A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA).
The PMS study was performed for ...all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly.
Adverse drug reactions (ADRs) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. "Infections" or "respiratory disorders" were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4% and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about 1 month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab.
This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA.
In the original Grover algorithm, an exact or almost exact search such that the success probability is unity or infinitesimally close to unity is possible only for certain values of the fraction λ =
...M
/
N
where
M
is the number of marked items that are stored in an unsorted database of
N
items. There are various modified algorithms with an adjustable phase or phases such that an exact search can be done for any value of λ by means of a finite number of Grover-type operations. Among them, the algorithm proposed by Long is the simplest in the sense that it has only one adjustable phase and that the phase can be obtained in a closed form. We show that other more general algorithms with additional phases are not more efficient than Long’s version with a single phase.
In patients with severe hemorrhage, complications such as shock or death may occur if the patient is not treated appropriately and expeditiously. To create a hemostat kit for severe hemorrhage, ...ultraviolet light irradiation was applied to photocrosslinkable chitosan hydrogel and calcium alginate. As a hemorrhage model, the femoral arteries and veins of anesthetized rats were cut. Hemodynamics and hematological parameters including red blood cell (RBC) count, hemoglobin concentration, hematocrit, white blood cell (WBC) count, and platelet count, and serum parameters including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as a marker of hemostasis. In rats for which no procedure was used, death occurred within 30 min. By using the hydrogel hemostat, the survival rate rose to 75% or more. RBC count, hemoglobin, hematocrit, and platelet levels were not significantly changed for 3 days. WBC count increased 1 day after hemostasis. AST and ALT increased 1 day after hemostasis, but it decreased 3 days later. The photocrosslinkable chitosan hydrogel and calcium alginate were biodegraded at 3 and 28 days, respectively, by neutrophils and keratinocyte chemoattractant.
An organic thyristor Terasaki, I; Sawano, F; Mori, H ...
Nature,
09/2005, Volume:
437, Issue:
7058
Journal Article
Peer reviewed
Thyristors are a class of nonlinear electronic device that exhibit bistable resistance-that is, they can be switched between two different conductance states. Thyristors are widely used as inverters ...(direct to alternating current converters) and for the smooth control of power in a variety of applications such as motors and refrigerators. Materials and structures that exhibit nonlinear resistance of this sort are not only useful for practical applications: they also provide systems for exploring fundamental aspects of solid-state and statistical physics. Here we report the discovery of a giant nonlinear resistance effect in the conducting organic salt -(BEDT-TTF)2CsCo(SCN)4, the voltage-current characteristics of which are essentially the same as those of a conventional thyristor. This intrinsic organic thyristor works as an inverter, generating an alternating current when a static direct-current voltage is applied. Whereas conventional thyristors consist of a series of diodes (their nonlinearity comes from interface effects at the p-n junctions), the present salt exhibits giant nonlinear resistance as a bulk phenomenon. We attribute the origin of this effect to the current-induced melting of insulating charge-order domains, an intrinsically non-equilibrium phenomenon in the sense that ordered domains are melted by a steady flow.
It is well-known that chronic exposure to large amounts of ligand leads to downregulation of its receptor. It is not known, however, whether a GLP-1R agonist downregulates its receptor. For this ...reason, our study examined whether GLP-1R expression is reduced after long-term exposure to dulaglutide (Dula) in non-diabetic and diabetic mice.
Seven-week-old male db/db and db/m mice were given either Dula (0.6mg/kg×2/week) or a control vehicle (CTL) for 17 weeks. Various metabolic parameters, such as glucose-stimulated insulin secretion (GSIS), insulin and TG content in islets, were evaluated after the intervention. β-cell-related gene expression was also analyzed by real-time RT-PCR.
In db/m mice, GLP-1R expression in β-cells did not decrease, not even after long-term administration of Dula, compared with control mice, while GLP-1R expression in 24-week-old db/db mice treated with Dula was augmented, rather than downregulated, compared with 24-week-old CTL db/db mice. This was probably due to improved glycaemic control. In db/db mice treated with Dula, food intake and blood glucose levels were significantly decreased up to 24 weeks of age compared with CTL db/db mice, and their expression levels of various β-cell-related genes, insulin content and GSIS were also enhanced. In contrast, oxidative and endoplasmic reticulum stress, inflammation, fibrosis and apoptosis were suppressed with Dula treatment.
Dula exerts beneficial effects on glycaemic control and has long-lasting protective effects on pancreatic β-cells. GLP-1R expression levels were not reduced at all in non-diabetic as well as diabetic mice despite long-term dulaglutide exposure.
Abstract
The Cherenkov Telescope Array (CTA) is the next-generation ground-based very-high-energy gamma-ray observatory. By using three types of telescopes CTA can cover a wide energy range (20 ...GeV–300 TeV) with an order of magnitude higher sensitivity than the current telescopes. The Large-Sized Telescope (LST) is designed to detect 20 GeV–1 TeV gamma rays thanks to the large light collection area, sensitive photosensors, a fast trigger system, and readout electronics. The camera readout system must have a high signal-to-noise ratio and a linear signal sampling with a large dynamic range in order to efficiently detect dim and low-energy atmospheric showers. To meet this requirement we use the Domino Ring Sampler version 4 (DRS4), which also enables ultra-fast sampling with low power consumption. Some of the intrinsic characteristics of DRS4 chips require software corrections. These procedures lower the effect of non-Gaussian noise contribution and improve the timing resolution of the system. In this contribution we discuss the calibration algorithms and the resulting performance.
Abstract Background Clinical studies of uterus transplantation have been performed to treat uterine factor infertility. Because the uterus is a pelvic visceral organ, the method of perfusion for the ...procurement of vital organs from a brain-dead donor should be modified for removal of the uterus. Herein, we report the results of a preliminary study in cynomolgus monkeys of a new perfusion method for uterus transplantation with assumed procurement of a uterus from a brain-dead donor. Methods Cynomolgus monkeys were used; thoracolaparotomy was performed on the donor. A perfusion catheter was then placed into the unilateral femoral artery and/or external iliac artery. Cross-clamping was performed for the aorta under the diaphragm and the inferior vena cava was divided in the pleural space. The perfusion solution was then administered via the catheter to perfuse all organs in the abdominal cavity, including those in the pelvic cavity. After the perfusion, gross observation and histopathological examination of abdominal organs were conducted. Results Gross findings showed that all abdominal organs turned white in all specimens, indicating favorable perfusion of the uterus and all other organs in the abdomen. Pathological findings showed that almost no hemocytes were observed in the vessels of each organ. Conclusions With perfusion via the femoral artery and/or external iliac artery, all organs in the abdominal cavity, including the uterus, could be perfused. It was suggested that this technique could be useful for uterus transplantation assuming the procurement of a uterus from a brain-dead donor.
The correlation between the charge density wave (CDW) and f local moments is observed in GdNiC2 by means of x-ray diffraction in a magnetic field. Various kinds of electronic states exist in the ...magnetic field. The intensity of the CDW peak changes in the successive transitions and the commensurate-incommensurate transition of the CDW takes place as well. The successive transitions are explained in terms of a cooperative effect of the Peierls instability and the spin Friedel oscillation, in which the antiferromagnetic order of the f local moments is coupled to the spin density wave coexisting with the CDW of the conduction electron.
Multiphase matching in the Grover algorithm Toyama, F. M.; van Dijk, W.; Nogami, Y. ...
Physical review. A, Atomic, molecular, and optical physics,
04/2008, Volume:
77, Issue:
4
Journal Article
PDF
