Biomedical subjects

N Tamaki

Publications and source records attributed to N Tamaki.

At least 19 recordsLinked to original sources

PubMed2005

Isolation and characterization of aminopeptidase from Capnocytophaga granulosa ATCC 51502.

There is evidence that enzymes from the genus Capnocytophaga play a role in dental calculus formation. Although most of the species in the genus produce aminopeptidases, there is a paucity of data on the purification and characterization of the enzyme, except in the case of Capnocytophaga gingivalis. The aim of this study was to purify aminopeptidase from culture supernatant of Capnocytophaga granulosa ATCC 51502, a new species of the genus. Purification was performed using ammonium sulfate fractionation and two chromatographic steps. The aminopeptidase was purified 158,433-fold with a yield of 12.0%. The enzyme appeared to be a trimer with a molecular mass of 270 kDa. The optimal pH of the aminopeptidase was 6.5 and its activity was completely inhibited by incubation at 50 degrees C for 10 min. The enzyme showed maximum specificity for basic amino acids (Arg and Lys) and also hydrolyzed noncharged amino acids (Met, Leu and Ala). Ca(2+), Zn(2+) and Fe(3+) activated the enzyme, while EDTA, Ag(+), Hg(+) and Cu(2+) inhibited it. These results suggest that aminopeptidase of C. granulosa is different from that of C. gingivalis but similar to aminopeptidase B.

Amino Acids↗

PubMed2005

SPET in cardiology. Diagnosis, prognosis, and management of patients with coronary artery disease.

Stress myocardial perfusion imaging has been considered as a most valuable means for diagnosis and treatment strategy in patients with suspected and known coronary artery disease. (99m)Tc perfusion imaging agents provide excellent myocardial perfusion images. In addition, greater photon flux from the tracer permits simultaneous assessment of regional perfusion and function with use ECG-gated acquisition. Gated SPET imaging technique has a potential for higher diagnostic accuracy for diagnosis of coronary artery disease and assessment of the disease severity. In addition, radionuclide imaging plays an important role to differentiate reversible ischemic myocardium which may improve LV function after revascularization from irreversible scar in patients with history of myocardial infarction. While FDG-PET is considered as a most reliable means for myocardial assessment, SPET imaging has been widely used for the viability assessment, with gaining higher accuracy for predicting reversible ischemia. Recently a variety of new radiopharmaceutical agents have been introduced to probe myocardial function in vivo. [(123)I]BMIPP, a branched fatty acid analog, has been used for metabolic imaging using SPET. Less uptake of BMIPP than perfusion is often observed in the ischemic myocardium. Such a perfusion metabolic mismatch which seems to be similarly observed in FDG-PET is identified in the stunned or hibernating myocardium with regional dysfunction. Severe ischemia is identified as reduced BMIPP uptake at rest, suggesting its role as an ischemic memory imaging. These new techniques will provide insights into new pathological states in the ischemic heart disease and enable to select optimal treatment of these patients.

Cardiology↗

PubMed2004

Effect of steroids on [18F]fluorodeoxyglucose uptake in an experimental tumour model.

BACKGROUND: It is well known that blood glucose level affects the uptake of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in tumours. Thus, the action of steroids on glucose metabolism may alter blood glucose levels and may affect FDG uptake in tumours in patients treated with steroids. To clarify this point, we determined the effects of steroids on FDG uptake in tumours in a rat model of a malignant tumour. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. They were fasted overnight and divided into three groups (n=5 in each group): (1) dexamethasone (DEX) pretreated (0.8 mg.kg(-1) body weight, i.m. injection 4 h before FDG i.v. injection); (2) prednisolone (PRE) pretreated (8 mg.kg(-1) body weight, i.m. injection 20 h before FDG i.v. injection); and (3) control (untreated) groups. Radioactivity in tissues was determined 1 h after i.v. injection of FDG. FDG uptake in the tumour was expressed as the percentage of injected dose per gram of tissue after normalization to animal's weight (%ID/g tissue/kg body weight). RESULTS: DEX and PRE pretreatments significantly increased the blood glucose levels to 128% and 145% of the control value. The levels of FDG uptake in the tumour were not significantly affected by DEX and PRE pretreatment (90% and 87% of the control value, respectively) (P=NS). CONCLUSIONS: These results demonstrate that FDG uptake in the tumour was not affected by pretreatment with steroids, in spite of a slight elevation in blood glucose level.

Animals↗

PubMed2004

Preparation and pharmaceutical evaluation for clinical application of high specific activity S-(-)[11C]CGP-12177, a radioligand for beta-adrenoreceptors.

BACKGROUND: Although S-(-)[C]CGP-12177 is a useful positron emission tomography (PET) ligand for beta-adrenoreceptors, the difficulty in radiolabelling the compound has prevented its extensive clinical application. Recently, we have developed a simple synthesis method for S-(-)[C]CGP-12177. In the present study, we attempted to prepare S-(-)[C]CGP-12177 with a high specific activity for intravenous injection which is feasible for the clinical evaluation of beta-adrenoreceptors. METHODS: The [C]methane produced during irradiation of a N2--H2 (95/5) mixture with an 18 MeV proton beam (20 microA, 30 min) was chlorinated using Cl2 to yield [C]carbon tetrachloride. S-(-)[C]CGP-12177 was synthesized by reacting the diamino precursor with [C]phosgene produced by oxidizing [C]carbon tetrachloride on a Fe--Fe2O3 column. The product was purified by using reversed phase, high-performance liquid chromatography (RP-HPLC) and the radioactive fraction containing S-(-)[C]CGP-12177 was collected and evaporated to dryness. S-(-)[C]CGP-12177 dissolved in physiological saline was sterilized through a 0.22 microm membrane filter. The radiochemical purity and the mass of the compound were determined with RP-HPLC. The residual organic solvents were determined with GC. Tests for sterility and the presence of bacterial endotoxins were also performed. RESULTS: S-(-)[C]CGP-12177 for intravenous injection was prepared in 25 min after the end of bombardment with a yield of 1.5+/-0.2 GBq. Specific activity was found to be 385.4+/-133.0 GBq/ micromol at the end of synthesis (EOS) (n=3). Radiochemical purity was found to be more than 99%. Toluene was not detected in the solution. The ethanol concentration was determined to be 60.3+/-52.5 ppm. Tests for sterility and bacterial endotoxins showed negative results. CONCLUSION: We successfully prepared S-(-)[C]CGP-12177 formulated for intravenous injection with high purity and high specific activity, which is feasible for the clinical evaluation of beta-adrenoreceptors.

Drug Evaluation, Preclinical↗

PubMed2003

Quantitative analysis of hyperosmotic and hypothermic blood-brain barrier opening.

Hyperosmotic opening of the blood-brain barrier (BBB) by mannitol is being used to enhance drug transport in human brains. Recently, cooling of the solution has been reported to have potential to open the BBB. However, the mechanism in barrier opening and closure remains elusive. We studied the rapid changes in cerebrovascular permeability after hyperosmotic and hypothermic BBB opening in rats, and then demonstrated that the Na+/Ca++ exchange blocker (KB-R7943) prolongs opening. BBB opening was attained by using intra-arterial infusion of hyperosmotic mannitol (1.6 M) and 1.1 M mannitol (which is less hyperosmotic than commonly used mannitol) at 4 degrees in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate-containing [14C]-sucrose was infused intra-arterially at different time points following hyperosmotic and hypothermic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. 1.6 M Mannitol produced opening of the BBB but the duration of the opening was less than 30 minutes. Use of 1.1 M Mannitol at 4 degrees indicated the same results. We then investigated the effect of a Na/Ca ion exchange blocker (KB-R7943) in both hyperosmotic and hypothermic BBB opening. KB-R7943 extended BBB opening up to 30 min without affecting the peak level of BBB permeability at 5 minutes. Our findings represent important experimental information regarding pharmacological manipulation of BBB opening. The possibility of prolonging the transient opening of the BBB has major clinical implications.

Animals↗

PubMed2003

Transient left ventricular dysfunction in ischaemic myocardium after stress: comparative study with exercise and pharmacological stress gated myocardial single photon emission computed tomography.

In ischaemic heart disease patients, transient left ventricular dysfunction is observed due to post-exercise stunning. The aim of this study was to determine whether transient left ventricular dysfunction could also be seen after short-acting pharmacological stress (adenosine triphosphate). A 1 day rest/stress gated myocardial single photon emission computed tomography was performed on 362 patients suspected of having ischaemic heart disease by exercise (n=199) or short-acting pharmacological stress (n=163). Left ventricular ejection fraction were estimated both at rest and stress. Based on perfusion findings, patients were subdivided into ischaemia, fixed defect and normal group. For the ischaemia and fixed defect group, left ventricular ejection fraction after stress was significantly decreased compared with the resting value by exercise stress (ischaemia group, 57.5+/-11.0 vs 60.4+/-10.4; fixed defect group, 47.7+/-16.7 vs 49.6+/-16.8; P<0.01), but not by pharmacological stress (ischaemia group, 55.8+/-13.4 vs 57.1+/-13.8; fixed defect group, 50.8+/-13.5 vs 50.6+/-13.1; P=NS). In the normal group, left ventricular ejection fraction after stress was not significantly changed by either exercise (65.7+/-10.4 vs 66.8+/-10.2; P=NS) or pharmacological stress (63.0+/-11.7 vs 64.0+/-12.1; P=NS). It is concluded that a transient decrease in left ventricular ejection fraction after stress was observed following post-exercise, not following a short-acting pharmacological stress in patients showing perfusion abnormalities. Transient left ventricular dysfunction may be the result of post-exercise stunning, not from subendocardial hypoperfusion induced by short-acting pharmacological stress.

Adenosine Triphosphate↗

PubMed2003

Prediction of functional recovery after coronary bypass surgery using quantitative gated myocardial perfusion SPECT.

Previous studies have demonstrated that myocardial perfusion imaging using 99mTc-tetrofosmin at rest allows viability assessment similar to that obtained with 201Tl imaging and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). The simultaneous assessment of perfusion and regional function is now available by quantitative gated myocardial perfusion single-photon emission computed tomography (SPECT). This study was designed to evaluate the utility of quantitative values of wall motion and wall thickening, calculated by quantitative gated myocardial perfusion SPECT, for the prediction of functional recovery after coronary bypass grafting (CABG). Fifty-six patients with coronary artery disease scheduled for CABG were included prospectively. All patients underwent 99mTc-tetrofosmin gated SPECT imaging at rest preoperatively and 3 months after CABG. The myocardium was divided into nine segments and the average quantitative values of regional perfusion (percentage uptake) (%), wall motion (mm) and wall thickening (%) were determined automatically using quantitative gated SPECT (QGS) software. The wall motion score was defined visually using a four-point scale (0, normal; 3, akinesis), and segments with severe asynergy (score of 2 or 3) with patent grafts were assessed. Of 77 segments with severe asynergy, 56 segments showed improved wall motion and 21 segments did not improve after CABG. The area under the receiver operating characteristic curve of wall thickening for the prediction of functional recovery was significantly higher (0.92) than that of the percentage uptake (0.77, P<0.017) or wall motion (0.60, P<0.0001). When each analysis used the optimal threshold, the wall thickening analysis (>or=10%) had a sensitivity of 95% and a specificity of 81%. These values tended to be higher than those of the percentage uptake (sensitivity, 86%; specificity, 67%). The wall motion analysis (>or=1.5 mm) had a significantly lower sensitivity of 75% and specificity of 43% than the wall thickening analysis (P=0.0038 and P=0.011, respectively). The results indicate that wall thickening, calculated by QGS software, may be more useful than regional perfusion or wall motion analysis for the prediction of functional recovery after CABG. The areas of asynergy with relatively preserved wall thickening may have the potential for improved function despite severely decreased perfusion.

Aged↗

PubMed2002

Haemodynamic assessment in patients with dural arteriovenous fistulae: dynamic susceptibility contrast-enhanced MRI.

Cerebral haemodynamics in patients with dural arteriovenous fistulae (DAVF) have not been fully investigated and their effects are not clear. Our purpose was to assess impaired haemodynamics in patients with DAVF using dynamic susceptibility contrast-enhanced MRI (DSC-MRI). We used this technique in eight control subjects (group I) and 17 patients with DAVF who were scheduled to undergo or had already undergone endovascular embolisation and/or surgical excision. There were seven patients with cavernous sinus DAVF (CSDAVF) and the other ten had unilateral transverse/sigmoid sinus DAVF. All patients with CSDAVF underwent DSC-MRI preoperatively (group II) and those with transverse/sigmoid sinus DAVF underwent preoperative DSC-MRI (group III) and postoperative (group IV) assessment. The ratios of relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and mean transit time (rMTT) were calculated relative to contralateral values. Patients in group II had no significant haemodynamic impairment in grey (GM) or white matter (WM), but cerebellar rMTT were significantly prolonged ( P<0.05). Group III showed haemodynamic impairment characterised by significant increase in rCBV, prolongation of rMTT and decrease in rCBF in GM ( P<0.05). Significantly increased rCBV and prolonged rMTT in the GM ( P<0.05) were obvious in group III patients irrespective of retrograde leptomeningeal venous drainage (RLVD). In group IV, rCBV and rCBF returned to normal values, whereas rMTT was still significantly prolonged in GM ( P<0.05). Our study indicates that patients with CSDAVF may have impaired cerebellar perfusion, and that those with transverse/sigmoid sinus DVAF can have disturbed cerebral haemodynamics, even in the absence of RLVD.

Arteriovenous Fistula↗

PubMed2002

Comparison of inhibitory activity on calcium phosphate precipitation by acidic proline-rich proteins, statherin, and histatin-1.

This study quantitatively compares the inhibition of calcium phosphate (CaP) precipitation by the salivary acidic proline-rich proteins (PRPs) statherin and histatin-1. Saliva and CaCl2 in 125 mM imidazole buffer (pH 7.0) were incubated with potassium phosphate and a hydroxyapatite (HAP) suspension, for 30 min at 25 degrees C, then filtered through nitrocellulose. The calcium (Ca) concentration in the filtrate was measured by atomic absorption spectrophotometry, then deducted from that in the initial solution to determine the amount of CaP precipitation after 30 min. The values of the inhibitory activities on CaP precipitation relative to crude parotid saliva were 4.7, 4.9, 6.9, and 65.8 for histatin-1, large PRPs, small PRPs, and statherin, respectively.

Adult↗

PubMed2002

Accuracy and reproducibility of left ventricular function from quantitative, gated, single photon emission computed tomography using dynamic myocardial phantoms: effect of pre-reconstruction filters.

We have investigated the accuracy and reproducibility of left ventricular (LV) functions using quantitative, gated, single photon emission computed tomography (SPECT) software dependent on critical frequencies of pre-reconstruction filters. This study incorporated dynamic myocardial phantoms (myocardial and cone shapes). Gated SPECT of 8-interval sets were pre-filtered with Butterworth filters (critical frequency varying between 0.16 and 1.16 cycles/cm, order 5) and with no filter. Phantoms were repositioned, and SPECT acquisitions were repeated. As the critical frequency increased, the estimated LV volume increased to reach a plateau at the level of the critical frequency, 0.54 cycles/cm. Conversely, the values of ejection fractions, wall motion and wall thickening with different filters which used critical frequency of > or =0.39 cycles/cm remained unchanged. However, LV functions and volumes were underestimated when any pre-reconstruction filter was used. Standard deviations of LV functions after repeated measurements were unaffected by different filters with critical frequencies of > or =0.39 cycles/cm. Standard deviations of LV volume, ejection fraction, wall motion and wall thickening were <2.2 ml, <0.9%, <0.6 mm and <8.7%, respectively. Therefore, with the exception of low critical frequencies, LV functions and volumes were highly reproducible when these routine reconstruction filters were used.

Algorithms↗

PubMed2002

Fluorodeoxyglucose uptake and glucose transporter expression in experimental inflammatory lesions and malignant tumours: effects of insulin and glucose loading.

The expression of glucose transporters (GLUTs) and its relationship to fluorodeoxyglucose accumulation in malignant tumours have been well investigated, while such a relation has not been studied in inflammatory lesions. The aim of the present study was to investigate the effects of insulin and glucose loading on the expression of GLUTs in inflammatory lesions and compare them with those in malignant tumours in relation to fluorodeoxyglucose accumulation. All tissue specimens used in this study were obtained in our previous study, in which rats were inoculated with allogenic hepatoma cells (KDH-8), Staphylococcus aureus, or turpentine oil into the left calf muscle and divided into three subgroups: insulin loaded, glucose loaded, and control groups. The expression of glucose transporters (GLUT-1 to GLUT-5) was investigated by immunostaining the lesions (n=5-6, for each group). In all control groups, the expression levels of GLUT-1 and GLUT-3 were significantly higher than those of GLUT-2, GLUT-4 and GLUT-5. Insulin loading did not significantly affect the expression levels of GLUT-1 and GLUT-3 in these lesions except for a significant but slight decrease in the GLUT-1 expression level in the inflammatory lesion of non-infectious origin (89% of the control value). Glucose loading significantly decreased the expression level of GLUT-1 in the inflammatory lesion of non-infectious origin (70% of the control value, P<0.01), and that of GLUT-3 in the inflammatory lesion of infectious origin (70% of the control value, P<0.05), while the expression levels of GLUT-1 and GLUT-3 in the tumour were not significantly affected. These results demonstrate the effects of insulin and glucose loading on the expression level of a molecule (GLUT proteins). The decreased GLUT-1 and GLUT-3 expression levels induced by glucose loading may partly explain the impaired FDG uptake observed in our previous study.

Animals↗

PubMed2002

Validation of left ventricular function from gated single photon computed emission tomography by using a scintillator-photodiode camera: a dynamic myocardial phantom study.

A scintillator-photodiode camera is able to acquire single photon emission computed tomography (SPECT) images by using a rotating chair system. We validated the left ventricular (LV) parameters of this camera system utilizing a dynamic myocardial phantom. Gated myocardial SPECT of a dynamic myocardial phantom (Hokkaido University type; end diastolic volume (EDV), 143 ml; end systolic volume (ESV), 107 ml; ejection fraction (EF), 25%) was performed with this scintillation camera. LV parameters were calculated using pre-installed software (Mirage Myocardial Perfusion SPECT) (study 1) and the other software (QGS; Cedars-Sinai) (study 2). For comparison, SPECT from a traditional Anger camera were processed by the QGS software (study 3). The estimated volumes were similar among the three studies (EDV, 110+/-8 ml in study 1, 112+/-2 ml in study 2 and 111+/-1 ml in study 3; ESV, 86+/-8 ml in study 1, 93+/-4 ml in study 2 and 91+/-2 ml in study 3). The estimated EFs were 23+/-3%, 17+/-2%, and 18+/-1%, respectively. The calculated volume within each study was underestimated by approximately the same degree. However, each estimated EF value for each study was close to the actual value. The estimated LV function using the scintillator-photodiode camera system may be considered as a suitable alternative to the traditional Anger camera system.

Algorithms↗

PubMed2002

Value and limitation of myocardial fluorodeoxyglucose single photon emission computed tomography using ultra-high energy collimators for assessing myocardial viability.

Single photon emission computed tomography (SPECT) using ultra-high energy collimators permits wide clinical application of (18)F-fluorodeoxyglucose (FDG) imaging without the use of expensive positron emission tomography (PET) cameras. This study was designed to evaluate the value of FDG SPECT using ultra-high energy collimators in assessing myocardial viability compared with FDG PET on a regional basis. We prospectively studied 33 patients with ischaemic heart disease. The patients were injected with 555 MBq of FDG under a hyperinsulinaemic glucose clamp, and FDG PET was performed 40 min later. FDG SPECT using ultra-high energy collimators was performed immediately after FDG PET. The images of the left ventricular myocardium were divided into nine segments and the regional defect score was assessed visually using a four-point scale (0=normal to 3=defect). Regional FDG uptake (%uptake) was quantitatively analysed using polar maps. In 297 segments of all the 33 patients, agreement between the defect scores based on FDG SPECT images and those based on FDG PET images was 70%, and agreement within one rank was 96% (kappa value=0.52). The %uptake based on FDG SPECT images significantly correlated with that based on FDG PET images (r=0.77, P<0.01). However, the defect scores in the inferior wall based on FDG SPECT images were higher (1.41+/-1.14) than those based on FDG PET images (1.06+/-1.12, P<0.01). When the viable region is defined as %uptake > or =50% in FDG PET studies, the optimal cut-off level of %uptake based on FDG SPECT images was 60% in the anterior wall, apex, septum and lateral wall (accuracies, 97%, 93%, 96% and 99%, respectively), and 45% in the inferior wall (accuracy, 99%). It is concluded that FDG SPECT using ultra-high energy collimators can be used for the assessment of myocardial viability as accurately as FDG PET. However, a slight difference was observed in the defect scores mainly due to attenuation in the inferior wall. Therefore, a slightly different cut-off level for assessing myocardial viability should be applied to the inferior wall when using FDG SPECT.

Adult↗

PubMed2001

Quantitative analysis of papaverine-mediated blood-brain barrier disruption in rats.

The blood-brain barrier (BBB) is a permeability barrier of interconnected brain capillary endothelial cells. Intraarterial infusion of papaverine relieves cerebral vasospasms by inhibiting smooth muscle contractions and it may simultaneously lead to a disruption of BBB permeability. To date, the mechanism underlying this phenomenon and the quantification of BBB disruption remains elusive. We first examined the changes in cerebrovascular permeability after an intracarotid infusion of papaverine (0.20%) in rats by an in situ brain perfusion technique. We then demonstrated that changes in cerebrovascular permeability depend on the concentration of papaverine. This is the first study in which the degree of BBB disruption was accurately quantified in terms of [(14)C]sucrose and it was demonstrated that papaverine has a prolonged effect on cerebrovascular permeability. This result suggests the importance of in vivo experiments for a precise evaluation of permeability for many other agents, particularly for the central nervous system.

Animals↗

PubMed2001

Selective cholinergic denervation inhibits expression of long-term potentiation in the adult but not infant rat hippocampus.

The present study assessed the role of the cholinergic systems on the expression of perforant path long-term potentiation (LTP) in rat hippocampal slices from the infant and adult brain. To denervate the cholinergic systems, 192 IgG--saporin was injected into the lateral ventricle of the infant (2-weeks-old) and adult (6-weeks-old) rat brain. There, choline acetyltransferase-immunoreactive fibers were barely detectable 2 weeks and 2 months after injection for both the groups. For the infant rats, perforant path LTP was not affected by selective cholinergic denervation; the probability of LTP development was 0.83 (five out of six slices) and 0.78 (seven out of nine slices) at 2 weeks and 2 months later in 192 IgG--saporin-treated slices, as compared with 0.83 at each period in control saline-treated slices. In contrast, the expression of the LTP was blocked by selective cholinergic denervation for the adult rats; the probability of LTP development was 0 (zero out of 10 slices) and 0.38 (three out of eight slices) at 2 weeks and 2 months later in 192 IgG--saporin-treated slices, as compared with 0.8 (eight out of 10 slices) and 0.83 (five out of six slices) at each period in control saline-treated slices. The results of the present study thus suggest that the cholinergic systems play a crucial role in the expression of LTP in the adult brain and that the denervated systems in the infant brain could be compensated by the sprouting of non-cholinergic fibers.

Age Factors↗

PubMed2001

Abnormal neuronal network in anorexia nervosa studied with I-123-IMP SPECT.

Single photon emission computed tomography was used to study 14 female patients with anorexia nervosa and 8 female normal comparison subjects. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Statistics across the entire brain were displayed as Z scores (threshold: P<0.05). Compared with the normal comparison subjects, the anorectic patients were characterized by hypoperfusion in the medial prefrontal cortex and the anterior cingulate gyrus, and hyperperfusion in the thalamus and the amygdala-hippocampus complex. These results suggest that a dysfunction in neuronal circuitry may be related to anorexia nervosa.

Adolescent↗

PubMed2001

The effects of the Na(+)/Ca(++) exchange blocker on osmotic blood-brain barrier disruption.

Osmotic disruption of the blood-brain barrier (BBB) by mannitol is currently being used to enhance drug delivery in human brains. Despite clinical and experimental interest, to date the time course in the early phase of disruption has not been accurately identified. The mechanism in barrier closure also remains elusive. We first studied the rapid change in cerebrovascular permeability after BBB disruption in rats, and then demonstrated that the Na(+)/Ca(++) exchange blocker (KB-R7943) prolongs osmotic disruption. Osmotic BBB disruption was attained by using intra-arterial infusion of hypertonic mannitol in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate containing [14C]-sucrose was infused intra-arterially at different time points following osmotic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. This is the first in vivo study demonstrating that osmotic disruption is prolonged by the Na(+)/Ca(++) exchange blocker, which did not affect the peak level of BBB disruption. The exact time course of cerebrovascular reversibility was studied and the earliest BBB disruption was seen to occur 5 min after osmotic stress. Histopathological examination after osmotic disruption with the Na(+)/Ca(++) exchange blocker showed no neuronal damage in rat brains. Our findings represent important experimental information regarding pharmacological manipulation of BBB disruption. The possibility of prolonging the transient opening of the BBB has major clinical implications.

Animals↗

PubMed2001

Surgical approaches and strategies for skull base chordomas.

OBJECT: The management of chordomas involving the skull base continues to present a number of treatment-related problems. Recently, both radical resection and charged-particle irradiation or stereotactic radiosurgery have reportedly been found effective for tumor control and for promoting a better quality of life in patients. In this article the authors analyzed the outcomes in 17 patients with skull base chordomas who were surgically treated at Kobe University Hospital between 1972 and 2000. METHODS: Preoperative radiological examinations included magnetic resonance imaging, computerized tomography, angiography, and balloon occlusion test of the internal carotid artery. Among the various surgical approaches used to remove the tumor were the frontoorbitozygomatic, transmaxillary, transcondylar, transsphenoidal, and the transbasal. Total removal was achieved in two (12%), near-total removal in three (18%), subtotal removal in nine (52%), and partial removal in three patients (18%). Since 1990, chordomas have been radically resected via various skull base approaches; the combined total or near-total removal rate has been 80% in this period. Radical removal of the tumors has not led to an increased risk. At the final follow-up review (mean 59.5 month), 75% of the patients were still alive, and 25% had died of chordoma recurrence. The overall recurrence-free survival rate was 82% at 3 years and 51% at 5 years. The 5-year recurrence-free survival rate in the five patients who underwent the operation during the past decade was 77% (mean follow up of 5.2 years). In two patients with recurrent tumors who underwent radiosurgery, no evidence of tumor regrowth was demonstrated at 3 years posttreatment. CONCLUSIONS: The authors suggest that for the treatment of skull base chordomas radical resection is a key factor for longer survival and improved quality of life. Patients with sufficiently small tumors, which show a favorable configuration and location, can be suitable candidates for stereotactic radiosurgery.

Adolescent↗