Withdrawing antihypertensive drugs.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
A Evans
Publications and source records attributed to A Evans.
Relationship between atrophy of the amygdala and ictal fear in temporal lobe epilepsy.
Viscerosensory and affective manifestations are often elicited by temporal lobe seizure discharges. They have been reproduced by amygdaloid stimulation in awake patients during stereotaxic exploration or neurosurgical procedures. They are not exclusively reproduced by stimulation of the amygdala, though most commonly they are evoked from it. Ictal fear is frequently, but not invariably, associated with a rising epigastric sensation, palpitations, mydriasis and pallor. We studied 50 patients (mean age 33 years) with intractable temporal lobe epilepsy (TLE): MRI volumetric measurements of amygdala and hippocampus were performed using a protocol previously described by our group (Watson et al., Neurology 1992; 42: 1743-50). All patients had extensive EEG investigation and at least two seizures recorded by video-EEG monitoring. Seventeen patients (34%) had a clear history of fear accompanied by a rising epigastric sensation as the initial manifestation of their habitual attacks. The amygdala volumes in this group were significantly (P = 0.001) smaller (mean 2131.6 mm3) compared with the volumes of the 33 patients without these symptoms (mean 2561.5 mm3). Both patient groups had smaller mean amygdala volumes compared with normal controls (mean 2828.2 mm3). Postoperative pathology correlated well with volumetric atrophy. In addition, we found that patients with more pronounced amygdaloid atrophy more commonly had prolonged febrile convulsions in early childhood and also more frequently secondarily generalized seizures. Results support the finding that ictal fear is related to pathology of the amygdala and that it, like the hippocampus, is an important substrate of TLE.
Adolescent↗
Different fates of camptothecin-induced replication fork-associated double-strand DNA breaks in mammalian cells.
The S phase cytotoxicity of camptothecin (CPT) requires both the formation of a covalent topoisomerase I-DNA complex and ongoing DNA replication. The interaction of DNA synthesis and the drug-induced complexes results in the production of DNA double-strand breaks (DSBs) concentrated in replicating DNA. These DSBs are likely to be extremely cytotoxic lesions and are likely to account for the S phase specificity of CPT. Here we show that a brief exposure to CPT results in replication-associated DSBs and, once formed, the fate of these DNA DSBs is different in human and Chinese hamster cell lines. In hamster CHO-KI, even at supra-lethal concentrations, CPT-induced DSBs in nascent DNA disappear within 5 h of drug removal. Those CHO-KI cells in S phase during treatment with toxic doses of CPT arrive at mitosis within 18 h, with potentially lethal chromatid aberrations. In human cells, CPT-induced DSBs are long lived, and are still detectable at least 24 h after drug removal. After toxic doses of CPT to S phase human cells, mitosis does not occur within 72 h of drug removal and there is an extended, perhaps permanent, cycle arrest in S/G2, possibly due to the presence of unrepaired DNA DSBs. These data, and the greater sensitivity of hamster than human cells to low doses of CPT, suggests that, besides the generation of replication fork-associated DNA DSBs, subsequent processing/repair of these lesions may modulate the sensitivity of cells to this important anti-tumour drug.
Animals↗
Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region.
An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, other genes possibly involved in the pathophysiology of AD and in strong linkage disequilibrium with the APOE locus may be responsible for this association. To test this hypothesis, we analysed the allelic distribution of four polymorphic genetic markers flanking the APOE gene (D19S178 (CA)n repeat, D19S47 (CA)n repeat, APOCI HpaI restriction fragment length polymorphism, APOCII (CA)n repeat). We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36). Early-onset cases were analysed for two cut-offs with late-onset: less than 60 and less than 65. We observed a significant increased frequency of the APOE epsilon 4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65. The adjusted odds ratio (OR) of the bearers of at least one APOE epsilon 4 allele was 4.10 ([1.84;9.16]) when estimated in both populations with a logistic regression model. Surprisingly, the odds ratio of the bearers of at least one APOE epsilon 2 allele was also significant and equal to 0.11 ([0.02;0.50]) suggesting a possible protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Age of Onset↗
Psychological development of technology-dependent children.
Reviewed the psychosocial and developmental challenges faced by technology-dependent children, their families, and their caregivers. Previous literature which has examined psychological outcome in children with repeated hospitalizations is presented. Psychosocial implications for programs addressing the needs of technology-dependent children are discussed.
Child↗
Financial incentives in residency recruiting for primary care: scope, characteristics, and students' perceptions.
BACKGROUND: One response to the decline in interest among medical students in residency training in primary care has been the offering, by residency programs and hospitals, of financial recruitment incentives to medical students during their residency interviews. Few data on the breadth and effectiveness of this practice have been available. METHOD: To gain insight into how hospitals and/or programs offered incentives, the authors compared 1990 and 1992 survey data on this topic from the members of the Association of American Medical Colleges' Council of Teaching Hospitals (AAMC/COTH) with 1992 data from the members of the Association for Hospital Medical Education (AHME), employing responses to identical questionnaire items. Complementary data on students' experiences with recruitment incentives in 1991 and 1992 were also analyzed. These data have been collected since 1991 in the Medical School Graduation Questionnaire (GQ) of the AAMC's Section for Educational Research, but little or no information had been available on medical students' perceptions of the effectiveness of these incentives. Therefore, one of the authors surveyed members of the classes of 1992 at four Midwestern medical schools about their residency interviewing experiences, including their reactions to financial incentives they encountered. RESULTS: The outcomes from these surveys indicate that, as expected, family practice, internal medicine, and pediatrics were the specialties most likely to offer financial incentives; that a wide variety of recruitment incentives was available to students; that the proportion of programs and hospitals offering such incentives was increasing (e.g., from 37% in the 1990 COTH survey to 54% in the 1992 survey); and that a large majority (79%) of students who encountered these incentives viewed them as at least somewhat effective in persuading them to consider matching with the programs that offered them. CONCLUSION: The prevalence and persuasiveness of financial incentives raise a number of serious questions, including whether competition for residents will divert funds from improving educational quality to recruitment.
Career Choice↗
Cytokine gene expression in intact anagen rat hair follicles.
Substantial cellular proliferative activity is necessary to produce a mature hair follicle. Therefore, it is likely that cytokines and their receptors play an important controlling role. To provide an understanding of the mechanisms involved during hair growth, we investigated the expression of cytokines in rat anagen hair follicles. A new technique was developed that allowed the rapid isolation of large numbers of intact, viable, anagen, rat pelage hair follicles. Total RNA was isolated from these follicles using an acid-phenol-chloroform extraction and analyzed for cytokine expression. Using the conventional technique of Northern blotting, it was only possible to detect transcripts for transforming growth factor beta (TGF beta) and insulin-like growth factor I (IGFI). Polymerase chain reaction amplification of reverse-transcribed mRNA detected cDNA fragments for TGF beta, IGF I, IGF II, nerve growth factor beta (NGF beta), and interleukin-1 alpha (IL-1 alpha). The amplified products were confirmed by digestion with restriction endonucleases. The proteins themselves for TGF beta and IGF I have been shown to be present within the anagen hair follicle using immunogold antibody labeling. This study has provided the first reported cytokine expression profile of rat anagen hair follicles. It is likely that the analysis of the pattern and timing of expression of these cytokines in the follicle will provide valuable insights into hair growth regulation.
Animals↗
Evaluation of sex education curricula: measuring up to the SIECUS guidelines. Sex Information and Education Council of the U.S.
Most sexuality education curricula developed the past 20 years were not thoroughly evaluated. This study provides results from a content analysis of 10 sexuality education curricula for junior and senior high school students. Nine nationally available sexuality education curricula and one curriculum guide comprised the sample. The basis for analysis was the Guidelines for Comprehensive Sexuality Education, developed by the Sex Information and Education Council of the U.S. (SIECUS) and an instrument developed to measure bias in the curricula. Trained coders found that Sex Respect and Teen Aid addressed less than half the topics suggested by the SIECUS guidelines. Several of the curricula contained gender and sexual orientation bias. Certain key concepts such as "Sexual Behavior" and "Society and Culture" were not adequately addressed by most of the curricula. Findings indicate that of 10 curricula, only six are considered acceptable for educating junior and senior high school students.
Adolescent↗
Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction. The ECTIM Study.
Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction.
BACKGROUND: The angiotensin-converting enzyme (ACE) plays an important role in the production of angiotensin II and the degradation of bradykinin, two peptides involved in cardiovascular homeostasy. Presence of a polymorphism in the ACE gene (ACE Ss) has been postulated from segregation analysis of plasma ACE in families. This putative polymorphism, which strongly affects the plasma and cellular levels of ACE, probably by modulating ACE gene transcription, has not yet been identified at the molecular level; however, an insertion/deletion polymorphism is present in the 16th intron of the ACE gene (ACE I/D) and appears to be a very good marker for ACE Ss. The biological role of ACE suggests that the ACE gene polymorphism could affect the predisposition to myocardial infarction (MI). METHODS AND RESULTS: We have recently shown, in a large case-control study (ECTIM), that the marker allele D of the ACE gene, which is associated with higher levels of ACE in plasma and cells, was more frequent in male patients with MI than in control subjects, especially in patients considered at low risk. ACE activity has now been measured from frozen aliquots of plasma in a large subsample of the ECTIM study (n = 1086). Plasma ACE level did not differ between patients and control subjects in the older age group (> or = 55 years) but was higher in patients than in control subjects in the younger age group (< 55 years); P < .005 after adjustment on ACE I/D and other risk factors. In patients, plasma ACE levels decreased with age (R = -.225, P < 10(-4)), but in control subjects no such trend was observed. In the low-risk group (ApoB < 1.25 mg/dL, body mass index < 26 kg/m2, and not treated with hypolipidemic drugs), plasma ACE level was increased in patients when compared with control subjects among homozygotes and heterozygotes for the ACE I allele (P < .015). Analysis of the distribution of plasma ACE by using commingling analysis conditional on the marker genotype ACE I/D enabled us to infer the frequencies and effects of the postulated ACE Ss genotypes. The results suggest that the higher plasma ACE levels in patients than in control subjects in the younger age group were due to a difference in frequency of the postulated S allele (.47 versus .36). CONCLUSIONS: These results extend our previous findings and indicate that plasma ACE level may be a risk factor for MI, independent of the ACE I/D polymorphism.
Alleles↗
Ductal carcinoma in situ of the breast: correlation between mammographic and pathologic findings.
OBJECTIVE: Ductal carcinoma in situ shows heterogeneous clinical behavior and response to treatment depending on its pathologic features. The aim of this study was to correlate the radiologic and pathologic features of ductal carcinoma in situ of the breast. Differences, if present, may allow refinement of diagnosis and selection of treatment options. MATERIALS AND METHODS: The mammograms of 128 patients with ductal carcinoma in situ of the breast were analyzed by a radiologist who knew that the patients had ductal carcinoma in situ but had no other pathologic information. The radiologic and pathologic features of subgroups characterized according to cell size and presence of necrosis were then compared. Statistical comparisons were made by using the chi 2- and Fisher's exact tests. RESULTS: Patients with small-cell ductal carcinoma in situ more commonly have a normal mammogram (28% vs 6%, respectively, p < .001) or an abnormal mammogram without calcification (42% vs 5%, respectively, p < .001) than do patients with large-cell ductal carcinoma in situ. Among patients with abnormal mammographic findings, calcification is present in 58% of those with small-cell ductal carcinoma in situ, compared with 95% of those with large-cell ductal carcinoma in situ (p < .001). No significant differences were found in the calcification morphology of small- and large-cell ductal carcinoma in situ. These features were seen more commonly in ductal carcinoma in situ with necrosis than in ductal carcinoma in situ without necrosis, respectively: abnormal mammographic findings (95% vs 73%, p < .001), calcification (96% vs 61%, p < .001), calcification with a ductal distribution (80% vs 45%, p < .005), and rod-shaped calcification (83% vs 45%, p < .001). An abnormal mammogram without calcification (39% vs 4%, p < .001) or predominantly punctate calcification (36% vs 13%, p < .05) was seen more commonly in ductal carcinoma in situ without necrosis than in ductal carcinoma in situ with necrosis, respectively. CONCLUSION: We have shown that the radiologic features of ductal carcinoma in situ vary according to cell size and the presence of necrosis in particular. Necrosis has been found to be a feature of more biologically aggressive in situ breast cancer, so these findings may be of practical value in deciding the management of indeterminate calcification clusters and whether to offer breast conservation.
Breast↗
Mechanisms of cyclosporine-induced interstitial fibrosis.
Explore the source record for details and available documents.
Animals↗
Patients who consult with tiredness: frequency of consultation, perceived causes of tiredness and its association with psychological distress.
BACKGROUND: Few prospective studies have been carried out in primary care on patients presenting with tiredness. AIM: A study was undertaken to describe patients whose main complaint was fatigue or of being "tired all the time'. METHOD: Over one year, doctors in four practices in Lancashire, Mid-Glamorgan, Suffolk and Surrey recruited 220 patients aged 16 years or more presenting with fatigue, and matched them with a comparison group from their lists. The general health questionnaire, a fatigue questionnaire and an attribution questionnaire were used to measure outcomes over six months. General practice records of consultations were also examined. RESULTS: Patients consulting for tiredness attended the doctor significantly more frequently than the comparison group both in the six months before and after entering the study. The frequency of attending could not be related to the duration or severity of fatigue alone. The majority consulting with tiredness scored highly on the general health questionnaire but so also did patients with equivalent fatigue scores in the comparison group. The correlation between fatigue and general health questionnaire scores was close for those patients who still had high fatigue scores six months later than it was for patients on entry to the study. Six months following study entry 61% of patients perceived the cause of the tiredness to be physical, while 57% of doctors viewed the problem as psychological. A small number of patients changed their views during the six months follow up from physical to psychological attributions. CONCLUSION: Patients consulting for tiredness are likely to report symptoms of psychological distress and attend more frequently than other patients. They tend to view the problem as physical while their doctors view the problem as psychological. Having established that there is no physical problem, doctors may need to focus more on sharing ideas and explanations when patients complain of being "tired all the time'.
Adolescent↗
Reliability of reported family history of myocardial infarction.
OBJECTIVE: To assess the reliability of reported family histories of myocardial infarction. DESIGN: A case-control study in which reported histories of first degree relatives were validated from death certificates, general practitioners' records, and hospital notes. SETTING: Participants enrolled in the Belfast centre of the World Health Organisation's study monitoring trends and determinants in cardiovascular disease (MONICA). SUBJECTS: 200 men who survived myocardial infarction and 200 age matched controls drawn randomly from the population. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, and proportion of overall agreement with validated records of reported family histories of myocardial infarction in first degree relatives; odds ratios for myocardial infarction, given at least one reported relative or at least one verified relative being affected. RESULTS: 349 of the 400 probands provided detailed family histories, reporting on 2812 first degree relatives. The overall sensitivity, specificity, and positive predictive value of reported histories were 67.3%, 96.5%, and 70.5% for cases and 68.5%, 97.7%, and 73.8% for controls. The kappa coefficients were modest: 0.65 for cases and 0.68 for controls. The odds ratios for myocardial infarction, given at least one affected relative, were not substantially inflated by recall bias. Some recall bias was evident for the probands' reports of their siblings' histories of myocardial infarction, the odds ratio for a reported history being 1.67 (95% confidence interval 1.09 to 2.57) and for the validated history 1.54 (1.01 to 2.37). CONCLUSIONS: Although the relative risk of disease is correctly estimated, the predictive accuracy of a casual family history of myocardial infarction may limit the effectiveness of targeted screening programmes. They may, however, complement other strategies based on genetic testing.
Case-Control Studies↗
Processing of chimeric mammalian cytochrome b5 precursors in Escherichia coli: reaction specificity of signal peptidase and identification of an aminopeptidase in post-translocational processing.
A chimeric precursor interlinked by an arginine residue between the full-length signal sequence of alkaline phosphatase and the eukaryotic cytoplasmic cytochrome b5 was constructed. Expression of the chimeric precursor protein in Escherichia coli resulted in efficient export of spectrally authentic cytochrome b5 into the periplasm [Karim, Harding, Evans, Kaderbhai and Kaderbhai (1993) Bio/Technology 11, 612-618]. On sequencing, the apparent absence of arginine at the N-terminus of the secreted cytochrome b5 implied that the chimera was either miscleaved by signal peptidase or further processed following signal excision by an uncharacterized peptidase. The influence of the N-terminal region of cytochrome b5 on the unusual processing of the chimeric precursor was investigated by engineering a number of variant forms in which the region between Arg+1 and the mature portion of cytochrome b5 was extended and varied. Observations of the in vivo processed patterns of these variant cytochrome b5 forms exported into the periplasm revealed that the absence of arginine was due to neither miscleavage of the translocated precursor by the signal peptidase nor the nature of the early region of cytochrome b5. In fact, the selective excision of the arginine residue occurred subsequent to signal sequence deletion by an aminopeptidase which was sensitive to the metal chelator o-phenanthroline. We show that this aminopeptidase also participates in the trimming of the N-terminal arginine residue of the bacterial alkaline phosphatase to generate the three isoenzymes in the periplasm.
Amino Acid Sequence↗
Patients with fatigue in general practice: a prospective study.
OBJECTIVE: To describe the characteristics of patients attending their general practitioners and complaining of fatigue or being "tired all the time." DESIGN: Prospective study of cohort aged 16 years and older with follow up at two weeks and by questionnaires at two and six months. SUBJECTS: 220 patients (164 women) with mean age 43 years and an age-sex matched comparison group. SETTINGS: Doctors and patients in four practices in Lancashire, Mid Glamorgan, Suffolk, and Surrey. MAIN OUTCOME MEASURES: General clinical data, results from standard group of laboratory tests, fatigue questionnaire, and 12 item general health questionnaire. RESULTS: Over twice as many patients with fatigue had high scores on the health questionnaire compared with the comparison group (156 (75%) v 69 (34%)). Results of laboratory tests were abnormal and contributed to the diagnosis in 19 patients. 59 out of 102 patients who responded had high fatigue scores six months later. Patients with persistent fatigue were more likely to have a history of anxiety or depression and to have had fatigue for more than three months on entry to the study. CONCLUSIONS: Women are particularly at risk of fatigue. The outcome is better if patients have had symptoms for three months or less or there is no history of emotional illness.
Adolescent↗
Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction.
In a European study an insertion (I)/deletion (D) polymorphism in the angiotensin converting enzyme (ACE) gene has been shown to be associated with the risk of myocardial infarction (MI). In the same study, we investigated the association of the polymorphism with a parental history of fatal MI. There was an excess of both DD (odds ratio 2.6, p = 0.02) and ID (odds ratio = 1.9, p = 0.08) genotypes among those having a parental history of MI, confirming that genetic variation in the ACE locus could be involved in the risk of MI.
Adult↗
Atrophy of mesial structures in patients with temporal lobe epilepsy: cause or consequence of repeated seizures?
We studied 70 epileptic patients by using magnetic resonance imaging volumetric measurements of amygdala (AM) and hippocampal formation (HF). Fifty patients presented with intractable temporal lobe epilepsy (TLE), 10 patients had focal extratemporal lobe epilepsy, and 10 had generalized epilepsy. In 91% of the 45 TLE patients without foreign tissue lesions, there was significant smallness of the AM and/or HF coinciding with the side of electroencephalographic seizure onset. No significant smallness or asymmetry was demonstrated in patients with focal extratemporal or generalized epilepsy. We performed a linear regression analysis, plotting the number of years of recurrent seizures and the estimated seizure frequency against the volumes of the AM and HF. There was no correlation between either of these two parameters and AM or HF volume (p > 0.9). There was also no correlation between the patient's age and volumetric measurements of AM or HF, nor did these measurements correlate with the occurrence of generalized seizures. On the other hand, patients with antecedent prolonged febrile convulsions in early childhood had significantly smaller AM and HF, compared with those without such a history (p < 0.001). The findings indicate that repeated seizures or longer duration of epilepsy do not cause increased atrophy of AM or HF that is measurable by volumetric magnetic resonance imaging.
Adolescent↗