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J C Hershey

Publications and source records attributed to J C Hershey.

At least 19 recordsLinked to original sources
PubMed1995

Angiotensin II-induced hypertrophy of rat vascular smooth muscle is associated with increased 18 S rRNA synthesis and phosphorylation of the rRNA transcription factor, upstream binding factor.

Hypertrophy of vascular smooth muscle cells (VSMC) is an important adaptive response of hypertension. Drug intervention studies have implicated a role for angiotensin II (A-II) in the mediation of VSMC hypertrophy in vivo, and A-II is a potent hypertrophic agent for VSMC in culture. Our laboratory has previously shown that A-II-induced hypertrophy of cultured VSMC is due in part to generalized increases in protein synthesis and increased content of rRNA. The aim of the present study was to determine if A-II stimulates rRNA gene synthesis and whether the rRNA transcription factor, upstream binding factor (UBF), is involved. Nuclear run-on analysis demonstrated that A-II induced a greater than 5-fold increase in rRNA gene synthesis within 6 h of stimulation. A-II also stimulated a rapid increase in UBF phosphorylation as well as nucleolar localization, but no changes in the content of UBF. Phosphoamino acid analysis showed that phosphorylation occurred only on serine residue(s). Results demonstrate that increased transcription of ribosomal DNA contributes to the A-II-induced increase in protein synthesis and VSMC hypertrophy, and suggest that an important regulatory event in this pathway may be the phosphorylation and/or nucleolar localization of UBF.

Angiotensin II↗
PubMed1995

Why some health policies don't make sense at the bedside.

Cost-effectiveness analysis and other forms of decision analysis are becoming more common in the medical literature and are increasingly influential in the development of health policy. Nevertheless, many clinicians find it difficult to apply policies developed from these analyses to individual encounters with patients. We examine the assumptions behind these analyses and argue that the perspective they embody can make clinical strategies appear to be less risky in theory than they are at the bedside. We believe that this problem underlies the intuitive concern many physicians have about policy analyses and calls into question the value of these analyses in shaping clinical practice. These analyses aggregate the benefits and burdens of alternative interventions across different individual persons. Thus, overall population risk appears blunted, as it would in a diversified portfolio of stocks that react differently to financial forces or in a herd of cattle that react differently to veterinary interventions. The assumptions behind these analyses make sense if aggregate outcome is what matters, but not if one cares about each individual investment or animal. Because such aggregation tends to understate individual risk, when applied to human health policy, it may misrepresent the interests of patients and cannot be assumed to provide useful guidelines for decision making at the bedside.

Cost-Benefit Analysis↗
PubMed1994

The influence of sympathoadrenal activation on skeletal muscle oxygen extraction during endotoxemia.

We have previously shown a direct relationship (r = .97) between the fall in arterial blood pressure and the increase in skeletal muscle oxygen extraction (MVO2) during canine endotoxemia. Since it is well known that hypotension activates the sympathetic system, the primary aim of these experiments was to determine if the increase in MVO2 during endotoxemia is a result of elevated levels of catecholamines due to increased sympathetic neural and/or humoral activity (sympathoadrenal system). Canine gracilis muscles were vascularly isolated and perfused in situ at a constant flow (6-7 ml/min/100 g). Endotoxemia was induced by a 30 min intravenous infusion of Escherichia coli endotoxin (2 mg/kg), which induced a 50% reduction in arterial pressure. Perfusion pressure, mean arterial pressure, and arteriovenous oxygen difference (a-v O2) were continuously measured. We found 1) no significant difference between the amount of O2 extracted by an innervated or a denervated muscle during endotoxemia; 2) the intra-arterial infusion of norepinephrine or epinephrine into a denervated gracilis muscle (plasma molar concentrations of; 10(-11), 10(-9), 10(-7), and 10(-5) failed to increase MVO2 to the level observed during endotoxemia; 3) pretreatment of a muscle with propranolol to block skeletal muscle beta-adrenergic receptors, did not suppress the endotoxin-induced rise in MVO2. We concluded that the increase in MVO2 seen after the administration of endotoxin is not due to either increased sympathetic nerve activity or elevated levels of circulating catecholamines. We speculate that the increased MVO2 during endotoxemia is caused by nonadrenergic mediators released by endotoxin rather than the hypotensive stimulus.

Adrenal Cortex↗
PubMed1993

Variation in physicians' decision-making thresholds in management of a sexually transmitted disease.

OBJECTIVE: To gain insight into the variation in physicians' clinical decisions and further understand the factors that influence physicians' thresholds for testing and treating. DESIGN: Written clinical scenarios were mailed to two groups of physicians who were asked to provide probability estimates of syphilis, how these estimates might change with new information, and when a diagnostic test would be ordered or treatment begun. A model was then used to calculate the probabilities at which physicians ordered tests or initiated treatment. PARTICIPANTS: Group 1 comprised 126 board-certified internists from metropolitan Philadelphia responding from a sample of 360 such physicians randomly selected from a directory. Group 2 consisted of 31 experts in sexually transmitted disease responding from a sample of 50 experts selected by the authors. MEASUREMENTS AND MAIN RESULTS: Experts were willing to obtain a serologic screening test at a lower likelihood of syphilis (0.013%) than were internists (0.034%), and they were willing to obtain a lumbar puncture at a lower likelihood of neurosyphilis (0.165%) than were internists (0.393%). The difference in the groups' thresholds to begin neurosyphilis treatment was not significant. A multivariate model showed that group differences were created by individual characteristics (years in practice, subspecialty board certification, and full-time nonacademic practice) that were associated with higher thresholds for serologic screening. CONCLUSIONS: There are differences in the diagnostic testing practices for syphilis between national experts and internists. Although status in one of these groups alone did not predict the threshold for obtaining syphilis tests, certain individual characteristics were predictive. Examination of physician characteristics helps to explain the variation observed in their practice patterns, and determination of physicians' thresholds aids in analyzing these variations.

Clinical Laboratory Techniques↗
PubMed1993

Reporting the results of cystic fibrosis carrier screening.

The recent discovery of the cystic fibrosis gene has offered the possibility of population-based cystic fibrosis carrier screening. Although > 100 distinct mutations have been identified, five of these in aggregate represent about 85% of the alleles in Britain and the United States. Screening programs that test for these five mutations can be designed to offer several alternative ways to communicate the risk to a pregnancy and several alternative ways to manage a pregnancy. At this time we favor a strategy of screening partners in a couple in sequence, screening the second partner only if the first is positive; nevertheless, different strategies will appeal to different couples.

Cystic Fibrosis↗
PubMed1993

Endotoxin induces metabolic dysregulation of vascular tone.

The goals of this study were to determine 1) if endotoxin alters vascular responsiveness to metabolic stimuli and 2) if the decompensatory loss of skeletal muscle vascular tone that occurs during endotoxemia is induced by increased muscle metabolism. Vascularly isolated and denervated canine gracilis muscles were perfused in situ at a constant flow. In the first set of experiments, gracilis muscle O2 extraction (MVO2) and perfusion pressure were continuously measured during direct electrical stimulation of the muscle mass. Endotoxemia was induced by a 30-min intravenous infusion of Escherichia coli endotoxin (2 mg/kg), and the stimulations were repeated 60 min postendotoxemia. Compared with the nonendotoxic control, the endotoxemic muscle stimulation resulted in a decreased MVO2, and the vascular response (dilation) was potentiated. In the second set of experiments, the MVO2 of the experimental muscle (GMe) was lowered by cooling the temperature of the blood perfusing the muscle to 22-24 degrees C while maintaining the temperature of the contralateral control muscle (GMc) at 34-35 degrees C. After the administration of endotoxin, arterial pressure fell and the GMc showed a progressive increase in MVO2 and loss of vascular tone (decompensation). Coincidently, the GMe showed no significant change in MVO2 and did not vasodilate. The major findings of this study are 1) endotoxin induces the vasculature to become more reactive to metabolic vasodilation, and 2) the decompensatory vasodilation typically observed during endotoxemia can be abolished if MVO2 (i.e., metabolism) is kept low by cooling the muscle. The data suggest that endotoxemia increases vascular sensitivity to vasodilatory metabolites, which allows local mechanisms to dominate extrinsic nonneural forces and control vascular tone, thus inducing vasodilation.

Animals↗
PubMed1992

Effect of ibuprofen upon denervated skeletal muscle resistance and compliance vessels during endotoxemia.

The primary aim of these studies was to specifically evaluate the non-neural role of the cyclooxygenase products on the peripheral vascular decompensation associated with endotoxemia. The constant-flow perfused, vascularly isolated, denervated double-canine gracilis muscle preparation in which one muscle is used as a control for the contralateral side was employed. The experimental muscle (GMi) received ibuprofen while the control (GMc) was infused with the vehicle. The results of these studies suggest that endotoxin increases the arterial conductance (i.e., arterial dilation) by 100% and venous compliance (i.e., venoconstriction) by 40%. These observations, which are consistent with venous pooling, were not significantly altered by the continuous intra-arterial infusion of ibuprofen at a peripheral blood concentration of 160 microM. Ibuprofen caused a small but statistically significant increase in the conductance/compliance ratio at 60, 75, and 90 min post endotoxin, suggesting that cyclooxygenase products may play a minor role in the non-neural regulation of capillary fluid dynamics during endotoxemia. Consequently, these studies do not provide convincing evidence that would support a non-neural cyclooxygenase role in the peripheral vascular decompensation reported to occur during systemic endotoxemia.

Animals↗
PubMed1991

Influence of histaminergic receptors on denervated canine gracilis muscle vascular tone during endotoxemia.

The purpose of this study was to determine if endogenously released histamine and its non-neural interaction with the H1- and H2-histaminergic receptors in the peripheral vasculature can account for the decompensatory loss of peripheral vascular tone associated with the hypotension occurring during endotoxemia. A denervated in situ constant flow double canine gracilis muscle preparation that permitted one muscle to serve as a control (GMc) for the contralateral experimental muscle (GMe) was used. Endotoxemia was induced by intravenous infusion of 2 mg.kg-1.30 min-1 endotoxin. The specific H1 and H2 antagonists diphen-hydramine and cimetidine were infused either together or separately in both high and low dosages into the GMe. Blockades were validated by intra-arterial injection of histamine or the specific agonists betahistine for H1 and dimaprit for H2 receptors. The results suggest that the high-dose diphenhydramine produced a nonspecific dilation not seen with the lower dose. Because both the blocked and unblocked vascular beds exhibited the same degree of vasodilation after endotoxin, these studies do not support the hypothesis that endogenously released histamine is responsible for the loss of vascular tone. These studies do verify, however, that a nonneurally mediated loss of skeletal muscle vascular tone is an important factor to consider in the overall cardiovascular hypotension occurring during endotoxin shock.

Adenosine↗
PubMed1988

Outcome bias in decision evaluation.

In 5 studies, undergraduate subjects were given descriptions and outcomes of decisions made by others under conditions of uncertainty. Decisions concerned either medical matters or monetary gambles. Subjects rated the quality of thinking of the decisions, the competence of the decision maker, or their willingness to let the decision maker decide on their behalf. Subjects understood that they had all relevant information available to the decision maker. Subjects rated the thinking as better, rated the decision maker as more competent, or indicated greater willingness to yield the decision when the outcome was favorable than when it was unfavorable. In monetary gambles, subjects rated the thinking as better when the outcome of the option not chosen turned out poorly than when it turned out well. Although subjects who were asked felt that they should not consider outcomes in making these evaluations, they did so. This effect of outcome knowledge on evaluation may be explained partly in terms of its effect on the salience of arguments for each side of the choice. Implications for the theory of rationality and for practical situations are discussed.

Decision Making↗
PubMed1988

Measuring the economic impact of perioperative total parenteral nutrition: principles and design.

Although the use of total parenteral nutrition (TPN) has been increasing in recent years, few studies have been performed on both its costs and its effectiveness or benefits. This paper provides a general review of the methods of cost-effectiveness and cost-benefit analysis, summarizes briefly the existing cost-analysis studies of TPN, and outlines the authors' proposed study design for their economic assessment of TPN.

Clinical Trials as Topic↗
PubMed1986

Comparing aggregate estimates of derived thresholds for clinical decisions.

Thresholds for medical decision making are the probabilities of disease at which clinicians choose to initiate testing or therapy. A descriptive analysis of clinicians' decision making can derive their test and test-treatment thresholds and has the potential to explain variations in test utilization. A previously described method summarizes thresholds for a group of clinicians by determining the range of probability which includes the maximum number of clinicians' individual thresholds. However, there is no statistical procedure to compare the summary measure of thresholds that is derived from the distribution of clinicians' thresholds. We describe two alternative methods of developing a summary measure of the thresholds for a group of clinicians. These alternative methods enable the analyst to apply standard statistical tests when analyzing the decision-making behavior of groups of clinicians. For the "Unweighted Mean of the Midpoints" method, confidence limits of means and standard t-tests can be used to compare different groups. For the "Weighted Mean of the Midpoints" method, a weighted standard error of the mean can be calculated to determine confidence intervals, and a weighted t-test or weighted regression can be used to compare weighted means of the midpoints of threshold ranges.

Angiography↗
PubMed1984

Health insurance under competition: would people choose what is expected?

To determine relative preferences for different cost-sharing options, we asked a 17% random sample of 2,754 nonunion employees to compare health insurance policies that differed in the level of 1) deductible amount, 2) coinsurance rate, 3) coinsurance limit, 4) maximum liability, and 5) price. Using conjoint analysis, we derived preference curves for each of the five components and measured preferences for the compromise between more coverage and the corresponding price increase. In contrast to other studies, our findings suggest that under fair market prices, respondents would choose policies with greater coverage for catastrophic illness, and they would as likely choose cost-sharing policies that contain incentives to reduce utilization as they would choose policies without these incentives.

Adult↗
PubMed1983

Derived thresholds. Determining the diagnostic probabilities at which clinicians initiate testing and treatment.

The medical decision making literature has previously considered the test and test-treatment thresholds in a normative fashion. In the normative approach, the analyst calculates the optimal threshold--the likelihood of disease at which testing or treatment should be undertaken. In contrast, we describe a method of deriving the threshold in a descriptive fashion, by determining the probabilities of disease at which clinicians actually make the decision to test or to initiate specific treatment without further testing. In applying this method, the analyst first asks clinicians to provide an estimate of the prior probability of disease, and to select one of three options: test, treat, or do neither. After receiving new information about the patient, the clinicians are asked to revise the probability estimate and to select a new option. Correlation of changes in the probability of a disease with changes in the clinicians' selections of options to test or treat enables the analyst to estimate the test and test-treatment thresholds used by the clinicians in medical decision making. Knowledge of these thresholds also enables the analyst to calculate the clinicians' ratio of the benefits to the costs of the therapy being considered, considering the risks of the test itself.

Cost-Benefit Analysis↗
PubMed1980

Patient compliance with antihypertensive medication.

Self-reported medication taking compliance behavior of 132 high blood pressure patients was analyzed using an expanded version of the health belief model. Subjects were selected through random sampling procedures from regular hypertension program sessions at a large urban hospital. A questionnaire was constructed to measure the model components, and interviews were conducted with each patient. Bivariate analysis showed that control over health matters, dependence on providers, perceived barriers, duration of treatment, and others' nonconfirming experience were significantly related to compliance (p < .05). Log-linear multivariate analysis revealed that three of these five variables--control over health matters, perceived barriers, and duration of treatment--contributed independently to patient compliance. Self-reported medication taking was significantly related to blood pressure control (p < .02). These data provide the basis for developing interventions for providers to facilitate the medication taking behavior of clinic patients.

Analysis of Variance↗
PubMed1980

Analysis of capacity decisions for progressive patient care hospital facilities.

In this study we provide a methodology for investigating the relationships between capacity decisions and selected performance measures for a progressive patient care facility. The methodology is illustrated with published data from a coronary care facility. The facility is modeled using a simulation approach. The utilization rate of each unit, the fraction of transfers blocked in each unit, and the proportion of each unit's patient-days resulting from inappropriate use are determined for a range of capacity levels. Finally, the results of this experimentation are transformed by regression analysis into prediction equations that give insight into the sensitivity of these performance measures to capacity levels and provide a useful tool for guiding resource allocation decisions.

Coronary Care Units↗
PubMed1979

A re-appraisal of the productivity potential and economic benefits of physician's assistants.

A combined optimization-simulation model is used to examine the extent of productivity and economic benefits to be gained from adding a physician's assistant to a one-physician ambulatory health care practice. It is shown that previous models (which have predicted productivity gains as large as 90 per cent) have overstated these benefits by ignoring offsetting changes in patients' waiting time, waiting room congestion, practice hours, and supervisory requirements. When all these factors are considered, the productivity gain may be as small as 20 per cent, and the increase in net income may be negligible. The sensitivity of productivity and net income to changes in supervisory requirements is also examined. This paper suggests that a rational explanation exists for the reluctance of physicians to adopt physician's assistants in their practices. The economic benefits derived from adding a physician's assistant may well have been overstated in the existing literature.

Ambulatory Care↗
PubMed1978

The productivity potential of physicians' assistants: an integrated approach to analysis.

Although many previous analytical studies indicate that physicians' assistants can substantially increase productivity and reduce costs, the utilization of physicians' assistants in ambulatory health care settings has grown at a disappointing rate. This apparent discrepancy may be explained in part through close examination of the models used in the analytical studies. This paper describes the limitations of previous studies and shows how analysis can be improved through the use of a combined optimization-simulation model. The model is applied to a hypothetical example to demonstrate how productivity and income benefits can be overstated, and to test the sensitivity of such benefits to a range of management policies for the ambulatory care practice regarding patient load, physical resources, appointment scheduling, and more flexible assignment of providers to patients.

Computers↗