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Biomedical subjects

R J Prescott

Publications and source records attributed to R J Prescott.

At least 55 records · Page 3Linked to original sources

Elective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs.

BACKGROUND: A previous retrospective study suggested that a policy of regular anti-pseudomonal antibiotic treatment improved pulmonary function and increased survival in patients with cystic fibrosis chronically infected with Pseudomonas species. The results of a prospective multicentre study to compare the effects on pulmonary function and mortality of three monthly elective anti-pseudomonal antibiotic treatment with conventional symptomatic treatment are reported. METHODS: Sixty patients with cystic fibrosis, chronically infected with P aeruginosa, were randomised to the two treatment arms (elective or symptomatic) and followed clinically at yearly reviews. The major end points were changes in forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). Survival was a secondary end point. RESULTS: Patients in the symptomatic group received a mean of three antibiotic treatments each year and those in the elective group received four antibiotic treatments during each year of the study. No significant differences in FEV(1) and FVC were found between the two groups after three years. There was a statistically non-significant higher rate of deaths in the elective group (n = 4), three of which were associated with B cepacia infection, compared with the symptomatic group (n = 0). CONCLUSIONS: This study did not demonstrate an advantage of a policy of elective antibiotic treatment over symptomatic treatment in patients with cystic fibrosis chronically infected with Pseudomonas species.

Adolescent↗

Repellent and antifeedant activity of salicylic acid and related compounds against the biting midge, Culicoides impunctatus (Diptera: Ceratopogonidae).

An artificial membrane, blood-feeding method was used to assess the repellent and antifeedant effects of derivatives of salicylic acid on the biting midge Culicoides impunctatus Goetghebeur. Trans-2-hydroxycyclohexanecarboxylic acid, 6-methylsalicylic acid, 2,6-dihydroxy-4-methylbenzoic acid, and salicyluric acid caused highly significant inhibition of feeding, with salicyluric acid performing significantly greater than the other compounds. Investigating the effects of alkyl substitution of salicylic acid, o-thymotic and o-cresotic acids were also effective. A pilot clinical trial using salicyluric acid indicated that it provided a protective effect and it was hypothesized that this may have resulted primarily from contact, because no significant repellent effects were shown for this compound in a microscope slide test, designed to demonstrate repellency with volatile compounds.

Animals↗

Randomised, double blind placebo controlled trial of pentoxifylline in the treatment of venous leg ulcers.

OBJECTIVE: To determine whether pentoxifylline 400 mg (Trental 400) taken orally three times daily, in addition to ambulatory compression bandages and dressings, improves the healing rate of pure venous ulcers. DESIGN: Randomised, double blind placebo controlled trial, parallel group study of factorial design, permitting the simultaneous evaluation of alternative pharmaceutical, bandaging, and dressings materials. SETTING: Leg ulcer clinics of a teaching and a district general hospital in southern Scotland. PARTICIPANTS: 200 patients with confirmed venous ulcers and in whom other major causal factors were excluded. INTERVENTIONS: Pentoxifylline 400 mg three times daily or placebo. MAIN OUTCOME MEASURE: Complete healing (full epithelialisation) of all ulcers on the trial leg. RESULTS: Complete healing occurred in 65 of the 101 (64%) patients receiving pentoxifylline and 52 of the 99 (53%) patients receiving placebo. CONCLUSIONS: The difference in the healing rates between patients taking pentoxifylline and those taking placebo did not reach statistical significance.

Adult↗

14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening.

BACKGROUND: The Edinburgh randomised trial of breast-cancer screening recruited women aged 45-64 years from 1978 to 1981 (cohort 1), and those aged 45-49 years during 1982-85 (cohorts 2 and 3). Results based on 14 years of follow-up and 270,000 woman-years of observation are reported. METHODS: Breast-cancer mortality rates in the intervention group (28,628 women offered screening) were compared with those in the control group (26,026) with adjustment for socioeconomic status (SES) of general medical practices. Rate ratios were derived by means of logistic regression for the total trial population and for women first offered screening while younger than 50 years. Analyses were by intention to treat. FINDINGS: Initial unadjusted results showed a difference of just 13% in breast-cancer mortality rates between the intervention and control groups (156 deaths [5.18 per 10,000] vs 167 [6.04 per 10,000]; rate ratio 0.87 [95% CI 0.70-1.06]), but the results were influenced by differences in SES by trial group. After adjustment for SES, the rate ratio was 0.79 (95% CI 0.60-1.02). When deaths after diagnosis more than 3 years after the end of the study were censored the rate ratio became 0.71 (0.53-0.95). There was no evidence of heterogeneity by age at entry and no evidence that younger entrants had smaller or delayed benefit (rate ratio 0.70 [0.41-1.20]). No breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years. Other-cause mortality rates did not differ by trial group when adjusted for SES. INTERPRETATION: Our findings confirm results from randomised trials in Sweden and the USA that screening for breast cancer lowers breast-cancer mortality. Similar results are reported by the UK geographical comparison, UK Trial of Early Detection of Breast Cancer. The results for younger women suggest benefit from introduction of screening before 50 years of age.

Age Factors↗

Prevalence of asthma and 'probable' asthma in the Asian population in Blackburn, U.K.

Local research had shown increased asthma admission rates in the Asian ethnic group in Blackburn, U.K. Patients also reported that asthma seemed to develop some years after first arrival in the U.K. A community prevalence survey of respiratory symptoms and asthma was undertaken in three practices with no special asthma interest. The questionnaire was administered by a Health Visitor and language link worker. Of the Asian patients in the practices, 96.6% were studied. The age distribution was similar to that of the local 1991 census. Of the patients, 181/1783 (10.2%) had diagnosed asthma but positive responses to individual questions suggested underdiagnosis of asthma. Asthma prevalence was higher in males up to age 20 (14.6% vs. 8.2%), and aged over 50 (16.5% vs. 10.5%), but higher in females aged 20-49 (5.6% vs. 9.2%). There were no correlations with social class or Jarman index, and no effect of country of origin or duration in the U.K. by multivariate analysis. The prevalence of diagnosed asthma at ages 5-9 and 10-14 was higher than in previous studies. Diagnosed asthma prevalence rates fell in the 20-49 age band but rose again in the over-50s. In all age groups the prevalence of asthma is probably underestimated. Asthma prevalence was not related to social factors. The data show that those born in the U.K. are more likely to describe regular symptoms and to be on regular treatment, but that for those born abroad there was an increasing rate of symptoms and medication use with increasing duration in the country. These observations confirm patient views but are explained by the age/sex distribution of those born in the U.K. compared to immigrants.

Adolescent↗

Dynamics of reactive oxygen intermediate production in human glioma: n-6 essential fatty acid effects.

BACKGROUND: Reactive oxygen intermediates (ROIs) are important signals controlling cell growth and cell death. Local essential fatty acid (EFA) deficiencies in tumour cells may limit tumour ROI generation. This deficiency may be rectified by the addition of exogenous EFA. MATERIALS AND METHODS: The n-6 EFA effects on tumour ROIs were analysed in terms of kinetics, dose-response and individual cell type responses using flow cytometry of intracellular 2',7'-dichlorofluorescin oxidation. ROI formation in 30 gliomas and five paired samples of normal brain tissue, > 500 000 cells per specimen, was analysed every 10 s for 0-25 min. RESULTS: Tumour cell basal ROI was lower than normal brain tissue ROI from the same subjects (P < 0.00002). Normal and tumour cell ROIs were stimulated by 4-40 micromol L-1 n-6 EFAs, arachidonic acid (AA) and gamma-linolenic acid (GLA). The stimulated ROI rate was exponential, with the maximum dependent on EFA concentration and tumour grade. CONCLUSIONS: EFAs stimulated tumour cells more than normal cells (P < 0.0000017, n = 71) and increased ROIs in glial fibrillary acidic protein-positive cells in tumours. This indicated high sensitivity of glioma cell ROIs to n-6 EFAs.

Adolescent↗

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Death, Sudden, Cardiac↗

Double blind, randomised, placebo controlled, crossover, multicentre study to determine the efficacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome.

BACKGROUND/AIMS: Hyaluronan (sodium hyaluronate) has been shown to confer objective and subjective improvement in patients with dry eye syndrome. This study compared the efficacy and safety of a 0.1% solution of hyaluronan with 0.9% saline, when administered topically to the eye, in the treatment of symptoms of severe dry eye syndrome. METHODS: A randomised, double blind, crossover clinical trial in which subjects were randomised to receive either hyaluronan or saline, applied as one or two drops to the eye, three or four times a day or as required. After 28 days' treatment, subjects crossed over to the other study medication for a further 28 days' treatment. RESULTS: 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer's score (p=0.0006) and rose bengal staining score (p=0.0001) were observed during treatment with hyaluronan. In a subjective assessment of the effectiveness of two treatments, a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness (p<0.001). No adverse events attributable to hyaluronan treatment were reported. CONCLUSION: The study demonstrates a clear benefit of hyaluronan over saline, in both subjective and objective assessments of dry eye syndrome. Hyaluronan was shown to be well tolerated.

Adult↗

Extension of the elbow and supracondylar fractures in children.

We tested the hypothesis that children who sustain a supracondylar fracture have a greater range of elbow hyperextension than those with a fracture of the distal radius. Three observers made 358 measurements in 183 children (114 boys and 69 girls). There were 119 fractures of the distal radius and 64 supracondylar fractures. Initially, the group with a supracondylar fracture appeared to have extension 1.7 degrees greater than that of the group with fracture of the distal radius. On average, there was a maximum variation of 3 degrees between observers. After allowing for age, gender and observer, there was no significant difference between the groups. Our study had greater than 80% power to detect a difference in hyperextension of 2 degrees at the 5% level with the above observer variability. When age and gender are taken into account, any variation in the amount of hyperextension at the elbow is not sufficient to explain the occurrence of a supracondylar fracture.

Adolescent↗

Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).

BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.

Aged↗

Uptake and acceptability of antenatal HIV testing: randomised controlled trial of different methods of offering the test.

OBJECTIVE: To determine the uptake and acceptability of different methods of a universal offer of voluntary HIV testing to pregnant women. DESIGN: Randomised controlled trial involving four combinations of written and verbal communication, followed by the direct offer of a test. The control group received no information and no direct offer of a test, although testing was available on request. SETTING: Hospital antenatal clinic covering most of the population of the city of Edinburgh. SUBJECTS: 3024 pregnant women booking at the clinic over a 10 month period. MAIN OUTCOME MEASURES: Uptake of HIV testing and women's knowledge, satisfaction, and anxiety. RESULTS: Uptake rates were 6% for those in the control group and 35% for those directly offered the test. Neither the style of leaflet nor the length of discussion had an effect on uptake. Significant independent predictors of uptake were a direct test offer; the midwife seen; and being unmarried, previously tested, and younger age. Knowledge of the specific benefits of testing increased with the amount of information given, but neither satisfaction nor anxiety was affected by the type of offer. CONCLUSIONS: The universal offer of HIV testing is not intrusive and is acceptable to pregnant women. A policy of offering the HIV test to all women resulted in higher uptake and did not increase anxiety or dissatisfaction. Uptake depends more on the midwife than the method of offering the test. Low uptake rates and inadequate detection of HIV infection point to the need to assess a more routine approach to testing.

Adult↗

The Darlington and Northallerton Prospective Asthma Study: best function predicts mortality during the first 10 years.

The Darlington/Northallerton prospective study of asthmatics referred to secondary care started in 1983, with review and new entry at 5-yr intervals. The principal outcome measures are: mortality (presented here), best function and therapeutic step. All adult asthmatics with > or = 15% peak flow (PEF) reversibility to > or = 200 l min-1 were included. Socio-demographic variables, PEF and spirometry were recorded prospectively. Best vital capacity (FVC) and PEF were assessed according to protocol. The mortality of the original cohort after 10 yr was expressed as standardized mortality ratio (SMR) against the local population, with history and pulmonary function at entry as explanatory variables. Ninety-five per cent follow-up was achieved in 628 subjects, with 173 deaths (29.1% of those traced). The excess death rate was nearly 50% (SMR 1.47, 95% CI 1.26-1.71), with 56% of deaths due to respiratory disease (expected 10%). After allowance for age and sex, there was a consistent inverse relationship between mortality and entry best FVC, increased risk of death 1.51 (95% CI 1.33-1.72) per 10% deficit of best FVC predicted. The risk of respiratory death was eight times greater, and of non-respiratory death three times greater, in the lowest compared with the highest quartile of best FVC. There were no interactions with smoking, but possible enhancement of the effect in the socially deprived. Best FVC was a particularly powerful predictor of mortality in subjects < 65 years at entry, in whom 64% of the excess deaths occurred. Most of the excess in respiratory deaths was not due to acute severe asthma but to the development of chronic obstructive pulmonary disease (COPD), as defined functionally, irrespective of smoking habit which made no further contribution to mortality.

Adult↗

Symptoms and pulmonary function in asthma.

The relationship between symptoms and pulmonary function in asthma is important if the latter is to be held relevant to management guidelines and their audit. Associations between reported symptoms, pulmonary function and therapy were studied in 824 asthmatics (mean FEV1 75.4% predicted; best FEV1 84.6% predicted; and actual/best peak flow (PEF) 87.5%). Bronchodilator usage (reflecting symptomatic wheeze) was evenly distributed up to eight times daily; 22.5% of subjects had nocturnal disturbance and 46.3% persistent daytime symptoms. The univariate relationships between symptoms and function were generally closer with best rather than actual/best. They were further explored using quintiles of function. Symptoms were consistently less as best function increased, but were highly significantly greater in the fifth than in the third and fourth quintiles of actual/best FEV1. There was a trend to a similar U-shaped relationship of actual/best PEF with nocturnal disturbance and daytime symptoms. Best function is a good determinant of expected symptom load in an asthmatic population. Below 85% actual/best function reflects the prevalence of symptoms. In asymptomatic patients a level of at least 85-90% is a useful check of physiological control but will not exclude some symptomatic patients, irrespective of best function.

Adult↗

The effect of monoclonal or ion-exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison.

The CD4 count has been reported to decline less rapidly in HIV-infected haemophiliacs treated with monoclonally purified factor VIII concentrates than in those using intermediate-purity concentrates. No survival advantage has been demonstrated for this effect, and it is unclear whether this effect occurs with all high-purity concentrates. Two cohorts of patients with severe haemophilia A and HIV treated with either ion-exchange-purified or monoclonally-purified concentrates were compared. The CD4 count, survival, AIDS-defining illnesses, CDC category and anti-retroviral therapy were recorded at 6-monthly intervals for 3 years following the change from intermediate to high-purity factor VIII. 116 patients were recruited, 37 of whom were treated with an ion-exchange purified factor VIII concentrate at three centres, mean (SD) age 31.1 (12.2) years, and 79 were treated with monoclonally purified factor VIII concentrate at two centres, mean (SD) age 29.8 (11.2) years. At the start of the study the median CD4 count was (monoclonal v ion-exchange) 0.30 v 0.16 x 10(9)/l. The CD4 count declined in both arms to a median of (monoclonal v ion-exchange) 0.16 v 0.08 x 10(9)/l at the final visit. Analysis of the (CD4 count)(1/2) over time, using a random coefficients model, found that the mean (SE) rates of decline were not statistically significantly different in the two treatment groups (monoclonal v ion exchange: -0.050 (0.008) v -0.034 (0.011) (CD4 count)(1/2) per year, P = 0.24). No statistically significant difference in survival (log-rank test: P = 0.33) was found. There was no difference in the proportion of individuals experiencing one or more AIDS-defining illnesses (P = 0.32) or in the proportion progressing to CDC category IV (P = 0.28) during the study. The CD4 count declined during the study at a rate similar to that previously reported in patients treated with intermediate-purity factor VIII concentrate, and there was no evidence of any difference between the two treatment groups.

Blood Component Transfusion↗