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Biomedical subjects

R D Thomas

Publications and source records attributed to R D Thomas.

At least 55 records · Page 3Linked to original sources
PubMed1994

Catalysis of the oxidation and reduction reactions of steroid and stilbene estrogens by nuclear enzymes.

We demonstrated for the first time that nuclei were able to convert a stilbene estrogen (diethylstilbestrol) to reactive metabolites, which covalently bind to nuclear proteins and DNA. Depending on the cofactor used, nuclear enzymes catalyzed oxidation and/or reduction of stilbene and steroid estrogens. 2-Hydroxyestradiol (a major metabolite of steroidal estrogen, 17 beta-estradiol) and diethylstilbestrol (DES) were oxidized to 2,3-estradiol quinone and DES quinone, respectively, by peroxide-supported nuclear cytochromes P450. A Lineweaver-Burk plot of rate of formation of DES quinone at various substrate concentrations yielded a Km = 15 microM and Vmax = 10 nmol/mg protein/min. The oxidation of DES to DES quinone by nuclei was drastically decreased by known inhibitors of cytochromes P450. DES quinone was reduced back to DES by nuclei in the presence of NADPH, presumably through cytochrome P450 reductase. The reduction of DES quinone to DES by nuclei was significantly inhibited by antibodies and inhibitors of cytochrome P450 reductase. Under reaction conditions similar to oxidation of DES to DES quinone by nuclei, it was observed that nuclear metabolic products of DES were able to covalently bind to nuclear proteins and DNA. The data reported here establish that DES and a catechol estrogen can be oxidized to quinones and that the quinones may be reduced back to the hydroquinones by nuclear preparations when fortified with an appropriate cofactor and that reactive intermediates are involved based on observed covalent binding to macromolecules. The significance of these events, and their possible role in toxicity/cancer/teratogenicity, however, is not at all clear.

Animals↗
PubMed1994

Environmental neurotoxic illness: research for prevention.

Recognition of the deleterious neurological effects of chemicals has evolved from anecdotal observation to studies of illness in persons exposed to high doses. Now, the more subtle effects of exposures to environmental neurotoxicants are being documented: reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alteration of behavior. Substances to which millions of persons are exposed occupationally and in the general environment that can result in such deficits include lead, organophosphorus pesticides, certain chlorinated hydrocarbons, carbon disulfide, solvents, and mercury. The first step in the prevention of neurological impairments due to environmental exposures is to assess the toxicity of chemicals. Fewer than 10% of the 70,000 chemicals in commercial use have been evaluated for neurotoxicity. This knowledge gap needs to be narrowed by building on existing systems of toxicity testing. Concurrent with assessment of chemicals will be tiers of in vivo screening tests to measure functional and structural changes following exposures in vitro. Epidemiologic surveillance of populations at high risk will continue to inform on the ranking of suspect or known neurotoxicants. Research and researchers must become more sophisticated in the development and application of refined biologic markers so the findings can be used to detect absorption of toxicants and early neurological or neurobehavioral dysfunction before disability occurs and to protect human health and the environment.

Biomarkers↗
PubMed1994

On their own.

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Colorado↗
PubMed1994

Increased mortality from inadequate provision of coronary care unit facilities.

Over a 6-month period, all patients admitted to the Royal United Hospital, Bath, with acute ischaemic heart disease were prospectively followed for the period of their hospital stay. Strict admission and discharge criteria were defined for the Coronary Care Unit (CCU), so that groups of patients could be identified in which the treatment was not ideal. The mortality in the groups of patients who were admitted to the CCU without delay and for an appropriate length of time was 5.1% (18/355). It was significantly higher overall in the groups of patients who were either not admitted (14.3%, 4/28) or whose admission was delayed (17.4%, 4/23). The results underline the importance of the provision of adequate coronary care facilities.

Aged↗
PubMed1993

Strategies for the prevention of environmental neurotoxic illness.

Toxic chemicals in the environment can cause a wide range of neurological disease. High-dose exposures to environmental neurotoxicants have produced encephalopathy in children ingesting chips of lead-based paint, blindness in persons who ingested methanol, blindness and ataxia in persons who consumed organic mercury, spinal cord degeneration and peripheral neuropathy in persons exposed to tri-ortho-cresyl phosphate (TOCP), and Parkinsonism in persons exposed to MPTP or to manganese. Environmental neurotoxicants have also been shown to produce a wide range of subclinical neurotoxic effects, including reduction in intelligence, impairment in reasoning ability, shortening of attention span, and alternation of behavior. The first step in the prevention of environmental neurotoxicity is to test chemicals for their toxic potential. More than 70,000 chemicals are currently in commerce. However, except for pharmaceuticals, fewer than 10% of these chemicals have been tested for neurotoxicity. A logical approach to neurotoxicologic assessment of chemical substances will build on and extend currently available test systems. It will have a tiered structure. The first or screening tier will consist of tests to measure obvious structural and functional changes, often a functional observational battery. Subsequent levels of testing will be guided by the results of initial screening. Toxicologic testing must be supplemented by epidemiologic surveillance of populations exposed to known and suspect neurotoxicants. Screening programs in these populations designed to detect excessive absorption of a neurotoxic agent or subclinical neurological dysfunction can be useful in identifying affected individuals before severe disability occurs.

Biomarkers↗
PubMed1993

A new frontier in understanding the mechanisms of developmental abnormalities.

Recent advancements in molecular developmental biology afford an opportunity to apply newly developed tools for understanding the mechanisms of both normal and abnormal development. Although a number of agents have been identified as causing developmental abnormalities, our knowledge of the mechanisms by which these alterations occur is minimal. This paper reviews some of the important issues in this area that may lead to understanding the basic developmental processes and mechanisms by which toxic agents may interfere with these processes. Approximately 70% of developmental defects are of unknown etiology. Historically, it has been assumed that these defects were most likely to be induced by exposure to chemical or physical agents during organogenesis. There is now convincing evidence that exposure during preorganogenesis developmental stages to certain agents can also lead to fetal abnormalities as a result of direct damage to the exposed early conceptus. Thus, pre- or postimplantation exposure of the developing conceptus to toxicants may result in a "derailment" in the genetic control of development and the coordinated cascade of events that occur during normal development. For example, developmental abnormalities may be induced by disrupting the coordinated expression of developmental genes involved in genomic imprinting, cell lineage specification, cell mixing and recognition, cell-cell interaction, cell migration and differentiation, and segmentation, depending on the time of exposure. Because of our lack of knowledge about the molecular and cellular bases of chemically induced abnormal development, a number of assumptions are currently used in the process of evaluating and interpreting data for developmental toxicity studies. The study of mechanisms of normal and abnormal development and the pharmacokinetic-pharmacodynamic relationships in humans and experimental animals are key to the development of appropriate risk assessment assumptions and dose-response models for characterizing the risk for developmental toxicity in the human population. This article summarizes the discussions of the workshop on developmental abnormalities organized by the Committee on Toxicology of the National Research Council.

Abnormalities, Drug-Induced↗
PubMed1993

Madelung's deformity masquerading as a bone tumour.

Madelung's deformity has classical clinical and radiological appearances; it is well recognised by both radiologists and orthopaedic surgeons. In this paper we report on two Madelung's deformities demonstrated on wrist radiographs that were misinterpreted as bone tumours, the patients having presented with unrelated trauma. Two further cases demonstrating similar features are illustrated. The radiological diagnosis of Madelung's deformity and its differential diagnosis is discussed.

Bone Diseases, Developmental↗
PubMed1993

Effective dose during screening monitored intussusception reduction.

A retrospective survey of 58 intussusception reductions in 55 patients is presented. During the period studied, the department changed from the use of barium to air as a reduction medium. The reduction rates were 86% with air (37 procedures) compared to 67% with barium (21 procedures). The complication rates were similar. The use of a dose-area product meter enables effective dose to the patient to be assessed. The median effective dose to the patient is 55 microSv, and the 75 percentile dose is 75 microSv. A table to estimate effective dose to the patient during the procedure is presented. This study confirms previously quoted advantages of pneumatic reduction over hydrostatic reduction of intussusception but finds no significant difference in dose between air and barium reduction. We believe that it should be possible to submit the patient to a dose of 75 microSv or less during intussusception reduction under screening control.

Air↗
PubMed1993

Ultrasound appearances of the rete testis.

Improved technology enables better visualization of normal anatomical structures. The rete testis is now visible as an ill-defined echo-poor region at the testicular hilum, sometimes with arboriform projections into the parenchyma. In a retrospective review of 100 cases of non-inflamed testes, the rete testis was seen in 18%. The anatomy was confirmed by scanning post-mortem specimens in a waterbath, marking the echo-poor region and then studying the histology. The spectrum of ultrasound appearances of the normal rete testis is presented. The rete testis can be distinguished easily from pathology because the parenchyma remains otherwise homogeneous and normal in appearance.

Humans↗
PubMed1993

Cardiac rhabdomyomas and their association with tuberous sclerosis.

A search for children presenting with signs or symptoms of cardiac rhabdomyomas was made through members of the paediatric section of the British Cardiac Society in order to establish their birth incidence, presenting features, clinical course, and the frequency of a concurrent diagnosis of tuberous sclerosis. Fifteen children were identified and 12 had tuberous sclerosis (80%). Heart failure was the presentation in six, five of whom died; six presented because of a murmur and three because of arrhythmias. The prevalence of echocardiographic evidence of cardiac rhabdomyomas in a population of patients with tuberous sclerosis was established. Twenty individuals had echocardiography and eight had echodensities consistent with cardiac rhabdomyomas. It is concluded that the minimum birth incidence for children presenting because of the effects of cardiac rhabdomyomas is 1/326,000 and a minimum of 80% have tuberous sclerosis. In a population of patients with tuberous sclerosis a minimum of 60% under 18 years have cardiac rhabdomyomas.

Echocardiography↗
PubMed1993

Stuck in a rut?

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Boredom↗
PubMed1993

Double lives.

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Career Mobility↗
PubMed1993

The write stuff.

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Dental Hygienists↗
PubMed1993

Calibration and validation for erythrocyte sedimentation tests. Role of the International Committee on Standardization in Hematology reference procedure.

The Westergren erythrocyte sedimentation rate (ESR) has been used for many years without any formal procedure for method validation or for quality assurance. In 1988, the International Committee on Standardization in Hematology (ICSH) (Leuven, Belgium) described an ESR validation procedure as well as a method for producing ESR reference material (ICSH reference method) in the laboratory where it is to be used. The ICSH proposal was tested in our laboratory during a consecutive period of 36 months. In this article, a new mathematical relationship between the ICSH recommendation and the Westergren method is developed, which can be easily used for method validation and/or quality assurance. A table has been made that establishes 95% action limits for Westergren ESRs based on ICSH reference ESRs from 5 through 105 mm/h. The table, derived from 36 months of data, has been tested against two new data sets and used to validate two commercial ESR methods. Analysis of outliers was performed with special attention to the mixing of whole blood samples with sodium citrate necessary for the Westergren ESR. This mixing process is best performed in a large-bore test tube as opposed to the use of the Westergren ESR tube as an aliquoting and mixing device.

Blood Sedimentation↗