Risk factors and prediction of bleeding after gastric endoscopic submucosal dissection in patients on antithrombotic therapy: newly developed bleeding prediction application software,SAMURAI model

Bleeding after gastric endoscopic submucosal dissection (ESD) remains problematic, especially in patients receiving antithrombotic therapy. Therefore, this study aimed to identify the risk factors. In this retrospective study, patients (n = 1,207) who underwent gastric ESD while receiving antithrombotic therapy were enrolled at Osaka Medical and Pharmaceutical University Hospital and 18 other referral hospitals in Japan. Risks of post-ESD bleeding were calculated using multivariable logistic regression. The dataset was divided into a derivation cohort and a validation cohort. We created a prediction model using the derivation cohort. The accuracy of the model was evaluated using the validation cohort. Post-ESD bleeding occurred in 142 (11.8%) participants. Multivariable analysis yielded an odds ratio of 2.33 for aspirin, 4.90 for P2Y12 receptor antagonist, 1.79 for cilostazol, 0.95 for other antithrombotic agents, 6.53 for warfarin, 5.65 for dabigatran, 7.84 for apixaban, 10.45 for edoxaban, 6.02 for rivaroxaban, and 1.46 for heparin bridging. The created prediction model was called safe ESD management using the risk analysis of post-bleeding in patients with antithrombotic therapy (SAMURAI). This model had good predictability, with a C-statistic of 0.77. In conclusion, use of the SAMURAI model will allow proactive management of post-ESD bleeding risk in patients receiving antithrombotic therapy.     

Age-dependent association of mannose-binding lectin polymorphisms with the development of pulmonary tuberculosis in Viet Nam

Mannose-binding lectin (MBL) binds to pathogens and induces complement-mediated opsonophagocytosis. Although the association between MBL2 polymorphisms and tuberculosis (TB) has been studied in various populations, the results are controversial. We explored the stages of TB associated with MBL2 polymorphisms. X/Y (rs7096206) and A/B (rs1800450) were genotyped in 765 new patients with active pulmonary TB without HIV infection and 556 controls in Hanoi, Viet Nam. The MBL2 nucleotide sequences were further analyzed, and plasma MBL levels were measured in 109 apparently healthy healthcare workers and 65 patients with TB. Latent TB infection (LTBI) was detected by interferon-gamma release assay (IGRA). The YA/YA diplotype, which exhibited high plasma MBL levels, was associated with protection against active TB in younger patients (mean age = 32) ≦ 45 years old (odds ratio, 0.61; 95% confidence interval, 0.46–0.80). The resistant diplotype was less frequently found in the younger patients at diagnosis (P = 0.0021). MBL2 diplotype frequencies and plasma MBL levels were not significantly different between the IGRA-positive and -negative groups. MBL2 YA/YA exhibited a protective role against the development of TB in younger patients, whereas the MBL2 genotype and MBL levels were not associated with LTBI. High MBL levels may protect against the early development of pulmonary TB after infection.     

Lack of correlated expression between the glutathione S-transferase P-form and the oncogene products c-Jun and c-Fos in rat tissues and preneoplastic hepatic foci

Since the expression of glutathione S-transferase P-form (GST-P)has been suggested from in vitro studies to be partly regulatedby the oncogene products, c-Jun and c-Fos, their distributionswere compared in normal rat tissues and preneoplastic hepaticlesions induced by the Solt—Farber protocol. Immunohistochemicallydemonstrated GST-P protein was positively correlated with expressionof both c-Jun and c-Fos in the epidermis of the skin and thesmooth muscle of adult lung and with either c-Jun or c-Fos respectivelyin the bile ducts and bronchial epithelium. However, GST-P expressionwas also observed in proximal and distal straight segments ofthe kidney and other tissues negative for c-Jun and c-Fos andboth c-Jun and c-Fos were present in the renal proximal anddistal convoluted tubules, where GST-P was lacking. Thus, thelocalization of GST-P was in some cases clearly separable fromthose of c-Jun or c-Fos. GST-P was found to be focally expressedfrom an early stage of hepatocarcinogenesis, when c-Jun wasnot detectable. At later stages, this oncogene product was stainedin 35.7% of GST-P-positive foci, with a clear relation to thedegree of GST-P staining. Since GST-P is not always accompaniedby appreciable c-Jun or c-Fos, these oncogene products are apparentlynot prerequisites for its expression. However, c-Jun may bepartly responsible for maintaining high levels of GST-P in hepaticfoci at later stages of hepatocarcinogenesis.     

Tropane alkaloids in adventitious root cultures of Physochlaina physaloides

Adventitious root cultures of Physochlaina physaloides were established and their growth and tropane alkaloid production were investigated. Although the roots cultured in Murashige-skoog liquid medium containing 1.0-3.0 mg/l IBA grew well, the addition of lower concentrations of auxins was more suitable for alkaloid production. The best alkaloid yield was obtained with 0.01 mg/l NAA in 1/2 MS liquid medium. In addition, the alkaloid differences between the cultured roots and the regenerated plant cultivated in the soil was studied. Cultured roots in this condition showed higher level of alkaloids when compared to leaf, stem and roots from the regenerated plant (3 months in field conditions).     

Catechol and hydroquinone have different redox properties responsible for their differential DNA-damaging ability.

We examined the redox properties of the "carcinogenic" catechol and the "noncarcinogenic" hydroquinone in relation to different DNA damaging activities and carcinogenicity using 32P-labeled DNA fragments obtained from the human genes. In the presence of endogenous NADH and Cu2+, catechol induces stronger DNA damage than hydroquinone, although the magnitudes of their DNA damaging activities were reversed in the absence of NADH. In both cases, DNA damage resulted from base modification at guanine and thymine residues in addition to strand breakage induced by Cu+ and H2O2, generated during the oxidation of catechol and hydroquinone into 1,2-benzoquinone and 1,4-benzoquinone, respectively. EPR and 1H NMR studies indicated that 1,2-benzoquinone is converted directly into catechol through a nonenzymatic two-electron reduction by NADH whereas 1,4-benzoquinone is reduced into hydroquinone through a semiquinone radical intermediate through two cycles of one-electron reduction. The reduction of 1,2-benzoquinone by NADH proceeds more rapidly than that of 1,4-benzoquinone. This study demonstrates that the rapid 1,2-benzoquinone two-electron reduction accelerates the redox reaction turnover between catechol and 1,2-benzoquinone, resulting in the enhancement of DNA damage. These results suggest that the differences in NADH-mediated redox properties of catechol and hydroquinone contribute to their different carcinogenicities.     

Quantitative analysis of cell-free Epstein-Barr virus genome copy number in patients with EBV-associated hemophagocytic lymphohistiocytosis

To determine whether the EBV genome content in serum or plasma reflects clinical features and outcome in EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), we quantified the cell-free EBV genome copy number by real-time PCR in 38 patients with EBV-HLH, and compared this to the values from 15 patients with infectious mononucleosis (IM). The median (range) cell-free EBV genome copy number at diagnosis was 3.0 x 10(3) (undetectable -5.5 x 10(7)) copies/ml in EBV-HLH, which was significantly higher than the 6.6 x 10(1) (undetectable -1.0 x 10(3)) copies/ml in IM (P = 0.0008). We serially analyzed cell-free EBV genome copy number in 10 cases of EBV-HLH up to 4 months from diagnosis. In four patients who achieved remission, the EBV genome became undetectable soon after starting therapy. In the remaining six patients who responded poorly to therapy, the EBV genome copy number in the serum or plasma remained at high levels except for one case. In addition, we confirmed that the EBV genome became undetectable after hematopoietic stem cell transplantation in 4 EBV-HLH cases. These results suggest that the quantitative analysis of cell-free EBV genome copy number is useful for evaluating disease activity and for predicting the response to therapy in EBV-HLH.     

Response of Japanese patients to the change of department name for the psychiatric outpatient clinic in a university hospital

There has long been controversy over the stigma associated with mental illness and psychiatric facilities. In Japan, the department name "Department of Psychiatry" (in Japanese, Seishin-ka) itself evokes the lay public's and psychiatric patients' feelings of stigma. This phenomenon may hamper psychiatric treatment of adequate duration and quality. On July 1st, 1999, the Juntendo University Hospital changed the department name from "Department of Psychiatry and Neurology" (in Japanese, Seishin-Shinkei-ka) to Mental Clinic, accompanied by an increased number of new outpatients, as reported previously. In the present study, we turn our attention to the opinions of those patients who have received treatment in the department under both names. Questionnaires asking for their opinions about the department names revealed that the majority have feelings of stigma associated with the name "Department of Psychiatry and Neurology." This result did not correlate with demographic factors or the length of psychiatric treatment. However, those who experienced psychiatric admission were significantly less uncomfortable with the name than those who did not. It was also revealed that the change in the name lessened their feelings of stigma and negative self-image as patients of a general hospital. These results suggest the importance of the name of the psychiatric department in general hospitals, in Japan, from therapeutic, psychosocial and ethical viewpoints.