The assessment of plasma fatty acid profiles in newly diagnosed treatment-naive paediatric Crohn's disease.

Fatty acid (FA) profiles as potentially relevant components of Crohn's disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn's Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naive newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.

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.

Markers of oxidative stress in diabetic mothers and their infants during delivery.

Oxidative stress is probably a pathophysiological process leading to disadvantageous outcomes in diabetic pregnancies. We aimed to map a complex of potential markers of oxidative stress in this condition. Diabetic mothers had significantly higher concentrations of thiobarbituric acid reactive substances in the plasma [TBARS] both before (p<0.0001) and after (p<0.001) delivery and also their newborns showed higher values of TBARS (p<0.0001) in comparison with the control group. Diabetic mothers also showed lower concentrations of reduced glutathione in erythrocytes [GSH] both before (p<0.05) and after (p<0.01) delivery and their infants also had lower levels of GSH (p<0.0001). We found a lower total antioxidative capacity of plasma [AOC] before delivery (p<0.05) in the diabetic group in comparison with the control group. Newborns of diabetic mothers had higher plasmatic concentrations of apolipoproteine B [apo B] (p<0.05), higher erythrocyte glutathione peroxidase [GPx] activity (p<0.05) and lower pH (p<0.001) in the umbilical cord blood, when compared with infants of control non-diabetic mothers. We conclude that pregestational and gestational diabetes mellitus represent increased oxidative stress for both mother and her infant. TBARS in plasma are a valuable marker of oxidative stress in this condition. Disruption of glutathione peroxidase/glutathione pattern can be involved in pathophysiology of enhanced oxidative stress in diabetic pregnancies.

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.

[Breastfeeding support in nine Czech maternity hospitals 1998-1999]. / Péce o kojení v devíti ceských porodnicích v letech 1998-1999.

OBJECTIVE: To find out the state of breastfeeding support in prenatal and perinatal care and infant feeding in first 6 months in 6 big cities of Czech Republic in 1998-1999. DESIGN: Cross-sectional multicentre descriptive study of 6 medical schools. SETTING: Centre of Preventive Medicine, 3rd Medical Faculty, Charles University, Prague. METHODS: In the first year of the study (1998), 1104 mothers were interviewed by neonatologists at the discharge from 9 maternity hospitals. After 6 months, 1019 mothers of the same sample were interviewed again by students and staff members of 6 medical schools. Obtained data were analyzed in EpiInfo 6 programme using ANOVA and x2 test. RESULTS: 29 percent of mothers participated in prenatal classes. 70 percent of newborns were put to the breast within two hours after birth. 44 percent of mothers reported problems with breastfeeding in the hospital. 77 percent of mothers appreciated the assistance with breastfeeding in the hospital. Mothers with higher education, living with partner or husband, mothers who participated in prenatal classes, mothers after vaginal labour, mothers whose children were put to the breast within two hours after birth and mothers who did not have problems with breastfeeding in the hospital were breastfeeding fully for significantly longer period. At the discharge from the hospital, 93.5 percent of newborns were fully breastfed. At the end of the 6th month, 23.1 percent of infants were fully breastfed and 29.9 percent of infants were breastfed while receiving complementary food. CONCLUSION: Breastfeeding rate at the end of the 6th month of age of infants increased apparently in mothers from 6 big cities of Czech Republic in comparison with national data from 1991.

[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.

Antibodies against oxidized LDL--theory and clinical use.

Modification of low density lipoprotein (LDL) particles due to oxidation, glycation and binding of advanced glycation end-products (AGEs) or malondialdehyde (MDA, a final product of lipid peroxidation) is considered most important in the process of atherogenesis. Oxidatively modified LDL are distinguished by another receptor type, which was discovered on the surface of macrophages and was called the scavenger receptor. Uncontrolled intake of LDL converts macrophages to foam cells; their accumulation under the vascular endothelium is considered as the first stage of atherosclerosis. Oxidation of LDL is a complex process taking place in both the extra- and intracellular space. At the end of this oxidative process, modified LDL particles show chemotactic, cytotoxic and immunogenic properties. Oxidized LDL express a large number of epitopes and cause production of polyclonal autoantibodies against these products, especially against apoB100 modified by MDA and 4-hydroxynonenal. IgoxLDL (antibodies against oxidized LDL) can be demonstrated either directly in intimal lesions or as a component of circulating immune complexes. IgoxLDL do not form a homogeneous group but a varied mixture of antibodies-isoantibodies caused by HDL and LDL polymorphism, antibodies against the lipid phase of LDL and antibodies against modified apoB100 of the immunoglobulin class IgA or IgG. Antibodies against oxLDL were found in many diseases other than atherosclerosis such as diabetes mellitus, renovascular syndrome, uremia, rheumatic fever, morbus Bechtjerev or lupus erythematodes. Newborns have practically the same levels of IgoxLDL as their mothers; however, these values did not differ from those in the healthy population of non-pregnant women of the same age. The decrease in IgoxLDL titer was very slow and lasted many months; that is why this parameter cannot be considered suitable for describing the rapid changes during oxidative stress of the organism. Positive correlation of IgoxLDL with antiphospholipids and other antibodies was repeatedly demonstrated; their determination can thus be used as a marker for the description of total production of autoantibodies in various diseases. The changes and correlations of IgoxLDL, anti-beta-2-glycoprotein I IgG and antiphospholipid antibodies support the immunological link between thrombotic and atherosclerotic processes in the human body.

[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.

Autoantibodies against oxidized LDL in the first phase of life. Low density lipoproteins.

The study presents a comparison of data concerning lipid metabolism and lipid oxidation (oxidative stress) in children at the time of their birth and 3 months later, as well as of their mothers at the time of delivery, compared to a control group of non-pregnant women of the same age. The data confirm that labour represents an oxidative stress for both mother and child; it is expressed as a significant increase of malondialdehyde concentration in mothers immediately after delivery in comparison with non-pregnant women (p<0.001). Its concentration in newborns was even higher than in their mothers (p<0.005). Concentration of antibodies against oxidized LDL (oxLDLAb) was comparable in mothers and newborns due to their transplacental transport. During the first three months of life these autoantibodies increased almost two-fold. The importance of this unique observation is discussed with respect to possible early atherogenesis.

[Lysosomal acid lipase deficiency. Overview of Czech patients]. / Deficit kyselé (lysozomální) lipázy. Prehled ceských pacientu.

Lysosomal lipase deficiency is a hereditary autosomal recessive enzymopathy leading to lysosomal storage of triacylglycerols (TAG) and cholesterol esters (CE). In particular cells with a permanently high receptor-mediated LDL endocytosis are affected (liver, kidneys). There are two basic phenotypes. The fatal infantile phenotype (Wolman's disease) with generalized storage of both types of apolar lipids. This form was diagnosed in this country only once. The opposite is the protracted, oligosymptomatic form encountered in all age groups. It is characterized by the storage of CE (which gave this entity the name of cholesteryl storage disease--CESD). Its main sign is affection of the liver (hepatomegaly, hepatopathy), which in some instances may lead to organ failure, directly or after cirrhotic transformation. Furthermore there is permanent hypercholesterolaemia (high LDL cholesterol) due to increased VLDL synthesis by hepatocytes, low HDL cholesterol and variably raised TAG. This constellation of blood lipids is a risk factor for the development of atherosclerosis. In the course of 25 years in the Czech Republic 13 cases of CESD were diagnosed in 11 families. Ten of these cases were characterized by clinically manifest hepatopathy with hepatomegaly, detected incidentally during medical examinations (at the age of 2-14 years). In three adult patients with permanent hypercholesterolaemia the storage process was subclinical and the diagnosis was established quite incidentally by examination of non-specific secondary and tertiary manifestations of the disease. The diagnosis was established in all cases of CESD at the tissue level (liver biopsy), at the biochemical (acid lipase deficiency) and molecular genetic level (mutation in enzyme locus). In all instances mutation of G934A was found leading to reduction and loss of the eighth exon. This mutation was present in five patients in a homozygous state. Six mutations were heterozygous. In one instance for technical reasons only one allele was analyzed. In three instances a point "missense" mutation was found: T323A (Trp74Arg), T4(75)A (Asp124Glu), A210T (Asp36Gl), in one instance a "nonsense" mutation: C233T (Arg44-stop) and twice a deletion mutation delta C673-5 and delta G1068-8 leading to impairment of the reading frame and to premature stop of the codon.

[Evaluation of diet in a sample of Czech mothers six months after delivery]. / Zhodnocení stravování vzorku ceských matek v sestém mesíci po porodu.

BACKGROUND: Health care of nursing mothers and their infants is an important priority of primary preventive care. The mother's diet plays an important role in this respect. The objective of the presented investigation was to assess the adequacy of the dietary intake of lactating mothers during the sixth month after delivery. METHODS AND RESULTS: Data on the education, body weight, height of the mother, dietary intake, evaluated from a three-day dietary record, were collected from 131 nursing mothers and compared with the Czech recommended dietary allowances for nursing mothers as well as with data from 265 controls, i.e. women who did no longer breastfeed their babies. From the results ensues a significantly higher calcium intake (937 mg; SD = 415, p < 0.001), vitamin B1 (1.1 mg, SD = 0.5, p < 0.001), total energy (8.7 MJ, SD = 2.6, p < 0.01), protein 75.4 g, SD = 18, p < 0.01), carbohydrates (281 g, SD = 112, p < 0.01) and riboflavin (1.3 mg, SD = 0.5, p < 0.01) in nursing women as compared with those not nursing. The nursing mothers, however, do not meet the Czech recommended dietary allowances as regards total energy, calcium, vitamin C, linoleic acid, vegetable proteins and iron. Other problematic nutrients-magnesium, zinc, folates, pyridoxine, selenium and iodine could not be assessed as they are not listed in the Czech food composition tables. In women with university education the energy and nutrient intake was in the majority more favourable than in women with elementary education. On the other hand no statistical differences were found in weight increments during the period from the beginning of gestation to the sixth month after delivery between nursing and not nursing mothers. CONCLUSIONS: The results of analysis of the dietary intake of nursing mothers indicate that the Czech recommended allowances are not met as regards energy, calcium, linoleic acid, protein and iron. Whether the intake is really inadequate or whether the recommended allowances are excessive remains an open question.