ABSTRACT
Renal function significantly influences the appropriate warfarin dosage. However, studies investigating the impact of genetic factors on warfarin dosage, considering renal function, are limited. This study aimed to assess the role of genetic polymorphisms in VKORC1, CYP2C9, CYP2C19, CYP4F2, GGCX, and APOE in warfarin dosage adjustment considering renal function. A total of 108 outpatients receiving warfarin treatment with controlled prothrombin time-targeted international normalized ratio (1.5-3.0) were included. Patient data, warfarin dosage, and laboratory results were collected from electronic medical records. Each SNP [VKORC1 rs9923231, CYP2C9 rs1057910, CYP4F2 rs2108622, CYP2C19* 2 (rs4244285) and* 3 (rs4986893), GGCX rs699664 and rs12714145, and APOE rs7421] was analyzed. Multiple regression analysis revealed estimated glomerular filtration rate as the most significant factor influencing warfarin dose (p <0.001) (ß = -0.445). VKORC1 rs9923231 AA, CYP4F2 rs2108622 CT/TT, GGCX rs12714145 CT/TT, and CYP2C9 rs1057910 AC carriers were associated with warfarin dose (p <0.001, 0.015, 0.020, 0.038 and ß = -0.317, 0.191, -0.188, -0.162, respectively); however, other genes showed no significant association. In conclusion, after adjusting for renal function, genetic factors of VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs12714145, and CYP2C9 rs1057910 were found to contribute to warfarin dosage, having impact in that order. In contrast, the contribution of other genes to warfarin dosage was absent or negligible.
Subject(s)
Anticoagulants , Polymorphism, Single Nucleotide , Warfarin , Humans , Warfarin/administration & dosage , Female , Male , Anticoagulants/administration & dosage , Aged , Middle Aged , Asian People/genetics , Japan , International Normalized Ratio , Dose-Response Relationship, Drug , Glomerular Filtration Rate , Vitamin K Epoxide Reductases/genetics , Aged, 80 and over , Cytochrome P450 Family 4/genetics , Genotype , Adult , East Asian PeopleABSTRACT
A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.
Subject(s)
Antiemetics , Neoplasms , Anorexia , Antiemetics/therapeutic use , Aprepitant , Carboplatin/adverse effects , Dexamethasone/therapeutic use , Female , Granisetron/therapeutic use , Humans , Nausea/chemically induced , Nausea/prevention & control , Paclitaxel/adverse effects , Palonosetron , Retrospective Studies , Vomiting/chemically induced , Vomiting/prevention & controlABSTRACT
A quasi-monoenergetic neutron field using the (7)Li(p,n)(7)Be reaction has been developed at the ring cyclotron facility at the Research Center for Nuclear Physics (RCNP), Osaka University. Neutrons were generated from a 10-mm-thick Li target injected by 250, 350 and 392 MeV protons and neutrons produced at 0 degrees were extracted into the time-of-flight (TOF) room of 100-m length through the concrete collimator of 10 x 12 cm aperture and 150 cm thickness. The neutron energy spectra were measured by a 12.7-cm diam x 12.7-cm long NE213 organic liquid scintillator using the TOF method. The peak neutron fluence was 1.94 x 10(10), 1.07 x 10(10) and 1.50 x 10(10) n sr(-1) per muC of 250, 350 and 392 MeV protons, respectively. The neutron spectra generated from various thick (stopping length) targets of carbon, aluminium, iron and lead, bombarded by 250 and 350 MeV protons, were also measured with the TOF method. Although these measurements were performed to obtain thick target neutron yields, they are also used as a continuous energy neutron field. These neutron fields are very useful for characterising neutron detectors, measuring neutron cross sections, testing irradiation effects for various materials and performing neutron shielding experiments.
Subject(s)
Lithium/chemistry , Neutrons , Particle Accelerators/instrumentation , Radiometry/instrumentation , Equipment Design , Equipment Failure Analysis , Japan , Radiation DosageABSTRACT
An irradiation field of high-energy neutrons produced in the forward direction from a thick tungsten target bombarded by 500 MeV protons was arranged at the KENS spallation neutron source facility. In this facility, shielding experiment was performed with an ordinary concrete shield of 4 m thickness assembled in the irradiation room, 2.5 m downstream from the target centre. Activation detectors of bismuth, aluminium, indium and gold were inserted into eight slots inside the shield and attenuations of neutron reaction rates were obtained by measurements of gamma-rays from the activation detectors. A MARS14 Monte Carlo simulation was also performed down to thermal energy, and comparisons between the calculations and measurements show agreements within a factor of 3. This neutron field is useful for studies of shielding, activation and radiation damage of materials for high-energy neutrons, and experimental data are useful to check the accuracies of the transmission and activation calculation codes.
Subject(s)
Construction Materials/analysis , Fast Neutrons , Models, Statistical , Particle Accelerators/instrumentation , Radiation Protection/instrumentation , Radiation Protection/methods , Radiometry/methods , Computer Simulation , Japan , Linear Energy Transfer , Materials Testing/methods , Monte Carlo Method , Radiation Dosage , SoftwareABSTRACT
STUDY OBJECTIVE: To assess the usefulness of preoperative respiratory muscle training to increase muscle strength and its effects on postoperative pulmonary complications. DESIGN: We measured maximum inspiratory (MIP) and maximum expiratory (MEP) mouth pressure before and after training in 50 patients undergoing thoracic surgery. For control purposes, MIP and MEP were measured in 50 age- and sex-matched healthy subjects at two different times without training. RESULTS: Preoperative respiratory muscle training increased both MIP and MEP significantly (p < 0.01), while the control subjects showed no increase in these parameters. Eight patients who had postoperative pulmonary complications had significantly lower values (p < 0.01) and did not show significant increases in either MIP or MEP even after the training, unlike the other patients, who were without postoperative pulmonary complications. On the other hand, there were also another six patients who had equally low MIP and MEPs before training, but who raised their values with training and avoided the postoperative pulmonary complications. CONCLUSION: Preoperative respiratory muscle training may prevent postoperative pulmonary complications by increasing both inspiratory and expiratory muscle strength in patients undergoing thoracic surgery. Patients with respiratory muscle weakness have a higher risk of postoperative pulmonary complications.
Subject(s)
Breathing Exercises , Pneumonectomy , Pneumonia/prevention & control , Postoperative Complications/prevention & control , Pulmonary Atelectasis/prevention & control , Respiratory Muscles/physiology , Thoracotomy , Female , Humans , Male , Middle Aged , Muscle Contraction/physiology , Pneumonia/epidemiology , Postoperative Complications/epidemiology , Preoperative Care , Pulmonary Atelectasis/epidemiology , Respiratory Function Tests , Risk FactorsABSTRACT
3 epoxy-resin hardeners, 4,4'-diaminodiphenyl ether (DDE), 4,4'-diaminodiphenylmethane (DDM), and 4,4'-diaminodiphenylsulfone (DDS), and their N-acetyl and N,N'-diacetyl derivatives were examined for their mutagenicity using Salmonella typhimurium TA98 and TA100 as the tester stains and an S9 mix containing a rat-liver 9000 X g supernatant fraction as the metabolic activation system. DDE and DDM were mutagenic towards TA98 and TA100 in the presence of S9 mix while DDS exhibited no significant mutagenic activity towards these tester strains. These epoxy-resin hardeners were metabolized in vivo and their N-acetyl and N,N'-diacetyl metabolites were found in the urine. Among these acetyl metabolites, only N-acetyl-DDE was found to be mutagenic towards TA98 and TA100 in the presence of S9 mix. None of these acetyl metabolites exhibited significant mutagenic activity towards these tester strains in the absence of S9 mix.
Subject(s)
Aniline Compounds/toxicity , Dapsone/toxicity , Phenyl Ethers/toxicity , Aniline Compounds/metabolism , Animals , Biotransformation , Dapsone/metabolism , Epoxy Resins , Male , Microsomes, Liver/metabolism , Mutagenicity Tests , Mutation/drug effects , Phenyl Ethers/metabolism , Rats , Rats, Inbred Strains , Structure-Activity RelationshipABSTRACT
Changes in respiratory muscle strength after lung resection were examined concerning age and procedures of thoracotomy. Maximum inspiratory (MIP) and expiratory (MEP) mouth pressure were measured before operation and 1, 2, 4, and 12 weeks after operation in 81 patients undergoing lung resection. In 48 patients undergoing pneumonectomy, lobectomy, or segmentectomy, patients older than 70 showed a significantly lower MIP and MEP before operation and throughout the postoperative period compared to younger ones (P < 0.01). Furthermore, the older patients showed a significantly lower percentage of postoperative MIP and MEP 4 weeks after operation than the younger ones (P < 0.01). In 31 patients undergoing lung wedge resection, patients undergoing limited thoracotomy (LT) and video-assisted thoracic surgery (VATS) showed significantly higher percentages of postoperative MIP and MEP than those undergoing posterolateral thoracotomy (PLT) 1 and 2 weeks after operation (P < 0.01 or 0.05). But there was no significant difference in the values between LT and VATS. We concluded that (1) elderly patients suffered respiratory muscle weakness before and after operation and their postoperative recovery of respiratory muscle strength was slower than in younger patients, and (2) VATS and LT resulted in more rapid recovery of respiratory muscle strength than PLT, but the difference between VATS and LT was not significant.
Subject(s)
Maximal Voluntary Ventilation/physiology , Pneumonectomy/methods , Postoperative Complications/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Muscles/physiopathology , Thoracotomy/methods , Adult , Aged , Aged, 80 and over , Endoscopy , Female , Humans , Male , Middle Aged , Pneumonia/physiopathology , Pulmonary Atelectasis/physiopathologyABSTRACT
It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease, but its relation to cerebral infarction is still controversial. Plasminogen activator inhibitor 1 (PAI-1) is also a predictor of risk of atherothrombotic disease. In this study we investigated the association of the ACE gene polymorphism and plasma PAI-1 levels in subjects with cerebral infarction. We evaluated the genotype of the ACE gene in 26 subjects with and 28 subjects without a history of ischemic stroke. The ACE genotype was analyzed by the polymerase chain reaction. Plasma PAI-1 antigen levels were measured by ELISA. There were no differences in accepted risk factors between the groups with or without cerebral infarction. However, the frequency of the D allele was significantly higher in subjects with cerebral infarction (0.63) than in those without infarction (0.39) (chi(2) = 6.306, P = 0.012). The frequency of the DD genotype of the ACE gene was also significantly higher in subjects with than in those without cerebral infarction (DD: 46.2%, ID: 34.6%, II: 19.2% vs. DD: 14.3%, ID: 50.0%, II: 35.7%, chi(2) = 6.689, P = 0.035). Plasma PAI-1 levels were not significantly different between groups with and without cerebral infarction. There was no association between the ACE genotype and PAI-1 levels. The DD genotype of the ACE gene is associated with cerebral infarction, which is independent of plasma PAI-1 level.
ABSTRACT
Irradiation experiments were performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility, National Institute of Radiological Sciences. The radioactive spallation products in a thick Cu target were obtained for Ar(230, 400 MeV per nucleon), Si(800 MeV per nucleon), Ne(100, 230, 400 MeV per nucleon), C(100, 230, 400 MeV per nucleon), He(100, 230 MeV per nucleon), p(100, 230 MeV) ions. The gamma-ray spectra from irradiated Cu samples inserted into the composite Cu target were measured with a high-purity germanium (HPGe) detector. From the gamma-ray spectra, we obtained the spatial distribution of radioactive yields of spallation products of 40 nuclides in the Cu sample in the Cu target. From the spatial distribution of radioactive yields, we estimated the residual activity and photon dose induced in the Cu target. The residual activity and photon dose become larger with the increase in projectile energy per nucleon and the range of the projectile beam for the same projectile energy per nucleon.
Subject(s)
Copper/radiation effects , Equipment Failure Analysis/instrumentation , Heavy Ions , Linear Energy Transfer , Photons , Radioisotopes/analysis , Radiometry/methods , Equipment Failure Analysis/methods , Half-Life , Particle Accelerators/instrumentation , Radiation Dosage , Radiometry/instrumentation , Reproducibility of Results , Sensitivity and Specificity , TransducersABSTRACT
Neutron activation cross sections for Bi and Co at 386 MeV were measured by activation method. A quasi-monoenergetic neutron beam was produced using the (7)Li(p,n) reaction. The energy spectrum of these neutrons has a high-energy peak (386 MeV) and a low-energy tail. Two neutron beams, 0° and 25° from the proton beam axis, were used for sample irradiation, enabling a correction for the contribution of the low-energy neutrons. The neutron-induced activation cross sections were estimated by subtracting the reaction rates of irradiated samples for 25° irradiation from those of 0° irradiation. The measured cross sections were compared with the findings of other studies, evaluated in relation to nuclear data files and the calculated data by Particle and Heavy Ion Transport code System code.
Subject(s)
Bismuth/chemistry , Cobalt/chemistry , Neutrons , Particle Accelerators , Radiometry/instrumentation , Radiometry/methods , Heavy Ions , Protons , Radiation Dosage , Radioisotopes/chemistry , Reproducibility of ResultsABSTRACT
The conversion coefficients, H'(d,α)/Φ, for monoenergetic positrons and positron-emitting radionuclides were calculated by using the user code UCICRPM of the Monte Carlo code EGS5 to estimate the radiation dose for medical staff involved in positron emission tomography examinations. From these coefficients, the dose equivalent rates per unit activity at 0.07 and 10 mm depths in a soft tissue for a straight-line source of 2-deoxy-2-[(18)F]fluoro-d-glucose ((18)F-FDG) were calculated by using the developed user code UCF18DOSE. The dose equivalent rates per unit activity at 0.07 and 10 mm depths were measured by using a personal dosemeter (DOSE(3)) under the same conditions as those considered in the calculation. The calculated dose equivalent rates per unit activity at 0.07 and 10 mm depths were 0.116 and 0.0352 pSv min(-1) Bq(-1), respectively, at 20 cm from the (18)F-FDG injection tube.