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Michael D. Walker, Eben Alexander Jr., William E. Hunt, Collin S. MacCarty, M. Stephen Mahaley Jr., John Mealey Jr., Horace A. Norrell, Guy Owens, Joseph Ransohoff, Charles B. Wilson, Edmund A. Gehan and Thomas A. Strike

✓ A controlled, prospective, randomized study evaluated the use of 1,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) and/or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma. A total of 303 patients were randomized into this study, of whom 222 (73%) were within the Valid Study Group (VSG), having met the protocol criteria of neuropathology, corticosteroid control, and therapeutic approach. Patients were divided into four random groups, and received BCNU (80 mg/sq m/day on 3 successive days every 6 to 8 weeks), and/or radiotherapy (5000 to 6000 rads to the whole brain through bilateral opposing ports), or best conventional care but no chemotherapy or radiotherapy. Analysis was performed on all patients who received any amount of therapy (VSG) and on the Adequately Treated Group (ATG), who had received 5000 or more rads radiotherapy, two or more courses of chemotherapy, and had a minimum survival of 8 or more weeks (the interval that would have been required to have received either the radiotherapy or chemotherapy). Median survival of patients in the VSG was, best conventional care: 14 weeks (ATG: 17.0 weeks); BCNU: 18.5 weeks (ATG: 25.0 weeks); radiotherapy: 35 weeks (ATG: 37.5 weeks); and BCNU plus radiotherapy: 34.5 weeks (ATG: 40.5 weeks). All therapeutic modalities showed some statistical superiority compared to best conventional care. There was no significant difference between the four groups in relation to age distribution, sex, location of tumor, diagnosis, tumor characteristics, signs or symptoms, or the amount of corticosteroid used. An analysis of prognostic factors indicates that the initial performance status (Karnofsky rating), age, the use of only a surgical biopsy, parietal location, the presence of seizures, or the involvement of cranial nerves II, III, IV, and VI are all of significance. Toxicity included acceptable, reversible thrombocytopenia and leukopenia.

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Michael D. Walker, Eben Alexander Jr., William E. Hunt, Carl M. Leventhal, M. Stephen Mahaley Jr., John Mealey, Horace A. Norrell, Guy Owens, Joseph Ransohoff, Charles B. Wilson and Edmund A. Gehan

✓ A controlled, prospective, randomized study evaluated the use of mithramycin in the treatment of anaplastic glioma compared to a similar group of patients receiving best conventional care. From a total of 116 patients in the study, 96 were within the valid study group. All patients were operated on, had histological confirmation of anaplastic glioma, and received radiotherapy at the discretion of the principal investigator. Fifty-two patients received mithramycin at a dose of 25 µg/kg/day for 21 days, while 44 patients were in the control group. There was no significant difference in the median survival from time of randomization in those receiving mithramycin (21 weeks) as compared to those not receiving mithramycin (26 weeks). There was no significant difference between the two groups in relation to age distribution, sex, location, diagnosis, tumor characteristics, signs or symptoms, or radiotherapy received. Duration of symptoms correlates positively with survival and was also significantly longer in the control group than in the treated group. This, however, did not account for the failure of mithramycin to be found an effective agent. Although the study was not designed to evaluate the efficacy of radiotherapy, patients who were so treated had a significant improvement in survival. The toxic complications of mithramycin included gastrointestinal symptoms, dermatological involvement, anemia, and liver dysfunction, indicating the need for close supervision.

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Melville Roberts, Peter A. Rinaudo, Juliet Vilinskas and Guy Owens

✓ A case is reported in which spinal cord compression was caused by a solitary sclerosing plasma-cell myeloma involving the T-9 vertebra.

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Melville Roberts and Guy Owens

✓ During 10 operative procedures on eight patients with various intracranial lesions a membrane mass spectrometer was used to measure the regional partial pressure of oxygen (pO2), carbon dioxide (pCO2), and argon (pA) in subcortical white matter. The pO2 varied from 12 to 49 mm Hg, and the pCO2 from 31 to 123 mm Hg. Lowering intracranial pressure to 0 by ventricular drainage increased the pO2 and argon washout values (except in necrotic brain where no increase occurred) and decreased the pCO2 values. In one patient restoration of intraventricular pressure to the initial level of 220 mm H2O resulted in a 20% decrease in pCO2, a 15% decrease in argon washout rate, and a 21% increase in pCO2. These data suggest that regional cerebral blood flow, pO2, and pCO2 are influenced by intracranial hypotension as well as the condition of local brain tissue.

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Melville Roberts, Guy Owens, Juliet Vilinskas and David D. Thomas

✓ Seizures were induced in 12 monkeys rendered hemiparetic by middle cerebral artery occlusion. In a control group of five hemiparetic monkeys seizures were not induced. A mass spectrometer was used to monitor regional oxygen tension (pO2), carbon dioxide tension (pCO2) and the partial pressure of argon (pA) within the ischemic brains. Seisure activity resulted in a 74.3% mean increase in pO2 and 16.9% mean decrease in pCO2. The mean argon washout time was decreased 29.1%. The changes were transient and recovery from hemiparesis was no better in the experimental group than in the control group.

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Ronald R. Reed, Conrad Ciesel and Guy Owens

✓ Intracerebral pO2, as measured in normal dog brains by a modified mass spectrometer, was found to increase following seizure activity and remain elevated at least 2 hours. These results were found with both drug- and electrically-induced seizures. The pO2 increased to a greater degree in brain tissue rendered ischemic by middle cerebral artery occlusion. A transient reflex hypertension was observed with seizure activity, but hypertension alone failed to produce significant pO2 changes. Since oxidative metabolism has been shown by other investigators to proceed at an elevated rate during seizure activity, the increased pO2 must reflect improved collateral circulation following seizure activity.

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Guy Owens, Lorenzo Belmusto and Sabbo Woldring

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Guy Owens, Merrill A. Blender and Monte Blau

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Monoventricular Hypothermic Perfusion

Cortical Electric Responses to Analeptic Agents

Maurice Costal, James Ausman, Sabbo Woldring and Guy Owens