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Biomedical subjects

J Higgins

Publications and source records attributed to J Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1992

Effects of antianginal therapy on left ventricular systolic and diastolic performance: comparison of the response to bepridil, propranolol, and diltiazem.

Abnormalities of left ventricular (LV) systolic performance develop during exercise in patients with coronary artery disease (CAD) as a result of ischemia-induced regional wall motion abnormalities. Like patients with hypertension and those with hypertrophic cardiomyopathy, patients with CAD display abnormalities of LV diastolic performance under basal conditions in the absence of ischemia. The purpose of these studies was to compare the effects of bepridil versus those of propranolol or diltiazem in patients with exertional angina pectoris. LV systolic and diastolic performance were assessed at rest and during peak upright bicycle exercise by first-pass radionuclide ventriculography. Compared with propranolol, bepridil increased exercise capacity, cardiac output, and stroke volume and decreased systemic vascular resistance. Compared with diltiazem, bepridil increased exercise capacity, peak filling rate, and early diastolic filling fraction and decreased systemic vascular resistance, heart rate, time to peak filling rate, and atrial filling volume. Bepridil therapy is associated with improved exercise capacity and decreased anginal frequency and nitroglycerin consumption. In addition, its use is accompanied by favorable changes in LV systolic and diastolic function at rest and during exercise. These changes are consistent with benefits resulting from resolution of myocardial ischemia as well as from positive lusitropic effects of bepridil on the ventricular myocardium.

Angina Pectoris↗
PubMed1992

Menopausal bone loss is partially regulated by dietary intake of vitamin D.

Five years ago we reported results from a cross-sectional study of the effect of nutritional factors on calcium-regulating hormones and bone loss in perimenopausal women. We found an inverse correlation between serum 25-hydroxyvitamin D (25OHD) and immunoreactive parathyroid hormone (PTH), and we postulated that over time, women with lower 25OHD would lose more bone because of increased bone remodeling induced by secondary hyperparathyroidism. We have followed 38 of these women for 5 years. Twenty-two have gone through menopause and we are reporting observations on these 22 subjects. Bone mineral analysis was performed twice a year at the distal and mid-radius using single-photon absorptiometry. The slope of the bone mineral content curve was calculated by least squares. Bone loss increased within 6 months of the rise in serum follicle stimulating hormone (FSH) to greater than 40 mIU/ml. We continued to see a negative correlation between 25OHD and PTH (r = -0.450, P = 0.03). Premenopause, PTH was negatively correlated with the proximal bone mineral content (PBMC) slope (-0.604, P = 0.002). The distal bone mineral content (DBMC) 5-year slope was correlated with dietary vitamin D (r = 0.509, P = 0.02), the higher the intake, the less negative the slope. The 5-year PBMC slope was negatively correlated with serum osteocalcin (OC) levels (r = -0.382, P = 0.08). Before menopause, the change in PBMC was positively correlated with OC (r = 0.450, P = 0.03). Postmenopause, the correlation with DBMC slope was negative (r = -0.506, P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D 2↗
PubMed1992

Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis.

Rats were exposed to saline or cadmium chloride (CdCl2) at 25, 100, or 400 micrograms/kg body weight by intratracheal instillation. At 3, 7, 14, and 28 days after exposure five animals/treatment were euthanized, the lungs were lavaged, and bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, N-acetylglucosamindase (NAG), and cell number, type, and viability. Lung hydroxyproline concentration was characterized as a marker of lung collagen. Alveolar macrophages (AM) obtained in BALF were cultured and the release of fibronectin and TNF was determined. Lung tissue was examined microscopically at 28 and 90 days after exposure. Exposure to CdCl2 resulted in lung injury and inflammation demonstrated by increases in BALF LDH, total protein, NAG, and inflammatory cells. AM TNF release was not significantly changed by CdCl2 treatment. All doses of CdCl2 stimulated AM fibronectin secretion, a response which persisted throughout the 28-day postexposure period examined. Pulmonary fibrosis was demonstrated biochemically and/or histologically (trichrome staining tissue) at all CdCl2 dose levels. The association of CdCl2-induced AM fibronectin release with lung fibrosis confirms and extends previous observations relating AM-derived fibronectin to the development of interstitial lung disease and provides further evidence that the persistent increase in AM fibronectin release represents an early indicator of fibrosis.

Animals↗
PubMed1992

Interaction of acute feline herpesvirus-1 and chronic feline immunodeficiency virus infections in experimentally infected specific pathogen free cats.

Cats with or without chronic feline immunodeficiency virus (FIV) infection were exposed to feline herpesvirus, type 1 (FHV-1). FIV infected cats became sicker than non-FIV infected cats and required more supportive treatment. However, there were no differences in the length of their illness or in the levels and duration of FHV-1 shedding. FHV-1 infection caused a transient neutrophilia at Day 7 with a rapid return to preinfection levels. The neutrophilia coincided with a transient lymphopenia that was accompanied by a decline in both CD4+ and CD8+ T-lymphocytes. A brief decrease in the CD4+/CD8+ T-lymphocyte ratio occurred at Day 14 in both FIV infected and non-infected cats. This decrease was mainly the result of an absolute and transient increase in CD8+ T-lymphocytes. CD4+ and CD8+ T-lymphocyte numbers and CD4+/CD8+ T-lymphocyte ratios returned to baseline within 4-8 weeks in both FIV infected and non-infected cats. FIV infected cats produced less FHV-1 neutralizing antibodies during the first 3 weeks of infection than non-FIV infected animals. The IgM FHV-1 antibody response was depressed in FIV infected cats whereas the IgG antibody response was unaffected. FHV-1 infection evoked a comparable transient loss of lymphocyte blastogenic responses to concanavalin A and pokeweed mitogen in both FIV infected and non-infected cats. However, response to pokeweed mitogen took longer to return to normal in FIV infected animals. Lymphocytes from FIV infected cats had a greater and more sustained proliferative response to FHV-1 antigen than non-FIV infected cats. The ongoing IgG antibody response to FIV was not affected by FHV-1 infection.

Acute Disease↗
PubMed1992

Effects of fosinopril on cardiac function in patients with hypertension. Radionuclide assessment of left ventricular systolic and diastolic performance.

Numerous pharmacologic agents are capable of lowering the blood pressure of hypertensive patients; however, each drug has a characteristic side effect profile and effect on cardiac performance. In this study, the hemodynamic effects of the angiotensin converting enzyme inhibitor fosinopril were assessed at rest and at peak upright bicycle exercise by first-pass radionuclide cineangiography in 12 patients with essential hypertension. Fosinopril reduced blood pressure at rest in the seated position from 152/101 to 131/85 mm Hg (P less than .01) and at peak exercise from 206/103 to 184/91 mm Hg (P less than .01). Fosinopril therapy was associated with an increase in stroke volume and cardiac output and a decrease in systemic vascular resistance at rest and during peak exercise. Both peak ejection rate and peak filling rate increased significantly at rest during fosinopril therapy. The unique cardiotropic response to fosinopril may reflect its effects on the myocardial renin-angiotensin system, and suggests that this agent may offer a therapeutic advantage compared with other angiotensin converting enzyme inhibitors.

Adolescent↗
PubMed1992

Comparison of the cardiac and hemodynamic effects of lisinopril and atenolol in patients with hypertension: therapeutic implications.

The antihypertensive and hemodynamic effects of lisinopril and atenolol were evaluated in 21 patients with mild-to-moderate essential hypertension. Left ventricular systolic and diastolic performances were assessed prior to and following treatment by first-pass radionuclide cineangiography at rest and during peak upright bicycle exercise. Both lisinopril and atenolol treatment significantly reduced the blood pressure. Lisinopril therapy was associated with a reduction in systemic vascular resistance and left ventricular end-diastolic and end-systolic volumes but no change in stroke volume, cardiac output, peak ejection rate, peak filling rate, time to peak ejection rate, or time to peak filling rate. In contrast, atenolol therapy was associated with an increase in end-diastolic volume and stroke volume but no change in cardiac output; the left ventricular peak ejection and peak filling rates were decreased by atenolol treatment. Although both lisinopril and atenolol each significantly reduced the blood pressure, lisinopril had no effect on left ventricular systolic or diastolic performance; in contrast, atenolol decreased both systolic and diastolic parameters of ventricular performance. Left ventricular function may be affected in significantly different ways despite apparent similarities in blood pressure control in patients who respond to angiotensin converting enzyme inhibition or beta-adrenergic receptor blockade. Differences in hemodynamic response to an antihypertensive agent may be important in the selection of a drug for the treatment of subsets of patients with cardiac function abnormalities.

Adult↗
PubMed1992

Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia.

BACKGROUND: The effect on colonic cell proliferation of poligeenan, a nongenotoxic polysaccharide that induces colon tumors in rats, was compared with guar gum and carrageenan. EXPERIMENTAL DESIGN: Fischer 344 rats were fed a basal diet supplemented with carrageenan and poligeenan fibers for up to 91 days. The quantitative levels of proliferation, location of the proliferating cells, and the ability of the mucosa to readapt by removing the experimental fibers from the diet were tested. RESULTS: The mucosal epithelium exhibited a 5-fold increase in thymidine kinase activity in both the carrageenan and poligeenan groups. Proliferating cells appeared at the luminal surface only in the poligeenan-treated rats, and the number of proliferating cells in the upper third of the crypt increased 35-fold. A second and third set of animals were fed one of the three test diets for either 28 or 64 days, followed by a 28-day recovery period. Proliferation in the guar- and carrageenan-treated groups returned to basal levels. In poligeenan-treated rats, thymidine kinase levels, and proliferating cells in the upper third of the crypt remained 2- and 11-fold, respectively, above controls. CONCLUSIONS: The difference in recovery time between the poligeenan group and the others, and the luminal location of proliferating cells may prove useful as markers in understanding early events in the carcinogenic process induced by a nongenotoxin.

Administration, Oral↗
PubMed1992

Study of patients who chose private health care for treatment.

A questionnaire survey was carried out in 1991 in Wessex regional health authority of a sample of private patients having inpatient treatment in eight independent hospitals, and in pay beds in three National Health Service hospitals. A total of 649 patients replied (response rate 60.7%). Sixty respondents to the questionnaire were also interviewed. The aim of the study was to discover which groups of people chose private care rather than using the NHS, and why. In view of the current emphasis on consumerism in health care, the study also aimed to examine how patients exercised choice in a market situation and how well informed they were when they did so. The questionnaire asked about the role and influence of the general practitioner in patients' decisions to use private health care for treatment. The largest group of respondents were in the 36-50 years age group (34.2%). Of the respondents 59.9% were women, 54.1% were in social class 2 and 77.3% were married or cohabiting. The most common reason for using private health care for treatment was to avoid NHS waiting lists (61.5% of respondents) although they did not necessarily know how long that wait would have been. Patients sought their general practitioner's opinion about whether to use private health care in 187 cases (28.8%). The majority of the 649 patients (71.2%) had decided to use private health care before consulting the general practitioner. However, patients were influenced by their general practitioner's advice on the choice of consultant and choice of hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Private patients' perceptions of nursing practice in the National Health Service.

A study of private patients (n = 649) was carried out in Wessex Region in January 1991 to discover why patients decide to go private rather than use the NHS for in-patient treatment. Relatively few patients complained of the attitudes of nurses in the NHS, but just over one third mentioned nursing as a significant problem in the NHS and, of this group, over half were critical of nurses' attitudes. Further analysis revealed that these perceptions were not based on direct experience (of those who said that nursing was a problem, only 5 per cent had been NHS in-patients since 1985), but alarm about the public image of nursing remains.

Adult↗
PubMed1991

Expanded clinical evaluation of lovastatin (EXCEL) study results: IV. Additional perspectives on the tolerability of lovastatin.

This randomized, double-blind, multicenter, diet-and-placebo-controlled study was designed to clarify the dose-response relationship of lovastatin therapy to lipid-modifying efficacy and drug-related adverse events. Exclusion criteria were minimized so that study patients were representative of the majority of patients with moderate hypercholesterolemia seen in medical practice. After 6 weeks on the American Heart Association Step 1 Diet, a total of 8,245 patients were randomly assigned to 48 weeks of treatment with diet and placebo or lovastatin at dosages of 20 or 40 mg once a day or 20 or 40 mg twice a day. All adverse events were monitored, with particular attention to evaluation of liver and muscle. Liver transaminase elevations suggestive of possible hepatotoxicity, defined as successive elevations in either aspartate transaminase or alanine aminotransferase greater than 3 times the upper limit of normal, occurred in equal numbers of placebo and lovastatin 20 mg/day treated patients (0.1%). The frequencies were higher in lovastatin 40 mg/day and 80 mg/day patient groups (0.9 and 1.5%, respectively). No patient was diagnosed as having clinically symptomatic hepatic dysfunction. Creatinine kinase (CK) elevations above the upper limit of normal occurred frequently in placebo- (29%), as well as lovastatin-treated patients (29-35%), and muscle symptoms were reported with similar frequency in all groups (7-9%). The combination of muscle symptoms with marked CK elevations (greater than 10 times the upper limit of normal) was seen in only five patients: one in a 40 mg/day dose group and four in the 80 mg/day dose group. No patient developed rhabdomyolysis. The incidence of clinical and laboratory adverse events requiring discontinuation was 6% for the placebo group and from 7% (20 mg/day) to 9% (80 mg/day) for lovastatin treatment groups. No new types of adverse experiences related to lovastatin treatment were reported. Lovastatin, as an adjunct to diet for the reduction of elevated LDL cholesterol, was generally very well tolerated.

Alanine Transaminase↗
PubMed1991

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.

In the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia. Patients were randomly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48 weeks. Lovastatin produced sustained, dose-related (P less than .001) changes as follows (for dosages of 20 to 80 mg/d): decreased low-density lipoprotein-cholesterol level (24% to 40%), increased high-density lipoprotein-cholesterol level (6.6% to 9.5%), decreased total cholesterol level (17% to 29%), and decreased triglyceride level (10% to 19%). The National Cholesterol Education Program's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L (160 mg/dL) was achieved by 80% to 96% of patients, while the less than 3.36 mmol/L (130 mg/dL) goal was achieved by 38% to 83% of patients. The difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small, ranging from 1.2% at 20 mg twice daily to 1.9% at 80 mg/d. Successive transaminase level elevations greater than three times the upper limit of normal were observed in 0.1% of patients receiving placebo and 20 mg/d of lovastatin, increasing to 0.9% in those receiving 40 mg/d and 1.5% in those receiving 80 mg/d of lovastatin (P less than .001 for trend). Myopathy, defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal, was found in only one patient (0.1%) receiving 40 mg once daily and four patients (0.2%) receiving 80 mg/d of lovastatin. Thus, lovastatin, when added after an adequate trial of a prudent diet, is a highly effective and generally well-tolerated treatment for patients with moderate hypercholesterolemia.

Adult↗
PubMed1991

Pulmonary response to inhaled silica or titanium dioxide.

The pulmonary response to mineral dust inhalation was investigated by characterizing markers of lung injury and inflammation, macrophage activation, dust clearance, and histopathology. Rats were exposed (6 hr/day x 5 days) to air or 50 mg/m3 crystalline silica (SiO2) or titanium dioxide (TiO2). At 7, 14, 28, and 63 days after exposure, bronchoalveolar lavage fluid (BALF) was analyzed for lactate dehydrogenase (LDH), total protein, and N-acetylglucosaminidase, as well as cell number, type, and viability. Alveolar macrophages (AM) obtained in BALF were cultured with or without LPS and release of interleukin-1 (IL-1) and fibronectin was determined. Histopathology was conducted at 28 and 63 days. The exposure protocol resulted in 1.8-1.9 mg of mineral dust being deposited in the pulmonary region. Clearance of SiO2 was significantly less than TiO2. SiO2 increased BALF neutrophils (Days 14, 28, and 63), total protein (Days 28 and 63), and LDH and lymphocytes (Day 63). SiO2 increased AM-derived fibronectin release (Day 63) and LPS-induced IL-1 release (all time points), but not spontaneous release of IL-1. TiO2 did not change BALF biochemical or cellular parameters or AM secretory activity. Histopathology revealed minimal interstitial inflammation with SiO2 and no significant response in control or TiO2 rats. These results demonstrate the pulmonary response to inhaled SiO2 can be differentiated from the relatively innocuous TiO2 by changes in BALF markers of injury and inflammation further supporting the use of BALF analysis to make relative assessments of pulmonary toxicity. The stimulation of macrophage fibronectin release by the fibrogenic dust SiO2 and not TiO2 is consistent with a role for this glycoprotein in lung injury and repair. Last, the early and persistent effect of SiO2 on LPS-induced AM IL-1 release indicates this response may represent a sensitive early marker of dust-induced changes in the AM population.

Administration, Inhalation↗
PubMed1991

Nifedipine improves left ventricular function in patients with hypertension.

The effects of the nifedipine gastrointestinal therapeutic system (GITS) on blood pressure (BP), systemic vascular resistance (SVR), and left ventricular (LV) performance were determined in eight patients with essential hypertension. LV systolic and diastolic performance were assessed by first-pass radionuclide cineangiography at rest and during upright bicycle exercise after initial and long-term BP reduction. After initial treatment, end-diastolic volume (LVEDV) increased in association with an increase in stroke volume (SV), cardiac output (CO), and peak ejection rate. After long-term treatment, LVEDV decreased, SV and CO returned to pretreatment values, early diastolic filling fraction increased, and time to peak filling rate decreased. These hemodynamic changes are consistent with an initial predominant effect of vasodilation on LV function. With long-term treatment, the effects on LV diastolic performance are consistent with a positive lusitropic effect of nifedipine GITS. Nifedipine GITS is an effective agent for control of hypertension; its hemodynamic effects are consistent with both an effect on SVR due to decreased vascular smooth muscle contraction and a direct lusitropic effect on myocardial function.

Adult↗
PubMed1991

Development of simian immunodeficiency virus isolation, titration, and neutralization assays which use whole blood from rhesus monkeys and an antigen capture enzyme-linked immunosorbent assay.

Assays that use rhesus macaque whole blood and an antigen capture enzyme-linked immunosorbent assay for the simian immunodeficiency virus (SIV) p27 core protein were developed for the isolation of SIV from the blood of infected animals, the titration of infectivity of SIV inocula, and the quantitation of virus neutralizing antibodies in serum. These assays required small amounts of whole blood, were adaptable to a microtiter format, and used substrates mainly of rhesus macaque origin.

Animals↗
PubMed1991

The acetylator phenotypes of Saudi Arabians with coronary arterial atheroma.

The acetylator phenotypes were determined by means of a sulfamethazine test in 101 Saudi Arabian patients with authenticated coronary atheroma; 65 were found to be slow acetylators. This distribution of phenotypes is not significantly different from that in 220 controls, 148 of whom were slow acetylators. This finding makes it unlikely that compounds containing a primary aromatic amino or a hydrazino group are involved in the aetiology or pathogenesis of coronary atheroma.

Acetylation↗
PubMed1990

Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.

The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy.

Adult↗