Search PubMed⌕ Search

Biomedical subjects

A Evans

Publications and source records attributed to A Evans.

At least 199 records · Page 11Linked to original sources
PubMed1998

Drug resistance in ovarian cancer - the role of p53.

The aims were to determine the importance of p53 and bcl-2 expression on the response to chemotherapy with alkylating agents in patients with ovarian cancer. We have followed the response to chemotherapy in a series of 59 patients with ovarian adenocarcinoma designated as p53 and bcl-2 positive or negative by immunocytochemistry. Of these cases, 50 received either cisplatin + treosulfan or treosulfan alone. Immunocytochemistry for p53 was positive in 28/59 tumors. Patients were grouped according to their response to chemotherapy (stable or progressive disease) assessed at 6, 12, and 18 months. There was increasing divergence of p53+ and p53- tumors over time. Of those which were p53+, 25% showed progression at 6 months, 80% at 12 months and 89% progression at 18 months. In contrast, 23%, 50%, and 67% of p53- tumors showed progression at 6, 12 and 18 months respectively. For bcl-2, in 23/55 positive tumors there was progression in 35%, 78% and 94% compared with 25%, 57% and 59% in bcl-2 negative tumors at 6,12 and 18 months respectively. Those tumors which were bcl-2 and p53 negative were most likely to progress, while those which were bcl-2 and p53 positive had the best prognosis. These differences did not translate into increased overall survival with minimum follow-up of 12 months. This data lends support to our suggestion that despite initially increased susceptibility to alkylating agents, enhanced genomic instability due to p53 inactivation may render tumors more likely to develop resistance to chemotherapy over time. This effect may be altered by bcl-2 function, lack of which will lead to a good response to chemotherapy as the tumor's ability to undergo apoptosis will not be compromised.

Adenocarcinoma↗
PubMed1998

Patient assessment: validation of a nursing instrument.

The aim of this study is to evaluate the reliability and validity of the Byron Physical Assessment Framework (BPAF). The BPAF is a systems based checklist of physiological measurements, signs, and symptoms designed to structure and document the assessment of a patients physical condition by nursing staff. Initially the BPAF was refined using extensive literature review and expert opinion to improve the comprehensiveness and clarity for its intended purpose. As a result the content validity of the BPAF was supported. Inter-rater reliability between both expert-expert and novice-expert pairings was assessed. A total of 68 assessments were conducted by pairs of qualified nurses with patients on general medical and surgical wards and a nursing-led unit in one London Hospital. Reliability of the dichotomous data items of the BPAF was found to be generally good (kappa > 0.6) with only one item showing a poor reliability (kappa < 0.20). Reliability for continuous items such as pulse and respiratory rate was surprisingly low with evidence of large variation between raters in addition to systematic bias. With relatively little teaching, novice assessors were able to use the BPAF and achieve good inter-rater reliability with expert assessors although this was lower than the reliability of the expert diads. The utilisation of the BPAF to fulfil intended purpose was assessed by examining completed assessments and the outcome in terms of nurses' actions in light of new abnormal findings. Both were found to be fair, showing that the BPAF does affect the actions of nurses although it could be utilised more.

Confounding Factors, Epidemiologic↗
PubMed1998

Depressor action of insulin on skeletal muscle vasculature: a novel mechanism for postprandial hypotension in the elderly.

OBJECTIVES: We sought to assess the role of insulin in postprandial blood pressure regulation in the elderly. BACKGROUND: Insulin is both a positive inotropic and chronotropic hormone that also vasodilates skeletal muscle vasculature. Insulin may thus mediate aspects of postprandial cardiovascular homeostasis. METHODS: Ten healthy elderly subjects were studied in the fasting state on three separate days. After baseline supine hemodynamic and neurohumoral measurements were taken (cardiac output and superior mesenteric artery blood flow were measured using Doppler ultrasound, and calf blood flow was measured using venous occlusion plethysmography), subjects ate on one occasion a 2.5-MJ high carbohydrate meal and on the other two occasions, an isoenergetic high fat meal. One high fat meal was accompanied by an insulin infusion reproducing the plasma insulin profile seen after a high carbohydrate meal while maintaining the glycemic profile seen after a high fat meal alone. After meal ingestion, measurements were repeated every 20 min for 2 h. RESULTS: After the three meals, there were similar increments in cardiac output and heart rate. After the high carbohydrate meal and high fat meal with insulin, mean arterial blood pressure fell by between 8 to 10 mm Hg, but did not change after the high fat meal. After the high carbohydrate meal and the high fat meal with insulin, calf vascular resistance did not change, whereas after the high fat meal, it increased by 15.5 +/- 4.4 U (mean +/- SEM). CONCLUSIONS: Insulin contributes to the failure of calf vasoconstriction seen after a high carbohydrate meal. By this vasodepressor action, insulin is at least in part responsible for the fall in blood pressure after a high carbohydrate meal.

Aged↗
PubMed1998

Polymorphisms of the tumour necrosis factor-alpha gene, coronary heart disease and obesity.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a cytokine that has multiple functions. Through its effects on lipid metabolism, coagulation, insulin resistance and endothelial function, TNF-alpha could be involved in cardiovascular pathophysiology. Given this possibility, we hypothesized that polymorphisms of the TNF-alpha gene might be associated with a predisposition to coronary heart disease (CHD). METHODS: The entire coding region and 1053 bp upstream of the transcription start site of the TNF-alpha gene were screened for polymorphisms using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequencing. Five polymorphisms were identified: four were located in the upstream region at positions -857, -851, -308, -238 from the first transcribed nucleotide and one was found in a non-translated region at position +691. Six-hundred and forty-one patients with myocardial infarction (MI) and 710 control subjects from the ECTIM Study were genotyped. RESULTS: The genotype frequencies were similar in cases and control subjects in the high-risk population of Belfast and in France; however, the TNF-alpha/-308A allele was more frequent in Belfast than in France (0.242 vs. 0.157; P < 0.0001), and carriers of this allele were more frequently obese than non-carriers [1.52 (1.15-1.99), P < 0.004]. No associations were found for the other polymorphisms. CONCLUSIONS: These results suggest that polymorphisms of the TNF-alpha gene are unlikely to contribute to CHD risk in an important way, but the TNF-alpha/-308 polymorphism should be investigated further in relation to obesity.

Adult↗
PubMed1998

Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial.

Mild hyperhomocysteinemia is accepted as a risk factor for premature cardiovascular disease. In a population with a high prevalence of cardiovascular disease, we screened a group of clinically healthy working men aged 30-49 y (n = 509) for plasma homocysteine and 5,10-methylene tetrahydrofolate reductase (MTHFR) genotype status. Those with mildly elevated homocysteine concentrations (> or = 8.34 micromol/L) were selected for intervention. In a randomized, factorial-design, controlled trial we assessed the effects of B-group vitamins and antioxidant vitamin supplementation on homocysteine concentrations. The 132 men were randomly assigned to one of four groups: supplementation with B-group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, and 0.02 mg cyanocobalamin), antioxidant vitamins alone (150 mg ascorbic acid, 67 mg RRR-alpha-tocopherol, and 9 mg beta-carotene), B-group vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-wk intervention. When homocysteine concentrations were analyzed by group, significant (P < 0.001) decreases (32.0% and 30.0%, respectively) were observed in both groups receiving B-group vitamins either with or without antioxidants. The effect of B-group vitamins alone over 8 wk was a reduction in homocysteine concentrations of 27.9% (95% CI: 22.0%, 33.3%; P < 0.001) whereas antioxidants alone produced a nonsignificant increase of 5.1% (95% CI: -2.8%, 13.6%; P = 0.21). There was no evidence of any interaction between the two groups of vitamins. The effect of B-group vitamin supplementation seemed to depend on MTHFR genotype. Supplementation with the B-group vitamins with or without antioxidants reduced homocysteine in the men with mildly elevated concentrations, and hence may be effective in reducing cardiovascular risk.

Adult↗
PubMed1998

The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction.

P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable angina. We investigated the P-selectin gene as a possible candidate for myocardial infarction (MI). The P-selectin gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17 exons. The sequences of the 5'-flanking region and exons of 40 alleles from patients with MI were screened for polymorphisms using polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing. Thirteen polymorphisms were identified: five in the 5'-flanking and eight in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp, Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of the P-selectin protein. All P-selectin polymorphisms as well as a common E-selectin polymorphism, Ser128Arg which has been reported as being associated with an increased risk of premature coronary heart disease (CHD), and is in tight linkage disequilibrium with several P-selectin polymorphisms, were investigated in 647 patients with MI and 758 control subjects from four regions of France and Northern Ireland (the ECTIM study). The entire set of P-selectin polymorphisms provided a heterozygosity of 91%. The polymorphisms were tightly associated with one another and displayed patterns of linkage disequilibrium suggesting the existence of highly conserved ancestral haplotypes. The five polymorphisms in the 5'-flanking region of the gene were unrelated to MI or any relevant phenotype measured in the ECTIM study. We inferred that the four missense variants identified in the coding region predicted eight common forms of the P-selectin protein. The Pro715 allele which characterizes one of these forms was less frequent in France than in Northern Ireland ( P < 0.002) and in cases than in controls ( P < 0.002; P < 0.02 after correction for the number of tests). We conclude that the P-selectin gene is highly polymorphic and hypothesize that the Pro715 variant may be protective for MI. Whether this variant affects the properties of the P-selectin protein in a way which is compatible with this hypothesis needs to be checked experimentally.

Adult↗
PubMed1998

New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. Etude Cas-Témoin de l'Infarctus du Myocarde.

OBJECTIVE: In an earlier report, we suggested that a polymorphism located in the 3' untranslated region of the angiotensin II type 1 receptor gene (AT1R+1166 A/C) might interact with the angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism to increase the risk of myocardial infarction. Since the AT1R+1166 A/C polymorphism does not appear to be functional, we postulated that it might be in linkage disequilibrium with an unidentified functional variant which would affect the regulation of the gene in response to angiotensin II. The present study was conducted to identify new polymorphisms of the AT1R gene that might be responsible for this interaction. METHODS: The first four exons, which are untranslated, and 2.2 kb in the 5' flanking region of the AT1R gene were explored by polymerase chain reaction/single-strand conformation polymorphism. Seven polymorphisms were detected in the 5' region at positions -1424, -810, -713, -521, -214, -213 and -153 upstream from the start of transcription. The genotypes of the -810, -713, -214, -213 and -153 polymorphisms were completely concordant. One substitution was detected at the 55th nucleotide of exon 4. These polymorphisms, together with the +1166 A/C polymorphism and a previously described T/C substitution at the 573th nucleotide of exon 5, were genotyped in the Etude Cas-Témoin de l'Infarctus du Myocarde (ECTIM) study, a multicentre study comparing 651 patients who had survived a myocardial infarction and 728 controls from Belfast (United Kingdom) and Lille, Strasbourg and Toulouse (France). RESULTS: The newly identified polymorphisms were not in linkage disequilibrium with the +1166 A/C polymorphism and therefore could not explain the interaction observed with ACE I/D. None of the polymorphisms was associated with blood pressure levels in control subjects. In the four populations, the A allele of the -810 polymorphism was associated with a lower risk of myocardial infarction (population-adjusted odds ratio of 0.80, confidence interval 0.65-0.97, P< 0.05). CONCLUSIONS: None of the newly identified polymorphisms could account for the previously described interaction between the AT1R+1166 A/C and the ACE I/D polymorphisms affecting the risk of myocardial infarction. However, the present study suggests that AT1R-810 T/A, or other polymorphisms which are in complete association with it, might be associated with the risk of myocardial infarction. Further studies are required to confirm this finding and to identify the functional variants.

Adult↗
PubMed1998

A high-resolution microsatellite map of the mouse genome.

The European Collaborative Interspecific Backcross (EUCIB) resource was constructed for the purposes of high-resolution genetic mapping of the mouse genome (). The large Mus spretus/C57BL/6 backcross of 982 progeny has a genetic resolution of 0.3 cM at the 95% confidence level ( approximately 500 kb in the mouse genome). We have used the EUCIB mapping resource to develop a genome-wide high-resolution genetic map incorporating 3368 microsatellites. The microsatellites are distributed among 2302 genetically separated bins with 1.46 markers per bin on average. Average bin separation is 0.61 cM. This high-resolution genetic map will aid the construction of a robust physical map of the mouse genome.

Animals↗
PubMed1998

Morphometric analysis of the temporal lobe in temporal lobe epilepsy.

PURPOSE: Using high-resolution magnetic resonance imaging (MRI), we examined the temporal neocortex and the underlying white matter in patients with unilateral temporal lobe epilepsy (TLE) and in control subjects. METHODS: The images of 27 patients and 42 control subjects were registered into stereotaxic space, corrected for image intensity inhomogeneity, and automatically segmented into gray matter, white matter, and cerebrospinal fluid (CSF) over a predetermined extent of the temporal lobe. The surface between the gray matter and CSF was extracted, indices of curvature (IOC) of the surface were calculated, and a frequency histogram of the IOC was obtained. RESULTS: There was significant bilateral reduction in the total volume of the temporal lobe and in the volume of gray matter. White matter volume was significantly reduced only in the temporal lobe ipsilateral to the seizure focus. There were significant changes in the position and amplitude of peaks in the frequency histogram of the IOC. CONCLUSIONS: The volume of gray matter was negatively correlated with duration of epilepsy, suggesting that neocortical changes may be a consequence of seizures. Changes in the frequency histogram of the IOC suggested an additional alteration in the surface morphology of the temporal lobe in TLE, possibly related to sulcal widening.

Adolescent↗
PubMed1998

Changes in cigarette smoking among adults in 35 populations in the mid-1980s. WHO MONICA Project.

OBJECTIVE: To examine changes in the prevalence of cigarette smoking in 35 study populations of the World Health Organisation's MONICA Project. DESIGN: Data from two independent, community-based surveys conducted, on average, five years apart. SETTING: Geographically defined populations in 21 countries mainly in eastern and western Europe. SUBJECTS: Randomly selected men and women aged 25-64 years. Numbers of participants in each study population ranged from 586 to 2817 in each survey. MAIN OUTCOME MEASURES: Changes in proportions of current smokers, ex-smokers, and never-smokers by age and sex using data collected by standardised methods. RESULTS: Among men, smoking prevalence decreased in most populations, by three to four percentage points over five years. In Beijing, however, it increased in all age groups--overall by 11 percentage points. Among women there were increases in smoking in about half the populations. The increases were mainly in the age group 35-54 years and often in those populations where smoking prevalence among women has been relatively low. CONCLUSIONS: Smoking initiation by middle-aged women in parts of southern and eastern Europe and among men of all ages in Beijing is a matter of concern. The various public health measures that have helped to reduce smoking among men in developed countries should be vigorously extended to these other groups now at growing risk of smoking-related disease.

Adult↗
PubMed1998

Analysis of the association of a heat shock protein70-1 gene promoter polymorphism with myocardial infarction and coronary risk traits.

Heat shock proteins (HSP) are induced during coronary ischaemia, and abnormal expression of one HSP gene may cause hypertension in rats. We examined association of a promoter polymorphism in the major stress-inducible hsp70 gene (hsp70-1 or HSP70A1) on chromosome 6 (p21.3) with coronary disease traits. This C-->A base substitution (AAACCCC) is at nucleotide position-110 in the heat shock transcription factor binding site (heat shock element, HSE). The first study sample (ECTIM), recruited from Belfast and three centers in France, consisted of 578 myocardial infarction cases and 698 age-matched controls. The frequency of the A-110 allele was 0.381 (95% CI = 0.35-0.41) and 0.384 (95% CI = 0.36-0.41) in cases and controls respectively. Homozygotes for the rarer A-110 allele had a higher BMI (27.3 kg/m2 +/- 3.9) compared with homozygotes for the common C-110 allele (26.3 kg/m2 +/- 3.3). The rarer homozygotes were shorter and heavier than the common homozygotes. A follow-up study involved 1431 healthy, middle aged men from the UK (NPHS II group). The frequency of the A-110 allele was 0.385 (95% CI = 0.37-0.40), and there was no association of genotype with BMI. Thus there appears to be no strong association of the Hsp70-1 promoter polymorphism with risk of myocardial infarction, BMI or any coronary disease traits analysed here.

Adult↗
PubMed1998

Regional cerebral blood flow and language dominance: SPECT during intracarotid amobarbital testing.

We examined the relation between language dominance and regional cerebral blood flow (rCBF) during the intracarotid amobarbital procedure (IAP). A previous report limited to three patients suggested that dominant rather than nondominant hemisphere IAP may have a differential effect on rCBF. Behavioral assessment during the IAP also suggests that dominant hemisphere injection results in a differential effect on memory and affective symptoms rather than nondominant injection. Thirteen patients were assessed using single-photon emission CT (SPECT) brain imaging during both left and right IAP. The SPECTs were coregistered with the individual's MRI. Changes in rCBF during each IAP were compared with the patient's baseline SPECT. Nine patients had left hemisphere dominance, two were right dominant, and two had bilateral speech representation. In the left dominant subjects, left-hemisphere injection had a consistently greater effect on rCBF than right-hemisphere injection in the anterior (p < 0.005) and posterior (p < 0.01) temporal neocortex. There was also a trend for greater hypoperfusion in the frontal lobe of the left hemisphere. rCBF in the ipsilateral hippocampus was not significantly different after each injection (p > 0.05). In the two patients with right hemisphere speech, the reverse pattern was seen, with greater hypoperfusion after right (dominant) hemisphere injection. There was no consistent asymmetry in the two patients with bilateral speech. Dominant hemisphere IAP results in significantly greater hypoperfusion than does nondominant injection. These data provide a physiologic basis for behavioral differences noted after dominant versus nondominant IAP.

Adolescent↗
PubMed1998

Changes in estimated coronary risk in the 1980s: data from 38 populations in the WHO MONICA Project. World Health Organization. Monitoring trends and determinants in cardiovascular diseases.

The World Health Organization (WHO) MONICA Project is a 10-year study monitoring trends and determinants of cardiovascular disease in geographically defined populations. Data were collected from over 100,000 randomly selected participants in two risk factor surveys conducted approximately 5 years apart in 38 populations using standardized protocols. The net effects of changes in the risk factor levels were estimated using risk scores derived from longitudinal studies in the Nordic countries. The prevalence of cigarette smoking decreased among men in most populations, but the trends for women varied. The prevalence of hypertension declined in two-thirds of the populations. Changes in the prevalence of raised total cholesterol were small but highly correlated between the genders (r = 0.8). The prevalence of obesity increased in three-quarters of the populations for men and in more than half of the populations for women. In almost half of the populations there were statistically significant declines in the estimated coronary risk for both men and women, although for Beijing the risk score increased significantly for both genders. The net effect of the changes in the risk factor levels in the 1980s in most of the study populations of the WHO MONICA Project is that the rates of coronary disease are predicted to decline in the 1990s.

Adult↗
PubMed1998

Simulated surgery.

Explore the source record for details and available documents.

Educational Measurement↗
PubMed1998

The histidin-rich glycoprotein Pro186/Ser polymorphism is not related to myocardial infarction in the ECTIM study.

The histidin-rich glycoprotein (HRG) may contribute to coronary heart disease as a consequence of its possible thrombophilic properties. To test this hypothesis we have investigated the Pro186/Ser polymorphism of the HRG gene, which is known to strongly affect plasma HRG levels, in a large multicenter case-control study of myocardial infarction (MI). The results failed to demonstrate any association between the polymorphism and MI or angiographically assessed coronary stenosis.

Adult↗
PubMed1998

Reform of the Medicare AAPCC: learning from previous proposals. Average Adjusted Per Capita Costs.

Since 1982, Medicare has contracted with health maintenance organizations (HMOs) on a risk-contract basis, paying plans based on Average Adjusted Per Capita Costs (AAPCCs). The calculation of the AAPCCs has been criticized on several fronts. A congressional proposal encompassed in the failed 1995 Balanced Budget Act would have altered the formula by which Medicare determines payments to risk-contracting HMOs. Many of its provisions were enacted through the 1997 Balanced Budget Act. This paper models the effect of the earlier proposal on AAPCC rates and discusses the extent to which the proposal and the reforms in the 1995 Balanced Budget Act would address shortcomings identified in the original rate formula.

Budgets↗