Differentiation therapy.
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Antineoplastic Agents↗
Biomedical subjects
C S Freeman
Publications and source records attributed to C S Freeman.
Surgical coronary revascularization in survivors of prehospital cardiac arrest: its effect on inducible ventricular arrhythmias and long-term survival.
In a selected subgroup of 50 survivors of cardiac arrest, the impact of surgical myocardial revascularization on inducible arrhythmias, arrhythmia recurrence and long-term survival was examined. The effects of several clinical, angiographic and electrophysiologic variables on arrhythmia recurrence and survival were also analyzed. All patients had a prehospital cardiac arrest and severe operable coronary artery disease and underwent myocardial revascularization. Preoperative electrophysiologic study was performed in 41 patients; 33 (80%) had inducible ventricular arrhythmias. Of 42 patients studied off antiarrhythmic drugs postoperatively, 19 (45%) had inducible ventricular arrhythmias. Thirty patients with inducible arrhythmias preoperatively underwent postoperative testing off antiarrhythmic drugs; arrhythmia induction was suppressed in 14 (47%). By multivariate analysis, the induction of ventricular fibrillation at the preoperative electrophysiologic study was the only significant predictor of induced ventricular arrhythmia suppression by coronary surgery (p less than 0.001). Inducible ventricular fibrillation was not present postoperatively in any of the 11 patients who manifested this arrhythmia preoperatively. In contrast, inducible ventricular tachycardia persisted in 80% of patients in whom preoperative testing induced this arrhythmia. Patients were followed up for 39 +/- 29 months. There were four arrhythmia recurrences; one was fatal. There were three nonsudden cardiac deaths and three noncardiac deaths. By life-table analysis, 5 year survival, cardiac survival and arrhythmia-free survival rates were 88%, 98%, and 88%, respectively. Depressed left ventricular ejection fraction and advanced age were predictive of death (p = 0.015 and 0.026, respectively) and cardiac death (p = 0.037 and 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Arrhythmias, Cardiac↗
Cardiac conduction abnormalities during percutaneous balloon mitral or aortic valvotomy.
To evaluate the electrophysiologic changes in the cardiac conduction system that occur during percutaneous mitral or aortic balloon valvotomy, we prospectively studied the conduction system in 19 patients (10 mitral, 8 aortic, and 1 both) undergoing this procedure. A His bundle electrogram was recorded in all patients, and when sinus rhythm was present, the atrioventricular (AV) node effective refractory period was measured. Holter monitoring was performed during and for 24 hours after the procedure. Follow-up electrocardiograms (ECG) were available in 11 patients 2.3 +/- 1.5 months after the procedure. The AV node effective refractory period before (276 +/- 86 msec) and after valvotomy (298 +/- 85 msec) were not significantly different. The maximum His-Purkinje conduction time (HV interval) observed during valvotomy (66 +/- 20 msec) was significantly longer (p less than 0.01) than that measured before (57 +/- 10 msec) or after (60 +/- 18 msec) valvotomy. The mean HV intervals before and after valvotomy were not significantly different. The mean QRS complex duration increased from 95 +/- 28 to 112 +/- 28 msec during valvotomy and remained significantly prolonged (109 +/- 26 msec) 24 hours after the procedure (p less than 0.01). A new intraventricular conduction defect (QRS complex duration greater than 100 msec) or bundle branch block occurred in five of 13 patients who had normal QRS duration before the procedure. The change in HV interval did not correlate with the change in QRS complex duration. In four patients, the newly acquired intraventricular conduction defect was still present on follow-up ECG tracing. Complete heart block was not observed in any patient.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Prediction of successful suppression of sustained ventricular tachyarrhythmias by serial drug testing from data derived at the initial electrophysiologic study.
This study investigated whether data available after the initial electrophysiologic study in patients with sustained ventricular tachyarrhythmia could identify those patients in whom serial drug testing is likely to be efficacious. One hundred six patients with inducible sustained ventricular tachyarrhythmia, whose initial study included short-term drug testing with intravenous procainamide, were evaluated. The baseline arrhythmia induced (in the absence of all antiarrhythmic drugs) was monomorphic tachycardia with a cycle length greater than 200 ms in 81 patients and ventricular flutter or fibrillation in the remaining 25 patients. After intravenous infusion of procainamide (1,250 +/- 300 mg), a ventricular tachyarrhythmia could still be induced in 80 patients during testing with up to three extrastimuli. Serial drug testing with one to four trials of oral conventional and investigational agents was then undertaken. Evaluation of 15 clinical, hemodynamic and electrophysiologic variables by stepwise logistic regression identified two independent predictors of successful response to oral antiarrhythmic drugs: 1) noninducibility of ventricular tachycardia after intravenous procainamide (p less than 0.001), and 2) left ventricular ejection fraction greater than or equal to 40% (p less than 0.05). Subgroup analysis combining each of these variables identified patients with a high, intermediate or low probability of finding a successful oral drug regimen. Patients whose arrhythmia was suppressed by intravenous procainamide had a 100% likelihood (if left ventricular ejection fraction was greater than or equal to 40%) or an 87% likelihood (if ejection fraction was less than 40%) of responding to an oral regimen.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Progesterone is not essential to the differentiative potential of mammary epithelium in the male mouse.
In pursuit of a model system in which to determine whether or not exposure to progesterone is necessary for mammary epithelial cells to develop their differentiative potential, we explored hormone-dependent growth of the mammary epithelial rudiment in adult male mice. Initiation of the formation of ductal cells can be effected by administration of estradiol in the absence of endogenous progesterone and glucocorticoid using adrenalectomized-castrated animals. The resulting epithelium contains three times more lactose synthetase activity per epithelial cell than that in midpregnant mice. The blood spermidine level in these doubly operated animals was similar to the concentration of spermidine required to substitute effectively for glucocorticoid during mammary differentiation in vitro. It is suggested that spermidine can partially supplant glucocorticoid in vivo in milk protein synthesis. We also concluded that, unlike other secondary sex tissues, mammary cells do not require exposure to progesterone during their ontogeny in order to realize their differentiative potential. The positive role of this steroid in mammary development is apparently limited to its effect on the formation of alveolar structures.
Adrenalectomy↗
Progesterone and glucocorticoid in relation to the growth and differentiation of mammary epithelium.
In pursuit of a model system in which to determine whether exposure to progesterone is necessary for mammary epithlial cells to develop their differentiative potential, hormone-dependent growth of the mammary epithelial rudiment in adult male mice has been reexplored. The formation of ductal cells can be effected by administration of estradiol in the absence of endogenous progesterone and glucocorticoid, using adrenalectomized-castrated animals. The resulting epithlium contains three times more lactose synthetase activity, per epithelial cell, than that in midpregnant mice. The blood spermidine level in these doubly operated animals was similar to the concentration of spermidine required to substitute effectively for glucocorticoid during mammary differentiation in vitro, It is suggested that spermidine can partially supplant glucocorticoid in vivo in milk protein synthesis. It is also concluded that, unlike other secondary sex tissues, mammary cells do not require exposure to progesterone during their ontogeny in order to realize their differentiative potential. The positive role of this steroid in mammary development is apparently limited to its effect on the formation of alveolar structures.
Adrenalectomy↗