Search

There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease (IBD) in the pediatric population. However, the results are contradictory. Therefore, we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD.We carried out a systematic search in databases from inception until 20 January 2022. We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity, inflammatory factors, and vitamin D and calcium levels in pediatric patients with IBD. Random effects models were used to combine the data. The main outcomes were then analyzed using weight mean difference (WMD) and respective 95% confidence interval (CI).Fifteen treatment arms met the eligibility criteria and were included. Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxyvitamin D3 [25(OH) D3] (pooled WMD of 17.662 ng/mL; CI 9.77-25.46; P 0.001), calcium (pooled WMD of 0.17 mg/dL; CI 0.04-0.30; P = 0.009), and inflammatory factors including C-reactive protein (CRP) (pooled WMD of -6.57 mg/L; CI -11.47 to -1.67; P = 0.009) and erythrocyte sedimentation rate (ESR) (pooled WMD of -7.94 mm/h; CI -12.65 to -3.22; P = 0.001) levels. In addition, this effect was greater for vitamin D levels at doses greater than 2000 IU, and when follow-up duration was more than 12 weeks.This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH) D3, calcium, and inflammatory factors in children and adolescents with IBD.

The present study includes a case report of a 9-year-old boy who came to our center with jaundice, elevated liver enzymes, and palpable liver. He was treated with ursodeoxycholic acid, but no improvement in symptoms was seen. Reverse transcription polymerase chain reaction and liver biopsy were positive for hepatitis C virus. He was treated with daclatasvir/sofosbuvir for 3 months. Daclatasvir/sofosbuvir might be effective against the treatment of hepatitis in children, with no report of remission and minimal side effects.

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose-response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15-95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15-39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0-0) and 0·603 (0·400-1·00) standard drinks per day, and the NDE varied between 0·002 (0-0) and 1·75 (0·698-4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0-0·403) to 1·87 (0·500-3·30) standard drinks per day and an NDE that ranged between 0·193 (0-0·900) and 6·94 (3·40-8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3-65·4) were aged 15-39 years and 76·9% (73·0-81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Research reported in this publication was supported by the Bill & Melinda Gates Foundation. S Afzal acknowledges the support for intellectual contributions to this manuscript by the Department of Community Medicine and Epidemiology at King Edward Medical University, Lahore, Pakistan. T Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. L Belo acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. D Bennett is supported by the UK Medical Research Council Population Health Research Unit at the University of Oxford (Oxford, UK). M Carvalho acknowledges support from FCT in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of UCIBIO and the project LA/P/0140/2020 of i4HB. L Castro-de-Araujo was funded by the Medical Research Council (UK), Grant no. MR/T03355X/1 and by the National Institute of Mental Health Grant no. R01MH128911. FJ Elgar is supported by the Canada Research Chairs program. F Greaves acknowledges support from the NIHR Applied Research Collaboration for NW London. V K Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. VB Gupta acknowledges funding support from the National Health and Medical Research Council (NHMRC), Australia. C Herteliu is partially supported by a grant from the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. C Herteliu is partially supported by a grant from the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. S Hussain was supported by the Operational Programme Research, Development and Education –Project, Postdoc2MUNI “(No. CZ.02.2.69/0.0/0.0/18_053/0016952). S M S Islam is funded by the National Health and Medical Research Council and received funding from the National Heart Foundation of Australia. The Serbian part of this GBD-related contribution has been co-financed through Grant OI 175 014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. M Kivimaki was supported by the Wellcome Trust (221854/Z/20/Z), the UK Medical Research Council (MR/S011676/1), the US National Institute on Aging (R01AG056477), and the Academy of Finland (350426). K Krishan is supported by the UGC Centre of Advanced Study (Phase II), awarded to the Department of Anthropology, Panjab University, Chandigarh, India. B Lacey acknowledges support from the UK Biobank, funded largely by the UK Medical Research Council and Wellcome. S Lorkowski acknowledges institutional support from the Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig (Germany; German Federal Ministry of Education and Research; grant agreement number 01EA1808A). G Lucchetti received a productivity scholarship from the Brazilian National Council for Scientific and Technological Development — CNPq (Level 1D). J McGrath was supported by the Danish National Research Foundation (Niels Bohr Professor). J McGrath is employed by the Queensland Centre for Mental Health Research (Australia), which receives support from the Queensland Health Department. C Parry acknowleges the South African Medical Research Council. A Peden is supported by a National Health and Medical Research Council Emerging Leadership Fellowship (Grant ID: APP2009306). M R Phillips was supported in part by the Global Alliance for Chronic Diseases - National Natural Science Foundation of China (NSFC. No. 81761128031). M Pinheiro acknowledges FCT for funding through program DL 57/2016 – Norma transitória. A Rahman acknowledges the support from the Data Science Research Unit in Charles Sturt University (Bathurst, NSW, Australia). U Saeed would like to acknowledge the International Center of Medical Sciences Research (ICMSR), Islamabad, Pakistan. A M Samy acknowledges support from Ain Shams University (Cairo, Egypt) and the Egyptian Fulbright Mission Program. N Senthil Kumar acknowledges the DBT, New Delhi sponsored Advanced State Level Biotech Hub (BT/NER/143/SP44475/2021), Mizoram University (Aizawl, Mizoram, India) for facilitating this work. F Sha is supported by the Shenzhen Science and Technology Program (Grant No. KQTD20190929172835662). A Shetty acknowledges Kasturba Medical College (Mangalore, India) and Manipal Academy of Higher Education (Manipal, India) for all the academic support. R Shrestha acknowledges a career development award from the National Institutes of Health (K01DA051346). D Silva was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES)-Finance Code 001 and is supported in part by CNPq - Brazil (309589/2021-5). D Sleet acknowledges partial support from Veritas Management Group, Inc and The Bizzell Group, LLC. S Trias-Llimós acknowledges research funding from the Juan de la Cierva-Formación program of the Spanish Ministry of Science and Innovation (FJC-2019-039314-I). Sí

INTRODUCTION Children with refractory constipation might not respond to conventional medical treatments. In this study, we assessed the effectiveness of intrarectal botulinum toxin type A/electromotive drug administration (BoNTA/EMDA) on constipation in these children and compared its efficacy with routine intrasphincteric BoNTA injection. METHODS From 2017 to 2019, 60 children aged 5-13 years who fulfilled Rome III criteria for intractable constipation were enrolled and randomly assigned into 2 treatment groups. EMDA group (n = 30) underwent BoNTA/EMDA, whereas the control group (n = 30) received injection of BoNTA into the internal anal sphincter. A complete bowel habit diary (with data on the frequency of defecation per week, stool form, and the number of fecal soiling episodes), a constipation score questionnaire, and a visual pain score were recorded before treatment and at 1 month and 6 months after treatment. In addition, children in both groups were assessed with a constipation-related quality of life questionnaire. RESULTS After 1-month follow-up, treatment reduced the number of patients fulfilling the diagnostic criteria in both EMDA (24/30, 80%) and injection (25/30, 83.3%) groups (P < 0.001). The stool form was normalized in 73.3% (22/30) in EMDA group and 80% (24/30) in injection group after treatment. The median of constipation score and pain score decreased significantly in both groups after treatment (P < 0.001 and P < 0.001, respectively). DISCUSSION BoNTA/EMDA seems to be as effective as intrasphincteric BoNTA injection for treatment of intractable constipation. In addition, this technique is associated with less comorbidity, is less costly, and can be performed in an office-based setting without general anesthesia.

We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the

Background: The diagnosis of esophageal varices (EV) is based on the findings of esophagogastroduodenoscopy (EGD), biopsy, and serum markers. Thus, noninvasive cost-effective tests through which high-risk EV children can be diagnosed are needed.Purpose: This cross-sectional study aimed to identify the noninvasive markers for EV in children with liver cirrhosis.Methods: A total of 98 children with liver cirrhosis were evaluated in this study. The spleen size, platelet count, serum albumin, liver function test results, and risk scores were evaluated prior to endoscopy. The endoscopic investigations aimed to identify the presence of EV and red signs, and determine varices sizes.Results: Endoscopy revealed varices in 43 subjects (43.9%). The spleen size, platelet count, international normalized ratio, aspartate aminotransferase to platelet ratio index (APRI), platelet count to spleen size ratio, and risk score differed significantly between patients with and without EV on univariate analysis; however, the logistic regression analysis showed no differences, indicating that none of these parameters were independently associated with the presence of EV.Conclusion: Platelet count, risk score, platelet count to spleen size, and APRI can be useful tools for the identification of highrisk patients with EV and might reduce the need for invasive methods like EGD.

There is evidence of inconsistency in sequelae of exclusive enteral nutrition (EEN) as induction therapy in paediatric patients with Crohn's disease (CD).To investigate the potential effects of EEN on paediatric Crohn's disease activity index (PCDAI), inflammation and biochemical parameters in paediatric patients with CD.We performed a comprehensive systematic search of PubMed/MEDLINE, Web of Science, SCOPUS and Embase until 8 January 2022 regardless of the time of publication or language. Random-effects model was applied to combine the datasets. The main outcomes were analysed through mean difference (MD) and its 95% confidence interval (CI).Forty six studies met eligibility criteria and were included in the meta-analysis. Pooled findings indicated that PCDAI score (MD of -27.24; 95% CI -31.84 to -22.64), calprotectin (MD of -842.83 mg/kg; CI -1018.24 to -667.42), CRP (pooled MD of -2.36 mg/dl; CI -2.68 to -2.03), and ESR (MD of -21.09 mm/h; CI -23.79 to -18.38), albumin (MD of 0.65 g/dl; CI 0.58 to 0.72), haemoglobin (MD of 1.12 g/dl; CI 0.87 to 1.37), weight (MD of 4.30 kg; CI 3.39 to 5.22), and height (MD of 0.98 cm; CI 0.35 to 1.62) improved significantly with EEN.Adherence to EEN can have significant, beneficial effects as induction therapy in paediatric patients with CD.

Functional constipation (FC) and Gastroesophageal Reflux Disease (GERD) are common gastrointestinal disorders in children. The aim of this study is to investigate the correlation between functional constipation and GERD in children.In this cross-sectional study, a total of 82 children aged16 years who referred to the pediatric gastroenterology clinic of (XXX) and were diagnosed with functional constipation according to ROME III criteria, and gastroesophageal reflux disease according to clinical history and DeMeester Score. Questionnaire was used to obtain the data regarding age, sex, cause of the visit, presence or absence of any symptom was noted, clinical examinations and difficulty in defecation.Of the 82 children with FC and GERD, 45 were boys and 37 were girls. Among children with FC and GERD, FC was reported in 50 (61%) cases prior to the onset of GERD, whereas 32 (39%) of the children had reflux before FC. The mean age of participants presented with FC was 5.66 ± 3.52 and that of GERD was 5.24 ± 2.83. The difference in mean age was not statistically significant. Of the children with gastroesophageal reflux disease, there were 13 (40.6%) males and 19 females while 32 (64%) males and 18 females had FC and the gender-based difference was statistically significant between the 2 groups.The prevalence of functional constipation in children was higher than gastroesophageal reflux disease. Gastroesophageal reflux disease and functional constipation should be simultaneously considered for therapeutic interventions and patients with functional digestive diseases should be monitored and followed-up.

Non-invasive biomarkers, for the diagnosis of celiac disease, can reduce the need for biopsy, particularly in pediatric patients. The aim of this study was to investigate the levels tissue transglutaminase antibody (tTG) and plasma citrulline and its correlation with intestinal biopsy.In this cross-sectional descriptive study, Pediatric patients with celiac disease referred to (XXX)were included. The patients underwent tTG antibody test along with plasma citrulline measurements using HPLC ((high performance liquid chromatography). Biopsy was performed in all the patients and clinical and demographic findings were recorded in a patient form. The data were statistically analyzed using SPSSv22.Of 118 patients with celiac disease, the mean level of citrulline in patients was 17.48 ± 6.92 and the mean tTG titer was 183.17 ± 41.25. The two variables were inversely correlated with each other, p 0.01. With an increase in Marsh levels, a significant reduction in citrulline levels and an increase in plasma tTG levels were seen, p 0.01, respectively. The mean citrulline and tTG titer was not associated with gender and the age of the patients.Our findings indicate that citrulline and tTG antibody titer are significant biomarkers for the diagnosis of celiac disease and the severity of intestinal atrophy among pediatric patients.

Introduction: Paris classification for the extent of inflammatory bowel disease (IBD) in children is based solely on macroscopic findings obtained via endo-colonoscopy. However, in some cases histologic findings may indicate more severe cases. Objectives: The aim of the present study was to compare the extent of pediatric IBD based on endo-colonoscopy and pathological findings. Methods: Data on 67 hospitalizations were collected from 51 children with IBD who had been admitted to the children’s medical center of Tehran. All subjects underwent endoscopy or colonoscopy and had a histological report. Results: Comparison of the endoscopic and histological findings in ulcerative colitis showed that, in 37% of cases, gastric involvement was reported in histology, while these cases were reported normal in endoscopy. In colonoscopy, the transverse colon was more involved, as compared with the results of histology, while in other parts of the colon, the histological involvement showed more severe findings. Considering Paris classification, in 25% of cases, the extent of the disease was higher in colonoscopy, and in 16% of cases, it was higher in histology. Of all children with Crohn’s disease, gastric involvement in 20% of cases and esophageal and duodenal involvement in 13% of cases were more reported in histology than in endoscopy. In the ascending colon, descending colon, and rectosigmoid, histological involvement was more than that observed in colonoscopy. Considering Paris classification, in 5% of cases, the extent of the disease was higher in colonoscopy, and in 9% of cases, it was higher in histology. Conclusion: Concurrent use of histological findings and endoscopic findings may help to better determine the severity and extent of the disease and facilitate the process of treatment.

Background: Benign esophageal strictures are not rare. Over the past two decades, endoscopic balloon dilatation (EBD) has been used to treat them. Objectives: The purpose of this study was to identify the most common causes of benign esophageal stricture in children determine the success rate of endoscopic balloon dilatation. Methods: Children younger than 16 years with benign esophageal strictures referred to the endoscopy department during one year (2016 - 2017) were enrolled. After obtaining written consent from parents, endoscopy balloon dilatation was performed with two types of balloon catheters. Response to treatment was evaluated based on clinical symptoms and was classified according to the Vantrappen table score. Results: In this study, thirty-one (31) children participated including 19 (61%) boys and 12 (39%) girls. The mean age was 5.1 ± 3.9 years. The most common causes of esophageal stricture were: achalasia (45%), esophageal atresia (19%), stenosis due to the caustic ingestion (19%), another congenital stenosis (16%). Overall, 27 children (87.1%) had a good response to treatment. In children with stenosis due to caustic ingestion, the inappropriate response was higher than the rest (33%). However, only in 4 (12.9%) patients, balloon dilatation failed. No complications were observed. Conclusions: Achalasia, esophageal atresia, and caustic ingestion are the most common cause of benign esophageal stricture in the children. EBD is an effective and safe treatment in these children, even in cases of previous surgery and recurrence. If this procedure is performed by an expert using appropriate balloon catheters, no complications will be created.

BACKGROUND The aim of the present study was to determine the effectiveness of a self-care education (SCE) discharge program with telephone follow-ups in managing hypertension (HTN) in older patients. METHODS The study was conducted on 56 older patients with HTN who had recently been discharged from the cardiac wards of hospitals in Isfahan, Iran, in 2017. Participants were randomly allocated to the intervention and control groups. The intervention was a 60-minute SCE discharge program with 4 re-educative telephone follow-ups every 2 weeks based on 4 chapters of the designed SCE program and booklet. After coding the data and entering them into SPSS software, data were analyzed for the comparison of mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) as well as frequency of managed HTN in the intervention and control groups at baseline (before discharge), and 2 and 3 months after discharge. RESULTS Statistical tests showed no significant difference in any of the demographic and confounding variables as well as baseline BPs (P > 0.050), but at post-intervention follow-ups, after Mauchly's sphericity test, repeated measurements ANOVA showed that the effect of time (P < 0.001) and group (P = 0.043) on SBP was significant. The effect of time (P = 0.036) and group (P = 0.047) on DBP was also significant. McNemar’s test showed that the frequency of managed HTN (normal BP), 3 months after discharge, was significantly higher in the intervention group compared to the control group [87.5% (n = 21) vs. 23.1% (n = 6), respectively] (P < 0.001). CONCLUSION SCE discharge program with telephone re-educative follow-ups was effective in reducing mean BP. The use of this program as a discharged plan for older adults with HTN and comparison of readmission rates for a longer period are recommended.

Aim of the study Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which could be associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The aim of this study was to compare GGT and IgG4 levels among children with UC with PSC and without PSC. Material and methods In this cross sectional study children with UC with PSC and UC without PSC were included. Serum immunoglobulin G4 (IgG4) and gamma-glutamyl transpeptidase (GGT) levels of the 90 UC patients with and without concomitant PSC were measured. Children with serum IgG4 concentration > 175 mg/dl were considered to have elevated IgG4. Results Elevated serum IgG4 was found in 8 of 30 (26.6%) patients with PSC vs. 3 of 60 (5.0%) patients without PSC. Compared with the group without symptoms of PSC, the group with PSC showed significantly higher levels of aspartate aminotransferases (AST; 22.5 U/l vs. 70.0 U/l, p < 0.001), alkaline phosphatase (ALP; 359.0 U/l vs. 602.0 U/l, p < 0.001), and IgG4 (56.0 vs. 73.0, p = 0.02). The odd ratio of the elevated IgG4 and GGT in predicting PSC was 6.9 (95% CI: 1.6-28.4) and 18 (95% CI: 5.7-55.9), respectively. Conclusions AST, alanine aminotransferase (ALT), GGT, ALP, and serum IgG4 were significantly higher in UC patients with sclerosing cholangitis (SC) compared to UC patients without SC. GGT and IgG-4 measurements are recommended for evaluation of UC.

Autoimmune hepatitis (AIH) is a chronic inflammation in hepatocellular tissues associated with circulating autoantibodies. Imbalance in T-cells population and dysregulation in several cytokine profiles has been implicated in pathogenesis of AIH. This study was performed to assess potential association of AIH with interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes single nucleotide polymorphisms (SNPs).Fifty-six patients with AIH and 139 healthy individuals were enrolled in this study. IL-2 and IFN-γ typing was performed, using polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The frequencies of alleles, genotypes and haplotypes in AIH patients were compared to healthy controls.IL-2 T allele at position +166 (rs2069763) showed significant higher frequency in AIH group (36%), compared to the controls (21%) (OR=2.06; 95% CI, 1.24-3.43, P-value0.01). The frequency of IL-2 TT genotype at +166 position was also associated with AIH (OR=18.68, 95% CI 3.74-126.04, P-value0.01). G/T alleles of IL-2 at -330 (rs2069762) and A/T alleles on UTR +5644 position at IFN-γ and their subsequent haplotypes, did not show significant association with AIH.This study identified IL-2T allele at +166 position and TT genotype as susceptibility gene in AIH which would provide better understandings into the mechanisms of AIH and potential immune modulation therapies.

Background: Gastroesophageal reflux disease (GERD) is associated with a number of comorbidities in pediatrics. However, its association with attention deficit hyperactivity disorder (ADHD) has not been reported. The aim of the present study was to investigate the prevalence of ADHD in pediatric patients newly diagnosed with GERD. Materials and Methods: Sixty newly-diagnosed treatment naive GERD patients and sixty healthy controls aging between 5 to 12 years referring to the Children and Adolescent’s medical center, Tehran, Iran were recruited in a case-control study during the year 2015. Then patients were evaluated for ADHD by a psychiatrist according to the DSM-IV criteria. The revised Conners' Parent Rating Scale (CPRS-R) was used for assessment of the symptoms of ADHD. To screen for psychiatry disorders other than ADHD, the Kiddie-Sads-Present and Lifetime Version (K-SADS-PL) questionnaire was used. Logistic regression analysis was used for modeling the association between GERD and ADHD in the study sample. Results: The mean age of GERD patients was 5.77±2.27 and for non-GERD controls was 6.03±2.52 (P= 0.543). Thirty-three out of 60 (55%) GERD patients and 37 out of 60(61.66%) non-GERD controls were male (P: 0.579). Prevalence of ADHD was 33.60 (55%) in GERD patients and 10.60 (16.66%) in non-GERD (P

Background: Effective and safe procedural sedation is necessary for percutaneous liver biopsy in children. There are a number of different protocols for this purpose. The current study investigated ketamine and DPT cocktail (meperidine (Demerol®) + promethazine (Phenergan®) + chlorpromazine (Thorazine®)). Methods: The current cohort of 80 Iranian children aimed at investigating percutaneous liver biopsy. Each of the 2 study groups (ketamine and DPT) included 40 patients. Both groups were matched by age (number of participants under and above 7 years old). The current study evaluated the efficacy of 2 protocols by CHEOPS (children’s hospital of Eastern Ontario pain scale) and visual analogue scale (VAS) pain scoring system and sedation scoring A,B,C, and D. Results: Ketamine group was sedated and recovered much more rapidly than the DPT receiving patients. Also, they had significantly less pain during the biopsy. The most common side effect of ketamine was vomiting (27%); in the other group, transient hypotension and tachycardia were more common. Conclusions: Ketamine is a safe and effective choice for procedural sedation in percutaneous liver biopsy in children.

Background: Autoimmune hepatitis (AIH) is a chronic long-lasting hepatocellular inflammation associated with circulating auto antibodies. In addition to the genetic component, several cytokines have been implicated to be involved in AIH. This study was performed to investigate potential associations of AIH with IL4 gene variants.Method: The studied alleles and genotypes included: IL4G/T allele polymorphisms at position -1098 and C/T allele polymorphisms at two positions (-33 and -590) on the IL4 gene, in addition to the A/G allele polymorphisms at position +1902 on the IL4RA gene.Result: The IL4 C allele and CC genotype at position -590 and TT genotype at position -33 had a significantly higher frequency in AIH patients.Conclusion: This study identified the IL4 C allele and CC genotype susceptibility gene in AIH, which will provide better insights into the mechanisms of AIH and potential therapeutic interventions.

Proper colon preparation in children has been a challenge for many years. Different regimens have been used for this purpose, but the best regimen is not determined. The aim of this study was to evaluate successful colon preparation before colonoscopy in children who were treated with one- or two-day regimen with polyethylene glycol (PEG) plus bisacodyl and clear liquids.In this randomized clinical trial, 100 children (2-14 years old) who were candidates for colonoscopy were enrolled and divided into two groups. The children in group one were started on 2 g/kg PEG powder (17 g in 240 mL water or another beverage) and 5 mg bisacodyl suppository (BD) the day before colonoscopy, whereas those in the other group were started on 1.5 g/kg PEG with fruit juices for two days and 5 mg bisacodyl suppository (BD) for two days before colonoscopy.Compliance rates, regimens, adverse effects, and complete colonoscopy were not significantly different between the two groups. The Boston score was excellent and good in 70% of group one and 72% of group two children, respectively. Compliance rate, adverse effects, and need for enema were similar in both groups. The rate of compliance and non-requirement of enema were significantly higher in children with satisfactory colon preparation.The one-day PEG plus bisacodyl regimen for bowel preparation is as effective as the two-day regimen in children; furthermore, it is well tolerated and has low adverse effects.

Summary Background and aims Autoimmune hepatitis is a chronic immune-mediated liver injury caused by dysregulated immune response to liver antigens. Genetic susceptibility is affected by multiple single nucleotide polymorphisms in immune-related genes. There are few reports on the association of TGF-β and IL-10 genetic variants with autoimmune hepatitis. Methods Allele frequency and genotype status of IL-10 −1082, −819, −592 and TGF-β +869 and +915 polymorphisms were investigated in 57 unrelated patients with autoimmune hepatitis and 140 healthy controls by polymerase chain reaction with sequence-specific primers. Results IL-10 −592 and −819 allele frequencies and genotypes were not associated with autoimmune hepatitis in our population, while IL-10 −1082 genotypes were. IL-10 −1082/−819/−592 “high-producing” haplotype GCC was significantly less frequent in patients. TGF-β +869 “high-producing” allele C and genotype CC were significantly more in autoimmune hepatitis, compared to controls; whereas, TGF-β +915 “low-producing” allele C and genotype CC were significantly more in autoimmune hepatitis compared to control. TGF-β +869/+915 haplotype TG was significantly less frequent in patients while CC haplotype was significantly more frequently observed in patients. Conclusion We identified a significant association between IL-10 −1082/−819 and TGF-β +869/+915 genotypes and haplotypes with autoimmune hepatitis in Iranians.

Celiac disease is a chronic autoimmune disease in which gene-environment interactions cause the immune system to unfavorably react to naturally gluten-containing foods. PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases. The present genetic association study was conducted to investigate the possible associations between PTPNTT single nucleotide polymorphisms (SNPs) and celiac disease in an Iranian population.The study population consisted of 45 patients with celiac disease and 93 healthy controls. The study genotyped five SNPs of the PTPN22 gene: rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601.Control and patient groups did not differ on the genotype distribution of four of five investigated SNPs in the PTPN22 gene, for example, rs12760457, rs2476601, rs1217414, and rs33996649. The only investigated PTPN22 variant, which could be associated with CD, was rs1310182. A significant increase in the carriage of the T allele of rs1310182 in CD patients was observed (OR (95% CI) = 11.42 (5.41, 24.1), p value0.0001). The TT genotype of this SNP was significantly associated with celiac disease. Our study suggests that the rs1310182 SNP of PTPN22 gene may be a predisposing factor of celiac disease in the Iranian population. Further studies are required to investigate the issue in other racial and ethnic subgroups.

Introduction: The Wilson disease is an autosomal recessive disease in which the liver, central nervous system, eyes, blood and other parts of the body involved. Timely diagnosis and appropriate treatment of the disease requires awareness of the clinical presentations of this disease in children.Methods: This case series study included 62 patients with Wilson disease who admitted to children's Medical Center in the years 2012-2003.Results: 56% of patients were male. The average age of diagnosis was 9.73 years old (5-17 years) and this was higher in patients with early neurologic symptoms (P = 0.85.( 64.5% of the patients had the hepatic symptoms at the time of diagnosis and the most common type of hepatic involvement was cirrhosis (39.3%) and hepatitis (17.5%) respectively. 17.7% of the patients also had early neurological symptoms. A positive family history for the Wilson Disease were found in 27.4% of patients. 74.2% of patients had KF ring and the frequency of these symptom was higher in patients with early neurological involvement. 83.9% of patients were treated successfully with D-penicillamine and In 30% of patients, adverse drug reactions were seen.Conclusion: Children with unknown liver disease should be evaluated for Wilson disease and the first-degree relatives of patients should be screened. . D-penicillamine have important side effects, but due to the low cost and the availability is an appropriate drug to treat the Wilson disease..Key words: Wilson Disease, Hepatic Involvement, Neurologic Involvement , KF ring ,D-Penicillamine.

Background: Helicobacter pylori (H.pylori) infection has an important role in promoting gastrointestinal disease in human. It may be acquired early in life, particularly in developing countries. The aim of this study is to evaluate the association between H.pylori infection and clinical manifestations in Iranian children.Materials and Methods: In this retrospective, cross-sectional study, H. pylori status was assessed by pathological examination of gastric biopsy in symptomatic children. A total of 266 patients were diagnosed as infected by H. pylori, compared with 268 uninfected patients matched by age and sex. Reported symptoms, endoscopic and pathological findings in the two groups were analyzed using chi square test. The limit of statistical significance was set at P

Background: Helicobacter pylori (H.pylori) infection has an important role in promoting gastrointestinal disease in human. It may be acquired early in life, particularly in developing countries. The aim of this study is to evaluate the association between H.pylori infection and clinical manifestations in Iranian children.Materials and Methods: In this retrospective, cross-sectional study, H. pylori status was assessed by pathological examination of gastric biopsy in symptomatic children. A total of 266 patients were diagnosed as infected by H. pylori, compared with 268 uninfected patients matched by age and sex. Reported symptoms, endoscopic and pathological findings in the two groups were analyzed using chi square test. The limit of statistical significance was set at P

Probiotics have become increasingly common within the past few years, owing to their benefits on human health. These are the strains of bacteria and yeast that are administered in the form of food products and supplements to provide lost-health benefits. They can also ameliorate symptoms of numerous diseases and provide protective effects against various pathologies. This review highlights some of the most frequent gastrointestinal problems in children and the therapeutic and preventive role of probiotics against them.

Neonates and young infants with human herpes virus 6 (HHV-6) may present with hepatitis, which is rarely fulminant. However, because HHV-6 is prevalent as a latent infection in humans, causality must be proven in patients with fulminant hepatitis. We describe a rare case of fulminant hepatitis induced by HHV-6 with concomitant central nervous system involvement and without any classic skin rash. An immunocompetent, breast-fed 14-month-old girl was admitted to our hospital because of gastrointestinal bleeding, fever, excessive sleepiness and inability to recognize parents, markedly elevated serum transaminase and severe coagulopathy. Cerebrospinal fluid polymerase chain reaction assay for viral agent was positive for HHV-6. Fortunately, the patient demonstrated a rapid improvement thereafter and did not require liver transplantation.

Girifl ve Amac: Kistik fibrozis en s›k karfl›lafl›lan kal›t›msal olumcul hastal›kt›r ve yenidoan taramas›n›n yap›lmad›¤› bolgeler- de hastalar gec tespit edilebilir. Erken tan› konulan kistik fibrozis hastalar›n›n sonuclar› dramatik olarak daha iyidir. Bu cal›fl- mada kistik fibrozis hastalar›nda ilk baflvuruda tespit edilen tan›ya goturen bulgular›n›n incelenmesi amaclanm›flt›r. Gerec ve Yontem: Bu cal›flma ‹ran'da birden cok pediatrik referans merkezinde gerceklefltirildi, hastalar›n tan› an›ndaki demografik, kli- nik ve labaratuvar verileri kontrol listesi ile kay›t alt›na al›nd›. Tum hastalar›n 2 adet ter klor testi mevcuttu. Bulgular: Kistik fibrozis tan›s› olan 197 hasta cal›flmaya dahil edildi. Bu hastalardan, 119'unun (%74) yafl› 6 aydan kucuktu ve 34 hastan›n (%21) yafl› 6-12 ay aras›ndayd›. En s›k karfl›lafl›lan klinik bulgular buyume gerilii (n=178; %90) , tekrarlayan akcier enfeksiyonlar› (n=139; %71) ve steatore (n=135; %69) olarak tespit edildi. En s›k karfl›lafl›lan radyolojik anormallik akcierlerde afl›r› havalan- mayd›. Terde tuz tad›, steatore, metabolik alkaloz, radyolojik anormallikler ve karacier testlerinde anormallik olan hastalar›n or- talama tan› yafl› dierlerine gore dufluk bulundu. Sonuc: Bu cal›flma sonuclar›na gore buyume gerilii, tekrarlayan solunum sis- temi enfeksiyonu, steatore, metabolik alkaloz ve tuzlu cilt tad› kistik fibrozis ile s›k karfl›lafl›lan bolgelerde klinikte uyar›c› olmal›- d›r. Bu bolgelerde, dikkat ve klinik fluphe ile hastalar›n erken tespit edilmesi mumkun olabilir. Anahtar kelimeler: Kistik fibrozis, tan›, klinik bulgular, tarama Background/aims: Cystic fibrosis is the most common inherited lethal disease, which could be frequently identified late in regi- ons without newborn screening. There are dramatically better outcomes in the early diagnosis of cystic fibrosis patients. This study aimed to evaluate the spectrum of manifestations of cystic fibrosis at first admission leading to diagnosis. Materials and Methods: This study was performed in a multi-referral pediatrics center in Iran. Data of patients with cystic fibrosis at the time of diagnosis were recorded based on a checklist denoting demographic characteristics, clinical and laboratory features. All of the patients had two documented sweat chloride tests. Results: One hundred and ninety seven patients with cystic fibrosis were enrolled in this study. Among them, 119 patients (74%) were less than six months and 34 patients (21%) were between 6 and 12 months of age. The most common clinical findings were failure to thrive, recurrent pulmonary infections, and steatorrhea in 178 (90%), 139 (71%), and 135 (69%) patients, respectively. The most common radiologic abnormality was hyperaeration. In patients with salty tasting skin, steatorrhea, metabolic alkalosis, radiologic findings, and liver function abnormalities, the mean age at the time of diagnosis was significantly low than in the subjects without these findings. Conclusion: This study suggests that some conditions such as failu- re to thrive, recurrent respiratory infections, steatorrhea, metabolic alkalosis, and salty tasting skin should be considered as clini- cal screening tools for cystic fibrosis, especially in regions with high rate of cystic fibrosis. In these regions, awareness and clinical suspicion of medical professionals are crucial for early diagnosis of cystic fibrosis patients in the pre-diagnostic period.

Background: Liver disease is increasingly common in pediatric cystic fibrosis (CF). Liver dysfunction in CF patients is an early complication and relatively common which may progress silently. Objectives: The purpose of this study was to determine the prevalence of abnormal liver architecture by Ultrasonography (US) and their associations to abnormal liver function tests particularly abnormal Gamma Glutamyl Transpeptidase (GGT), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) level for its early detection before the complications occur. Patients and Methods: This study as a cross-sectional study was performed at the Children's Medical Center Hospital, Pediatrics Center of Excellence in Tehran, Iran. In all, 114 patients with cystic fibrosis (70 boys, 44 girls) were enrolled. Sample blood test including AST, ALT, GGT and abdominal Sonography was obtained from all patients. Abnormal liver function test was defined by two consecutive occasions; ALT and/or AST levels were ≥ 2 times the upper limit of normal values. GGT normal values were defined by patient age. Data were analyzed using χ2 test and independent T test. Statistical significance was defined as P values of < 0.05 by SPSS ver.19 software. Results: Abnormal liver function test was detected in CF patients. As well, liver sonogram was abnormal in approximately one-third of the patients. This study showed a higher prevalence of biochemical abnormality in patients with abnormal livers ultrasonography. Conclusions: Noninvasive paraclinical evaluation methods could be recommended in the patients with CF for early detection of silent liver abnormalities before progression to end stage liver disease.

Background/Aims Gastroesophageal reflux disease (GERD) is common in children. Recurrent exposure to gastric acid in GERD may contribute to tooth erosion. Methods In this prospective study, 54 GERD patients qualified according to endoscopy, pH-metry, and the GERD questionnaire and 58 healthy controls qualified by the GERD questionnaire were assessed. Two groups underwent dental evaluations for the presence, severity, and patterns of erosion and for the stage of dentition using a Tooth Wear Index. The health care providers who performed the dental exams did not know which children had been diagnosed with GERD. Results A total of 112 children, 3 to 12 years old were enrolled in the study, and 53 of 54 (98.1%) GERD patients and 11 of 58 (19.0%) controls had dental erosions (p

Background: Diarrhea infection has been established as one of the major etiologies and risk factors of malnutrition in children. Objectives: The aim of this study was to assess the maternal knowledge, attitude and practices when treating diarrhea in their children less than 5 years old in the Zahedan, south-east province of Iran. Materials and Methods: This cross-sectional study was conducted in urban health centers in Zahedan. Three hundred mothers who had less than five years old children and had been referred to the health centers for six months duration had been included. The questions were about demographic characteristics, knowledge and practice regarding childhood diarrhea, and had been designed to obtain information through an interview. Results: The findings indicated that knowledge of the majority of mothers (64.3%) regarding diarrhea and diet was moderate and only 3.7% had good knowledge. The majority of mothers (56%) had a moderate practicing knowledge of diarrhea and diet and only 2.3% had a good practice. Conclusions: Based on the low level of knowledge and practice among the study population, the usual practice of focusing on a target group would be necessary. Our findings indicated a serious lack of competence in dealing with this problem.

Joubert syndrome and related disorders (JSRDs) are a group of anomalies characterized by hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and apnea and hyperpnea in infancy with multiorgan involvement in which the pathognomonic “the molar tooth sign” is present on the brain magnetic resonance imaging. In this paper, we reported on a patient with JSRD who presented with congenital hepatic fibrosis, autosomal recessive polycystic kidney disease, and pigmentary retinopathy.

Cases with Hirschsprung’s disease show the functional intestinal obstruction. Obstruction in these patients may lead to bacterial overgrowth with stasis and inflammation of the colon. Bacterial overgrowth can cause hyperammonemia that makes lethargy and loss of conscious and finally admitting in ICU. The purpose of this case report is to present a case that had Hirschsprung’s disease and referred to Children’s Medical Center with serum hyper-ammonium caused by bacterial overgrowth that induced coma and altered level of consciousness then made her to admit to PICU. A 15-year-old female referred to Children’s Medical Center with lethargy and low grade diarrhea. She had hypocalcemia and hypoalbuminemia with high PT and INR. Because of loss of conscious, she admitted at PICU. Laboratory findings showed hyperammonemia in this case, but other criteria were normal. Administration of antibiotic and lactulose therapy was started that lead to a reduction in serum ammonium level and discharging of the case. Thirteen days later she referred again with mentioned symptoms, and clinical evaluations showed high serum ammonium level. This time because of loss of conscious she had to admit at PICU and used NG tube. Administration of lactulose syrup and sodium benzoate make her in a better condition. Narrowing rectum toward the sigmoid and highly enlarged intestinal lopes was on behalf of Hirschsprung’s disease. Finally, the patient with the acceptable situation and oral periodic metronidazole discharged. It is essential to check serum ammonium level in the cases with loss of conscious. The choice for controlling hyperammonemia is lactulose therapy.

Cases with Hirschsprung's disease show the functional intestinal obstruction. Obstruction in these patients may lead to bacterial overgrowth with stasis and inflammation of the colon. Bacterial overgrowth can cause hyperammonemia that makes lethargy and loss of conscious and finally admitting in ICU. The purpose of this case report is to present a case that had Hirschsprung's disease and referred to Children's Medical Center with serum hyper-ammonium caused by bacterial overgrowth that induced coma and altered level of consciousness then made her to admit to PICU. A 15-year-old female referred to Children's Medical Center with lethargy and low grade diarrhea. She had hypocalcemia and hypoalbuminemia with high PT and INR. Because of loss of conscious, she admitted at PICU. Laboratory findings showed hyperammonemia in this case, but other criteria were normal. Administration of antibiotic and lactulose therapy was started that lead to a reduction in serum ammonium level and discharging of the case. Thirteen days later she referred again with mentioned symptoms, and clinical evaluations showed high serum ammonium level. This time because of loss of conscious she had to admit at PICU and used NG tube. Administration of lactulose syrup and sodium benzoate make her in a better condition. Narrowing rectum toward the sigmoid and highly enlarged intestinal lopes was on behalf of Hirschsprung's disease. Finally, the patient with the acceptable situation and oral periodic metronidazole discharged. It is essential to check serum ammonium level in the cases with loss of conscious. The choice for controlling hyperammonemia is lactulose therapy.

We present a girl afflicted by Fasciola hepatica who was firstly considered to have other causes of jaundice and abdominal pain;however, she had eosinophilia. The clinicians initially ruled out the possibility parasitic infection via having one negative stool examination. According to the epidemiologic characteristics of the region, the patient belonged to hypereosinophilia and hyper IgE; we repeated the stool exam 3 times and the experienced parasitologist confirmed the diagnosis.

Objectives The aim of the study was to compare the quality of sedation with 3 different sedation regimens in upper gastrointestinal endoscopy (UGIE) in pediatric patients. Methods One hundred fifty consecutive children who underwent UGIE were randomly assigned to 1 of the 3 medication regimens. Patients in group A (n = 49) received placebo. Forty-five minutes after the placebo was given, repeated intravenous (IV) doses of 0.1 mg/kg midazolam were administered titrated to achieve a level of deep sedation. Patients in group B (n = 51) received oral ketamine instead of placebo, and patients in group C (n = 50) received oral fentanyl instead of placebo with the same methodology and sedation endpoint. Results The mean dose of midazolam administered in group B patients was remarkably lower compared with that of groups A and C. Patients in group B showed less distress in IV line placement and separation from parents, higher comfort level, more endoscopist satisfaction, and higher sedation depth compared with groups A and C. The recovery time was significantly shorter in group B. All of the 3 regimens were safe. All of the complications were managed successfully. Conclusions Our data suggest that synergistic sedation with oral ketamine and IV midazolam for UGIE in children is a suitable and safe sedation. The higher rate of vomiting in group B in contrast to previous studies must be caused mainly by the oral route of ketamine administration.

Background Anaphylaxis is an acute, systemic, and potentially fatal allergic reaction. Many things can cause anaphylaxis potentially but some agents are more common like some foods (milk, egg, soy, wheat, peanut, tree nut, shellfish, and fish), insect stings, medications, latex, and food-dependent exercise-induced anaphylaxis. The goal of this study is to show the common causes of anaphylaxis among the children with anaphylaxis history who were referred to the Immunology, Asthma and Allergy Research Institute (IAARI) during a 4-year period (2005-2009).Methods and Materials During those 4 years, we registered all children (

We aimed at determining the pattern of liver disease in the Iranian children referred to the Medical Center of Children affiliated with the Tehran University of Medical Sciences. Materials and Methods: In a cross-sectional study conducted over 2 years, 425 liver needle biopsies were sent to the pathology laboratory of our center. Slides were prepared from paraffin-embedded blocks, stained by routine H & E and special stains and were then reviewed. The frequency of each disorder, separately and in combination with the age group or gender of the patients was calculated and compared with other similar studies. Results: The male to female ratio was 1.42:1. The age range was between 1 month and 18 years old and 41.4% were less than 2 years old. The most common histological diagnosis was iron overload due to major thalassemia (17.5%) followed by biliary atresia (9.7%), no significant pathologic change (8.7%), neonatal hepatitis (8.7%), chronic hepatitis (8.5%), cirrhosis (6.5%), metabolic disease (5.5%) and progressive familial intrahepatic cholestasis (5%). Results of the hemosiderosis grading in patients with thalassemia revealed no or minimal, mild, medium, or marked increase in 10%, 27.1%, 10%, 21.4% and 31.5% of the cases, respectively and the degree of iron deposition rose in parallel with age and also the stage of fibrosis (p< 0.05). Conclusion: A liver biopsy is a useful and practical tool for the appropriate diagnosis of pediatric liver diseases. Also, we found that in non thalassemic children, biliary atresia, chronic hepatitis and neonatal hepatitis, in the stated order, are the most prevalent histologic diagnoses in Iranian pediatrics.

Objective: To study the clinical presentation, histology and colonoscopic features of lower gastrointestinal polyps in Iranian children. Material and Methods: Medical reports of children with colorectal polyps were retrospectively reviewed from 1996 to 2005 at the Children’s Medical Center Hospital, Iran. A total of 563 cases were studied. Data related to age, sex, family history, signs and symptoms, the size, location, polyp types and associated lesions were collected and analyzed. Results: The mean age of children was 5.66 ± 2.88 years (range 2 months to 17 years), with a male-to-female ratio of 1.61:1.0. The highest incidence was between ages 2 and 10 years (85.1%). Rectal bleeding was the presenting symptom in 78.5% cases. The polyps were solitary in 94% of cases. A majority of polyps (86.3%) were juvenile and 86.7% located in the rectosigmoid area. Three percent of cases had a positive family history. One case of Turcot syndrome was also identified. Conclusion: Juvenile polyps remain the most common polyps in Iranian children. Although the presence of a solitary polyp in the rectosigmoid colon is more prevalent, in a significant number of cases they are multiple and located in proximal parts. Polyps must be removed even when asymptomatic because of their probable neoplastic potential.

Background:: Adenosine, a signaling nucleoside, is controlled in part by the enzyme adenosine deaminase (ADA). There are rare reports on the role of adenosine levels and ADA in cystic fibrosis (CF) patients. Objectives:: The aim of this study was to assess serum ADA in CF patients in order to find whether the severity of lung disease in CF is related to significant changes of ADA or not. Patients and Methods:: Venous blood serum ADA was measured in CF patients (3-15 years) and 49 healthy children (3-15 years) referred to Children’s Medical Center. Classification of respiratory and gastrointestinal disease severity in CF patients as well as Body Mass Index (BMI) was performed. The results were compared with values obtained from healthy children matched for age and gender. Results:: This study included 49 children of both genders (20 females and 29 males) with CF (mean age: 6.36 ± 2.22 years). Mean serum ADA in CF patients group and control group was 9.38 ± 2.72 and 16.04 ± 1.27, respectively (P value = 0.001). Mean serum ADA in CF patients with normal BMI was higher than in patients with low BMI (P value = 0.002). Conclusions:: In this study the lower serum level of ADA was seen in CF patients compared to control group. The clinical symptoms, especially respiratory symptoms, in CF patients might be associated with reduction of serum ADA and rising serum adenosine; therefore, further studies on the use of ADA enzyme therapy in CF patients are highly recommended.

Background/Aims: There is little data concerning the incidence of alpha-1-antitrypsin”(AAT) deficiency, the most common genetic cause of liver disease, among children with neonatal cholestasis in Iran. Thus, this study was performed to analyze AAT deficiency in this group of patients. Materials and Methods: DNA samples from patients with neonatal cholestasis were investigated for Pi S and Pi Z alleles, using polymerase chain reaction–restriction fragment length polymorphism. Results: Thirty patients with neonatal cholestasis were enrolled. Among those who underwent biopsies, the results revealed neonatal hepatitis in 19, bile duct paucity in 1, steatohepatitis in 1, bile duct proliferation in 1, cirrhosis in 2, fibrosis in 2, and extrahepatic biliary atresia in 1 patient. No mutant allele was found in any patient. Conclusion: The incidence of AAT deficiency is very low in Iran; therefore, screening for AAT is not recommended for patients with neonatal cholestasis in Iran.

Dear Editor, Cystic Fibrosis (CF), characterized by abnormal transport of chloride and sodium ion across the epithelium, leads to thick, viscous secretions (1). The hallmark signs and symptoms of cystic fibrosis are salty tasting skin, poor growth and poor weight gain despite a normal food intake, accumulation of thick, sticky mucus, frequent chest infections, and coughing or shortness of breath. Males can be infertile due to congenital obstruction of vas deferens. Symptoms often appear in infancy and childhood, such as bowel obstruction due to meconium ileus in newborn babies (2, 3). Cystic fibrosis may be diagnosed by many different methods including newborn screening, sweat testing, and genetic testing (4). The prognosis for cystic fibrosis has improved due to earlier diagnosis through screening, better treatment and access to health care (5). This disease is specified by very wide spectrum of clinical manifestations for which many differential diagnoses have to be considered. We studied 300 patients of CF in Children’s Medical Center in Tehran, during 2006 to 2012. Necessary information including age, sex, and symptoms of patients such as cough, hemoptysis, recurrent pulmonary infection, nasal polyposis, recurrent sinusitis, intestinal obstruction, intussusception, reflux, rectal prolapse, pancreatitis, fatty diarrhea, edema and hypo-albuminemia, anemia, vomiting and dehydration attack, cirrhosis, biliary atresia, portal hypertension, salty skin, failure to thrive (FTT), clubbing, coagulation disorder, bone fracture and nyctalopia was entered in the checklists. First manifestation of each patient was also noted. The main complaint of patients was isolated FTT and this complication had occurred in 74 (24.7%) patients. In addition, FTT with another complication was observed in 28 (9.3%) patients at the beginning of the disease; in other words, isolated failure to thrive or FTT associated with other symptoms of the disease was seen as first clinical presentation in about one-third of the patients (that is, 102 patients). The most common complication next to FTT was pulmonary infection which was seen in 47 (15.7%) patients. Other common first clinical presentations of cystic fibrosis include: attacks of vomiting and dehydration in 45 (15%), cough in 25 (8.3%), intestinal obstruction (meconium ileus) in 23 (7.7%), fatty diarrhea in 18 (6%), FTT with fatty diarrhea in 11 (3.7%), edema and Hypo-albombinemia in 10 (3.3%), and biliary atresia in 6 (2%) patients. Other symptoms including anemia, salty skin, coagulation disorders, gastro esophageal reflux, and sinusitis were seen in less than five patients. In 30 (10%) patients, two of the mentioned complications were observed simultaneously. At onset of disease, among a total of 300 patients, 182 (60.7%) had gastrointestinal symptoms, and 72 (24%) patients had respiratory tract symptoms. CF may be diagnosed after a long period of illness, by different symptoms and laboratory tests (6). In a similar study by Fallahi et al. in Iran, prevalence of first clinical presentations of CF patients before the diagnosis was as follow: gastro intestinal symptoms in 152 (62.6%), respiratory symptoms in 93 (38.3%), isolated FTT or in combination with other symptoms in 34.9%, diarrhea in 28.8%, vomiting in 15.6%, cough in 30% and respiratory distress in 23.9% patients (6). As mentioned before, the first complication in 7.7% of our patients was ileus meconium which is similar to results of other studies (4). According to this study, gastrointestinal symptoms were the most common symptoms associated with CF disease. In a study by McCloskey more than two thirds of patients presented with respiratory symptoms including chronic sino-pulmonary disease, nasal polyps or recurrent respiratory tract morbidity. This study tried to bring up the most common presenting symptoms of CF. With more attention to the symptoms of this disease, the diagnosis could be established earlier and upcoming complications prevented.

Iron deposition in liver is a major finding in thalassemic patients and because of direct iron toxicity to liver it is associated with several consequences for example liver fibrosis. Liver biopsies from 63 patients were evaluated, 40 (63.5%) were male and 20 (36.5%) were female. The mean age of the patients was 8.01 ± 3.7 and the age range was from 1.8 to 15 years. Histologic grading and staging was performed for each case according to modified HAI (Hepatitis Activity Index) system. Iron scoring was performed according to Sindram & Marx and MTK1-3 scoring systems. The mean (SD) dry weight (dw) of liver specimens was 1.34 (0.11) mg (range 0.20 to 3.80 mg). The mean (SD) of hepatic iron concentration was 230.9 (121.2)μmol/g dry weight. The relationship between the variables HIC, HII (hepatic iron index) and all histological gradings of iron (S&M and MTK1-3) was very strong. The relationship between the HIC and staging by HAI method was good. Significant differences were identified between the mean HIC in scores 1&2 of all histological iron scorings (S&M and MTK1-3), but no significant differences identified between mean HIC in other adjacent scores in all histological iron scorings (S&M and MTK1, 2 and 3). New scoring system introduced by us in this study which considered size and density of iron granules as well as zone of iron deposition was very much the same as simple Sindram and Marx classification.

Introduction: Functional constipation (FC) is one of the most common gastrointestinal problems among children. This study was designed to investigate the effectiveness of pelvic floor muscle exercise on treatment of FC. Materials and Methods: In this study which was conducted in Children’s Medical Center, children with a diagnosis of FC (aged 4-18 y) who did not respond to medical treatment, performed sessions of pelvic floor muscle exercise at home twice a day for 8 wk. Frequency of defecation, overall improvement of constipation, stool withholding, painful defecation and stool consistency were measured at the final week of the intervention compared to baseline. Results: Forty children (16 males, 24 females mean age 5.6±1.03 y) completed the 8-wk exercise program. Subjective overall improvement of the symptoms was present in 36 patients (90%). The changes in stool frequency, stool diameter and consistency were statistically significant. However, there were no statistically significant differences in the stool withholding, fecal impaction, fecal incontinence and painful defecation. Conclusion: Pelvic floor muscle exercise is an effective nonpharmacologic treatment for Paediatric FC.

Dear Editor, Neonatal cholestasis (NC) is defined as prolonged elevation of serum levels of conjugated bilirubin beyond two weeks of life. The two most common causes of NC are biliary atresia (BA) and idiopathic neonatal hepatitis (INH). Early and accurate differentiation of these two entities is very important and determines the prognosis and curability of cholestasis. BA requires surgical intervention as soon as possible; whereas, INH needs medical management (1-3). There is no single non-invasive test that can definitely differentiate these two entities. The gold standard for the diagnosis of BA is intraoperative cholangiography. Liver biopsy is the investigation with high diagnostic usefulness in NC. Its diagnostic accuracy for NC has been more than 90% in several studies (1, 4-6). Alagille identified four clinical features that, although nonspecific, supported the correct diagnosis of intrahepatic or extrahepatic cholestasis in 82% of the cases. These clinical variables included stool color within 10 days of admission, age at onset of acholic stools, birth weight, and the features of hepatic involvement, specifically the presence of hepatomegaly and consistency of the liver in palpation (6). We conducted a retrospective study between March 1996 and March 2007 to review medical records of infants with NC. Patients were all admitted in Children’s Hospital Medical Center affiliated to Tehran University of Medical Sciences, which is the major tertiary pediatric referral center in Iran. We reviewed medical records of 250 infants with NC. Infants were excluded if they did not have liver biopsy results, definite diagnosis or complete data on their medical records. Ultimately, 88 infants with BA confirmed by exploratory laparotomy or INH confirmed by liver biopsy were enrolled into the study. In this study, the gold standard tests were liver biopsy and exploratory laparotomy in INH and BA cases, respectively. The sensitivity, specificity and predictive values of HIDA scan and Alagille criteria were evaluated in comparison with liver biopsy and surgical findings. Chi-square test was used for comparison and P < 0.05 was taken as significant. There were 88 infants with NC, including 49 (55.7%) boys and 39 (44.3%) girls. Of these, 63 (37 boys, 26 girls) were diagnosed to have INH and the remaining 25 (12 boys, 13 girls) had BA, according to liver biopsy (P = 0.361). Laparotomy confirmed liver biopsy results in all 25 cases of BA. It means that liver biopsy had 100% accuracy in diagnosing BA. Thirty-three patients had HIDA scan. Among the 23 cases with a positive scan for BA (Figure 1), 14 of them also had BA in liver biopsy (P = 0.031). Among 15 patients with a positive liver biopsy for INH, HIDA scan had shown INH in only two cases (P = 0.15). Figure 1. HIDA scan report of a patient with biliary atresia Among 18 cases who had all four criteria of Alagille accommodated with INH, 14 (77.8%) cases had INH in liver biopsy (P = 0.0514). Of the five patients who had all four Alagille criteria accommodated with BA, in two (40%) cases, liver biopsy showed BA (P = 0.554). So the accuracy of Alagille criteria in our study is lower than what is reported in the pediatric GI textbooks. HIDA scan had a diagnostic accuracy of 60% and 11% for BA and INH, respectively. In conclusion, there is not a single imaging test or clinical feature that has sufficient sensitivity and specificity to differentiate BA from INH, but according to our study hepatobiliary scintigraphy had a good sensitivity for diagnosing BA and the presence of acholic stools and hepatomegaly is significantly higher in infants with BA. So, scintigraphy and clinical features can help in the assessment of any infant with NC to arrive at a timely diagnosis for appropriate management. Since percutaneous liver biopsy is highly accurate in diagnosing BA, in developing countries such our country, using this modality is cost-effective, and it can preclude unnecessary surgical exploration.

Introduction: Iron deposition in liver is a major finding in thalassemic patients. Histologic grading of iron deposition is widely used in many institutions and various grading systems have been introduced. The aim of this study was to introduce a new histologic scoring system (Markaze Tebbi Koodakan: MTK 1, 2 and 3) which considers size and density of iron granules as well as zone of iron deposition and verify this system with atomic absorption spectrometry (AAS method). Materials and methods: Liver biopsies from 63 patients were evaluated, 40 (63.5%) were male and 20 (36.5%) were female. The mean age of the patients was 8.01±3.7 and the age range was from 1.8 to 15 years. Iron scoring was performed according to Sindram & Marx and MTK 1-3 scoring systems.Paraffin blocks were processed for AAS and the results of the iron analysis (HIC: hepatic iron concentration) were reported as µmol/g dry liver weight. The statistical analysis was performed using SPSS, version 16 (SPSS Inc., Chicago, IL, USA). Results: The mean (SD) of hepatic iron concentration was 230.9 (121.2) µmol/g dry weight. The relationship between the variables HIC, HII (hepatic iron index) and all histological grading of iron (S&M and MTK1-3) was very strong. Significant differences were identified between the mean HIC in scores 1 & 2 of all histological iron scorings (S&M and MTK 1-3), but no significant differences identified in other adjacent scores in all histological iron scorings (S&M and MTK 1, 2 and 3). Discussion and conclusion: New scoring system introduced by us in this study was very much the same as simple Sindram and Marx classification. So it is concluded that although size of iron granules is important in lower scores, but in higher scores it is not as much important as the zone in which iron granules are deposited.

Zinc deficiency, which is common in patients with cystic fibrosis (CF), can lead to several complications that may increase the number of hospital admissions in this group of patients. As supplementary zinc can prevent such complications, this study was performed to evaluate the effect of supplementary zinc on body mass index (BMI), forced expiratory volume in one second (FEV1) and number of hospitalizations in CF patients. In this study, 30 children with CF, who were referred to the Digestive Diseases Clinic of the Children's Medical Center in Tehran, were enrolled. Supplementary zinc of 2 mg/kg per day was administered to all patients. Serum level of zinc, alkaline phosphatase, and albumin as well as BMI, FEV1, and number of hospitalizations were compared before and after zinc administration. Height (p0.001), weight (p0.001) and BMI (p=0.001) were significantly increased after zinc, while the number of hospitalizations was significantly decreased (p=0.023). In contrast to patients with normal pulmonary function tests who received supplement therapy, BMI was not increased in those with abnormal pulmonary function after supplementary zinc. Supplementary zinc can increase BMI in CF patients, mostly in those with normal pulmonary function. While supplementary zinc may decrease the number of hospitalizations, other factors can also influence the hospitalization number.

Objective: Celiac disease is an autoimmune disorder in which the risk of autoimmune liver disease is high. Autoimmune hepatitis is a chronic and progressive entity and the risk of its being associated with other autoimmune disorders such as celiac disease is high also. The aim of this study was to determine the prevalence of celiac disease in patients with autoimmune hepatitis and vice versa. Methods: In a cross-sectional study children with autoimmune hepatitis underwent serological screening and endoscopy for celiac disease. In patients with celiac disease, serum aminotransferases were measured and, if abnormal, autoantibodies related to autoimmune hepatitis were checked and needle liver biopsy was performed. Findings: Of the 96 patients, 64 had autoimmune hepatitis and 32 celiac disease. Among patients with autoimmune hepatitis only three (4.7%) were compatible with celiac disease. In the group of patients with celiac disease, autoimmune hepatitis was confirmed in four (12.5%) cases. We consider important to state that 3.1% of this group had celiac hepatitis. Conclusion: Autoimmune liver disease is sometimes associated with latent celiac disease. Serological screening for celiac disease should be routinely done in patients with abnormal serum aminotransferases, particularly those with chronic liver disease. On the other hand, celiac disease is often accompanied by other autoimmune diseases, including autoimmune hepatitis.

Mast cells are related to certain gastrointestinal complaints. Mast cell density has not been studied in cardio-esophageal region to the best of our knowledge. In this study we wanted to obtain an estimate of mast cell density in this region and compare it with mast cell density in antrum. From April 2007 till March 2010, we chose children (14 years old) who underwent upper endoscopy and from whom the taken biopsy was stated to be from lower third of esophagus, but in microscopic examination either cardio- esophageal mucosa or only cardiac mucosa was seen. Mast cells were counted by Giemsa stain at × 1000 magnification in 10 fields. 71 children (14 years old) were included in this study of which, 63.4% (n=45) were female and 36.6% (n=26) were male. The mean age of patients was 7.20 ± 4.21 years (range: 0.2 -14 years). The most common clinical manifestations were recurrent abdominal pain (64.8%) and vomiting (23.9%) followed by symptoms of gastro-esophageal reflux disorder, poor weight gain, hematemesis and dysphagia. The mean mast cell density in the cardiac mucosa was 33.41 ± 32.75 in 0.25 mm2 (range: 0-155), which was two times of that in antral mucosa. We found a significant but weak positive correlation at the 0.05 level between mast cell density of cardiac mucosa and the antrum. Higher mast cell counts were seen in cardiac mucosa in this study. Significant positive correlation between mast cell density of cardiac mucosa and the antrum could hint to a single underlying etiology for the inflammatory process in gastro- esophageal junction and gastric mucosa.

Objective: Extrahepatic biliary atresia (EHBA) is one of the main causes of neonatal cholestasis. Its early diagnosis could increase the survival of the infants with early surgery. We evaluated the diagnostic accuracy of procalcitonin and apolipoprotein E (Apo-E) levels in infants with and without EHBA. Methods: This prospective study included 18 infants with EHBA and 15 infants with other causes of cholestasis. Blood samples were taken from each patient and different markers including procalcitonin and Apo-E levels were measured. ROC analysis was used to define sensitivity, specificity, positive and negative predictive value (PPV and NPV) for procalcitonin and Apo-E. Findings : There was a significantly positive correlation between Apo-E and SGOT (r=0.37, P=0.03), SGPT (r=0.38, P=0.02) and GGT (r=0.38, P=0.02), and an inverse correlation between procalcitonin and GGT (r=-0.45, P=0.01). Area under curve (AUC) for procalcitonin was 0.69 (P=0.05) with cut-point of 0.735 ng/ml. The sensitivity, specificity, PPV and NPV was 67%, 61%, 69% and 59%, respectively. AUC for Apo-E was 0.68 (P=0.06) for cut-point of 61.25 ng/ml with sensitivity, specificity, PPV and NPV of 67%, 67%, 71% and 67%, respectively. Conclusion: Both PCT and Apo-E have relatively good accuracy in diagnosing EHBA cases; we could not rely on these markers for diagnosis of EHBA, however, combinations of these biomarkers with other markers and imaging tests could improve their accuracy and may help to achieve a rapid and accurate diagnosis of EHBA.