The proteome pattern cGvHD_MS14 allows early and accurate prediction of chronic GvHD after allogeneic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be curative, but is associated with significant morbidity and mortality. Chronic graft-versus-host disease (cGvHD), characterized by inflammation and fibrosis of multiple target organs, considerably contributes to the morbidity and mortality even years after allo-HSCT. Diagnosis of cGvHD is based on clinical features and histology of biopsies. Here, we report the generation of a urinary cGvHD-specific proteome-pattern (cGvHD_MS14) established by capillary electrophoresis-mass spectrometry to predict onset and severity of cGvHD as an unbiased laboratory test. cGvHD_MS14 was evaluated on samples from 412 patients collected prospectively in four transplant centers. Sensitivity and specificity was 84 and 76% by cGvHD_MS14 classification. Sensitivity further increased to 93% by combination of cGvHD_MS14 with relevant clinical variables to a logistic regression model. cGvHD was predicted up to 55 days prior to clinical diagnosis. Acute GvHD is not recognized by cGvHD_MS14. cGvHD_MS14 consists of 14 differentially excreted peptides, six of those have been sequenced to date and are fragments from thymosin ß-4, eukaryotic translation initiation factor 4γ2, fibrinogen ß-chain or collagens. In conclusion, the cGvHD_MS14-pattern allows early, highly sensitive and specific prediction of cGvHD as an independent diagnostic criterion of clinical diagnosis potentially allowing early therapeutic intervention.

Early determinants of childhood overweight and adiposity in a birth cohort study: role of breast-feeding.

BACKGROUND: The prevalence of adiposity in childhood is increasing. Is breast-feeding protective as suggested by cross-sectional studies? OBJECTIVE: In a longitudinal birth cohort study, we tested whether breast-feeding for more than 2 months has preventive effects against overweight and adiposity at 6 y. DESIGN: Of 1314 children representing the catchment areas of six delivery units, 918 could be followed up to the age of 6 y. Height, weight, and skin-fold thickness were measured at regular visits. As the criteria of overweight, obesity, and adiposity in the children, the 90th and the 97th percentiles of BMI and skin-fold values were used. Parents with a BMI at or above the 90th percentile, which was 27 kg/m(2) or more, were considered overweight. Infants bottle-fed from birth or breast-fed for less than 3 months were classified as 'bottle-fed' (BO), and those breast-fed for 3 months and more as 'breast-fed' (BR). Univariate comparisons and logistic regression analysis were performed applying SAS 6.12. The final logistic model consisted of the 480 cases for whom complete data for all variables were available. The potential effect of loss to follow-up was analysed by the Cochran-Mantel-Haenzel test: the outcomes were not significantly influenced by loss to follow-up. RESULTS: At birth BMIs were nearly identical in both groups. By 3 months, BO had significantly higher BMIs and thicker skin folds than BR. From 6 months on, compared to BR, a consistently higher proportion of BO children exceeded the 90th and the 97th percentile of BMI and skin-fold thickness reference values. From the age of 4 y to 5 and 6 y, in BO the prevalence of obesity nearly doubled and tripled, respectively. With only minor changes of obesity prevalence in BR, the difference of BMI and skin-fold thickness between groups became statistically significant. Logistic regression analysis revealed that overweight of the mother, maternal smoking during pregnancy, bottle feeding, and low social status remained important risk factors for overweight and adiposity at 6 y of age. CONCLUSION: A maternal BMI of > or =27, bottle-feeding, maternal smoking during pregnancy, and low social status are risk factors for overweight and adiposity at 6 y of age. Early bottle-feeding brings forward the obesity rebound, predictive of obesity in later life.

Reduced risk of hay fever and asthma among children of farmers.

BACKGROUND: The prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy. OBJECTIVES: To test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions. DESIGN: Cross-sectional survey among children entering school (aged 5-7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. SETTING: School health entry examination in two Bavarian districts with extensive farming activity. SUBJECTS: 10 163 children. MAIN OUTCOME MEASURES: The prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report. RESULTS: Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0. 52, 95% CI 0.28-0.99), asthma (0.65, 0.39-1.09), and wheeze (0.55, 0. 36-0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full-time basis as compared with families with part-time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23-0.74). CONCLUSIONS: Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.

Systemic meningococcal infection: which children may benefit from adjuvant haemostatic therapy? Results from an observational study.

UNLABELLED: The potential benefits of haemostatic therapy (heparin, antithrombin (AT) concentrate, fresh frozen plasma (FFP)) in severe systemic meningococcal infections (SMI) are controversial. A reduction of the still high case fatality rate would be an important indicator for potential benefits of adjuvant haemostatic therapy in children with SMI. Observational data from nationwide, active surveillance for SMI in children under 16 years in all German paediatric hospitals over a one-year period were used to assess whether potentially beneficial effects of haemostatic therapy are related to the severity of disease. The Neisseria sepsis index (NESI), which grades the severity of SMI from 0 to 8 and has proven to be a reliable tool for predicting the outcome of children with SMI, was used as an indicator of the severity of SMI. During the study period from July 1994 to June 1995, 305 children met the case definition; for 176 of these, complete data sets providing information on parameters underlying the NESI index and regarding the specific haemostatic therapy were available. As all recorded children with NESI 0-2 (n = 129; 73%) survived, a potential impact of haemostatic therapy (given to 45 of them) on survival would be undetectable in this group. A NESI between 3 and 8 was found in 47/176 patients (24%), 35 of whom received some kind of haemostatic therapy. The survival rates were 80% in children with haemostatic therapy (n = 35) and 50% in those without (n = 12) (odds ratio 0.25; 95% confidence interval 0.06-0.98). A subgroup analysis of patients with NESI 3-5 versus those with NESI scores above 5 showed that the beneficial effect of haemostatic therapy was almost confined to children in the NESI 3-5 subgroup. In this subgroup there were 28/31 (90%) survivors with, and 6/11 (55%) survivors without adjuvant haemostatic therapy, whereas none of the patients (n = 5) with a NESI of 6-8 survived, although 4 had received adjuvant haemostatic therapy. CONCLUSION: Studies on the impact of adjuvant haemostatic therapy on survival in children with SMI should focus on those with NESI scores 3-5. The data from this population-based, observational study suggests that haemostatic therapy might reduce the case fatality rate in these children. The optimal dosage and choice of preparations remains to be established. Alternative adjuvant therapeutic strategies may be required in children with SMI and NESI scores > 5.

Road injuries in school age children: relation to environmental factors amenable to interventions.

OBJECTIVES: To assess the impact of potentially modifiable environmental factors on the risk for pedestrian and cyclist injuries among school age children. SETTING: Population of school age children in Düsseldorf (population 570,000) in the west of Germany. All pedestrian and cyclist injuries involving children between 6 and 14 years brought to the attention of the police between January 1993 and March 1995 were eligible. METHODS: A case-control design was used, with controls matched by age and sex. Criteria for inclusion of cases were: residence in Düsseldorf, and injury within 500 meters from home. A random sample of 174 cases was selected. For each an age-sex matched child, resident in Düsseldorf, was randomly selected from a list of all school age children. The environment within a radius of 500 meters around the homes of cases and controls was analysed by blinded on site investigators. These used a standardized questionnaire to assess the number of streets with speed limits of 30 kph, the number of pedestrian crossings with traffic lights per street with speed limits of 50 kph or above, and the number of playgrounds for children. RESULTS: Complete information was available for 170 cases and 168 controls. There were significantly more streets with a speed limit of 30 kph around the homes of controls (p = 0.0003; mean 9.5; 95% confidence interval (CI) 8.8 to 10.1) than cases (mean 7.8; 95% CI 7.3 to 8.3). For every five streets with a speed limit of 30 kph injury risk was reduced by nearly 50% (odds ratio 0.57; 95% CI 0.43 to 0.76). There were also significantly more pedestrian crossings with traffic lights on streets with a speed limit 50 kph or above around the homes of controls (p = 0.0004; mean 2.7; 95% CI 2.4 to 2.9) compared with cases (mean 2.1; 95% CI 1.9 to 2.3). Finally there were significantly more playgrounds around the houses of controls (p = 0.04; mean 1.9; 95% CI 1.7 to 2.2) compared with the houses of cases (mean 1.7; 95% CI 1.4 to 2.0). CONCLUSIONS: Significant associations with injury risk were identified for some prespecified modifiable environmental factors.

Haemophilus influenzae b-vaccination: the urgency for timely vaccination.

UNLABELLED: In Germany the annual number of systemic Haemophilus influenzae cases in unvaccinated children aged 3-60 months has recently been exceeded by the number of cases in children vaccinated at least once with the PRP-D, HbOC or OMP vaccines, which until 1995 have almost exclusively been used for H. influenzae b (Hib) vaccination. Most of the vaccinated children however could already have had more vaccinations at onset of disease. How much does an age-related suboptimal vaccination status increase the risk for systemic H. influenzae infections? A case control study was performed in West Germany. Cases with systemic H. influenzae infections were ascertained between 7/92 and 8/ 94 with an ongoing active hospital surveillance programme. Six age-matched population controls per case were recruited at random. Only vaccinated cases and controls were included in the study. The main exposure analysed in this study was suboptimal vaccination at censoring; for censoring ages (age at disease onset in cases and corresponding age in matched controls) > 6 months: one vaccination in 1st year only; > 18 months: two (three for combined vaccines with Hib + DT or DPT in one syringe) vaccinations in the 1st year of life but no booster vaccination. Suboptimal vaccination for age increased the risk for systemic H. influenzae infections by a factor of 4.74 (95%-CI 2.17-10.34). Following adjustment for confounders the odds ratio was 4.39 (95%-CI 1.74-11.07). Subgroup analyses showed that this risk was not related to the type of vaccine used. The risk for "no booster vaccination" in children aged > 18 months appeared even greater than the risk associated with one vaccination in the 1st year only. CONCLUSIONS: On schedule and complete Hib vaccinations are essential for an optimal effectiveness of Hib vaccination programmes. Booster vaccinations between 12 and 18 months are important if the PRP-D, HbOC and OMP vaccines are used for primary vaccination.

Pregnancy outcomes in mothers with pregestational diabetes: a population-based study in North Rhine (Germany) from 1988 to 1993.

UNLABELLED: The purpose of this study was to estimate the proportion of pregnancies with pregestational diabetes in Germany, to compare the outcome of these pregnancies to pregnancies in nondiabetic mothers and to identify risk factors for poor pregnancy outcomes in mothers with pregestational diabetes. Data of the "Perinatalerhebung Nordrhine" from 1988-1993 were analysed. The Perinatalerhebung is an ongoing quality assurance programme of prenatal and perinatal care in the region of North Rhine (South Western part of North Rhine-Westphalia). During the observation period a proportion of 93%-100% of the annual births in the region (n = approximately 100000) were included in the study. Their data had been documented by the obstetricians in a standard multiple choice questionnaire. The outcome parameters perinatal mortality, macrosomia, prematurity, and malformations were analysed in relation to several defined explanatory variables. There were 2,402 births in mothers with pregestational diabetes (0.4% of all births). The proportions of poor pregnancy outcomes in women with pregestational diabetes were 2.8% for perinatal mortality, 27.6% for macrosomia, 21.1% for prematurity and 2.1% for malformations . The respective relative risks compared to the non diabetic mothers were 4.3 (95% CI 3.4-5.5) for perinatal mortality, 3.1 (95% CI 2.9-3.3) for macrosomia, 2.7 (95% CI 2.5-2.9) for prematurity and 1.7 (95% CI 1.3-2.3) for malformations . The main risk factor for perinatal mortality in children of diabetic mothers after adjustment for maternal smoking, ethnicity, parents' professional achievement, type of obstetric hospital, and maternal age was substandard use of prenatal care. CONCLUSIONS: The prevalence of births from mothers with pregestational diabetes and their pregnancy outcomes were similar to those in other Western countries. The standard for non-diabetic mothers has not been reached yet. Further improvements may be achieved if all diabetic women are convinced to use the standard prenatal care facilities throughout pregnancy.

[Metric examinations on the development of apical dendrites of cortical pyramidal cells during the postnatal time in the rat]. / Metrische Untersuchungen zur Entwicklung der apikalen Dendriten von corticalen Pyramidenzellen während der Postnatalzeit der Ratte.

1. It is explained the postnatal evolution of some selected features of Golgi-impregnated layer V pyramidal neurons in the rat sensorimotor cortex from the 1st to the 90th day after birth (13 stages) quantitatively. Especially it is reported about the development of the length and the quantity of apical main dendrites and of the apical lateral branches from the 1st to the 3rd order as well as the branching behaviour of the dendrites (free ends of dendrites, branching points, ramification index). 2. The evolution of mean length of apical dendrites is represented by a sigmoidal polygon trace - like the classic growing curve. 3. During the 3rd month of the postnatal life the lateral branches of the apical dendrites show a distinct growing increase relating to the mean values of the total length of dendrites, their quantity and the branching behaviour. This intensification of growth is in contrast to the growing stagnation of the apical main dendrites in this time. 4. From this point of view it is deduced that relating to the maturation of pyramidal cells - contrary to the papers of other writers and contrary to a previous private conception - albino rats in the age of 3 months do not are differentiated cortical completely. 5. The several marks of pyramidal dendrites do not form themselves in the same time but successively. The maturing process of new dendrites or dendrite branches is the base of significant increase of the length. 6. It seems, that the formation of dendritic "tree" takes place in growing batches. In this context there are discussed the correlations between the morphometric conceivable changes in the cortical pyramids and the accession of functions in the animal.

[Radiotherapy of the prostate carcinoma (author's transl)]. / Strahlentherapie des Prostatakarzinoms.

41 patients were submitted to telecobalt irradiations of the prostate and the adjoining lymph drain regions. The absence of remote metastases was verified by X-ray examinations of the skeleton and bone scintigrams, and stades were divided by means of lymphography. The overall 3,5-year survival rate was 79.9%, the 3,5-year survival rate of the patients without lymph node metastases was 100% and that of the group with lymph node metastases was 25%. 69,6% of all patients had no recurrences after 3.5 years, the corresponding rate for the patients without lymph node metastases was 84% and that for the patients with lymph node metastases was 24.6%. The difference between patients with and patients without lymph node metastases demonstrated by lymphography was statistically significant and decisive for the prognosis. The clinically judged local tumor control was 100% for those patients who were observed during a period of more than one year after the radiotherapy. Lymph nodes which were also irradiated underwent an involution in all cases. Different differentiation degrees responded in the same way to radiotherapy. A dependence of rectal complications on the dose could be demonstrated. The results were not ameliorated by additional hormonal therapy.