Monitoring treatment in congenital adrenal hyperplasia. Use of serial measurements of 17-OH-progesterone in plasma, capillary blood, and saliva.
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Biomedical subjects
Publications and source records attributed to D R Fahmy.
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Circadian breast skin temperature rhythms were characterised throughout the menstrual cycle, for various locations on the left breast of ambulatory women. All subjects exhibited highly significant circadian rhythms (P less than 0.001). Changes in rhythm parameters, such as the mesor, amplitude and acrophase, were observed during the menstrual cycle. No consistent trend in these rhythm parameters was observed between subjects in relation to menstrual cycle stage. Experimental and statistical techniques used to characterise circadian rhythms in pre-menopausal women were applied to a post-menopausal woman with primary breast cancer. Comparison of rhythm parameters associated with the tumour area and corresponding site on the contralateral breast showed abnormal thermal characteristics such as elevated mesor values, decreased amplitude as well as changes in the timing of the acrophase. These properties may be exploited for the early detection of breast cancer. The project also involved the design and testing of an ambulatory device, known as the 'chronobra', for the measurement of breast skin temperature. The performance of the chronobra was in close agreement with reliable, conventional equipment. The chronobra now allows studies of breast skin temperature rhythms associated with breast disease to be extended.
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42 patients with metastatic breast carcinoma were treated with aminoglutethimide, which inhibits adrenal steroid hormone synthesis. Treatment was stopped in 2 patients before response could be assessed; of the other 40, 15 (37.5%) had an objective response, 1 (2.5%) showed a response in bone but not in soft tissue, and 4 (10%) had complete or very great relief of metastatic bone pain but no radiological evidence of improvement. 19 (53%) of 36 patients with bone metastases responded to treatment (15 had X-ray evidence and 4 had pain relief), as did 5 (45%) of 11 patients with soft tissue metastases, 2 (25%) of 8 with malignant marrow infiltration, 1 (14%) of 7 with lung metastases, and none of 13 with liver metastases. Response was commonest in patients who had previously responded to other forms of endocrine therapy. Side-effects, usually mild and transient, occurred in a few patients; the most important were an initial period of somnolence in 9 patients and a rash in 5.
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An enzymeimmunoassay for plasma progesterone was established using progesterone covalently linked to the enzyme, horseradish peroxidase, as the 'label'. Separation of free and bound steroid was effected by Sepharose-coupled antiprogesterone-11alpha-hemisuccinyl bovine serum albumin antiserum (Sepharose-antisera). The enzymeimmunoassay satisfied the normal criteria of specificity, precision and accuracy. Comparison of assay results obtained by radioimmunoassay (with and without thin-layer chromatography) and enzyme-immunoassay (with and without thin-layer chromatography) showed excellent agreement of results in all cases (r greater than 0.98). This enzymeimmunoassay is particularly applicable to the routine determination of plasma progesterone in the smaller clinical laboratory.
A radioimmunoassay for plasma cortisol featuring the gamma-emitting radioligand 125I-iodohistamine, coupled to cortisol-3-(O-carboxymethyl)-oxime, is described. The new procedure retains much of the specificity associated with the use of anti-cortisol-3-BSA sera with tritium-labelled radioligands, and has the further advantages that running costs are lower and there is a greater potential for automation. Cortisol values obtained by this procedure agree well with those obtained by a published specific radioimmunoassay using the tritiated cortisol radioligand. Specificity of the procedure was checked by comparing values obtained with and without thin-layer chromatography purication: correlation was excellent (r = 0.96). Satisfactory levels of sensitivity, precision, and accuracy were obtained.
Multiple plasma-hormone concentrations were measured in sequential plasma-samples from six women with breast cancer and were compared to concentrations in six control women matched for age, years since menopause, and parity. All hormone concentrations in all the women studied were within normal limits. However, within the normal range the plasma-testosterone concentrations in each cancer patient were significantly higher than in each matched control.
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