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Biomedical subjects

C Wyndham

Publications and source records attributed to C Wyndham.

At least 19 recordsLinked to original sources

Chlorobenzoate catabolic transposon Tn5271 is a composite class I element with flanking class II insertion sequences.

The structure of a transposon specifying the biodegradation of chlorobenzoate contaminants is described. Tn5271 is a 17-kilobase (kb) transposon that resides in the plasmid or chromosome of Alcaligenes sp. strain BR60 and allows this organism to grow on 3- and 4-chlorobenzoate. The transposon is flanked by a directly repeated sequence of 3201 base pairs (bp), which in turn is flanked by 110-bp inverted repeats. The 3.2-kb repeated sequence, designated IS1071, exists in multiple copies in the genome of Alcaligenes sp. strain BR60 and is involved in recombination of the catabolic genes into the chromosome of this strain. Sequence analysis revealed that the inverted repeat of IS1071 and the derived amino acid sequence of the single open reading frame within IS1071 are related to the inverted repeats and transposase (TnpA) proteins of the class II (Tn3 family) transposable elements. The absence of a resolvase gene within IS1071 suggests that this element is capable of determining the first step in class II transposition only. This was confirmed by observations on the IS1071-dependent formation of stable cointegrates in a recombination-deficient Escherichia coli. These results support an evolutionary scheme in which the class II transposable elements descended from simple insertion sequences.

Alcaligenes↗

Electrophysiologic effects of ouabain in patients with preexcitation and circus movement tachycardia.

Effects of intravenous ouabain were evaluated in 19 patients with an anomalous conduction pathway (14 with manifest and 5 with concealed preexcitation (utilizing intracardiac stimulation and recording. Anterograde conduction through the anomalous pathway was present in all 14 patients with manifest preexcitation at a maximal atrial paced rate of 140 to 250 beats/min (mean +/- standard error of the mean 214 +/- 7.2) before and at 150 to 240 beats/min (mean 206 +/- 7.1) after ouabain (difference not significant [NS]). The anterograde effective refractory period of the anomalous pathway, measured at an equivalent atrial paced rate in 10 patients, was 250 to 450 ms (mean 309 +/- 19.7) before and 260 to 450 ms (mean 300 +/- 17.2) after ouabain (NS). Retrograde conduction through the anomalous pathway was possible at maximal ventricular paced rates (17 patients) of 160 to 250 beats/min (mean 222 +/- 6.6) before and 190 to 250 beats/min (mean 221 +/- 4.4) after ouabain (NS). Sustained atrioventricular (A-V) reentrant paroxysmal supraventricular tachycardia was inducible in all 19 patients before and in 17 patients (89 percent) after ouabain (tachycardia could not be induced in two patients because of increased A-V nodal refractoriness). The mean cycle length of tachycardia in the 17 patients was 320 +/- 6.7 ms before and 340 +/- 8.1 ms after ouabain (p < 0.01). In conclusion, ouabain has no significant effect on either anterograde or retrograde anomalous pathway refractoriness. Although ouabain slightly increases the cycle length of tachycardia, it does not interfere with induction of tachycardia in most patients with preexcitation. Oral cardiac glycosides alone would appear to be of limited value in patients with preexcitation and recurrent supraventricular tachycardia.

Adolescent↗

Assessment of left ventricular function by radionuclide angiography during induced supraventricular tachycardia.

Electrocardiographically synchronized radionuclide angiography was performed before, during and after induced paroxysmal supraventricular tachycardia in 13 patients. Data were acquired with a computer-interfaced Anger camera in a left anterior oblique projection. No data were acquired during tachycardia until tachycardia had been sustained for 1 minute. Patients ranged in age from 20 to 64 years (mean +/- standard deviation 42 +/- 14.5). Three patients had organic heart disease and 10 did not. Baseline and tachycardia heart rates (beats/min) were 59 to 99 (73 +/- 11) versus 141 to 228 (157 +/- 22). Baseline and tachycardia left ventricular measurements (mean +/- standard error) were as follows: ejection fraction 64 +/- 2 versus 62 +/- 4 percent (not significant), ejection rate 3.0 +/- 0.1 versus 4.3 +/- 0.4 mean ventricular counts/s (p less than 0.001), normalized end-diastolic counts 72.7 +/- 7.8 versus 48.7 +/- 6.7 X 10(3) counts (p less than 0.001), normalized stroke counts 37.1 +/- 3.4 versus 23.3 +/- 2.7 X 10(3) counts (p less than 0.001) and normalized count cardiac output 2,717.5 +/- 273.0 versus 3,620.2 +/- 403.7 X 10(3) counts/min (p less than 0.005). Although ejection fraction for the whole group did not change significantly, it decreased during tachycardia by 5 percentage points or more in five patients. These were the three patients with heart disease and the two normal patients with the fastest heart rate during tachycardia (228 and 214 beats/min, respectively). In summary, paroxysmal supraventricular tachycardia was characterized by a marked decrease in left ventricular end-diastolic and stroke volumes but increased ejection rate and cardiac output without significant change in ejection fraction. Heart disease or rapid heart rate during tachycardia appeared to have a deleterious effect on ejection fraction.

Adult↗

Natural history of chronic second-degree atrioventricular nodal block.

This report details our experience with documented chronic second-degree atrioventricular (AV) nodal block (proximal to His [H]) in 56 patients. Forty-six men (82%) and 10 women (18%), ages 18-87 years, were studied. Nineteen of the patients (34%) had no organic heart disease (including seven trained athletes) and 37 (66%) had organic heart disease. ECGs in all patients demonstrated episodes of type I second-degree block; five patients also had periods of 2:1 block. Prospective follow-up patients with no organic heart disease (157-2280 days, mean 1395 +/- 636 days) revealed one patient with clear indication for permanent pacing because of bradyarrhythmic symptoms (permanently placed on day 220 of follow-up). Two patients died nonsuddenly. In patients with organic heart disease (prospective follow-up of 60-2950 days, mean 1347 +/- 825 days), pacemakers were implanted in 10 patients, primarily for treatment of congestive heart failure in eight and syncope in two. Sixteen patients died -- three suddenly, seven with congestive heart failure, two of an acute myocardial infarction and four of causes unrelated to cardiac disease. In summary, chronic second-degree AV nodal block has a relatively benign course in patients without organic heart disease. In patients with organic heart disease, prognosis is poor and related to the severity of underlying heart disease.

Adolescent↗

Left-to-right shunt via left superior vena cava communication with left atrium.

The findings in a 22-year-old man with Ebstein's anomaly of the tricuspid valve, Wolff-Parkinson-White syndrome, and a persistent left superior vena cava are reported. This is the first reported case of this combination of anomalies in which the atrial septum was intact and the left superior vena cava communicated with the left atrium. Uniquely, blood was shunted left to right via the left superior vena cava from the left atrium. Only one previous case of left-to-right shunting via a left superior vena cava (in the absence of mitral valvular disease or cor triatriatum) has been reported (associated with aortic coarctation). Angiograms demonstrated the left atrial connection of the left superior vena cava to be at the entrance of the right superior pulmonary vein into the left atrium. In the absence of demonstrable left-sided heart disease, this anatomic juxtaposition is suggested as a possible explanation for the direction of shunting.

Adult↗

Cardiac conduction defects in polymyositis: electrophysiologic studies in four patients.

The clinical electrophysiologic findings in four patients with biopsy-proven polymyositis and bifascicular block are described. Atrioventricular (AV) block developed in two of these four patients, and intracardiac electrophysiologic studies documented the site of spontaneous block to be distal to the His bundle in one, whereas in the second marked His-ventricular prolongation was found, and distal block developed at low paced atrial rates. Sinus node and AV nodal function were normal in all four. These electrophysiologic data provide the first documentation of the site of AV block in patients with polymyositis and correlate well with findings of previous pathologic studies that have shown extensive fibrosis of the distal His bundle and bundle branches.

Electrophysiology↗

Infiltrative cardiomyopathy with conduction disease and ventricular arrhythmia: electrophysiologic and pathologic correlations.

Two cases are described, one of cardiac sarcoidosis and another of primary cardiac amyloidosis, in which correlation was made between electrophysiologic and postmortem conduction system studies. In Case 1 the electrocardiogram revealed right bundle branch block with first degree and intermittent third degree atrioventricular (A-V) block and recurrent unifocal paroxysmal ventricular tachycardia. Electrophysiologic studies disclosed normal sinus rhythm with prolonged A-H (175 ms) and H-V (60 MS) intervals and extrastimulus induction of repetitive ventricular firing. Postmortem examination revealed a sarcoid aneurysm of the posterior left ventricle and granulomatous infiltration of the A-V node, His bundle and bundle branches. In case 2 the electrocardiogram revealed sinus bradycardia, a prolonged S-T interval and recurrent ventricular fibrillation. Electrophysiologic studies demonstrated a prolonged sinus nodal recovery time (6,080 ms) and H-V (85 ms) interval. Postmortem examination revealed marked amyloid infiltration of the sinoatrial node, atria, proximal bundle branches and left and right ventricular myocardium. There was thus excellent correlation between electrophysiologic and pathologic findings. These cases indicate the importance of making a clinical diagnosis of the disease that might in some cases allow specific therapeutic intervention in addition to antiarrhythmic therapy.

Adult↗

Chronic longterm electrophysiologic study of paroxysmal ventricular tachycardia.

Nine patients with recurrent paroxysmal ventricular tachycardia underwent chronic electrophysiologic studies to delineate effective drug therapy for prevention of recurrence of this arrhythmia. The frequency of attacks of ventricular tachycardia necessitating hospitalization ranged from 2 to 12 (mean 5 +/- 4) attacks per year. Pacing induction of ventricular tachycardia was performed prior to and following intravenous or oral administration of procainamide (eight patients), disopyramide phosphate (nine patients), aprindine (five patients) and propranolol (four patients). Successful drug response (prevention of ventricular tachycardia induction or induction of nonsustained episodes of tachycardia) was noted in six of nine patients (66 percent). Lack of drug effect on the ability to sustain ventricular tachycardia was noted in three patients (34 percent). In addition, a deleterious drug response, manifested by potentiation of ventricular flutter or fibrillation, was observed in two of the three patients who failed to respond to drugs. Chronic drug therapy based on successful response in six patients resulted in cure of ventricular tachycardia in five of six patients (83 percent), one patient having one attack necessitating hospitalization. Of the three patients who demonstrated lack of drug effect during chronic electrophysiologic studies, one died suddenly and two had recurrent episodes of ventricular tachycardia while receiving a drug that did not prevent induction of ventricular tachycardia.

Adult↗

Incidence and site of atrioventricular block in patients with chronic bifascicular block.

Four hundred fifty-two patients with chronic bifascicular block and initially intact atrioventricular (AV) conduction were detected, studied, and prospectively followed between January 1970 and March 1978. There were 360 males and 92 females, ages 18--93 years (mean +/- SD, 62 +/- 15 years). Follow-up ranged from 29-2804 days (mean 1066 +/- 97 days). AV block (2 degrees or 3 degrees) developed in 29 patients, nine with apparent cause and spontaneously in 20. Cumulative annual incidence of all heart block for 1--5 years was, respectively, 4%, 5.9%, 8.7%, 10.1% and 11.3%, and for spontaneous block was 2%, 3.1%, 5.2%, 6.7%, and 7.1%. Sites of spontaneous block were probably or definitely AV nodal in ten, His bundle in one, and trifascicular in nine. Cumulative incidence of AV block in surviving bifascicular block patients is 11% at 5 years, with 7% reflecting spontaneous block. The probable or definite site of AV block varies and is trifascicular in less than half of the patients. The small incidence of trifascicular block probably explains the difficulty in predicting this complication with electrophysiological studies.

Adolescent↗

Effects of atropine on induction and maintenance of atrioventricular nodal reentrant tachycardia.

The electrophysiologic effects of atropine were studied in 14 patients with dual atrioventricular (AV) nodal pathways and recurrent paroxysmal supraventricular tachycardia (PSVT). During PSVT, all patients used a slow pathway (SP) for antegrade and fast pathway (FP) for retrograde conduction. Atropine enhanced both SP antegrade and FP retrograde conduction, shown by a decrease in paced cycle lengths (atrial and ventricular) producing AV and ventriculoatrial block. Five patients had induction of sustained PSVT before and after atropine. Seven patients failed to induce or sustain PSVT before atropine, because of retrograde FP refractoriness. All seven had induction of sustained PSVT after atropine due to facilitation of FP retrograde conduction. Two patients had only single atrial echoes before atropine, reflecting SP antegrade refractoriness. After atropine, sustained PSVT was inducible in one, and nonsustained in the other, PSVT cycle length could be compared in seven patients before and after atropine and decreased from 383 +/- 25 to 336 +/- 17 (p less than 0.05). Thus, in patients with dual AV nodal pathways, atropine facilitated SP antegrade and FP retrograde conduction, shortened cycle length of PSVT and potentiated ability to sustain PSVT.

Adult↗

Significance of chronic bifascicular block without apparent organic heart disease.

Eighty-six of 452 patients (19%) with chronic bifascicular block were found to have no clinically apparent associated organic heart disease (OHD) and were defined as having primary conduction disease (PCD). Comparison of patients with PCD and OHD revealed a significantly lower incidence of the following clinical variables in the PCD patients (p less than 0.001): exertional angina, dyspnea, congestive heart failure, cardiomegaly, functional class I (all by study design), left bundle branch block and premature ventricular contractions. Both mean AH and HV intervals were significantly shorter in patients with PCD (p less than 0.01). The incidence of HV prolongation was 21% in PCD and 41% in OHD patients (p less than 0.001). All patients were prospectively followed for 21-2998 days with a mean +/- SEM of 1209 +/- 66 days for PCD and 1172 +/- 36 days for OHD. Atrioventricular (AV) block developed in three patients from the PCD group and 26 from the OHD group (NS), with spontaneous block occurring in one (1%) PCD patient and 19 (5%) OHD patients (p less than 0.05). Annual mortality due to sudden death as well as total cardiovascular mortality (including sudden death) for the 5-year follow-up was significantly lower in patients with PCD. Patients with PCD have significantly lower incidence of electrophysiologic abnormalities and subsequent spontaneous AV block as well as cardiovascular and sudden death mortality. The diagnosis of PCD based on clinical criteria probably underestimates the presence of underlying OHD, as suggested by a small but definite risk of cardiovascular mortality.

Adult↗

Significance of block distal to the His bundle induced by atrial pacing in patients with chronic bifascicular block.

Twenty-one of 496 (4%) patients with chronic bifascicular block, studied and followed prospectively, had block distal to the His bundle (BDH) induced by atrial pacing during initial electrophysiologic studies. In six, BDH was noted during pacing-induced atrioventricular (AV) nodal Wenckebach periods (at paced rates of 150--190 beats/min), with BDH in the short HH cycles after the AV nodal blocked P (lond cycle). The AH interval was normal in all six patients and HV was normal in four. None of the six patients has developed AV block during a mean follow-up of 5.33 +/- 0.48 years. In 15 patients, pacing-induced BDH was noted during intact AV nodal conduction (paced rate of 80--200 beats/min). The AH interval was prolonged in one, and HV was prolonged in 10 of the 15 patients. During a mean follow-up of 3.4 +/- 0.59 years, seven of these patients developed AV block, one had treadmill-provoked AV block, and two died suddenly (major morbid event in 10 of 15 patients). In conclusion, BDH induced by atrial pacing is an infrequent finding in patients with bifascicular block, and can be a functional as well as a pathologic response. The latter is associated with a high risk of major morbid events (AV block and sudden death).

Adolescent↗

Failure of surgery in preexcitation. Correlation with pathologic findings.

A 37-year-old man with mitral stenosis and recurrent drug-resistant paroxysmal atrial fibrillation, paroxysmal supraventricular tachycardia, and preexcitation, underwent two surgical attempts to ablate an anomalous pathway (AP). Electrophysiologic study demonstrated a left posterior AP with a short antegrade refractory period. Epicardial mapping at the time of mitral valve replacement (left lateral thoracotomy) suggested a posterior right AP. Mitral valve replacement and incision of the left atrial wall failed to cure preexcitation. Epicardial mapping at a second operation (median sternotomy) demonstrated a subepicardial left posterior AP. Right atrial and atrial septal incisions failed to cure preexcitation. Serial section of the atrioventricular rings and conduction system demonstrated an intact left posterior anomalous atrioventricular muscle bundle with surgical incision placed above the plane of the mitral anulus.

Adult↗

Paroxysmal supraventricular tachycardia induction in patients with Wolff-Parkinson-White syndrome.

In 54 patients with pre-excitation, 30 (56%) had inducible A-V re-entrant paroxysmal tachycardia. Of these 30, 20 had spontaneous paroxysmal tachycardia (four also had atrial fibrillation), four had spontaneous paroxysmal atrial fibrillation, five had a history of palpitation without arrhythmia, and one was asymptomatic. In 24 patients (44%), paroxysmal tachycardia was not inducible. Of these 24, none had documented paroxysmal tachycardia, four had atrial fibrillation, none had palpitation without arrhythmia, and 11 were asymptomatic. The incidence of documented paroxysmal tachycardia was higher in the patients with inducible tachycardia (P less than 0.001). Tachycardia induction was noted in 20 of 20 patients with spontaneous paroxysmal tachycardia, eight of 12 patients with paroxysmal atrial fibrillation, five of 14 patients with palpitation and no arrhythmia, and one of 12 asymptomatic patients. The frequency of ability to induce paroxysmal tachycardia was significantly higher in both the patients with documented spontaneous paroxysmal tachycardia and the patients with paroxysmal atrial fibrillation than in the asymptomatic group (P less than 0.01).

Adolescent↗