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Biomedical subjects

A B Jones

Publications and source records attributed to A B Jones.

At least 73 records · Page 4Linked to original sources

Fetal mouse susceptibility to transplacental lung and liver carcinogenesis by 3-methylcholanthrene: positive correlation with responsiveness to inducers of aromatic hydrocarbon metabolism.

The role of metabolic activation of carcinogens in fetal tissue as a determinant of sensitivity in transplacental carcinogenesis was investigated in a pharmacogenetic experiment utilizing backcrosses of C57BL/6 (AhbAhb, responsive to induction of aromatic hydrocarbon metabolism) and DBA/2 (AhdAhd, non-responsive) mice. Responsive (C57BL/6 X DBA/2)F1 and non-responsive DBA mothers, all carrying both responsive (AhbAhd) and non-responsive (AhdAhd) fetuses, were given i.p. doses of the carcinogen 3-methylcholanthrene (MC) ranging from 5 to 175 mg/kg on gestation day 17. At 10 months of age the metabolic phenotype of each offspring was determined, and correlated with number of lung and liver tumors. Both male and female AhbAhd (responsive) offspring in most dose groups presented a consistent two- to three-fold higher incidence of lung tumors than did non-responsive AhdAhd littermates. The difference held for offspring of both (C57BL/6 X DBA)F1 and DBA mothers and it was of statistical significance for one or both sexes at most dosage levels. Hepatocellular tumors were also significantly more frequent in responsive male AhbAhd progeny of (C57BL/6 X DBA/2)F1 mothers than in non-responsive AhdAhd littermates. Progeny of the DBA mothers exhibited significantly more liver and lung tumors than did those of the (C57BL/6 X DBA/2)F1 mothers receiving the same dose. These results suggest that in this model system both maternal and fetal genotype for responsiveness to induction of aromatic hydrocarbon metabolism are important factors modulating fetal carcinogenic risk.

Animals↗

Development and evaluation of enteric-coated penicillamine tablets.

Commercially available 250-mg penicillamine tablets were converted into enteric-coated tablets. Based on in vitro dissolution and disintegration tests, tablets coated with five layers of a cellulose acetate phthalate formulation by a modified pan coating technique were judged to be superior to other coated tablets. These tablets resisted disintegration in simulated gastric fluid over a 4-h period and disintegrated in an average of 21 min in simulated intestinal fluid. Enteric-coated penicillamine tablets were tested in vivo in nine weanling pigs divided into three groups: a negative control group, a test group dosed with enteric-coated penicillamine tablets, and a positive control group dosed with uncoated tablets. The incidence of GI tract bleeding, as determined by daily occult blood tests of the stools, was significantly less in the animals receiving the enteric-coated tablets when compared with the positive control group. The enteric-coated dosage form appeared to decrease GI tract irritation caused by penicillamine. Plasma concentration-time curves for penicillamine in the pigs were similar in shape to those reported in humans. Atypical double peaks occur in both species. Relative bioavailability of the enteric-coated tablet was found to be 67% when compared with the uncoated tablet. This apparent reduction is probably due to a large intrasubject variation in areas under the plasma concentration-time curves and not to a dosage form effect.

Animals↗

Comparison of high-performance liquid chromatography and radioimmunoassay in the determination of content uniformity of digoxin tablets.

Digoxin 0.25-mg tablets were dissolved and assayed by the standard high-performance liquid chromatography (HPLC) method specified in USP XX and by a radioimmunoassay (RIA) method modified for the assay of tablet solutions. For the RIA method, the filtrate was diluted to a theoretical concentration of 5 ng/ml. Aliquots of this dilution were then assayed for digoxin content using a commercial digoxin 125I RIA kit. Results from both methods were extrapolated to total tablet content and compared with the labeled amount for 20 individual tablets. All tablet assay results were within the USP standards for content uniformity of individual tablets. The individual tablet deviations from labeled amount by the RIA method were smaller when compared with the USP XX-specified HPLC method. Comparison of individual tablet assays show the RIA method to be both as precise and as accurate as the USP XX-specified HPLC method.

Chromatography, High Pressure Liquid↗

Effect of cannabichromene on hepatic microsomal enzyme activity in the mouse.

1. Pretreatment with a Cannabis constituent, cannabichromene (CBC), i.p., had no effect on in vitro hepatic microsomal enzyme activity compared to a known inhibitor of these systems, SKF 525-A. 2. The results indicate that the previously reported CBC potentiation of CNS depressant-induced hypnosis is not mediated by the hepatic microsomal enzyme system.

Aminopyrine N-Demethylase↗

Pharmacokinetic interactions of tolazamide and oxyphenbutazone in dogs.

The described pharmacokinetic analysis involved two separate studies on nine dogs randomly assigned to three groups of three dogs each. In the first study, the effect of varying the dosage of tolazamide was examined. The second study concerned the effect of varying the dosage of oxyphenbutazone on tolazamide. A 3 x 3 Latin square was used to study both effects. Each group received each treatment, with a minimum of 1 week separating each session. THe pharmacokinetics of tolazamide followed a two-compartment open model. The hybrid rate constants, alpha and beta, were not significantly different at the three dosages when measured by a three-way analysis of variance. The only significant difference at the three dosage levels of tolazamide was in the apparent volume of distribution. In the pharmacokinetic interaction associated with intravenous administration of one dose of tolazamide and three doses of oxyphenbutazone, the apparent volume of distribution and the hybrid rate constant alpha did not change significantly while the hybrid rate constant for tolazamide, beta, seemed to decrease with increasing oxyphenbutazone.

Animals↗

Tenure in medical schools in the 1980s.

Tenure in American medical schools is a personnel policy which exists in relation to institutional policies and realities. It is related to the functions of academic institutions and their capacity for carrying out these functions, and it arises from the needs of an open society to sustain critical and innovative roles for its universities, the necessity for universities to support and protect their faculties, the optimization of their capability to react to new opportunities, and the demands of ever shifting social circumstances. The relation between society and its universities and the balance among the various roles of the universities have not been stable in the past and will not be so in the future. Tenure policies will continue to be modified. The leadership of institutions needs to be aware of the fact that the modifications will occur and of what might be termed the plasticity of tenure.

Faculty, Medical↗

Determination of cannabidiol in plasma by electron-capture gas chromatography.

A procedure was developed for the analysis of cannabidiol (CBD) in blood plasma. Tetrahydrocannabidiol was used as an internal standard and was added prior to extraction. The plasma extracts were derivatized with pentafluorobenzyl bromide and the produce purified on a mini-column of Florisil. The pentafluorobenzyl derivatives were then analyzed by gas chromatography on a 5% OV-225 column using an electron-capture detector. A detection limit of 50 ng CBD per ml of plasma was observed. The procedure was used to study the plasma level of CBD after its oral and intravenous administration to monkeys.

Animals↗

Effect of docusate sodium on drug release from a controlled-release dosage form.

This study was designed to determine the effect of a clinically used surfactant, docusate sodium, on the release of chlorpheniramine from a controlled-release dosage form (encapsulated coated pellets). In vivo treatments consisted of the controlled-release capsule alone or with 200 mg of docusate sodium. Plasma chlorpheniramine levels were determined, and the AUC was calculated. No significant difference in AUC values was observed between the two treatments. At a concentration below the CMC, docusate sodium enhanced the in vitro drug release rate. The surfactant exerted a greater effect on the release of the first one-third of the drug contained in nonwax-coated pellets. At the CMC, 0.02% (w/v), docusate sodium rapidly entrapped chlorpheniramine in micelles. The overall enhanced dissolution rate in vivo may have been offset by micellar drug entrapment.

Biological Availability↗

In vitro evaluation of hemolytic and cell culture toxicity potential of residual ethylene oxide in selected medical materials.

The hemolytic potential of pure ethylene oxide in solution was evaluated as a function of initial ethylene oxide concentration in three test systems, diluted whole blood in isotonic saline, erythrocytes washed and resuspended in isotonic saline, and erythrocytes washed and resuspended in isotonic phosphate buffer. Concentrations of 2 mg/ml (2000 ppm) were necessary before cell lysis was observed in either of the isotonic saline systems. This value increased to 10 mg/ml 10,000 ppm) in the isotonic buffer system. Efforts have been made to correlate the hemolysis and cell culture toxicity of residual ethylene oxide in five medical materials to the toxicity of pure ethylene oxide. Only materials exhibiting a low order of inherent toxicity showed any correlation. In poly(vinyl chloride) tubing containing 1.8 and 2.1 mg ethylene oxide per gram of material, a small amount of toxicity was seen in the cell culture system but toxicity was absent in the hemolysis test.

Blood↗

Departmental review in medical schools: focus and functions.

Approximately two-thirds of all U.S. and Canadian medical schools have provisions for the evaluation of their departments on a periodic or ad hoc basis. Most of these institutions have initiated the departmental review process since 1970. It appears that use of the practice is increasing and is becoming an important tool in providing guidance for departmental activities, programs, and leadership. Departmental review may be conducted in a variety of ways with varying levels of intensity, flexibility, and skill, depending on the environment, resources, dean, department chairmen, faculty, and attitudes of university administrators. Departmental review may be employed to identify, elaborate, document, and/or contribute to the resolution of current and potential organizational concerns. When carefully administered, the process can be a stabilizing rather than a disruptive force; however, by itself, it does not solve major institutional problems.

Canada↗

Upper extremity total joint replacement.

Current techniques of total joint replacement surgically correct badly destroyed joints by the insertion of plastic and metal components, which are secured to the skeleton by methylmethacrylate cement. This approach began in England in 1962 and in the United States in 1967. Recent development in the field of upper extremity joint replacement allow implementation of refined total shoulder, elbow, and wrist prostheses. Although less experience has been gained with these prostheses than with total hip and knee replacements, preliminary results are encouraging.

Arm↗

Spontaneous perforation of the bile ducts in infancy.

The clinical features of spontaneous perforation of the bile ducts in infancy differ sufficiently from those of other causes of neonatal jaundice to allow early preoperative diagnosis as demonstrated by a report of this condition in a 6-week-old infant. Despite its rarity, the clinician should be aware of this entity because early recognition and surgery will ensure cure in almost all cases. The cause of spontaneous perforation of the bile ducts is unknown. Trauma, congenital weakness and abnormal bile are considered as possible etiologic factors.

Age Factors↗

Taming effects of p-chlorophenylalanine on the aggressive behavior of septal rats.

Septal irritability and shock-induced aggression were suppressed by the administration of p-chlorophenylalanine (PCPA) to septal rats. The levels of septal irritability and shock-induced fighting were significantly lower in septal, PCPC-treated rats than in nontreated septal rats. Since both parameters of septal aggression were reduced by PCPA, and while PCPA has no effect on shock-induced fighting of unlesioned rats under similar parameters, it appears that both forms of aggression may function through a common neural mechanism.

Aggression↗