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Biomedical subjects

A Hirayama

Publications and source records attributed to A Hirayama.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.

BACKGROUND: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. OBJECTIVES: We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. METHODS: DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. RESULTS: DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). CONCLUSIONS: When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.

Aged↗
PubMed2006

Effect of spontaneous exercise on antioxidant capacity in rat muscles determined by electron spin resonance.

AIMS: The effect of physical activity on antioxidant capacity in muscle remains unknown. This study investigated the effect of spontaneous exercise on antioxidant capacity in rat muscles determined by electron spin resonance (ESR), which is a technique for the direct detection of free radicals. METHODS: Ten-week-old male Wistar rats were housed individually in cages with a running wheel. Rats were classified as high activity (HA), middle activity (MA) or low activity group (LA), based on an assessment of running distance covered over a 23-week period. After 23 weeks of housing, soleus (Sol), plantaris (Pl), gastrocnemius [deep/surface portions (GasD/GasS)] and heart (Hrt) muscles were isolated, and scavenging activity against superoxide anions (O(2)(*-)) and hydroxyl radicals (HO(*)) was determined by ESR using a spin-trap chemical. The citrate synthase (CS) activity was used as a marker of mitochondrial oxidative phosphorylation capacity. RESULTS: Among the parameters measured, only O(2)(*-) scavenging activity in GasD significantly correlated with the running distance. The highest scavenging activity was observed in Hrt of HA rats. The O(2)(*-) scavenging activity in Pl of MA rats was significantly higher than that of LA rats. The O(2)(*-) scavenging activity of Sol and GasS was not significantly different between the three groups. Furthermore, the HO(*) scavenging activity of any muscle specimens was similar among the three groups and did not correlate with running distance at all. CS activity did not significantly differ between the three groups. CONCLUSION: These data suggest that O(2)(*-) scavenging activity in specific types of muscle tissues would increase especially in spontaneously active animals. However, HO(*) scavenging activity would not.

Animals↗
PubMed2005

Radiofrequency thermal ablation for recurrent meningioma extending extracranially.

BACKGROUND: Image-guided and temperature-controlled radiofrequency thermal ablation techniques were applied to reduce tumor volume and relieve the symptoms caused by extracranial extension of recurrent meningioma. METHOD: We treated two patients with recurrent meningioma, an 81-year-old woman presenting with bulging of the temple and a 68-year-old woman presenting with visual disturbance, facial disfigurement, and sensory disturbance. Neuroimaging in both patients, revealed a large tumor extending extracranially and involving the infratemporal fossa. To avoid injury to important anatomical structures either compressed or entrapped by the tumor, the spatial relation between the planned ablation volume and these structures was confirmed by 3-D reconstruction of the ablation target. During the ablation procedure, local temperatures over the tissue being cauterized were continuously monitored to limit the ablation area to that within the planned volume adjusting RF power. FINDING: Radiofrequency ablation produced tumor necrosis as planned without adverse effects and resulted in swift relief of symptoms and signs with shrinkage of the tumor. CONCLUSION: This technique may be an effective alternative for recurrent meningiomas extending extracranially and for which radical surgical procedures are not indicated.

Aged↗
PubMed2005

Serial changes in plasma brain natriuretic peptide concentration at the infarct and non-infarct sites in patients with left ventricular remodelling after myocardial infarction.

OBJECTIVES: To clarify the role of infarct and non-infarct sites on left ventricular (LV) remodelling after myocardial infarction by measuring brain natriuretic peptide (BNP) from each site. METHODS AND RESULTS: BNP from the aorta and the anterior interventricular vein (AIV) was measured in 45 patients with first anterior myocardial infarction at one, six, and 18 months. The LV was significantly dilated (> 10 ml/m(2) of end diastolic volume from one to 18 months) in 20 patients (remodelling (R) group) but not in 25 others (non-remodelling (NR) group). Patient characteristics and LV functions did not differ significantly at one month but plasma BNP concentration was higher in group R than in group NR (336 (288) v 116 (106) pg/ml, p < 0.01), predicting the degree of LV dilatation. The difference in BNP concentration between the aortic root and AIV (DeltaBNP), reflecting BNP secreted from the infarct site, did not differ at one month. In both groups BNP and DeltaBNP significantly decreased from one to six months (p < 0.05) and decreased from six months to 18 months, but the change was not significant. BNP and DeltaBNP were significantly higher in group R than in group NR after six months, when LV dilatation was not evident in both groups. CONCLUSION: Enhanced BNP secretion at one month in the non-infarct and infarct ventricular sites predicts subsequent LV dilatation (that is, remodelling). The slower process of LV remodelling decreased BNP secretion at both sites. Thus, BNP concentration should be useful for monitoring ventricular remodelling after infarction.

Cardiomyopathy, Dilated↗
PubMed2004

Nutcracker syndrome associated with severe anemia and mild proteinuria.

A 70-year-old man was referred to our hospital with the chief complaint of gross hematuria. Urinalysis revealed gross hematuria (3+, RBC 100/HPF or more) and mild proteinuria (3+, 1.8 g/day) with no urinary casts. Computed tomography of the abdomen showed compression of the left renal vein between the superior mesenteric artery and the aorta. Ultrasonography showed an increased flow velocity at the stenotic portion of the left renal vein. An aortography and selective left renal arteriography showed that there was no evidence of tumor vessels or arterial abnormalities in the arterial phase. However, the venous phase revealed a stenosis of the left renal vein just lateral to the aorta as well as a reflux of contrast material toward the left gonadal vein which was dilated. In addition, cystoscopy revealed left ureteral bleeding. Based on these findings, we made the diagnosis of gross hematuria caused by nutcracker syndrome (NCS). We concluded that the main cause of the anemia and proteinuria in our patient was leakage of blood and this is confirmed by the relationship of red blood cells to protein in the urine because we proved whole blood and plasma protein loss in the urine by calculation. Fourteen months after discharge, both the gross hematuria and proteinuria spontaneously disappeared. This case strongly suggested that the first therapy for hematuria and proteinuria with NCS should be observation.

Aged↗
PubMed2003

The antioxidant EPC-K1 ameliorates brain injury by inhibiting lipid peroxidation in a rat model of transient focal cerebral ischaemia.

BACKGROUND: Cerebral ischaemia-reperfusion injury is associated with the generation of reactive oxygen species during the early phases of reoxygenation. EPC-K1, a phosphate diester of vitamins C and E, has been reported to possess potent hydroxyl radical scavenging activity. This study was performed to investigate the effectiveness of EPC-K1 in attenuating cerebral ischaemia-reperfusion injury in a rat model of transient focal cerebral ischaemia. METHOD: We evaluated the efficacy of EPC-K1 by measuring the concentration of cerebral thiobarbituric acid reactive substances (TBARS), an indicator of the extent of lipid peroxidation by free radicals, and infarct size in rats subjected to one hour of cerebral ischaemia and 4, 24, or 72 hours of reperfusion. FINDINGS: EPC-K1 significantly reduced both the cerebral TBARS level and the infarct size in a rat model of transient focal cerebral ischaemia. These results indicate that EPC-K1 administration during the early stages of reperfusion ameliorates ischaemic brain injury by inhibiting lipid peroxidation. INTERPRETATION: This report is the first to describe the protective mechanism of EPC-K1 by measuring both the TBARS level and infarct size in a rat model of transient focal cerebral ischaemia, and may suggest a potential clinical approach for the treatment of ischaemic cerebrovascular disease.

Animals↗
PubMed2003

Glomerular crescents predominantly express cadherin-catenin complex in pauci-immune-type crescentic glomerulonephritis.

AIMS: To investigate the expression of the cadherin complex in human crescentic glomerulonephritis to elucidate the role of intercellular adherens junction molecules in crescent formation. METHODS AND RESULTS: Immunostaining revealed cadherin complexes localized in Bowman's epithelial cells, but not in podocytes, of normal human glomeruli. Eight adult cases with myeloperoxidase anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA)-related (pauci-immune type) crescentic glomerulonephritis were examined on immunofluorescence microscopy with anti-pan cadherin, p120 catenin, and beta-catenin antibodies. The specimens provided six cellular crescents, 12 fibrocellular crescents, and four fibrotic crescents. Immunofluorescence was semiquantitatively estimated by the rate of the field of localization within the whole area of the crescent, according to the four-grade system [(-) - (++)]. All the tested molecules consisting of the cadherin complex were abundantly observed in cytokeratin-positive epithelial components in crescents, each with an equivalent area of localization. The expression of the cadherin complex was closely associated with that of cytokeratin and both diminished as the crescents developed from cellular to fibrotic. CONCLUSIONS: The cadherin-catenin complex is a specific marker of Bowman's epithelial cells in human glomeruli. The cellular crescents in pauci-immune-type crescentic glomerulonephritis possess adherens junction molecules, indicating a principle parietal epithelial cell phenotype.

Adherens Junctions↗
PubMed2001

Up-regulation of E2F-1 in Down's syndrome brain exhibiting neuropathological features of Alzheimer-type dementia.

We studied the expression of the apoptosis-related protein, E2F-1, in Down's syndrome (DS) brains. The immunoreactivity for E2F-1 was detected in the pyramidal neurons of the cerebral cortex from DS brains exhibiting the neuropathological features of dementia of Alzheimer type (DAT), in accordance with the amyloid beta protein (A beta) deposition in the neuron. Therefore, the implication is that A beta deposition may trigger E2F-1-mediated neuronal apoptosis in DS brains with DAT.

Adolescent↗
PubMed2001

Effects of soft-diet feeding on synaptic density in the hippocampus and parietal cortex of senescence-accelerated mice.

Some investigators have proposed that extracting of the teeth of rats or mice impairs their acquisition of spatial memory, implying that alterations of the neural networks in the brain result from a reduction of masticatory work. To evaluate numerical alterations of synapses in the cerebral cortex caused by reduced masticatory movements, two strains of the senescence-accelerated mouse, SAMR1 and SAMP8, were fed either a pelleted (hard-diet groups, R1-H and P8-H) or a powdered diet (soft-diet groups, R1-S and P8-S) after weaning. Radioimmunoassay using a monoclonal anti-synaptophysin antibody (SY38) revealed that the synaptophysin content in the whole cortex was significantly lower in P8-H compared with R1-H from 3 months to 12 months of age. The soft-diet feeding reduced the synaptophysin content in the cerebral cortex of both strains after 3 months of age. Immunohistochemistry and electron microscopy on the hippocampal formation and parietal cortex of 6-month-old mice showed that synaptic formation was significantly decreased in these areas in both R1-S and P8-S. The reduction rate of synaptic density due to soft-diet feeding was larger in the hippocampus than in the parietal cortex. The working memory of the four groups was tested at 6 months of age on an eight-arm radial maze. Performance significantly differed between R1-H and P8-H, between R1-H and R1-S, and between P8-H and P8-S. The results indicated that soft-diet feeding after weaning period reduces synaptic formation in the cerebral cortex and impairs the ability of spatial learning in adulthood.

Aging, Premature↗
PubMed2001

Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study.

OBJECTIVES: To test our hypothesis that the development of vulnerable plaques is not limited to the culprit lesions, but is a pan-coronary process, we directly observed all three major coronary arteries by angioscopy and evaluated the prevalence of yellow plaques in patients with myocardial infarction (MI). BACKGROUND: Although pathologic studies have suggested that the disruption of atheromatous plaque plays a major role in the development of acute MI, the prevalence of yellow plaques in the whole coronary arteries of patients with MI has not been clarified. METHODS: Thirty-two patients undergoing follow-up catheterization one month after the onset of MI were prospectively and consecutively enrolled in this study. The prevalence of yellow plaques and thrombus in the major coronary arteries was successfully evaluated in 20 patients (58 coronary arteries, 21 culprit lesions) by coronary angioscopy. The diameter stenosis (DS) of the culprit lesions and the maximal diameter stenosis (maxDS) of nonculprit segments were angiographically measured for each coronary artery. RESULTS: The DS of the culprit lesions and maxDS were 27 +/- 17% and 19 +/- 13%, respectively. Yellow plaques and thrombus were detected in 19 (90%) and 17 (81%) of 21 culprit lesions, respectively. Yellow plaques were equally prevalent in the infarct-related and non-infarct-related coronary arteries (3.7 +/- 1.6 vs. 3.4 +/- 1.8 plaques/artery). However, thrombus was only detected in the nonculprit segments of one (2%) coronary artery. CONCLUSIONS: In patients with MI, all three major coronary arteries are widely diseased and have multiple yellow though nondisrupted plaques. Acute MI may represent the pan-coronary process of vulnerable plaque development.

Aged↗
PubMed2001

Coronary endothelial dysfunction in the insulin-resistant state is linked to abnormal pteridine metabolism and vascular oxidative stress.

OBJECTIVES: We investigated whether abnormal pteridine metabolism is related to coronary endothelial dysfunction in insulin-resistant subjects. BACKGROUND: Depletion of tetrahydrobiopterin (BH(4)) and elevation of the 7,8-dihydrobiopterin (BH(2)) (activating and inactivating cofactors of nitric oxide synthase [NOS], respectively) contribute to impairment of NO-dependent vasodilation through reduction of NOS activity as well as increased superoxide anion generation in insulin-resistant rats. METHODS: Thirty-six consecutive nondiabetic, normotensive and nonobese subjects with angiographically normal coronary vessels were studied. Traditional coronary risk factors, plasma pteridine levels, activities of erythrocyte dihydropteridine reductase (DHPR), the recycling enzyme that converts BH(2) to BH(4) and lipid peroxide (LPO) levels were measured and coronary endothelial function was assessed with graded infusions of acetylcholine (ACh). RESULTS: When we divided patients into tertiles based on insulin sensitivity, we observed stepwise decreases in the maximal ACh-induced vasodilation and plasma BH(4)/7,8-BH(2) ratio, and increases in coronary LPO production as insulin sensitivity decreased. The ACh-induced vasodilation was positively correlated with insulin sensitivity, BH(4)/7,8-BH(2) ratio and DHPR activity. Furthermore, BH(4)/7,8-BH(2) was inversely correlated with DHPR activity and insulin sensitivity. In multiple stepwise regression analysis, BH(4)/BH(2) was independently related to ACh-induced vasodilation and accounted for 39% of the variance. However, no significant correlation existed between other traditional risk factors and BH(4)/7,8-BH(2). CONCLUSIONS: These results indicate that both abnormal pteridine metabolism and vascular oxidative stress are linked to coronary endothelial dysfunction in the insulin-resistant subjects.

Acetylcholine↗
PubMed2001

The healing process of infarct-related plaques. Insights from 18 months of serial angioscopic follow-up.

OBJECTIVES: To clarify the healing process of disrupted culprit plaques of acute myocardial infarction (MI), we serially observed the culprit plaques for 18 months after the onset of acute MI by angioscopy. BACKGROUND: Although it has been reported that disruption of the yellow plaque and subsequent thrombosis cause acute MI and that the thrombogenicity of the plaque lasts for a month, the healing process of the plaque after disruption has not been clarified. METHODS: Eighty-five patients with acute MI were prospectively and consecutively enrolled. Angioscopic studies were performed immediately and at 1, 6 and 18 months after successful reperfusion. The prevalence of yellow plaques and thrombus was examined. The color grade of the plaque was determined as 0 (white), 1 (light yellow), 2 (yellow) or 3 (bright yellow). RESULTS: Although yellow plaque was present at the culprit lesion in most patients throughout follow-up, its color grade was reduced from one to six months (1.9 +/- 0.6 vs. 1.1 +/- 0.7, p = 0.0003) after reperfusion, especially in the patients without hyperlipidemia (HL). The incidence of thrombus was 92.5% immediately after reperfusion, which was reduced significantly to 63.8%, 4.8% and 11.8% at 1, 6 and 18 months, respectively. The incidence of thrombus (77.8% vs. 45.0%, p = 0.03) at one month was higher in the patients with diabetes mellitus (DM). CONCLUSIONS: The healing process of yellow plaques at the culprit lesions of MI was detected by angioscopy as reductions of color grade and thrombogenicity at six months and partially at one month after the onset of acute MI. This healing process appears to deteriorate by complicating cases of DM or HL.

Aged↗
PubMed2001

Renal arteriovenous fistula developing after tumor enucleation using a microwave tissue coagulator.

With the increase in detection of incidental renal cell carcinoma, nephron-sparing surgery for small renal cell carcinomas is now recognized as one of the surgical options. We report a case of renal arteriovenous fistula developing after non-ischemic tumor enucleation of a small renal cell carcinoma using a microwave tissue coagulator. A 50-year-old Japanese man presented with right flank pain and gross hematuria. The patient had undergone non-ischemic tumor enucleation for right renal cell carcinoma, 2 cm in diameter, 1 month previously. Doppler ultrasound revealed the formation of an arteriovenous fistula at the enucleated portion. Transcatheter super-selective occlusion of the feeding artery was successfully performed with two metallic coils. The patient has been followed up with no sign of recanalization of the fistula. In this case, the tumor was located close to the renal hilus with thick arterial branches around the tumor. Additional microwave coagulations against arterial bleeding from the cutting surface might have been the cause of the fistula formation of this case. Non-ischemic tumor enucleation using a microwave tissue coagulator is a relatively easy and secure nephron-sparing surgical procedure. Excessive coagulation, however, should be avoided, since it might be the cause of unexpected postoperative vascular complications.

Arteriovenous Fistula↗
PubMed2001

Nrf2-deficient female mice develop lupus-like autoimmune nephritis.

BACKGROUND: NF-E2-related factor 2 (Nrf2) is a basic leucine zipper transcriptional activator essential for the coordinate transcriptional induction of antioxidant enzymes and phase II drug metabolizing enzymes through the antioxidant response element/electrophile response element. The Nrf2-deficient mice were found to develop normally under standard laboratory conditions. However, upon closer examination, we found that aged female Nrf2-deficient mice displayed a shortened lifespan and developed severe glomerulonephritis. The present study investigated the glomerulonephritis findings in Nrf2-deficient mice. METHODS: To evaluate glomerular lesions of Nrf2-deficient mice, histological and functional analyses were performed. The amounts of serum immunoglobulins, anti-double-stranded (ds) DNA antibody, and lipid peroxidation using thiobarbituric acid reactive substances (TBARS) also were measured. RESULTS: Nrf2-deficient female mice over 60 weeks of age developed severe nephritis characterized by cellular proliferation, lobular formation, crescent formation, and subepithelial electron-dense deposits. In immunofluorescent assays, Nrf2-deficient female mice showed mesangial deposits and massive granular deposits of IgG, IgM, and C3 along the capillary walls. Higher serum levels of IgG, anti-dsDNA antibody, lower creatinine clearance, and slight splenomegaly also were found in Nrf2-deficient female mice. A higher concentration of TBARS also was found in Nrf2-deficient female mice. CONCLUSIONS: These data indicate that the aged Nrf2-deficient female mice develop lupus-like autoimmune nephritis and suggest that nrf2 is one of the genes determining susceptibility to autoimmune disease. Analysis of nephritis in the Nrf2-deficient female mouse may clarify the mechanisms leading to the development of lupus disease.

Animals↗
PubMed2001

Uremic concentrations of guanidino compounds inhibit neutrophil superoxide production.

BACKGROUND: In uremia, diminished reactive oxygen intermediate (ROI) production is an important consequence of impaired neutrophil function. We have studied the effect of guanidino compounds, known uremic toxins, on neutrophil ROI production in vitro. METHODS: Neutrophils from healthy volunteers were exposed for three hours to individual or mixed guanidino compounds (GCmix) at concentrations encountered in uremic plasma. After removal of guanidino compounds, neutrophils were activated by adhesion, N-formyl-methionyl-leucyl-phenyalanine (fMLP), phorbol 12-myristate 13-acetate (PMA), or opsonized zymosan, and superoxide production was measured by lucigenin chemiluminescence (CL). The direct effect of guanidino compounds on superoxide production in activated neutrophils was also measured. The energy status (ATP and creatine phosphate), antioxidant status (total glutathione), and glycolytic flux (lactate production) were measured. RESULTS: The GCmix pretreatment decreased the superoxide production in activated neutrophils (fMLP or zymosan) by 50% (P < 0.01) and the ATP concentration by 60% (P < 0.05), and it inhibited glycolytic flux (lactate production) by 45% (P < 0.01), but did not alter glutathione concentration. Simultaneous exposure to GCmix and activation did not inhibit nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in cell lysates, but inhibited superoxide formation in zymosan-activated intact neutrophils, and this inhibition was reversed following removal of the guanidino compounds. CONCLUSION: Guanidino-succinate, -propionate, and -butyrate were individually as potent as the GCmix. Inhibition of neutrophil superoxide generation by guanidino compounds results from a depressed energy status. Uremic concentrations of guanidino compounds significantly inhibit neutrophil metabolism, and this has serious implications for their function in host defense.

Adenosine Triphosphate↗
PubMed2001

Role of nitric oxide in the synthesis of guanidinosuccinic acid, an activator of the N-methyl-D-aspartate receptor.

BACKGROUND: We propose that reactive oxygen and argininosuccinic acid (ASA) form guanidinosuccinic acid (GSA). An alternative to this hypothesis is the so-called guanidine cycle, which consists of a series of hydroxyurea derivatives that serve as intermediates in a pathway leading from urea to GSA. We compare the role of the guanidine cycle to that of nitric oxide (NO) in the synthesis of GSA. METHODS: The members of the guanidine cycle (hydroxyurea, hydroxylamine plus homoserine, L-canaline, and L-canavanine) were incubated with isolated rat hepatocytes. The known NO donors, NOR-2, NOC-7, and SIN-1, were incubated with ASA in vitro. Ornithine, arginine, or citrulline, which increase arginine, a precursor of NO, were incubated with isolated rat hepatocytes. GSA was determined by high-performance liquid chromatography. RESULTS: None of guanidine cycle members except for urea formed GSA. SIN-1, which generates superoxide and NO formed GSA, but other simple NO donors, did not. Both carboxy-PTIO, a scavenger of NO, and dimethyl sulfoxide, a hydroxyl radical scavenger, completely inhibited GSA synthesis by SIN-1. GSA formation by SIN-1 reached a maximum at 0.5 mmol/L and decreased at higher concentrations. GSA synthesis, stimulated by urea in isolated hepatocytes, was inhibited by ornithine, arginine, or citrulline with ammonia, but not by ornithine without ammonia, where arginine production is limited. CONCLUSION: GSA is formed from ASA and the hydroxyl radical. When arginine increased in hepatocytes, GSA synthesis decreased. These data suggest that increased NO, which results from high concentrations of arginine, or SIN-1 scavenges the hydroxyl radical. This may explain the decreased GSA synthesis in inborn errors of the urea cycle where ASA is decreased, and also the diminished GSA excretion in arginemia.

Animals↗
PubMed2001

Intracavitary chemotherapy with 5-fluoro-2'-deoxyuridine (FdUrd) in malignant brain tumors.

BACKGROUND: After completing basic research on the anti-tumor effects and neurotoxicity of 5-fluoro-2'-deoxyuridine (FdUrd) and the balance of thymidine kinase and thymidine phosphorylase activities and confirming the safety of intrathecal FdUrd administration in a previous clinical study of meningeal carcinomatosis, intracavitary administration of FdUrd was performed as a second trial in patients with malignant glioma and metastatic brain tumors. METHODS: The study population consisted of 13 patients, six with glioblastoma, one with anaplastic astrocytoma and six with metastatic brain tumors. This treatment was applied for cystic, small-volume residual or recurrent tumors. FdUrd (1-10 microg) was administered every day at least 25 times through an Ommaya device placed in the cyst or closed postoperative cavity reconstructed with a patch of galea aponeurotica. Intracavitary chemotherapy with FdUrd was preceded by radiation therapy in two patients but no other adjuvant therapy was performed. RESULTS: No side effects such as headache, nuchal pain, convulsive attack, bone marrow suppression or liver dysfunction were observed during the course of chemotherapy. Seven of the 13 patients showed responses: complete response six, minor response one, no change two and progressive disease four after the twenty-fifth intracavitary administration of FdUrd when tumor sizes on CT scans and MRI before and after intracavitary chemotherapy were compared. CONCLUSIONS: Intracavitary FdUrd chemotherapy may be useful for the treatment of small-volume tumors.

Adult↗