PubMed Health⌕ Search

Biomedical subjects

R Mueller

Publications and source records attributed to R Mueller.

117 records · Page 7Linked to original sources
PubMedDate not supplied

Ketoconazole-induced hepatic phospholipidosis in the mouse and its association with de-N-acetyl ketoconazole.

Ketoconazole (KC), an orally effective systemic antifungal agent, has been associated with symptomatic hepatotoxicity with an incidence as low as 1 in 2000. Studies from this laboratory have shown that in the mouse ketoconazole elicit a biphasic effect on drug metabolism and induced phospholipidosis. The pathogenesis of the latter, however, has never been established. Studies in mice demonstrated that ketoconazole administration induced phospholipid accumulation in the liver in a dose and time dependent fashion; and de-N-acetyl ketoconazole (DAKC), a major hepatic metabolite of KC was associated with this biochemical change. A comparative biochemical study following equimolar (0.47 nmol/kg p.o. x 7 days) administration of these two compounds indicated that hepatic phospholipids were elevated to a greater extent by DAKC treatment than by KC. Hepatic profiles of KC, DAKC, and other metabolites at 2, 7.5 and 24 h following single and multiple dosing regimens with either KC or DAKC indicated that KC was readily metabolized to DAKC whereas, DAKC appeared to be recalcitrant to metabolism and accumulated in the liver. In contrast to the biphasic effects of KC on hepatic enzyme activity observed previously following the administration of KC (enzyme inhibition as well as induction), the biological effects of DAKC were consistent with only an enzyme inhibitory effect: liver microsomal protein was not elevated; cytochrome P-450 was depressed; and ethylmorphine N-demethylase and benzphetamine N-demethylase were inhibited. Consequently the induction of phospholipidosis and the inhibition of drug metabolism associated with ketoconazole treatment were attributed to DAKC, whereas the inductive properties of KC were ascribed to the unchanged drug. The dramatic difference in the biological effects of these two compounds was attributed to differences in the orientation of these agents in lipid membranes. These results offer an explanation for the previously observed apparent inhibitory effects of KC on enzyme activities (Whitehouse et al. (1990b) Hepatic effects of ketoconazole in the male Swiss Webster mouse: temporal changes in drug metabolic parameters. Can. J. Physiol. Pharmacol., 68, 1136-1142) and suggest that DAKC may be the chemical entity responsible for the induction of phospholipidosis following ketoconazole administration.

Administration, Oral↗
PubMedDate not supplied

Evaluation of a self-teaching program.

A self-teaching booklet on hypertension was evaluated in two populations: clients attending public health screening clinics and inpatients at a Veterans Administration hospital. Participants were randomized into an education or a control group. Evaluation consisted of measuring knowledge gained from the booklet immediately after reading it and retention of key concepts two weeks later. Men did better than women, and VA education participants did better than VA controls. No differences were detected between the public health education and control groups or the combined VA and public health) education and control groups. The self-teaching booklet alone did not appear to yield a measurable amount of new knowledge. Health professionals, when educating patients and evaluating programs, should consider combinations of educational methods when using self-teaching programs.

Adult↗
PubMedDate not supplied

DFNB20: a novel locus for autosomal recessive, non-syndromal sensorineural hearing loss maps to chromosome 11q25-qter.

Autosomal recessive non-syndromal deafness is an extremely heterogeneous condition with at least 19 loci (DFNB1-19) already described. We have used autozygosity mapping to localise a further novel locus, DFNB20, to chromosome 11q25-qter in a consanguineous family originating from Pakistan. A region of homozygosity was observed in affected individuals spanning the interval D11S969-qter.

Chromosome Mapping↗
PubMedDate not supplied

Unenhanced helical CT using increased pitch for suspected renal colic: an effective technique for radiation dose reduction?

PURPOSE: To determine the accuracy and utility of unenhanced helical CT for suspected renal colic, using a pitch of either 2.5 or 3.0. METHODS: 59 consecutive patients underwent unenhanced helical CT. 5 mm contiguous images were obtained at a kVP of 120 and an mA of 260. Thirty-four patients were imaged at a pitch of 2.5, and 25 patients were imaged at a pitch of 3.0. Two radiologists, an attending (reader 1), and a second-year resident (reader 2), independently and retrospectively reviewed the CT images, blinded to the clinical outcome. The presence or absence of a ureteral stone was recorded and image quality was graded. A third radiologist determined accuracy for each reader. Average entrance exposure was estimated using a CT phantom at a variety of pitches. RESULTS: Overall sensitivity, specificity, and accuracy for reader 1 were 91, 96, and 93%. For reader 2, they were 86, 93, and 90%. There was no significant difference in accuracy using a pitch of 3.0 compared with 2.5 for either reader. Readers 1 and 2 rated image quality at 2.5 pitch as excellent for 88 and 76% of scans, respectively; at 3.0 pitch the scans were rated by both readers as excellent for 40% and acceptable for 60%. Average entrance exposures were estimated at 461, 553. and 913 mR at pitches of 3.0, 2.5, and 1.5. CONCLUSION: Increasing the pitch on unenhanced helical CT for suspected renal colic to 2.5 or 3.0 appears to be an effective method of reducing radiation dose. Although accuracy of the technique did not significantly change using a pitch of 3.0 in one group of patients, compared with a pitch of 2.5 in another group of patients, image quality did decrease.

Adult↗