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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 505 records · Page 28Linked to original sources
PubMed1985

Risk factors for ischaemic heart disease: the prospective phase of the British Regional Heart Study.

Risk factors for major ischaemic heart disease (acute myocardial infarction or sudden death) have been investigated in a prospective study of 7735 men aged 40-59 years drawn from general practices in 24 British towns. After a mean follow-up of 4.2 years, there have been 202 cases of major ischaemic heart disease. Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol, HDL-cholesterol and triglyceride concentrations, systolic and diastolic blood pressures, cigarette smoking, and body mass index are all associated with increased risk of ischaemic heart disease. Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease. All these factors were then considered simultaneously using multiple logistic models. Definite myocardial infarction on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease, after allowance for all other risk factors. Serum total cholesterol, blood pressure, and cigarette smoking each remained as highly significant independent risk factors whereas overweight, above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors. Men with and without pre-existing ischaemic heart disease were examined separately in the same way (using multiple logistic models). The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease, only age and serum total cholesterol remaining highly significant. Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease. Modification of these risk factors in the general population constitutes an important national priority.

Adult↗
PubMed1985

Biochemical and haematological response to alcohol intake.

In a clinical survey of 7735 middle-aged men, alcohol consumption has been related to 25 biochemical and haematological measurements obtained from a single blood sample. Most measurements showed some association with alcohol consumption, gamma-glutamyl transferase (GGT) being the most strongly associated. Lead, mean corpuscular haemoglobin (MCH), mean corpuscular volume, high-density lipoprotein-cholesterol (HDL-C), urate and aspartate transaminase also showed substantial associations with alcohol intake. Using a discriminant analysis technique, a simple score based on five variables (GGT, HDL-C, urate, MCH and lead) provided the best discrimination between heavy drinkers (e.g. more than three pints of beer daily) and occasional drinkers, but still failed to identify more than half of the heavy drinkers. This combined score may prove a useful measure of an individual's biochemical/haematological response to alcohol consumption for use in epidemiological and clinical studies of alcohol related disorders. The use of such indices should complement but not replace measures of alcohol intake derived from questionnaires.

Adult↗
PubMed1985

Mast cells and their degranulation in the Tsk mouse model of scleroderma.

The Tsk mouse is a genetically transmitted example of cutaneous fibrosis which has been compared with human scleroderma. During a systematic histopathological study of the Tsk mouse, both an increased number and an increased proportion of degranulated mast cells were observed. The consistent association of mast cells and fibrosis in scleroderma, graft-vs-host reactions (GVHR), and now the Tsk mouse raises the question of a pathogenetic role for mast cells in fibrotic disorders in general.

Age Factors↗
PubMed1985

Immunogenicity and antigenicity of immunoglobulins. XII. Intact light chain and heavy chain isotype-restricted Vk-associated epitopes.

Immunization with intact IgG has allowed the isolation of four hybridomas producing antibodies recognizing epitopes expressed within subpopulations of human kappa light chains unrelated to known polymorphisms (Km) and previously defined V-region subgroups. The V-region-associated epitopes recognized are conformation-dependent, being expressed on intact light chain but not on isolated VK or CK fragments. The frequency of expression within paraprotein panels of different heavy chain isotypes varied between individual antibodies. An epitope recognized by B2A6, expressed by greater than 85% IgGK paraproteins, was not represented in 16 IgM paraproteins tested, suggesting that association of VK with mu chains does not result in display of the epitope recognized, or alternatively, that selective association between VK and CH gene products occurs. These data contrast with the reactivity of other McAb for CK epitopes which were reactive with isolated CK fragments, and for all kappa-bearing paraproteins, regardless of heavy chain isotypes.

Antibodies, Monoclonal↗
PubMed1985

Modulation of in vitro cellular immune response by histamine agonists or antagonists in murine species.

The generation of secondary cytotoxic T-lymphocyte (CTL) responses in vitro toward allogeneic P815 mastocytoma cells were suppressed 60-80% when 10(-4) mol/l histamine, 10(-5) mol/l dimaprit (S-[3-(N,N-dimethylamino) propyl]isothiourea dihydrochloride) or 10(-5) mol/l impromidine were present in the culture. Three lines of evidence suggest this observation was a result of an active suppression mechanism and not a result of drug toxicity: Control level activity was obtained when Interleukin-2/T-cell growth factor (IL-2) containing supernatants were added to suppressed cultures. Removal of drug after incubation resulted in control level responses upon reculture. The addition of these H2 agonists to spleen cells from nonimmune animals did not affect the primary CTL response to P815. The effects of H1 and H2 antagonists were also tested in this model. The observed suppression was abrogated by the H2 antagonists cimetidine and mifentidine but not by the H2 antagonist ranitidine nor H1 antagonists, chlorpheniramine, pyrilamine or diphenhydramine. These results suggest regulation of CTL differentiation to alloantigens can be modulated by H2 reactive entities.

Animals↗
PubMed1985

B-cell lymphoma in two monogamous homosexual men.

Opportunistic infections and malignant neoplasms have been described in homosexual men in association with immunologic abnormalities. We observed the development of malignant B-cell lymphomas in two homosexual men who had had a monogamous relationship for two years. Patient 1 had an aggressive, monoclonal, small, noncleaved, non-Burkitt's lymphoma ("undifferentiated lymphoma"), associated with severe immunocompromise. Patient 2 manifested a monoclonal, small, cleaved, follicular center cell lymphoma, with a follicular pattern, two months later. No common acute infection was detected. Staining for Epstein-Barr nuclear antigen in malignant tissue was negative in the second patient. However, the possibility of a transmissible agent as a causative factor cannot be excluded, and further study of similar patients is warranted.

Adult↗
PubMed1985

Effects of intraoperative irradiation on gastric and urinary bladder incisions in the dog.

Fourteen adult dogs of mixed breeding were given intraoperative irradiation (25 Gy) after surgical incisions were made into the greater curvature of the stomach and the ventral surface of the urinary bladder. Sequential biopsy samples were obtained 10 days to 180 days after surgical operation. All irradiated stomachs developed gastritis and persistent ulceration of the irradiated field. Microscopic changes induced by irradiation of both the bladder and stomach progressed from severe submucosal edema to severe submucosal fibrosis. A parallel progression of fibrinoid degeneration of the small blood vessels was seen in both organs. Severe gastric ulceration persisted up to 180 days after irradiation, although a degree of mucous neck cell and gastric gland regeneration did occur. Pathologic changes were less severe in the bladder than in the stomach. The bladder had greater resiliency and capability for healing and, in contrast to the stomach, showed a capability to reepithelialize the radiation-induced ulcers. Conclusions of this study are as follows: (a) the canine urinary bladder tolerated intraoperative radiation therapy after tissue resection better than did the canine stomach, (b) the combination of surgical operation and irradiation resulted in a more prolonged and complicated healing pattern than did either procedure alone, and (c) the introduction of a surgical procedure upon irradiated tissue within an undetermined time span relative to irradiation resulted in a similar pattern of disturbed healing.

Animals↗
PubMed1984

Clostridium difficile colitis in surgical patients.

The clinical course of 75 patients with diarrhea and positive C. difficile toxin stool assays has been examined. The mean age of the patients was 68 years. Five of 25 surgical nursing units accounted for two thirds of the cases. Many patients were immuno-suppressed with cancer, sepsis, or diabetes mellitus. The median onset of diarrhea was 2.7 days after initial administration of antibiotics. Fever and leukocytosis were frequently seen. Diarrhea ceased in 30 percent of the patients after withdrawal of the offending antibiotics. The remainder required specific therapy with vancomycin, bacitracin, or metronidazole. Two deaths were directly attributable to C. difficile colitis. The hospital stay was prolonged in many patients. C. difficile colitis should be suspected in any patient in whom diarrhea develops during or after a course of antibiotics. Enteric precautions may prevent clustering in these cases and colonization in other susceptible patients.

Adult↗
PubMed1984

Comparison of prophylactic antibiotic regimens in patients undergoing vascular surgery.

An unacceptably high infection rate in patients undergoing vascular surgery prompted two studies on these patients. The first study confirmed the problem and described antibiotic usage which was not standardized. A second double blind randomized study compared antibiotic usage in two groups of patients, receiving vein grafts or synthetic grafts. Patients receiving vein grafts were randomized either to placebo or cefazolin 2 g 1 h pre-operatively and every 6 h for 48 h. Patients receiving synthetic grafts were randomized either to cefazolin 1 g or to cefazolin 2 g 1 h pre-operatively and every 6 h for 48 h. Four of 50 vein graft patients developed a purulent discharge. Two of these infected patients received placebo and two received the cefazolin 2 g protocol. Of 90 patients receiving a synthetic graft, four became infected. Three patients were randomized to the cefazolin 1 g protocol and one to the cefazolin 2 g protocol. No statistically significant differences were observed.

Adult↗
PubMed1984

Prevalence of ischaemic heart disease in middle aged British men.

The prevalence of ischaemic heart disease was determined by an administered questionnaire and electrocardiography in 7735 men aged 40-59 years drawn at random from general practices in 24 British towns. Overall, one quarter of these men had some evidence of ischaemic heart disease on questionnaire or electrocardiogram or both. On questionnaire, 14% of men had possible myocardial infarction or angina, with considerable overlap of the two syndromes. The prevalence of possible myocardial infarction combined with angina and of definite angina only showed a fourfold increase over the age range studied. Electrocardiographic evidence of ischaemic heart disease (definite or possible) was present in 15% of men, there being myocardial infarction in 4.2% and myocardial ischaemia in 10.3%. Electrocardiographic evidence of myocardial infarction increased fourfold over the age range studied. There was considerable overlap of questionnaire and electrocardiographic evidence of ischaemic heart disease. Nevertheless, more than half of those with possible myocardial infarction combined with angina had no resting electrocardiographic evidence of ischaemic heart disease, and half of those with definite myocardial infarction on electrocardiogram had no history of chest pain at any time. This national population based study strongly suggests that the prevalence of ischaemic heart disease in middle aged British men is greater than has been indicated by previous studies based on occupational groups.

Adult↗
PubMed1984

Recall of diagnosis by men with ischaemic heart disease.

In a study of the prevalence of ischaemic heart disease in middle aged men in 24 British towns, the subjects were asked whether a doctor had ever told them that they had any form of cardiovascular disease. Their recall of various diagnoses was related to evidence of ischaemic heart disease obtained by an administered questionnaire on chest pain and electrocardiography. Twenty one per cent of men recalled a diagnosis of cardiovascular disease, in one quarter of whom it was ischaemic heart disease. There was a sixfold increase in the prevalence of recall of a diagnosis of ischaemic heart disease over the age range studied. Only one third of the men with possible myocardial infarction on questionnaire recalled such a diagnosis having been made by a doctor. Only half of those with a definite myocardial infarction on an electrocardiogram could recall a diagnosis of ischaemic heart disease. Even in severe (grade 2) angina 40% could not recall being told that they had heart disease. Overall, only one in five of those regarded as having ischaemic heart disease was able to recall such a diagnosis having been made by a doctor, and these were likely to be those most severely affected. Ischaemic heart disease is common in middle aged British men, but most of those affected are apparently not aware of their condition. This low level of awareness among patients and doctors may contribute to a lack of public concern regarding the need for action to reduce the incidence of ischaemic heart disease in Great Britain.

Adult↗
PubMed1984

Mechanisms of catecholamine effects on ketogenesis.

Ketogenesis may be controlled at several sites. Lipolysis with release of plasma nonesterified fatty acid (NEFA) substrate is the first step. Plasma NEFA are taken up by the liver in a concentration-dependent fashion and, after conversion to the acyl-CoA derivative, may either be reesterified or enter the mitochondria via the carnitine shuttle. After beta-oxidation the resultant acetyl-CoA may either be converted to ketone bodies that are then released into the circulation or be condensed with oxaloacetate and enter the tricarboxylic acid cycle, the third potential control point. In humans, infusion of epinephrine causes a transient two- to threefold increase in fatty acids, glycerol, and ketone bodies. Insulin levels show a small absolute increase. Norepinephrine has similar effects, although insulin levels tend to be suppressed and glucagon levels rise somewhat. If somatostatin is added simultaneously, the lipolytic and ketogenic effects are accentuated and prolonged. Dopamine, in a high dose, has no effect on ketone bodies alone but shows small increases in NEFA and ketone bodies in the presence of somatostatin and may play a modulatory role in ketogenesis. The ketogenic effect of catecholamines could thus be in the adipocyte or in the liver. Studies with perfused liver or hepatocytes showed only trivial effects on ketogenesis even with supraphysiological doses of catecholamines. Furthermore infusion studies in rats showed decreased rather than increased ketogenesis with no change in NEFA levels. The data suggest that a) there are species differences, and b) in humans epinephrine- and norepinephrine-induced increases in ketogenesis are secondary to increases in NEFA substrate supply.

Animals↗
PubMed1984

Absorption of some glycol ethers through human skin in vitro.

To assist evaluation of the hazards of skin contact with selected undiluted glycol ethers, their absorption across isolated human abdominal epidermis was measured in vitro. Epidermal membranes were set up in glass diffusion cells and, following an initial determination of permeability to tritiated water, excess undiluted glycol ether was applied to the outer surface for 8 hr. The appearance of glycol ether in an aqueous "receptor" phase bathing the underside of the epidermis was quantified by a gas chromatographic technique. A final determination of tritiated water permeability was compared with initial values to establish any irreversible alterations in epidermal barrier function induced by contact with the glycol ethers. 2-methoxyethanol (EM) was most readily absorbed (mean steady rate 2.82 mg/cm2/hr), and a relatively high absorption rate (1.17 mg/cm2/hr) was also apparent for 1-methoxypropan-2-ol (PM). There was a trend of reducing absorption rate with increasing molecular weight or reducing volatility for monoethylene glycol ethers (EM, 2.82 mg/cm2/hr; 2-ethoxyethanol, EE, 0.796 mg/cm2/hr; 2-butoxyethanol, EB, 0.198 mg/cm2/hr) and also within the diethylene glycol series: 2-(2-methoxyethoxy) ethanol (DM, 0.206 mg/cm2/hr); 2-(2-ethoxyethoxy) ethanol (DE, 0.125 mg/cm2/hr) and 2-(2-butoxyethoxy) ethanol (DB, 0.035 mg/cm2/hr). The rate of absorption of 2-ethoxyethyl acetate (EEAc) was similar to that of the parent alcohol, EE. Absorption rates of diethylene glycol ethers were slower than their corresponding monoethylene glycol equivalents. Combination of intrinsic toxicity and ability to pass across skin contribute to assessment of hazards of contact with undiluted glycol ethers.

Chromatography, Gas↗