Hideo Hamada

Growth Inhibition and Radiosensitization of Cultured Glioma Cells by Nitric Oxide Generating Agents

The authors examined the effect of nitric oxide (NO) generating agents on the growth and radiosensitivity of cultured glioma cells. Three glioma, rat C6, and human T98G and U87 cell lines were treated with the NO generating agents, S-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP). These agents released NO in the cell culture media and inhibited the growth of the glioma cells. Growth-inhibition was attenuated by hemoglobin, a known inhibitor of NO, suggesting it is mediated by NO. When C6 and T98G cells were irradiated in the presence of SNAP or SNP at 100 µM, radiosensitization was observed. SNAP at 100 µM exhibited a sensitizer enhancement ratio (SER) of 1.4 for C6 cells and 1.8 for T98G cells. SNP at 100 µM only radiosensitized T98G cells with a SER of 1.9. The effect of SNP on radiosensitization of C6 cells was unclear. We conclude that NO generating agents are potential growth inhibitors and radiosensitizers for malignant glioma cells. NO mediated radiosensitization of glioma cells by NO generating agents may offer a new therapeutic approach for malignant glioma.

A case of delayed brain abscess due to a retained intracranial wooden foreign body: a case report and review of the last 20 years

SummaryA 13-year-old female is presented. When she was six years old, she had fallen, holding wooden chopsticks and got stuck with a chopstick in the right upper eyelid. She was brought to a physician immediately, but a residual foreign body was missed and no particular symptom had developed during 7 years. She visited our department with fever and headache, and a brain abscess and an intracranial foreign body were found on computed tomography (CT) and magnetic resonance image (MRI) 7 years after the penetrating injury. She underwent removal of the object and abscess by craniotomy and recovered without neurological abnormalities. Since intracranial retained wooden foreign bodies frequently cause delayed complications of severe central nervous system infection, surgical removal is necessary even in the absence of symptoms.

Independent Predictors of Late Hydrocephalus in Patients with Aneurysmal Subarachnoid Hemorrhage – Analysis by Multivariate Logistic Regression Model

Object: We determined independent variables contributing to the development of late hydrocephalus after subarachnoid hemorrhage (SAH). Methods: A total of 114 consecutive patients who underwent surgery for aneurysms within 72 h after SAH were studied. Thirty-nine patients underwent ventriculoperitoneal shunt (VPS) placement (14 patients within 30 days and 25 patients more than 30 days after onset). Univariate and multivariate analyses were performed to assess relationships among various variables and shunt placement. Results: Three variables were found to be independently associated with VPS patients: (1) the rate of SAH clearance; (2) the duration of external cerebrospinal fluid drainage, and (3) presence of neurological deficits 2 weeks after surgery, which indicates brain damage mainly caused by intraoperative manipulation and cerebral vasospasm. Conclusion: As in previous reports, intraoperative clot removal and duration of external CSF drainage were found to be closely related to the incidence of hydrocephalus. Brain damage due to intraoperative manipulation and cerebral vasospasm is seemed to be involved in the occurrence of late hydrocephalus in this study.

Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia

Background and Purpose— Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults. Methods— Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively. Results— Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (P<0.05) lower in transgenic mice (1.30±0.72, 1.12±0.04, and 14.0±7.7%, respectively) than in wild-type mice (2.56±0.93, 1.23±0.12, and 31.9±9.7%, respectively). Percentages of apoptotic cells were also significantly (P<0.001) lower in transgenic mice (cortex, 5.2±3.3%; hippocampus, 3.4±7.0%) than in wild-type mice (cortex, 41.1±16.9%; hippocampus, 58.9±15.3%). Conclusions— These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.

Effect of arachnoid plasty using fibrin glue membrane after clipping of ruptured aneurysm on the occurrence of complications and outcome in the elderly patients

SummaryBackground. In elderly patients with aneurysmal subarachnoid hemorrhage (SAH), complications including vasosopasm, subdural effusion, and late hydrocephalus, are liable to occur even after aneurysmal surgery. We examined prospectively the efficacy of arachnoid plasty using fibrin glue membrane during surgery of ruptured aneurysms in the elderly patients for preventing complications. The effects on the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) 3 months after SAH were noted.Methods. Total of 31 patients aged more than 70 years selected from a consecutive series of patients with aneurysmal SAH, were divided into two groups alternately, a group with arachnoid plasty (n = 16) and a control group without arachnoid plasty (n = 15). Statistical analyses were performed to assess relationships among various clinical and neuroradiological variables, especially between arachnoid plasty and occurrence of symptomatic vasospasm, subdural effusion, late hydrocephalus, or outcome such as mRS and GOS 3 months after onset.Findings. Statistical analyses revealed that arachnoid plasty were associated with late hydrocephalus and subdural effusion negatively, but with better mRS at 3 months after SAH. A tendency to be associated with less frequent symptomatic vasospasm was also noted.Conclusion. Arachnoid plasty using fibrin glue is suggested to be effective in preventing complications associated with SAH and aneurysmal surgery. A better outcome in the elderly patients can be achieved.

Intramedullary spinal teratoma with spina bifida

Abstract Spinal intramedullary teratoma is a rare tumor. We report a case of intramedullary teratoma of the conus medullaris with spina bifida. A 5-year-old boy was admitted to our hospital for removal of a lumbosacral tumor sited in an intramedullary location at the conus medullaris, which was totally resected with neuroendoscopic assistance. The pathological diagnosis was mature teratoma consisting of three germ cell layers. The pathogenesis of spinal intramedullary teratoma is discussed with special reference to spina bifida.

A newly designed training tool for microvascular anastomosis techniques: Microvascular Practice Card.

BACKGROUND We report a newly designed training card (Microvascular Practice Card) that is a non-animal practice tool for surgical training and practicing the skills for microvascular anastomosis techniques. METHODS The Microvascular Practice Card is a pocketbook-sized card that has silicone tubes affixed to it. On the card, 6 small-diameter, 4-cm-long tubes side by side are arranged in 4 directions with both ends secured. The tubes are available in diameters of 2.0, 1.0, 0.5, and 0.3 mm. The thickness of the tube wall is 0.05 or 0.1 mm. The card includes a record area that allows records to be written. Four directional tubes are arranged on one card, making it possible to practice various directional suturing and anastomosing. RESULTS Beginners begin to practice suturing with larger diameter tubes (2.0 mm) and refine their skills using 1.0 mm diameter tubes as they get used to the practice. For vascular anastomosis, the card provides for end-to-end anastomosis, end-to-side anastomosis, and side-to-side anastomosis. Furthermore, superfine diameter tubes (0.5 and 0.3 mm) help microsurgeons to gain experience at higher magnifications. Training on this card is performed through a plastic box with a small hole using long microinstruments. CONCLUSION Microvascular Practice Card is a new training tool for repeatedly practicing microvascular anastomosis in various situations. This non-animal practice tool would help trainees practice under safe and hygienic conditions and reduce the number of laboratory animals used during technical training.

Pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. Case report.

The authors report on a rare case of pilomyxoid astrocytoma in a patient presenting with fatal hemorrhage. This 5-year-old boy presented to the outpatient clinic with headache and vomiting. Computed tomography and magnetic resonance imaging studies revealed a mass lesion with partial hemorrhage in the suprasellar region extending into the third ventricle. Partial resection via a transcallosal approach was performed. Because the pathological diagnosis was pilomyxoid astrocytoma, chemotherapy was administered. However, 4 months after the first operation, during chemotherapy, the boy presented with massive intratumoral and intraventricular hemorrhage with hydrocephalus. Although emergent external ventricular drainage was performed, the patient died. In this report, the authors review the literature and discuss the clinical features and treatment of pilomyxoid astrocytoma.

New Dried Human Amniotic Membrane Is Useful as a Substitute for Dural Repair after Skull Base Surgery

Objectives Cerebrospinal fluid (CSF) leakage is an undesirable complication of skull base surgery. We used dried human amniotic membrane (AM) as a patch graft for dural repair to determine its efficacy in preventing CSF leakage. Design Frontoparietal craniotomy and removal of dura were performed in 20 Wistar rats. A dried AM was placed to cover the dural defect without suturing in 16 animals. In four animals, an expanded polytetrafluoroethylene was implanted. At 2 weeks and 1, 3, and 6 months, histological examination was performed. Dried AM was also used as a substitute in 10 patients who underwent skull base surgery, after approval by the Ethics Committee of the University of Toyama. Results At 2 weeks after implantation, thick connective tissue completely enclosed the dried AM. At 1 month after implantation, the connective tissue became thin and the implanted AM shortened. At 3 and 6 months after implantation, histological examination revealed disappearance of the dried AM and formation of membranous tissue. In the clinical study, neither CSF leakage nor clinical adverse reactions directly related to the dried AM were observed. Conclusion Dried human AM appears to be an ideal substitute for dura, since it is replaced by natural tissue.

A development of atheromatous plaque is restricted by characteristic arterial wall structure at the carotid bifurcation

BACKGROUND It is said atheromatous plaque is located very focally, but there have been few reports regarding this matter. Various aspects of the pathogenesis of the development of atheromatous plaque at the carotid bifurcation have previously been discussed. We have noted the correlation of plaque localization with characteristics of the cervical carotid artery wall. METHODS Morphological and histopathologic changes in the carotid bifurcation were examined in 72 cadaver cases with or without atheromatous plaque. We determined the level at which the wall structure changed to muscular artery from elastic artery and analyzed its influence on the development of atheromatous plaque. RESULT Atheromatous plaques at the distal site of the ICA extended within 0 to 37 mm from the carotid bifurcation. The proximal side of the CCA more than 5 mm away from the bifurcation was elastic artery, whereas the distal side of the ICA more than 15 mm from the bifurcation was muscular artery. The area of the carotid bifurcation between elastic artery and muscular artery was a transitional zone. Approximately 80% of them were located within 15 mm, and these areas were coincident with the transitional zone. CONCLUSION Most atheromatous plaque was located in the transitional zone. The arterial wall structure is related to the development of atheromatous plaque at the cervical carotid bifurcation.