Thomas Waldhör

Clinical relevance of serum interleukin-6 in Crohn's disease: single point measurements, therapy monitoring, and prediction of clinical relapse

OBJECTIVE:To investigate the clinical relevance of interleukin-6 (IL-6) serum levels in patients with Crohns disease (CD), single point IL-6 measurements in sera from consecutive CD patients and healthy donors (HD), as well as longitudinal measurements during the course of steroid therapy for active CD were performed. Patients with steroid-induced remission were followed until clinical relapse.METHODS:One hundred thirty-six CD patients without steroid or other immunosuppressive treatment within 2 months and surgical procedures within 3 months before study entry were investigated; 63 patients with active CD were enrolled into the follow-up program. Clinical activity was evaluated by the Crohns disease activity index (CDAI) and serum IL-6 levels measured by enzyme-linked immunosorbent assay.RESULTS:IL-6 serum levels were significantly elevated in CD patients compared to HD (p < 0.001). In individual patients serum IL-6 levels correlated with corresponding CDAI scores in a subgroup referred to as primarily inflammatory patients presenting without bowel stenosis, previous intestinal resection, or concomitant inflammatory disorders (r = 0.72, p < 0.001). Primarily inflammatory patients displayed higher serum IL-6 levels (median: 6.0 pg/ml; range: 1.3–25) than CD patients with bowel stenosis (median: 2.0; range: 1.3–4.9; p < 0.01) or extensive intestinal resection (median: 1.5; range: 1.3–13.7; p < 0.001). Longitudinally measured serum IL-6 levels reflected the clinical response during steroid therapy and predicted clinical relapse after steroid-induced remission at week 9 of the treatment protocol.CONCLUSIONS:Serum IL-6 is a clinically relevant parameter for CD that correlates with inflammatory activity and implies a prognostic value after steroid-induced remission.

Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade.

Expression of inducible nitric oxide synthase (iNOS) by tumor cells has been suggested to abrogate metastasis in several tumor models, whereas constitutive NOS expression correlated positively with tumor grade in human breast carcinoma. Whether or not expression of one of the various NOS isoforms could predict the prognosis of breast cancer, however, has not been established. In the present report we investigated the cellular distribution of NOS isoforms in a series of benign and malignant breast tumors and in normal breast tissue. Immunohistochemistry revealed that in samples of benign disease the number of iNOS + epithelial cells or total epithelial cells was 69 ± 16% (n=50). In samples of grade II invasive ductal breast carcinomas the number of iNOS+ tumor cells or total tumor cells was 62 ± 20 (n=40), compared to 12 ± 9 (n=40) in samples of grade III carcinomas (P < 0.0001). iNOS protein was also identifiable in most of the epithelial cells of normal breast tissue (n=4). In contrast, eNOS protein was restricted to vascular endothelial cells in all of the specimens studied. Since the presence of tumor cell iNOS protein is inversely related to the tumor’s metastatic potential, we conclude that endogenous tumor cell mediated iNOS expression might have an inhibitory effect on the metastatic process in breast cancer.

The spatial autocorrelation coefficient Moran's I under heteroscedasticity

The spatial distribution of rates used in epidemiology often raises questions concerning the randomness of the observed pattern. In order to provide a first answer to this kind of question, the well-known spatial autocorrelation coefficient Morans I is frequently used. Unfortunately, under heteroscedasticity, that is, unequal variances of the rates due to different population sizes, the moments of the test distribution of Morans I under H(0) differ from the usually used moments. To obtain a less biased test, it is proposed in this paper and validated by simulation results, to approximate the moments of Morans I by means of incorporating population size into the covariance matrix of the rates.

Type 2 diabetes mellitus is rare but not absent in children under 15 years of age in Austria

Until recently, most children with diabetes mellitus had type 1 diabetes (T1DM). The prevalence of type 2 diabetes (T2DM) is on the rise in North America, especially in risk populations such as the American Indians. Few epidemiological data on the incidence of the disease exist in Europe. In a prospective population-based epidemiological study, all newly diagnosed cases of diabetes mellitus in patients under 15 years of age were registered nation-wide in Austria between 1999 and 2001. Differential diagnosis (according to the American Diabetes Association diagnostic criteria) was based on clinical case definition. During the 3 years of the study period, 529 cases of DM <15 years were documented, of which 510 were clinically assigned to T1DM (271 boys, 239 girls) resulting in an incidence rate of 12.4/100,000. In the same network, eight cases were diagnosed as T2DM (one boy, seven girls) and two cases with an atypical form of T2DM (two girls). The age of onset of T2DM was 12–15 years and all patients were overweight (body mass index >90th percentile).The calculated incidence for T2DM <15 years in Austria was 0.25/100,000. Conclusion: at present, type 2 diabetes mellitus is rare but exists in children aged under 15 years in Austria. Follow-up of this registration will help to describe the secular trend.

Screening detected celiac disease in children with type 1 diabetes mellitus : Effect on the clinical course - (A case control study)

Objective: To investigate clinical and metabolic characteristics of diabetic children with screening detected celiac disease in a multicenter case-control study. Methods: Cases: 98 diabetic patients were diagnosed as having silent celiac disease by screening with endomysial antibodies and subsequent biopsy. Controls: two controls in the same center were chosen, (stratified by age and age-at-diabetes onset) who were negative for endomysial antibodies (n = 195). Height, weight, HbA1c, insulin dosage and acute complications were documented for at least 1 year of follow up. Results: Mean age of diabetes manifestation was 6.5 ± 4.1 years and diagnosis of celiac disease was made at 10.0 ± 5.4 years. Biopsy showed total or subtotal mucosal atrophy in 74 patients. The mean observation period after the diagnosis of celiac disease was 3.3 ± 1.9 years. Mean HbA1c levels were similar between cases and controls (8.63% ± 1.45% versus 8.50% ± 1.39%; P = 0.35). There was also no difference in the frequency of severe hypoglycemia, ketoacidosis and the applied insulin dosage (P = 0.45). Body mass index-standard deviation score at celiac disease diagnosis (0.57 ± 1.24 versus 0.52 ± 1.07) and height-standard deviation score (0.14 ± 1.13 versus 0.30 ± 0.95) did not differ between cases and controls. After diagnosis of celiac disease, weight gain was diminished in boys with celiac disease compared with their controls (P < 0.05). Female cases also had a lower body mass index than female controls (P = 0.067). Conclusion: In a cohort of diabetic children, silent celiac disease had no obvious effect on metabolic control but negatively influenced weight gain.

Perspectives of longitudinal growth in cystic fibrosis from birth to adult age

The longitudinal growth in 139 patients with cystic fibrosis (CF) was investigated from birth until the age of 19 years. Already at birth weight and length were reduced (weight: −0.83±0.13 SDS in girls, −0.44±0.13 SDS in boys; length: −0.55±0.13 SDS in girls, −0.39 ±0.14 SDS in boys; mean ± SEM). Both variables showed a further decline until diagnosis was established (weight: −1.57±0.21 SDS in girls, −1.46±0.25 SDS in boys; length: −1.15±0.32 SDS in girls, −1.03 ±0.52 SDS in boys; mean ± SEM). Six to 12 months after diagnosis length improved and reached the 25th percentile in both sexes. Height and weight followed the 25th percentile throughout childhood. Growth velocity was fairly normal during this period. There was a loss in percentiles of both height and weight after the age of 8 years and the pubertal growth spurt was delayed and reduced. However, the 25th percentile was reached again in the adolescent period. At the age of 19 years median height was 161,5 cm in girls and 173 cm in boys, both representing the 25th percentile. Using a sensitive statistical method for analysis of growth data we present CF specific growth curves for height, weight and growth velocity. There was no significant effect of pulmonary colonization withPseudomonas aeroginosa on growth velocity.

Inducible nitric oxide synthase (iNOS) expression may predict distant metastasis in human melanoma

SummaryExpression of inducible nitric oxide synthase (iNOS) and its cellular localization was investigated in subcutaneous or lymph node metastases of human melanoma. Immunohistochemistry revealed that iNOS expression was limited to melanoma cells. In samples of patients without distant metastases, the number of iNOS+ tumour cells/total tumour cells was 55% ± 17% (n = 12) compared with 9% ± 8% when distant metastases of lung, liver or brain occurred within an observation period of 3 years (n = 10) (P < 0.001). Western blotting confirmed the expression of iNOS protein in select cases. Notably, iNOS is expressed in regional melanoma metastases and its expression is inversely related to the tumour’s metastatic potential. Thus, iNOS expression may have predictive value for the development of distant metastases of human melanoma.

Symptoms suggestive of atopic rhinitis in children aged 6–9 years and the indoor environment

Background: We aimed to investigate the influence of indoor factors on the prevalence of symptoms suggestive of atopic rhinitis in children aged 6–9 years in Upper Austria.

Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: the randomized, controlled thromboVIT trial.

Background: Secondary thrombocytosis is a common clinical feature. In patients with cancer, it is a risk factor for venous thromboembolic events. In inflammatory bowel disease (IBD), thrombocytosis is so far considered a marker of active disease and may contribute to the increased thromboembolic risk in this population. Observed effects of iron therapy on normalization of platelet counts led us to hypothesize that iron itself may regulate megakaryopoiesis. Here, we want to test the effect of iron replacement on platelet count and activity in IBD-associated thrombocytosis. Methods: We performed a randomized, single-blinded placebo-controlled trial testing the effect of ferric carboxymaltose (FCM) in patients with IBD with secondary thrombocytosis (platelets > 450 G/L). Changes in platelet counts, hemoglobin, iron parameters, disease activity, megakaryopoietic growth factors, erythropoietin, and platelet activity were assessed. Patients received placebo or up to 1500 mg iron as FCM. Endpoints were evaluated at week 6. Results: A total of 26 patients were included in the study, 15 patients were available for the per protocol analysis. A drop in platelets >25% (primary endpoint) was observed in 4 of 8 (50%, iron group) and 1 of 7 patients (14%, placebo group, P = 0.143). Mean platelet counts dropped on FCM but not on placebo (536 G/L to 411 G/L versus 580 G/L to 559 G/L; P = 0.002). Disease activity and megakaryopoietic growth factors remained unchanged and hemoglobin and iron parameters increased on FCM. The normalization of platelet counts was associated with a decrease in platelet aggregation and P-selectin expression. Conclusion: FCM lowers platelet counts and platelet activation in patients with IBD-associated secondary thrombocytosis.

Risk factors for type I diabetes mellitus in children in Austria

Abstract The aim of this study was to investigate environmental risk factors in the development of type 1 diabetes mellitus in a population-based case-control study. Parents of all patients with manifestation of type 1 diabetes between 1989 and 1994 in Vienna were asked to complete a questionnaire (n = 114). Control children (n = 495), matched for age and sex, were randomly recruited from all schools in Vienna. Fathers of diabetic children were significantly older at the time their children were born than fathers of control children (P = 0.015). Children with diabetes were more likely to be second- or third-born children (P < 0.05) and fewer went to kindergarten than the control group children (P = 0.007). No significant difference in duration of gestation, percentage of delivery by caesarean section, birth weight or length was found. Neonatal jaundice was more often observed in the patient group (P = 0.038). Breast feeding was reported by 82.7% of mothers of diabetic children and by 81% of mothers of control children, and the duration of breast feeding was longer in patients than in controls (n.s.). Conclusion In our study, the development of type 1 diabetes mellitus was associated with higher paternal age and neonatal jaundice. No correlation could be found with dietary intake of cows milk products in early infancy, vaccination and other environmental factors.