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Biomedical subjects

W Yamamoto

Publications and source records attributed to W Yamamoto.

At least 19 recordsLinked to original sources
PubMed2001

Statistical analysis of marginal count failure data.

Manufacturers want to assess the quality and reliability of their products. Specifically, they want to know the exact number of failures from the sales transacted during a particular month. Information available today is sometimes incomplete as many companies analyze their failure data simply comparing sales for a total month from a particular department with the total number of claims registered for that given month. This information--called marginal count data--is, thus, incomplete as it does not give the exact number of failures of the specific products that were sold in a particular month. In this paper we discuss nonparametric estimation of the mean numbers of failures for repairable products and the failure probabilities for nonrepairable products. We present a nonhomogeneous Poisson process model for repairable products and a multinomial model and its Poisson approximation for nonrepairable products. A numerical example is given and a simulation is carried out to evaluate the proposed methods of estimating failure probabilities under a number of possible situations.

Algorithms↗
PubMed2001

Active transepithelial transport of irinotecan (CPT-11) and its metabolites by human intestinal Caco-2 cells.

Irinotecan (CPT-11) is a camptothecin analog with low (about 10--20%) and variable oral bioavailability in animal models. Here, Caco-2 cells were used to evaluate the transepithelial transport of CPT-11 and its metabolites. Caco-2 cells demonstrated significant expression of P-glycoprotein (P-gp), multidrug resistance-associated protein and canalicular multispecific organic anion transporter. Both the lactone and carboxylate forms of CPT-11 and SN-38 were actively transported across the cell monolayers, mainly by the apical-localized P-gp pump. Cellular permeability of CPT-11 at a concentration of 17 microM converted from active to passive-diffusional transport between the 2 and 6 h exposure time points. Antiproliferative effects of CPT-11 were related to permeability of the lactone form, whereas for SN-38 efficacy was dependent on lactone accumulation. Exposure of CPT-11 with cyclosporin A significantly enhanced its efficacy, whereas this was not observed with verapamil and R101933. In contrast, SN-38 efficacy decreased in the presence of P-gp inhibitors due to active transport toward the basolateral side, thereby reducing drug accumulation. Hence, multiple-active transport systems could be demonstrated to be responsible for not only accumulation profiles but also cytotoxic efficacy of CPT-11 and SN-38 in the intestinal Caco-2 cells. It is suggested that CPT-11 might act in a time-dependent manner and that SN-38-mediated cytotoxicity relates to (dose-dependent) lactone kinetics. The results detailed in this report could contribute toward the development of a clinically useful oral formulation of CPT-11 with improved absorption characteristics and suggest that cyclosporin A is a suitable agent for further research of this concept.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Intense uptake of technetium-99m tetrofosmin by lactating breasts.

A 38-year-old woman was hospitalized for syncope. Because an electrocardiogram showed intermittent ventricular tachycardia, myocardial perfusion imaging with technetium-99m tetrofosmin was performed to screen for coronary artery disease. Left ventricular myocardial perfusion was within normal limits. However, symmetric bilateral breast uptake was noted. According to her clinical history, she had been breast-feeding her 5-month-old infant until this admission. In these circumstances, the breast uptake of Tc-99m tetrofosmin was thought to be physiologic and related to lactation.

Adult↗
PubMed2001

Helicobacter pylori infection and coronary heart disease in Japanese patients.

Although several independent studies have claimed a link between Helicobacter pylori infection and coronary heart disease (CHD), this association has not been established conclusively. The aim was to determine whether an association between H. pylori infection and CHD can be demonstrated in Japanese patients. Three-hundred and four patients who underwent consecutive coronary arteriography were investigated. Ninety-four patients had single-vessel coronary stenosis and 112 had multi-vessel stenosis. The remaining 98 patients had no significant stenosis in any coronary arteries. H. pylori infection was diagnosed serologically and the association between infection and CHD was estimated by the odds ratio. The serum pepsinogen (PG) I-II ratio was used to estimate the degree of gastric atrophy. Seropositivity for H. pylori was significantly higher in the patients with CHD (67%) than in the controls (50%; p = 0.006). The odds ratio for CHD after having H. pylori infection was estimated as 1.35 (95% confidence interval 1.03-1.78; p = 0.028), after adjustment for the common risk factors of CHD in a logistic regression analysis. The association between CHD and H. pylori infection was more significant among patients without any history of diabetes or smoking. The PG I-II ratio in H. pylori-positive patients was significantly higher in the multi-vessel group (3.46) than in the control or single-vessel group (2.86, p = 0.030; 2.78, p = 0.008; respectively). H. pylori infection was shown to be an independent risk factor for CHD in Japanese patients, especially among those who did not have a history of diabetes or smoking. These data imply that the association between H. pylori infection and CHD is clinically relevant.

Adult↗
PubMed2001

[A case report of chronic chyluria probably due to Bancroftian filariasis, which showed hypoproteinemia].

Proteinuria is commonly observed in patients with chyluria due to Bancroftian filariasis. However, whether or not hypoalbuminemia is caused by chyluria alone is still a matter of debate. This is because various forms of glomerulonephritis are complicated in such patients. Herein, we report a case we have recently encountered. A 72-year-old male was admitted to our division for further evaluation of nephrotic syndrome. He was from the Southernmost part of Japan, where Bancroftian filariasis has been epidemic, and had developed persistent chyluria over a period of nearly 50 years. There was no other past history of illness except for diabetes mellitus(DM) pointed out 3 months prior to admission. The physical and laboratory examinations on admission fulfilled the diagnostic criteria for nephrotic syndrome. Lymphoscintigraphy showed an intense tracer accumulation in both kidneys. A renal biopsy was performed. At the light microscopic level, the glomeruli looked normal. Edema of the tubulointerstitium was noted. At the electron microscopic level, effacement of podocyte foot processes was not observed. Immunofluorescent study did not show glomerular deposition of immunoglobulins and complements. He also had persistent microscopic hematuria. Automated urinary sediment analysis by real-time confocal scanning laser microscopy revealed red blood cells of the non-glomerular type. Taken together, these findings strongly indicated that hypoalbuminemia of this patient was caused by chyluria alone. In conclusion, a report of the present case provides strong evidence that hypoalbuminemia of a patient with Bancroftian filariasis could be caused by chyluria alone.

Aged↗
PubMed2001

[Assessment of intra and extrahepatic perfusion during hepatic artery infusion chemotherapy using slow-injected gadolinium-enhanced MR imaging through implanted catheter-port-system].

Twenty-four studies of intra-arterially slow-injected gadolinium-enhanced MR imaging through an implanted catheter-port system (reservoir-MR) were carried out in 15 patients with liver tumor. The flow rate of gadolinium injection was 0.1 ml/sec and a total of 3 mL was injected. Six consecutive phases, each with an acquisition time of 14 seconds, were obtained every 30 seconds. In all studies, the signal intensity of the drug delivery portion became very high. Twenty-three of 24 studies showed intrahepatic perfusion in the first phase. The hepatic vein was enhanced at the first phase in 10 and the second phase in 14. The abdominal aorta was enhanced at the second phase in all 24 studies. The portal vein was enhanced at the first phase in 4, the second phase in 13, and the third phase in 7 studies. Both intra- and extrahepatic perfusion were more clearly demonstrated by reservoir-MRI than by digital subtraction angiography through an implanted catheter-port system (reservoir-DSA); however, morphological changes in the hepatic artery were better demonstrated by reservoir-DSA than by reservoir-MRI.

Adult↗
PubMed2001

Comparison of cardiac sympathetic nervous function with left ventricular function and perfusion in cardiomyopathies by (123)I-MIBG SPECT and (99m)Tc-tetrofosmin electrocardiographically gated SPECT.

UNLABELLED: The objective of this study was to clarify the relationship between cardiac sympathetic nervous function (CSNF) and left ventricular (LV) function and perfusion in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). METHODS: Thirty-eight cases (32 males, 6 females; mean age, 56 +/- 15 y), consisting of 5 healthy control subjects, 15 patients with DCM, and 18 patients with HCM, were studied with (123)I-metaiodobenzylguanidine (MIBG) and (99m)Tc-tetrofosmin SPECT. CSNF was evaluated from cardiac uptake and washout of MIBG, whereas LV perfusion and function were evaluated from tetrofosmin uptake and wall thickening on electrocardiographically gated SPECT. As quantitative parameters of global cardiac MIBG uptake and washout, the heart-to-mediastinum ratio (H/M) and percentage washout were calculated from early and delayed planar images. As quantitative regional parameters, the regional uptake and percentage washout of MIBG were calculated from SPECT images dividing the left ventricle into 12 segments. In the tetrofosmin study, the H/M and LV ejection fraction were calculated as the parameters of global LV perfusion and function. As quantitative regional parameters, the regional uptake and wall thickening were also calculated for the 12 myocardial segments using the quantitative gated SPECT software. Multiple linear regression analysis was performed to investigate the correlations between the parameters from the 2 studies. RESULTS: In DCM and HCM, multiple linear regression analysis of the regional parameters showed significant correlations between LV function and CSNF (P < 0.0001) and between LV perfusion and CSNF (P < 0.0001). According to the partial correlation coefficients, washout and early uptake of MIBG were the most significant factors for predicting LV function and LV perfusion, respectively. CONCLUSION: In cardiomyopathies, CSNF was closely related to LV function. The quantitative parameters of MIBG washout could reflect cardiac functional impairment. Early MIBG uptake might be determined by myocardial perfusion in cardiomyopathies.

3-Iodobenzylguanidine↗
PubMed2001

[Assessment of intraperitoneal drug distribution during intraperitoneal chemotherapy using saline-injected MR imaging through an implanted catheter-port system].

Intraperitoneal saline-injected MR imaging through an implanted catheter-port system (saline-MRI) was conducted in 7 patients with ovarian tumor after surgical removal of the primary tumor. Two types of T2 weighted coronal images of the abdomen were obtained after saline injection through the implanted catheter-port system. One uses long TE (about 1000 msec) with fat-saturation and thick slices (100 mm thickness) to depict the injected saline alone. The other uses medium TE (about 100 msec) without fat-saturation and thin slices (10 mm thickness) to depict both intraperitoneal saline and abdominal structures. Saline sequentially fills the Douglas pouch, paracolic gutter, Morison's pouch and subphrenic space in most patients. The relation between injected saline and abdominal structures was seen well on T2-weighted images using medium TE. Adhesions of the peritoneum were well demonstrated. In one patient, a catheter perforation to the bowel loop was diagnosed, because the small bowel loop was immediately filled with injected saline. Saline-MRI can be used to depict intraperitoneal drug distribution during intraperitoneal chemotherapy and can diagnose complications related to intraperitoneal chemotherapy.

Adolescent↗
PubMed2000

Protein-loss into retroperitoneal lymphangioma: demonstration by lymphoscintigraphy and blood-pool scintigraphy with Tc-99m-human serum albumin.

A rare, benign congenital lymphangioma has been reported to occur frequently in the neck and axilla, but rarely in the retroperitoneal space. We report a case of a retroperitoneal lymphangioma associated with hypoproteinemia caused by protein-loss into the tumor. In this case, lymphoscintigraphy with subcutaneously injected Tc-99m-human serum albumin (HSA) disclosed the communication between the tumor and the lymphatic system, and sequential abdominal scintigraphy with intravenously injected Tc-99m-HSA revealed the protein loss into the tumor. Abdominal scintigraphy with Tc-99m-HSA injected intravenously or subcutaneously is occasionally useful for determining the etiology of hypoproteinemia.

Adolescent↗
PubMed2000

NADPH/quinone oxidoreductase is a priority target of glioblastoma chemotherapy.

We attempted to determine a target of chemotherapy specific to glioblastoma cells to ensure a favorable response to anticancer drugs, through comparison in biologic nature related to drug resistance with other types of cancer cells. Using 13 human cancer cell lines including 3 glioblastoma lines, gene expression analysis and biochemical quantitative assay were performed for a total of 12 properties, which have been linked to drug action. Although most of genes related to drug resistance, such as MDR1, MRP, MGMT and GSTpi, were overexpressed in T98G, U-373MG, and U-251MG glioblastoma cells, Topo I (topoisomerase I) expression was relatively low and alpha- and beta-TUB (tubulin) expression was comparable to other types of 10 cell lines. The glioblastoma cell lines also showed an increased expression of NADPH/quinone oxidoreductase gene (NQO1), but the respective enzyme NQO activated MMC. Among the drugs targeting such properties, MMC was more active than Topo I inhibitors and docetaxel (TXT) due to the lack of other sensitivity (resistance) determinants. Differing from MMC, MGMT was shown to participate in the resistance of Topo I inhibitors (CPT-11, SN-38 and DX-8951f), while GSTpi and MDR1 were involved in docetaxel (TXT) resistance. MMC was also more active than ACNU and CDDP in the three glioblastoma cells. NQO may be a priority target of glioblastoma chemotherapy suitable for biochemical nature of the cells, and expression analysis of NQO1, alpha-TUB, beta-TUB, MGMT, MDR1 and GSTpi may help to seek a truly active drug against glioblastomas.

Antineoplastic Agents↗
PubMed2000

Factors involved in prolongation of the terminal disposition phase of SN-38: clinical and experimental studies.

The active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxycamptothecin (SN-38), is either formed through enzymatic cleavage of CPT-11 by carboxyl esterases (CEs) or through cytochrome P-450 3A-mediated oxidation to 7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin (NPC) and a subsequent conversion by CE. In the liver, SN-38 is glucuronidated (SN-38G) by UGT1A1, which also conjugates bilirubin. Fourteen patients were treated with 350 mg/m2 CPT-11, and we performed pharmacokinetic analysis during a 500-h collection period. The half-life and area under the plasma concentration-time curve of SN-38 were 47+/-7.9 h and 2.0+/-0.79 microM x h, respectively, both representing a 2-fold increase as compared with earlier reported estimates (A. Sparreboom et al, Clin. Cancer Res., 4: 2747-2754, 1998). As an explanation for this phenomenon, we noted substantial formation of SN-38 from CPT-11 and NPC by plasma CE, consistent with the low circulating levels of NPC observed. In addition, transport studies in Caco-2 monolayers indicated that nonglucuronidated SN-38 could cross the membrane from apical to basolateral, indicating the potential for recirculation processes that can prolong circulation times. Interestingly, individual levels of fecal beta-glucuronidase, which is known to mediate SN-38G hydrolysis, were not related to any of the SN-38 kinetic parameters (r = 0.09; P = 0.26), suggesting that interindividual variation in this enzyme is unimportant in explaining SN-38 pharmacokinetic variability. We have also found, in contrast to earlier data, that SN-38G/SN-38 plasma concentration ratios decrease over time from approximately 7 (up to 50 h) to approximately 1 (at 500 h). This decrease could be explained by the fact that glucuronidation of SN-38 and bilirubin is increasingly competitive at lower drug levels. In addition, no evidence was found for SN-38G transport through the Caco-2 cells. Our findings indicate that until now the circulation time of SN-38 has been underestimated. This is of crucial importance to our understanding of the clinical action of CPT-11 and for future pharmacokinetic/pharmacodynamic relationships.

Adult↗