Action of danazol on the conversion of estrone sulfate to estradiol and on the sulfatase activity in the MCF-7, T-47D and MDA-MB-231 human mammary cancer cells.

In the present studies the action of Danazol on the conversion of estrone sulfate (E1S) to estradiol (E2) as well as on the sulfatase activity in the MCF-7 and T-47D, hormone-dependent, and MDA-MB-231, hormone-independent, mammary cancer cell lines was explored. Using intact cells we observed that Danazol blocks very significantly the radioactivity uptake and the conversion of [3H]E1S to E2 in all the cells studied. In particular, a very strong effect (85% decrease of these parameters versus the control values) is observed in the T-47D cells. In another series of studies using cell homogenates it is observed that Danazol inhibits the sulfatase activity in all these cell lines. The effect of Danazol is dose-dependent and significant from a concentration of 1 microM. At concentrations of 8 microM E1S, 10(-5) M Danazol, the inhibition of sulfatase activity is 38% in MCF-7, 36% in MDA-MB-231, and 27% in T-47D cells. Analysis by Lineweaver-Burk plot shows that the inhibitory effect is competitive. As E1S is one of the main sources of E2 in human mammary tumors, the present data could open new possibilities for therapeutic applications in hormone-dependent breast cancer.

Effects of sustained-release diltiazem on blood pressure and serum lipids: a multicenter, randomized, placebo-controlled study.

A randomized, double-blind dose-response study on the antihypertensive action of sustained-release diltiazem was performed in four parallel groups. The aim of the trial was to evaluate the antihypertensive efficacy of sustained-release diltiazem and its dose-dependent clinical and biological tolerance. The four homogeneous groups consisted of 25 patients each who had presented with mild to moderate hypertension (diastolic blood pressure of 95-115 mm Hg) in the supine position. The study protocol comprised three successive periods: a placebo period lasting 14 days to verify the persistence of arterial hypertension under placebo; a first therapeutic period during which each of the 25 patients of the four groups received a single daily dose every morning at 9 a.m. of a capsule containing 0.240, 300, or 360 mg of sustained-release diltiazem over a period of 28 days; and a second therapeutic period during which the patients of the four groups received 240, 300, 360, and 300 mg, respectively. All other antihypertensive treatment had been suspended at least 15 days before the initial period under placebo. The results were evaluated with respect to clinical parameters such as systolic blood pressure, diastolic blood pressure, and heart rate, which were measured at 9 a.m. 24 h after the last administration of the drug on days 14, 28, and 56. The plasma serum levels of diltiazem were measured on days 28 and 56, the biological parameters, including measurements of hepatic and renal function as well as lipid and glucose levels, on days 14 and 56, and electrocardiography was performed on days 14, 28, and 56.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study on monotherapy with sustained-release diltiazem 300 mg and enalapril 20 mg in mild to moderate arterial hypertension.

The antihypertensive efficacy of sustained-release diltiazem 300 mg at a single daily dose was evaluated and compared to that of enalapril 20 mg at a single daily dose, and to a combination therapy of enalapril 20 mg with sustained-release diltiazem 300 mg in patients with mild to moderate arterial hypertension (supine diastolic blood pressure between 95 and 115 mm Hg). After a washout period and a placebo period, each lasting 2 weeks, 96 patients were randomized in this double-blind study to three parallel groups that were treated for 28 days. In the groups treated with diltiazem, enalapril, or the combination of both, the drop in arterial blood pressure was 20, 11, and 19 mm Hg for supine diastolic blood pressure (supine DBP): 18, 12, and 19 mm Hg for standing diastolic blood pressure (standing DBP); 22, 20, and 23 mm Hg for supine systolic blood pressure (supine SBP); and 21, 19, and 24 mm Hg for standing systolic blood pressure (standing SBP), respectively. The reduction in DBP was significantly more pronounced in the group treated with sustained-release diltiazem 300 mg than in the group treated with enalapril 20 mg. Cardiac tolerance was good for patients treated with sustained-release diltiazem 300 mg alone or the combination therapy: no orthostatic hypotension or lengthening of the PR interval in the electrocardiogram was observed. Although side effects of sustained-release diltiazem 300 mg occurred more frequently, they were not severe and disappeared immediately when treatment was suspended.

[Fetal death caused by myocarditis and isolated congenital auriculoventricular block]. / Mort foetale par myocardite et bloc auriculo-ventriculaire congénital isolé.

A 26-year old woman gave birth, at term, to a child with isolated complete heart block. A second pregnancy was interrupted by foetal death. Among other immunological abnormalities, this young woman had an antibody resembling the anti-SS-B antibody. At pathological examination the foetus' heart was found to be free of malformation but presented with subacute myocarditis associated with microcalcifications of the conductive tissue. Such findings suggest that an incipient myocarditis may either result in foetal death or lead to fibrosis of conduction pathways with isolated complete heart block.

Clonidine, acebutolol and their interaction in essential hypertension: effects on blood pressure and the control of water and electrolyte balance.

The effects of 0.5 mg of slow-release (sr) clonidine, 800 mg of acebutolol, and of both drugs combined on blood pressure and the water-salt balance were compared in 10 patients with essential hypertension. An initial placebo period was followed by three 72-h periods during which 5 patients were given sr-clonidine, acebutolol plus sr-clonidine, and acebutolol, respectively in that order whereas the other 5 received the same drugs in the opposite order. Placebo and active medications were given once a day, and the recorded variables were measured 24 h after the last intake. Sr-clonidine, acebutolol and their combined administration reduced mean blood pressure by 23, 16 and 39 mmHg, respectively, indicating first, that single daily doses of sr-clonidine and/or acebutolol constitute satisfactory antihypertensive treatments and second, that the interaction of these drugs is additive. All three treatments reduced plasma renin activity significantly and similarly. A reduction in plasma and urinary aldosterone was observed with sr-clonidine, and a decrease in plasma noradrenaline with the combined treatment. Both water diuresis and natriuresis rose significantly during combined therapy. The additive antihypertensive effects of sr-clonidine and acebutolol might be due to the parallel inhibition observed in the renin and sympathetic systems, and to the increase in natriuresis.

[Gougerot-Sjögren syndrome, periarteritis nodosa, non-Hodgkin's lymphoplasmocytic lymphoma and acquired C4 deficiency]. / Syndrome de Gougerot-Sjögren, périartérite noueuse, lymphome non hodgkinien lymphoplasmocytaire et déficit acquis en C4.

A Sjögren syndrome was confirmed histologically in a 19 year old woman. Four years later, periarteritis nodosa (PAN) with characteristic vascular lesions on muscle biopsy occurred simultaneously with lymphatic hyperplasia comprising splenomegaly and polyadenopathy. The PAN was cured with corticosteroids and cyclophosphamide and the lymphadenopathy regressed. Several months after treatment was stopped the lymphadenopathy recurred which histologically resembled a malignant non-hodgkin lymphoplasmocytoma secreting an IgM kappa monoclonal immunonoglobulin. During the PAN and the establishment of the lymphoproliferative syndrome a severe C4 deficit was detected which disappeared after chemotherapy.

["Deep scleroderma" or diffuse fibromatous scleroderma. A case-report of uncertain nosologic classification (author's transl)]. / "Sclérodermie profonde" ou fibromatose diffuse. A propos d'un cas de nosologie incertaine.

An unusual form of scleroderma, seen in one patient, is described. Clinical and histological examinations demonstrated no dermal changes. Both the subcutaneous tissue and the fascias were involved. This case can be distinguished from Shulman fasciitis, on both histological and biological grounds, as well as from scleroderma, since Raynaud phenomena, sclerodactylia, and visceral involvement were lacking.

[Serum immune complexes and cardiopulmonary bypass. A review of thirty-four cases (author's transl)]. / Immuns complexes circulants et circulation extra-corporelle. A propos de trente-quatre cas.

The immunologic status of patients undergoing cardiopulmonary bypass as investigated. Rheumatoid factor, cryoglobulinemia and serum immune complexes were looked for. Studies were performed before the operation and eight or fifteen days later. From the results, it is concluded that the immunologic changes that occur in the immediate postoperative period cannot be interpreted because of the profound modifications resulting from cardiopulmonary bypass.

[Intra-uterine detection of atrio-ventricular block in two children whose mother had Sjögren's syndrome]. / Blocs auriculo-ventriculaires détectés in utero chez 2 enfants dont la mère a un syndrome de Sjögren.

A woman with isolated juvenile Sjögren's syndrome gave birth, at 3 years' interval, to two children with complete atrio-ventricular heart block (AVB). This is the first published case of AVB in children of mothers with Sjögren's syndrome without any clinical and laboratory evidence of connective tissue disease, notably lupus. Ultrasonography showed that the AVB was acquired in utero and occurred during the 23rd week of gestation. In both children the AVB was isolated, without any symptom of congenital malformation of the heart; there were no abnormalities of conduction in the mother. Early corticosteroid treatment of the mother's disease had no beneficial effect on AVB in the foetuses. Attempts to reproduce the condition experimentally met with failure.