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Biomedical subjects

D Keefe

Publications and source records attributed to D Keefe.

At least 37 records · Page 2Linked to original sources
PubMed1991

Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women.

The secretory pattern of oxytocin was determined in blood samples taken at 1-minute intervals for 30 minutes from 32 parturient women. The samples were collected in a manner that minimized degradation by plasma oxytocinase, and a highly specific antibody was used for the radioimmunoassay. The results indicated that oxytocin is secreted in discrete pulses of short duration. The frequency of the pulses was significantly higher during spontaneous labor than before the onset of labor. The mean pulse frequencies per 30 minutes were 1.2 +/- 0.54 before labor, 4.2 +/- 0.45 during the first stage, and 6.7 +/- 0.49 during the second and third stages of labor. The mean pulse durations in these three groups were 1.2 +/- 0.20, 1.9 +/- 0.28, and 2.0 +/- 0.26 minutes, respectively. The amplitude of the pulses was variable with no significant differences between the groups, the majority being around 1.0 microU/ml. The spontaneous pulses were of similar magnitude as those measured in 18 women after intravenous injections of 4 to 16 mU of oxytocin, which doses stimulated uterine contractions. We therefore conclude that the pulses of oxytocin observed at increasing frequency during spontaneous labor are of physiologic significance and provide evidence for the participation of oxytocin in the onset and maintenance of spontaneous labor.

Analysis of Variance↗
PubMed1990

Estrogen effects on the synaptology and neural membranes of the rat hypothalamic arcuate nucleus.

The concept of estrogen-induced "sexual differentiation of the brain" has been a useful focus for investigation. However, it has become clear that the action of estrogen on the rat brain is lifelong, including effects on neurogenesis in the fetus, synaptogenesis in the newborn, and synaptic remodeling in the adult. Estrogen imparts sex differences in the rat's brain by shaping synaptology, postsynaptic membranes, and glia within the arcuate nucleus. These effects of estrogen on the arcuate nucleus also could underlie sexual maturation in both sexes and the development of senescent constant estrus in females.

Animals↗
PubMed1989

Cardiac screening for pregnant intravenous drug abusers.

We performed screening two-dimensional and M-mode echocardiograms on 23 pregnant intravenous drug abusers who had systolic murmurs that clinically appeared physiologic. Although no patient had symptoms or a history of cardiac disease, all but two of the women were evaluated as having unexpected cardiac valvular changes. The majority of morphologic valvular findings on echocardiography consisted of either a mitral valve prolapse or valvular leaflet thickening. However, two of these 21 women were identified as having a previously undiagnosed aortic or tricuspid vegetation for which they subsequently received prophylactic antibiotic therapy during labor and delivery. Notably, two additional women among the group with morphologic valvular changes ultimately developed subacute bacterial endocarditis. Atypically, the clinical illness occurred antenatally for one of the two women with a mitral valve prolapse and 18 months postpartum for another women with unexplained valvular thickening. On the basis of these observations, a more liberal use of echocardiography in the care of the pregnant intravenous drug abuser population is suggested for evaluation of otherwise seemingly innocuous systolic murmurs.

Adult↗
PubMed1987

Effect of congestive heart failure on the pharmacokinetics of cibenzoline.

Six patients with chronic congestive heart failure (CHF) (New York Heart Association functional class II or III) and five healthy subjects completed this study designed to determine if CHF alters the pharmacokinetics and absolute bioavailability of cibenzoline when compared with healthy subjects. Each subject or patient was administered a one-hour intravenous infusion of 80 mg of 15N2-cibenzoline and simultaneously received an 80-mg oral dose of cibenzoline that allowed for analytic separation of each route of administration. Resulting plasma concentration-time profiles and urinary excretion rate data were used to determine pharmacokinetic parameters for cibenzoline. There were no statistically significant differences in any pharmacokinetic parameter between patients with CHF and healthy subjects. The absolute bioavailability ranged from 74% to 97% in those with CHF. The volume of distribution following the intravenous dose ranged from 3.4 to 6.1 L/kg, and plasma clearance ranged from 245 to 642 mL/min, with an apparent elimination half-life of approximately ten hours. Approximately 60% of the dose was recovered in the urine. Overall, the pharmacokinetics of cibenzoline in patients with chronic CHF do not differ from those observed in healthy subjects.

Aged↗
PubMed1987

Comparative efficacy of pirmenol and procainamide in a drug-resistant population with ventricular tachycardia.

The acute antiarrhythmic properties of pirmenol were studied in 12 patients who failed clinical oral drug therapy with a history of a cardiac arrest or sustained ventricular tachycardia (VT). Programmed electrical stimulation studies were performed in ten men and two women with a mean age of 63 +/- 2 years. All patients had inducible ventricular tachycardia by programmed electrical stimulation when they were off all antiarrhythmic therapy. Patients were then tested on procainamide, 1000 mg, administered intravenously, and ventricular tachycardia could be provoked in nine of twelve patients. Pirmenol was given intravenously, 1.1 mg/kg bolus followed by 40 micrograms/kg/min over 40 minutes prior to drug testing. Pirmenol did not significantly change the baseline heart rate, blood pressure, or measured electrocardiographic values from control values. Ten of 12 patients were still inducible to ventricular tachycardia on pirmenol. Procainamide protected one of nine patients against VT induction. In patients still inducible on drug therapy, the VT rate was significantly slowed from 221 beats/min to 166 beats/min on pirmenol and to 200 beats/min on procainamide. The effects of this new antiarrhythmic agent were similar to procainamide in this drug-resistant study population.

Anti-Arrhythmia Agents↗
PubMed1987

Antiarrhythmic effects of indecainide in a drug-resistant population with ventricular tachycardia at programmed electrical stimulation.

The antiarrhythmic properties of indecainide were studied in 15 patients with a history of a cardiac arrest or ventricular tachycardia. Programmed electrical stimulation studies were performed in nine men and six women with a mean age of 68 +/- 2 years and a mean left ventricular ejection fraction of 41 +/- 4%. All patients had inducible ventricular tachycardia by programmed electrical stimulation while off all antiarrhythmic therapy. Patients were then tested on procainamide, 1000 mg, administered intravenously, and ventricular tachycardia could be provoked in 10 of 15 patients. Indecainide was given intravenously, 1 mg/kg. Indecainide did not significantly change the baseline heart rate, blood pressure, and QTc interval from control values. The PR and QRS intervals were significantly prolonged. Twelve of 15 patients were still inducible for ventricular tachycardia on indecainide. Procainamide protected 5 of 15 patients against ventricular tachycardia induction. In patients still inducible on indecainide therapy, the ventricular tachycardia rate was significantly slowed, from 281 bpm to 224 bpm on indecainide and to 215 bpm on procainamide. The effects of this new class IC antiarrhythmic agent appears similar to procainamide in patients with serious life-threatening tachyarrhythmias.

Aged↗
PubMed1986

Safety and efficacy of flestolol, a new ultrashort-acting beta-adrenergic blocking agent, for supraventricular tachyarrhythmias.

Flestolol, a new ultrashort-acting (half-life 6.9 minutes) beta-blocking drug, was administered by intravenous infusion to 18 patients with new-onset atrial fibrillation or flutter and rapid ventricular response (120 beats/min or more for at least 30 minutes). Drug dose of flestolol was progressively increased until at least 1 of 3 endpoints was achieved: at least a 20% reduction in heart rate from baseline, heart rate 100 beats/min or less, or conversion to normal sinus rhythm. Flestolol was then administered as a maintenance infusion up to 24 hours. When flestolol was discontinued, patients were monitored for 1 additional hour. The mean ventricular response at baseline of 133 +/- 12 beats/min decreased to 103 +/- 20 beats/min at the end of flestolol titration (p less than 0.0001). Fourteen patients (78%) achieved defined endpoints. All 14 patients who continued to receive maintenance infusion had a sustained response. When flestolol was discontinued, ventricular response increased 33 +/- 23% within 60 minutes. The only adverse effect seen was hypotension in 2 patients. Flestolol is effective in slowing ventricular response in new-onset atrial fibrillation and flutter, maintains a therapeutic effect during continuous infusion and rapidly loses therapeutic effect when discontinued.

Adrenergic beta-Antagonists↗
PubMed1986

Antiarrhythmic drug efficacy at electrophysiology testing: predictive effectiveness of procainamide and flecainide.

In an effort to assess the ability of procainamide to predict effectiveness of antiarrhythmic agents at programmed electrical stimulation (PES) testing, we compared the result of procainamide at PES testing with that of all of the other agents studied. One hundred fifty-three patients underwent PES studies because of either sustained or nonsustained ventricular tachycardia (VT). Procainamide prevented VT induction in 79 of 153 patients. Seventy-four of the remaining 153 were inducible for VT on procainamide, with 55 of these being protected by another antiarrhythmic agent (p less than 0.001). If procainamide failed to prevent VT induction, other conventional and experimental agents were equally as likely to be effective in preventing VT induction. Analysis of flecainide acetate as a predictor of efficacy was also evaluated. Fifty-five patients received flecainide and 29 of these were protected at PES testing; 26 of these patients were also protected with another agent. When VT was inducible in patients who received flecainide, 15 of these 26 patients were protected by another agent, either conventional or experimental (p less than 0.01). Thus, if procainamide or flecainide prevented VT induction they accurately predicted effectiveness of other drugs; however, when they did not prevent VT induction, they served as a poor predictor of the possible effectiveness of other drugs. Serial drug testing at PES studies with multiple conventional and experimental drugs increases the likelihood of finding an effective antiarrhythmic agent.

Anti-Arrhythmia Agents↗
PubMed1986

Lorcainide therapy in a cardiac arrest population.

Thirty-eight patients with prior history of cardiac arrest underwent programmed electrical stimulation (PES) studies and serial drug testing. Lorcainide was tested acutely in all 38 patients and prevented ventricular tachycardia (VT) or ventricular fibrillation (VF) induction in 14 patients and failed in 24 (efficacy rate 37%). Procainamide had failed clinically (cardiac arrest or breakthrough VT) in 16 patients, seven patients had previously severe adverse side effects, and thus only 15 were tested on procainamide at PES testing with seven protected. Following initial studies, 14 patients were started on lorcainide oral therapy and 24 on other therapy determined effective at PES testing (N-acetylprocainamide-two, flecainide-nine, bethanidine-three, slow-release procainamide hydrochloride-three, quinidine-two, cibenzoline-one, amiodarone-four). After 29 +/- 7 months follow-up, three are alive on lorcainide therapy, five discontinued therapy due to side effects; six died--three sudden deaths (33%) and two cardiac deaths (both myocardial infarctions). Twenty out of 24 patients are alive who were started on PES predicted effective therapy other than lorcainide; four died--three sudden deaths (13%) and one cardiac nonsudden death. Antiarrhythmic therapy guided by PES studies gives overall encouraging results in a cardiac arrest group of patients. Lorcainide, however, is not tolerated well and affords less protection against a sudden death recurrence than is noted in a population on other antiarrhythmic therapy predicted effective at PES testing.

Arrhythmias, Cardiac↗
PubMed1986

Antiarrhythmic efficacy of ethmozine in patients with ventricular tachycardia as determined by programmed electrical stimulation.

The antiarrhythmic properties of ethmozine were studied in 27 patients with a history of a cardiac arrest or symptomatic ventricular tachycardia. Programmed electrical stimulation studies were performed in 20 men and seven women with a mean age of 62 years and a mean left ventricular ejection fraction of 43%. All patients had inducible ventricular tachycardia by programmed electrical stimulation while off all antiarrhythmic therapy. Patients were then tested on procainamide if their treatment with this drug orally had not previously failed. Procainamide, 1000 and 1500 mg, was administered intravenously, and ventricular tachycardia could be provoked in 14 of 18 patients. Ethmozine was given in an oral loading regimen starting 24 to 36 hours later. After 500 mg oral ethmozine, patients were given 15 mg/kg ethmozine every 8 hours for seven to nine doses prior to drug testing. Ethmozine did not significantly change the baseline heart rate, blood pressure, and QTc interval from the initial drug-free values. The PR and QRS intervals were significantly prolonged. Seven patients were protected on oral ethmozine; 14 patients still had ventricular tachycardia inducible at programmed electrical stimulation testing, and six patients developed ventricular tachycardia spontaneously on ethmozine and were not tested in the programmed electrical stimulation laboratory. One patient had gastrointestinal complaints and was not discharged on the drug. The five patients who tolerated the oral protocol without side effects and who were protected against programmed stimulation induction of ventricular tachycardia were discharged on oral therapy. One patient on long-term therapy appeared to develop an allergic reaction to the agent with unexplained fevers and was switched to amiodarone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

QT prolongation and the antiarrhythmic efficacy of amiodarone.

Amiodarone is an antiarrhythmic agent known to cause prolongation of action potential duration which is reflected in the electrocardiogram as a prolongation of the QT interval. Prolongation of the QT interval in patients dying suddenly was compared with that in patients who remained alive to determine whether a difference existed between these two groups. The electrocardiogram and amiodarone levels were evaluated in 33 patients who presented with cardiac arrest and symptomatic ventricular tachycardia in whom no other antiarrhythmic agent was found effective in preventing induction of ventricular tachycardia during electrophysiologic studies. There were 30 men and 3 women (mean age 52 +/- 10 years). Twenty-three are alive after a mean follow-up period of 12 +/- 7 months. Ten died: six suddenly, three of non-cardiac causes and one of congestive heart failure. Using a two-way analysis of variance, the percent change in QT, QTc, JT and JTc intervals before and after amiodarone therapy was analyzed. Marked prolongation in the QT interval was present in patients who remained alive with amiodarone therapy. A significant difference in percent QT prolongation was seen between the latter patients and those who died suddenly (p less than 0.005). No difference was observed in the percent change in QRS interval between the two groups. The levels of amiodarone (2.5 versus 3.2 micrograms/ml) and its metabolite (desethylamiodarone) were not significantly different between the living patients and those who died suddenly. These findings suggest that a prolongation of the QT interval may be a marker for the therapeutic antiarrhythmic effect of amiodarone.

Aged↗
PubMed1986

Atrial contraction is an important determinant of pulmonary venous flow.

Pulmonary venous flow has two phases (systolic and diastolic) in normal subjects when studied by pulsed Doppler echocardiography. Only one phase of pulmonary venous flow (diastolic) was observed in six patients without synchronous atrial contraction (four patients with atrial fibrillation and two with complete atrioventricular [AV] block). This pattern reversed to normal (biphasic) when AV synchrony was reestablished by cardioversion to sinus rhythm in patients with atrial fibrillation and by AV sequential pacing in patients with complete AV block. Thus, both atrial and ventricular contraction and relaxation are important determinants of pulmonary venous flow.

Adult↗
PubMed1986

Endocarditis of a tricuspid prosthesis causing valvular stenosis and shunting through a patent foramen ovale.

A young intravenous drug user presented with Staphylococcus aureus endocarditis involving the tricuspid valve, which was replaced with a Hancock bioprosthesis. She presented again with fever and dyspnea five months later and was found to be cyanotic. Recurrent endocarditis involving the prosthesis with right-to-left shunting through a patent foramen ovale was documented by echo and confirmed at autopsy.

Adult↗
PubMed1986

N-acetylprocainamide's antiarrhythmic action in patients with ventricular tachycardia.

Antiarrhythmic properties of N-acetylprocainamide, an active metabolite of procainamide, were studied in 15 patients who presented with a cardiac arrest or documented sustained ventricular tachycardia. Programmed electrical stimulation studies were performed. All patients tested had inducible ventricular tachycardia by programmed electrical stimulation techniques while off all antiarrhythmic therapy. Patients were then tested on procainamide 1000 mg administered intravenously, and ventricular tachycardia could be provoked in 8 of 10 patients. Twenty-four to 36 hours later, N-acetylprocainamide was administered, intravenously, and programmed stimulation was performed after 20 minutes. N-acetylprocainamide did not significantly change heart rate, mean arterial blood pressure, electrocardiographic intervals, A-H or H-V conduction times. N-acetylprocainamide prevented ventricular tachycardia induction in 6 of 15 patients. The mean serum N-acetylprocainamide levels in the group protected was 15.7 +/- 4 micrograms/ml and 16.2 +/- 4 micrograms/ml in the group not protected. These 6 patients were discharged on N-acetylprocainamide 1.5 grams orally every 8 hours. Three patients have been maintained on chronic N-acetylprocainamide every 8 hours. Three patients have been maintained on chronic N-acetylprocainamide therapy (6 +/- 2 months), two patients had breakthrough ventricular tachycardia on follow-up Holter monitoring and alternative therapy was given. N-acetylprocainamide has antiarrhythmic efficacy in preventing induction of ventricular tachycardia by programmed electrical stimulation in a high risk group of patients. On chronic oral therapy, N-acetylprocainamide appears to be well tolerated with antiarrhythmic efficacy that may be enhanced with further upward dose titration.

Acecainide↗
PubMed1985

Electrophysiologic evaluation of the antiarrhythmic effects of N-acetylprocainamide for ventricular tachycardia secondary to coronary artery disease.

Antiarrhythmic properties of N-acetylprocainamide (NAPA), an active metabolite of procainamide, were studied in 12 patients with coronary artery disease who presented with cardiac arrest or documented sustained ventricular tachycardia (VT). Programmed electrical stimulation (PES) studies were performed in 10 men and 2 women, aged 52 to 80 years (mean 63), who had a left ventricular ejection fraction of 16 to 69% (mean 33). All patients tested had inducible VT provoked by PES without antiarrhythmic therapy. Patients were then tested with procainamide, 1,000 mg administered intravenously. VT could be provoked after procainamide treatment in 8 of 10 patients. Twenty-four to 36 hours later NAPA was administered, 18 mg/kg body weight intravenously, and PES was performed after 20 minutes. NAPA did not significantly change heart rate, mean arterial blood pressure, electrocardiographic intervals and AH or HV conduction times. The QT interval lengthened, but not significantly. The mean serum NAPA levels were 15.7 +/- 4 micrograms/ml in the group protected by NAPA and 16.2 +/- 4 micrograms/ml in the group not protected by NAPA. Five patients were discharged with NAPA therapy, 1.5 g orally every 8 hours. Two patients have been maintained with chronic NAPA therapy (10 +/- 3 months), and 2 patients had breakthrough VT on follow-up Holter monitoring and alternative therapy was given. One patient died while taking oral therapy. NAPA demonstrates antiarrhythmic efficacy in preventing induction of VT by PES in a high-risk group of patients. During chronic oral therapy in some patients, NAPA appears to be well tolerated, with antiarrhythmic efficacy that may be enhanced with further upward dose titration.

Acecainide↗
PubMed1985

Long-term lorcainide therapy in patients with ventricular tachycardia.

One hundred patients inducible at electrophysiologic studies underwent serial drug testing with procainamide, lidocaine, and lorcainide to determine comparative efficacy. Acute intravenous administration was followed by repeat programmed electrical stimulation (PES) studies on separate days for each antiarrhythmic drug. Lorcainide prevented ventricular tachycardia (VT) induction in 69% of the 100 patients studied, procainamide was effective in 50% of the 75 patients studied, and lidocaine prevented VT induction in 30% of 53 patients. Following PES and serial drug testing, 46 patients were started on lorcainide, nine patients on procainamide, and 45 patients were started on other antiarrhythmic drug regimens. Seventy percent of the patients have remained on lorcainide therapy, while 47% have continued on other drug therapies started over a 20.5 +/- 3.2-month mean follow-up period. Despite sleep-wake disturbances and a need for sedation at night, lorcainide therapy was tolerated well in this population and remained an effective antiarrhythmic with prolonged administration.

Benzeneacetamides↗