Gastrointestinal bleeding and blood transfusion in the elderly in Japan.

BACKGROUND/AIMS: The incidence of gastrointestinal bleeding (GIB) increases with age and blood transfusion is frequently given for the management of GIB. In this report, we summarized our data of the patients with GIB and discussed the relationship between blood transfusion and age in patients with GIB. METHODOLOGY: The patients were divided into two groups according to age, following elderly (≥75 years old) and younger (<75 years old) group. The causes and clinical outcome (blood transfusions, management) of each group were compared. RESULTS: One-hundred and twenty patients with GIB were hospitalized (59 men, 61 women) with a mean age of 72.0±15.8 years (range 16-96 years old). Thirty-one patients (25.8%) received blood transfusion. The mean pre-transfusion hemoglobin was 6.4±1.2g/dL (elderly 6.3±1.4, younger 6.6±1.0g/dL) and the mean amount of blood transfusion was 2.8±1.6U (elderly 3.2±1.8, younger 2.3±0.9U). The elderly patients using antithrombotic drugs need greater amounts of blood transfusion than younger patients using antithrombotic drugs. The hemoglobin level of the elder patients without antithrombotic drugs was significantly lower than that of younger patients without antithrombotic drugs. CONCLUSIONS: Our data suggest that our blood transfusion strategy seems to be in tolerance level with restrictive blood transfusion strategy.

Gastrointestinal bleeding associated with antithrombotic therapy in the elderly in Japan.

BACKGROUND/AIMS: We summarize data of patients with gastrointestinal bleeding (GIB) and discuss the relationship between antithrombotic drug use and age in patients with GIB. METHODOLOGY: One-hundred and twenty patients with GIB were divided into two groups according to age (=75 years old and <75 years old). The causes and clinical outcome of each group were compared. RESULTS: Forty-two patients received antithrombotic therapy. The main antithrombotic drugs were low dose aspirin (38 patients), ticlopidine (5 patients) and warfarin (3 patients). Compared with younger GIB patients, elderly patients had more coexisting illness and antithrombotic drugs. In patients taking antithrombotic drugs, upper GIB is more frequent than those not taking antithrombotic drugs (p<0.05) and antithrombotic drugs were the risk for GIB from erosive lesions of the esophagus or stomach. In the lower gastrointestinal tract, there was no difference of incidence related to antithrombotic use. The initial endoscopic hemostasis was performed in 14 patients. Eight varices patients received endoscopic vanding and 6 of 43 gastroduodenal ulcer patients had mechanical clip hemostasis. CONCLUSIONS: From our findings, antithrombotic drugs were considered to be a risk for GIB. It might be important to prevent or minimize GIB in elderly patients prescribed antithrombotic drugs.

Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers apoptotic cardiomyopathy.

Loss of cardiomyocytes through programmed cell death is a key event in the development of heart failure, but the inciting molecular mechanisms are largely unknown. We used microarray analysis to identify a genetic program for myocardial apoptosis in Gq-mediated and pressure-overload cardiac hypertrophy. A critical component of this apoptotic program was Nix/Bnip3L. Nix localized to mitochondria and caused release of cytochrome c, activation of caspase-3 and apoptotic cell death, when expressed in HEK293 fibroblasts. A previously undescribed truncated Nix isoform, termed sNix, was not targeted to mitochondria but heterodimerized with Nix and protected against Nix-mediated apoptosis. Forced in vivo myocardial expression of Nix resulted in apoptotic cardiomyopathy and rapid death. Conversely, sNix protected against apoptotic peripartum cardiomyopathy in G(alpha)q-overexpressors. Thus, Nix/Bnip3L is upregulated in myocardial hypertrophy, and is both necessary and sufficient for Gq-mediated apoptosis of cardiomyocytes and resulting hypertrophy decompensation.

Ischemic protection and myofibrillar cardiomyopathy: dose-dependent effects of in vivo deltaPKC inhibition.

To delineate the in vivo cardiac functions requiring normal delta protein kinase C (PKC) activity, we pursued loss-of-function through transgenic expression of a deltaPKC-specific translocation inhibitor protein fragment, deltaV1, in mouse hearts. Initial results using the mouse alpha-myosin heavy chain (alphaMHC) promoter resulted in a lethal heart failure phenotype. Viable deltaV1 mice were therefore obtained using novel attenuated mutant alphaMHC promoters lacking one or the other thyroid response element (TRE-1 and -2). In transgenic mouse hearts, deltaV1 decorated cytoskeletal elements and inhibited ischemia-induced deltaPKC translocation. At high levels, deltaV1 expression was uniformly lethal, with depressed cardiac contractile function, increased expression of fetal cardiac genes, and formation of intracardiomyocyte protein aggregates. Ultrastructural and immunoconfocal analyses of these aggregates revealed focal cytoskeletal disruptions and localized concentrations of desmin and alphaB-crystallin. In individual cardiomyocytes, cytoskeletal abnormalities correlated with impaired contractile function. Whereas desmin and alphaB-crystallin protein were increased approximately 4-fold in deltaV1 hearts, combined overexpression of these proteins at these levels was not sufficient to cause any detectable cardiac pathology. At low levels, deltaV1 expression conferred striking resistance to postischemic dysfunction, with no measurable effects on basal cardiac structure, function, or gene expression. Intermediate expression of deltaV1 conferred modest basal contractile depression with less ischemic protection, associated with abnormal cardiac gene expression, and a histological picture of infrequent cardiomyocyte cytoskeletal deformities. These results validate an approach of deltaPKC inhibition to protect against myocardial ischemia, but indicate that there is a threshold level of deltaPKC activation that is necessary to maintain normal cardiomyocyte cytoskeletal integrity.