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Biomedical subjects

Takaaki Kirino

Publications and source records attributed to Takaaki Kirino.

At least 19 recordsLinked to original sources

Intracerebroventricular delivery of dominant negative prion protein in a mouse model of iatrogenic Creutzfeldt-Jakob disease after dura graft transplantation.

We have developed a novel procedure in which a small collagen sheet (3 mm x 3 mm) absorbing prion-infected brain homogenates was transplanted onto the brain surface of highly prion-susceptible transgenic mice (Tg(MoPrP)4053/FVB), as an animal model of iatrogenic Creutzfeldt-Jakob disease (iCJD) caused by prion-contaminated cadaveric dura graft transplantation. Using the iCJD model, we further investigated the in vivo efficacy of dominant negative recombinant prion protein with lysine substitution at mouse codon 218 (rPrP-Q218K), which is known to inhibit prion replication in vitro (H. Kishida, Y. Sakasegawa, K. Watanabe, Y. Yamakawa, M. Nishijima, Y. Kuroiwa, N.S. Hachiya, K. Kaneko, Non-glycosylphosphatidylinositol (GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrPSc replication in vitro, Amyloid, vol. 11, 2004, pp. 14-20.). Following 7-day intracerebroventricular administration of the rPrP-Q218K via an indwelling catheter connected to the implanted osmotic pump, the median incubation period of Tg(MoPrP)4053/FVB was prolonged considerably from 117 days to 131 days (p=0.016, log-rank test) in the rPrP-Q218K-treated group, even after a lengthy latency period of as long as 30 days by starting the rPrP-Q218K injection. Whether wild-type rPrP, other mutant rPrPs, or the combination of rPrP-Q218K with other anti-prion compounds might extend the survival period in that condition must be further investigated.

Animals↗

p53 potentiates hippocampal neuronal death caused by global ischemia.

Although p53 controls cell death after various stresses, its role in neuronal death after brain ischemia is poorly understood. To address this issue, we subjected p53-deficient (p53-/- and p53+/-) mice (backcrossed for 12 generations with C57BL/6 mice) and wild-type mice (p53+/+) to transient global ischemia by the three-vessel occlusion method. Despite similar severity of ischemia, as shown by anoxic depolarization and cortical blood flow, neuronal death in the hippocampal cornus ammonis (CA)1 region was much more extensive in p53+/+ than in p53-/- mice (surviving neuronal count, 9.3%+/-3.0% versus 61.3%+/-34.0% of nonischemic p53+/+ controls, respectively, P<0.0037). In p53+/- mice, a similar trend was also observed, though not statistically significant (43.5% of nonischemic p53+/+ controls). In p53+/+ mice, p53-like immunoreactivity in hippocampal CA1 neurons was enhanced at 12 h after ischemia, and messenger ribonucleic acid for Bax, a direct downstream target of p53, was also increased. These results indicate that p53 potentiates ischemic neuronal death in vivo and suggest that this molecule could be a therapeutic target in neuronal death after cerebral ischemia.

Animals↗

Endoscopic microneurosurgery: usefulness and cost-effectiveness in the consecutive experience of 210 patients.

OBJECTIVE: Indications, usefulness, and cost-effectiveness of the endoscope in routine microneurosurgery are not clear. To delineate such aspects, we assessed our experience of endoscopic application and additional cost to use an endoscope. METHODS: Endoscopes were used in 210 patients with cranial base and cisternal pathological features in the previous 7 years. Lesions were located in the extradural cranial base in 78 patients and in the cistern in 132 patients. Rigid lens endoscopes 2.7 to 4 mm in width, 11 to 20 cm in length, and 0 to 70 degrees in angle were used. RESULTS: Endoscopes were used for primary or a significant part of the surgery in 64% of the extradural cranial base procedures. Although endoscopes were used only for visual assistance in 82% of cisternal pathological features, significant benefit was noted in 9% and was not different from cranial base lesions. Eleven patients may have had complications if the endoscope had not been used, and 10 procedures would have been impossible without endoscopic use. Therefore, the number of patients need to treat to experience significant benefits by endoscope was 10. Endoscopic equipment costs an additional 326 US dollars per patient and, hence, significant benefit was the equivalent of 3260 US dollars. No permanent complications resulted from the use of the endoscope. CONCLUSION: The endoscope can be applied safely in routine microsurgery with specific equipment and has proven useful in 1 of 10 patients. To perform more effective procedures using endoscopes, we need to develop specially designed instruments usable through a narrow corridor and in an angled field.

Cisterna Magna↗

Sarcomatous transformation of clival chordoma after charged-particle radiotherapy. Report of two cases.

Skull base chordomas containing a sarcomatous component are extremely rare. Here the authors report two new cases in which a recurrent tumor with a sarcomatous component appeared after the patient had undergone charged-particle radiotherapy. Histological examinations performed in Case 1 revealed some retention of epithelial features in the sarcomatous component, whereas no such regions were observed in Case 2. Both patients had rapidly deteriorating clinical courses and died within 6 months after diagnosis of the recurrent tumor. The authors discuss the significance of the histological subtypes of these tumors for long-term prognosis and their pathogenetic mechanisms in relation to radiotherapy. Although these sarcomatous transformations are rare in conventional chordomas, a careful histological examination and thorough follow-up imaging studies are crucial when treating patients with such lesions.

Adult↗

Role of the bloodstream impacting force and the local pressure elevation in the rupture of cerebral aneurysms.

BACKGROUND AND PURPOSE: Inertial force of the bloodstream results in the local elevation of intravascular pressure secondary to flow impact. Previous studies suggest that this "impacting force" and the local pressure elevation at the aneurysm may have a large contribution to the development of cerebral aneurysms. The goal of the present study is to evaluate how the bloodstream impacting force and the local pressure elevation at the aneurysm influences the rupture of cerebral aneurysms. METHODS: A total of 29 aneurysms were created in 26 patient-specific vessel models, and computer simulations were used to calculate pressure distributions around the vessel branching points and the aneurysms. RESULTS: Direct impact of the parent artery bloodstream resulted in local elevation in pressure at branch points, and bends in arteries (231.2+/-198.1 Pa; 100 Pa=0.75 mm Hg). The bloodstream entered into the aneurysm with a decreased velocity after it impacted on the branching points or bends. Thus, the flow impact at the aneurysm occurred usually weakly. At the top or the rupture point of the aneurysm, the flow velocity was always delayed. The local pressure elevation at the aneurysm was 119.3+/-91.2 Pa. CONCLUSIONS: The pressure elevation at the area of flow impact and at the aneurysm constituted only 1% to 2% of the peak intravascular pressure. The results suggest that the bloodstream impacting force and the local pressure elevation at the aneurysm may have less contribution to the rupture of cerebral aneurysms than was expected previously.

Aged↗

A meta-clustering analysis indicates distinct pattern alteration between two series of gene expression profiles for induced ischemic tolerance in rats.

We have developed a visualization methodology, called a "cluster overlap distribution map" (CODM), for comparing the clustering results of time series gene expression profiles generated under two different conditions. Although various clustering algorithms for gene expression data have been proposed, there are few effective methods to compare clustering results for different conditions. With CODM, the utilization of three-dimensional space and color allows intuitive visualization of changes in cluster set composition, changes in the expression patterns of genes between the two conditions, and relationship with other known gene information, such as transcription factors. We applied CODM to time series gene expression profiles obtained from rat four-vessel occlusion models combined with systemic hypotension and time-matched sham control animals (with sham operation), identifying distinct pattern alteration between the two. Comparisons of dynamic changes of time series gene expression levels under different conditions are important in various fields of gene expression profiling analysis, including toxicogenomics and pharmacogenomics. CODM will be valuable for various types of analyses within these fields, because it integrates and simultaneously visualizes various types of information across clustering results.

Algorithms↗

The risk of hemorrhage after radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: Angiography shows that stereotactic radiosurgery obliterates most cerebral arteriovenous malformations after a latency period of a few years. However, the effect of this procedure on the risk of hemorrhage is poorly understood. METHODS: We performed a retrospective observational study of 500 patients with malformations who were treated with radiosurgery with use of a gamma knife. The rates of hemorrhage were assessed during three periods: before radiosurgery, between radiosurgery and the angiographic documentation of obliteration of the malformation (latency period), and after angiographic obliteration. RESULTS: Forty-two hemorrhages were documented before radiosurgery (median follow-up, 0.4 year), 23 during the latency period (median follow-up, 2.0 years), and 6 after obliteration (median follow-up, 5.4 years). As compared with the period between diagnosis and radiosurgery, the risk of hemorrhage decreased by 54 percent during the latency period (hazard ratio, 0.46; 95 percent confidence interval, 0.26 to 0.80; P=0.006) and by 88 percent after obliteration (hazard ratio, 0.12; 95 percent confidence interval, 0.05 to 0.29; P<0.001). The risk was significantly reduced during the period after obliteration, as compared with the latency period (hazard ratio, 0.26; 95 percent confidence interval, 0.10 to 0.68; P=0.006). The reduction was greater among patients who presented with hemorrhage than among those without hemorrhage at presentation and similar in analyses that took into account the delay in confirming obliteration by means of angiography and analyses that excluded data obtained during the first year after diagnosis. CONCLUSIONS: Radiosurgery significantly decreases the risk of hemorrhage in patients with cerebral arteriovenous malformations, even before there is angiographic evidence of obliteration. The risk of hemorrhage is further reduced, although not eliminated, after obliteration.

Adult↗

Functional identification of the primary motor area by corticospinal tractography.

OBJECTIVE: For quick and stable identification of the primary motor area (PMA), diffusion tensor imaging (DTI) data were acquired and corticospinal tractography was mathematically visualized. METHODS: Data sets of DTI, anatomic magnetic resonance imaging, and functional magnetic resonance imaging with finger-tapping tasks were acquired during the same investigation in 30 patients with a brain lesion affecting the motor system. Off-line processing of DTI data was performed to visualize the corticospinal tract, placing a seed area in the cerebral peduncle of the midbrain, where the corticospinal tract is densely concentrated. Somatosensory evoked magnetic fields and intraoperative cortical somatosensory evoked potentials were recorded with electrical stimulation of the median nerve to confirm the results of the corticospinal tractography. RESULTS: Functional magnetic resonance imaging and somatosensory evoked magnetic fields failed to identify the PMA in eight patients (16.7%) and one patient (3.8%) investigated, respectively, because of cortical dysfunctions caused by brain lesions. DTI data were acquired within 3 minutes without patient tasks. Using the appropriate seed area and fractional anisotropy, corticospinal tractography successfully indicated the PMA location in all patients. The suspected PMA and central sulcus locations were confirmed by the cortical somatosensory evoked potentials. CONCLUSION: Corticospinal tractography enables identification of the PMA and is beneficial, particularly for patients who present with dysfunction of the PMA.

Adolescent↗

Functional monitoring for visual pathway using real-time visual evoked potentials and optic-radiation tractography.

OBJECTIVE: It has been difficult to obtain anatomic and functional information about the visual pathway during neurosurgical operations. The aim of this study was to combine the information of the visual evoked potentials (VEPs) and the anatomic navigation of the optic radiation by diffusion tensor imaging-based tractography for functional monitoring of the visual pathway. METHODS: The subjects were two patients with brain lesions adjacent to the visual pathway. Diffusion tensor imaging-based tractography of the optic radiation was performed by selecting appropriate regions of interest and by fractional anisotropy. During surgery, cortical VEPs were recorded continuously under general anesthesia with sevoflurane. In Patient 2, the results of optic radiation tractography were imported to a neuronavigation system to better understand the spatial relationships between the lesions and the visual pathway (functional neuronavigation). RESULTS: In Patient 1, the lesion did not seem to be attached to the optic radiation, and VEP profiles remained stable during resection. In Patient 2, who had a lesion adjacent to the posterior horn of the lateral ventricle, VEPs suddenly diminished when resection reached the optic radiation as illustrated on the neuronavigation system. As a result, complete left hemianopia developed after surgery in Patient 2. CONCLUSION: We confirmed functional correlations of the results of diffusion tensor imaging-based tractography by monitoring intraoperative VEPs. The combination of continuous VEP and optic-radiation tractography is reliable to monitor the visual function and is helpful in performing neurosurgical planning near the visual pathway.

Adult↗

Multifocal pilocytic astrocytomas with ependymal differentiation in the bilateral medial temporal lobes: case report.

A 7-year-old boy presented with headache, visual disturbance, and psychomotor seizures persisting for 7 months. He had mild hemiparesis and homonymous hemianopia on the left. Neuroimaging showed bilateral temporal lobe masses with calcification and cysts. The right temporal mass was subtotally resected. The histological diagnosis was pilocytic astrocytoma with ependymal differentiation and a MIB-1 staining index of up to 8.0%. Postoperatively his hemiparesis and psychomotor seizures disappeared. Adjuvant chemotherapy consisting of carboplatin and vincristine was given followed by radiotherapy. Neuroimaging showed that the bilateral tumors had disappeared and showed no recurrence for 29 months after the diagnosis. Pilocytic astrocytoma usually presents as a solitary mass in the cerebellum or optic pathway with low proliferative activity, but should be included in the differential diagnosis of multifocal tumors arising in the bilateral temporal lobes. Ependymal differentiation with extremely high proliferative activity might be related to this unusual clinical presentation. Intensive treatment is recommended for patients with such specific neuroimaging and histological features.

Antibodies, Antinuclear↗

Subdural hematoma associated with dural metastasis--case report--.

A 56-year-old female presented with acute subdural hematoma associated with dural metastasis. The patient had been treated for breast cancer with disseminated bone and lung metastases. Evacuation of the hematoma with local management of the tumor and bleeding successfully improved her neurological condition and she underwent postoperative radiotherapy. This condition is especially associated with dural metastasis from adenocarcinoma (most frequently stomach cancer) and the clinical outcome depends on the general condition of the patient and the status of the coagulation disorders. If the tumors are multiple, as in this case, extreme caution should be paid to recurrent bleeding in the ipsilateral or contralateral side.

Adenocarcinoma↗

Risk of rupture associated with intact cerebral aneurysms in the Japanese population: a systematic review of the literature from Japan.

OBJECT: Knowing the rate of rupture associated with unruptured cerebral aneurysms (UCAs) can help surgeons determine a case management strategy in patients harboring these lesions. According to large-scale cohort studies involving populations in North America and Europe, small unruptured aneurysms carry a very low risk of rupture. In Japan, however, there have been sporadic reports of higher rates of rupture. To identify the rupture risk associated with UCAs in the Japanese population, the authors systematically reviewed retrospective studies of the natural course of these lesions. METHODS: The authors searched Medline and the Japan Medical Abstract Society Index for reports of UCAs in Japan. Two of the authors verified the eligibility of the reports and extracted data independently. Additional information was directly obtained from the authors of the original reports. Thirteen reports covering a total of 3801 patient-years fulfilled the criteria for our study. Subsequent rupture was documented in 104 patients and the annual rupture rate was 2.7% (95% confidence interval 2.2-3.3%). Large, posterior-circulation, and symptomatic aneurysms were associated with significantly higher rates of rupture (relative risks 6.4, 2.3, and 2.1, respectively). The risk of rupture determined by the authors' review was significantly higher than that reported by investigators from international cohort studies. CONCLUSIONS: Although a selection bias of patients may be the cause of the higher rupture risk, untreated UCAs that have been followed in Japanese institutions have a considerably high rate of rupture. The natural course of UCAs should be carefully estimated in countries not included in the international studies.

Aneurysm, Ruptured↗

Combined use of tractography-integrated functional neuronavigation and direct fiber stimulation.

OBJECT: The aim of this study was better preoperative planning and direct application to intraoperative procedures through accurate coregistration of diffusion-tensor (DT) imaging-based tractography results and anatomical three-dimensional magnetic resonance images and subsequent importation of the combined images to a neuronavigation system (functional neuronavigation). METHODS: Six patients with brain lesions adjacent to the corticospinal tract (CST) were studied. During surgery, direct fiber stimulation was used to evoke motor responses to confirm the accuracy of CST depicted on functional neuronavigation. In three patients, stimulation of the supposed CST elicited the expected motor evoked potentials. In the other three, stimulation at the resection borders more than 1 cm away from the supposed CST showed no motor response. All patients underwent appropriate tumor resection with preservation of the CST. CONCLUSIONS: Integration of the DT imaging-based tractography information into a traditional neuronavigation system demonstrated spatial relationships between lesions and the CST, allowing for the avoidance of tract injury during lesion resection. Direct fiber stimulation was used for real-time reliable white matter mapping, which served to adjust for any discrepancy between the neuronavigation system data and potentially shifted positions of the brain structures. The combination of these techniques enabled the authors to identify accurate positions of the CST during surgery and to accomplish optimal tumor resections.

Adult↗

Integration of three-dimensional corticospinal tractography into treatment planning for gamma knife surgery.

OBJECT: In the radiosurgical treatment of critically located lesions, the effort to minimize the risk of complication is essential. In this study the integration of diffusion-tensor (DT) imaging-based tractography was clinically applied to treatment planning for gamma knife surgery (GKS). METHODS: Seven patients with cerebral arteriovenous malformations located adjacent to the corticospinal tract (CST) underwent this technique. Data provided by DT imaging were acquired before the frame was affixed to the patient's head and the CST of the DT tractography was created using our original software. Stereotactic three-dimensional imaging studies were obtained after frame fixation and then coregistered with the data from DT tractography. After image fusion of the two studies, the combined images were transported to a GKS treatment-planning workstation. The spatial relationship between the dose distribution and the CST was clearly demonstrated within the 2 hours it took to complete the entire imaging process. The univariate logistic regression analysis of transient or permanent motor complications revealed a significant independent correlation with the volume of the CST that received 25 Gy or more and with a maximum dose to the CST (p < 0.05). CONCLUSIONS: The integration of DT tractography into the GKS treatment planning was highly useful in confirming the dose to the CST during treatment planning.

Adult↗

Risk of hemorrhage from an arteriovenous malformation confirmed to have been obliterated on angiography after stereotactic radiosurgery.

OBJECT: Radiosurgery has been widely adopted for the treatment of cerebral arteriovenous malformations (AVMs) in which the practical endpoint is angiographic evidence of obliteration, presumed to be consistent with elimination of the risk of hemorrhage. To test this unverified assumption, the authors followed 236 radiosurgery-treated AVMs between 1 and 133 months (median 77 months) after angiographic evidence of obliteration. METHODS: Four patients experienced hemorrhage between 16 and 51 months after angiographic confirmation of AVM obliteration, and two underwent resection. The histological findings in these patients showed occlusion of the AVM by thickening of the intimal layer with dense hyalinization as well as a small amount of residual AVM vessels and a tiny vasculature. The risks of hemorrhage from these presumaby obliterated AVMs were 0.3% for the annual bleeding risk and 2.2% for the cumulative risk over 10 years. Continuous enhancement of the nidus on computerized tomography (CT) or magnetic resonance (MR) imaging was the only significant factor positively associated with hemorrhage in the statistical analysis (p = 0.0212). CONCLUSIONS: Because the study was based on limited follow-up data, its significance for defining predictive features of hemorrhage after angiographic evidence of obliteration is still indeterminable. Nevertheless, disappearance of the AVM on angiography after radiosurgery does not always indicate total elimination of the disease, especially when CT or MR imaging continues to demonstrate an enhancing lesion. The authors therefore recommend continual follow up even after evidence of AVM obliteration on angiography.

Adolescent↗

Gamma knife surgery for arteriovenous malformations involving the corpus callosum.

OBJECT: The purpose of this study was to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of arteriovenous malformations (AVMs) involving the corpus callosum. METHODS: Thirty-two patients aged from 7 to 65 years (median 25 years) with AVMs of the corpus callosum underwent GKS between 1990 and 2002. The maximum AVM diameter was more than 3 cm in 11 patients (34%). The AVM volume ranged from 0.1 to 19.1 cm3 (median 1.6 cm3). The median dose to the AVM margin was 20 Gy (range 17-28 Gy). Patients were followed for 1 to 12 years (median 9 years). The angiographically confirmed actuarial obliteration rate was 64% and 74% at 4 and 6 years, respectively. Younger patient age (p < 0.05) and lower radiosurgery-based grading score (calculated from the patient age and AVM volume; p < 0.01) were the significant factors affecting successful AVM obliteration. No patient suffered a hemorrhage after GKS, although 28 patients (88%) had a history of hemorrhage from their AVMs. Radiation-induced neurological deficit was observed only in one patient (3%) who had undergone previous radiotherapy (50 Gy). No patient experienced complications of occlusion or stenosis of the normal vascular structures adjacent to the AVM. CONCLUSIONS: Gamma knife surgery is a safe and effective treatment for selected patients with AVMs involving the corpus callosum, and it carries a low risk of damaging adjacent critical vascular structures. Even ruptured AVMs with relatively large diameter can be successfully treated, especially in younger patients, with minimal morbidity and a low risk of repeated hemorrhage.

Adolescent↗

Microsurgical robotic system for the deep surgical field: development of a prototype and feasibility studies in animal and cadaveric models.

OBJECT: To enhance the surgeon's dexterity and maneuverability in the deep surgical field, the authors developed a master-slave microsurgical robotic system. This concept and the results of preliminary experiments are reported in this paper. METHODS: The system has a master control unit, which conveys motion commands in six degrees of freedom (X, Y, and Z directions; rotation; tip flexion; and grasping) to two arms. The slave manipulator has a hanging base with an additional six degrees of freedom; it holds a motorized operating unit with two manipulators (5 mm in diameter, 18 cm in length). The accuracy of the prototype in both shallow and deep surgical fields was compared with routine freehand microsurgery. Closure of a partial arteriotomy and complete end-to-end anastomosis of the carotid artery (CA) in the deep operative field were performed in 20 Wistar rats. Three routine surgical procedures were also performed in cadavers. The accuracy of pointing with the nondominant hand in the deep surgical field was significantly improved through the use of robotics. The authors successfully closed the partial arteriotomy and completely anastomosed the rat CAs in the deep surgical field. The time needed for stitching was significantly shortened over the course of the first 10 rat experiments. The robotic instruments also moved satisfactorily in cadavers, but the manipulators still need to be smaller to fit into the narrow intracranial space. CONCLUSIONS: Computer-controlled surgical manipulation will be an important tool for neurosurgery, and preliminary experiments involving this robotic system demonstrate its promising maneuverability.

Anastomosis, Surgical↗

Differences in infarct evolution between lipopolysaccharide-induced tolerant and nontolerant conditions to focal cerebral ischemia.

OBJECT: Although brain tissue may be protected by previous preconditioning, the temporal evolution of infarcts in such preconditioned brain tissue during focal cerebral ischemia is largely unknown. Therefore, in this study the authors engaged in long-term observation with magnetic resonance (MR) imaging to clarify the difference in lesion evolution between tolerant and nontolerant conditions. METHODS: Bacterial lipopolysaccharide (LPS; 0.9 mg/kg) was administered intravenously to induce cross-ischemic tolerance. Focal cerebral ischemia was induced 72 hours later in spontaneously hypertensive rats. Serial brain MR images were obtained 6 hours, 24 hours, 4 days, 7 days, and 14 days after ischemia by using a 7.05-tesla unit. Lesion-reducing effects were evident 6 hours after ischemia in the LPS group. Preconditioning with LPS does not merely delay but prevents ischemic cell death by reducing lesion size. Lesion reduction was a sustained effect noted up to 14 days after ischemia. Reduction of local cerebral blood flow (ICBF) in the periinfarct area was significantly inhibited in the LPS group, which was correlated with endothelial nitric oxide synthase (eNOS) expression. CONCLUSIONS: Significant preservation of ICBF in the periinfarct area, which is relevant to sustained upregulation of eNOS, could be a candidate for the long-term inhibiting effect on infarct evolution in the LPS-induced tolerant state.

Animals↗