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Biomedical subjects

B J Ward

Publications and source records attributed to B J Ward.

At least 37 records · Page 2Linked to original sources
PubMed1998

A beta-actin isotype is present in rat cardiac endothelial cells but not in cardiac myocytes.

OBJECTIVE: Active constriction in cardiac capillary endothelial cells (CCECs) is controversial. It is thought by many researchers that CCECs are not actively involved in constriction; others believe that these cells do contribute some of the force required for capillary constriction. Because actin is a major component of most contractile mechanisms responsible for changing cell shape, we compared two probes as potential monitors of actin distribution in CCECs in situ. METHODS: We used SDS-PAGE, Western blotting, electron microscopy, conventional epifluorescence and confocal microscopy to evaluate an antibody against non-muscle beta-actin and fluorescently labeled phalloidin to detect actin in CCECs. RESULTS: Fluorescently labeled phalloidin detected actin in cardiac muscle and faintly in CCECs. The antibody probe detected non-muscle beta-actin CCECs. However, this actin isotype did not occur in cardiac myocytes. In endothelial cells non-muscle beta-actin was concentrated at the cell periphery, and arranged as bundles of fibers, not as typical stress fibers. CONCLUSIONS: Phalloidin is not suitable as a probe to monitor actin distribution in CCEC's in situ. The antibody is a potentially useful tool in monitoring the actin cytoskeleton and determining the capacity of CCECs for active vasoconstriction in vivo. Non-muscle beta-actin in CCECs is arranged in filament bundles which are not typical stress fibers.

Actins↗
PubMed1997

Diabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: The Cardiovascular Health Study.

This report describes the relation among diabetes, blood pressure, and prevalent cardiovascular disease, and echocardiographically measured left ventricular mass and filling (transmitral valve flow) velocities in the Cardiovascular Health Study, a cohort of 5201 men and women > or = 65 years of age. Ventricular septal and left posterior wall thicknesses were greater in diabetic than in nondiabetic subjects, showing a significant linear trend (p = 0.025 for ventricular septal thickness in both sexes combined, p = 0.002 for posterior wall thickness) with increased duration of diabetes. Increased wall thickness of the ventricular septum or the left posterior wall was not associated with prevalent coronary heart disease (CHD) in the cohort. Increased left ventricular mass was associated with diabetic persons not reporting CHD and with all subjects with CHD regardless of glucose tolerance status. After adjusting for body weight, blood pressure, heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as measured by glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination) remained an independent predictor of increased left ventricular mass among men and women (174.2 gm in diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in normal women, p = 0.043 for both sexes combined). Both early and late diastolic transmitral peak flow velocities were higher with increased duration of diabetes, but the calculated ratio of the early peak flow velocity to the late velocity (E/A ratio) did not differ significantly between subjects with historical diabetes and those with normal fasting glucose (both genders combined, p = 0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination were significant independent predictors of the late transmitral peak flow velocity and its integrated flow-velocity curve but not for the integral of the early peak flow velocity or the E/A ratio. Diabetes is associated with abnormal left ventricular structure and function in elderly persons. This association persists after adjustment for body weight, blood pressure, heart rate, and reported coronary or cerebrovascular disease.

Aged↗
PubMed1997

Structural changes in the cardiac microvasculature of the rat in response to acute high glucose levels: a comparison with diabetes.

OBJECTIVE: Isolated rat hearts were used to determine whether structural changes in the coronary microcirculation caused by diabetes mellitus occur soon after the onset of hyperglycemia and whether early changes might be reversed by return to normoglycemic conditions. METHODS: Three experimental groups of hearts were used. The perfusate was Krebs-Henseleit medium with the addition of (a) 25 mmol/L glucose for 60 minutes, (b) as (a) followed by 5 mmol/L glucose for 30 minutes, and (c) hearts from diabetic rats perfused for 15 minutes. All the hearts were fixed and processed for electron microscopy. Measurements were made of various capillary dimensions and basal lamina thickness. RESULTS: The high glucose concentration caused an overall reduction in capillary dimensions which was partly reversed by reperfusion with 5 mmol/L glucose. Diabetic hearts showed enlarged whole capillary and luminal area and thinning of the endothelial cells without any change in cross-sectional area. Endothelial gaps, consistent with increased permeability, were observed in the high glucose group but not in diabetic hearts. The basal lamina was thickened in all three experimental groups compared with controls. CONCLUSIONS: The results show that morphological changes in the microcirculation occur much earlier than was previously thought and, with the possible exception of the basal lamina thickening may be reversible.

Animals↗
PubMed1996

Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus.

BACKGROUND: We investigated an outbreak of acute clinical illness among 19 people who ate raw fish (sashimi) prepared from the white sucker, Catostomus commersoni, caught in a river north of Montreal, Canada. METHODS: We collected epidemiological, clinical, laboratory, and serological data on 19 individuals who ate the sashimi and six who did not. Because of the suggestive clinical picture, we set out to recover helminth parasites from uneaten fish. FINDINGS: The illness consisted of persistent upper abdominal pain, low grade fever, high blood eosinophil concentrations, and raised liver enzymes. After 10 days, opisthorchild-like eggs were found in stools. Symptoms persisted for 3 days to 4 weeks without treatment, but responded rapidly to praziquantel therapy. Necropsy of golden hamsters infected with metacercariae from uneaten fish revealed adult flukes identified as Metorchis conjunctus. INTERPRETATION: We describe an acute illness caused by the North American liver fluke M conjunctus. This is a new human disease and is the first report of a common-source outbreak of an acute illness caused by liver flukes of the family Opisthorchiidae.

Adult↗
PubMed1996

Retinol (vitamin A) supplements in the elderly.

Aging is associated with many changes in epithelial tissues, immune function and haematopoiesis-myelopoiesis. There is increasing evidence that retinoids can significantly influence some of these changes. Retinoids may also have anticancer effects and protect against age-associated conditions such as macular degeneration. However, retinol (vitamin A) can be toxic when taken in excess and the elderly may be at particular risk for hypervitaminosis A. Evaluation of elderly people ingesting significantly more or less than the recommended daily intake of retinol requires an understanding of the biology of retinoids and consideration of the relative risks and benefits of supplementation.

Aged↗
PubMed1996

Asthma and its association with cardiovascular disease in the elderly. The Cardiovascular Health Study Research Group.

Cardiovascular disease (CVD) is more prevalent in elderly than in middle-aged patients. Symptoms such as intermittent wheezing with dyspnea may then be due to either CVD or asthma. The objective of this study was to determine the prevalence and correlates of asthma in the elderly and their associations with CVD and CVD risk factors. A community sample of 5201 elderly persons from the Cardiovascular Health Study was asked if they had a physician diagnosis of asthma, and multiple cardiovascular risk and disease variables were measured. Six percent of the participants (309) recalled a history of asthma, and half of these were never smokers. Thirty percent of those with asthma were currently taking a bronchodilator, 14% inhaled steroids, and 10% oral prednisone. Men and women with asthma who were cigarette smokers were more likely to report a concurrent diagnosis of congestive heart failure than smokers without asthma (p = .04). However, when we determined the independent CVD correlates of asthma in this cohort, controlling for smoking status, age, gender, and diagnoses of chronic bronchitis and emphysema, only higher levels of high-density lipoprotein cholesterol (HDL-C) and higher plasma fibrinogen levels were significantly associated with asthma. It was concluded that asthma is as prevalent in the elderly as in middle-aged persons and is associated with higher HDL-C and higher fibrinogen levels, but not with prevalent cardiovascular disease.

Aged↗
PubMed1995

The influence of hypoxia on transvascular leakage in the isolated rat heart: quantitative and ultrastructural studies.

1. The multiple indicator dilution method was used to study the transvascular movement of gamma-globulin, bovine serum albumin, insulin and cyanocobalamin in the isolated rat heart. 2. Perfusion of the heart with well-oxygenated solution for 75 min (constant flow) did not produce a significant change either in the total area under the dilution curve or the 'leakage index' (an arbitrary measure of transvascular flux) for all the tracers. 3. Perfusion of the heart with hypoxic solution produced a significant increase in leakage of gamma-globulin of 38.6 +/- 18, 48.5 +/- 17.6, 60.5 +/- 24 and 58 +/- 20% after 15, 30, 45 and 60 min, respectively, compared with the well-oxygenated equilibration period. Permeability- surface area products (PS) for the smaller diffusible solutes, therefore, could not be estimated. 4. The flux of albumin, insulin and cyanocobalamin in response to hypoxia was similar to that of gamma-globulin. 5. Ultrastructural examination of well-oxygenated hearts revealed that Monastral Blue-labelled albumin remained within the lumen and that endothelial integrity remained intact. 6. Conversely biopsies from hypoxic hearts showed that the labelled albumin had passed to the interstitium through gaps (approximately 3 microns) in venular endothelium. 7. The results showed that, in intact hearts, hypoxia produced gaps in the endothelium of venules and that these gaps could be the possible route for transvascular leakage of macromolecules.

Animals↗
PubMed1995

Measles, mumps, and rubella antibodies in children 5-6 years after immunization: effect of vaccine type and age at vaccination.

The levels of antibody against measles, mumps, and rubella were determined at 5-6 years postimmunization in 468 children vaccinated with two different trivalent vaccines. The proportions of children without detectable antibody levels were 12 and 3.6% for measles (p < 0.001), 14.9 and 7% for mumps (p = 0.006), and 3.3 and 3.1% for rubella (p = 0.88), respectively, in MMR II and Trivirix recipients. A higher proportion of those vaccinated at younger ages had undetectable or low levels of measles antibody. These data indicate that a large proportion of children vaccinated under routine conditions do not have detectable measles and mumps antibody.

Age Factors↗
PubMed1995

Endothelial cell "swelling" in ischaemia and reperfusion.

The endothelial cells of cardiac capillaries have been reported to swell as a result of ischaemia and reperfusion although there has not previously been any attempt to quantify this observation. Whole capillary and luminal cross-sectional areas, abluminal and luminal membrane lengths were measured from electron micrographs of isolated rat hearts subjected to 30 or 60 min of global ischaemia both with and without subsequent reperfusion for 15 min. All the experimental protocols resulted in capillaries which appeared swollen by electron microscopy. Measurements, however, showed that, after 30 and 60 min ischaemia, this appearance was brought about by a decrease in both whole capillary and luminal area causing an increase in the distance between abluminal and luminal membranes without any change in the endothelial cell cross-sectional area. Reperfusion after 30 min caused an increase in capillary dimensions to larger than control levels. Only after 60 min ischaemia with reperfusion were the cells really swollen with an increase in cross-sectional area. We conclude that (1) we may be observing capillary constriction and (2) the word "swelling" in this context should be used with caution.

Animals↗
PubMed1995

Measles vaccine efficacy during an outbreak in a highly vaccinated population: incremental increase in protection with age at vaccination up to 18 months.

During a large measles outbreak in Quebec City in 1989, two investigations conducted in parallel evaluated the relative risk of measles and measles vaccine effectiveness with respect to age at vaccination. The study was a school-based case-control study including 563 cases and 1126 classmate controls. The second was a cohort study of the siblings of school cases including 493 siblings aged between 1 and 19 years. The relative risks (RR) of measles were similar in both settings and the trend towards increased vaccine efficacy with increasing age at vaccination was highly significant (P < 0.001). Vaccine efficacy rose from 85% in children vaccinated at 12 months of age to > or = 94% in those vaccinated at 15 months and older. Even for children vaccinated at or after 18 months of age, the RR of measles was reduced when compared with children vaccinated between 15 and 17 months of age (RR 0.61, CI 95% 0.33-1.15). Small changes in the timing of initial measles vaccination can have a major impact on vaccine efficacy.

Age Distribution↗
PubMed1995

Cellular immunity in measles vaccine failure: demonstration of measles antigen-specific lymphoproliferative responses despite limited serum antibody production after revaccination.

Measles antigen-specific immune responses were evaluated 1 and 6 months after revaccination in 60 previously vaccinated subjects (9.4 +/- 3.4 years of age) who had either undetectable or low plaque reduction neutralization (PRN) titers (< 200). PRN titers were increased in all subjects at 1 month (590 +/- 61; range, 129-2513) but fell again in 66% of subjects by 6 months (214 +/- 29; range, 30-794). At 6 months, 23 (38%) had subprotective (< 120) or borderline (< 200) PRN titers. Lymphoproliferative responses to measles virus antigens were low overall before revaccination (mean stimulation index [SI], 2.6 +/- 0.4; range, 0.5-13.5) but were readily detectable at 1 (SI, 145.8 +/- 2.6; range, 1.4-80) and 6 months after revaccination (SI, 9.4 +/- 1.8; range, 1.1-87). Before revaccination, 10 of the subjects (50%) with low positive PRN titers had SIs > or = 3. At 6 months after revaccination, 18 subjects (78%) with PRN titers < or = 200 had SIs > or = 3. These data suggest that cellular responses to measles virus may be better sustained than antibody titers after vaccination and revaccination in some subjects.

Antibodies, Viral↗
PubMed1994

Attitudes among NHS doctors to requests for euthanasia.

OBJECTIVES: To explore NHS doctors' attitudes to competent patients' requests for euthanasia and to estimate the proportion of doctors who have taken active steps to hasten a patient's death. DESIGN: Anonymous postal questionnaire, with no possibility of follow up. The survey was conducted from December 1992 to March 1993. SUBJECTS: All (221) general practitioners and 203 hospital consultants in one area of England. RESULTS: 273 doctors responded to a question on whether a patient had ever asked them to hasten death. Of these, 163 had been asked to; 124 of these had been asked to take active steps to hasten death; 38 of 119 (32%) of these had complied with such a request (95% confidence interval 23% to 40%). This proportion represented 12% of all those who returned a completed questionnaire and 9% of all those who had been sent a questionnaire (95% confidence interval 6.3% to 11.7%). A larger proportion of the respondents (142/307 (46%)), however, would consider taking active steps to bring about the death of a patient if it was legal to do so. CONCLUSIONS: Many doctors face difficult decisions about euthanasia. For the benefit of both patients and doctors euthanasia should be discussed more openly.

Advance Directives↗
PubMed1994

The endothelial vesicular system in cardiac capillaries subjected to hypoxia.

The precise role of the numerous plasmalemmal vesicles in capillary endothelia is unclear. They undoubtedly play a part in macromolecular transport across the endothelium but, as serial section studies have shown the vast majority of vesicles to be attached to either the luminal or abluminal membrane, it is possible that transport is not their primary role. The suggestion that vesicles form a membrane reserve was explored in capillaries of isolated perfused rat hearts subjected to hypoxia, which has been reported to cause endothelial cell swelling. Luminal, "cytoplasmic," and abluminal vesicles were counted and their diameters measured in well-oxygenated and hypoxic hearts and a number of other endothelial cell parameters were measured. Total capillary and luminal cross-sectional area and luminal and abluminal membrane length decreased in hypoxia. There was no change in endothelial cell cross-sectional area despite an appearance of swelling. The numbers of abluminal and "cytoplasmic" vesicles did not change as a result of hypoxia. Luminal vesicles were, however, reduced in number but increased in size and density. The results are consistent both with the theory that the vesicles are a membrane reserve and that they may be present in order to expose membrane enzymes and receptors on the cell surface or internalise them in response to a variety of external stimuli.

Animals↗
PubMed1994

Pathogenesis of measles virus infection: an hypothesis for altered immune responses.

Measles virus causes a severe systemic illness. The rash occurs simultaneously with the onset of the effector phase of the antiviral immune response and substantial evidence of immune activation. This immune response is effective in clearing virus and in establishing long-term resistance to reinfection but is associated with immune suppression, autoimmune encephalomyelitis, and increased susceptibility to secondary infections. This apparent paradox may be explained in part by preferential long-term activation of type 2 CD4+ T cells by measles virus infection. Preferential stimulation of type 1 CD4+ T cells by inactivated virus vaccines is hypothesized to play a role in subsequent development of atypical measles.

Antibodies, Viral↗
PubMed1994

Relation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group.

BACKGROUND: Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease. METHODS AND RESULTS: We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P < .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (> or = 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P < .0001). CONCLUSIONS: These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease.

Aged↗