Search

Purpose This paper aims to study the problem of the steady plane oblique stagnation-point flow of an electrically conducting Newtonian fluid impinging on a heated vertical sheet. The temperature of the plate varies linearly with the distance from the stagnation point. Design/methodology/approach The governing boundary layer equations are transformed into a system of ordinary differential equations using the similarity transformations. The system is then solved numerically using the “bvp4c” function in MATLAB. Findings An exact similarity solution of the magnetohydrodynamic (MHD) Navier–Stokes equations under the Boussinesq approximation is obtained. Numerical solutions of the relevant functions and the structure of the flow field are presented and discussed for several values of the parameters which influence the motion: the Hartmann number, the parameter describing the oblique part of the motion, the Prandtl number (Pr) and the Richardson numbers. Dual solutions exist for several values of the parameters. Originality value The present results are original and new for the problem of MHD mixed convection oblique stagnation-point flow of a Newtonian fluid over a vertical flat plate, with the effect of induced magnetic field and temperature.

The comparison of hemodilution at the end of surgery is of limited use as it represents only a snapshot of a dynamic phenomenon. This study was undertaken to compare the perioperative hemoglobin curves of isolated coronary artery bypass grafting performed with minimized extracorporeal circulation, traditional cardiopulmonary bypass, and off-pump technique. The propensity score method was used to select three groups of patients, homogenous regarding preoperative and operative data, who underwent isolated coronary artery bypass grafting. A generalized linear mixed model was used for estimating differences in perioperative hemoglobin trends among groups. The three groups were each composed of 50 patients with no differences in demographic data, preoperative risk profile, preoperative hemoglobin, or type of surgery. There was no significant difference in major postoperative complications. The pattern of the hemodilution curves was similar in patients operated with mini-circuit and off-pump technique (P > 005). Mini-circuit led to a 3.1 ± 11.9% hemoglobin reduction, which was similar to the off-pump group (1.6 ± 8.9%, P = 0.99 at ANOVA) and significantly different from the standard extracorporeal circuit group (16.0 ± 10.3%, P < 0.001 at ANOVA). The generalized linear mixed model determined that the standard circuit was the only independent predictor for increased hemodilution. Its effect on hemodilution was time-dependent and the slope of the hemoglobin curve was more pronounced between systemic heparinization and the end of surgery. Perioperative hemoglobin trends of patients who underwent myocardial revascularization with mini-circuit were similar to those of off-pump surgery and significantly less pronounced than those of standard extracorporeal circulation.

Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)–DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA–DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA–DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01–2.26). MDA–DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16–2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA–DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04–2.20) and 1.45 (1.02–2.07)). Lung cancer cases with levels of MDA–DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65–9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency.

The comparison of hemodilution at the end of surgery is of limited use as it represents only a snapshot of a dynamic phenomenon. This study was undertaken to compare the perioperative hemoglobin curves of isolated coronary artery bypass grafting performed with minimized extracorporeal circulation, traditional cardiopulmonary bypass, and off-pump technique. The propensity score method was used to select three groups of patients, homogenous regarding preoperative and operative data, who underwent isolated coronary artery bypass grafting. A generalized linear mixed model was used for estimating differences in perioperative hemoglobin trends among groups. The three groups were each composed of 50 patients with no differences in demographic data, preoperative risk profile, preoperative hemoglobin, or type of surgery. There was no significant difference in major postoperative complications. The pattern of the hemodilution curves was similar in patients operated with mini-circuit and off-pump technique (P005). Mini-circuit led to a 3.1 ± 11.9% hemoglobin reduction, which was similar to the off-pump group (1.6 ± 8.9%, P = 0.99 at ANOVA) and significantly different from the standard extracorporeal circuit group (16.0 ± 10.3%, P0.001 at ANOVA). The generalized linear mixed model determined that the standard circuit was the only independent predictor for increased hemodilution. Its effect on hemodilution was time-dependent and the slope of the hemoglobin curve was more pronounced between systemic heparinization and the end of surgery. Perioperative hemoglobin trends of patients who underwent myocardial revascularization with mini-circuit were similar to those of off-pump surgery and significantly less pronounced than those of standard extracorporeal circulation.

Background. Interleukin-2 (IL-2) has shown antitumor activity in some neoplasms, such as melanoma and renal carcinoma, but toxicity derived from bolus administration is significant, particularly at the cardiorespiratory level. Methods. To test feasibility, antitumor activity, pulmonary and systemic immunologic effects, and pulmonary function changes of continuous-infusion recombinant IL-2 given to patients with non-small cell lung cancer, eleven subjects with Stage III-IV disease were treated in a standard pulmonary medicine unit with a dose of 18 million IU/m2/day from day 1 to day 13 with 1-day rest on day 7. A second induction course was given after a 3-week rest. In patients with nonprogressive disease, four maintenance courses of 6 days' duration at the same dose were planned. Immunologic tests, including lymphocyte phenotype analysis and assays for the detection of tumor necrosis factor (TNF) and of anti-IL-2 antibodies, were performed before and after treatment in serum and bronchoalveolar lavage fluid (BAL). Cardiopulmonary function tests, including spirometry, arterial blood gas analysis, diffusion capacity, and echocardiography, were obtained before, during, and after treatment. Results. Twenty-one cycles (15 induction courses plus 6 maintenance courses) were administered. No patient was able to complete the six planned courses, and only 3 patients entered the maintenance phase. Reasons for discontinuation included progressive disease in five cases, toxicity in three cases, and patient request in three cases. The most common side effects were fever, hypotension, oliguria, and elevated serum creatinine and liver enzyme levels. No patient required intubation or intensive care. No objective response was seen, and the median survival time was 10 months. Lymphocytosis and eosinophilia were observed in all patients. Surface marker analysis revealed a statistically significant increase in the percentage of CD3+, CD4+, CD25+ and DR+ cells in peripheral blood. Lymphoid cells derived from BAL disclosed an increased natural killer activity after IL-2 treatment, and TNF was increased in BAL fluid. Pulmonary function tests evidenced an increased alveolararterial difference for oxygen allied with a decrease of forced expiratory volume in 1 second, forced vital capacity, and carbon monoxide transfer coefficient consistent with a significant, albeit not clinically relevant, interstitial lung defect. Conclusion. Continuous-infusion IL-2 is feasible in patients with advanced lung cancer even outside an intensive care unit, but overall compliance is poor. Although clinical pulmonary toxicity is negligible, small but statistically significant alterations of the pulmonary function are evident. In addition, this regimen produces a significant activation of the immune system at the pulmonary level. Cancer 1994; 73:1353–60.

The role of CYP1A1, GSTM1, GSTT1, EPHX1, and NAT2 genotypes in susceptibility to malignant mesothelioma (MM) was compared in two case-control studies, previously conducted in two countries where different types of asbestos fibers have been used [Hirvonen et al., 1995. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 55, 2981-2983; Hirvonen et al., 1996. Glutathione S-Transferase and N-Acetyltransferase genotypes and asbestos-associated pulmonary disorders. J. Natl. Cancer Inst.88, 1853-1856; Neri et al., 2005. Pleural malignant mesothelioma, genetic susceptibility and asbestos exposure. Mutat. Res. 592, 36-44]. Fifty-seven asbestos-exposed MM patients and 255 controls were recruited in Italy, 48 cases and 121 controls in Finland. In order to make the two studies comparable, they have been updated and new genotyping analyses have been performed. The NAT2 fast acetylator and EPHX1 low-activity genotypes were positively associated with MM in the Italian study, while they were negatively associated with this malignancy in the Finnish one. A combined significant effect was also observed in the Italian study for the NAT2 fast acetylator and EPHX1 low-activity genotypes, while this combination was protective in the Finnish study. Combination of NAT2 fast acetylator and GSTM1 null genotype posed a significantly increased risk of MM in the Italian, but not in the Finnish study. The opposite results obtained in Finland and Italy may be ascribed to random chance, but a role may be hypothesized for the fact that different types of asbestos have been used in the two countries. This work was supported by the EU funded ECNIS network of excellence, by the Italian Ministry of Health and by “Fondazione ONLUS-Buzzi”. The work of MN was partially supported by AIRC (Italian Association for Cancer Research).

Pleural malignant mesothelioma (MM) is a rare but extremely aggressive cancer. The limited impact of standard therapeutic treatments on survival rates makes the identification of factors that increase the individual risk a leading priority. The high proportion of cases explained by exposure to asbestos has guided intervention policies to an effective ban of this compound from our environment. However, MM cannot be solely attributed to this agent, and the role of predisposing factors and their interaction with asbestos exposure is increasingly studied. The role of mEH, GSTM1, GSTT1, NAT2, and CYP1A1 genotypes in modulating susceptibility to MM was examined in a case-control study of 80 subjects with a confirmed diagnosis of MM and 255 controls. Subjects with low mEH activity showed a significantly increased risk of MM (OR, 2.51; 95% CI, 1.11-5.68). The association was stronger in the group with low asbestos exposure (OR, 7.83; 95% CI, 0.98-62.60). A significant increased risk of MM was also found in NAT2 fast acetylators (OR, 1.74; 95% CI, 1.02-2.96). The presence of synergisms between genotypes, i.e., mEH and NAT2 (LRT for heterogeneity p0.023), mEH and GSTM1 (LRT p0.061), and NAT2 and GSTM1 (LRT p0.049), combined with the interaction observed with exposure to asbestos, suggests the presence of gene-environment and gene-gene interactions in the development of MM, although the size of the study group does not allow to draw clearcut conclusions. Since genetic polymorphisms can also modify the extent of genetic damage occurring in subjects exposed to carcinogens, we measured the frequency of micronuclei in peripheral blood lymphocytes of a subgroup of MM cases. The limited number of cases (28) did not allow to observe significant effects. In conclusion, these results strengthen the hypothesis that individual susceptibility to MM can be modulated by the interaction between polymorphic genes involved in the metabolism and the intensity of asbestos exposure.

This study assesses the feasibility and toxicity of adoptive immunotherapy with tumor infiltrating lymphocytes and recombinant interleukin-2 in 29 patients who underwent resection for stage III non-small-cell lung cancer. In five patients cultures yielded no growth of tumor infiltrating lymphocytes. In the remaining 24 patients (stage IIIa, 14 cases; stage IIIb, 10 cases) tumor infiltrating lymphocytes were in vitro expanded from surgically obtained tissue samples, including samples from both the tumor and surrounding lung. A number of tumor infiltrating lymphocytes, ranging from 4 to 70 billion cells, were reinfused intravenously 4 to 6 weeks after operation. Interleukin-2 was administered subcutaneously at escalating doses for 2 weeks and then at reduced doses for 2 to 3 months. Median survival was 14 months, and the 2-year survival was 40%. Three patients remain alive and disease-free at more than 2 years after operation. Two of these patients did not have complete resection at thoracotomy. Multivariate analysis showed no correlation between the factor of incomplete resection and survival. Intrathoracic recurrence without concomitant distant failure was documented in two patients only and none of the patients with incomplete resection (12 cases) had relapse within the thorax. The present experience demonstrates that adoptive immunotherapy may be applied with safety in patients operated on for stage III non-small-cell lung cancer and suggests that it can be useful, notably in patients with locally advanced disease. (J THORAC CARDIOVASC SURG 1995;109:1212-7)

The aim of this study was to compare the effect of intermittent antegrade warm blood cardioplegia and intermittent antegrade cold blood cardioplegia on myocardial metabolism and free radical generation of the ischemic-reperfused human myocardium. Thirty patients undergoing mitral valve procedures were randomly allocated to two groups: group 1 (15 patients) received warm blood cardioplegia and group 2 (15 patients), cold blood cardioplegia. Myocardial metabolism was assessed before aortic clamping, 1 minute after crossclamp removal, and after 20 minutes of reperfusion, by collecting blood simultaneously from the radial artery and coronary sinus. All samples were analyzed for lactate, creatine kinase, reduced and oxidized glutathione, ascorbic acid, fluorescent products of lipid peroxidation, and leukocyte activation (elastase). In all patients, early reperfusion was associated with significant coronary sinus lactate release. In group 2, but not in group 1, significant coronary sinus release of reduced and oxidized glutathione, fluorescent products of lipid peroxidation, and creatine kinase was also found; moreover, arterial-coronary sinus difference of ascorbic acid content was increased only in group 2, suggesting a transmyocardial consumption of this antioxidant vitamin. After 20 minutes of reperfusion, coronary sinus lactate release was no longer present in group 1, whereas significant production was still evident in group 2. In this group, significant coronary sinus release of fluorescent products of lipoperoxidation and reduced and oxidized glutathione was also observed at this time. No significant release of elastase from the coronary sinus was noted in the two groups throughout the study. The left ventricular stroke work index measured at the end of the study indicated a better functional recovery in group 1 than in group 2. In conclusion, intermittent antegrade warm blood cardioplegia protects the myocardium from ischemia-reperfusion injury better than intermittent antegrade cold blood cardioplegia; this phenomenon may be partly due to the decreased tissue oxidant burden mediated by intermittent warm blood cardioplegia. (J THORAC CARDIOVASC SURG 1995;109:787-95)

Intermittent antegrade warm blood cardioplegia has been used routinely at our institution over the last 3 years. We report here a comparison between the first 250 consecutive patients undergoing elective coronary artery bypass grafting in which intermittent antegrade warm blood cardioplegia was used (group A) and the last 250 consecutive patients who received intermittent antegrade cold blood cardioplegia, during bypass grafting (group B). There were no differences in sex, age, number of grafts, and functional status between the two groups; left ventricular ejection fraction was lower in group A. The overall mortality rate in group A was 0.8% versus 3.6% in group B (p0.05). There was no in-hospital mortality among high-risk patients (ejection fractionor = 0.35) in group A (0/53) versus two deaths in group B (2/28) (p0.05). No patient in group A needed circulatory assistance; 4 patients in group B received intraaortic balloon pumping. Only 1 patient in group A required inotropic support versus 20 patients in group B (p0.0005), and 5 patients in group A received lidocaine hydrochloride for ventricular arrhythmias versus 18 in group B (p0.01). The rates of myocardial infarction and stroke were not different between the two groups. The peak concentration of the myocardial-specific isoenzyme of creatine kinase were higher in group B in absolute value (51 +/- 30 IU/L) than in Group A (38 +/- 38 IU/L) (p0.0005) and in percent of total creatine kinase (8.2% +/- 4.1% versus 6.2% +/- 2.9%, respectively).