Characterization of reentrant circuit in macroreentrant right atrial tachycardia after surgical repair of congenital heart disease: isolated channels between scars allow "focal" ablation.

BACKGROUND: The purpose of this study was to characterize the circuit of macroreentrant right atrial tachycardia (MacroAT) in patients after surgical repair of congenital heart disease (SR-CHD). METHODS AND RESULTS: Sixteen patients with atrial tachycardia (AT) after SR-CHD were studied (atrial septal defect in 6, tetralogy of Fallot in 4, and Fontan procedure in 6). Electroanatomic right atrial maps were obtained during 15 MacroATs in 13 patients, focal AT in 1 patient, and atrial pacing in 2 patients without stable AT. A large area of low bipolar voltage (/=2 scars forming narrow channels. Ablation within the channels eliminates MacroAT.

Ablation strategies reflect evolving concepts of atrial fibrillation mechanisms.

Atrial fibrillation (AF) is the most common arrhythmia seen in clinical practice and results in the largest number of arrhythmia related hospital admissions. Despite the enormity of its impact on patients and the health care system, current medical therapy for AF is inadequate. Therapeutic approaches have been guided by understanding of fibrillation mechanisms. AF results from multiple simultaneous reentrant wavefronts. This is a diffuse and dynamic substrate with no discrete anatomic target. The catheter mediated "Maze" procedure employs creation of linear lesions to divide the atria into segments too small to support reentrant activation. Using current catheter technology this is a challenging procedure with low success rates and high complication rates. The observation that rapid focal firing of atrial myocytes within the pulmonary veins initiates fibrillation in the majority of paroxysmal AF patients has led to an entirely new ablation strategy. The sites of firing that initiate AF are targeted for ablation. Thus the paradigm for AF ablation has changed dramatically from altering the substrate of ongoing fibrillation to elimination of the triggers that initiate fibrillation. Initial experience revealed that multiple sites in the pulmonary veins are capable of rapid firing. Unfortunately not all sites fire during an ablation procedure. Sites that are quiescent during an ablation procedure may result in AF recurrence despite acute success. Ablation strategy has thus changed yet again to electrical isolation of all pulmonary venous tissue from the left atrium. The evolution of ablation strategies has paralleled our understanding of AF mechanisms. Elucidation of the mechanisms responsible for venous firing may lead to more specific therapy for the prevention of AF in the future.

Age differences in coping and locus of control: a study of managerial stress in Hong Kong.

The present study involved data collection from 3 samples of Hong Kong managers to examine mechanisms by which age would relate to work well-being. A total of 634 managers was drawn by random sampling and purposive sampling methods. The results showed that age was positively related to well-being (job satisfaction and mental well-being). Furthermore, older managers reported fewer sources of stress, better coping, and a more internal locus of control. Multiple regression analyses suggested that the relations of age with 2 well-being indicators can be attributed to various combinations of coping, work locus of control, sources of stress, managerial level, and organizational tenure.

Lidocaine-induced conduction disturbance in patients with systemic hyperkalemia.

We report 2 cases in which lidocaine, given for wide-complex tachycardia in the presence of hyperkalemia, precipitated profound conduction disturbance and asystole. The electrophysiologic effects of hyperkalemia and its interaction with lidocaine are reviewed. In patients with known hyperkalemia and wide-complex tachycardia, treatment should be directed at hyperkalemia, rather than following treatment algorithms for wide-complex tachycardia.

A longitudinal study of relations between job stressors and job strains while controlling for prior negative affectivity and strains.

Interpretation of observed relations between job stressors and job strains in cross-sectional surveys is often ambiguous because of possible 3rd variables (both stable background factors, such as personality, and transitory occasion factors, such as mood). In this longitudinal study, negative affectivity (NA) and strains were assessed both in college and later on the job. Stressors were assessed only on the job. Evidence was found that some background factors affected measures of job stressors and job strains in that college measures were significantly related to subsequent measures on the job. Relations between job stressors and job strains, however, were in most cases not affected significantly when prior strains and NA were controlled for. Furthermore, the results suggested that NA measures are subject to occasion factors.

Using the Job-Related Affective Well-Being Scale (JAWS) to investigate affective responses to work stressors.

Prior research linking job stressors to psychological strains has been limited to a small number of emotional reactions. This article describes research linking job stressors to a wide range of affective states at work. In Study 1, a multidimensional scaling procedure was used on a matrix of similarity judgments by 51 employees of 56 job-related affective statements to support a 2-dimensional view of affective well-being. In Study 2, ratings of the affect statements by 100 employees further supported the contention that the dimensions were pleasure-displeasure and degree of arousal. In Study 3, 114 full-time university employees responded to the Job-Related Affective Well-Being Scale, which was found to be related to measures of job stressors as well as job satisfaction and physical symptoms.

Potassium channelopathies.

The molecular diversity of K(+)-selective channels far exceeds any other group of voltage- or ligand-gated channels, reflecting their early ancestral origin. This diversity is mirrored by the broad spectrum of physiological functions subserved by these proteins. Potassium channels modulate the resting potential and action potential duration of neurons, myocytes and endocrine cells and stabilize the membrane potential of excitable and nonexcitable cells. In addition to channel diversity, differential cellular expression of K+ channels determines the specific electrical responses to stimuli in a particular cell or tissue. This study reviews the recent genetic and physiological studies of congenital disorders caused by mutations in genes encoding K+ channels. These include the human disorders of episodic ataxia with myokymia, long QT syndrome and Bartter's syndrome, and weaver ataxia in mice. An understanding of the molecular basis of these diseases could facilitate the discovery and development of specific pharmacological therapies.

Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.

The slowly activating delayed-rectifier K+ current, I(Ks), modulates the repolarization of cardiac action potentials. The molecular structure of the I(Ks) channel is not known, but physiological data indicate that one component of the I(Ks), channel is minK, a 130-amino-acid protein with a single putative transmembrane domain. The size and structure of this protein is such that it is unlikely that minK alone forms functional channels. We have previously used positional cloning techniques to define a new putative K+-channel gene, KVLQT1. Mutations in this gene cause long-QT syndrome, an inherited disorder that increases the risk of sudden death from cardiac arrhythmias. Here we show that KVLQT1 encodes a K+ channel with biophysical properties unlike other known cardiac currents. We considered that K(V)LQT1 might coassemble with another subunit to form functional channels in cardiac myocytes. Coexpression of K(V)LQT1 with minK induced a current that was almost identical to cardiac I(Ks). Therefore, K(V)LQT1 is the subunit that coassembles with minK to form I(Ks) channels and I(Ks) dysfunction is a cause of cardiac arrhythmia.

Covariability of V3 loop amino acids.

We reanalyzed for covariability a set of 308 human immunodeficiency virus type 1 (HIV-1) V3 loop amino acid sequences from the B envelope sequence subtype previously analyzed by Korber et al.,1 as well as a new set of 440 sequences that also included substantial numbers of sequences from subtypes A, D, and E. We used the measure employed by Korber et al., essentially the likelihood ratio statistic for independence, plus two additional measures as well as clade information to examine the new set and both data sets simultaneously. We set forth the following conclusions and observations. The eight most highly connected sites identified through these statistical approaches included all of the six residues previously shown to have determining roles in structure, immunologic recognition, virus phenotype, and host range; each of the seven pairs of covariant sites found by Korber were signaled by our additional two measures in the set of 308 sequences, although 2 or 3 dropped out of the examination of the set of 440 when the requirement of stringent significance was applied for some or all of the three tests, respectively; using the same criteria, a total of 20 (including 5 Korber et al. pairs) or a total of 6 (including 4 Korber et al. pairs) were found when the set of 440 was added. Several limitations to statistical analysis of this type of HIV sequence data were also noted. For example, the data sets were, by historical necessity, collected haphazardly. For example, it was not possible to separate substantially sized groups out according to time of or since infection, disease status, antiviral treatment, geography, etc. There was also an enormous "wealth of significance" within the data. For example, for one measure the 440 data set showed 233 of the 465 pairs of sites with a likelihood ratio statistic of < 0.001. Last, most sites had consensus amino acids in 80% or more of the sequences; hence, there was an absence of data on many combinations of amino acids. Given the observed linkage between sites shown to be covariable and those known to have critical biological function, the statistical approaches we and Korber et al. have outlined may find use in predicting critical structural features of HIV proteins as targets for therapeutic intervention.

Fast inactivation causes rectification of the IKr channel.

The mechanism of rectification of HERG, the human cardiac delayed rectifier K+ channel, was studied after heterologous expression in Xenopus oocytes. Currents were measured using two-microelectrode and macropatch voltage clamp techniques. The fully activated current-voltage (I-V) relationship for HERG inwardly rectified. Rectification was not altered by exposing the cytoplasmic side of a macropatch to a divalent-free solution, indicating this property was not caused by voltage-dependent block of outward current by Mg2+ or other soluble cytosolic molecules. The instantaneous I-V relationship for HERG was linear after removal of fast inactivation by a brief hyperpolarization. The time constants for the onset of and recovery from inactivation were a bell-shaped function of membrane potential. The time constants of inactivation varied from 1.8 ms at +50 mV to 16 ms at -20 mV; recovery from inactivation varied from 4.7 ms at -120 mV to 15 ms at -50 mV. Truncation of the NH2-terminal region of HERG shifted the voltage dependence of activation and inactivation by +20 to +30 mV. In addition, the rate of deactivation of the truncated channel was much faster than wild-type HERG. The mechanism of HERG rectification is voltage-gated fast inactivation. Inactivation of channels proceeds at a much faster rate than activation, such that no outward current is observed upon depolarization to very high membrane potentials. Fast inactivation of HERG and the resulting rectification are partly responsible for the prolonged plateau phase typical of ventricular action potentials.

Spectrum of HERG K+-channel dysfunction in an inherited cardiac arrhythmia.

Long QT syndrome (LQT) is an autosomal dominant disorder that can cause sudden death from cardiac arrhythmias. We recently discovered that mutations in HERG, a K+-channel gene, cause chromosome 7-linked LQT. Heterologous expression of HERG in Xenopus oocytes revealed that HERG current was similar to a well-characterized cardiac delayed rectifier K+ current, IKr, and led to the hypothesis that mutations in HERG reduced IKr, causing prolonged myocellular action potentials. To define the mechanism of LQT, we injected oocytes with mutant HERG complementary RNAs, either singly or in combination with wild-type complementary RNA. Some mutations caused loss of function, whereas others caused dominant negative suppression of HERG function. These mutations are predicted to cause a spectrum of diminished IKr and delayed ventricular repolarization, consistent with the prolonged QT interval observed in individuals with LQT.

Class III antiarrhythmic drugs block HERG, a human cardiac delayed rectifier K+ channel. Open-channel block by methanesulfonanilides.

We recently reported that mutations in HERG, a potassium channel gene, cause long QT syndrome. Heterologous expression of HERG in Xenopus oocytes revealed that this channel had biophysical properties nearly identical to a cardiac delayed rectifier K+ current I(Kr), but had dissimilar pharmacological properties. Class III antiarrhythmic drugs such as E-4031 and MK-499 are potent and specific blockers of I (Kr) in cardiac myocytes. Our initial studies indicated that these compounds did not block HERG at a concentration of 1 micromol/L. In the present study, we used standard two-microelectrode voltage-clamp techniques to further characterize the effects of these drugs on HERG channels expressed in oocytes. Consistent with initial findings, 1 micromol/L MK-499 and E-4031 had not effect on HERG when oocytes were voltage clamped at a negative potential and not pulsed during equilibration with the drug. However, MK-499 did block HERG current if oocytes were repetitively pulsed, or clamped at a voltage positive to the threshold potential for channel activation. This finding is in contrast to previous studies that showed significant block of I(Kr) in isolated myocytes by similar drugs, even in the absence of pulsing. This apparent discrepancy may be due to differences in channel characteristics (HERG versus guinea pig and mouse I (Kr)), tissue (oocytes versus myocytes), or specific drugs. Under steady state conditions, block of HERG by MK-499 was half maximal at 123 +/- 12 nmol/L at a test potential of -20 mV. MK-499 (150 nmol/L) did not affect the voltage dependence of activation and rectification nor the kinetics of activation and deactivation of HERG. These data indicate that MK-499 preferentially blocks open HERG channels and further support the conclusion that HERG subunits form I(Kr) channels in cardiac myocytes.

The impact of cross-training on team functioning: an empirical investigation.

The effects of cross-training (presence vs. absence) and workload (high vs. low) on team processes, communication, and task performance were examined. Eighty male undergraduate students were randomly assigned to one of four training conditions: cross-training, low workload; cross-training, high workload; no cross-training, low workload; and no cross-training, high workload. Results indicated that cross-training was an important determinant of effective teamwork process, communication, and performance. Predicted interactions between cross-training and workload were not supported. Implications for the design and implementation of cross-training as a means to improve team functioning are discussed.

The clinical nurse specialist and psychiatrist in joint practice.

The authors describe a joint practice model between a clinical nurse specialist and psychiatrist. The authors address factors to consider in establishing a joint practice--negotiation of roles and benefits as well as clinical supervision. In addition, specific clinical responsibilities for the nurse specialist, as well as potential expanded duties, are outlined.

Negative affectivity as the underlying cause of correlations between stressors and strains.

The extent to which negative affectivity (NA), the tendency to experience a wide range of negative emotions, inflated correlations between chronic job stressors and strains was examined in this study. NA was found to account for a large proportion of shared variance between stressors and physical strains (as indicated by absence, doctor visits, and physical symptoms). Contrary to the results of Brief, Burke, George, Robinson, and Webster (1988), NA did not account for much of the variance shared by stressors and affective strains (job satisfaction, anger, and feelings of stress and frustration). Reasons for the failure of this and several earlier studies to successfully replicate Brief et al.'s results are explored.

Relations of job characteristics from multiple data sources with employee affect, absence, turnover intentions, and health.

Much of the evidence in support of job characteristics theory is limited to incumbent reports of job characteristics. In this study, job characteristics data from three independent sources--incumbents, ratings from job descriptions, and the Dictionary of Occupational Titles--were used. Convergent validities of incumbent reports with other sources were quite modest. Although incumbent reports of job characteristics correlated significantly with several employee outcomes (job satisfaction, work frustration, anxiety on the job, turnover intentions, and number of doctor visits), the other sources showed few significant correlations, except for number of doctor visits. Caution is urged in the use of incumbent self-reports of job characteristics as indicators of actual work environments. New methods for studying job characteristics are suggested.

Benefits of the CO2 laser for verruca resistant to other modalities of treatment.

The benefits of the carbon dioxide (CO2) laser in the treatment of verruca resistant to other forms of treatment have been studied. Twenty-five patients with warts unsuccessfully treated from one to five times previously were treated with the laser, followed for a minimum of 6 months, and evaluated. Eight of these patients (32%) gained a total permanent cure. An additional five treatments resulted in a subtotal (over 75%) cure but some warts remained. Thus, 13 of 25 patients (52%) experienced complete or partially successful treatment. The CO2 laser is a valuable modality in the treatment of recalcitrant warts but cannot be expected to cure all such warts.