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Biomedical subjects

A Evans

Publications and source records attributed to A Evans.

At least 217 records · Page 12Linked to original sources

Simulated surgery in the summative assessment of general practice training: results of a trial in the Trent and Yorkshire regions.

BACKGROUND: General practice registrars are now required to undertake a summative assessment of their consulting skills. Simulated surgeries have been developed as an alternative to the existing method of assessing video-recorded consultations. AIM: To evaluate the simulated surgery assessment method, developed in the General Practice Postgraduate Education Department in Leicester, for use in assessing general practice consultation skills. METHOD: General practice registrars in Leicester performed two eight-patient simulated surgeries separated by four weeks. Assessment outcomes were compared to demonstrate the consistency of the method. Pilot surgeries in Yorkshire were videotaped, and then rated by video-raters trained for summative assessment. RESULTS: The method consistently identified those registrars who were competent and those who were not yet competent in consulting skills. It proved acceptable to candidate doctors and has fewer resource requirements for both examiners and candidates than other consulting skills assessment methods. CONCLUSION: The method developed in Leicester and successfully transferred to Yorkshire is feasible on a large scale, and offers an acceptable alternative to other consulting skills assessment methods. In this study it consistently identified competent from incompetent candidate doctors.

Clinical Competence↗

Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles.

The microsomal triglyceride transfer protein (MTP) catalyzes the transfer of triglyceride, cholesteryl ester, and phosphatidylcholine between phospholipid surfaces. The 97-kD subunit imparts lipid transfer activity and thus plays a role in the assembly of apolipoprotein B (apoB)-containing lipoproteins. We tested whether polymorphisms in the promoter region of the large subunit of the MTP gene might be related to different plasma lipid variables, atherosclerosis, and the risk of myocardial infarction (MI). We screened 838 bp in the promoter region of the MTP gene by PCR-SSCP and identified two polymorphisms at positions -400 (MTP/-400 (A-->t)) and -164 (MTP/-164 (T-->c)), the latter being situated on a putative sterol responsive element (SRE) consensus sequence. The two polymorphisms, investigated in 622 male patients with MI and in 728 age-matched controls participating in the ECTIM Study, were in nearly complete linkage disequilibrium (|D'| = +0.98, less frequent alleles being preferentially associated, P < 0.001). There were no significant differences in genotype or allele frequencies between patients with MI and controls. Moreover, no significant associations between the two promoter polymorphisms and several lipid variables measured in the control groups of the ECTIM Study or coronary artery stenosis, angiographically assessed in patients with MI, were detected. We conclude that these MTP polymorphisms are unrelated to lipid variables or coronary heart disease in this study. Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles.

Adult↗

Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction--the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction.

The contribution of coagulation factors and fibrinolytic variables to the development of ischaemic arterial disease is still not clearly established. The PRIME study is a prospective cohort study of myocardial infarction in men aged 50-59 years and recruited from three MONICA field centers in France (Lille, Strasbourg and Toulouse) and the center in Northern Ireland (Belfast). Baseline examination included measurement of plasma fibrinogen, factor VII, and PAI-1 activity in over 10,500 participants. We investigated the associations of these haemostatic variables with cardiovascular risk factors, prevalent atherosclerotic disease and geographical area. Fibrinogen level increased with age, smoking, waist-to-hip ratio, LDL-cholesterol, and it decreased with educational level, leisure physical activity, alcohol intake and HDL-cholesterol. Factor VII activity increased with body mass index, waist-to-hip ratio, triglycerides. HDL- and LDL-cholesterol. PAI-1 activity increased with body mass index, waist-to-hip ratio, triglycerides, alcohol intake, smoking, and decreased with leisure physical activity. PAI-1 level was higher in diabetic subjects than in subjects without diabetes. Cardiovascular risk factors explained 8%, 9%, and 26% of the total variance in fibrinogen, factor VII, and PAI-1, respectively. Compared with participants without prevalent cardiovascular disease, those with previous myocardial infarction (n = 280), angina pectoris (n = 230), or peripheral vascular disease (n = 19) had significantly higher levels of fibrinogen. but those with stroke (n = 67) had not. PAI-1 activity showed a similar pattern of association. The odds ratio for cardiovascular disease associated with a rise of a one standard deviation in fibrinogen and PAI-1 was 1.31 (95% confidence interval: 1.20 to 1.42, p <0.001) and 1.38 (95% confidence interval: 1.27 to 1.49, p<0.001), respectively. After adjustment for cardiovascular risk factors, these associations were attenuated but remained highly significant. There was no significant association between factor VII activity and prevalent cardiovascular disease. Fibrinogen level and, to a lesser extent, factor VII and PAI-1 activity were higher in Northern Ireland than France after adjustment for the main cardiovascular risk factors. These geographical variations are consistent with the 2 to 3-fold higher incidence of myocardial infarction in Northern Ireland than France. Our results provide further epidemiological evidence for a possible role of fibrinogen and PAI-1 in the pathogenesis of coronary heart disease.

Alcohol Drinking↗

Cutaneous malignant melanoma in Scotland: incidence, survival, and mortality, 1979-94. The Scottish Melanoma Group.

OBJECTIVE: To determine the changing incidence of and mortality from cutaneous malignant melanoma in Scotland from 1979 to 1994. DESIGN: Detailed registration of clinical and pathological features, surgical and other treatment, and follow up of all cases of cutaneous malignant melanoma diagnosed from 1979 to 1994 and registered with specialist database for Scotland. SETTING: Scotland. SUBJECTS: 6288 patients with invasive primary cutaneous malignant melanoma diagnosed between 1 January 1979 and 31 December 1994. RESULTS: The annual age standardised incidence of cutaneous malignant melanoma rose significantly from 3.5 to 7.8 per 100,000 per year in men and from 6.8 to 12.3 per 100,000 per year in women (P < 0.001 for both). World standardised rates increased from 2.7 to 6.0 per 100,000 per year in men and 4.6 to 8.50 per 100,000 in women. The incidence of melanoma continued to increase significantly in men of all ages during the study, but the rate stabilised in women after 1986. Mortality from cutaneous malignant melanoma was 1.3 per million per annum in men in 1979, rising to 2.3 per million per annum in 1994 (P < 0.01); it was 2.4 per million per annum in women in 1979, falling to 1.9 per million per annum in 1994 (P = 0.09). The underlying mortality trends showed a continuing rise for men but a downward trend for women that was not significant (P = 0.09). In men, melanoma free survival was 69% at 5 years and 61% at 10 years; in women the corresponding rates were 82% and 75%. Younger patients had higher survival rates, which were not entirely explained by thinner tumours. Over the 15 year period, survival rates improved by 12% overall, only partly owing to thinner tumours. CONCLUSIONS: In Scotland the incidence of melanoma in women has stabilised, while mortality associated with melanoma in women shows a downward trend.

Adolescent↗

PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis.

Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission tomography (PET) imaging with [11C]-PK11195 showed ligand uptake only at sites of active MS lesions defined by magnetic resonance imaging criteria. Our results indicate the potential to develop markers suitable for both in vitro and in vivo use, which will serve to help correlate phenotypic and functional properties of cells which participate in disease or injury responses within the CNS.

Animals↗

Specificity of volumetric magnetic resonance imaging in detecting hippocampal sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI)-based volumetric measurements of the hippocampal formation are useful in detecting unilateral hippocampal sclerosis (HS) in patients with temporal lobe epilepsy. In this pathologic entity, volumetric MRI analysis shows the epileptogenic structure to be atrophic when compared with the normal, nonepileptogenic side. Some authors have suggested that the radiological features of atrophy of medial temporal lobe structures are common in patients with complex partial seizures, but also are seen frequently in other seizure types and can occur even in patients without epilepsy. OBJECTIVE: To determine if seizures originating in extrahippocampal sites cause gliosis, cell loss, and atrophy of medial temporal lobe structures (i.e., HS). METHODS: We studied 110 patients with chronic epilepsy using volumetric MRI measurements of the hippocampal formation. Seventeen patients had pathologically proven HS, 27 patients had seizures due to extratemporal structural lesions, 15 patients had seizures caused by extrahippocampal temporal lobe lesions, 29 patients had primary generalized epilepsy, and 22 patients had secondary generalized epilepsy. RESULTS: All 17 patients with HS showed significantly reduced absolute hippocampal formation volumes of greater than 2 SDs below the mean of the control groups. The preoperative hippocampal formation volume measurements correlated well with the severity of HS on pathological examination. Hippocampal volumes were within the normal range in all patients with primary generalized epilepsy, secondary generalized epilepsy, extratemporal structural lesions, and extrahippocampal temporal lobe lesions. CONCLUSIONS: Seizures originating at extrahippocampal sites do not cause gliosis, cell loss, or atrophy of medial temporal structures. Significant reduction in hippocampal volumes is a specific marker for HS.

Adolescent↗

Assessment of the functional effect of the intracarotid sodium amobarbital procedure using co-registered MRI/HMPAO-SPECT and SEEG.

We studied the functional effect of injection of sodium amobarbital (SA) in 10 patients with intractable epilepsy. During the intracarotid amobarbital procedure, we measured delta activity in EEG recording from implanted electrodes and regional cerebral blood flow (rCBF) using HMPAO-SPECT co-registered with MRI. SA injection resulted in an increase in delta activity and a decrease in rCBF in all areas examined. Direct functional changes were observed in structures perfused by the carotid artery injected. In addition, we observed indirect effects, probably owing to deafferentation of neuronal pathways connecting these structures to ipsilateral and contralateral regions, including middle and posterior hippocampus.

Amobarbital↗

Incorporating prior knowledge into image registration.

The first step in the spatial normalization of brain images is usually to determine the affine transformation that best maps the image to a template image in a standard space. We have developed a rapid and automatic method for performing this registration, which uses a Bayesian scheme to incorporate prior knowledge of the variability in the shape and size of heads. We compared affine registrations with and without incorporating the prior knowledge. We found that the affine transformations derived using the Bayesian scheme are much more robust and that the rate of convergence is greater.

Adolescent↗

Effects of amlodipine in patients with chronic heart failure.

The role of calcium antagonists in patients with ischemic heart failure is currently unclear. We examined the effects of amlodipine on exercise capacity and central and regional hemodynamics in 32 patients with mild to moderate chronic heart failure in a single-center, double-blind, randomized placebo-controlled trial. All were taking at least 40 mg of furosemide daily with an angiotensin-converting enzyme inhibitor. Ischemic heart disease was the most common cause of heart failure, but no patient had symptom-limiting angina. Mean treadmill exercise capacity in patients taking amlodipine increased by 96 seconds (95% confidence interval -23 to 215) and 50 seconds (-34 to 135) in the placebo group; mean difference in change between treatments was 70 seconds (-90 to 233), p = 0.38. Active treatment with amlodipine did not affect self-paced corridor walking times. Similarly, there were no significant effects on cardiac output, oxygen uptake, heart rate, and mean arterial pressure at rest or during exercise. Calf and renal blood flow were also unchanged by treatment. The lack of significant effect demonstrated by these data suggests a limited role for amlodipine in patients with ischemic cardiomyopathy, although it may prove beneficial in those with nonischemic disease. More data are required before amlodipine can be recommended for all patients with chronic heart failure.

Aged↗

Distribution of apolipoprotein E between apo B- and non apo B-containing lipoproteins according to apo E phenotype.

Apolipoprotein E (apo E) is a component of all the classes of lipoproteins and can be distributed among apo B- (LpB) and non apo B-containing lipoproteins (Lp-non-B). Using a new electroimmunoassay kit, plasma apo E, apo E in Lp-non-B (apo E-Lp-non-B) and apo E in LpB (apo E-LpB) levels were measured in healthy control subjects (n=481) from 3 centers participating in the ECTIM study (Etude Cas-Témoins sur l'Infarctus du Myocarde), a population-based study on myocardial infarction. The distribution of apo E among lipoproteins was analyzed according to the apo E phenotype after adjustment for center, body mass index, tobacco use, alcohol consumption and triglycerides. Apo E was higher (average excess: + 0.32; P < 0.0001) and lower (average excess: -0.12; P < 0.0001) in subjects carrying the allele epsilon2 and the allele epsilon4 respectively, than in apo E3/3 subjects. These differences are the consequence of variations in apo E-Lp-non-B which clearly differed between the groups classified according to their apo E phenotype (P < 0.0001). The average excess of apo E Lp non-B compared to apo E3/3 subjects was + 0.43 (P < 0.0001) and -0.22 (P < 0.0001) for the epsilon2 and epsilon4 alleles respectively. Apo E-LpB was lower in subjects carrying the epsilon2 allele (P < 0.02) while the presence of the epsilon4 allele did not modify this parameter. The proportion of apo E within HDL was clearly higher and lower in subjects carrying apo E2 and apo E4 respectively than in apo E3/3 subjects. Although triglyceride levels were dependent on the apo E phenotype, the adjustment of the proportion of apo E in HDL for triglycerides hardly modified the results. For the first time, these results, using direct measurements on a large number of subjects, confirm the greater preference of apo E4 over apo E2 for LpB and vice versa for Lp-non-B. They also show a greater affinity of apo E2 for HDL compared to apo E3. This high affinity of apo E2 for HDL could be due to the formation of the apo E-A-II complex. These results indicate that apo E phenotype modulates the distribution of apo E among lipoproteins and suggest differences in lipoprotein metabolism between apo E2, apo E3 and apo E4.

Adult↗

Effect of beta-endorphin C-terminal peptides on glucose uptake in isolated skeletal muscles of the mouse.

The uptake of a nonmetabolizable derivative of glucose, [3H]2-deoxy-D-glucose was examined in isolated slow (soleus) and fast (extensor digitorum longus, EDL) muscles of adult mice. An analogue of beta-endorphin (28-31), Ac-Lys-D-Lys-Sar-Glu, which is stable to proteolytic digestion, enhanced the uptake of glucose into the slow and fast muscles. The muscles of male mice were more sensitive to the peptide than those of female mice. The maximum uptake seen in the presence of the peptide was similar to that seen with insulin in the soleus muscle and greater than that seen with insulin in the EDL muscle.

Animals↗

Female adolescents and onset of sexual intercourse: a theory-based review of research from 1984 to 1994.

PURPOSE: To review a decade of research on the correlates of early onset of sexual intercourse among female adolescents in the United States, using Social Cognitive Theory as a framework for classification. METHODS: Forty-nine studies published in peer-reviewed journals between 1984 and 1994 were reviewed and their findings coded by two independent coders. RESULTS: Findings indicate that most of the studies emphasized quantitative methodologies, using cross-sectional designs and univariate statistical analyses. Many studies lacked a theoretical framework or conceptual model to guide their investigations. When evaluating empirical findings, 61% of the studies found environmental correlates and 47% found biological factors (e.g., age and pubertal development) to be significantly associated with early initiation of sexual intercourse. CONCLUSION: These findings raise important questions about the quality of research on adolescent sexuality, as well as its relationship to the development of risk-reduction programs which tend to focus mainly on intrapersonal factors (such as attitudes, knowledge, and expectancies.

Adolescent↗

Routine audit of breast fine needle aspiration (FNA) cytology specimens and aspirator inadequate rates.

In an attempt to improve the quality of the breast FNA specimens we instigated a continuing audit of this procedure in this hospital. All FNAs since 1990 have had the following recorded: mode of aspiration, e.g. freehand or image guided, patient presentation (screening or symptomatic), patient diagnostic category, cytological diagnosis and final histological diagnosis. Aspirator performance was assessed by means of the inadequate aspiration rate (IR) of FNAs performed on patients with a final diagnosis of cancer (FDC) and diagnostic category A patients (clinically or radiologically malignant lesions). An ongoing annual review of the performance of all the aspirators was undertaken, all of whom received individual feedback. Counselling and further training were offered where indicated by poor performance. Over the period 1990-1995 a total of 13537 FNAs were performed by 27 aspirators. The IR on category A and FDC cases over this period was 16.0% and 18.1%. The best performance achieved by an aspirator in a calendar year was an IR of 3.6% with no inadequate specimens in either FDC or category A lesions, and the best performance over the entire period was an average IR of 11.75% and 14.25% for FDC and category A groups, respectively. The overall IR on category A patients ranged from 15.9% to 23.8% and on FDC cases from 12.2% to 21.7%. There was a significant improvement in individual junior aspirator performance when their first year was compared with their last year on the unit. In some cases a deterioration in intra-aspirator performance was observed, from an IR of 6% to 33%. The overall IR rate of the unit remained stable for FDC patients, 15.5% in 1990 compared with 15.1% in 1995. This appeared to be largely due to a high proportion of the aspirations being performed by experienced personnel with consistent IRs. However, concealed within the overall rate there were some poor performers who benefited from counselling and/or further training. These results indicate an important role for audit in identifying poor aspirators who benefit from targeted training and advice, thereby improving the quality of FNA specimens, and ultimately patient care.

Biopsy, Needle↗

Short stature and heart disease: nature or nurture? The EARS Group.

BACKGROUND: Previous studies have demonstrated that short men are at increased risk of coronary heart disease (CHD). It has been suggested that the inverse relationship between adult height and CHD risk could be attributable to the fetal origins of CHD. METHOD: The hypothesis that transmissible factors could partly explain the association has been tested in the European Atherosclerosis Research Studies (I and II), in which a sample of healthy university students (cases), drawn from 18 European countries (male: n = 721; female: n = 330), whose fathers had had a documented myocardial infarction before the age of 55 years were compared to age- and sex-matched controls (male: n = 1056; female: n = 638). Information about lifestyle and birthweight was collected and a fasting blood sample was obtained from each subject. RESULTS: In females there was no difference in height between cases and controls but male cases were shorter than controls, on average by one cm, both in the EARS I (P = 0.02) and the EARS II studies (P = 0.01) and this difference was independent of reported birthweight and the fathers' educational attainment. In logistic regression the relationship was independent of the subjects' apolipoprotein B level, the other major biological discriminator of case-control status. CONCLUSION: In men at least, height appears to be an independent transmissible risk factor for CHD.

Adolescent↗

A double-blind, cross-over comparison of the effects of a loop diuretic and a dopamine receptor agonist as first line therapy in patients with mild congestive heart failure.

We compared the effects of the orally active dopamine agonist ibopamine with the loop diuretic frusemide as first-line therapy in patients with mild congestive heart failure. Fourteen patients with New York Heart Association class II congestive heart failure were enrolled in a double-blind, cross-over study. After baseline measurements of clinical and symptomatic status, modified Bruce exercise time, high-level exercise time, corridor walk time, regional blood flow, pedometer scores, 24 h urine volume and sodium excretion and neurohumoural factors, patients were randomly allocated to receive either frusemide 40 mg o.d. or ibopamine 100 mg t.d.s. for 8 weeks. Assessments were performed at 2 weekly intervals. After 8 weeks, patients crossed over into the alternate treatment arm for a further 8 weeks, with further assessments performed every 2 weeks. There were four exacerbations of heart failure during ibopamine treatment and none during frusemide treatment. After 8 weeks of treatment, modified Bruce exercise time was 901 +/- 73 s with frusemide and 646 +/- 134 s with ibopamine (P < 0.05). Twenty-four hour urinary sodium excretion at weeks 2 and 4 (P < 0.05), and 24 h urinary volume at week 2 (P = 0.0001) were lower during ibopamine treatment. At week 8, supine (P = 0.076) and erect renin (P = 0.05) were lower with ibopamine treatment. In conclusion, ibopamine is ineffective as first line therapy for congestive heart failure, probably because of a lesser diuretic potency than frusemide.

Adult↗

High-throughput microsatellite analysis using fluorescent dUTPs for high-resolution genetic mapping of the mouse genome.

The use of fluorescent end-labeled primers has proved successful for rapid, semiautomated genotyping of microsatellite loci. However, custom synthesis is expensive and costs can be prohibitive when a wide range of markers is to be analyzed for only a few genotypings. This particularly applies to high-resolution genetic mapping in the mouse either in the construction of global maps or in the production of local high-resolution genetic maps for positional cloning. We demonstrate here the use of fluorescent dUTPs for cost-effective, high-throughput microsatellite genotyping in the mouse. This alternative to the use of fluorescent end-labeled primers for semiautomated genotyping is potentially applicable to the construction of linkage maps in other species.

Animals↗