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Biomedical subjects

J P Wight

Publications and source records attributed to J P Wight.

16 recordsLinked to original sources

Regional differences in the provision of adult renal dialysis services in the UK.

BACKGROUND: Provision of renal dialysis varies between UK regions. AIM: To analyse these differences in provision and investigate their causes. DESIGN: Questionnaire-based survey. METHODS: A questionnaire was posted to all renal provider units and renal commissioning groups in the UK. Questions covered issues such as dialysis modalities and patient choice. Data were collected by telephone interview (or post in some cases) and analysed using SPSS. RESULTS: All renal provider units in the UK responded. A full range of modalities was provided by the majority of units. Clear variations in the level and quality of dialysis provision were seen between the UK regions. These included variation in choice of dialysis modality, provision of high-cost drugs, vascular access waiting times, number of support staff and availability of spare dialysis slots. DISCUSSION: The considerable variation between UK regions in the provision of adult renal dialysis services cannot be entirely explained by age or ethnic variation, and is in part due to limited bed space, dialysis machines and support staff, as well as changes in commissioning arrangements. To meet the requirements of the renal national service framework in most regions, changes to policy and funding will be required, such that the relatively new commissioning groups implement more appropriate funding structures in closer dialogue with their provider units.

Adult↗

A systematic review of the clinical effectiveness of pioglitazone in the treatment of type 2 diabetes mellitus.

BACKGROUND: Pioglitazone is a member of a recently developed class of glucose-lowering agents, the thiazolidinediones, used in the treatment of type 2 diabetes mellitus. In the United States, it is approved for use both as monotherapy and in combination with metformin, a sulfonylurea, or insulin; in Europe, it is approved for use in combination with metformin or a sulfonylurea but not insulin. OBJECTIVE: This article presents a systematic review of the published literature on the effectiveness of pioglitazone in the treatment of type 2 diabetes, both as monotherapy and in combination with other antidiabetic agents. METHODS: The peer-reviewed English- and foreign-language literature was searched using MEDLINE, PubMED, EMBASE, Science Citation Index, the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, the UK National Health Service Centre for Reviews and Dissemination databases, and the Office of Health Economics Health Economic Evaluations Database. Searches were not limited to specific publication types, study designs, dates, or languages. The latest search was performed in March 2001. For a trial to be included in the review, at least 1 outcome measure had to involve the effects of pioglitazone on glycemic control or cardiovascular risk factors, or its side effects. Because of the heterogeneity of studies, no formal meta-analysis was performed. RESULTS: Eleven studies met the inclusion criteria, 6 involving pioglitazone monotherapy and 5 involving combination therapy. Full reports were available for only 6 of the 11 studies. No studies directly compared pioglitazone with other antidiabetic drugs. Both as monotherapy and in combination therapy, pioglitazone produced decreases in blood glucose levels (up to 95 mg/dL) and glycosylated hemoglobin (up to 2.6%). At doses of > or = 30 mg/d, pioglitazone was associated with reductions in triglyceride levels (-30-70 mg/dL) and increases in high-density lipoprotein cholesterol (HDL-C) levels (-4-5 mg/dL). Pioglitazone treatment was associated with significant weight gain (up to 4 kg over 16 weeks). Adverse effects included mild edema (in up to 11.7% of patients) and a clinically nonsignificant decrease in hemoglobin concentrations. Abnormal results on liver function testing were no more common in treated patients than in control groups. CONCLUSIONS: Pioglitazone has been shown to reduce blood glucose levels in patients with type 2 diabetes. Although the observed decreases in triglyceride levels and increases in HDL-C levels could be expected to lead to a reduction in cardiovascular risk, the effects of weight gain may counteract this benefit. The evidence suggests that the preferred role for pioglitazone may be as an adjunct to metformin or a sulfonylurea in patients whose condition is not well controlled with monotherapy and for whom a metformin-sulfonylurea combination is contraindicated. There is a need for large-scale, long-term studies comparing the effectiveness of combination therapy that includes pioglitazone with that of other combinations of antidiabetic drugs.

Adult↗

The SF36 as an outcome measure of services for end stage renal failure.

OBJECTIVE: To evaluate the use of the short form 36 (SF36) as a measure of health related quality of life of patients with end stage renal failure, document the results, and investigate factors, including mode of treatment, which may influence it. DESIGN: Cross sectional survey of patients with end stage renal failure, with the standard United Kingdom version of the SF36 supplemented by specific questions for end stage renal failure. SETTING: A teaching hospital renal unit. SUBJECTS AND METHODS: 660 patients treated at the Sheffield Kidney Institute by haemodialysis, peritoneal dialysis, and transplantation. Internal consistency, percentage of maximal or minimal responses, SF36 scores, effect sizes, correlations between independent predictor variables and individual dimension scores of the SF36. Multiple regression analysis of the SF36 scores for the physical functioning, vitality, and mental health dimensions against treatment, age, risk (comorbidity) score, and other independent variables. RESULTS: A high response rate was achieved. Internal consistency was good. There were no floor or ceiling effects other than for the two "role" dimensions. Overall health related quality of life was poor compared with the general population. Having a functioning transplant was a significant predictor of higher score in the three dimensions (physical functioning, vitality, and mental health) for which multiple regression models were constructed. Age, sex, comorbidity, duration of treatment, level of social and emotional support, household numbers, and hospital dialysis were also (variably) significant predictors. CONCLUSIONS: The SF36 is a practical and consistent questionnaire in this context, and there is evidence to support its construct validity. Overall the health related quality of life of these patients is poor, although transplantation is associated with higher scores independently of the effect of age and comorbidity. Age, comorbidity, and sex are also predictive of the scores attained in the three dimensions studied. Further studies are required to ascertain whether altering those predictor variables which are under the influence of professional carers is associated with changes in health related quality of life, and thus confirm the value of this outcome as a measure of quality of care.

Data Collection↗

Outbreaks of food poisoning in adults due to Escherichia coli O111 and campylobacter associated with coach trips to northern France.

Thirty-seven out of 48 people on a coach excursion to northern France developed gastrointestinal symptoms within 4 days of the trip. Twenty-six had stool samples positive for Escherichia coli O111, 8 were also positive for Campylobacter species, and 1 was positive for campylobacter alone. Strains of E. coli were positive for the effacing and attaching protein (eaeA) gene, but negative for other E. coli virulence genes, and therefore belonged to the enteropathogenic E. coli (EPEC) group. Twenty-two out of 37 people in a second party which followed the same itinerary 2 weeks later also became ill. One had a stool sample positive for E. coli O111. Analytical epidemiology suggested that the source of infections was a restaurant in northern France at which both parties had eaten.

Adhesins, Bacterial↗

Four outbreaks of Salmonella enteritidis phage type 4 food poisoning linked to a single baker.

An outbreak of gastrointestinal illness occurred among a party of diners at a hotel in South Yorkshire. A case control study identified a gateau, from an outside supplier, as the likeliest vehicle of infection. Further gateaux from the same baker's premises and other outlets were examined microbiologically. Three other outbreaks of food poisoning in neighbouring districts were recognised and found to be associated with gateaux supplied by the same baker. A total of 32 cases were identified. Stool specimens from 24 cases grew Salmonella enteritidis phage type (PT) 4. The same organism was also grown from gateau in the domestic refrigerator of the chef of one hotel, cheesecake made by the same baker, and a gateau and ingredients from the baker's premises. The isolates of S. enteritidis PT4 were all fully sensitive to antibiotics, and had the same plasmid and pulsed field gel electrophoresis profiles. It is most likely that cross contamination occurred from infected raw eggs on the baker's premises. The control measures instituted probably prevented two further outbreaks, and the baker now uses only pasteurised eggs. The benefits of close cooperation between different local and health authority districts in the investigation of the outbreaks are discussed.

Disease Outbreaks↗

Survey of employers' policies on HIV and AIDS in North Nottinghamshire.

To ascertain the extent to which local employers in North Nottinghamshire currently have policies for dealing with AIDS/HIV in the workplace, and the areas covered by any such policies, a survey of 148 companies was carried out. Eighty-six companies returned completed questionnaires (58 per cent). Of these, 17 reported that they had policies. These were more likely to be local outlets of national or regional companies. Companies with policies had larger workforces than those without (p < 0.0001). It is concluded that few companies have AIDS/HIV policies, despite the potential benefits to themselves and employees. Departments of public health should encourage companies to adopt such policies.

Acquired Immunodeficiency Syndrome↗

Effect of control of hypertension on progressive renal failure.

This study assesses the direct effect of different degrees of blood pressure control on the progression of chronic renal failure (CRF) in 18 patients with nephropathies of varying etiology (Glomerular filtration rate [GFR]: 14.99 +/- 5.94 ml/min/1.73 m2). The study involves three consecutive phases; Phase 1 consisted of a retrospective analysis of blood pressure and biochemical data: mean diastolic blood pressure (MDBP) was 89.9 +/- 7.9 mmHg and the mean rate of decline in renal function was -68.9 1/mol of creatinine/month. Phase 2 consisted of a 6 months prospective period of frequent (monthly) follow-up and optimization of blood pressure control when MDBP was reduced to 83.9 +/- 6.5 mmHg (p < 0.001 cf phase 1) and the rate of decline in renal function fell to -25.2 1/mol/month (p < 0.05 cf phase 1). Phase 3 consisted of another 6-month period when further reduction of MDBP 77.1 +/- 6.6 mmHg (p < 0.01 cf phase 2) was brought about by the addition of the calcium antagonist nifedipine (10 mg thrice/daily). This was not associated with further improvement in the rate of decline of renal function as in this phase the rate of decline was -53.2 1/mol/month. This study confirms that frequent follow-ups with improved blood pressure control slow the rate of decline in renal function. Further reduction of diastolic blood pressure to below 80-85 mmHg could not be shown to confer additional benefit.

Adult↗

Differential effect of L-nitroarginine methyl ester on urinary cGMP and kidney growth in the conscious rat following uninephrectomy.

The role of cGMP in compensatory renal growth (CRG) is uncertain, since inconsistent changes in renal cGMP have been reported following uninephrectomy (UNx) in the rat. The aim of this study was to reassess the change in cGMP following UNx in the conscious rat by sequential measurements of cGMP excretion and to determine the contribution of nitric oxide, an activator of guanylate cyclase, using L-NAME an inhibitor of nitric oxide synthase. In the conscious rat a sustained increase in the urinary excretion of cGMP was produced in the 7-day period following UNx. L-NAME (20 mg/kg per day) prevented the increase in cGMP excretion following UNx, but not compensatory renal growth. Total kidney DNA, however, was reduced by L-NAME. These observations dissociate the increase in cGMP after UNx from the process of renal hypertrophy.

Animals↗

Natural history of chronic renal failure: a reappraisal.

In this retrospective study we have analysed the rate of progression of renal insufficiency, ascertained from the slopes of the plot of inverse serum creatinine against time, of 102 patients with moderate to severe chronic renal failure (CRF). We have applied 'breakpoint' analysis of the slopes to identify changes in the rate of progression and attempted to determine the factors associated with these changes. Seventy-one patients were found to have progressive CRF, while the remaining 31 had stable or improving renal function. Of the parameters studied, using weighted least-squares analysis, proteinuria was the most significant predictor of progression (regression coefficient: -0.1775, P = 0.0075, adjusted r2 = 0.1059). A positive correlation was observed between proteinuria and diastolic blood pressure (DBP) (r = 0.336, P = 0.0054). Once the predictive value of proteinuria was taken into account, there was no difference in the progression rate between diagnostic groups, other than those patients with polycystic kidney disease who had a significantly faster rate of progression (P = 0.0037). In 49 patients, there was at least one change in the rate of progression with time. There was an inverse correlation between change in slope and a change in DBP (r = -0.352, P = 0.003). We conclude that changes in DBP are often associated with the frequent changes in the rate of progression of CRF. However, a causal link could not be established as in a large number of cases the two changes appeared to occur simultaneously in the absence of changes in antihypertensive therapy.

Adult↗

Short-term effects of calcium antagonists on renal haemodynamics in patients with chronic renal failure.

Experimental evidence suggests that pharmacological manipulations of glomerular haemodynamics may affect the progression of chronic renal insufficiency and scarring. In this study, we have investigated the short-term (4 weeks) renal haemodynamic effects of nifedipine and nitrendipine (10 mg/thrice daily) in two separate groups of 6 patients with stable chronic renal failure (CRF) (glomerular filtration rate, GFR: 9.7-47.8 ml/min/1.73 m2). Patients were studied on three occasions: (1) before the administration of the calcium antagonist, (2) after 4 weeks of treatment and (3) 4 weeks after the discontinuation of the drug. Mean arterial pressure fell significantly on nifedipine: from 116.33 +/- 12.25 to 107.22 +/- 18.67 mm Hg, p less than 0.05, and on nitrendipine: from 112.22 +/- 10.04 to 102.22 +/- 13.77 mm Hg, p less than 0.05. There was no significant effect of either calcium antagonist on GFR, effective renal plasma flow (ERPF), proteinuria or natriuresis. Consequently, renal vascular resistance (RVR) fell in both experimental groups, nifedipine: from 51.40 +/- 28.77 to 44.97 +/- 30 dyn s cm-5 x 10(3) (mean +/- SD), and nitrendipine: from 37.04 +/- 18.46 to 30.47 +/- 15.56 dyns s cm-5 x 10(3), p less than 0.05. These results show that calcium antagonists reduce systemic blood pressure whilst GFR and ERPF are maintained. The fall in the RVR of patients with CRF treated with calcium antagonists may confer on these agents a therapeutic advantage in the management of progressive renal insufficiency.

Adolescent↗

Effect of antihypertensive therapy in experimental chronic renal failure.

In this study, the effect of the antihypertensive agents nifedipine (4.5 mg/day) and hydralazine (50-200 mg/l of drinking water) on the progression of chronic renal failure and scarring was evaluated in rats submitted to subtotal (5/6) nephrectomy (SNx). The effect of blood pressure reduction was studied in groups of rats fed either a medium-protein diet (24%) or high-protein diet (50%). SNx rats fed a high-protein diet had significantly higher levels of proteinuria and severer renal scarring at sacrifice (120 days after SNx). Nifedipine reduced proteinuria in SNx rats fed a high-protein diet. Both drugs significantly reduced systemic hypertension in SNx rats. Hydralazine and nifedipine also reduced hypertriglyceridaemia but had no effect on blood cholesterol levels. However, in spite of adequate control of systemic hypertension with the agents studied, the severity of renal scarring (glomerular sclerosis or tubulo-interstitial scarring) was not affected by treatment. We confirm that the control of systemic hypertension is not sufficient to prevent renal scarring in rats submitted to extensive renal ablation.

Animals↗

Effect of treatment with enalapril, verapamil and indomethacin on compensatory renal growth in the rat.

Renal growth often precedes scarring in experimental models of chronic renal failure in rats. Its control may therefore influence the subsequent development of renal scarring and failure in these animals. In this study we have attempted to manipulate, by pharmacological interventions, compensatory renal growth in rats who have undergone uninephrectomy. The effects of three drugs--enalapril, verapamil and indomethacin--were investigated. Compensatory renal growth was found to be 15.33 +/- 13.76% (mean +/- SD) 1 week after uninephrectomy in control adult male Wistar rats. Compensatory renal growth was significantly inhibited by pretreatment with enalapril 7.38 +/- 8.88% (P less than 0.05) but was unaffected by indomethacin; the effect of verapamil was inconclusive. In controls, both the protein and DNA content of the remaining kidney increased, indicating a mixed hypertrophic and hyperplastic response. Enalapril inhibited the hyperplastic component of compensatory renal growth. We conclude that following uninephrectomy in rats, compensatory hypertrophy can be manipulated by pharmacological interventions, in particular angiotensin-converting-enzyme inhibition by enalapril.

Animals↗