Comparative Efficacy of Transcutaneous Functional Electrical Stimulation With or Without Biofeedback Therapy on Functional Non-retentive Fecal Incontinence in Children: A Randomized Clinical Trial.

BACKGROUND: We compared the effects of transcutaneous functional electrical stimulation (TFES) and biofeedback therapy with TFES alone in a cohort of children with functional non-retentive fecal incontinence (FNRFI). METHODS: This prospective, single-center randomized clinical trial was performed on 40 children with FNRFI. Patients were randomly allocated into two equal treatment groups. Group A (n = 20) underwent TFES + biofeedback therapy, and group B (n = 20) received TFES alone. All patients were assessed with a pediatric fecal incontinence (FI) score questionnaire, a visual pain score, and a bowel habit diary both before and at the end of treatment sessions and also at 6 months of follow-up. In addition, a FI quality-of-life (QoL) questionnaire was recorded for all patients before and 6 months after the treatment. RESULTS: FI significantly improved in 13/20 (65%) patients in group A and 11/20 (55%) patients in group B (P < 0.05). A significant reduction in FI score was seen in each group at the end of treatment sessions and maintained at 6 months of follow-up (P < 0.05). A significant improvement in FI-QoL scores was seen in both groups at 6 months of follow-up in which there was no significant difference in terms of FI-QoL scores improvement between both groups after treatment. CONCLUSIONS: The use of electrical stimulation in combination with other treatment methods improves symptoms in patients with FNRFI who are refractory to conventional treatment.

Intrarectal Electromotive Botulinum Toxin Type A Administration in Children With Intractable Constipation: A Randomized Clinical Trial.

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.

Association of IL-10 and TGF-beta cytokine gene polymorphisms with autoimmune hepatitis.

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-ß and IL-10 genetic variants with autoimmune hepatitis. METHODS: Allele frequency and genotype status of IL-10 -1082, -819, -592 and TGF-ß +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-ß +869 "high-producing" allele C and genotype CC were significantly more in autoimmune hepatitis, compared to controls; whereas, TGF-ß +915 "low-producing" allele C and genotype CC were significantly more in autoimmune hepatitis compared to control. TGF-ß +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-ß +869/+915 genotypes and haplotypes with autoimmune hepatitis in Iranians.

IgG4 subclass and gamma-glutamyl transferase in children with ulcerative colitis with primary sclerosing cholangitis and without sclerosing cholangitis.

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.

Association of Interleukin-6 and Interleukin-1 Family Gene Polymorphisms in Autoimmune Hepatitis.

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 sequencespecific primers (PCR-SSP) assay: IL-1a (C/T -889), IL-1α (C/T -511), IL-1ß (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 < 0.0001). 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.

Effects of Interferential Electrical Stimulation Plus Pelvic Floor Muscles Exercises on Functional Constipation in Children: A Randomized Clinical Trial.

OBJECTIVES: Functional constipation is a common condition in children. We assessed the effectiveness of combined interferential (IF) electrical stimulation and pelvic floor muscle (PFM) exercises on functional constipation in children. METHODS: We conducted a single-center, double-blind randomized clinical trial study during 2014-2017 in Tehran, Iran. Ninety children, aged 5-13 years, who fulfilled Rome III criteria were enrolled and randomly assigned into two treatment groups. Case group (n=45) underwent IF electrical stimulation and PFM exercises, whereas the control group (n=45) received PFM exercises plus sham stimulation. A complete bowel habit diary (with concerning 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, after the treatment and 6 months later for all participants. In addition, children in both groups were assessed with a constipation-related quality-of-life questionnaire before, after the end of treatment sessions, and 6 months after the treatment. RESULTS: Treatment success was achieved for 88.4% of children in the case group compared with 43.2% of children in the control group after the treatment (P<0.003). The median constipation score was reduced in both groups, with the cases having significantly lower scores after the treatment (4 vs. 8, P<0.000). Stool form normalized in 75.6% of the cases and 45.5% of the controls after the treatment (P<0.01). CONCLUSIONS: Our results showed that using IF electrical stimulation as an adjuvant therapy to the medical and rehabilitation programs significantly boosts the effects of treatment among these patients.

Association of PTPN22 Single Nucleotide Polymorphisms with Celiac Disease.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS AND CONCLUSIONS: 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 value < 0.0001). 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.

Gastroesophageal Variceal Bleeding as a Complication of Cystic Fibrosis in a 3-Month-Old Patient.

Cystic fibrosis (CF) is a hereditary disease of mucous and sweat glands, which affects the respiratory and gastrointestinal systems. Herein, we describe a 3-month-old girl with a history of recurrent episodes of urinary tract infections that required hospitalization. She was referred to our center at the age of three months, with massive gastroesophageal variceal bleeding. In physical examination, she had clubbing, hepatosplenomegaly, and mild ascites. Laboratory studies revealed high serum levels of liver enzymes and low level of Albumin. As of suspicious to CF, sweat tests were performed twice which confirmed the diagnosis of CF. Gastrointestinal bleeding due to gastroesophageal varices is a rare complication of CF, which could result as a consequence of hepatobiliary involvement of disease. Early diagnosis of CF could prevent severe complications and even death in this group of patients.

Evaluation of antibody response to polysaccharide vaccine and switched memory B cells in pediatric patients with inflammatory bowel 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.

The effect of probiotics on fecal calprotectin in patients with cystic fibrosis.

Cystic fibrosis (CF) is a common autosomal recessive disorder with different clinical manifestations, mainly in the gastrointestinal and respiratory tracts. This study was performed to access the effect of probiotics in the status of intestinal inflammation in a group of children with CF by measuring the calprotectin level in the fecal samples. Forty-seven patients with CF were enrolled in this study. The fecal calprotectin levels were measured by enzyme linked immunosorbent assay. In a randomized systematic method, the children were divided into two groups - one group received probiotic powder and another received placebo for four weeks. After this period, fecal calprotectin was re-measured. Thirty-one of 47 enrolled patients (65.9%) had abnormal fecal calprotectin levels (>50 g/g). After the intervention, the fecal calprotectin levels decreased in 29 patients (21 patients in the drug group, and only 8 patients in the placebo group; p<0.001). This study showed that about two-thirds of patients with CF had intestinal inflammation based on fecal calprotectin levels. Probiotic administration was shown to decrease calprotectin concentrations and subsequently intestinal inflammation in CF patients.

The clinical and laboratory manifestations of Iranian patients with cystic fibrosis.

Cystic fibrosis (CF) is a hereditary disease, characterized by chronic pulmonary disease, pancreatic insufficiency and abnormal electrolytes in the sweat. In order to evaluate the clinical manifestations and laboratory findings of Iranian children with CF during a 10-year period, 243 CF patients, with a median age of 5 months, were investigated in this study. The most common manifestations were gastrointestinal disorders and respiratory manifestations. Cough was the most common symptom, followed by malnutrition, diarrhea, respiratory distress, and vomiting. The frequency of these findings after treatment was significantly decreased in comparison with the period before diagnosis. During the mean follow-up of 40.9 months, seven cases died due to severe infections. Cystic fibrosis as a common genetic disorder should be considered in any child with recurrent gastrointestinal and respiratory manifestations, since delayed diagnosis could lead to severe complications and even death in this group of patients.

Screening for celiac disease in diabetic children from Iran.

Celiac disease has been shown to be associated with type 1 diabetes mellitus. We conducted this study to determine the frequency of celiac disease in a group of Iranian diabetic children. Ninety-six patients with type 1 diabetes mellitus were tested for anti-tissue transglutaminase antibodies. Six patients (6.25%) were seropositive, and histopathological changes were compatible with celiac disease in intestinal biopsy.

Clinical characteristics of Iranian pediatric patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a group of disorders, including Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis (IC). Small intestine and colon are primarily affected in this group of disorders. PURPOSE: This single center study was performed to define demographic features and clinical characteristics of Iranian pediatric patients with IBD. METHOD: Fifty nine patients with IBD, who have been referred to Children's Medical Center Hospital during a 10-year period, were investigated in this study. The data was gathered by interviewing the patients and their families, as well as reviewing their medical records. RESULTS: Among 59 patients with IBD, 23 cases had UC and 19 cases had CD, while the remaining 17 cases had IC. Patients with UC were significantly younger at the time of diagnosis in comparison with patients with CD. The most common symptoms were abdominal pain, diarrhea, fever and growth failure. Hepatobiliary abnormalities and arthritis were common extra intestinal manifestations. The median Pediatric Crohn's Disease Activity Index was 42.5 (range 20-60), whereas the median Pediatric Ulcerative Colitis Activity Index was 40 (range 20-70). Seven of 23 UC (30.4%) had proctatis, while 16 (69.6%) had extensive colitis. In CD, 11 of 19 (57.9%) had involvement of terminal ileum and colon, while inflammation was limited to the colon in 8 cases (42.1%). The colonoscopic findings in the IC group were heterogeneous. CONCLUSION: This study provides epidemiological data on pediatric patients with IBD, which could be useful for health care workers in prompt diagnosis and appropriate treatment of early onset IBD.

Congenital choledochal cyst in an infant with cystic fibrosis.

Congenital choledochal cyst is malformation of the biliary ductal system, which rarely occur. We describe here a 4-month old boy, who was referred to our center with respiratory distress and low level consciousness. In physical examination, a mass was detected in right upper quadrant of abdomen. Sonographic examination indicated a cystic structure representing the choledochal cyst. Further evaluation confirmed the diagnosis of cystic fibrosis in this patient. Although choledochal cyst is considered as a rare disease, it is the most frequent malformation of the extrahepatic biliary ducts, which easily could be misdiagnosed.

Liver needle biopsy in Iraninan pediatric patients: diagnostic significance and pattern of liver diseases.

UNLABELLED: 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.

Helicobacter pylori culture and antimicrobial resistance in Iran.

OBJECTIVE: Helicobacter pylori is considered as an important etiologic factor in pathogenesis of peptic ulcer disease, chronic gastritis and gastric cancer. To eradicate this micro-organism, numerous regimens containing various antimicrobial agents have been suggested. However, H pylori antimicrobial resistance is a leading factor to treatment failure and recurrence of the disease. The aim of the study was to evaluate the prevalence of H pylori resistance to metronidazole, clarithromycin, tetracycline, amoxicillin, erythromycin and furazolidone in authors pediatric patients. METHODS: Antral biopsy of all pediatric patients with negative history of receiving anti-H pylori regimen and endoscopic findings of nodular gastritis or peptic ulcer without previous history of NSAID consumption, burning and trauma were performed for H pylori histology, urease test and culture. All positive cultures were tested for antimicrobial susceptibility. RESULTS: Twenty four patients (14 male and 10 female) between 3.5 and 14 years of age were culture positive. 54.16% of the isolates were resistant to metronidazole, 8.33% to amoxicillin, 4.16% to erythromycin and 4.16% to clarithromycin. None of authors patients were resistant to tetracycline and furazolidone. CONCLUSION: H. pylori antimicrobial resistance could be a major contributor to failure of H pylori eradication. Continuous prospective surveillance of H. Pylori is essential. Moreover, culture and antimicrobial susceptibility test is recommended for resistant cases after the first failure to therapy.

Antimicrobial resistance of Helicobacter pylori isolates from Iranian adults and children.

BACKGROUND: Helicobacter pylori isolates from 84 adults and 51 children were assessed during the period of 2001 through 2004 to find out whether their susceptibilities to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone differ between the two groups or have changed compared with the results from our previous study done between 1997 - 2000. METHODS: Biopsies from 135 dyspeptic patients were cultured on Brucella blood agar. Pure cultures of H. pylori isolates were used for antibiotic susceptibility tests. Disk diffusion method was recruited to assess the susceptibility of H. pylori isolates to different dilutions of the above mentioned antimicrobials. Results obtained from the two groups were compared and minimum inhibitory concentrations determined. RESULTS: Thirty-five percent of H. pylori isolates from adults and 37% from children were resistant to metronidazole. Clarithromycin resistance rate was 2.4% and 5.9% in H. pylori isolates from adults and children, respectively. Amoxicillin resistance was 2.4% in isolates from adults and 5.9% in isolates from children. Tetracycline resistance rate was 0% in H. pylori isolates from adults and 2.0% in isolates from children. Resistance to furazolidone was not observed. CONCLUSION: Resistance rates of H. pylori isolates from adults and children to metronidazole, clarithromycin, amoxicillin, tetracycline, and furazolidone are similar and not significantly affected by age and time.