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Biomedical subjects

U Busch

Publications and source records attributed to U Busch.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pharmacokinetics and metabolic pattern after intravenous infusion and oral administration to healthy subjects.

Meloxicam [4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H- 1,2-benzothiazine-3-carboxamide-1,1-dioxide] is a new nonsteroidal antiinflammatory drug belonging to the enolic acid group. In a crossover study, 30 mg 14C-labeled meloxicam was administered to four male healthy volunteers as a short-term infusion and as an oral solution. The objectives of the study were to determine the mode of elimination, the excretion balance, the in vivo binding characteristics to serum proteins, and to investigate the metabolic pattern in plasma, urine, and feces. A comparison of plasma concentration measurements of unchanged drug by a specific HPLC assay and total radioactivity by liquid scintillation counting revealed a very close conformity. Over 90% of the plasma radioactivity was represented by unchanged drug. Its terminal and dominant half-life of elimination from plasma, as determined from plasma and urinary data in this study, ranged from 12 to 17 hr in the volunteers. The serum protein binding of the radioactivity from in vivo samples was very high (99.1-99.7%). The excretion balance was complete after 6 days. Average urinary excretion of 14C-radioactivity accounted for 43% of the dose, with the remainder appearing with the feces. Meloxicam was extensively metabolized, with only traces of the drug appearing unchanged in urine and feces. The main metabolites were formed by hydroxylation and further oxidation of the methyl group of the thiazolyl moiety. In addition, two further metabolites were found, particularly in urine. Altogether, > 95% of the dose excreted could be accounted for by the metabolites identified or the parent compound itself.

Administration, Oral↗
PubMed1994

Emergency coronary stenting for dissection during percutaneous transluminal coronary angioplasty: angiographic follow-up after stenting and after repeat angioplasty of the stented segment.

OBJECTIVES: The purpose of this study was to assess the angiographic results after emergency coronary stenting and after repeat angioplasty for restenosis within the stent. BACKGROUND: There is still little angiographic information about lumen renarrowing and its correlates after emergency stenting, and data with regard to the angiographic outcome of repeat angioplasty within the stent are almost nonexistent. METHODS: This study was based on the quantitative evaluation of angiograms performed before and immediately after intervention and at 6-month follow-up. The study included 164 of the 183 eligible patients with emergency Palmaz-Schatz stent implantation and 31 of those with restenosis within the stent who had repeat angioplasty. RESULTS: Stenting produced an improvement in minimal lumen diameter from 0.82 +/- 0.41 to 2.76 +/- 0.47 mm (mean +/- SD) and in diameter stenosis from 74.9 +/- 11.5% to 18.3 +/- 8.1%. Elastic recoil was 0.51 +/- 0.34 mm, or 16%. At 6-month follow-up, 32.3% of the patients had restenosis (> or = 50% stenosis). Minimal lumen diameter decreased to 1.84 +/- 0.78 mm, and diameter stenosis increased to 41.7 +/- 21.0%. The degree of lumen loss correlated significantly with the length of the original stenosis and the initial lumen gain achieved by stenting. Thirty-one patients with in-stent restenosis underwent repeat angioplasty. The primary success rate was 100%, and no abrupt vessel closure was verified. Minimal lumen diameter increased from 0.85 +/- 0.35 to 2.18 +/- 0.39 mm, and diameter stenosis decreased from 69.7 +/- 12.9% to 28.6 +/- 9.4%. Elastic recoil was 0.82 +/- 0.38 mm, or 27%. At follow-up, 38.5% of the patients had restenosis. Minimal lumen diameter was reduced to 1.72 +/- 0.67 mm, and diameter stenosis increased to 42.4 +/- 18.1%. CONCLUSIONS: Angiographic results of emergency coronary stenting compare favorably with those of conventional angioplasty. In-stent balloon redilation in patients with restenosis is associated with excellent short-term results and a restenosis rate not different from that reported for nonstented vessels.

Aged↗
PubMed1993

Pharmacokinetics of dirithromycin.

Dirithromycin is a new member of the macrolide class of antibiotics and has been developed for oral administration. Dirithromycin is a 14-membered lactone ring macrolide and is the C9-oxazine derivative of erythromycylamine. The human pharmacokinetics and clinical pharmacology of dirithromycin have been studied. Dirithromycin has unique pharmacokinetics which distinguish it from erythromycin. In man, following an oral 500 mg dose of dirithromycin, a mean peak plasma concentration (Cmax) of 0.48 mg/L (range 0.1-1.97) was observed at 4 h. The mean area under the plasma concentration versus time curve (AUC0-24h) measured 3.37 mg.h/L (range 0.39-17.16). No plasma accumulation was observed with multiple-dose administration. Dirithromycin may be taken without regard to meals, although food and H2-receptor antagonists may increase the systemic bioavailability in some patients. Based upon drug interaction studies performed with antipyrine and theophylline, dirithromycin has shown less potential to interact with other drugs metabolized by the cytochrome P450 system that does erythromycin. Plasma concentrations and AUCs were low due to rapid movement of the drug from the vascular space to the extravascular compartment, as reflected by tissue concentrations, which exceeded plasma concentrations 4 h after dosing. Dirithromycin achieves relatively high tissue concentrations (approximately 0.8-5.0 mg/kg) 4-24 h after dosing. The extensive tissue penetration is reflected in a large mean apparent volume of distribution of 800 L (range 504-1041). Dirithromycin is rapidly converted by non-enzymatic hydrolysis during absorption to erythromycylamine, which is microbiologically active. In a 14C-radiolabelled study, 60-90% of the administered dose was hydrolysed to erythromycylamine within 35 min of infusion. After 1.5 h, conversion to erythromycylamine in serum was virtually complete. Plasma protein binding was determined to be 15-30% by ultracentrifugation. Dirithromycin is characterized by a plasma elimination half-life of 44 h (range 16-65 h) that permits once-daily administration. Total body clearance was 226-1040 mL/min in the 14C-radiolabelled study. The primary route of elimination of dirithromycin/erythromycylamine was faecal/hepatic. Following intravenous administration, approximately 17-25% of the radioactivity appeared in the urine and 62-81% appeared in the stool, indicating predominantly hepatic excretion. With oral administration 1.2-2.9% of the radioactivity appeared in the urine and 81-97% in the stool. The major part of urinary excretion occurs within the first 48 h post-administration; however, urinary excretion of radioactivity lasted longer than 240 h. The absolute bioavailability calculated from dose-corrected urinary excretion data was 10% (6-14%).

Absorption↗
PubMed1993

The Sukhumi primate monkey model for viral lymphomogenesis: high incidence of lymphomas with presence of STLV-I and EBV-like virus.

T-cell leukemia virus-like proviral sequences (STLV-I) as well as EBV-like sequences were detected in PBLs and tissues of non-human primates (Papio hamadryas baboons, Green monkeys and Macaca arctoides; Sukhumi Primate Center/Georgia) by PCR. Surprisingly, two different types of STLV-I within Papio hamadryas baboons were found. One of its represents the baboon prototype STLV-I-Su described earlier, present in lymphomatous baboons from the "high-lymphoma stock", which shows about 83% homology to HTLV-I and 85% to STLV-I in the env and tax genes. The inter-individual variability within this subtype is very low (about 1% in the tax gene). The second subtype was mainly found in asymptomatic animals from the control colony and showed in the env gene 95% homology to HTLV-I, but only 82% to the prototype baboon sequence. The presence of two subtypes within the Sukhumi baboon population might be interesting in respect to the inoculation experiments with human leukemic blood and to possible interspecies transmissions. The nature of the Herpes Papio-virus was elucidated as EBV-like and the homology to the human EBV was > 90% in the polymerase gene. The homologies between different monkey species were between 92 and 96% and also here two subtypes within the baboons were detected. This is the first direct demonstration by sequencing that the Herpes Papio virus is closely related to EBV. For further studies of this animal model, rabbits were inoculated with cells originated from lymphomatous baboons and macaques. The rabbits developed generalized lymphomas lethal within 1-2 months. EBV-like and STLV-I-like sequences could be detected by PCR and sequencing showed 99-100% identity to the inoculum, indicating in fact the transmission from monkey to rabbit. These animal models seem to be very suitable for the elucidation of the pathogenesis of human HTLV-I associated T-cell leukemia/lymphoma and might be further on used for therapeutical and preventative studies.

Animals↗
PubMed1991

Sex hormone concentrations in men with angiographically assessed coronary artery disease--relationship to obesity and body fat distribution.

The relationship between circulating sex hormone levels and the occurrence of coronary artery disease (CAD) was studied in a group of 274 men undergoing coronary angiography. Hormone levels in men with CAD (n = 200) were compared to those in men found to be free of coronary lesions (n = 74). No significant differences were found for serum concentrations of estradiol, total testosterone, sex-hormone-binding globulin, free androgen index, dehydroepiandrosterone sulfate, or cortisol between the two groups. Serum androgens were negatively correlated to age in both groups, whereas estradiol was weakly associated with total cholesterol in the group of men without CAD. No consistent associations were detected between sex hormone levels and the degree of obesity or the distribution of body fat, the latter being assessed by the ratio of waist-to-hip circumferences. The results of this study do not support a significant role of sex steroid hormones in coronary artery disease in men.

Adult↗
PubMed1990

The concept and treatment of osteoporosis.

Osteoporosis is a dynamic process, thought to be caused by an uncoupling between osteoblast and osteoclast activity. Altered pulsatile secretion of growth hormone and parathyroid hormone (PTH) have been proposed as pathogenetic factors for this unbalanced coupling. The anatomical lesions are believed to be reversible until trabecular perforations develop, if fractures already occurred the anatomical defect is permanent. It is helpful to classify osteoporosis in stages of increasing severity depending on bone density and the presence of fractures. Theoretically, if the bone density is above the fracture threshold, then the only therapeutic goal is to maintain the bone mass. If instead the mineral density is below the threshold, an active therapy is needed with drugs that can possibly increase the skeletal mass. Osteoporosis with multiple fractures cannot be reversed. The authors propose a promising pharmacologic treatment for osteoporosis, based on the combination of human PTH-(1-38) and intranasal salmon calcitonin. If started in the early stages of the osteoporotic process, this regimen may restore the initial bone mass. In more advanced stages, only a correction of the metabolic defect is possible, but the irreversible vertebral deformities are not affected. On the basis of the results, cyclic therapy with human PTH-(1-38) and salmon calcitonin represents a good treatment choice for osteoporosis.

Bone Density↗
PubMed1990

Experimental pancytopenia of the peripheral blood with granulocytopoietic bone marrow hyperplasia in the beagle-dog.

During subacute and chronic toxicity studies on beagle dogs with the platelet aggregation inhibitor UH-A 46 XX, a suboxicam derivative, a pancytopenia of the peripheral blood with granulocytopoietic bone marrow hyperplasia was induced. Our observations are based on the results of a 13 week routine experiment (control group and dosage groups 5-, 50- and 700 mg/kg per day UH-A 46 XX) and on a special open-ended reversibility study (control group and dosage groups 50- and 700 mg/kg). The reversibility study included closely monitored hematological controls, bone-marrow cytology from sternal punctures and plastic section histology of iliac crest biopsies. During this study, plasma levels of the substance were estimated. The reproducible syndrome described was similar in the dogs in both studies. As early as the 8th week, but mostly between the 9th and 12th experimental weeks, one third of the animals treated orally with 700 mg/kg b.wt. UH-A 46 XX per day developed an acute fever (10 out of 30 animals). Four died several days later. Dogs treated with 5 or 50 mg/kg UH-A 46 XX remained unaffected. In the diseased dogs in both studies, proven pancytopenia was associated with the occurrence of numerous hematopoietic, especially granulocytopoietic precursors. The hyperplastic bone marrow showed a massive increase in granulocytopoiesis with considerable maturation arrest. These processes were accompanied by suppression or reduction of erythropoiesis. In addition, histological findings in the animals that died showed extramedullary hematopoiesis in different organs. During the second study, the reversibility was investigated in sick animals. If substance administration was terminated when the illness had reached its peak, normalization occurred quickly within 2 to 3 weeks. The animals remained healthy until the end of the long term follow-up which varied from 9 to 10 months. The pathogenesis of pancytopenia caused by UH-A 46 XX seems to be a chemically induced hyperdestruction of the peripheral blood cells. This appraisal is supported by the clear degenerative alterations in the granulocytic cells of the peripheral blood. An additional inhibitory effect of UH-A 46 XX on cellular maturation processes of hematopoiesis can be assumed.

Administration, Oral↗
PubMed1990

Distribution of [14C]meloxicam in joints of rats with adjuvant arthritis.

Using the new non-steroidal anti-inflammatory agent meloxicam (Mel), comparative investigations on pharmacokinetics and metabolism show good agreement between results in man and in the rat. To demonstrate preferential localization of the compound in inflamed sites, the distribution of the radiolabelled compound in arthritic joints of rats was studied using autoradiography. For that purpose an arthritis-inducing antigen was given to male albino rats. Twenty one days after antigen injection, all animals were given [14C]Mel orally. At three different times after receiving the labelled compound, the animals were sacrificed under anaesthesia. Tissue sections from each leg of each animal were taken for autoradiography. Sections were stained after film exposure using Masson-Goldner staining. The radiolabelled compound was preferentially localized in the areas which stained for inflamed connective tissue. The distribution pattern described persists beyond 24 h post-application. The figures indicate a highly efficient distribution of the radioactivity into chronically inflamed tissue of the hind foot-pads. Since negligible radioactivity was found in the front foot-pads, it is concluded that uptake into inflamed tissue is favoured.

Animals↗
PubMed1990

[Reduction in left ventricular volume and improvement in hemodynamics following intravenous administration of pimobendan (UDGG 115 BS) in dilated cardiomyopathy].

Acute cardiovascular effects of 5 mg (group I, n = 6) and 10 mg (group II, n = 6) i.v. pimobendan (UDCG 115 BS) were studied by right and left heart catheterizations in patients suffering from idiopathic dilated cardiomyopathy (NYHA II and III). Before and 2.5 h after application of pimobendan left ventricular volumes and left ventricular dP/dtmax were evaluated by left heart catheterization. Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCP), cardiac output (CO), heart rate, and systemic blood pressure were assessed before and 2.5, 4, and 6 h after administration of pimobendan. PCP was reduced from 12.2 +/- 7.5 to 8.3 +/- 7.1 mm Hg (p less than 0.05) by 5 mg of pimobendan, and from 18.3 +/- 6.2 to 6.2 +/- 3.4 mm Hg (p less than 0.005) by 10 mg of pimobendan. Reduction of RAP was significant only in group II (from 6.2 +/- 3.2 to 1.2 +/- 0.9 mm Hg; p less than 0.05). In contrast to other hemodynamic parameters, the significant increase of CO exhibited no dose-dependency. Only 10 mg of pimobendan induced a temporary reduction of mean arterial blood pressure. An increase in heart rate occurred only in group I and was merely transient. Left ventricular end diastolic and end systolic volume indices were clearly reduced by 5 mg as well as by 10 mg of pimobendan. A significant rise of left ventricular ejection fraction occurred only in group II. However, left ventricular dP/dtmax was increased significantly in both groups. No adverse effects were noted during acute administration of pimobendan. Therefore, intravenous pimobendan may be a useful drug in the treatment of acute cardiac failure.

Adult↗