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Biomedical subjects

R L Stiller

Publications and source records attributed to R L Stiller.

At least 73 records · Page 4Linked to original sources
PubMed1985

Cardiovascular and pharmacodynamic effects of high-dose fentanyl in newborn piglets.

To understand better the hemodynamic effects of fentanyl anesthesia on the developing newborn, the authors studied the changes in cardiac output and its four determinants (preload, afterload, heart rate, and contractility) and plasma fentanyl kinetics in newborn piglets following the administration of high-dose fentanyl with or without atropine premedication. Twenty-five healthy farm piglets were divided into four groups. Hemodynamic studies were conducted on five who received 50 micrograms/kg intravenous fentanyl, five controls who received only 0.01-0.03 mg/kg intravenous atropine, and nine who received both agents. Fentanyl pharmacokinetics were determined by radioimmunoassay in six additional piglets. Mean plasma fentanyl concentrations were 25.4, 12.7, and 7.9 ng/ml at 5, 15, and 30 min postbolus, respectively, with an elimination phase half-life of 35.8 min. In piglets given fentanyl alone, the maximum significant (P less than 0.05) hemodynamic changes from baseline occurred at 5 min: mean aortic pressure (MAP) +42%, cardiac output -42%, heart rate -36%, left ventricular end-diastolic pressure +81%, and total peripheral resistance index +93%. The latter four hemodynamic variables were highly correlated with the logarithm of the plasma fentanyl concentration (R2 greater than 0.96, P less than or equal to 0.05). In control animals given atropine alone, only MAP changed significantly (+12-14%) during the study. Contractile indices (echocardiographic shortening fraction and left ventricular peak dP/dT) did not change significantly in any group. Piglets given fentanyl-atropine had no significant hemodynamic change during the study other than a 7-15% increase in MAP.

Anesthesia, Intravenous↗
PubMed1983

Experience with ketoconazole in three major manifestations of progressive coccidioidomycosis.

Forty-seven courses of oral ketoconazole therapy administered to 46 patients with progressive coccidioidomycosis were evaluated. Responses, of varying degrees evaluated by a point system, occurred in 81, 94, and 91 percent of courses evaluated for skeletal, chronic pulmonary, and cutaneous disease, respectively. Presumed side effects occurred in 26 percent of courses and were generally minor and reversible. Relapse occurred in 33, 33, and 11 percent of evaluable responding patients with skeletal, chronic pulmonary and cutaneous disease, respectively. From this experience, ketoconazole appears to be an important advance in the therapy of chronic coccidioidomycosis. Whether cure is possible will require further study and follow-up.

Adult↗
PubMed1983

Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model.

The in vitro susceptibility of Candida albicans isolates to flucytosine was compared to therapeutic effect in experimental murine candidiasis (candidosis). Four groups of 10 isolates were chosen, based upon their broth dilution minimal inhibitory concentrations (MICs), from a group of 402 isolates from patients without prior flucytosine therapy. Group I MICs were less than 12.5 micrograms/ml after seven days, whereas group II, III, and IV MICs exceeded 12.5 micrograms/ml on days 7, 2, and 1, respectively. Pilot experiments selected challenge inocula of similar virulence. Mice were infected intravenously and given various flucytosine doses. Significant prolongation of survival correlated with MICs and with agar disk-diffusion zone diameters (P less than 0.05). In vivo response to therapy was more favorable for group I isolates compared with group IV isolates (P less than 0.01). The present study demonstrates in this animal model that in vitro susceptibility does correlate with in vivo response to therapy, although exceptions occur with individual isolates.

Animals↗
PubMed1983

Analysis of Candida albicans phenotypes from different geographical and anatomical sources.

Strain phenotypes of 330 Candida albicans isolates from five areas in the United States were determined on the basis of nine biochemical tests. Statistical analysis of the distribution of phenotypes revealed no significant differences among types from different anatomical sources. However, there were some differences among the phenotypes of strains from the different geographical areas, and there were substantial differences in biochemical phenotypes associated with strains susceptible and resistant to 5-fluorocytosine and between strains of serotypes A and B. Geographical differences in phenotypes of C. albicans were also noted between the 330 U.S. isolates and 247 isolates from Britain. Cluster analysis of the U.S. strains alone and of all of the U.S. and U.K. strains showed that C. albicans phenotypes can be grouped into fewer than 20 clusters with common biochemical properties.

Candida albicans↗
PubMed1983

Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. National Institute of Allergy and Infectious Diseases collaborative antifungal study.

The pharmacology, in vitro mycologic activity, toxicity, and efficacy of ketoconazole were studied in a Phase-II evaluation by the National Institutes of Health and National Institute of Allergy and Infectious Disease Mycoses Study Group. This report emphasizes the toxicity and clinical response data in 52 patients with the following systemic mycoses: blastomycosis in 16 patients; nonmeningeal coccidioidomycosis in 13; histoplasmosis in 8; nonmeningeal cryptococcosis in 7; sporotrichosis in 7; and both blastomycosis and nonmeningeal coccidioidomycosis in 1. Maximum daily doses of ketoconazole were 100 mg in 1 patient; 200 mg in 23; 400 mg in 12; and 600 mg in 16. In 52% of the patients, duration of therapy ranged from less than 1 to 6 months, whereas in 35%, duration ranged from 7 to 12 months, and in 13%, from 12 to 22 months. In 35 patients (67%), evidence of toxicity was not seen. Nausea, anorexia, or vomiting occurred in 21%. Cure or marked improvement was shown in 27 patients (52%), whereas failure of the primary course was seen in 14 (27%) and relapse after ketoconazole was discontinued in 11 (21%). Although this evaluation did not provide clear-cut clinical response data, our results indicate that ketoconazole, in the dosage regimens used, was more effective in patients with histoplasmosis and nonmeningeal cryptococcosis than in patients with blastomycosis and nonmeningeal coccidioidomycosis, and least effective in patients with sporotrichosis.

Adolescent↗
PubMed1982

Gas chromatographic analysis of ketamine and norketamine in plasma and urine: nitrogen-sensitive detection.

A sensitive gas chromatographic method for quantitative analysis of ketamine and norketamine in human and animal biological fluids is described. The nitrogen-sensitive detection procedure used is more stable than electron-capture detection and reduced analysis time. The method used bromo-ketamine as an internal standard for quantitation and is linear from 10-25,000 ng/ml. No interferences were shown with drugs commonly associated with cardiac surgery with cardiopulmonary by-pass. This assay is sensitive, specific, using either native or derivatized drugs and can be used for routine analysis of ketamine and norketamine in plasma or urine.

Adult↗
PubMed1982

Oral ketoconazole for dermatophyte infections.

Nineteen patients with chronic dermatophyte infections were treated with 200 to 400 mg per day of ketoconazole orally. Sixteen had had their disease for 2 years or more. Sixty-three per cent achieved cure, and an additional 26% showed clinical improvement. Clearing of lesions occurred in 10 weeks (mean). The dose was increased to 600 mg per day in four patients. Of these, two achieved cure, for an overall cure rate of 74%. Seventy-five percent of patients who previously failed to respond to griseofulvin were cured or improved by ketoconazole. Four of eight patients with onychomycosis were cured, and the rest improved on therapy. One patient developed a generalized drug eruption after the first dose of ketoconazole, and possible minor side effects were noted in five. Three of eight patients followed off therapy after apparent cure subsequently showed relapse. The drug appears to have great potential value for the therapy of dermatomycoses.

Administration, Oral↗
PubMed1982

Susceptibility to 5-fluorocytosine and prevalence of serotype in 402 Candida albicans isolates from the United States.

Candida albicans isolates from 402 patients with no prior history of treatment with 5-fluorocytosine were collected at five medical centers from different areas of the United States. Isolates could be separated into four groups based on their minimum inhibitory concentrations (MICs) to 5-fluorocytosine. Group I isolates (60%) had MICs less than or equal to 12.5 micrograms/ml after 7 days, whereas groups II (22%), III (14%), and IV (4%) demonstrated MICs greater than 12.5 micrograms/ml on days 7, 2, and 1, respectively. Serotypes A and B accounted for 50.7 and 49.3%, respectively, of the 398 isolates typed. Serotype B was less prevalent in group I (26%), but predominated in the more resistant groups, groups II (85%), III (86%), and IV (53%). The common practice of identifying as "resistant" those isolates with MICs greater than 12.5 micrograms/ml after 48 h of incubation would yield a resistance rate in the United States of 11.5 to 15.5% in four centers and 35% in the fifth. Although serotype B and small agar disk diffusion zone sizes correlated with poor 5-fluorocytosine susceptibility, their ability to predict tube dilution MICs was limited. The true predictive value of such tests awaits correlation with in vivo studies.

Candida albicans↗
PubMed1975

Synthesis of threo-4,5-dihydroxy diastereomers of sphinganine;.

The threo-4,5-dihydroxy diastereomers of sphinganine were prepared by the following sequence of reactions: (a) benzoylation of sphingenine to the tribenzoyl derivative; (b) osmylation followed by resolution of the mixture of threo-4,5-dihydroxy tribenzoyl (DHTBS) diastereomers; and (c) alkaline hydrolysis to yield the threo-4,5-dihydroxysphinganines (DHS). Carbon atoms 4 and 5 of the high and low melting threo-4,5-DHTBS diastereomers and the compounds derived from them were tentatively assigned 4R, 5S and 5R configurations, respectively;

Amino Alcohols↗