Different behavioral deficits are induced by anoxia/hypoxia in neonatal and senescent rats: blockade by MK-801

Rats exposed on their first postnatal day to 100% nitrogen for 25 min developed hyperactivity and lower performance in passive avoidance task during development. Administration of MK-801 (0.5 mg/kg i.p.) 1 h before anoxia or (0.25 and 0.5 mg/kg) 1 h after completely reversed this behavioral impairment. Senescent rats (24-26 months) exposed to hypoxia (92% N2 + 8% O2) for 5 h failed in their performance in C.A.R., 30 days later. Pretreatment with MK-801 (1 mg/kg i.p.) completely reversed this impairment. These data suggest that activation of endogenous NMDA receptors produces different behavioral consequences in neonatal and senescent rats and that MK-801 administration close to exposure of animals to anoxia or hypoxia can prevent such damage, thus preventing behavioral impairments in postnatal as well as in senescent rats.     

Breast-saving operations in breast cancer

Breast preserving surgery or conservative surgery consists at present of a combination of a reduced operation--tumorectomy or wedge resection or subcutaneous mastectomy--with adequate radiotherapy whereby a doses of 40-50 Gy is used with or without an additional booster dose of 10 Gy. Recent studies of 5-year- and 10-year-survival rates after conservative management have been shown to be identical with radical operations (Rotter-Halsted, Patey-Auchincloss). In the Departments of Gynecology and Obstetrics of the Universities of Münster and Rostock the partial bilateral subcutaneous mastectomy with lymphadenectomy and irradiation is the preferred method of conservative management for breast cancer. Indications and technique are discussed.     

Effects of castration, exogenous testosterone and estrogen on endotoxin response in male rats

Using an experimental model of continuous endotoxin infusion, the effects of castration, testosterone and estrogen substitution on disseminated intravascular coagulation in male rats were investigated. Male rats which are not pretreated react in the same way to an endotoxin infusion as female animals, with an increase in free plasma hemoglobin, decrease of fibrinogen level, decrease of hematocrit and platelets and glomerular fibrin depositions. Different experimental groups of testectomized rats were pretreated with (i) 0.3 micrograms (pregnancy-conserving dose) or (ii) 30 micrograms ethinylestradiol (ovulation-suppression dose) or (iii) 250 mg testosterone. They were then compared to groups of animals treated with sesame oil as well as untreated group of rats. The pretreatment with testosterone and estrogens in the small-dose group had only an insignificant effect on the shock sequence. Only those animals which were treated with a high dose of estrogens showed a dramatic enhancement of their endotoxin sensitivity. It was also shown that in male animals an increased estrogen level might mediate a state of 'preparation', but testosterone does not 'prepare' castrated rats for the generalized Schwartzman reaction. The possible significance of enhancement of endotoxin toxicity by estrogens in explaining some pathophysiological characteristics of disseminated intravascular coagulation in pregnancy is discussed.     

Hepatic Function and Fibrinolysis in Patients with Hereditary Angioedema Undergoing Long-Term Treatment with Tranexamic Acid

Prophylactic treatment with antifibrinolytic agents, epsilon-aminocapriod and tranexamic acid, reduces the incidence and severits of attacks in patients with hereditary angioedema. Long-term ellectivenessor risk of antifibrinolytic agents has not been established. Sixteen patients needing continuous prophylaxis because of frequency and severity of attacks were treated with tranexamic acid. In four patients this treatment was ineffective and the drug was withdrawn after 2 months. A remission or reduction in the frequency or serverity of attacks was observed in 12 patients treated for a period ranging from 8 to 34 months. Hepatic tests and blood fibrinolytic activity were not influenced by long term oral treatment with tranexamic acid.     

Interleukin-1 dysregulation is an intrinsic defect in macrophages from MRL autoimmune-prone mice

Macrophages (M?) from pre-diseased autoimmune-prone MRL mice (both MRL/+ and MRL/1pr) dramatically underproduce the cytokine interleukin-1 (IL-1) in comparison to M? from a number of normal strains. In this study we show that IL-1 dysregulation by MRL M? is fully expressed at birth, and that this defect does not change with time or the development of disease. We also constructed adult irradiation chimeras (consisting of A/J → MRL and MRL → A/J mice), and show that M? isolated from these chimeras display a pattern of IL-1 production indistinguishable from that of the donor strain controls. Moreover, when we constructed a mixed chimera (A/J + MRL → A/J), the A/J and MRL M? coexisting within the same animal retained their individual patterns of IL-1 production when isolated by negative selection. Taken together, these results provide the first substantive evidence for an intrinsic defect (IL-1 dysregulation) in M? from MRL autoimmune-prone mice.