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Biomedical subjects

R A Wright

Publications and source records attributed to R A Wright.

At least 91 records · Page 5Linked to original sources

Transdermal nicotine and gastroesophageal reflux.

OBJECTIVES: Studies have shown that cigarette smoking acutely increases gastroesophageal reflux (GER). Patients prescribed transdermal nicotine often complain of pyrosis. The purpose of this study was to ascertain the effect of transdermal nicotine on GER. METHODS: Twenty volunteers (12 smokers and eight nonsmokers) were studied with a 24-h pH/motility apparatus while wearing a placebo patch for 24 h and a nicotine patch for a subsequent 24-h period. Each subject completed the entire 48-h monitoring session. RESULTS: A significant increase in the total acid score (p = 0.005), duration of acid exposure (p = 0.010), and supine duration of acid exposure (p = 0.004) were noted with transdermal nicotine versus placebo. There were no significant differences in esophageal motility after transdermal nicotine. CONCLUSIONS: Whether enhanced supine reflux is related to lower esophageal sphincter dysfunction, increased acid secretion, or defective acid clearance is not clear. Nonetheless, it may be prudent to recommend removal of the transdermal nicotine patch at night in the patient with symptomatic nocturnal GERD.

Administration, Cutaneous↗

The long-term effects of metoprolol and epanolol on tissue-type plasminogen activator and plasminogen activator inhibitor 1 in patients with ischaemic heart disease.

This double-blind, randomized parallel group study investigated the effect of 6 months beta-adrenoceptor antagonist therapy with either metoprolol (beta 1-selective without intrinsic sympathomimetic activity [ISA]) or epanolol (beta 1-selective with ISA) on markers of endogenous fibrinolysis in 20 patients with chronic stable angina receiving concurrent treatment with nifedipine. Neither drug had an effect on tissue-type plasminogen activator or plasminogen activator inhibitor type 1 (PAI-1). A significant correlation between fasting insulin and PAI-1 has previously been described and was confirmed in this study. The group treated with metoprolol showed a significant rise in fasting insulin after 6 months with no change in PAI-1. This suggests that the previously described link between these two may not be causal.

Adrenergic beta-Antagonists↗

Small bowel endometriosis masquerading as regional enteritis.

A 35-year-old female presented with recurrent right lower quadrant pain, nausea, and vomiting. She was afebrile with diffuse abdominal tenderness. Plain x-ray of abdomen revealed small bowel obstruction. A barium x-ray of the small bowel showed stricture of the terminal ileum. A CT scan of the abdomen showed a 6-cm mass in right lower quadrant. She was empirically managed as having Crohn's disease. She underwent laparotomy after failure of medical management with high-dose steroids. There was ulceration and narrowing of terminal ileum. Frozen sections revealed endometriosis. Ileocecectomy was performed. Histopathology of resected specimen confirmed the diagnosis of endometriosis, and there was no evidence of chronic inflammatory bowel disease or neoplasia. Ileal endometriosis should be considered in the differential diagnosis of Crohn's disease in menstruating females presenting with perimenstrual symptoms.

Adult↗

Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction.

OBJECTIVES: This study investigated the effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. BACKGROUND: Angiotensin-converting enzyme inhibitors reduce the incidence of acute coronary syndromes in patients with mild left ventricular dysfunction after myocardial infarction. Abnormal endogenous fibrinolysis, reflected in increased levels of endogenous tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 activity, is associated with an increased risk of myocardial infarction in patients with ischemic heart disease. METHODS: In a randomized, double-blind crossover study beginning 8 weeks after uncomplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each treatment period, we measured t-PA antigen and plasminogen activator inhibitor type 1 antigen and activity. RESULTS: Median values in the 15 patients after placebo and in 12 normal men matched for age and body mass index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0.001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 13.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with captopril in the 15 patients, the estimated (95% confidence interval) median reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0.001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1.5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to -4.3 AU/ml, p = 0.02). CONCLUSIONS: Treatment with captopril after uncomplicated myocardial infarction is associated with a significant decrease in elevated levels of t-PA antigen and plasminogen activator inhibitor type 1 activity. This may help to explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors.

Captopril↗

Distribution and ontogeny of 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive and quisqualate-insensitive [3H]glutamate binding sites in the rat brain.

Displacement of [3H]glutamate by 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid and quisqualate (in the presence of saturating concentrations of ionotropic glutamate receptor agonists) was used to characterize optimal ionic conditions, distribution, and the ontogeny of glutamate receptor binding sites in rat brain. Using rat forebrain membranes or receptor autoradiography, optimal 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive [3H]glutamate binding was found in the presence of 100 mM bromide ions and in the absence of calcium ions. Under these conditions, [3H]glutamate binding was relatively quisqualate insensitive. In regions of the neonatal (11-day-old) and adult rat brain, this [3H]glutamate binding was highest in forebrain (striatum, cerebral cortex, and hippocampus) and hypothalamus/mid-brain but was lower in the cerebellum, olfactory bulb, and pons/medulla regions. 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid-sensitive and quisqualate-insensitive [3H]glutamate binding was present in the rat forebrain at 1 day of age and gradually increased more than twofold by day 50 (adult). Thus, in the presence of bromide ions and in the absence of calcium ions, [3H]glutamate labels a subpopulation of metabotropic glutamate receptors that are sensitive to 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid but insensitive to quisqualate. Expression of [3H]glutamate binding under these conditions was both regionally and developmentally regulated in rat brain, suggesting that [3H]glutamate is labeling a distinct population of metabotropic glutamate receptors.

Animals↗

Vascular and metabolic factors in the pathogenesis of experimental diabetic neuropathy in mature rats.

The complex interrelationships between metabolic factors (increased nerve glucose, fructose and sorbitol and decreased nerve myo-inositol levels) and ischaemic-hypoxic vascular factors [decreased nerve blood flow (NBF) and increased nerve vascular resistance (NVR)] in the pathogenesis of diabetic neuropathy are incompletely understood. This study evaluates, in mature animals, the time course and magnitude of changes in factors postulated to be of importance in the pathogenesis of experimental diabetic neuropathy (EDN). Hyperglycaemia was induced in mature 9-month-old male Sprague-Dawley rats with streptozocin (as in studies utilizing immature rats it has been difficult to separate effects which are due to the growth retardation and maturational delay induced by hyperglycaemia from those arising from diabetes per se). Groups of age-matched control and diabetic animals were compared 1, 2, 4, 8, 16 and 24 weeks after injection. In diabetic animals NBF was decreased and NVR was increased after 1 week (P < 0.05); sciatic nerve glucose, sorbitol and fructose levels were increased after 1 week (P < 0.05). These changes were maintained for the duration of the experiment. Sciatic and caudal nerve conduction velocities were significantly decreased after 16 weeks (P < 0.05), although trends were apparent after 4 weeks. Diabetic animals showed decreased sciatic nerve myo-inositol levels between 2 and 16 weeks (P < 0.05), but there was no significant difference at 24 weeks. There were no significant differences in sciatic nerve total (Na+K+)ATPase concentrations. Early and sustained alterations in vascular indices (NBF and NVR) support the postulate that ischaemic-hypoxic factors may play a role in the causation of EDN. The ischaemic-hypoxic postulates do not, however, diminish the obvious importance of the multitude of metabolic alterations which also occur very early after the onset of hyperglycaemia.

Animals↗

The prevalence of smoking amongst patients attending an out-patient lipid clinic.

The smoking habits of 184 attendees (mean age 47 years, 101 men) at a hospital-based lipid clinic were reviewed in conjunction with a measurement of serum thiocyanate level which is a marker for smoking over the previous two weeks. Advice against smoking is routinely given at the clinic. We found 84 (46%) patients to remain active smokers of whom 78 admitted to smoking and 6 were identified on the basis of a serum thiocyanate level greater than 100 micromol/l. Smoking was more prevalent amongst women than men (52% v 33%). We have identified a high proportion of patients attending an outpatient lipid clinic as remaining active smokers despite receiving advice against cigarette smoking. This emphasises the need for more effective counselling against smoking in a multiple risk factor intervention approach to ischaemic heart disease.

Adult↗

Hyperinsulinaemia in ischaemic heart disease: the importance of myocardial infarction and left ventricular function.

Elevated circulating insulin levels have been reported in ischaemic heart disease, and may be of aetiological importance. Previous studies have not considered the potential influence of heart failure or of previous myocardial infarction, as opposed to stable angina. We therefore measured the insulin response to a 75 g oral glucose tolerance test in five groups with normal glucose tolerance, comparing normal male controls to men with chronic stable angina, men with recent myocardial infarction (two groups, 3 weeks and 3 months post infarction), and men with chronic severe heart failure. Only patients with chronic heart failure had fasting hyperinsulinaemia, probably reflecting associated neuroendocrine abnormalities. Stimulated hyperinsulinaemia was present in all patient groups, but was less pronounced and of shorter duration in patients with angina. At 120 min, only patients with heart failure or previous myocardial infarction were hyperinsulinaemic. The degree of stimulated hyperinsulinaemia was not influenced by the presence of heart failure or by the length of time from infarction. Hyperinsulinaemia is associated with impaired peripheral muscle glucose uptake and metabolism, and might contribute to muscular fatigue on exertion in patients with previous myocardial infarction or heart failure.

Administration, Oral↗

Community-oriented primary care. The cornerstone of health care reform.

The current high-cost health care delivery system, which places greater emphasis on acute hospital care than on community-based primary and preventive care, is no longer viewed by policymakers, politicians, and the American public as the ideal model for organizing and providing health care services. Americans want change; however, politicians are responding with a barrage of disjointed finance and cost-containment proposals that fail to address the organization and provision of health care services. Nevertheless, to adequately address problems of cost, access, and quality, reform proposals will need to consider delivery models that create a balance between medical care and health care, between public health and personal health services, and between curative and preventive care. The community-oriented primary care model and the discipline of community and socially responsive medicine is a process for making a health care system more rational, accountable, appropriate, and socially relevant to the public. Consequently, this model, which is now at a pivotal point in its evolution, may serve as a paradigm for reforming the organization and provision of health care services in America.

Community Health Services↗

Differing patterns of cardiac parasympathetic activity and their evolution in selected patients with a first myocardial infarction.

OBJECTIVES: The purpose of the study was to compare cardiac parasympathetic activity during the early and convalescent phases of acute anterior and inferior myocardial infarction. BACKGROUND: Previous studies have shown that cardiac parasympathetic activity may vary with the site of infarction and that recovery may occur after infarction. METHODS: Cardiac parasympathetic activity was measured from 24-h electrocardiograms by counting the number of times that successive RR intervals (counts) differed by > 50 ms. Recordings began within 12 h of admission and at 7, 42 and 140 days after acute myocardial infarction in 20 patients (mean age 57 +/- 7.9 years). All patients were treated with streptokinase, aspirin and oral beta-adrenergic blocking agents. RESULTS: For the entire group, mean total 24-h RR counts increased from 592 (range 78 to 3,812) at 48 h to 648 (range 109 to 5,473) at 7 days, 1,145 (range 162 to 6,268) at 42 days and 1,958 (range 344 to 9,632) at 140 days. Patients with anterior infarction had significantly lower counts (mean 277, range 78 to 2,708; n = 11) compared with those with inferior infarction (mean 2,172, range 897 to 3,812; n = 9) at 48 h (p < 0.05). There was no significant difference in counts between patients with anterior (mean 1,051, range 212 to 6,268) and inferior (mean 1,321, range 162 to 3,265) infarction after 42 or after 140 days (anterior: mean 1,655, range 344 to 9,632; inferior: mean 2,588, range 1,700 to 5,767). CONCLUSIONS: These data suggest that after anterior myocardial infarction there is impaired cardiac parasympathetic function that improves within 6 weeks, whereas in inferior infarction there is relative preservation of cardiac parasympathetic function.

Adult↗

Exercise tolerance in angina is improved by mivazerol--an alpha 2-adrenoceptor agonist.

In a double-blind, placebo-controlled, randomized trial of treadmill exercise tolerance in six patients with chronic stable angina, intravenous mivazerol 1 microgram, 2 micrograms, and 3 micrograms/kg increased the time to onset of angina by 39%, 48%, and 76%; the time to 1-mm ST depression by 36%, 76%, and 104%; and total exercise duration by 15%, 23%, and 30%, respectively. In a subsequent double-blind, placebo-controlled, randomized trial involving a further 12 patients, a single oral dose of mivazerol of 800 micrograms, 1200 micrograms, and 1600 micrograms increased the time to onset of angina by 4%, 11%, and 30%; the time to 1-mm ST depression by 33%, 43%, and 53%; and the total exercise duration by 10%, 18%, and 23%, respectively. Mivazerol is an imidazole derivative with agonist properties at the alpha 2-adrenoceptor and appears to be an effective antianginal. Mivazerol may improve exercise performance by attenuating the effects of exercise-induced sympathetic nervous system activity on the ischemic myocardium.

Administration, Oral↗

Difficulty as a determinant of cardiovascular response: moderating effect of instrumentality in an alleviation paradigm.

Female subjects performed 40 trials of an easy or difficult digit-recognition task while being exposed to intermittent presentations of a noxious noise. Half (high instrumentality) were told that, if they performed well, there was a high chance that they would work without noise in a subsequent trial period. The rest (low instrumentality) were told that, if they performed well, there was a low chance that they would work without noise in the subsequent trial period. Thus, a good performance insured either a high or low probability of alleviating the aversive stimulus. Results indicated that systolic responsiveness was proportional to task demand when the instrumentality of alleviative behavior was high, but low under both task conditions when the instrumentality of alleviative behavior was low. Reaction time and performance data were generally consistent with the view that these effects were due to group differences in task engagement, or 'active coping'. The main findings conceptually replicate and extend results from two previous studies that crossed difficulty and instrumentality manipulations. They also call further into question familiar theoretical conceptions that intimate direct effects of incentive value and perceived control on cardiovascular reactivity.

Adaptation, Psychological↗

Blood pressure responses and incentive appraisals as a function of perceived ability and objective task demand.

This experiment examined the role perceptions of ability may play in determining the impact of task demand on cardiovascular responses indicative of active coping. Subjects first performed a scanning task and received feedback indicating that they had either low or high scanning ability. They then were presented with the opportunity to earn one of two incentives by attaining either an objectively low or objectively high standard of performance on a second scanning task. Immediately prior to and during the 1-min performance period, systolic and diastolic blood pressure responses were greater in the difficult standard condition than in the easy standard condition for those who received high-ability feedback but were somewhat diminished in the difficult standard condition as compared with the easy standard condition for those who received low-ability feedback. Whereas high-ability subjects tended to have less pronounced pressor responses than did low-ability subjects when the second task was objectively easy, they had more pronounced pressor responses than low-ability subjects when the second task was objectively difficult. Analysis of goal attractiveness ratings obtained just prior to task performance showed a general correspondence between subjects' anticipatory blood pressure responses and their appraisals of the incentives. Implications for several lines of investigation are discussed.

Adaptation, Psychological↗

Does physiologic gastroesophageal reflux affect heart rate or rhythm?

An acid-induced, cholinergic esophagocardiac reflex has been observed in humans. Decrements of heart rate can be induced by direct intraesophageal acid infusion. To ascertain whether this reflex occurs during physiologic reflux and whether stimulation of this reflex might precipitate dysrhythmias, a prospective study was performed. Twenty consecutive patients referred for 24-h ambulatory intraesophageal pH monitoring underwent simultaneous 24-h cardiac holter monitoring. Analyses were performed only on gastroesophageal reflux episodes which resulted in esophageal acidification to pH < 4 for 60 sec or more. Evaluable cardiac holter variables included premature ventricular contractions (PVCs), premature atrial contractions (PACs), tachycardia (heart rate, > 110/min), and bradycardia (heart rate, < 50/min). Measurements were made for 60 sec before and after onset of esophageal acidification. No relationship was noted between physiologic episodes of gastroesophageal reflux and PVCs (p = 0.29), PACs (p = 0.12), tachycardia (p = 0.33), or bradycardia (p = 0.78). No statistically significant correlations were noted between total 24-h acid exposure (minutes/24h) and mean heart rate (p = 0.07), number of PVCs (p = 0.41), and number of PACs (p = 0.39). Analyses of reflux episodes lasting more than 5 min with intraesophageal pH < 2 also failed to show changes in pulse rate (p = 0.22). Physiologic gastroesophageal reflux does not induce changes in heart rate or rhythm in humans. It is possible that esophagocardiac reflexes noted during intraesophageal acid infusion are related to lower pH values or to other factors such as osmolarity, temperature, or site-specific receptors.

Adult↗

Interactive effects of difficulty and instrumentality of avoidant behavior on cardiovascular reactivity.

College-aged subjects performed 35 trials of an easy or difficult digit-recognition task. Half were told that a good performance would ensure a high chance of avoiding a blast of noise, and half were told that a good performance would ensure a low chance of avoiding the noise. Results indicated that heart rate and systolic blood pressure reactivity were higher in the difficult condition than in the easy condition only when the probability of avoiding the noise (given success) was high. When the probability of avoiding the noise (given success) was low, heart rate and systolic responsivity were low regardless of task difficulty. It also was found that (1) performance quality was poorer overall among difficult subjects than among easy subjects, and (2) that the difference in performance quality between the easy and difficult groups was somewhat (not significantly) greater in the low-probability conditions than in the high-probability conditions. Major findings are considered in terms of Obrist's reasoning regarding the psychophysiological consequences of active coping and a motivational model by Brehm, which specifies conditions under which individuals will be more and less task engaged.

Adaptation, Psychological↗

Obstructive jaundice secondary to primary biliary involvement with Hodgkin's disease.

A 41-yr-old man presented with jaundice, night sweats, and weight loss. The patient had been on phenytoin for seizure disorder. The drug was discontinued, and a diminution of bilirubin and transaminases occurred over several weeks. Percutaneous liver biopsy revaled cholestasis at the time of maximal hyperbilirubinemia. Recurrent jaundice ensued several weeks later, and an ERCP revealed a common bile duct lesion. Laparotomy revealed Hodgkin's disease involving the common bile duct and periportal node. This cause represents the first report of extrahepatic biliary obstruction from Hodgkin's disease.

Adult↗