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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 73 records · Page 4Linked to original sources
PubMed2000

Lack of linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and bipolar disorder.

The serotonin transporter (5HTT) gene appears to be of particular interest as 5HTT is the selective site of action of selective serotonin reuptake inhibitors (SSRIs) that successfully treat bipolar depression (BP). The 5HTT gene is located on chromosome 17q11.1-q12 and has a 44 bp deletion/insertion functional polymorphism in the promoter region (SLC6A4). Results from association studies on SLC6A4 and BP disorder are conflicting. The aim of the present study was to investigate for the presence of linkage disequilibrium between SLC6A4 and BP disorder. One hundred thirty-three Bipolar I or Bipolar II probands with their living parents were recruited. Diagnoses were assessed by the structured interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition [DSM-IV, American Psychiatric Association, 1994] (SCID-I). Genotyping was performed with standard procedures and data were analyzed using the Transmission Disequilibrium Test [TDT, Spielman et al., 1993: Am J Hum Genet 52: 506-516]. One hundred two triads were informative for the analysis. Each of the two alleles of the SLC6A4 was transmitted at the same rate to bipolar probands (chi(2) = 0.692, df = 1, P = NS). Thus, it appears unlikely that the SLC6A4 plays a fundamental role in the pathogenesis of BP disorder. However, further studies focusing on the role of the 5HTT gene in predicting the response to SSRIs in BP patients might be worthwhile.

Adult↗
PubMed2000

Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men.

BACKGROUND: Studies are needed to test claims that potentially virulent strains of Helicobacter pylori are more strongly related to coronary heart disease (CHD) than are other strains. METHODS AND RESULTS: We measured serum IgG antibodies to mixed H pylori antigens and separately to the virulence-associated H pylori antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls "nested" in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for H pylori antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1. 90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with H pylori-seronegative individuals, the odds ratio for CHD was 1. 42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%) H pylori-seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA-seropositive men. No strong associations were observed between H pylori seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine. CONCLUSIONS: H pylori infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.

Antibodies, Bacterial↗
PubMed2000

Characteristics of older men who lose weight intentionally or unintentionally.

In most prospective studies involving older subjects, weight loss is associated with increased mortality. The authors examined the characteristics and health status of middle-aged men from 24 towns (the British Regional Heart Study), who reported that they had lost weight intentionally or unintentionally as they aged. Questionnaires were completed at screening (1978-1980), 5 years later, and in 1992 and 1996. This paper concerns the 4,713 men who reported their weight in 1992 and 1996 and their perceived weight change over this period. Weight loss was reported by 847 men (18%), of whom 39% stated that it was intentional. Compared with intentional weight loss, unintentional weight loss was associated with lower social class, more smoking, less obesity, and less physical activity and with the highest rates of "poor health,"long-standing disability, cancer, and respiratory diseases. The rates of recalled heart attack, stroke, diabetes, and cardiovascular hospitalization were higher than among men whose weight was stable. Men who lost weight intentionally had been more obese than those who lost weight unintentionally and had high rates of obesity-related conditions. Thus, both intentional and unintentional weight loss may follow the development of disease. These findings probably account for the lack of benefit and the increased mortality associated with weight loss observed in most large-scale prospective studies.

Age Distribution↗
PubMed2000

Global biodiversity scenarios for the year 2100.

Scenarios of changes in biodiversity for the year 2100 can now be developed based on scenarios of changes in atmospheric carbon dioxide, climate, vegetation, and land use and the known sensitivity of biodiversity to these changes. This study identified a ranking of the importance of drivers of change, a ranking of the biomes with respect to expected changes, and the major sources of uncertainties. For terrestrial ecosystems, land-use change probably will have the largest effect, followed by climate change, nitrogen deposition, biotic exchange, and elevated carbon dioxide concentration. For freshwater ecosystems, biotic exchange is much more important. Mediterranean climate and grassland ecosystems likely will experience the greatest proportional change in biodiversity because of the substantial influence of all drivers of biodiversity change. Northern temperate ecosystems are estimated to experience the least biodiversity change because major land-use change has already occurred. Plausible changes in biodiversity in other biomes depend on interactions among the causes of biodiversity change. These interactions represent one of the largest uncertainties in projections of future biodiversity change.

Agriculture↗
PubMed2000

Evidence that single nucleotide polymorphism in the uncoupling protein 3 (UCP3) gene influences fat distribution in women of European and Asian origin.

AIMS/HYPOTHESIS: Uncoupling proteins are mitochondrial transmembrane carriers implicated in the regulation of energy balance. Dysfunction of UCP3 (the predominant uncoupling protein in skeletal muscle) might therefore be expected to reduce thermogenic capacity, alter energy homeostasis and influence predisposition to obesity and Type II (non-insulin-dependent) diabetes mellitus. A variant in the putative promoter region of UCP3 (-55 c-->t) has recently been identified, and an association with obesity reported in French subjects. Our aim was to study the pathophysiological role of this variant in diabetes-related and obesity-related traits using two distinct ethnic populations. METHODS: The -55 c-->t variant was genotyped in 85 South Indian and 150 European parent-offspring trios ascertained through Type II diabetic probands and in 455 South Indian subjects initially recruited to an urban survey into the prevalence of diabetes. RESULTS: In South Indian and European parent-offspring trios there was no preferential transmission of either allele at the -55 c-->t polymorphism to diabetic offspring (South Indians, p = 0.60; Europeans, p = 0.15). When family members were analysed for intermediate traits, the t-allele was associated with increased waist-to-hip ratio but only in females (South Indian mothers p = 0.036, daughters p = 0.032: European mothers p = 0.037, daughters p = 0.14). These findings were replicated in South Indian females from the population-based survey (p = 0.039). CONCLUSION/INTERPRETATION: The consistent association between the t-allele at this locus and increased waist-to-hip ratio in women from three separate data sets indicates that variation at this polymorphism (or another locus with which it is in linkage disequilibrium) influences fat distribution but that this effect is restricted to females.

Adipose Tissue↗
PubMed2000

Recognition of vertebral fracture in a clinical setting.

Osteoporosis-related vertebral fractures have important health consequences for older individuals, including disability and increased mortality. Because these fractures can be prevented with appropriate medications, recognition and treatment of high-risk patients is warranted. A cross-sectional survey was carried out in a large, regional hospital in New England to examine the frequency with which vertebral fractures are identified and treated by clinicians in a population of hospitalized older women who have radiographic evidence of fractures. The study population consisted of 934 women aged 60 years and older who were hospitalized between October 1, 1995 and March 31, 1997, and who had a chest radiograph obtained. Vertebral fractures in the thoracic region were identified by two radiologists. Discharge diagnoses, medical record notes and radiology reports were compared with the results of the radiologists' readings to determine the frequency with which fractures were identified and appropriate, osteoporosis-preventing medications prescribed. Moderate or severe vertebral fractures were identified for 132 (14.1%) study subjects, but only 17 (1.8%) of the 934 participants had a discharge diagnosis of vertebral fracture. Of these 132, only 17% had fracture noted in the medical record or discharge summary; 50% of contemporaneous radiology reports identified a fracture as present; and 23% of the time it was found in the radiologist's summary impression. Only 18% of medical records indicated that fracture patients had been prescribed calcium, vitamin D, estrogen replacement or an antiresorptive agent. Relatively few hospitalized older women with radiographically demonstrated vertebral fractures were thus identified or treated by clinicians, suggesting a need for improved recognition.

Aged↗
PubMed2000

Temporal lobe epilepsy with and without psychosis: exploration of hippocampal pathology including that in subpopulations of neurons defined by their content of immunoreactive calcium-binding proteins.

We have investigated relationships between hippocampal/temporal lobe neuropathology and psychosis in subjects with temporal lobe epilepsy, paying particular attention to possible differences in density of hippocampal neurons immunoreactive for calcium-binding proteins. There was a trend for a greater prevalence of left handedness in the psychotic (n = 6) than the non-psychotic (n = 26) cases (P = 0.0504). Psychotic cases also differed from non-psychotic ones in having: (1) more focal lesions outside the hippocampus (P = 0.006); (2) less severe CAI neuron loss (P = 0.015); and (3) a trend, after Bonferroni correction, for a higher density of calbindin-immunoreactive neurons in the CA4 (P = 0.022). An additional finding was that dentate granule cell dispersion was significantly associated with the presence of a reduced density of calretinin-immunoreactive neurons in CA4 (P = 0.002) and with a more severe loss of CA4 neurons visible with Nissl stain (P = 0.003). Thus, cases of temporal lobe epilepsy with psychosis were distinguishable on the basis of a higher density of calbindin-reactive neurons in CA4 as well as on more general aspects of their pathology.

Adolescent↗
PubMed2000

Longitudinal evaluation of supervised versus unsupervised exercise programs for the treatment of osteoporosis.

The efficacy of an exercise program was investigated in a study of 89 post-menopausal women with osteoporosis over a 5-year follow-up period. The study attempted to examine and compare potential differences in bone mineral density (BMD), incidence of fracture, and loss of height, between a group of patients (n = 42) who attended the supervised exercise program in the hospital, and a group (n = 47) who exercised at home. Habitual physical activity, as estimated using the Harvard Alumni Questionnaire, and a Physical Activity Index were combined to obtain an estimate of overall weekly caloric expenditure over the 5-year period. The exercise program involved weight-bearing aerobic activities of moderate intensity, and muscle strengthening exercise using free weights. The mean percentage change for the lumbar BMD was + 4.4% in the hospital group and +3.4% in the home group while for the femoral neck BMD was + 1.1% in the hospital group and -0.9% in the home group. There was a significant reduction in the number of fractures and no significant loss of height over the 5-year follow-up period for both groups. As the correlation between BMD and weekly caloric expenditure of the subjects was not significant, no conclusion can be drawn as to the minimum level of caloric expenditure necessary in order to retard bone loss. It was concluded that for the post-menopausal women with osteoporosis who participated in the program it was possible to stabilize their height and the BMD of the lumbar site, and to reduce fractures over the 5-year study period regardless if they exercised in a supervised or in an unsupervised setting.

Aged↗
PubMed2000

Femoral atherosclerosis in an older British population: prevalence and risk factors.

Most estimates of the prevalence of peripheral atherosclerosis have been based on intermittent claudication or lower limb blood flow. The aim of this study was therefore to determine the prevalence of underlying femoral plaque, and to determine its association with other cardiovascular disease and risk factors. Presence of plaque was identified using ultrasound in a random sample of men (n=417) and women (n=367) aged 56-77 years. Coexistent cardiovascular disease, exercise and smoking were determined by questionnaire, blood pressure was recorded, and serum cholesterol and plasma fibrinogen were determined. Of the 784 subjects that were scanned, 502 (64%) demonstrated atherosclerotic plaque. Disease prevalence increased significantly with age (P<0.0001), and was more common in men (67.1 vs. 59.4%, P<0.05). Subjects with femoral plaque had a significantly greater odds of previous ischaemic heart disease (OR 2. 2, 95% CI 1.3, 3.7) and angina (OR 1.7, 95% CI 1.03, 2.7), but not of stroke or leg pain on exercise. Current and ex-smoking, raised serum total cholesterol and plasma fibrinogen levels, but not blood pressure, were associated with an increased risk of femoral plaque, independent of age and sex. Frequent exercise and a high HDL cholesterol were significantly associated with lower risk. In conclusion, therefore, atherosclerotic disease of the femoral artery affects almost two-thirds of the population in late middle age. It is associated with an increased prevalence of ischaemic heart disease and angina, but whether detecting at risk individuals using ultrasound offers advantages over simpler and less expensive risk factor scoring requires evaluation in trials.

Age Distribution↗
PubMed2000

Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major.

Clinical complications of transfusional iron overload are still common in patients with thalassaemia major (TM) and it is not clear how best to monitor body iron stores during long-term follow-up to anticipate tissue damage. In this study, we have reviewed a group of 32 patients who underwent liver biopsy between 1984 and 1986. We developed a method of assessing the trend in serum ferritin (TSF) during long-term monitoring and compared this with mean serum ferritin (MSF) and initial liver iron (LI) concentration to determine whether, individually or in combination, they were accurate in predicting clinical outcome. LI levels were low (< 7 mg/g), medium (7-15 mg/g) and high (> 15 mg/g dry weight) in 15, 7 and 10 patients respectively. MSF was low (< 1500 microg/l), medium (1500-2500 microg/l) and high (> 2500 microg/l) in 10, 14 and 8 patients. TSF was low, medium and high risk in 9, 9 and 11 out of 29 evaluable patients. During a median follow-up of 13.6 years (range 2.3-14.8 years) after biopsy, nine patients died and an additional three patients developed heart failure. Hypothyroidism developed in five, hypoparathyroidism in four, and diabetes mellitus in seven patients. Cirrhosis developed in four of 10 evaluable patients. The clinical end-point of death or cardiac failure was significantly associated with increasing iron load using all three means of assessment. Although numbers were insufficient for statistical analysis, MSF or TSF were more closely associated with complications of iron overload than LI. There was no clear additional value in combining LI with MSF or TSF. The data show that quantitation of liver iron from a single liver biopsy has little value in long-term monitoring of iron stores. Most complications can be avoided if ferritin levels can be brought down to <1500 microg/l.

Adolescent↗
PubMed2000

An internet-based learning portfolio in resident education: the KOALA multicentre programme.

CONTEXT AND OBJECTIVES: To describe the Computerized Obstetrics and Gynecology Automated Learning Anaalysis (KOALAtrade mark), a multicentre, Internet-based learning portfolio and to determine its effects on residents' perception of their self-directed learning abilities. METHODS: The KOALA programme allows residents to record their obstetrical, surgical, ultrasound, and ambulatory patient encounters and to document critical incidents of learning or elements of surprise that arose during these encounters. By prompting the student to reflect on these learning experiences, KOALA encourages residents to articulate questions which can be directly pursued through hypertext links to evidence-based literature. Four Canadian residency training programmes participated in the pilot project, from February to May 1997, using a dynamic relational database with a central server. All participants completed the Self-directed Learning Readiness Scale and a learning habits questionnaire. The impact of the KOALA programme on residents' perception of their self-directed learning abilities was measured by comparing KOALA-naive schools (schools 2, 3, and 4) with school 1 (exposed to the KOALA prototype for 1 year). Ordered variables were compared using the Mann-Whitney U test and continuous variables with the Student t test (statistical significance P < 0. 05). RESULTS: During the study period, 7049 patient and 1460 critical incidents of learning were recorded by 41 residents in the four participating universities. Residents at the exposed school (school 1) had a significantly higher perception of their self-directed learning (P < 0.05) and believed their future learning was less likely to be from continuing medical education (P < 0.028), textbooks (P < 0.04), and didactic lectures (P < 0.011) and would be derived from a learning portfolio with online resources. CONCLUSION: This Internet-based, multi-user, multicentre learning portfolio has a significant effect on residents' perception of their self-directed learning abilities.

Canada↗
PubMed2000

Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril.

AIMS: The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus. METHODS: Insulin sensitivity was assessed after an acute dose (day 3) and 19 days continuous treatment (days 3-21) using the isoglycaemic, hyperinsulinaemic glucose clamp with D[3-3H] labelled glucose, a variable D[3-3H] priming dose and a 'hot' glucose infusion. Rates of glucose appearance (Ra) and glucose disappearance (Rd) were isotopically determined during the basal and insulin stimulated periods of the clamp. Twenty-four (5 female) hypertensive (blood pressure >75th centile for age and sex) patients with Type 2 diabetes mellitus were studied. Patients were randomized, in a double-blind manner, to either trandolapril 4 mg daily (T) or placebo (P). RESULTS: Baseline (day 1) systolic (mean +/- SD; P 164+/-14 and T 168+/-13 mm Hg) and diastolic (P 93+/-6, and T 98+/-10 mm Hg) blood pressures were comparable. On days 3 and 21, significant reductions were observed in both groups (P<0.001). In the trandolapril-treated group, serum trandolapril concentrations were >200 pg/ml on days 3 and 21, in all patients apart from one subject at a single visit, while trandolapril was undetectable in the placebo group. Body mass index (BMI) was greater in T compared with P (32.2+/-5.4 v. 28.3+/-4.6, P = 0.07). After correcting for BMI, basal hepatic glucose output (HGO) P 2.6 (95% CI 2.23-3.13) and T 1.91 (1.33-2.51) mg x kg(-1) x min(-1) and clamped HGO P 0.32 (-0.44-1.09) and T 0.87 (0.40-1.34) mg x kg(-1) x min(-1) were similar in both groups. The insulin sensitivity index was comparable in both groups on all days. Total cholesterol concentrations were similar in both groups throughout the study. Triglyceride concentrations were significantly lower in group P 1.38 (1.07-1.68); T 2.14 (1.70-2.58) mmol/l, P<0.01), no significant treatment effect being observed. CONCLUSIONS: An acute dose and 19 days' continuous treatment with trandolapril resulted in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension. These data support the metabolic neutrality of trandolapril in patients with Type 2 diabetes mellitus and hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

The natural history of prevalent ischaemic heart disease in middle-aged men.

OBJECTIVE: To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. METHODS: 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. RESULTS: At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event. CONCLUSIONS: Differing manifestations of prevalent ischaemic heart disease are associated with widely differing outcome, and the majority of middle-aged men in the community who have evidence of ischaemic heart disease short of myocardial infarction survive for 15 years without heart attack or stroke. The excess risk associated with myocardial infarction appears more persistent than that associated with angina and other ischaemic heart disease, remaining high even after 10 years of event-free survival.

Adult↗
PubMed2000

Most microsatellite unstable sporadic colorectal carcinomas carry MBD4 mutations.

The MBD4 gene is involved in the repair of mutation at methyl-CpG dinucleotides. In microsatellite unstable tumours MBD4 can itself be mutated at an exonic polynucleotide tract. By analysing DNA from microdissected tumour samples we have found that both frequency and pattern of mutation are more significant than originally reported.

Colorectal Neoplasms↗