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Biomedical subjects

A Evans

Publications and source records attributed to A Evans.

At least 91 records · Page 5Linked to original sources

Are the results of randomized controlled trials on anticoagulation in patients with atrial fibrillation generalizable to clinical practice?

BACKGROUND: Randomized trials demonstrate a clear benefit of anticoagulation in patients with atrial fibrillation at risk of stroke, but the proportion of eligible patients who are treated with anticoagulants remains low. The reluctance to treat all eligible patients with anticoagulants may be due to studies in clinical practice showing variable risk-benefit, raising concerns about application to general medical practice. METHODS: A systematic review of published medical literature was performed to identify studies of patients with atrial fibrillation who were treated with warfarin in actual clinical practice. Data from these studies were compared with pooled data from randomized controlled trials. RESULTS: Three studies met the predefined criteria, each in a different health care setting, totaling 410 patients with 842 patient-years of follow-up. Patients in clinical practice were older and had more comorbid conditions compared with trial participants. However, the ischemic stroke rate was similar between clinical practice and randomized studies (1.8% [95% confidence interval (CI), 0.9%-2.7%] vs 1.4% [95% CI, 0.9%-2.0%]). Intracranial hemorrhage (0.1% [95% CI, 0%-0.3%] vs 0.3% [95% CI, 0.06%-0.5%]) and major bleeding (1.1% [95% CI, 0.4%-1.8%] vs 1.3% [95% CI, 0.8%-1.8%]) rates were also similar. There was a higher rate of minor bleeding in clinical practice than in trials (12.0% [95% CI, 9.7%-14.3%] vs 7.9% [95% CI, 6.6%-9.2%]). CONCLUSIONS: Patients who undergo anticoagulation for atrial fibrillation in actual clinical practice differ from those in randomized trials, but have similar rates of stroke and major bleeding. The risk of minor bleeding is higher and may require more intensive monitoring in practice.

Aged↗

The size and albedo of the Kuiper-belt object (20000) Varuna.

Observations over the last decade have revealed the existence of a large number of bodies orbiting the Sun beyond Neptune. Known as the Kuiper-belt objects (KBOs), they are believed to be formed in the outer reaches of the protoplanetary disk around the young Sun, and have been little altered since then. They are probably the source of short-period comets. The KBOs are, however, difficult objects to study because of their distance from earth, so even basic physical properties such as their sizes and albedos remain unknown. Previous size estimates came from assuming an albedo with the canonical value being 0.04. Here we report simultaneous measurements of the thermal emission and reflected optical light of the bright KBO (20000) Varuna, which allow us to determine independently both the size and the albedo. Varuna has an equivalent circular diameter of D = 900+129-145 km and a red geometric albedo of pR = 0.070+0.030-0.017. Its surface is darker than Pluto's, suggesting that it is largely devoid of fresh ice, but brighter than previously assumed for KBOs.

Journal Article↗

Haemostasis in relation to dietary fat as estimated by erythrocyte fatty acid composition: the prime study.

We investigated whether haemostatic variables were related with dietary fatty acid composition as estimated by the fatty acid content of erythrocytes. Subjects were a subsample (n=283) of the participants in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study. Factor VII, fibrinogen, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor type 1 (PAI-1), D-dimer and von Willebrand factor (vWf) were measured and the fatty acid composition was determined in the phospholipids of total erythrocytes by gas chromatography. Statistical analyses were performed using multiple linear regression analyses with adjustment for age, center and body mass index. tPA-ag was significantly related to the n-3 fatty acids derived from fish. This was reflected in an inverse association of all n-3 fatty acids combined with tPA-ag (beta=-0.37 ng/ml/%, 95% confidence intervals: -0.45, -0.29, P<.01). Positive and significant associations of D-dimer with arachidic and eicosamonoenoic acid were observed (P<.01). No relationships were found between fatty acids and fibrinogen, vWf, PAI-1 or factor VII. The results of this study suggest that consumption of n-3 fatty acids derived from fish may favourably influence tPA-ag.

Body Mass Index↗

Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy.

BACKGROUND: -Hypertrophic cardiomyopathy (HCM), the most common cause of sudden cardiac death in the young, is characterized by cardiac hypertrophy, myocyte disarray, and interstitial fibrosis. We propose that hypertrophy and fibrosis are secondary to the activation of trophic and mitotic factors and, thus, potentially reversible. We determined whether the blockade of angiotensin II, a known cardiotrophic factor, could reverse or attenuate interstitial fibrosis in a transgenic mouse model of human HCM. METHODS AND RESULTS: We randomized 24 adult cardiac troponin T (cTnT-Q(92)) mice, which exhibit myocyte disarray and interstitial fibrosis, to treatment with losartan or placebo and included 12 nontransgenic mice as controls. The mean dose of losartan and the mean duration of therapy were 14.2+/-5.3 mg. kg(-1). d(-1) and 42+/-9.6 days, respectively. Mean age, number of males and females, and heart/body weight ratio were similar in the groups. Collagen volume fraction and extent of myocyte disarray were increased in the cTnT-Q(92) mice (placebo group) compared with nontransgenic mice (9.9+/-6.8% versus 4.5+/-2.2%, P=0.01, and 27.6+/-10.6% versus 3.9+/-2.3%, P<0.001, respectively). Treatment with losartan reduced collagen volume fraction by 49% to 4.9+/-2.9%. The expression of collagen 1alpha (I) and transforming growth factor-beta1, a mediator of angiotensin II profibrotic effect, were also reduced by 50%. Losartan had no effect on myocyte disarray. CONCLUSIONS: Treatment with losartan reversed interstitial fibrosis and the expression of collagen 1alpha (I) and transforming growth factor-beta1 in the hearts of cTnT-Q(92) mice. These findings suggest that losartan has the potential to reverse or attenuate interstitial fibrosis, a major predictor of sudden cardiac death, in human patients with HCM.

Angiotensin Receptor Antagonists↗

Three-dimensional probabilistic atlas of the human orbitofrontal sulci in standardized stereotaxic space.

A quantitative analysis of the variability of human orbitofrontal anatomical landmarks is required if one is to describe properly the location of functional or structural changes within this brain region. The present study investigated the orbitofrontal sulci in 100 normal adult human cerebral hemispheres using magnetic resonance images that were transformed into the standardized proportional stereotaxic space most commonly used, that of Talairach and Tournoux (1988). Four orbitofrontal sulci were identified and marked on each hemisphere: the olfactory, the medial, the lateral, and the transverse orbital sulci. Probability maps were then constructed for each sulcus. These maps provide a statistical description of the variability of the location of each orbitofrontal sulcus within the three-dimensional coordinate system of Talairach and Tournoux (1988). These probability maps may be directly compared with any image transformed into the same standardized space, providing a valuable tool for identifying and describing the location of functional or structural changes in the orbitofrontal region of the human brain.

Adult↗

Interleukin-6 gene polymorphisms and susceptibility to myocardial infarction: the ECTIM study. Etude Cas-Témoin de l'Infarctus du Myocarde.

There is growing evidence that interleukin (IL) 6 plays an important role in the atherosclerotic process because of its role in mediating immune and inflammatory responses and inducing cell proliferation. The present study examined whether molecular variations at the IL-6 locus are involved in the predisposition to myocardial infarction. The entire coding region, 1,158 bp of the 5' flanking region and 237 bp of the 3' flanking region of the IL-6 gene were screened. We detected three nucleotide substitutions in the 5' region at positions -174 (G/C), -572 (G/C), and -596 (G/A) from the transcription start site, and one insertion/deletion in the 3' region at position +528 after the Stop codon. These polymorphisms were genotyped in the Etude Cas-Témoin de l'Infarctus du Myocarde study comparing male patients (n=640) and age-matched controls (n=719) from Northern Ireland and France. The IL-6/G-174C and IL-6/G-596A polymorphisms were in nearly complete association. Carriers of the IL-6/-174 C allele were more frequent in patients than in controls. The population-adjusted odds ratio for myocardial infarction associated with genotype CC+CG vs. GG was estimated as 1.34. In French patients the number of coronary arteries with greater than 50% stenosis was assessed by angiography. The IL-6/-174 C allele was more frequent in patients with two or fewer stenosed vessels than in patients with three-vessel lesions. These results suggest that genetic variation at the IL-6 locus is associated with susceptibility to myocardial infarction, especially events occurring on less extended lesions. These findings would be compatible with a lower IL-6 secretion associated with the IL-6/-174 C allele, itself or in combination with other promoter polymorphisms, leading to more unstable plaques.

Adult↗

Imaging features of primary malignant rhabdoid tumour of the brain.

Primary malignant rhabdoid tumour of the central nervous system is a rare neoplasm affecting children. We present a pathologically proven case, which was initially referred to the paediatric surgeons as a sebaceous cyst, and highlights the importance of imaging prior to surgery of potentially innocuous scalp lesions. Imaging features on CT and MRI are presented, which show bony involvement not previously reported in the literature.

Brain Neoplasms↗

Emergency department admissions to inpatient cardiac telemetry beds: a prospective cohort study of risk stratification and outcomes.

PURPOSE: Little is known about physicians' use of inpatient cardiac telemetry units among emergency department patients at risk for cardiac complications. We therefore studied the outcomes of patients admitted to inpatient telemetry beds to identify a subset of patients from whom cardiac monitoring could be withheld safely. SUBJECTS AND METHODS: We conducted a prospective cohort study of 1, 033 consecutive adult patients admitted to an inpatient telemetry unit from the emergency department of a 700-bed urban public teaching hospital. Subjects with or without chest pain were risk-stratified using a prediction rule and observed for in-hospital cardiac complications, acute myocardial infarction, and transfer to an intensive care unit (ICU). RESULTS: There were no significant differences between patients with (n = 677) or patients without chest pain (n = 356) in the rates of major cardiac complications, myocardial infarctions, or transfers to an ICU. Among 318 patients with chest pain who were classified as being very low risk, none suffered major complications (negative predictive value 100%; 95% confidence interval [CI]: 98.8% to 100%). Among 214 very low risk patients without chest pain, 1 (0.5%) had a major complication (negative predictive value 99.5%; 95% CI: 97.4% to 99.9%). CONCLUSIONS: The prediction rule accurately identified patients with or without chest pain who were at very low risk of major complications, identifying a subset from whom cardiac monitoring could be withheld safely.

Adolescent↗

Relationships between alcoholic beverages and cardiovascular risk factor levels in middle-aged men, the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction Study.

The relationships between alcoholic beverages and cardiovascular risk factors were assessed in 6730 men living in France or Northern Ireland. In France, all alcoholic beverages were significantly correlated with body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), high density lipoprotein (HDL) parameters, PAI-1 and Factor VII, whereas only wine was negatively related with fibrinogen levels. After adjusting for center, age, BMI, educational level, smoking and marital status, wine had a lesser effect on blood pressure, triglyceride, apo B and LpE:B levels than beer. Wine was associated with lower fibrinogen levels and beer with higher PAI-1 activity levels independent of the amount of alcohol consumed. In Northern Ireland, wine was negatively correlated with BMI, triglycerides, LpE:B and fibrinogen, whereas beer was positively correlated with SBP and DBP, triglycerides, HDL, apoprotein A-I and fibrinogen. Multivariate analysis showed wine to be positively associated with HDL parameters, and negatively with fibrinogen levels. Wine was also associated with higher LpA-I levels and lower fibrinogen levels independent of the amount of alcohol consumed. We conclude that alcohol consumption is related to lipid, lipoprotein and haemostatic variables, but the magnitude of the relationships depends on the type of alcoholic beverage. Also, some effects might be related to non-alcoholic components.

Alcohol Drinking↗

The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations.

Epidemiological evidence has revealed that an elevated plasma homocysteine level (hyperhomocysteinemia) confers an increased risk of cardiovascular disease and neural tube defects. Hyperhomocysteinemia is caused by both nutritional (e.g. folate, vitamins B(6) and B(12)) and genetic factors, including functional polymorphisms of key enzymes involved in homocysteine metabolism. One such enzyme, methionine synthase reductase (MTRR), maintains adequate levels of methylcob(III)alamin, the activated cofactor for methionine synthase, which catalyzes the remethylation of homocysteine to methionine. A common MTRR polymorphism, i.e. a 66 A-->G substitution specifying an isoleucine to methionine substitution (I22M), was recently identified. To assess the influence of this polymorphism on total plasma homocysteine (tHcy), we undertook a genotype/phenotype analysis in a study population of 601 Northern-Irish men, aged 30--49, for which biochemical and genetic data relevant to folate/homocysteine metabolism had already been acquired. The 66AA genotype has a frequency of 29% in this population. We established that there was a significant influence of MTRR genotype on tHcy ranking (P=0.004) and that the 66AA genotype contributes to a moderate increase in tHcy levels across the distribution [OR 1.59 (95% CI: 1.10--2.25) for the 66AA genotype to be in the upper half of the tHcy distribution, P=0.03]. The homocysteine-elevating effect of the 66AA genotype is independent of serum folate, vitamin B(12) and vitamin B(6) levels. Based on published estimates of the enhanced cardiovascular disease risk conferred by defined increments of plasma tHcy, we estimate that 66AA homozygotes have, on average, an approximately 4% increase in cardiovascular disease risk compared to 66GG homozygotes. This study provides the first evidence that the MTRR A66G polymorphism significantly influences the circulating tHcy concentration.

Adult↗

Treatment of metastatic pancreatic adenocarcinoma: a comprehensive review.

The current standard therapy for metastatic pancreatic adenocarcinoma is the single-agent gemcitabine, by the increasingly used fixed rate infusion of 10 mg/m2/min. There is strong reason to anticipate that additional benefits will accrue with gemcitabine-based combination chemotherapy. Gemcitabine and CPT-11 are synergistic with many drugs and non-cross-resistant with each other. Rigorous clinical investigations will be performed in an effort to identify optimal drug sequence and schedules for these novel combinations.

Adenocarcinoma↗

Therapy for regionally unresectable pancreatic cancer.

Chemoradiotherapy for unresectable LAPA is associated with a median survival time of 9 months or more and manageable toxic side effects. Experience with RT-FSP provides evidence that chemoradiotherapy may extend survival time with or without resection. Chemoradiotherapy or entry into clinical trials is the standard for LAPA. The next generation of clinical trials for LAPA will incorporate newer agents, such as gemcitabine and irinotecan into chemoradiotherapy regimens. Novel agents, such as matrix-metaloproteinase inhibitors, transcription factor inhibitors, antiangiogenic factors, cyclooxegenase-2 inhibitors, and agents that target the K-ras point mutations associated with 90% of pancreatic cancers, are in early phases or clinical development and may have activity for micrometastic or minimal residual disease. Lower toxicity makes these drugs attractive agents for maintenance therapies. The multitude of new agents provides hope to patients and a welcome challenge for further investigation.

Adenocarcinoma↗

Maintaining prevention in practice: survival of PPIP in primary care settings. Put Prevention Into Practice.

INTRODUCTION: Put Prevention Into Practice (PPIP) consists of a kit of office-based tools intended to support the provision of preventive services by primary care providers. The purpose of this study was to examine the institutionalization of PPIP within five primary care clinics funded by the Texas Department of Health to implement PPIP, and to examine the organizational determinants of program institutionalization. METHODS: We utilized an adaptation of the Level of Institutionalizaton (LoIn) scales for qualitative data collection and for development of an institutionalization score for each site. The determinants of institutionalization were derived from the organizational behavior and health promotion literatures and used as categories for analysis. In addition, for purposes of triangulation, chart audit data for three documentation behaviors were also collected. RESULTS: PPIP has been maintained--at varying degrees of integration--in four of the five sites studied, for 6 years after adoption. Organizational factors that facilitated the institutionalization process were the site's institutional strength, the integration of PIPP within extant programs and services, visibility of the program within and outside the site, planning for the termination of grant funding, and presence of a program champion with mid- to upper-level managerial authority. Successful initiation of the program was not a predictor of institutionalization outcomes. CONCLUSIONS: We have highlighted the need to consider organizational determinants of institutionalization in relation to their specific sociopolitical contexts, and in relation to each other, not in isolation.

Health Plan Implementation↗

Searching for sexually explicit materials on the Internet: an exploratory study of college students' behavior and attitudes.

The convergence of sexuality messages with a computerized medium (specifically, the Internet) represents an unprecedented phenomenon with, as of yet, unknown outcomes. Despite the Internet's widespread use, little is known about users' behaviors and attitudes when searching for sexually explicit materials online. This study examined specific behaviors and outcome expectations and expectancies (or attitudes) of a sample of 506 undergraduate students at a public university in Texas. Data were collected through a self-administered questionnaire, designed and pretested by the authors. Main results revealed that most students in the sample were infrequent and relatively new users of the Internet. Forty-three percent (43.5%) of students had sometime accessed sexually explicit materials through the Internet, but the practice was not very common. Only 2.9% said they accessed these materials "frequently." Male students were significantly more likely to have accessed the Internet for viewing sexually explicit materials and to claim curiosity about sex as their motivation for this behavior. Women were significantly more likely to have experienced sexual harassment while online. In terms of attitudes, this sample did not appear to value highly or exhibit strong beliefs about the potential outcomes associated with accessing the Internet for sexually explicit materials. Competing explanations as well as the limitations of this study are discussed.

Adult↗

A comparison of CRT and digital stimulus delivery methods in the multifocal ERG.

The purpose of this paper is to compare and evaluate the multifocal ERG response from raster based CRT and Digital Projection (LCD) stimulus delivery systems. A custom built p.c. based multifocal system was used to generate a 61 hexagonal element stimulus array. The stimulus was presented on a high luminance CRT display and on a back projected screen using a Digital polysilicon projection system. A fast response photodiode was used to analyse the stimulus pulse characteristics of both systems. A number of recordings were performed to assess the effect of stimulus delivery on a standard m-sequence response, inserted full-field filler response and on separation of onset and offset components. The pulse width for a CRT system is dependant on the type of phosphor and is typically 2 msec whereas the Digital Projection system produces a 13.3 msec pulse equivalent to the frame rate for the system. Slowing down the m-sequence by a factor of eight results in a pulse width of 106 msec which should enable the recovery of true offset responses. The CRT stimulus consists of a series of eight pulses of 2 msec duration each separated by 11.3 msec. First order responses are larger from the CRT system and second order responses larger from the Digital system. In conclusion, there are fundamental differences in the two delivery systems. The CRT system may have more potential in examining non-linear aspects of the multifocal response. Although both systems may be able to record offset responses, the Digital system will generate true offset responses whereas the CRT system may not allow true separation of these components.

Adult↗

Leisure-time physical activity and regular walking or cycling to work are associated with adiposity and 5 y weight gain in middle-aged men: the PRIME Study.

OBJECTIVE: To examine the influence of physical activity on body mass index (BMI), waist circumference (W) and body mass changes (DeltaBMI) in middle-aged men, with special regard to moderate-intensity activities. DESIGN: Longitudinal study of adults who participated in the PRIME Study. SUBJECTS: A cohort of 8865 men aged 50-59 y, free of coronary heart disease. MEASUREMENTS: BMI and W at baseline, body mass changes over a 5 y period. Detailed baseline assessment of net energy expenditure due to physical activity (PAE) in the preceding year, according to category of activity, by means of the MOSPA Questionnaire. PAE was expressed in weekly metabolic equivalent scores (MET h/week). RESULTS: After adjustment for confounders, the multiple regression analyses indicated that BMI, W and DeltaBMI were inversely associated with PAE spent in getting to work (P<10(-5), <10(-5) and 0.04, respectively) and practice of high-intensity (>or=6 MET) recreational activities (<0.01, <10(-5) and <0.01). Men who regularly spent more than 10 MET h/week in walking or cycling to work had a mean BMI, W and DeltaBMI respectively 0.3 kg/m(2), 1 cm and 0.06 kg/m(2) lower than those who did not expend energy in getting to work. In the subgroup of subjects who did not perform high-intensity activities, the level of recreational PAE was inversely associated with BMI and W but not with subsequent weight-gain. CONCLUSION: These findings indicate that, in middle-aged men, physical activities of moderate-intensity, which are probably easier to promote than more vigorous activities and, in particular, a more current daily activity, walking or cycling to work, may have a favourable effect on body fat markers and body mass gain.

Activities of Daily Living↗