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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 109 records · Page 6Linked to original sources
PubMed1992

Lung cancer mortality among workers in the European production of man-made mineral fibers--a Poisson regression analysis.

One hundred and eighty-one lung cancer deaths among workers during 301,085 person-years in European man-made mineral fiber production between 1930-1955 and 1982 were analyzed according to Poisson regression models including age, calendar period, country, and exposure variables. Time since first employment was the variable most strongly associated with lung cancer risk in both the rock-slag wool and glass wool subcohorts. Workers in the early technological phase were at higher risk than those in other categories, particularly in rock-slag wool production. No clear trend with duration of employment was suggested. No major changes occurred in the interpretation of the results when workers with less than one year of employment or less than 20 years since first exposure were excluded. The original results, based on analyses for standardized mortality ratios, were confirmed, and workers with a short duration of employment or a short time since first employment did not need to be excluded from the analysis.

Air Pollutants, Occupational↗
PubMed1992

Leukemia in children and paternal radiation exposure at the Sellafield nuclear site.

Childhood cancer around nuclear installations has been studied in recent years, particularly in the United Kingdom but also in other countries. The early studies were prompted by the suggestion of a 10-fold raised level of childhood leukemia around the Sellafield nuclear site in England, which was confirmed and followed by the identification of generally smaller excesses around some (but not all) other nuclear sites in the United Kingdom. Marked excesses have not been reported in other countries. The increased leukemia rate around Sellafield has been further investigated by examining individual cases in detail in epidemiological cohort and case-control studies. The raised incidence seems to have been concentrated in children born in the local area but not among children who moved in after birth and was particularly associated with fathers who had experienced higher levels of occupational external ionizing radiation exposure at Sellafield before their children's conception. The underlying cause of this statistical association is not yet clear, but the findings have important potential implications for radiobiology and for protection of radiation workers and their children.

Adult↗
PubMed1991

Induction of fluconazole metabolism by rifampin: in vivo study in humans.

The effects of rifampin on the pharmacokinetics of fluconazole were analyzed in an open-label, placebo-controlled, parallel study. Sixteen healthy male volunteers, randomized into two groups, received 200 mg of oral fluconazole on days 1 and 22. On days 8 through 27, group I received oral rifampin, 600 mg/d, and group II received placebo. Fluconazole in serum was analyzed by HPLC. On days 1 and 22, respectively, the AUC (micrograms.hr/mL) (mean +/- SD) was 160.5 +/- 19.5 and 124 +/- 22.2 in group I, 152 +/- 25 and 152.8 +/- 33.9 in group II; the Kel (hr-1) was .0211 +/- .0030 and .0264 +/- .0040 in group I, .0219 +/- .0036 and .0216 +/- .0053 in group II. Cmax and Tmax did not change significantly in either group. Urinary 6 beta-hydroxycortisol/cortisol increased from 3.47 +/- 1.04 to 15.2 +/- 5.07 in group I, but was unchanged (3.54 +/- 1.33-4.26 +/- 2.36) in group II on days 1 and 22, respectively. The findings in this study indicate that rifampin induces the metabolism of fluconazole.

Administration, Oral↗
PubMed1991

Approaches to investigating clusters: by example, childhood leukaemia near Sellafield.

There is occasionally concern about suspected clusters of disease in geographically localised areas among members of the general public or other groups. These occurrences need a systematic approach to their investigation. Such an approach needs to consider the definition and characteristics of the cluster and of the putative environmental cause for concern. Depending on the outcome of these considerations there will be different actions, possibly involving epidemiological studies. The necessary components of the approach and resulting actions are outlined in this paper, and illustrated by the example of childhood leukaemia rates around the Sellafield nuclear plant.

Case-Control Studies↗
PubMed1991

Organisation and expression of small subunit ribosomal RNA genes encoded by a 35-kilobase circular DNA in Plasmodium falciparum.

A restriction map of the 35-kb circular DNA molecule of Plasmodium falciparum showed that a region of about 6 kb, encoding both a large and a small subunit ribosomal RNA gene, has been duplicated in inverted orientation. The complete sequence of one small subunit rRNA gene is presented as well as an analysis of transcripts from erythrocytic stage parasites. Comparative sequence analysis of the rRNA gene and the proposed secondary structure of the rRNA suggest that it is of organellar origin. Intriguingly, while some characteristics of the small subunit rRNA gene are similar to mitochondrial sequences, others are more like those of plastids. The origin of the circular DNA molecule and evolutionary implications of its genetic content are discussed.

Animals↗
PubMed1991

A circular DNA in malaria parasites encodes an RNA polymerase like that of prokaryotes and chloroplasts.

A 3.5-kb Sau3AI fragment was cloned from a circular DNA molecule isolated from the human malaria parasite Plasmodium falciparum and found to contain two contiguous open reading frames. These encode portions of beta and beta' subunits of an RNA polymerase similar to prokaryotic and chloroplast RNA polymerases, and contain highly conserved structural elements. The Plasmodium genes are arranged in a polycistronic transcription unit, as in both Escherichia coli and chloroplast genomes, and are transcribed in erythrocytic stages. These results suggest that the circular DNA may be an unusual mitochondrial DNA, or derived from an unidentified organelle. Because the beta subunit of prokaryotic RNA polymerases is the specific target of the antibiotic rifampicin, our observations may explain the high sensitivity of P. falciparum to this drug in vitro and indicate a new target for chemotherapy.

Amino Acid Sequence↗
PubMed1991

Have malaria parasites three genomes?

Recent efforts to define the mitochondrial genome of malaria parasites have uncovered an unexpected complexity: there are two almost totally dissimilar organellar DNA molecules. lain Wilson, Malcolm Gardner, Jean Feagin and Donald Williamson discuss the surprising possibility that Plasmodium may have, in addition to the nuclear genome, two unrelated organellar genomes, one evidently mitochondrial and the other of unknown function.

Journal Article↗
PubMed1991

8th Duncan Memorial Lecture. Childhood cancer and nuclear installations.

So where are we now? I think the first thing to say is that there is a well-established excess around Sellafield of childhood leukaemia, although excesses around other nuclear sites are of a lower magnitude. The excess near Sellafield is strongly associated with fathers having high exposure to external whole-body penetrating radiation while working at the installation before their child's conception. But is this association pointing towards a causal mechanism? One possibility is genetic damage, but most geneticists and radiobiologists would consider that the levels of occupational exposure, even at Sellafield, are too low for this to be a plausible pathway on current knowledge. This is based to some extent on the lack of any similar effect among children born subsequently to Japanese survivors of the atomic bombs--however, the scenario is somewhat different contrasting a high short-term exposure with a lower long-term exposure. As well, some workers at Sellafield will also be exposed to radionuclides, such as plutonium, which we have not yet been able to analyse for. In addition, there are other exposures in a complex environment which may or may not be relevant. One experimental study in the laboratory using animals supports the idea that a pathway through irradiation of the parents is plausible, although this one result needs replication. Other causes have been suggested for the excess childhood leukaemia levels in particular around nuclear establishments--these include population movement, implicating viruses that have long been considered to be associated with childhood leukaemia, high rates in isolated communities, and also selection of areas for nuclear sites that have a natural propensity to high rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Effect of fluconazole on the disposition of phenytoin.

In a randomized, placebo-controlled, parallel study, phenytoin was given in the presence and absence of fluconazole. Twenty healthy male subjects received phenytoin, 200 mg orally, on study days 1 to 3 and 18 to 20 and 250 mg intravenously on study days 4 and 21. Ten subjects received fluconazole, 200 mg orally, and 10 received placebo daily on study days 8 to 21. Serial blood samples were collected during a 24-hour period after the intravenous phenytoin dose. Fluconazole trough concentrations were determined on days 14, 18, and 21. Serum phenytoin area under the concentration-time curve from 0 to 24 hours increased 75% and minimum plasma drug concentration increased 128% after administration of fluconazole, 200 mg/day, for 14 days. These values were significantly greater than the 5% increase in area under the concentration-time curve from 0 to 24 hours and 11.6% increase in minimum plasma drug concentration in the placebo group. Fluconazole trough concentrations remained unchanged during the coadministration of phenytoin. The increased phenytoin concentrations in the presence of fluconazole suggest that fluconazole inhibits phenytoin metabolism. Serum concentration monitoring with a reduction in phenytoin dosage is clinically warranted in patients receiving phenytoin and concomitant fluconazole therapy.

Administration, Oral↗
PubMed1991

Interaction between cyclosporine and fluconazole in renal allograft recipients.

To determine the effect of fluconazole on cyclosporine concentrations, we used a randomized, double-blind, placebo-controlled study design to evaluate 16 stable renal transplant recipients receiving a constant cyclosporine dose. The two groups of patients were given identical capsules of either placebo or fluconazole 200 mg daily for 14 days. Compliance with the protocol was ensured by watching each patient take all the drug doses. Frequent whole-blood cyclosporine trough concentrations, measured by high-performance liquid chromatography, and two area under the blood concentration time curves were determined before and after 14 days of fluconazole or placebo. The results show that cyclosporine trough concentrations, in patients given fluconazole, increased from a mean +/- SD of 27 +/- 16 to 58 +/- 28 ng/ml (P = 0.001) while patients given placebo did not change--35 +/- 26 vs. 37 +/- 35 ng/ml (P = 0.7). Mean cyclosporine AUC increased in the fluconazole patients from 2167 +/- 1039 to 3989 +/- 1675 ng.hr/ml (P = 0.02) while the placebo patients did not change, 3089 +/- 2439 vs. 2954 +/- 2216 ng.hr/ml (P = 0.9). The pre- and post-treatment cyclosporine AUC difference (day 16 minus day 2) for fluconazole vs. placebo was 1822 +/- 1083 vs. -134 +/- 831 ng.hr/ml (P = 0.001). Mean cyclosporine clearance decreased an average of 55% in the fluconazole patients from 1.2 +/- 0.5 to 0.7 +/- 0.4 ml/hr.kg (P = 0.03); the placebo patients did not change--1.4 +/- 1.1 vs. 1.7 +/- 2.3 ml/hr.kg (P = 0.07). During the study period, serum creatinine concentrations did not increase after fluconazole vs. placebo treatment; they were 1.4 +/- 0.3 vs. 1.3 +/- 0.3 mg% (P = 0.8) initially, and 1.4 +/- 0.2 vs. 1.3 +/- 0.3 mg% (P = 0.5) after 14 days. This study indicates that fluconazole 200 mg daily can slowly increase cyclosporine concentrations over two weeks of therapy, approximately doubling the cyclosporine trough concentrations. The management of this interaction requires prospective planning for adjustments in the cyclosporine dosage, guided by cyclosporine concentrations, while transplant recipients are receiving fluconazole.

Adolescent↗
PubMed1991

Father's occupational exposure to radiation and the raised level of childhood leukemia near the Sellafield nuclear plant.

The first indications that childhood leukemia rates may be raised near the Sellafield nuclear plant in West Cumbria, England, came from largely anecdotal evidence in a television program "Windscale: The Nuclear Laundry" shown during 1983. During subsequent years, various epidemiological studies have investigated the claim in more detail. Geographical analyses of childhood leukemia incidence in the northern region and mortality in England and Wales using routinely available data made the first contribution. As a result, it was confirmed that leukemia rates in the area, particularly the neighboring village of Seascale, were high compared to other districts, although not totally extreme. Cohort studies of children born in Seascale or attending schools in Seascale were carried out to resolve some of the difficulties of interpretation of geographical analysis. Cohort studies indicated that the excess of leukemia was concentrated among children born in Seascale and was not found among those moving in after birth and suggested that any causal factors may be acting before birth or very early in life. A case-control study of leukemia (and lymphoma) among young people in West Cumbria has examined potentially important individual factors in detail. The study demonstrated a relationship between the raised incidence of leukemia in children and father's recorded external radiation dose during work at Sellafield before his child's conception. The association can effectively explain statistically the observed geographical excess.

Adolescent↗
PubMed1990

More informative abstracts revisited.

Following proposals in 1987 and 1988, several medical journals have provided more informative abstracts ("structured abstracts") for articles of clinical interest. Structured abstracts for original studies require authors to systematically disclose the objective, basic research design, clinical setting, participants, interventions (if any), main outcome measurements, results, and conclusions; and for literature reviews the objective, data sources, methods of study selection, data extraction and synthesis, and conclusions. More informative abstracts of this kind can facilitate peer review before publication, assist clinical readers to find articles that are both scientifically sound and applicable to their practices, and allow more precise computerized literature searches. We review the feasibility, acceptability, and dissemination of structured abstracts, reassess the underlying strategy, and describe modifications of the approach. This innovation can aid communication from scientists to clinicians, and other clinical journals are invited to join this effort.

Abstracting and Indexing↗