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Biomedical subjects

R A Keith

Publications and source records attributed to R A Keith.

72 records · Page 4Linked to original sources
PubMed1983

Cost-benefits of medical rehabilitation: review and critique.

Evidence of the cost-benefits and cost-effectiveness of medical rehabilitation is reviewed. In stroke rehabilitation, favorable evidence was found, but also the contrary. For spinal cord injury, studies of effectiveness and costs have shown the value of specialized rehabilitation centers. For other areas of medical rehabilitation, investigations have given hints regarding cost-effectiveness but little firm evidence. In allied areas--rehabilitative alternatives in long-term care, vocational rehabilitation, and medical care in general--studies were identified that hold valuable lessons for future study of cost-benefits. A concluding critique identifies obstacles to the study of cost-benefits and makes specific suggestions. Improved experimental designs are required to control for selection biases. Alternatives to ongoing practice need to be entertained if cost-benefit study is to be useful.

Cerebrovascular Disorders↗
PubMed1982

Vascular tolerance to nitroglycerin and cyclic GMP generation in rat aortic smooth muscle.

Recent reports have suggested that cyclic guanosine 3', 5'-monophosphate (cGMP) may mediate drug-induced vascular smooth muscle relaxation. This hypothesis was examined by correlating increases in cGMP formation with vascular smooth muscle relaxation after sensitivities to nitroglycerin and nitroprusside were altered. Both nitroglycerin and nitroprusside produced a concentration-dependent increase in rat aortic cGMP levels, which preceded relaxation. A specific inhibition of nitroglycerin relaxation was accomplished by pretreating helical rat aortic strips with 5.5 X 10(-4) M nitroglycerin for 1 hr (in vitro nitroglycerin tolerance). Both nitroglycerin and nitroprusside were inhibited by pretreating tissues with 10(-5) M methylene blue for 1 hr. Whenever nitroglycerin or nitroprusside relaxation was inhibited, there was a corresponding inability to generate cGMP. Vascular tissues derived from nitroglycerin-tolerant animals (in vivo tolerance) exhibited a profile of cGMP reduction that closely resembled that of the in vitro model. Vascular smooth muscle relaxation induced by 8-bromoguanosine-3', 5'-monophosphoric acid was not inhibited by either in vitro nitroglycerin tolerance or methylene blue, suggesting that the subsequent action of cGMP, once formed, is not impaired. The results of this study support the contention that cGMP generation may be an important step in the promotion of vascular smooth muscle relaxation by nitroglycerin and nitroprusside.

Animals↗
PubMed1979

An ecological study of the recently discharged chronic psychiatric patient.

In order to examine the reasons for repeated rehospitalizations of chronic psychiatric patients, 53 patients were interviewed four days after discharge. A retrospective behavior mapping method reconstructed in detail their activities, locations, and interactions. Results show that many such patients lived alone or in someone else's residence and that they had limited social contacts outside of the home. A majority had a territorial range of less than one block; most did not know the location of common community facilities nor had they used them. The most basic self-help skills were not used by a significant number. To stem rehospitalizations, chronic patients need better and more timely aftercare efforts.

Aftercare↗
PubMed1977

Rehabilitation hospital patient characteristics from the Hospital Utilization Project (HUP) system.

The Hospital Utilization Project (HUP), in collaboration with rehabilitation associations in California and Pennsylvania, instituted on July 1, 1974, a patient data system for rehabilitation hospitals. This is a report of the first year's aggregate of 5,427 patients from 20 hospitals in six states. Of this total, 4,662 were admitted for a full rehabilitation program, and 765 for short-term. Nearly half of the patients admitted for a full program were 65 years or older; 31% were stroke victims, by far the largest single diagnosis. Eighty percent of full program admissions were accounted for by the following six categories (reported with average lengths of stay): stroke (33.7 days), other brain injury and disease (35.9 days), amputations (30.6 days), fractures (29.6 days), arthritis (25.9 days) and spinal cord injury (59.3 days). In the total sample 74% were discharged to a private residential setting. The accumulation of patient data from a number of hospitals will give medical rehabilitation important information regarding its contribution to health care delivery as well as providing data which can be used for PSRO guidelines and for third-party payers. The HUP system is currently receiving discharge abstracts from 42 hospitals in 14 states.

Age Factors↗
PubMedDate not supplied

Conceptual basis of outcome measures.

Because of its treatment configuration and the assumption of long-term benefit, rehabilitation has had a continuing interest in the measurement of outcomes. The utility of outcome indicators rests on their conceptual foundations, the technical development of measures and validation research. Some measures, particularly of functional status, have become increasingly sophisticated with the application of psychometric and statistical analysis techniques. Less effort has been devoted to an elaboration of their theoretical basis. A first step is an examination of the assumptions underlying outcome measures, the purpose of this article. Central to an understanding is clarification of definitions of key terms such as outcomes, independence, impairment, disability and handicap. All outcome measures must be seen as part of a social context of norms and expectations. However, most norms in rehabilitation are implied rather than explicit. The assumptions behind several common outcomes are examined with suggestions for ways to increase their utility. The ability of rehabilitation to compete in the current climate, stressing cost-effectiveness, will depend heavily on the robustness of outcome measures.

Activities of Daily Living↗
PubMedDate not supplied

Facilitating patient learning during medical rehabilitation: a research agenda.

Although patient learning is widely acknowledged to be an integral part of many medical rehabilitation practices, it has been the subject of little systematic research. A workshop conducted August 18 to 19, 1997, was organized by the National Center for Medical Rehabilitation Research (National Institute of Child Health and Human Development, National Institutes of Health) and several co-sponsoring organizations to formulate recommendations concerning learning-oriented rehabilitation practices. The recommendations and their supporting rationale are summarized in the topic areas of motor learning and control, cognitive learning, recovery of functioning, generalization and transfer of training, and applications for patients with strokes, traumatic brain injury, amputations, and infants and children.

Amputation, Surgical↗
PubMedDate not supplied

Relationship between primitive reflexes in stroke patients and rehabilitation outcome.

The reappearance of developmental reflexes in the aged has been found to be associated with severe, diffuse cerebral damage. This study examined the relationship between the presence of such reflexes in stroke patients and the outcome of rehabilitation. Tests for the presence of snout, suck, jaw-jerk and palmomental reflexes were tested in 106 consecutive stroke patients admitted for rehabilitation treatment. A mental status test was also included in the usual medical admission examination. Functional status ratings for self-care and mobility at discharge, and the setting to which the patient was discharged, were used as outcome criteria. All of the reflex signs were negatively related to a favorable outcome, but the correlations were not high enough for predictive value. The mental status measures were more highly related to rehabilitation outcome than were the presence of developmental reflexes.

Adult↗
PubMedDate not supplied

S-Methylation of D- and L-penicillamine by human erythrocyte membrane thiol methyltransferase.

Human red blood cell (RBC) membranes contain a thiol methyltransferase activity that catalyzes the S-methylation of 2-mercaptoethanol (2-ME). These experiments were performed to determine whether human RBC membranes contain enzymes that can catalyze the S-methylation of D- and L-penicillamine, to determine whether those enzymes are similar to the RBC membrane thiol methyltransferase that catalyzes the S-methylation of 2-ME, and to determine whether lipophilic conjugates of the S-methyl metabolites of D- and L-penicillamine are formed by RBC membranes. Human RBC membranes were able to catalyze the S-methylation of D- and L-penicillamine. The apparent Michaelis (Km) constants for D- and L-penicillamine were 7.53 and 7.27 mM, respectively. However, the Vmax value for L-penicillamine was more than 2.5 times greater than the Vmax value for D-penicillamine. D- and L-Penicillamine methyltransferases and 2-ME thiol methyltransferase were similar with respect to their subcellular distributions, inhibitor sensitivities, and thermal stabilities. In addition, when methyltransferase activities for 2-ME and for D- and L-penicillamine were measured in RBC membranes from 19 individual subjects, there were highly significant correlations among all three activities (r greater than 0.98, p less than 0.001 for all three comparisons). These observations suggest either that a single enzyme in the human RBC membrane catalyzes the S-methylation of all three compounds, or, less likely, that these reactions are catalyzed by three separate enzymes that are regulated in parallel and have similar properties. Experiments were then performed to identify the products of the penicillamine methylation reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Mouse liver thiol methyltransferase. Assay conditions, biochemical properties, and strain variation.

Thiol methyltransferase (TMT) catalyzes the S-methylation of aliphatic sulfhydryl drugs and xenobiotic compounds. It would be useful if there were an experimental animal model in which the regulation and function of TMT could be studied. Therefore, TMT activity was measured in hepatic microsomes from A/J mice. Substrate kinetics for mouse liver microsomal TMT, like those for the enzyme in human red blood cell membranes and human kidney microsomes, were biphasic, with apparent "high" and "low" affinity forms of TMT with 2-mercaptoethanol as the methyl acceptor substrate. Apparent Michaelis (Km) constants of the high and low affinity activities for 2-mercaptoethanol were 30 microM and 12 mM, respectively. Apparent Km values of the high and low affinity activities for S-adenosyl-L-methionine, the methyl donor for the reaction, were 47 microM and 61 microM, respectively. The optimal pH for the high affinity activity was between 7.2 and 8.1, whereas the optimal pH for the low affinity activity was approximately 9.2. Differential centrifugation showed that more than 85% of both activities was associated with membrane fractions. SKF 525A, a potent inhibitor of TMT in human tissues, inhibited mouse liver high and low affinity TMT activities by 88% and 46%, respectively, at a concentration of 0.5 mM. TMT activities were then measured in hepatic microsomes from nine additional inbred strains of mice. High affinity TMT activities varied 1.7-fold, whereas low affinity activities varied 2.1-fold among these strains. Since the properties of TMT in mouse liver are similar to those of the enzyme in human tissue, the inbred mouse will be a useful experimental animal model in which to study the regulation and function of TMT.

Animals↗
PubMedDate not supplied

Human erythrocyte membrane thiol methyltransferase. S-methylation of captopril, N-acetylcysteine, and 7 alpha-thio-spirolactone.

Thiol methylation is an important pathway in the biotransformation of sulfhydryl drugs such as captopril. Human red blood cell (RBC) membranes contain a thiol methyltransferase (TMT) activity that catalyzes the S-methylation of 2-mercaptoethanol (2-ME). These experiments were performed to determine whether human RBC membranes contained enzymes that could catalyze the S-methylation of thiol drugs, and, if so, to determine whether those enzymes were similar to the RBC membrane TMT that catalyzes the S-methylation of 2-ME. Human RBC membranes were able to catalyze the methylation of captopril, N-acetylcysteine, and 7 alpha-thio-spirolactone, a sulfhydryl metabolite of spironolactone. Those activities and 2-ME TMT were similar with respect to subcellular distribution, inhibitor sensitivity, and thermal stability. When activities of the methyltransferase enzymes for 2-ME and for the three thiol drugs were measured in RBC membranes from 19 individual subjects, there were highly significant correlations among all four activities (r greater than 0.96 for all comparisons). These observations suggested either that a single enzyme in the human RBC membrane catalyzed the S-methylation of all of these compounds, or, less likely, that these were four separate activities regulated in parallel with similar properties. Experiments were then performed to identify the products of the enzyme reactions. The product of the reaction performed with 7 alpha-thio-spirolactone was the expected S-methyl derivative, 7 alpha-thiomethyl-spirolactone. However, it was found that lipophilic conjugates of the S-methyl derivatives of captopril and N-acetylcysteine were formed during the in vitro enzyme reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗