Functional characterisation of the neuropeptide Y receptor mediating feeding in the rat.
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Animals↗
Biomedical subjects
S Wilson
Publications and source records attributed to S Wilson.
Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1.
We have evaluated solid-phase ELISA IgG antibody avidity studies as a means of identifying cases of recent HIV-1 infection. Although separate studies on the avidity of anti-gp41 and anti-p24 antibodies in seroconvertors have been reported, a comparison of the ability of patients to simultaneously mature their immune response to more than one HIV antigen immediately following seroconversion appears to be lacking. We have demonstrated a maturation in anti-gp41 avidity which reflects the time since seroconversion in all cases. In contrast, however, only some patients produced high-avidity anti-p24 or anti-p17 antibodies during the same time span. While the avidity of anti-gp41 antibodies remained high in cases of non-recent HIV infection, even in the face of advanced disease, we have confirmed the findings of others that the avidity of anti-p24 falls before the onset of ARC or AIDS. Therefore, whilst the avidity of anti-gp41 antibodies could reliably be of value in identifying cases of recent HIV infection, the avidity of anti-p24 or anti-p17 antibodies could not, but may be of prognostic value, even at an early stage. The time taken to reach maximum anti-p17, anti-p24 and anti-gp41 titres was variable, but anti-gp41 titres, like anti-gp41 avidity, remained high. In contrast, anti-p24 titres fell, even during the early followup period in some seroconvertors. Anti-p24 antibody avidity, however, appeared to be a better predictor of disease progression in 'remote' cases than anti-p24 titre. The avidity and titres of these antibodies are presented in relation to the clinical details, p24 antigen status, CD4 and CD8 counts where these are known.
Adult↗
Structural determinants within the subunit protein of Ty1 virus-like particles.
The Ty virus-like particles (VLPs) are functionally analogous to retroviral particles. They package the enzymes and the RNA necessary for retrotransposition, and mediate the integration of the reverse-transcription product into the genome of the host cell. Here we map three structural determinants of particle assembly in the subunit protein. We have also identified key residues in these regions that seem to be involved in subunit interaction and particle morphology. In particular, two point mutations in putative amphipathic helices have remarkable effects on VLP morphology, increasing the diameter as much as eightfold.
Amino Acid Sequence↗
United Kingdom national audit of breast fine needle aspiration cytology in 1990-91--organization and level of activity.
A survey amongst members of the British Society for Clinical Cytology (BSCC) was performed in 1990 and 1991 into their experience of fine needle aspiration (FNA) cytology of the breast. Here we present the findings of that part of the survey covering organizational aspects of the service and methods of specimen handling. The replies demonstrate differences in approach to many of the topics covered. There is a preference for the examination of direct smears (rather than cytospins) with air dried Giemsa staining and wet fixation Papanicolaou staining finding nearly equal favour. Some perceived problems were highlighted, including availability and funding of training and quality assurance as well as facilities for liaison between pathologists, clinicians and radiologists.
Biopsy, Needle↗
UK national audit of breast fine needle aspiration cytology in 1990-91: diagnostic criteria.
A survey into the practice of fine needle aspiration cytology of the breast amongst members of the British Society for Clinical Cytology in 1990 and 1991 was performed. This paper presents their reported use of diagnostic categories in reporting and the criteria found useful in the diagnosis of benign and malignant disease. A wide variety of diagnostic categories are in use. The criteria used in diagnosis largely follow recommendations found in standard textbooks, but some less well recognized features were also suggested.
Biopsy, Needle↗
Leeds Undergraduate Medical Education Conference, 7-8 July 1995.
The Leeds Undergraduate Medical Education Conference (LUMEC) was held on 7-8 July 1995. This conference, devoted entirely to undergraduate medical education, was unique in that it was organized entirely by four medical students. It attracted a wide and enthusiastic audience and excellent speakers. Professor Charles George (Chairman, Education Committee, General Medical Council) spoke about Tomorrow's Doctors, Dr Mark Bailey (Part-chairman, Medical Students' Committee of the British Medical Association) responded with 'Today's Students on Tomorrow's Doctors', and Dr Fleur Fisher (Ethics, Science and Information Division, British Medical Association) focused on the central place of ethics and communication skills in medicine. Professor Sam Leinster (Director of Medical Studies, Liverpool University) and Professor Tim de Dombal (Director, Clinical Information Science Unit, Leeds University) debated the need for new technology and radical change in the curriculum. Finally, Dr Stella Lowry (International Division, British Medical Association) considered the assessment of staff and Mrs Joy Crosby (Curriculum Facilitator, Dundee Medical School) discussed the assessment of students. Discussions focused on a variety of areas, including the need for change, the control of the money available for teaching and the problems of assessment.
Education, Medical, Undergraduate↗
Case for active physician involvement in US practice.
PURPOSE: To assess the benefit of active physician involvement in ultrasound (US) examinations. MATERIALS AND METHODS: Concordance of findings by technologists and physicians was assessed prospectively for examinations of 1,510 consecutive patients who underwent US during regular working hours. RESULTS: Overall concordance was generally good (74%). However, in cases in which a major or minor new diagnosis was made from the US scan, concordance rates were substantially lower (36% and 32%, respectively). Agreement varied with the type of examination. The discordance rate for obstetric examinations (17%) was only half that for abdominal and pelvic examinations (31%). Concordance improved with increasing years of experience of the technologist. CONCLUSION: An active role of physicians in the overall conduct of US examinations is essential to optimize provision of a complete, accurate report.
Diagnostic Errors↗
Alveolar tissue inflammation in asthma.
As physiologic and autopsy evidence suggests that peripheral airways and parenchyma are involved in asthma, we hypothesized that significant alveolar tissue inflammation is present in patients with stable, chronic asthma. Eleven patients with nocturnal asthma (NA) and 10 patients with non-nocturnal asthma (NNA) were studied. Each subject underwent two bronchoscopies with proximal airway endobronchial and distal alveolar tissue transbronchial biopsy in a random order at 4:00 P.M. and 4:00 A.M. Morphometric analysis was used to determine the number per volume (Nv) of inflammatory cells. Between-group comparisons showed that the Nv of eosinophils was greater in the NA alveolar tissue 4:00 A.M. compared with the subjects with NNA (40.2 x 10(3) [26.4-57.1 x 10(3), IQ] versus 15.7 x 10(3) [2.1-35.2 x 10(3), IQ], p = 0.05). In regard to the airway biopsies, no difference in the inflammatory and epithelial cells between the two groups was seen at either time. The NA group exhibited greater eosinophils and macrophages in the alveolar tissue at 4:00 A.M. compared with 4:00 P.M. (40.2 x 10(3) [26.4-57.1 x 10(3), IQ] versus 10.3 x 10(3) [2.7-16.8 x 10(3), IQ], p = 0.016 for eosinophils and 215.1 x 10(3) [129.9-356.1 x 10(3), IQ] versus 166.3 x 10(3) [150.7-212.6 x 10(3), IQ], p = 0.031 for macrophages). Only alveolar tissue eosinophils, not proximal airway tissue eosinophils, correlated with the nocturnal decrement in lung function (r = -0.54, p = 0.03). These findings suggest that eosinophils and macrophages accumulate to a greater extent in the alveolar tissue and these changes contribute more to the variation in lung function compared with inflammation in the more proximal tissue.
Adult↗
Reliability of underlying incidence rates for estimating the effect and efficiency of screening for breast cancer.
The process of setting screening performance targets requires an estimate of what the incidence of breast cancer would have been in the population invited for screening if there had not been a screening programme. Before the introduction of the National Health Service breast screening programme in 1988 the incidence of breast cancer was already increasing in the population targeted for screening. To establish the incidence before screening the most recent complete data from all the regional cancer registries were collated. An age-period model was constructed to predict what these incidence rates might now have been if the screening programme had not been introduced. The model predicted that if prescreening trends continued (between 1987 and 1995) underlying incidence over this period would increase by 2.3 per 10,000 in women aged 50-54, 2.6 per 10,000 in women aged 55-59, and 2.9 per 10,000 in women aged 60-64. If the prescreening trends have continued then the use of a universal rate, applied across all calendar years and age groups, would seem to be inappropriate when setting targets.
Adult↗
Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects: a placebo-controlled parallel group study.
The anti-inflammatory effects of oral theophylline on cells in bronchial biopsies of symptomatic atopic asthmatic subjects were investigated. Following a 2 week run-in period, asthmatic subjects were randomly assigned to either placebo (n=11) or theophylline (n=15). Bronchial biopsies were taken at fibre-optic bronchoscopy at the beginning and end of a 6 week period, during which subjects took placebo or theophylline medication at a dose intended to produce therapeutic concentrations. Nine of the placebo subjects and 12 of the theophylline subjects completed the study. Improvement in asthma control was seen in the theophylline-treated group. The mean (SD) theophylline blood level at the end of the study was 10.9 (6.0) microg x mL-1. A significant decrease in interleukin (IL)4 expression from 1.38 to 1.04 cells x mm-2 (<0.05) and a trend to a reduction in IL-5 from 1.29 to 0.48 cells x mm-2 (NS) were seen in biopsies from the theophylline-treated group compared with placebo, although there was no change in mast cell numbers (judged by tryptase expression). A decrease in epithelial CD8+ cells from 2.60 to 0.53 cells x mm-1 of surface (<0.05) was noted. This study shows an anti-inflammatory effect of theophylline in asthmatic bronchi, both in cell numbers and in the expression of IL-4, believed to be an important cytokine in the pathophysiology of asthmatic inflammation. We speculate that theophylline induces downregulation in vivo of cytokine production, accounting for the known inhibitory effect of theophylline on the late asthmatic reaction.
Administration, Inhalation↗
'Audible thoughts' and 'speech defect'.
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Hallucinations↗
How should we investigate women with postmenopausal bleeding?
OBJECTIVE: To evaluate the optimum method(s) of investigating women with postmenopausal bleeding. DESIGN: Prospective study of 76 postmenopausal women. SETTING: Teaching Hospital. Interventions. All women had pipelle endometrial biopsy in outpatient clinic. Prior to inpatient hysteroscopy and uterine curettage, each woman had pelvic ultrasonography to measure the endometrial thickness and to exclude ovarian pathology. RESULTS: Pipelle biopsy was successful in 70% of cases and has a sensitivity of 70%. Hysteroscopy has superior diagnostic capabilities allowing direct visualisation of the endometrial cavity with directed biopsies. Endometrial thickness of > 5 mm used as an indicator of endometrial pathology compared to uterine curettage has a sensitivity of 83%, a specificity of 77%, and a positive predictive value of 54%. Ultrasound also detected five ovarian tumors, two of which were malignant and three missed by pelvic examination alone. CONCLUSIONS: We recommend the routine use of pelvic ultrasonography in all women with postmenopausal bleeding as it is an invaluable diagnostic tool in excluding ovarian pathology. In addition, sampling of the endometrial cavity, preferably with outpatient hysteroscopy, is mandatory for histological diagnosis. Overall, the combination of ultrasound and outpatient endometrial sampling would spare hospital admission for at least 60% of women with postmenopausal bleeding.
Biopsy↗
Unusual course of the gonadal vein: a case report of postpartum ovarian vein thrombosis mimicking acute appendicitis clinically and sonographically.
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Adult↗
Consumer empowerment in the mental health field.
This article is an overview of consumer empowerment and involvement in the mental health field, with a focus on some recent Canadian developments as described in the formal literature. A brief description of traditional approaches to treatment and support for persons with serious mental health problems is provided, followed by a discussion of the principles of consumer empowerment and involvement. Three categories of involvement are described with a discussion of some of the associated benefits and barriers and methods for overcoming them. A discussion of directions for future work is also included.
Community Participation↗
The GLAM test: a flow cytometric assay for the detection of leukocyte antibodies in autoimmune neutropenia.
The GLAM assay, a combined flow cytometric immunofluorescence test that simultaneously detects antibodies to granulocytes, lymphocytes, and monocytes, was used in the investigation of autoimmune neutropenia. This method avoids the need for a succession of immunofluorescence tests, first against granulocytes and then against lymphocytes, in order to distinguish granulocyte-specific from granulocyte/lymphocyte-reactive antibodies, such as noncomplement- fixing anti-HLA sera. Samples from 18 patients with a suspected diagnosis of autoimmune neutropenia were referred for investigation. Leukocytes were harvested in sufficient quantities from 10 of the patients such that neutrophil and lymphocyte direct antiglobulin tests (DATs) and antibody screening and identification could be undertaken (in one case the results were inconclusive). Only three of these 10 patients had DAT-positive granulocytes, and one of these three also had DAT-positive lymphocytes. One further patient demonstrated DAT-positive lymphocytes in the absence of granulocyte-bound IgG, despite a presumed diagnosis of autoimmune neutropenia, rather than pancytopenia. This was the only patient in this cohort who had demonstrable leukocyte antibodies reacting with lymphocytes but not granulocytes. Of the remaining eight patients (not evaluable for granulocyte or lymphocyte DATs), five had free leukocyte antibodies in the serum; three of these five had both granulocyte- and lymphocyte-reactive antibodies free in the serum and two only had granulocyte-specific antibodies.
Journal Article↗
Prospects for beta 3-adrenoceptor agonists in the treatment of obesity and diabetes.
beta 3-Adrenoceptor (beta 3-AR) agonists were first identified more than twelve years ago and were found to be remarkably effective in animal models of obesity and Type II (non-insulin dependent) diabetes. Those that have been taken forward to clinical studies have not, however, proved so effective in humans: they have either been of limited efficacy, or their activities have been accompanied by significant side-effects. Reasons for the failure of some beta 3-AR agonists in humans have included a poor pharmacokinetic profile and, possibly, a failure of prodrugs to be metabolised to selective beta 3-AR agonists. A more fundamental problem, however, is that the human and rat beta 3-AR differ pharmacologically, and those compounds that have been evaluated in humans have much lower efficacy at the human than the rat receptor. This problem may be compounded by there being a low number of beta 3-AR relative to beta 1-AR and beta 2-AR in those tissues that mediated thermogenesis in humans, so that low efficacy compounds tend to exhibit mainly beta 1-AR or beta 2-AR-, rather than beta 3-AR-mediated effects, despite their having selective affinity for human beta 3-AR. Nevertheless, studies using CGP 12177, which is an agonist at beta 3-AR but an antagonist at beta 1-AR and beta 2-AR, demonstrate that functional beta 3-AR are present in human adipose tissue. Moreover, the association of a polymorphism in the human beta 3-AR with obesity and diabetes demonstrates that this receptor is relevant to these diseases in humans. Thus the true potential of beta 3-AR agonists in humans can only be evaluated when a compound with good selectivity and efficacy at the human beta 3-AR, coupled with a long duration of action in vivo, has been identified.
Adrenergic beta-Agonists↗
Physiologic definitions of obliterative bronchiolitis in heart-lung and double lung transplantation: a comparison of the forced expiratory flow between 25% and 75% of the forced vital capacity and forced expiratory volume in one second.
BACKGROUND AND METHODS: A comparison of the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25-75) and forced expiratory volume in 1 second (FEV1) was conducted for the detection of obstructive airway disease as an early manifestation of obliterative bronchiolitis. Pulmonary function tests performed on heart-lung and double lung transplant recipients between March 1981 and March 1983 were reviewed. Thirty patients were identified who showed progressive deterioration in pulmonary function after transplantation. Ratios determining proportionate decreases were calculated from measurements of absolute values for the FEF25-75 and FEV1 at the point when the FEF25-75 reached < 70% and < or = 30% of predicted, divided by baseline values obtained before the decline in function. Similar ratios were obtained for FEV1 and FEF25-75 at the point the FEV1 declined > or = 20% from its baseline value. RESULTS: Comparison of the ratios for the FEF25-75 and FEV1 at FEF25-75 values < 70% and < or = 30% of predicted and a similar comparison when the FEV1 declined > or = 20% from baseline showed a greater proportional decrease in FEF25-75 than FEV1 (p < 0.01). With the use of the FEF25-75, declines in airway function were detected earlier. After transplantation a decline in FEF25-75 to < 70% of predicted occurred approximately 112 days before a 20% decline a FEV1. CONCLUSION: The FEF25-75 is more sensitive than the FEV1 for the early detection of obliterative bronchiolitis. A presumptive diagnosis of obliterative bronchiolitis can be made with physiologic criteria, providing infection or acute rejection has been ruled out. When conducting epidemiologic studies or for vital statistics we propose that a decline in FEF25-75 to < 70% be used to define the onset of obliterative bronchiolitis.
Adult↗
Feasibility of high-volume screening sigmoidoscopy using a flexible fiberoptic endoscope and a disposable sheath system.
OBJECTIVES: Sigmoidoscopy is an effective screening test for colorectal cancer but has yet to have a major impact on mortality because, in part, of inadequate utilization by physicians. To address concerns of inefficient use of time and resources, we examined the feasibility of high volume, single-day flexible sigmoidoscopy (FS) screening sessions using an innovative fiberoptic sigmoidoscope with a disposable sheath system. METHODS: All City of Boston employees over the age of 50 yr (n = 6137) were invited by mail to undergo a screening FS at Boston City Hospital (BCH). Respondents (n = 564) were contacted by phone by the program coordinator on receipt of a prepaid postcard and were scheduled (n = 227) consecutively into 15-min slots on 1 of 6 1/2-day (3-h) weekend sessions. Preregistration was completed at BCH during the week before each session and included enrollment, completion of a brief risk questionnaire, documentation of informed consent, and bowel prep instructions. Procedures were performed by three physician endoscopists rotating among four endoscopy rooms per session. Each room was staffed with a nurse to aid in patient care and a technician to set up equipment. RESULTS: A total of 198 of the 227 (87%) scheduled patients underwent screening FS during the three sessions. Physicians performed a mean of 3.5 procedures per room per hour, or 4.7 procedures per hour overall, with a mean depth of scope insertion of 51 +/- 10 cm and a mean procedure time of 4.7 +/- 3.3 min. Equipment set-up time and patient turnaround time averaged 4.6 +/- 1.7 min and 11.0 +/- 6.0 min, respectively. Polyps were detected in 29 (14.6%) patients, and a Dukes' A cancer was detected in one (0.5%). The only complication was a cardiac arrhythmia. A crude estimate of direct costs approximated $ 75 per examination. CONCLUSION: High volume, single-day FS using the fiberoptic sigmoidoscope with a disposable sheath system offers an effective strategy for enhancing physicians compliance, and possibly patient compliance, with screening sigmoidoscopy through more efficient use of time and resources.
Aged↗