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Biomedical subjects

J Colbert

Publications and source records attributed to J Colbert.

12 recordsLinked to original sources
PubMed2000

College men's health in practice: a multidisciplinary approach.

After a needs assessment indicated that male students underutilized campus health services, the San Francisco State University Student Health Service developed a coordinated complement of outpatient health services for men. The authors review their experience in developing, implementing, operating, and evaluating this ongoing clinical service. The needs assessment and subsequent program evaluation data suggest that male students on a large, culturally diverse, urban campus would respond favorably to targeted, multidisciplinary health initiatives that incorporate the principles of health promotion and disease prevention.

Adult↗
PubMed1996

Theophylline metabolism in human liver microsomes: inhibition studies.

In this paper we describe the kinetics of formation of 1-methylxanthine (1-MX), 3-methylxanthine (3-MX) and 1,3-dimethyluric acid (1,3-DMU) from theophylline in human liver microsomal incubations and use the selective inhibitor approach to define the role of the individual cytochrome P450s (CYP) in each pathway. A biphasic model fitted the data best for the formation of each metabolite. The high-affinity site Km and Vmax values were: 1-MX, Km = 0.29 +/- 0.21 mM, Vmax = 5.92 +/- 3.74 pmol.mg(-1).min(-1) (mean +/- S.D.; n = 4); 3-MX, Km = 0.28 +/- 0.08 mM, Vmax = 3.32 +/- 2.19 pmol.mg(-1).min(-1); 1,3-DMU,Km = 0.31 +/- 0.14 mM, Vmax = 43.3 +/- 9.3 pmol.mg(-1).min(-1). The relative contribution of the high- and the low-affinity enzymes in 1,3-DMU formation was calculated based on the enzyme kinetic parameters. To characterize the high-affinity site, a range of CYP isozyme substrates and inhibitors were incubated with 100 microM theophylline. The CYP1A2 inhibitors furafylline, ellipticine and alpha-naphthoflavone were potent inhibitors of both 1-MX and 3-MX formation with more that 80% of N-demethylase activities inhibited below a concentration of 5 microM. These compounds also markedly inhibited 1,3-DMU formation. Enzyme kinetic and selective inhibition data indicated that about 80% of 1,3-DMU formation was catalyzed by the high-affinity isoform (CYP1A2) at a theophylline concentration of 100 microM. To investigate the role of other isoforms in 8-hydroxylation, experiments were performed involving incubation with a combination of inhibitors. It is evident that in addition to CYP1A2, CYP2E1 has a minor role om 8-hydroxylation. This based on the fact that 80% inhibition was seen on preincubation with furafylline and about 90% inhibition on preincubation with furafylline plus diethyldithiocarbamate. Low concentrations of ketoconazole (selective for CYP3A4) only produced marginal inhibition of 1,3-DMU and, therefore, CYP3A4 is only of minor significance in this reaction. Human B-lymphoblastoid cell lines expressing CYP1A2 catalyzed theophylline metabolism with formation of 1-MX, 3-MX and 1,3-MDU. CYP2E1 cells also catalyzed formation of 1,3-DMU. The CYP3A4 cell line did not catalyze theophylline metabolism.

Cells, Cultured↗
PubMed1994

Vancomycin-induced neutropenia during treatment of endocarditis in a pediatric patient.

OBJECTIVE: To report a case of reversible vancomycin-associated neutropenia occurring during long-term therapy with vancomycin using weight and age-adjusted dosing. CASE SUMMARY: A 2-year-old boy was started on vancomycin therapy for presumed endocarditis resulting from his ventriculoseptal defect. After 18 days of treatment, neutropenia with an absolute neutrophil count (ANC) of 990 x 10(6) cells/L was noted. The neutropenia progressed over the next 3 days and reached a nadir concentration of 459 x 10(6) cells/L. Vancomycin therapy was discontinued after 17 days (antibiotic day 20). A rise in the ANC occurred within 2 days of discontinuation. An improved ANC of 1672 x 10(6) cells/L occurred within 5 days. Vancomycin serum concentrations remained within an acceptable range: a peak of 30 micrograms/mL and a trough of 9 micrograms/mL. DISCUSSION: Case reports in the literature of vancomycin-associated neutropenia in adults were briefly reviewed and compared. The onset and resolution and mechanism of vancomycin-induced neutropenia were studied. The potential relationship between vancomycin, weight-, and age-adjusted dosing and the occurrence of neutropenia in our pediatric patient was postulated. CONCLUSIONS: Vancomycin is identified as a possible cause of drug-induced neutropenia. More data are needed that clearly indicate vancomycin as the offending agent in children. The vancomycin-induced neutropenia is believed to be immunologically based and independent of drug concentrations.

Child, Preschool↗
PubMed1992

Extrahepatic metabolism of zidovudine.

The metabolism of zidovudine (3'-azido-3'-deoxythymidine; AZT) has been studied in human renal, gut and hepatic microsomes. Metabolism of AZT to the ether glucuronide (3'azido-3'-deoxy-5'-beta-D-glucopyranosyl thymidine; GAZT) occurred in the kidney with Km and Vmax values of 1.50 +/- 0.49 mM and 14.5 +/- 2.6 nmol h-1 mg-1 respectively (mean +/- s.d.; n = 3 batches of microsomes from a single kidney). Comparative values obtained in liver were 2.19 +/- 0.6 mM and 43.0 +/- 9.5 nmol h-1 mg-1, respectively. Morphine caused inhibition of AZT conjugation in kidney microsomes. Metabolism of AZT by the kidney could contribute significantly to the overall elimination of AZT. In contrast to the kidney findings, AZT was not metabolised to GAZT by either non-activated (Brij-58) or activated gut microsomes.

Adolescent↗
PubMed1988

A comparative study of the formation of chemically reactive drug metabolites by human liver microsomes.

1. The metabolism of amodiaquine (A), ethinyloestradiol (E), mianserin (M), phenytoin (Ph), sulphanilamide (S) and paracetamol (Pa) to both stable and chemically reactive, i.e. irreversibly protein bound, metabolites was investigated using microsomes prepared from histologically normal human liver obtained from eight kidney donors. 2. All drugs, except amodiaquine, were metabolized by NADPH-dependent microsomal enzymes to chemically reactive metabolites. The degree of NADPH-dependent binding varied between drugs (E, 11.5 +/- 5.8% incubated drug; M, 3.0 +/- 1.9%; Ph, 0.10 +/- 0.09%; S, 0.57 +/- 0.38%; Pa, 1.2 +/- 1.2%; mean of eight livers +/- s.d.). 3. Inclusion of glutathione (1 mM) or ascorbic acid (1 mM) in the incubation reduced the NADPH-dependent binding for all substrates, indicating the involvement of electrophilic oxidation products. 4. Binding of M and Pa correlated with each other (Spearman's r = 0.86) and with total cytochrome P-450 content (r = 0.76 and 0.78 respectively). E binding also correlated with the binding of M (r = 0.79) and Pa (r = 0.81) but not with cytochrome P-450. Binding of Ph and S did not correlate with any of the other measured metabolic parameters.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines.

1. A number of compounds have been examined for their ability to inhibit tolbutamide hydroxylase activity in human liver microsomes (control value at a substrate concentration of 150 microM being 0.27 +/- 0.12 nmol min-1 mg-1 protein; mean +/- s.d.; n = 7). 2. IC50 (concentration of inhibitor producing 50% inhibition) values were determined for a range of sulphonamides, imidazoles and aminoquinoline compounds. The most potent inhibition was evident with the 1-substituted imidazole antimycotic drugs ketoconazole, clotrimazole and miconazole and the sulphonamide sulphaphenazole (IC50 values of 16.5, 2.5, 0.85 and 0.5 microM respectively). A number of compounds showed little or no inhibition of tolbutamide hydroxylase as judged by an IC50 of greater than or equal to 500 microM. 3. The Km value for tolbutamide hydroxylase was 125 microM and Vmax, 0.44 nmol min-1 mg-1 protein. All the substituted imidazoles examined in kinetic studies 1v vs 1s, Line-weaver-Burk plots) produced either non-competitive or mixed inhibition. The sulphonamides exhibited competitive inhibition, the Ki for sulphaphenazole being 0.22 microM. Primaquine showed mixed inhibition. Dixon plots confirmed the type of inhibition produced. 4. Although the competitive inhibition between some sulphonamides and tolbutamide is consistent with metabolism by the same isozyme of cytochrome P-450 it does not prove it and further studies with purified enzymes will be necessary to confirm this.

Adolescent↗