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M Walker

Publications and source records attributed to M Walker.

At least 343 records · Page 19Linked to original sources
PubMed1994

Case study of the relation between census reduction and injuries to residents in an ICF/MR.

We compared the frequency and severity of injuries of adults living in an ICF/MR for one year before and one year after the census of their cottage was reduced from 28 to 19. These residents had severe or profound mental retardation, few sensory deficits, and limited communication skills; most had severe behavior problems. Results showed a decrease from 23.3 to 13.3 injuries per person for the 18 men who resided in the building after census reduction. A larger decrease in injuries requiring versus not requiring medical attention (71.7% vs. 38.9%) was also found. A control group of 18 similar male residents showed only a slight decrease (16.9 vs. 16.2) in injury reports over the same time period. Results suggest that a lower census was clearly related to reduced number of injuries.

Case-Control Studies↗
PubMed1994

Segregation analysis of complex phenotypes: an application to schizophrenia and auditory P300 latency.

Traditional models of the genetic transmission of human diseases have often assumed that the phenotype is a simple dichotomous trait, which is unrealistic for many psychiatric conditions, and may result in loss of valuable information. We describe a new model for complex phenotypes, implemented in the program COMDS, which subclassifies normal and affected individuals into polychotomies correlated with the underlying genetic liability to the disorder. The model is applied to 18 Scottish pedigrees ascertained for schizophrenia, in which auditory P300 latency had been measured as a possible correlate of the genetic predisposition to schizophrenia. The results suggest that there may be a major locus for schizophrenia, but that there are also other familial determinants, possibly a second modifier locus. In addition, the results indicate that auditory P300 latency may be a useful measure of the genetic predisposition to schizophrenia among asymptomatic relatives, although the relationship between P300 latency and the degree of genetic predisposition in clinical cases was not significant, presumably because other factors are operating on P300 latency. Because of the possible selection biases in this sample, there is a need to replicate these findings in systematically ascertained pedigrees.

Discriminant Analysis↗
PubMed1994

Maternal factors and development of cardiovascular risk: evidence from a study of blood pressure in children.

It has been suggested that risks of hypertension and cardiovascular disease begin in utero and that maternal nutrition plays an important role. We have examined the relation between maternal factors and BP in a study of 1,311 children in which physical measurements at 9-11 years of age have been linked to a parental questionnaire; birth record data were also available in a subsample of 662 children. Maternal height was inversely related to childhood BP after adjustment for the child's current height. However, several social factors related to maternal nutrition in pregnancy in earlier studies (including social class, housing tenure, maternal educational attainment and maternal smoking in pregnancy) showed weak and inconsistent relations with BP at 9-11 years. Minimum maternal haemoglobin in pregnancy and change in mean corpuscular volume in pregnancy (identified as potentially important markers of maternal nutrition in earlier studies) showed no consistent relationships either with placental weight to birthweight ratio or with childhood BP, although both factors showed strong inverse associations with birthweight. The association between maternal height and childhood BP may reflect the influence of early life factors on cardiovascular risk. However, the absence of consistent relationships between social factors and BP in offspring provides little support for the possibility that maternal diet is an important influence on cardiovascular risk factors in childhood. Minimum maternal haemoglobin and change in maternal mean corpuscular volume are unlikely to be specific markers of maternal nutrition in pregnancy. More specific hypotheses relating maternal nutrition to the development of cardiovascular risk in offspring are required.

Adult↗
PubMed1994

Physical activity, hypertension and risk of heart attack in men without evidence of ischaemic heart disease.

The role of hypertension in the increased rate of heart attack reported in vigorously active subjects was examined in a large prospective study of 7735 middle-aged men drawn from general practices in 24 British towns (The British Regional Heart Study). Analyses were restricted to 5694 men with no evidence of pre-existing ischaemic heart disease or stroke at screening, in whom there were 311 major ischaemic heart disease events after 9.5 years follow-up. Risk of major ischaemic heart disease events decreased significantly with increasing physical activity to levels of moderate/moderately vigorous activity, with a 50% reduction in risk compared with inactive men after adjustment for age, body mass index, smoking, heavy drinking, social class and blood cholesterol. However, at the highest level of physical activity (vigorous group) risk of major ischaemic heart disease events was increased above that seen in the moderate/moderately vigorous group (rr = 1.68, P = 0.05). When separated into normotensives (n = 3888) and hypertensives (n = 1806; SBP > or = 160 mmHg or DBP > or = 90 mmHg or on regular antihypertensive treatment), the increased risk of major ischaemic heart disease events in the vigorous group was only evident in hypertensive men. They showed more than a twofold increase in risk compared with the moderate and moderately vigorous group (rr = 2.7, P < 0.05). In normotensive men, risk was significantly lowered in those engaged in moderate activity with no further decline in rate of heart attack at increasing levels of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Single-photon emission computed tomography with 99mTc-exametazime in unmedicated schizophrenic patients.

We examined 20 actively psychotic unmedicated schizophrenic patients and 20 matched control subjects by using single-photon emission, computed tomography (SPECT) with 99mtechnetium-exametazime. Patients showed a hyperfrontal pattern of tracer uptake with significant relative increases in superior prefrontal cortex. This abnormality was less pronounced in patients with higher symptom scores for psychomotor poverty. In addition, patients showed associations between certain schizophrenic syndrome scores, such as psychomotor poverty, disorganization, and reality distortion, and tracer uptake to a number of cortical and subcortical brain regions. This syndrome-related pattern of tracer uptake was, at least in part, consistent with similar associations previously reported in chronically medicated schizophrenic patients. SPECT therefore provides a readily available method to examine the relationship between symptom pattern and regional brain metabolism in psychotic patients. Any observed patterns of association will depend on the current mental and medication status of the patients examined.

Adult↗
PubMed1993

Comparison of eating disorders and other dietary/weight groups on measures of perceived control, assertiveness, self-esteem, and self-directed hostility.

Anorexic and bulimic patients were compared to obese dieters, nonobese dieters, and normal controls on measures of perceived control, assertiveness, self-esteem, self-directed hostility, and psychiatric caseness. The anorexic and bulimic groups both scored significantly differently in the expected direction from the other three groups on all measures. There were no significant differences between the anorexic and bulimic groups and in turn, no significant differences among the obese, nonobese dieters, and normal controls. Results are in keeping with the notion that perceived control, low assertiveness, low self-esteem, and self-directed hostility are characteristics of eating disorder patients that differentiate them from individuals who display dietary/weight features, as well as from normal controls.

Adult↗
PubMed1993

Erythrocyte sodium-lithium countertransport activity and total body insulin-mediated glucose disposal in normoalbuminuric normotensive type 1 (insulin-dependent) diabetic patients.

Insulin resistance in Type 1 (insulin-dependent) diabetes mellitus may be associated with raised erythrocyte sodium-lithium countertransport activity in patients with hypertension, or nephropathy, or both. However, in these circumstances it is difficult to separate the impact of hypertension, hyperlipidaemia and nephropathy on erythrocyte sodium-lithium countertransport from that of insulin resistance. We have therefore examined the relationship between insulin-mediated glucose disposal and erythrocyte sodium-lithium countertransport in 41 normotensive (mean blood pressure 120/74 mmHg), normoalbuminuric (mean albumin excretion 6.2 micrograms/min), normolipidaemic (mean serum cholesterol 4.3 mmol/l and mean serum triglycerides 1.0 mmol/l) Type 1 diabetic patients. Erythrocyte sodium-lithium countertransport was on average 0.31 mmol Li.h-1.l erythrocytes-1 (range 0.07-0.69). Nine patients had values above 0.40 mmol Li.h-1.l erythrocytes-1 (0.51 +/- 0.10 mmol Li.h-1.l erythrocytes-1). The patients with high erythrocyte sodium-lithium countertransport were matched for age, sex, BMI, HbA1 and duration of diabetes, with nine patients with normal erythrocyte sodium-lithium countertransport. Insulin-mediated glucose disposal was evaluated during the last hour of a euglycaemic clamp (insulin 0.015 U.kg-1.h-1; blood glucose clamped at 7.0 mmol/l). The free insulin levels were comparable between the patients with high and normal erythrocyte sodium-lithium countertransport (37.2 +/- 14.7 mU/l and 34.7 +/- 17.2 mU/l respectively). Insulin-mediated glucose disposal was on average 3.1 +/- 1.5 (range 0.8-6.8) mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Acipimox increases glucose disposal in normal man independent of changes in plasma nonesterified fatty acid concentration and whole-body lipid oxidation rate.

The short-term administration of a nicotinic acid analogue (acipimox) increases insulin sensitivity and consequently glucose disposal, both in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in patients with cirrhosis. This effect has been attributed to a decrease in plasma nonesterified fatty acid (NEFA) levels and fatty acid oxidation rates, and a corresponding increase in carbohydrate oxidation. The aim of the present study was to determine whether acipimox influenced glucose disposal independent of changes in lipid metabolism. Seven normal men (age, 31 +/- 4 years; body mass index, 23.2 +/- 1.8 kg.m-2; fat-free mass [FFM], 66.8 +/- 4.2 kg) were studied on two separate occasions with hyperinsulinemic (0.06 U.kg FFM-1.h-1) euglycemic clamps (duration, 150 minutes). A primed (150 U), continuous (0.4 U.kg-1.min-1) infusion of heparin together with 10% intralipid (25 mL.h-1) was infused in both studies from -90 to 150 minutes to maintain comparable levels of plasma NEFA and lipid oxidation rates. Acipimox (500-mg capsules) or placebo were administered orally in a double-blind random fashion at t = -90 and t = 0 minutes. Whole-body lipid and carbohydrate oxidation were measured in the last 30 minutes of both the basal (preclamp) period (-30 to 0 minutes) and the clamp period (120 to 150 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Peripheral and hepatic insulin sensitivity in non-insulin-dependent diabetes mellitus: effect of nonesterified fatty acids.

Plasma nonesterified fatty acid (NEFA) levels are increased in the insulin-stimulated state in non-insulin-dependent diabetes mellitus (NIDDM) and may contribute to the decrease in peripheral and hepatic insulin sensitivity. To test this hypothesis and to avoid the confounding effect of obesity, we examined the effect of decreasing plasma NEFA levels on peripheral and total glucose metabolism in eight non-obese, NIDDM patients. Each received 250 mg Acipimox (a nicotinic acid analogue) or placebo at 0 and 120 minutes on separate occasions. [6,6-2H2]-glucose (0 to 300 minutes) and insulin (120 to 300 minutes) were infused in each study, and isoglycemia was maintained. Plasma NEFA levels (140 +/- 30 v 600 +/- 70 mumol/L [SEM]; P < .001) and forearm NEFA uptake measured with [1-14C]-palmitate (+93 +/- 21 v +313 +/- 42 nmol x 100 mL forearm-1; P < .001) were decreased with acipimox during the basal period (90 to 120 minutes), with no change in forearm glucose uptake (+334 +/- 80 and +330 +/- 60 nmol x 100 mL forearm-1 x min-1) and hepatic glucose output ([HGO] 13.6 +/- 0.9 and 13.4 +/- 0.7 mumol.kg-1 x min-1). Serum insulin (256 +/- 12 and 266 +/- 18 pmol/L) and plasma glucose (9.5 +/- 0.6 and 9.4 +/- 0.5 mmol/L) levels were comparable during the clamp period (270 to 300 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1993

Different patterns of regulation of the genes encoding the closely related 56 kDa selenium- and acetaminophen-binding proteins in normal tissues and during carcinogenesis.

A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN-induced liver tumours in vivo. The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms.

Acetaminophen↗
PubMed1993

Forearm muscle metabolism in primary hypothyroidism.

Thyrotoxicosis is associated with increased skeletal muscle glucose metabolism and lipid oxidation in the fasted state. Conversely, in hypothyroidism, glucose metabolism is reduced. The present study has assessed in patients the effects of chronic thyroid hormone deficiency, on insulin-stimulated skeletal muscle metabolism, using a combination of the forearm and hyperinsulinaemic euglycaemic clamp techniques. Seven female patients presenting with primary auto-immune hypothyroidism were studied at presentation and 4-9 months after being rendered biochemically euthyroid. No significant differences were demonstrated between the hypothyroid and euthyroid states in forearm muscle blood flow, or in glucose or lipid metabolism.

Adult↗
PubMed1993

The role of plasma non-esterified fatty acids during exercise in type 2 diabetes mellitus.

Elevated fasting plasma non-esterified fatty acid (NEFA) levels have been reported in Type 2 diabetes. We examined whether such changes persist during low-grade exercise and influence carbohydrate metabolism. Eight Type 2 diabetic patients with moderate glycaemic control and eight healthy controls received the anti-lipolytic agent, acipimox, or placebo on separate occasions before exercising for 45 min at 35% pre-determined VO2max. Fasting plasma NEFA levels were similar (0.40 +/- 0.06 (SEM) and 0.45 +/- 0.05 mmol l-1; healthy and Type 2 diabetic subjects) following placebo, and increased to comparable levels with exercise (0.73 +/- 0.07 and 0.73 +/- 0.10 mmol l-1). Acipimox lowered basal NEFA levels (0.14 +/- 0.03 and 0.28 +/- 0.04 mmol l-1; both p < 0.05 vs placebo), and prevented the rise with exercise. Blood glucose (p < 0.001) and serum insulin (p < 0.01) levels were higher in the Type 2 diabetic patients (vs controls) for both treatments. Whole body lipid oxidation increased from baseline to a comparable degree with exercise following placebo (3.2 +/- 0.3 and 2.8 +/- 0.3 mg kg-1 min-1; healthy and Type 2 diabetic subjects, both p < 0.02). Although less marked, the same was also observed following acipimox (2.0 +/- 0.4 and 2.1 +/- 0.5 mg kg-1 min-1; both p < 0.05). Carbohydrate oxidation increased with exercise in both subject groups, but with no significant difference between the treatments. Thus, the metabolic response to low-grade exercise was normal in Type 2 diabetic patients with moderate glycaemic control, but occurred against a background of hyperinsulinaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1993

Decreased plasminogen activator inhibitor-1 activity in newly diagnosed type 2 diabetic patients following dietary modification.

Increased plasminogen activator inhibitor-1 (PAI-1) activity has been reported in Type 2 (non-insulin-dependent) diabetes and is a recognized risk factor for coronary artery disease. Fourteen newly diagnosed Type 2 diabetic patients were studied before and 3 months after standard clinical dietary modification. To assess the effect of improved metabolic control on PAI-1 activity, nine Type 2 diabetic patients established on diet therapy and with previous stable glycaemic control served as controls. In the newly diagnosed patients diet therapy resulted in a significant decrease in HbA1c levels (8.3 +/- 0.5 vs 5.2 +/- 0.3% (mean +/- SEM); p < 0.001), and this was accompanied by a fall in fibrinogen (4.3 +/- 0.3 vs 3.0 +/- 0.2 g.l-1; p < 0.01) concentration, and PAI-1 (18.7 +/- 2.3 vs 12.2 +/- 0.9 arbitrary units ml-1; p < 0.02) and factor VIII (147 +/- 17 vs 115 +/- 13%; P < 0.01) activities. PAI-1 activity was correlated with triglyceride levels at the first assessment in the newly diagnosed patients (r = 0.66; p < 0.01), and this was the only independent association by multiple regression analysis when all patients (n = 23) were considered (r = 0.62; p < 0.002). However, there was no association between the changes in PAI-1 activity and the changes in HbA1c BMI, and serum triglyceride levels following treatment in the newly diagnosed patients. Serum triglyceride concentrations, HBA1c, PAI-1 activity, and the coagulation factors remained unchanged in the control group over the same treatment period.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1993

Heart rate, ischaemic heart disease, and sudden cardiac death in middle-aged British men.

OBJECTIVE: To examine the relation between resting heart rate and new major ischaemic heart disease events in middle aged men with and without pre-existing ischaemic heart disease. DESIGN: Prospective study of a cohort of men with eight years follow up for cardiovascular morbidity and mortality for all men. SETTING: General practices in 24 British towns (the British Regional Heart study). SUBJECTS: 7735 men aged 40-59 years drawn at random from the age-sex registers of one general practice in each town. MAIN OUTCOME MEASURES: Major ischaemic heart disease events such as sudden cardiac death, other deaths attributed to ischaemic heart disease, and non-fatal myocardial infarction. RESULTS: During the follow up period of eight years, 488 men had a major ischaemic heart disease event (217 fatal and 271 non-fatal). Of these, 117 were classified as sudden cardiac death (death within one hour of the start of symptoms). The relation between heart rate and risk of all major ischaemic heart disease events, ischaemic heart disease deaths, and sudden cardiac death was examined separately in men with and without pre-existing ischaemic heart disease. In men with no evidence of ischaemic heart disease, there was a strong positive association between resting heart rate and age adjusted rates of all major ischaemic heart disease events (fatal and non-fatal), ischaemic heart disease deaths, and sudden cardiac death. This association remained significant even after adjustment for age, systolic blood pressure, blood cholesterol, smoking, social class, heavy drinking, and physical activity, with particularly high risk in those with heart rate > or = 90 beats/min. The increased risk seen in those with increased heart rate was largely due to a significantly increased risk of sudden cardiac death, which was five times higher than in those with heart rate < 60 beats/min. The effect of heart rate on sudden cardiac death was present irrespective of blood pressure or smoking state. In men with pre-existing ischaemic heart disease a positive association was seen between raised heart rate and risk of all major ischaemic heart disease events, ischaemic heart disease death, and sudden cardiac death, but the effect was less noticeable than in men without pre-existing ischaemic heart disease. CONCLUSION: In this study of middle aged British men increased heart rate > or = 90 beats/min) is a risk factor for fatal ischaemic heart disease events but particularly for sudden cardiac death. The effect is not dependent on the presence of other established coronary risk factors and is most clearly seen in men free of pre-existing ischaemic heart disease at initial examination.

Adult↗