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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: Severe congenital neutropenia (SCN4) caused by mutations in glucose-6- phosphatase catalytic subunit 3 (G6PC3) is characterized by recurrent infections due to severe neutropenia, may be accompanied by other extra-hematopoietic manifestations; including structural heart defects, urogenital abnormalities, prominent superficial venous markings, growth retention, and inflammatory bowel diseases with rare incidence. The homozygous or compound heterozygous mutations of G6PC3 are responsible for most cases of autosomal recessive SCN4. Herein, we present two cases of SCN4 affected by novel mutations in the G6PC3, in addition to a summarized list of variants in G6PC3 gene that are reported as pathogenic and related to the SCN4 phenotype. Case presentation: Herein, we present two cases of SCN4; the first case was a three-months old boy with severe neutropenia and prior history of hospitalization due to umbilical separation, umbilical herniation, omphalitis, and pyelonephritis; and the second case was an eight-year-old with a history of neutropenia, recurrent and severe episodes of intractable diarrhea, refractory rectovaginal and rectoperineal fistula, congenital inguinal hernia, and ASD type 2. Whole exome sequencing was performed for both cases, which revealed two novel homozygous missense mutations in G6PC3 that were predicted to be deleterious; c.337G>A, p. Gly113Arg in the first case and c.479C>T; P. Ser160Leu in the second case. To our knowledge, both of these two mutations have not been reported in the G6PDC3 gene. Conclusions: In patients with severe neutropenia with varying extra hematopoietic syndrome, mutation of G6PC3 should be suspected after ruling out other mutations related to neutropenia. This study pointed toward novel G6PC3 mutations that should be considered in order to diagnose patients with severe congenital neutropenia.

Background: Celiac disease is an immune-mediated systemic disease, in which gluten ingestion causes different symptoms. HLA-DQ2 is positive in 90% - 95% of celiac patients. HLA has been considered to inhibit antibody production against the hepatitis B virus vaccine. Considering that celiac disease affects about 1% of the population, this phenomenon could be a significant factor in immunization programs. On the other hand, HLA-DQ2 positive patients not only are at the risk of HBV infection themselves but also have the potential to be an important source of HBV dissemination in the world. Objectives: This study was carried out to evaluate the responsiveness of celiac-affected children to HBV vaccination in Iran. Methods: This case-control prospective study was performed on 62 Iranian children (31 children with confirmed celiac disease before introducing a gluten-free diet and 31 healthy children). HBS Ab (antibody against hepatitis B virus surface antigen) titer was checked in the patients and compared between the two groups. Results: It was shown that 67.7% of cases and 64.5% of controls had HBS Ab titer above 10 mIU/mL, but the difference was not significant statistically. After matching for the time interval from the last HBV vaccination, it was observed that although non-significantly, celiac disease can decrease the chance for anti-HBS production up to 30%. Conclusions: This study did not confirm non-responsiveness against the HBV vaccine in celiac disease in children. This may be due to genetic factors or type of vaccine. Moreover, in our study, responsiveness was assessed qualitatively in the two groups (HBS Ab > 10 mIU/mL was considered as a responder).

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.

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.

Introduction and aim. Autoimmune hepatitis (AIH) is an immune-mediated destruction of liver cells, in recognition of interface hepatitis, seropositivity for autoantibodies, and interface hepatitis in histology sections. Hepatocyte destruction in AIH is the direct result of CD4+ T-cell destruction. Yet, Th17 mediated immune attach and a diversity of cytokine networks, including pro-inflammatory cytokines such as Interleukin 1 (IL-1) and Interleukin 6 (IL-6), set the stage for the destructive liver damage. Material and method. Peripheral blood samples from 57 patients, with AIH, recruited from referrals to the main pediatric hospital in Tehran. Single nucleotide polymorphisms for the following cytokines genes, were evaluated through, polymerase chain reaction with sequence-specific primers (PCR-SSP) assay: IL-1a (C/T -889), IL-Ια (C/T -511), IL-1 β (C/T +3962), IL-1 receptor (IL-1R; C/T Pst-I 1970), IL-1RA (C/T Mspa-I 11100), and IL-6 (C/G -174 and A/G nt565). Results. Significant higher frequency of genotype AA was detected in patients in IL-6 at position nt565 (15.8% in AIH patients vs. 2.9% in controls, p = 0.003). The haplotype GA of IL-6 at -174 and nt565, was significantly overrepresented in the AIH group, compared to (20.9% of AIH vs. 1.4% in controls p Conclusion. Results of our study, indicate significant deviation toward high yield IL-6 polymorphisms, in AIH patients. These data could bring new insights in pathophysiology of disease, which could contribute to developing novel treatments for AIH.

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: Constipation is a frequent complication in pediatrics, most of which is habitual, comprising 25% of visits in pediatric gastroenterology clinics. Objectives: The main object of this study was to investigate clustering of habitual constipation among families of pediatric patients. Methods: This case-control study was conducted on families of 150 children < 18 years old with chronic habitual constipation alongside families of 150 healthy children as controls. The cases were enrolled in the study according to the Rome IV criteria for constipation. The parents and siblings were evaluated regarding constipation. Data were analyzed using SPSS-16, χ2 and t-test were used for comparison. Results: A total of 300 children and their families participated in the study. No significant differences were found between the study and the control groups in age, sex, or BMI. However, the siblings or parents from the study group had significantly higher rates of constipation compared with the control group. Conclusions: Considering different survey findings, a correlation between “habitual constipation” and “familial background” seems to exist in children. A clear pathophysiological explanation for this phenomenon is not yet available.

Ascites is not a usual finding in prehepatic portal hypertension, including portal vein thrombosis, but when portal vein thrombosis is acute and massive, ascites can be a presenting feature. We report a 9-year-old boy with tense ascites and portal and superior mesenteric vein thrombosis. A 9-year-old boy was evaluated for tense ascites which led to umbilical hernia since one month before admission. He did not have any clinical or laboratory stigmata of parenchymal liver disease. Imaging studies showed superior mesenteric and portal vein thrombosis. In laboratory tests for pre-thrombotic states, he suffered from significant protein S deficiency. Thrombophilic states like protein S deficiency predispose patient to vascular thrombosis. This vascular thrombosis can be present with signs and symptoms related to their territories. Prevention of thrombosis and rethrombosis with anticoagulant therapy is recommended.

Summary Background Allergic colitis (AC) is one of the most common etiologies of rectal bleeding in infants aged one to six months. Aim The aim of this study is to apply step-by-step dietary restrictions in the mother's diet or change of infant formula fed thereby, to evaluate the subsequent clinical response. Methods Sixty healthy infants whose clinical and evaluation results indicated proctocolitis in our outpatient gastroenterology clinic were included in this. They were divided into three groups according to the type of feeding; group 1 were exclusively breast fed, group 2 were exclusively formula fed and group 3 were fed with combination of both. In breast feeding women, discontinuation was allergenic food was studied in four stages; cow-related dairy products, soy, sesame and fast food (stage A), egg (stage B), corn, nuts and fish (stage C) and wheat (stage D). Results Sixty newborns with age at symptom onset 3 days–20 days participated in the study. Up to the time of our initial evaluation, the mean age and weight of infants was 73.34 ± 1.00 day and 3292.71 ± 367.93 g, respectively. There was no significant difference in sex and the type of labor between the groups. Thirty-three infants had a history of eczema and the parents of 47 infants had a history of allergy, with the greatest prevalence in group one. Rectal bleeding in 50% of infants was halted after the elimination of allergenic feed in mother (15 in stage A, 8 in stage B and 7 in stage C). Ten infants needed extensive hydrolyzed formula and 20 needed amino acid-based formulas. Conclusions There is no need for immediate use of amino acid or extensive hydrolyzed formulas in the first stage of blood in stool, perhaps discontinuing allergenic food in mothers could be the primary measure.

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.

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.

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.

Background & Aims The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. Methods We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. Results Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61–99.99); the PPV was 100.00 (95% CI, 98.68–100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67–99.96) to 100.00 (95% CI, 99.23–100.00). Conclusions Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.

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.

Background: Chronic abdominal pain in children is a common disorder. For an accurate diagnosis of its cause, sometimes invasive diagnostic procedures such as endoscopy should be performed. Objectives: The purpose of the study was to evaluate the fecal calprotectin in children with upper gastrointestinal signs and symptoms and to compare it with endoscopic findings. Methods: A total of 131 children aged 1-14 years with upper gastrointestinal symptoms were enrolled during 2012 - 2013 at two centers. One hundred and twenty patients underwent endoscopy and biopsy. Before endoscopy, the level of calprotectin was measured by the enzyme-linked immunosorbent assay test in stool samples and the results were compared with the endoscopic and pathology findings. Results: Of the 120 children included in this study, 71 (59.2%) were males and 49 (40.8%) females with a mean age of 93.6 months. Of the 112 patients in whom biopsies were taken, 16 had esophagitis, 89 chronic gastritis (79.5%) and 57 colonization with Helicobacter pylori. Conclusions: There was a statistically significant correlation between fecal calprotectin and gastritis and severity of H. pylori infection. Fecal calprotectin level measurement can avoid unnecessary endoscopies and is also useful for evaluation of therapy response.

Background/Aims: Cystic fibrosis (CF), the most common hereditary, life-threatening disease, is caused by a mutation in the CFTR gene. Because different mutations can affect clinical manifestations of patients, this study was conducted to investigate the possible genotype-phenotype relationship in a group of Iranian patients with CF. Materials and Methods: This case-series study was conducted in 30 patients with CF who were referred to a tertiary pediatric hospital in Tehran. In this study, the DNA of the patients was evaluated for delta F508 mutation, whereas some parameters such as the age at diagnosis, the sweat chloride level, and clinical manifestations related to pancreatic insufficiency and pulmonary involvement were also assessed. Results: Among all the studied patients, 16.6% had a delta F508 mutation, either homozygote or heterozygote. The mean age at diagnosis was lower in patients with the delta F508 mutation, but the sweat chloride level tended to be higher in these patients. All the patients with the delta F508 mutation had exocrine pancreatic insufficiency, which tended to be higher than 84% in those without this mutation. In addition, all of these patients had pulmonary involvement, which tended to be higher than 64% in those with negative delta F508 mutation. Conclusion: According to the results of this study, the frequency of delta F508 mutations in Iranian patients appears to be much lower than what is seen in American and the European patients. In those with the delta F508 mutation, pulmonary involvement and pancreatic insufficiency are more common; the sweat chloride level tended to be higher, but the age at diagnosis was lower, all of which resemble a more severe form of disease.

Background/Aims Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. Methods Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. Results Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. Conclusions A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.

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.

Introduction Poor weight gain is one of the most important mortality hazards in cystic fibrosis (CF) patients. The mechanisms that may hinder body weight regulation are not completely understood. Leptin and its role in fat mass could be related to control of weight gain in CF patients. As the previous data are conflicting, we aimed to investigate serum leptin level in Iranian CF children compared to a control group. Material and methods Forty-three CF patients aged from 3 to 120 months and 43 age-matched controls were enrolled. Patients were recruited from the outpatient clinic of the Children's Medical Center Hospital. Controls were visited in the general outpatient clinic for an annual check-up. Both groups were divided into three subgroups based on age: 3 to 12 months, 13 to 48 months, and 49 to 120 months. Body mass index (BMI) was calculated for all the participants. Serum leptin levels were measured applying a solid phase enzyme-linked immunosorbent assay (ELISA). Results Leptin levels and BMI values were significantly different between patients and controls (p = 0.02, p < 0.001, respectively) but only patients aged 13–48 months had significantly higher levels of leptin than age-matched controls (p = 0.016). Overall male patients’ mean leptin level was significantly higher than in female patients (p = 0.032) and male controls (p < 0.001). Conclusions Leptin level in our patients was significantly higher than controls. It seems that leptin levels during infancy are higher than in adult patients. Further studies are required on specific genotypes, gender and age to reveal the probable correlation with BMI and leptin levels in CF patients from different ethnic groups.

Although several invasive and noninvasive tests have been developed for the diagnosis of Helicobacter pylori infection, all of the tests have their limitations. We conducted a study to investigate and compare the suitability of rapid urease test (RUT), serology, histopathology and stool antigen tests with polymerase chain reaction (PCR) for detection of H. pylori, and correlate the diagnostic methods with PCR. Eighty nine patients (61 adults, 28 children) referred to the Firoozgar Hospital and Children Medical Center Hospital for diagnostic upper gastrointestinal endoscopy entered to the study and noninvasive tests such as immunoassay for serological antibodies against H. pylori and detection of its antigen in feces were measured. The biopsies were utilized for histological examination, RUT and PCR. The H. pylori statuses were evaluated by the positivity of ureC PCR in biopsy specimens and 53 subjects had H. pylori positive result. Histopathology showed high overall performance in adults and children with sensitivity and specificity 100% and 90%, respectively. Sensitivity, specificity, and accuracy for stool antigen test were 87.8%, 75% and 82%, respectively. Correlation of RUT, serology (IgG), histopathology and stool antigen tests with PCR were 0.82, 0.32, 0.91 and 0.63, respectively. In conclusion, the RUT and histopathology are as accurate as the PCR of biopsy and stool antigen test can consider as appropriate noninvasive test for detection of H. pylori infection.

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. Eosinophilic esophagitis is an inflammatory condition where there is a dense infiltration of eosinophils typically exceeding fifteen cells per high power field. Familial Mediterranean fever is an autosomal recessive disorder characterized by brief, acute, and self-limited episodes of fever and polyserositis that recur at irregular intervals. Case Presentation. A three-year-and-nine-month-old Iranian girl was admitted to our center. The patient’s parents complained of a history of abdominal pain, poor appetite, and poor weight gain from 1.5 years ago and episodes of food impaction after starting solid foods. Eosinophilic esophagitis was diagnosed based on histology. Because of continuing abdominal pain after treatment of eosinophilic esophagitis, the episodic nature of disease, and the presence of fever with pain, screening for familial Mediterranean fever mutation was performed and the patient was found to be heterozygote for Mediterranean fever. Conclusion. We have reported a case of eosinophilic esophagitis coexisting with familial Mediterranean fever which has not been described previously.

INTRODUCTION: Cystic fibrosis (CF) is a common genetic disorder as a result of mutation in the CF transmembrane conductance regulator gene. Weight loss in CF patients seems to be multifactorial and metabolic factors, inflammation, recurrent infections and poor appetite are possible candidates. Ghrelin affects energy hemostasis by stimulating growth hormone secretion, glucose and lipid metabolism alteration and inhibition of the inflammatory system. Data on the role of ghrelin in energy deficiency in CF patients are sparse and controversial. The study was done to compare the plasma levels of the acylated form of ghrelin in CF patients with healthy participants. MATERIAL AND METHODS: Thirty cystic fibrosis patients (aged 1-168 months) and thirty healthy matched participants were enrolled in the study. Plasma ghrelin and albumin levels were measured and body mass index (BMI) was calculated as well. RESULTS: Plasma levels of acylated ghrelin in CF patients were significantly higher than the control group (mean 25-75%: 14.5 vs. 2.7, p = 0.032). Body mass index measurements in CF patients were significantly lower than the control group (p < 0.001). Using regression analysis there was no statistically significant correlation between plasma ghrelin levels and serum albumin, weight, height or BMI values in CF patients and controls. CONCLUSIONS: The acylated ghrelin levels are increased in CF. So plasma levels of acylated ghrelin could be used as an indicator of food uptake and energy balance in them. Further studies should be established to find out the exact role of factors affecting energy metabolism.

Introduction Infection is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Antimicrobial resistance of the bacterial spp. particularly methicillin resistance in Staphylococcus aureus has caused a lot of attention. The aim of this study was to describe the prevalence of S. aureus, Pseudomonas aeruginosa and Burkholderia cepacia-complex as well as their antimicrobial susceptibility patterns in CF patients in an Iranian referral pediatrics Hospital. Material and methods From March 2011 until February 2012, 172 samples were collected at the Children Medical Center (CMC), an Iranian referral hospital in Tehran, Iran. Sputum specimens were cultured for the following bacterial pathogens: P. aeruginosa, S. aureus, B. cepacia complex. Antimicrobial susceptibility was performed according to the Clinical Laboratory Standards Institute recommendations. Results In our study, 54% of the patients (n = 93) harbored at least once S. aureus, 30% (n = 52) P. aeruginosa, and 2% (n = 3) Burkholderia cepacia. In 40 patients (23%), none of these organisms was grown. An increasing colonization rate of P. aeruginosa in the second decade of life was found. In contrast, the colonization rate of S. aureus was constant in both decades of life. Methicillin resistant S. aureus (MRSA) was detected in 40 isolates (43%). Among MRSA, no resistance against vancomycin, linezolid and quinupristin/dalfopristin occurred. The susceptibility of P. aeruginosa isolates to meropenem, imipenem, doripenem, levofloxacin and polymixin B were more than 90%. Conclusion The prevalence of MRSA has been rising. Since its impact on clinical outcomes, optimal prevention and treatment strategies are unclear, further studies to expand the knowledge about the infection control strategies and MRSA treatment are highly recommended.

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.

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/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.

Helicobacter pylori infection is acquired mainly in childhood, especially in developing countries, where a low-cost, rapid diagnostic technique which is reliable for all age groups may be useful for the management of H. pylori infection. For this purpose, we used an HpSA test (Equipar) to detect H. pylori infection in children and adolescents from Tehran, Iran. Thirty-five children who were positive or negative for H. pylori infection by endoscopy-based tests were used as positive and negative controls for the HpSA test. Stools were collected from 430 randomly selected children and adolescents (4 to 18 years old) from southwest, near the center, and northwest of Tehran. A questionnaire that included presence of recurrent abdominal pain (RAP), family history of infection and/or peptic ulcer disease (PUD), and income of parents was completed. A good agreement was found between the results of endoscopy-based tests and those of the HpSA test; the sensitivity and specificity of the Equipar-HpSA test were 100% and 83.4%, respectively. Among 430 children and adolescents, 47% were positive by the HpSA test, of whom 82% had RAP. No difference in incidence was observed between the two sexes; the various categories of age showed an increasing incidence, ranging from 24% (ages 4 to 6) to 58% (ages 16 to 18). The rate of infection in children and adolescents from the southwest was significantly higher (70%) than the rate in those from the northwest (32%), and a family history of H. pylori infection or PUD was observed in 59% of the HpSA positive subjects. The HpSA test is a useful test to detect H. pylori infection in children and adolescents from developing countries.

Bacillus Calmette-Guérin (BCG) vaccine, which is a widely practiced vaccine in some regions, could lead to a variety of complications. Herein, a 2-month-old infant is presented who was referred because of hepatosplenomegaly and diarrhea. Liver biopsy indicated multiple small and large granulomas composed of epithelioid histiocytes; granulomas resided in portal or lobular areas. The diagnosis of granulomatous hepatitis was made, and treatment with isoniazid, rifampine, and ethambutol were started. Liver function tests were normalized and hepatosplenomegaly was reduced in an 8-month follow-up. The presence of epithelioid cell granuloma in the liver may indicate a diagnosis of disseminated BCG as a rare complication of vaccination. Prompt diagnosis and appropriate treatment could prevent further complications in the affected patients.

Introduction Protein losing enteropathy is a symptom characterized by loss of protein in intestines resulting in low protein levels in serum and generalized edema. Several causes are reported for this condition. Hereby we report an as yet unreported cause of protein losing enteropathy that we named meso-intestinal fibrosis. Case Report A 2.5-year-old girl referred with features of partial intestinal obstruction and underwent laparotomy. She had history of protein losing enteropathy since 16 months of age with generalized edema and received albumin every other week. Workup of protein losing enteropathy was inconclusive and only a histology report denoted increase in eosinophils in lamina propria of small intestine and hypoallergenic diet was started for her, but no significant response was noted. Laparotomy revealed lace-like white areas in meso of small intestine and intestinal wall was firm in palpation in some areas. Biopsy was taken from these sites and histology revealed severe fibrosis of meso overlying muscularis propria and also patchy fibrosis of intestinal meso led to severe lymphangiectasis in submucosa of small intestine. Discussion Secondary lymphangiectasis due to obstruction of lymphatic flow is mentioned as cause of protein losing enteropathy. Meso-intestinal fibrosis seen in this case that led to secondary lymphangiectasis and also motility disorder has not been reported as yet.

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.

Morbus Crohn (MC) ist eine chronisch entzundliche Erkrankung des Verdauungstrakts. Die genaue Atiologie der Erkrankung ist zwar immer noch unbekannt, aber mehrere Studien haben in Assoziation mit MC uber Mutationen im CARD15/NOD2-Gen berichtet. Die vorliegende Studie wurde durchgefuhrt, um herauszufinden, ob das CARD15/NOD2-Gen padiatrische Patienten im Iran zu MC pradisponiert. Alle 12 kodierenden Exons des CARD15/NOD2-Gens wurden bei 16 Crohn-Patienten mit Krankheitsbeginn im Kindesalter sequenziert. Die Sequenzierung des CARD15/NOD2-Gens ergab keine Mutationen. Zwei Patienten hatten jedoch einen Polymorphismus in diesem Gen. Bei einem 10-jahrigen Madchen mit mild verlaufendem MC, das eine rektovaginale und perianale Fistel und multiple Marisken hatte, wurde der heterozygote SNP (Single Nucleotide Polymorphism) rs3135500 C > Y im Exon 12.3 gezeigt. Ein 5-jahriger Junge mit moderatem bis schwerem MC sowie einer Anamnese von perianalen Fissuren und oraler Candidiasis hatte einen heterozygoten SNP in den Exons 4.1 and 12.1. Die Ergebnisse dieser Studie zeigen, dass CARD15/NOD2-Mutationen bei iranischen Patienten mit MC-Beginn im Kindesalter nicht fur die Pathogenese der Erkrankung verantwortlich sind.

Abetalipoproteinemia (ABL), or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder of lipoprotein metabolism, characterized by fat malabsorption, hypocholesterolemia retinitis pigmentosa, progressive neuropathy and acanthocytosis from early infancy. We describe the clinical and molecular characterization of a 6-month-old infant born of consanguineous, apparently healthy parents from Iran. The patient was hospitalized because of failure to thrive, greasy stool and vomiting. The patient's serum lipid profile, the clinical phenotype and the duodenal histology suggested the clinical diagnosis of ABL. The MTP gene analysis by direct sequencing revealed a novel homozygous mutation (c.1586 A > G-H529R). The parents were heterozygotes for the same mutation and interestingly the father showed a lipid profile characterized by a slight reduction of total and LDL-cholesterol plasma levels.

Background/Aims Gastroesophageal reflux disease (GERD) and cow's milk allergy (CMA) are two common conditions that occur in infancy. This study was performed to investigate the frequency of CMA in a group of patients with GERD. Methods Eighty-one children with signs and symptoms of GERD were enrolled in this study. All subjects received omeprazole for 4 weeks after the initial evaluation. Empirical elimination of cow's milk from the diet was started for the patients who did not respond to the omeprazole treatment. Results Seventy-two cases presented with gastrointestinal signs and symptoms, whereas the remaining nine cases presented with respiratory complaints. After the initial treatment with omeprazole, two thirds of the cases (54 patients, 66.7%) responded well, and all of their symptoms were resolved. Cow's milk was eliminated from the diets of the remaining 27 patients. All signs and symptoms of GERD were resolved in this group after a 4 week elimination of cow's milk from the diet. Conclusions A diagnosis of CMA was considered in one third of the pediatric cases with signs and symptoms of GERD. This finding shows that CMA can mimic or aggravate all signs and symptoms of severe GERD during infancy.

Crohn's disease (CD) and ulcerative colitis (UC) are two inflammatory bowel diseases (IBD) characterized by chronic intestinal inflammation. In this study, the clinical characteristics of a cohort of pediatric patients with IBD are reviewed and their responses to induction therapy are evaluated. The severity of disease for 43 patients (20 with CD and 23 with UC) was determined using the PCDAI and PUCAI and based on the initial severity, before treatment was started. Following treatment, the severity of disease was re-evaluated at 6 months after the initial diagnosis. The patients in both groups had mild-to-severe disease. The mean PCDAI and PUCAI values were 60.62 +/- 16.48 and 50.95 +/- 9.35, for CD and UC patients, respectively. Most patients (83.7 %) responded to standard treatments with a significant reduction in the PCDAI and PUCAI scores from baseline (p value < 0.001). At the primary endpoint of 24 weeks, 54 % of all patients were in clinical remission; 16 of 23 in the UC group (70 %) and 6 of 20 in the CD group (30 %). The results of this study provide evidence that subgrouping pediatric patients with IBD into distinct clinical phenotypes based on severity of the initial presentation may provide better means of management of this group. This approach can result in a better response to treatment and reduce the side effects of unnecessary therapy.

Aim of Study: Chronic gastritis is defined as the presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia. This condition constitutes a background for dysplasia and thereby carcinoma. Detection of exact histopathology of inflammatory process is necessary in biopsy specimen. We designed the current study to determine the value of taking more sections in small gastric biopsies for better histopathologic evaluation. Materials and Methods: Gastric biopsy specimen of children who suffered from gastrointestinal (GI) symptoms was sent in 10% formalin to our laboratory. After routine processing, three slides with several sections on them were taken from the specimen: t0 he first was named the superficial section, the second was stained by Giemsa and the third was named deep section (further sections after this slide will diminish in size). The slides were not taken exactly consecutively but several sections were discarded between them. The purpose of this study is to compare the superficial and deep sections for detection of inflammatory processes. Results: In 1062 specimens the results of superficial section and deep section were the same (87.1%) and in 158 specimens the results were different. In 88 (7.2%) specimens deep section was diagnostic. The difference was seen usually as normal tissue in superficial sections but presence of lymphoid follicle in deep sections. The difference between superficial and deep sections was statistically significant. Although obtaining more sections will put an economic burden on the laboratory, we propose that in small gastric biopsies, it is helpful in better evaluation of histopathological changes.

Object Previous studies have shown nutritional benefits of breastfeeding for a child's health, especially for protection against infection. Protective factors in human milk locally and systemically prevent infections in the gastrointestinal as well as upper and lower respiratory tracts. It remains unclear whether breastfeeding protects infants against ventriculoperitoneal (VP) shunt infection. Methods A cohort study was conducted from December 2003 to December 2006 at Children's Hospital Medical Center in Tehran, Iran. A total of 127 infants with hydrocephalus who were treated using a VP shunt in the first 6 months of life were enrolled. Each infant's breastfeeding method was classified as either exclusively breastfed (EBF), combination feedings of breast milk and formula (CFBF), or exclusively formula-fed (EFF). Infants were followed up to determine the occurrence of shunt infection within 6 months after operation. Statistical analysis was performed using survival methods. Results Infants ranged in age from 4 to 170 days at the time of shunt insertion (mean 69.6 days), and 57% were males. Regarding the breastfeeding categories, 57.5% were EBF, 25.2% were CFBF, and 17.3% were EFF. During the follow-up, shunt infection occurred in 16 patients, within 15 to 173 days after shunt surgery (median 49 days). The 6-month risk of shunt infection was 8.5% (95% confidence interval [CI] 4–18%) in the EBF group, 16.5% (95% CI 7–35%) in the CFBF group, and 26.0% (95% CI 12–52%) in the EFF group. There was no statistically significant difference between these 3 groups (p = 0.11). The trend test showed a significant trend between the extent of breastfeeding and the risk of shunt infection (p = 0.035), which persisted even after adjustment for potential confounding variables (hazard ratio = 2.01, 95% CI 1.01–4). Conclusions This study supports the protective effect of breastfeeding against shunt infection during the first 6 months of life and the presence of a dose–response relationship, such that the higher the proportion of an infant's feeding that comes from human milk, the lower the incidence of shunt infection. Encouraging mothers of infants with VP shunts to breastfeed exclusively in the first 6 months of life is recommended.

Introduction Several conditions are considered in differential diagnosis of neonatal cholestasis. Of these the most important is extrahepatic biliary atresia (EHBA), while prompt diagnosis and surgical correction of obstruction can ameliorate clinical symptoms, provides long term survival for about one fourth of patients and serves as an important bridge to transplantation for many others. From histopathologic standpoint, features of EHBA overlaps with other diagnoses and so ancillary tests such as immunohistochemical staining for CD56 is suggested by some authors as a helpful tool in differential diagnosis. Hereby we wanted to examine this staining in our center which is a referral children hospital and to prove its efficacy in our problematic cases. Materials and Methods By retrospective review of pathology records during 2000 to 2006 in Markaze Tebbi Koodakan (children hospital related to Tehran University of Medical Sciences), we selected 17 cases of EHBA as patients and 12 cases with other diagnoses as controls, both with some degree of bile ductular proliferation in liver biopsies. EHBA cases were all proved by surgery. Four of control cases also underwent surgery but proved to have open ducts by intra-operative cholangiography. Long term follow up and other tests ruled out EHBA in other 8 cases. Hematoxylin-Eosin stains of paraffin blocks were studied again and freshly prepared sections were immunostained for CD56. Results Bile ducts and proliferating bile ductules were strongly positive for CD56 in 6 of 17 cases of EHBA. In 7 out of 17, positivity were seen in more than two thirds of portal tracts. In controls, one case showed strong positivity and 6 out of twelve showed positivity in more than two thirds of portal tracts. The intensity and distribution of CD56 staining did not differ significantly between two groups. Discussion Despite findings of previous studies, we have shown that CD56 staining can not help as an ancillary test in differential diagnosis of neonatal cholestasis and perhaps other markers should be tested in this regard.

We evaluated two protocols for isolation of Helicobacter pylori in stool from biopsied and nonbiopsied children. Twenty-three child patients whose presumptive positivity or negativity was diagnosed by endoscopy and a rapid urease test at site were used to compare biopsy-based tests with stool-based tests (H. pylori stool antigen test and stool culture). Their gastric activity and bacterial density were graded by the updated Sydney system. Biopsy and stool specimens were cultured on Campy-blood and Belo horizonte agar plates after enrichment in selective Campy-Thio medium. To compare two stool culture protocols, stools from 20 nonbiopsied children were tested by the HpSA test and cultured either as above or after treatment with cholestyramine. Grown colonies were screened by Gram staining, slide agglutination using anti-H. pylori monoclonal IgG; positive isolates were tested by biochemical tests and polymerase chain reaction for H. pylori-specific ureA gene. Coccoid H. pylori was isolated in stool samples from the biopsied patients whose bacterial density was two to four in histology. Their oxidase was slightly positive but became positive after two subcultures, while additional biochemical tests confirmed the isolation of H. pylori. Similar coccoid but oxidase positive H. pylori was isolated from three nonbiopsied children with the protocol of cholestyramine treatment only. The density of bacteria in the stomach may influence the recovery of H. pylori from stool; inactivation of bile with cholestyramine improves the yield in culture and favors isolation of an enhanced metabolic form of bacteria.

Antibiotic susceptibility testing of 70 pediatric Helicobacter pylori isolates was performed by using screening agar and disk diffusion methods. Resistance to metronidazole and tinidazole was 72 to 79% and 71 to 81% by modified disk diffusion and 77% and 78% by screening agar, respectively. Susceptibilities to amoxicillin, ampicillin, clarithromycin, tetracycline, erythromycin, and ciprofloxacin were 58, 69, 75, 68, 68, and 65%, respectively.

Introduction Extra-hepatic biliary atresia (EHBA) is an important cause of neonatal cholestasis. Several infectious agents have been proposed as etiologic factors such as Rotavirus and Reovirus. There is limited data on the role of Epstein Barr virus (EBV) infection in EHBA, so we decided to study the presence of EBV virus in a series of 16 proven EHBA cases by Chromogenic in situ hybridization (CISH) technique. Methods In the current study a total of 16 liver wedge biopsies of proven cases of EHBA were selected in a period of 4 years. CISH staining for EBV-encoded RNA (EBER) transcript was performed. Results The review of H&E-stained slides of liver biopsies revealed fibrosis and marked ductular proliferation. In CISH-stained slides, EBV trace was observed in hepatocytes in two cases and in biliary epithelium in one case of EHBA. Discussion Considering the association of hepatitis with the Epstein-Barr virus in later life, it is likely that EBV hepatitis and its complications occur in the neonatal/perinatal period. Since EHBA is a relatively rare disease, a similar study on wedge biopsies of this number of proven cases of EHBA has not been performed to date. Current observation proposes the need for a study of larger series and employing other methods for confirming the etiologic role of EBV in EHBA cases.

AIM: To study the effect of oral garlic on arterial oxygen pressure in children with hepatopulmonary syndrome. METHODS: Garlic powder in a capsule form was given to 15 children with hepatopulmonary syndrome (confirmed by contrast echocardiography) at the dosage of 1 g/1.73 m2 per day. Patients were evaluated clinically and by arterial blood gas every four weeks. RESULTS: The garlic capsule was administered to 15 patients with hepatopulmonary syndrome. There were 10 boys and 5 girls with a mean age of 9.4 ± 3.9 years. The underlying problems were biliary tract atresia (4 patients), autoimmune hepatitis (4 patients), cryptogenic cirrhosis (4 patients) and presinusoidal portal hypertension (3 patients). Eight patients (53.3%) showed an increase of 10 mmHg in their mean arterial oxygen pressure. The baseline PaO2 was 65.6 ± 12.1 mmHg in the responder group and 47.1 ± 11.2 mmHg in non-responder group. At the end of treatment the mean PaO2 in responders and non-responders was 92.2 ± 7.75 mmHg and 47.5 ± 11.87 mmHg, respectively (P < 0.01). CONCLUSION: Garlic may increase oxygenation and improve dyspnea in children with hepatopulmonary syndrome.