Search PubMed⌕ Search

Biomedical subjects

S Walters

Publications and source records attributed to S Walters.

At least 37 records · Page 2Linked to original sources
PubMed2000

CD8+ T cells are capable of rejecting pancreatic islet xenografts.

BACKGROUND: In this study, the capacity of CD8+ T cells to act as a potential effector mechanism in pancreatic xenograft rejection was examined. METHODS: The fate of pancreatic islet xenografts was studied in mice deficient in MHC class II molecules and CD4+ T cells. Fetal pig pancreas (FPP) or Wistar rat islets (RI) were transplanted into nondiabetic or streptozotocin-induced diabetic I-A knock-out (CII K/O) mice. RESULTS: CII K/O mice were capable of rejecting both RI and FPP grafts. RI graft survival was not prolonged compared with wild type C57BL/6 controls. However, FPP grafts did survive longer in CII K/O recipients than in C57BL/J6 mice. Both RI and FPP graft rejection were CD8+ T-cell phenomena in CII K/O mice, as anti-CD8 monoclonal antibody prolonged graft survival, there were increased CD8+ T cells in the grafts and spleens of CII K/O recipients, and cell-mediated cytotoxicity was a CD8+ T-cell phenomenon associated with activation of the perforin/granzyme B system. By contrast, RI and FPP graft rejection was a CD4+ T cell-dependent phenomenon in wild type C57BL/6 mice with graft survival prolonged by anti-CD4 monoclonal antibody. There were increased numbers of CD4+ T cells, and cell-mediated cytotoxicity was a CD4+ T-cell phenomenon associated with activation of the Fas/FasL lytic pathway. CONCLUSIONS: The results demonstrate that, in the absence of CD4+ T cells, CD8+ T cells were capable of rejecting both rat and pig pancreatic islet xenografts.

Animals↗
PubMed2000

Costs and effectiveness of community postnatal support workers: randomised controlled trial.

OBJECTIVES: To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives. DESIGN: Randomised controlled trial with six month follow up. SETTING: Recruitment in a university teaching hospital and care provided in women's homes. PARTICIPANTS: 623 postnatal women allocated at random to intervention (311) or control (312) group. INTERVENTION: Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker. MAIN OUTCOME MEASURE: General health status as measured by the SF-36 and risk of postnatal depression. Breast feeding rates, satisfaction with care, use of services, and personal costs. RESULTS: At six weeks there was no significant improvement in health status among the women in the intervention group. At six weeks the mean total NHS costs were pound 635 for the intervention group and pound 456 for the control group (P=0.001). At six months figures were pound 815 and pound 639 (P=0.001). There were no differences between the groups in use of social services or personal costs. The women in the intervention group were very satisfied with the support worker visits. CONCLUSIONS: There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36. There were no savings to the NHS over six months after the introduction of the community postnatal support worker service.

Adolescent↗
PubMed2000

Oral calorie supplements for cystic fibrosis.

BACKGROUND: Poor nutrition occurs frequently in children and adults with cystic fibrosis and is associated with a number of other adverse outcomes. Oral calorie supplements are used to try and increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns that they may lead to a reduction in the amount of food eaten and no overall improvement in energy intake. OBJECTIVES: To examine the evidence that in patients with cystic fibrosis, oral calorie supplements increase daily calorie intake, improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess possible adverse effects associated with use of oral calorie supplements. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. The companies which market oral calorie supplements were also contacted. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: indices of nutrition and growth, anthropometric measures of body composition, calorie intake (total, from oral calorie supplements and from food), nutrient intake, eating behaviour, quality of life, specific adverse effects, lung function and mortality. MAIN RESULTS: Two trials which reported results from a total of 29 patients were suitable for inclusion in the review. From the data provided in the published reports only one item (change in weight) could be extracted from one trial for inclusion in the review. This showed no difference between intervention and comparison group. REVIEWER'S CONCLUSIONS: Oral calorie supplements are very widely used around the world in an attempt to improve nutritional status in patients with cystic fibrosis, at some considerable cost. It is therefore very disappointing that their effectiveness has not been assessed by adequate clinical trials. No conclusions can be made about the use of oral calorie supplements in cystic fibrosis from the information currently available and clinicians must balance potential benefits against possible adverse effects of treatment in making decisions about individual patients. This systematic review has clearly identified the need for a well designed, adequately-powered, multicentre, randomised controlled trial assessing the effectiveness and possible adverse effects of oral calorie supplements in cystic fibrosis.

Adult↗
PubMed2000

Prophylactic antibiotics for cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are sometimes prescribed antibiotics to take continuously on a prophylactic (preventative) basis. This approach is most commonly used in infants where the objective is to reduce pulmonary infection with Staphylococcus aureus and prevent lung damage. This approach may also be used in older patients. This review evaluates the evidence for the effectiveness of this approach and considers potential adverse effects. OBJECTIVES: To compare continuous oral antibiotic prophylaxis with no prophylaxis (short courses of oral antibiotics given as clinically indicated) in patients with cystic fibrosis. This review considers both the effectiveness of prophylaxis (bacteria isolated from the respiratory tract, requirement for additional antibiotic treatment, lung function, survival) and the adverse effects. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group clinical trials register was used. This comprises references identified from a comprehensive search of electronic databases, as well as hand searching relevant journals and conference abstracts. Companies manufacturing anti-staphylococcal antibiotics were also approached for unpublished data. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudo-randomised trials where continuous oral prophylactic antibiotics, given for a period of at least one year, were compared to intermittent antibiotic therapy given "as required." Cystic fibrosis patients of any disease severity were considered. DATA COLLECTION AND ANALYSIS: Trials were assessed for eligibility, methodological quality and data extraction by two reviewers (AS & SW). The following outcomes were assessed: lung function; nutrition (weight standard deviation score); survival; requirement for additional antibiotic treatment; isolates of pathogens from the respiratory tract; occurrence of adverse reactions to prophylactic antibiotics. MAIN RESULTS: Only two studies, totalling 66 patients (over half of whom were infants), were suitable for inclusion in the review. A reduced prevalence of Staphylococcus aureus in the respiratory secretions was seen in children receiving anti-staphylococcal antibiotic prophylaxis, although no effect was seen on other common pathogens. This is associated with a reduced requirement for additional courses of oral antibiotics and fewer hospital admissions in the first two years of life in patients receiving prophylaxis. No effect on infant lung function has been shown after one year of prophylactic treatment. Data are not available on adverse effects of the interventions. As the duration of the studies reviewed has been of two years or less, conclusions cannot be drawn about the long term effects of prophylaxis on acquisition of Pseudomonas aeruginosa and survival. REVIEWER'S CONCLUSIONS: Anti-staphylococcal antibiotic prophylaxis may be of benefit when commenced early in infancy and continued up to two years of age. There is insufficient evidence from this review to say whether use in older children, or adults, or for periods of over two year is beneficial.

Adult↗
PubMed2000

Inhaled corticosteroids for cystic fibrosis.

BACKGROUND: Maintenance of optimal lung function is an important therapeutic goal in cystic fibrosis as it is lung damage that, in the long term, is responsible for most premature death among affected people. Inhaled corticosteroids are being increasingly used to treat children and adults with cystic fibrosis. The rationale for their use is that they have the potential to reduce lung damage arising from inflammation. However chronic use of inhaled steroids may also have adverse effects. It is thus important to establish the current level of evidence about the potential benefits and harms of this practice. OBJECTIVES: The objective of this review is to assess the effectiveness of regular use of inhaled corticosteroids when compared to no inhaled corticosteroids, in the management of patients with cystic fibrosis. SEARCH STRATEGY: Trials were ascertained from the Cochrane Cystic Fibrosis and Genetic Disorders Specialised Register of Controlled Trials which includes published and unpublished trials identified through electronic databases such as Medline and Embase as well as those identified from handsearching of journals and conference proceedings. Pharmaceutical companies manufacturing inhaled corticosteroids were also contacted to identify any trials of inhaled corticosteroids in cystic fibrosis. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All trials, both published and unpublished, in which inhaled corticosteroids were compared to either placebo or standard treatment in patients with cystic fibrosis. Trials employing random treatment allocation and those using quasi-random allocation methods such as alternate allocation to treatment and control group were included. DATA COLLECTION AND ANALYSIS: The following outcomes were assessed: objective measures of lung function, respiratory exacerbations, use of intravenous antibiotics, hospital admissions, nutritional status, symptoms, quality of life, survival and frequency of adverse effects. Methodological quality of trials was assessed independently using established criteria by two reviewers, who also extracted relevant data independently using standard proformas. Differences were resolved by discussion. MAIN RESULTS: Nine trials were identified reporting the use of inhaled steroids in 266 subjects aged between seven and 45 years with cystic fibrosis. Methodological quality was difficult to assess from published information, specifically with respect to concealment of allocation and method used to generate random sequence. Trials were heterogeneous with respect to inclusion criteria, specifically age, severity of pulmonary involvement, clinical diagnosis of asthma and pulmonary colonisation with Pseudomonas aeruginosa. Trials also differed in type and duration of treatment. Beclomethasone was given for periods of between four and 22 weeks in four trials, budesonide for six weeks and six months respectively in two, and fluticasone for periods of between six weeks and two years in the remaining three. Measures of the volume of air breathed out on a forcible expiration (forced expiratory volumes) were reported in most trials but these data could not be combined for this review partly because reports differed in the way data were summarised and partly because some data were not included in published reports. Outcomes of potentially greater relevance to affected individuals such as nutritional status or quality of life were not reported in any trial. Survival was not reported in any trial, but this may reflect the fact that maximum duration of follow up was too short to allow this outcome to be meaningfully assessed. Adverse effects were systematically documented in only two trials. Although one trial was halted prematurely because a proportion of all those taking part had acquired chronic lung infections with Pseudomonas aeruginosa, no conclusions can be reached from this one small trial as to whether this risk is increased as

Administration, Inhalation↗
PubMed2000

Impact of correcting peak flow for nonlinear errors on air pollutant effect estimates from a panel study.

Air pollutant effects are commonly investigated using panel studies employing daily measurement of changes in peak expiratory flow (PEF). Variable orifice PEF meters are inaccurate with a nonlinear relationship to actual PEF. The impact on a panel study of correcting these errors was examined. Twice-daily PEF readings were taken by 147 9-yr old children for 8 weeks and corrected using an equation derived from the response of 32 Vitalograph meters to a servomechanism-controlled pump. Pollutant effect estimates for corrected and uncorrected readings were derived using a regression approach incorporating appropriate confounders. Correction impacted little on mean PEF values (333.1-334.2 L x min(-1)), but did alter effect sizes. Nonsignificant nitrogen dioxide estimates for the entire panel decreased by up to 73%, but, for symptomatic/atopic children, a significant 5-day mean result was lost (decrease in effect size from -2.53 to -0.90% per 10 parts per billion (ppb)) and lag 0 became significant (decrease from -0.51 to -1.22% per 10 ppb). Mass concentration estimates of particles with a 50% cut-off aerodynamic diameter of 2.5 microm moved in both directions (-0.22 changed to 0.11% per 10 microg x m(-1) lag 3 and -0.29 to -0.73% per 10 microg x m(-3) for the 5-day mean). Correction of nonlinearity of peak expiratory flow meters influenced the overall outcome of this panel study, and the changes in effect estimates would be sufficient to alter the interpretation of some studies. For adults, a greater change in effect estimates may follow the larger correction required for their usual peak expiratory flow range.

Adult↗
PubMed2000

High-dose growth hormone does not affect proinflammatory cytokine (tumor necrosis factor-alpha, interleukin-6, and interferon-gamma) release from activated peripheral blood mononuclear cells or after minimal to moderate surgical stress.

High-dose GH therapy, with GH doses 10-20 times the normal replacement dose for GH-deficient adults, has been used as an anti-catabolic agent in a number of different patient groups. A recent study, however, has shown an increase in mortality in critically ill patients treated with high-dose GH. The increased mortality was associated with multiorgan failure, septic shock, and uncontrolled infection, suggesting that GH may have altered the immune response. The GH receptor and GH are both expressed in peripheral blood mononuclear cells (PBMCs); thus, GH could act as either an endocrine or an autocrine modulator of the immune response. We have examined the hypothesis that high-dose GH therapy may induce proinflammatory cytokines, which are implicated in septic shock. To do this we measured cytokine production by PBMCs incubated in conditions that simulated high-dose GH therapy, and we measured cytokine levels in patients undergoing laparoscopic cholecystectomy who were randomized to receive either high-dose GH therapy (13 IU/m2 x day) or placebo. To confirm the biological activity of GH in our cell culture system we used a Stat5 functional assay. In this assay GH induced a bell-shaped curve, with a maximal response at GH levels between 100-1,000 ng/mL. PBMCs from healthy volunteers were incubated with GH in doses from 1-1,000 ng/mL for 6-72 h under resting conditions and after activation with endotoxin and the mixed lymphocyte reaction. Studies were repeated with PBMCs from six individuals using a GH dose of 100 ng/mL (the level of GH found after high-dose GH therapy) and an endotoxin dose that gave a submaximal response (0.01 ng/mL). GH had no effect on cell proliferation or the production of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), or interferon-gamma (IFNgamma). In patients undergoing laparoscopic cholecystectomy there was a time-related effect of surgery on cytokine levels. There was a rise in IL-6 and a fall in TNFalpha at 24 h after surgery; however, high-dose GH therapy had no effect on the cytokine response. We considered the possibility that endogenous GH production by PBMCs could influence the cytokine response in activated PBMCs; however, incubation of PBMCs in the presence of the GH receptor antagonist, B2036, had no effect on TNFalpha, IL-6, or IFNgamma production by PBMCs in either the mixed lymphocyte reaction or when activated by endotoxin. These results suggest that high-dose GH therapy does not alter the proinflammatory cytokine response to surgery or endotoxin. The results do not exclude an effect of GH on the immune response, but they suggest that the mortality seen in critically ill patients may be due to factors other than immune modulation.

Adult↗
PubMed2000

General practitioners' perceptions of store-and-forward teledermatology.

We studied the views of 26 general practitioners (GPs) towards store-and-forward tele-dermatology before its introduction into their practices. A postal questionnaire was developed using Likert-type questions with respondents able to explain their answers in free text. Questions related to the GPs' knowledge, perceptions and expectations of tele-dermatology, as well as their attitudes towards being part of a research trial. Most of the GPs had limited prior knowledge of tele-dermatology. They perceived its role to relate to quicker access to specialist opinions, decreased referrals, increased convenience for patients, diagnosis, and education and teaching. There was an overwhelming view that any system needed to be quick, easy to use, efficient and reliable. Concerns were expressed about being part of the clinical trial, using new technology and an increased workload. The future of tele-dermatology was thought to depend on the clinical adequacy of the system.

Attitude of Health Personnel↗
PubMed2000

A comparison of cause of death determination in men previously diagnosed with prostate cancer who died in 1985 or 1995.

PURPOSE: We quantified the agreement between the underlying cause of death determination from information in hospital medical records and on death certificates, and determined whether the frequency of assigning death from prostate cancer had changed since the introduction of testing for prostate specific antigen. MATERIALS AND METHODS: We retrospectively reviewed and analyzed the information in hospital medical records and on death certificates for men previously diagnosed with prostate cancer who died in 1985 or 1995. RESULTS: The underlying cause of death determinations from a review of 201 hospital medical records agreed with those from information on part 1 of the death certificate in 87% of cases and with those using the International Classification of Diseases-9 system coding rules in 80%. Agreement was higher in men who were older than those who were younger at the time of death, and higher in those diagnosed with prostate cancer several years before death than in those diagnosed shortly before death. CONCLUSIONS: There was a high level of agreement concerning the underlying cause of death after a review of the information in hospital medical records and on death certificates for men with prostate cancer when cause of death was viewed as a dichotomous variable. The International Classification of Diseases-9 coding rules concerning the underlying cause of death favor overreporting rather than underreporting prostate cancer deaths compared with a review of hospital medical records. Cause of death determination does not appear to have changed after the introduction of prostate specific antigen testing.

Age Distribution↗
PubMed2000

Costs and benefits of community postnatal support workers: a randomised controlled trial.

OBJECTIVES: This study aimed to measure the effect and the total cost per woman of providing postnatal support at home, based on a Dutch model. The research hypothesis was furnished by some existing evidence that postnatal support could reduce the risk of postnatal depression and encourage breastfeeding. DESIGN: The randomised controlled trial aimed to measure differences in health status in a group of women who were offered postnatal support from a community midwifery support worker (SW) compared with a control group of women who were not offered this support. Women were followed-up by postal questionnaire at 6 weeks and 6 months postnatally. SETTING AND SUBJECTS: All women who delivered a baby at the recruiting hospital were eligible to take part in the trial if they lived within the study area, were aged 17 years or over, and could understand English. INTERVENTION: The intervention consisted of the SW offering practical and emotional support and to help women rest and recover after childbirth. The SW offered ten visits in the first 28 days postnatally, for up to 3 hours per day. The SW's activities included housework, talking with the mother, and care for the baby or other siblings. The service was provided in addition to routine visits by the community midwife. MAIN OUTCOME MEASURES: The primary outcome was the general health perception domain of the Short Form-36 at 6 weeks. Secondary outcomes were mean Edinburgh Postnatal Depression Scale (EPDS), Duke Functional Social Support (DUFSS) scores and breastfeeding rates. RESULTS: The 623 randomised women were well-matched by group with a good response to follow-up. At 6 weeks there was no evidence of a significant difference between the two groups for the primary outcome. There was a non-significant trend for the control group to have better mean DUFSS and EPDS scores at 6 weeks. Breastfeeding rates were not significantly different at follow-up. At 6 months, both groups had similar health status. Satisfaction with the service was higher than for all other services received. The incremental cost of introducing the service comprised setting up and running the service. There were no differences between the groups in other resource use (general practitioner contacts, hospital services, prescriptions or medicines bought for mothers and babies) to 6-month follow-up. The total mean NHS cost to 6-month follow-up for the intervention group was pound180 per woman greater than for the control group (confidence interval, pound79.60, pound272.40). CONCLUSIONS: Although women valued the service, there was no evidence of any health benefit at the 6-week or 6-month follow-up, no difference in use of NHS services, and the additional cost of the service provision would be around pound 180 per woman.

Adolescent↗
PubMed1999

General practice and the care of children with HIV infection: 6 month prospective interview study.

OBJECTIVES: To describe the use of primary care services by children infected with HIV and to explore the attitudes of their parents to the role of general practitioners in their children's care. DESIGN: A 6 month prospective study. Quantitative analysis of "contact diaries" kept by parents; qualitative analysis of face to face interviews with parents. PARTICIPANTS: Parents of children receiving care at a regional referral centre in London. RESULTS: Twenty four families (80% response rate) were recruited to the study. In 19 families the mother was black African. Half the children had been diagnosed with symptomatic HIV infection, half with AIDS. All the children were registered with a general practitioner who knew of the child's HIV infection. In five families there had initially been tensions in their relationship with their general practitioner but by the time of the study all but one family had established at least an "acceptable" relationship. Children with symptomatic HIV infection saw their general practitioner a mean of 7.5 times per patient year; for children with AIDS the figure was 5.8. Parents regarded the paediatric HIV team at the hospital as their primary source of medical care. Three factors constrained their use of general practice: their own anxieties about distinguishing "normal" symptoms from those related to HIV infection; their view that their general practitioner did not feel competent to treat HIV infected children; and their concerns about maintaining confidentiality in the surgery. CONCLUSIONS: Parents remain oriented towards the paediatric HIV team as their primary source of medical care and use general practice largely for routine prescriptions for their children. Any further development of the general practitioner's role will need to build on existing relationships with specialist providers and take account of parents' concerns.

Child↗
PubMed1999

Daily hospital respiratory admissions and winter air mass types, Birmingham, UK.

A synoptic climatological approach is used to investigate linkages between air mass types (weather situations), the daily mean particulate matter with a size of 10 microns or less (PM10) concentrations and all respiratory hospital admissions for the Birmingham area, UK. Study results show distinct differential responses of respiratory admission rates to the six winter air mass types identified. Two of the three air masses associated with above average admission rates (continental anticyclonic gloom and continental anticyclonic fine and cold) also favour high PM10 levels. This association is suggestive of a possible linkage between weather, air quality and health. The remaining admissions-sensitive air mass type (cool moist maritime) does not favour high PM10 levels. This is considered to be indicative of a direct weather-health relationship. A sensitising mechanism is proposed to account for the linkages between air mass type, PM10 concentrations and respiratory response.

Air↗