perforation of bile duct (SPBD) is a rare and often misdiagnosed entity. Though rare, it is the second most common surgical cause of jaundice in infants, after biliary atresia. This study was planned to determine the clinical presentation, study different diagnostic modalities, treatment and outcome of patients with spontaneous perforation of bile duct.

Methods: This descriptive case series, comprising 22 patients with spontaneous perforation of bile duct over a period of 24 months. Clinical presentation, biochemical abnormalities, imaging details, treatment options and outcome were studied.

Results: Total 22 patients (12 Males and 10 Females) between ages of 1.5-36 months were studied. Associated anatomical defects included choledochal cyst in 7 (31.8%) while acquired biliary atresia in 1 (4.5%). Elevated liver enzymes (ALT and AST) were present in 16 patients (72.7%) and 5 (22.7%) had bilirubin above 3 mg/dl. Coagulopathy was seen in 8 (36.6%) patients. Abdominal USG showed presence of ascites in all 22 (100%), hydrocele in 2 (9.0%), inguinal hernia in 1 (4.5%), choledochal cyst in 7 (31.8%) and atretic gall bladder suggestive of acquired biliary atresia in one (4.5%) patient. HIDA scan was diagnostic in all 17 (77.27%) in which it was performed. MRCP was done in 3 (13.6%) patients. Mortality frequency was 3/22 (13.6%); one died of post-surgical sepsis second one was cirrhotic at time of presentation and didn't make It. Two were lost to follow up one which died at home while we lost contact with fourth patient.

Conclusions: Spontaneous perforation of bile duct can present and should be suspected as an important cause of neonatal biliary ascites or peritonitis. Most patients can be managed with intravenous antibiotics, percutaneous drainage and ttube insertion while patients with choledochal cysts required cholecystectomy with roux en y choledochjejunostomy. Timely recognition and intervention is associated with favourable outcome.
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December 2017

Detrimental Complications Of Meconium Aspiration Syndrome And Their Impact On Outcome.

J Ayub Med Coll Abbottabad 2016 Jul-Sep;28(3):506-509

Department of Statistics The Children's Hospital & The Institute of Child Health, Lahore, Pakistan.

Background: Meconium aspiration syndrome (MAS) is respiratory distress in an infant born through meconium stained amniotic fluid (MSAF) whose signs cannot be otherwise explained. MAS is associated with different complications. Many studies have been conducted in developed world to find the outcome associated with MAS but data from developing countries is lacking. Present study was conducted to determine the impact of chemical pneumonitis, pulmonary hypertension (PHN) and air leak on outcome of new-borns with MAS.

Methods: This cross sectional descriptive study was conducted in a tertiary care Neonatology unit. The babies diagnosed with MAS were included in the study. All patients were monitored for development of complications. Outcome in terms of mortality was recorded. Outcome was compared by chisquare test and p-value <0.05 is considered significant.

Results: Seventy two babies were included in the study. Mean gestation was 37±0.56 weeks and birth weight was 2.87±0.49 kg. Male to female ratio was 1.57:1 and mean age of admission was 9.59±5.27 hours. Chemical pneumonitis, PHN and chemical pneumonitis with PHN were observed in 23.6%, 20.8% and 26.4% neonates respectively. Mortality rate was 19.44%. The mortality was highest in babies having chemical pneumonitis with PHN (p-value=0.013) followed by chemical pneumonitis group (p-value=0.02) and PHN group (p-value=0.032).

Conclusions: About three fourth babies with MAS developed one or more complications. Mortality is significantly increases with the development of complications so as more the complications more is the mortality.
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December 2017

Causes Of Chronic Non-Infectious Diarrhoea In Infants Less Than 6 Months Of Age: Rarely Recognized Entities.

J Ayub Med Coll Abbottabad 2017 Jan-Mar;29(1):78-82

Department of Paediatric Gastroenterology & Hepatology, The Children's Hospital and Institute of Child Health Lahore, Pakistan.

Background: Non-infectious causes of chronic diarrhoea are important and easily missed. The study was done with the objectives to identify different causes of chronic non-infectious diarrhoea in infants less than 6 months of age.

Methods: All patients less than 6 months of age presenting for the first time to a Paediatric Gastroenterology tertiary care centre with a history of chronic diarrhoea and negative stool cultures were enrolled over a period of 8 months. Demographical profile and various factors under observation were recorded in this observational study. Collected data was analysed using SPSS version 20. Chi square test was applied as a test of significance for any qualitative variable, p value (p<0.05) was taken as significant.

Results: Among 72 enrolled patients, female to male ratio was1.05:1. Age at onset of symptoms was between 15 days to 6 months. Aetiology found was Cow's milk protein allergy (CMPA) in 58 (80.6%), Primary intestinal lymphangiectasia (PIL) 6 (8.3%), Cystic fibrosis (CF) 3 (4.2%), Immunodeficiency (SCID) 2 (2.8%), 1 (1.4%) for each Abetalipoproteinemia (ABL), Glucose galactose malabsorption (GGM) and Congenital chloride diarrhoea (CCD).

Conclusions: Among noninfectious causes of chronic diarrhoea in early infancy, cow's milk protein allergy is most common followed by Primary intestinal lymphangiectasia and Cystic fibrosis.
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April 2019

Clinical Spectrum Of Solitary Rectal Ulcer In Children Presenting With Per-Rectal Bleed.

J Ayub Med Coll Abbottabad 2017 Jan-Mar;29(1):74-77

Department of Paediatric Gastroenterology, Hepatology & Nutrition, The Children's Hospital & The Institute of Child Health, Lahore, Pakistan.

Background: Solitary rectal ulcer syndrome (SRUS) is a benign and chronic disorder well known in young adults and less common in children. The objective of this study was to determine the frequency and clinical spectrum of solitary rectal ulcer in children with bleeding per rectum.

Methods: This study was conducted in the Department of Paediatric Gastroenterology Hepatology& Nutrition; The Children's Hospital & The Institute of Child Health, Lahore, from January-December 2015. Total 187 children presenting with per-rectal bleeding who underwent colonoscopy were entered in the study. Demographic and presenting clinical features; colonoscopy and histopathology findings were recorded. Data was analysed using SPSS-20.

Results: Out of a total of 187 children with bleeding per rectum, 21 (11.23%) were diagnosed with solitary rectal ulcer. Males were 15 (71.43%) and females were 6 (28.57%) with age range 8-12 years. Mucus in stool 14 (66.7%), constipation 12 (57.1%) and tenesmus 10 (47.6%) were the most common clinical presentations. Colonoscopic finding are solitary erythmatous ulcerative lesion was seen in 8 (38.09%) children, multiple ulcerative lesions in colon 6 (28.57%), multiple ulcerative lesions in rectum 5 (23.81%), polypoidal growth in colon and hyperaemic rectal mucosa in 1 (4.76%) each. Histopathological findings were consistent with SRUS in all the cases.

Conclusions: The frequency of SRUS was high (19.6%) in patients with per-rectal bleed. Mucus in stool, constipation and tenesmus were the most common clinical presentations. Colonoscopic and histopathological findings were helpful in the confirmation of the underlying aetiology.
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April 2019

Mucopolysaccharidoses - Clinical Spectrum and Frequency of Different Types.

J Coll Physicians Surg Pak 2017 02;27(2):80-83

Department of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital and The Institute of Child Health, Lahore.

Objective: To determine the relative frequency and clinical features of different varieties of mucopolysaccharidosis.

Study Design: Descriptive study.

Place And Duration Of Study: Department of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital and The Institute of Child Health, Lahore, from January 2013 to December 2015.

Methodology: All patients who had any feature suggestive of mucopolysaccharidosis were screened with detailed history, clinical examination and skeletal survey. Urine samples for glycosaminoglycan (GAGs) levels and dried blood samples for enzyme analysis were sent. Patients who were confirmed to be suffering from mucopolysaccharidosis were included in the study. The data was analysed using SSPS version 20.

Results: A total of 90 confirmed MPS cases, 52 males and 38 females, median age 42 months, were included. Hurler/Hurler-Scheie syndrome was the most frequent (75, 83.33%) followed by Morquio (6, 6.67%), Sanfilippo (5, 5.56%), Maroteaux-Lamy (3, 3.33%) and Hunter (1, 1.11%) syndromes. Consanguinity was present in 79 (87.78%) cases. Common features were hepatomegaly (80, 88.89%), coarse facies (70, 77.78%), splenomegaly (67, 74.44%), and bone disease (48, 53.33%).

Conclusion: Most common variety of mucopolysaccharidosis was Hurler/Hurler Scheie followed by Morquio syndrome. Most of the patients were born to consanguineous parents. Common clinical features were coarse facies, hepatosplenomegaly and dysostosis multiplex.
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February 2017

Diarrheal Versus Non-diarrheal Presentations of Paediatric Celiac Disease.

J Coll Physicians Surg Pak 2016 Aug;26(8):662-6

Department of Paediatrics, Benazir Bhutto Hospital, Rawalpindi.

Objective: To compare the frequencies and clinical features of diarrheal versus non-diarrheal presentation of celiac disease (CD).

Study Design: Cross-sectional study.

Place And Duration Of Study: Paediatric Department, Benazir Bhutto Hospital, Rawalpindi, from January to December 2013.

Methodology: Children with celiac disease, newly diagnosed on the basis of tissue transglutaminasel (TTG) and intestinal histopathology, were included in the study by consecutive non-probability sampling. Patients were divided into diarrheal and non-diarrheal groups on the basis of presence or absence of chronic or recurrent diarrhea. Comparison between two groups was done and a p-value < 0.05 was considered significant.

Results: Total patients were 54 (26 males, 28 females) with mean age of 6.67 ±3.35 years. Chronic diarrhea was present in 31 (57.4%) and absent in 23 (42.6%). Patients in non-diarrheal group were diagnosed at a significantly later age (p=0.038) and had a greater frequency of severe malnutrition (p=0.02). Short stature, anemia, rickets, clubbing and abdominal distension were equally prevalent. There was no significant difference in TTG value and intestinal histopathology among two groups.

Conclusion: Children with atypical presentation of CD had significant severe malnutrition and higher age at diagnosis than at diarrheal presentation.
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http://dx.doi.org/2400DOI Listing
August 2016

Accuracy of Anti-Tissue Transglutaminase IgA Antibody in the Diagnosis of Paediatric Celiac Disease.

J Coll Physicians Surg Pak 2016 Apr;26(4):263-6

Department of Medicine, Benazir Bhutto Hospital, Rawalpindi.

Objective: To determine the accuracy of anti-tissue transglutaminase IgA (TTG) antibody titer in the diagnosis of celiac disease, taking small intestine histopathology as the gold standard.

Study Design: Cross-sectional analytical study.

Place And Duration Of Study: Department of Paediatrics, Benazir Bhutto Hospital, Rawalpindi, from February to July 2013.

Methodology: Sixty patients aged 2 - 13 years, admitted in the Paediatric Department of Benazir Bhutto Hospital, Rawalpindi, having at least 3 features from chronic diarrhea, malnutrition, short stature, anemia, abdominal distension and clubbing, were included. Age, gender, weight and height were recorded. Abdominal distension and clubbing were clinically noted. For hemoglobin, blood complete picture was done. For determination of nutritional status and short stature, standard centile charts were used. TTG titer upper GI endoscopy, duodenal biopsy, and histopathology were done in all cases.

Results: There were 60 patients; 32 males, 28 females with mean age of 5.85 &plusmn;3.36 years. Frequency of CD was 63.33% in study population. Sensitivity of TTG was 86.84%, with 81.82% specificity, 89.19% positive predictive value, and 78.26% negative predictive value for diagnosing CD. TTG titre more than 50 iu/ml had a 100% positive predictive value.

Conclusion: TTG is an excellent screening test for the diagnosis of paediatric CD. TTG value &gt; 50 IU/ml has 100% positive predictive value.
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http://dx.doi.org/2288DOI Listing
April 2016

CLINICAL PRESENTATION, AETIOLOGY AND COMPLICATIONS OF PANCREATITIS IN CHILDREN.

J Ayub Med Coll Abbottabad 2015 Jul-Sep;27(3):628-32

Background: Childhood Pancreatitis is an uncommon but serious condition with incidence on the rise. It manifests as acute or chronic form with epigastric pain, vomiting and elevated serum -amylase and lipase. This study was conducted with the aim to determine the clinical presentation, aetiology, and complications of pancreatitis in children.

Methods: This descriptive case series was conducted in the Department of Paediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital & the Institute of Child Health, Lahore from 1st January to 31st December 2014. Seventy-two patients up to the age of 15 years having abdominal pain, Amylase >200 IU/L and/or lipase >165 IU/L, with features of acute or chronic pancreatitis on abdominal imaging; were included in study. Data analysis was done using SPSS-20.

Results: Of the total 72 patients, 43 (60%) had acute pancreatitis, males were 25 (58%) and females 18 (42%) and chronic pancreatitis was diagnosed in 29 (40%), males 10 (34%) and females 19 (66%). Common clinical features were abdominal pain (100%), nausea and vomiting (79%). Common aetiologies were idiopathic (40%) while choledochal cyst 8%, hyperlipidaemia 7%, biliary tract stones/sludge 7% and abdominal trauma 6%. Complications were more frequently associated with acute pancreatitis (60%) than with chronic pancreatitis (34%). Common complications were pseudo-pancreatic cyst (36%), ascites (17%) and pleural effusion (4%).

Conclusion: Abdominal pain, nausea and vomiting were common presenting features of childhood pancreatitis. Common aetiologies were idiopathic hyperlipidemia, biliary tract stones/sludge, choledochal cyst and abdominal trauma. Common complications were Pseudo-pancreatic cyst, ascites and pleural effusion.
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February 2016