Biomedical subjects
B Marchant
Publications and source records attributed to B Marchant.
The disposition and metabolism of flurbiprofen in several species including man.
Flurbiprofen was rapidly absorbed in all species studied. 2. Half-lives of elimination measured 0 to 12 h after a single dose were: mouse 3.4 h, rat 2.5 h, dog 10.1 h, baboon 3.1 h and man 3.9 h. A second phase of elimination was seen in the dog. Flurbiprofen accumulated in the circulation of the dog on repeated dosing. 3. After dosing with [14C]flurbiprofen, tissue levels of radioactivity in dog and baboon were similar to that in plasma. In the rat, levels were slightly elevated in liver, kidney, large intestine and thyroid after repeated dosing. 4. The dog excreted equal amounts of radioactivity in urine and faeces. In other species renal excretion was the more important route. 5. Six metabolites have been detected, the most important being: 2-(2-fluoro-4'-hydroxy-4-biphenylyl)propionic acid (metabolite 1), 2-(i-fluoro-3',4'-dihydroxy-4-biphenylyl)propionic acid (metabolite 2) and 2-(2-fluoro-3'-hydroxy-4'-methoxy-4-biphenylyl)propionic acid (metabolite 3). The proportions of the metabolites and the extents of their conjugation varied among the species. 6. Metabolites were detected in the circulation of rat, mouse and baboon but not in dog and man. 7. Flurbiprofen did not affect the hepatic drug-metabolizing enzyme system of rat. 8. Flurbiprofen was extensively bound to serum protein of rat, dog, baboon and man.
The metabolism of dothiepin hydrochloride in vivo and in vitro [proceedings].
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The placental transfer of propylthiouracil, methimazole and carbimazole.
The placental transfer of 35S-labelled methimazole (MMI), carbimazole and propylthiouracil (PTU) has been examined in the rat in late pregnancy and in patients undergoing therapeutic abortion. Although rapid equilibrium of fetal and maternal serum radioactivity (FS:MS ratio 1:1) occurred after iv administration of 35S-carbimazole or 35S-MMI in rats, a persistent fetal to maternal ratio of less than one was observed after 35S-PTU administration. Results from human studies after a single oral dose indicate that, as in the rat, the placenta appeared to be more permeable to 35S-MMI than to 35S-PTU as shown by the marked difference in fetal serum:maternal serum ratios and amounts accumulated in the fetus. Localization of radioactivity in the human fetal thyroid was also observed after administration of 35S-labelled MMI, carbimazole or PTU.
35-S-antithyroid drug concentration and organic binding of iodine in the human thyroid.
35S-methimazole (MMI), 35S-carbimazole or 35S-propylthiouracil (PTU) were given orally to fifty-five patients at various times up to 12 h before surgical thyroidectomy. The amount of 35S radioactivity and labelled drug in thyroid and plasma samples was measured. Intrathyroidal inhibition or organic binding of iodine by MMI, carbimazole and PTU was measured after intravenous administration of 131I, 132I or 125I-iodide. After administration of 35S-carbimazole or 35S-MMI the thyroid to serum (T/S) ratio of 35S radioactivity was greater in thyrotoxic glands than in non-toxic adenoma tissue. 35S-MMI was found in thyroid and plasma samples after administration of 35S-carbimazole. The T/S 35S-MMI was greater than 1 in most but not all patients. 35S radioactivity was also concentrated in the thyroid after administration of 35S-PTU. In thyrotoxic glands there was an 80% inhibition of iodine organification in patients receiving MMI and 60% for those receiving PTU. It is suggested that carbimazole and MMI can be given once or twice daily in some patients but PTU would be less suitable for this dose schedule.
Relation between thyroid iodine content and the accumulation and oxidation of [35-S] Methimazole in the rat.
The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid.
The metabolism of 35S-labelled antithyroid drugs in thyrotoxic, adenomatous, neoplastic and normal human thyroid.
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Accumulation of 35 S-thiouracil by the rat thyroid gland.
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Biliary excretion of 35 S-labelled propylthiouracil, methimazole and carbimazole in untreated and pentobarbitone pretreated rats.
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The thyroid accumulation, oxidation and metabolic fate of 35 S-methimazole in the rat.
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The acclumulation of 35 S-antithyroid drugs by the thyroid gland.
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Localisation of 35S-propylthiouracil in thyroid.
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Concentration of 35S-propylthiouracil by the thyroid gland and its relationship to anion trapping mechanism.
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Thyroxine utilization in lambs in natural and controlled environments.
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TGF-beta3 in the treatment of pressure ulcers: a preliminary report.
OBJECTIVE: To determine the safety, tolerability, and efficacy of TGF-beta3 in the treatment of chronic, nonhealing pressure ulcers. DESIGN: A subset analysis of data from a randomized, blind, parallel, placebo-controlled trial involving 270 patients. SETTING: University of Michigan Wound Care Center. PATIENTS: A total of 14 patients (6 women and 8 men aged > or = 18 years) with pressure ulcers were randomly assigned to 1 of 3 groups to receive once daily topical application of recombinant TGF-beta3 or placebo gel for a period of no more than 16 weeks. Group 1 (n=4) received 1.0 microg/cm2 of TGF-beta3, Group 2 (n=5) received 2.5 microg/cm2 of TGF-beta3, and Group 3 (n=5) received placebo gel. All subjects received standardized wound care as well. Weekly evaluations were performed for efficacy, determined by relative wound surface areas and volumes, and were compared with initial baseline values and safety parameters. MAIN OUTCOME MEASURE: Reduction in pressure ulcer area and volume. MAIN RESULTS: Group 2 had a significantly increased rate of wound healing at the fourth visit (P<.05). No significant difference was observed in the healing rate among the groups at the termination of the study. Treatment with TGF-beta3 was well tolerated and there were no significant adverse reactions. CONCLUSION: The findings of this study indicate that the topical application of TGF-beta3 is safe and useful in the treatment of pressure ulcers and is most effective at the earliest stages of therapy.
Osteomyelitis related to pressure ulcers: the cost of neglect.
Twelve patients with documented chronic osteomyelitis of the pelvis resulting from truncal pressure ulcers were examined retrospectively to identify the cost of treatment for this significant health care problem. The retrospective review of each case spanned an 18-month period--6 months prior to the initial positive bone biopsy to 1 year following bone biopsy. The financial charges associated with treatment of osteomyelitis were identified using the University of Michigan Health System's databases for hospital charges, professional charges, and pharmacy charges. Prior treatment of these patients included surgical debridement of the pressure ulcer, pelvic bone biopsy, and culture-specific antibiotic therapy. The total charges for this group of 12 patients was $715,204, or an average charge of $59,600 per patient. Each patient was hospitalized, with hospitalization charges of $587,212, or an average of $48,934 per patient. Pharmacy charges for culture-specific antibiotics totaled $85,217 for the 12 patients. Six of 8 flap repairs achieved successful surgical closure of the pressure ulcer (75%) postantibiotic therapy. Surgery charges are not included in the totals.
Circadian rhythms and ischaemic heart disease.
Circadian rhythms have an important influence on normal heart function and are frequently disturbed in cardiac disease states. This may influence the manifestation of the disease and the study of such rhythms can throw light on some of the pathophysiological factors involved.