Search PubMed⌕ Search

Biomedical subjects

D J Reynolds

Publications and source records attributed to D J Reynolds.

At least 19 recordsLinked to original sources
PubMed1999

Actions of 5-HT on human neocortical neurones in vitro.

Using intracellular recordings, we have studied the action of 5-hydroxytryptamine (5-HT) on slices of human temporal, occipital and frontal cortex maintained in vitro. The recordings were usually made 1.2 to 1.5 mm down from the pial surface, in or around layer III. The action of 5-HT (30-50 microM) was studied on 21 cells (from 12 individuals) which had electrophysiological characteristics of glutamatergic pyramidal neurones. 5-HT depolarised the majority (11) of these cells with a median response of 5 mV. It produced a hyperpolarising response in five neurones (median=-4 mV) and a combined hyperpolarising/depolarising response in two others. No response was detected in three cells. The depolarising response was probably mediated by reducing a resting potassium conductance. Ketanserin (0.1 and 1.0 microM) and spiperone (1 microM) reduced the response indicating that it was likely mediated by 5-HT2A receptors. The hyperpolarising response was associated with the opening of ion channels and was blocked by the selective 5-HT1A receptor antagonist WAY-100635 (100 nM). 5-HT inhibited spontaneous synaptic potentials. This effect was reduced by ketanserin (1 microM) but not by WAY-100635 (100 nM). It is concluded that human neocortical neurones in vitro can be depolarised via 5-HT2A receptors and hyperpolarised via 5-HT1A receptors.

Electrophysiology↗
PubMed1999

Cost-effectiveness of ondansetron for postoperative nausea and vomiting.

The decision as to whether prophylaxis against postoperative nausea and vomiting is better than treatment of established postoperative nausea and vomiting could be made on the basis of cost-effectiveness. The cost-effectiveness of ondansetron was calculated using data from published quantitative systematic reviews of randomised trials. Milligrams of ondansetron required to achieve a desired endpoint were chosen as a cost unit. Modelling was based on a cohort of 1000 patients, and examined control event rates (i.e. incidence of postoperative nausea and vomiting without prophylaxis) of between 10 and 90%. In a sensitivity analysis, cost-effectiveness of recommended intravenous doses (4 mg for treatment and prophylaxis) was compared with minimal effective doses as shown by meta-analysis (1 mg for treatment, 8 mg for prophylaxis). Fewer patients experience any postoperative nausea and vomiting symptoms with prophylaxis compared with treatment. But prophylaxis is only marginally more effective than treatment, and treatment of established postoperative nausea and vomiting with effective doses (i.e. 1 or 4 mg) is more cost-effective and safer than prophylaxis with effective doses (i.e. 4 or 8 mg). Reasons for this are the selective treatment of patients who actually need treatment, the high success rate with a lowest dose tested (1 mg) in established postoperative nausea and vomiting, and the disappointing antinausea effect of prophylactic ondansetron even at an eight-fold higher dose.

Antiemetics↗
PubMed1998

Efficacy of 5-HT3 receptor antagonists in radiotherapy-induced nausea and vomiting: a quantitative systematic review.

5-HT3 receptor antagonists are used to treat radiation-induced sickness. The purpose of this study was to define anti-emetic efficacy and potential for harm of these drugs in radiotherapy. A systematic search, critical appraisal and quantitative analysis of relevant data using the number-needed-to-treat or harm (NNT/H) were conducted. Acute (0 to 24h) and delayed (beyond 24 h) anti-emetic efficacy were analysed separately. Data from 1,404 patients were found in 40 trials published in 36 reports. Data from 197 patients receiving ondansetron or granisetron in five randomised trials were regarded as valid according to preset criteria. One placebo-controlled trial had 10 patients per group and in this ondansetron was not significantly different from placebo. In a larger (n = 105) placebo-controlled trial, ondansetron was significantly more efficacious than metoclopramide for complete control of acute vomiting (NNT 2.2, 95% confidence interval (CI) 1.7-3.3) and acute nausea (NNT 3.6, 95% CI 2.2-10.2). Three trials reported delayed outcomes with ondansetron or granisetron: there was no evidence of any difference compared with placebo or other anti-emetics. Two trials reported no acute or delayed but a 'worst day' outcome; in these ondansetron's antivomiting effect was significantly better than placebo (NNT 4.4, 95% CI 2.5-23) or prochlorperazine (NNT 3.8, 95% CI 2.4-10.3), but not its antinausea effect. Constipation and headache were associated significantly with 5-HT3 receptor antagonists compared with other anti-emetics or placebo (NNH 6.4 and 17.1, respectively). Only 14% of published data enabled valid estimation of the anti-emetic efficacy of 5-HT3 receptor antagonists in radiotherapy. There was some evidence that these drugs prevent acute vomiting: 40% of treated patients will benefit (NNT approximately 2.5). The evidence for nausea was less clear. There was no evidence that these drugs are of any benefit beyond 24 h. There was evidence that they produce specific adverse effects.

Antiemetics↗
PubMed1998

Delay in presentation of patients with acute stroke to hospital in Oxford.

We identified prospectively all patients (181 patients, 183 episodes) admitted to hospital in Oxford with acute stroke from 1 January to 30 June 1997. Data were inadequate in 30, leaving 153 episodes in 151 patients (63 men, 90 women). Structured interviews were used to investigate the timing of events preceding admission. Most strokes (91%) occurred at home, and 36% of patients were alone. After a median delay of 15 min, 56% called a GP (median 30 min response), 41% an ambulance (median 48 min to admission), and 3% went directly to A&E. Median time from hospital admission to doctor assessment was 69 min. Factors reducing delay were: initially calling an ambulance rather than a GP (p < 0.0001); onset not at home (p < 0.001); symptoms improving between onset and admission (p < 0.002); and altered consciousness (p < 0.002). The stroke was not recognized by 44% of patients, but no significant delay resulted. Overall, 31% were admitted within 3 h of onset, 46% within 6 h. Initial contact with the GP is a major determinant of delay. If acute therapies for stroke become available, GPs should be the primary targets for an educational initiative.

Acute Disease↗
PubMed1997

Impact of covert duplicate publication on meta-analysis: a case study.

OBJECTIVE: To quantify the impact of duplicate data on estimates of efficacy. DESIGN: Systematic search for published full reports of randomised controlled trials investigating ondansetron's effect on postoperative emesis. Abstracts were not considered. DATA SOURCES: Eighty four trials (11,980 patients receiving ondansetron) published between 1991 and September 1996. MAIN OUTCOME MEASURES: Percentage of duplicated trials and patient data. Estimation of antiemetic efficacy (prevention of emesis) of the most duplicated ondansetron regimen. Comparison between the efficacy of non-duplicated and duplicated data. RESULTS: Data from nine trials had been published in 14 further reports, duplicating data from 3335 patients receiving ondansetron; none used a clear cross reference. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports not subject to duplicate publication, three reports subject to duplicate publication, and six duplicates of those three reports. The number needed to treat to prevent vomiting within 24 hours was 9.5 (95% confidence interval 6.9 to 15) in the 16 non-duplicated reports and 3.9 (3.3 to 4.8) in the three reports which were duplicated (P < 0.00001). When these 19 were combined the number needed to treat was 6.4 (5.3 to 7.9). When all original and duplicate reports were combined (n = 25) the apparent number needed to treat improved to 4.9 (4.4 to 5.6). CONCLUSIONS: By searching systematically we found 17% of published full reports of randomised trials and 28% of the patient data were duplicated. Trials reporting greater treatment effect were significantly more likely to be duplicated. Inclusion of duplicated data in meta-analysis led to a 23% overestimation of ondansetron's antiemetic efficacy.

Antiemetics↗
PubMed1997

A quantitative systematic review of ondansetron in treatment of established postoperative nausea and vomiting.

OBJECTIVES: To test the evidence for a dose-response with ondansetron for treatment of postoperative nausea and vomiting and to establish whether differences in efficacy between doses are of clinical relevance. DESIGN: Quantitative systematic review of published randomised controlled trials. DATA SOURCES: Seven trials from 1991 to January 1996 retrieved from a systematic literature search (Medline, reference lists, hand searching of anaesthetic journals, manufacturer's database); no restriction on language. MAIN OUTCOME MEASURES: Estimation of efficacy (incidence of complete control of further nausea and vomiting) by using odds ratios and the "number needed to treat" method for early (within 6 hours of administration) and late (within 24 hours) periods. RESULTS: Four placebo controlled trials with 1043 patients studied intravenous ondansetron 1 mg, 4 mg, or 8 mg. All doses were more efficacious than placebo in preventing further episodes of nausea or vomiting. For combined data, the point estimates for the number needed to treat were between 3.1 (8 mg) and 3.8 (1 mg) for early efficacy and between 4.1 (8 mg) and 4.8 (1 mg) for late efficacy, without significant differences between doses. No difference was found between ondansetron and droperidol in two trials with 129 patients or between ondansetron and metoclopramide in one trial with 80 patients. CONCLUSIONS: Further nausea and vomiting could be prevented with ondansetron compared with placebo in 25% of patients who had nausea or vomiting (number needed to treat, about 4). There was no evidence of a clinically relevant dose-response between 1 mg and 8 mg or a difference between ondansetron and either droperidol or metoclopramide in a limited dataset. A false impression of ondansetron's efficacy may arise because a quarter of all relevant published reports are duplicates, and reporting of study results is uncritical.

Antiemetics↗
PubMed1997

A transplacental carcinogenicity bioassay in CD-1 mice with zidovudine.

In oral carcinogenicity bioassays, zidovudine (ZDV) induced vaginal epithelial cell tumors in mice given 30 or 40 mg/kg/day and rats given 300 mg/kg/day. To determine if lifetime exposure to ZDV, beginning perinatally, would alter this pattern of carcinogenicity, two groups of 60 pregnant CD-1 mice were given 20 or 40 mg/kg/day of ZDV in 0.5% methyl cellulose from Gestation Day 10 through Lactation Day 21. At weaning, 2 pups per sex from each of 35 litters in each group were assigned to the study and given 20 or 40 mg/kg/day of ZDV in the drinking water until 17-35 days of age, followed by daily gavage for 24 months. Two additional groups of 60 pregnant CD-1 mice each were given 40 mg/kg/day of ZDV daily from Gestation Day 10 through Lactation Day 21; in one, ZDV treatment was halted at weaning and in the other, treatment was stopped 90 days after weaning. Two other groups of 60 pregnant CD-1 mice were left untreated (environmental control) or were given 0.5% methyl cellulose beginning on Gestation Day 10 (vehicle control). Vehicle control progeny received plain drinking water for 17-35 days postweaning and then 0.5% methyl cellulose daily by gavage for 24 months. ZDV treatment did not affect survival or body weight in either sex. In females given 20 or 40 mg/kg/day of ZDV for 24 months there was mild macrocytic anemia. Similar, non-dose-related changes were seen in males in these groups. ZDV-related tumor findings were limited to the vagina, where there were 2 and 11 vaginal squamous cell carcinomas in mice given 20 or 40 mg/kg/day of ZDV daily, respectively. This incidence was not remarkably different from that seen in previously reported bioassays. It was concluded that lifetime oral treatment of mice with ZDV, beginning perinatally, did not alter the previously reported pattern of carcinogenicity and that under the conditions tested ZDV was not a transplacental carcinogen.

Animals↗
PubMed1997

Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials.

OBJECTIVE: The authors reviewed efficacy and safety data for ondansetron for preventing postoperative nausea and vomiting (PONV). METHODS: Systematically searched, randomized, controlled trials (obtained through MEDLINE, EMBASE, Biological Abstracts, manufacturer's database, manual searching of journals, and article reference lists) were analyzed. Relevant end points were prevention of early PONV (within 6 h after surgery) and late PONV (within 48 h) and adverse effects. Relative benefit and number-needed-to-treat were calculated. The number-needed-to-treat indicated how many patients had to be exposed to ondansetron to prevent PONV in one of them who would have vomited or been nauseated had he or she received placebo. RESULTS: Fifty-three trials were found that had data from 7,177 patients receiving 24 different ondansetron regimens and from 5,712 controls receiving placebo or no treatment. Average early and late PONV incidences without ondansetron were 40% and 60%, respectively. There was a dose response for oral and intravenous ondansetron. Best number-needed-to-treat to prevent PONV with the best documented regimens was between 5 and 6. This was achieved with an intravenous dose of 8 mg and an oral dose of 16 mg. Antivomiting efficacy was consistently better than antinausea efficacy. Efficacy in children was poorly documented. Ondansetron significantly increased the risk for elevated liver enzymes (number-needed-to-harm was 31) and headache (number-needed-to-harm was 36). CONCLUSIONS: If the risk of PONV is very high, for every 100 patients receiving an adequate dose of ondansetron 20 patients will not vomit who would have vomited had they received placebo. The antinausea effect is less pronounced. Of these 100, three will have elevated liver enzymes and three will have a headache who would not have had these adverse effects without the drug.

Antiemetics↗
PubMed1996

Riluzole.

Explore the source record for details and available documents.

Humans↗
PubMed1996

Assessing the quality of reports of randomized clinical trials: is blinding necessary?

It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.

Double-Blind Method↗
PubMed1996

Adverse drug reactions in a hospital general medical unit meriting notification to the Committee on Safety of Medicines.

1. We have retrospectively analysed data collected by a local adverse drug reactions reporting scheme in an acute hospital medical setting and have determined the numbers and types of reactions that would have merited notification as yellow card reports according to the guidelines of the Committee on Safety of Medicines. 2. The data related to 20,695 consecutive acute general medical admissions on seven general medical wards (140 beds) and were collected over 3 years, from April 1990 to March 1993. 3. Over 3 years there were 1420 reports of suspected adverse drug reactions, a rate of 68.7 per 1000 admissions. 4. If the guidelines for reporting issued by the Committee on Safety of Medicines had been strictly followed, 477 yellow cards would have been sent (23.1 per 1000 admissions). In 357 of these reports (74.8%), the reaction had caused admission to hospital. Only 31 of the 477 potential cards (6.5%) involved black triangle drugs and 10 of these were for minor reactions. 5. Only 30 of the 477 potential yellow cards (6.3%) were known to have been sent. The majority of those reactions not reported were for drug-related admissions, most of which were for well-known reactions to established drugs. 6. We have confirmed and quantified the extent of under-reporting of serious suspected adverse drug reactions to the Committee on Safety of Medicines from our hospital medical unit.

Adverse Drug Reaction Reporting Systems↗
PubMed1995

Outbreak of vesicular dermatitis among horses at a midwestern horse show.

Dermatitis consisting of blisters on the nose and other parts of the body was reported among horses at a Midwestern horse show. Some horses also had jaundice, hematuria and anorexia. An outbreak investigation was initiated, and of 239 horses for which information could be obtained, 58 (24%) were found to have been affected. Median duration of illness was 5 days, and all horses recovered. Age, sex, water source, grain source, and stabling location were not associated with illness. The use of wood shavings bedding obtained at the show grounds was the factor most strongly associated with the development of vesicular lesions. Horses that became ill were 43 times more likely to have been bedded on wood shavings obtained from the show grounds than were horses that did not become ill. Among horses bedded on shavings from the show grounds, the risk was further increased by a factor of 5 if the shavings had been wetted. Neither organic nor heavy metal toxicants were identified in the samples of the wood shavings. However, samples did contain plant tissues originating from a tree belonging to the family Simaroubaceae, some species of which are known to cause vesicular eruptions in people.

Animals↗
PubMed1995

New characterization of infectious mononucleosis and a phenotypic comparison with Hodgkin's disease.

Recent nucleic acid hybridization studies have implied that Reed-Sternberg/Hodgkin (RS/H) cells are infected with Epstein-Barr virus (EBV) before malignant transformation, and hence, that Hodgkin's disease could develop as a consequence of malignant transformation of an EBV-infected cell. This study is a detailed immunohistochemical and in situ hybridization characterization of the various lymphoid cells in nine cases of infectious mononucleosis (IM), the acute manifestation of EBV infection. The RS/H-like cells of IM were similar in most respects to their morphologically identical counterparts in Hodgkin's disease; they expressed the EBV-encoded protein LMP1, EBV EBER1 transcripts, and CD30 and rarely, if ever, expressed CD45/LCA or T cell markers. Dissimilarities were limited to CD15 negativity and the absence of a collarette of T cells around the RS/H-like cells of IM compared with their Hodgkin's counterparts. Expression of the immortalizing bcl-2 oncoprotein was variable in the RS/H-like cells of IM, as has been demonstrated in the RS/H cells of Hodgkin's disease by other investigators. An apoptosis assay suggested that many apoptotic cells in IM were EBV-infected T cells, in keeping with the previous in vitro observation that IM-derived T cells succumb to apoptosis. Additionally, the apoptosis assay suggested that RS/H-like cells of IM can succumb to programmed cell death, reminiscent of the mummified RS/H cells seen in Hodgkin's disease. The accumulation of evidence suggests that RS/H-like cells of IM are more similar to true RS/H cells than previously recognized.

Adolescent↗