In most mammals, labor is heralded by progesterone withdrawal, which is believed to be related to the activation of multiple pathways leading to parturition. In humans, despite no decrease in placental progesterone production, activation of similar pathways preceding labor suggests the presence of an endogenous antiprogestin, which we reasoned might be cortisol, whose secretion from the fetal adrenal rises markedly at the end of human gestation. We report that in primary cultures of human placenta, cortisol is able to compete with the action of progesterone in the regulation of the corticotropin-releasing hormone (CRH) gene. CRH is a peptide highly expressed in human placenta at the end of gestation, which has been suggested to be involved in regulating the timing of parturition. These findings provide a model for functional progesterone withdrawal at the end of human pregnancy, which may be involved in the initiation of labor.

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Sepsis is a major cause of morbidity and mortality in patients with trauma. To elucidate factors that might lead to infection, we studied the epidemiologic characteristics of nosocomial infections in our patient population with trauma. During a 3.5-year period, 2496 patients were entered into our hospital trauma registry and cross-matched with hospital infection control surveillance information. Two hundred twenty-nine patients with trauma and nosocomial infections were identified (9.2%), a figure that was nearly twice the nosocomial infection rate for the general hospital population. The majority of those infected were either orthopedic (51%), general surgical (25%), or neurosurgical (13%) patients. The most common sites of first infection were urinary tract (61%) or respiratory system (14%). Patients developing nosocomial infections were significantly older and had a higher Injury Severity Score than those who did not. Injury site was related to risk of infection with injuries of the spine, chest, and extremity showing the most significant relationship. The length of stay as well as hospital charges were significantly related to the occurrence of infectious complications. By determining the patient with trauma at risk for infection, treatment strategies can be designed to minimize septic complications.

Many human small-cell lung carcinoma culture lines grow as multicellular aggregate spheroids, for which high Ldopa decarboxylase activity is a marker. During the initial cell aggregation and the exponential growth phase, there is a marked increase in ornithine decarboxylase activity and an accumulation of polyamines. a-Difluoromethylornithine, a specific enzyme-activated, irreversible ornithine decarboxylase inhibitor, blocks the increase in ornithine decarboxylase activity and in polyamines and inhibits human small-cell lung carcinoma cell growth. After the onset of a decreased proliferation rate, the multicellular spheroid aggregates become poorly formed, cell loss ensues, and there is a decrease in L-dopa decarboxylase activity. These findings support the hypothesis that ornithine decarboxylase and the polyamines play an essential role not only in the proliferative phase but also in the viability of human small-cell lung carcinoma cells in culture. The results suggest that ai-difluoromethylornithine, a virtually nontoxic compound, may be potentially useful in the therapy of this human tumor.