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Biomedical subjects

K Takakura

Publications and source records attributed to K Takakura.

At least 91 records · Page 5Linked to original sources

Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group.

BACKGROUND AND PURPOSE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of acute ischemic stroke was evaluated in a multicenter, placebo-controlled, double-blind clinical trial. METHODS: Patients diagnosed as having acute ischemic stroke who could receive drug treatment within 48 hours of stroke onset were enrolled. Oral administration of ebselen granules suspended in water (150 mg BID) or placebo was started immediately after admission and was continued for 2 weeks. The major end points were the Glasgow Outcome Scale scores at 1 month and 3 months after the start of treatment. The modified Mathew Scale and modified Barthel Index scores at 1 month and 3 months were also studied as secondary outcome measures. RESULTS: Three hundred two patients were enrolled in the trial. Intent-to-treat analysis of 300 patients (151 given ebselen and 149 given placebo) revealed that ebselen treatment achieved a significantly better outcome than placebo at 1 month (P = .023, Wilcoxon rank sum test) but not at 3 months (P = .056, Wilcoxon rank sum test). The improvement was significant in patients who started ebselen within 24 hours of stroke onset but not in those who started treatment after 24 hours. There was a corresponding improvement in the modified Mathew Scale and modified Barthel Index scores. CONCLUSIONS: Early treatment with ebselen improved the outcome of acute ischemic stroke. Ebselen may be a promising neuroprotective agent.

Acute Disease↗

Arteriovenous malformations in the basal ganglia and thalamus: management and results in 101 cases.

OBJECT: Because arteriovenous malformations (AVMs) in the basal ganglia and thalamus are difficult to treat, the authors conducted a retrospective study to determine the best management strategy for these lesions. METHODS: The authors reviewed the management and outcome in 101 patients with AVMs treated between 1971 and 1995. In 15 conservatively treated patients, hemorrhage occurred in 71.4% (annual rate 11.4%), and the morbidity and mortality rates were 7.1% and 42.9%, respectively, during a mean follow-up period of 6.6 years. Total microsurgical resection was performed in 15 patients with no mortality resulting, but motor function deteriorated permanently in three of them (20%). Postoperative morbidity correlated well with the location of the AVM and with preoperative motor function. In cases of lenticular AVMs without motor weakness, a postoperative decrease in motor function was significantly more common than in the remaining patients. In patients with motor weakness before surgery, AVMs in the thalamus or caudate nucleus were successfully resected. Among 66 patients treated with gamma knife radiosurgery, three had permanent radiation-induced neurological deficits, and three others experienced bleeding (new bleeding in one case and rebleeding in two). The treatment-associated morbidity rate was 6.7%, and the actuarial rate of complete obliteration was 85.7% at 2.5 years. In five patients treated with embolization alone, the morbidity and mortality rates associated with the procedure or bleeding were 40% and 20%, respectively. The morbidity and mortality rates in the pre-gamma knife era were 22.2% and 22.2%, whereas those for the post-gamma knife era are currently 10.4% and 1.5%, respectively. CONCLUSIONS: These results indicate that conservatively treated AVMs are more likely to bleed and thus produce a high incidence of patient mortality. Multimodal treatment including radiosurgery, microsurgery, and embolization improved clinical outcomes by making it possible to treat difficult cases successfully.

Adolescent↗

[Efficacy of nicardipine prolonged-release pellet on cerebral vasospasm in dogs].

A drug delivery system using copoly (lactic/glycolic acid) was developed for the intrathecal administration of nicardipine. This system was tested to determine its efficacy in preventing cerebral vasospasm in dogs. A rod-shaped implant (1-mm diameter, 10-mm long and which contained approximately 10% of nicardipine) was prepared by a heat compression method. In in vitro studies, 8% of the actual nicardipine loaded was released during day 1, 17% within day 2, 62% within day 4, and 96% within day 10. In in vivo studies, 12 dogs were assigned to two groups: the placebo group and the group treated with nicardipine. Angiography before the experiment was performed followed by right craniectomy and induction of subarachnoid hemorrhage by the placement of a clot in the Sylvian fissure. Eight pellets, either containing 8 mg of nicardipine or without nicardipine were placed in the cistern. On day 7, the angiography was repeated and cerebrospinal fluid was removed from the cisterna magna. The animals were then sacrificed, and the brain and blood clot were taken out. Cerebral vessels were measured three times with a calibrated optical micrometer, and the mean value was obtained. Average reduction of vessel diameters on the clot side in the placebo and nicardipine groups were -37% and -10% on the internal carotid (IC), -48% and -3% on the middle cerebral (MC), and -28% and -1% on the anterior cerebral artery (AC), respectively. There were significant differences in vessel diameters of IC (p < 0.05), MC (p < 0.005), and AC (p < 0.05) between these groups. No vasospasm was found in the left side. The nicardipine concentration in the clot was determined by high performance liquid chromatography. The mean concentration of nicardipine in the clot was 1.5 x 10(-4)M, at which concentration sufficient relaxation is evoked in vitro. The pellets did not last beyond day 7. Regarding the histological findings, there was a marked difference in vessel diameters between the placebo and the nicardipine treated groups. The arteries were surrounded with red blood cells and inflammatory cells. There were no specific changes related to the pellets and no sign of meningoencephalitis. A prolonged-release preparation of nicardipine that can be implanted intracranially at the time of surgery prevented vasospasm significantly in dogs. These results suggest that this new drug delivery system might be put into effect favorably in patients suffering from vasospasm due to subarachnoid hemorrhage.

Animals↗

[Usefulness of positron emission tomography to STA-MCA anastomosis for the case with cerebral infarction].

The ischemic area surrounding the cerebral infarction in the eloquent area was salvaged by STA-MCA bypass surgery. Both the misery perfusion area evaluated by positron emission tomography (PET) using the [15O] gas inhalation steady-state method and clinical symptoms improved within a year after surgery. To confirm the ischemic area and select the suitable recipient artery was important for successful bypass surgery, because only an artery covering the ischemic area is expected to have low resistance. In this case a large ischemic area with disturbed, vasodilatation by Diamox was detected on the SPECT. However, PET clearly exposed the localized misery perfusion area in the overestimated ischemic area by SPECT. We describe our experience and discuss the technique and efficacy of PET for STA-MCA anastomosis surgery.

Cerebral Arteries↗

[Clinical evaluation of intraoperative radiotherapy using photon radiosurgery system for brain tumors].

The photon radiosurgery system is a miniature X-ray generator that can be placed stereotactically and intraoperatively into intracranial tumors to deliver a single fraction of high-dose interstitial irradiation. This battery-powered device produces low energy X-ray photons in a spherical and symmetrical pattern at the probe tip. Dose rates of up to 200 cGy/Mim are possible, allowing for the administration of 15 Gy to a lesion 3 cm in diameter in less than 1 hr. Background exposure is minimal, and no special shielding of the patient or health care personnel is required. Thirty-nine patients with brain tumor were treated in this method. There were no adverse effects. During the follow-up period of 1-30 months, 3 cases with 5 metastatic brain tumors died about 8 months after this treatment. Five recurrent cases of 21 malignant gliomas died about 4 months after treatment. Interstitial radiotherapy using photon the radiosurgery system promises to be a useful treatment for brain tumors.

Aged↗

[Spontaneous resolution of idiopathic spinal subdural hematoma: case report].

A 32-year-old female presented with about a week's history of dull pain in the head and neck pain. On the day of admission, she experienced a sudden onset of severe pain, extending from the occipital to the lower back region and hypesthesia and paresthesia of the right C8-Th3 dermatome. On admission, she was alert but there was a band of hypesthesia and paresthesia at the level of C8-Th3. Cervical X-ray, computed tomography scan (CT) and magnetic resonance images (MRI) of the head revealed no definite abnormalities. The peripheral blood picture was normal, and the bleeding and clotting times were in the normal range. The cerebrospinal fluid (CSF) was bloody and the CSF pressure was 220 mm H2O. An emergent 4-vessel intracranial angiography disclosed no abnormal findings. MRI and myelography revealed an intradural extramedullary lesion extending from the Th2 to the Th5 levels, ventral to the spinal cord. A T1-weighted MR image showed iso-low intensity and a T2-weighted MR image showed low intensity at these lesions. Spinal angiography revealed no abnormal vessels. In one month, spinal compression cleared gradually without surgery and her clinical symptoms disappeared about 40 days after admission. Spontaneous spinal subdural hematoma is uncommon and only 28 cases have been reported. 15 cases have been treated with surgical procedure, but spinal compression cleared spontaneously in this case. This spontaneous recovery is such a rare event that only 3 such cases have been reported in the literature. However, with the prevailing MRI, this disease will be detected more frequently in the future.

Adult↗

High-affinity binding of bioactive glycosylation-inhibiting factor to antigen-primed T cells and natural killer cells.

High-affinity binding was demonstrated between suppressor-T-cell-derived bioactive glycosylation-inhibiting factor (GIF) and helper T hybridomas and natural killer cell line cells. Inactive GIF present in cytosol of suppressor T cells and Escherichia coli-derived recombinant human GIF (rhGIF) failed to bind to these cells. However, affinity of rhGIF for the target cells was generated by replacement of Cys-57 in the sequence with Ala or of Asn-106 with Ser or binding of 5-thio-2-nitrobenzoic acid to Cys-60 in the molecule. Such mutations and the chemical modification of rhGIF synergistically increased the affinity of GIF molecules for the target cells. The results indicated that receptors on the target cells recognize conformational structures of bioactive GIF. Equilibrium dissociation constant (Kd) of the specific binding between bioactive rGIF derivatives and high-affinity receptors was 10-100 pM. Receptors for bioactive GIF derivatives were detected on Th1 and Th2 T helper clones and natural killer NK1.1(+) cells in normal spleen but not on naive T or B cells. Neither the inactive rGIF nor bioactive rGIF derivatives bound to macrophage and monocyte lines or induced macrophages for tumor necrosis factor alpha production.

Alanine↗

Superior sagittal sinus thrombosis treated with combined local thrombolytic and systemic anticoagulation therapy.

We recently encountered a patient with thrombosis of the superior sagittal sinus of an idiopathic cause. The patient was treated initially with combined local thrombolytic therapy through the burr hole over the superior sagittal sinus and systemic anticoagulant therapy. Continuous ventricular drainage and hyperbaric oxygenation therapy were used to control the increased intracranial pressure. The superior sagittal sinus was successfully recanalized. Whereas the patient suffered a complication with subacute subdural haematoma, he was successfully treated with the combination of these therapies. The rationale and approach are discussed.

Anticoagulants↗

Expression and role of cadherins in astrocytic tumors.

Cadherins are Ca(2+)-dependent cell adhesion molecules that play an important role in tissue formation and morphogenesis in multicellular organisms. In recent years, there have been reports of cadherin involvement in tumor invasion and metastasis. Twenty-two surgical specimens and some cultured cells were studied by immunohistochemical staining. No significant difference was observed in the patients with anaplastic astrocytoma, whereas decreased expression of N-cadherin was detected at the time of recurrence in those with glioblastoma. In these groups, cerebrospinal fluid dissemination was found, and contralateral cerebral metastases and extracranial metastases were observed. We conclude that decreased N-cadherin expression at the immunohistochemically demonstrated time of recurrence correlates with tumor invasion and dissemination of cerebrospinal fluid.

Adult↗

Induction of the 2B9 antigen/dipeptidyl peptidase IV/CD26 on human natural killer cells by IL-2, IL-12 or IL-15.

Activation of human natural killer (NK) cells involves sequential events including cytokine production and induction of cell surface molecules, resulting in the enhancement of cytolytic activity. To delineate the activation process of NK cells, we generated murine monoclonal antibodies (mAbs) against YT, a human large granular lymphocyte/natural killer (LGL/NK) cell line. Among the mAbs reactive with YT cells, one mAb, termed 2B9, was noted because of the lack of reactivity with most of the human T- and B-cell lines tested. In fresh peripheral blood mononuclear cells (PBMC), however, the majority of cells expressing this antigen (Ag) were T cells but not CD16+ nor CD56+ NK cells. Since YT cells showed an activated phenotype expressing interleukin-2 (IL-2) receptor alpha chain, we examined whether 2B9 Ag could be induced on normal human peripheral blood NK cells by cytokines known to activate NK cells. The 2B9 Ag was induced on NK cells by IL-2, IL-12 or IL-15 while no induction was observed by interferon-gamma (IFN-gamma). Biochemical analysis showed that anti-2B9 mAb recognized a 115 kDa molecule in YT cells. A cDNA clone encoding the 2B9 Ag was isolated from a cDNA expression library of YT cells and its sequence was identical to CD26 cDNA although it was not of full length. Transient expression of the 2B9 cDNA on COS-7 cells revealed that this cDNA encodes the antigenic epitope(s) recognized by anti-2B9 mAb as well as Ta1, an anti-CD26 mAb. These results showed that the 2B9 Ag is identical to CD26, and demonstrated that CD26 is an activation antigen on CD16+ CD56+ NK cells inducible by IL-2, IL-12 or IL-15.

Antibodies, Monoclonal↗

Nitric oxide produced by inducible nitric oxide synthase delays gastric emptying in lipopolysaccharide-treated rats.

BACKGROUND: Endotoxin induces nitric oxide synthase (NOS), resulting in relaxation of gastric smooth muscle. The authors examined the effect of NO produced in response to lipopolysaccharide (LPS) treatment on gastric emptying in rats, and they also examined the effects of a selective inhibitor of inducible NOS (iNOS), aminoguanidine, and a suppressor of iNOS gene expression, dexamethasone. METHODS: Male Wistar rats weighing 200-250 g were used. LPS-treated rats received LPS (0.2-10 mg/kg) diluted in physiologic saline intraperitoneally. Before and at different intervals up to 8 h after administration of LPS, measurements of gastric emptying were performed in groups of 3-5 rats, by determining the amount of phenol red remaining in the stomach 20 min after intragastric instillation. In additional group of LPS (2 mg/kg)-treated rats, the gastric fundus was isolated 6 h after administration, and the tension changes in response to L-arginine, a substrate for NOS, and electrical transmural stimulation (3 Hz, 5 s) were recorded isometrically. RESULTS: (1) Gastric emptying was delayed by pretreatment with LPS in a dose- and time-dependent fashion (reduction from 68 +/- 12% to 22 +/- 7% with a dose of 2 mg/kg for 6 h). Aminoguanidine (50 mg/kg) or dexamethasone (5 mg/kg) partially inhibited the delay (to 39 +/- 4% or to 40 +/- 10%, respectively). (2) L-arginine (0.1 mM) produced a relaxation (28 +/- 2% reduction in active tension) in the gastric fundus strips isolated from LPS-treated rats but not from LPS-untreated rats. The relaxation was inhibited by aminoguanidine (1 mM). In contrast, the relaxation response to the electrical stimulation was not affected by aminoguanidine (0.1-1 mM). CONCLUSION: The present study suggests that NO, probably produced by iNOS, is one of the factors involved in the delay of gastric emptying in the LPS-treated rats and probably in those with sepsis.

Animals↗

Split cannula method for accurate placement of an electrode for deep brain stimulation: technical note.

OBJECTIVE: We describe a "split cannula method" for accurate placement of a deep brain stimulation electrode. This method eliminates the risk of displacement of the electrode when withdrawing the outer guide cannula. METHOD: A separate short guide cannula is covered over the distal part of a long cannula for microrecording or macrostimulation. After confirmation of the stimulation point, the short cannula is fixed with an accessory-holding device and the long cannula is pulled out. The electrode for deep brain stimulation is inserted through the short cannula. Because this cannula is much shorter than the electrode, securing the stimulation electrode at any withdrawal stage of the outer guide cannula is always possible. RESULTS AND CONCLUSION: With this simple method, we experienced no displacement of the stimulation point during stereotactic insertion of a deep brain stimulation electrode. This method can be easily adapted to any stereotactic frame.

Brain↗

Development of a frameless and armless stereotactic neuronavigation system with ultrasonographic registration.

OBJECTIVE: We have developed a frameless stereotactic neuronavigation system that allows navigation during neurosurgical procedures through an image formed from integrating ultrasonography and preoperative magnetic resonance (MR) imaging and/or x-ray computed tomography. METHODS: The system consists of a ultrasound imaging scanner, a workstation with an image capture board, and an ultrasonic tracking sensor with a 5-MHz ultrasonographic transducer. The ultrasonic tracking sensor measures the position and orientation of the ultrasonographic transducer. The oblique plane of the MR/computed tomographic image corresponding to the ultrasound image is then displayed on the workstation monitor. A three-dimensional computer graphic representation of the integrated image is also reported as a preliminary test. For the patient-image registration, the coordinates of digitized and imaged markers on a specifically developed reference frame are used. The reference frame is noninvasive because it is not bolted but only fastened to the patient's head with silicon. RESULTS: Based on the findings from the clinical application of the system in three cases, the system was advantageous because of the surgical procedures could be controlled by intraoperative ultrasonography as well as by preoperative MR/computed tomographic images. Missing parts in the ultrasonogram were supplemented with preoperative MR/computed tomographic images. At other times, spatial positioning and visualization by ultrasonography were useful for identifying anatomical objects in the image. CONCLUSION: This preliminary study of the frameless integration of ultrasonography into stereotactic space demonstrated its clinical usefulness. We believe that the concept of pre- and intraoperative image-guided surgery presented here will find increasing use in the future.

Adolescent↗

Current treatment of brain abscess in patients with congenital cyanotic heart disease.

OBJECTIVE: The goal of this study was to define clearly the role of management in patients with cyanotic heart disease and brain abscesses by evaluating retrospectively the factors influencing poor outcome in these patients. METHODS: This study included 62 patients with cyanotic heart disease and brain abscesses diagnosed in the computed tomography era. Basic characteristic parameters (number, size, location, computed tomographic classification and organism type of abscess, convulsion, type of cyanotic heart disease, age distribution, immunocompromised status, pretreatment neurological state, and intraventricular rupture of brain abscess [IVROBA]) and therapeutic parameters (type of antibiotics and duration of administration, steroid medication and therapeutic modalities, aspiration with or without cerebrospinal fluid drainage, total extirpation after aspiration, or primary extirpation and medical treatment) were evaluated as independent predictors of poor outcome (totally disabled state or death) by using univariate and multivariate logistic regression analysis. We also statistically estimated the possible causes of IVROBA and the multiplicity of brain abscess. RESULTS: Although there were no statistically significant correlations between patients with good and poor outcomes in regard to other basic characteristic and therapeutic parameters, patients with poor outcomes were older (P < 0.02), more frequently had IVROBA (P < 0.005), and had a higher frequency of neurological deterioration (P < 0.01) than those with good outcomes. Multiple logistic regression analysis predicted that poor outcome increased the relative risk of IVROBA by a factor of 18.9 (odds rate, 18.9; 95% confidence interval, 1.7-211.6; P < 0.02). More patients with multiple abscesses had positive immunocompromised states than those with single abscesses (P < 0.01). Deep-located abscesses also more frequently had IVROBA (P < 0.005) and abscesses located in the parieto-occipital region ruptured into the occipital horn of the lateral ventricle in a short period (P < 0.02). CONCLUSIONS: Our findings suggest that IVROBA strongly influences poor outcome in patients with cyanotic heart disease. The key to decreasing poor outcomes may be the prevention and management of IVROBA. To reduce operative and anesthetic risk in these patients, abscesses should be managed by less invasive aspiration methods guided by computed tomography. Abscesses larger than 2 cm in diameter, in deep-located or parieto-occipital regions, should be aspirated immediately and repeatedly, mainly using computed tomography-guided methods to decrease intracranial pressure and avoid IVROBA. IVROBA should be aggressively treated by aspiration methods for the abscess coupled with the appropriate intravenous and intrathecal administration of antibiotics while evaluating intracranial pressure pathophysiology.

Adolescent↗

[Colonization types of Escherichia coli in experimental urinary tract infection in compromised mice treated with hydrocortisone].

We studied the experimental urinary tract infections (UTIs) on compromised mice with Escherichia coli to elucidate the effects of three factors (bacterial strains, doses of hydrocortisone, infectious periods) on the bacterial colonization in the bladders. We selected three strains from the stock of E. coli isolated from the urine or feces of patients with lower UTI, because each of the three strains showed a tendency in colonization in previous experiments: One strain, which was named H70, showed a relative slight and intracellular colonization; the H99, an extracellular and the K88, both intracellular and extracellular growths which were large. The rate of bacterial microscopic recovery from the bladders of mice inoculated strains H70, H99 and K88 were 25.0, 41.7 and 79.2% respectively. And the recovery from the mice inoculated cortisone, 0, 2, 4 and 8 mg/mouse were 38.9, 55.6, 55.6 and 44.4% respectively. The detections of various colonizations at 3, 6 and 24 hr after the bacterial inoculation were that extracellular types were 45.8, 20.8 and 20.8%, intracellular types were 4.2, 16.7 and 12.5%, simultaneous colonizations were 4.2, 16.7 and 4.2% and the detections of at least one of them were 54.2, 54.2 and 37.5% respectively. Thus, the global findings were that extracellular growth of the bacteria were predominant at first, then the bacteria invaded the mucosal cells and the intracellular bacteria stayed after the voiding of extracellular bacteria. Intracellular colonizations seemed more strongly interacting with hosts than extracellular types, because cortisone enhanced the intracellular colonizations more strongly than the others. However, it seemed that urinary tract infections were not simple events but the results of the interactions of the bacterial strains and hosts, because the locations and degrees of the bacterial colonization and the effects of hydrocortisone on them were different in each bacterial strain and infectious period.

Animals↗

Is stereotactic surgical treatment still necessary for Parkinson's disease in the contemporary trend of medical therapy with dopamine receptor agonist?

Clinical experience with the use of pergolide is presented in 55 patients with Parkinson's disease. Fifty to 900 micrograms/day (mean 242.73, SD 217.51) of pergolide and 0.64-17.05 micrograms/kg/day (mean 4.58, SD 4.25) pergolide was given together with L-carbidopa to 29 males and 26 females for a period of up to 2 years 7 months. Low-dose pergolide together with L-carbidopa is effective in the treatment of parkinsonism without side effects, even in advanced stages of the disease. No patients required surgical treatment such as pallidotomy or deep brain stimulation recommended by other investigators. We emphasize that parkinsonism can be sufficiently treated with pergolide and L-dopa and that surgical treatment should be minimized unless there is no alternative.

Aged↗