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Biomedical subjects

H L Stone

Publications and source records attributed to H L Stone.

At least 19 recordsLinked to original sources

Alternative medical school curriculum design: the independent study program.

The University of Wisconsin Medical School established an alternative Independent Study Program (ISP) in the basic medical sciences in 1972. This program enabled class size to be increased without increasing laboratory teaching space, provided better education for students with diverse educational backgrounds, permitted individual progress, and promoted independent study. When compared to the most receptive oriented regular curriculum students (RCR) and those most discovery oriented (RCD), the preferred learning style of self-selected ISP students was more discovery or self-directed. They retained that style after graduation, while RCD students frequently became less discovery oriented. The ISP group was older, had more females, and had more advanced degrees. Although they had lower undergraduate grade point averages, they did well on the Verbal, General Information, Problem-Solving, and Quantitative sections of the MCAT. They also did well scholastically in Medical School, scored well on the National Boards Medical Examination, had the same distribution of residencies, and obtained the same quality of residency placement for medicine, surgery, and pediatrics. They have been very supportive of the program and feel that it was valuable in developing their abilities for continued self education.

Achievement

Class mentors: a step toward implementing the GPEP report.

The University of Wisconsin Medical School began a class mentor program in the fall of 1985. Five senior physician faculty members, all in their 60s, have served as mentors thus far, one for each entering class since 1985. Each is asked to spend at least half of his or her time attending courses through four years with the assigned class. The program objectives are to use the experience of senior clinical faculty to help students realize how the information and concepts they learn are important in the practice of medicine, to help with understanding clinical decision making, to provide unique feedback to the faculty and administration on the curriculum and quality of teaching, and to have respected senior faculty serve as advocates for incorporating current education concepts into the medical education program. The mentors have no preset agenda or procedures to accomplish these objectives; each uses his or her own style and interests. Reaction to the program from all parties has been highly favorable: students have been enthusiastic about their encounters with the mentors; the mentors have experienced a new lease on life; and the medical school administration has continued the program as a way of implementing the GPEP recommendation that deans and department chairmen exhibit their commitment to education by their own attitudes and actions.

Costs and Cost Analysis

Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation.

The effect of daily exercise on the coronary resistance vessel sensitivity to intracoronary infusion of several pharmacological agents was assessed in 12 conscious adult mongrel dogs. alpha-Adrenergic receptor agonists (norepinephrine and phenylephrine) significantly decreased coronary blood flow velocity. beta 2-Adrenergic receptor agonists (isoproterenol and zinterol) and a metabolic vasodilator (adenosine) significantly increased coronary blood flow velocity. These responses occurred without altering factors that influence myocardial metabolism. Daily exercise significantly enhanced the coronary vascular sensitivity to each of the pharmacological agents. These results suggest that a nonspecific potentiation to pharmacological activation occurs after daily exercise. After left stellate ganglionectomy, intracoronary infusions of each pharmacological agent had similar effects on coronary blood flow velocity as presented for the intact dogs; however, daily exercise did not enhance the coronary vascular sensitivity to the pharmacological agents. These results demonstrate the need for an intact nervous system for the vascular adaptations associated with daily exercise.

Adenosine

Role of beta 2-adrenergic receptors on coronary resistance during exercise.

The effects of regional alpha- and specific beta 2-adrenergic receptor blockade on measurements of late diastolic coronary resistance (LDCR) and mean coronary blood flow velocity (CBFV) during exercise were examined in 14 conscious adult mongrel dogs. Specific beta 2-adrenergic receptor blockade (ICI 118.551) significantly decreased CBFV and increased LDCR by blockade of beta 2-vasodilator tone independent of alpha-adrenergic receptor-mediated tone and independent of altering myocardial metabolism. alpha-Adrenergic receptor blockade (phentolamine, 1 mg) significantly increased CBFV and decreased LDCR by blocking sympathetically mediated vasoconstrictor tone. There was no significant difference in the magnitude of response between alpha- and beta 2-adrenergic receptor blockade. These results demonstrate that alpha- and beta 2-adrenergic receptors have a significant and evidently equal influence on CBFV and LDCR during exercise. Four weeks of daily exercise and left stellate ganglionectomy (LSGx) prevented phentolamine-induced vasodilation but not ICI 118.551-induced vasoconstriction. This suggests that daily exercise and LSGx significantly decreased the alpha-adrenergic receptor-mediated vasoconstrictor tone on the coronary circulation, resulting in an apparently greater role for the coronary vascular beta 2-adrenergic receptor on the control of CBFV and LDCR during exercise.

Adrenergic beta-Antagonists

The effect of plasma volume expansion on the response to carotid occlusion in the non-human primate.

The purpose of this study was to investigate the effects of plasma volume expansion on the cardiac and peripheral components of the baroreceptor reflex. Nine male Rhesus monkeys were chronically instrumented to measure arterial pressure and aortic blood flow. The aortic arch was denervated at the time of surgery. Bilateral carotid artery occlusion (BCO) was used to elicit the carotid sinus reflex both before and after 25% plasma volume expansion with an iso-osmotic dextran solution. The BCO elicited significant increases in heart rate (HR, 29.8 +/- 5.3 bpm) mean arterial pressure (MAP, 55.0 +/- 8.2 mm Hg) and total peripheral resistance (TPR, 0.076 +/- 0.01 mm Hg/ml/min) coupled with a significant reduction in mean aortic flow (AF, -246.9 +/- 55.3 ml/min) and stroke volume (SV, -2.86 +/- 0.36 ml). Volume expansion significantly attenuated the HR (15.2 +/- 5.8 bpm), MAP (30.4 +/- 4.4 mm Hg) and TPR (0.036 +/- 0.006 mm Hg/ml/min) response to carotid sinus hypotension. The changes in mean AF and SV elicited by BCO, however, were not significantly different between the control and volume expansion conditions. These data suggest that plasma volume expansion significantly attenuates the baroreceptor reflex control of circulation with a similar reduction in both the peripheral resistance and heart rate components of the response.

Anesthesia

Effect of beta 1-receptor blockade on coronary resistance in partially trained dogs.

Selective beta 1-receptor blockade with atenolol (1 mg X kg-1, i.v.) was used to determine the effect of partial exercise training on diastolic coronary resistance (DCR) during sub-maximal exercise. Seven conscious dogs were studied in the untrained (UT) and partially trained (PT) conditions. The conditioning regime consisted of treadmill running 5 d X wk-1 for 4 to 5 wk. Left circumflex coronary flow, aortic pressure, and heart rate were measured, and DCR and myocardial oxygen consumption were calculated. During sub-maximal exercise, DCR in the UT dogs decreased from a resting value of 4.08 +/- 0.18 mm Hg X ml-1 X min-1 to 1.91 +/- 0.17 mm Hg X ml-1 X min-1 at a workload of 6.4 kph (speed)/16% (grade). During exercise, DCR was significantly greater in UT than in PT dogs. Atenolol significantly increased DCR at all levels of sub-maximal workload in both UT and PT dogs. However, the percent increase in DCR with atenolol was significantly greater in the PT dogs compared to UT dogs. These findings suggest that daily exercise for 4 to 5 wk may decrease beta 2-receptor activity of the coronary vasculature during sub-maximal exercise.

Adaptation, Physiological

Cardiovascular results from a rhesus monkey flown aboard the Cosmos 1514 spaceflight.

Pressure and flow relationships to the head were measured before and during spaceflight by means of a chronically implanted cuff placed about the left common carotid artery in one of two rhesus monkeys flown aboard Cosmos 1514. Measurements were obtained daily for 4 min every 2 h during the 5-d spaceflight and compared to identical recordings obtained during a 35-h pre-flight control period 9 d before flight and a 12-h period while on the launch pad. Mean arterial pressure demonstrated a 10% increase compared to control levels immediately on insertion into orbit and maintained a 16-27% increase over the first few hours of flight before returning to baseline levels. Blood flow velocity showed a marked increase (approximately 8 cm/s) compared to pre-flight control while on the launch pad which was maintained over the duration of the flight. Blood flow showed reciprocal changes to pressure on orbital insertion. Cardiovascular system changes persisted into the second day of flight and were most clearly indicated by a decrease in relative differences between blood flow to the head and total cardiac output as measured by impedance plethysmography. Signs of adaptation appeared on days 3-5 of flight.

Animals

Education in cancer prevention for primary care clinicians.

In response to increased public interest in cancer prevention and rapidly escalating health care costs, the National Cancer Institute supported the development of cancer prevention courses for health professionals. A multidisciplinary group of physicians, behavioral scientists, and educators developed, field-tested, revised, and evaluated a 12-module, 24-classroom-hour clinical preventive oncology course for primary care physicians. A rationale for education in cancer prevention is presented, the new clinical discipline of preventive oncology is defined, and contributory disciplines are identified. A curriculum based upon detailed learning objectives is described, short-term evaluation data are presented, and a methodology for incorporating a didactic course into a residency program is suggested. The positive reception given to this course by residents warrants optimism concerning application of a biopsychosocial or self-regulative model rather than the traditional biomedical one to clinical medicine and its teaching.

Attitude of Health Personnel

Exercise tolerance and compensatory sympathetic tone during beta-blockade after myocardial infarction.

Using chronically instrumented dogs with a healed anterior wall myocardial infarction, we have assessed the effect of acute beta-adrenergic blockade on exercise tolerance, left ventricular (LV) performance, and myocardial VO2. Mongrel dogs were instrumented with Doppler flow probes around the left circumflex coronary artery, LV pressure cells, epicardial ECG electrodes, and left atrial and coronary sinus catheters. Myocardial infarction was produced by ligation of the left anterior descending coronary artery at time of instrumentation (approximately 20% LV mass). After a 1-month recovery period, dogs were subjected to two identical submaximal graded exercise tests on a treadmill on separate days, once without (control) and once with (propranolol, 1 mg X kg-1, i.v.) acute beta-adrenergic blockade. Heart rate, LV pressure, dP/dt max, left circumflex blood flow velocity, and myocardial VO2 index were measured at each stage of the graded exercise test. All variables were significantly reduced from control during beta-block in exercise. beta-Adrenergic blockade in the presence of a 1-month-old anterior wall myocardial infarction did not compromise exercise capacity during submaximal exercise.

Adrenergic beta-Antagonists

Cardiac response to submaximal exercise in dogs susceptible to sudden cardiac death.

The hemodynamic response to submaximal exercise was investigated in 38 mongrel dogs with healed anterior wall myocardial infarctions. The dogs were chronically instrumented to measure heart rate (HR), left ventricular pressure (LVP), LVP rate of change, and coronary blood flow. A 2 min coronary occlusion was initiated during the last minute of an exercise stress test and continued for 1 min after cessation of exercise. Nineteen dogs had ventricular fibrillation (susceptible) while 19 animals did not (resistant) during this test. The cardiac response to submaximal exercise was markedly different between the two groups. The susceptible dogs exhibited a significantly higher HR and left ventricular end-diastolic pressure (LVEDP) but a significantly lower left ventricular systolic pressure (LVSP) in response to exercise than did the resistant animals. (For example, response to 6.4 kph at 8% grade; HR, susceptible 201.4 +/- 5.1 beats/min vs. resistant 176.2 +/- 5.6 beats/min; LVEDP, susceptible 19.4 +/- 1.1 mmHg vs. resistant 12.3 +/- 1.7 mmHg; LVSP, susceptible 136.9 +/- 7.9 mmHg vs. resistant 154.6 +/- 9.8 mmHg.) beta-Adrenergic receptor blockade with propranolol reduced the difference noted in the HR response but exacerbated the LVP differences (response to 6.4 kph at 8% grade; HR, susceptible 163.4 +/- 4.7 mmHg vs. resistant 150.3 +/- 6.4 mmHg; LVEDP susceptible 28.4 +/- 2.1 mmHg vs. resistant 19.6 +/- 3.0 mmHg; LVSP, susceptible 122.2 +/- 8.1 mmHg vs. resistant 142.8 +/- 10.7 mmHg). These data indicate that the animals particularly vulnerable to ventricular fibrillation also exhibit a greater degree of left ventricular dysfunction and an increased sympathetic efferent activity.

Adrenergic beta-Antagonists

Effect of short-duration constant exercise on permeability of cockerel aorta to 125I-albumin.

To determine quantitatively the effect of short duration constant exercise on the rate of uptake (U) of intravenously injected 125I-labeled cockerel albumin (A) by the aorta of the adult cockerel, 24 birds divided into age-matched pairs, each pair consisting of an exercised and nonexercised control bird, were studied. The time period of heparinization, anesthesia, and time from injection of A (each member of each pair received about 50 microCi from the same batch) to the death of the animal (T) was identical for each member of each pair. The exercised animal was exercised at a constant speed of 3.2 kph at 0 degrees elevation for between 2 and 5 min on a treadmill. U was defined as accumulated wall radioactivity (dpm)/plasma radioactivity (dpm/ml) X endothelial surface area (cm2) X T (s). Free 125I in the injectate amounted to 1.29 +/- 0.31% (mean +/- SD). Free 125I in the plasma and the wall in the exercise and control animals was not significantly different: plasma 0.84 +/- 0.34% (mean +/- SD) and 0.55 +/- 0.18 (P less than 0.20); wall 3.38 +/- 5.64% and 6.42 +/- 4.72 (P less than 0.04). Injected A remaining in the blood at between 8 and 16 min after intravenous injection was 83 +/- 8.7% (n = 10) in the exercised and 82 +/- 10% (n = 7) in the control (P less than 0.2). U was greater in the exercise group in 9 out of 12 matched pairs (P less than 0.05). We conclude that U increases for short periods of constant exercise.

Animals

Neural regulation of the cardiovascular system during exercise.

Neural components important in control of the cardiovascular system during exercise can be divided into central nervous system (CNS) components and peripheral components. CNS components would include the cerebral cortex, cerebellum, medullary region of the brain stem, and the spinal cord. Peripheral components would include the efferent limbs of the autonomic nervous system and afferent fibers carrying information to the CNS. The neural pathways involved in the control of cardiovascular system during exercise and the relationship between the various neural components have been actively pursued in the last few years. Several new studies suggest that information arising from the active muscles and the cardiovascular system itself may be important in the control of the cardiovascular system during exercise. The cerebellum may play a modulating role in the cardiovascular response. The information from the peripheral afferent fibers, the cerebellum, and the cerebral cortex is integrated in the brain to result in overall neural control. Exercise training probably modifies the central integration of information and modifies the cardiovascular response to exercise and other stresses.

Afferent Pathways

Hormonal and renal response to plasma volume expansion in the primate Macaca mulatta.

The purpose of this study was to investigate the hormonal and renal response to plasma volume expansion in the ketamine-anesthetized rhesus monkey. The blood volume was determined in nine animals and found to be 6% of the body weight. Six monkeys received isoncotic isotonic fluid amounting to 25% of the blood volume. Plasma volume expansion led to significant decrease in the plasma concentrations of antidiuretic hormone (46.7%) and aldosterone (78.4%) as well as plasma renin activity (50.0%). The mean arterial pressure, plasma osmolality, and plasma concentrations of Na+ and K+ were unaffected by plasma volume expansion. However, renal plasma flow, glomerular filtration rate, the excretion of Na+ and K+, and urine flow increased. It was concluded that, in the ketamine-anesthetized rhesus monkey, circulating hormones contribute to blood volume homeostasis presumably through a neural mechanism similar to that observed in dogs and humans.

Aldosterone

Left stellectomy and denervation supersensitivity in conscious dogs.

The possibility that denervation supersensitivity might result from left stellectomy was investigated because of its potential clinical implications. The study was conducted in 12 conscious dogs by injecting norepinephrine as a bolus dose or as an infusion before and 2 to 4 weeks after left stellectomy. The variables analyzed were the first derivative of left ventricular pressure (dP/dt max) and the number of premature ventricular complexes. Under control conditions dP/dt max was unaffected by left stellectomy (3,572 +/- 280 versus 3,549 +/- 235 mm Hg/s). Bolus injections and infusions produced the same results and showed no difference in the increases in dP/dt max produced by norepinephrine observed before and after left stellectomy. For example, with the largest dose of norepinephrine, 1.25 microgram/kg, the changes from the control value were 4,533 +/- 269 and 5,032 +/- 668 mm Hg/s, respectively (difference not significant). The number of premature ventricular complexes resulting from the two largest doses of norepinephrine was significantly decreased after left stellectomy (85 +/- 12 versus 46 +/- 14, P less than 0.05), and ventricular tachycardia, which occurred in three dogs under control conditions, was never observed after left stellectomy. This study reveals another aspect of the antiarrhythmic effect of left stellectomy and demonstrates that it does not produce denervation supersensitivity.

Animals

Coronary blood flow changes following activation of adrenergic receptors in the conscious dog.

The role of coronary vascular adrenergic receptors in changing coronary flow was studied in dogs instrumented to measure left circumflex artery blood flow (CBF), mean coronary artery blood pressure (CBP), and heart rate (HR). Norepinephrine (NE), isoproterenol (IP), and phenylephrine (PH) were injected into the left circumflex artery before and after selective intracoronary alpha- and beta 1- or combined beta 1- and beta 2-receptor blockade. NE, IP, and PH did not alter CBP (112 +/- 6 mmHg). In addition, IP and PH did not affect HR (103 +/- 4 beats/min). NE increased HR to 150 +/- 6 beats/min, which was eliminated by blocking beta 1-receptors with atenolol and by removing the left stellate ganglion. IP increased CBF from 65 +/- 9 to 115 +/- 16 ml/min (mediated by both beta 1- and beta 2-receptors). PH caused an alpha-receptor-mediated coronary vasoconstriction (42 +/- 5 ml/min), which was potentiated by beta 1- and beta 2-receptor blockade. NE caused a biphasic flow response. CBF initially increased to 117 +/- 14 ml/min (mediated predominantly by beta 1-receptors) followed by a prolonged decrease to 54 +/- 7 ml/min (mediated by alpha-receptors). Removing the left stellate ganglion did not affect the CBF response to NE. These data indicate that PH directly stimulates coronary alpha-receptors and IP stimulates myocardial beta 1- and coronary beta 2-receptors. NE also stimulates myocardial cells causing a reflex that increases HR and indirectly increases CBF. The vasoconstriction to NE and PH was not evident after pentobarbital anesthesia, whereas the coronary vasodilation and increase in HR to NE was still present.

Animals