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Biomedical subjects

J D Garcia

Publications and source records attributed to J D Garcia.

14 recordsLinked to original sources

Designing blood oxygenators.

Extracorporeal blood oxygenators are used to provide cardiopulmonary support during open heart surgery. In the study reported here, mass transfer correlations were determined for commercially available blood oxygenators. Two configurations used commercially, flow outside and across bundles of hollow fibers and flow in thin channels between parallel flat sheet membranes, were investigated. Water and glycerol/water mixtures were used as a substitute for blood. Diffusion of oxygen into and out of these solutions was studied. For flow across bundles of hollow fibers, the mass transfer correlations derived here are in agreement with analogous correlations for crossflow heat exchangers. However, for flow in thin channels, the rate of mass transfer is often less than predicted from theory. This compromised mass transfer can be explained by considering slight variations in the thickness of the blood flow channels. The mass transfer correlations developed here could be used to design better blood oxygenators.

Blood↗

A review of the cardiac systemic side-effects of antihistamines: ebastine.

The cardiac safety of ebastine, a long-acting, non-sedating antihistamine, has been thoroughly assessed in phase I-III clinical studies. Ebastine alone at the recommended doses of 10 mg and 20 mg has no clinically relevant effect on QTc interval in adults and in special patient populations (elderly, children or subjects with hepatic or renal impairment). Ebastine administered at 60 and 100 mg/day (3-5 times the maximum recommended dose) for 1 week had statistically significantly smaller effects (3.7 and 10.3 msec, respectively) on the QTc interval than terfenadine (18 msec) at three times the recommended dose (360 mg/day). The mean QTc interval prolongation observed with ebastine 100 mg/day was small and not clinically meaningful, although the results were statistically significant vs. placebo. The effect of ebastine 60 mg/day was not statistically different from placebo. Steady-state drug interaction studies demonstrated that the co-administration of ebastine 20 mg with ketoconazole or erythromycin produced significant increases in systemic exposure for ebastine, which were accompanied by small increases in QTc (approximately 10 msec above ketoconazole or erythromycin alone). Results from individual studies suggest that, when coadministered with ketoconazole, ebastine produces similar changes in QTc interval measurements compared to loratadine and cetirizine. Pooled data from clinical efficacy trials of ebastine 1-30 mg/day administered for 2-3 weeks showed no clinically relevant cardiac effects as assessed by serial electrocardiographs and Holter monitoring. The overall cardiac safety profile based on currently available information suggests that ebastine, like loratadine and cetirizine, has a lower potential for causing adverse cardiovascular effects than terfenadine.

Adult↗

Clinical evaluation of triamcinolone acetonide nasal aerosol in children with perennial allergic rhinitis.

Triamcinolone acetonide aerosol (TAA), a topical corticosteroid, now available for intranasal use, has been shown to be highly effective in the treatment of both seasonal and perennial allergic rhinitis (PAR) in adults. To evaluate the efficacy and safety of TAA in children, 210 patients (ages 4 to 12 years) with PAR were randomly assigned to one of three treatment groups (placebo, TAA 82.5 micrograms/day, or TAA 165 micrograms/day). Medication was given tid over 12 weeks in a double-blind fashion. Response to medication was evaluated using symptom scoring, physician evaluation, and, in 44 patients, nasal airflow determinations by anterior rhinomanometry. The higher dose of TAA (165 micrograms/day) significantly improved rhinitis symptoms relative to placebo: the total nasal symptom score and most individual symptom scores (eg, nasal stuffiness, itch, sneezing) were significantly better, duration of rhinitis symptoms (hours per day) was significantly reduced, and nasal airflow in a subset of patients showed significant improvement. The lower dose of TAA (82.5 micrograms/day) was superior to placebo by the same parameters as the higher dose, but this improvement was not as consistently significant as the higher dose. There were no clinically significant adverse events; nasal irritation and epistaxis were rare with a similar incidence among treatment groups. In conclusion, TAA at 165 micrograms/day was effective in controlling the symptoms of PAR and in improving nasal airflow in pediatric patients; the lower dose (82.5 micrograms/day) was marginally effective. Both doses were safe and well-tolerated in the children studied.

Administration, Inhalation↗

Electron-transport cytochrome P-450 system is involved in the microsomal metabolism of the carcinogen chromate.

The kinetics of chromate reduction by liver microsomes isolated from rats pretreated with phenobarbital or 3-methylcholanthrene with NADPH or NADH cofactor have been followed. Induction of cytochrome P-450 and NADPH-cytochrome P-450 reductase activity in microsomes by phenobarbital pretreatment caused a decrease in the apparent chromate-enzyme dissociation constant, Km, and an increase in the apparent second-order rate constant, kcat/Km, but did not affect the kcat of NADPH-mediated microsomal metabolism of chromate. Induction of cytochrome P-448 in microsomes by 3-methylcholanthrene pretreatment did not affect the kinetics of NADPH-mediated reduction of chromate by microsomes. The kinetics of NADH-mediated microsomal chromate reduction were unaffected by the drug treatments. The effects of specific enzyme inhibitors on the kinetics of microsomal chromate reduction have been determined. 2'-AMP and 3-pyridinealdehyde-NAD, inhibitors of NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase, inhibited the rate of microsomal reduction of chromate with NADPH and NADH. Metyrapone and carbon monoxide, specific inhibitors of cytochrome P-450, inhibited the rate of NADPH-mediated microsomal reduction of chromate, whereas high concentrations of dimethyl-sulfoxide (0.5 M) enhanced the rate. These results suggest that the electron-transport cytochrome P-450 system is involved in the reduction of chromate by microsomal systems. The NADPH and NADH cofactors supply reducing equivalents ultimately to cytochrome P-450 which functions as a reductase in chromate metabolism. The lower oxidation state(s) produced upon chromate reduction may represent the ultimate carcinogenic form(s) of chromium. These studies provide evidence for the role of cytochrome P-450 in the activation of inorganic carcinogens.

Animals↗