Subarachnoid hemorrhage not due to ruptured aneurysm in moyamoya disease.

A patient with moyamoya disease presenting with subarachnoid hemorrhage (SAH) is reported. A 38-year-old Japanese woman developed a sudden onset headache and nausea during hospitalization for a cerebral infarct in the right frontal lobe. CT scan showed SAH in the left frontal sulci. Cerebral angiogram showed stenosis of the distal bilateral internal carotid arteries with moyamoya vessels, and significant transdural anastamoses from the left external carotid artery to cortical arteries on the left frontal cortex. The patient was kept normotensive and underwent a right-sided surgical revascularization procedure, remaining well for three years. SAH not due to ruptured aneurysm in moyamoya disease is rare. The cause of the SAH was thought to be disruption of the transdural anastomotic vessels. Recognition of these fragile vessels in moyamoya disease is essential.

[Prediction of stroke, coronary heart disease, cardiovascular disease, cancer, and total death based on results of annual health checkups].

OBJECTIVE: We aimed to predict mortality rate from the findings of annual health checkups for men and women. METHOD: The subjects were 31,053 men and 61,224 women who were living in Ibaraki prefecture (Japan), aged 40 to 79 years, without history of any stroke and coronary heart disease, and who participated in annual health checkups in 1993. They were followed until the end of 2001, with a systemic review of resident registration and death certificates. The Cox's proportional hazards model with step-down procedure was used to estimate predictive model. RESULTS: During the 8.0 years follow-up, there were 5260 deaths (710 from stroke, 389 from coronary heart disease and 2,322 from cancer). The predictive factors for all causes were advanced age, high systolic blood pressure, medication for hypertension, low serum HDL cholesterol, high or low serum creatinine, high AST or ALT, diabetes, low body mass index, current smoking, heavy drinking, and urinary protein among men. The predictive factors for cardiovascular disease were advanced age, high systolic blood pressure, medication for hypertension, low or high serum total cholesterol, low serum HDL cholesterol, high serum creatinine, diabetes, low body mass index, current smoker, and urinary protein, and those for cancer were advanced age, medication for hypertension, low serum HDL cholesterol, low serum creatinine, high AST or ALT, diabetes, low body mass index, current smoking, heavy drinking and urinary protein. Furthermore, those for stroke were advanced age, high systolic blood pressure, medication for hypertension, low serum HDL cholesterol, high serum creatinine, high AST or ALT, low body mass index, current smoking, while for coronary heart disease they were advanced age, high systolic blood pressure, high serum total cholesterol, low serum HDL cholesterol, diabetes, current smoking, and urinary protein among men. For women, similar predictive factors were obtained, although some of them did not reach statistical significance. CONCLUSION: We could construct predictive models for 5-year mortality rate from results of annual health checkups. These findings should prove useful for computerized health education on the prevention of stroke, coronary heart disease, and cancer.

Age-specific relationship between blood pressure and the risk of total and cardiovascular mortality in Japanese men and women.

To examine the impact of age on the relationship between blood pressure (BP) levels and each of cardiovascular disease mortality and all-cause mortality, a total of 30,226 men and 58,798 women aged 40-79 years who had no history of stroke or heart disease underwent health checkups in Ibaraki-ken, Japan, in 1993 and were followed through 2002. Risk ratios for mortality by BP category based on the 1999 WHO-ISH guidelines were calculated by age subgroups (40-59 years, 60-79 years) using a Cox proportional hazards model. Compared with optimal BP levels, the multivariate risk ratios of cardiovascular mortality for stage 2 or 3 hypertension were 5.99 (95% confidence interval: 2.13-16.8) in middle-aged men and 4.09 (1.70-9.85) in middle-aged women. These excess cardiovascular mortality risks were larger in the 40-59 years age group than in the 60-79 years age group for both genders (p for interaction = 0.01 for both). In men, the population attributable risk percents of cardiovascular mortality were 60% for younger men and 28% for older men, while for women they were 15% for younger women and 7% for older women. Weaker but significant excess risks of total mortality were observed for stage 2 or 3 hypertension in men of both age groups and in the older age group for women. The impact of BP on the risk of cardiovascular mortality was larger among middle-aged persons than among the elderly in both men and women. Our findings indicate the importance of BP control to prevent cardiovascular disease among middle-aged individuals.

Traumatic central cord syndrome: analysis of factors affecting the outcome.

BACKGROUND: The indications and timing of treatment, as well as the best treatment method for traumatic central cord syndrome (CCS), remain controversial. The aims of this study are to determine the prognostic factors of traumatic CCS and to determine appropriate surgical indications. METHODS: We reviewed the clinical and radiological data of 47 patients with this syndrome. The data collected included age, neurological status as measured on a scale defined by the Japanese Orthopaedic Association (JOA), anteroposterior (AP) diameter of the spinal canal on computed tomography, signal intensity change of the spinal cord on T2-weighted magnetic resonance imaging (MRI), associated spinal diseases, and the type of treatment received. The correspondence between the clinical and radiological findings and the neurological outcome was investigated. RESULTS: The patient's age, JOA score on admission, signal intensity change of the spinal cord on MRI, and associated spinal diseases were not significant in predicting the patient's recovery. On the other hand, the AP diameter of the spinal canal (P = .0402) and the interval between injury and surgery (P < .0001) were factors predictive of excellent recovery. In the surgical treatment group, timely surgery was found to improve the outcome, while conservative treatment did not improve the outcome of patients with a low JOA score, a relatively small AP diameter of the spinal canal, or a positive signal intensity change of the spinal cord on T2-weighted MRI. CONCLUSION: The AP canal diameter of the spinal canal and the interval between injury and surgery may be reliable predictors of excellent recovery in patients with CCS. We recommend timely surgery, preferably within 2 weeks of injury, to achieve a better functional outcome in selected patients.

[Development of a tool for assessment of local government health policy].

OBJECTIVE: A tool was developed for assessment of health status in communities to help formulate health policy of local governments and allow estimates of magnitude of changes in mortality with modification of selected risk variables. MATERIALS AND METHODS: A total of 25,201 men and 51,776 women aged 40-69 years who underwent health checkups in Ibaraki-ken, Japan, in 1993 were followed through 2002. Risk ratios for all cause, cardiovascular disease, cerebrovascular disease, ischemic heart disease, all cancer, and lung cancer deaths were calculated according to smoking, heavy alcohol consumption, obesity, hypertension, hypercholesterolemia, low high-density lipoprotein cholesterol, and diabetes using a Cox proportional hazards model. Regression coefficients for body mass index, systolic blood pressure, serum total cholesterol, serum high-density lipoprotein cholesterol, and plasma glucose were also calculated by the model with quadratic terms. On the basis of the results, we developed a tool using Microsoft EXCEL, allowing estimation of the magnitude of changes in death rates according to variation in mean and standard deviation values for risk factors by impact fraction. RESULTS: The developed tool facilitates estimation of magnitude of changes in death rates with alteration in exposure rates and means/standard deviations of risk variables with intervention. The best magnitude of decline for all cause mortality with a 50% reduction of exposure to smoking was 10% in men. The magnitudes of decline in cardiovascular disease mortality with a 50% reduction in hypertension were 12% in men and 11% in women. Furthermore, the magnitude of decline in cardiovascular disease mortality if a 10% lowering of mean systolic blood pressure were achieved would be 22% in men and 18% in women. CONCLUSIONS: Our developed tool may be useful to assess health status in communities with cooperation between municipal and prefectural governments.

Anti-vascular endothelial growth factor antibody and nimustine as combined therapy: effects on tumour growth and angiogenesis in human glioblastoma xenografts.

We evaluated the effectiveness of vascular endothelial growth factor (VEGF) blockade alone and in combination with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU, nimustine), a cytotoxic agent commonly used in the treatment of malignant gliomas, to eradicate tumors of human glioblastoma cell lines implanted in SCID (severe combined immunodeficiency) mice. ACNU, but not cisplatin and etoposide, elevated VEGF expression in a glioma cell line in vitro. VEGF antibody alone inhibited glioma growth in vivo as a result of angiogenesis inhibition. The combination with ACNU resulted in an additive effect for inhibition of glioma growth. ACNU also induced VEGF up-regulation in glioma tissues, which was decreased with VEGF antibody treatment. One of the mechanisms of the additive effect of the VEGF antibody and ACNU combination is the blockade of VEGF up-regulation induced by ACNU. As such, the combination of antiangiogenic therapy with conventional therapy is promising for glioma treatment in the future.

ESR spin trapping of hydroxyl radicals in aqueous solution irradiated with high-LET carbon-ion beams.

The aim of this study was to quantify the hydroxyl radicals (*OH) produced when aqueous solutions are decomposed by high-linear energy transfer (LET) 290 MeV/nucleon carbon-ion beams using an electron spin resonance (ESR) spectrometer. Aerated cell culture medium containing 200 mM 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was irradiated with doses of 0 to 20 Gy with an LET of 20 to 90 keV/ micro m. We were able to obtain ESR spectra 10 min after irradiation, and the formation of *OH and hydrogen atoms was confirmed by radiolysis of deuterium oxide and ethanol containing DMPO. Our results showed that the yield of *OH by carbon-ion radiolysis increased in proportion to the absorbed dose over the range of 0 to 20 Gy. Furthermore, we discovered that the yield of *OH decreased linearity as LET increased logarithmically from 20 to 90 keV/ micro m. The generation of *OH by carbon-ion radiolysis at LETs of 20, 40, 60, 80 and 90 keV/ micro m was 64, 58, 52, 49 and 50%, respectively, of that for low-LET X radiolysis. These unique findings provide a further understanding of the indirect effect of high-LET radiation.

Characterization of neutron beams for boron neutron capture therapy: in-air radiobiological dosimetry.

The survival curves and the RBE for the dose components generated in boron neutron capture therapy (BNCT) were determined separately in neutron beams at Japan Research Reactor No. 4. The surviving fractions of V79 Chinese hamster cells with or without 10B were obtained using an epithermal neutron beam (ENB), a mixed thermal-epithermal neutron beam (TNB-1), and a thermal (TNB-2) neutron beam; these beams were used or are planned for use in BNCT clinical trials. The cell killing effect of the neutron beam in the presence or absence of 10B was highly dependent on the neutron beam used and depended on the epithermal and fast-neutron content of the beam. The RBEs of the boron capture reaction for ENB, TNB-1 and TNB-2 were 4.07 +/- 0.22, 2.98 +/- 0.16 and 1.42 +/- 0.07, respectively. The RBEs of the high-LET dose components based on the hydrogen recoils and the nitrogen capture reaction were 2.50 +/- 0.32, 2.34 +/- 0.30 and 2.17 +/- 0.28 for ENB, TNB-1 and TNB-2, respectively. The RBEs of the neutron and photon components were 1.22 +/- 0.16, 1.23 +/- 0.16, and 1.21 +/- 0.16 for ENB, TNB-1 and TNB-2, respectively. The approach to the experimental determination of RBEs outlined in this paper allows the RBE-weighted dose calculation for each dose component of the neutron beams and contributes to an accurate inter-beam comparison of the neutron beams at the different facilities employed in ongoing and planned BNCT clinical trials.

Stable nitroxide Tempol ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischemia.

Oxygen free radicals have been implicated in the pathogenesis of cerebral ischemia and reperfusion injury. 4-Hydroxy-2,2,6,6-tetramethylpiperidene-1-oxyl (Tempol) has been reported as a stable nitroxide and a membrane-permeable free radical scavenger. This study was performed to investigate the mechanism of Tempol in attenuating ischemia-reperfusion injury in a rat model of transient focal cerebral ischemia. We measured the cerebral 2,3-dihydroxybenzoic acid (DHBA) level as the amount of hydroxyl radical production using a microdialysis technique with salicylic acids trapping during ischemia and reperfusion. The concentration of cerebral thiobarbituric acid reactive substances (TBARS), representing the extent of lipid peroxidation by free radicals, and the area of cerebral infarction were also measured. The level of cerebral 2,3-DHBA was increased during ischemia and reperfusion, especially during the early reperfusion stage at the periphery of the infarct area (nearly 500-fold). Intravenous administration of Tempol at the time of reperfusion reduced 2,3-DHBA production (Vehicle group: 472.2+/-196.2, Tempol group: 238.3+/-77.2) and the cerebral TBARS level (Vehicle group: 541.7+/-84.7, Tempol group: 339.0+/-147.2 nmol/g), and decreased the size of the cerebral infarction (Vehicle group: 202.2+/-98.4, Tempol group: 98.5+/-13.7 mm(3)). In contrast, Tempol administered 15 min prior to reperfusion reduced neither the TBARS level nor the size of the infarction. These results indicate that Tempol administration at the time of reperfusion reduced lipid peroxidation by scavenging free radicals, resulting in a reduction of the infarct size.

Comparison of gadobenate dimeglumine and gadopentetate dimeglumine: a study of MR imaging and inductively coupled plasma atomic emission spectroscopy in rat brain tumors.

BACKGROUND AND PURPOSE: After the advent of extracellular contrast media, hepatobiliary-specific gadolinium chelates were developed to improve the diagnostic value of MR imaging of the liver. Gadobenate dimeglumine (Gd-BOPTA) is a new paramagnetic contrast agent with partial biliary excretion that produces prolonged enhancement of liver parenchyma on T1-weighted images. However, whether Gd-BOPTA is useful as a contrast agent in central nervous system disease, particularly in brain tumors, is unclear. METHODS: The behavior of Gd-BOPTA as a brain tumor-selective contrast agent was compared with that of gadopentetate dimeglumine (Gd-DTPA), an MR contrast agent used in central nervous system disease, in a common dose of 0.1 mmol/kg. An MR imaging study of these two contrast agents was performed, and tissue concentrations were measured with inductively coupled plasma atomic emission spectroscopy (ICP-AES). RESULTS: Gd-BOPTA showed better MR imaging enhancement in brain tumors than did Gd-DTPA at every time course until 2 hours after administration and no enhancement in peritumoral tissue and normal brain. Corresponding results with ICP-AES showed significantly greater uptake of Gd-BOPTA in tumor samples than that in peritumoral tissue and normal brain 5 minutes after administration. Gadolinium was retained for a longer time in brain tumors when Gd-BOPTA rather than Gd-DTPA was administered. CONCLUSION: Gd-BOPTA is a useful contrast agent for MR imaging in brain tumors and possibly an effective absorption agent for neutron capture therapy.

Repair of a tear at the base of a blister-like aneurysm with suturing and an encircling clip: technical note.

OBJECTIVE: An aneurysm can produce large defects in the parent vessel if the aneurysm tears at the neck of the vessel. The authors present a technique to repair a tear at the base of a blister-like aneurysm encountered during microsurgical clipping of an anterior wall aneurysm of the internal carotid artery. METHODS: The repair technique involved suturing and covering the aneurysm with an encircling aneurysm clip. A large tear had destroyed the vessel's tubular structure, and repair was not sufficient using an encircling clip alone. Two microsuture stitches were placed on the tear, so that a split artery re-formed a tubular structure. The lesion was then covered with Surgicel (Ethicon, Inc., Somerville, NJ) and fibrin glue. When the Surgicel and fibrin glue were applied, the temporary clip on the distal internal carotid artery was removed for a moment, allowing retrograde blood flow to provide the counterforce necessary to maintain the vessel's tubular structure. An encircling clip was then applied to cover the entire circumference of the lesion. RESULTS: This method required only a short occlusion time for arterial repair, thus helping avoid ischemic complications. The patient awoke with transient hemiparesis, but recovery was prompt. CONCLUSION: This technique is useful for repairing an aneurysmal tear at its base, especially if the tear is large.

Ruptured aneurysm of the ophthalmic artery trunk demonstrated by three-dimensional rotational angiography: case report.

OBJECTIVE AND IMPORTANCE: Aneurysms arising from the ophthalmic artery are extremely rare, compared with carotid-ophthalmic aneurysms arising from the wall of the internal carotid artery. We present a very unusual type of aneurysm arising from the ophthalmic artery itself. CLINICAL PRESENTATION: A 54-year-old man presented with a sudden onset of headache and was transferred to a local hospital. Computed tomography demonstrated subarachnoid hemorrhage around the left anterior clinoid process, but digital subtraction angiography failed to localize the source of the hemorrhage. The patient was referred to our hospital for further evaluation and treatment. Conventional cerebral angiography did not reveal the source of the hemorrhage, but three-dimensional rotational angiography clearly demonstrated an aneurysm arising from the ophthalmic artery trunk, apart from the internal carotid artery. INTERVENTION: The patient underwent microsurgical clipping of the aneurysm via a left pterional craniotomy. The aneurysm originated from the bifurcation of the ophthalmic artery and a perforating artery to the optic nerve. The aneurysm was successfully obliterated, and the postoperative course was uneventful. CONCLUSION: This report is the first to describe a case of a ruptured aneurysm arising from the ophthalmic artery trunk. We discuss the clinical significance of an aneurysm at this site, as well as the role of three-dimensional rotational angiography in determining the source of subarachnoid hemorrhage.

Multiple intracranial arterial stenoses around the circle of Willis in association with Graves' disease: report of two cases.

OBJECTIVE AND IMPORTANCE: The association of Graves' disease with multiple intracranial arterial stenoses is rare. CLINICAL PRESENTATION: We report on two Japanese women who experienced the concurrence of Graves' disease and cerebral ischemia attributable to multiple intracranial arterial stenoses around the circle of Willis. Clinically, these patients demonstrated hyperthyroidism, goiter, ophthalmopathy, and ensuing ischemic strokes. Cerebral angiography demonstrated multiple intracranial arterial stenoses around the circle of Willis in both cases. These cases did not meet the full diagnostic criteria for moyamoya disease, in that there were no abnormal, net-like, collateral vessels, but the other clinical and angiographic findings were consistent with this condition. INTERVENTION: After normalization of their hormonal conditions, the patients underwent cerebral revascularization procedures. Both patients achieved excellent recoveries and returned to normal daily life after treatment. CONCLUSION: Multiple intracranial arterial stenoses and Graves' disease may occur simultaneously. Such cases may offer new insights into the pathogenesis of these two conditions. It is important to study more patients with this dual condition, to obtain more evidence of the relationship between genetic and immunogenic backgrounds.

Small unruptured cerebral aneurysms presenting with oculomotor nerve palsy.

OBJECTIVE: Symptomatic unruptured aneurysms have been considered at relatively high risk for future rupture, and the majority of aneurysms that cause symptoms of mass effect are large. Unruptured aneurysms smaller than 1 cm in diameter sometimes cause neurological symptoms, but their clinical aspects remain obscure. In this article, we review our experience with small unruptured aneurysms presenting with oculomotor nerve palsy. METHODS: Sixteen patients with unruptured aneurysms smaller than 1 cm presenting with oculomotor nerve palsy were included in this study. The patients' clinical profiles were reviewed, and factors affecting the recovery of oculomotor function were determined. RESULTS: The mean size of the aneurysms was 5.8 +/- 1.4 mm. Eleven patients (68.8%) had preceding retrobulbar pain. Fifteen patients underwent successful microsurgical clipping or intravascular embolization, but one patient died of aneurysm rupture before surgery. Seven patients (43.8%) had a complete recovery of oculomotor function, six (37.5%) had an incomplete recovery, and two (12.5%) remained unchanged after treatment. The mean interval between the onset of oculomotor nerve palsy and treatment was 4.7 +/- 3.3 days in patients with complete recovery, 24.2 +/- 15.5 days in patients with incomplete recovery, and 41.0 +/- 12.7 days in unchanged patients. Early surgery resulted in more complete recovery of neural function (P < 0.01). CONCLUSION: Unruptured aneurysms smaller than 1 cm can cause neurological symptoms of mass effect. We recommend timely surgery, preferably within 5 days, to avoid not only aneurysm rupture but also functional disability even in patients with unruptured aneurysms smaller than 1 cm.

Cervical spondylotic myelopathy: surgical results and factors affecting outcome with special reference to age differences.

OBJECTIVE: A variety of factors may affect the surgical outcome in patients with cervical spondylotic myelopathy. The aim of this study is to analyze the prognostic factors by comparing younger and elderly patient groups on the basis of preoperative radiological and clinical data. METHODS: To assess the prognostic factors after surgery had been performed, the clinical and radiological data of 64 patients who underwent expansive laminoplasty were reviewed. Patients were classified into two groups, a younger patient group (<65 yr of age; n = 29) and an elderly patient group (>/=65 yr of age; n = 35). The neurological status of the patients was assessed by use of the Japanese Orthopaedic Association scale. Radiological features were examined with computed tomographic myelography and magnetic resonance imaging. The effects of the clinical and radiological findings on neurological outcome were investigated. RESULTS: The preoperative and postoperative mean Japanese Orthopaedic Association scores in elderly patients were significantly lower than those in younger patients. For elderly patients, the transverse area of the spinal cord at the level of maximum compression and symptom duration were the factors that predicted an excellent recovery. In contrast, the transverse area was the only predictor of excellent recovery in younger patients. Age, preoperative Japanese Orthopaedic Association score, canal diameter, and an intensity change on the spinal cord were not predictive in either age range. CONCLUSION: The transverse area of the spinal cord may be a reliable predictor of excellent recovery in both younger and elderly patient groups. Shorter symptom duration was an important factor in the excellent recovery of elderly patients.

Reversible dementia in patients with chronic subdural hematomas.

OBJECT: Neuropsychiatric changes following surgery for chronic subdural hematomas (CSDHs) were analyzed in 26 patients (21 men and five women) by using the Mini-Mental State Examination (MMSE) and the Hasegawa Dementia Scale-Revised (HDS-R) to determine factors that potentially contribute to neuropsychiatric recovery. METHODS: Burr hole irrigation was performed in every patient to treat the CSDH. The patients' profiles, including age and sex, neuroimaging findings (such as hematoma volume and thickness, as well as midline shift), and preoperative and postoperative scores on the MMSE, HDS-R, and activities of daily living (ADL) scale were recorded. According to preoperative MMSE scores, eight patients (30.8%) were classified as mentally healthy and 18 (69.2%) as suffering from dementia before surgery. Nine of the 18 patients with dementia recovered to a normal psychological state following surgery. Surgery improved not only the patients' independence in ADL (p = 0.0026), but also their neuropsychiatric functions such as orientation and calculation, as estimated by scores on the MMSE (p = 0.0002) and the HDS-R (p = 0.0008). Factors affecting neuropsychiatric status on admission were midline shift (p = 0.0398) and ADL score (p = 0.0124); factors that could be used to predict neuropsychiatric recovery after surgery were patient age (p = 0.0027) and ADL score (p = 0.0193). The results of a logistic regression analysis demonstrated that significant predictors of neuropsychiatric recovery after surgery include the following: patient age (p = 0.0049, odds ratio [OR] = 0.842) and preoperative ADL (p = 0.0056, OR = 0.471), MMSE (p < 0.0001, OR = 1.895), and HDS-R (p = 0.0073, OR = 1.303) scores. Results of subgroup analyses demonstrated that patients younger than 74 years of age and those who had preoperative scores lower than 5 on the converted ADL scale, higher than 10 on the MMSE, or higher than 9 on the HDS-R on admission were found to have a significantly better recovery of neuropsychiatric functions after surgery. CONCLUSIONS: Dementia is reversible in many patients with CSDH, and surgery can improve not only independence in ADL, but also neuropsychiatric functions. Patients who are younger and/or those who have lower preoperative ADL scores and/or higher preoperative MMSE or HDS-R scores will achieve a good recovery with regard to neuropsychiatric functions after surgery. Estimations of neuropsychiatric function based on MMSE and HDS-R scores were found to be useful in predicting functional outcomes in patients with CSDH.

Increased levels of lipid peroxides as predictive of symptomatic vasospasm and poor outcome after aneurysmal subarachnoid hemorrhage.

OBJECT: Cerebral vasospasm remains a devastating medical complication of aneurysmal subarachnoid hemorrhage (SAH). Reactive oxygen species and subsequent lipid peroxidation are reported to participate in the causes of cerebral vasospasm. This clinical study was performed to investigate the relationships between levels of lipid peroxides in cerebrospinal fluid (CSF) and both delayed cerebral vasospasm and clinical outcome after SAH. METHODS: Levels of phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH) in the CSF were measured in 20 patients with aneurysmal SAH. The patients' CSF was collected within 48 hours of hemorrhage onset and on Day 6 or 7 post-SAH. On Day 7, angiography was performed to verify the degree and extent of the vasospasm. The relationship between the patients' clinical profiles and the levels of lipid peroxides in the CSF were investigated. Both PCOOH and CEOOH were detectable in CSF, and their levels decreased within 7 days after onset of SAH. The levels of CEOOH within 48 hours after onset of hemorrhage were significantly higher in patients in whom symptomatic vasospasm later developed than in patients in whom symptomatic vasospasm did not develop (p = 0.002). Levels of PCOOH measured within 48 hours after onset of hemorrhage were significantly higher in patients with poor outcomes than in patients with good outcomes (p = 0.043). CONCLUSIONS: Increased levels of lipid peroxides measured in the CSF during the acute stage of SAH were predictive of both symptomatic vasospasm and poor outcome. Measurements of lipid peroxides in the CSF may be useful prognostically for patient outcomes as well as for predicting symptomatic vasospasm.

Significance of a small bulge on the basilar artery in patients with perimesencephalic nonaneurysmal subarachnoid hemorrhage. Report of two cases.

Perimesencephalic nonaneurysmal subarachnoid hemorrhage (SAH) is a distinct type of hemorrhage with a characteristic bleeding pattern and an excellent clinical outcome. The cause of this benign form of SAH remains unknown. The authors report on two cases of perimesencephalic nonaneurysmal SAH in which a small bulge on the basilar artery (BA) was demonstrated on three-dimensional rotational angiography studies. Based on data from these cases, one may infer that the lesion on the BA is responsible for the SAH. The possible pathogenesis is discussed.

Reduction of nitroxides and radioprotective ability in glioblastoma cells.

Electron spin resonance (ESR) analyses were performed to clarify whether glioblastoma cells scavenge hydroxyl radicals (*OH) generated by x-ray irradiation. The rate of bioreduction of nitroxides by three human glioblastoma cells was also evaluated by the same technique and compared with their x-ray sensitivity. Aerated culture media containing 200mM of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) with or without U87MG cells were irradiated with x-rays at a dose of 20Gy. ESR was measured immediately after each irradiation. Continuous changes of the ESR spectra of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) were analyzed in cell suspensions of TK1, U87MG, and A172 at a concentration of 1.0 x 10(7) cells/ml containing 5 microM Tempol. As a result, the signal of DMPO-OH in the U87MG cell suspension decayed faster than that in the control culture media without cells, and the rate of bioreduction of Tempol in each glioblastoma cell suspension was correlated with the x-ray sensitivity defined from the colony-forming assay in those cell lines. It was indicated that the resistance of glioblastoma cells to ionizing radiation could be closely related to their ability to scavenge radical species generated by ionizing radiation.

Autologous natural killer cell therapy for human recurrent malignant glioma.

BACKGROUND: Natural killer (NK) cells are highly efficient in the cellular immune response against malignant tumors without restriction of major histocompatibility complex. However clinical studies using autologous NK cells have been reported in only a very limited number of cases, due to the fact that selective NK expansion is difficult to achieve in this patient population. Here, we report the results of adoptive immunotherapy in patients with recurrent malignant gliomas using autologous NK cells that were expanded ex vivo by a novel method. PATIENTS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were prepared from patients with malignant gliomas, and were co-cultured with an irradiated human feeder cell line (HFWT) in RHAM-alpha medium supplemented with 5% autologous plasma and interleukin-2. The resulting NK cell-rich effector cells were injected into 9 patients (16 courses) with recurrent malignant glioma (6 cases of WHO grade-3 glioma and 3 cases of grade-4 glioma). RESULTS: The mean frequency of NK cells among lymphocytes was 82.2 +/- 10.5%. A combination of focal and intravenous injections was peformed in 10 courses. Intravenous injection alone was performed in 6 courses. Further, intravenous injection of low-dose interferon beta (6x10(6) IU/week) was performed as an adjuvant therapy in all courses to achieve maximum benefit for enrolled patients. Clinical evaluation demonstrated 3 PR, 2 MR, 4 NC and 7 PD in a total of 16 courses of treatment. Severe neurological toxicity was not observed in any of the patients. CONCLUSION: It was demonstrated that NK cell-rich effector cells were expanded ex vivo from PBMCs in all nine cases of recurrent malignant glioma and that NK cell therapy was safe and partially effective in patients with recurrent malignant gliomas.