Gut peptide hormones and pediatric type 1 diabetes mellitus.

The aims of our study were to evaluate plasma levels of gut hormones in children with Type 1 diabetes mellitus (T1DM) in comparison with healthy controls and to correlate plasma concentrations of gut hormones with blood biochemistry, markers of metabolic control and with anthropometric parameters. We measured postprandial levels of specific gut peptide hormones in T1DM children. Amylin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), ghrelin, leptin, pancreatic polypeptide (PP), and polypeptide YY (PYY) were assessed in 19 T1DM children and 21 healthy reference controls. Multiplex assay kit (LINCOplex(®)) was used for determination of the defined plasma hormone levels. T1DM subjects had significantly reduced amylin (p<0.001) and ghrelin (p<0.05) levels, whereas GIP (p<0.05) was elevated when compared with healthy controls. Plasma levels of other measured hormones did not differ statistically between the studied groups. Further analysis of T1DM patients demonstrated an association between body mass index and GLP-1 (r=0.4642; p<0.05), leptin (r=0.5151; p<0.05), and amylin (r=0.5193; p<0.05). Ghrelin levels positively correlated with serum HDL cholesterol (r=0.4760; p<0.05). An inverse correlation was demonstrated with triglycerides (TG) (r= -0.5674; p<0.01), insulin dosage (r= -0.5366; p<0.05), and HbA1c% (r= -0.6864; p<0.01). Leptin was inversely correlated with TG (r= -0.6351; p<0.01). Stepwise regression analysis was performed to enlighten the predictive variables. Our study demonstrated an altered secretion pattern of gut peptide hormones in T1DM children. A close correlation was revealed between these peptides as well as with blood biochemistry, markers of metabolic control and with anthropometric parameters. Further studies are essential to explore this issue in T1DM children.

Reactivity to Helicobacter pylori antigens in patients suffering from thyroid gland autoimmunity.

The role of infection in autoimmunity is widely discussed. In this study we concentrated on relationship between HELICOBACTER PYLORI as a very important gastroduodenal pathogen and autoimmune thyroiditis (AT). Forty seven AT patients and 34 healthy controls were enrolled. They were split into: THP ( H.PYLORI positive patients, n=17), THN ( H.PYLORI negative patients, n=30), CP ( H.PYLORI positive controls, n=17) and CN groups ( H.PYLORI negative controls, n=17). By protein microarray we analysed production of 23 cytokines and chemokines prior and post stimulation with H.PYLORI lysate and its lipopolysaccharide (LPS). Reactivity to lysate as well as to bacterial LPS differed within groups. The lowest basal cytokine and chemokine production was observed in CN group but these subjects reacted significantly to specific stimulation by increasing IFN-gamma (in comparison with THP p=0.01 for LPS and p=0.004 for H.PYLORI lysate) and TGF-beta production (p=0.015 for LPS). In contrast, IL-10 and IL-5 were decreased in this group. In CP, THN and THP groups, we observed in general higher chemokine response. THP group increased proinflammatory IL-6 after specific stimulation as well (in comparison with CP p<0.0001 for LPS stimulation). We observed different "reactivity pattern" to H.PYLORI within groups with low basal cytokine and chemokine production in healthy H.PYLORI negative controls but with clear specific response in IFN-gamma and TGF-beta production in this group. Adequate immune reaction which is joined to appropriate immunoregulation leads to prevention of the chronic infection and on the other hand may prevent the development of "connected" diseases such as autoimmune.

Asymmetric dimethylarginine and the effect of folate substitution in children with familial hypercholesterolemia and diabetes mellitus type 1.

A recently discussed cardiovascular risk factor, asymmetric dimethylarginine (ADMA), is known to act as an endogenous inhibitor of endothelial nitric oxide synthase. The aim of this study was to establish 1) the relationship between ADMA and ultrasonographically or biochemically determined endothelial dysfunction in children, and 2) the effect of folate supplementation on these parameters. The study cohort included 32 children with familial hypercholesterolemia (FH), 30 with diabetes mellitus type 1 (DM1) and 30 age-matched healthy children as the control group. Furthermore, twenty-eight randomly selected FH and DM1 children were re-examined after 3-months supplementation with folic acid. Baseline levels of ADMA and oxidized low density lipoproteins (oxLDL) were significantly higher in FH group than in DM1 and healthy children. Children in DM1 group had significantly lower concentration of homocysteine, but ADMA levels were normal. Folic acid supplementation significantly lowered homocysteine and hsCRP levels in both FH and DM1 group; however, ADMA and oxLDL concentrations remained unaltered. In conclusion, ADMA and oxLDL appear to be associated with endothelial dysfunction in children with FH. Administration of folic acid did not influence these markers in both FH and DM1 children.

[Current epidemiological and clinical issues regarding Helicobacter pylori infection in childhood]. / Soucasná epidemiologicko-klinická problematika infekce Helicobacter pylori v detském veku.

H. pylori infection is common worldwide, and is acquired primarily during childhood. The mechanism of acquisition is not clear. In recent years the main focus of interest has been on the transmission of infection from family members to children. The main risk factor for acquiring the infection seems to be low socioeconomic status. H. pylori is associated with gastritis, duodenal ulcers, MALT lymphoma, and gastric adenocarcinoma. Extra-intestinal clinical manifestations have also been reported. However, the infection is often asymptomatic in children and the role of H. pylori infection in gastric manifestations is the subject of conflicting reports. Methods for the diagnosis of H. pylori infection in children are subdivided into invasive and noninvasive. There is a lack of consensus on treatment. The treatment of H. pylori is hampered by high macrolide-resistance. Treatment with proton pump-based triple therapy for 1-2 weeks gives the best eradication rates when combined with supplements containing probiotics. Multinational, multicentre studies in childhood are essential to extend current knowledge to avoid long-term gastroduodenal disease sequelae.

[Marfan's syndrome--application of revised criteria and differential diagnosis in clinical practice]. / Marfanuv syndrom--aplikace revidovaných kritérií a diferenciální diagnostika v klinické praxi.

PURPOSE OF THE STUDY: To design a system of diagnostic criteria that would allow us to differentiate benign articular hyperelasticity from Marfan's or Ehlers-Danlos syndromes and, on the basis of clinical, anthropometric, radiological, biochemical and densitometric findings, their specificity and statistical significance, to draw definitive conclusions for clinical practice. MATERIAL: A total of 240 patients who presented with the diagnosis of one of connective tissue disorders were included. They all were examined and, in 182 of them, the findings were completed to meet the criteria required by differential diagnosis. METHODS: Revised criteria were used for Marfan's syndrome (MFS), Ehlers-Danlos syndrome (EDS), osteogenesis imperfecta (OI), juvenile idiopathic osteoporosis (JIO), cutis laxa (CL) or benign articular hyperelasticity (BAH). All patients provided their medical histories, and underwent clinical, radiological, anthropometric, echocardiographic and biochemical examinations, including that for markers of bone formation and resorption. The anteroposterior bulb length was assessed by ultrasonography; densitomery was performed and vital capacity was measured. All data obtained were processed by computer software and the definitive diagnosis was established. RESULTS: Out of 82 patients initially diagnosed with MFS, only 43 (52.4%) met the revised criteria; of the 53 EDS patients initially, 30 (56.6%) met the revised criteria. Four patients who had been referred to us with MFS were found to meet the criteria for EDS (two) and OI (two). Out of 35 patients with OI, 22 (62.8%) met the diagnostic criteria. All 24 patients with BAH were confirmed to have this diagnosis. On the basis of the revised criteria, none of the patients was diagnosed as having JIO or CL. DISCUSSION: The authors compare their results of decreased levels of procollagen I, the occurrence of scoliosis or acetabular protrusion and reduced vital capacity with the relevant reports in the literature. CONCLUSIONS: The specific criteria for Marfan's syndrome include lens dislocation or an anteroposterior bulb axis longer than 24 mm, ascending aortic dilatation, greater body height and the ratio of lower extremities to the body and that of arm-span to height higher than 1.05. However, some criteria, such as the metacarpal-phalangeal index, are not characteristic of Marfan's syndrome only and, therefore, cannot be regarded as a major diagnostic feature of this disorder.

Helicobacter heilmannii gastroduodenal disease and clinical aspects in children with dyspeptic symptoms.

AIM: To evaluate the occurrence and clinical characteristics of Helicobacter heilmannii infection among children presenting with dyspeptic symptoms. METHOD: Prospective cohort study of 580 patients. RESULTS: Of all examined dyspeptic children, 26.4% were infected with spiral-shaped organisms, and 0.9% of patients were found to be infected with spiral H. heilmannii-like organisms. CONCLUSION: In children with dyspeptic symptoms, the possible presence of gastroduodenal disease due to H. heilmannii should be considered. Further studies are needed to clarify H. heilmannii-related gastroduodenal pathology in the paediatric population.

[Diagnosis of Helicobacter pylori infection in childhood with a novel immunoenzyme method (HpStAR) which detects antigens in feces using monoclonal antibodies ]. / Diagnostika infekce Helicobacter pylori v detském veku novou enzymoimunoanalytickou metodou stanovením antigenu ve stolici (HpStAR) pomocí monoklonálních protilátek.

BACKGROUND: Premier Platinum HpSA EIA is an enzyme immunoassay developed for diagnosis of H. pylori infection using polyclonal antibodies against H. pylori in human stool. A new H. pylori stool antigen test, based on monoclonal antibodies, has been developed. Our aim was to evaluate prospectively the accuracy of the novel antigen stool test (DAKO HpStAR) using monoclonal antibodies for detection of H. pylori infection in children. METHODS AND RESULTS: Total of 93 children undergoing upper gastrointestinal endoscopy were included in the study. Biopsy specimens were sampled from the gastric antrum and from the corpus. Patients were classified as H. pylori positive if histology and urease test were positive. All children provided a stool sample within 3 days after gastroscopy. IgG serology against H. pylori was also employed. HpStAR test was performed according to the manufacturers protocol. Results were read at 450/630 nm by spectrophotometry (cut-off point 0.150). Of the 93 children, 26 were H. pylori positive (13.1 +/- 3.2 yr), and 67 patients were H. pylori negative (12.8 +/- 4.7 yr). Only 2 children were misclassified (1 false negative, and 1 false positive). Sensitivity was 96.1%, specificity 98.5%, the positive and negative predicting values were 96.1% and 98.5%, respectively. Serology showed sensitivity 88.5%, specificity 70.2%; the positive and negative predicting values were 53.5% and 94% respectively. CONCLUSION: HpStAR test based on monoclonal antibodies can be considered an accurate, non-invasive, reliable method for the diagnosis of H. pylori infection in children.

[Symptomatology and specific characteristics of chronic gastritis caused by Helicobacter pylori infection in children in the Czech population--epidemiologic, clinical, endoscopic and histomorphologic study]. / Symptomatologie a specifické rysy chronické gastritidy zpusobené infekcí Helicobacter pylori v detském veku v ceské populaci--epidemiologicko-klinická, endoskopická a histomorfologická studie.

BACKGROUND: H. pylori infection is associated with gastritis and peptic ulcer in children and adults. H. pylori acquisition seems to occur predominantly in childhood. Some data have reported H. pylori non-related chronic gastritis. Little information is available about the relationship between H. pylori, clinicopathologic features and long-term effects of infection in childhood. The purpose of this study was to compare the differences between chronic gastritis due to H. pylori with those of chronic gastritis not associated with H. pylori infection. METHODS AND RESULTS: 92 children (13.8 +/- 3.5 years) were take into they shaded group. 51 children were H. pylori positive, 41 children had no evidence of H. pylori. Epidemiological and clinical data, endoscopic appearance and histologic examination were evaluated. There were no differences in age and gender among the children. There was a significant correlation between H. pylori infection and parental education (p < 0.05) and habitat crowding (the number of rooms). There were no differences in clinical diagnosis and occurrence of any predominant symptom between the two groups. There was an association with a detrimental influence on daily life and activities in H. pylori patients (p < 0.01). Extradigestive symptoms (chronic urticaria, sideropenic anemia) were significantly more common in the H. pylori positive group (p < 0.05). 21 children (41.6%) were H. pylori positive/cagA positive, 15 of them (30.3%) were H. pylori positive/vacA positive. Findings of antral nodularity were more frequent in H. pylori positive children than in H. pylori negative (p < 0.000001). There were no differences in erythematous gastritis, haemorrhage and mucosal ulceration. H. pylori density score did not differ in various part of the gastric mucosa (antrum, corpus). Chronic gastritis was found to be more severe in patients with H. pylori infection compared with H. pylori-negative gastritis. Statistically significant was the increased presence of neutrophils, edema, monocytes, lymphoid follicles, the intensity of inflammation and mucosal oedema in the gastric mucosa in H. pylori positive children. There were no differences in the incidence of foveolar hyperplasia, mucosal atrophy, intestinal metaplasia and erosion. CONCLUSION: H. pylori related chronic gastritis may be considered as a specific form of inflammation and it may be associated with a typical clinical symptomatology in a subgroup of children in Czech population. Precautions in life style may diminish H. pylori-related disease in children.

[Accurate noninvasive diagnosis of Helicobacter pylori infection using antigen determination in the feces in the pediatric population]. / Presná neinvazivní diagnostika infekce Helicobacter pylori pomocí stanovení antigenu ve stolici v detské populaci.

BACKGROUND: H. pylori can cause several gastroduodenal diseases. Because H. pylori infection is usually acquired in childhood, accurate diagnosis of the infection in the pediatric population is important. Tests for the diagnosis of H. pylori infection can be divided into invasive and noninvasive. The aim of our study was to compare invasive tests (endoscopy, gastric mucosal biopsy, histology) and the noninvasive, newly developed stool antigen test to diagnose H. pylori infection. METHODS AND RESULTS: 91 children (40 boys, 51 girls, mean age 12.6 +/- 3.5 years) with dyspeptic symptoms were tested for H. pylori infection using endoscopy and gastric biopsy and a new antigen test in stool samples (immunoassay). Thirty-one of the children (34.1%) with dyspepsia were found positive for H. pylori according to histologic examination and rapid urease test. In 28 of the 31 patients, H. pylori stool antigen could be detected (sensitivity 90.3%). Of the 60 patients with negative direct histologic examination and rapid urease test, 60 were H. pylori--negative in stool antigen test (specificity 100%). Positive predictive value of stool antigen test is 100% and negative predictive value is 95.2%. CONCLUSIONS: The stool antigen test is highly sensitive and specific. It will be potentially very helpful in the diagnosis of H. pylori infection and can replace endoscopy for detection of H. pylori infection in children with comparable accuracy and reliability.

[Hypergastrinemia associated with Helicobacter pylori infection and sideropenic anemia in a 15-year-old girl]. / Hypergastrinémie spojená s infekcí Helicobacter pylori a sideropenickou anémií u patnáctileté dívky.

H. pylori is a major cause of primary chronic gastritis and peptic ulcer disease in children. The authors give an account of H. pylori infection (cagA+, vacA+) in a 15-year-old girl where the initial clinical features included fatigue, collapses, and anorexia, elevated serum gastrin level (> 1000 mIU/l) raised the suspicion of gastrinoma. H. pylori gastric infection was also associated with iron-deficiency anemia. After treatment for H. pylori infection (omeprazole, clarithromycin, amoxycillin), clinical symptoms improved consistently, the serum gastrin level was repeteadly quite normal and hematologic and iron profiles were within the normal range. There is compelling evidence that H. pylori must be taken into account as a cause of hypergastrinemia other than gastrinoma in childhood.

[Autoimmune enteropathy with onset in early infancy: clinico-morphologic and immunologic manifestations]. / Autoimunní enteropatie se zacátkem v casném kojeneckém veku: klinicko-morfologické a imunologické projevy.

This paper describes a severely affected male infant with serious protracted diarrhoea caused by a rare autoimmune enteropathy. The disease began at 6 weeks of age of the child and it was associated with small bowel villous atrophy and the presence of circulating antienterocyte antibodies. The child was treated with steroids and with parenteral and special enteral nutrition. The patient showed clinical improvement as documented by decreased stool output and possibility to terminate the parenteral nutrition. The small biopsy samples showed a return to normal. Antienterocyte antibodies were negative after the treatment. The patient has been followed up for at least 18 months and was in a clinical remission. We recommend that autoantibodies tests should be performed in all infants with unexplained protracted diarrhoea. The use of potent immunosuppressive drugs and the increasing experience with parenteral and enteral nutrition can improve the perspective of these previously fatal disorders.

[Organ-specific antibodies in children with idiopathic inflammatory bowel disease and their use in clinical practice]. / Orgánove specifické protilátky u detí s idiopatickými strevními zánety a jejich uzití v klinické praxi.

BACKGROUND: Ethiopathogenesis of the idiopathic inflammatory bowel disease has not been yet fully explained. Several abnormalities of the humoral immunity supporting the concept of autoimmune character of the disease have been identified. The aim of our study was to characterise occurrence of the organ specific antibodies against the intestinal goblet cells and against acinar cells of the exocrine pancreatic tissue and to evaluate their significance for the diagnostics of the idiopathic inflammatory bowel disease. METHODS AND RESULTS: 69 children were included in the study. The group consisted of 20 patients with idiopathic proctocolitis (11 boys and 9 girls, 6 to 18 years old, average age 15.5) and 14 patients with Crohn's disease (9 boys and 5 girls, 5 to 18 years old, average age 14.7). Control group included 35 children (20 boys and 15 girls, average age 14.7). In patients of the idiopathic proctocolitis group, antibodies against the intestinal goblet cells were assayed by indirect immunofluorescence method in 55%. In patients with Crohn's disease, antibodies against acinar cells of the exocrine pancreatic tissue were found in 64.2%. Differences in manifestation of antibodies against acinar cells of the exocrine pancreatic tissue in Crohn's disease were statistically significant (p = 0.001). Statistically significant (p = 0.01) was also the difference of levels of antibodies against the intestinal goblet cells in patients with idiopathic proctocolitis when compared to patients with Crohn's disease. Statistically significant difference (p = 0.01) was found in levels of antibodies against acinar cells of the exocrine pancreatic tissue in Crohns disease and antibodies against the intestinal goblet cells in patients with idiopathic proctocolitis. CONCLUSION: Testing on presence of specific antibodies against acinar cells of the exocrine pancreatic tissue and against intestinal goblet cells is a valuable tool for the diagnostics of the idiopathic inflammatory bowel disease in childhood and adolescence.