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John Calogero, David C. Crafts, Charles B. Wilson, Edwin B. Boldrey, Alan Rosenberg and K. Jean Enot

✓The authors present three patients who, after excision and irradiation of their brain tumors, were treated with BCNU for recurrence. All three patients responded well and now are without evidence of tumor, 37, 30, and 36 months after BCNU was stopped. Although these patients represent only a small fraction of those treated with BCNU, they indicate the potential role of chemotherapy in the management of glial tumors.

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Experimental cervical myelopathy

Effects of ischemia and compression of the canine cervical spinal cord

Michael R. Gooding, Charles B. Wilson and Julian T. Hoff

✓ The authors report experiments designed to test the effect of regional ischemia induced by selective vascular ligations and anterior compression of the cervical cord at two adjacent segments (C-4, C-5) in the same dog. They conclude that local ischemia of the cervical cord, caused by local deformation, when superimposed on a regional reduction in spinal cord blood flow, accounts for the myelopathy of cervical spondylosis whether produced experimentally in animals or occurring naturally in man.

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Takao Hoshino and Charles B. Wilson

✓ The authors review and discuss the basic concepts of cell kinetics as applied to brain tumors. Uncontrolled growth of a neoplasm represents an expanding tumor cell population. Four growth parameters characterize the behavior of a neoplastic population: cell cycle time, growth fraction, tumor doubling time, and cell loss. The concept of provisionally nondividing cells explains the disparity between cell cycle time and tumor doubling time. Human gliomas, like many non-neural solid tumors, contain variable proportions of actively proliferating and nonproliferating tumor cells; this ratio is expressed by the growth fraction. The major kinetic difference between glioblastomas and differentiated astrocytomas resides in their respective growth fractions, in all likelihood an inherent biological characteristic of each tumor. Glioblastoma proliferates at a rapid rate, and only a high rate of cell loss prevents this tumor from doubling its volume in less than 1 week. The selection of drugs and design of drug schedules for treatment of glioblastomas should be made with the knowledge that 60% to 70% of the cells in this tumor are resting (nonproliferating). If experience with other solid tumors is any guide, judicious selection and combined use of drugs according to kinetically sound schedules will produce more effective chemotherapy of brain tumors.

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A. R. Vasantha Kumar, Justin Renaudin, Charles B. Wilson, Edwin B. Boldrey, K. Jean Enot and Victor A. Levin

✓ A series of 43 patients, all of whom were deteriorating due to progression of primary or metastatic brain tumors, were treated daily with n-isopropyl-α-(2-methylhydrazine)-p-toluamide hydrochloride (matulane, Procarbazine hydrochloride: NSC-77213, 150 mg./m2) for 30 consecutive days, with a 30-day rest interval between treatments. Of 29 patients evaluated, 12 showed a definite clinical response to therapy and two a probable response, for a response rate of 48%. Reversible myelosuppression was the major toxic effect encountered. Combination with other chemotherapeutic agents may enhance the drug's effectiveness against brain tumors.

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E. Fletcher Eyster, Surl L. Nielsen, Glenn E. Sheline and Charles B. Wilson

✓ Two years after undergoing irradiation for a malignant ethmoid tumor, a 50-year-old man developed signs of increased intracranial pressure, an expanding right frontal lobe mass, and tentorial herniation. Operation revealed a mass that grossly appeared to be a glioma, but microscopically proved to be radiation necrosis of the brain.

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William Mathews and Charles B. Wilson

✓ The authors report a case in which a chordoma ballooned an otherwise intact sella. Following almost total removal of the lesion, the patient recovered normal vision and returned to work. Neoplastic transformation of ectopic notochordal tissue is suggested as an explanation for the unique intrasellar origin of this tumor.

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Anthony D. Oliver, Charles B. Wilson and Edwin B. Boldrey

✓ Two cases of spinal arteriovenous malformation (AVM) are reported because of a previously unobserved clinical feature: recurrent transient postprandial paresis of the legs. The authors believe the paresis was caused by chronic shunting of blood away from the cord and into the low-resistance AVM. Symptomatic cord ischemia might then be precipitated by vasodilatation in other areas of the body such as the splanchnic, brachial, or uterine vessels. We believe that in some instances this mechanism should be considered as an explanation for episodic neurological deficits seen in association with spinal AVM's.

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Justin Renaudin, Derek Fewer, Charles B. Wilson, Edwin B. Boldrey, John Calogero and K. Jean Enot

✓ Twenty patients seriously ill following subtotal excision of brain tumors were given unusually large doses of Decadron to restrain peritumoral edema. The prompt clinical effect was strikingly favorable in 11. The dosage of Decadron above which no additional anti-edema effect occurs must be established for each individual patient. No significant complications occurred under dosages ranging from 32 to 96 mg/day. Brain scintiscans performed after rapid clinical improvement in five cases showed no change.

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Sinsuke Hukuda and Charles B. Wilson

✓ Maximal tolerable compression was produced in 28 dogs by advancing a screw through the anterior portion of the C-5 vertebral body into the spinal canal until limb weakness occurred. Chronic vascular insufficiency was established in the cervical cord of 17 dogs by blocking or ligating the spinal and vertebral arteries and their branches in various combinations. Vascular insufficiency was also established in combination with maximal compression. Neurological, microangiographic, and histological findings in all groups of dogs were compared. Dogs in the last group with the most severe injury had more abnormal findings in surface vessels than did all other dogs. When the dogs were bled to the point of weakness, that point also appeared soonest in the last group. From these findings, the authors conclude that the effects of vascular insufficiency and compression are additive and that this may be an explanation of the clinical signs in patients with cervical spondylotic myelopathy who appear to have relatively slight mechanical compression.

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Graded cryohypophysectomy in the rhesus monkey

Histopathology and endocrine function

Suleyman Saglam, Clifford L. Kragt, Charles B. Wilson, Selna L. Kaplan and Marvin Barker

✓ Histopathology and endocrine function of the pituitary gland of rhesus monkeys subjected to graded cryohypophysectomy were compared with the histopathology and endocrine function in hypophysectomized and sham-operated monkeys. Freezing at −50°, −100°, and −150°C destroyed 72.3%, 78.3%, and 93.1% of the pituitary respectively. The posterior lobe was more resistant to the damaging effects of cold. A nearly complete (96.3%) histological hypophysectomy was accomplished at −190°C; nearly all remaining viable tissue was in the posterior lobe. Freezing at −150°C appears to result in a complete functional hypophysectomy. Of the adenohypophyseal cells, the gonadotropin-secreting cells were the most susceptible to cold, with the growth-hormone-producing cells next in susceptibility. Adrenocorticotropin-secreting cells were more resistant. Cells producing thyroid-stimulating hormones were not susceptible, and the pituitary stalk was quite resistant to the damaging effects of freezing at these temperatures. Thus, a predictable partial hypophysectomy by means of cryosurgery seems feasible, and, with a predetermined time, it is evident that the degree of cold is critical in achieving a complete cryohypophysectomy.