Physiological and functional impact of an unsupervised but supported exercise programme for claudicants.

OBJECTIVES: To evaluate an unsupervised home-based exercise programme for physiological, functional, and quality of life impact in patients with symptomatic peripheral arterial disease. DESIGN: Prospective cohort with exercise intervention. MATERIALS: Human performance laboratory with non-invasive haemodynamic assessment facilities. METHODS: Forty-seven patients with symptomatic peripheral arterial disease (mean age 67.6+/-7 years, 33 males) participated in an unsupervised home-based exercise programme. Heart rate (HR), ankle brachial blood pressure index (ABPI), leg blood flow (BF), and blood lactate were measured before and after a graded treadmill walk at baseline and after the 12-week exercise programme. Maximum walking distance (MWD) during the treadmill walk was measured at baseline and 12 weeks. Exercise compliance, functional parameters, and quality of life (VascuQoL) were assessed by questionnaire. RESULTS: MWD, leg BF, and VascuQoL scores increased significantly, while resting HR, exercise HR, and end of walk rate-pressure-product (RPP) decreased significantly after 12 weeks. Exercise compliance was significantly correlated with increase in MWD (r=0.89, p<0.001) and QOL score improvement (r=0.61, p<0.001). CONCLUSIONS: This supported but unsupervised exercise programme generated improvements in walking distance and leg blood flow without detectable increases in cardiorespiratory work. Exercise compliance is related to MWD and VascuQoL score in a dose-response manner.

Prognostic value of stress echocardiography in women with high (> or = 80%) probability of coronary artery disease.

OBJECTIVE: To assess the prognostic significance of stress echocardiography in women with a high probability of coronary artery disease (CAD). SETTING: Secondary and tertiary cardiology unit at a university teaching hospital. PARTICIPANTS: A total of 135 women (mean (SD) age 63 (9) years) with pre-test probability of CAD > or = 80% were selected from a database of patients investigated by treadmill or dobutamine stress echocardiography between 1995 and 1998. MAIN OUTCOME MEASURES: Patients were followed up for occurrence of subsequent cardiac events (cardiac death, myocardial infarction, admission with unstable angina, and revascularisation) using a structured telephone interview and case note review. RESULTS: Each patient had between two and seven (mean 3.5) CAD risk factors and pre-test probability of CAD > or = 80%. Ninety three patients (68.9%) had negative stress echocardiography. Mean (SD) follow up was 20.1 (8.5) months. There were six events in the positive stress echocardiography group (two cardiac deaths, one unstable angina, three revascularisations), and one event in the negative stress echocardiography group. Cox regression analysis showed positive stress echocardiography (p = 0.02) and age (p = 0.03) to be the only univariate predictors and positive stress echocardiography to be the only independent predictor of future cardiac events (relative risk 8.9, confidence interval 1.0 to 76.5, p = 0.04). Cumulative event free survival to 38 months was 98% in the negative stress echocardiography and 50.7% in the positive stress echocardiography groups. CONCLUSION: In women with high pre-test likelihood of CAD: (1) negative stress echocardiography identifies a subgroup with low risk of cardiac events who do not require further invasive investigation and (2) positive stress echocardiography identifies a subgroup with increased risk of subsequent cardiac events.

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret.

Enhanced NR2A subunit expression and decreased NMDA receptor decay time at the onset of ocular dominance plasticity in the ferret. The NMDA subtype of glutamate receptor is known to exhibit marked changes in subunit composition and functional properties during neural development. The prevailing idea is that NMDA receptor-mediated synaptic responses decrease in duration after the peak of cortical plasticity in rodents. Accordingly, it is believed that shortening of the NMDA receptor-mediated current underlies the developmental reduction of ocular dominance plasticity. However, some previous evidence actually suggests that the duration of NMDA receptor currents decreases before the peak of plasticity. In the present study, we have examined the time course of NMDA receptor changes and how they correlate with the critical period of ocular dominance plasticity in the visual cortex of a highly binocular animal, the ferret. The expression of NMDA receptor subunits NR1, NR2A, and NR2B was examined in animals ranging in age from postnatal day 16 to adult using Western blotting. Functional properties of NMDA receptors in layer IV cortical neurons were studied using whole cell patch-clamp techniques in an in vitro slice preparation of ferret primary visual cortex. We observed a remarkable increase in NR1 and NR2A, but not NR2B, expression after eye opening. The NMDA receptor-mediated synaptic currents showed an abrupt decrease in decay time concurrent with the increase in NR2A subunit expression. Importantly, these changes occurred in parallel with increased ocular dominance plasticity reported in the ferret. In conclusion, molecular changes leading to decreased duration of the NMDA receptor excitatory postsynaptic current may be a requirement for the onset, rather than the end, of the critical period of ocular dominance plasticity.

Suppression of NMDA receptor function using antisense DNA block ocular dominance plasticity while preserving visual responses.

Pioneering work has shown that pharmacological blockade of the N-methyl-D-aspartate (NMDA) receptor channel reduces ocular dominance plasticity. However, the results also show that doses of NMDA receptor antagonists that have an effect on ocular dominance plasticity profoundly reduce sensory responses and disrupt stimulus selectivity of cortical cells. It is, therefore, not possible to determine whether effects of NMDA receptor blockade on visual plasticity result from a specific role of NMDA receptors or from the reduction in sensory response. We have used an alternate approach to examine this question. We performed knockdown experiments using antisense oligodeoxynucleotides (ODNs) complementary to mRNA coding the NR1 subunit of the NMDA receptor. After 5 days of antisense, but not sense, ODN treatment NMDA receptor-mediated synaptic transmission was reduced markedly relative to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor response, as indicated by whole cell patch-clamp recordings in the cortical slice preparation. This suppression of NMDA receptor-mediated currents was due to a selective reduction in the NR1 protein near the injection site relative to the untreated hemisphere in the same animal, as indicated by immunocytochemistry and Western blotting. In contrast, AMPA receptors were not affected by the antisense ODN treatment indicating specificity of effects. Another major effect of this treatment was to decrease ocular dominance plasticity. Ferrets that were monocularly deprived 1 wk during the antisense ODN treatment had ocular dominance histograms similar to those found in untreated, nondeprived animals. In contrast, ferrets treated with sense ODN and monocularly deprived had ocular dominance histograms resembling those of untreated, monocularly deprived animals. The effects on ocular dominance plasticity did not result from a disruption of sensory responses because maximum responses as well as orientation and direction selectivity of cortical cells were not affected by the treatment. In conclusion, the present results show that antisense techniques can accomplish more selective manipulations of cortical function than is possible with traditional pharmacological agents. Use of this approach also provides unambiguous evidence for a specific role of NMDA receptors in visual plasticity.

A systems view of the smoking problem: perspective and limitations of the role of science in decision-making.

The complex issues and relationships surrounding the smoking problem indicate the desirability of a system dynamics computer simulation model for policy development and analysis. This paper describes an initial model-building effort, including reports of initial policy and sensitivity testing of the model. The lack of scientific research on most of the relationships and parameters required in such a model forced heavy reliance upon intuition in the model development. The sensitivity of simulated model outcomes to many of these assumptions demonstrates the need for a more concentrated multi-disciplinary research effort if forecasting and policy determination are to be carried out with confidence.

A systems intervention for improving medical-school-hospital interrelationships.

The large number of affiliations between medical schools and hospitals resulting from recently increased size of schools has typically been accompanied by both school-hospital and hospital-hospital interrelationship problems involving faculty and administrative personnel in all departments and at all levels. In this paper the authors describe a new technique, "systems intervention," designed specifically to deal with problems of needed change in complex organizational settings, and they illustrate its use by reporting a case study of the relationships between Tufts University School of Medicine and its associated hospitals. The process combines system analysis and behavioral science techniques to promote understanding and overcome barriers to change. Changes attributed to the systems intervention at Tufts are outlined.

A medical education program strategy for community hospitals.

Community hospital physicians, nurses, and other health care practitioners should be involved in their institution's educational planning activities. Strategic planning that considers both internal and external pressures is required. All programs should have clear, measurable goals; be flexible; and subjected to continuous reassessment. All efforts must be related to quality of patient care as judged by community standards.

Strategic modelling for health care managers.

The Medical Director of a new HMO thinks the patient load warrants hiring three new internists. What additional factors should he consider? How will this move affect the other needs and plans of the HMO? What effect will it have on the organization's financial condition? Here's the way a large corporation would tackle these questions.

Systems intervention: new help for hospitals.

Systems intervention is a dynamic approach to dynamic problems. By illustrating evolution and change in the nature of the problems--and the solutions--it provides a structure that encourages healthy interchange, discourages debilitating conflict, and ensures continuing commitment.