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Biomedical subjects

D J Reynolds

Publications and source records attributed to D J Reynolds.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Acute toxic and teratogenic effects of cyclic imides in rodents.

Four structurally different cyclic imides or related derivatives (o-(N-phthalimido)acetophenone (1), 2,3-dihydrophthalazine-1,4-dione (2), N-(4-methylphenyl)diphenamide (3), and 4,6-dihydro-5H-dibenz[c,e]azepine (4) were examined for acute toxicity in mice at multiple doses, for long term toxicity at a single dose in rats, and for deleterious effects on fertility and pup development in rodents. No deleterious effects were observed when mice were administered agents at 20, 50, and 100 mg/kg/day for seven days. All other measured characteristics and values were normal for the four compounds. The principle effect of the compounds was to reduce the percent pregnancies in treated mice compared to the controls. Compound 2 afforded the greatest reduction of pregnancy (54%) at 100 mg/kg/day. Compounds 3 and 4 caused a minor reduction in pregnancy (12-20%). The compounds did not appear to cause measureable teratogenic effects; pups of treated rodents thrived and survived as well as controls. There were no effects on murine male fertility when compounds were administered at 20, 50, and 100 mg/kg/day for six weeks.

Animals↗
PubMed1994

Evidence for cholinergic vagal afferents and vagal presynaptic M1 receptors in the ferret.

The distribution of muscarinic receptor binding was examined in the ferret brainstem vagal nuclei using the non-selective ligand [3H]quinuclidinyl benzilate and the relatively M1 receptor-selective ligand [3H]pirenzepine. The highest density of receptor sites are found in the subnucleus gelatinosus and lower levels in the other subnuclei of the nucleus of the tractus solitarius and in the area postrema and dorsal motor nucleus of the vagus nerve. Dense binding was also seen in the adjacent hypoglossal nucleus. Following unilateral cervical nodose ganglion excision binding in the subnucleus gelatinosus was attenuated ipsilateral to the lesion compared with the contralateral side. In contrast, [3H]pirenzepine binding was only seen in the subnucleus gelatinosus and in no other region at this level of the brainstem. This binding was reduced in the subnucleus as a whole by 52% ipsilateral to a cervical vagotomy. In the more rostral parts of the subnucleus gelatinosus, binding was undetectable ipsilateral to the lesion but more caudally, appreciable levels of binding persisted. This distribution parallels the known rostro-caudal variation in cross-over of vagal afferent fibres in the ferret dorsal vagal complex and indicates a presynaptic localization of [3H]pirenzepine binding sites on vagal afferent terminals. The distribution of binding of the high affinity choline uptake site blocker, [3H]hemicholinium-3, was also examined in the ferret brainstem using autoradiography. High densities of [3H]hemicholinium-3 binding were seen in the hypoglossal nucleus, the subnucleus gelatinosus and in the area postrema, with lower levels in the dorsal motor nucleus of the vagus, the trigeminal nucleus and other subnuclei of the nucleus of the tractus solitarius.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The epidemiology of carcinoid tumours in England and Scotland.

Relatively little is known about the epidemiology of carcinoid tumours in contrast to the extensive information available on their biochemical effects and natural history. Accordingly, we have used cancer registrations in England from 1979 to 1987, and in Scotland from 1980 to 1989, to estimate the incidence of carcinoid tumours in Britain. Age-standardised incidence rates for England, based on 3,382 registrations, were 0.71 (0.68-0.75) for men and 0.87 (0.83-0.91) for women, per 100,000 per year. The equivalent rates for Scotland, based on 639 registrations, were 1.17 (0.91-1.44) for men and 1.36 (1.09-1.63) for women. There was a consistent female excess of carcinoid tumours in the reproductive years, which was reversed after the age of 50. The female excess was most striking for gastrointestinal carcinoid tumours in women aged 15-19 years (F:M ratio = 2.14). The sex differences are probably due in part to incidental diagnosis of carcinoid tumours during abdominal procedures, which are more common in women than men at ages 15-49 years. However, there is some evidence to suggest a true sex difference in incidence, particularly the fact that the sex ratio for thoracic tumours varies with age in a similar way to that for gastrointestinal tumours. Hormonal factors may, therefore, be important in the aetiology of carcinoid tumours.

Adolescent↗
PubMed1994

Characteristics of Helicobacter pylori growth in a defined medium and determination of its amino acid requirements.

A defined medium has been developed for Helicobacter pylori that gives growth characteristics (growth rate, maximum cell number and maximum colony-forming-unit count) comparable to those in a complex medium (Isosensitest broth + 5%, v/v, foetal bovine serum). Differences found in the death rate reflected a partial (50%) conversion to a coccoid cell form of the organism in the stationary and death phase in the defined medium, versus the almost complete (> 99%) conversion seen in the complex medium. The medium was used to study the amino acids required for growth by 10 strains of H. pylori. All strains required arginine, histidine, isoleucine, leucine, methionine, phenylalanine and valine, and eight of the strains also required alanine; five of the strains required serine. In the absence of glucose none of the 20 amino acids tested elicited growth when added at high concentration. However, in the presence of glucose, alanine induced considerably enhanced growth over that seen in the control, consistent with its use either as a nitrogen source or possibly an additional carbon source. The medium described will facilitate investigations into the metabolism and physiology of H. pylori, previously only possible with sophisticated approaches such as nuclear magnetic resonance spectroscopy.

Amino Acids↗
PubMed1993

Low-nutrient induction of abnormal chlamydial development: a novel component of chlamydial pathogenesis?

The intracellular development of chlamydiae in McCoy cells incubated in Eagle's minimal essential medium lacking all 13 amino acids was examined both by fluorescence and electron microscopy and by infectivity titration. Aberrant development occurred in almost all inclusions of strains of Chlamydia trachomatis and C. psittaci with the production of abnormal forms which differed in size, shape and internal structure from normal reticulate and elementary body forms. Detailed analysis of the response of C. trachomatis L2 strain 434 to graded reductions in amino acid level showed that infectivity was reduced and morphological abnormality increased as amino acid concentrations were lowered from 33 to 0% of amino acids present in minimal essential medium. Reversion of inclusions to normal and reappearance of infectious forms occurred on restoration of amino acids and further incubation. It is suggested that aberrant development may account for the presence in vivo of non-cultivable chlamydiae and that such development can arise via tryptophan deprivation mediated by local release of interferon gamma.

Amino Acids↗