Clinical features of symptomatic primary biliary cirrhosis initially complicated with esophageal varices

Background Esophageal varices (EV), one feature of portal hypertension, have been regarded as a late complication of liver diseases. However, accumulating evidence indicates that EV sometimes develop early during the course of primary biliary cirrhosis (PBC). The prognosis is usually poorer for patients with symptomatic PBC than for those with asymptomatic PBC. Nevertheless, the clinical features and prognosis of patients with PBC whose initial symptoms are EV have not been clarified. Methods The clinical features and the prognosis of patients who initially developed EV without other symptoms (v-PBC) were retrospectively investigated in 54 patients with symptomatic PBC. Results The leukocyte and platelet counts were lower in patients with v-PBC than in those with PBC accompanied by other symptoms (s-PBC). Liver function tests, autoantibodies, and histological stage did not differ between patients with v-PBC and those with s-PBC. Although the prognosis did not differ, the incidence of hepatocellular carcinoma was significantly higher in v-PBC than in s-PBC (P = 0.0037). Conclusions These data indicate that v-PBC is a hypercarcinogenic state and constitutes a new subgroup of PBC.     

Use of a wire-guided cannula for radial arterial cannulation

We compared the success rates of arterial cannulation with a wire-guided cannula (WGC) and the direct technique with a conventional non-wire-guided cannula (non-WGC). A total of 100 adult patients requiring an arterial line in the operating room were assigned randomly to undergo radial arterial cannulation either with the WGC or with the non-WGC. No significant difference in success rates and insertion times could be demonstrated between the WGC and the non-WGC (78.4% vs 67.3% and 22.6 ± 13.2 s vs 23.0 ± 19.3 s, respectively). Among the less experienced operators, insertion time was shorter with the WGC than with the non-WGC (27.7 ± 11.9 s vs 39.8 ± 20.4 s; P < 0.05), although the success rate was similar for the two types of cannula. Patient characteristics did not affect either the success rates or the insertion times for the two types of cannula. In conclusion, we have confirmed that the success rates of radial arterial cannulation for patients whose physical status is relatively good were similar with the use of the WGC and the non-WGC. Presented in part at the 52nd Annual Meeting of the Japanese Society of Anesthesiologists, Kobe, Japan, June 2–4, 2005     

Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas

Intraductal papillary–mucinous neoplasms of the pancreas show characteristic clinicopathological and molecular pathobiological features which are distinct from those of conventional ductal adenocarcinomas. Alterations of KRAS, AKT/PKB, CDKN2A, TP53, SMAD4, STK11/LKB1, and DUSP6, and other molecular alterations, including global expression studies as well as their clinical implications, are discussed.     

WRN functions in a RAD18-dependent damage avoidance pathway

Werner syndrome (WS), caused by mutations in a gene (WRN) that encodes a RecQ DNA helicase, is characterized by premature aging and cancer predisposition. Cells derived from WS patients show sensitivity to several DNA damaging agents. Previous studies revealed that the WRN protein plays roles in DNA repair or damage tolerance, although it was not yet assigned to a specific pathway. Here we examined the relationship between WRN and the post-replication repair protein RAD18 by generating deletion derivatives in chicken DT40 cells. The frequency of spontaneous sister chromatid exchange in WRN(-/-)/RAD18(-/-) double mutant cells was slightly increased compared to that of either single mutant. However, the sensitivity of WRN(-/-)/RAD18(-/-) cells to 4-nitroquinoline 1-oxide and methyl methanesulfonate was almost the same as that of RAD18(-/-) cells. Moreover, the cisplatin sensitivity of RAD18(-/-) cells was slightly suppressed by disruption of WRN. These data suggest that WRN functions in a pathway involving RAD18 under damage-inducing conditions.     

Oxidative stress in methamphetamine-induced self-injurious behavior in mice

Previous studies have shown that N-methyl-D-aspartate, the formation of free radicals and poly(ADP-ribose) polymerase are related to methamphetamine-induced neurotoxicity. This study was designed to investigate the involvement of oxidative stress in methamphetamine-induced self-injurious behavior in mice. In this study, methamphetamine (20 mg/kg) induced continuous self-injurious behavior in six of seven mice. N-methyl-D-aspartate-receptor antagonists (MK801 and 3-((R)-2-carboxypiperazin-4-yl) propyl-1-phosphonic acid) significantly attenuated this methamphetamine-induced self-injurious behavior. These results suggest that the activation of N-methyl-D-aspartate receptors is involved in methamphetamine-induced self-injurious behavior. Furthermore, we found that the nonselective nitric oxide synthase inhibitor l-N-nitro-L-arginine methyl ester hydrochloride and the neuronal nitric oxide synthase inhibitor 7-nitroindazole, but not the inducible nitric oxide synthase inhibitor aminoguanidine, the free-radical inhibitors fullerene and 3-methyl-1-phenyl-2-pyrazolin-5-one-186, or the poly(ADP-ribose) polymerase inhibitor benzamide, significantly attenuated methamphetamine-induced self-injurious behavior. The present results show that oxidative stress, which is mediated by the activation of neuronal nitric oxide synthase, is associated with methamphetamine-induced self-injurious behavior. These findings may help us to better understand the clinical phenomenon of self-injurious behavior.     

Usefulness of Positron Emission Tomography in the Evaluation of Distribution and Activity of Systemic Lesions Associated with Autoimmune Pancreatitis

Background/Aims: Autoimmune pancreatitis (AIP) is an lgG4-related systemic disease often accompanied with a variety of lesions outside of the pancreas and is treated with steroid therapy. The aim of this study is to analyze the usefulness of positron emission tomography with ¹⁸F-fluorodeoxyglucose (FDG-PET) in the evaluation of distribution and activity of systemic lesions of AIP during steroid therapy. Methods: Eleven cases of AIP had their FDG-PET images evaluated before and 3 months after steroid therapy and another 2 cases only before therapy. AIP activity was determined by the level of serum markers, IgG and lgG4, and compared with findings of PET. Results: In all 13 cases of AIP, a moderate to intense level of FDG accumulation was recognized in the pancreatic lesion before steroid therapy. Of 13 patients, 11 (84.6%) showed FDG accumulation in the multiple organs, such as mediastinal and other lymph nodes, salivary gland, biliary tract, prostate, and aortic wall. In 11 patients who underwent PET before and after steroid therapy, FDG accumulation was diminished in almost all systemic lesions, with a mean of maximum standardized uptake value (SUV_max) in the pancreatic lesion from 5.12 to 2.69. Similar to the SUV level, serum IgG and lgG4 were decreased in most of the cases after steroid therapy. Conclusions: FDG-PET is an effective modality to evaluate the response of steroid therapy and the distribution and activity of various systemic lesions of AIP.