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K Takakura

Publications and source records attributed to K Takakura.

At least 19 recordsLinked to original sources

Postoperative flow cytometry crossmatch in living donor liver transplantation: clinical significance of humoral immunity in acute rejection.

BACKGROUND: The role of humoral immunity in acute rejection in solid organ transplantation remains controversial, although it is known that the presence of antidonor antibodies may precipitate graft rejection. We investigated the clinical relevance of antidonor humoral immunity for living donor liver transplantation (LDLT) by means of flow cytometry crossmatch (FCXM). METHODS: T cell FCXM using fresh donor peripheral lymphocytes was performed before and up to 1 month after LDLT in 58 patients. Ten patients received ABO-incompatible grafts. IgM and IgG antidonor antibodies were analyzed in relation to clinical acute rejection as defined by liver function tests with or without histological evidence. RESULTS: Pretransplantation FCXM was positive for five patients (8.6%), resulting in two cases of positive posttransplantation FCXM and two rejection episodes. Twelve patients (20.7%) showed positive posttransplantation FCXM. The incidence of acute rejection within 1 month was 100% in FCXM-positive patients and 17.4% in FCXM-negative patients (P<0.001). Thirteen (76.5%) of 17 rejection episodes in ABO-compatible cases were associated with concomitant antidonor IgM antibody. IgG antibody was also identified in six of these episodes. Antidonor antibodies disappeared after rejection treatments in all cases, but with some delay in clinical improvement. On the other hand, no antidonor antibodies were detected in any of the four rejection episodes in ABO-incompatible cases. CONCLUSIONS: Early acute rejection in LDLT is significantly associated with antidonor T cell antibody formation in ABO-compatible cases. This suggests a definite role for donor-specific humoral immunity in acute rejection. Rejection episodes without antidonor antibodies may suggest graft injury by pure cellular immunity, or possibly the presence of humoral immunity triggered by antigens not present on donor T cells.

ABO Blood-Group System

Heterozygous gsp mutation renders ion channels of human somatotroph adenoma cells unresponsive to growth hormone-releasing hormone.

Ionic mechanisms play an important role in the regulation of hormone secretion. The GHRH-induced GH release by human GH-secreting cells is transmitted through protein kinase A (PKA), which activates nonselective cation current (NSCC) and induces membrane depolarization, intracellular Ca2+ increase, and GH secretion. To evaluate whether ionic mechanisms have pathophysiological significance in GH oversecretion of GH-secreting pituitary adenomas, we examined four adenomas with constitutively active Gs alpha mutation (gsp mutation) and compared with three gsp-negative adenomas. In primary-cultured cells of gsp-positive adenomas, GHRH did not increase the NSCC under voltage-clamp experiments. Detailed examination showed that NSCC was maximally activated at the basal level and application of GHRH did not increase the current in these adenomas. Furthermore, by using single-cell RT-PCR method, we demonstrated for the first time at the single cell level that gsp mutation is heterozygous in GH-secreting pituitary adenomas. These indicate that heterozygous gsp mutation fully activates NSCC at the basal level, which may account for the GH oversecretion in gsp-positive GH-secreting pituitary adenomas.

8-Bromo Cyclic Adenosine Monophosphate

[Selective peripheral denervation for spasmodic torticollis involving the levator scapulae muscle].

Patients with laterocollis or rotatory type torticollis tend to show abnormal contraction of the levator scapulae muscle and the scalene muscles. These muscles are innervated from the anterior branches of the cervical spinal nerves. Because of this, the traditional Bertrand operation dealing with posterior branches does not adequately affect the symptoms of laterocollis. The authors report selective denervation of the levator scapulae muscle in three patients and discuss its rationale. All the three patients underwent denervation of both the C1-C6 posterior spinal rami and the branches from the C3 and C4 anterior rami to the levator scapulae muscle. We added myotomy of the scalene muscle in one patient, and denervation of the omohyoid muscle which is innervated from the ansa cervicalis and the descending branch of the hypoglossal nerve. The pre/post-operative Tsui scores were 12/4, 15/1, and 14/3 respectively. There were no complications. We conclude that selective peripheral denervation of the levator scapulae muscle is safe and effective in the treatment of laterocollic type torticollis.

Adult

Augmented reality visualization system for intravascular neurosurgery.

We aimed to construct an augmented reality-based visualization system to support intravascular neurosurgery and evaluate it in clinical environments. Three-dimensional (3D) vascular models are overlaid on motion pictures from X-ray fluoroscopy by 2D/3D registration using fiducial markers. The models are reconstructed from 3D data obtained from X-ray computed tomographic angiography or from magnetic resonance angiography using the marching-cube algorithm. Intraoperative X-ray images are mapped as texture patterns on a screen object which is displayed with the vascular models. Distortion of X-ray fluoroscopy is eliminated by a new technique of screen mesh deformation. A quantity called reprojection distance was introduced to evaluate the reliability of the displayed images. It predicts the maximum registration error around the registered objects. Analyses of reprojection distances were performed using synthetic data consisting of marker coordinates with 2D or 3D errors. The tolerance of reprojection distance for the clinical environment was determined to be 3.0 mm. The system was tested in two clinical cases in which reprojection distances of 2.6 and 2.09 mm were obtained. Construction and evaluation of our prototype system were successfully carried out. Further development is planned employing a range sensor to permit markerless registration.

Computer Graphics

Endotracheal administration of lidocaine inhibits isoflurane-induced tachycardia.

PURPOSE: Rapid increase in inspired isoflurane concentration increases heart rate and arterial blood pressure. To investigate whether the responses to isoflurane were elicited from stimulation of lower airway and/or lungs, haemodynamic responses to isoflurane administered after tracheal intubation were measured with or without endotracheal or intravenous administration of lidocaine. METHODS: Seventy-two ASA physical status 1 patients, aged 21-50 yr, were randomly allocated to one of four groups. After tracheal intubation, anaesthesia was maintained with oxygen 100% and isoflurane 1.0% with controlled ventilation. After stabilization for 15 min, the isoflurane concentration was rapidly increased to 3.0% in three groups. An endotracheal lidocaine group received pretreatment with endotracheal 0.4 ml lidocaine 8% spray, an intravenous lidocaine group received pretreatment of 32 mg lidocaine i.v., and an isoflurane 3% group received not pre- treatment. In a control group, inspired isoflurane concentration was maintained at 1.0%. Heart rate, systolic blood pressure and end-tidal isoflurane concentration were measured every minute for 10 min. RESULTS: The rapid increase in isoflurane concentration increased heart rate (25 +/- 12% increase from baseline; P < 0.05) but the increase was reduced by endotracheal lidocaine (9 +/- 9%), but not by intravenous lidocaine (22 +/- 13%). The plasma concentration of lidocaine was lower in the endotracheal lidocaine group (0.4 +/- 0.3 microgram.ml-1) than in the i.v. lidocaine group (1.5 +/- 0.2 micrograms.ml-1). CONCLUSION: The isoflurane-induced tachycardia is reduced by pre-treatment with endotracheal lidocaine.

Administration, Inhalation

Kabuki make-up syndrome and report of a case with hydrocephalus.

We report a 22-year-old man with hydrocephalus caused by aqueductal stenosis. The patient was diagnosed with Kabuki make-up syndrome based on associated findings such as a peculiar facies, postnatal growth deficiency, brachydactyly of the fifth fingers, undescended testes, and malrotation of the colon. Kabuki make-up syndrome, recognized in Japan in 1981, is characterized by five cardinal manifestations: a peculiar facies, skeletal anomalies, dermatoglyphic anomalies, slight to moderate mental retardation, and postnatal dwarfism. Neurological anomalies have been reported to include neonatal hypotonia, feeding problems, seizures, West syndrome, microcephaly, brain atrophy, GH deficiency, precocious puberty, delayed sexual development, and diabetes insipidus. Aqueductal stenosis may be caused by part of the series of midline anomalies. Physicians should pay attention to associated anomalous characteristics suggesting a malformation syndrome when they encounter nontumoral aqueductal stenosis in adolescents or adults.

Abnormalities, Multiple

Thrombin activity in CSF after SAH is correlated with the degree of SAH the persistence of subarachnoid clot and the development of vasospasm.

We previously reported that the coagulation system in cerebrospinal fluid (CSF) is strongly activated in the early stage of a subarachnoid haemorrhage (SAH). We evaluated the relationship among thrombin activity, degree of SAH, amount of clearance of SAH, and vasospasm. The CSF levels of fibrinopeptide A (FPA) were measured by radio-immunoassay in 36 SAH patients, who were diagnosed by computerized tomography (CT) within 12 hours and on whom surgery was performed within 48 hours. Clearance of SAH (%) was evaluated as the size of the clot in the basal cistern visualized between the initial and postoperative CT. The mean level of FPA in the patients of Group 3 (Fisher's CT classification) (182.2 ng/ml) was significantly higher than those in the patients of Group 2 (36.2 ng/ml). There was a significant difference in the mean level of FPA between patients with (47.6 ng/ml) and without infarction (408.3 ng/ml). In 18 of the 27 patients of Group 3 for whom the clearance of the SAH was determined, the patients showing a lower clearance rate (< 50%) of SAH demonstrated a significantly higher rate of infarction and a significantly higher level of FPA (466.6 ng/ml) than did the patients with a higher clearance rate (> 50%) of SAH (79.2 ng/ml). These results suggest that, the thrombin activity in CSF is correlated with the degree of SAH, the persistence of subarachnoid clot and the development of vasospasm.

Cerebral Infarction

Current treatment strategies and factors influencing outcome in patients with bacterial brain abscess.

We clearly determined the key to managing patients with brain abscess by retrospectively evaluating the factors affecting poor outcome in these patients. This study included 113 patients with brain abscess diagnosed in the CT era. Basic characteristics and therapeutic parameters were estimated as independent predictors of poor outcome by using univariate and multivariate logistic regression analysis. Patients with poor outcomes more frequently had deeply-located abscesses (p < 0.02), IVROBA (intraventricular rupture of brain abscess (p < 0.001) and were in a severely deteriorated neurological state (p < 0.001) than those with good outcomes. Multiple logistic regression analysis predicted that IVROBA (ORs, 24.5; 95% CI, 3.04 to 197.9) and severely deteriorated cases (ORs, 13.7; 95% CI, 2.34 to 80.8) resulting from IVROBA increased the relative risk of poor outcome. Patients with IVROBA more frequently had also deeply-located abscesses (p < 0.005), positively immunocompromised states (p < 0.05) and were in a severely deteriorated condition (p < 0.003) than those without IVROBA. Patients with metastatic abscess had also IVROBA (p < 0.006). Multiple logistic regression analysis anticipated that deeply-located abscess (ORs, 3.90; 95% CI, 1.38 to 11.04), and metastatic abscess (ORs, 12.26; 95% CI, 1.35 to 111.2) increased the relative risk of IVROBA. Patients in an obtunded state and with marked neurological deficit had IVROBA more often than patients in an alert state and/or mild neurological deficit (ORs, 3.23; 95% CI, 1.17 to 8.86, p < 0.03) before treatment. Our findings suggest that IVROBA strongly influences poor outcome in patients with brain abscess. The key to decreasing poor outcomes may be the prevention and management of IVROBA, by evaluating intracranial pressure pathophysiology. IVROBA should be aggressively treated by aspiration methods for the abscess coupled with appropriate intravenous and intrathecial administration of antibiotics.

Adolescent

Treatment of ornithine transcarbamylase deficiency in girls by auxiliary liver transplantation: conceptual changes in a living-donor program.

BACKGROUND/PURPOSE: Ornithine transcarbamylase (OTC) deficiency is an X-chromosome-linked genetic disorder resulting in hyperammonemia hepatic dysfunction, coma, and serious neurological sequelae. This report describes an experience in treating this condition with living-related liver transplantation. METHODS: Three children with OTC were treated with a living-related liver transplantation. Potential donors were evaluated with the allopurinol loading test to exclude heterozygotes. FK506 and low-dose steroids were used for immunosuppression. Auxiliary partial orthotopic transplantation (APOLT) was used in two of the cases. RESULTS: All three children survived and are doing well without protein restriction. CONCLUSIONS: These observations suggest that in OTC removal of the native liver is not necessary because (1) a partial liver segment with normal enzyme activity corrects the hyperammonemia, (2) in case of graft failure the native liver is an available backup, and (3) the native liver has the ability to recover function. As long as living-related donors serve as the main source of donor organs, APOLT is a safer approach to liver transplantation in OTC.

Amino Acid Metabolism, Inborn Errors

Prophylactic effect of papaverine prolonged-release pellets on cerebral vasospasm in dogs.

OBJECTIVE: A drug delivery system using copoly(lactic/glycolic acid) was developed for the intracranial administration of papaverine. A rod-shaped implant prepared by a heat compression method was tested to determine its efficacy in preventing cerebral vasospasm in dogs. METHODS: Sixteen dogs were randomly assigned to one of two groups, i.e., placebo or papaverine. Control angiography was performed, followed by right craniectomy and the induction of subarachnoid hemorrhage by the placement of a clot in the Sylvian fissure. Two pellets, containing either 25 mg of papaverine or no papaverine, were placed in the cistern. In in vitro studies, 56% of the actual papaverine loading was released in the first 4 days and 78% within 8 days. On Day 7, angiography was repeated and the animals were killed. A similar experiment using low-dose pellets containing 5 mg of papaverine, half of which was released within 7 days, was performed with 16 mongrel dogs. RESULTS: There were significant differences between the papaverine- and placebo-treated groups in the reductions of vessel diameters of the internal carotid, middle cerebral, and anterior cerebral arteries on the clot side. The mean concentration of papaverine in the clot was 4.5 x 10(-4) mol/L. The low-dose pellet failed to prevent cerebral vasospasm, although the mean concentration of papaverine in the clot was 2.3 x 10(-5) mol/L. CONCLUSION: A prolonged-release preparation of papaverine that could be implanted intracranially at the time of surgery prevented vasospasm significantly while maintaining an appropriate concentration of papaverine in the cistern.

Animals

Neuroprotective effect of an antioxidant, ebselen, in patients with delayed neurological deficits after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: The effect of ebselen, a seleno-organic compound with antioxidant activity through a glutathione peroxidase-like action, on the outcome of subarachnoid hemorrhage was evaluated in a multicenter placebo-controlled double-blind clinical trial. METHODS: Patients who suffered aneurysmal subarachnoid hemorrhages of Hunt and Kosnik Grades II through IV at admission and were able to start drug treatment within 96 hours of the ictus were enrolled. Early surgery was performed whenever possible. Oral administration of ebselen granules suspended in water (150 mg, twice a day) or placebo was started immediately after admission and continued for 2 weeks. The major end points were the Glasgow Outcome Scale at 2 weeks, 1 month, and 3 months after the start of treatment. The incidence of delayed ischemic neurological deficits clinically diagnosed as resulting from vasospasm and the incidence and extent of low-density areas on postoperative computed tomographic scans were also studied as secondary outcome measures. RESULTS: Intent-to-treat analysis of the 286 patients enrolled in the trial (145 patients administered ebselen and 141 administered placebo) revealed that the incidence of clinically diagnosed delayed ischemic neurological deficits was unaltered. There were 52 (receiving ebselen) and 58 (receiving placebo) patients with delayed deficits; however, a significantly better outcome was observed after ebselen treatment than after placebo (P = 0.005, chi2 test). There was a corresponding decrease in the incidence and extent of low-density areas (P = 0.032, Wilcoxon rank sum test). CONCLUSION: Ebselen reduced brain damage in patients with delayed neurological deficits after subarachnoid hemorrhage and may be a promising neuroprotective agent.

Aged

Metabolic profiles of patients with subarachnoid hemorrhage treated by early surgery.

OBJECTIVE: This study was conducted to evaluate the metabolic response of patients with subarachnoid hemorrhage (SAH) and to determine whether the severity of hemorrhage influenced the response. METHODS: Resting energy expenditure, nitrogen balance, and serum rapid-turnover proteins were studied for 3-day periods at Day 4, Day 10, and before discharge in patients with SAH who underwent surgical clipping within 2 days after the onset. The patients were divided into two groups according to the Hunt and Hess classification system; there were 17 patients with Grade I or II (mild group) and 19 patients with Grade III, IV, or V (severe group). RESULTS: The mean resting energy expenditures (mean+/-standard deviation) were highest on Day 10, which were 146+/-24% and 198+/-78% of basal energy expenditure in the mild and severe groups, respectively. The nitrogen balance levels of the mild group on Days 4 and 10 were -3.0+/-3.5 g per day and -4.5+/-2.9 g per day, and those of the severe group were -7.5+/-3.2 g per day and -9.2+/-4.1 g per day, respectively. There was a significant difference in the nitrogen balance over time between the two groups (P=0.0037). Serum transferrin, prealbumin, and retinol-binding protein levels were lowest on Day 4 and gradually increased. There were no significant differences in these parameters between the two groups. CONCLUSION: SAH treated by surgery induces a profound stress response. A significant difference of increased catabolism but not decreased anabolism between the mild and severe groups was noted.

Aged

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