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Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68±14 days. The response rates (CR+PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.

Measurement of oxygen pressure (pO2) in tumor tissue is important, because pO2 is a major factor for radiosensitivity in malignant glioma treatment. We attempted to elucidate the changes in pO2 level in glioblastoma tissue of patients under various conditions. Eighteen patients with newly diagnosed glioblastoma were recruited to this study. Disposable Clark-type electrodes were inserted using CT guided stereotactic surgery under local anesthesia and left in the intra- and peritumoral regions. pO2 was measured in patients under conditions of being awake and asleep, inhaling 100% O2, being administered osmotic diuretics and following hyperbaric oxygen exposure (HBO). Peritumoral tissue had a significantly higher pO2 value in both awake and sleeping patients. O2 inhalation could not significantly increase the pO2 level, whereas administration of osmotic diuretics induced an increase in pO2 levels in peritumoral tissue alone. The pO2 levels were significantly increased in both regions after HBO, and a high pO2 level was maintained until 15 min after HBO in both regions. It is possible that the pO2 level in peritumoral tissue is affected by intracranial pressure, whereas that in the intratumoral tissue is usually low. HBO was the optimal procedure for oxygenation, but its benefit was reduced over time.

Chronic neuropsychiatric symptoms after carbon monoxide (CO) poisoning are caused by demyelination of cerebral white matter fibers. We examined whether diffusion tensor imaging can sensitively represent damage to fibers of the centrum semiovale in the subacute phase after CO intoxication.Subjects comprised 13 adult patients with CO poisoning, classified into three groups according to clinical behaviors: group A, patients with transit acute symptoms only; group P, patients with persistent neurological symptoms; and group D, patients with "delayed neuropsychiatric sequelae" occurring after a lucid interval. Median fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the centrum semiovale bilaterally at 2 weeks were compared between these groups and a control group of ten healthy volunteers. Myelin basic protein (MBP) concentration in cerebrospinal fluid was examined at 2 weeks to evaluate the degree of demyelination in patients.MBP concentration was abnormal or detectable for all group P and group D patients but was undetectable for all patients assigned to group A. Low FA values in groups P and D displaying chronic neurological symptoms clearly differed from those in controls and group A without chronic neurological symptoms, but ADC showed no significant differences between patient groups.MBP concentration at 2 weeks after CO inhalation confirmed a certain extent of demyelination in the central nervous system of patients who would develop chronic neurological symptoms. In these patients, FA sensitively represented damage to white matter fibers in the centrum semiovale in the subacute phase after CO intoxication.

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.

Measurement of oxygen pressure (pO2) in tumor tissue is important, because pO2 is a major factor for radiosensitivity in malignant glioma treatment. We attempted to elucidate the changes in pO2 level in glioblastoma tissue of patients under various conditions. Eighteen patients with newly diagnosed glioblastoma were recruited to this study. Disposable Clark-type electrodes were inserted using CT guided stereotactic surgery under local anesthesia and left in the intra- and peritumoral regions. pO2 was measured in patients under conditions of being awake and asleep, inhaling 100% O2, being administered osmotic diuretics and following hyperbaric oxygen exposure (HBO). Peritumoral tissue had a significantly higher pO2 value in both awake and sleeping patients. O2 inhalation could not significantly increase the pO2 level, whereas administration of osmotic diuretics induced an increase in pO2 levels in peritumoral tissue alone. The pO2 levels were significantly increased in both regions after HBO, and a high pO2 level was maintained until 15 min after HBO in both regions. It is possible that the pO2 level in peritumoral tissue is affected by intracranial pressure, whereas that in the intratumoral tissue is usually low. HBO was the optimal procedure for oxygenation, but its benefit was reduced over time.