Inhibitory effect of deuterium oxide on cerebral vasospasm after experimental subarachnoid hemorrhage in a rabbit model.

OBJECT: We wished to determine the inhibitory effect of deuterium oxide (D(2)O) on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS AND RESULTS: An established rabbit single-hemorrhage was used. Thirty-five rabbits were randomly divided into four groups: non-treatment, sham control, lower-D(2)O, and higher-D(2)O treatment groups. Angiography was performed before (day 0) and after (day 2) SAH and the CVS ratio was calculated by comparing the diameter of the basilar artery (BA) on day 2 with that on day 0. After death, blood clot volume was assessed and the BA was dissected from the brain for histological examination. The CVS ratio in D(2)O-treatment groups was significantly higher in comparison with that in non-treatment and sham control groups (p < 0.0001). Furthermore, the volume of blood clot around the BA was reduced significantly in D(2)O-treatment groups, compared with those in both the non-treatment and the sham control groups (p < 0.05). Histological examination showed that the BA represented less folding of the internal elastic lumina in D(2)O-treatment groups, while a corrugation of the intima with the thickened vessel wall was seen in both the non-treatment and sham control groups. CONCLUSION: Therapeutic administration of D(2)O into the cisterna magna exhibited an inhibitory effect on CVS after SAH in rabbits.

Supratentorial primitive neuroectodermal tumor in an aged patient--case report--.

An 88-year-old woman presented with a supratentorial primitive neuroectodermal tumor (PNET) manifesting as disturbance of consciousness and left hemiplegia. Magnetic resonance imaging showed a large mass lesion in the right frontotemporal region. She underwent biopsy of the lesion that confirmed the diagnosis of PNET. Her poor condition only allowed chemotherapy with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), vincristine, and prednisolone to be performed. The patient died approximately 6 months after diagnosis due to enlargement of the tumor. Supratentorial PNET is a rare tumor, especially in adults. Multimodal therapy consisting of gross total or subtotal resection, radiation therapy, and chemotherapy is generally considered necessary for patients with supratentorial PNET. However, the condition of each patient should be considered in determining the therapeutic plan, especially in the case of extremely aged patients, since supratentorial PNET is malignant and long-term survival is rare despite aggressive treatment.

Experimental validation of deuterium oxide-mediated antitumoral activity as it relates to apoptosis in murine malignant astrocytoma cells.

OBJECT: Deuterium oxide (D2O), or heavy water, affects a variety of biological activities different from those of water. The authors examined the antitumoral effect of D2O on brain neoplasms and demonstrated D2O-mediated cytotoxicity by using a Rous sarcoma virus-induced murine malignant astrocytoma cell line, RSVM. The mechanism of the observed cytotoxicity may involve D2O-induced apoptosis and cell-cycle modulation. METHODS: The authors performed an assay with methylthiazol tetrazolium bromide and a trypan blue dye exclusion test to confirm in vitro D2O-mediated cytotoxicity for RSVM cells. At D2O concentrations of 10 to 50%, the cytotoxic effect was dose and time dependent. Flow cytometry analysis revealed programmed cell death (apoptosis) and the accumulation of RSVM cells during the G2/M phase. By applying the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method, fluorescein isothiocyanate-annexin V and propidium iodide double staining, and caspase-family protease activity analysis, the authors demonstrated both DNA fragmentation and enhancement of caspase activity after a 48-hour treatment with D2O, thus indicating that D2O induces apoptosis in RSVM cells. Apoptotic DNA fragmentation was completely abolished by the caspase inhibitor Z-VAD-FMK (benzyloxycarbonil-Val-Ala-Aps-fluoromethylketone). The findings indicate that the caspase activation pathway may be involved in D2Oinduced apoptosis. CONCLUSIONS: The authors found that D2O is cytotoxic to malignant astrocytoma cells. The mechanism of D2O-mediated cytotoxicity involved the induction of apoptosis and cell accumulation during the G2/M phase. This D2O-induced apoptosis is modulated through the caspase activation pathway.

Integration of ultrasonography and endoscopy into transsphenoidal surgery with a "picture-in-picture" viewing system--technical note.

A technique to integrate ultrasonography and endoscopy is described for transsphenoidal surgery to prevent intraoperative internal carotid artery (ICA)-related, life-threatening complications such as aneurysmal formation and carotid-cavernous fistula. The ultrasound unit helps avoid direct injury to the ICA. The technical advantage of this system is the miniature 1-mm diameter microvascular probe, which does not disturb the operative field. An arterial or venous flow source of even an invisible vessel can be detected easily, noninvasively, and reproducibly. Real-time information with a 100% detection rate for the ICA is helpful for predicting localization even in the intracavernous portion, where the ICA is invisible. The endoscope unit can visualize the dead angle areas of the operating microscope by varying the endoscopic gateways and display on a "picture-in-picture" system. The advantage of both devices is the integration with a video processor, so that the real-time information from each unit can be switched intraoperatively onto the display as required. This method is of particular help for removing lesions with intracavernous invasion or encasement of the ICA.