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The site of action for the sleep-promoting effect of prostaglandin (PG) D2 was extensively examined in the brain of adult male rats (n = 231). PGD2 was administered at 100 pmol/0.2 pI per min for 6 hr (2300-0500 hr) through chronically implanted microdialysis probes or infusion cannulae. Among the administrations of PGD2 by dialysis probes (n = 176), only those (n = 8) to a ventro-rostral part of the basal forebrain by the probes implanted on the midline consistently increased slow-wave sleep (SWS), by 51 ± 6 min (mean ± SEM) above the baseline value (111 ± 11 min). Since this area is separated by a cleft into right and left regions, the results were interpreted to mean that, through this cleft, PGD2 diffused in the subarachnoid space over the adjacent ventral surface, where it had the effect ofpromoting sleep. When PGD2 was directly infused into the subarachnoid space (n = 55), extraordinary increases exceeding 90 min were consistently attained for the SWS at sites located between 0.5 and 2 mm rostral to the bregma and between 0 and 1.2 mm lateral to the midline defined according to the stereotaxic coordinates adopted from the brain atlas of Paxinos and Watson [Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates (Academic, San Diego)]. Thus, we demarcated a "PGD2-sensitive, sleep-promoting zone" within this region in the ventral surface of the rostral basal forebrain. During the bilateral infusion of PGD2 into the subarachnoid space of this zone, the hourly mean SWS level of the nocturnal animals (n = 6) in the night reached the maximum at the second hour of the infusion period; this maximum hourly SWS level, corresponding to the daytime level of the same animals, lasted until the end of PGD2 infusion.Prostaglandin D2 (PGD2) has been postulated as one of the endogenous sleep-promoting substances in rats and other mammals including humans (1). PGD2 has been implicated in the physiological regulation of sleep by the fact that sleep in rats was markedly suppressed by intracerebroventricular (2) or intravenous (3) administration of inorganic selenium compounds, which are inhibitors of PGD synthase (EC 5.3.99.2), the enzyme responsible for the synthesis of PGD2 in the rat brain (4).The preoptic area (POA) has long been proposed as a sleep center since the experimental study by Nauta in 1946 (5). The site of action for the sleep-promoting effect of PGD2 has been postulated to be located in or near the POA since an increase in the amount of sleep was first demonstrated with PGD2 in 1982 by a microinjection study (6). Subsequent studies in monkeys (7) and rats (8) also supported the assumption that the site of action is located in a rostral and ventral region, adjacent to the third cerebral ventricle; however, the exact site of action has not yet been clearly defined.In this paper, the site most effective in promoting sleep with PGD2 administration was extensively studied by use of the microdialysis technique and the continuous infusion method. The results clearly define the site of action ...
The outcome following intra-operative radiation therapy in the treatment of osteosarcoma in the extremity in 33 patients was evaluated for oncological and functional results. Local recurrence occurred in seven cases, six of which were in a non-irradiated region, indicating inappropriate planning of the radiation field. Twenty-one patients underwent either prosthetic replacement (14) or amputation (7). Irradiated tumours were left in situ in the remaining 12 patients. In this latter group no degenerative joint changes were observed radiologically. Twenty-six patients experienced local complications, of which fracture of the irradiated bone was the most significant. Associated intramedullary nailing showed encouraging results in preventing fracture. Although IORT is effective for the local control of osteosarcoma in extremities, critical patient selection and improvements of treatment protocol are required in order to obtain a satisfactory outcome.Résumé On a examiné les résultats oncologiques et fonctionnels de 33 patients ayant reçu une radiothérapie peropératoire pour un ostéosarcome d'une extrémité. Sur les sept cas de récidive locale identifiés, six se situaient dans une région apparemment non irradiée, ce qui indique que la défaillance locale pourrait être due à un dé-faut de détermination du territoire irradié. Sur les 33 patients, 14 ont reçu une endoprothése et 7 été amputés après la radiothérapie. Les tumeurs irradiées ont été laissées in situ chez les 12 patients restants. Dans ce dernier groupe, l'examen radiologique n'a révélé aucune dégé-nérescence au niveau des articulations. Des complications locales ont été observées chez 26 patients sur 33. La complication la plus problématique était la fracture de l'os irradié. La consolidation par enclouage médullai-re a donné des résultats encourageants pour la prévention des fractures. Bien que la radiothérapie peropératoire soit efficace pour la maitrise locale de l'ostéosarcome des extrémités, la sélection judicieuse des patients et l'amélioration de la procédure sont nécessaires pour obtenir un membre fonctionnel à long terme.
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