PubMed Health⌕ Search

Biomedical subjects

R A Elliott

Publications and source records attributed to R A Elliott.

At least 19 recordsLinked to original sources
PubMed2006

Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.

AIMS: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. METHODS: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. RESULTS: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. CONCLUSIONS: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.

Adolescent↗
PubMed2006

A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modelling.

OBJECTIVES: To assess the relative effectiveness, patient acceptability, costs and cost-effectiveness of four strategies for the prevention of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal (GI) toxicity: (1) Cox-1 NSAIDs plus histamine-2 receptor antagonist (H2RA), (2) Cox-1 NSAIDs plus proton pump inhibitors (PPIs), (3) Cox-1 NSAIDs plus misoprostol, and (4) Cox-2 NSAIDs (later expanded to 4a Cox-2 coxibNSAIDs and 4b Cox-2 preferential NSAIDs). DATA SOURCES: Electronic databases up to May 2002. REVIEW METHODS: Relevant studies were selected, assessed and analysed. Pooled relative risk ratios (RR) from the systematic review were combined with up-to-date UK resource use and unit costs data in an incremental economic analysis. A probabilistic decision-analytic model was designed and populated with data to carry out incremental economic analysis. Incremental cost-effectiveness ratios (ICERs) were generated for the outcome measure, endoscopic ulcer or serious GI event averted, against total cost, and non-parametric bootstrapping was used to simulate variance of these ICERs. RESULTS: Of 118 selected trials, including 125 relevant comparisons (which included 76,322 participants) only 138 deaths and 248 serious GI events were reported. Seven comparisons were judged to be at low risk of bias. Comparing the gastroprotective strategies against placebo, there was no evidence of effectiveness of H2RAs against any primary outcomes (few events reported), PPIs may reduce the risk of symptomatic ulcers [RR 0.09, 95% confidence interval (CI) 0.02 to 0.47], misoprostol reduces the risk of serious GI complications (RR 0.57, 95% CI 0.36 to 0.91) and symptomatic ulcers (RR 0.36, 95% CI 0.20 to 0.67), Cox-2 'preferentials' reduce the risk of symptomatic ulcers (RR 0.41, 95% CI 0.26 to 0.65) and Cox-2 'coxibs' reduce the risk of symptomatic ulcers (RR 0.49, 95% CI 0.38 to 0.62) and possibly serious GI events (RR 0.55, 95% CI 0.38 to 0.80). All strategies except Cox-2 'preferentials' reduce the risk of endoscopic ulcers. There were only 12 direct comparisons between gastroprotective strategies. All they suggest is that Cox-2 preferentials are better than misoprostol for preventing GI complications. Indirect comparisons suggested that PPIs may prevent symptomatic ulcers better than Cox-2 coxibs, but this is very weak evidence. For prevention of endoscopic ulcers PPIs and misoprostol appear more successful than H2RAs and misoprostol is better than Cox-2 preferentials. There were no UK head-to-head published economic analyses with regard to the main gastroprotective strategies. There were generally insufficient data with regards to cardiac or renal outcomes, serious GI outcomes or life-years gained to populate the mode. Mean (2.5th and 97.5th percentile) costs per endoscopic ulcer averted compared with Cox-1 NSAIDs alone were as follows: Cox-1 plus H2RAs, -186 pounds (-555 to 804); Cox-1 plus PPIs, 454 pounds (251 to 877); Cox-1 plus misoprostol, 54 pounds (-112 to 238); Cox-2 selective NSAIDs, 263 pounds (-570 to 1280), or Cox-2 specific NSAIDs, 301 pounds (189 to 418). With regard to the prevention of endoscopic ulcers, Cox-1 NSAID plus H2RA is a dominant option. Cost-effectiveness acceptability analysis showed a 95% probability that this combination was less costly and more effective. Cost-effectiveness acceptability frontiers showed that if the decision-maker is willing to pay up to 750 pounds to avoid an endoscopic ulcer, then Cox-1 plus H2RA is the optimal strategy. If the decision-maker is willing to pay over 750 pounds, the optimal strategy is NSAID plus misoprostol. Between 1900 pounds and 3750 pounds, Cox-2 selective inhibitors are optimal, and over 3750 pounds, Cox-2 specific inhibitors become optimal. NSAID plus PPI is never the optimal strategy. Sensitivity and subgroup analyses suggest that Cox-1 NSAID plus H2RA and Cox-1 NSAID plus misoprostol become more cost-effective in the older age group. Some conclusions were associated with high levels of uncertainty. CONCLUSIONS: Although there is a very large body of evidence comparing Cox-2 NSAIDs with Cox-1 NSAIDs, this is not matched by studies of the other types of gastroprotectors or by studies directly comparing active gastroprotective strategies. This lack of direct comparisons led to the use of indirect comparisons to help understand the relative efficacy of these strategies. Indirect evidence in itself is weak and was also hampered by lack of evidence in the underlying studies (where the gastroprotectors were compared with placebo). Economic modelling suggests that Cox-1 NSAID plus H2RA or Cox-1 NSAID plus PPI are the most cost-effective strategies for avoiding endoscopic ulcers in patients requiring long-term NSAID therapy. All strategies other than Cox-2 selective inhibitors reduce the rate of endoscopic ulcer compared with Cox-1 alone. The economic analysis suggests that there may be a case for prescribing H2RAs in all patients requiring NSAIDs. Misoprostol is more effective, but is associated with a greater cost and GI side-effects which may be unacceptable for patients. However, when assessing serious GI events, the economic analysis is sufficiently weakened by the data available as to render clear practice recommendations impossible. Further large, independent RCTs directly comparing various gastroprotective strategies are needed. These should report items such as major outcomes, primary data, adverse events, assessment of practice and patient preference.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model.

OBJECTIVES: To compare patient outcomes, resource use and costs to the NHS and NHS Blood Transfusion Authority (BTA) associated with cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion. DATA SOURCES: Electronic databases covering the period 1996-2004 for systematic reviews and 1994-2004 for economic evidence. REVIEW METHODS: Existing systematic reviews were updated with data from selected randomised controlled trials (RCTs) that involved adults scheduled for elective non-urgent surgery. Any resource use or cost data were extracted for potential use in populating an economic model. Relative risks or weighted mean difference of each outcome for each intervention were assessed, taking into account the number of RCTs included in each outcome and intervention and the presence of any heterogeneity. This allowed indirect comparison of the relative effectiveness of each intervention when the intervention is compared with allogeneic blood transfusion. A decision analytic model synthesised clinical and economic data from several sources, to estimate the relative cost-effectiveness of cell salvage for people undergoing elective surgery with moderate to major expected blood loss. The perspective of the NHS and patients and a time horizon of 1 month were used. The economic model was developed from reviews of effectiveness and cost-effectiveness and clinical experts. Secondary analysis explored the robustness of the results to changes in the timing and costs of cell salvage equipment, surgical procedure, use of transfusion protocols and time horizon of analysis. RESULTS: Overall, 668 studies were identified electronically for the update of the two systematic reviews. This included five RCTs, of which two were cell salvage and three preoperative autologous donation (PAD). Five published systematic reviews were identified for antifibrinolytics, fibrin sealants and restrictive transfusion triggers, PAD plus erythropoietin, erythropoietin alone and acute normovolaemic haemodilution (ANH). Twelve published studies reported full economic evaluations. All but two of the transfusion strategies significantly reduced exposure to allogeneic blood. The relative risk of exposure to allogeneic blood was 0.59 for the pooled trials of cell salvage (95% confidence interval: 0.48 to 0.73). This varied by the type and timing of cell salvage and type of surgical procedure. For cell salvage, the relative risk of allogeneic blood transfusion was higher in cardiac surgery than in orthopaedic surgery. Cell salvage had lower costs and slightly higher quality-adjusted life years compared with all of the alternative transfusion strategies except ANH. The likelihood that cell salvage is cost-effective compared with strategies other than ANH is over 50%. Most of the secondary analyses indicated similar results to the primary analysis. However, the primary and secondary analyses indicated that ANH may be more cost-effective than cell salvage. CONCLUSIONS: The available evidence indicates that cell salvage may be a cost-effective method to reduce exposure to allogeneic blood transfusion. However, ANH may be more cost-effective than cell salvage. The results of this analysis are subject to the low quality and reliability of the data used and the use of indirect comparisons. This may affect the reliability and robustness of the clinical and economic results. There is a need for further research that includes adequately powered high-quality RCTs to compare directly various blood transfusion strategies. These should include measures of health status, health-related quality of life and patient preferences for alternative transfusion strategies. Observational and tracking studies are needed to estimate reliably the incidence of adverse events and infections transmitted during blood transfusion and to identify the lifetime consequences of the serious hazards of transfusion on mortality, health status and health-related quality of life.

Aminocaproates↗
PubMed2005

Preventing non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: are older strategies more cost-effective in the general population?

OBJECTIVES: To assess the relative cost-effectiveness of five gastroprotective strategies for patients in the general population not judged to be at high gastrointestinal (GI) risk requiring regular traditional (t) non-steroidal anti-inflammatory drugs (NSAIDs) for over 3 weeks: tNSAID/H(2) receptor antagonists (H(2)RAs); tNSAID/proton pump inhibitors (PPIs); tNSAID/misoprostol; COX-2 preferential NSAIDs or COX-2-specific NSAIDs (COXIBs). METHODS: A systematic review of outcomes and UK cost data were combined in an incremental economic analysis. Incremental cost-effectiveness ratios were generated for quality-adjusted life years (QALYs) gained. RESULTS: Cost-utility analysis showed a tNSAID with a H(2)RA is safer and less costly than tNSAIDs alone, and equally effective and less costly than COXIBs. tNSAID/misoprostol was also dominated by tNSAID/H(2)RA due to withdrawal caused by side-effects reducing overall health status. The incremental increase in QALYs gained by using COXIBs instead of tNSAID/H(2)RA would cost 670,000 pounds per QALY gained. The incremental increase in QALYs gained by using tNSAID/PPI instead of COXIBs would cost 26,000 pounds per QALY gained. If the decision-maker will pay up to 140,000 pounds per extra QALY, the optimal strategy is tNSAID/H(2)RA. If the decision-maker will pay over this the optimal strategy is tNSAID/PPI. CONCLUSION: The economic analysis suggests that there may be a case for prescribing H(2)RAs in all patients requiring NSAIDs. Our recommendations are tentative due to the quality of the data available and the assumptions we have had to make in our model, and it is possible that other strategies may be preferred in patients with higher baseline GI risk.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Clinical and economic choices in the treatment of respiratory infections in cystic fibrosis: comparing hospital and home care.

BACKGROUND: A cost-effectiveness evaluation comparing home-based and hospital-based treatment with intravenous antibiotics for respiratory exacerbations in adults with cystic fibrosis (CF) has not been previously undertaken. METHODS: The study was conducted in a UK adult CF centre from a health service perspective. Clinical outcome and resource use data were obtained from a retrospective one-year study and combined with unit cost data in an incremental economic analysis. The primary outcome measure was percentage change in FEV(1); "effectiveness" was defined as maintenance of baseline average FEV(1) over the one-year study period. RESULTS: 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year, there had been a mean percentage decline in FEV(1) compared with baseline average for home-treated patients but an improvement for hospital-treated patients (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). Treatment was deemed "effective" in more hospital (58.8%) than home (42.6%) patients. The cost of hospital treatment was higher than home treatment (mean difference 9,005 pounds, 95% CI 3,507 to 14,700, p<0.001). The mean ICER was 46,098 pounds (2.5th and 97.5th percentiles -374,044 and 362,472). CONCLUSIONS: Hospital treatment was more effective but more expensive than home treatment. Potential methods to improve outcome at home should be considered but these may have resource implications.

Analysis of Variance↗
PubMed2004

Systematic review of the analgesic efficacy and tolerability of COX-2 inhibitors in post-operative pain control.

OBJECTIVE: To evaluate the relative analgesic efficacy and tolerability of single-dose COX-2 inhibitors in post-operative pain management. METHOD: Systematic review of randomized controlled trials (RCTs). OUTCOME MEASURES: The area under the pain relief vs. time curve was used to evaluate the proportion of patient achieving at least 50% pain relief using validated equations. The proportions of patients experiencing any adverse event or specific adverse events were also examined. RESULTS: In all, 18 RCTs were included which contained 2783 patients. The results of the effects of single-dose analgesics on the basis of 50% of patients achieving pain relief over 6 h from dental pain models suggested that oral rofecoxib 50 mg was more effective than codeine/paracetamol 60/600 mg, and the rate ratio (RR) was 2.11 (95% CI 1.6-2.75). Valdecoxib 40 mg was also more effective than oxycodone/paracetamol 10/1000 mg (RR 1.34; 95% CI 1.11-1.62). There was no significant differences between other oral COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs), except that celecoxib 200 mg was less effective than ibuprofen 400 mg (RR 0.66; 95% CI 0.48-0.90) and rofecoxib 50 mg (RR 0.65; 95% CI 0.49-0.87). The results from orthopaedic pain model showed no significant difference between rofecoxib 50 mg and naproxen sodium 550 mg (RR 1.04; 95% CI 0.73-1.49). The adverse effects of single-dose COX-2 inhibitor used in short-term post-operative pain management were generally mild and less than non-selective NSAIDs, although there was no significant difference. CONCLUSIONS: The analgesic efficacy and tolerability of single-dose COX-2 inhibitors were more effective than opioid-containing analgesics and similar to non-selective NSAIDs in post-operative pain management. Further studies are needed to examine the efficacy and tolerability of COX-2 inhibitors compared against active comparators over a longer duration to assess whether these short-term effects are mirrored by longer-term outcomes and to determine their ultimate risk-benefit profile.

Analgesics, Non-Narcotic↗
PubMed2003

Anaesthetic agents in adult day case surgery.

This study reports a review of all comparative published studies of adult day case anaesthesia in the English language up to December 2000. Ten databases were searched using appropriate keywords and data were extracted in a standardized fashion. One hundred-and-one published studies were examined. Recovery measurements were grouped as early, intermediate, late, psychomotor and adverse effects. With respect to induction of anaesthesia, propofol was superior to methohexital, etomidate and thiopental, but equal to sevoflurane and desflurane. Desflurane and sevoflurane were both superior to thiopental. There was no detectable difference between sevoflurane and isoflurane. With respect to the maintenance of anaesthesia, isoflurane and halothane were the worst. There were no significant differences between propofol, desflurane, sevoflurane and enflurane. Propofol is the induction agent of choice in day case patients. The use of a propofol infusion and avoidance of nitrous oxide may help to reduce postoperative nausea and vomiting.

Adult↗
PubMed2003

Anaesthesia for day case surgery: a survey of adult clinical practice in the UK.

BACKGROUND AND OBJECTIVE: In October 2000, we conducted a national postal survey of consultant day case anaesthetists in the UK to explore the range and variation in the practice of anaesthetizing a patient for day case surgery (paediatrics, urology and orthopaedics). The survey was carried out as part of a larger study that comprised a major two-centre randomized controlled trial designed to investigate the costs and outcome of several anaesthetic techniques during day care surgery in paediatric and adult patients (cost-effectiveness study of anaesthesia in day case surgery). We report the findings of this national survey of adult urology and orthopaedic day case anaesthetic practice in the UK. METHODS: The survey used a structured postal questionnaire and collected data on the duration of the surgical procedure; the use of premedication; the anaesthetic agents used for induction and maintenance; the fresh gas flows used for anaesthesia; the use of antiemetics; and the administration of local anaesthesia and analgesia. RESULTS: The overall response rate for the survey was 74% (63% for urology, 67% for orthopaedics). The survey indicated the following practice in adult urology and adult orthopaedic day case surgery: 6 and 12% used premedication; propofol was the preferred induction agent (96 and 97%) and isoflurane the preferred maintenance agent (56 and 58%); 32 and 41% used prophylactic antiemetics; 86 and 93% used a laryngeal mask. CONCLUSIONS: This survey identifies the variation in current clinical practice in adult day surgery anaesthesia in the UK and discusses this variation in the context of current published evidence.

Adult↗
PubMed2003

Anaesthesia for day case surgery: a survey of paediatric clinical practice in the UK.

BACKGROUND AND OBJECTIVE: In October 2000, we conducted a national postal survey of day case consultant anaesthetists in the UK to explore the range and variation in practice of anaesthetizing a patient for day case surgery (paediatrics, urology and orthopaedics). This paper reports the findings of this national survey of paediatric day case anaesthetic practice carried out as part of a major two-centre randomized controlled trial designed to investigate the costs and outcome of several anaesthetic techniques during day care surgery in paediatric and adult patients (cost-effectiveness study of anaesthesia in day case surgery). METHODS: The survey used a structured postal questionnaire and collected data on the duration of surgical procedure; the use of premedication; the anaesthetic agents used for induction and maintenance; the fresh gas flow rates used for general anaesthesia; the use of antiemetics; and the administration of local anaesthesia and analgesia. RESULTS: The overall response rate for the survey was 74 and 63% for the paediatric section of the survey. Respondents indicated that 19% used premedication, 63% used propofol for induction, 54% used isoflurane for maintenance, 24% used prophylactic antiemetics and 85%, used a laryngeal mask. The findings of this national survey are discussed and compared with published evidence. CONCLUSIONS: This survey identifies the variation in clinical practice in paediatric day surgery anaesthesia in the UK.

Ambulatory Surgical Procedures↗
PubMed2003

Clinical and economic choices in anaesthesia for day surgery: a prospective randomised controlled trial.

We compared the cost-effectiveness of general anaesthetic agents in adult and paediatric day surgery populations. We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups. Total costs were calculated from individual patient resource use to 7 days post discharge. Incremental cost-effectiveness ratios were expressed as cost per episode of postoperative nausea and vomiting (PONV) avoided. In adults, variable secondary care costs were higher for propofol induction and propofol maintenance (propofol/propofol; p < 0.01) than other groups and lower in propofol induction and isoflurane maintenance (propofol/isoflurane; p < 0.01). In both studies, predischarge PONV was higher if sevoflurane/sevoflurane (p < 0.01) was used compared with use of propofol for induction. In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).

Adolescent↗
PubMed2003

Propofol and halothane versus sevoflurane in paediatric day-case surgery: induction and recovery characteristics.

BACKGROUND: The aim of this study was to compare the induction and recovery characteristics associated with propofol induction and halothane maintenance with sevoflurane anaesthesia in paediatric day surgery. METHODS: In total, 322 children were assigned randomly to i.v. propofol induction and halothane/nitrous oxide maintenance or sevoflurane/nitrous oxide alone. The patients' age, sex, and type of surgery were recorded, as were the times required for anaesthetic induction, maintenance, recovery and time to discharge home. Postoperative nausea and vomiting, and the incidence of adverse events during induction and recovery were also noted. RESULTS: No significant differences were detected in age, sex, type of surgery performed or intraoperative opioid administration. Excitatory movement was more common during induction with sevoflurane. The mean time required for induction with propofol was 3.1 min compared with 5 min in the sevoflurane group (P<0.001). The recovery time was shorter in the sevoflurane group compared with propofol/halothane (23.2 vs 26.4 min, P<0.002). The incidence of delirium in recovery was greater in the sevoflurane group (P<0.001). There was no difference between groups in the time spent on the postoperative ward before discharge home. On the postoperative ward the incidence of both nausea and vomiting was significantly higher in the sevoflurane group (P=0.034). Five children were admitted to hospital overnight, none for anaesthetic reasons. CONCLUSIONS: The increased incidence of adverse events during induction, postoperative nausea and vomiting and postoperative delirium in the sevoflurane group suggests that sevoflurane is not ideal as a sole agent for paediatric day case anaesthesia.

Adolescent↗
PubMed2001

Improving benzodiazepine prescribing for elderly hospital inpatients using audit and multidisciplinary feedback.

BACKGROUND: Benzodiazepines are commonly prescribed for older people. Inappropriate benzodiazepine prescribing may result in serious adverse effects, including confusion and falls. AIMS: To determine the prevalence and appropriateness of benzodiazepine prescribing for elderly inpatients at nine public hospitals in Victoria, Australia, and to assess the impact of multidisciplinary feedback on quality of benzodiazepine prescribing. METHODS: Clearance for the study was obtained from ethics committees of participating hospitals. Medication charts for 1301 patients aged 65 years and over were reviewed to identify patients prescribed a benzodiazepine. Using an evidence-based indicator of prescribing appropriateness, cross-sectional notes-based audits were conducted at three time points (baseline, 4-8 weeks and 6 months). Feedback of baseline audit results was provided to medical, pharmacy and nursing staff at multidisciplinary meetings. Changes in benzodiazepine prescribing over the following 6 months were assessed. RESULTS: At baseline, benzodiazepines were prescribed for 36% of patients, and 20% of prescriptions were appropriate. Four to six weeks after feedback, the proportion of patients prescribed a benzodiazepine had not changed significantly (31%, P = 0.125); however, more prescriptions were appropriate (44%, P < 0.0001). For patients who were using a benzodiazepine prior to admission and had a contraindication, there were more attempts to withdraw or reduce the dose (47% vs 21%, P = 0.002) and more prescriptions were for acceptable indications (7.4% vs 2.6%, P = 0.024). Six months after feedback, appropriateness of prescribing remained improved compared with baseline (50%, P = 0.002). CONCLUSIONS: Benzodiazepines were prescribed for approximately one in three elderly hospital inpatients and a large proportion was inappropriate. A multidisciplinary intervention based on audit and feedback improved prescribing and the impact of the intervention was still evident after 6 months.

Aged↗
PubMed2001

Inhibition of the contractile responses of isolated human and rat bladders by clenbuterol.

PURPOSE: We investigated the inhibition of the contractile responses of human continent and unstable detrusor muscle by the beta2 agonist clenbuterol as well as the inhibition of electrical field stimulation evoked contractile responses of isolated rat bladder muscle strips by orally administered clenbuterol. MATERIALS AND METHODS: The contractile responses of human continent and unstable detrusor muscle strips to electrical field stimulation (0.05 milliseconds, 0.5 to 80 Hz.) were measured before and after adding 10(-9) to 10(-4) M. clenbuterol in vitro. In addition, 6 rats per group were dosed orally with 2 microg x kg(-1) clenbuterol daily acutely (1 dose) or chronically (1 dose daily for 8 days), or with distilled water to serve as controls. The contractile response to electrical field stimulation of strips of isolated detrusor muscle was then measured. Serum clenbuterol levels were analyzed in duplicate by enzyme-linked immunosorbent assay and high performance liquid chromatography. RESULTS: In vitro clenbuterol significantly inhibited the electrical field stimulation evoked contractile responses of detrusor muscle strips from unstable but not continent human bladders. A significant inhibitory effect of clenbuterol on the electrical field stimulation evoked contractile response of rat detrusor muscle was observed after chronic but not acute oral dosing (p <0.01). Serum clenbuterol levels measured by enzyme-linked immunosorbent assay and high performance liquid chromatography were not significantly different. CONCLUSIONS: Clenbuterol or related beta2-adrenoceptor agonists may represent a useful therapeutic strategy for detrusor muscle overactivity.

Adrenergic beta-Agonists↗
PubMed2000

K(ATP) channels mediate the beta(2)-adrenoceptor agonist-induced relaxation of rat detrusor muscle.

We propose that ATP-sensitive K(+) (K(ATP)) channels are normally inactive but involved in beta(2)-adrenoceptor stimulated relaxation of the rat bladder. Spontaneous detrusor muscle contractions were unaffected by glibenclamide (K(ATP) channel blocker) but were reduced when pinacidil (K(ATP) channel opener) concentrations exceeded 10(-5) M. Inhibition by beta(2)-adrenoceptor agonist clenbuterol [10(-6) M] of 1 Hz electrical field stimulated contractions was abolished by glibenclamide [10(-6) M]. Glibenclamide [10(-6) M] decreased forskolin-induced relaxation [10(-9)-10(-4) M] in bladder muscle stimulated with 1 Hz electrical field. In the presence glibenclamide (10(-6) M) or myristoylated protein kinase A inhibitor (2)x[10(-6) M], clenbuterol [10(-9)-10(-5) M] failed to inhibit bladder contraction in response to 1 Hz electrical field stimulation. Therefore, K(ATP) channel opening and the subsequent hyperpolarization of cell membranes in response to beta(2)-adrenoceptor activation is mediated by raised cyclic-AMP levels and activation of protein kinase A. This counteracts ATP-stimulated depolarization in bladder muscle, thereby reducing cell contraction.

Adenosine Triphosphate↗
PubMed2000

Inhibition of the contractile response of the rat detrusor muscle by the beta(2)-adrenoceptor agonist clenbuterol.

The action of clenbuterol, beta(2)-adrenoceptor agonist, on the contractile response of isolated rat detrusor muscle strips was investigated in vitro. Clenbuterol (10(-5) M) inhibited the detrusor muscle frequency response (1-40 Hz, p<0.02) with a more pronounced effect at 1 Hz than 40 Hz. Clenbuterol (10(-6) M) significantly inhibited the contractile response to exogenous ATP (10(-4) to 10(-2) M, p<0.05) but not to carbachol (10(-9) to 10(-4) M). The presence of 10(-5) M ICI 118, 551, beta(2)-adrenoceptor antagonist, shifted significantly the clenbuterol dose-response to 1 Hz electrical field stimulation (EC(50) 3.4x10(-6) M (+/-2.2x10(-6) M) for clenbuterol alone, to 4.1x10(-4) M (+/-8.8 x10(-5) M), P<0.05). In conclusion, clenbuterol inhibits electrical field and ATP-stimulated contractions of detrusor muscle. Reversal of the clenbuterol inhibition of detrusor muscle contraction by ICI 118, 551 shows that clenbuterol is probably acting through postsynaptic beta(2)-adrenoceptors, which modulate the response to ATP released from purinergic nerves.

Adenosine Triphosphate↗
PubMed2000

Inhibition of isolated rat and human detrusor muscle contraction by disopyramide.

1. The aim of this study was to investigate the effect of in vitro and in vivo disopyramide treatment on human and rat isolated detrusor muscle contractile response. Muscle strips were suspended in an organ bath chamber containing Kreb's solution at 37 degrees C aerated with 95% oxygen and 5% carbon dioxide. 2. Disopyramide antagonized significantly the contractile response of isolated human detrusor muscle to carbachol stimulation, shifting the concentration-response curve to the right in a parallel manner. The pA2 for competitive inhibition was estimated to be 6.4 with a slope of 0.64 for disopyramide. 3. Rat detrusor muscle contractile response to electrical field stimulation (EFS) was inhibited by 28% (P < 0.01) after in vitro administration of disopyramide (7.5 x 10(-6) M). Disopyramide had no effect on the atropine-resistant component of the response to EFS or on spontaneous contractions of isolated rat detrusor muscle strips. The concentration-response curve to carbachol was competitively antagonized by disopyramide with a pA2 of 6.3 and a Schild curve a slope of 0.85. 4. Disopyramide (7.5 x 10(-6) M) had no effect on rat detrusor contractile response to low concentrations of KCl but at high concentrations contraction was reduced significantly by 16% (P < 0.01). 5. In vivo treatment of rats with disopyramide for 8 days or with a single dose had a significant inhibitory effect on the contractile response of detrusor muscle strips. 6. In conclusion, disopyramide had a significant anticholinergic effect on isolated human and rat detrusor muscle contraction.

Aged↗