Single extreme low dose/low dose rate irradiation causes alteration in lifespan and genome instability in primary human cells.

To investigate the long-term biological effect of extreme low dose ionising radiation, we irradiated normal human fibroblasts (HFLIII) with carbon ions (290 MeV u(-1), 70 keV microm(-1)) and gamma-rays at 1 mGy (total dose) once at a low dose rate (1 mGy 6-8 h(-1)), and observed the cell growth kinetics up to 5 months by continuous culturing. The growth of carbon-irradiated cells started to slow down considerably sooner than that of non-irradiated cells before reaching senescence. In contrast, cells irradiated with gamma-rays under similar conditions did not show significant deviation from the non-irradiated cells. A DNA double strand break (DSB) marker, gamma-H2AX foci, and a DSB repair marker, phosphorylated DNA-PKcs foci, increased in number when non-irradiated cells reached several passages before senescence. A single low dose/low dose rate carbon ion exposure further raised the numbers of these markers. Furthermore, the numbers of foci for these two markers were significantly reduced after the cells became fully senescent. Our results indicate that high linear energy transfer (LET) radiation (carbon ions) causes different effects than low LET radiation (gamma-rays) even at very low doses and that a single low dose of heavy ion irradiation can affect the stability of the genome many generations after irradiation.

COPD may increase the incidence of refractory supraventricular arrhythmias following pulmonary resection for non-small cell lung cancer.

PURPOSE: This study investigated the association of COPD and postoperative cardiac arrhythmias, specifically supraventricular tachycardia (SVT), as well as mortality in patients undergoing pulmonary resection for non-small cell lung cancer (NSCLC). METHODS: A retrospective chart review of 244 patients who had undergone lung resection for NSCLC at Indiana University Hospital between 1992 and 1997 was undertaken. COPD, which was defined as an FEV(1) of < or = 70% predicted and an FEV(1)/FVC ratio of < or = 70% based on the results of a preoperative pulmonary function test (PFT), was diagnosed in 78 of the 244 patients (COPD group). In the remaining 166 patients, the results of preoperative PFTs did not meet these criteria (non-COPD group). Both groups were otherwise well-matched with respect to multiple variables, including age, comorbid conditions, extent of pulmonary resection, and final pathologic stage. The incidence of cardiac arrhythmias and operative mortality were compared between the two groups using univariate and multivariate analysis. RESULTS: Seventy-six patients (31.9%) experienced new onsets of postoperative SVT, with 58 of these patients (76.3%) demonstrating atrial fibrillation. The COPD group had a 58.7% incidence of SVT (n = 44) compared to a 27.0% incidence (n = 44) in the non-COPD group (p < 0.0 0 1). Moreover, following initial digoxin therapy, the COPD group required more second-line antiarrhythmic therapy than did the non-COPD group (66.7% vs 37.8%, respectively; p = 0.0 03). Overall, there were 16 operative deaths (6.6%), and the mortality rate was significantly higher in the COPD group (14.1%) than in the non-COPD group (3.0%; p = 0.0 04). Patients who developed SVT had a significantly longer hospital course than did patients who did not (p < 0.0001). Thirteen of the 16 patients who died experienced SVT; however, SVT was not an independent risk factor for death. Finally, of the 19 variables evaluated, major resection (ie, pneumonectomy and bilobectomy) and COPD were identified as independent risk factors for the development of cardiac arrhythmias (p = 0.0 033 and p = 0.0 009, respectively). CONCLUSION: Patients with COPD, as defined by the results of preoperative PFTs, are at significantly higher risk for SVT, and in particular SVT refractory to digoxin, following pulmonary resection for NSCLC. Although SVT was not an independent risk factor for death, a significantly longer hospitalization was observed.

Pulmonary hypertension after operations for congenital heart disease: analysis of risk factors and management.

BACKGROUND: Management of pulmonary hypertension, a potentially fatal complication of operations to correct congenital heart disease, has evolved through the last 15 years. Monitoring of pulmonary arterial pressure and mixed venous saturation became available, and prophylactic use of alpha-blockers and other vasodilators increased. This study examines risk factors for morbidity and mortality from pulmonary hypertension after operations to correct congenital heart disease and evaluates the impact of management changes on outcomes. METHODS: By means of multivariable logistic regression analysis, 880 high-risk patients with congenital heart disease (of 2484 patients undergoing cardiopulmonary bypass between January 1980 and December 1994) were analyzed to determine which were at risk for postoperative pulmonary hypertension and its associated morbidity and mortality. RESULTS: Patients with atrioventricular canal (n = 182), truncus arteriosus (n = 47), total anomalous pulmonary venous connection (n = 90), transposition of great arteries (n = 97), hypoplastic left heart syndrome (n = 50), and ventricular septal defect (n = 414) demonstrated a higher risk of postoperative pulmonary hypertension. By multivariable logistic regression, preoperative pulmonary hypertension (p < 0.0001), absence of mixed venous saturation monitoring (p < 0.0001), and absence of prophylactic alpha-blockade (p = 0.0004) significantly increased postoperative pulmonary hypertension. Preoperative pulmonary hypertension (p < 0.001) and absence of prophylactic alpha-blockers (p = 0.0004) were significant risk factors for in-hospital death related to pulmonary hypertension. Repair at older age (except in the case of total anomalous pulmonary venous connection) was a significant risk for postoperative pulmonary hypertension (p = 0.03). CONCLUSION: Mixed venous saturation monitoring and alpha-receptor blockade reduced the incidence of pulmonary hypertension after operations for congenital heart disease. Early definitive repair reduced morbidity and mortality from postoperative pulmonary hypertension.

Adjuvant activity of the cell wall of Bifidobacterium infantis for in vivo immune responses in mice.

We examined the adjuvant activity of the Bifidobacterial Cell Wall preparation (WPG) for in vivo immune responses in mice. We studied three classical immune responses, which are thought to be T-cell mediated responses, to evaluate the adjuvant activity of WPG. The delayed type hypersensitivity (DTH) responses of sheep blood red cell (SRBC)-sensitized mice were significantly augmented by WPG, although the enhancement varied with the timing, route and dosage of injection. The adjuvant activity of WPG was also confirmed by using a glutaraldehyde treated- and Concanavalin A associated- tumor vaccine (G-Con A tumor vaccine) system. BALB/c mice sensitized with G-Con A tumor vaccine and WPG improved synergistically in survival time and cure rate compared with those given G-Con A vaccine alone. Spleen cells of Meth A tumor-bearing mice induced antitumor neutralizing activity with the growth of tumor but the activity declined and disappeared at the late stage of tumor growth (over 28 days after tumor transplantation). On the other hand, antitumor neutralizing immunity was prolonged for as long as 33 days in mice inoculated with Meth A tumor and WPG. The requirement of a T-cell subpopulation in the spleen cells of tumor plus WPG treated mice was confirmed using anti-Thy 1.2 antiserum + complement to deplete them. The adjuvant activities of the Bifidobacterial cell wall demonstrated by the in vivo immune responses predict that Bifidobacteria may play a role as an immunomodulator in human and animal intestines.