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Biomedical subjects

H Schumacher

Publications and source records attributed to H Schumacher.

At least 19 recordsLinked to original sources

[Exercise performance after long-term administration of enalapril or metoprolol. A randomized double-blind study of hypertensive leisure-time sportsmen].

A randomized double-blind trial was conducted in 36 leisure-time sportsmen (mean age 40.1 +/- 5.4 years) with mild or moderate essential hypertension (WHO groups I or II) to find out whether an 8-week antihypertensive treatment with daily 10-20 mg enalapril or 100-200 mg metoprolol changed their exercise performance. This was measured by bicycle spiroergometry together with determination of lactate levels, before and at the end of the treatment period. Maximal oxygen uptake rose by 1.86 ml/kg.min during enalapril administration and by 1.06 ml/kg.min at the individual anaerobic threshold. But under metoprolol these parameters fell by 6.57 ml/kg.min and 4.61 ml/kg.min, respectively. After treatment with these two drugs 3 and 15 patients, respectively, had the sensation of greater exercise performance at identical exercise levels. The differences in exercise between the two drugs using the stated three primary criteria were statistically significant. The Watt-time product decreased in only one of the patients of the enalapril group, but in 17 of the metoprolol group. Only metoprolol significantly reduced exercise heart rate. Both drugs caused a similar fall in systolic blood pressure during exercise.

Adult

Stimulation of testosterone production by atrial natriuretic peptide in isolated mouse Leydig cells results from a promiscuous activation of cyclic AMP-dependent protein kinase by cyclic GMP.

The aim of this study was to examine the possibility that atrial natriuretic peptide-stimulated testosterone production by mouse Leydig cells results from an activation of cAMP-dependent protein kinase (kinase A) by cGMP. In these cells, both 8Br-cGMP and 8Br-cAMP could stimulate testosterone production, though the latter was approximately 50-fold more potent. Following the stimulation of the cells with the atrial peptide, a dose-related decrease in the cellular protein-bound cAMP accompanied by a concomitant increase in the protein-bound cGMP was observed. The steroidogenesis stimulated by both human chorionic gonadotrophin (hCG) and atrial peptide was inhibited in a dose-dependent manner by a cAMP antagonist, adenosine 3',5'-cyclic monophosphothioate, Rp-isomer (RpcAMPS). In a cell-free [3H]cAMP binding assay, we have shown that unlabelled cGMP and RpcAMPS could competitively inhibit the [3H]cAMP binding, confirming that cAMP, RpcAMPS and cGMP could bind to the same binding protein. Finally, in a cell-free kinase A assay system, we have demonstrated that in lysates prepared from either atrial peptide or hCG-stimulated cells, the cellular kinase A was activated to an equal extent. We conclude from the data obtained that cGMP can bind to the cAMP-binding sites of kinase A and thereby brings about a promiscuous activation of this kinase. This appears to be an underlying mechanism by which atrial peptide hormone is able to stimulate the steroidogenesis in mouse Leydig cells.

1-Methyl-3-isobutylxanthine

Screening method for beta-lactamase substrate profiles.

A disc diffusion method, based on the idea of Klundert, for screening of substrate profiles of beta-lactamases was developed in order to perform epidemiological studies. The method was tested against 30 different reference beta-lactamases and 59 clinical isolates known to produce TEM-1, SHV-1 and BRO-1. The reproducibility and discriminating power of the disc diffusion method made it possible to differentiate between eight types of substrate profiles for the 30 reference beta-lactamases and to differentiate between TEM-1, SHV-1 and BRO-1 from clinical isolates. In combination with analytical isoelectric focusing the disc diffusion method gives a reliable identification of beta-lactamases.

Anti-Bacterial Agents

In vitro effects of tumor necrosis factor-alpha on human thyroid follicular cells.

Tumor necrosis factor-alpha is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-alpha with an average of 9,300 receptors/cell (Kd = 1.9 x 10(-10) mol). The effects of the cytokine on thyroid cell proliferation were assessed by 3H-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-alpha resulted in a moderate stimulation of cell proliferation with an increase of 3H-thymidine incorporation from 44,613 +/- 7,989 cpm under basal conditions to 63,326 +/- 6,822 cpm after 100 U/l tumor necrosis factor-alpha (p < 0.01). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-alpha. The maximum effect was observed after 1,000 U/l tumor necrosis factor-alpha (281.5 +/- 107.0 vs 114.5 +/- 33.6 fmol cAMP/micrograms protein under basal conditions: p < 0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-alpha binding. We conclude that in vitro tumor necrosis factor-alpha modulates in addition to its well known synergistic effect on interferon-gamma induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors.

Adult

beta-lactamases in Shigella.

The occurrence of resistance and production of beta-lactamases was investigated in 60 Shigella strains. Ampicillin resistance was found in 28 (47%) of the isolates, the resistance being more frequent in Sh. flexneri than in Sh. sonnei. All strains were susceptible to cefotaxime, mecillinam, and ciprofloxacin. The beta-lactamases produced by Shigella were similar to TEM-1, OXA-1, or the low-level chromosomally mediated cephalosporinase produced by Escherichia coli. The beta-lactamases produced by Sh. flexneri were most often the OXA-1-like enzymes.

Anti-Bacterial Agents

[Advice on intravenous treatment with beta-lactams].

Beta-lactams (BL) are administered at present in dosages which are based only partly on controlled clinical investigations as these are difficult to carry out for all types of infections. Investigations of well-defined infections and animal experiments suggest that the optimal effect is obtained when the BL concentration is kept above the minimal inhibiting concentration (MIG) during treatment. In cases of intermittent BL treatment of serious infections and treatment of patients with compromised immune defence, it is considered advisable to keep the serum concentration constantly above the anticipated limit of sensitivity or MIC. On the basis of a review of the most important pharmacokinetic properties of BL, methods of measurement of the sensitivity of bacteria to BL and development of bacterial resistance to BL, a method is presented of calculating the individual doses and the intervals between doses as regards the sensitivities of the commonest human pathological bacteria to BL although the proposed dosages have not been tested clinically for all types of infections. Employing this, BL may easily be administered individually according to the severity of the infection and possible special conditions in the underlying disease in the patients. The individual doses and intervals between doses recommended in The Danish Medical Codex from 1988 are presented in tabular form and are compared with calculations of the time in which the serum concentration remains above the anticipated limit of sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Cephalosporins

Implication of prior treatment with drug combinations including inhibitors of topoisomerase II in therapy-related monocytic leukemia with a 9;11 translocation.

The present case, together with other reports reviewed herein, defines a new subtype of therapy-related acute myeloid leukemia (t-AML). This variant of t-AML is characterized by a short interval from initial drug therapy to bone marrow dysfunction and monocytic morphology without trilineage dysplasia. Unlike classic t-AML, which frequently has abnormalities of chromosomes 5 and/or 7, this new subtype is characterized by rearrangements involving band q23 of chromosome 11, most commonly a 9;11 translocation. The majority of patients with this subtype t-AML had prior cytotoxic therapy with topoisomerase II-reactive drugs including anthracyclines, epipodophyllotoxins, or actinomycin D, combined with either an alkylating agent or cisplatin. This association of prior therapy which includes topoisomerase II-reactive agents and a rapidly appearing t-AML involving the monocytic line and chromosome 11 requires additional study.

Alkylating Agents

Lymphoblastic crisis of chronic myelogenous leukemia. Hand mirror variant.

We present, to our knowledge, the first extensively studied case of lymphoid L2 blast crisis of chronic myelogenous leukemia with a hand mirror cell (HMC) variant. Special stains revealed the leukemic cells to be terminal deoxynucleotidyl transferase positive by immunofluorescence and cytochemically positive for alpha-naphthyl acetate esterase and acid phosphatase (diffuse granular). Immunophenotyping identified the major leukemic cell population as B-cells that expressed CD10+, CD19+, and HLA-DR+. It was not possible to separate the HMC and the non-HMC leukemic population by gating various cell populations, dual staining, cytochemistry, or by terminal deoxynucleotidyl transferase. Gene rearrangements were observed in both Ig heavy-chain alleles and one T-cell antigen receptor gamma-subunit allele. The rearrangements occupied all of the cells, indicating that the HMC and non-HMC were of a common clonal origin. The patient had a mosaic karyotype, with 90% of the cells having t(9;22), t(8;14), and t(9;15) translocations, an additional chromosome 8, and deleted chromosomes 9 and 15. Antibodies to simian sarcoma-associated virus and baboon endogenous virus were isolated in the patient's peripheral blood plasma.

Antigens, Neoplasm

[Enoxacin concentration in seminal fluid, in prostate secretions and in prostatic adenoma tissue following oral administration or intravenous infusion].

In eleven volunteers and 39 patients undergoing transurethral resection of the prostate or bladder tumor, concentrations of enoxacin were measured in seminal fluid (volunteers), in prostatic fluid (volunteers, patients) and in prostatic adenoma tissue (patients) after oral (400 mg) administration and intravenous (428 mg) infusion (60 min) of enoxacin. Simultaneously 2.534 g of iothalamic acid was i.v. injected to identify possible urinary contamination. The concentrations of enoxacin in seminal fluid after 2-4 h and in prostatic tissue after about 1-4 h and 14-16 h exceeded plasma concentrations more than two-fold. The concentrations in prostatic fluid after 1-4 h were about half the plasma concentrations. Venous blood samples were taken after intravenous infusion at intervals of up to 24 h in a total of 14 patients. The mean plasma concentration of enoxacin decreased from its maximum of 6.9 mg/l at the end of infusion to 0.5 mg/l at 12 h after administration. A terminal half life of 6.65 h was calculated according to an open two-compartment model.

Administration, Oral

In-vitro activity of fleroxacin against isolates causing complicated urinary tract infections and concentrations in seminal and prostatic fluid and in prostatic adenoma tissue.

Fleroxacin is a new fluoroquinolone with a broad antibacterial spectrum and a serum half-life of about 8-12 h. Eighty percent of 400 isolates from complicated or hospital-acquired urinary tract infections were inhibited by a concentration of 1 mg/l and 95% by 4 mg/l. As with other quinolones, fleroxacin is less active in acid urine (pH 5.4) than in Mueller-Hinton broth (pH 7.4). In 12 healthy volunteers the concentrations of fleroxacin were measured in plasma and seminal and prostatic fluid 2, 4 and 12 h after an oral dose of 400 mg. The mean plasma concentrations of three or four volunteers at each time were 4.2, 3.6 and 1.2 mg/l, respectively. The corresponding prostatic fluid/plasma ratios were 0.30, 0.27 and 1.96, respectively. By concomittant administration of ioxitalamic acid it could be demonstrated that in samples obtained 12 h after administration urinary contamination must be considered. Fleroxacin is concentrated in seminal fluid by a median ratio of 1.7. In 13 elderly patients the prostatic fluid and prostatic adenoma tissue concentrations were determined one to four hours following oral administration of 400 mg. The concentrations in prostatic fluid were similar to those of volunteers. The tissue concentrations exceeded plasma concentrations by only about 10% (median). Fleroxacin is very active against isolates causing complicated UTI. Concentrations in seminal and prostatic fluid and prostatic adenoma tissue are sufficiently high to treat bacterial prostatitis or vesiculitis caused by susceptible bacterial strains.

Adult

Penetration of fleroxacin into prostatic secretion and prostatic adenoma tissue.

In 12 elderly patients, plasma, prostatic secretion and adenoma tissue concentrations of fleroxacin were determined 1-4 h following oral administration of 400 mg. The plasma concentrations ranged between 0.4 and 5.5 micrograms/ml (median 3.7 micrograms/ml), the mean tissue concentrations were slightly higher. The concentrations in prostatic secretion were about one third of the simultaneous plasma concentrations. High concentrations of the concomitantly administered ioxithalamic acid in prostatic secretion are considered as indicative of urinary contamination, and in this case the fleroxacin concentrations are questionable. The drug levels in prostatic adenoma tissue were similar to the concomitantly measured plasma levels.

Administration, Oral

[The course of functional psychoses (author's transl)].

Functional psychoses correspond to a universal reduction of mental and intellectual function which, fundamentally reversible and unspecific, appear as sequelae of disturbances of cerebral function. They are the most common psychoses in medical practice and in hospitals. With the Syndrome Short Test and Functional Psychosis Scale B we now have a mutually equilibrated test system for the measurement of the whole range of severity of functional psychoses. With these two psychopathometric methods a relatively differentiated investigation of cross section and course can be performed, for example in arriving at a diagnosis, checking medical measures, monitoring the effect of drugs and in the prognosis of a disease.

Adult

Developing the medical curriculum at King Abdulaziz University.

The kingdom of Saudi Arabia has placed a high priority on medical education. King Abdulaziz University is developing a medical curriculum aimed at being responsive to the health needs of the people of the kingdom. In creating the curriculum, planners devoted considerable time and effort to studying health manpower resources and needs, regional developments, demographic patterns, socioeconomic and cultural factors, general education development plans, vital statistics, and existing and projected health facilities. These and many other factors played a role in determining the format and the content of the curriculum, which is intended to produce individuals for leadership roles as medical educators, medical practitioners, and researchers.

Adolescent

[Drug-related increase of intelligence level. Considerations and a double-blind-study with flunarizin (sibelium) (author's transl)].

Fluid and crystallized intelligence are two second-order factors that are differentiated within the intelligence model by R.B.Cattell. Fluid intelligence is considered to be a biological capacity relatively independent of environmental influences. Crystallized intelligence, however, is connected to accultured skills and knowledge. The capacity of fluid intelligence decreases by non-optimal states of general activation, functional psychosis (physically founded reversible psychosis) or defect-syndromes (physically founded irreversible psychosis). Fluid intelligence can increase by drugs only, if the functional psychosis is diminished or if the state of activation is optimized. There is no drug-effect on crystallized intelligence but an indirect influence via fluid intelligence. The hypothesis of the drug-related increase of fluid intelligence as a correlate to the diminuition accompanying the functional psychosis should be confirmed by a clinical experiment. Therefore two samples of 20 patients each with a functional psychosis following cerebral blood-flow disturbances received flunarizine (Sibelium) and placebo respectively during a double-blind study lasting 12 weeks. Under the activ substance to be applied for amelioration of peripheral and central blood-flow the measured values of fluid intelligence increased six weeks after starting therapy, while there were no changes under placebo. In the end of the investigation the measured intellectual capacity had increased by 50 per cent under flunarizine.

Aged