New sesquiterpenes from Capsicum annuum

The ethyl acetate soluble fraction of a MeOH extract of the dried stems and roots of Capsicum annum gave 10 new sesquiterpenoids (1-10) and nine known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic evidence. The isolated new compounds were evaluated for their cytotoxic activities.     

The intubating laryngeal mask for a patient with cerebrospinal fluid rhinorrhea and pneumocephalus

A 53-year-old male was scheduled for repairs of cerebrospinal fluid (CSF) rhinorrhea and pneumocephalus under general anesthesia. He had undergone a neck clipping for a ruptured anterior communicating aneurysm 13 days before. As he had a difficult airway, Trachlight was used for successful tracheal intubation. To avoid tension pneumocephalus, an intubating laryngeal mask (ILM) was inserted with rapid sequence induction without positive pressure ventilation. A 7.0 mm ID straight silicone reinforced tube was then inserted through the ILM using a fiberscope. A fiberscope guided tracheal intubation via the ILM is recommended for patients with CSF rhinorrhea and pneumocephalus especially when the trachea is difficult to intubate under direct laryngoscopy.     

Adenovirus-mediated gene transfer of ICOSIg fusion protein ameliorates ongoing experimental autoimmune myocarditis

Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. We previously demonstrated that blockade of B7/CD28 or CD40/CD40 ligand (CD40L) had a potential preventive effect on EAM, but less therapeutic effect on ongoing EAM. Thus, we searched for the involvement of other costimulatory molecules in EAM. We demonstrated the expression of inducible costimulator (ICOS)/ICOSL molecules in the lymph nodes, spleen, and heart in the EAM rat. We constructed adenovirus vectors containing ICOSIg (Adex1CAICOSIg) to achieve effective inhibition of ICOS/ICOSL interaction, and examined the effects of Adex1CAICOSIg on EAM. Adex1CAICOSIg treatment shortly after the immunization did not inhibit the onset and severity of EAM compared to control rats. On the other hand, delayed treatment with Adex1CAICOSIg significantly inhibited ongoing EAM. The survival rate in rats treated with Adex1CAICOSIg was significantly higher than that of the control group. Furthermore, the affected area ratio of the Adex1CAICOSIg treatment group was significantly lower than that of the control group. This study indicates that ICOS/ICOSL costimulation makes an important contribution to the progression of EAM and that the blockade of this pathway by gene transfer has therapeutic potential for ongoing autoimmune myocarditis.     

Usefulness of blood parameters, especially viscosity, for the diagnosis and elucidation of pathogenic mechanisms of the hand-arm vibration syndrome

In the present study it was found that, in vibrating-tool operators with Raynaud's phenomenon, whole blood viscosity was significantly higher than in operators without Raynaud's phenomenon at shear rates from 230 to 11.5 s-1. In addition rats were experimentally exposed to local vibration (60 Hz, 5 g) on their hind limbs for 4 h/d for 30 or 90 d. In the case of 30-d exposure, the small arteries in the exposed site did not change. However, after exposure for 90 d, disruption of the internal elastic lamina was observed in the small arteries. The disruption was followed by focal cell proliferation with regenerative formation of collagen and elastic fibers. The fibro-cellular thickening of the intima was further augmented, and, in addition, a complete stenosis of the small lumen of the small artery was observed. Medial thickness did not show significant differences between the control and exposed groups for either exposure duration. The whole blood viscosity was significantly increased by the 90-d but not by the 30-d exposure. These results suggest that there are some relationships between the increase in whole blood viscosity and the intimal thickening of some small arteries in the exposed site.     

Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine

Gemcitabine is widely used for the treatment of advanced biliary tract cancer (BTC) as first-line chemotherapy. However, there is no standard chemotherapy for patient with advanced BTC refractory to gemcitabine. We conducted a multicenter phase II study of S-1 monotherapy as second-line chemotherapy for patients with advanced BTC that were refractory to gemcitabine. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks. Tumor response was assessed every two cycles using the Response Evaluation Criteria in Solid Tumors version 1.0. Twenty-two patients were enrolled between March 2007 and January 2010, with 14 patients (64%) representing cases of recurrence after surgery. The overall response rate was 22.7%, and the overall disease control rate was 50.0%. The median overall survival time was 13.5 months (95% CI, 7.1-23.1 months) and the median time-to-progression was 5.4 months (95% CI, 2.6-17.2 months). Grade 3/4 toxicities included neutropenia (5%) and anemia (5%). The most common non-hematological toxicities were nausea (27%), anorexia (55%), and pigmentation (32%). In conclusion, S-1 monotherapy is feasible and moderately efficacious second-line chemotherapy for advanced BTC.     

Influence of local vibration on plasma creatine phosphokinase (CPK) activity.

This study was designed to obtain basic information about the mechanism of the occurrence of muscular disorders after exposure to vibration. The hind legs of rats were exposed to acute and chronic local vibration at frequencies of 30, 60, 120, 240, 480, and 960 Hz with a constant acceleration of 50 m/sec2. The exposure time was four hours for acute, and four hours a day for two weeks continuously for chronic exposure. Blood was collected after exposure to measure plasma creatine phosphokinase (CPK) activity. In both exposure groups the activity of plasma CPK was significantly higher at 30, 60, 120, 240, and 480 Hz compared with the control group and was especially high at 30 Hz; there was no significant change at 960 Hz. As a result of an analysis of the CPK isoenzymes, the increase in plasma CPK activity was shown to be due to the activity of the plasma CPK-MM fraction, originating in the skeletal muscle. Plasma CPK activity showed a tendency to decrease gradually with the increase in vibration frequency during acute exposure but showed no such tendency during chronic exposure. There was no remarkable pathohistological change in muscle preparations from the hind legs, hence it was presumed that the increase in plasma CPK activity was caused not by the morphological changes of muscle but by other mechanisms, such as an increase in the permeability of the cell membrane.     

Drug-induced liver injury in Japan: An analysis of 1676 cases between 1997 and 2006

At the 44th Annual Meeting of the Japan Society of Hepatology, 1674 cases of drug-induced liver injury (DILI), occurring between January 1997 and December 2006, were reviewed. Data were obtained by questionnaires completed by the 29 presenters of the special DILI session during the meeting. This article presents the review's findings, including the role of dietary supplements and Chinese herbal medicines in DILI.     

Reliability of cardiac output measurements using LiDCOrapid™ and FloTrac/Vigileo™ across broad ranges of cardiac output values

Knowing a patient’s cardiac output (CO) could contribute to a safe, optimized hemodynamic control during surgery. Precise CO measurements can serve as a guide for resuscitation therapy, catecholamine use, differential diagnosis, and intervention during a hemodynamic crisis. Despite its invasiveness and intermittent nature, the thermodilution technique via a pulmonary artery catheter (PAC) remains the clinical gold standard for CO measurements. LiDCOrapid? (LiDCO, London, UK) and FloTrac/Vigileo? (Edwards Lifesciences, Irvine, CA) are less invasive continuous CO monitors that use arterial waveform analysis. Their calculations are based on arterial waveform characteristics and do not require calibration. Here, we evaluated LiDCOrapid? and FloTrac/Vigileo? during off-pump coronary artery bypass graft (OPCAB) and living-donor liver transplantation (LDLT) surgery. This observational, single-center study included 21 patients (11 OPCAB and 10 LDLT). We performed simultaneous measurements of CO at fixed sampling points during surgery using both devices (LiDCOrapid? version 1.04-b222 and FloTrac/Vigileo? version 3.02). The thermodilution technique via a PAC was used to obtain the benchmark data. LiDCOrapid? and FloTrac/Vigileo? were used in an uncalibrated fashion. We analyzed the measured cardiac index using a Bland–Altman analysis (the method of variance estimates recovery), a polar plot method (half-moon method), a 4-quadrant plot and compared the widths of the limits of agreement (LOA) using an F test. One OPCAB patient was excluded because of the use of an intra-aortic balloon pumping during surgery, and 20 patients (10 OPCAB and 10 LDLT) were ultimately analyzed. We obtained 149 triplet measurements with a wide range of cardiac index. For the FloTrac/Vigileo?, the bias and percentage error were ?0.44 L/min/m² and 74.4 %. For the LiDCOrapid?, the bias and percentage error were ?0.38 L/min/m² and 53.5 %. The polar plot method showed an angular bias (FloTrac/Vigileo? vs. LiDCOrapid?: 6.6° vs. 5.8°, respectively) and radial limits of agreement (?63.9 to 77.1 vs. ?41.6 to 53.1). A 4-quadrant plot was used to obtain concordance rates (FloTrac/Vigileo? vs. PAC and LiDCOrapid? vs. PAC: 84.0 and 92.4 %, respectively). We could compare CO measurement devices across broad ranges of CO and SVR using LDLT and OPCAB surgical patients. An F test revealed no significant difference in the widths of the LoA for both devices when sample sizes capable of detecting a more than two-fold difference were used. We found that both devices tended to underestimate the calculated CIs when the CIs were relatively high. These proportional bias produced large percentage errors in the present study.