Biomedical subjects

B Butler

Publications and source records attributed to B Butler.

At least 37 records · Page 2Linked to original sources

PubMed1986

The sex-determining gene tra of Drosophila: molecular cloning and transformation studies.

In Drosophila, the primary signal for sex determination is given by the ratio of X chromosomes to sets of autosomes (X:A). The primary signal is read by a key gene (Sxl) and transmitted down to the differentiation genes by the subordinate control genes tra, tra-2, ix and dsx. Mutations in tra transform chromosomal females (X/X; tra/tra) into sterile males (pseudomales). We have cloned the tra region by microdissection and chromosomal walking. We identified the gene using deficiency breakpoints, DNA aberrations in three different alleles of tra and by P-mediated transformation. A 3.8-kb fragment perfectly rescued the mutant phenotype of X/X; tra/tra flies, showing that it contained all the necessary information to restore female-specific functions in the mutant flies. We present evidence that most of the function of tra can be provided by a subsegment of 2 kb that is differentially transcribed or processed in males and females.

Animals↗

PubMed1985

Alternative processing and developmental control of the transcripts of the Drosophila abl oncogene homologue.

Drosophila sequences homologous to the abl oncogene are located near the 5' end of a gene (Dash). The Dash gene is transcribed to give long RNAs (5-6 kb) and short RNAs (3.0 kb) that lack some of the internal exons of the gene including some of the sequences coding for the protein kinase domain. The gene is composed of at least five short exons and a long 3' exon. The 3' exon is processed in several alternative ways. It contains an intronic sequence which is spliced out in approximately 50% of the transcripts. S1 mapping shows the existence of five different 3' ends, presumed polyadenylation sites, differing by up to 1 kb. Three of these are maternal-specific while the other two are utilised during development. Dash RNA is most abundant in eggs and early embryos, becomes very rare during larval development and returns in a burst of activity in early pupae.

Animals↗

PubMed1985

Prolongation of QT interval and antiarrhythmic action of bepridil.

Studies were undertaken with bepridil, a new calcium blocker that prolongs the QT interval, to determine the antiarrhythmic and possible arrhythmogenic properties of this agent. The technique of programmed electrical stimulation was employed to evaluate bepridil in 15 patients with symptomatic ventricular tachycardia (VT). Bepridil prevented VT induction in 7 of 15 patients. Bepridil prolonged the QT and refractoriness and a linear correlation could be demonstrated between the percent change in QTc and refractory period prolongation for the bepridil-protected group. Bepridil in one patient reduced by one the number of stimuli required to induce VT, but no spontaneous arrhythmias were noted. Bepridil thus possesses antiarrhythmic properties with a minimal proarrhythmic effect.

Aged↗

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↗

PubMed1985

Antiarrhythmic effects of cibenzoline.

Thirty-three patients with ventricular tachyarrhythmias were referred for evaluation of their arrhythmias using programmed electrical stimulation to guide antiarrhythmic therapy. Cibenzoline succinate, a new antiarrhythmic agent, was compared to procainamide in patients with ventricular tachycardia. Cibenzoline was given intravenously, initially 1.0 mg/kg, then in 1 mg/kg increments to a maximum of 3.0 mg/kg, during electrophysiologic testing. The results were compared to procainamide, which was also administered intravenously to 1000 and then to 1500 mg. Cibenzoline provided protection against ventricular tachycardia induction in 16 of 33 patients. The PR interval increased 13%, QRS duration widened 26%, and QTc interval was prolonged by 7%. There was a 9% fall in mean arterial blood pressure. Procainamide prevented ventricular tachycardia induction in 21 out of 31 patients tested. The PR interval increased 11%, QRS duration widened 27%, and QTc interval prolonged by 8%. Cibenzoline was given orally to 13 patients for chronic treatment. Chronic oral cibenzoline therapy after a mean follow-up of 8.8 months caused a reduction of ventricular ectopy from 666 to 190 beats/hr. Ventricular tachycardia events decreased per Holter monitor recording from 6 to 0.6. Cibenzoline therapy was discontinued in 5 of 13 patients due to break-through arrhythmias (nonsustained ventricular tachycardia on Holter monitor and recurrence of symptoms). Cibenzoline may be an effective antiarrhythmic agent in selected patients.

Adult↗

PubMed1985

Therapy for late post infarction ventricular tachycardia.

Non-sustained ventricular tachycardia (VT) in the late post myocardial infarction (MI) period (7-21 days) has been reported to be a predictor of sudden death. We suspected that patients with 3 beat VT on Holter monitoring in the late infarction period would demonstrate electrical instability at electrophysiologic studies. Forty-seven patients were identified as having at least 3 beat VT on Holter monitoring. Eighteen patients refused electrophysiologic studies or were not referred by their attending physician. The mean ejection fraction of this group was 43 +/- 16%. Eight patients have died, 3 sudden deaths in 13 +/- 5 months, a 17% incidence of sudden death. Twenty-nine patients underwent invasive electrophysiologic studies. Their mean ejection fraction was 37 +/- 7%, and 28 had inducible, 18 sustained ventricular tachycardia and 10 non-sustained VT. No complications were noted with electrophysiological testing in the post infarction patients. Using programmed electrical stimulation studies an effective antiarrhythmic agent preventing VT induction (usually experimental) could be found for each patient. After a mean follow-up of 12.5 +/- 4 months, the patient without inducible VT is alive and 26 of the 28 "inducible" patients are alive and well. Two patients died, one of stroke and one due to pump failure following a second MI. No sudden deaths were observed in this group. Two patients had breakthrough arrhythmias and were treated by alternative antiarrhythmic therapy that was also effective at the initial electrophysiologic studies. Thus, PES studies post MI are safe and may be an effective way to assess therapy for patients in the early post MI period, identified at high risk for sudden death.

Aged↗

PubMed1985

Long term lorcainide therapy guided by electrophysiology studies.

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 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, 9 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.

Administration, Oral↗

PubMed1984

Lorcainide therapy for the high-risk patient post myocardial infarction.

Nonsustained ventricular tachycardia (VT) in the late period (7 to 21 days) after myocardial infarction (MI) is reported to be a predictor of sudden death. Patients with 3-beat VT on Holter monitoring in the late infarction period would be suspected to demonstrate electrical instability on electrophysiologic studies. Forty-seven patients were identified as having at least 3-beat VT on Holter monitoring. Eighteen patients refused electrophysiologic studies or were not referred. Eight patients died; 3 were sudden deaths in 13 +/- 5 months, a 17% incidence. Twenty-nine patients underwent invasive electrophysiologic studies and 28 had inducible VT, 18 sustained and 10 nonsustained. Lorcainide prevented VT induction in 21 of the 28 patients, whereas 12 of the 22 patients studied on procainamide were protected. Lidocaine, tested in 21 patients, prevented VT induction in only 5. Lorcainide and procainamide prolonged refractoriness in those patients protected at programmed electrical stimulation (PES), whereas the QT interval was prolonged in patients in whom VT could still be induced. Twenty-seven of the 28 patients were placed on drugs predicted to be effective by PES studies, 19 on lorcainide. After a mean follow-up of 12.5 +/- 4 months the patient with noninducible arrhythmia is alive and 26 of the 28 patients with inducible arrhythmia are alive and well. Two patients died, 1 of stroke and 1 of pump failure after a second MI. No sudden deaths were observed in this group. Two patients had breakthrough arrhythmias and were treated by alternative antiarrhythmic therapy that was also effective on initial electrophysiologic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1984

Evaluation of lorcainide in patients with symptomatic ventricular tachycardia.

One hundred patients with inducible ventricular tachycardia (VT) on 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 agent. Lorcainide prevented VT induction in 69% of the 100 patients studied, procainamide in 50% of the 75 patients studied and lidocaine in 30% of 53 patients. After PES and serial drug testing, 46 patients were started on lorcainide, 9 on procainamide and 45 on other antiarrhythmic drug regimens. Eighty percent of the patients have remained on lorcainide therapy, whereas 47% have continued on other drug therapies started over 17.5-month mean follow-up period. Despite sleep-wake disturbances and a need for sedation at night, lorcainide therapy was well tolerated in this population and remained an effective antiarrhythmic agent with prolonged administration.

Anti-Arrhythmia Agents↗

PubMed1984

Comparison of noninvasive arrhythmia induction techniques with electrophysiologic studies and evaluation of lorcainide in patients with symptomatic ventricular tachycardia.

Twenty-six patients (19 men and 7 women) with symptomatic ventricular tachycardia (VT) were studied using invasive and noninvasive techniques to induce VT. Of the study population, 12% had syncope and VT on Holter monitoring, 30% had cardiac arrest and 58% had symptomatic VT. All patients had antiarrhythmic agents stopped 5 half-lives before evaluation and then had autonomic profile (upright tilt, cold pressor test, exercise testing and hand grip) as well as programmed electrical stimulation studies performed. Autonomic profile testing induced VT in 5 of 26 patients (19%) and in only 1 patient was the arrhythmia reproducibly induced. All 26 patients had VT induced on electrophysiologic testing; 9 patients had nonsustained and 17 had sustained VT. Lorcainide administered intravenously prevented VT induction in 20 of 26 patients tested, whereas procainamide was effective in 11 of 24 patients. Ten of the 13 not protected by procainamide were protected by lorcainide. Twenty patients were started on long-term lorcainide therapy and followed up for 29 +/- 3.4 months. Five patients have discontinued therapy, 2 because of breakthrough arrhythmias, 2 because of severe sleep-wake disturbances and 1 because of private physician preference. An additional 3 patients died during therapy because of myocardial infarction in 1, progressive myopathy in 1 and sudden death in 1. Sixty percent of patients started on lorcainide therapy have continued. In this patient population, noninvasive induction of VT is not a sensitive or reproducible technique in assessing antiarrhythmic therapy. Furthermore, when selected on the basis of electrophysiologic testing, lorcainide is a well-tolerated and effective antiarrhythmic agent.

Aged↗

PubMed1984

Antiarrhythmic action of bethanidine.

Studies were performed in 20 patients with symptomatic ventricular tachycardia (VT) to determine the efficacy of bethanidine compared with procainamide in preventing VT induced by programmed electrical stimulation. Before administering bethanidine, 5 to 10 mg/kg, the patients received 15 mg of protriptyline orally 24 and 2 hours before electrophysiologic studies to prevent the orthostatic hypotensive effects of bethanidine. Sustained VT (VT not spontaneously stopping) was induced in 8 and nonsustained VT (10 beats or more, terminating spontaneously) was induced in 4 patients. Bethanidine, 5 mg/kg, protected in 7 patients, and 10 mg/kg protected 1 additional patient. Procainamide, 1,000 and 1,500 mg intravenously, protected 8 of 16 patients. Bethanidine prevented VT induction in 50% of the patients not protected by procainamide. Bethanidine facilitated VT induction in 3 patients, while procainamide facilitated VT induction in 1 patient. Four patients with symptomatic VT have received bethanidine therapy for an average of 11 +/- 1.3 months, without clinical recurrence of their VT. Concomitant administration of protriptyline attenuated the acute hemodynamic changes caused by bethanidine and chronic combined therapy of protriptyline and bethanidine abolished the severe orthostatic changes in blood pressure caused by bethanidine. These studies show that bethanidine is effective in preventing VT induction and, thus, its use may not be restricted only to cases of primary ventricular fibrillation.

Bethanidine↗

PubMed1984

The efficacy of cibenzoline in preventing PES induction of ventricular tachycardia in the dog.

The electrophysiologic effects of cibenzoline were studied using programmed electrical stimulation (PES) techniques and were compared to those of quinidine. Cibenzoline, like the conventional class 1 agent quinidine, was effective in preventing arrhythmia induction. Twelve dogs were given 0.02 mg/kg digoxin intravenously for seven days to achieve a steady-state digoxin level. On the eighth day, cibenzoline was administered in incremental doses (0.5 to 10.5 mg/kg) and PES was performed at 30-minute intervals. A mean dose of 2.6 +/- 0.8 mg/kg cibenzoline prevented ventricular tachycardia induction. At this dose, cibenzoline had no significant effect on mean arterial blood pressure, but PR interval increased by 17 +/- 9 per cent, QRS duration by 27 +/- 14 per cent, and the ventricular refractory period (ERP) for the first extra stimulus increased by 35 +/- 9 per cent. A gradual decrease in heart rate and an increase in PR interval and QRS duration was caused by incremental doses of cibenzoline. In six additional animals, quinidine was administered in incremental doses (1 to 30 mg/kg) and PES performed at 30-minute intervals. A mean of 15 +/- 5 mg/kg prevented induction of ventricular tachycardia in five animals. No significant change in heart rate, PR, QRS, and ERP was found at the effective dose.

Animals↗

PubMed1984

The effect of bepridil, verapamil, and quinidine in the prevention of ventricular tachycardia induced by programmed electrical stimulation in the digitalized dog.

Bepridil, a new antianginal agent, has calcium channel-blocking activity and antiarrhythmic properties. To test the efficacy of bepridil as an antidysrhythmic agent, we looked at its effect on the induction of ventricular tachycardia (VT) in dogs, utilizing programmed electrical stimulation (PES). Incremental doses of bepridil up to 20 mg/kg were given to five nondigitalized dogs and verapamil up to 20 mg, and PES was performed at each dose. Both drugs were not found to facilitate arrhythmia induction. Seventeen dogs were chronically digitalized and following digitalization, VT could be induced in all animals by PES. Six dogs were given bepridil and PES was reperformed at each dose. An average of 1.8 mg/kg was found to protect against induction of VT. Five dogs received verapamil and none was protected (all had VT induced), while five of six dogs given quinidine were protected at an average dose of 15.4 mg/kg. Bepridil produced a significant decrease in heart rate. A significant correlation was found at the effective antiarrhythmic dose of bepridil between percentage change in the effective refractory period for the first extrastimulus (ERP S2) and QTc (r = 0.96), suggesting that a parallel and homogeneous prolongation in repolarization and refractoriness is essential for the antiarrhythmic effect of bepridil. Bepridil is thus an effective antiarrhythmic agent that affords protection against induction of VT, and this action is similar to the conventional class I antiarrhythmic agent, quinidine, while lacking in another calcium channel blocker, verapamil.

Animals↗

PubMed1984

Studies on the possible mechanisms of lidoflazine arrhythmogenicity.

Lidoflazine is a calcium channel blocking agent that is effective and safe in the treatment of angina pectoris, but has been reported to be associated with sudden death when administered for the treatment of supraventricular arrhythmias. Studies were performed in dogs to determine if lidoflazine caused a rise in serum digoxin concentration that could cause arrhythmias or if it was directly arrhythmogenic. Dogs received chronic injections of digoxin and then digoxin in combination with lidoflazine. No increase in digoxin concentration was found. Dogs also underwent programmed electrical stimulation while not receiving medications and then after incremental doses of lidoflazine administered intravenously. Lidoflazine did not cause spontaneous ventricular tachycardia and did not lower the threshold of ventricular tachycardia induction. Combined administration of lidoflazine and digoxin did not facilitate arrhythmia induction. These studies do not support a digoxin-lidoflazine interaction or a direct arrhythmogenic action of lidoflazine.

Animals↗

PubMed1983