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M Kowada

Publications and source records attributed to M Kowada.

At least 37 records · Page 2Linked to original sources

Chemoembolization of head and neck cancer with carboplatine microcapsules.

Fourteen patients with malignant tumor in the head and neck region were treated with infusion of carboplatine microcapsules (CBDCA-mc) via percutaneous super-selective catheterization. A microcatheter was advanced into a feeding artery using a coaxial catheter system. Eleven patients had over 30% reduction of the tumor size on CT within 1 month after embolization. Twelve patients had an increased amount of low attenuation tissue in the tumor on CT after embolization, suggesting increased necrosis in the tumor. No definite hematologic toxicity was found. A majority of patients complained of moderate pain in the embolized region immediately after embolization, easily relieved by i.v. analgesics. Chemoembolization using CBDCA-mc may be an effective therapeutic modality in advanced cases of head and neck cancer.

Aged↗

[Sequential analysis of the integrated images of PET, CT and MR in malignant brain tumors before and after radiotherapy].

11C-methyl-L-methionine (C-11 Met)PET, CT and MR imaging were performed in eleven patients with malignant brain tumors before and after RT to evaluate the usefulness of positron emission tomography (PET) in monitoring tumor response to radiotherapy (RT). The subjects included five cases of intracranial malignant lymphoma (ICML) and six cases of glioma. C-11 Met uptake by the tumor (T) and the contralateral gray matter (NT) was calculated on the PET images. The mean T/NT ratio of the ICMLs and gliomas changed from 2.33 and 1.87, respectively, before RT to 1.31 and 1.58, respectively, after RT.No significant difference was found between the T/NT ratios before and after RT in either the ICMLs or the gliomas (t-test). We tentatively defined the minimum T/NT ratio, 1.2, as the threshold between tumor and nontumor regions. Tumors with a ratio of 1.2 or more were imaged as "hot" (MET) and coincided with CT or MR image lesions which were visualized as contrast-enhancing (CE) and low-density (LD) or high-intensity (HI). The relationships between PET, CT and MRI lesions were classified as follows: Type I (MET < or = CE), Type II [CE < MET < LD (HI)], Type III [LD(HI) < or = MET]. MET lesions extending regionally ( > 1 cm) beyond the respective CT or MR image lesions were designated "MET-extension" and LD (HI) lesions protruding ( > 1 cm) beyond the MET lesions were recorded as "LD (HI)-extension" on the integrated images. The type II pattern of the MET areas in all five cases of ICML before RT had changed to Type I in one case, Type III in one case and Type II in three cases, after RT, while the two Type II patterns and four Type III patterns of the gliomas had converted to four Type II and two Type III patterns. These findings indicate that gliomas tend to invade into areas of peritumoral edema more than ICMLs. There were two ICML MET-extension sites in the cortex before RT, as opposed to two in the cortex, one in the basal ganglia, one in the thalamus, and one in the corpus callosum among the gliomas. On follow-up CT or MR images MET-extension (75%) had converted to a CE or LD (HI) region. Four ICML LD (HI)-extension sites before RT were found in periventricular white matter, versus one in the cortex and three in the white matter among the gliomas. LD (HI)-extension appeared to represent vascular edema because it decreased or diminished after completion of therapy. Sequential analysis of integrated C-11 Met PET, CT and MR images is useful in detecting the extent of tumor infiltration by ICMLs and gliomas, particularly at an early stage, and for evaluating the effect of RT in the treatment of both.

Adult↗

[Recanalization of dural sinus occlusion following the disappearance of dural arteriovenous fistula: report of a case].

A 73-year-old female was admitted to our hospital because of disturbed consciousness and left-sided motor weakness. Computed tomographic scans demonstrated a hemorrhagic infarction in the right parietal region. Right carotid angiograms showed both the posterior portion of the superior sagittal sinus (SSS) and the entire left transverse sinus simultaneously occluded. Left carotid angiograms revealed an enlarged occipital artery, which had direct communications to the left sigmoid sinus and the superior petrosal sinus. These findings were consistent with dural arteriovenous fistula (D-AVF). The laboratory examinations yieled normal results. The patient was managed conservatively with glyceol and anticonvulsants for four weeks and eventually recovered with complete resolution of hemiparesis. Follow-up angiography carried out 6 weeks later showed the SSS, partially stenotic, but recanalized with no evidence of venous congestion. The D-AVF still remained opacified, but there was a marked reduction in retrograde flow to the sigmoid sinus. Further repeated angiograms obtained at 10 months after the onset confirmed complete recanalization of the SSS and disappearance of the D-AVF. From the timing of the angiographies, we considered that the sinus occlusion was caused by the high arterial flow to the fistula and its disappearance made recanalization of SSS possible.

Aged↗

[Usefulness and problems of high dose chemotherapy using CBDCA, VP-16, and MCNU with peripheral blood stem cell transplantation in pediatric malignant brain tumors].

The aim of this study was to evaluate efficacy of high dose chemotherapy and restoration of hamatopoiesis following peripheral blood stem cell transplantation (PBSCT). Three patients with pediatric malignant brain tumors (two medulloblastomas and one medullomyoblastoma) underwent high dose chemotherapy including CBDCA, VP-16, and MCNU with PBSCT. Postcontrast-MR images revealed no abnormal enhancing lesions after high dose chemotherapy in all patients. One patient with medulloblastoma has remained complete remission one year and seven months after the termination of treatment. Another patient with medullomyoblastoma died of respiratory distress syndrome one month after the second course of high dose chemotherapy. The other patient with medulloblastoma, which received PBSCT and high dose chemotherapy at the time of tumor recurrence after failure of initial treatment, suffered from multiple disseminated lesions five months after the treatment. PBSCT contributed prompt recovery from hematopoietic dysfunction in all patients. These results indicate that PBSCT may play an important adjuvant to chemotherapy and further offer a safer and more effective high dose chemotherapy in pediatric malignant brain tumor patients.

Adolescent↗

[Chondrosarcoma of the skull base associated with fatal intratumoral hemorrhage : report of an autopsy case and review of the literature].

We report a case of intracranial chondrosarcoma of the skull base with fatal intra- and peritumoral hemorrhage. A 75-year-old woman complained of right blepharoptosis and diplopia in 1989. An initial diagnosis of Tolosa-Hunt syndrome was made, and the patient was treated with steroid hormone therapy at a local hospital. Because the symptoms had not been relieved, she was admitted to our hospital. Computed tomography (CT) scan and magnetic resonance (MR) images demonstrated a large mass extending from the right side of the clivus to the parasellar region and petrous apex. The mass was partially calcified and had destroyed the base of the middle cranial fossa. The lesion had homogeneous enhancement with contrast medium. Preoperative diagnosis was chordoma or chondroma. A biopsy of the tumor was made. The pathological diagnosis of biopsy specimen was chondroid chordoma. The patient was followed up but no palliative treatment such as radiotherapy was given. On June 25, 1991, she suffered from cerebral infarction. On June 29, 1993, she died of sudden respiratory failure. Autopsy was performed. It revealed intra- and peritumoral hematoma compressing the medulla oblongata, pons and midbrain. Histologically immature chondroid cells proliferated in a myxoid-rich extracellular matrix. The tumor cells were composed of hyperchromatic nuclei and eosinophilic cytoplasm, but there was no evidence of notochordal differentiation. Compared with biopsy findings, the tumor showed high cellular density. Immunohistochemically, the tumor cells reacted positively for S - 100 protein, vimentin and cytokeratin, but negatively for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In view of these histopathological findings, the diagnosis of low-grade myxoid chondrosarcoma was established. Intratumoral hemorrhage often occurs in malignant brain tumors such as glioblastoma and metastatic brain tumor, but chondroid tumors rarely develop a fatal type of intratumoral hemorrhage. Only 8 cases have been reported in detail to date. We discuss the immunohistochemical features and spontaneous intratumoral hemorrhage of chondrosarcoma.

Aged↗

[Hemocirculation and metabolism in intraventricular tumors: kinetic analysis of glucose metabolism].

To estimate hemocirculation and proliferating activity of intraventricular tumor, we measured kinetic rate constants (k1, k2, k3) and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with intraventricular tumor. The subjects included ten patients, five males and five females, aged from 13 to 53 years with a mean age of 32 years old. Eight tumors were located in the lateral ventricle and two extended into the third ventricle through the foramen of Monro. Another two tumors were located in the fourth ventricle. Histological diagnosis was as follows: five cases of central neurocytoma, one subependymal giant cell astrocytoma, one ependymoma, one choroid plexus carcinoma, one subependymoma, and one meningioma. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Hemocirculation (rCBF, rCBV) of the tumor was similar to or higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Oxygen metabolic parameters (rOEF, rCMRO2) were significantly lower than those of the contralateral gray matter. Especially, low rOEF resulted in an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl), as compared with that of meningiomas or malignant gliomas, suggested aerobic glycolysis. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three-compartment model of 18F-fluorodeoxyglucose (18FDG). Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRGl were lower in six of eight patients. These six patients have been free from tumor recurrence or regrowth, postoperatively. In the other two patients, tumor kinetic-rCMRGl was similar to or higher than that of the contralateral gray matter, suggesting high activity of proliferation. However, one patient received irradiation and has been followed up, and the other received total resection and has shown no recurrence. Functional information concerning intraventricular tumor is obtained by PET analysis, and kinetic analysis of the rate constants is useful for interpreting a detailed metabolic process of glucose, and provides additional information on intraventricular tumor aggressiveness.

Adolescent↗

[Positron emission tomographic evaluation for frontal hypertrophic cranial pachymeningitis using 11C-methyl-L-methionine].

A case of frontal hypertrophic cranial pachymeningitis was presented with positron emission tomography (PET) using (11C-methyl)-L-methionine (11C-Met). A 55-year-old male developed right hemiparesis after generalized tonic convulsion one month prior to admission. MR images revealed patchy enhancement extending from the dura mater to the cerebral parenchyma surrounding high T2-weighted signal in the left frontal region. Left carotid angiogram showed atresia of the rostral superior sagittal sinus and obliteration of the cortical veins associated with compensatory venous channels coursing in the frontal deep white matter. PET demonstrated high 11C-Met uptake in the area corresponding to the enhancing lesion on the MR images. The ratio of lesion/normal cortex was 1.58 as an indicator of selective uptake in the lesion. The contralateral temporal gray matter was representative of a normal cortex. In contrast, 11C-Met did not accumulate in the frontal white matter where T2-weighted MR images showed abnormal high intensity lesion. This suggested that the frontal white matter lesion was derived from vasogenic edema due to venous infarction. The patient underwent an uneventful exploratory biopsy. The dura mater had proliferated to a thickness of 3.5mm and was tightly adherent to the left middle frontal gyrus. Microscopically, the thickened dura mater where the tracers had accumulated was composed of abundant collagenous fibers together with diffuse infiltration of inflammatory cells, including predominantly lymphocytes, plasma cells, and neutrocytes. The lymphocytes, which proved positive in both UCHL-1 and L26 staining, had no atypism. Histological findings corresponded to hypertrophic pachymeningitis. Met-PET clearly represented viable and infiltrative zones of inflammatory cells. The patient's neurological symptoms and signs gradually improved. Follow-up MR images three months after the surgery showed the enhancing lesion to be diminished and a marked regression of the vasogenic edema. Spatial determination of viable lesions permitting differentiation from biological inactive or vasogenic edema is an important guideline in selecting an appropriate surgical procedure in the diagnosis and treatment of hypertrophic cranial pachymeningitis. Met-PET would appear useful in delineating inflammatory lesions such as hypertrophic cranial pachymeningitis.

Carbon Radioisotopes↗

Blood flow and metabolism of central neurocytoma: a positron emission tomography study.

BACKGROUND: New World Health Organization classifications have categorized central neurocytomas as neuronal tumors. The differential diagnosis between central neurocytomas and other tumors is important for selection of the optimal therapy modality for the management of intraventricular tumors. To characterize the pathophysiology and proliferating activity of central neurocytoma accurately, cerebral blood flow and metabolism in five patients with central neurocytoma were studied using positron emission tomography (PET). METHODS: Tracers used for the present study included C15O2, C15O, 15O2, and 18F-fluorodeoxyglucose (FDG). Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction fraction (rOEF), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose (rCMRGl) were quantitatively analyzed in tumor lesions and the contralateral gray matter. Four patients with central neurocytoma underwent a complete PET study, including all circulatory and metabolic parameters; one patient was studied with 11C-methyl-L-methionine and FDG tracers. RESULTS: Tumor rCBF and rCBV were higher than comparable values in the contralateral gray matter in three of four patients. This high level of perfusion corresponds to angiographic findings that show intense tumor staining in tumors fed by perforated arteries. Tumor rOEF and rCMRO2 were significantly lower than corresponding values in the gray matter (rOEF, P < 0.01; rCMRO2, P < 0.05 by Student's t test). Tumor rCMRGl ranged from 2.68 to 6.26 mg/100 ml/minutes and did not exceed contralateral gray matter values in any of the five patients. Tumor rCMRGl was significantly lower (P < 0.02) than the gray matter rCMRGl. One tumor exhibited a relatively high value of rCMRGl (comparable to gray matter rCMRGl), and increased in size 4 months after partial resection. No other tumors appeared during postoperative follow-up periods that ranged from 4 to 135 months. CONCLUSIONS: Circulation and metabolism parameters measured by PET offer insight into the biologic characteristics of central neurocytoma. Tumor rCMRGl may be an indicator of the proliferating activity in central neurocytoma.

Adult↗

Differential inactivation of O6-methylguanine-DNA methyltransferase activity by O6-arylmethylguanines.

Activity of O6-methylguanine-DNA methyltransferase (MGMT) is well related with drug resistance of tumor cells to chloroethylnitrosoureas (CENUs), because MGMT removes CENU-induced O6-alkylguanines in DNA by accepting the alkyl group at a cysteine moiety. Inactivation of MGMT is a feasible way to overcome MGMT-related resistance of tumor cells to CENUs. O6-Benzylguanine is known to be a strong depleter of MGMT. We previously reported the potentiation effect of O6-arylmethylguanine derivatives on cytotoxicity of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), a CENU, for HeLa S3 cells. In this study, we tested the activity of these O6-arylmethylguanine derivatives as depleters of MGMT using HeLa S3 cell-free extract. The O6-arylmethylguanine derivatives tested were O6-benzylguanine (1), O6-(4-, 3-, and 2-fluorobenzyl)guanines (2-4), O6-(4, 3-, and 2-trifluoromethylbenzyl)guanines (5-7), O6-(4-, 3-, and 2-pyridylmethyl)guanines (8-10), and O6-(2- and 1-naphtylmethyl)guanines (11,12). Among these, compounds 1-3, 5, 8, 9 and 11 showed a strong MGMT depletion activity, whereas compounds 4, 6, 7, 10 and 12 were inactive. These inactive compounds, except for 6, have a substituent at the alpha position of the benzyl group (4, 7, 12) or are an alpha nitrogen analogue of 1 (10). There was a good relation (r = -0.856, p < 0.001) between the MGMT depletion activity of O6-arylmethylguanine derivatives and their potentiation activity of ACNU cytotoxicity. These results suggest that the alpha position of the benzyl group plays an important role in the interaction of O6-arylmethylguanine derivatives with MGMT to result in the inactivation of MGMT. Potent MGMT inactivators (1-3, 5, 8, 9, 11) sensitize tumor cells to CENU chemotherapy.

Antineoplastic Agents↗

Hypoplasia of the internal carotid artery associated with spasmodic torticollis: the possible role of altered vertebrobasilar haemodynamics.

We describe an unusual case of hypoplasia of the left internal carotid artery associated with an anomalous origin of the ipsilateral middle cerebral artery in a patient with spasmodic torticollis. Collateral circulation to the territory of the middle cerebral artery was through the vertebrobasilar circulation, and the left vertebral artery was dilated and compressing the ventrolateral aspect of the cervicomedullary junction, as evidenced by MRI. We believe this to be the first report of unilateral hypoplasia of the internal carotid artery associated with spasmodic torticollis. Compression of the left accesory nerve by the dilated vertebral artery as a result of altered haemodynamics was thought to cause spasmodic torticollis.

Accessory Nerve↗

Positron emission tomographic assessment of cerebral hemocirculation and glucose metabolism in malignant glioma following treatment with intracarotid recombinant human tumor necrosis factor-alpha.

Cerebral hemocirculation and glucose metabolism in a malignant astrocytoma were repeatedly quantified before and after intracarotid injection of recombinant human tumor necrosis factor-alpha (rH-TNF) using positron emission tomography (PET). The patient received an intracarotid injection of a 3 x 10(4) U/m2 dose of rH-TNF three times over a two week period. PET was performed prior to and 24 hr after the first injection, and two weeks after the third injection. Prior to the first rH-TNF treatment, two lesions demonstrating high perfusion and hypermetabolism of glucose were noted in the right frontal and temporal regions. The frontal hypermetabolic lesion showed decreases in hemocirculation and metabolism 24 hr after the first injection and then increases beyond the pre-treatment level two weeks after the third treatment, whereas the temporal lesion remained unchanged during the follow-up period. No appreciable changes were noted in the adjacent cortex where rH-TNF was perfused, with the exception of a transient decrease in regional blood volume. Magnetic resonance images of the tumor showed no changes as a result of treatment with intracarotid rH-TNF. Intracarotid rH-TNF preferentially affects tumor tissue as opposed to normal cortex.

Astrocytoma↗

White matter hyperintensity in neurologically asymptomatic subjects.

Recent advances in magnetic resonance imaging (MRI) technology have had a great impact on the delectability of minute, asymptomatic lesions of the central nervous system. The clinical significance and treatment modes of these lesions, such as white matter hyperintensity (WMH) lesions detected by T2 MRI, remain controversial. To address these problems, we retrospectively evaluated WMH lesions in relation to clinical parameters for 240 neurologically asymptomatic persons who had visited a hospital for a medical check-up of the brain. Proton and T2-weighted MRI were obtained using a 0.5 T superconducting MR imager using the spin echo technique with a repetition time (TR) of 2800 msec. An echo delay times (TE) of 40 msec was used for the proton MRI, and a TE of 100 msec was used for the T2-weighted MRI. The images were visually analyzed according to a four-point grading system. The MRI findings were correlated with clinical parameters including age, gender, presenting symptoms, and hypertension. The overall frequency of WMH increased with age. Grades 2 and 3 of WMH were more frequent in aged persons, whereas the occurrence of grade 1 WMH remained relatively constant across age groups. Based on multiple regression analysis, age was the most significant variable influencing the frequency of WMH, followed by hypertension. These results imply that WMH lesions may simply be a phenomenon of aging, or may be an indicator of prepathologic state in an ischemic brain.

Adolescent↗

[Kinetics of glucose metabolism in central neurocytomas].

To estimate proliferating activity of central neurocytoma, we measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGI) using dynamic positron emission tomography (PET), as well as autoradiographic rCMRG1 (arg-rCMRG1), in patients with histologically verified central neurocytoma. The subject included five patients, four males and one female, aged from 23 to 53 years with a mean age of 41 years old. All tumors were located in the lateral ventricle and two extended into the third ventricle through the forearm of Monro. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment 18F-fluorodeoxyglucose (FDG) model. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRG1 were exceedingly lower in three of five patients. These three patients have been free from tumor recurrence or regrowth, postoperatively. The other two patients, tumor kinetic-rCMRG1 was similar to or higher than that of the contralateral gray matter. One patient suffered from tumor regrowth shortly after resection, and the other has been followed up postoperatively. Thus, k3 and kinetic-rCMRG1 are indicative parameters of proliferative activity in central neurocytoma.

Adult↗

[Kinetic analysis of glucose metabolism in meningiomas--comparison with malignant gliomas].

We measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with meningioma. Ten patients including one recurrent case, two males and eight females aged from 44 to 71 years with a mean age of 54 years old, were studied prior to surgical interventions. Histological diagnosis was as follows: seven cases of meningothelial type, two cases of angiomatous type and one fibrous type. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter in comparison with eight cases with malignant gliomas (five cases of malignant astrocytoma and three cases of glioblastoma, aged from 14 to 70 years with a mean age of 41 years old). Hemocirculation of the tumor was exceedingly higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Low rOEF implicated an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl) suggested rather aerobic glycolysis as compared with malignant gliomas. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment model of 18F-fluorodeoxyglucose (FDG). Tumor k1 and k2 values markedly increased in all examined cases, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Vasoreactivity of normal brain tissue in cases of arteriovenous malformations--evaluation by 123I-IMP SPECT using acetazolamide].

Arteriovenous malformations (AVMs) are usually associated with diminished cerebral blood flow (CBF) in the parenchyma surrounding AVMs because of the steal phenomenon. Vasoreactivity in the parenchyma surrounding AVMs may change because of ischemia and abnormal hemodynamics. The aim of this study was to investigate vasoreactivity in parenchyma surrounding AVMs. Quantitative single-photon emission computed tomography using N-isopropyl-p-I-123 iodoamphetamine (IMP-SPECT) was performed before and after intravenous administration of acetazolamide (Diamox). Diamox is a potent cerebral vasodilator which causes tissue acidosis, and IMP-SPECT was performed 10 min after intravenous infusion of a 1g dose. The subjects were 8 patients with AVMs. The AVM was in the frontal lobe in 3 patients, the temporal lobe in 1 patient, the lateral ventricle in 1 patient, the midbrain in 1 patient, the basal ganglionic region in 1 patient, and the vein of Galen in 1 patient. A rotating gamma camera with two heads was used to perform SPECT. IMP was injected into an arm vein, and a 5-min period of blood withdrawal, 1 ml/min, was started simultaneously from a small catheter placed in the radial artery. Kuhl's method was used to quantify cerebral blood flow (CBF). Multiple contiguous 6-pixel-diameter region of interest (ROI) circles along the cerebral cortex and cerebellar hemisphere were used, and ROIs which included the AVM nidus, draining veins or infarctions were excluded from the study. Vascular territories containing arteries feeding the AVM were defined as near-ROIs on SPECT, and all other ROIs were defined as far-ROIs. (ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

[Positron emission tomographic findings of subependymal giant cell astrocytoma developed in tuberous sclerosis--a case report].

Tuberous sclerosis (TS) is well known to be occasionally associated with subependymal giant cell astrocytoma (SGCA). SGCA is considered to be a benign tumor in its clinical course and morphology. However, this tumor is grown sometimes so rapid and caused hydrocephalus. To our knowledge, little is known about hemocirculation and metabolism, particularly in relation with proliferating activity of TS and SGCA. We measured hemocirculation and metabolism of SGCA developed in a case of TS using positron emission tomography (PET). A 13-year-old-boy who had frequently developed convulsions four months after birth. He was diagnosed as TS and had been medically treated with anticonvulsants, since multiple intraventricular calcifications were detected by CT, at the age of five months. The convulsions had been well controlled. In March 1993, he presented with syncopal attack and admitted to our hospital. CT showed multiple subependymal nodules. Among the nodules, one of the left anterior horn exceeded 2cm in size obliterated Monro's foramen. The tumor was homogeneously enhanced with contrast medium. The lesion detected by postcontrast T1-weighted MR imaging had almost the same status as that by CT. T2-weighted image revealed cortical tubers as high intensity area at the left frontal and parietooccipital regions. PET was performed with the Headtome IV. Hemocirculation of the tumor was lower than that of contralateral gray matter, which suggested poor blood supply. The oxygen and glucose metabolism of the tumor were decreased compared with contralateral gray matter, indicative of a low activity of proliferation and a clinically benign tumor in the present case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Enhancing effect of O6-alkylguanine derivatives on chloroethylnitrosourea cytotoxicity toward tumor cells.

O6-Alkylguanine derivatives are well known as chemical modulators of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). Depletion of the enzyme by these derivatives leads to increase sensitivity of tumor cells to chloroethylnitrosoureas. We tested the effect of O6-methylguanine, O6-benzylguanine, O6-(p-methylbenzyl)guanine, O6-(p-chlorobenzyl)guanine, O6-(p-methoxybenzyl)guanine, O6-methylhypoxanthine and O6-benzylhypoxanthine on the sensitivity of tumor cell lines to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) using a colorimetric cytotoxicity assay. The sensitivity of MGMT-proficient tumor cells including HeLA S3, C6-1, C6-2/ACNU, U-138 MG and U-373 MG cells was greatly enhanced by 2 hr pretreatment of 10-100 microM O6-benzylguanine, O6-(p-methylbenzyl)guanine and O6-(p-chlorobenzyl)guanine, but not by O6-methylguanine or O6-methylhypoxanthine. O6-(p-methylbenzyl)guanine moderately sensitized the 2 cell lines, HeLa S3 and C6-1, tested in our study to ACNU cytotoxicity. O6-Benzylhypoxanthine at the high concentration (100 microM) sensitized, to some extent, 3 MGMT-proficient cell lines. Lesser degrees of enhancement by the O6-benzylguanine derivatives were noted in MGMT-deficient tumor cells. Biological effects of O6-alkylguanine derivatives on enhancing ACNU cytotoxicity of tumor cells suggest that the exocyclic 2-amino and O6-benzyl groups in O6-benzylguanine skeleton are both essential for the inhibition of MGMT activity.

Animals↗

Perfusion and metabolism in predicting the survival of patients with cerebral gliomas.

BACKGROUND: Noninvasive measurements of cerebral circulation and metabolism may be useful for diagnosis in patients with brain tumors. The authors tested the prognostic significance of circulatory and metabolic values or ratios determined by positron emission tomography (PET) in patients with gliomas. METHODS: The subjects were 23 patients, who underwent a complete PET study of cerebral circulation and metabolism with long-term follow-up of at least 57 months. Regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction, and the metabolic rates of oxygen (rCMRO2) and glucose (rCMRGl) were measured before treatment. Data regarding tumors, the contralateral gray matter and white matter, and the ratio between tumor and gray matter or between tumor and white matter were compared with survival time from the time of the PET study. Prognostic factors were tested using Cox's regression analysis. RESULTS: Among clinical parameters, histologic grade and performance status were important variables regulating survival. When survival times of patients with values or ratios equal to or higher than the median were compared to those of patients with values or ratios lower than the median, significant determinant PET measurements were tumor rCMRGl and the ratios of tumor:gray rCMRGl and tumor:white rCMRGl. Median survival time in the patients with an rCMRGl value of 4.4 mg/100ml/minute (median value) or more indicated 9 months, which was significantly shorter than greater than 113 months in the patients with a value lower than the median (P = 0.003 by the generalized Wilcoxon test). Patients with a higher value of gray rCBF, rCBV, or rCMRO2 had significantly longer survival times than those with a lower value. CONCLUSIONS: Cerebral circulation and metabolism as determined by PET can be of ancillary significance in predicting the prognosis of patients with gliomas.

Adolescent↗