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Vladimir V. Didenko, Hop N. Ngo, Candace Minchew and David S. Baskin

Object. The goal of this study was to investigate whether apoptosis occurs in T lymphocytes that invade Fas ligand (FasL)—expressing glioblastomas multiforme (GBMs) and if its induction could be mediated by Fas.

Methods. Apoptotic T lymphocytes were detected in GBMs by using detection of cell-type markers combined with active caspase-3 immunohistochemical analysis, a recently introduced apoptosis-specific in situ ligation assay, as well as by examining morphological criteria. Apoptotic T cells expressed Fas and were localized in the vicinity or in direct contact with FasL-expressing tumor cells. The T lymphocytes were undergoing apoptosis in spite of Bcl-2 expression. Expression of Bax was also detected in dying T cells, which can explain the absence of the protective effect of Bcl-2, because Bax inhibits Bcl-2 death-repressor activity.

Conclusions. On the basis of the data presented in this paper, the authors suggest that GBM cells that express FasL can induce apoptosis in invading immune cells. This phenomenon may play an important role in these tumors' maintenance of immune privilege and evasion of immune attacks. Awareness of this phenomenon should be helpful for the development of novel strategies for treatment of malignant gliomas.

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Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data

Results of the second National Acute Spinal Cord Injury Study

Michael B. Bracken, Mary Jo Shepard, William F. Collins Jr., Theodore R. Holford, David S. Baskin, Howard M. Eisenberg, Eugene Flamm, Linda Leo-Summers, Joseph C. Maroon, Lawrence F. Marshall, Phanor L. Perot Jr., Joseph Piepmeier, Volker K. H. Sonntag, Franklin C. Wagner Jr., James L. Wilberger, H. Richard Winn and Wise Young

✓ The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.

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Robert E. Harbaugh, Teddi M. Reeder, Howard J. Senter, David S. Knopman, David S. Baskin, Francis Pirozzolo, Helena Chang Chui, Andrew G. Shetter, Roy A. E. Bakay, Richard Leblanc, Robert T. Watson, Steven T. DeKosky, Frederick A. Schmitt, Stephen L. Read and Jimmie T. Johnston

✓ The use of intracerebroventricular bethanechol chloride infusion in patients with Alzheimer's disease was first reported in 1984. An initial trial in four patients demonstrated the feasibility of this approach for cholinergic drug delivery to the brain, but objective improvement in cognitive function was not documented. A collaborative placebo-controlled double-blind crossover study has now been carried out in 49 patients with biopsy-documented Alzheimer's disease. The results demonstrate a statistical improvement in Mini-Mental State scores and significantly slower performance on Trails A testing during drug infusion. Other neuropsychological test scores were not similarly affected. The degree of improvement was not sufficient to justify further treatment of Alzheimer's disease patients by intracerebroventricular infusion of bethanechol chloride. The drug delivery system used in the study was well tolerated, with two irreversible complications in more than 50,000 patient days.

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David S. Baskin and Charles B. Wilson

✓ A series of 74 patients with craniopharyngiomas were treated during a 15-year period. Of the 74 patients, 40 were males and 34 were females, with a mean age of 27 years (range 3 to 65 years). Twenty-eight patients (38%) were less than 18 years of age. Remission was defined as clinical improvement with stable ophthalmological and neurological status, radiological evidence of a decrease in tumor size, and either a continued decrease or a stable tumor size on follow-up radiological evaluations. A fair result was considered remission with new neurological deficits related to surgical intervention. All other results were considered a failure. The mean follow-up period in this study was 4 years, with 100% of the patients monitored.

In children, the most common presentation was that of growth failure (93%). In adults, sexual dysfunction was the most common presentation, with 88% of males presenting with impotence or marked decrease in sexual drive, and 82% of females presenting with primary or secondary amenorrhea, often associated with galactorrhea. Considering the pediatric and adult populations together, the most common presenting symptom was visual dysfunction, with 71% of patients presenting in this manner. Fifty percent of patients presented with severe headache. The most frequent preoperative finding was a visual field defect, with 72% of patients so affected; 42% of patients had preoperative hypothyroidism and 24% had hypoadrenalism. Diabetes insipidus was present preoperatively in 23%. Hydrocephalus was uncommon, being present in only 15%.

A subfrontal craniotomy was used in 47% of patients, a transsphenoidal approach in 39%, a subtemporal approach in 11%, a transcallosal approach in 5%, and a suboccipital craniectomy in 2%. Multiple procedures were required in 15% of patients in order to provide significant relief of compressive symptomatology. The results of therapy indicate that total tumor removal was deemed to have been achieved in only seven patients, six of whom have had no recurrence. However, 91% of patients are in remission, one had a fair result, and two died as a direct result of surgical intervention. One patient died from uncontrolled disease, and three patients died from unrelated causes. The results of this study indicate that radical subtotal removal followed by radiotherapy is an acceptable treatment for craniopharyngioma.

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Treatment of experimental stroke with opiate antagonists

Effects on neurological function, infarct size, and survival

David S. Baskin, Yoshio Hosobuchi and Joachim C. Grevel

✓ The effects are reported of acute and long-term continuous administration of three opiate antagonists — naloxone, naltrexone, and diprenorphine — on neurological function, survival, and infarct size in a feline model of acute focal cerebral ischemia. All three drugs produced statistically significant improvement in motor function following acute administration without concomitant changes in level of consciousness; saline had no effect. Naloxone and naltrexone significantly prolonged survival (p < 0.01); diprenorphine did not. Infarct size was not altered by any treatment administered. These findings confirm previous work suggesting that, with the appropriate methodology, treatment with opiate antagonists partially reverses neurological deficits. They also show that opiate antagonists prolong survival in certain conditions of acute and subacute focal cerebral ischemia without altering the area of infarcted tissue.

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David S. Baskin and Charles B. Wilson

✓ Thirty-eight patients underwent transsphenoidal microsurgical treatment of non-neoplastic intrasellar cysts: 36 had cyst drainage and biopsy of the cyst wall, and in two the cyst was totally removed. Surgical morbidity was 8%. The mean follow-up time was 46.3 months; 100% patient follow-up evaluation was achieved. Sixteen female patients (mean age 24.6 years) had pars intermedia cysts: 88% had menstrual irregularities, 63% had galactorrhea, 31% had headache, and 56% had hyperprolactinemia. Within these groups, menstrual cycles returned in 86%, galactorrhea ceased in 90%, headaches resolved in 80%, and serum prolactin levels were restored to normal in 66%. Eight females and three males had Rathke's cleft cysts (mean age 34.0 years): of these 11 patients, 91% had headaches and 18% had hyperprolactinemia; of the eight females, 63% had amenorrhea and 63% had galactorrhea. Within these groups, serum prolactin levels normalized in 50%, and 80% noted reduced headache. Of the females, 80% had return of menses and 50% noted cessation of galactorrhea. Six males and two females had arachnoid cysts (mean age 42.2 years): 50% had headaches; 50% were asymptomatic. Preoperatively, 50% of these patients had hypothyroidism and 25% had adrenal hypofunction. Postoperatively, 75% of patients with headache noted improvement, and 33% of patients with abnormal thyroid function had normal function. Adrenal function did not improve. Three patients had an intrasellar cysticercosis cyst, epidermoid cyst, and postoperative cyst, respectively. All had evidence of partial hypopituitarism; none improved postoperatively. The results indicate that different types of pituitary cysts produce different clinical syndromes, and suggest that simple transsphenoidal drainage and partial removal of the cyst wall can provide safe and effective therapy.