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Biomedical subjects

J R Carpenter

Publications and source records attributed to J R Carpenter.

32 records · Page 2Linked to original sources

A method for presenting and comparing dose-response curves.

When dose-response curves are replicated, averaging the responses to each dose of drug reduces the slope of the mean curve. The shape of the curve can be preserved, however, by first normalizing each dose-response curve and then interpolating log concentrations that induce predetermined responses. These log concentrations are averaged, and then the responses are scaled to the mean maximal response. Mean dose-response curves obtained using this method were compared with mean curves obtained by the conventional method. It was found that this method did not distort the slope of the curve, and smaller differences were detected as significant. Neither method was found to be satisfactory for obtaining a truly representative mean curve for biphasic dose-response curves. The nature of the distribution of EC50 and maximal response was investigated, and it was confirmed that EC50 are log-normally distributed, whereas maximal responses are normally distributed.

Adrenergic beta-Antagonists↗

Enhancement of ovulation in the rat by DL-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase.

Spontaneously cycling Sprague-Dawley Rats were treated with the irreversible ornithine decarboxylase (ODC) inhibitor DL-alpha-difluoromethylornithine (DFMO) on the day of proestrus. This treatment completely suppressed both the rise in ovarian ODC and the associated increase in putrescine concentration and increased the number of eggs released the next day by 91%. At the next oestrus (5 days after DFMO) there was a increase of 53% but at the third oestrus after DFMO (9 days) there was no significant change in the number of eggs released. A model is proposed in which ornithine decarboxylase forms part of a local inhibitory feed-back system controlling the number of follicles which develop to maturity and rupture during each cycle.

Animals↗

Prospective study of immune response to hydralazine and development of antideoxyribonucleoprotein in patients receiving hydralazine.

To examine the relationship between the immune responses to hydralazine, a drug known to induce systemic lupus erythematosus, and to deoxyribonucleoprotein (DNP) we followed prospectively 21 hypertensive patients treated with hydralazine for the first time. Within one year, antibodies to hydralazine developed in 16 of these patients and anti-DNP in seven of these. In one patient whose serum had a positive antinuclear antibody test prior to treatment, a mild hydralazine systemic lupus erythematosus syndrome developed preceded by rises in the levels of both anti-hydralazine and anti-DNP. Studies by radioimmunoassay on serums of three additional patients, not followed in this study but known to have hydralazine-induced systemic lupus erythematosus, revealed no evidence for either (1) cross-reactivity between anti-DNP and anti-hydralazine or (2) antibodies specific for a hydralazine-DNP complex. In some way, perhaps related to the mechanism by which carrier molecules enhance the immunogenuity of haptens, hydralazine increases the antigenicity of DNP. This effect depends on the development of immunity to hydralazine as well.

Antibodies↗

Survival in polymyositis: corticosteroids and risk factors.

Thirty-one polymyositis patients treated with low-dose corticosteroid were age and sex matched with 31 polymyositis patients treated with high-dose corticosteroid. Although disease severity at onset of the study was similar in the groups, no statistically significant difference in survival was found. The death rate in each group was greater than normal. The presence of dysphagia or severe muscle weakness lessened the chances of survival. Controlled trials with other drugs should be carried out.

Adrenal Cortex Hormones↗

Release of [3H]noradrenaline from perfused rat hearts by potassium and its modifications by 6-hydroxydopamine and reserpine.

The sources of noradrenaline (NA) released by excess potassium from isolated perfused rat hearts were investigated by labelling the hearts from normal, reserpine-treated, and 6-hydroxydopamine-treated (6-OHDA-treated) rats with [3H]HA, and measuring the increased rate of efflux induced by perfusion with a Krebs solution containing varying amounts of excess potassium. The [3H]NA and its metabolites in the effluent were separated by adsorption on alumina and a cation-exchange resin (Dowex-50). The release induced by potassium was a linear function of the log of the increased potassium concentration. Following a 1-h efflux period after labelling with [3H]NA, the hearts from reserpine-treated rats retained 1/5 as much [3H]NA, and released, in response to a 56mM elevation in the potassium concentration, less than 1/6 as much tritium label as the hearts from untreated (control) animals. In contrast, the hearts form 6-OHDA-treated animals retained 1/15 of the amount of [3H]NA and released 1/50 of the 3H label as did the control hearts. The potassium-induced increase of 3H-labelled substances in the effluent from the control hearts showed a large (threefold) percentage increase in the [3H]NA fraction, whereas the effluents from the hearts of reserpine- and 6-OHDA-treated animals contained only small increases in the [3H]NA fraction. Based on the assumptions that reserpine prevented retention of NA in the storage granules whereas 6-OHDA prevented almost all neuronal storage, it was concluded that more than 80% of the NA released by potassium excess from perfused normal hearts originated from the storage vesicles of the nerves, the remainder being largely from the cytoplasm of the nerves, with only a small portion from extraneuronal sources.

Animals↗

Ultrasound evaluation of the popliteal space. Comparison with arthrography and physical examination.

Ultrasound scanning techniques were used to examine the popliteal space in 102 knees. In 30 of 34 knees in which arthrograms were also obtained, the information obtained from both tests was the same. In two instances in which there were different results, the presence of palpable popliteal cysts was confirmed by ultrasound scans but not by arthrography, and in two other cases, small asymptomatic cysts were seen on arthrograms but not on ultrasound scans. In the 68 other knees, ultrasound scans were helpful in the differential diagnosis of popliteal cysts, popliteal artery aneurysms, thrombophlebitis, and a solid poplitieal mass. The results indicate that ultrasound scanning is a valuable, rapid, safe, accurate technique in evaluating patients with symptoms or findings related to the popliteal space.

Aneurysm↗