Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists.

The purpose of this study was to investigate the effectiveness of oral treatment with the endothelin (ET) A/B receptor antagonist Ro 47-0203, 4-tert-butyl-N-[6-(hydroxy- ethoxy)-5-(2-methoxy-phenoxy)-2'-bipyrimidin-4-yl]-benzenesulfonam ide (bosentan), and the ET A receptor antagonist 2-benzo[1,3]dioxol-5-yl-3-benzyl-4-(4-methoxy- phenyl)-4-oxo-but-2-enoic acid monosodium salt (PD155080), in the prevention of subarachnoid hemorrhage (SAH)-induced delayed cerebral vasospasm. Double hemorrhage in the rabbit constricted the basilar artery to 34% if control as determined by angiography. Oral bosentan and PD155080 administration after the initial SAH decreased the magnitude of constriction to 9% and 16% of control, respectively. Plasma and cerebrospinal fluid bosentan levels and plasma PD155808 levels were consistent with concentrations reported to inhibit ET-1 constriction of blood vessels in vitro. These results support the use of oral administration of ET A/B and ET A receptor antagonists as potential specific treatment for vasospasm resulting from SAH in humans.

Radiation-associated cerebral gliomas. A report of two cases and review of the literature.

Two cases are reported in which a cerebral glioma developed after radiation therapy for a different primary tumor. The first case was a boy, who presented a right thalamic anaplastic astrocytoma 7 years after irradiation for a left temporal polymorphic cell sarcoma. The second case was a woman, with a right temporal anaplastic astrocytoma occurring 8 years after irradiation for a GH-secreting pituitary adenoma. Thirty-five other cases of radiation-associated cerebral gliomas had already been reported in the literature. The possible causal role of radiation therapy in inducing cerebral gliomas is discussed on the basis of these observations.