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Biomedical subjects

D Q Miller

Publications and source records attributed to D Q Miller.

3 recordsLinked to original sources

Doxycycline revisited.

Although several new antibiotics have recently become available, in several clinical instances conventional antibiotics may be equally efficacious at a considerably lower cost. In today's era of cost containment, it is particularly relevant to revisit older, inexpensive antibiotics to reexplore their role in the face of the emergence of resistant microorganisms and competition from newer agents. Doxycycline is one such antibiotic. It is an inexpensive, broad-spectrum antimicrobial agent that remains the drug of first choice for several infections. In addition, it can be used for a variety of other indications. Adverse effects are infrequent and relatively minor. While interactions occur with several medications, none of these interactions has significant adverse consequences.

Animals↗

Insulin-like growth factors (IGFs) as autocrine/paracrine regulators of granulosa cell differentiation and growth: studies with a neutralizing monoclonal antibody to IGF-I.

Evidence that granulosa cells secrete and respond to insulin-like growth factors (IGFs) suggests, but does not prove, the importance of IGFs as intraovarian regulators. To further assess the role of these peptides in ovarian function, a neutralizing monoclonal antibody to IGF-I was employed to block the actions of IGFs in porcine follicular fluid and in granulosa cell-conditioned medium. In one series of experiments, granulosa cells from immature porcine follicles were cultured in medium containing porcine follicular fluid that had been charcoal-treated to remove steroids. As noted before, fluid from large follicles (LFF) stimulated progesterone production in a dose-dependent manner. The stimulatory effect of LFF (30% v/v) could be inhibited by greater than 50% by the anti-IGF monoclonal antibody. This inhibitory action was specific for the anti-IGF antibody and could be overcome by the addition of excess exogenous IGFs. In another series of experiments, granulosa cells were made dependent on endogenously produced IGFs by culturing them in a serum-free medium without exogenous growth factors. The effects of follicle-stimulating hormone (FSH), estradiol (E2), growth hormone (GH), and combinations thereof on progesterone production were inhibited by approximately 50% by the anti-IGF antibody. The effects of IGFs on indices of cell growth (judged by the criterion of being inhibited by the anti-IGF antibody) were less dramatic. A modest 18% increase in cell number was observed with FSH and E2 treatment in serum-free medium; this effect was virtually abolished by the antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Carbamazepine protein binding and disposition in pregnancy.

The pregnancies of five women with epilepsy treated with carbamazepine monotherapy were studied prospectively. Free and total serum concentrations of carbamazepine and its epoxide and dihydrodiol metabolites were analyzed at monthly intervals from the first trimester through 8 weeks postpartum. Assays were by high performance liquid chromatography, and free compounds were separated by ultrafiltration. The mean intrinsic clearance of carbamazepine (clearance of free drug corrected for changes in maternal body weight) did not change appreciably during pregnancy and the postpartum period. The mean free fractions of carbamazepine and the epoxide were elevated during pregnancy (0.25 and 0.50) compared with postpartum (0.22 and 0.43). Mean total maternal carbamazepine and epoxide concentrations were 40 and 48% higher than neonatal levels at birth, but maternal and neonatal free concentrations agreed closely. The ratio of epoxide to parent drug increased during pregnancy, as reported by other authors. Evidence is presented that this may be a result of inhibition of further biotransformation of the epoxide rather than of increased production. Two patients missed at least one dose of carbamazepine during labor, resulting in markedly reduced serum concentrations at delivery.

Adult↗