Treatment of primary hypogonadism in men by the transdermal administration of testosterone

We tested the efficacy of a thin flexible testosterone-impregnated membrane applied to the scrotum for the long term treatment of male hypogonadism. Ten men with primary hypogonadism were treated for 3 months (2 men) or 13 months (8 men). Serum testosterone concentrations increased in all 10 men, to within the normal range in 8. Serum dihydrotestosterone concentrations increased to supranormal values in all of the men, decreased to the normal range in 6, indicating the biological effectiveness of the testosterone in those subjects. Two men whose serum LH concentrations did not fall to normal had small or distorted scrotal surfaces. Seven of the 8 men whose serum testosterone concentrations became normal said that their hypogonadal symptoms were corrected by this treatment. We conclude that the transdermal administration of testosterone is an effective means of treating the majority of hypogonadal men who have a normal scrotum.     

A giant fusiform basilar aneurysm treated by bilateral vertebral artery occlusion.

OBJECTIVE AND IMPORTANCE: Fusiform aneurysms of the vertebrobasilar arteries that progressively enlarge causing symptomatic brainstem compression are dangerous and their treatment is difficult. A patient with such an aneurysm treated successfully with staged, microsurgical occlusions of the proximal vertebral arteries is described, and the literature pertaining to this rare condition is briefly reviewed. CLINICAL PRESENTATION: A 48-year-old man with a fusiform basilar trunk aneurysm of uncertain etiology presented initially with transient ischemic attacks (TIAs) of the posterior circulation that ceased with anticoagulation. Four years later he presented again with progressive ataxia, dysphagia and dysphonia due to considerable enlargement of the aneurysm causing brainstem compression. INTERVENTION: Staged microsurgical vertebral artery occlusions proximal to the aneurysm were performed. The second (left) vertebral artery was clipped only after the patient passed its temporary occlusion with an endovascular test balloon. The aneurysm subsequently thrombosed, the distal basilar artery kept patent by a single (left) posterior communicating artery. The patient's clinical condition improved markedly over a number of months as the aneurysm mass atrophied. CONCLUSION: Giant vertebrobasilar aneurysms are rare but treacherous lesions, sometimes justifying aggressive management. Carefully selected patients with progressive and severe symptoms due to brainstem compression may tolerate proximal vertebral artery occlusions, provided there is adequate collateral flow to the basilar termination and all of its perforating branches.     

A dosage study of the effect of the 21-aminosteroid U74006F on chronic cerebral vasospasm in a primate model

The efficacy of the 21-aminosteroid U74006F was investigated using different dosages in a restricted, randomized, placebo-controlled trial. Forty cynomolgous monkeys were divided into five groups of eight. There were two groups given treatment with placebos, one being saline and the other the vehicle in which U74006F was delivered. There were three U74006F treatment dosage groups: 0.3, 1.0, and 3.0 mg/kg. Each monkey underwent baseline cerebral angiography followed by right-sided craniectomy and subarachnoid placement of a clot around the middle cerebral artery (MCA). Treatment was administered intravenously every 8 hours for 6 days. Seven days after experimental subarachnoid hemorrhage, angiography was repeated, and the animals were killed. In both saline or vehicle placebo treatment groups, significant vasospasm (VSP) occurred on the clot side in the extradural internal carotid artery (C3), the intradural internal carotid artery, the precommunicating segment of the anterior cerebral artery (A1,) and the MCA (P less than 0.01). After U74006F treatment, significantly less VSP developed in the A1 on the clot side (0.3 mg/kg U74006F treatment group) and the MCA (all U74006F treatment groups, P less than 0.05). When the percentages of change from the baseline for the vessel diameters on the clot side were compared, VSP was attenuated in the A1 (P less than 0.05) and MCA (P less than 0.001) of all U74006F treatment groups as compared with the placebo treatment groups. Only 0.3 mg/kg of U74006F significantly prevented VSP in C3 (P less than 0.01). Although the 0.3 mg/kg dosage appeared to have the most favorable effect, no significant differences were observed among the three dosage groups. Electron microscopy of the MCA on the clot side in the animals treated with U74006F still showed luminal convolutions and morphological changes in the endothelial cells. These changes appeared less prominent in those MCAs with milder VSP. If these results in primates are applicable to humans, U74006F would be useful in reducing VSP after aneurysmal subarachnoid hemorrhage.