Biomedical subjects
D Rieves
Publications and source records attributed to D Rieves.
Clinical trial (GUSTO-1 and INJECT) evidence of earlier death for men than women after acute myocardial infarction.
Epidemiologic studies of acute myocardial infarction (AMI) have described gender differences in the time of death after infarction, with greater numbers of men dying before hospitalization than women. However, in controlled, hospital-based clinical trials, women die at higher rates than men. We hypothesized that evidence of a gender difference in the time of death following AMI may be found in controlled studies of hospitalized AMI patients. We performed a retrospective analysis of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) and International Joint Efficacy Comparison of Thrombolytics (INJECT) trial databases using logistic regression modeling and time-to-death analyses. The age-adjusted female-to-male odds ratio for mortality was 1.4 (95% confidence interval 1.3 to 1.5) in GUSTO-1 and 1.5 (95% confidence interval 1.3 to 1.8) in INJECT. GUSTO-1 showed that among patients dying during the first 24 hours after symptom onset, men died an average of 1.7 hours earlier than women (p<0.001). This difference was due to earlier deaths among men < or =65 years of age. Furthermore, in GUSTO-1, the analysis of time to death in hour increments demonstrated that greater proportions of men died at earlier time points than women and a disproportionate number of early deaths occurred among younger men than among women of any age or older men. In INJECT, where time to death could only be analyzed in 1-day increments, no gender differences were evident. These results raise the possibility that the pattern of earlier death for men in thrombolytic clinical trials represents the continuation of a gender-specific mortality pattern that began before hospitalization. The death of a disproportionate number of men before hospitalization may represent an inherent gender bias for clinical studies enrolling only hospitalized patients. More high-risk men would be excluded from these studies than women because of death before hospitalization. Hence, gender comparisons of in-hospital mortality rates may artificially inflate values for women.
Use of a monoclonal antibody enzyme-linked immunosorbent assay to measure human respiratory glycoprotein production in vitro.
High-molecular-weight glycoprotein from human airway cultures was used to generate murine monoclonal antibodies, one of which recognizes a high-molecular-weight, hyaluronidase-resistant glycoprotein localized by immunofluorescent microscopy and immunogold electron microscopy to the secretory granules of human airway submucosal gland mucous cells and goblet cells. This monoclonal antibody was used to develop an enzyme-linked immunosorbent assay (ELISA) that was adapted to the study of respiratory glycoprotein secretion from human airways in vitro. Using the assay, the effect of a known mucus secretagogue, the cholinergic agonist methacholine, was studied on explant cultures of tissue from human bronchus or from human nasal mucosa. In studies of human bronchus explants, methacholine, 100 and 10 microM, stimulated increased secretion of respiratory glycoprotein (RGP) by 109 +/- 8% (n = 14; P less than 0.001) and 96 +/- 14% (n = 9; P less than 0.001), respectively, above control values. In studies of human nasal turbinate mucosal explants, methacholine, 100 and 10 microM, stimulated increased secretion of RGP by 75 +/- 28% (n = 7; P less than 0.01) and 70 +/- 21% (n = 4; P less than 0.01) above control values. An ELISA for the measurement of RGP secretion may provide a sensitive and more specific method for the performance of in vitro studies of RGP secretion from human tissues.
Tularemia and rhabdomyolysis.
Rhabdomyolysis as a complication of tularemia occurred in four patients in Tennessee over a four-year period. All patients were severely ill and had renal failure. Tularemia was not suspected initially in any of these patients. One patient died of complications of rhabdomyolysis. At autopsy, multiple abscesses were present within skeletal muscle, suggesting that rhabdomyolysis resulted from direct muscle involvement with Francisella tularensis. Tularemia should be considered in the differential diagnosis of patients with an acute febrile illness and rhabdomyolysis. Conversely, in patients with acute tularemia, the possibility of rhabdomyolysis should be entertained early, especially in those with evidence of myoglobinuria and/or impaired renal function.