Biomedical subjects
A Evans
Publications and source records attributed to A Evans.
Richard and Emma Stevens and the new photography.
Richard and Emma Stevens were an enterprising couple from an Indian Army background. When they were stationed at Athlone with the Royal Engineers in the 1890s they visited Birr Castle Observatory and later built their own reflector telescope. Less than a year after the publication of Röntgen's discovery of X-rays, they were producing their own radiographs. Some images and also some of the equipment which they used have survived. The couple subsequently returned to India where Captain Stevens died in 1900. Emma, possibly the first woman to take X-rays, survived into old age and enjoyed a varied and interesting life.
Neostigmine for acute colonic pseudo-obstruction.
Explore the source record for details and available documents.
Hard to swallow.
Explore the source record for details and available documents.
Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis.
BACKGROUND: Gelatinase B, a matrix metalloproteinase that has proteolytic activity against connective tissue proteins, has been suggested to be important in the connective tissue remodeling processes associated with atherogenesis and plaque rupture. This study tested the hypothesis that sequence variation in the promoter region of the gelatinase B gene influences its expression, predisposing individuals carrying certain genetic variants to more severe atherosclerosis. METHODS AND RESULTS: Single-strand conformation polymorphism analysis was carried out to search the promoter region of the gene encoding gelatinase B for naturally occurring genetic variation. As a result, an unreported common polymorphism was detected, which arose from a cytosine (C) to thymidine (T) transition at position -1562 relative to the start of transcription. Transient transfection experiments and DNA-protein interaction assays indicated that the T allele had a higher promoter activity than the C allele, which appeared to be due to preferential binding of a putative transcription repressor protein to the C allelic promoter. A sample of 584 male patients with myocardial infarction and 645 age-matched male healthy control subjects were genotyped. The allele frequencies were not significantly different between the cases and control subjects. However, in 374 patients with available angiographic data, 26% of those carrying 1 or 2 copies of the T allele had >50% stenosis in 3 coronary arteries, whereas only 15% of C/C homozygotes had triple-vessel disease. CONCLUSIONS: These data suggest that this functional genetic variation influences gelatinase B gene promoter activity in an allele-specific manner and has an effect on atherosclerotic phenotype.
Stereo-specific cytotoxic effects of gossypol enantiomers and gossypolone in tumour cell lines.
The naturally occurring compound, gossypol, has been previously used as a male oral contraceptive, for the treatment of benign gynaecological conditions and cancer patients. Long-term daily dosing with gossypol is associated with minimal side effects and no myelosuppression. Since gossypol exhibits atropisomerism due to the restricted rotation about the 2,2' carbon bond, we have isolated the l- and d-isomers by Schiff's base formation using a chiral amine and regenerated the enantiomers by acid hydrolysis. The enantiomers and the proposed oxidative metabolite, gossypolone, were characterized by HPLC, 1H-NMR and optical rotation. The cytotoxicity was assessed in cell cultures derived from melanoma, lung, breast, cervix, and leukaemia using the MTT viability assay. The cytotoxicity of gossypolone was similar to racemic gossypol in five out of the six cell lines studied. The l-enantiomer of gossypol induced a dose-dependent cell kill in all cell lines with a mean IC50 of 20 microM and was significantly more potent than racemic gossypol, the d-enantiomer of gossypol and gossypolone. In addition, when the leukaemia line was exposed to l-gossypol (0.5-10 microM) over a 4-day period, a schedule-dependent decrease in cell viability was observed. l-Gossypol was also compared with respective drugs used to treat patients with melanoma, lung cancer and leukaemia. The data indicate that l-gossypol was significantly more active than cisplatin, melphalan and dacarbazine in the two melanoma lines, cisplatin and daunorubicin in the lung line and hydroxyurea and busulphan in the leukaemia line. Preliminary studies using one melanoma line showed that the l-isomer induced cell shrinkage, membrane blebbing and DNA fragmentation, characteristics suggestive of apoptotic cell death.
Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study.
BACKGROUND: Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence. METHODS: To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions. RESULTS: A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups. CONCLUSIONS: Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.
Histological study of hair follicles treated with a 3-msec pulsed ruby laser.
BACKGROUND AND OBJECTIVE: Ruby laser energy at 694 mn is moderately absorbed by melanin and minimally absorbed by other skin chromophores. This property and its depth of penetration into dermis permit absorption into pigmented hair follicles, thus making it suited to photothermolysis of these appendages. Clinical reports of the efficacy of such lasers for removal of unwanted hair are emerging in large numbers, but scientific data regarding the exact mechanism of action is still lacking. This study aims to evaluate and define further the histological responses of hair follicles to 3-msec pulsed ruby laser light. STUDY DESIGN/MATERIALS AND METHODS: Twenty-four patients with brown or black axillary or groin hair were treated with a 3-msec ruby laser at fluences from 10 to 40 J/cm2 on one, two, or three occasions. Biopsies were taken at various intervals from immediately to 8 weeks after treatments. Biopsies were fixed and stained with either nitroblue tetrazolium chloride or hematoxylin and eosin for histological examination. RESULTS: One treatment induced changes typical of catagen followed by telogen at all fluences. The papillae always remained viable. Two and three treatments resulted in atypical telogen, with infundibular dilatation and plugging, and marked proliferation of the stem outer sheath. New anagen follicles were evident even after three treatments at 12- and then 8-week intervals and were biopsied 6 weeks later, but there were no hairs extending to or through the epidermis. CONCLUSION: There was no evidence of permanent follicle death after one ruby laser treatment. However, despite evidence of persistence of follicular elements after two and three treatments, it is possible that laser-induced damage to the isthmus and upper stem may interfere with the interaction between dermal and epidermal germinative cells, thus inhibiting or altering the normal hair cycle.
Three-dimensional MRI atlas of the human cerebellum in proportional stereotaxic space.
We have prepared an atlas of the human cerebellum using high-resolution magnetic resonance-derived images warped into the proportional stereotaxic space of Talairach and Tournoux. Software that permits simultaneous visualization of the three cardinal planes facilitated the identification of the cerebellar fissures and lobules. A revised version of the Larsell nomenclature facilitated a simple description of the cerebellum. This atlas derived from a single individual was instrumental in addressing longstanding debates about the gross morphologic organization of the cerebellum. It may serve as the template for more precise identification of cerebellar topography in functional imaging studies in normals, for investigating clinical-pathologic correlations in patients, and for the development of future probabilistic maps of the human cerebellum.
Performance and potential impact of a chest pain prediction rule in a large public hospital.
PURPOSE: To evaluate the performance of a previously validated prediction rule for patients presenting to the emergency department with chest pain and the potential impact of the rule on triage decisions. SUBJECTS AND METHODS: In a prospective cohort study, physician investigators interviewed consecutive patients admitted for suspected acute ischemic heart disease (n = 207) by emergency department attending physicians who had not used the prediction rule. We measured the accuracy of the rule in predicting cardiac complications in these patients, and compared actual triage decisions with those that might have been recommended by use of the prediction rule. We also measured comorbid illnesses among patients stratified as very low risk by the prediction rule, as well as the effect of standardizing the definition of unstable angina and interpretation of electrocardiograms (ECG) on the rule's sensitivity and specificity. RESULTS: Overall, the rate of major cardiac complications (4.3%) was similar to that reported in the original study (3.6%). The prediction rule performed well in predicting these complications in our patients (area under receiver operating characteristic curve 0.84 versus 0.80 in the original study; difference 0.04, 95% confidence interval [CI] -0.07, 0.14). Standardized definitions of unstable angina and interpretation of ECGs improved the specificity of the prediction rule in predicting complications (55% versus 47%; difference 8%, 95% CI 1.5%, 13.7%). The prediction rule recommended admission to telemetry units in 65 fewer patients than actually occurred (31% of the entire cohort). None of these patients had major complications. A substantial minority of "very low risk" patients (27%) had comorbid illnesses requiring inpatient treatment. CONCLUSIONS: This independent validation of the prediction rule suggests that it can improve triage decisions for patients admitted with suspected acute ischemic heart disease. Additional studies are needed to test prospectively the performance of the prediction rule in actual decision making, its acceptance by clinicians, and its cost effectiveness.
Sequence polymorphisms in the apolipoprotein(a) gene and their association with lipoprotein(a) levels and myocardial infarction. The ECTIM Study.
Lp(a) concentrations are largely determined by apo(a) isoform size, but several studies have shown that apo(a) isoforms could not entirely explain the increase of Lp(a) levels observed in patients with coronary heart disease (CHD). Since up to 90% of the variance in Lp(a) levels has been suggested to be attributable to the apo(a) locus, the hypothesis that polymorphisms of the apo(a) gene other than size could contribute to the increase of Lp(a) levels in CHD patients must be considered. This hypothesis was tested in the ECTIM Study comparing 594 patients with myocardial infarction and 682 control subjects in Northern Ireland and France. In addition to apo(a) phenotyping, five previously described polymorphisms of the apo(a) gene were genotyped: a (TTTTA)n repeat at position -1400 from the ATG, a G/A at -914, a C/T at -49, a G/A at -21 and a Met/Thr affecting amino acid 4168. As reported earlier [Parra HJ, Evans AE, Cambou JP, Amouyel P, Bingham A, McMaster D, Schaffer P, Douste-Blazy P, Luc G, Richard JL, Ducimetiere P, Fruchart JC, Cambien F. A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM study. Arterioscler Thromb 1992; 12:701-707], mean Lp(a) levels were higher in cases than in controls (20.7 vs 14.6 mg/dl in Belfast, 17.2 vs 8.9 mg/dl in France, P < 0.001 for case-control and population differences). In the present study, mean apo(a) isoform size differed significantly between cases and controls (25.7 vs 26.6 kr in Belfast, 25.9 vs 27.4 kr in France, P < 0.001 for case-control and P = 0.13 for population difference). After adjustment for apo(a) isoforms, Lp(a) levels remained significantly higher in cases than in controls (difference, 4.6 mg/dl; P < 0.001). Genotype and allele frequencies did not differ significantly between cases and controls for any of the five polymorphisms studied. The five polymorphisms were in strong linkage disequilibrium and had a combined heterozygosity of 0.83. In multivariate regression analysis adjusted for apo(a) isoforms, only the (TTTTA)n polymorphism was significantly associated with Lp(a) levels; it explained 4.5% of Lp(a) variability in cases and 3.1% in controls. The Lp(a) case/control difference was not reduced after taking into account the (TTTTA)n effect. We conclude that the increase of Lp(a) levels observed in MI cases, and which was not directly attributable to apo(a) size variation, was not related to the five polymorphisms of the apo(a) gene considered.
Antioxidants, but not B-group vitamins increase the resistance of low-density lipoprotein to oxidation: a randomized, factorial design, placebo-controlled trial.
We have conducted an intervention trial to assess the effects of antioxidants and B-group vitamins on the susceptibility of low-density lipoprotein (LDL) to oxidation. A total of 509 men aged 30-49 from a local workforce were screened for total plasma homocysteine. The 132 selected (homocysteine concentration > or = 8.34 mumol/l) men were randomly assigned, using a factorial design, to one of four groups receiving supplementation with B group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, 0.02 mg cyanocobalamin), antioxidant vitamins (150 mg ascorbic acid, 67 mg alpha-tocopherol, 9 mg beta-carotene), B vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-week study. The lag time of LDL isolated ex vivo to oxidation (induced by 2 mumol/l cupric chloride) was increased in the two groups receiving antioxidants whether with (6.88 +/- 1.65 min) or without (8.51 +/- 1.77 min) B-vitamins, compared with placebo (-2.03 +/- 1.50) or B-vitamins alone (-3.34 +/- 1.08) (Mean +/- S.E., P < 0.001). Antibodies to malondialdehyde (MDA) modified LDL were also measured, but there were no significant changes in titers of these antibodies in any group of subjects whether receiving antioxidants or not. Contrast analysis showed that there was no interaction between antioxidants and B-group vitamins. This study indicates that while B-group vitamins lower plasma homocysteine they do not have an antioxidant effect. Thus B-group vitamins and antioxidants appear to have separate, independent effects in reducing cardiovascular risk.
Lack of association between genetic variations of apo A-I-C-III-A-IV gene cluster and myocardial infarction in a sample of European male: ECTIM study.
The goal of the present study was to compare the allele frequency of four polymorphisms at the apo A-I C-III A-IV cluster gene locus-ApoA-I: XmnI and PstI; ApoC-III: SstI; ApoA-IV: XbaI-between male patients who had had a myocardial infarction (n= 614) and matched controls (n = 764). The association with a number of lipid lipoprotein, apolipoprotein and lipoprotein particle variables was also assessed. Patients and subjects were recruited in Belfast, Lille, Strasbourg and Toulouse in the framework of the ECTIM study. In the control group, the frequencies of the different polymorphic alleles were homogeneous among recruitment centres suggesting the absence of any European North to South gradient for these cluster polymorphisms. There was no evidence for a significant difference in allelic distribution between cases and controls suggesting that apo A-I, C-III, A-IV gene cluster polymorphisms do not explain MI survival in this sample of European men. There was no statistically significant association between apo A-I C-III A-IV cluster gene polymorphisms and lipid, lipoprotein, apolipoprotein, and lipoprotein particle levels. In conclusion, in the ECTIM study, the apo A-I, C-III, A-IV gene cluster polymorphism is associated with neither circulating plasma variables nor MI survival.
Polymorphisms of the endothelin-A and -B receptor genes in relation to blood pressure and myocardial infarction: the Etude Cas-Témoins sur l'Infarctus du Myocarde (ECTIM) Study.
Endothelin-1 is a potent vasoconstrictor that has also mitogenic properties, stimulating the synthesis and secretion of several vasoactive molecules. There is much evidence to suggest that endothelin-1 might be involved in the pathogenesis of hypertension, atherosclerosis, and ischemic heart disease. Endothelin-1 exerts its effects through at least two receptors, ET(A) and ET(B), which are encoded by different genes and have separate tissue distributions and biologic properties. The objective of this study was to identify polymorphisms of the ET(A) and ET(B) receptor genes and to study their association with myocardial infarction (MI) and blood pressure. The coding regions and 1.3 kb upstream of the ET(A) and ET(B) receptor genes were explored by polymerase chain reaction/single strand conformation polymorphism. Six polymorphisms were found in the ET(A) receptor gene and three in the ET(B) receptor gene. Most of these polymorphisms were frequent. Associations between the detected polymorphisms, blood pressure, and MI were examined in the ECTIM study, a multicenter study comparing 652 patients having survived an MI and 773 controls from Belfast (Northern Ireland) and France. Alleles at the different polymorphic sites were similarly distributed in patients with MI and controls. Allele frequencies were similar in both countries, except for the ET(A)/-231 G allele, which appeared more frequently in France than in Belfast (P < .01). The mean systolic and diastolic blood pressure levels did not significantly differ between genotypes. However, a C/T substitution located in the nontranslated part of exon 8 of the ET(A) receptor gene (ET(A)/EX8nt1363) was associated with pulse pressure (P < .005). These results do not support an involvement of the endothelin receptor genes in a predisposition to MI or the determination of blood pressure levels, but suggest that a polymorphism of the ET(A) receptor gene might influence the pulse pressure. This result will have to be confirmed in other studies.
Transepidermal elimination of urate-like crystals: a new perforating disorder?
We report two men who developed a transient perforating disorder characterized by transepidermal elimination of negatively birefringent needle-shaped crystals similar to monosodium urate. This striking clinical presentation has not previously been described and we propose that it be added to the group of diseases known as the primary perforating disorders.
Polymorphisms of the endothelial nitric oxide synthase gene - no consistent association with myocardial infarction in the ECTIM study.
BACKGROUND: Our aim in the present study was to determine whether endothelial NO synthase gene (ecNOS) polymorphisms are associated with myocardial infarction (MI). METHODS: Forty chromosomes from patients with MI were screened for polymorphisms of the ecNOS gene using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Ten polymorphisms were detected: three in the 5' flanking sequence at positions -1474, -924 and -788, two in coding sequences 774C --> T (silent) and G894 --> T (Glu-298 --> Asp) and five in introns 2, 11, 12, 22 and 23. Five hundred and thirty-one patients with MI and 610 control subjects recruited in France and Northern Ireland in the ECTIM study were genotyped for these polymorphisms. RESULTS: Glu-298 homozygotes were more frequent among patients with MI than in control subjects in the French population [OR = 1.47 (1.03-1.97), P < 0.009], but no such difference was observed in Northern Ireland. No significant difference between cases and control subjects was detected for the other polymorphisms. Our search for a possible association of the combination of ecNOS polymorphisms with MI by logistic regression analysis was also negative. CONCLUSIONS: We have explored a set of polymorphisms of the ecNOS gene in a large case-control study of MI and found that the polymorphisms were not consistently associated with MI.
Sclerotherapy for leg telangiectasia--a blinded comparative trial of polidocanol and hypertonic saline.
BACKGROUND: Hypertonic saline (HS) and polidocanol (POL) have been in use around the world for sclerotherapy of telangiectasia for many years. However, despite numerous articles in the literature extolling the virtues of their individual use, few studies scientifically compare their relative efficacies. OBJECTIVE: To compare, in a statistically significant number of female patients, the relative efficacy of hypertonic saline and polidocanol as sclerosants of leg telangiectasia and reticular feeding veins, using each patient as her own control. METHODS: Eighty-one women with roughly matching leg telangiecasia were treated with sclerotherapy. One leg was injected with 20% saline/2% lignocaine, the other with 1% polidocanol, with the patients blinded as to the sclerosant used for each leg. Assessment of percent reduction of vessels, and the complications of matting and hemosiderin staining was conducted at 2 months by 3 methods: the patient's satisfaction, the treating physician's evaluation, and blinded assessment of before and after photographs. RESULTS: There was no statistically significant difference between HS and POL treated legs when assessed clinically or photographically. However, POL caused more staining and matting, and despite patients finding HS more painful at injection, patient satisfaction at follow-up was higher with the HS treated leg. CONCLUSION: 20% HS and 1% POL have equal efficacy in sclerosing leg telangiectasia and reticular feeding veins. POL causes more adverse sequelae, although these may be related to the solution concentration.
Tiredness as a ticket of entry. The role of patients' beliefs and psychological symptoms in explaining frequent attendance. General Practice Fatigue Group.
OBJECTIVES: To test when patients presented with fatigue whether their beliefs about its cause was related to their frequency of attending; and to measure the association between their fatigue and psychological symptoms and their frequency of attendance during the study year. DESIGN: A cohort study. SETTING: Primary health care. PATIENTS: Patients presenting with fatigue as their main symptom. MAIN OUTCOME MEASURES: A fatigue questionnaire, the general health questionnaire (GHQ), an attribution scale, and measurement of consulting frequency during the 6 months before and after the patient presented. RESULTS: Patients who believed their fatigue was due to a physical or costly physical cause consult for any reason significantly more frequently than patients who reported that psychological as well as physical problems might have caused their fatigue. Patients' psychological distress measured with the GHQ was more closely associated with frequent attendance than their level of fatigue was. CONCLUSIONS: When patients present with fatigue it is important to inquire about their beliefs and psychological symptoms; these factors may be more important than the fatigue itself in explaining their help-seeking behaviour.