Biomedical subjects

John A Clark

Publications and source records attributed to John A Clark.

4 recordsLinked to original sources

PubMed2005

Hypersensitivity reactions and deaths associated with intravenous iron preparations.

BACKGROUND: Parenteral iron therapy is an accepted adjunctive management of anaemia in kidney disease. Newer agents may have fewer severe hypersensitivity adverse events (AE) compared with iron dextrans (ID). The rate of type 1 AE to iron sucrose (IS) and sodium ferric gluconate (SFG) relative to ID is unclear. We used the US Food and Drug Administration's Freedom of Information (FOI) surveillance database to compare the type 1 AE profiles for the three intravenous iron preparations available in the United States. METHODS: We tabulated reports received by the FOI database between January 1997 and September 2002, and calculated 100 mg dose equivalents for the treated population for each agent. We developed four clinical categories describing hypersensitivity AE (anaphylaxis, anaphylactoid reaction, urticaria and angioedema) and an algorithm describing anaphylaxis, for specific analyses. RESULTS: All-event reporting rates were 29.2, 10.5 and 4.2 reports/million 100 mg dose equivalents, while all-fatal-event reporting rates were 1.4, 0.6 and 0.0 reports/million 100 mg dose equivalents for ID, SFG and IS, respectively. ID had the highest reporting rates in all four clinical categories and the anaphylaxis algorithm. SFG had intermediate reporting rates for urticaria, anaphylactoid reaction and the anaphylaxis algorithm, and a zero reporting rate for the anaphylaxis clinical category. IS had either the lowest or a zero reporting rate in all clinical categories/algorithm. CONCLUSIONS: These findings confirm a higher risk for AE, especially serious type 1 reactions, with ID therapy than with newer intravenous iron products and also suggest that IS carries the lowest risk for hypersensitivity reactions.

Adverse Drug Reaction Reporting Systems↗

PubMed2005

National differences in reporting 'pneumonia' and 'pneumonia interstitial': an analysis of the WHO International Drug Monitoring Database on 15 drugs in nine countries for seven pulmonary conditions.

PURPOSE: Increased post-marketing reports of 'interstitial pneumonia' as an adverse drug reaction (ADR) from the use of gefitinib, irinotecan, or leflunomide among patients in Japan have not been noted in other countries. The WHO International Drug Monitoring Database was analyzed to examine Japan's pattern of reporting the term 'pneumonia interstitial' for 15 selected drugs with a mixed history of association with pulmonary ADRs. METHODS: ADR counts from the WHO Database for 1992-2001 were obtained for 15 disparate drugs (three androgen blockers, eight cytotoxics, one proton pump inhibitor, one monoclonal antibody, and two anti-epileptics) from nine countries (Australia, France, Germany, Italy, Japan, Spain, Thailand, U.K., and U.S.A.) for seven pulmonary ADR terms (alveolitis fibrosing, pneumonia, pulmonary fibrosis, lung fibrosis interstitial, pulmonary infiltration, interstitial lung disease, and pneumonia interstitial). Statistical analyses included estimating Poisson-distributed expected rates, observed/expected (O/E) ratios, and 95% confidence intervals (CI). The overlapping nature and changes in definition over time of these terms in medical texts and in the WHO-ART, COSTART, J-ART, and MedDRA coding systems is also noted. RESULTS: Compared to other countries, both Japan and France did not have higher O/E reporting ratios for all seven pulmonary ADRs combined, but did have higher O/E ratios for 'pneumonia interstitial' and lower O/E ratios for 'pneumonia' for the same drugs. CONCLUSIONS: Japan and France were found to preferentially use the term 'pneumonia interstitial' for ADR where other countries used 'pneumonia.' This cultural pattern coincides with the fact that 'pneumonia interstitial' in older versions of COSTART, J-ART, and MedDRA were subsumed under infectious pulmonary diseases.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

The gene suicide system Ntr/CB1954 causes ablation of differentiated 3T3L1 adipocytes by apoptosis.

The feasibility of ablating differentiated adipocytes and the mechanism of cell ablation with a suitable prodrug activating system is described. The system is based on the use of E. coli nitroreductase (NTR) enzyme that activates certain nitro compounds, such as the antitumor drug CB1954, into cytotoxic DNA interstrand cross-linking agents. Differentiated preadipocyte cells (3T3L1) transfected with an aP2 driven nitroreductase construct were efficiently killed after incubation with medium containing the prodrug CB1954, while untransfected cells were not affected. It was demonstrated that the mechanism of cell ablation is apoptosis and that the system has a bystander effect mediated by a toxic metabolite of the prodrug. The described system should provide a good alternative approach for gene therapy studies and a new inducible approach to manipulating the number of cells in tissues of transgenic animals and the ability to study the recovery of the tissue from cell damage or loss.

3T3-L1 Cells↗

PubMed2003

Not impressed.

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Humans↗