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Biomedical subjects

A Grant

Publications and source records attributed to A Grant.

At least 55 records · Page 3Linked to original sources
PubMed2001

Expression of rat aldehyde reductase AKR7A1: influence of age and sex and tissue-specific inducibility.

The regulation of the aldo-keto reductase AKR7A1 was examined in the livers of male and female rats during development by using Western blots, and its contribution to carbonyl metabolism was assessed by using enzyme assays. Hepatic levels of AKR7A1 are low in fetal rats and rise to a peak at around 6 weeks of age in animals of both sexes. Higher levels of the enzyme are found in adult male rat liver than in adult female rat liver. The reductase, therefore, appears to be subject to sex-specific regulation. The effect of growth hormone in mediating this difference in expression was examined by using hypophysectomized animals whose serum growth hormone levels had been feminized by continuous administration. Results demonstrate that such treatment leads to a reduction in AKR7A1 expression. AKR7A1 was found to be constitutively expressed in rat tissues such as liver, kidney, small intestine, and testis, but it was not detected in nasal mucosa, skeletal muscle, heart, adrenal gland, brain, or spleen. However, AKR7A1 was inducible by the synthetic antioxidant ethoxyquin in liver, kidney, and small intestine, but not in the other tissues examined. These results show that levels of this important detoxication enzyme vary considerably according to age and sex and that dietary antioxidants can also influence its level in several tissues.

Age Factors↗
PubMed2001

Double bag or Y-set versus standard transfer systems for continuous ambulatory peritoneal dialysis in end-stage renal disease.

BACKGROUND: Peritonitis is the most frequent serious complication of continuous ambulatory peritoneal dialysis (CAPD). It has a major influence on the number of patients switching from CAPD to haemodialysis and has probably restricted the wider acceptance and uptake of CAPD as an alternative mode of dialysis. OBJECTIVES: This systematic review sought to determine if modifications of the transfer set (Y-set or double bag systems) used in CAPD exchanges are associated with a reduction in peritonitis and an improvement in other relevant outcomes. SEARCH STRATEGY: A broad search strategy was employed which attempted to identify all RCTs or quasi-RCTs relevant to the management of end-stage renal disease (ESRD). Five electronic databases were searched (Medline 1966-1999, EMBASE 1984-1999, CINAHL 1982-1996, BIOSIS 1985-1996 and the Cochrane Library), authors of included studies and relevant biomedical companies were contacted, reference lists of identified RCTs and relevant narrative reviews were screened and Kidney International 1980-1997 was hand searched. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing double bag, Y-set and standard CAPD exchange systems in patients with ESRD. DATA COLLECTION AND ANALYSIS: Data were abstracted by a single investigator onto a standard form and subsequently entered into Review Manager 4.0.4. Odds Ratio (OR) for dichotomous data and a (Weighted) Mean Difference (WMD) for continuous data were calculated with 95% confidence intervals (95% CI). MAIN RESULTS: Twelve eligible trials with a total of 991 randomised patients were identified. In trials comparing either the Y-set or double bag systems with the standard systems significantly fewer patients (OR 0.33, 95% CI 0.24 to 0.46) experienced peritonitis and the number of patient-months on CAPD per episode of peritonitis were consistently greater. When the double bag systems were compared with the Y-set systems significantly fewer patients experienced peritonitis (OR 0.44, 95% CI 0.27 to 0.71) and the numbers of patient-months on CAPD/ episode of peritonitis were also greater. REVIEWER'S CONCLUSIONS: Double bag systems should be the preferred exchange systems in CAPD.

Humans↗
PubMed2001

Comparison of cellulose, modified cellulose and synthetic membranes in the haemodialysis of patients with end-stage renal disease.

BACKGROUND: When the kidney fails the blood borne metabolites of protein breakdown and water cannot be excreted. The principle of haemodialysis is that such substances can be removed when blood is passed over a semipermeable membrane. Natural membrane materials can be used including cellulose or modified cellulose, more recently various synthetic membranes have been developed. Synthetic membranes are regarded as being more "biocompatible" in that they incite less of an immune response than cellulose-based membranes. OBJECTIVES: To assess the effects of different haemodialysis membrane material in patients with end-stage renal disease (ESRD). SEARCH STRATEGY: We searched Medline (1966 to December 2000), Embase (1981 to November 2000), PreMedline (29 November 2000), HealthStar (1975 to December 2000), Cinahl (1982 to October 2000), The Cochrane Controlled Trials Register (Issue 1, 1996), Biosis (1989 to June 1995), Sigle (1980 to June 1996), Crib (10th edition, 1995), UK National Research Register (September 1996), and reference lists of relevant articles. We contacted biomedical companies, investigators and we hand searched Kidney International (1980 to 1997). Date of the most recent searches: November 2000. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials comparing different haemodialysis membrane material in patients with ESRD. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of studies. Data was abstracted from included studies onto a standard form by one reviewer and checked by another. MAIN RESULTS: Twenty seven studies met our inclusion criteria and where possible data from these were summated by meta-analyses (Peto's odds ratio (OR) and weighted mean difference (WMD) with 95% confidence intervals (CI)). Twenty two outcome measures were sought in 10 broad areas. For two (number of episodes of significant infection per year and quality of life) no data were available. For the comparison of cellulose with synthetic membranes, data for 12/20 outcome measures were available in only a single trial. For modified cellulose and synthetic membranes, data for three outcome measures were available in one trial only and for 12 of the outcomes no data were found, crossover studies were analysed separately and studies which randomised by patient yet analysed by dialysis sessions adjusted for clustering. Pre-dialysis beta2 microglobulin concentrations were significantly lower at the end of the studies in patients treated with synthetic membranes (WMD - 14.5; 95% CI -17.4 to -11.6). One crossover study showed a lowering of beta2 microglobulin when low flux synthetic membranes were used. When analysed for a change in beta2 microglobulin across a trial a fall was only noted when high flux membranes were used. In one very small study the incidence of amyloid was less in patients who were dialysed for six years with high flux synthetic membranes (OR 0.05; 95% CI 0.01 to 0.18). In the single study which measured triglyceride values there was a significant difference in favour of the synthetic (high flux) membrane (WMD -0.66; 95% CI -1.18 to -0.14). Serum albumin was higher in patients treated with synthetic membranes (both low and high flux) although this just bordered statistical significance (WMD -0.09; 95% CI -0.18 to 0.00). Dialysis adequacy measured by Kt/V was marginally higher when cellulose membranes were used (WMD 0.10; 95% CI 0.04 to 0.16). There was no significant difference between these membranes for any of the other clinical outcomes measures but confidence intervals were generally wide. No differences were found between modified cellulose and synthetic membranes although many fewer trials were carried out for this comparison. REVIEWER'S CONCLUSIONS: For clinical practice This systematic literature review has generated no evidence of benefit when synthetic membranes were used compared with cellulose/modified cellulose membranes in terms of reduced mortality nor reduction in dialysis related adverse symptoms. Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life. End-of-study beta2 microglobulin values, and possibly the development of amyloid disease, were less in patients treated with synthetic membranes compared with cellulose membranes. Plasma triglyceride values were also lower with synthetic membranes in the single study that measured this outcome. Differences in these outcomes may have reflected the high flux of the synthetic membrane. Serum albumin was higher when synthetic membranes of both high and low flux were used. Kt/V and urea reduction ratio were higher when cellulose or modified cellulose membranes were used in the few studies that measured these outcomes. We are hesitant to recommend the universal use of synthetic membranes for haemodialysis in patients with ESRD because of; the small number of trials (particularly for modified cellulose membranes, most with low patient numbers), the heterogeneity of many of the trials compared, the variations in membrane flux, the differences in exclusion criteria, particularly relating to comorbidity and the relative lack of patient-centred outcomes studied. Such evidence as we have favours synthetic membranes but even if we assume extra benefit it may be at considerable cost, particularly if high flux synthetic membranes were to be used. For further research A further systematic review of RCTs comparing high and low flux haemodialysis membranes, subgrouped according to membrane composition (cellulose, modified cellulose, synthetic) and reporting clinical outcomes of major importance to patients needs to be undertaken. Further pragmatic RCTs are required to compare the different dialysis membranes available. We recommend that they: - Take into account other properties including flux as well as the material from which the membrane is made and test modified cellulose membranes as well as standard ones. - Record an agreed minimum dataset on primary outcomes of major importance to patients. - Explicitly record whether symptoms are patient- or staff-reported recognising that generally patient reporting will be more appropriate for evaluating effectiveness but staff reported data may be necessary for calculating the cost of treating complications. - Be multi-centre (and possibly multinational) to have sufficient patients to complete the study to allow for a considerable number of withdrawals and dropouts. - Have sufficient length of follow up to draw conclusions for important clinical outcome measures and continue to follow patients who have renal transplants. - Include older patients and those with comorbid illnesses and take into account age and comorbidity when assessing outcomes (possibly by stratification at trial entry). - Carry out, in parallel, an economic evaluation of the different policies being compared in the trial.

Cellulose↗
PubMed2001

Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients.

BACKGROUND: Treatment with recombinant human erythropoietin (rHu EPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHu EPO use in pre-dialysis patients. There is a concern that rHu EPO may accelerate the deterioration in renal function, however the opposing view is that if rHu EPO is as effective in pre-dialysis patients that by improving the patients sense of well-being the onset of dialysis could be delayed. OBJECTIVES: To assess the effects of rHu EPO use in pre-dialysis patients with renal anaemia. SEARCH STRATEGY: We searched MEDLINE (1980 to May Week 3 2001), EMBASE (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October 1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996), SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14TH consolidation, September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997), IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant articles. We contacted biomedical companies and investigators in the field and we hand searched Kidney International (including all supplements but excluding all conference proceedings except for 1994) July 1983 to May 1997 inclusive. The internet was also searched on: August 1997. We had also identified some studies from a previous broad search for all randomised controlled trials (RCTs) relevant to the management of end-stage renal disease. Date of the most recent search: June 2001. SELECTION CRITERIA: RCTs or quasi-RCTs comparing the use of rHu EPO with no rHu EPO or placebo in pre-dialysis patients. DATA COLLECTION AND ANALYSIS: Only published data were used. Data were abstracted by a single investigator onto a standard form. A sample of the data abstracted was double-checked by another reviewer. The data abstracted were relevant to the predetermined outcome measures. Some authors were contacted to clarify how patients were allocated to groups. All authors from included studies were contacted for missing information. MAIN RESULTS: Twelve studies with a total of 232 participants met the inclusion criteria and where possible data from these were summated by meta-analyses (Peto's Odds Ratio (OR) and Weighted Mean Difference (WMD)). The majority of the trials included small numbers and were of short duration (8-10 weeks) with the exception of three trials. There was a marked improvement in haemoglobin (mean difference 2.3g/dL, 95% CI 1.37 to 3.23) and haematocrit (WMD 9.92%, 95% CI 8.78 to 11.05) with the treatment and a decrease in the number of patients requiring blood transfusion (OR 0.25, 95% CI 0.09 to 0.69). The data from all studies which reported quality of life or exercise capacity demonstrated an improvement in the rHu EPO group. None of the measures of progression of renal disease (when a summary statistic was calculated) demonstrated a statistically significant difference. Though the requirement for antihypertensive treatment appears to be increased by rHu EPO (OR 1.84, 95% CI 1.02 to 3.32), there was no other statistically significant increase in adverse events. Based on the limited current evidence, decisions therefore have to be made on whether the putative benefits in terms of quality of life identified in the review are worth the extra costs of pre-dialysis rHu EPO. REVIEWER'S CONCLUSIONS: This review has shown that treatment with rHu EPO in pre-dialysis patients corrects anaemia and avoids the requirement for blood transfusions. There are also improvements in quality of life and exercise capacity. There may be increased hypertension. Most of the trials were not of sufficient duration to assess the effects of rHu EPO on progression of renal disease. In the long term, questions still remain about whether pre-dialysis rHu EPO either speeds up or delays the onset of dialysis. Thus there is insufficient evidence on the total costs and benefits of treating pre-dialysis patients with rHu EPO.

Anemia↗
PubMed2001

Copurification of the Lac repressor with polyhistidine-tagged proteins in immobilized metal affinity chromatography.

One of the commonly used resins for immobilized metal affinity purification of polyhistidine-tagged recombinant proteins is TALON resin, a cobalt (II)--carboxymethylaspartate-based matrix linked to Sepharose CL-6B. Here, we show that TALON resin efficiently purifies the native form of Lac repressor, which represents the major contaminant when (His)(6)-tagged proteins are isolated from Escherichia coli host cells carrying the lacI(q) gene. Inspection of the crystal structure of the repressor suggests that three His residues (residues 163, 173, and 202) in each subunit of the tetramer are optimally spaced on an exposed face of the protein to allow interaction with Co(II). In addition to establishing a more efficient procedure for purification of the Lac repressor, these studies indicate that non-lacI(q)-based expression systems yield significantly purer preparations of recombinant polyhistidine-tagged proteins.

Aspartic Acid↗
PubMed2001

Strategic information management plans: the basis for systematic information management in hospitals.

Information management in hospitals is a complex task. In order to reduce complexity, we distinguish strategic, tactical, and operational information management. This is essential, because each of these information management levels views hospital information systems from different perspectives, and therefore uses other methods and tools. Since all these management activities deal only in part with computers, but mainly with human beings and their social behavior, we define a hospital information system as a sociotechnical subsystem of a hospital. Without proper strategic planning it would be a matter of chance, if a hospital information system would fulfil the information strategies goals. In order to support strategic planning and to reduce efforts for creating strategic plans, we propose a practicable structure.

Hospital Information Systems↗
PubMed2001

Physicochemical studies of caroubin: a gluten-like protein.

It has been reported that caroubin, a protein mixture obtained from carob seeds, has rheological properties similar to those of gluten. Comparative studies of the effects of hydration and temperature on caroubin and gluten were carried out with the aid of NMR, FTIR, scanning electron microscopy, and differential scanning calorimetry techniques. The results show that caroubin has a more ordered structure than gluten and that hydration has little effect on its secondary structure when compared to gluten. Caroubin is more easily accessible to water than gluten, suggesting that caroubin is more hydrophilic in nature. On hydration, caroubin, like gluten, forms fibrillar structures and sheets.

Calorimetry, Differential Scanning↗
PubMed2001

The optimal form of urinary drainage after acute retention of urine.

OBJECTIVE: To assess the outcome of different forms of urinary drainage, particularly for urinary tract infection (UTI), operative findings and patient preference, in patients treated for acute urinary retention (AUR). PATIENTS AND METHODS: A feasibility trial was conducted of men presenting with AUR; after a short period of indwelling catheterization (IDC) patients were taught how to use clean intermittent self-catheterization (CISC). Patients who failed this were re-catheterized and taught to manage a valve, or failing this a leg bag, and then discharged home. The patients were followed to assess the occurrence of spontaneous voiding, UTI, findings at prostatectomy and patient satisfaction. RESULTS: The CISC group (34 men) had a higher rate of spontaneous voiding than the IDC group (16 men; 56% vs 25%). The incidence of UTI was 32% in the CISC and 75% in the IDC group. At TURP, 20% in the CISC group had a UTI, compared with 69% in the IDC group. Patients using CISC preferred it and had fewer complications than the IDC group. The CISC group had a similar ability to manage and similar acceptance of their method of drainage as the IDC group. CONCLUSION: CISC is managed and accepted well by patients who can use the technique and results in fewer UTIs. It should be considered in patients who present with AUR, and it may delay surgery.

Acute Disease↗
PubMed2001

The Ipswich childbirth study: one year follow up of alternative methods used in perineal repair.

OBJECTIVE: To assess the long term implications of four alternative approaches to postpartum perineal repair. DESIGN: A stratified randomised controlled trial using a 2x2 factorial design. SETTING: Original recruitment at the Maternity Unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994. SAMPLE: Seven hundred and ninety three women who had participated in the Ipswich Childbirth Study--a trial among women who had required repair of episiotomy or first or second degree tears--at least one year previously. METHODS: Self-completed postal follow up at least one year after recruitment to trial comparing 1. two-stage repair leaving the skin unsutured with standard three-stage repair, and 2. polyglactin 910 with chromic catgut as suture material for the repair. MAIN OUTCOME MEASURES: Failure to resume pain-free intercourse; persistent perineal pain; perineum feeling different; resuturing; time to resume pain-free intercourse; and dyspareunia. RESULTS: Fewer women allocated two-stage repair reported that the perineum felt different (30% versus 40%; RR 0.75; 95% CI 0.61 to 0.91; 2P < 0.01); otherwise there were no clear differences between the two methods. Women allocated polyglactin 910 were less likely to have dyspareunia (8% versus 13%; RR 0.59, 95% CI 0.39 to 0.91; 2P = 0.02) and less likely to fail to resume pain-free intercourse (8% versus 14%; RR 0.57, 95% CI 0.38 to 0.87; 2P < 0.01). CONCLUSION: Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce the likelihood of the perineum feeling different from before delivery, in addition to less pain and dyspareunia initially; there were no apparent disadvantages. Polyglactin 910 reduces dyspareunia long term, indicating that the short term benefits of this material over chromic catgut persist.

Adult↗