[The benefit of systematic hearing screening of school-age children]. / Bénéfice d'un dépistage systématique de la surdité chez l'enfant en âge scolaire.

The hearing is routinely tested in all newborns in most European countries. Thereafter, no hearing test is performed in a systematic way, despite the many conditions that can cause hearing loss in the first years of life. If language acquisition is possible with only one ear, even a unilateral hearing loss can be the cause of learning difficulties at school. In Geneva, a screening program for hearing deficit was introduced in 1955 in all primary schools of the canton. This paper shows the efficiency of the program, which can detect unnoticed deafness, sometimes in children whose neonatal screening had proved normal. Such a program should be applied to all private schools and to schools for disabled children.

Effects of the prostaglandins PGF2alpha and PGE2 on calcium signaling in rat hepatocyte doublets.

Coordination of intercellular Ca2+ signals is important for certain hepatic functions including biliary flow and glucose output. Prostaglandins, such as PGF2alpha and PGE2, may modify these hepatocyte functions by inducing Ca2+ increase, but very little is known about the organization of the Ca2+ signals induced by these agonists. We studied Ca2+ signals induced by PGF2alpha and PGE2 in fura-2 AM-loaded hepatocyte doublets. Even though both prostaglandins induced Ca2+ oscillations, neither PGF2alpha nor PGE2 induced coordinated Ca2+ oscillations in hepatocyte doublets. Gap junction permeability (GJP), assessed by fluorescence recovery after photobleaching, showed that this absence of coordination was not related to a defect in GJP. Inositol (1,4,5)trisphosphate [Ins(1,4,5)P3] assays and the increase in Ins(1,4,5)P3 receptor sensitivity to Ins(1,4,5)P3 observed in response to thimerosal suggested that the absence of coordination was a consequence of the very small quantity of Ins(1,4,5)P3 formed by these prostaglandins. Furthermore, when PGE2 and PGF2alpha were added just before norepinephrine, they favored the coordination of Ca2+ signals induced by norepinephrine. However, GJP between hepatocyte doublets was strongly inhibited by prolonged (>or=2 h) treatment with PGF2alpha, thereby preventing the coordination of Ca2+ oscillations induced by norepinephrine in these cells. Thus, depending on the time window, prostaglandins, specially PGF2alpha, may enhance or diminish the propagation of Ca2+ signals. They may therefore contribute to the fine tuning of Ca2+ wave-dependent functions, such as nerve stimulation, hormonal regulation of liver metabolism, or bile secretion, in both normal and pathogenic conditions.

Tissue levels of histamine, PAF-acether and lysopaf-acether in carrageenan-induced granuloma in rats.

The tissue concentrations of several inflammatory mediators were determined from day 0 to day 60 in granuloma induced in rats (n = 105) by injection of carrageenan in the fascia of the latissimus dorsi muscle. Noncollagen proteins (NCP) and the number of polymorphonuclear leukocytes (PMN) and mast cells were also assessed. In comparison with the tissue at time 0, we noted in the inflamed tissue (at 4 h) an increase in total proteins (4.0 +/- 3.0 vs. 84 +/- 12.0%, mean +/- SEM) and PMN (0.0 +/- 0.0 vs. 43.3 +/- 13.4%), and a fall in histamine concentration (from 30.0 +/- 9.0 to 9.0 +/- 4.0 ng/ml). A partial disappearance of mast cells and an increase of PAF-acether (PAF) levels (1.0 +/- 1.0 vs. 30.0 +/- 22.0 ng/ml) was noted at 16 h, whereas lysopaf remained unchanged (3.7 +/- 4.0 vs. 3.5 +/- 1.0 ng/ml). During evolution towards chronic inflammation (day 10-60), NCP decreased, PMN disappeared and mast cells reappeared; the histamine level rose to 11.0 +/- 2.0 mg/ml, thus not reaching back baseline values. Lysopaf rose to 7.1 +/- 12.2 ng/ml and PAF levels increased further to reach 240.0 +/- 153.0 ng/ml at day 10. This study suggests that PAF may contribute to the acute phase of an inflammatory state such as the carrageenan-induced granuloma and that it is also present during the chronic process.

Effects of long-term treatment with D-penicillamine on antigen-induced arthritis in rabbits: studies on in vivo articular chondrocyte damage and in vitro collagen biosynthesis by cultured chondrocytes.

The effects of a long-term (120 days) treatment with D-penicillamine (DP) (50 mg/kg/day; i.v.) on antigen-induced arthritis were studied in rabbit. They were investigated by the terminal histological examination of the joints of different groups of rabbits (unimmunized treated or untreated, immunized treated or untreated) and the study of collagen and non-collagen protein biosynthesis by cultured chondrocytes obtained from articular cartilage of the same groups of animals. Treatment with D-penicillamine diminished the intensity of the erosions of cartilage and subchondral bone, the severity of the inflammatory synovitis, and the loss of chondrocyte clusters found in cartilage sections. In cultures of chondrocytes obtained from immunized treated rabbits, a partial or complete inhibition of the decreased biosynthesis of collagen and non-collagen proteins seen in culture of chondrocytes obtained from immunized untreated animals was observed. These results show that DP could be effective in preventing damage of chondrocytes and inhibition of collagen biosynthesis in them, phenomena important in cartilage destruction induced by a chronic immunological inflammation.

Comparison of effects of D. Penicillamine and dexamethasone on the articular and non articular lesions in immune connective tissue disease induced in rabbits.

The effect of D. Penicillamine (DP) at the dose of 50 mg/kg/day, on an immune induced connective tissue disease in rabbit, is compared to that of dexamethasone (Dexa) at the doses of 0.15 and 0.075 mg/kg/day. This model includes polyarthritis and lesions of connective tissue of liver, kidneys and lungs. The result of immunization is initially a non-specific macrophage infiltration and secondarily a specific lymphocyte and plasma-cell infiltration. In short treatment, high dose of Dexa inhibits the non-specific and specific responses while DP modifies only non specific response. In long treatment, Dexa at low dose and DP inhibit the two responses. Data suggest that, in vivo, macrophages is the target cell of DP.

[N1-substituted 1H-indazole-3-ethyl carboxylates and 1H-indazole-3-hydroxamic acids]. / 1H-Indazole carboxylates d'éthyle-3 N1-substitués et acides 1H-indazole hydroxamiques-3.

Sixty five new derivatives of ethyl-1H-indazole-3-carboxylate are described; they contain in N1 various aliphatic or aromatic acyl radicals. Moreover halogens or methyl groups are present as substituents at the 5 position or methyl groups at 5,6. The synthesis of seven 1H-indazole-3-hydroxamic acids, substituted at 6 and/or 5 as above, is also described. Some of the synthesized derivatives have preliminarily been tested on rats to investigate acute toxicity, possible antiarthritic effects on primary or secondary arthritis, and their action on weight gain. Some of these indazole derivatives had an antiarthritic effect at doses much lower than the toxic ones; among the compounds tested up to now, the ethyl-5-methyl-N1-p-chlorobenzoyl-1H-indazole-3-carboxylate gave the best results. Weight gain as not affected by any of the examined compounds.