Somatostatin receptors and regulation of cell proliferation.

Somatostatin is an inhibitory neuropeptide, which acts on various targets throughout the body to regulate a variety of physiological functions including inhibition of endocrine and exocrine secretions, modulation of neurotransmission, motor and cognitive functions, inhibition of intestinal motility, absorption of nutrients and ions, vascular contractility and inhibition of normal and tumour cell proliferation. It exerts its effects through interaction with five somatostatin receptors (sst1-sst5), which belong to the family of G-protein-coupled receptors with seven transmembrane spanning domains and are variably expressed in a variety of tumours such as gastroenteropancreatic tumours, pituitary tumours, and carcinoid tumours. This review covers the present knowledge regarding the molecular mechanisms involved in somatostatin antineoplastic activity. Evidence that sst2 receptor acts as a tumour suppressor is also discussed.

[Regulation of cell proliferation by somatostatin]. / Contrôle de la prolifération cellulaire par la somatostatine.

Somatostatin and its stable analogues (octreotide, lanreotide and vapreotide) exert an antiproliferative effect on various normal and cancerous cells both in vitro and in vivo. This effect results from different mechanisms: an indirect effect by the inhibition of release of growth factors and trophic hormones (GH, IGF-1, insulin, gastrin, EGF), an inhibition of angiogenesis processes (endothelial cell proliferation, VEGF release, monocyte activity), an immunomodulatory effect (lymphocyte proliferation, interleukine or cytokine release, NK activity) and a direct effect on target cells. This direct antiproliferative effect is mediated through specific somatostatin receptors. Among them, sst(1), sst(2), sst(4) and sst(5) have been implicated in vitro in the G1-G0 cell cycle blockade, sst(3) and sst(2) mediating the apoptotic effect of somatostatin. In addition, sst(2) acts as an antioncogene in human pancreatic cancer cells. Coupling to membrane tyrosine phosphatases (SHP-1, SHP-2) is the main transduction pathway involved in the antiproliferative effect mediated by sst receptors. The dissociation observed clinically between a frequent antisecretory response and an inconstant antitumor effect after administration of somatostatin analogues may reflect an absence of expression or coupling of the receptor(s) involved in antiproliferative effect. Moreover, a desensitization or mutation of these receptors may also occur in tumors. All the potential mechanism involved should be elucidated in order to improve or better target the antitumor effect of somatostatin analogues clinically used.

Libman-Sacks endocarditis: the diagnostic importance of two-dimensional echocardiography.

In 1980, a 44-year-old woman with the diagnosis of systemic lupus erythematosus presented with fever and mitral and aortic valvular insufficiency. Blood cultures were sterile. M-mode echocardiograms of the mitral valve revealed an image resembling vegetations of infective endocarditis. The diagnosis was rejected after two-dimensional echocardiography which failed to demonstrate vegetation. Two-dimensional echocardiography should therefore be systematically utilized in the diagnosis of valvular lesions in patients with systemic lupus erythematosus.

[Consequences of continuous positive airway pressure (CPAP) on left ventricular function. Assessment by M-mode echocardiography (author's transl)]. / Effets de la ventilation spontanée en pression positive permanente (CPAP) sur la fonction ventriculaire gauche. Appréciation par échographie en mode M.

The consequences of continuous positive airway pressure (CPAP) on left ventricular function are uncertain. Left ventricular function was assessed by M-mode echocardiography in 8 young normal subjects during CPAP via face mask. Heart rate and arterial pressure did not change. End-diastolic volume and stroke volume significantly decreased. Ejection fraction remained unchanged. The slight decrease of stroke volume induced by increasing positive airway pressure is in relation to decreased left ventricular preload.

[Echocardiography in the evaluation of constrictive pericarditis. 25 cases]. / L'échocardiographie dans le bilan des péricardites constritives. A propos de 25 cas.

Twenty five patients with constrictive pericarditis underwent cross-sectional and M-mode echocardiography before pericardectomy. The numerical data were compared with those in thirty healthy subjects. The various parameters noted regarding the left cavities were as follows: --The presence of a pericardial detachment which may sometimes be quite large (more than 10 mm in 6 cases); the degree of parallelism of the pericardial membranes in systole, which is all the less maintained as the detachment is severe. --The increase in size of the right ventricle and decrease of the left, with p less than 0.001 in both cases. --The absence of posterior motion of the left side of the septum in systole in 22 cases, followed by a sudden posterior displacement during the rapid filling stage, after which there is virtually no motion until the end of diastole. --The presence at the level of the posterior wall of a so-called slow filling slope, which is smaller (1.9 +/- 1.5 mm/s) than in the normal subject (p less than 0.001). --A change in left ventricular endocavitary diameter variations, which results from the two previous findings. The tracings thus show the compliance disorder with a very steep rapid filling slope and a plateau during the slow filling stage. --Finally the changes in mitral kinetics involving an earlier (p less than 0.001) and lower (p less than 0.001) F point than in the control series and on the other hand an larger E wave, sometimes forming a summation with A wave in sinus rhythm and a false A wave in atrial fibrillation. We think this type of motion is due to the disturbances in the two mechanisms (recirculation, breaking of a jet) which in physiological conditions seem to combine to chose the mitral valve at point F and account for the valve position in mid-diastole.

[Results of open heart mitral commissurotomy in 85 patients]. / Commissurotomie mitrale à coeur ouvert. Résultats chez 85 opérés.

Open heart mitral commissurotomy was performed in 85 patients between January 1973 and January 1976. This series comprised 38 patients with pure mitral stenosis and 47 patients with associated mitral and aortic or tricuspid lesions. Mitral commissurotomy, always complete, was associated with correction of mitral incompetence, either preexisting or peroperative, in 19 cases; in 44 cases with correction of an aortic lesion and in 10 cases with correction of a tricuspid lesion. The surgical mortality was 2.3 p. 100 (2 deaths); one post-operative myocardial infarction and one spontaneously regressive post-operative jaudice was observed. No cases of post-operative systemic embolism was observed. A short apical systolic murmur was detected in 12 cases. The results of this series together with those already published suggest that the indications of this operation should be widened and that it should be employed whenever the best immediate anatomical result and long-term prognosis are desired.