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Biomedical subjects

Yukitaka Ushio

Publications and source records attributed to Yukitaka Ushio.

At least 19 recordsLinked to original sources

A long-term ventricular drainage for patients with germ cell tumors or medulloblastoma.

BACKGROUND: Hydrocephalus associated with intracranial germ cell tumors or disseminated medulloblastoma has been treated with ventriculoperitoneal shunt. However, this procedure has a potential risk of intraperitoneal metastasis of these brain tumors. To prevent this potential risk and to minimize the risk of infection, we developed a percutaneous long-tunneled ventricular drainage (PLTVD). To confirm the effectiveness, we retrospectively analyzed the results of this procedure. METHODS: From 1979 to 2003, we have treated 96 patients with germ cell tumors and medulloblastoma in our hospital. Of 96 patients, 59 (germ cell tumor, 31; medulloblastoma, 28) had hydrocephalus and 13 needed long-term cerebrospinal fluid drainage to manage the obstructive hydrocephalus due to persistent tumor or communicating hydrocephalus due to dissemination. We performed PLTVD for these cases using a flow-controlled shunt device and percutaneous long-tunneled shunt tube (peritoneal catheter) exiting at the upper abdomen and connecting to a closed drainage system. The occurrence of extraneural metastasis and the incidence of infection were evaluated. RESULTS: The average duration of drainage was 74 days (range, 34-115 days). All 13 cases received full-dose chemotherapy and radiotherapy without infectious complications or extraneural metastasis. CONCLUSIONS: Percutaneous long-tunneled ventricular drainage was an effective method to manage long-lasting obstructive or communicating hydrocephalus with germ cell tumors and medulloblastoma.

Adolescent↗

Recurrent intracranial germinoma outside the initial radiation field: a single-institution study.

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.

Adolescent↗

Cerebral thrombosis in a postmenopausal woman on HRT.

We report stroke in a 62-year-old woman who had been on hormone replacement therapy (HRT), estrogen plus progestin, for more than 8 years. She experienced two episodes of transient ischemic attack (TIA), manifesting as right-sided weakness, that persisted for 10-20 min. Magnetic resonance angiography (MRA) obtained before complete stroke, demonstrated severe stenosis of the left middle cerebral artery, without evidence of cerebral infarction. Twenty days after the TIA she suffered a complete stroke corresponding with the site of stenosis. Her protein S activity was low 29%. In the context of the recent findings of the US Women's Health Initiative, we concur that the safety of long-term HRT should be considered carefully, especially in women with a history of TIA and confirmed cerebral artery stenosis.

Brain↗

Frontal skull base surgery combined with endonasal endoscopic sinus surgery.

BACKGROUND: Postoperative infection remains a serious complication after radical resection of anterior skull base lesions because intracranial, nasal, and paranasal cavities are opened during surgery. To prevent complications from postoperative infection, we combined endonasal endoscopic sinus surgery (ESS) with the frontal transbasal approach in patients with skull base lesions. METHODS: Patients (n = 16) with anterior skull base lesions extending to the paranasal or nasal cavity underwent surgical resection via the frontal transbasal approach. After removal of the lesion via the transcranial approach, enlargement of the ostium or sinusotomy was performed bilaterally using our endonasal ESS procedure. The main purpose of ESS is the establishment of a wide drainage route to avoid dead space and postoperative infection. Furthermore, we confirmed the absence of residual lesion and leakage of cerebrospinal fluid (CSF), endoscopically. RESULTS: The frontal transbasal approach combined with endonasal ESS was performed in 16 patients with frontal skull base lesions. There were 8 malignant tumors, 6 benign tumors, and 2 mucoceles. Although 11 patients had preoperative active paranasal sinusitis, most frequently at the ethmoid sinus, none experienced postoperative infection. There was no complication related to ESS procedure. Furthermore, leakage of CSF and extracranial residual tumor were not found. CONCLUSION: Endonasal ESS after frontal skull base surgery is a highly useful technique for preventing postoperative infection, especially for the cases with large skull base tumors extending into other regions involving the paranasal sinuses or nasal cavity and with active paranasal sinusitis.

Adolescent↗

Skull metastasis from clear cell chondrosarcoma.

A 67-year-old man presented with left lower cranial nerve paresis and dysfunction of the left cerebellar hemisphere 4 years after amputation of the left lower leg because of clear cell chondrosarcoma (CCC). Neuroimaging studies showed an osteolytic extradural mass with homogeneous enhancement in the left posterior fossa. Bone scintigraphy disclosed a single high-uptake lesion at the same site. The tumor was removed totally via a left suboccipital craniotomy. Histological examination found mainly clear cells arranged in a microlobular pattern separated by thin fibrovascular stroma. The nuclei were regular with few mitotic figures. Immunohistochemical staining showed the tumor cells reacted intensely for both S-100 protein and vimentin. Osteoclast-like multinucleated giant cells were found at the periphery of the lobules. The primary tumor showed the same findings and the metastatic tumor manifested no malignant change. The histological diagnosis was metastatic CCC. CCC is a very rare neoplasm with slow growth and low-grade malignancy. Distant metastasis is rare but can occur in the skull base bone despite radical resection of the primary tumor. Osteolytic findings of homogeneous enhancement on magnetic resonance imaging and a high uptake on bone scintigraphy are indicative of metastatic tumor from previous CCC.

Aged↗

Effect of surgical removal on survival and quality of life in patients with supratentorial glioblastoma.

The relationship between the extent of tumor resection and the progression-free survival, overall survival, and quality of life was evaluated retrospectively in 105 consecutive adult patients with supratentorial hemispheric glioblastoma not primarily involving the basal ganglia, thalamus, or hypothalamus. All patients underwent multidisciplinary treatment including tumor removal and postoperative adjuvant therapy in prospective randomized trials designed to test several chemotherapy regimens. Magnetic resonance imaging with contrast medium was used to determine the extent of tumor resection. Gross total resection (GTR) was performed in 35 patients (33%), partial resection (PR) in 57 (54%), and biopsy in 13 (12%). Univariate and multivariate analysis was performed to assess the prognostic relevance of the extent of resection. The Karnofsky performance status (KPS) improved from 78% to 83% in the GTR group. The difference was not statistically significant. There was no significant change in the PR (from 70% to 72%) and the biopsy groups (from 64% to 62%). Progression- free survival was significantly longer in the GTR group (median survival time [MST] 10.3 months) than in the PR (MST 5.2 months) and the biopsy groups (MST 3.6 months). The overall survival was significantly longer in the GTR group (MST 20 months) than in the PR (MST 14.2 months) and the biopsy groups (MST 8.3 months). The difference in survival between the PR and the biopsy groups was not statistically significant. GTR prolongs the survival of patients with glioblastoma compared to PR or biopsy.

Adolescent↗

Effect of oral colestimide on the elimination of high-dose methotrexate in patients with primary central nervous system lymphoma--case report.

Delayed methotrexate (MTX) elimination occurred in two patients with primary central nervous system lymphoma undergoing high-dose MTX treatment. Oral administration of the anion exchange resin colestimide, which binds MTX effectively in vitro, effectively accelerated MTX elimination. Colestimide probably interrupts the enterohepatic circulation, and is a potential oral antidote to MTX toxicity.

Administration, Oral↗

Spindle checkpoint function is required for mitotic catastrophe induced by DNA-damaging agents.

Mitotic catastrophe is an important mechanism for the induction of cell death in cancer cells by antineoplastic agents that damage DNA. This process is facilitated by defects in the G1 and G2 checkpoints of the cell cycle that are apparent in most cancer cells and which allow the cells to enter mitosis with DNA damage. We have now characterized the dynamics of mitotic catastrophe induced by DNA-damaging agents in p53-deficient cancer cells. Cells that entered mitosis with DNA damage transiently arrested at metaphase for more than 10 h without segregation of chromosomes and subsequently died directly from metaphase. In those metaphase arrested precatastrophic cells, anaphase-promoting complex appeared to be inactivated and BubR1 was persistently localized at kinetochores, suggesting that spindle checkpoint is activated after the DNA damage. Furthermore, suppression of spindle checkpoint function by BubR1 or Mad2 RNA interference in the DNA damaged cells led to escape from catastrophic death and to subsequent abnormal mitosis. Dysfunction of the spindle checkpoint in p53-deficient cancer cells is thus likely a critical factor in resistance to DNA-damaging therapeutic agents.

Base Sequence↗

Stereotactic biopsy for multifocal, diffuse, and deep-seated brain tumors using Leksell's system.

Using the Leksell stereotactic system, we selectively performed 91 biopsies for surgically inaccessible brain lesions. There were 25 multiple (27.5%), 15 diffuse (16.5%), and 51 (56.0%) deep-seated lesions. However, we avoided subjecting the patients with lesions adjacent to major vascular trunks or complex vascular structures such as the cavernous sinus, peri-insular regions and the pineal regions to stereotactic biopsy. The diagnosis was histologically confirmed in 84 cases (92.3%). Sixty-nine (75.8%) lesions were primary tumors; 44 (48.4%) were malignant gliomas, 18 (19.8%) malignant lymphomas, and five (5.5%) low-grade gliomas. Thirteen (14.3%) cases had previously undergone radiation and/or chemotherapy for brain tumors, seven had recurrent glioma (five with malignant transformation) and six manifested radiation necrosis. None of the patients died due to the stereotactic procedure; one (1.1%) exhibited morbidity due to complicated hemorrhage. We found asymptomatic minor bleeding occurred in nine (9.9%) patients; the rate of hemorrhage was significantly higher in patients with preoperative angiographic evidence of tumor stain. Two patients (2.2%) suffered seizures, in one case seizure was induced by electric stimulation test at the target site. All five patients younger than 15 years underwent the procedure without complications. The Leksell stereotactic system is useful for diagnostic tissue sampling and contributes effectively to the selection of appropriate therapy in patients with malignant brain tumors. While it carries a low morbidity rate without mortality in our series, care must be taken for selected target sites in highly vascularized lesions exhibiting positive tumor stains.

Adolescent↗

Diffusion weighted image negative transient ischaemic attack and reversible ischaemic neurological deficit. A report of 10 patients with complete recovery.

Diffusion-weighted magnetic resonance imaging (DWI MRI)-negative transient ischaemic attack (TIA) in hyperacute stroke is a well-known clinical entity. However, no precise analysis of this phenomenon has been reported. We identified 10 patients with TIA or reversible ischaemic neurological deficits (RIND) with no focal hyperintensity on DWI MRI among 108 consecutive acute stroke patients who underwent DWI MRI. In these patients, we analysed the apparent diffusion coefficient (ADC) and determined the ipsilateral/contralateral ratio (IC ratio) to elucidate factors that may contribute to this phenomenon. Each patient also underwent simultaneous magnetic resonance angiography (MRA). The mean IC ratio in our study population was 0.976. Of the 10 patients, 7 had a proximal vascular stenosis on MRA. We discuss the pathophysiology underlying negative DWI MRI results in patients with TIA or RIND.

Adult↗

Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke: their role in the formation of stable and unstable carotid atherosclerotic plaques.

BACKGROUND: The angiotensin-converting enzyme/angiotensin II (ACE/Ang II) system is a strong contributor to intimal hyperplasia in atherosclerotic lesions. To illuminate its role in ischemic stroke, we examined the expression of ACE/Ang II in stable and unstable carotid atherosclerotic plaques from symptomatic and asymptomatic patients. METHODS: Using immunohistochemical methods, we studied differences between carotid atherosclerotic lesions obtained at carotid endarterectomy (CEA) from symptomatic (n = 36) and asymptomatic (n = 28) patients. The specimens were classified as stable (n = 30) and unstable (n = 34) plaques, and their fibrous cap, lipid core, and shoulder lesion were examined. We used antibodies against smooth muscle cells (SMC), macrophages, endothelial cells (EC), ACE, and Ang II. RESULTS: Of 28 lesions from asymptomatic patients, 20 (71.4%) manifested features characteristic of stable plaques: the expression of ACE/Ang II co-localized with SMC, EC, and macrophages in the shoulder lesion. In contrast, 26 of 36 symptomatic lesions (72.2%) exhibited the typical features of unstable plaques: dense accumulations of macrophages near the luminal surface in the shoulder lesion and weak immunoreactivity for ACE/Ang II, EC, and SMC. Furthermore, most of the lesions were accompanied by early stage atherosclerotic lesions (satellite lesions) that were strongly immunoreactive with macrophages, EC, and ACE/Ang II. CONCLUSIONS: ACE/Ang II expression may induce the proliferation of SMC and EC and result in the formation of carotid atherosclerotic plaques with a thick fibrous cap. Notably, the shoulder lesion of unstable plaques exhibited a thin fibrous cap and faintly expressed ACE/Ang II. Lack of the ACE/Ang II system may contribute to the final step in plaque rupture.

Actins↗

Combination electro-gene therapy using herpes virus thymidine kinase and interleukin-12 expression plasmids is highly efficient against murine carcinomas in vivo.

We report the use of plasmid DNA-mediated combination gene therapy for tumor-bearing mice using in vivo electroporation, also called electro-gene therapy (EGT), that resulted in uncomplicated and complete cures in more than 90% of the mice. Subcutaneously inoculated CT26 tumors in syngeneic BALB/c mice were subjected to repeated EGT treatments consisting of intratumoral co-injection of naked plasmids encoding the cytokine interleukin-12 (IL-12) (p35 and p40 subunits) and the suicide gene herpes simplex virus thymidine kinase (HSV-tk), followed by in vivo electroporation. The early anti-tumor effect was always stronger, and the rate of cure, as seen in the long-term follow-up, was always greater in the groups treated with combination EGT than in those treated with IL-12 or HSV-tk EGT alone. Systemic levels of IL-12 and IFN-gamma increased in both combination and IL-12-alone EGT-treated groups. Moreover, combination EGT for established subcutaneous tumors strongly reduced hematogenous lung metastases and increased survival time when live CT26 tumor cells were injected through the tail vein. Limited experiments on C57/B16 mice with murine melanoma also showed very similar trends. These results suggest that this simple and safe method of plasmid-mediated combination EGT may provide a potentially effective gene therapy for cancer.

Animals↗

Up-regulation of endothelial nitric oxide synthase via phosphatidylinositol 3-kinase pathway contributes to ischemic tolerance in the CA1 subfield of gerbil hippocampus.

We here investigated endothelial nitric oxide synthase (eNOS) expression after 10 minutes of forebrain ischemia. Real-time polymerase chain reaction, immunoblots and immunohistochemical studies revealed up-regulation of eNOS expression in the hippocampal CA1 subfield of gerbil. Immunoreactivity of eNOS significantly increased in endothelium but neither in neurons nor astrocytes after 6 to 168 hours of reperfusion. An increased Akt activity preceded the postischemic eNOS up-regulation. Intracerebroventricular injection (i.c.v.) of wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI-3K), significantly inhibited the increases in both eNOS mRNA and its protein with concomitant inhibition of Akt activation. The significant increase in the eNOS expression was also evident following preconditioning 2-minute ischemia. Both eNOS up-regulation and acquisition of ischemic tolerance observed at 3 days after preconditioning ischemia were significantly inhibited by pretreatment with wortmannin. Administration (i.c.v.) of N-nitro-L-arginine methyl ester, but not 7-nitroindazole, 30 minutes prior to lethal 10-minute ischemia, significantly abolished the acquired tolerance. Intraperitoneal injections of aminoguanidine at immediately after, 24, and 48 hours after preconditioning had no effects on the tolerance. These results suggest that eNOS expression is up-regulated in the endothelium via PI-3K pathways after transient forebrain ischemia, and that preconditioning-induced eNOS expression plays an important role in neuroprotection in the ischemic tolerance.

Androstadienes↗

Incidence and early prognosis of aneurysmal subarachnoid hemorrhage in Kumamoto Prefecture, Japan.

OBJECTIVE: We analyzed the community incidence and early prognosis of first-ever aneurysmal subarachnoid hemorrhages (SAHs) to obtain the same prognostic information used by physicians and families in a defined geographic area in Japan. METHODS: During the 5-year period from January 1, 1996, to December 31, 2000, 2115 patients were registered in the Data Bank for Cerebral Aneurysms of Kumamoto Prefecture, a defined area in Japan with a population of 1.86 million. Registration was based on a comprehensive referral system for SAH patients; computed tomographic scans were available for all patients, including those who were moribund or dead on arrival. We compared the treatment outcomes at 3 months after the first-ever SAH in surgically and conservatively treated patients. RESULTS: The age-adjusted annual incidence of SAH for men, women, and both sexes was 15.9, 26.6, and 21.6 per 100,000 person-years, respectively. In men, the incidence reached a plateau after age 40 years. In women, conversely, it rose after age 40 and peaked in the 9th decade of life. Of the 1634 surgically treated patients, 1153 (70.6%) had a favorable outcome; this was true for only 27 of 477 (5.7%) conservatively treated patients. Four patients were lost to follow-up. The clinical outcome did not differ between patients treated by open surgery and those treated endovascularly. Approximately 30% of our patients were older than 70 years at the time they experienced their first SAH. CONCLUSION: The incidence of SAH obtained in this study was similar to earlier Japanese reports and Finnish studies. The importance of managing elderly patients with cerebral aneurysms will continue to increase.

Adolescent↗

Correlation between promoter hypermethylation of the O6-methylguanine-deoxyribonucleic acid methyltransferase gene and prognosis in patients with high-grade astrocytic tumors treated with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea-based chemotherapy.

OBJECTIVE: O(6)-Methylguanine-deoxyribonucleic acid methyltransferase (MGMT) is a deoxyribonucleic acid repair protein associated with the chemoresistance of chloroethylnitrosoureas. We investigated whether MGMT promoter hypermethylation is associated with prognosis in patients with high-grade astrocytic tumors treated uniformly with surgery, radiotherapy, and 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-based chemotherapy. METHODS: Using the methylation-specific polymerase chain reaction, we assayed promoter hypermethylation of the MGMT gene in tumor deoxyribonucleic acid from 116 adult patients with supratentorial high-grade astrocytic tumors (42 anaplastic astrocytomas [AAs] and 74 glioblastomas multiforme [GBMs]). The Cox proportional hazards model was used in forward stepwise regression to assess the relative role of prognostic factors (i.e., age at surgery, sex, Karnofsky Performance Scale score, extent of surgical resection, methylation status of the MGMT promoter, and association between MGMT promoter methylation and survival). RESULTS: MGMT promoter hypermethylation was confirmed in 19 (45.2%) of 42 AA patients and 33 (44.6%) of 74 GBM patients. It was significantly associated with both longer overall and progression-free survival time in AA but not GBM patients. CONCLUSION: Our results demonstrate that MGMT promoter hypermethylation is associated with longer survival time in patients with AA who were treated with surgery, radiotherapy, and ACNU-based chemotherapy but not in patients with GBM.

Adolescent↗

Spinal arachnoid cyst containing nevus cells in a patient with a large congenital melanocytic nevus: case report.

OBJECTIVE AND IMPORTANCE: Spinal arachnoid cysts are rare, and their cause and pathogenesis remain controversial. We experienced a rare case with a large congenital melanocytic nevus in which a spinal arachnoid cyst contained nevus cells, suggesting the congenital nature of a spinal arachnoid cyst. CLINICAL PRESENTATION: A 37-year-old Japanese man had been born with a large melanocytic nevus on his back. He experienced intermittent pain radiating to both thighs and to the lower back and waist. A magnetic resonance imaging study disclosed the presence of a posterior intradural extramedullary arachnoid cyst extending from T10 through T12. His spinal cord was displaced anteriorly and flattened. INTERVENTION: An osteoplastic laminoplasty was performed, and the arachnoid cyst was totally removed. The cyst membrane exhibited many foci of brown deposits, and histological examination disclosed the presence of melanin-containing cells in the cyst membrane. Morphologically and immunohistochemically, the melanin-containing cells in the cyst membrane were similar to nevus cells in the dermis. CONCLUSION: The histological findings of our case suggest that the patient's spinal arachnoid cyst was formed at the same stage of development as the melanocytic nevus.

Adult↗

Successful treatment of a ruptured dissecting basilar artery aneurysm. Case report.

Dissecting basilar artery (BA) aneurysms in patients presenting with subarachnoid hemorrhage are life threatening, especially in those who experience subsequent bleeding or progressive dissection, and immediate surgical or endovascular intervention may be necessary. The authors report on a 52-year-old woman whose dissecting BA aneurysm was treated successfully with proximal occlusion and flow reversal. Clipping of the proximal BA above the level of the anterior inferior cerebellar arteries facilitated retrograde flow from a radial artery graft placed between the left vertebral artery and the left posterior cerebral artery, thereby providing continuous perfusion of the BA and its branches. Postoperative angiograms obtained 1 year later revealed good retrograde flow through the BA and dilation of the radial arterial graft. There were no episodes of recurrent hemorrhage.

Anastomosis, Surgical↗