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Biomedical subjects

E H Cameron

Publications and source records attributed to E H Cameron.

At least 37 records · Page 2Linked to original sources

Propranolol in the treatment of thyrotoxicosis by subtotal thyroidectomy.

Subtotal thyroidectomy was performed in 40 patients with thyrotoxicosis in whom propranolol alone was used as preparation for surgery. Propranolol was given orally in a dose of 40 mg every 6 h for a mean preoperative period of 17 days (range 4-60 days) and continued for seven days after operation. The mean +/- SE blood loss at operation was only 160 +/- 20 ml. The period of follow-up was from three to nine months. Recurrent thyrotoxicosis has not occurred in any patient. Low levels of total serum triiodothyronine (T3) and total serum thyroxine (T4) were observed in the early postoperative weeks in some patients and were associated with symptoms of mild hypothyroidism, but by six months in the presence of a raised serum thyrotropin (TSH) the thyroid hormone levels returned to normal. Permanent hypothyroidism developed in only two patients. Despite normal or low total serum T3 and T4 levels, the TSH response to thyrotropin-releasing hormone (TRH) was absent in all patients one week after operation. At four weeks and at eight weeks, the response was absent or sub-normal in 70% and 20% of the patients respectively, indicating a delay in the recovery of the hypothalamo-pituitary axis previously exposed to high levels of T3 and T4. It is considered that subtotal thyroidectomy for thyrotoxicosis in patients prepared with propranolol is an acceptable procedure which has some advantages over the conventional preparation with carbimazole and potassium iodide, not the least of which are the potential reduction in preparation time, the more flexible timing of operation, and the reduced operative blood loss.

Female↗

Measurement of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma during the perinatal period.

A method is described for the resolution and individual quantitation of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma. The steroids were extracted by solvent partition and separated by LH-20 Sephadex column chromatography. Radioimmunoassay was used for the measurement of 11-deoxycortisol and cortisone and competitive protein-binding for corticosterone and cortisol. The relative levels of these steroids in the plasma of chronically catheterized sheep foetuses from 12 days before birth to term and then in the newborn lamb until 2 days of age are recorded. Cortisol gradually increased from a basal concentration of between 0 - 5 and 3 - 0 mug/100 ml plasma between days 12 and 5 pre partum, and then rose rapidly to 10 mug/100 ml plasma during the last 5 days of pregnancy to reach a maximum during or just after birth. Two days post partum the levels had fallen to approximately 3 mug/100 ml plasma. The mean value for 11-deoxycortisol between days 8 and 3 pre partum was 0 - 4 mug/100 ml plasma and increased in the final days before delivery to 1 - 0 mug/100 ml. Corticosterone initially showed slightly higher levels (approximately 1 - 5 mug/100 ml) in the earlier period of investigation but then fell during the immediate pre-partum period to 0 - 8 mug/100 ml. Cortisone was not detected at any stage of the investigations. The relationship between levels of cortisol and 11-deoxycortisol in foetal plasma and myometrial contractility is shown. An increase in uterine activity was seen to occur at the time that cortisol levels were at their maximum. The 11-deoxycortisol values throughout this particular study remained low. The results are discussed in relation to recorded levels in the adult and to previous studies in vitro with regard to changing steroid biosynthetic enzyme activity.

Animals↗

Thyroid function in the long-term follow-up of patients treated with iodine-131 for thyrotoxicosis.

In February, 1972, 58% of patients euthyroid after iodine-131 therapy for thyrotoxicosis between 1954 and 1966 had a raised plasma thyroid-stimulating-hormone (T.S.H.) (greater than 7-4 mU/l) and 42% a normal T.S.H. level. A group of 69 of the euthyroid patients with a raised plasma T.S.H. (25-0 +/- 2-0 mU/l) in 1972 was re-examined annually for three years. There was no apparent change in the mean plasma T.S.H. level between 1972 and 1975 in the patients remaining euthyroid, but overt hypothyroidism developed in 3 patients in 1973, in a further 3 patients in 1974, and in 1 patient in 1975. In contrast, none of a group of 61 patients, euthyroid with a normal plasma T.S.H. (4-0 +/- 0-2 mU/l) in 1972, developed overt hypothyroidism over the next three years, although slightly raised T.S.H. levels were recorded in 3 patients in 1974 and in a further 6 patients in 1975. Both the mean serum T-4 and T-3 in the euthyroid patients with a raised plasma T.S.H. were significantly lower, but still in the respective normal ranges, than those in the euthyroid patients with a normal plasma T.S.H. No significant difference in the fasting serum-cholesterol or triglyceride levels could be demonstrated between the two groups. Since no patient with a normal plasma T.S.H. after iodine-131 treatment for thyrotoxicosis six to eighteen years earlier developed overt hypothyroidism over a three-year period, the follow-up of such patients need not be so frequent as that of similarly treated euthyroid patients with a raised plasma T.S.H. in whom overt hypothyroidism develops at the rate of 2-5% per year.

Cholesterol↗

Urinary aetiocholanolone in patients with early breast cancer from South East Scotland and South Wales.

Urinary aetiocholanolone levels have been measured in 417 women aged between 20 and 70 years. The women were drawn from South East Scotland and South Wales and consisted of patients with either benign or malignant disease of the breast and control patients suffering from no detectable breast disorder. The pattern of aetiocholanolone excretion with respect to age and menopausal status has been defined in each group of patients. No significant differences in urinary levels have been detected between patients with breast disease, whether benign or malignant, and control patients. More detailed examination of the 201 women with early cancer of the breast has also shown that there is no consistent correlation between pre-operative aetiocholanolone levels and factors of prognostic significance detectable at the time of primary treatment-tumour size, grade, round cell infiltration, histological involvement of nodes by tumour and the clinical palpability of lymph nodes. It would seem, therefore, that the prognostic value of pre-operative aetiocholanolone measurements is somewhat limited in patients with early breast cancer. It is noted, however, that low levels of aetiocholanolone are associated with post-menopausal patients, a group in which the prognosis is generally poorer than that in pre-menopausal women.

Adenofibroma↗

Subcellular localization and properties of mouse adrenal C19-steroid 5beta-reductase.

The localization and some characteristics of mouse adrenal C19-steroid 5 beta-reductase were determined by the incubation of subcellular fractions of mouse adrenal tissue with [7 alpha-3H]androst-4-ene-3,17-dione. This enzyme was present only in the soluble fraction and was NADPH-dependent, although a small activity in the presence of NADH was also detected. The soluble fraction also contained 3alpha-, 3beta- and a small amount of 17 beta-hydroxy steroid dehydrogenase. These and other steroid-metabolizing enzymes present in the remaining subcelluar fractions are also described briefly. To measure 5 beta-androstane-3,17-dione production by the mouse adrenal soluble fraction, all 5 beta products first had to be oxidized to 5 beta-androstane-3,17-dione, and the recovery of radio-activity between the substrate androst-4-ene-3,17-dione and product 5 beta-androstane-3,17-dione of 96.1 +/-3.2% validated this technique. C19-steroid 5 beta-reductase has a pH optimum of 6.5 and at low substrate concentrations the Km and Vmax. for 5 beta reduction of [7 alpha-3H]androst-4-ene-ene-3,17-dione was 2.22 times 10(-6) "/- 0.48 times 10(-6) M and 450+/- 53 pmol/min per mg of protein respectively. At high substrate concentration, inhibition of the reaction occurred, which was shown to be due to increasing product concentration.

Adrenal Glands↗

Metabolism of androst-4-ene-3,17-dione by subcellular fractions of rat adrenal tissue with particular reference to microsomal C19-steroid 5alpha-reductase.

The location and some characteristics of rat adrenal C(19)-steroid 5alpha-reductase were investigated by using [7alpha-(3)H]androst-4-ene-3,17-dione and [7alpha-(3)H]testosterone as substrates. The enzymes system was shown to be NADPH-dependent and associated with the microsomal fraction. In addition, some evidence was also obtained for the existence of a separate NADH-dependent system in the soluble fraction. Further investigation of androst-4-ene-3,17-dione metabolism by subcellular fractions indicated the presence of NADH-dependent 3alpha- and 3beta-hydroxy steroid dehydrogenase systems in the microsomal pellet. This pellet also appeared to contain an NADH-dependent 17beta-hydroxy steroid dehydrogenase system, and a similar though separate system was detected in the cytosol. Malate (20mm) effectively inhibited the microsomal C(19)-steroid 5alpha-reductase, which showed similar values for K(m) and V(max.) when either androst-4-ene-3,17-dione or testosterone was used as substrate. Cytochrome c was added to all incubation mixtures used for the determination of these values to inhibit the formation of metabolites other than 5alpha-androstane-3,17-dione and 5alpha-dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one) respectively. It was also found that corticosterone did not inhibit the 5alpha-reduction of androst-4-ene-3,17-dione under these conditions, indicating that separate enzymes exist for the 5alpha-reduction of C(19)- and C(21)-steroids in the rat adrenal.

17-Ketosteroids↗