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Biomedical subjects

C Donaldson

Publications and source records attributed to C Donaldson.

At least 19 recordsLinked to original sources
PubMed2005

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 include 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, EMBASE, PreMEDLINE, HealthStar CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), Biosis, SIGLE, CRIB, UK National Research Register and reference lists of relevant articles. We contacted biomedical companies, known investigators and handsearched selected journals and conference proceedings. Date of most recent search: June 2004. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs 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 onto a standard form by one reviewer and checked by another. Relative Risk (RR) and weighted mean difference (WMD) with 95% confidence intervals (CI)) MAIN RESULTS: Thirty two studies were identified. Pre-dialysis ss(2) microglobulin concentrations were not significantly lower in patients treated with synthetic membranes (WMD -14.67, 95% CI -33.10 to 4.05). When analysed for change in ss(2) microglobulin, a fall was only noted with high-flux membranes. The incidence of amyloid was less in patients who were dialysed for six years with high-flux synthetic membranes (one study, RR 0.03, 95% CI 0.00 to 0.54). There was a significant difference in favour of the synthetic (high-flux) membrane in comparison to cellulose membranes for triglycerides (WMD -0.66; 95% CI -1.18 to -0.14) but not for modified cellulose membranes. Dialysis adequacy measured by Kt/V was marginally higher when cellulose membranes were used (WMD -0.10; 95% CI -0.16 to 0.04), whereas synthetic membranes achieved significantly higher Kt/V values when compared with modified cellulose membranes (WMD 0.20, 95% 0.11 to 0.29) . There were no data on quality of life measures. AUTHORS' CONCLUSIONS: We found no evidence of benefit when synthetic membranes were compared with cellulose/modified cellulose membranes in terms of reduced mortality no 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.

Cellulose↗
PubMed2005

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 which may accelerate the deterioration of renal function. However the opposing view is that if rHu EPO is as effective in pre-dialysis patient's, improving the patients sense of well-being may result in the onset of dialysis being delayed. OBJECTIVES: To assess the effects of rHu EPO use in pre-dialysis patients with renal anaemia. SEARCH STRATEGY: The initial search included 13 electronic databases (1980 to May 2001) an internet search (August 1997), handsearching of Kidney International (1983 to May 1997), contact with known investigators and biomedical companies, and reference list of relevant articles. For this update we searched the Cochrane Renal Group's specialised register (June 2004) and The Cochrane Library (Issue 3, 2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing the use of rHu EPO with no treatment or placebo in pre-dialysis patients. DATA COLLECTION AND ANALYSIS: Only published data were used. Quality assessment was performed by two assessors independently. Data were abstracted by a single author onto a standard form, a sample of which was checked by another author. Results were expressed as relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Fifteen trials (461 participants) were included. There was a marked improvement in haemoglobin (WMD 1.82 g/dL, 95% CI 1.35 to 2.28) and haematocrit (WMD 9.85%, 95% CI 8.35 to 11.34) with treatment and a decrease in the number of patients requiring blood transfusions (RR 0.32, 95% CI 0.12 to 0.83). The data from studies reporting quality of life or exercise capacity demonstrated an improvement in the treatment group. Most of the measures of progression of renal disease showed no statistically significant difference. No significant increase in adverse events was identified. AUTHORS' CONCLUSIONS: Treatment with rHu EPO in pre-dialysis patients corrects anaemia, avoids the requirement for blood transfusions and also improves quality of life and exercise capacity. We were unable to assess the effects of rHu EPO on progression of renal disease, delay in the onset of dialysis or adverse events. Based on the current evidence, decisions on the putative benefits in terms of quality of life are worth the extra costs of pre-dialysis rHu EPO need careful evaluation.

Anemia↗
PubMed2005

Frequency of administration of recombinant human erythropoietin for anaemia of end-stage renal disease in dialysis patients.

BACKGROUND: The benefits of recombinant human erythropoietin (rHuEPO) administration in dialysis patients have been demonstrated, however the optimal frequency regimen have yet to be established. OBJECTIVES: To assess the effects of different frequency regimens of rHuEPO administration in dialysis patients on anaemia correction, quality of life and optimal use. SEARCH STRATEGY: We searched 13 electronic databases (1980 to May 2001) the internet (August 1997), handsearched Kidney International (1983 to May 1997), contacted known investigators, biomedical companies, and screened reference lists of relevant articles. Most recent search: The Cochrane Renal Group's specialised register (June 2004) and The Cochrane Library (Issue 3, 2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing different frequencies of rHuEPO administration in dialysis patients. We compared haemodialysis and CAPD patients and subcutaneous and intravenous administration. DATA COLLECTION AND ANALYSIS: Quality assessment was performed by two assessors. Data were abstracted by a single author onto a standard form, and a sample was checked by another author. Results were expressed as relative risk (RR) or weighted mean difference (WMD) with 95% confidence intervals (CI). MAIN RESULTS: Eleven studies (719 patients) were included. There was no significant difference in maintaining target haemoglobin for once versus twice weekly administration (one study, 20 patients: RR 1.00, 95% CI 0.42 to 2.40) or mean haemoglobin after 12 weeks of therapy between haemodialysis and CAPD patients (two studies: WMD -0.21 g/dL, 95% CI -0.98 to 0.56) At the end of study for once versus thrice weekly administration (three studies: SMD -0.31, 95% CI -0.67 to 0.06) and at the end of maintenance phase (one study: WMD -0.2 g/dL, 95% CI -0.65 to 0.25) there was no significant difference. More rHuEPO was required by haemodialysis patients receiving once weekly versus twice weekly doses (WMD 12.0 U/kg, 95% CI 0.24 to 23.76). No difference was found for CAPD patients alone or combined (WMD 4.38 U/kg, 95% CI -11.28 to 20.04). Once versus thrice weekly administration was not significant (WMD 10.00 U/kg, 95% CI -80.87 to 100.87). There was no difference in the frequency of adverse events. AUTHORS' CONCLUSIONS: There is no significant difference between once weekly versus thrice weekly subcutaneous administration of rHuEPO. Once weekly administration would require an additional 12 U/kg/wk for patients on haemodialysis, however this is based on one very small study. Cost of additional rHuEPO needs to assessed with regard to patient preference and compliance.

Anemia↗
PubMed2005

An interinstitutional comparative study and validation of computer aided drusen quantification.

AIMS: To assess the portability and clinical applicability of a software program based on Photoshop (Adobe Systems Inc, San Jose, CA, USA) for digital drusen quantification. METHODS: Independent graders from the Digital Fundus Photo Reading Center of Columbia University and King's College Hospital used macular background levelling software to quantify the percentage of drusen in the central and middle Wisconsin subfields. 100 images of consecutive patients with choroidal neovascularisation in one eye and significant drusen in the other eye were analysed to determine suitability, and 10 were chosen for assessment by this software. RESULTS: Of the 10 images used in the interinstitutional validation, the random effects ANOVA for the central and middle subfields showed a high degree of interobserver agreement. The ICC for interobserver reliability was 0.83 (95% CI: 67 to 95) for the central subfield and 0.84 (95% CI: 69 to 99) for the middle subfield. Overall agreement with the manual grading results was good and the within patient coefficient of variation was about 20% for all the pairwise comparisons between observers and the manual stereo gradings. Of the 100 images used to assess practical applicability of the software, 79 were suitable for semiautomated analysis. 13 had extensive mixed retinal pigment epithelial (RPE) changes limiting drusen identification, five had a significant number of reticular drusen, which are poorly identified by the software, and three had multiple small areas of RPE atrophy, which are difficult to distinguish from drusen. CONCLUSIONS: The software was successfully used by two institutions demonstrating portability, with good correlation between graders and to the manual stereo grading. Digital drusen quantification was possible in 79% of the images analysed.

Analysis of Variance↗
PubMed2004

Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or home haemodialysis for end-stage renal disease in adults.

BACKGROUND: Renal replacement therapy (RRT) with dialysis and transplantation is the only means of sustaining life for patients with end-stage renal disease (ESRD). Although transplantation is the treatment of choice, the number of donor kidneys are limited and transplants may fail. Hence many patients require long-term or even life-long dialysis. Continuous ambulatory peritoneal dialysis (CAPD) is an alternative to hospital or home haemodialysis for patients with ESRD. OBJECTIVES: To assess the benefits and harms of CAPD versus hospital or home haemodialysis for adults with ESRD. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL in The Cochrane Library), the Cochrane Renal Group's specialised register, MEDLINE (1966 - May 2002), EMBASE (1980 - May 2002), BIOSIS, CINAHL, SIGLE and NRR without language restriction. Reference lists of retrieved articles and conference proceedings were searched and known investigators and biomedical companies were contacted. Date of most recent search January 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing CAPD to hospital or home haemodialysis for adults with ESRD were to be included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assess the methodological quality of studies. Data was abstracted from included studies onto a standard form by one reviewer and checked by another. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: One trial, reported in abstract form only, was located in the most recent search. There was no statistical difference in death or quality adjusted life years score at 2 years between peritoneal dialysis or haemodialysis patients. REVIEWERS' CONCLUSIONS: There is Insufficient data to allow conclusions to be drawn about the relative effectiveness of CAPD compared with hospital or home haemodialysis for adults with ESRD. Efforts should be made to start and complete adequately powered RCTs, which compare the different dialysis modalities.

Adult↗
PubMed2004

Rumination, mood and social problem-solving in major depression.

BACKGROUND: Ruminating when depressed is thought to lower mood and impair problem-solving, while distraction is thought to alleviate mood and assist problem-solving. The present study investigates each of these proposals using both naturally occurring and experimentally induced rumination and distraction in a sample of patients with major depression. METHOD: Thirty-six patients with major depression and 36 control participants were randomly allocated to either a rumination or distraction induction condition. Levels of trait rumination and distraction were measured at baseline, mood and problem-solving were measured before and after the inductions. RESULTS: In terms of trait measures, depressed patients with higher levels of trait rumination reported poorer mood and gave less effective problem solutions than those who were less ruminative. Trait distraction was not associated with mood or problem-solving. In terms of induced responses, depressed patients who were made to ruminate experienced a deterioration in their mood and gave poorer problem solutions. For those receiving the distraction induction, mood improved in all patients and problem-solving improved in patients who were not naturally ruminating at a high level. Neither induction had an impact on mood or problem-solving in control participants. CONCLUSIONS: Treatment for depression associated with adverse life events may need to target rumination as well as problem-solving deficits if interventions are to be effective. The differential effects of self-applied versus experimentally induced distraction require further investigation. Future research will need to consider that high levels of trait rumination may interfere with the impact of experimental inductions.

Adolescent↗
PubMed2004

Naratriptan has a selective inhibitory effect on trigeminovascular neurones at central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine therapy.

The triptans are agonists at serotonin (5-HT)1B/1D receptors; however, they are also active at 5-HT1A and 5-HT1F receptors. We conducted this series of experiments to further elucidate the site of action of naratriptan using a well-established animal model of trigeminovascular stimulation. Following electrical stimulation of the superior sagittal sinus of the cat, single cell responses (n=83) were recorded in the trigeminal nucleus caudalis. Most cells (91%) also responded to electrical and mechanical stimulation of cutaneous or mucosal facial receptive fields. The microiontophoretic application of naratriptan resulted in a significant suppression of the response to sagittal sinus stimulation (response suppressed by 47 +/- 4%, P<0.001). The effect of naratriptan was significantly attenuated by application of either the 5-HT(1B/1D) receptor antagonist GR-127935 (P<0.001) or the 5-HT1A antagonist WAY-100635 (P<0.05). The response of single cells to receptive field stimulation was also suppressed by microiontophoretic application of naratriptan, but by only 20 +/- 3%. Intravenous administration of naratriptan resulted in a similar selective suppression of sagittal sinus vs. receptive field responses in trigeminal neurones. These results indicate that naratriptan has a central effect in the trigeminovascular system, selectively inhibiting afferent activity in craniovascular neurones, via both 5-HT(1B/1D) and 5-HT1A receptors.

Action Potentials↗
PubMed2004

Effectiveness and efficiency of guideline dissemination and implementation strategies.

OBJECTIVES: To undertake a systematic review of the effectiveness and costs of different guideline development, dissemination and implementation strategies. To estimate the resource implications of these strategies. To develop a framework for deciding when it is efficient to develop and introduce clinical guidelines. DATA SOURCES: MEDLINE, Healthstar, Cochrane Controlled Trial Register, EMBASE, SIGLE and the specialised register of the Cochrane Effective Practice and Organisation of Care (EPOC) group. REVIEW METHODS: Single estimates of dichotomous process variables were derived for each study comparison based upon the primary end-point or the median measure across several reported end-points. Separate analyses were undertaken for comparisons of different types of intervention. The study also explored whether the effects of multifaceted interventions increased with the number of intervention components. Studies reporting economic data were also critically appraised. A survey to estimate the feasibility and likely resource requirements of guideline dissemination and implementation strategies in UK settings was carried out with key informants from primary and secondary care. RESULTS: In total, 235 studies reporting 309 comparisons met the inclusion criteria; of these 73% of comparisons evaluated multifaceted interventions, although the maximum number of replications of a specific multifaceted intervention was 11 comparisons. Overall, the majority of comparisons reporting dichotomous process data observed improvements in care; however, there was considerable variation in the observed effects both within and across interventions. Commonly evaluated single interventions were reminders, dissemination of educational materials, and audit and feedback. There were 23 comparisons of multifaceted interventions involving educational outreach. The majority of interventions observed modest to moderate improvements in care. No relationship was found between the number of component interventions and the effects of multifaceted interventions. Only 29.4% of comparisons reported any economic data. The majority of studies only reported costs of treatment; only 25 studies reported data on the costs of guideline development or guideline dissemination and implementation. The majority of studies used process measures for their primary end-point, despite the fact that only three guidelines were explicitly evidence based (and may not have been efficient). Respondents to the key informant survey rarely identified existing budgets to support guideline dissemination and implementation strategies. In general, the respondents thought that only dissemination of educational materials and short (lunchtime) educational meetings were generally feasible within current resources. CONCLUSIONS: There is an imperfect evidence base to support decisions about which guideline dissemination and implementation strategies are likely to be efficient under different circumstances. Decision makers need to use considerable judgement about how best to use the limited resources they have for clinical governance and related activities to maximise population benefits. They need to consider the potential clinical areas for clinical effectiveness activities, the likely benefits and costs required to introduce guidelines and the likely benefits and costs as a result of any changes in provider behaviour. Further research is required to: develop and validate a coherent theoretical framework of health professional and organisational behaviour and behaviour change to inform better the choice of interventions in research and service settings, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.

Cost-Benefit Analysis↗
PubMed2003

Continuous ambulatory peritoneal dialysis (CAPD) versus hospital or home haemodialysis for end-stage renal disease in adults.

BACKGROUND: Renal replacement therapy (RRT) with dialysis and transplantation is the only means of sustaining life for patients with end-stage renal disease (ESRD). Although transplantation is the treatment of choice, the number of donor kidneys are limited and transplants may fail. Hence many patients require long-term or even life-long dialysis. Continuous ambulatory peritoneal dialysis (CAPD) is an alternative to hospital or home haemodialysis for patients with ESRD. OBJECTIVES: To assess the benefits and harms of CAPD versus hospital or home haemodialysis for adults with ESRD. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), the Cochrane Renal Group's Specialised Register (May 2002), MEDLINE (1966 - May 2002), EMBASE (1980 - May 2002), BIOSIS, CINHAL, SIGLE and NRR without language restriction. Reference lists of retrieved articles and conference proceedings were searched and known investigators and biomedical companies were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing CAPD to hospital or home haemodialysis for adults with ESRD were to be included. DATA COLLECTION AND ANALYSIS: Two reviewers were to independently assess the methodological quality of studies. Data was to be abstracted from included studies onto a standard form by one reviewer and checked by another. Statistical analyses were to be performed using the random effects model and the results to be expressed as relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Despite extensive searching, no RCTs or quasi-RCTs were identified. REVIEWER'S CONCLUSIONS: Data are not available to allow conclusions to be drawn about the relative effectiveness of CAPD compared with hospital or home haemodialysis for adults with ESRD. Efforts should be made to start and complete adequately powered RCTs, which compare the different dialysis modalities.

Adult↗
PubMed2003

Tools of the trade: a comparative analysis of approaches to priority setting in healthcare.

In many countries, local managers and clinicians have been given responsibility to set health priorities and allocate resources accordingly. Although tools have been suggested for use in aiding this process, knowledge of these tools within health regions is lacking and comparative analysis in the literature is limited. Several approaches to priority setting are critiqued from both practical and theoretical perspectives, and a tangible way forward for such activity is provided. The approaches analysed include: needs assessment, core services, economic evaluation including quality-adjusted life year league tables, and programme budgeting and marginal analysis (PBMA). Needs assessment fails to recognize underlying economic principles of opportunity cost and the margin, while core services ignores the margin and has had limited impact in practice. Economic evaluations can consider marginal costs and benefits, but cannot always be used to inform decisions in a timely manner. PBMA is based on underlying economic principles and can pragmatically respond to objectives related to both efficiency and equity. Although PBMA is not without challenges, from an economic perspective, it does seem to "get the thinking right", and, importantly, as a process, can incorporate some of the other approaches to priority setting discussed in this paper.

Budgets↗
PubMed2003

Residues in the C-terminal region of activin A determine specificity for follistatin and type II receptor binding.

Activin is a secreted growth factor that signals by binding two related classes of single transmembrane receptors at the cell surface. The interaction of activin with its receptors is highly regulated by other cell surface receptors, antagonistic ligands, and high affinity extracellular binding proteins such as follistatin. Two activin A mutants, the deletion mutant des[85-109]-activin A and the point mutant K102E-activin A (K102E), were investigated with respect to their ability to bind cell surface receptors and the binding protein follistatin. The deletion mutant exhibits low affinity for both receptors and follistatin whereas the point mutant fails to bind cell surface receptors but binds follistatin-288 with high affinity. K102E is able to compete with wild type activin to bind to follistatin and can thus increase the concentration of activin available for receptor binding and signaling. These findings underline the importance of the C-terminal region of activin for binding interactions and show that different residues in this region are involved in cell surface receptor and follistatin interactions.

Activins↗
PubMed2003

Quality of life in patients treated with hemodialysis or peritoneal dialysis: what are the important determinants?

BACKGROUND: Patients with end-stage renal disease (ESRD) have significant impairments in health-related quality of life (HRQOL). In part, this is due to the intrusiveness of the treatment (hemodialysis or peritoneal dialysis) that is required. It is unclear whether hemodialysis or peritoneal dialysis is associated with a higher HRQOL. METHODS: 192 prevalent patients who self-selected treatment with hemodialysis (either in-center, satellite or home/self-care hemodialysis) or peritoneal dialysis were studied to determine whether treatment with hemodialysis or peritoneal dialysis is associated with a higher HRQOL. Demographic, laboratory and clinical information (including the presence of comorbid conditions using the Charlson comorbidity index) was assessed at baseline. The outcome of interest was HRQOL, which was measured using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), the Short-Form 36 (SF-36) and the EuroQol EQ-5D at baseline and after 6 and 12 months of follow-up. RESULTS: There was no significant difference in HRQOL scores for the SF-36, the EQ-5D and for 9 of 11 KDQOL dimensions for patients treated with hemodialysis or peritoneal dialysis at baseline. As expected, HRQOL was significantly lower for patients who had more comorbid disease, required assistance with their daily care, and for patients with less than a grade 12 education. After controlling for the effect of other important variables, HRQOL (as measured by the EQ-5D visual analog or index scores) did not differ between hemodialysis and peritoneal dialysis patients. HRQOL was stable over time, both for patients who started on hemodialysis or peritoneal dialysis. CONCLUSIONS: There is no significant difference in HRQOL for prevalent ESRD patients treated with hemodialysis or peritoneal dialysis. It will be important to determine if this finding holds true for incident patients treated with hemodialysis or peritoneal dialysis.

Female↗
PubMed2002

Suppression by eletriptan of the activation of trigeminovascular sensory neurons by glyceryl trinitrate.

The effect of intracarotid arterial infusions of glyceryl trinitrate (GTN), a substance known to precipitate vascular headache, on the spontaneous activity of trigeminal neurons with craniovascular input was studied in cats. Cats were anaesthetised with alpha-chloralose, immobilised and artificially ventilated. The superior sagittal sinus (SSS) was isolated and stimulated electrically. Facial receptive fields (RF) were also stimulated. Single neurons were recorded from the trigeminal nucleus caudalis with a metal microelectrode equipped with six glass barrels for microiontophoresis. Infusions of GTN were administered via a catheter inserted retrogradely into the common carotid artery through the lingual artery. Infusions of GTN (mean rate 19+/-7, range 5-100 microg kg(-1) min(-1), in a volume of 2 ml min(-1)) increased the spontaneous discharge rate of second-order neurons which received dural and facial sensory input to 429+/-80% of control. Iontophoretic application of the 5-HT(1B/1D) receptor agonist eletriptan (50 nA) at the peak of the response decreased the discharge rate of neurons towards pre-GTN control levels. In the presence of continuous iontophoretic application of the 5-HT(1B/1D) receptor antagonist GR127935, the decrease in discharge rate caused by eletriptan was antagonised. We conclude (1) that GTN activates craniovascular sensory pathways at a site at, or peripheral to, the second-order neuron and that such an action may account for at least the acute-onset headache induced by GTN and (2) that the antimigraine agent eletriptan is able to selectively suppress noxious sensory information from the dura, induced by GTN, via an action at 5-HT(1B/1D) receptors.

Animals↗
PubMed2002

Frequency of administration of recombinant human erythropoietin for anaemia of end-stage renal disease in dialysis patients.

BACKGROUND: Although the benefits of recombinant human erythropoietin (rHu EPO) administration in dialysis patients have been demonstrated the optimal frequency regimen has not as yet been established. Treatment with rHu EPO is expensive, there is therefore a need for optimising the efficiency of its administration. OBJECTIVES: The objectives of this review were to assess the effects of different frequency regimens of rHu EPO administration in dialysis patients in terms of i) effectiveness (correction of anaemia, quality of life and freedom from adverse events) ii) efficiency (optimal resource use) of different rHu EPO dose regimen policies. 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: All randomised or quasi randomised controlled trials comparing different frequencies of rHu EPO administration in dialysis patients. Subgroup analyses were performed comparing haemodialysis and CAPD patients and also subcutaneous and intravenous administration. DATA COLLECTION AND ANALYSIS: Only published data were used. Data were abstracted by a single investigator on to a standard form. The data abstracted were relevant to the predetermined outcome measures: measures of correction of anaemia, rHu EPO dose, quality of life measures, adverse events, number of withdrawals from study, mortality. Where appropriate, a summary relative risk (RR) was calculated for dichotomous data and a weighted mean difference (WMD) or standardised mean difference (SMD) for continuous data. MAIN RESULTS: Eight studies met our inclusion criteria. When once a week administration was compared with twice weekly there was no significant difference in the ability to maintain the target haemoglobin (RR 1.00, 95% CI 0.42 to 2.40). Mean haemoglobin after twelve weeks of therapy was not different between the two groups (WMD -0.21g/dl, 95% CI -0.98 to 0.56). No difference was found in mean haemoglobin or haematocrit at the end of any studies which compared once with thrice weekly administration of rHu EPO (SMD -0.31, 95% CI -0.67 to 0.06). A single study which compared once with more that thrice weekly administration showed no significant difference in mean haemoglobin at the end of the maintenance phase (mean difference -0.2g/dl, 95% CI -0.65 to 0.25). The dosage of erythropoietin required by those on haemodialysis receiving rHu EPO once weekly was just significantly more (WMD 12.0 U/kg, 95% CI 0.24 to 23.76) than those receiving it twice weekly but the confidence interval is wide. No such difference was found for CAPD patients nor when the results were combined (WMD 5.15 U/kg, 95% CI -3.74 to 14.05). The result was not significant when comparing once weekly with thrice weekly administration (WMD 10.00 U/kg, 95% CI -80.87 to 100.87). There was no difference in the frequency of adverse events between any of the groups studies. REVIEWER'S CONCLUSIONS: There is no significant difference between once weekly versus thrice weekly subcutaneous administration of rHu EPO. Once weekly administration of rHu EPO would require an additional 12U/kg/week for patients on haemodialysis, however this is based on one very small study. The cost of this additional hRu EPO nee, however this is based on one very small study. The cost of this additional hRu EPO needs to assessed, in particular with regard to patient preference and compliance.

Anemia↗
PubMed2002

Health economic evaluation.

A glossary is presented on terms of health economic evaluation. Definitions are suggested for the more common concepts and terms.

Cost-Benefit Analysis↗
PubMed2001

Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor.

The corticotropin-releasing factor (CRF) family of neuropeptides includes the mammalian peptides CRF, urocortin, and urocortin II, as well as piscine urotensin I and frog sauvagine. The mammalian peptides signal through two G protein-coupled receptor types to modulate endocrine, autonomic, and behavioral responses to stress, as well as a range of peripheral (cardiovascular, gastrointestinal, and immune) activities. The three previously known ligands are differentially distributed anatomically and have distinct specificities for the two major receptor types. Here we describe the characterization of an additional CRF-related peptide, urocortin III, in the human and mouse. In searching the public human genome databases we found a partial expressed sequence tagged (EST) clone with significant sequence identity to mammalian and fish urocortin-related peptides. By using primers based on the human EST sequence, a full-length human clone was isolated from genomic DNA that encodes a protein that includes a predicted putative 38-aa peptide structurally related to other known family members. With a human probe, we then cloned the mouse ortholog from a genomic library. Human and mouse urocortin III share 90% identity in the 38-aa putative mature peptide. In the peptide coding region, both human and mouse urocortin III are 76% identical to pufferfish urocortin-related peptide and more distantly related to urocortin II, CRF, and urocortin from other mammalian species. Mouse urocortin III mRNA expression is found in areas of the brain including the hypothalamus, amygdala, and brainstem, but is not evident in the cerebellum, pituitary, or cerebral cortex; it is also expressed peripherally in small intestine and skin. Urocortin III is selective for type 2 CRF receptors and thus represents another potential endogenous ligand for these receptors.

Amino Acid Sequence↗
PubMed2001

Phosphorylation of xanthine dehydrogenase/oxidase in hypoxia.

The enzyme xanthine oxidase (XO) has been implicated in the pathogenesis of several disease processes, such as ischemia-reperfusion injury, because of its ability to generate reactive oxygen species. The expression of XO and its precursor xanthine dehydrogenase (XDH) is regulated at pre- and posttranslational levels by agents such as lipopolysaccharide and hypoxia. Posttranslational modification of the protein, for example through thiol oxidation or proteolysis, has been shown to be important in converting XDH to XO. The possibility of posttranslational modification of XDH/XO through phosphorylation has not been adequately investigated in mammalian cells, and studies have reported conflicting results. The present report demonstrates that XDH/XO is phosphorylated in rat pulmonary microvascular endothelial cells (RPMEC) and that phosphorylation is greatly increased ( approximately 50-fold) in response to acute hypoxia (4 h). XDH/XO phosphorylation appears to be mediated, at least in part, by casein kinase II and p38 kinase as inhibitors of these kinases partially prevent XDH/XO phosphorylation. In addition, the results indicate that p38 kinase, a stress-activated kinase, becomes activated in response to hypoxia (an approximately 4-fold increase after 1 h of exposure of RPMEC to hypoxia) further supporting a role for this kinase in hypoxia-stimulated XDH/XO phosphorylation. Finally, hypoxia-induced XDH/XO phosphorylation is accompanied by a 2-fold increase in XDH/XO activity, which is prevented by inhibitors of phosphorylation. In summary, this study shows that XDH/XO is phosphorylated in hypoxic RPMEC through a mechanism involving p38 kinase and casein kinase II and that phosphorylation is necessary for hypoxia-induced enzymatic activation.

Animals↗