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A 61-year-old woman presented with pancytopenia and underwent a bone marrow biopsy. The patient was diagnosed with nonsecretory myeloma (plasmablastic type) based on both the bone marrow biopsy findings and her laboratory data. Fluorine-18 fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) was performed prior to chemotherapy showing diffuse bone marrow uptake, splenic uptake, and focal uptake of the right anterior chest wall. The patient underwent an (18)F-FDG-PET examination to evaluate the curative effects after three cycles of chemotherapy, and no abnormal uptake on (18)F-FDG-PET was found. Bone marrow biopsy to evaluate the curative effect showed no viable tumor cells. We present a rare case of nonsecretory plasmablastic myeloma detected by (18)F-FDG-PET. [ABSTRACT FROM AUTHOR]

Introduction: To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes. Case Report: A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m(2)) on days 1, 8 and 15 in combination with docetaxel (60 mg/m(2)) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs. Conclusion: The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities. [ABSTRACT FROM AUTHOR]

Summary:Hepatic veno-occlusive disease (VOD) is a severe complication of hematopoietic stem cell transplantation (SCT). When monitored with hand-held color Doppler ultrasonography during day −7 to +35 around SCT, reversed blood flow in the segmental branches of the portal vein was detected in nine of 56 patients who had undergone SCT. Three of nine patients had clinical evidence of VOD, but six patients did not fulfill the criteria for diagnosis of VOD initially. Two patients progressed to clinical VOD at a later date and the reversed portal flow disappeared with or without treatment for VOD in the other four patients. Monitoring for reversed portal flow with color Doppler ultrasonography may be a useful tool for the early diagnosis of VOD, and may improve prognosis by allowing early initiation of treatment.Bone Marrow Transplantation (2005) 36, 1071–1075. doi:10.1038/sj.bmt.1705170; published online 10 October 2005 [ABSTRACT FROM AUTHOR]

The purpose of this research was to investigate the possible orthodontic application of the hollow super-elastic Ti–Ni alloy wire, which was thought not only to deliver much lower and more continuous orthodontic force than conventional Ti–Ni wires, but also be able to be applied as a compound wire when combined with another wire. The examinations of bending properties were performed by the three-point bending test. The following results were obtained. 1. The hollow wire had lower load in the super-elastic range, smaller load-deflection rate and stress hysteresis in comparison with the conventional wire of the same diameter. 2. The load of the hollow wire was controllable by heat treatment. The stress hysteresis was further decreased by a two-step heat treatment. 3. The compound wire formed by inserting other types of wires into the hollow core exhibited changes in various bending properties such as increased load or load-deflection rate, according to the types and diameters of the inserted wire. The hollow wire delivers much lighter and more continuous orthodontic force, and, through heat treatment or deployment as a compound wire, it is possible to alter various bending properties. Therefore, this hollow wire was evaluated as a promising candidate for orthodontic application. [ABSTRACT FROM AUTHOR]

The purpose of this research was to devise a method for transforming the cross-section of the hollow super-elastic Ti-Ni alloy round wire and to examine the changes in its bending properties for clinical orthodontic application. The specimen wires were pressed with the use of heated pliers to transform the cross-sectional shape. As a result, transformation of the wire cross-section with super-elasticity was possible. As a verified by cantilever test and three-point bending test of the transformed specimens, a two-dimensional orthodontic force, which was different in each bending direction, was obtained. The hollow wire showed considerably high load level in the long axis along with markedly low load level in the short axis, which was mainly caused by the change in the moment of inertia by transforming the cross-section. It was revealed that, by transforming the wire cross-section of the hollow super-elastic Ti-Ni alloy round wires, anisotropic orthodontic force in bending properties could be obtained with super-elasticity. [ABSTRACT FROM AUTHOR]

Background: Little is known about differences in the disposition kinetics and pharmacological effects on gastrin levels between lansoprazole and rabeprazole given in a repeated dosing scheme with respect to the polymorphic CYP2C19. Aim: To provide preliminary information that should be considered when prescribing proton-pump inhibitors (PPIs) for the treatment of acid-related diseases with reference to the CYP2C19 genotypic status. Methods: Helicobacter pylori-negative healthy volunteers were divided into the following three groups (n=5 each) on the basis of genotyping for CYP2C19: homozygous (hmEMs) and heterozygous extensive metabolizers (htEMs), and poor metabolizers (PMs). All received once-daily 30-mg doses of lansoprazole or 10-mg doses of rabeprazole during an 8-day course in a crossover manner. Results: The relative values for the area under the serum concentration–time curve (AUC) of lansoprazole and rabeprazole in the hmEMs, htEMs, and PMs after the final doses were 1:1.7:3.9 and 1:1.7:3.8, respectively. The relative AUCs of gastrin in the hmEMs, htEMs, and PMs were 1.6:2.6:3.1 for lansoprazole and 1.6:2.6:2.9 for rabeprazole, respectively. Conclusion: The disposition kinetic behavior of the two PPIs is co-segregated with CYP2C19. The magnitude of CYP2C19-dependent drug availability in the systemic circulation and resulting gastrin response appears to be fairly similar between the two drugs within the same CYP2C19 genotypic groups after a multiple-dosing regimen. [ABSTRACT FROM AUTHOR]

Objectives: Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. Methods: A single dose of diclofenac was administered orally to 12 healthy subjects in whom the genotype of CYP2C9 had been determined previously. The disposition kinetics of diclofenac were compared between homozygotes for the wild type (CYP2C9*1/*1, n=6) and heterozygotes for the Leu359 variant (CYP2C9*1/*3, n=6). Results: For diclofenac, the following kinetic parameters were observed in the CYP2C9*1/*1 and CYP2C9*1/*3 subjects, respectively (mean ± SD): apparent oral clearance (ml/kg/h) 355.8 ± 56.9 and 484.4 ± 155.3; area under plasma concentration–time curve (μg h/ml) 2.7 ± 0.7 and 1.9 ± 0.6. The formation clearance of 4′-hydroxydiclofenac (ml/kg/h) was 63.6 ± 19.1 in the CYP2C9*1/*1 subjects compared with 75.9 ± 27.6 in the CYP2C9*1/*3 subjects. There were no significant differences in any of the kinetic parameters for either diclofenac disposition or formation clearance of 4′-hydroxydiclofenac between the two genotype groups. Conclusion: Since the disposition kinetics of diclofenac does not change in subjects with the single CYP2C9*3 mutant allele, it is suggested that the effects of CYP2C9 polymorphisms on the drug metabolism tend to be substrate specific. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. Methods: A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid. All patients were classified into three groups by CYP2C19 genotyping: G1, G2 and G3 were homozygous for the wild type of CYP2C19 (*1/*1), heterozygous extensive metabolizers (EMs), (*1/*2 or *1/*3), and poor metabolizers (PMs), (*2/*2, *2/*3), respectively. All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype. Results: Thirty-three patients belonged to G1 (44.6%), 35 to G2 (47.3%), and 6 to G3 (8.1%). The total clearance (CL) of PB significantly decreased by 18.8% in PMs (G3) relative to EMs (G1 and G2). The CL tended to be lower in G2 than in G1. Conclusion: In this study, we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping. The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be elucidated; however, it appears that the disposition of PB is mediated in part by this enzyme. The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient. [ABSTRACT FROM AUTHOR]