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Biomedical subjects

M Woodruff

Publications and source records attributed to M Woodruff.

At least 19 recordsLinked to original sources

Pharmacokinetics, safety, and tolerability of BAY 12-9566 and nonsteroidal anti-inflammatory agents (naproxen, ibuprofen) during coadministration in patients with osteoarthritis.

The pharmacokinetic interactions between BAY 12-9566 and two nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen and ibuprofen, were investigated in osteoarthritis (OA) patients. The study comprised six groups: two NSAID groups with three levels of treatment (BAY 12-9566 400 mg, BAY 12-9566 100 mg, and placebo). Plasma pharmacokinetic parameters (AUC(0-tau), Cmax, and tmax) were determined for each treatment group following 5 days of NSAID administration, 14 days of BAY 12-9566 administration, and 14 days of concurrent NSAID and BAY 12-9566 administration. For most conditions, the total plasma drug concentrations of both NSAID and BAY 12-9566 were diminished by coadministration; total plasma BAY 12-9566 was not affected by ibuprofen treatment. Importantly, the free drug concentrations were largely unaffected by coadministration. Most side effects were mild or moderate in intensity, and all events, with the exception of headache, were reported in both NSAID groups and in both placebo and BAY 12-9566 groups.

Adult↗

Chromatographic aspects in high throughput liquid chromatography/mass spectrometry.

Important parameters to consider when developing a liquid chromatography/mass spectrometry (LC/MS) method are buffer type and concentration, and column geometry. In the work presented here the choice of buffer for the analysis of basic compounds using a polar embedded phase (HyPURITYtrade mark ADVANCE) is illustrated for the analysis of tricyclic antidepressants. Method transfer from a 4.6 mm i.d. column to a 2.1 mm i.d. column is demonstrated for the analysis of triazines and anabolic steroids and their metabolites, with no change in selectivity and with added speed of analysis. Analysis of eight beta-blockers is achieved in 65 seconds by using a short 30 x 4.6 mm C18 column.

Adrenergic beta-Antagonists↗

Pharmacokinetics of a once-daily oral dose of moxifloxacin (Bay 12-8039), a new enantiomerically pure 8-methoxy quinolone.

The pharmacokinetics, safety, and tolerability of oral moxifloxacin, a new 8-methoxy quinolone, were assessed in a randomized, double-blind, placebo-controlled study in which healthy male and female volunteers received either 400 mg of moxifloxacin once daily (n = 10) or a placebo once daily (n = 5) for 10 days. Plasma moxifloxacin concentrations on days 1 and 10 were measured by high-performance liquid chromatography and fluorometric detection. Standard pharmacokinetic parameters were estimated by noncompartmental methods. Natural logarithmic estimates for each pharmacokinetic variable of each subject were analyzed by a two-way analysis of variance. Hematology, blood chemistry, vital signs, and adverse events were monitored, and electrocardiograms (ECG) were performed. Plasma moxifloxacin concentrations of predicted therapeutic relevance were achieved in this study. For day 1, the mean maximum concentration of drug in serum (C(max)) and the area under the concentration-time curve from 0 to 24 h (AUC(0-24)) were 3. 4 mg/liter and 30.2 mg. h/liter, respectively. Corresponding means on day 10 were 4.5 mg/liter and 48 mg. h/liter, respectively. On day 10, the mean elimination half-life was approximately 12 h. Plasma moxifloxacin concentrations exceeded the MIC for Streptococcus pneumoniae throughout the 24-h dosing period. The day 1 and day 10 mean AUC/MIC ratios were 121 and 192, respectively, and the mean C(max)/MIC ratios were 13 and 18, respectively. Moxifloxacin was well tolerated; no clinically relevant changes in the standard laboratory tests, vital signs, or ECG were observed. Pharmacokinetic parameters demonstrated linearity, and estimates of pharmacokinetic/pharmacodynamic ratios (AUC/MIC and C(max)/MIC) indicate that the regimen of 400-mg once daily should be effective for treating a variety of infections. Moxifloxacin was found to be safe and well tolerated in healthy volunteers when it was given as a single daily 400-mg dose for 10 days.

Adolescent↗

Pseudorabies in captive coyotes.

Pseudorabies (Aujeszky's disease) was diagnosed in three adult captive coyotes (Canis latrans) from southern Indiana (USA). The coyotes died in their outdoor enclosure within a 48 hr period. Histopathology revealed multifocal, nonsuppurative meningioencephalitis and eosinophilic intranuclear inclusion bodies within neurons. Samples of brain were positive for pseudorabies virus by fluorescent antibody testing and virus isolation. Source of infection was the probable consumption of pseudorabies virus-infected pig carcasses.

Animals↗

A phase-II trial of Corynebacterium parvum as adjuvant to surgery in the treatment of operable lung cancer.

A phase-II randomized trial has been undertaken in 49 patients with operable lung cancer, to determine the effect of a single IV infusion of killed C. parvum vaccine as an adjuvant to surgery. The number of patients was insufficient to provide a decisive result, but analysis 6 years after the last patient was admitted shows that the adjuvant therapy certainly did not shorten, and may well have prolonged, survival. Of the patients with squamous cell carcinoma who were alive 1 year after operation all except one in the C. parvum-treated group were alive 4 years later, whereas five in the control group died during this interval. Judgement concerning the value of IV administration of CP as adjuvant therapy in patients with operable lung cancer should be deferred until further evidence is available.

Adjuvants, Immunologic↗

Cellular basis for the loss of carcinogen from methylcholanthrene-impregnated Millipore membrane.

Millipore 'discs' impregnated with methylcholanthrene dissolved in wax or in crystalline form implanted subcutaneously in mice evoke an early intense macrophage and giant cell reaction; later the discs become covered with connective tissue, and eventually fibrosarcomas develop in their vicinity. Studies with tritium-labelled material show that under these conditions methylcholanthrene (MC) is removed from the discs and broken down rapidly (half life about 7 days) to a water-soluble product, which diffuses locally, is distributed widely via the blood stream, and is excreted in faeces and urine. Removal of label is halted by whole-body irradiation (550 R) with the disc area shielded; this observation, in conjunction with the histological and autoradiographic findings and the paucity of label in cells stripped from excised discs, points to the conclusion that the removal of MC from impregnated discs, and its subsequent degradation, depend on the presence of macrophages and the continual replacement of spent macrophages by new cells generated centrally. The rate of disappearance of label from implanted [3H]MC discs was not altered by administration of Corynebacterium parvum; this, however, does not exclude the possibility that the metabolic pathways involved in the removal of MC are altered. To investigate this it is proposed to study, in both normal mice and mice treated with C. parvum, the extent to which cytochrome P450 and other enzymes concerned in the activation and detoxification of polycyclic hydrocarbons by liver microsomal fractions are inducible in the macrophages that accumulate in inflammatory exudates. This histological techniques used should be readily applicable to the study of the early stages of chemical carcinogenesis and the host reaction to transformed cells.

Animals↗

Problem-solving in science.

Problem-solving is a characteristic activity of scientists, Theoretical problems are formulated as a consequence of scientists' thirst for knowledge, and their solutions take the form of general propositions, termed hypotheses, which are consistent with, and provide provisionally satisfactory explanations of, empirical observations. Practical problems appear as the result of feedback from the extra-scientific world of everyday life, industry and professional practice. Their solutions provide an improved basis for decision-making in terms of existing options or increase the number of options from which a choice may be made. The categories theoretical and practical are not mutually exclusive: practical problems often generate interesting theoretical problems, and the solution of a theoretical problem may entrain the solution of a host of practical problems. All hypotheses are provisional because it is impossible to establish the truth of a generalization by rigorous deduction from any number of particular instances, though a single instance may suffice to refute it. This asymmetry forms the basis of Popper's analysis of scientific methodology. This analysis, though acceptable in the main, is open to criticism in the following respects; (1) it ignores the contribution to scientific progress made by unplanned perceptions; (2) it ignores the contribution of hypotheses which do not generate testable predictions; (3) it does not do justice to the extra-logical component in knowing (Polanyi's tacit dimension); and (4) its treatment of practical problems in inadequate.

Decision Making↗