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Biomedical subjects

M Walker

Publications and source records attributed to M Walker.

At least 271 records · Page 15Linked to original sources
PubMed1996

Cardiovascular risk factors in British children from towns with widely differing adult cardiovascular mortality.

OBJECTIVE: To examine whether cardiovascular risk factors differ in children from towns in England and Wales with widely differing adult cardiovascular death rates. DESIGN: School based survey conducted during 1994 in 10 towns, five with exceptionally high adult cardiovascular mortality (standardised mortality ratio 131-143) and five with exceptionally low adult cardiovascular mortality (64-75). Towns were surveyed in high-low pairs. SUBJECTS: 3415 white children aged 8-11 years with physical measurements (response rate 75%), including 1287 with blood samples (response rate 64%), of whom 515 had blood samples taken 30 minutes after a glucose load. RESULTS: Children in towns with high cardiovascular mortality were on average shorter than those in towns with low mortality (mean difference 1.2 cm; 95% confidence interval 0.3 to 2.1 cm; P = 0.02) and had a higher ponderal index (0.34 kg/m3; 0.16 to 0.52 kg/m3; P = 0.006). Mean systolic pressure was higher in high mortality towns, particularly after adjustment for height (2.0 mm Hg; 0.8 to 3.2 mm Hg; P = 0.009). Mean waist:hip ratio, total cholesterol concentration, and 30 minute post-load glucose measurements were similar in high and low mortality towns. The differences in height and blood pressure between high and low mortality towns were unaffected by standardisation for birth weight. CONCLUSIONS: The differences in height, ponderal index, and blood pressure between towns with high and low cardiovascular mortality, if persistent, may have important future public health implications. Their independence of birth weight suggests that the childhood environment rather than the intrauterine environment is involved in their development.

Adult↗
PubMed1996

Human insulin receptor substrate-1: variant sequences in familial non-insulin-dependent diabetes mellitus.

The aetiology of NIDDM is uncertain, although family and twin studies indicate an important role for genetic factors in disease onset. The function and position of IRS-1 within the insulin signalling pathway make it a prime candidate gene for the development of insulin resistance and NIDDM. Insulin resistant families were identified by studying unaffected first degree relatives from families with 2 or more living NIDDM subjects. Insulin sensitivity was determined in the relatives using the insulin tolerance test, and 15 families were identified as insulin resistant. One NIDDM subject from the 10 most resistant families was selected and the entire coding region of IRS-1 analysed by SSCP analysis. Four normoglycaemic subjects with no family history of diabetes served as controls. Five variant sequences of IRS-1 were identified with the NIDDM subjects; 2 silent polymorphisms at codons 235 (GGG to GGA) and 893 (CCG to CCC): 2 non-conservative mutations (Ala513Pro; Gly972Arg) and a codon deletion (Ser681-7 to Ser681-6). The influence of the non-conservative mutations alone, and in combination with other abnormalities of the insulin signalling pathway on peripheral insulin action, remains to be determined.

Base Sequence↗
PubMed1996

Relationship between insulin sensitivity and insulin receptor substrate-1 mutations in non-diabetic relatives of NIDDM families.

Insulin receptor substrate-1 (IRS-1) occupies a key position in the insulin-signalling pathway. Two mutations of the IRS-1 gene (Gly(972)Arg and Ala(513)Pro) have been described, although their roles in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Insulin resistance has been described in non-diabetic relatives of NIDDM families, suggesting that it may be due to an inherited defect of insulin action. We therefore examined the relationships between the two mutations and insulin sensitivity in 93 non-diabetic first degree relatives from North European families with 2 or more living NIDDM subjects. Anthropometric measurements, an oral glucose tolerance test, and an insulin tolerance test to assess insulin sensitivity (K(ITT)) were performed. Basal insulin sensitivity was assessed by homeostasis model assessment (HOMA). Comparisons were made between the following relative subgroups: with (n = 9) and without (n = 84) the 972 mutation; with (n = 5) and without (n = 88) the 513 mutation; and with either one or both mutations (n = 13) or without either (n = 80). General linear model analysis was used to compare K(ITT) and HOMA between the subgroups with the anthropometric variables known to influence insulin sensitivity as covariates. There were no significant differences between the subgroups for K(ITT) and HOMA. In conclusion, the 513 and 972 mutations, alone and in combination, are not associated with decreased insulin sensitivity in non-diabetic relatives of NIDDM families.

Adult↗
PubMed1996

The sonographic finding of persistent umbilical cord cystic masses is associated with lethal aneuploidy and/or congenital anomalies.

Advancements in sonographic technology have led to improved prenatal detection of fetal anomalies. Umbilical cord cystic masses are being detected prenatally and several case reports have appeared in the literature. We report three new cases in which umbilical cord cystic masses were detected prenatally; two cases in the later half of pregnancy and one case in the first trimester. The literature was reviewed and summaries of the 23 reported cases of persistent second- and third-trimester umbilical cord cystic masses and their implications are discussed. There is a high association (18 of 23 cases) with lethal chromosomal anomalies and/or congenital malformations suggesting that the finding of an isolated umbilical cord cystic mass should lead to further detailed sonographic evaluation.

Adult↗
PubMed1996

Variant sequences of the Hexokinase II gene in familial NIDDM.

UNLABELLED: Hexokinase II (HKII) plays a central role in the intracellular metabolism of glucose in skeletal muscle, catalysing the phosphorylation of glucose to glucose 6-phosphate. It is therefore considered to be a potentially important candidate gene in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to screen the HKII gene for mutations in NIDDM subjects from insulin-resistant families. Insulin sensitivity was assessed in unaffected first degree relatives from families with two or more living NIDDM subjects, and 15 families were identified as being insulin resistant. In 15 NIDDM subjects (one from each family) and 4 normoglycaemic control subjects, all 18 exons of the HKII gene were amplified by the polymerase chain reaction, and the products screened for mutations using a combination of single-stranded conformational polymorphism analysis and direct sequencing. Six sequence variations were detected in the NIDDM subjects; four silent polymorphisms [GAT vs GAC at codon 251 in exon 7, AAT vs AAC at codon 692 in exon 15, CCG vs CCC at codon 736 in exon 15, and CTG vs CTA at codon 766 in exon 16]; a single base change [T-->C], 22 base pairs distal to the exon-intron junction of exon 17 in the 5'-splice donor; and a single amino acid substitution [Gln142-->His] in exon 4, which was identified in 6 of the 15 NIDDM subjects. The frequency of the mutated codon 142 allele however, was comparable between NIDDM subjects with familial NIDDM (n = 56) and normoglycaemic control subjects (n = 48) (18.8% and 14.6% for NIDDM subjects and control subjects respectively; chi 2 = 0.6, p > 0.25). In addition, measures of insulin sensitivity were comparable in normal glucose tolerant subjects with (n = 20) and without (n = 40) the codon 142 polymorphism. IN CONCLUSION: (1) mutations in the coding regions of the HKII gene are unlikely to be major determinants in the development of insulin resistance and familial NIDDM; although (2) the influence of the codon 142 mutation in combination with other abnormalities of the insulin-signalling pathway on insulin action remain to be addressed.

Amino Acid Sequence↗
PubMed1996

Lipoprotein (a) concentrations and apolipoprotein (a) phenotypes in normoglycaemic relatives of type 2 diabetic patients.

Serum lipoprotein (a) concentrations (Lp(a)) are largely under genetic control, and are strong predictors of coronary heart disease. It has been hypothesised that Lp(a) may contribute to the increased risk of coronary heart disease in familial Type 2 diabetes mellitus. We therefore examined the Lp(a) concentrations and the apolipoprotein (a) (apo(a)) phenotypes in 126 normoglycaemic first degree relatives from families with two or more living Type 2 diabetic patients. These were compared with 147 sex matched normoglycaemic control subjects with no family history of diabetes. Lp(a) concentrations were measured using an enzyme-linked immunosorbent assay (ELISA), and apo(a) isoforms were determined and classified according to the relative mobility of apo(a) on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), relative to that of apolipoprotein B-100. There were no significant differences in Lp(a) concentrations between the relatives (R) and controls (C): 11.2 (R) vs. 11.1 (C) mg/dl (median). The distribution of apo(a) phenotypes was not significantly different between groups 0.65 (R) vs. 0.67 (C). These results show that first degree relatives at risk of developing Type 2 diabetes do not have abnormal Lp(a) concentrations or apo(a) phenotypes.

Adult↗
PubMed1996

Suicide in the elderly. Recognizing the signs.

We wish to stress the importance of remaining alert to the possibility of both depression and suicidality in the geriatric population. There is also a need for flexibility in assessing the elderly who may present with atypical symptoms of depression and who may not express their distress directly. The interaction of risk factors may be instrumental in determining the risk for suicide in a particular patient. In our case, we have identified an impaired ability to communicate, intractable tinnitus, and feelings of helplessness.

Age Factors↗
PubMed1996

An outbreak of cutaneous aspergillosis in a tertiary-care hospital.

A cluster of four cases of surgical and burn wound aspergillosis occurred in a 900-bed, adult, tertiary-care hospital. The source was traced to the outside packages of dressing supplies, which had become contaminated during construction in the central Inventory Control area. This resulted in patients with large exposed surface areas being inoculated directly with Aspergillus spores.

Adult↗
PubMed1996

Epidural analgesia.

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Analgesia, Epidural↗
PubMed1996

Cigarette smoking in British men and selection for coronary artery bypass surgery.

OBJECTIVE: To examine the relation between smoking status, clinical need, and likelihood of coronary artery bypass grafting in middle aged men. DESIGN: A prospective study of cardiovascular disease in British men aged 40 to 59 years, screened in 1978-80 and followed until December 1991. SUBJECTS AND SETTING: 7735 men drawn from one general practice in each of 24 British towns. MAIN OUTCOME MEASURE: Coronary artery bypass graft surgery. RESULTS: Of the 3185 current smokers, 38 (1.03/1000/year) underwent coronary artery bypass surgery compared with 47 of 2715 (1.45/1000/year) ex-smokers, and 19 of 1817 (0.85/1000/year) never-smokers. Ex-smokers had a lower incidence of major ischaemic heart disease during follow up than current smokers. After adjustment for incidence of ischaemic heart disease during follow up, the hazard ratio of coronary artery bypass surgery for ex-smokers compared with smokers was 1.52 (95% confidence interval 0.99 to 2.34). Ex-smokers were more likely at screening to recall a doctor diagnosis of ischaemic heart disease than smokers (7.1% v 5.3%), but among those who recalled a doctor diagnosis, smokers were less likely to undergo coronary artery bypass surgery than ex-smokers (9.4% v 3.5%, P = 0.026). By 1992, men defined as smokers at screening were no less likely than ex-smokers to have been referred to a cardiologist (18.5% v 18.8%), nor to report having undergone coronary angiography less frequently than ex-smokers (12.7% v 11.4%). CONCLUSION: Even allowing for the strong relation between coronary artery bypass surgery and clinical need, continuing smokers were less likely to undergo coronary artery bypass surgery than ex-smokers. A complex interplay exists between the men's experience of heart disease, the decision to stop smoking, and the willingness of doctors to consider coronary artery bypass surgery.

Adult↗
PubMed1996

Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men.

OBJECTIVE: To determine whether Helicobacter pylori, a chronic bacterial infection often acquired in childhood, is associated with increased risk of coronary heart disease and stroke later in life. DESIGN: Nested case-control study. SETTING: Prospective study of cardiovascular disease in men aged 40-59 years at entry (1978-1980) in 24 British towns. SUBJECTS: 135 cases of myocardial infarction and 137 cases of stroke occurring before December 1991; 136 controls were identified, frequency matched to cases by town and age group. METHODS: Serum samples stored at entry were analysed by an enzyme linked immunosorbent assay for the presence of H pylori specific IgG antibodies. RESULTS: 95 of the myocardial infarction cases (70%) and 93 (68%) of the stroke cases were seropositive for H pylori compared with 78 (57%) of the controls (odds ratio for myocardial infarction 1.77, 95% confidence interval (CI) 1.06 to 2.95, P = 0.03; odds ratio for stroke 1.57, 95% CI 0.95 to 2.60, P = 0.07). Helicobacter pylori infection was associated with manual social class, residence in Northern England or Scotland, cigarette smoking, higher systolic pressure and blood glucose, and a lower height-standardised forced expiratory volume in one second. Adjustment for these factors attenuated the relation between H pylori and myocardial infarction (odds ratio = 1.31, 95% CI 0.70 to 2.43, P = 0.40) and effectively abolished the relation with stroke (odds ratio = 0.96, 0.46 to 2.02, P = 0.92). The relation between helicobacter infection and fatal myocardial infarction was slightly stronger (odds ratio 2.41, 95% CI 1.13 to 5.12) but was also markedly attenuated after adjustment (1.56, 95% CI 0.68 to 3.61). CONCLUSION: In this prospective study the association between Helicobacter pylori infection and increased risk of myocardial infarction and stroke was substantially confounded by the relation between this infection, adult social class, and major cardiovascular risk factors.

Adult↗
PubMed1996

Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors.

PURPOSE: To perform a phase I clinical and pharmacologic study of ZD1694 (Tomudex, Alderley Park, United Kingdom), a new folate-based thymidylate synthase (TS) inhibitor, in patients with advanced malignancy. PATIENTS AND METHODS: From February 1991 to January 1993, 61 patients with a range of solid tumor received 161 courses of ZD1694 given as a single 15-minute intravenous infusion every 3 weeks, at escalating doses from 0.1 to 3.5 mg/m2. Pharmacokinetic (PK) analysis was performed with the first two courses of treatment. There were 33 men and 28 women with a median age of 53 years (range, 21 to 73). Fifty-five patients (90%) had previously received chemotherapy. RESULTS: Reversible liver toxicity and dose-related gastrointestinal (GI) and bone marrow toxicity occurred at > or = 1.6 mg/m2. Liver function usually returned to normal with repeated treatment, but GI and bone marrow toxicities generally became more severe. No renal toxicity was observed. The maximum-tolerated dose (MTD) was 3.5 mg/m2, at which, in addition to antiproliferative toxicities, four of six patients (67%) developed severe malaise that consisted of anorexia, nausea, and asthenia, with rapidly decreasing performance status that limited re-treatment. Abnormal liver function was also seen in four patients (67%). At 3.0 mg/m2, grades III and IV diarrhea were seen in six of 23 patients (26%) and grade IV myelosuppression in two others. Liver toxicity was self-limiting and not associated with severe malaise. Two patients had a partial response to treatment. PK analysis showed that plasma elimination was triexponential, with pronounced variability in the mean terminal half-life (t1/2gamma) for a given dose ranging from 8.2 to 105 hours. There was a linear relationship between dose and both the area under the concentration-time curve (AUC) and maximum concentration (Cmax), but no clear association between these parameters and response or toxicity. CONCLUSION: The dose of ZD1694 recommended for phase II trials is 3.0 mg/m2.

Adult↗
PubMed1996

Safety and activity of zalcitabine and zidovudine combination in HIV-positive people with CD4 cell counts < or = 300 cells/mm3. The Roche M50002 Study Group.

We carried out an open-label, single-arm, multicentre 1-year study of the safety and activity of therapy with a zalcitabine-zidovudine combination in 561 patients with CD4 cell counts < or = 300 cells/mm3 who were either established on zidovudine or had not previously received antiretroviral therapy. Additionally, we assessed the impact of baseline characteristics on clinical outcome during therapy. The study used specialist HIV-care centres in Argentina, Belgium, Brazil, Hungary, Italy, Luxembourg, Mexico, Peru, Spain and Venezuela. Participants were regularly assessed for adverse experiences, changes in laboratory values and clinical progression. A total of 561 patients entered the study, with 353 completing 12 months of follow-up. The 492 zidovudine-experienced patients had a mean duration of previous therapy of 18.5 months. No unexpected adverse events were reported. Peripheral neuropathy was observed in 12.7% of patients and was more common in participants with CD4 cell counts < or = 100 cells/mm3 at baseline. Clinical disease progression was significantly associated with lower baseline CD4 cell counts, a history of previous AIDS-defining events and a baseline haemoglobin < 11 g/dl. The median CD4 cell count at baseline was 141.5 cells/mm3, rising to 174 cells/mm3 after 12 weeks and to 148 cells/mm3 at 12 months. In conclusion, zalcitabine-zidovudine combination therapy was found to be well tolerated in this patient population, although patients with CD4 cell counts < or = 100 cells/mm3 were found to require more intensive monitoring for toxicities and disease events. The changes in the CD4 cell count seen in this study and in others provide evidence of the therapeutic activity of this combination.

Adult↗
PubMed1996

Doppler bubble detection after hyperbaric exposure.

A review of the literature on the use of transcutaneous Doppler to detect circulating venous bubbles occurring after hyperbaric exposure, with emphasis on the detection of bubbles occurring after relatively small decrements in pressure, is presented. The correlation between circulating bubbles and the occurrence of decompression illness is examined.

Blood Gas Analysis↗