PubMed Health⌕ Search

Biomedical subjects

C Baur

Publications and source records attributed to C Baur.

At least 37 records · Page 2Linked to original sources

A pharmacokinetic model to describe toxicokinetic interactions between 1,3-butadiene and styrene in rats: predictions for human exposure.

Co-exposure to vapours of 1,3-butadiene and styrene occurs in the styrene-butadiene polymer manufacturing industry. Both compounds are biotransformed during a first step by cytochrome P450-dependent mono-oxygenases to epoxides--intermediates which are proven carcinogens. In a previous publication, we reported that metabolism of butadiene in rats was inhibited by simultaneous exposure to styrene, whereas butadiene had no effect on the kinetics of styrene. In order to translate these results into conditions of human exposure, we developed a physiologically based pharmacokinetic (PBPK) model, which is presented here. Maximal metabolic rates (Vmax) and Ostwald's partition coefficients were obtained using liver microsomes and tissues from rat and man. Apparent Michaelis (Km) and inhibition (Ki) constants were derived from previously published data on rats and were considered to be species-independent. The model was used to simulate human exposure to atmospheric mixtures of 5 and 15 ppm butadiene with 0.20 and 50 ppm styrene. It predicts that the presence of styrene significantly inhibits butadiene metabolism in man: At exposures up to 15 ppm, the amounts of butadiene metabolized can be expected to be reduced to 81 and 63% with co-exposure to styrene at 20 and 50 ppm, respectively.

Administration, Inhalation↗

An immunoglobulin-specific autoantibody occurring during alloimmunization suppresses the antibody response.

Our previous studies showed that a broadly reactive immunoglobulin G (IgG) anti-immunoglobulin (IgG-anti-Ig) autoantibody is induced during the immune response of LEW rats to BN blood cells. The present experiments analyze the immunoregulatory effect of this physiological autoantibody on antigen receptor-activated B cells in cell cultures. The results show that: (a) At 0.9 pg IgG-anti-Ig/10(6) B cells, an almost complete suppression of the antibody response is induced: we calculated that a few IgG-anti-Ig molecules are sufficient to suppress the antibody response of one B cell; (b) IgG-anti-Ig-induced B-cell suppression is dose-dependent; (c) IgG-anti-Ig suppresses B cells contained in their natural environment (mixed spleen cell population). These data demonstrate that the IgG-anti-Ig autoantibody is an extremely efficient regulatory molecule of the alloimmune response.

Animals↗

[Which factors determine the critical hematocrit as an indication for transfusion?].

The question as to what extent the hematocrit (Hct) is a strong indicator for or against the need for transfusion of whole blood or blood products is still controversial. In order to enable the clinician to make a definite decision, a number of aspects have to be taken into consideration. The human organism has only limited oxygen reserves, and these are even more limited under pathological conditions. Oxygen flux - the amount of oxygen transported by the blood in 1 min - is a critical factor in the oxygenation of the human body. Another critical factor is oxygen consumption, which is highly variable depending on the presence of conditions such as rest, shivering, seizures, hypothermia, etc. Furthermore, different organ systems have different oxygen consumption rates. The ratio of oxygen consumption to oxygen flux is referred to as the oxygen extraction rate or oxygen utilization. Under normal conditions oxygen uptake is independent of oxygen flux, and thus independent of blood flow. Under conditions of organ dysfunction, however, oxygen deficiency may be present without being recognized on standard clinical diagnostic parameters. The normal human organism has a number of possibilities to compensate for acute or chronic anemia, i.e., increases in cardiac output, organ perfusion, 2,3-DPG content, a shift in the oxygen dissociation curve, etc. These compensatory mechanisms may, however, be restricted or cease to function under conditions of acute or chronic disease. Arterial and mixed-venous PO2 and oxygen content are some of the parameters used to assess the oxygen reserves available to the organism even under critical conditions. Although oxygen content is the most significant of these parameters, accurate measurement of this parameter remains a problem of laboratory medicine. PVO2 is of only limited importance under conditions of anemia. Minimum oxygen content or minimum oxygen flux values should under no conditions be approximated during anesthesia or intensive care. The critical Hct as an indicator for or against transfusion of blood or blood products is considerably modified by restricted organ function, anesthesia, intensive care treatment, resuscitation, etc.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia↗

[Negligence of the physician's duty to care during "therapeutic local anesthesia"].

Therapeutic local anaesthesia, although a seemingly simple procedure, requires informed consent by the patient as well as proper indication and careful execution. Four cases selected from a medico-legal experience illustrate some severe complications. Nausea, dyspnoea and respiratory arrest (anaphylactic shock) occurred in a 34-year-old woman shortly after injection of 0.5% Bupivacaine into the paravertebral musculature for the treatment of acute neck pain. She had to be hospitalized for 18 days, at times requiring mechanical ventilation. Three other patients (women aged 40, 43 and 52 years, respectively) developed a pneumothorax after supposedly intramuscular injection of a local anaesthetic. They were hospitalized for 7 to 12 days for treatment by drainage. Anatomical variations were excluded by ultrasound in the 40- and 43-year-old patients. These case reports demonstrate that doctors performing such procedures do not always possess the necessary anatomical knowledge, and the possible occurrence of complications is underestimated.

Adult↗

Enzyme specific kinetics of 1,2-epoxybutene-3 in microsomes and cytosol from livers of mouse, rat, and man.

Kinetics of the metabolism of 1,2-epoxybutene-3 (butadiene monoxide) were investigated in liver fractions of mouse, rat, and man. In these species similar enzyme characteristics were found. In microsomes, no NADPH-dependent metabolism of butadiene monoxide was detectable. Epoxide hydrolase activity was found only in microsomes. The Vmax [nmol butadiene monoxide/(mg protein x min)] was 19 in mouse, 17 in rat, and 14 in man and the apparent Km (mmol butadiene monoxide/l incubate) was 1.5 in mouse. 0.7 in rat, and 0.5 in man. Glutathione S-transferase activity was found in cytosol only, revealing first order kinetics in the measured range. The ratio Vmax/Km [(nmol butadiene monoxide x 1)/(mg protein x min x mmol of butadiene monoxide)] was 15 in mouse, 11 in rat, and 8 in man. The data obtained were used to extrapolate on the total rate of butadiene monoxide metabolism for each species in vivo: it was calculated to be 1.3 times higher in mice and 2.3 times lower in man compared to rats, when corrected for body weight.

Animals↗

A B cell-suppressive IgG-antiimmunoglobulin antibody induced by alloimmunization.

This study is an extension of our previous report that alloimmunization produces a serum factor that suppresses the lymphocytotoxic antibody response. The experiments presented herein show that: (1) serum and IgG of pretreated rats contain an antibody directed against the constant region of IgG; (2) the anti-IgG has strong anti-Fc-gamma and weak anti-Fab activity; (3) the antibody also reacts with IgM; (4) the antiimmunoglobulin is an autoantibody; and (5) the antiimmunoglobulin suppresses the primary B cell response in vitro.

Animals↗

[DNA analysis of HLA class II and III genes in sudden infant death (SIDS)].

In 39 cases of SID we studied the polymorphism of HLA-class II genes DRB and DQB and HLA-class III genes C4 (C4A and C4B, genes encoding the fourth complement component) and 21-hydroxylase (21OH-A and 21OH-B, genes encoding the enzyme 21-hydroxylase of the cortisol pathway) by DNA analysis. This study was performed in cooperation with the Institute of Legal Medicine, University of Munich. Compared to healthy controls the percentage of C4B gene deletions, C4B gene duplications (C4B "short") and 21OH-A gene deletions is increased in SIDS. The deviations are statistically not significant. The analysis of the HLA-DR alleles revealed a significant decrease of HLA-DR2 in SIDS compared to controls (p = 0.0016, pc = 0.016). The results of this study indicate a possible role of C4B/21OH-A gene defects as a risk factor in a subgroup of SID cases. This hypothesis has to be confirmed by studying further cases.

Chromosome Aberrations↗

[Species identification by fragmented DNA].

The species of raw meat as well as heat-processed meat can be determined by DNA dot-blot hybridization-techniques. We investigated on artificially degraded DNA whether various DNA qualities could influence the validity of the experiment results. We demonstrated that degraded DNA could also react according to the species. The shorter the DNA fragments, the discreter was the reaction when high molecular weight DNA was used as a probe. This effect is not observed with degraded DNA as a probe.

Animals↗

[Differentiation of food composition in the digestive tract].

Plant DNA was isolated from the contents of the stomach and hybridized with DNA isolates from the contents of different parts of the bowels. By this procedure we pursued the passage of the chyme. The possible predictions of this investigation concerning the shortest interval between the last meal and death will be discussed.

DNA Probes↗

[Species identification in traces using molecular biology methods].

The species of a biological sample (blood, hairs) was determined by hybridization of its DNA with specific control DNA using either the former or the latter as probe. The labelling of the probes occurred with radioactive nucleotides by random priming or by the non-radioactive sulfonation of cytosine residues. Species identification by means of DNA hybridization is practicable even after denaturing the sample by heat or after treatment with H2O2. In case of a human sample, the sex of the donor can be determined, too.

Animals↗

Cefodizime in acute purulent exacerbations of chronic respiratory disease.

Clinical, microbiological and pharmacokinetic studies were carried out after 1 or 2 g intramuscular injections bd of cefodizime (HR 221), a new aminothiazolyl cephalosporin, in 41 patients hospitalized for acute purulent exacerbations of chronic respiratory disease. Treatment was for 10 days. Serum Cmax values of 54.8 and 84.7 mg/l were recorded approximately 2 hours after the injections, the corresponding sputum values averaging 1.01 and 2.58 mg/l. Penetration from blood to sputum was 2 to 3.6%. The elimination phase half-life in serum was approximately 4.5 h. Clinical, microbiological and pharmacokinetic studies were carried out after 1 or 2 g intramuscular injections bd of cefodizime (HR 221), a new aminothiazolyl cephalosporin, in 41 patients hospitalized for acute purulent exacerbations of chronic respirators disease. Treatment was for 10 days. Serum Cmax values of 54.8 and 84.7 mg/l were recorded approximately 2 hours after the injections, the corresponding sputum values averaging 1.01 and 2.58 mg/l. Penetration from blood to sputum was 2 to 3.6%. The elimination phase half-life in serum was approximately 4.5 h.

Adult↗

Lead in human bones. Investigations on an occupationally non-exposed population in southern Bavaria (F.R.G.). I. Adults.

The concentration of lead in three different bones (pelvic bone, cortical part of the mid-femur, petrous portion of the temporal bone) of 240 occupationally non-exposed adults who died between October 1983 and February 1985 was determined by electrothermal atomic absorption spectrometry. As far as sex, age and domicile (urban and rural) are concerned, a balanced distribution was achieved (for each age decade 10 urban females, 10 rural females, 10 urban males and 10 rural males). The predominantly cortical femur (geom. mean, 3.86 mg Pb/kg bone wet wt.) and temporal bones (5.59) showed higher Pb concentrations than the trabecular pelvic bone (1.65) (in each case n = 240). For each of the three types of bone, the mean lead content of the males (n = 120) was significantly higher than those of the females (n = 120): e.g. for pelvic bone by 38.3%, mid-femur by 51.3% and temporal bone by 24.8%. No statistically significant difference was obtained when comparing residents of Munich (population greater than 1 X 10(6] (n = 120) with people in the remaining parts of Southern Bavaria (n = 120). The Pb content of the temporal bone increased steadily with age. In contrast, in the mid-femur and the pelvic bone the Pb content reaches a plateau in middle age with a decrease at higher ages; this decline is more distinct for females. The mean lead body burden was calculated to be 41.4 +/- 24.2 mg for all males (n = 120) and 24.1 +/- 12.5 mg for all females (n = 120). We conclude that the lead burden, at least in the area investigated, has been reduced in the last decade, probably because of a reduction in the lead content of petrol.

Adolescent↗

Amoxycillin/clavulanate in acute purulent exacerbations of chronic bronchitis.

Twenty patients, all admitted to hospital with acute purulent exacerbations of chronic bronchitis associated with Haemophilus influenzae, Streptococcus pneumoniae or beta-lactamase producing Branhamella catarrhalis were treated twice daily for ten days with amoxycillin/clavulanate. Ten patients were first given 1000 mg amoxycillin with 200 mg potassium clavulanate intravenously bd for three days, before crossing to the standard oral regimen of 1000 mg amoxycillin + 250 mg potassium clavulanate bd. Clinical results on day 10 were excellent in 16/20 patients, but 14 patients developed recurrences or reinfections within a week of the end-of-treatment, five of them with beta-lactamase producing B. catarrhalis. Bacteriological and kinetic studies showed that the branhamella beta-lactamases were inhibited by 0.25 mg/l clavulanic acid and that the mean sputum concentration of clavulanic acid was 0.16 mg/l, that of amoxycillin being 0.92 mg/l. The importance of the follow-up of such infections is stressed.

Aged↗

Studies on a new formulation of ceftazidime--ceftazidime arginine--in patients with recurrent chest infections.

One hundred hospital patients with respiratory infections were treated with 1 or 2 g intramuscular injections of ceftazidime sodium or of a new formulation of ceftazidime with arginine three times daily. Clinical and microbiological assessments showed no significant differences in efficacy between the two preparations. Local pain necessitating lignocaine was noted in five of 49 evaluable patients given ceftazidime sodium (10.2%) but in none of the 50 receiving ceftazidime arginine. No other unwanted effects were recorded. The pharmacokinetic results after the 1 g injections showed slightly higher Cmax values with ceftazidime arginine with correspondingly greater 0-7 h AUC values. The mean AUCs were almost identical after the 2 g injections.

Aged↗

Penetration of ofloxacin from blood to sputum.

Serum and sputum concentrations of ofloxacin were measured by a microbiological agar-well diffusion assay in nearly 100 patients after single 400, 600 or 800 mg doses of ofloxacin. All patients were admitted to hospital because of acute purulent exacerbations of chronic respiratory disease, and the concentration studies were performed on the first treatment day while the sputum was still purulent. Both blood and sputum samples were tested at standardised time intervals after dosage, and concentration-time curves were constructed. Cmax values in serum and sputum were 3.7 and 2.7 mg/L after 400 mg ofloxacin, 7.1 and 6.1 mg/L after 600 mg and 8.8 and 6.3 mg/L after 800 mg. Penetration from blood to sputum, as judged from ratio of AUC values for sputum and serum, varied from 78 to 103%.

Anti-Infective Agents↗

The use of quinolones in respiratory tract infections.

In a prospective (and continuing) trial, a total of 271 patients with acute purulent exacerbations of chronic respiratory disease (bacteriologically confirmed) were treated with various new oral quinolones including enoxacin (26), pefloxacin (50), ciprofloxacin (80) and ofloxacin (115). Various therapeutic schedules were employed, with differing drug dosages, frequencies of administration and durations of treatment. All patients were investigated microbiologically during and immediately after treatment and after 7 days of follow-up. The best clinical results were noted after ofloxacin 800 mg once daily for 7 days, which showed excellent gastrointestinal absorption and rapid penetration through to the sputum. Some of the treatment failures with enoxacin and pefloxacin could be ascribed to the development of resistance during treatment, rises in minimal inhibitory concentrations (MICs) being noted with Streptococcus pneumoniae and Pseudomonas aeruginosa.

Anti-Infective Agents↗