Biomedical subjects
B Smith
Publications and source records attributed to B Smith.
Risk factors and costs associated with an asthma attack.
BACKGROUND: A study was undertaken to identify asthma patients at risk of an attack and to assess the economic impact of treatment strategies. METHODS: A retrospective cohort analysis of a representative data set of 12 203 patients with asthma in the UK over a one year period was performed. Logistic multiple regression was used to model the probability of an attack occurring using a set of categorised predictor factors. Health service costs were calculated by applying published average unit costs to the patient resource data. The main outcome measures were attack incidence, health service resource use, drug treatment, and cost estimates for most aspects of asthma related health care. RESULTS: Children under five years of age accounted for 597 patients (5%), 3362 (28%) were aged 5-15 years, 4315 (35%) 16-44, 3446 (28%) 45-74, and 483 (4%) were aged over 74 years. A total of 9016 patients (74%) were on some form of prophylactic asthma medication; 2653 (22%) experienced an attack in the year data collection occurred. Overall health care expenditure was estimated at pound2.04 million. The average cost per patient who had an attack was pound381 compared with pound108 for those who did not, an increase of more than 3.5 times. In those aged under five and those over 75 years of age there were no significant markers to identify risk, but both groups were small in size. The level of treatment step in the British Thoracic Society (BTS) asthma guidelines was a statistically significant factor for all other age groups. Night time symptoms were significant in the 5-15, 16-44 and 45-74 age groups, exercise induced symptoms were only significant for the 5-15 age group, and poor inhaler technique in the 16-44 age group. CONCLUSIONS: Patients at any treatment step of the BTS asthma guidelines are at risk of an asthma attack, the risk increasing as the treatment step increases. Poorly controlled asthma may have a considerable impact on health care costs. Appropriate targeting of preventive measures could therefore reduce overall health care costs and the growing pressures on hospital services associated with asthma management.
Predictors of physical fitness in a college sample.
The present study examined the relationships among self-reported amounts of exercise, body composition, age, weight, blood pressure, and physical fitness. Participants reported their duration and frequency of exercise, which were combined to obtain individual indexes of exercise. VO2 max predicted from a 1-mi. walk test, percent body fat via sum of skinfolds, blood pressure, and flexibility of the lower back and posterior thigh were measured. Findings indicated that age and exercise index were significant predictors of fitness for women, and percent body fat was a significant predictor for men. Results suggest individuals' exercise index moderately correlates with fitness, although it is not the only contributing factor.
Lidocaine-prilocaine patch decreases the pain associated with the subcutaneous administration of measles-mumps-rubella vaccine but does not adversely affect the antibody response.
BACKGROUND: Topical lidocaine 2.5% and prilocaine 2.5% (EMLA) is effective in decreasing the pain associated with minor procedures including immunization, although the effect on the antibody response to vaccine constituents has not been assessed. OBJECTIVE: To measure the antibody response to measles-mumps-rubella (MMR) vaccine, as well as pain reduction associated with the use of the EMLA patch. PARTICIPANTS AND SETTING: One hundred sixty healthy infants at least 12 months old undergoing their first MM immunization in an ambulatory setting. DESIGN AND INTERVENTIONS: Randomized, double-blind, controlled trial of EMLA patch (5%-1 g) or placebo before MMR immunization. Blood sampling before and 28 to 35 days after immunization. OUTCOME MEASURES: The primary outcome measure was the antibody response to measles by plaque reduction neutralization and to mumps and rubella by enzyme immunoassay. The secondary outcomes were pain scores by the Modified Behavioral Pain Scale and drug- and vaccine-associated adverse events. RESULTS: There was no difference in the antibody response between the EMLA- and placebo-treated groups. The response rates in the EMLA group were 89.7%, 88.3%, and 92.3% to measles, mumps, and rubella, respectively, compared with rates of 91.1%, 94.9%, and 93.7% in the placebo group (P >.05 for all comparisons). EMLA recipients had less pain after immunization (mean Modified Behavioral Pain Scale score increase 3.1 compared with 3.8; P =.043) and less irritability (16% compared with 31%; P =.040) than did placebo recipients. CONCLUSIONS: The EMLA patch has no adverse effect on the antibody response to MMR vaccine and significantly reduces the pain associated with the subcutaneous administration of the vaccine.
Which method of communication do GPs prefer to use?
Explore the source record for details and available documents.
Scottish Asthma Management Initiative.
OBJECTIVES: To describe the development process of a system that links audit, research and patient care and to detail the lessons learned from establishing a Scotland wide asthma management initiative. DESIGN, SETTING AND SUBJECTS: Health Boards and practices throughout Scotland were invited to participate in an initiative which links review of care, guideline implementation, chronic disease management (CDM) approval and post-graduate education for doctors (PGEA) and nurses (PREP). Participating practices were given the materials to review 30 patients randomly selected from their asthma register. Health service resource use and drugs prescribed over a retrospective 12 month period were recorded for each patient using paper or electronic materials. All patients were invited for clinical assessment. RESULTS: A two-tier management system proved effective. Twelve of the 15 Scottish health authorities agreed to recognise the audit for automatic CDM approval although the negotiation process was prolonged; 566 practices from all parts of Scotland have expressed an interest in the initiative. Provision of distance learning material linked to PGEA accreditation is free to general practitioners (GP's) and is a useful incentive for participation. To date 42 GPs have completed the distance learning element. CONCLUSION: The Scottish Asthma Management Initiative has provided the opportunity for all sectors of the health service in Scotland to work together to explore innovative ways to improve the management and care of chronic disease. Participation in an initiative linked to guidelines, education and CDM approval is an excellent way to facilitate health professionals to improve care.
A South Australian population survey of the ownership of asthma action plans.
OBJECTIVE: To examine the relationships between ownership of written asthma action plans, asthma morbidity, use of devices, and patients' perceptions of their asthma management. DESIGN AND SETTING: A random population survey (in 1996) of the South Australian population aged 15 years or over, using interviewers to administer a questionnaire. PARTICIPANTS: People who reported that they had current, doctor-diagnosed asthma. MAIN OUTCOME MEASURES: Prevalence of written asthma action plans; night-time awakenings from asthma; ownership of peak flow meters; and people's perceptions of their asthma management. RESULTS: The ownership of asthma action plans by people with self-reported asthma was 33% and has declined since 1995 (42%; P < 0.001). Fifteen per cent were awakened weekly or more frequently by asthma symptoms. These people were more likely to have a peak flow meter and a written action plan, but less likely to consider they had been provided with enough information about their asthma, to feel comfortable managing their asthma, or to find it easy to see their doctor. Having a written asthma action plan was associated with regular corticosteroid use, understanding asthma, having enough information and owning a peak flow meter. CONCLUSIONS: Ownership of asthma action plans in South Australia is suboptimal. Before we develop new strategies to improve asthma outcomes, we must determine whether there is a need to target people with less severe asthma and/or improve the use of guidelines by health professionals.
Field research on the relationship between stress and disease activity in rheumatoid arthritis.
We review empirical evidence from two field studies for the role of stressful life events in disease flare-ups among patients with rheumatoid arthritis (RA). RA patients were expected to be more vulnerable psychologically, and physiologically, to stressful events in their everyday lives than other arthritis patients without an autoimmune disease. Findings from two studies are reviewed both for their substantive contribution, but also to provide guidance on measurement issues in future field research of this kind. One study included 41 patients with RA, who were interviewed weekly and called to a clinic for blood work and joint examinations when their levels of interpersonal stress increased significantly. A second study used a similar design but included comparison samples of patients with osteoarthritis (OA) and healthy controls of similar age and the same gender as the RA sample. The findings provided support for the proposition that interpersonal stressors are predictive of increases in disease activity. Not all RA patients, however, showed these relationships, and there was evidence that some participants with OA who were depressed also showed higher disease activity following interpersonal stressors. Significant individual differences in the stress-disease relationship were uncovered that deserve greater attention in future studies. Important improvements in the assessment of stressful events and refinements in panel study design are also presented as guides to research on the role of stress in disease processes.
Quality of care at a children's hospital: the parent's perspective.
OBJECTIVES: To develop a measure of parental perceptions of pediatric inpatient quality of care, to identify processes of care that influence these perceptions, and to describe these perceptions of care. DESIGN: An interdisciplinary team modified an existing measure of inpatient care for adults using focus groups and expert review. The resulting survey was administered by telephone. SETTING: Tertiary care pediatric hospital. PATIENTS: Trained telephone interviewers obtained reports from parents of children discharged from the hospital during specified months. This report is based on the answers to 122 questions provided by 3622 (77%) of 4724 parents who responded when surveyed from 1991 through 1995. MAIN OUTCOME MEASURES: Parents provided reports about specific clinical experiences, overall ratings of care, and patient demographic and illness characteristics 2 weeks after patient discharge from the hospital. The analysis classified reports about pediatric care as either problems or not problems. Problems in different areas of care were averaged to create scores for the dimensions. RESULTS: Parents most often noted problems related to hospital discharge planning (18%) and pain management (18%) and less often reported problems concerning communication about surgery (10%) or transmission of information to children (6%). Problems in communication between clinicians and parents correlated most strongly with overall quality ratings by parents (r=0.59). Parents' specific reports of problems with care accounted for 42% of the variation in their overall assessments of the inpatient care experience. CONCLUSIONS: Parental assessment of inpatient pediatric care rests heavily on the quality of communication between the clinician and parent. Specific processes of care strongly influence overall assessments. Such reports could be used to focus the quality-improvement activities of hospitals and increase the accountability of providers of care to children and families.
Comparison of cytotoxic T-lymphocyte responses to hepatitis C virus core protein in uninfected and infected individuals.
Cytotoxic T lymphocytes have been implicated in the control of hepatitis C virus (HCV) infection. Recognition by cytotoxic T lymphocytes of epitopes within HCV core protein has been defined previously by in vitro stimulation with synthetic peptides. The aim of this study has been to examine cytotoxic T-lymphocyte responses generated against peptides produced naturally following intracellular processing of viral protein. Antigen-specific cytotoxic T-lymphocyte lines were generated from both HCV uninfected and infected individuals by culturing CD8+ T cells with autologous dendritic cells loaded intracytoplasmically with recombinant HCV core protein. Analysis of the epitopes recognized by core protein-specific cytotoxic T lymphocytes used synthetic peptides that were selected based on their predicted binding to HLA-A*0201 molecules. Core protein-specific cytotoxic T lymphocytes derived from HCV uninfected and infected individuals were able to lyse autologous target cells pulsed with each of 5 predicted epitopes. Generation of HCV-specific cytotoxic T lymphocytes using dendritic cells as antigen presenting cells provides a method of comparing the potential repertoire of cytotoxic T-lymphocyte responses to the responses that occur in chronically infected individuals. No evidence of a qualitatively different response by patient cytotoxic T lymphocytes was apparent which might explain persistence of the virus.
Detection of DNA fragmentation and endonucleases in apoptosis.
DNA degradation during apoptosis is endonuclease mediated and proceeds through an ordered series of stages commencing with the production of large DNA pieces of 300 kb which are then degraded to fragments of 50 kb. The 50-kb fragments are further degraded, in some but not all cells, to smaller pieces (10-40 kb) releasing the small oligonucleosome fragments that are detected as a characteristic DNA ladder on conventional agarose gels. Methodology is presented for the detection of both DNA ladders and the initial stages of DNA fragmentation using pulsed-field gel electrophoresis. We have developed electrophoresis conditions that resolve large fragments of DNA and also retain the smaller fragments on the same gel. Methods for the detection of endonuclease activities responsible for the cleavage of DNA during apoptosis are also presented.
Direct observation of one-dimensional diffusion and transcription by Escherichia coli RNA polymerase.
The dynamics of nonspecific and specific Escherichia coli RNA polymerase (RNAP)-DNA complexes have been directly observed using scanning force microscopy operating in buffer. To this end, imaging conditions had to be found in which DNA molecules were adsorbed onto mica strongly enough to be imaged, but loosely enough to be able to diffuse on the surface. In sequential images of nonspecific complexes, RNAP was seen to slide along DNA, performing a one-dimensional random walk. Heparin, a substance known to disrupt nonspecific RNAP-DNA interactions, prevented sliding. These observations suggest that diffusion of RNAP along DNA constitutes a mechanism for accelerated promoter location. Sequential images of single, transcribing RNAP molecules were also investigated. Upon addition of 5 microM nucleoside triphosphates to stalled elongation complexes in the liquid chamber, RNAP molecules were seen to processively thread their template at rates of 1.5 nucleotide/s in a direction consistent with the promoter orientation. Transcription assays, performed with radiolabeled, mica-bound transcription complexes, confirmed this rate, which was about three times smaller than the rate of complexes in solution. This assay also showed that the pattern of pause sites and the termination site were affected by the surface. By using the Einstein-Sutherland friction-diffusion relation the loading force experienced by RNAP due to DNA-surface friction is estimated and discussed.
Perineal one-stage pull-through for Hirschsprung's disease.
PURPOSE: The aim of this study was to present the strategy of a one-stage repair of Hirschsprung's Disease (HD) performed via a transanal approach. METHODS: Ten consecutive neonates and one toddler underwent transanal repair for biopsy-proven HD. A rectosigmoid transition zone was suggested by contrast enema in all patients. The mean age at operation for the neonates was 4 days. A mucosal dissection was begun 0.5 cm proximal to the dentate line. Once the correct plane was established, up to 15 cm of bowel can be resected without ligating vessels or performing a transabdominal dissection. The proximal extent of dissection was delineated by the presence of ganglion cells seen on frozen section analysis. RESULTS: The mean operating time was 105 minutes. There were no intraoperative or postoperative complications. All children had the presence of ganglion cells confirmed postoperatively on permanent sections. The mean hospital stay was 2 days. All children averaged three to six bowel movements per day without oral or enema therapy. CONCLUSIONS: The perineal one-stage operative pull-through (POOP) procedure for Hirschsprung's disease is a quick and easy adaptation of a well-described technique of transanal mucosectomy. Long-term follow-up will be required to determine whether bowel function is better that that seen after traditional staged repairs.
Determining the geographic origin of potatoes with trace metal analysis using statistical and neural network classifiers.
The objective of this research was to develop a method to confirm the geographical authenticity of Idaho-labeled potatoes as Idaho-grown potatoes. Elemental analysis (K, Mg, Ca, Sr, Ba, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, S, Cd, Pb, and P) of potato samples was performed using ICPAES. Six hundred eight potato samples were collected from known geographic growing sites in the U.S. and Canada. An exhaustive computational evaluation of the 608 x 18 data sets was carried out using statistical (PCA, CDA, discriminant function analysis, and k-nearest neighbors) and neural network techniques. The neural network classification of the samples into two geographic regions (defined as Idaho and non-Idaho) using a bagging technique had the highest percentage of correct classifications, with a nearly 100% degree of accuracy. We report the development of a method combining elemental analysis and neural network classification that may be widely applied to the determination of the geographical origin of unprocessed, fresh commodities.
Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia.
We previously reported that the arteriolar input in window chamber tumours is limited in number and is constrained to enter the tumour from one surface, and that the pO2 of tumour arterioles is lower than in comparable arterioles of normal tissues. On average, the vascular pO2 in vessels of the upper surface of these tumours is lower than the pO2 of vessels on the fascial side, suggesting that there may be steep vascular longitudinal gradients (defined as the decline in vascular pO2 along the afferent path of blood flow) that contribute to vascular hypoxia on the upper surface of the tumours. However, we have not previously measured tissue pO2 on both surfaces of these chambers in the same tumour. In this report, we investigated the hypothesis that the anatomical constraint of arteriolar supply from one side of the tumour results in longitudinal gradients in pO2 sufficient in magnitude to create vascular hypoxia in tumours grown in dorsal flap window chambers. Fischer-344 rats had dorsal flap window chambers implanted in the skin fold with simultaneous transplantation of the R3230AC tumour. Tumours were studied at 9-11 days after transplantation, at a diameter of 3-4 mm; the tissue thickness was 200 microm. For magnetic resonance microscopic imaging, gadolinium DTPA bovine serum albumin (BSA-DTPA-Gd) complex was injected i.v., followed by fixation in 10% formalin and removal from the animal. The sample was imaged at 9.4 T, yielding voxel sizes of 40 microm. Intravital microscopy was used to visualize the position and number of arterioles entering window chamber tumour preparations. Phosphorescence life time imaging (PLI) was used to measure vascular pO2. Blue and green light excitations of the upper and lower surfaces of window chambers were made (penetration depth of light approximately 50 vs >200 microm respectively). Arteriolar input into window chamber tumours was limited to 1 or 2 vessels, and appeared to be constrained to the fascial surface upon which the tumour grows. PLI of the tumour surface indicated greater hypoxia with blue compared with green light excitation (P < 0.03 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). In contrast, illumination of the fascial surface with blue light indicated less hypoxia compared with illumination of the tumour surface (P < 0.05 for 10th and 25th percentiles and for per cent pixels < 10 mmHg). There was no significant difference in pO2 distributions for blue and green light excitation from the fascial surface nor for green light excitation when viewed from either surface. The PLI data demonstrates that the upper surface of the tumour is more hypoxic because blue light excitation yields lower pO2 values than green light excitation. This is further verified in the subset of chambers in which blue light excitation of the fascial surface showed higher pO2 distributions compared with the tumour surface. These results suggest that there are steep longitudinal gradients in vascular pO2 in this tumour model that are created by the limited number and orientation of the arterioles. This contributes to tumour hypoxia. Arteriolar supply is often limited in other tumours as well, suggesting that this may represent another cause for tumour hypoxia. This report is the first direct demonstration that longitudinal oxygen gradients actually lead to hypoxia in tumours.
Use of rituximab and irradiated donor-derived lymphocytes to control Epstein-Barr virus-associated lymphoproliferation in patients undergoing related haplo-identical stem cell transplantation.
Epstein-Barr virus-associated lymphoproliferative disorder (EBV-LPD) is an uncommon but potentially fatal complication of allogeneic stem cell transplantation. We report here two patients who underwent T cell-depleted mismatched-related stem cell transplantation for hematologic malignancies and required aggressive post-transplant immunosuppression for graft-versus host disease (GVHD). Both patients subsequently developed markedly elevated EBV-DNA titers in association with monoclonal, light chain-restricted B cell populations in the blood. Although immunosuppressive medications were rapidly tapered, neither patient could receive potentially curative therapy with unmanipulated donor-derived lymphocyte infusions (DLI) because of the substantial risk of severe GVHD. Therefore, both patients received repeated courses of rituximab, an anti-CD20 monoclonal antibody, in combination with irradiated DLI. This therapeutic strategy resulted in normalization of the elevated EBV-DNA titers and disappearance of the monoclonal B cell populations. Our results suggest that rituximab and possibly irradiated DLI played an important role in controlling early EBV-LPD in these two patients and may be an effective alternative therapeutic strategy for patients who develop EBV-LPD post transplant and are unable to receive unmanipulated DLI.
Cloning, sequencing and mapping the pig gene for the muscle-specific intermediate filament protein desmin (DES).
Explore the source record for details and available documents.
A custom designed chip to control an implantable stimulator and telemetry system for control of paralyzed muscles.
A custom designed chip has been developed for the control of paralyzed muscles. The system is capable of fulfilling the stimulus and telemetry needs of advanced functional neuromuscular stimulation (FNS) applications requiring multiple channels of stimulation and multiple channels for sensor or biopotential sensing. An inductive radiofrequency link provides power to the implant device as well as 2 way transcutaneous communication. An application specific integrated circuit (ASIC) decodes the commands and provides functional control within the implant, and modular circuitry provides specific implant functions. The ASIC chip provides up to 32 independent channels of stimulation with independent control of stimulus pulse duration, pulse amplitude, interphase delay, recharge phase duration, and pulse interval. It can also control up to 8 independent back telemetry analog channels with independent control of sampling rate and pulse powering parameters (amplitude and duration). The mixed analog digital chip has been fabricated in 1.2 microm n-well CMOS technology.