Nutritional status and body composition in children with inflammatory bowel disease: a prospective, controlled, and longitudinal study.

BACKGROUND: Malnutrition and growth retardation (GR) are major extraintestinal presentations of inflammatory bowel disease (IBD) in childhood and are especially prevalent among those with Crohn's disease (CD). We aimed to evaluate nutritional and growth status and body composition (BC) of children with IBD during a 1-year follow-up. METHODS: Thirty-eight children with IBD and 57 age- and sex-matched controls were recruited prospectively. Anthropometry (weight, height, body mass index (BMI), and triceps skinfold thickness (TSFT) indicated as z scores for age and sex and mid-arm circumference) and bioelectrical impedance analysis were performed at baseline (T0) and after 1 year (T1). Disease activity was evaluated by clinical scoring systems. GR was defined as HAZ < -2, undernutrition as WAZ < -2, severe malnutrition (SM) as BMIZ < -2, and obesity was defined as BMIZ > +2. A p value of <0.05 was considered statistically significant. RESULTS: Thirty-six children with IBD (22 ulcerative colitis, 12 CD, and 2 indeterminate colitis) and 43 controls completed the study. Most patients were in remission during the study period (T0:71.4%; T1:72.2%). No significant differences were found regarding the frequency of GR (5.6%/8.3%), undernutrition (11.1%/2.8%), and SM (11.1%/5.6%) between T0 and T1 in the IBD group. The changes in anthropometrics and BC measurements during the study period did not differ between the groups except for the TSFT z score. CONCLUSION: Most patients with IBD were well nourished and grown, although some children were underweight and had GR. Our results suggest that, in IBD patients, the fat mass (FM) showed a gradual increase over time compared with controls.

Caloric restriction improves the redox homeostasis in the aging male rat heart even when started in middle-adulthood and when the body weight is stable.

Evidence indicates that maintenance of redox homeostasis is fundamental for cellular longevity. Caloric-restriction (CR) is said to decrease the formation of oxidatively modified cellular macromolecules and improve health. On the other hand, some studies indicate that many CR studies are flawed, because ad libitum fed rats are not well-controlled. Thus, it is claimed that purported beneficial effects of CR could be not due to real CR effect, but due to control animals going obese. Also, it remains to be elucidated whether effects of CR could be observed even when CR is started in mid-adulthood. Male Sprague-Dawley rats were grouped as: non-CR 6-month-old rats (n = 7), 24-month-old rats subjected to 40% CR for 6 months between 18th and 24th months (n = 8), and non-CR 24-month-old animals (n = 8). We investigated 16 previously validated biomarkers of macromolecular redox homeostasis, ranging from protein and lipid oxidation to glycation and antioxidative capacity. In the present study, the protein, lipid and antioxidant capacity redox homeostasis biomarkers overwhelmingly indicate that, CR, even though not started very early in adulthood, could still offer potential therapeutic effects and it could significantly improve various redox homeostasis biomarkers associated with disease reliably in the heart tissue of aging male Sprague-Dawley rats. Therefore, the effects of CR likely operate through similar mechanisms throughout adulthood and CR seems to have real ameliorative effects on organisms that are not due to confounding factors that come from ad libitum fed rats.

INFLAMMATORY BOWEL DISEASE-LIKE PHENOTYPE IN A YOUNG GIRL WITH PROLIDASE DEFICIENCY: A NEW SPECTRUM OF CLINICAL MANIFESTATION.

Prolidase deficiency (PD) is an inherited disorder associated with cutaneous ulcers, intellectual disability, unusual facial appearance, skeletal deformities, hematological anomalies, splenomegaly, and chronic infections. We report a girl with PD who presented with early inflammatory bowel disease (IBD). A 2-month-old girl with a dysmorphic face presented with recurrent respiratory tract infections, vomiting, diarrhea and hepatosplenomegaly. She had steatorrhea, abnormal liver enzymes, hypergammaglobulinemia, autoantibody positivity and steatohepatitis in liver biopsy. On follow-up, skin lesions, pruritus and developmental delay were added. At the age of 21 months, IBD was diagnosed with persistent diarrhea, fever, hypoalbuminemia, elevated inflammatory markers, fecal leukocytes and aphthous ulcers in colon. Remission was achieved with prednisone and continued with mesalasine. Thrombocytopenia developed after 3 years. Her findings prompted us to further investigations. PD as the underlying molecular cause of the disease was detected by exome sequencing. In conclusion, PD should be considered in the differential diagnosis of some IBD patients.

Diagnosing oesophagitis in children: how discriminative is histology?

BACKGROUND AND STUDY AIMS: We set out to evaluate the discriminatory value of currently available histologic criteria in the differential diagnosis of reflux oesophagitis and eosinophilic oesophagitis in children. PATIENTS AND METHODS: We evaluated the oesophageal biopsies of 145 children and selected 28 demonstrative cases of clinically confirmed eosinophilic oesophagitis (n = 7), and reflux oesophagitis (n = 11) with a control group with normal histology (n = 10). Histological assessment was performed for the presence of papillary elongation, dilatation of intercellular spaces, basal cell hyperplasia and the number of intraepithelial eosinophils, lymphocytes and neutrophils. RESULTS: Among 28 children, there were 3 boys and 4 girls in eosinophilic oesophagitis group, 8 boys and 3 girls in reflux group, and 5 boys and 5 girls in normal group. The mean age was 10,4 years. Basal cell hyperplasia was observed in 12 cases while papillary elongation was found in 25, and dilated intercellular spaces were present in 20 cases. Lymphocyte and neutrophil counts were significantly higher in reflux group when compared to eosinophilic oesophagitis and normal group. Eosinophil counts were significantly higher in eosinophilic group. CONCLUSIONS: Results of the present study suggest that, basal cell hyperplasia, papillary elongation, and dilated intercellular spaces all seem to be markers of oesophagitis regardless of the underlying pathology and etiology, thereby, highlighting their rather nonspecific nature in the differential diagnosis of various types of oesophagitis. The additional information on inflammatory cell counts may help to distinguish reflux oesophagitis from other causes of oesophagitis including EoO.

The value of the levels of acute phase reactants for the prediction of familial Mediterranean fever associated amyloidosis: a case control study.

In order to determine the role of levels of acute phase proteins (APPs) for the development of amyloidosis in familial Mediterranean fever (FMF) patients, the levels of serum amyloid A (SAA), C reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate were measured in paired sera of 36 FMF patients during and in between acute attacks, 39 of their healthy parents (obligate heterozgotes), and 15 patients with FMF associated amyloidosis. To compare the levels of APPs, 39 patients with chronic infections or inflammatory diseases who may develop secondary amyloidosis, 20 patients with acute infections who are known to have elevated acute phase response but will never develop amyloidosis and 19 healthy controls were included. The median levels of all APPs are increased in the patients with FMF during attacks and a significant decrease was observed after the attack was over. The level of SAA was above reference range in all FMF patients during the attack free period and the level of at least one other APP was also above normal in 64% of the patients. Both CRP and SAA levels were found to be higher in obligate heterozygotes compared to controls. The levels of SAA in patients with FMF during the attack-free period, obligate heterozygotes and patients with FMF-amyloidosis were found to be similar. The levels in each group were found to be higher than SAA levels found in healthy controls yet lower than the levels measured in the patients with acute infections and patients with chronic inflammation or chronic infections. In conclusion, our results show that SAA level reflects subclinical inflammation with high sensitivity but its value for the prediction of amyloid formation process seems to be low.

Toxic hepatitis in a case of Angelman syndrome associated with Lennox-Gastaut syndrome.

We report a 26-month-old boy with Angelman syndrome associated with Lennox-Gastaut syndrome, who developed a rash and a persistent toxic hepatitis after lamotrigine was added to valproate therapy. The patient had typical findings of both Angelman and Lennox-Gastaut syndromes. Chromosome analysis performing by FISH analysis showed a deletion in chromosome 15 (q11.2 q11.2). Although some cases of Angelman syndrome associated with Lennox-Gastaut syndrome were reported in the literature, valproate and/or lamotrigine induced toxic hepatitis in Angelman syndrome has hitherto never been described. We conclude that VPA and LTG combination should be given with great caution or avoided in patients with Angelman syndrome.

Hypertrophic osteoarthropathy in a child with biliary atresia.

Hypertrophic osteoarthropathy is a syndrome characterized by clubbing of the digits of the hand/foot, periosteal reaction and arthralgia or arthritis which is usually secondary to cyanotic congenital heart disease and chronic pulmonary infections. This syndrome rarely occurs in association with chronic liver disease in childhood. Here, we report on a child with biliary atresia who developed arthralgia and arthritis during follow-up and which was diagnosed as hepatic hypertrophic osteoarthropathy. It is emphasized that hypertrophic osteoarthropathy should be considered in the differential diagnosis of arthralgia and arthritis in children with long-standing chronic liver diseases, especially if finger clubbing is also present.

Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood.

OBJECTIVES: Celiac disease (CD), a common cause of malabsorption, is known to be associated with disorders of the skeleton, but there are conflicting data about the effect of diet on bone metabolism. The aims of this study were to investigate the prevalence of osteopenia; to identify the relationship between bone mineral density (BMD), serum calcium, and parathyroid hormone levels; and to determine the effect of gluten-free diet on BMD in children with celiac disease. DESIGN: The study included 32 patients with CD (group 1) and 82 healthy controls (group 2). The patients with CD were evaluated under 2 subgroups, ie, 16 patients with recent diagnosis (group 1a) and 16 patients who follow their diet strictly (group 1b). BMD values and concentrations of calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone were determined on entry to the study and at 12 months in celiac patients. These values were compared with those of healthy control participants. RESULTS: BMD and bone mineral content values in patients with recent diagnosis were found to be significantly lower than the control group. The BMD values in patients with recent diagnosis were significantly increased after a gluten-free diet for 1 year. Osteopenia was found more commonly in patients with recent diagnosis than patients in whom a gluten-free diet had been instituted. At 1-year follow-up, osteopenia was not resolved with the gluten-free diet, and this was especially true in patients without gastrointestinal manifestation. In patients with recent diagnosis (group 1a), the mean calcium level was found to be lower than the patients who follow their diet strictly (group 1b). There was a positive correlation between calcium level and BMD and bone mineral content. CONCLUSIONS: BMD is almost invariably low in newly diagnosed celiac patients in childhood. We therefore recommend that BMD should be evaluated in patients with CD. Strict gluten avoidance promoted a significant increase in BMD. However, values still remained markedly low after 1 year of follow-up in some patients. These patients should be followed for longer periods of time with yearly BMD evaluation, as 1 year of diet therapy was found to be insufficient for osteopenia to be resolved.

Effects of cisapride on ventricular repolarization in children.

Life-threatening ventricular dysrhythmias mainly attributed to QTc prolongation have been reported in adults and children who were using cisapride, a prokinetic agent that facilitates gastrointestinal motility. Recent adult and paediatric case reports have suggested an association of malignant ventricular dysrhythmias with administration of cisapride in conjunction with drugs that inhibit its cytochrome P-450 metabolism. Therefore, to analyse the time- and dose-related effects of cisapride on ventricular repolarization, we prospectively studied infants and children receiving cisapride with no concomitant medications. Standard 12-lead resting ECGs were obtained from 38 patients (mean age: 6.6 +/- 4.4 y) before the first dose of cisapride (0.8-1.2 mg/kg/d) therapy, and 3 d, 7 d and 1 mo after the first dose of continuing cisapride therapy. The corrected QT interval (QTc), dispersion of QT and QTc (QTD, QTcD) were calculated. Patients were divided into two groups according to dose of cisapride: Group 1 (n = 22) (0.8 mg/kg/d), Group 2 (n = 16) (1.2 mg/ kg/d). Data obtained from these patients were compared with a control group consisting of 372 normal children. No clinical adverse effects such as palpitations, presyncope or syncope were noted during the study. Baseline QTc, QTD and QTcD measurements of the study group were not different from those of the control group. Mean QTc values of the study group on days 7 and 30 of cisapride therapy were found to be significantly higher than those of the control group (p < 0.001 and <0.0001, respectively). Mean QTc values of the study group on days 7 and 30 of therapy were also significantly higher than those of baseline value (p < 0.01 and <0.001, respectively). Mean QTD and mean QTcD values that were recorded throughout the cisapride treatment in the study group were not found to be different from the baseline values and the values of the controls. Mean QTD and QTcD were also not found to be different between Groups 1 and 2. However, mean QTc was found to be more significantly increased from baseline at the first month of therapy in Group 2 (p < 0.05). The results of this study suggest that cisapride treatment cause prolongation of ventricular repolarization without causing increased heterogeneity of repolarization (QT dispersion). However, the clinical significance of this effect is unclear, because all the patients in this study group remained asymptomatic, without signs of dysrhythmia.

Celiac disease in Turkish short-statured children and the value of antigliadin antibody in diagnosis.

BACKGROUND: It is generally accepted that celiac disease (CD) must always be taken into consideration when dealing with children manifesting growth failure. It is, therefore, important to have laboratory tests capable of detecting patients who should undergo intestinal biopsy. In this study, we have prospectively evaluated clinical characteristics, gliadin antibody measurements and duodenal biopsies in 47 children with short stature and without gastrointestinal symptoms, in order to determine the incidence of CD and the diagnostic value of immunoglobulin (Ig)A and IgG antigliadin antibodies (AGA) for CD. METHODS: Anthropometric parameters and IgA- and IgG AGA were evaluated in 47 children with short stature. Antigliadin antibodies were measured by enzyme-linked immunosorbent assay (Euroimmun kit). Endoscopic intestinal biopsies were taken from all children. RESULTS: On the basis of intestinal biopsy, 26 (55.3%) patients were found to be probable CD. Sensitivity, specificity, positive predictive (PPV) and negative predictive value (NPV) for IgA AGA was found to be 23, 90, 75 and 48%, respectively. Sensitivity, specificity and PPV for IgG AGA was 100, 0 and 55%, respectively. The NPV for IgG AGA was not determined. CONCLUSIONS: The results of our study demonstrated that because of their incomplete sensitivity, specificity, PPV and NPV, intestinal biopsy can not be replaced by these tests.

Isolated deficiency of glucocorticoids presenting with cholestasis.

BACKGROUND: Isolated deficiency of glucocorticoids is characterized by elevated levels of adrenocorticotropin (ACTH) and normal aldosterone production. It is rare for isolated deficiency of glucocorticoids to be associated with liver involvement. A case of an infant with isolated deficiency of glucocorticoids presenting with cholestasis is presented in this article. A male infant on his 39th postnatal day was referred to our hospital for evaluation of prolonged jaundice and convulsion. He had two episodes of hypoglycemic convulsion on postnatal 8th and 39th day, after which he was admitted to our hospital. RESULTS: Physical examination revealed systemic jaundice, hyperpigmentation of the skin, hepatomegaly and splenomegaly on admission. He had normal male genitalia with 3.5 cm of penis and bilateral scrotal testes. Laboratory values were as follows: glucose 45 mg/dL, total biluribin 18.14 mg/dL, direct biluribin 6.54 mg/dL, aspartate aminotransferase 378 IU/L, alanine aminotransferase 46 IU/L, and alkaline phosphatase (ALP) 1302 IU/L. In abdominal ultrasound and biliary tract scanning, extra- and intrahepatic biliary tracts were shown to be normal. Finally, biopsy of the liver revealed cholestasis. An endocrinological evaluation showed high levels of adrenocorticotropin (ACTH, 1000 pg/mL), low levels of cortisol (1 microgram/dL) and normal aldosterone levels. CONCLUSIONS: The diagnosis of cholestasis secondary to isolated glucocorticoid deficiency was suspected with clinical and laboratory findings. Hydrocortisone treatment (30 mg/m2 per day) was initiated after which hyperpigmentation and jaundice decreased and ACTH and ALP levels reduced to 39 pg/mL and 440 IU/l, respectively. We emphasize that cholestasis in infants may be a component of isolated deficiency of glucocorticoids.

Hepatic damage in gluten sensitive enteropathy.

BACKGROUND: Gluten sensitive enteropathy has been reported to occur concomitantly with liver abnormalities, such as primary biliary cirrhosis, chronic active hepatitis and primary sclerosing cholangitis. METHODS: Duodenal biopsy was performed in nine children (all with short stature, five with chronic diarrhea and three with hepatosplenomegaly of unknown etiology) with a possible diagnosis of gluten sensitive enteropathy. All of the patients had different abnormalities in serum aminotransferase levels. With the help of laboratory investigations, viral, autoimmune, metabolic and toxic etiologies which cause hepatic damage were excluded. Liver biopsy was performed in five of these patients, two showing fibrosis and three nonspecific reactive changes. Gliadin antibodies were measured in six cases. RESULTS: Intestinal mucosal histopathology was compatible with gluten sensitive enteropathy in all patients. While immunoglobulin (Ig) G gliadin antibodies were positive in all cases, only three cases were found to have positive IgA gliadin antibodies. After a gluten-free diet, levels of transaminases fell to normal within 3 months and remained so in seven of these patients. A second intestinal biopsy, which was performed after 1 year of gluten-free diet revealed normal intestinal mucosa in all patients. CONCLUSION: Gluten sensitive enteropathy should be considered when evaluating a child with elevated levels of serum transaminase and in cases with cryptogenic liver disease.

Hereditary pancreatitis: report of a family from Turkey.

Chronic pancreatitis is a rare disease in children and is usually secondary to underlying diseases such as hereditary pancreatitis, cystic fibrosis, hyperlipidemia, prolonged malnutrition, gallstones or anomalies of the biliary-pancreatic duct system. Hereditary pancreatitis is a common cause of chronic pancreatitis in children but is often unrecognized until months or years later. We report here a family with hereditary pancreatitis in which four members are affected.

Vaginal ectopic ureter in a duplex system with renal dysplasia. A case report.

A 12-year-old girl with vaginal ectopic ureter in a duplex system associated with an extremely dysplastic upper segment who presented with a complaint of vaginal discharge is reported. The diagnostic approach with special reference to ultrasonography and computerized tomography is discussed.