A case of graft replacement of the ascending aorta to the aortic arch and the partial descending aorta in a single stage for thrombosed aortic dissection (debakey type II + IIIB)

We report here a case of graft replacement of the ascending aorta to the aortic arch and the middle portion of the descending aorta in a single stage for thrombosed aortic dissection. The patient was a 53-year-old male who was transfered to our hospital with a diagnosis of thrombosed aortic dissection. Conservative therapy was continued but three weeks after the onset, chest enhanced CT scan and digital subtraction angiography revealed an opacified false lumen in the ascending aorta and a ulcer like projection in the middle portion of the descending aorta. He was therefore diagnosed as having redissection in DeBakey type II + IIIb thrombosed aortic dissec- tion. Graft replacement of the ascending aorta, the aortic arch, and a part of the descending aorta was performed in a single stage via median stenotomy with the aid of extracorporeal circulation and selective cerebral perfusion. Postoperative digital subtraction angiography showd satisfac- tory reconstruction of the thoracic aorta. The patient is still leading a normal life two years after the operation.     

Unrelated-Donor Bone Marrow Transplantation with a Conditioning Regimen Including Fludarabine, Busulfan, and 4 Gy Total Body Irradiation

We investigated the feasibility of reduced-intensity conditioning with 4 Gy total body irradiation, fludarabine (30 mg/m2 for 6 days), and busulfan (4 mg/kg for 2 days) for bone marrow transplantation from a serologically HLA-matched unrelated donor. Seventeen adult patients (median age, 55 years; range, 27-67 years) with various hematologic malignancies (6 in remission, 11 not in remission) were treated. Successful engraftment was achieved in all patients at a median of day 18 (range, day 14-35) after transplantation, although subsequent secondary graft failure was observed in 2 patients. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV at day 100 was 48%. With a median follow-up of 286 days (range, 56-687 days), the rates of 1-year overall survival, 100-day nonrelapse mortality, and 1-year nonrelapse mortality were 41%, 14%, and 46%, respectively. Eleven patients died, and the causes of death were relapse (n = 4), pulmonary complications (n = 4), acute GVHD (n = 2), and sepsis (n = 1). The remaining 6 patients (at transplantation, 2 were in remission, and 4 were not in remission) are currently still in remission. These results suggest that this regimen reduces the risk of graft failure, but further studies are needed to ameliorate transplantation-related toxicities, primarily GVHD and/or pulmonary complications.     

Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis

Background/Aims: We evaluated patients with nonalcoholic fatty liver disease (NAFLD) and compared the clinical and pathological features to identify the risk factors for NAFLD with severe fibrosis. Methods: One hundred and eighty‐two patients with biopsy‐confirmed NAFLD from various medical centres were recruited into this study. Results: The variables that were significantly associated with severe steatosis were male gender (mild:severe=36%:53%, P=0.02), younger age (mild:severe=57%:82%, P>0.001) and absence of type 2 diabetes (mild:severe=43%:71%, P>0.001). There was no significant difference in the degree of inflammation among the clinical groups. The variables that were significantly associated with severe fibrosis were female gender (mild:severe=54%:84%, P=0.002), older age (≥60 years old) (mild:severe=29%:53%, P=0.020), type 2 diabetes (mild:severe=42%:71%, P=0.020) and hypertension (mild:severe=24%:53%, P=0.002). Although there were more obese patients in the group with severe fibrosis, the association was not statistically significant (mild:severe=67%:78%, P=0.229). The prevalence of high serum triglyceride levels was similar between the two groups. The N (Nippon) score (total number of risk factor) could significantly predict severe fibrosis in NAFLD patients (1.48 ± 1.14 vs. 2.66 ± 0.94, P<0.001). Conclusions: The N score can be used to predict severe fibrosis in cases of NAFLD.     

Suppressing effects of daily oral supplementation of beta-glucan extracted from Agaricus blazei Murill on spontaneous and peritoneal disseminated metastasis in mouse model

Purpose: The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer. Methods: We examined whether beta-(1–6)-D-glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model. Results: Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies. Conclusion: Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents.     

Cryopyrin-associated periodic syndromes: background and therapeutics

Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations of the gene encoding the NLR family protein NLRP3, which together with caspase-1 and adaptor proteins constitutes a protein complex termed the inflammasome. In innate immune reactions, a variety of stimuli activate the NLRP3 inflammasome, triggering caspase-1 to process proIL-1 and thus to produce mature IL-1. Excessive production of IL-1 by monocytes/macrophages is the central pathophysiology of CAPS, and daily injection of the IL-1 receptor antagonist anakinra rapidly ameliorates the inflammatory symptoms in most cases. Furthermore, double-blind, placebo-controlled clinical trials have recently confirmed the efficacy and safety of rilonacept, a fusion protein of the IL-1 receptor and IgG Fc, and canakinumab, a human anti-IL-1 monoclonal antibody, as novel long-lasting agents for treating CAPS.     

Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins

We have established an experimental model of oral contraceptive-inducedhepatocellular carcinomas (HCCs) in female Wistar rats, revealingthat ethynylestradiol (EE) and norethindrone acetate have actionsas both initiators and promoters. The present time—sequencestudy was undertaken to clarify the role of free radicals inestrogen induction of HCC by measuring detoxifying enzyme activitiesand levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessingthe effects of concomitant vitamin C, vitamin E or ß-caroteneadministration on hepatocarcinogenesis. During 12 months oraladministration of EE (0.075 or 0.75 mg/day), the 8-OH-dG levelsreached peak values after 1 month, when they were significantlyelevated as compared with the controls. Glutathione peroxidasedemonstrated a tendency to decrease. Histologically, pre-neoplasticlesions assessed by immunohistochemical staining for placentalglutathione S-transferase (GST-P) were first observed at 2 monthsin the groups given 0.075 and 0.75 mg/day of EE alone, withincidences of HCC at 12 months being 8.7% and 38.5% respectively.Combined administration of vitamins with 0.075 mg EE/day reducedthe elevation of the 8-OH-dG levels. GST-P-positive lesionswere first observed at 4 months in the vitamin E group and at6 months in the vitamin C and ß-carotene groups. Ascompared with the value in the 0.075 mg EE alone group, vitaminadministration significantly reduced the numbers of GST-P-positivefoci after 12 months of treatment The incidences of HCC at 12months were 0% in the vitamin C group, 4.5% in the vitamin Egroup and 4.8% in the ß-carotene group, i.e. administrationof the vitamins inhibited the development of GST-P-positivefoci, with suppression of HCC. The results thus suggest thatfree radicals play an important role in the induction of HCCby estrogen.