The protective effect of high-titer anti-lipid A hyperimmune globulin with respect to the course of the disease and the mortality rate was studied in patients with septicemia verified by positive blood cultures. Six patients were treated with anti-lipid A in an open study. Dramatic improvement in fever curves and clinical condition in some of the patients encouraged us to start a randomized double blind study. So far, 17 patients have entered the study, 16 of whom were evaluable. Immediately after a positive blood culture was found, patients received either high doses of anti-lipid A or placebo (saline solution) on two subsequent days. Before and after each infusion blood samples were taken in order to assess serum bactericidal activity and anti-lipid A titers. Because of the still small numbers of patients the results of both studies were summarized. In all patients treated with anti-lipid A clear-cut increases in anti-lipid A titers were shown. Patients with repeated gram-negative infections showed higher median anti-lipid A titers than patients without such a history. The patients treated with anti-lipid A immune globulin ran a significantly milder course than the placebo group. The severe signs of septic shock were reversed in seven of 15 patients on anti-lipid A compared to two of seven patients treated with placebo. In the anti-lipid A-treated group, three of 15 patients died, and in the placebo group two of seven. This difference is not statistically significant.

Aged↗

PubMedDate not supplied

Ranitidine treatment and cortisol metabolism in man.

Experimental evidence suggested that H2-receptor antagonists may inhibit not only hepatic but also adrenal cytochrome P-450 dependent monooxygenases. Therefore, the effects of ranitidine (150 mg b.i.d. over 14 days) on cortisol metabolism and antipyrine clearance have been investigated in nine healthy volunteers. Urinary excretion of 6 beta-hydroxycortisol (6 beta-OHC) and 17-hydroxycorticosteroids (17-OHCS) remained unaffected by ranitidine pretreatment, as did the calculated 6 beta-OHC/17-OHCS ratio. Only marginal effects were observed on antipyrine kinetics and metabolite formation. We conclude that neither adrenal production of corticosteroids nor their hepatic metabolism is affected by ranitidine administration.

17-Hydroxycorticosteroids↗

PubMedDate not supplied

Fluorescence-labeled octapeptides as substrates for histone deacetylase.

The determination of histone deacetylase (HDAC) activity and the screening of potential inhibitors is gaining increasing importance due to the involvement of HDAC in transcription regulation. The level of histone acetylation can be modulated by HDAC inhibitors resulting in differentiation and/or apoptosis in cancer cells. We have previously reported the development of a nonisotopic assay for HDAC using a fluorescent derivative of epsilon-acetyl lysine. Here we report fluorescein-labeled octapeptides which are substrates for HDAC that bear closer resemblance to the native substrate. HPLC with fluorescence detection is successfully applied to the analysis of the time- and site-dependent deacetylation. LC-MS analyses are used to confirm the findings. The observed selectivity toward one of two possible deacetylation sites might result from steric hindrance by the label but the methodology presented here could be applied to similar larger peptides which might be improved tools to characterize HDAC site selectivity in vitro.

Animals↗

PubMedDate not supplied

The German Environmental Survey 1990/1992 (GerES II): a representative population study.

The German Environmental Survey (GerES) is a large-scale population study which has repeatedly been carried out in Germany. GerES I was conducted in 1985/1986 followed by GerES IIa in 1990/1991 (West Germany) and GerES IIb in 1991/1992 (East Germany). GerES III is currently run in both parts of Germany. The main goal of the surveys is to analyse and document the extent, distribution and determinants of the exposure to environmental pollutants of the German general population. Field work is conducted using a combination of several tools, including questionnaires, interviews, human biomonitoring, and indoor and outdoor environmental samplings. This paper describes the design of GerES II, and gives a general outline of the field work and the analytical procedures used. In GerES II, about 4000 adults were representatively selected from the German population with regard to age, gender and community size. Approximately 700 children were also included. Arsenic, cadmium, copper, chromium, lead, and mercury were determined in blood, morning urine and/or scalp hair. In addition, samples were taken and analysed to characterise exposure in the domestic environment (indoor air, house dust, drinking water). The contribution to exposure of food was also studied. Exposure to volatile organic compounds (VOCs) was determined by personal sampling.

Adolescent↗

PubMedDate not supplied

The German Environmental Survey 1990/1992 (GerES II): cadmium in blood, urine and hair of adults and children.

As a follow-up of an earlier population study carried out in West Germany in 1985/1986 (GerES I), a nationwide Environmental Survey was conducted in Germany in 1990-1992 (GerES II). It was the aim of these studies to obtain representative data on the population's body burden and the quality of their indoor environment and immediate surroundings. The present paper reports on cadmium levels in blood, urine and hair of 4021 adults aged 25-69 and 736 children aged 6-14. The statistical analysis included both descriptive and inferential methods. The data were classified according to social factors, lifestyle characteristics, and environmental exposures. Moreover, regression analysis was used to determine the predictors of cadmium concentrations in the types of sample studied. Active cigarette smoking was found to be dominant in affecting blood and urine cadmium levels in adults, but less important for cadmium levels in hair. Age and creatinine level in urine were additional important factors influencing the cadmium concentration in urine, especially in women. Environmental and occupational exposures to cadmium played only a minor role in the exposure models for German adults. The cadmium concentration in blood and urine was generally lower in children than in adults, while no significant difference for cadmium in hair could be detected. The cadmium concentrations in all three samples were significantly higher in East German children than in West German children.

Adolescent↗

PubMedDate not supplied

The German Environmental Survey 1990/92 (GerES II): sources of personal exposure to volatile organic compounds.

In the framework of the second German Environmental Survey carried out in the Western part of Germany in 1990/91 (GerES IIa) 113 adults aged 25-69 years were selected at random from the total study population of about 2500 to investigate personal exposure to about 70 volatile organic compounds (VOCs). Each subject wore a diffusive badge-type sampler for 1 week. The VOCs determined included alkanes, aromatics, aliphatic halocarbons, terpenes, and oxygen-containing compounds. Multivariate regression analysis was carried out to determine and quantify the major sources of personal exposure to various VOCs. In this paper, results are given for benzene, and C8- and C9-aromatics. Being subject to environmental tobacco smoke was found to be the most important determinant of benzene exposure, but automobile-related activities such as driving a car or refuelling, were also associated with significantly increased levels of benzene. The major determinant of C8- and C9-aromatics concentrations was occupational exposure. Emissions from paints, lacquers, newspapers, magazines and print-works were also important contributors to C8-aromatics exposure. Renovation, painting and smoking were associated with a significant increase of the exposure to C9-aromatics.

Adult↗