[Prevalence of an association between coeliac disease and vitiligo]. / Prävalenz der Assoziation von Zöliakie und Vitiligo.

Coeliac disease and vitiligo are immune-mediated disorders that are often associated with other immune-mediated disorders. In a prospective study we included 174 patients with vitiligo between the ages of 3 and 79 years (mean 38.2 years) to investigate whether there is an increased risk for coeliac disease in patients with vitiligo. We determined immunoglobulin A and IgA- and IgG-antibodies against tissue transglutaminase, while also optionally measuring blood count, ferritin, and endomysial-IgA-antibodies. In 3 of 174 (1.7%) vitiligo patients, coeliac disease was diagnosed serologically and by duodenal biopsy. Assuming a coeliac disease prevalence of less than 0.0033%, the incidence is statistically significant. In two other patients with vitiligo, coeliac disease was already known and confirmed with biopsy. If these two patients are included in the calculation, 2.8% (5 von 176) of vitiligo patients have coeliac disease. This value is statistically significant even with a higher coeliac disease prevalence of 0.01. Thus, it is recommended that celiac-disease-specific antibodies also be determined during routine blood workup in vitiligo patients. In case of positive results, a gastroduodenoscopy with biopsy of the small intestine is recommended for diagnosis confirmation. If celiac disease is unlikely, a trial of gluten-free diet for a specific time should nevertheless be discussed with individuals affected by vitiligo because repigmentation appears possible.

CANDIS treatment program for cannabis use disorders: findings from a randomized multi-site translational trial.

BACKGROUND: In a recent paper, we reported the efficacy of a modular cognitive-behavioral intervention for treating adolescents and adults with cannabis use disorders (CUD). In this study, we examine the outcome of this intervention after translating it into clinical practice. METHODS: A multi-site, randomized controlled trial of 279 treatment seekers with ICD-10 cannabis use disorders aged 16- 63 years was conducted in 11 outpatient addiction treatment centers in Germany. Patients were randomly assigned to an Active Treatment (AT, n=149) or Delayed Treatment Control (DTC, n=130). Treatment consisted of 10 sessions of fully manualized individual psychotherapy that combined Cognitive-Behavioral Therapy, Motivational EnhancementTherapy and problem-solving training. Assessments were conducted at baseline, during each therapy session, at post-treatment and at three and six month follow-ups. RESULTS: At post assessment 53.3% of AT patients reported abstinence (46.3% negative urine screenings) compared to 22% of DTC patients (17.7% negative drug screenings) (p<0.001, Intention-to-treat analysis). AT patients improved in the frequency of cannabis use, number of cannabis dependence criteria, severity of dependence, as well as number and severity of cannabis-related problems. Effect sizes were moderate to high. While abstinence rates in the AT group decreased over the 3-month (negative urine screenings: 32.4%) and 6-month (negative urine screenings: 35.7%) follow-up periods, the effects in secondary outcomes were maintained. CONCLUSIONS: The intervention can successfully be translated to and applied in clinical practice. It has the potential to improve access to evidence-based care for chronic CUD patients.

Efficacy of a targeted cognitive-behavioral treatment program for cannabis use disorders (CANDIS).

AIMS: To examine the efficacy, 3- and 6-month follow-up effects of a psychological treatment for older adolescents and adults with DSM-IV cannabis use disorders. The program was tailored to the needs of this patient population. EXPERIMENTAL PROCEDURES: A randomized controlled clinical trial of 122 patients aged 16 to 44 years with DSM-IV cannabis dependence as the main substance use diagnosis was conducted. Patients were randomly assigned to either Active Treatment (AT, n = 90) or a Delayed Treatment Control group (DTC, n = 32). Treatment consisted of 10 sessions of therapy, detailed in a strictly enforced manual. Assessments were conducted at baseline, during each therapy session, at post treatment and at follow-up assessments at 3 and 6 months. RESULTS: The treatment retention rate was 88%. Abstinence was achieved in 49% of AT patients and in 13% of those in DTC (p < 0.001; intend-to-treat (ITT) analysis). Further, AT patients improved significantly (p < = 0.001) in the frequency of cannabis use per week, addiction severity, number of disability days, and overall level of psychopathology. Program effects were maintained over a 3-month- (abstinence rate: 51%) and 6-month follow-up (45%) period. CONCLUSION: The treatment program is effective in obtaining abstinence as well as reducing cannabis use and improves the associated social and mental health burden.

Identification of GP2, the major zymogen granule membrane glycoprotein, as the autoantigen of pancreatic antibodies in Crohn's disease.

BACKGROUND AND AIMS: The aetiopathogenesis of Crohn's disease, an inflammatory bowel disease (IBD), is not yet fully understood. Autoimmune mechanisms are thought to play a role in the development of Crohn's disease, but the target antigens and the underlying pathways have not been sufficiently identified. METHODS: Based on data from immunoblotting and matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry, the major antigenic target of pancreatic autoantibodies (PABs), which are specific for Crohn's disease, was identified. Specificity of autoantibody reactivity was confirmed by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) using purified rat and human recombinant GP2 synthesised in transiently transfected mammalian HEK 293 cells. Real-time polymerase chain reaction (rt-PCR) and IIF were used to detect mRNA and antigen localisation in human colon biopsies. RESULTS: The major zymogen granule membrane glycoprotein 2 (GP2) was identified as the autoantigen of PABs in Crohn's disease. PAB-positive sera from patients with Crohn's disease (n = 42) displayed significantly higher IgG reactivity to rat GP2 in ELISA than either PAB-negative sera (n = 31), or sera from patients with ulcerative colitis (n = 49), or sera from blood donors (n = 69) (p<0.0001, respectively). Twenty-eight (66%) and 18 (43%) of 42 PAB-positive sera demonstrated IgG and IgA reactivity to human recombinant GP2 in IIF, respectively. Patients with PAB-negative Crohn's disease (n = 31) were not reactive. GP2 mRNA transcription was significantly higher in colon biopsies from patients with Crohn's disease (n = 4) compared to patients with ulcerative colitis (n = 4) (p = 0.0286). Immunochemical staining confirmed GP2 expression in human colon biopsies from patients with Crohn's disease. CONCLUSION: Anti-GP2 autoantibodies constitute novel Crohn's disease-specific markers, the quantification of which could significantly improve the serological diagnosis of IBD. The expression of GP2 in human enterocytes suggests an important role for anti-GP2 response in the pathogenesis of Crohn's disease.

Probiotic Escherichia coli Nissle 1917 (EcN) for successful remission maintenance of ulcerative colitis in children and adolescents: an open-label pilot study.

Since about 20 % of patients with ulcerative colitis (UC) are children and adolescents there is a need for therapeutic options custom-tailored to the children's needs. E. coli Nissle 1917 (EcN) as an evidence-based probiotic alternative to mesalazine (5-ASA) in adult UC remission maintenance is a promising agent for such a therapy. The present open-labelled pilot study was undertaken to investigate the clinical benefit of EcN for maintenance therapy in young UC patients. 34 patients with UC in remission aged between 11 and 18 years were allocated either to EcN (2 capsules o. d., n = 24) or 5-ASA (median 1.5 g/d, n = 10) and observed over one year. As a result, the relapse rate was 25 % (6 / 24) in the EcN group and 30 % (3 / 10) in the 5-ASA group. Data on the patients' global health and development were favourable and no serious adverse events were reported. In conclusion, maintenance therapy for UC with the probiotic EcN is effective also in young patients.

[Pitfalls in diagnosis of celiac disease]. / Fallstricke bei der Zöliakiediagnostik.

Both serology and histology remain cornerstones in the diagnosis of coeliac disease. IgA class antibodies against tissue transglutaminase and endomysium have the highest specificity and sensitivity in comparison with other serological tests. An IgA deficiency in serum must always be excluded. Antigliadin antibodies have, because of their low positive predictive value apart from in early childhood, no value as a diagnostic tool in coeliac disease. Intestinal biopsies should be evaluated according to the revised Marsh criteria. A discrepancy between serology and histology requires a competent evaluation by a gastroenterologist and, if necessary, further diagnostic procedures.

[Definitions of celiac disease--statement of an expert group from the German Society for Celiac Disease]. / Verlaufsformen und Definitionen der Zöliakie--Stellungsnahme einer Expertengruppe der Deutschen Zöliakie-Gesellschaft.

Celiac disease may have different manifestations and the clinical course can be very heterogeneous. Thus, management and treatment of celiac disease can be difficult and therefore requires individual patient care. In this article an expert group from the German Society for Celiac Disease (Deutsche Zöliakie-Gesellschaft) defines the different manifestations of celiac disease. In the past these definitions were often used differently. The consequent usage of these definitions may diminish uncertainties in clinical practice and lead to a more standardized management of the disease which is likely to improve patient care.

[Prevalence of type 1 diabetes-specific autoantibodies and of certain HLA patterns in celiac disease]. / Prävalenz Typ 1-Diabetes-spezifischer Autoantikörper und bestimmter HLA-Muster bei Zöliakie.

BACKGROUND AND OBJECTIVE: An association between type 1 diabetes mellitus and celiac disease has been known for some time. One in ten type 1 diabetics have immunological markers for celiac disease (CD). But is there, conversely, an increased risk of CD for diabetics? This study was undertaken to answer this question by determining diabetes-associated antibodies and genetic factors in patients with a gluten-sensitive enteropathy (CD). PATIENTS AND METHODS: 68 patients with CD (48 females and 20 males) were investigated by determining the diabetes-associated serological marker GADA (glutamic acid decarboxylase antibodies). 1A-2A (insulinoma-associated protein 2 antibodies), ICA (Islet cell antibodies) and IAA (insulin autoantibodies). Among this cohort were 60 patients up to the age of 25 years and eight adults (average age 41.7 years). In 36 of these patients the HLA was also determined. RESULTS: GADA was found in 6 patients (9%), 1A-2A in eight (12%) and IAA in 21. ICA were not demonstrated in any. Five of the CD patients were positive for several markers. One child, positive for autoantibodies already had manifest diabetes at the time of investigation. None of the patients with autoantibodies had an abnormal glucose metabolism one year later. HLA-DR3, that occurs in both CD and diabetes, was demonstrated in 78% of the patients with CD. The most common constellation, HLA-DR3-DQ2/HLA-DR7-DQ2, was found in 31%. CONCLUSION: This investigation indicates a genetic association between celiac disease and diabetes. Nonetheless, the risk of developing diabetes mellitus is only minimally higher in patients with CD than in the normal population. Therefore, general screening cannot be recommended at present. Further studies will be needed.

[Prevalence of asymptommatic coeliac disease in children and adults in the Dresden region of Germany]. / Prävalenz der asymptomatischen Zöliakie bei Kindern und Erwachsenen in der Region Dresden.

BACKGROUND AND OBJECTIVE: Coeliac disease (CD) can be present without any, only a few, or many symptoms. Since asymptomatic CD can have the same complications and also carries the same risk for malignant disease as clinically typical CD inadequately treated by diet, early diagnosis is essential. The prevalence of asymptomatic CD in the Dresden region was determined by antibody screening. At the same time the sensitivity and specificity of the different antibodies were calculated. MATERIAL AND METHODS: Anti-gliadin and endomysium antibodies and total IgA content were measured in the serum of 3004 children (group A), aged 5-12 years, and of 4313 blood donors (group B), aged 17-64 years. Small-intestine biopsies were recommended if either (1) endomysium antibodies (EmA) or (2) anti-gliadin antibodies (ACA) and clinical symptoms or (3) AGA-IgG in the presence of total IgA deficiency and clinical symptoms had been demonstrated. RESULTS: EmA were demonstrated in 0.17% of group A and in 0.28% of group B. But AGA were found much more frequently (group A: 3.89%, group B: 3.76%). The number of cases of CD confirmed by biopsy indicated a prevalence of asymptomatic CD of 1 in 500 children and 1 in 540 adults. Sensitivity and specificity of EmA were significantly higher than those of AGA. CONCLUSION: Compared with a previous study on the prevalence of clinically typical CD in the same region, the present investigation indicates a four-fold higher prevalence of asymptomatic CD. Coeliac-specific antibodies should, therefore, be measured much more widely in the presence of certain symptoms and risk factors. While in adults the measurement of EmA is sufficient to provide the indication for a small-intestine biopsy, both EmA and AGA should be determined before a biopsy is undertaken in children.

Successful treatment of gut-caused halitosis with a suspension of living non-pathogenic Escherichia coli bacteria--a case report.

UNLABELLED: In up to 90% of cases, severe halitosis is a result of gastrointestinal or orolaryngeal problems. This case study reports on a girl with bad breath caused by increased formation of malodorous intestinal gases (halitosis), which could be successfully treated with a suspension of living non-pathogenic bacteria Escherichia coli. CONCLUSION: in unclear cases of bad breath, an increased formation of intestinal gases should also be considered.

Pancreatic elastase 1 in feces of preterm and term infants.

BACKGROUND: Determination of fecal pancreatic elastase 1 (E1) is a reliable and noninvasive test of exocrine pancreatic function. Adult reference values of greater than 200 microg E1/g feces do not seem to be applicable to early infancy because of immature pancreatic function. Because reference values for infants do not exist, the current study was aimed to define reference values for preterm and term infants up to 12 months of age. METHODS: The authors measured pancreatic E1 concentration in feces of 148 infants up to 12 months of age. Infants with known bowel or pancreatic disorders were excluded from the study. RESULTS: The authors found that 96.8% of all children had E1 concentrations greater than an adult lower limit after 2 weeks of life, independent of gestational age. Up to 48 hours after birth, none of the preterm infants had an E1 concentration of greater than 30 microg/g meconium, whereas 43% of the term infants had normal adult values. CONCLUSIONS: The adult reference value for pancreatic E1 of greater than 200 microg/g feces can be applied to infants older than 2 weeks, independent of gestational age, birth weight, and the type of nutrition.

Detection of four human milk groups with respect to Lewis-blood-group-dependent oligosaccharides by serologic and chromatographic analysis.

Oligosaccharides from human milk samples obtained from individual donors were analyzed using high-pH anion-exchange chromatography. Three patterns of neutral oligosaccharides were detected corresponding to milk groups already described. These oligosaccharide groups correspond to the Lewis blood types Le(a-b+), Le(a+b-), and Le(a-b-). A new carbohydrate pattern was detected in a milk sample from a Le(a-b-) person in which only nonfucosylated oligosaccharides and compounds bearing alpha1,3-linked fucosyl residues were found. This finding led to the hypothesis that there exist 4 different oligosaccharide milk groups that fit well to the genetic basis of the Lewis blood group system.

Simultaneous determination of fecal fat, nitrogen, and water by near-infrared reflectance spectroscopy.

BACKGROUND: Determinations of fecal fat and nitrogen reveal evidence of malabsorption and assist in estimating the efficacy of pancreatic enzyme treatment. Seventy-two-hour stool collection, with chemical analysis of fecal fat, and Kjeldahl's method for measurement of fecal nitrogen are generally accepted as standard methods for making these determinations. However, these traditional methods are expensive, time-consuming, and cumbersome. This study evaluated the efficiency and validity of an alternative method, using near-infrared reflectance spectroscopy (NIRS) and compared results with those of the standard methods. METHODS: Near-infrared reflectance spectroscopy is a secondary method: The instrument first has to be calibrated with samples analyzed by the standard method. Sixty-three stool samples with known fat content (range 4.79-292.5 mg/g), 24 samples with known nitrogen content (range 5.36-19.38 mg/g), and 24 samples with known water concentration (range 60.1-82.22%) served for calibration. A further 69 samples were analyzed to validate the procedure. RESULTS: There was a satisfactory correlation between the measurements produced by near-infrared reflectance spectroscopy and those produced by standard methods: fat r = 0.97; nitrogen r = 0.94; water r = 0.96. CONCLUSIONS: Near-infrared reflectance spectroscopy appears to be a reliable, simple, and rapid method of measuring different fecal components-as precise and accurate as the standard methods. Stool samples should be analyzed immediately after collecting or stored only a few days before analyzing.

Gastrointestinal lymphonodular hyperplasia and lymphoid polyps of the rectum--a rare coincidence.

Lymphoid polyps of the rectum are rare lesions. We report on an 8 1/2-year-old boy, who presented with hematochezia and abdominal pain. Flexible endoscopy revealed large sessile polyps of the rectum and lymphonodular hyperplasia of the duodenum, terminal ileum und descending colon. One rectal polyp was excised in toto, microscopically it revealed the typical features of a lymphoid polyp. Based on the distinct follicular architecture, the cytomorphology and the immunohistochemical findings of the lymphatic infiltrate we were able to distinguish this lesion from malignant lymphoma. The coincidence of lymphoid polyps and gastrointestinal lymphonodular hyperplasia gives evidence that both entities are different variations of the same benign lymphoproliferative process. Lymphoid polyps of the rectum should be treated by local excision for diagnostic purposes. Immunohistochemical staining of fresh, nonfixed tissue is a useful ancillary technique in distinguishing these benign lesions from lymphoma of mucosa associated lymphoid tissue (MALT-lymphoma).

Sensitivity and specificity of quantitative determination of pancreatic elastase 1 in feces of children.

BACKGROUND: The secretin-pancreozymin test has been accepted as the gold standard for testing exocrine pancreatic function. However, this test is invasive, time-consuming, and expensive. Therefore, in daily practice, more simple, indirect methods are proposed. METHODS: The fecal concentration of human pancreatic elastase (E1) has been assessed for diagnostic sensitivity and specificity. For sensitivity, fecal E1 determination in 23 healthy children were studied. RESULTS: Sensitivity to detect pancreatic insufficiency was 100% and specificity 96%. CONCLUSIONS: Fecal E1 concentration appears to be a more sensitive and specific test of pancreatic function than other tests.

Detection of four human milk groups with respect to Lewis blood group dependent oligosaccharides.

Neutral oligosaccharides in human milk samples from approximately 50 women were analysed applying a recently developed high-pH anion-exchange chromatographic method. Three different oligosaccharide patterns could be detected in accordance with milk groups that had been already described. These oligosaccharide groups correspond to the Lewis blood types Le(a-b+), Le(a+b-) and Le(a-b-). In addition to these oligosaccharide patterns, a new carbohydrate pattern was detected in a milk sample from a Le(a-b-) individual. Here, only nonfucosylated oligosaccharides and compounds bearing alpha1,3 linked fucosyl residues were found, whereas structures with alpha1,2 and alpha1,4 fucosyl linkages were missing. This finding led to the hypothesis that there are four different oligosaccharide milk groups that fit well to the genetic basis of the Lewis blood group system.

Indirect parameters of pancreatic function in cystic fibrosis (CF) during a controlled double-blind trial of pancreatic supplementation.

During two treatment periods (4 weeks each), serum immunoreactive trypsin (IRT), immunoreactive human lipase in stool (IRL), and chymotrypsin (CT) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion (72-h sampling). Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients (X = 13.7 +/- 9.0 g/24 h) in at least one study period. Stool fat excretion was highest in underweight adolescents and adults. Comparison of IRT and IRL with stool fat values showed no significant statistical correlation. IRT values revealed an inverse exponential correlation with age, with a steep decline at the age of 5 years. CT levels were very high in 14 of our 16 patients during supplementation therapy, whereas 2 patients showed subnormal CT values. We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion, stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis. Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate.

Variations of neutral oligosaccharides and lactose in human milk during the feeding.

There exist only few data concerning the variation of oligosaccharides in human milk. In this study the variations of neutral oligosaccharides and of lactose in human milk during the feeding were determined from five women at day 8 and at day 57 post partum. The milk of the investigated feedings was divided in four parts of equal volumes during sampling; the concentrations of neutral oligosaccharide fractions were determined by gel permeation chromatography on Fractogel TSK HW 40 (S) columns. No significant differences in the concentrations of the neutral oligosaccharide groups monofucosyllactoses, difucosyllactose, lacto-N-tetraoses, monofucosyllacto-N-tetraoses and difucosyllacto-N-tetraoses and of lactose were found in the four milk parts. The results of this study favor the use of so-called mid-feed samples, a simple and convenient sampling method for analytical studies of human milk. Mid-feed samples are representative of the whole feeding as concerned for neutral oligosaccharides.

[Epidemiologic studies of celiac disease in childhood in the Dresden district]. / Epidemiologische Untersuchungen zur Zöliakie im Kindesalter im Bezirk Dresden.

The incidence and prevalence of celiac disease in children aged 0-16 years during the years 1970-1986 have been studied prospectively in a geographic defined area of Germany. The celiac disease has been diagnosed due to the criteria of ESPGAN. During the mentioned time period, 170 patients with confirmed celiac disease and 399,477 live births were registered. This corresponds to an incidence of 1:2060. In December 1986 384,840 children in the age between 0 and 16 years were living in the region of Dresden. This corresponds to a prevalence of 44/100,000 inhabitants. Girls were more often affected than boys (1.8:1).