Search Results

You are looking at 1 - 10 of 105 items for

  • Author or Editor: Neal F. Kassell x
  • Refine by Access: all x
Clear All Modify Search
Restricted access

Charles George Drake, M.D. 1920–1998

An obituary

Neal F. Kassell

Restricted access

Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part II. A cooperative study in North America

Giuseppe Lanzino, Neal F. Kassell, and the Participants

Object. To test the safety and efficacy of high-dose (15 mg/kg/day) tirilazad mesylate in women suffering from aneurysmal subarachnoid hemorrhage (SAH), a prospective randomized, double-blind, vehicle-controlled trial (parallel to the one conducted in Europe, Australia, New Zealand, and South Africa) was performed at 65 North American neurosurgical centers.

Methods. Of the 832 patients who were randomized, 823 received at least one dose of tirilazad (410 patients) or placebo vehicle containing citrate (413 patients). The two groups were similar with respect to their prognostic factors for overall outcome and delayed cerebral ischemia. There were no differences in medical and surgical interventions including hyperdynamic therapy (intentional hypervolemia, induced hypertension, and/or hemodilution) between the two treatment groups.

In contrast to the accompanying study, the protocol for the North American study was formally amended, in that a sequential analysis of the primary efficacy end point, mortality rate at 91 days postdosing, was performed. This analysis revealed a statistically significant difference in mortality rates, favoring the study drug, among patients who were neurological Grade IV or V at admission (24.6% compared with 43.4% in the placebo-treated group, p = 0.016). No significant differences, however, were found when the entire patient population was considered (15.6% in the placebo-treated group and 13% in the tirilazad-treated group). Other major and secondary end points, which included rate of favorable outcome (74% in the placebo-treated group and 71% in the tirilazad-treated group); symptomatic vasospasm (38% in the placebo-treated group and 35% in the tirilazad-treated group); and vasospasm severity (severe symptomatic vasospasm in 14% of patients in both groups), were also not significantly different between the two groups. In patients with neurological Grades I through III, rates of favorable outcome advantageous to the vehicle-treated group were observed (83.3% compared with 76.7%, p = 0.04).

Conclusions. High-dose tirilazad mesylate is well tolerated in women with aneurysmal SAH. Sequential analysis revealed a significant reduction in mortality rates among patients with neurological Grades IV and V, favoring the study drug and confirming the same effect observed in male patients in previous large studies. No beneficial effect was observed in patients who were in a good neurological grade at admission.

Full access

Introduction

Focused ultrasound surgery

W. Jeffrey Elias and Neal F. Kassell

Restricted access

Acute Brain Swelling in Neurosurgical Patients

Thomas W. Langfitt and Neal F. Kassell

Restricted access

Angiography After Aneurysm Surgery

Restricted access

Induction of tolerance against ischemia/reperfusion injury in the rat brain by preconditioning with the endotoxin analog diphosphoryl lipid A

Tomikatsu Toyoda, Neal F. Kassell, and Kevin S. Lee

Object. Inflammatory responses and oxygen free radicals have increasingly been implicated in the development of ischemic brain injury. In some cases, an attenuation of inflammation or free-radical injury can provide tissue protection. Diphosphoryl lipid A (DPL) is a detoxified derivative of a lipopolysaccharide (endotoxin) of Salmonella minnesota strain R595, which is capable of stimulating the immune system without eliciting direct toxic effects. In this study the authors examined the influence of preconditioning with DPL on ischemia/reperfusion injury in rats.

Methods. Sprague—Dawley rats were injected intravenously with either DPL or vehicle. Twenty-four hours later, some animals were tested for superoxide dismutase (SOD) activity. Others were subjected to a 3-hour period of focal cerebral ischemia and, after a reperfusion period of 24 hours, were killed. Infarction volume, SOD activity, and myeloperoxidase (MPO) activity were assayed in the postischemic animals.

Pretreatment with DPL produced significant reductions in cerebral infarction and MPO activity in the ischemic penumbra. A significant enhancement of basal SOD activity was observed 24 hours after DPL treatment (that is, before ischemia), and a further enhancement of SOD activity was seen in the ischemic penumbra 24 hours after reperfusion.

Conclusions. These data provide the first evidence of a neuroprotective effect of preconditioning with DPL in an in vivo model of cerebral ischemia. Although the precise mechanisms through which DPL exerts its neuroprotective influence remain to be established, an inhibition of the complex inflammatory response to ischemia and an enhancement of endogenous antioxidant activity are leading candidates.

Restricted access

Editorial

Unruptured aneurysms

Aaron S. Dumont, Giuseppe Lanzino, and Neal F. Kassell

Restricted access

The Etiology of Acute Brain Swelling Following Experimental Head Injury

Thomas W. Langfitt, Howard M. Tannanbaum, and Neal F. Kassell

Restricted access

Letters to the Editor: Gamma Knife thalamotomy

Neal F. Kassell and G. Frederick Wooten

Restricted access

The natural history of aneurysms and arteriovenous malformations

John A. Jane, Neal F. Kassell, James C. Torner, and H. Richard Winn

✓ The authors summarize the findings of previous studies relating to the natural history of aneurysms and arteriovenous malformations (AVM's). Ruptured aneurysms have their highest rate of rebleeding on Day 1, and at least 50% will rebleed during the 6 months after the first hemorrhage. Thereafter, the rate drops to at least 3% a year. This is the same rate as seen in anterior and posterior communicating artery aneurysms treated by anterior cerebral artery clipping and carotid ligation; these operations provide immediate protection but do not result in long-term diminution of the risk of rebleeding. Patients with unruptured incidental and unruptured multiple aneurysms rebleed at a rate of 1% per year, as do patients with subarachnoid hemorrhage of unknown etiology. The risk of rebleeding for AVM's is 3% a year.