Biomedical subjects
J H Grubbs
Publications and source records attributed to J H Grubbs.
A competency-based promotion program for part-time student employees.
Explore the source record for details and available documents.
Modified processing of prescriptions for discharged patients.
A process for designing and implementing a new procedure for handling discharge prescriptions is described. Hospital administration requested that the pharmacy department develop a new procedure to handle discharge medications. The old procedure, in which discharge prescriptions were filled by decentralized pharmacy personnel and delivered to patients' rooms, resulted in lost revenues from third-party payers and in delays for patients leaving the hospital. Under the new procedure, prescriptions are given to patients at the time of discharge; these prescriptions then may be filled either at the central ambulatory-care pharmacy or at a community pharmacy. This new procedure was designed and implemented according to a planned approach: (1) reviewing the problem, (2) evaluating the arguments for and against change, (3) using strategies to minimize resistance, and (4) evaluating the results. Resistance of pharmacy personnel, physicians, nurses and patients to the new procedure was managed by allowing pharmacy personnel to participate in the design of the new procedure; educating all affected hospital staff members about the procedure; structuring the procedure to address the problems of delayed discharge and patient ability to pay for medications; and negotiating with ambulatory-care pharmacists and technicians about the increased workload. The new procedure was implemented on July 1, 1987. The new procedure was evaluated to determine how well it worked and whether continuity of care had been compromised. As a result of this evaluation, the level of staffing and hours of operation of the ambulatory-care pharmacy were increased. A planned approach to implementing a change in the procedure for handling discharge medications was successful in identifying and overcoming resistance to that change.
Time course of the carbon tetrachloride-induced decrease in mitochondrial aldehyde dehydrogenase activity.
Hepatic microsomal enzymes like cytochrome P-450 and glucose 6-phosphatase are inhibited after exposure to CCl4 in vivo. Since comparatively less is known about the effects of CCl4 on nonmicrosomal enzymes, we investigated the rapidity by which CCl4 inhibits the low Km mitochondrial aldehyde dehydrogenase (ALDH) isozyme, an enzyme known to be inhibited 24 hr after CCl4 treatment. The activity of this ALDH isozyme was significantly lowered 6 and 12 hr after a single 1 ml/kg intragastric dose of CCl4. The mitochondrial low Km ALDH specific activities exhibited a similar pattern of destruction/inhibition to the documented target enzyme microsomal cytochrome P-450 in that lowest values were observed 6 hr after CCl4. These values were 44 and 37% of control for cytochrome P-450 content and the low Km ALDH activity, respectively. Alcohol dehydrogenase activity, expressed as activity per gram liver, was depressed 12 hr after CCl4 dosing. Finally, the activity of the low Km cytosolic ALDH, the isozyme that metabolizes malondialdehyde at low concentrations, was not affected by CCl4 treatment. The CCl4-induced decline in the activity of the matrix ALDH isozyme occurs earlier than previously reported mitochondrial damage. The study of sensitive enzymes like the low Km ALDH may provide valuable information by which it may be possible to determine the relationship of the truly rapid biochemical effects of CCl4 such as microsomal lipid peroxidation with later effects on nonmicrosomal components.
Inhibition of mitochondrial aldehyde dehydrogenase by malondialdehyde.
Rat liver mitochondria contain an aldehyde dehydrogenase (ALDH, EC 1.2.1.3) with a low Km for acetaldehyde (2 microM) which is susceptible to inhibition by a variety of agents including p-chloromercuribenzoate and arsenite. This low Km ALDH isozyme has been shown to be decreased in activity following CCl4 treatment in vivo and by lipid peroxidation in vitro. Malondialdehyde, the most studied product of lipid peroxidation, was investigated for possible inhibitory effects on the low Km ALDH for rat liver mitochondria. Malondialdehyde was found to be a potent inhibitor of the enzyme. The enzyme was equally sensitive to inhibition when intact mitochondrial preparations were compared with disrupted mitochondria. The extent of enzyme inhibition was dependent on malondialdehyde concentration and time of incubation. High concentrations of malondialdehyde completely inhibited low Km mitochondrial ALDH activity. Malondialdehyde was found to inhibit the low Km ALDH irreversibly. The rate of ALDH inactivation exhibited two phases, one a rapid rate phase (5-15 s) and a second slower rate phase, both of which showed rates which were dependent on malondialdehyde concentration. These data show that malondialdehyde is a potent, high affinity, irreversible inhibitor of the low Km ALDH of rat liver mitochondria. This ALDH isozyme is considered to be the most important enzyme in acetaldehyde metabolism. Malondialdehyde inhibition of the low Km ALDH may be important since both ethanol and acetaldehyde are thought to stimulate hepatic lipid peroxidation.
Inhibition of rat liver aldehyde dehydrogenase by carbon tetrachloride.
Current data suggests that aldehydic products of lipid peroxidation possess substantial cytotoxic properties. Carbon tetrachloride (CCl4), a potent stimulator of hepatic lipid peroxidation, was tested for possible effects on hepatocellular aldehyde metabolism. CCl4 (1 ml/kg) produced an elevation in serum alanine aminotransferase activity, hepatic fatty infiltration, centrilobular necrosis and significant decreases in the content of hepatic microsomal cytochrome P-450. Concurrently, the aldehyde dehydrogenase (E.C. 1.2.1.3) activity of mitochondrial and cytosolic fractions was significantly depressed. The lower Km aldehyde dehydrogenase located in the mitochondria showed the largest degree of inhibition (46%). An in vitro system which contained the low Km mitochondrial aldehyde dehydrogenase was employed to determine the role of microsomal lipid peroxidation in the inhibition of the enzyme. Aldehyde dehydrogenase was shown to be extremely sensitive to inhibition under conditions of NADPH or NADPH and CCl4-stimulated lipid peroxidation. Reduced glutathione (6 mM) provided complete protection of aldehyde dehydrogenase activity under conditions of NADPH-stimulated lipid peroxidation but could not protect activity loss during CCl4-stimulated microsomal lipid peroxidation. The degree of enzyme activity loss related well with the amount of thiobarbituric reacting substances present in the incubation mixture. These findings show that CCl4 decreases the activity of the aldehyde oxidizing enzyme, aldehyde dehydrogenase. This effect may accentuate cytotoxic effects of reactive aldehydic products generated during lipid peroxidation.
Operational definitions for service, training, education, and learning.
The terms "service," "training," "education," and "learning" are ambiguous and lead to confusion in medical education. An alternate method of defining the terms is explored from the point of view of the role changes which students experience as they become medical practitioners. New definitions are developed. Repetitive activities or role changes not based on the acquisition of new knowledge and skills or supervision are called "noneducational." Role refinements and changes based on the acquisition of new knowledge and skills only are called "educational." Role refinements and changes based on the acquisition of new knowledge and skills and guided by supervision are called "training." These operational definitions permit new approaches to program evaluation and a new basis for discourse between students and their teachers.
Medical student education in psychiatry.
The authors interpret data obtained from 99 medical schools which submitted grant applications for support of either undergraduate psychiatric education programs or human behavior programs. They tentatively conclude that high-quality programs for teaching medical students psychiatry are characterized by a well-rounded faculty, a psychodynamic orientation, a greater commitment to medical student education than to resident training, varied teaching methods, enthusiastic student response, and systematic evaluation that produces change in subsequent years.
Psychiatry and the primary care physician.
Psychiatry makes an important contribution to the training and practice of primary care physicians by emphasizing a holistic approach to patient care, by teaching psychiatric skills and by providing knowledge that enables primary care physicians to give basic psychological care to the large numbers of their patients who need it. Consultation-liaison psychiatry and psychiatry education programs for medical students, both of which are given high priority for support by the Psychiatry Education Branch of National Institute of Mental Health (NIMH), are model settings in which to teach the psychiatric aspects of primary care.