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Biomedical subjects

D Coward

Publications and source records attributed to D Coward.

4 recordsLinked to original sources
PubMed2003

Cardiovascular disease as a long-term complication of treatment for testicular cancer.

PURPOSE: To assess the risk of cardiovascular morbidity and cardiac risk factors in long-term survivors of testicular cancer according to treatment received. PATIENTS AND METHODS: All resident male patients registered in the United Kingdom between 1982 and 1992 attending for follow-up were eligible for recruitment. Patients completed a current health questionnaire and underwent clinical review, along with hematologic, biochemical, and hormonal profiles. For patients not under routine review, follow-up information was sought from their general practitioner and mortality data were sought from the Office of National Statistics. Descriptive analysis was performed on all variables and comparisons were made among patients treated by orchidectomy and follow-up only, chemotherapy alone (C), radiotherapy alone (RT), and radiotherapy and chemotherapy (C/RT). RESULTS: Data on cardiovascular events were available on 992 patients. After a median follow-up of 10.2 years, 68 events had been reported, including 18 deaths. After adjusting for age, increased risk for cardiac events was seen after C (relative risk [RR] = 2.59; 95% confidence interval [CI], 1.15 to 5.84; P =.022), RT (RR = 2.40; 95% CI, 1.04 to 5.45; P =.036), and C/RT (RR = 2.78; 95% CI, 1.09 to 7.07; P =.032). There were no significant differences in cardiac risk factors. On multivariate analysis, age, treatment group, free thyroxine, protein, and magnesium levels were associated with cardiovascular disease. CONCLUSION: In long-term survivors of testicular cancer, we observed a two-fold or greater risk of developing cardiovascular disease. This was not due to increases in cardiac risk factors, which suggests a direct or indirect treatment effect. These data support the continued research into the minimization of treatment in good-prognosis testicular cancer.

Adult↗
PubMed1989

Partial brain dopamine D2 receptor agonists in the treatment of schizophrenia.

Partial dopamine agonists showing high affinity but low efficacy at D2 receptors can act as dopaminergic "buffers," reducing dopaminergic activity when it is excessive, and promoting it when reduced. This makes them of interest as potential therapeutic agents for the treatment of both positive and negative symptoms in schizophrenia, where they should also result in fewer or less severe motor disturbances than classical neuroleptics. SDZ 208-911 and SDZ 208-912 are amino-ergolines exhibiting partial agonistic properties in the rat, where they inhibit apomorphine-induced stereotypies, are only weakly cataleptogenic, induce varying degrees of circling behavior after unilateral lesioning of the nigrostriatal pathway, and strongly suppress prolactin secretion. The least agonistically acting agent, SDZ 208-912, should be effective against positive symptoms, whereas SDZ 208-911 could be suitable for the treatment of negative symptoms. In addition to possible therapeutic effects, the clinical testing of this class of agent should help to elucidate the status of central dopaminergic function in schizophrenic psychosis.

Brain Chemistry↗
PubMed1987

Binding of 3H-spiperone and 3H-(-)-sulpiride to dopamine D2 receptors in rat striatal membranes: methodological considerations and demonstration of the identical nature of the binding sites for the two ligands.

In order to test the hypothesis emerging from the literature that 3H-sulpiride and 3H-spiperone might label different subclasses of dopamine D2 receptors in the brain, the binding properties of the two ligands were compared under optimized conditions. 3H-sulpiride was found to show a very fast rate of dissociation from the receptor. Furthermore, with this ligand, an apparently "specific" binding to glass fiber filters was observed. A centrifugation assay was therefore used for the characterization of 3H-sulpiride binding. The binding of 3H-spiperone was measured in a way which prevented its attachment to sites other than D2 receptors. Under these conditions, the two ligands were found to label identical dopaminergic recognition sites (D2 receptors) according to the following criteria: 3H-sulpiride and 3H-spiperone both labelled only one single site with a comparable density. Identical changes in the receptor number for both ligands were found in the tissue from animals with nigrostriatal 6-hydroxydopamine lesions. The potencies of various dopamine agonists and antagonists in displacing 3H-sulpiride or 3H-spiperone from their binding sites showed a highly significant one to one correlation. Finally, the binding of both ligands could be inactivated by pretreatment of the membranes with N-ethylmaleimide, with or without Na+-ions being present. This inactivation followed exactly the same kinetics for both radioligands. Thus, no indication supporting the hypothesis that 3H-sulpiride and 3H-spiperone might label different subsets of dopamine D2 receptors in the rat brain could be found.

Animals↗