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Biomedical subjects

C E Cook

Publications and source records attributed to C E Cook.

At least 37 records · Page 2Linked to original sources

Application of countercurrent chromatography/thermospray mass spectrometry for the identification of bioactive lignans from plant natural products.

The versatility and resolving power of countercurrent chromatography (CCC) has been demonstrated with a newly developed analytical high-speed planet centrifuge system. Interfacing countercurrent chromatography with mass spectrometry (MS) provides a new analytical methodology that integrates the advantages of countercurrent chromatography with the low detection limit and identification capability of mass spectrometry. In this paper the capability of thermospray CCC/MS is demonstrated in identifying and validating the bioactive and structurally known lignans from a crude extract of Schisandra rubriflora Rhed et Wils, a traditional Chinese herbal medicine for treatment of hepatitis.

Chromatography

Interaction between marihuana and ethanol: effects on psychomotor performance.

This is a report of the results of a placebo-controlled study in which the effects of the interaction between ethanol and marihuana on drug plasma concentrations, subjective ratings of intoxication, heart rate acceleration, and psychomotor performance were investigated. Six healthy, male, paid volunteers, moderate users of ethanol and marihuana, participated in the study. Ethanol (0.42 g/kg, 0.85 g/kg, or placebo) was administered over a 30-min interval. Fifteen minutes later the subjects smoked, in their customary manner, NIDA cigarettes containing 2.4% or 0.0004% (placebo) delta-9-tetrahydrocannabinol (THC). Each subject was tested in a single-blind, latin-square crossover design with the following six conditions: placebo ethanol/placebo marihuana; low dose ethanol/placebo marihuana; high dose ethanol/placebo marihuana; placebo ethanol/marihuana; low dose ethanol/marihuana; and high dose ethanol/marihuana. The variables measured in the study were: (a) subjective rating of ethanol and/or marihuana intoxication; (b) heart rate; (c) accuracy and latency of response in the Simulator Evaluation of Drug Impairment (SEDI) task; (d) blood ethanol concentration by gas chromatography; and (e) plasma concentration of THC by radioimmunoassay. The results indicate that the decrements due to ethanol in performance of skills necessary to drive an automobile were significantly enhanced by marihuana in an additive and perhaps synergistic manner. The administration of ethanol prior to marihuana smoking did not produce significant effects on the subjective rating of "high," heart rate acceleration, or THC plasma concentration.

Adult

Mammogram interpretation by physician assistants.

The objective of this study was to determine whether a health maintenance organization (HMO) desirous of providing low-cost, quality mammography could employ physician assistants (PAs) to interpret mammograms under the supervision of HMO radiologists. After intensive training in mammographic interpretation, four PAs individually interpreted 727 mammograms of 470 normal breasts, 75 breasts with benign breast masses, and 182 breasts with cancer. The interpretations by the PAs were more sensitive and as specific as those made by six HMO radiologists who interpreted the same cases, and as effective as those by radiologists described in the literature. In receiver-operating-characteristic curve analysis, the areas under curves for PAs were larger than those under curves for radiologists. Interpretations by PAs took less time and cost less than did those by radiologists; the dispositions recommended by PAs were similar to those recommended by radiologists. We conclude that properly trained, evaluated, and supervised PAs can interpret mammograms. Legal, practical, and ethical considerations dictate that this can best be accomplished under the direction of radiologists who are well trained in mammography.

Female

Evidence that "vaginal peptidase" is a bacterial gene product.

A peptidase has been described in vaginal samples, termed "vaginal peptidase." This enzyme has been proposed as a tissue specific marker for vaginal debris. We have explored the presence of this enzyme in vaginal swabs from alleged sexual assault victims and volunteer donors as well as bacterial cultures. These studies reveal that "vaginal peptidase" is composed of a family of peptidase isozymes that originate from several bacterial species. The characterization of "vaginal peptidase" as a tissue specific marker for vaginal debris is premature.

Bacteria

Pharmacokinetics of pentobarbital enantiomers as determined by enantioselective radioimmunoassay after administration of racemate to humans and rabbits.

Radioimmunoassays were developed for R- and S-pentobarbital. The optical isomers of pentobarbital were individually alkylated to N-crotonic acid analogs that were coupled to bovine serum albumin. Immunization of rabbits with the conjugates, which were enantiomerically pure at the asymmetric' carbon of the pentobarbital moiety, led to formation of antisera that selectively bound the predicted enantiomer. In displacement studies with enantiomerically pure radioligands, the opposite enantiomer showed 1.0 to 1.4% cross-reaction. Similar selective binding was observed for enantiomers of secobarbital, thiopental and thiamylal. Assays were developed and used to determine enantiomer pharmacokinetics in rabbits and humans given racemic pentobarbital. In rabbits, difference in clearance of the two isomers was minimal, the result of a slightly larger volume of distribution of the R-enantiomer combined with a slightly higher value of the elimination rate constant beta for the S-enantiomer. In humans, the volume of distribution was 12% greater for the R-enantiomer, but the value of beta was 14% higher for this isomer as well. Thus, the median clearance of the S-enantiomer (1.96 liters/h) was 25% less than that of the R-isomer (2.58 liters/h). The S-enantiomer was also more strongly protein bound in plasma (73.5% vs 63.4% for the R-enantiomer), which is consistent with its structural congruence to S-warfarin, S-phenprocoumon and S-glifumide.

Animals

Resident and faculty differences in student evaluations: implications for changes in a clerkship grading system.

Data were collected for 163 students completing a surgical clerkship including scores on patient write-ups, ward performance evaluations, oral examinations, and National Board of Medical Examiners (NBME) Surgery subscores. Oral examination scores and patient write-ups were rated from 74 (failing) to 100 (honors) by faculty members. The ward performance evaluation included ratings on nine components of ward performance from 1 (unsatisfactory) to 4 (superior) and an overall ward score of 74 (failing) to 100 (honors). Similarities and discrepancies in the way that evaluators viewed clerks were found. Weights given to ward component ratings in relationship to the overall ward score were equivalent for faculty members and residents. Residents rated clerks higher than faculty members on five ward components. Faculty ratings were poorly correlated with resident ratings. Faculty members and residents gave different ratings to the same students in contrast to the similarities in which faculty members and residents gave weight to the ward component ratings. Resident ratings were better than faculty ratings in predicting the NBME Surgery subscore. Although these results suggest that residents are better evaluators of a clerk's performance than are faculty members, other studies indicated the opposite. The elimination of participation of either faculty or residents in the grading of students is unwise. Periodic monitoring of evaluation practices is necessary to ensure fairness in grading procedures.

Clinical Clerkship

Paired-ion liquid chromatographic method for the analysis of a phenanthrenemethanol antimalarial in whole blood.

A sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of the candidate antimalarial (+/-)-(1,3-dichloro-6-trifluoromethyl-9-phenanthryl)-3-di-(n-butyl )aminopropanol hydrochloride in whole blood. A reversed-phase, paired-ion (lauryl sulfate) system achieved separation of the antimalarial and internal standard from interfering constituents with a sensitivity limit of 10 ng/mL by UV detection (254 nm). Chromatographic variables (counterion concentration, pH, and column temperature) were examined to determine their effect on assay characteristics (retention, efficiency, and relative response) in clinical analysis. The antimalarial was isolated from 2.0 mL of whole blood using overnight extraction with 30% ethyl acetate in hexane followed by an acid/base partition sequence to remove major interferences. Overall recovery for the antimalarial was 84% with a CV of 5.0%, and the recovery of the internal standard was 81% (CV = 3.6%). The assay was validated by analysis of both intra- and interlaboratory samples. The assay was applied to the analysis of whole blood samples taken from a 30-year-old healthy human male who had received a single 14.1-mg/kg oral dose. The stability of the antimalarial in whole blood for up to 4 months and in sample extracts for up to 34 d at -17 degrees C was also demonstrated.

Animals

Pyrolysis products of heroin.

Heating of heroin hydrochloride or of heroin at 250 degrees C led to extensive degradation. Major components of the pyrolysate were identified as heroin, 6-acetylmorphine, N,6-diacetylnormorphine, and N-acetylnorheroin by comparison of mass spectra and 13C- and 1H-nuclear magnetic resonance (NMR) spectra with those of authentic compounds. There was evidence for degradation of the piperidino moiety and the structure 3,4-diacetoxyphenanthrene was proposed for a minor product.

Chemical Phenomena

Effect of influenza vaccine on warfarin anticoagulation.

Recent studies have indicated that viral infections, influenza vaccination, or drugs that increase interferon synthesis all decrease hepatic drug metabolism. We report a case in which influenza vaccination was temporally related to an increased anticoagulant effect of warfarin. A prospective study evaluating the effect of influenza vaccination on the prothrombin time of eight patients anticoagulated over the long term showed that there was prolongation of prothrombin time of 40%. In a second study, the effect of influenza vaccination on warfarin t1/2 was determined in healthy subjects. No significant effect on warfarin metabolism was observed after vaccination. We conclude that influenza vaccination is associated with increased anticoagulant response in some patients receiving anticoagulants over a long term. This effect appears to be related to some step in the coagulation pathway and not to decreased warfarin metabolism and a subsequent rise in serum concentration.

Adult