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Biomedical subjects

P Hewitt

Publications and source records attributed to P Hewitt.

At least 37 records · Page 2Linked to original sources
PubMed1992

Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro: further validation of an in vitro model by comparison with in vivo data.

The in vitro percutaneous absorption of three model compounds, nicotinic acid, phenol and benzoic acid, and the herbicide triclopyr butoxyethyl ester (triclopyr BEE) has been investigated in flow-through diffusion cells using skin from male Fischer 344 rats and humans. After the application of the four chemicals to the epidermal surface of unoccluded full-thickness rat skin, the absorption of each compound across the skin and into the receptor fluid at 72 hr reached 3.7 +/- 0.3, 5.7 +/- 0.6, 26.7 +/- 3.7 and 48.3 +/- 1.2% (mean +/- SD, n = 2-7) of the applied dose for triclopyr BEE, nicotinic acid, phenol and benzoic acid, respectively. After the application of the four chemicals to the epidermal surface of unoccluded full-thickness human skin, the absorption of each compound across the skin and into the receptor fluid at 72 hr was significantly (P < 0.05) less than through rat skin, reaching 0.7 +/- 0.1, 0.7 +/- 0.2, 18.8 +/- 1.3 and 37.8 +/- 6.9% (mean +/- SD, n = 2-7) of the applied dose for triclopyr BEE, nicotinic acid, phenol and benzoic acid, respectively. Occlusion of the skin surface with teflon caps often significantly (P < 0.05) enhanced the percutaneous absorption of the model compounds, although this effect was not uniform, varying with the compound under study and the skin (rat or human) used. When rat skin was occluded with teflon caps, the extent of absorption at 72 hr reached 8.6 +/- 0.8, 36.2 +/- 1.7 and 51.8 +/- 3.3% (mean +/- SD, n = 3-4) for nicotinic acid, phenol and benzoic acid, respectively. Corresponding values for human skin occluded with teflon caps were 3.3 +/- 1.6, 47.1 +/- 0.5 and 65.5 +/- 7.1% (mean +/- SD, n = 3-4). The experiments on the absorption of each model compound through rat and human skin were repeated and there was generally good agreement between the results from the two sets of experiments. The in vitro data reported compare favourably with data obtained by other workers using both in vitro and in vivo methodologies. The in vitro: in vivo correlation supports the use of the flow-through diffusion cell system as a model for the prediction of percutaneous absorption in vivo in the rat and in humans.

Absorption↗
PubMed1992

Genetic characterization of Legionella pneumophila serogroup 1 associated with respiratory disease in Australia.

Techniques were developed for genetic characterization of Legionella pneumophila serogroup 1 by using restriction fragment length polymorphism analysis. Allozyme analysis provided an index of the discrimination achieved by restriction fragment length polymorphism. Isolates from human cases of legionellosis were examined by both methods, and their profiles were compared with reference strains of L. pneumophila serogroup 1 obtained from the American Type Culture Collection. Eighteen distinct clones were evident among the isolates examined. Both methods could be used to trace the source of an outbreak of legionellosis caused by L. pneumophila serogroup 1.

Australia↗
PubMed1990

Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. A meta-analysis of randomized control trials.

Because individual studies evaluating the role of quinidine in the maintenance of sinus rhythm after cardioversion from chronic atrial fibrillation have involved relatively few patients, a meta-analysis of randomized control trials was performed. Six trials published between 1970 and 1984 were selected by two blinded reviewers based on study design and statistical analysis. Data from these six trials involving 808 patients were pooled after testing for homogeneity of treatment effects across trials. Life table estimates of the percent of patients still in sinus rhythm at 3, 6, and 12 months after cardioversion were constructed for quinidine and control groups. The proportion of patients remaining in sinus rhythm in the quinidine group was 69%, 58%, and 50% at 3, 6, and 12 months postcardioversion respectively. The proportion of patients remaining in sinus rhythm in the control group was 45%, 33%, and 25% at the same time intervals. The pooled rate difference, or difference in proportion of patients in sinus rhythm between quinidine and control groups, was 24%, 23%, and 24% at 3, 6, and 12 months of follow-up (p less than 0.001 at all time intervals). The unadjusted total mortality rate in the quinidine-treated patients was 2.9% and in the control group was 0.8%. The odds of dying in the quinidine-treated group were approximately three times that of the control group ("typical" odds ratio = 2.98, p less than 0.05). Thus, quinidine treatment is more effective than no antiarrhythmic therapy in suppressing recurrences of atrial fibrillation but appears to be associated with increased total mortality.

Adolescent↗
PubMed1989

Meta-analytic evidence against prophylactic use of lidocaine in acute myocardial infarction.

Although lidocaine prophylaxis reduces the incidence of ventricular fibrillation during acute myocardial infarction (AMI), randomized control trials (RCTs) have not demonstrated any significant mortality effect of this therapy. We conducted a meta-analysis of 14 RCTs of lidocaine prophylaxis during AMI to detect any mortality effect. Six prehospital- and eight hospital-phase RCTs that randomized totals of 7656 and 1407 patients, respectively, were selected and reviewed in a blinded fashion. Mortality data were evaluated according to therapy type, reporting interval, and patient category. The prehospital-phase RCTs showed no meaningful mortality effect (risk difference, 0.0184; 95% confidence interval, -0.048 to +0.012). The hospital-phase RCTs showed a statistically significant increase in mortality during the treatment period for lidocaine recipients (risk difference, 0.029; 95% confidence interval, +0.004 to +0.055). These results confirm that lidocaine administered to monitored patients during the prehospital phase of AMI will not reduce mortality by a clinically important amount and suggest that lidocaine administered in the hospital phase of monitored, uncomplicated AMI may increase mortality among recipients with proved AMI.

Clinical Trials as Topic↗
PubMed1988

Meta-analysis of randomized controlled trials as a method of estimating rare complications of non-steroidal anti-inflammatory drug therapy.

The design of randomized controlled trials to assess the efficacy of pharmacological measures for the prevention of the gastrointestinal side-effects of anti-inflammatory drugs requires an accurate estimate of excess risk under controlled conditions. Photocopies of 952 randomized controlled trial publications were obtained after scanning titles and abstracts of a MEDLINE computer search, 427 were excluded for obvious reasons, and 525 were again photocopied after obliterating source and results. Selection criteria were: the presence of a non-anti-inflammatory drug control group; at least 4 days of therapy; at least 3 days without anti-inflammatory drugs before randomization; no complicating background drugs; mention of side-effects; and a clear differentiation of gastrointestinal complications. Observer error, with two independent readings, for inclusion suitability in the study was 19% for Methods and 9% for Results. For the 44 aspirin trials, the mean therapy duration was 357 days; the unweighted rate difference between therapy and control groups ( +/- 1 S.E.M.) for ulcer was 0.006 +/- 0.003, for gross haemorrhage 0.006 +/- 0.002 and for unspecified gastric symptoms 0.03 +/- 0.01. In 123 non-aspirin non-steroidal anti-inflammatory drug (NA-NSAID) trials, the mean duration was 67 days; the unweighted rate difference for ulcer was 0.0005 +/- 0.0003, for gross haemorrhage 0.007 +/- 0.004 and for unspecified gastric symptoms 0.02 +/- 0.005. Risk differences were also pooled using the DerSimonian and Laird method, which weights studies inversely according to variance. Using this method, only the unspecified gastric symptoms for non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) and the haemorrhage for aspirin were found to be statistically significant. Longer studies have higher risk differences. Randomized control trials to determine prophylactic efficacy against haemorrhage (that is, to demonstrate a reduction of ulcer rate in the therapy group to the rate of controls) would require 190 patients in each group for NA-NSAIDs in studies of 2-6 months; 950 subjects would be needed to detect a 50% reduction. Randomized control trials to determine a reduction in ulcer rate to that of controls in patients on aspirin for more than 6 months would require 700 subjects in each group; 3346 subjects would be needed to detect a 50% reduction. Such studies are feasible.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

HIV infection due to a platelet transfusion after allogeneic bone marrow transplantation.

A 30-yr-old man with chronic granulocytic leukaemia received a bone marrow transplant from his histocompatible sister in December 1982. His post-transplant course was complicated by Grade III graft-versus-host disease and multiple infectious episodes until his death from pneumonia on d + 190. He was later found to be seropositive for anti-HIV at the time of his death. Retrospective analysis of stored sera showed a transient period of seropositivity from d + 11 to d + 20 thought to reflect passive transfer of antibody from a blood product transfused prior to d + 11 when he was also exposed to infectious virus. He remained seronegative until d + 78 when anti-HIV was again found. Seropositivity persisted until his death and was attributed to endogenous antibody response. Although it is unclear whether his clinical course was due to AIDS, exposure of an immunosuppressed patient to HIV may be associated with more rapid development of clinical disease.

Acquired Immunodeficiency Syndrome↗
PubMed1986

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National Library of Medicine (U.S.)↗
PubMed1986

Contrast, coagulation, and fibrinolysis.

Some adverse clinical effects of intravascular radiologic contrast agents have been attributed to their interference with the normal hemostatic processes. This study compares the effects of the low osmolality agents with those of the conventional agents by in vitro studies of platelet function, fibrin formation, and fibrinolytic activation. In various degrees, all the contrast agents studied inhibit platelet aggregation and fibrin formation but show virtually no direct activation of fibrinolysis. The new low osmolality agents generally show lesser inhibitory effects on the hemostatic mechanisms. Some clinical implications are discussed.

Blood Coagulation↗
PubMed1986

AIDS: a problem for the transfusion service?

The first case of AIDS associated with blood transfusion was described in 1982. Over the following two years great advances were made in the understanding and prevention of this new hazard associated with blood transfusion, culminating in 1985 with the introduction of a screening test for blood donation.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Perusing the literature: comparison of MEDLINE searching with a perinatal trials database.

The existence of a Register of Controlled Trials in Perinatal Medicine (National Perinatal Epidemiology Unit, Oxford, England) has offered an opportunity to assess the efficacy of online searching of MEDLINE, an example of a broad bibliographic database. Retrieval of all relevant randomized control trials (RCTs) in a given field is important in analyses in which results are pooled (meta-analyses). Reports of RCTs of prevention and treatment of neonatal hyperbilirubinemia and prevention of intraventricular hemorrhage (IVH) for the years 1966-1983 were sought in both the Register and MEDLINE files. Comparison of subject searches revealed a number of unlisted papers in each file that were then found to be present by an author search. In the MEDLINE searching an amateur was clearly less efficient than an expert, but the expert recovered only 29% of the relevant hyperbilirubinemia papers available in MEDLINE, and only 56% of the identified IVH RCTs. Some of the deficiencies in recovery have been corrected by indexing improvements, such as the capability of identifying text words in abstracts, and the addition of new medical subject heading terms (MeSH) such as RANDOM ALLOCATION. Efficiency will be best facilitated by authors and editors keeping the MeSH terms used by MEDLINE indexers in mind when they compose titles and abstracts.

Cerebral Hemorrhage↗