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The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients with primary adenocarcinoma of the lung. K-ras mutations were detected in the primary tumor using an allele-specific ligation assay. Ninety-two of the 106 patients (87%) with lung adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K-ras mutations were detected in 40 of 106 tumors (38%) and were significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy. Cancer 2001;92:1525–30. © 2001 American Cancer Society.

Because of divergent conclusions in the literature regarding the effects of temperature on end-diastolic compliance in the canine left ventricle (LV), pressure-volume relationships at normothermia and hypothermia (28° C) were studied with two-dimensional ultrasound in nine dogs on cardiopulmonary bypass (open pericardium) over a range of left ventricular end-diastolic pressure (LVEDP) from 0 to 22 mm Hg. Three perpendicular echocardiographic sections were used with Simpson's rule to measure LV volume and mass at end-diastole for each level of LVEDP. Temperature was varied between 37° and 28° C by systemic cooling, and heart rate was allowed to slow spontaneously with temperature reduction. There was no change in left ventricular end-diastolic pressure-volume (LVEDP-LVEDV) relationships at lower temperature provided that ventricular relaxation was complete at end-diastole. In addition, serial postmortem pressure-volume curves carried out by direct saline infusion into sealed ventricles at 38° and 28° C in three additional dogs demonstrated no temperature effects on postmortem LV compliance. Postmortem mass correlated well with echocardiographically determined LV mass, which showed a significant increase during the period of cardiopulmonary bypass, correlating with the development of myocardial edema. In summary, there appears to be no effect of moderate hypothermia on LVEDP-LVEDV relationships, provided the heart is in true diastasis at end-diastole. In addition, echocardiographic techniques can be used to study LV mass change on cardiopulmonary bypass.

• Adenocarcinoma of the esophagus is no longer rare and is treated by resection. To determine whether the approach used for resection influences outcome, we studied 88 patients who underwent resection; 14 had stage I or II disease, 74 had stage III, and 40 had stage IV. One third of those with Barrett's esophagus were noted on screening endoscopy to have potentially curable disease; the others were diagnosed with stage III or IV disease. Transhiatal esophagectomy was performed in 63 patients; 24 patients underwent transthoracic esophagectomy. We found no difference in survival or morbidity between transhiatal and transthoracic esophagectomy. Overall 5-year survival for stage I and II disease was 86%. For stage III and IV disease, 5-year survival was 14.5%. Aggressive surveillance of Barrett's esophagus facilitates the discovery of early disease. Esophagectomy for adenocarcinoma can result in cure of early cancers and improved palliation of more advanced disease.(Arch Surg. 1992;127:951-955)

Quantitative two-dimensional echocardiography was evaluated in 39 open-chest dogs placed on cardiopulmonary bypass. The correlation coefficient of left ventricular end-diastolic volume against postmortem pressure-volume curves was r = 0.89 to 0.93 (347 measurements in 15 dogs, 0 to 24 mm Hg). Ejection fraction was validated against roller pump flow and echo left ventricular end-diastolic volume (r = 0.83, n = 13). Left ventricular mass in vivo was compared with postmortem left ventricular mass (r = 0.81 in 21 early studies, r = 0.91 in 10 later studies with updated equipment) and was found to increase with ischemic injury as well as cardiopulmonary bypass with hemodilution. Left ventricular mass increased (p < 0.001) from 119 ± 5 (standard error of the mean) to 138 ± 6 gm (n = 23) after 2½ hours on cardiopulmonary bypass and moderate hemodilution. With the addition of ischemic arrest, left ventricular mass increased from 119 ± 7 to 148 ± 11 gm (p < 0.01, n = 8), and myocardial water content increased by 2.0% ± 0.4%, which accounted for at least 65% of the observed mass change. Mean left ventricular wall thickness increased from 13.8 to 15.5 mm (p = 0.02) after ischemia. Ventricular shape became more spherical with increasing left ventricular end-diastolic pressure. We conclude that two-dimensional echocardiography can be reliably used for accurate, serial measurements in physiological studies. The demonstrated variability in left ventricular mass is important, yet frequently ignored. Recognizing left ventricular mass changes may facilitate the detection of myocardial injury reflected as edema.

In 31 dogs chronically beta blocked with oral propranolol (12 to 14 mg/kg/day), glucagon (20 üg/kg) and combined dopamine (10 üg/kg/min) and isoproterenol (0.2 üg/kg/min) were given intravenously and tested for hemodynamic efficacy. Dogs were divided into four groups. Basal hemodynamics were obtained in Group I (n = 8) without cardiopulmonary bypass. In Group II (n = 8), hemodynamics were studied after 15 minutes of global ischemia during cardiopulmonary bypass. In Group III (n = 8), hemodynamics were studied after regional ischemia produced by ligation of the proximal left anterior descending coronary artery. In Group IV (n = 7), myocardial oxygen consumption and left ventricular mechanics were studied before and after 1 hour of cardiopulmonary bypass. Our results indicate the following: (1) Dopamine-isoproterenol improves hemodynamics in basal, post-global ischemic, and post-regional ischemic states. Glucagon improves hemodynamics either insignificantly or to a lesser extent than dopamine-isoproterenol. Furthermore, glucagon produces a larger increase in heart rate, which is not desirable. (2) Both dopamine-isoproterenol and glucagon increase myocardial oxygen consumption in comparison with control.