The effect of the antiprogestin RU 486 on uterine contractility and sensitivity to prostaglandin and oxytocin

Summary. The effect of RU 486, a steroid acting as an antiprogestin at the receptor level, on uterine contractility and sensitivity to the prostaglandin analogue, 16-phenoxy-PGE₂ methyl sulfonylamide (16-phe-noxy-PGE₂) and to oxytocin was studied in 29 women in early pregnancy. Seven untreated women at the same stage of pregnancy served as controls. In the untreated women no spontaneous uterine contractility was recorded and the response to 0.25 mg 16-phenoxy-PGE, was characterized by an increase in uterine tonus with superimposed irregular contractions of low amplitude. Treatment with 25 mg RU 486 twice daily resulted in the appearance of regular uterine contractions at 24 h in two out of five patients and in all patients at 36, 48 and 72 h after the start of RU 486 treatment. The withdrawal of progesterone influence changed the inactive early pregnant uterus into an active organ. Administration of 16-phenoxy-PGE₂ caused an obvious stimulation of both frequency and amplitude of the contractions. In addition, the significantly increased sensitivity to the prostaglandin analogue, but not to oxytocin, was already apparent 24 h after the start of RU 486 treatment. We have previously shown that the addition of one intramuscular injection of 16-phenoxy-PGE₂ on the fourth day of treatment with RU 486 (25 mg twice daily) significantly increased the abortifacient effect of the antiprogestin during early pregnancy. The present study suggests that a shorter treatment may be possible.     

Early exercise testing after coronary care for suspected unstable coronary artery disease -- safety and diagnostic value

The safety of and the diagnostic information provided by a predischargeexercise test performed 2-7 days after admission to the coronarycare unit (CCU) was evaluated in 400 patients less than 65 yearsof age with suspected unstable coronary artery disease, i.e.probable or definite non-transmural myocardial infarction, progressiveangina pectoris or recurring chest pain of recent onset (‘newchest pain’). No serious complications occurred. Signsof ischaemia during exercise tests were more common in olderthan in younger men and more often found in subjects with thanwithout pathological findings in resting ECGs in the CCU. Above45 years of age, more than half of the men with progressiveangina or non-transmural MI had SI depression 2 mm and/or limitingchest pain, whereas men less than 45 years of age had a 10–25%incidence of corresponding findings in the test. In women above55 years with progressive angina or non-transmural MI, 30–35%had ST depression and/or limiting chest pain at the test while20–30% of women below 55 years of age had similar findingsat the test. Beta-adrenoceptor blockade was used by half ofthe patients but did not seem to conceal signs of severe ischaemia.Thus a predischarge exercise test can be performed safely inpatients with suspected unstable coronary artery disease inorder to support or reduce the suspicion of severe disease.     

Predictors of cardiac events in high-risk patients undergoing emergency surgery

Background: The aim of this study was to determine the incidence of myocardial damage and left ventricular myocardial dysfunction and their influence on outcome in high-risk patients undergoing non-elective surgery.
Methods: In this prospective observational study, 211 patients with American Society of Anesthesiologists classification III or IV undergoing emergent or urgent surgery were included.
Troponin I (TnI) was measured pre-operatively, 12 and 48 h post-operatively. Pre-operative N-terminal fragment of B-type natriuretic peptide (NT-proBNP), as a marker for left ventricular systolic dysfunction, was analyzed. The diagnostic thresholds were set to TnI >0.06 μg/l and NT-proBNP >1800 pg/ml, respectively. Post-operative major adverse cardiac events (MACE), 30-day and 3-months mortality were recorded.
Results: Elevated TnI levels were detected in 33% of the patients post-operatively. A TnI elevation increased the risk of MACE (35% vs. 3% in patients with normal TnI levels, P <0.001) and 30-day mortality (23% vs. 7%, P =0.003). Increased concentrations of NT-proBNP were seen in 59% of the patients. Elevated NT-proBNP was an independent predictor of myocardial damage post-operatively, odds ratio, 6.2 [95% confidence interval (CI) 2.1–18.0] and resulted in an increased risk of MACE (21% vs. 2.5% in patients with NT-proBNP ≤1800 pg/ml, P <0.001).
Conclusion: Myocardial damage is common in a high-risk population undergoing unscheduled surgery. These results suggest a close correlation between myocardial damage in the post-operative period and increased concentration of NT-proBNP before surgery. The combinations of TnI and NT-proBNP are reliable markers for monitoring patients at risk in the peri-operative period as well as useful tools in our risk assessment pre-operatively in emergency surgery.     

Prognostic importance of early exercise testing in men with suspected unstable coronary artery disease

In 276 men with suspected unstable coronary artery disease i.e.recurring chest pain of new onset, increasing symptoms of anginalchest pain in formerly stable angina pectoris or suspected non-Q-waveinfarction, an exercise test was performed 2–7 days afteradmission. Coronary events i.e. cardiac death (N=4), Q-waveinfarction (N=11) and coronary artery bypass grafting (N=34),were registered during one year follow-up. The indication forbypass grafting was incapacitating angina pectoris despite medication,and suitable coronary anatomy. Stepwise multiple regressionanalysis showed that S–T segment depression and limitingchest pain were the most important prognostic parameters regardingcoronary events. In patients with S–T segment depression>0.1 mV or limiting chest pain (N=94) the occurrence of Q-wavemyocardial infarction or cardiac death was 10.6% (N=10) comparedto 2.8% (N=5) in patients without these criteria (N=182) (P<0.01).Coronary arterty bypass graft surgery was performed in 33% (N=31)of the group with S–T segment depression >0.1mV orlimiting chest pain but in only 1.7% (N=3) of the other patients(P<0.001). Thus, in patients with suspected unstable coronaryartery disease, whose symptoms and signs of ischaemia are stabilizedby medication, an exercise test can safely be performed aftera few days ambulation in the ward. The early exercise test providesimportant prognostic information regarding the risk for severecoronary events within the next year.     

Prognostic importance of early exercise testing in men with suspected unstable coronary artery disease

In 276 men with suspected unstable coronary artery disease i.e.recurring chest pain of new onset, increasing symptoms of anginalchest pain in formerly stable angina pectoris or suspected non-Q-waveinfarction, an exercise test was performed 2–7 days afteradmission. Coronary events i.e. cardiac death (N=4), Q-waveinfarction (N=11) and coronary artery bypass grafting (N=34),were registered during one year follow-up. The indication forbypass grafting was incapacitating angina pectoris despite medication,and suitable coronary anatomy. Stepwise multiple regressionanalysis showed that S–T segment depression and limitingchest pain were the most important prognostic parameters regardingcoronary events. In patients with S–T segment depression>0.1 mV or limiting chest pain (N=94) the occurrence of Q-wavemyocardial infarction or cardiac death was 10.6% (N=10) comparedto 2.8% (N=5) in patients without these criteria (N=182) (P<0.01).Coronary arterty bypass graft surgery was performed in 33% (N=31)of the group with S–T segment depression >0.1mV orlimiting chest pain but in only 1.7% (N=3) of the other patients(P<0.001). Thus, in patients with suspected unstable coronaryartery disease, whose symptoms and signs of ischaemia are stabilizedby medication, an exercise test can safely be performed aftera few days ambulation in the ward. The early exercise test providesimportant prognostic information regarding the risk for severecoronary events within the next year.