Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction.

Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha-myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function.

Preoperative identification of patients at risk for delirium after major head and neck cancer surgery.

This study was performed to determine preoperative criteria for identifying patients at risk for delirium after major head and neck cancer surgery. The authors prospectively evaluated 138 consecutive patients undergoing head and neck cancer surgery lasting more than 2 hours at the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, from July 1993 through May 1994. Postoperative delirium developed in 24 of 138 patients (17%; 95% confidence interval 11% to 24%). The strongest univariate predictors of delirium were living alone (P = .005), the American Society of Anesthesiologists class (P = .003), and the preoperative white blood cell count (P < .0001). A predictive model for delirium using five criteria--age of 70 or more years, alcohol abuse, poor cognitive status, poor functional status, and markedly abnormal serum sodium, potassium, or glucose level--stratified the patients into three cohorts with an increasing risk of postoperative delirium (i.e., 9%, 19%, and 25%).

Identifying high-risk patients before head and neck oncologic surgery.

Patients from the Comprehensive Cancer Center of the Arthur G. James Cancer Hospital and Research Institute, Ohio State University, Columbus, who were undergoing major head and neck oncologic surgery were prospectively studied to determine predictors of postoperative medical complications and wound infection. Of 119 patients studied, 28 (24%) had at least one postoperative medical complication. The strongest predictors of medical complication were poor functional capacity as assessed by the Specific Activity Scale questionnaire and alcohol abuse. Thirteen patients (11%) developed wound infections. The strongest predictors of wound infection were an elevated preoperative platelet count and prolonged surgery. Wound infection was the strongest correlate of prolonged hospital stay. These findings suggest that the Specific Activity Scale questionnaire identifies patients at risk for medical complication, that alcohol abuse should be managed aggressively, and that thrombocytosis identifies patients at risk for wound infection.

Nonvenomous snakebite in Massachusetts: prophylactic antibiotics are unnecessary.

STUDY OBJECTIVE: To investigate wound infection in nonvenomous snakebite. DESIGN: Prospective clinical series. SETTING: Massachusetts Poison Control System. PARTICIPANTS: Seventy-two consecutive children and adults with nonenvenomated snakebite wounds. INTERVENTIONS: Patients were examined and advised that there was no published clinical evidence that prophylactic antibiotics were beneficial for nonenvenomated snakebites. They were re-examined five to ten days after the bite. MAIN RESULTS: Four patients used prophylactic antibiotics; 68 did not. There were no wound infections. Plain radiographs revealed a snake tooth fragment in the persistently tender wound of one patient bitten by his pet python. CONCLUSION: Despite reports that pathogenic bacteria can be isolated from snakes' mouths, nonenvenomated snakebites in Massachusetts usually do not require prophylactic antibiotic therapy. Radiography is occasionally indicated for persistently tender wounds inflicted by large snakes.

Research, academic rank, and compensation of women and men faculty in academic general internal medicine.

OBJECTIVE: To evaluate the status of men and women faculty in academic general internal medicine, including their professional training, faculty responsibilities, research performance, academic rank, and compensation, to determine whether systematic differences exist by gender. DESIGN/SETTING: The authors analyzed responses to a 55-part questionnaire sent to all full-time general internal medicine faculty at the major teaching hospitals in the United States. Unadjusted means were generated for men versus women faculty in demographics, training background, hours of work, professional time allocations, institutional support, professional self-assessment, research performance, academic rank, and compensation. Means were recalculated after adjusting for other variables using multivariate methods. RESULTS: The authors found no significant difference in the frequency of fellowship training between men and women faculty. Women and men perform similar professional activities, but even after multivariate adjustment, women devote less time to research and perceive less research skill and institutional support for their research, but have similar numbers of grants, abstracts, and publications in refereed journals and have similar academic ranks. Women faculty, however, receive lower compensation than do men faculty, even after adjustment. CONCLUSION: While the characteristics of men and women faculty are quite similar, including those defining their academic productivity, important differences exist in research time, perceived institutional support, and compensation. These differences cannot be explained by such obvious factors as age differentials, academic rank, or hours of work per week.

Pulmonary "capillary" wedge pressure not the pressure in the pulmonary capillaries.

In 1949, Hellems, Haynes, and Dexter proposed that the pressure in a catheter wedged so as to occlude a pulmonary artery was an "estimate" of the pressure in the pulmonary capillaries. Their report led to the designation of this pulmonary artery wedge pressure as the pulmonary "capillary" wedge pressure. In fact, the pulmonary artery wedge pressure is a distorted measure of the pressure in the pulmonary veins. Usually this pressure differs only slightly from the capillary pressure, and the misconception fostered by the inaccurate name is inconsequential; however, sometimes this misconception leads to errors in diagnosis. This report briefly reviews the early history of pulmonary vascular catheterization, offers an explanation of pulmonary artery wedge pressure, and discusses a disease in which pulmonary artery wedge pressure is normal, even though capillary pressure is elevated.

Poliovirus metabolism and the cytoskeletal framework: detergent extraction and resinless section electron microscopy.

The association of poliovirus metabolism with the cytoskeleton was investigated. Infected cells were extracted by using the nonionic detergent Triton X-100 in the physiological cytoskeleton buffer. The skeletal framework obtained was examined by transmission electron microscopy of resinless sections. The fibers of the framework were grossly distorted in infected cells. No virions or procapsids were seen but many virus-specific spheroidal bodies were associated with the framework. They had a diameter of 40 to 70 nm, were characterized by a dense core and a translucent periphery, and occurred in strings, often near the remnants of flattened vesicles. These spheres may correspond to virus-synthesizing bodies. The metabolism of poliovirus RNA was shown to be associated with the skeletal framework by pulse-labeling cells with [3H]uridine and measuring the RNA retained on the framework. 20S double-stranded RNA, a form of poliovirus RNA found only in the replication complex, was attached to the skeleton throughout a 60-min pulse-label. 35S single-stranded viral RNA, a form found in virions, in polyribosomes, and in the replication complex, appeared first on the framework but after a few minutes was also found in the soluble cytoplasmic phase, encapsidated in virions. In contrast to viral RNA, viral proteins exhibited a varied association with the skeletal framework. Viral proteins were pulse-labeled with [35S]methionine and chased with unlabeled methionine. Although all of the virus-specific proteins were found, to some extent, in the skeletal fraction, the derivatives of P2 (P2-X and P2-5) and a derivative of P3 (P3-2) showed a preferential association with the skeletal framework. Virions and procapsids, on the other hand, were not associated with the cytoskeleton; both they and their component proteins (P1-VP0, P1-VP1, P1-VP2, and P1-VP3) were found dominantly in the soluble cytoplasmic phase. The pathway of poliovirus assembly can be inferred from the above data. It is different from that found previously for the enveloped vesicular stomatitis virus and may be representative of encapsidated cytoplasmic virus assembly.

Protection against dimethylhydrazine-induced adenomatous tumors of the mouse colon by the dietary addition of an extract of soybeans containing the Bowman-Birk protease inhibitor.

Dimethylhydrazine (DMH) induces adenocarcinomas of the colon and rectum in rodents; this animal cancer model system is thought to closely resemble human colorectal cancer. An extract of soybeans containing the Bowman-Birk protease inhibitor added to the diet of DMH-treated mice resulted in a significant suppression of adenomatous tumors of the colonic mucosa. Non-treated mice maintained on the same diet for most of their natural life-span (1.5 years) showed no observable health problems.