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Biomedical subjects

J K Cooper

Publications and source records attributed to J K Cooper.

At least 55 records · Page 3Linked to original sources
PubMed1988

Enantioselective gas chromatographic assay with electron-capture detection for dl-fenfluramine and dl-norfenfluramine in plasma.

An enantioselective gas chromatographic assay utilising electron-capture detection has been developed for the simultaneous quantitation of enantiomers of fenfluramine and nonfenfluramine in plasma. The assay involves the conversion of the enantiomers of both fenfluramine and norfenfluramine into their corresponding diastereomeric amide derivatives by an acylation reaction with n-heptafluorobutyryl-S-prolyl chloride under Schotten-Baumann conditions prior to gas chromatographic separation on an achiral polar OV-225 capillary column. Linear and reproducible standard curves were obtained over the concentration ranges 4.30-86.3 ng/ml per enantiomer and 1.25-42.25 ng/ml per enantiomer for the enantiomers of fenfluramine and norfenfluramine, respectively. The method was applied to a single-dose pharmacokinetic study in a healthy adult subject. Stereoselective differences were observed in the plasma concentration versus time profiles of the enantiomers of both fenfluramine and norfenfluramine. The area under the plasma concentration versus time curve values obtained for the l-isomers of fenfluramine or norfenfluramine were higher than the values of their corresponding d-antipodes.

Chromatography, Gas↗
PubMed1988

An ultrasensitive method for the measurement of haloperidol and reduced haloperidol in plasma by high-performance liquid chromatography with coulometric detection.

A new analytical method has been developed for the simultaneous quantitation of haloperidol and reduced haloperidol in plasma. The method is based on high performance liquid chromatography (HPLC) with coulometric detection. The extraction and sample clean up procedures are simple and rapid to execute, yet yield chromatograms virtually free of interference from endogenous plasma constituents, such that the extraordinary sensitivity of the coulometric detector can be exploited fully. The detection limits for haloperidol and reduced haloperidol are 20 pg/ml plasma, and the limits of quantitation are 50 pg/ml for both drug and metabolite. Standard curves were linear down to 50 pg/ml with coefficients of variation of less than 7.0% at the limits of quantitation. The method was applied to the study of the plasma levels of haloperidol and reduced haloperidol in two healthy subjects. It was possible to monitor the plasma levels of haloperidol for at least 96 h (4 days) after the administration of a 5-mg oral dose of haloperidol. It was also possible to monitor reduced haloperidol levels over 96 h in one subject, although the metabolite was not detectable in the plasma of the other at any stage.

Chromatography, High Pressure Liquid↗
PubMed1987

Nutrition and immune function in the geriatric population.

Aging in experimental animals and in man is associated with a significant defect of helper/inducer T-lymphocytes. This quantity deficiency is paralleled by a qualitative deficiency of T-lymphocyte number and function. Similar defects have been observed in protein calorie malnutrition and zinc deficiency, and there is evidence that both may exist in the aged ill and perhaps even in aged healthy individuals. Nutritional support improves the immune defect in aged ill patients and it may be of value in improving this deficiency, even when administered to aged healthy subjects.

Age Factors↗
PubMed1987

Therapeutic monitoring of chlorpromazine. IV: Comparison of a new high-performance liquid chromatographic method with radioimmunoassays for parent drug and some of its major metabolites.

A new high-performance liquid chromatographic (HPLC) procedure for the simultaneous determination of chlorpromazine and its six metabolites, namely, 7-hydroxy-chlorpromazine, N-monodesmethyl-chlorpromazine, 7-hydroxy-N-monodesmethyl-chlorpromazine, chlorpromazine-sulfoxide, chlorpromazine N-oxide, and N-monodesmethyl-chlorpromazine-sulfoxide, in plasma was developed and compared with four radioimmunoassay (RIA) procedures that measured separately chlorpromazine, 7-hydroxy-chlorpromazine, chlorpromazine-sulfoxide, and chlorpromazine N-oxide. The results of this study for the determination of plasma levels in four healthy volunteers given a 100-mg single oral dose of chlorpromazine hydrochloride demonstrated that in some cases, strong correlations could be found between the plasma levels determined by the HPLC and RIA procedures, whereas in other cases, there was a lack of strong correlation. The discrepancies observed were not only due to nonspecificity of the immunoassay procedures employed, but also to a lack of rigorous specificity of the HPLC procedure in plasma samples from dosed humans. These findings clearly indicate that even a chemical method of analysis, such as HPLC, has its limitations in its application to multianalyte analysis, as is the case with drugs like chlorpromazine.

Chlorpromazine↗
PubMed1986

Decision analysis for tuberculosis preventive treatment in nursing homes.

There are differing opinions on whether or not to use isoniazid (INH) preventive treatment in older people with significantly reactive ("positive") tuberculin skin tests and fibrotic changes on chest roentgenogram. To assist the clinician facing this decision, a Decision Analysis was completed. Using available data, it is seen that using INH will not have much impact on five-year survivorship, but will reduce the number of tuberculosis disease cases, thus having an overall beneficial impact. Where tuberculosis incidence is higher, the benefit of INH preventive treatment is correspondingly higher.

Aged↗
PubMed1986

The influence of rural physicians' perception on referral patterns to a university hospital.

The patient referral process is based on a complex set of social rewards and costs for the referring physician. For the physician or institution potentially receiving referrals, a key question is, why is one institution selected over other available choices? Factor analysis of a survey of rural physicians revealed five factors of reward and cost associated with the choice of where to refer patients. Further analysis of these factors suggested that the ability to have patients admitted and treated when necessary is central to the satisfaction of the referring physician and their willingness to continue the consultant relationship. Adequate information about the consultants was also important to satisfaction. Other factors have less influence. Further, "admissions when necessary" was the only reward/cost factor which predicted physicians who referred more to the university hospital than to other hospitals. If a university hospital wants to develop strategies to encourage referrals from rural physicians, it must be cognizant of these social reward-cost factors.

Data Collection↗
PubMed1986

Evaluation of medical center support for rural physicians.

Professional isolation remains a problem for rural physicians. To address the problem, a university medical center established a Physician Support Office (PSO). The PSO offered rural physicians toll-free telephone access to patient referral, patient follow-up, library reference, and drug information services. A newsletter was also published. The service was evaluated using a quasi-experimental design. Physicians in the experimental area felt there was improvement in several medical center services, compared to physicians in the control area. Provision of library services, referral services and a newsletter contributed significantly to the usefulness of the PSO program. Nevertheless, the PSO did not produce a significant improvement in rural physicians' overall feeling of general medical center support.

Appalachian Region↗
PubMed1985

Therapeutic monitoring of chlorpromazine I: Pitfalls in plasma analysis.

Pooled plasma from healthy volunteers was spiked with pure, synthetic chlorpromazine (CPZ), chlorpromazine sulfoxide (CPZSO), or chlorpromazine N-oxide (CPZNO), and then made alkaline with either sodium hydroxide or sodium carbonate. The samples were allowed to stand at room temperature for various timed intervals before extraction with organic solvent. It was found that CPZNO was reduced to CPZ in plasma made alkaline with sodium hydroxide, but not in protein-free buffer solution at high pH nor in plasma made alkaline with sodium carbonate. The reaction appears to take place through reducing equivalents generated by the action of sodium hydroxide on plasma proteins. Thus, apparent concentrations of CPZ in plasma from patients were elevated by as much as 343% when sodium hydroxide was used compared with concentrations in aliquots of the same plasma samples alkalinized with sodium carbonate. The amount of CPZ produced from CPZNO depends on the type of extraction procedure employed as well as on the quantity of sodium hydroxide added to the plasma. By contrast, no interconversion between CPZ and CPZSO or CPZNO and CPZSO was observed in plasma alkalinized and extracted under any of the conditions tested.

Chlorpromazine↗
PubMed1985

Therapeutic monitoring of chlorpromazine II: Pitfalls in whole blood analysis.

Pooled whole blood from healthy volunteers was spiked with pure, synthetic chlorpromazine, chlorpromazine sulfoxide, or chlorpromazine N-oxide and then made alkaline with either sodium hydroxide or sodium carbonate. The addition of alkali causes lysis of red cells, the contents of which spill into the plasma. The lysed samples were allowed to stand at room temperature for various timed intervals before extraction with organic solvents and analysis by high performance liquid chromatography. It was found that a portion (10-14%) of the chlorpromazine spike was oxidised to chlorpromazine sulfoxide, whether the blood was made alkaline with sodium hydroxide or sodium carbonate. Chlorpromazine N-oxide added to whole blood was entirely destroyed in the presence of alkali. The chlorpromazine N-oxide was rapidly reduced to chlorpromazine, a portion of which subsequently underwent oxidation to chlorpromazine sulfoxide. We have found that chlorpromazine N-oxide resides almost entirely in the plasma with only a small portion (less than 4%) distributed into the red cells. Hence, it is essential that red cells and plasma be separated before analysis. Chlorpromazine and chlorpromazine N-oxide can then be extracted from plasma by a method that does not lead to reduction of chlorpromazine N-oxide. Alkaline extraction methods must be avoided in the analysis of chlorpromazine in the red cell fraction.

Chlorpromazine↗
PubMed1984

Radioimmunoassay for psychotropic drugs. III: Synthesis and properties of haptens for trifluoperazine and fluphenazine.

For the development of radioimmunoassay procedures for trifluoperazine and fluphenazine, three haptens, N-(2-carboxyethyl)desmethyltrifluoperazine, N-(4-carboxybutyl)desmethyltrifluoperazine, and 10-[3-(4-carboxyethylpiperazinyl)-3-oxopropyl]-2-trifluoromethyl-+ ++10H- phenothiazine, were synthesized and characterized. Each hapten was coupled to bovine serum albumin, and the number of hapten residues per mole of bovine serum albumin was calculated by UV spectrophotometric methods. Antibodies to each hapten-protein conjugate were developed in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the tritiated drug.

Animals↗
PubMed1984

Relative bioavailability of a commercial trifluoperazine tablet formulation using a radioimmunoassay technique.

The relative bioavailability of a new conventional tablet formulation (5 mg) of trifluoperazine dihydrochloride was studied in 24 healthy volunteers. Using a sensitive radioimmunoassay technique, plasma trifluoperazine concentrations were measured up until 24 h following ingestion of single 5-mg doses of trifluoperazine. The mean +/- SD for the peak concentration (Cmax), time to Cmax, area under the curve from 0 to 24 h (AUC240), and terminal elimination half-life following the administration of the test formulation were 2.15 +/- 1.07 ng/mL, 4.10 +/- 1.38 h, 21.04 +/- 11.92 ng X h/mL, and 9.5 +/- 7 h, respectively. Following the ingestion of the original trifluoperazine tablet formulation (5 mg) these same parameters were estimated to be 1.92 +/- 0.88 ng/mL, 4.02 +/- 1.10 h, 18.03 +/- 10.11 ng X h/mL, and 9.3 +/- 7 h, respectively. Large intersubject variations in Cmax and AUC240 were observed. The relative bioavailability of the test formulation was calculated to be 106.5 +/- 25.5%.

Adult↗
PubMed1984

Subnanogram quantitation of chlorpheniramine in plasma by a new radioimmunoassay and comparison with a liquid chromatographic method.

A new radioimmunoassay (RIA) procedure for the quantitation of chlorpheniramine in plasma is described. The assay allows the determination of chlorpheniramine levels up to 96 h after oral administration of a single 4-mg tablet to healthy volunteers. This procedure was sensitive to a 156-pg/mL plasma concentration when a 100-microL plasma sample was used. The mean coefficient of variation over the linear range of the assay from 0.156 to 20 ng/mL was 3.79%. The specificity of the assay was investigated, and the antisera showed 7% cross-reactivity with the N,N-didemethyl analogue and 17% cross-reactivity with the N-demethyl analogue. This high degree of specificity was also evident from the findings that the plasma concentrations determined by this newly described RIA procedure in samples of two healthy male volunteers who were administered 4 mg of chlorpheniramine maleate orally gave a strong correlation (r2 = 0.88) with values obtained by an HPLC-UV procedure. The antiserum cross-reacted 100% with brompheniramine and, thus, can be used for its analysis in plasma. The described RIA procedure is precise, simple, and capable of handling a large number of plasma samples with a minimal turnaround time.

Blood Specimen Collection↗
PubMed1984

The effect of sample storage on the stability of chlorpromazine in plasma and whole blood.

The stability of chlorpromazine in heparinized whole blood and plasma was investigated at three different concentrations (5, 20, and 50 ng/ml) after storage at -20 degrees C for 0, 7, 14, 28, 56, and 84 days. A statistical analysis was done to determine whether there was any significant difference between the concentration of chlorpromazine in these body fluids as determined on day one versus each of the later dates of analysis. The results indicate that no significant difference was found over the course of these investigations.

Chlorpromazine↗