Protecting action of aspartate on the hepatic changes induced by D-galactosamine.

The protective action of aspartic acid on isolated and perfused rat liver was studied. In case of D-galactosamine intoxication the GOT, GPT and SDH activity and the lactate and pyruvate concentration in the perfusion medium were less augmented and the glycogen level in hepatic tissue was less diminished in animals treated with aspartic acid, as compared to controls. The histochemical applied (PAS reaction for glycogen, nucleic acids, NADH2-diaphorase, glucose-6-phosphatase and membrane-ATP-ase), also stated a protecting effect in the treated animals. The protective action of aspartate is hypothetically considered to be exerted by its capacity to reestablish the cellular deficit of pyridine nucleotides and thus to improve the synthesis of nucleic acids, glycoprotein and glycolipids or/and by its participation in various metabolic pathways.     

Fibrin formation during asanguinous normothermic perfusion of the isolated rat liver

A progressive accumulation of fibrin in the small vessels of the isolated perfused rat liver was documented by both histological and autohistoradiographic techniques. These changes occurred initially in the sinusoids and later extended to the interlobular branches of the portal vein. Fibrin deposition was accompanied by a reduction of perfusion flow, an increase of the lactate-pyruvate ratio in the perfusion medium, and a depletion of liver tissue glycogen. All of these changes were prevented by adding streptokinase to the perfusing solution. Mechanisms leading to intravascular accumulation of fibrin and the possible involvement of this process in failure of prolonged liver preservation, hemorrhagic accidents following liver transplantation, and liver allograft rejection are discussed. The use of fibrinolytic agents for perfusion preservation of the isolated liver appears promising.

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Résumé L'accumulation progressive de la fibrine dans les petits vaisseaux du foie isolé de rat, perfusé à l'aide d'un système modifié après Scholz, a été démontrée à l'aide des techniques histologiques et autohistoradiographiques. Dans un état initial on constate que les sinusoïdes sont afféctés, puis les modifications s'étendent vers les branches interlobulaires. La déposition de la fibrine a été accompagnée par la réduction du débit de perfusion, par l'accroissement du rapport lactate-pyruvate dans le milieu de perfusion et la diminution du glycogène tissulaire. Toutes ces modifications ont été prévenues par l'adjonction de la streptokinase dans le milieu de perfusion. Les mécanismes qui déterminent l'accumulation intravasculaire de la fibrine et leurs possibles implications dans l'échec de la conservation prolongée du foie, dans l'apparition des accidents hémorragiques du transplant hépatique aussi que dans la réaction de rejet des greffes sont mis en discussion. De même on fait des appréciations sur les perspectives offertes par l'utilisation des agents fibrinolytiques dans la conservation du foie.

     

Participation of gonads in pulmonary silicosis]

A survey is given on the participation of endocrine glands in the pulmonary silicosis. At the same time a new clinical and experimental contribution to the question of the appearance of a hypogonadotropic hypogonadism is given. The frequency of this hypogonadism increases with the severity of the pulmonary silicosis. The immunological opinions as well as the neuroergonal ones concerning the pathogenesis of pulmonary silicosis gave the possibility of a better explanation of the mechanisms, by means of which also other organs may be attacked in pulmonary silicosis. The neuroendocrine system gives a defensive answer to the aggressive silicotic pulmonary process, which in general slowly progresses, but which may also be certain hormones from the group of the glucocorticosteroids in the adrenal cortex. The intervention into the axis hypothalamus-hypophysis-adrenal cortex has been provided in all defence processes of the organism against every aggression. By the functional or organic damage of the neuroendocrine system, by the immediate toxic effect of silicium dioxide or the monosilicium acid as well as by the effect of the secondary hypoxia in pulmonary silicosis an insufficiency in the stimulation and excretion of certain hormones develops. The origin of this insufficiency is found in the hypothalamo-hypophyseal centres, and the effects extend to all endocrine glands which depend on the system hypothalamus-hypophysis. This mechanism is made responsible for the appearance of a hypogonadotropic insufficiency of gonads in the course of a pulmonary silicosis and is proved clinically and experimentally in the cases investigated by the authors     

Double atrial parasystole. Case report.

A 62 year-old man with hiatal hernia and complex atrial arrhythmia is reported. On the standard electrocardiogram a double atrial parasystole is found, with reversed coupling. During carotid sinus massage only one of the parasystolic foci is not influenced, and assumes the atrial activity, regularizing the cardiac rhythm.     

Statistical methodology of phase III cancer clinical trials: advances and future perspectives

The methodology for conducting cancer clinical trials has undergone enormous changes over the past 25-30 years since the EORTC Data Center was created. The purpose of this paper is to highlight and to provide a historical perspective for the main methodological concepts, both practical and theoretical, which form the basis for the design and analysis of phase III cancer clinical trials within the EORTC Data Center. Some statistical aspects of other associated topics such as quality of life, health economics, meta-analysis and treatment outcome will also be briefly discussed. Finally, some future perspectives and topics for further statistical methodological research will be presented in order to spur statisticians to meet the challenge of efficiently designing and analysing the clinical trials of tomorrow.     

Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy for acute lymphoblastic leukaemia, without radiotherapy: long term results of the EORTC CLG 58881 trial

From June 1989 through to November 1998, 121 children with newly diagnosed T-cell lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted by the Children's Leukaemia Group. The therapy regimen was based on a Berlin-Frankfurt-Munster protocol, for a total duration of 24 months. Cranial irradiation, prophylactic cranial and local, was omitted, even for patients with central nervous involvement at diagnosis. In total, 119 patients were evaluable. The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at 6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an isolated central nervous system relapse. For patients with complete response (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14% (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy regimen without irradiation leads to a high cure and survival rate in childhood T-LBL without an increased CNS recurrence. This suggests that prophylactic cranial irradiation can safely be omitted. Response to the prephase appeared to be a strong prognostic factor for EFS.