Biomedical subjects

C A McPherson

Publications and source records attributed to C A McPherson.

17 recordsLinked to original sources

PubMed2000

Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators.

BACKGROUND: The incidence of sudden cardiac death increases in populations who experience disasters such as earthquakes. The physiological link between psychological stress and sudden death is unknown; one mechanism may be the direct effects of sympathetic arousal on arrhythmias. To determine whether mental stress alters the induction, rate, or termination of ventricular arrhythmias, we performed noninvasive programmed stimulation (NIPS) in patients with defibrillators and ventricular tachycardia (VT), which is known to be inducible and terminated by antitachycardia pacing, at rest and during varying states of mental arousal. METHODS AND RESULTS: Eighteen patients underwent NIPS in the resting-awake state (nonsedated). Ten underwent repeat testing during mental stress (mental arithmetic and anger recall). Induced VT was faster in 5 patients (P=0.03). VT became more difficult to terminate in 5 patients during mental stress; 4 required a shock (P=0.03). There was no change in ease of induction with mental stress. There was no evidence of ischemia on ECG or continuous ejection fraction monitoring. Eight patients received a shock in the resting-awake state and did not perform mental stress. Four underwent repeat NIPS after sedation; 3 then had induced VT terminated with antitachycardia pacing. All patients with an increase in norepinephrine of >50% had alterations in VT that required shock for termination (P<0.01). CONCLUSIONS: Mental stress alters VT cycle length and termination without evidence of ischemia. This suggests that mental stress may lead to sudden death through the facilitation of lethal ventricular arrhythmias.

Aged↗

PubMed1999

Failure to improve left ventricular function after coronary revascularization for ischemic cardiomyopathy is not associated with worse outcome.

Background-Preoperative identification of viable myocardium in patients with ischemic cardiomyopathy is considered important because CABG can result in recovery of left ventricular (LV) function. However, the hypothesis that lack of improvement of LV function after CABG is associated with poorer patient outcome is untested. Methods and Results-Outcome was compared in patients with ischemic LV dysfunction (LVEF </=0.30) with and without improvement in LVEF after CABG. Of 135 consecutive patients, 128 (95%) survived CABG and 104 (77%) had pre- and post-CABG LVEF assessment. Of these 104 patients, 68 (65%) had >0.05 increase in LVEF (group A) and 36 (35%) had no significant change, or </=0.05 decrease in LVEF (group B) compared with pre-CABG LVEF. No significant differences existed in age, gender, comorbidities, baseline symptoms, baseline LVEF, or intraoperative variables between groups A and B. Group A increased LVEF from 0.24+/-0.05 to 0.39+/-0.1 (P<0.005). In Group B, LVEF did not change significantly postoperatively, 0.24+/-0.05 to 0.23+/-0.06 (P=NS). Postoperative improvement in angina and heart failure scores were similar between the 2 groups. Survival free of cardiac death was similar for both groups (93% in group A and 94% in group B, P=NS) at a mean follow-up of 32+/-23 months. Conclusions-Lack of improvement of global LVEF after CABG is not associated with poorer outcome compared with that of patients with improved LVEF, presumably because effective revascularization of ischemic myocardium, even without improvement in ventricular function, protects against future infarction and death.

Adult↗

PubMed1999

Effect of erythromycin on myocardial repolarization in patients with community-acquired pneumonia.

BACKGROUND: Erythromycin has been associated with prolongation of myocardial repolarization and torsades de pointes (TdP). METHODS: To determine the frequency, dose-response, and risk factors for erythromycin-associated prolongation of myocardial repolarization, we observed data of patients admitted to our hospital with pneumonia who were treated with erythromycin. RESULTS: In 35 women and 28 men enrolled in this study, the QTc increased from 434 +/- 4 milliseconds at baseline to 464 +/- 5 milliseconds after receiving a cumulative dose of 3.2 +/- 0.2 g of erythromycin. Neither age, sex, presence of preexistent congestive heart failure/coronary artery disease, electrolyte values, nor cumulative dose of erythromycin was associated with QTc prolongation. In 27 patients who received intravenous erythromycin for 3 days, the QTc increased from 427 +/- 5 milliseconds before to 461 +/- 8 milliseconds at 24 hours but did not increase further by day 3 (457 +/- 10 milliseconds). No patient in this cohort had TdP. CONCLUSIONS: Erythromycin therapy is associated with prolongation of myocardial repolarization that manifests after the first few doses in a majority of patients.

Administration, Oral↗

PubMed1998

Inappropriate sensing of atrial stimuli in patients with third-generation defibrillators and DDD pacemakers.

Although the problem of ICD sensing of paced ventricular stimuli has been resolved by incorporation of VVI pacing into current ICDs, many patients required separate DDD pacemakers. We report a problematic PM-ICD interaction: the inability to prevent sensing of paced atrial stimuli ("atrial sensing") leading to double-counting in DDD-PM-requiring patients with transvenous (TV) ICDs with aggressive autogain sensing (CPI Ventak PRxII or III). Four of eight patients receiving both transvenous DDD PMs and ICDs (CPI Endotak lead, at the RV apex), had atrial sensing, leading to double counting, despite intraoperative testing of multiple atrial locations with an active fixation lead. Five patients had a PRxII/III ICD, four with atrial sensing (80%), and three a PRx without atrial sensing. Patients with atrial sensing were not distinguished by any clinical or device related variable. In patients with atrial sensing (all with heart block), the PM was programmed to VDD mode. No patient has received inappropriate therapy or failed to sense VF in follow-up. In many patients with TV ICDs who required DDD pacing, no atrial position can be found without ICD sensing of atrial stimuli. While in patients with heart block this problem can be circumvented by programming to the VDD mode, in patients with sinus incompetence it may only be resolved by the combination ICD-DDD PM, currently in development.

Aged↗

PubMed1993

A bifunctional enzyme, with separate xylanase and beta(1,3-1,4)-glucanase domains, encoded by the xynD gene of Ruminococcus flavefaciens.

Adjacent regions of a Ruminococcus flavefaciens 17 DNA fragment were found to encode xylanase and beta(1,3-1,4)-glucanase activities. Sequencing of this fragment showed that both activities are encoded by a single 2,406-bp open reading frame corresponding to the xynD gene. The predicted product has a characteristic signal sequence that is followed by an amino-terminal domain related to family G xylanases, while the carboxyterminal domain is related to beta(1,3-1,4)-glucanases from several other bacterial species. These two domains are connected by a region of unknown function that consists of 309 amino acids and includes a 30-amino-acid threonine-rich sequence. A polypeptide having a molecular weight of approximately 90,000 and exhibiting xylanase and beta(1,3-1,4)-glucanase activities was detected in Escherichia coli cells carrying the cloned xynD gene. This is one of the first cases in which a microbial polysaccharidase has been shown to carry separate catalytic domains active against different plant cell wall polysaccharides within the same polypeptide. xynD is one of a family of related genes in R. flavefaciens that encode enzymes having multiple catalytic domains, and the amino terminus of XYLD exhibits a high degree of similarity with the corresponding regions of another xylanase, XYLA, which carries two different xylanase catalytic domains.

Amino Acid Sequence↗

PubMed1991

Sequence of a cellulase gene from the rumen anaerobe Ruminococcus flavefaciens 17.

A cellulase gene (endA) was isolated from a library of Ruminococcus flavefaciens strain 17 DNA fragments inserted in pUC13. The endA product showed activity against acid-swollen cellulose, carboxymethyl-cellulose, lichenan, cellopentaose and cellotetraose, but showed no activity against cellotriose or binding to avicel. Nucleotide sequencing indicated an encoded product of 455 amino acids which showed significant sequence similarity (ranging from 56% to 61%) with three endoglucanases from Ruminococcus albus, and with Clostridium thermocellum endoglucanase E. Little relatedness was found with a cellodextrinase previously isolated from R. flavefaciens FD1.

Amino Acid Sequence↗

PubMed1991

Expression of two xylanase genes from the rumen cellulolytic bacterium Ruminococcus flavefaciens 17 cloned in pUC13.

Two distinct xylanase genes (designated xynA and xynB) were subcloned in pUC13 from non-homologous restriction fragments of Ruminococcus flavefaciens 17 DNA originally isolated in lambda EMBL3. The products of the two genes showed similar pH optima for hydrolysis of oat spelt xylan (around 5.5) and had little or no activity against carboxymethylcellulose. Trace activities against p-nitrophenyl (pNP) cellobioside and pNP-xyloside were detected in clones containing xynA, but not in one harbouring xynB. The xylanase associated with clones carrying xynA produced mainly xylobiose and xylose from xylan and did not give hydrolysis of xylobiose, while that encoded by xynB produced mainly xylobiose and higher xylo-oligosaccharides from xylan. There was evidence of increased expression, at the RNA level, of these two genes, and of another cloned region encoding multiple activities including xylanase, in R. flavefaciens 17 grown with xylan, as compared with cellobiose, as energy source. Total cell-associated xylanase and beta-xylosidase activities, and supernatant xylanase activity, were shown to be similarly induced in xylan-grown R. flavefaciens, 17.

Animals↗

PubMed1989

Rapid self-terminating ventricular tachycardia induced during electrophysiologic study: a prospective evaluation.

The clinical significance of rapid self-terminating ventricular tachycardia induced during electrophysiologic study was prospectively evaluated in three patient groups with clinical ventricular arrhythmias. Group A (11 patients) had inducible rapid self-terminating ventricular tachycardia only (mean cycle length less than or equal to 250 ms and greater than or equal to 10 beats in duration). In Group B (22 patients) induction of this arrhythmia was followed by the induction of sustained ventricular tachycardia. In Group C (82 patients) sustained ventricular tachycardia was induced without preceding rapid self-terminating ventricular tachycardia. All clinical characteristics of Group B patients were similar to those of Group C patients but differed markedly from those of Group A patients. Compared with Group A patients, Group B patients had a lower left ventricular ejection fraction (32 +/- 13% versus 52 +/- 17%, p = 0.004) and a greater prevalence of coronary artery disease (82% versus 0%, p less than 0.0001), structural heart disease and a history of clinical sustained ventrical arrhythmias. Similarly, the induced self-terminating ventricular tachycardia differed in Group A and Group B patients. The arrhythmias in Group B patients were more often monomorphic, were more often induced with one or two extrastimuli and had a longer cycle length than those in Group A patients. In Group B patients, the electrophysiologic characteristics of the self-terminating and the sustained induced ventricular tachycardias were similar. Cardioversion was required in 50% of Group B patients compared with 27% of Group C patients (p = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Molecular cloning of genes from Ruminococcus flavefaciens encoding xylanase and beta(1-3,1-4)glucanase activities.

Clones expressing activity against xylan or beta(1-3,1-4)glucan (lichenan) were isolated from a library of Ruminococcus flavefaciens 17 DNA made in bacteriophage lambda EMBL3. Hybridization analyses indicated the recovery of four separate genes encoding xylanases that showed no detectable associated carboxylmethylcellulase activity. One of these genes was associated with clones that also expressed beta(1-3,1-4)glucanase and beta-xylosidase activities.

Animals↗

PubMed1988

Electrophysiologic effects of thrombolytic therapy in patients with a transmural anterior myocardial infarction complicated by left ventricular aneurysm formation.

To assess the effects of early thrombolytic therapy on the incidence of clinical and induced ventricular arrhythmias in high risk postmyocardial infarction patients, 32 patients with a transmural anterior myocardial infarction complicated by left ventricular aneurysm formation were prospectively evaluated. Sixteen patients (Group A) received routine care because of contraindication to thrombolytic therapy or other factors and 16 (Group B) received either tissue plasminogen activator or streptokinase within 6 h of the onset of chest pain. The two groups were similar in left ventricular ejection fraction (mean +/- SD, 28 +/- 9% [Group A] versus 30 +/- 8% [Group B]) and occurrence of spontaneous nonsustained ventricular tachycardia, new bundle branch block and congestive heart failure. Group B patients had higher peak creatine kinase MB levels (446 +/- 336 versus 205 +/- 120 IU; p = 0.017) and earlier time to peak creatine kinase values (13.4 +/- 6.6 versus 19.1 +/- 6.1 h; p = 0.006). Twenty patients who had no clinical sustained ventricular arrhythmias underwent electrophysiologic study 13 +/- 6 days after infarction. Ventricular tachycardia was induced during the study in 7 (88%) of 8 Group A patients, but in only 1 (8%) of 12 Group B patients given thrombolytic therapy (p = 0.0008). During a mean follow-up period of 11 +/- 8 months, eight Group A patients (50%) died suddenly or were resuscitated from sustained ventricular tachycardia; all Group B patients are alive and have had no clinical arrhythmic events (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1987

Situational panic attacks. Behavioral, physiologic, and biochemical characterization.

To investigate the pathophysiology of nonpharmacologically induced panic attacks, 18 drug-free agoraphobic patients and 13 matched healthy subjects underwent structured exposure to phobic situations. Heart rate, blood pressure, and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, growth hormone, and prolactin levels were measured before, during, and after exposure. Fifteen patients experienced situational panic attacks during exposure. Panicking patients displayed significantly greater increases in heart rate but not blood pressure or plasma free MHPG or cortisol in comparison with the healthy subjects. Growth hormone and prolactin responses tended to be smaller in the patients. If brain noradrenergic hyperactivity occurs during situational panic attacks, it may be too brief or too restricted in regional localization to affect MHPG levels in plasma. Chronically recurrent attacks may cause an adaptation of neuroendocrine mechanisms activated by anxiety or stress.

Adult↗

PubMed1987

Dissociation of electrophysiologic and pharmacologic stability during an abbreviated oral loading regimen of amiodarone.

Thirty-three patients treated with an abbreviated oral amiodarone loading regimen for ventricular tachycardia underwent electrophysiologic testing in the control state, after 1 week of high-dose (1170 +/- 88 mg/day) inpatient therapy; and after an 8-week intermediate (669 +/- 129 mg/day) dosing phase. Serum levels of amiodarone and desethylamiodarone were measured by high-pressure liquid chromatography during follow-up electrophysiologic studies. Although the corrected sinus node recovery time, sinoatrial conduction time, and AH and HV intervals remained unchanged throughout the loading period, the sinus cycle length, Wenckebach cycle length, atrial and ventricular refractory periods, and ventricular tachycardia mean and return cycle lengths lengthened significantly by 1 week. They then remained stable for the remainder of the treatment period (control less than 1 and 8 weeks, p less than 0.05). In contrast, amiodarone and especially desethylamiodarone levels rose from 1 to 8 weeks: 1.29 +/- 0.56 to 1.97 +/- 0.90 micrograms/ml (p = 0.001) and 0.63 +/- 0.29 to 1.29 +/- 0.61 micrograms/ml (p less than 0.0001), respectively. Because this regimen produces relatively prompt electrophysiologic changes, which then stabilize, early outpatient management becomes feasible before pharmacologic steady state is attained.

Aged↗

PubMed1987

Factors affecting the rate of breakdown of bacterial protein in rumen fluid.

1. The cellular proteins of Butyrivibrio fibrisolvens, Lactobacillus casei, Megasphaera elsdenii, Selenomonas ruminantium and Streptococcus bovis were labelled by growth in the presence of L-[14C]leucine, and the breakdown of labelled protein was measured in incubations of these bacteria with rumen fluid to which unlabelled 5 mM-L-leucine was added. The rate of protein breakdown was estimated from the rate of release of radioactivity into acid-soluble material. 2. Protein breakdown occurred at different rates in different species. The mean rates for B. fibrisolvens, L. casei, M. elsdenii, Sel. ruminantium and Str. bovis were 28.6, 18.1, 17.7, 10.5 and 5.3%/h respectively in samples of strained rumen fluid (SRF) with different protozoal populations. Rates of 3%/h or less were found in SRF from ciliate-free sheep or in faunated SRF from which protozoa had been removed by centrifugation. Further removal of mixed rumen bacteria had little effect. Suspensions of washed protozoa degraded bacterial protein at rates which were of the same order as those found in SRF. 3. The rate of breakdown of bacterial protein in different samples of SRF tended to increase as the numbers of small entodiniomorphid protozoa increased. The numbers of larger entodiniomorphs and holotrichs had no obvious influence on this rate. 4. Autoclaved and u.v.-treated bacteria were generally no different from live bacteria in their susceptibility to breakdown in SRF from faunated sheep, indicating that endogenous protein turnover was not a significant cause of bacterial protein catabolism. 5. The rate of bacterial protein breakdown was unrelated to the proteolytic activity of SRF. 6. It was concluded that predation by small protozoa is by far the most important cause of bacterial protein turnover in the rumen, with autolysis, other lytic factors and endogenous proteolysis being of minor importance.

Animals↗

PubMed1986

Mechanisms and relevance of arrhythmias induced by high-current programmed ventricular stimulation.

Programmed ventricular stimulation was performed at 10 mA with up to 3 extrastimuli in 15 patients studied for indications other than sustained ventricular tachycardia and with no sustained arrhythmias induced at twice diastolic threshold. Stimulation with 10 mA produced 6 new instances of ventricular fibrillation (VF), 1 of which may have been clinically relevant. No sustained ventricular tachycardia was induced. VF was induced with triple extrastimuli in 5 of 6 cases. The increased arrhythmogenicity of 10-mA stimulation was related to shortened ventricular refractory periods (S2 267 +/- 21 vs 231 +/- 22 ms, p less than 0.0001; S3 217 +/- 15 vs 178 +/- 15 ms, p less than 0.0005) and did not occur without at least 2 extrastimulus coupling intervals being less than was possible at twice diastolic threshold. Stimulation with 10 mA also resulted in greater increments in extrastimulus local conduction time (27 +/- 19 vs 54 +/- 15 ms, p less than 0.001) and intraventricular conduction time (27 +/- 17 vs 45 +/- 18 ms, p less than 0.005) as coupling intervals were shortened from 360 ms to just beyond ventricular refractoriness. VF was induced more frequently in patients with cardiomyopathy (p less than 0.05). Thus, the increase in arrhythmogenicity with 10-mA stimulation with triple extrastimuli is predominantly manifest as VF, which occurs with considerable frequency and is of uncertain clinical significance. This technique should be used with great caution, and only after other stimulation modalities have been attempted.

Aged↗

PubMed1986

Ventricular tachycardia induction: comparison of triple extrastimuli with an abrupt change in ventricular drive cycle length.

This study compares two stimulation protocols in 47 patients not inducible with double extrastimuli administered during two paced cycle lengths at the right ventricular apex. Method I uses triple extrastimuli; method II, an abrupt short-to-long change in cycle length, single and double extrastimuli. Clinical arrhythmias included sustained ventricular tachycardia or fibrillation (11 patients; group I); nonsustained ventricular tachycardia (27; group II); and no documented ventricular arrhythmia (9; group III). Together, methods I and II rendered 21 of 47 patients inducible; seven were inducible by both methods. No group III patient became inducible. The two techniques were equally likely to produce tachycardias in groups I and II; to induce rapid, pleomorphic, or sustained tachycardias, and tachycardias greater than 10 beats. Since both methods can be applied at the right ventricular apex and increase sensitivity without producing tachycardia in patients with a low suspicion for ventricular arrhythmias, they may facilitate serial drug testing with an indwelling catheter, reducing the need for left-sided studies.

Adult↗

PubMed1985

Evaluation by serial electrophysiologic studies of an abbreviated oral loading regimen of amiodarone.

Optimal loading and maintenance regimens for amiodarone are undefined. Serial electrophysiologic testing was used in 25 patients with ventricular tachycardia to assess the adequacy of a 1-week oral loading regimen at 1,200 mg/day, to modify maintenance dosing at the conclusion of loading, and to evaluate the appropriateness of maintenance dosing after 2 months of therapy. During the loading period, highly significant (p less than 0.001) increases occurred in the AH interval (88 +/- 22 vs 120 +/- 31 ms), HV interval (49 +/- 10 vs 61 +/- 11 ms), AV nodal Wenckebach cycle length (390 +/- 92 vs 537 +/- 147 ms), ventricular refractory period (247 +/- 17 vs 276 +/- 23 ms), mean ventricular tachycardia cycle length (254 +/- 38 vs 298 +/- 52 ms) and return cycle length (294 +/- 55 vs 360 +/- 87 ms). Ventricular tachycardia inducibility decreased in only a minority of cases, and when observed in association with a more than 10% increase in ventricular refractory period, resulted in a lower maintenance dose. After 2 months of maintenance therapy no additional change occurred in any of these parameters except for an increase in ventricular tachycardia cycle length (298 +/- 52 vs 330 +/- 65 ms, p less than 0.017). Ventricular tachycardia inducibility again showed no consistent response. It is concluded that patients can be discharged after 1 week of therapy with oral amiodarone loading at 1,200 mg/day and that maintenance dosing modified by electrophysiologic assessment results in steady perpetuation of the cardiac amiodarone effect, as indicated by the time course of change in electrophysiologic variables consistently affected.

Administration, Oral↗

PubMed1985

Day-to-day reproducibility of responses to right ventricular programmed electrical stimulation: implications for serial drug testing.

The day-to-day reproducibility of responses to right ventricular programmed electrical stimulation was analyzed in 77 patients studied in the baseline state twice within 72 hours. Of 66 in whom ventricular tachycardia (VT) was inducible at the first study (C1), VT was reproduced in 53 (80%) at the second control study (C2). Among 41 patients in whom VT was inducible using 1 or 2 programmed electrical stimuli (PES) at C1, VT remained inducible in 39 (95%) at C2, whereas only 14 of 25 patients (56%) who required 3 or more PES for VT induction at C1 had VT reproduced at C2. The difference in the reproducibility of VT induction in these 2 patient groups was highly significant (p less than 0.001). Although VT was inducible in 50% of patients using the identical stimulation mode at each study, 35% required a more intense mode for VT induction at C2; this included 11 of 35 patients (31%) in whom VT was initially inducible with 1 or 2 PES who required 3 or more PES for induction of VT at C2. Thus, patients in whom VT is initially inducible with 1 or 2 PES demonstrate reproducible day-to-day responses to programmed electrical stimulation and appear to be excellent candidates for electrophysiologically guided antiarrhythmic drug therapy. Because VT induction was significantly less reproducible in patients who required 3 or more PES at C1, day-to-day reproducibility of VT induction should be confirmed in such patients if electropharmacologic therapy is attempted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗