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Biomedical subjects

A J Moss

Publications and source records attributed to A J Moss.

At least 145 records · Page 8Linked to original sources
PubMed1991

Efficacy of permanent pacing in the management of high-risk patients with long QT syndrome.

BACKGROUND: From the international long QT syndrome (LQTS) study, 30 patients with corrected QT interval (QTc) of more than 0.44 second 1/2 were identified who had permanent pacemakers implanted for management of recurrent syncope or aborted cardiac arrest. METHODS AND RESULTS: Pacemakers were implanted on average 7 years after the onset of the first syncopal episode. Most of the patients were female (87%), the average age at implantation was 19 +/- 13 years, the mean QTc was 0.55 +/- 0.08 second, and 57% were receiving antiadrenergic treatment for LQTS when the pacemaker was placed. Using birth as the time origin, the median cardiac event rate was significantly (p less than 0.001) reduced by pacing from 0.5 to 0 events per patient per year, with 21 patients experiencing no cardiac events during an average pacemaker follow-up of 49 months per patient. In 10 patients in whom the demand atrial pacing rate was faster than the intrinsic sinus rate, the average heart rate was increased 23 beats/min (from 58 to 81 beats/min) with pacing with reduction in the QT interval from 0.59 seconds to 0.46 seconds. CONCLUSIONS: The beneficial effects of pacing in high-risk LQTS patients probably relate to the prevention of bradycardia, pauses, and the shortening of long QT intervals--factors that are known to be arrhythmogenic in this syndrome. Permanent cardiac pacing reduces the rate of recurrent syncopal events in high-risk LQTS patients, but it does not provide complete protection.

Adult↗
PubMed1991

Pathophysiologic factors influencing prognosis after myocardial infarction.

The major determinants of outcome after surviving the acute phase of myocardial infarction include the extent of cumulative myocardial damage, infarct type and location, ventricular electrical instability, the extent of residual jeopardized ischemic myocardium, rheologic conditions, and neurohumoral factors. These several factors are intimately related to each other, yet each contributes prognostic information. Patients with multiple myocardial infarctions are at considerably greater mortality risk than those with first infarctions. Patients with first infarctions are approximately 2 years younger, have less advanced coronary disease, have less left ventricular dysfunction, and have a better outcome than those with one or more prior infarctions. Recently, the importance of nonfatal reinfarction as a time-dependent predictor of subsequent cardiac death has been appreciated. The relative contribution of nonfatal reinfarction to the risk of cardiac death is highest in patients with a first myocardial infarction. These findings indicate that prevention of further myocardial damage (reinfarction), optimization of left ventricular function, and reduction in myocardial ischemia should improve prognosis after myocardial infarction.

Humans↗
PubMed1991

Stress and sudden death. The case of the long QT syndrome.

The idiopathic long QT syndrome (LQTS) represents a unique clinical example of stress-related sudden cardiac death. LQTS is characterized by the association of several distinctive electrocardiographic features, among which prolongation of the QT interval is the best known, with life-threatening arrhythmias that usually occur under conditions of physical or psychological stress. Effective therapies exist and are represented by antiadrenergic interventions; beta-adrenergic-blocking agents are the treatment of choice. When they fail, left cardiac sympathetic denervation has also proven to be very effective. The latter result suggests a role for alpha-adrenergic mechanisms in the arrhythmias of LQTS. The stressors more frequently associated with syncopal events in LQTS patients include fear, exercise fraught with emotions, swimming, and awakening because of a loud noise. Experimentally, life threatening arrhythmias have been induced during a highly emotional situation in conscious cats with normal hearts in which right stellate ganglia have been ablated, resulting in QT interval prolongation. This selective denervation creates a sympathetic imbalance of the type proposed by one of the pathogenetic hypotheses for LQTS.

Animals↗
PubMed1990

Identification of patients at increased risk for potentially malignant arrhythmias.

This review discusses the substrate and triggers of ventricular tachyarrhythmias or fibrillation and highlights the concepts that underlie risk stratification. Topics covered include the risks posed by arrhythmias in patients with: a) postinfarction, b) cardiomyopathy c) mitral valve prolapse, d) Wolff-Parkinson-White syndrome, and e) the long QT syndrome. Appropriate identification of patients at high risk for malignant ventricular arrhythmias requires subclassification by disease entity, historic information about syncopal episodes, noninvasive testing, and invasive electrophysiologic studies in selected patients.

Arrhythmias, Cardiac↗
PubMed1990

Predicting 1-year outcome following acute myocardial infarction: physicians versus computers.

Whether decision rules derived statistically from patient data can produce better decisions than an expert clinician or a model of the expert clinician (expert system) is controversial. We examined this issue in the context of predicting cardiac death by 1 year for patients discharged from the hospital following acute myocardial infarction. Decision rules were derived from a base sample of 781 patients. These decision rules and three experienced cardiologists then estimated probability of death by 1 year for each patient in a separate test sample (n = 400). In our evaluation of the performance of the decision rules and physicians, we detected no differences, although the decision rules and physicians tended to classify the patients somewhat differently. Further multivariate analyses on the physicians' predictions showed that two of the physicians paid attention to somewhat different variables than the third physician. Lack of agreement among expert cardiologists would complicate modeling of a consensual decision-making process within the framework of an expert system.

Aged↗
PubMed1990

Cultured Chinese hamster cells undergo apoptosis after exposure to cold but nonfreezing temperatures.

Cultured Chinese hamster V79 fibroblast cells at the transition from logarithmic to stationary growth have been shown to undergo apoptosis (programmed cell death) after cold shock [B. L. Soloff, W. A. Nagle, A. J. Moss, Jr., K. J. Henle, and J. T. Crawford, Biochem. Biophys. Res. Commun. 145, 876-883 (1987)]. In this report, we show that about 95% of the cell population was susceptible to cold-induced apoptosis, and the amount of cell killing was dependent on the duration of hypothermia. Cells treated for 0-90 min at 0 degrees C exhibited an exponential survival curve with a D0 of 32 min; thus, even short exposures to the cold (e.g., 5 min) produced measurable cell killing. The cold-induced injury was not produced by freezing, because similar results were observed at 6 degrees C, and cell killing was not influenced by the cryoprotective agent dimethyl sulfoxide. Cold-induced apoptosis was inhibited by rewarming at 23 degrees C, compared to 37 degrees C, by inhibitors of macromolecular synthesis, such as cycloheximide, and by 0.8 mM zinc sulfate. The results suggest that apoptosis represents a new manifestation of cell injury after brief exposure to 0-6 degrees C hypothermia.

Animals↗
PubMed1990

Preprocessing of Holter ECGs for analysis of the dynamic interrelations between heart rate and ventricular repolarization duration variabilities.

The use of approved commercial digital Holter systems as equipment for data acquisition in cardiologic research presents several potential advantages. In fact, it may provide a standard data acquisition procedure that allows the scientists to concentrate on the data processing phase. As a consequence, it may contribute to the comparability of results among different laboratories. In general, some steps of preprocessing are needed before performing the final analysis on the data. In case of study on the variabilities of the heart rate and the duration of repolarization, preprocessing consists of beat-by-beat measurement time intervals in the 24-hour electrocardiograms. Further preprocessing steps may be required, depending on the particular analysis technique that will be applied to the data. In particular, the present study introduces an operator-free method of preprocessing Holter electrocardiograms for time series analysis of signals related to heart rate variability and variability in the duration of ventricular repolarization.

Adult↗
PubMed1990

The prognostic significance of first myocardial infarction type (Q wave versus non-Q wave) and Q wave location. The Multicenter Diltiazem Post-Infarction Research Group.

The prognostic significance of the type of first acute myocardial infarction (Q wave versus non-Q wave) and Q wave location (anterior versus inferoposterior) was determined from a multicenter data base involving 777 placebo-treated patients who were participants in the Multicenter Diltiazem Post-Infarction Trial. There were 224 patients (29%) with a non-Q wave infarction, 326 (42%) with an inferoposterior Q wave infarction and 227 (29%) with an anterior Q wave infarction. Mean left ventricular ejection fraction was significantly (p less than 0.001) lower in patients with an anterior Q wave infarction than in the other two groups (anterior Q wave 0.39; inferior Q wave 0.52; non-Q wave 0.53). Nevertheless, the total cardiac mortality rate during the follow-up period (average 25 months per patient) was only marginally higher (p = 0.42) in the anterior Q wave group (8.4%) than in the other two groups (inferoposterior Q wave 7.1%; non-Q wave 6.3%). The total first recurrent cardiac event was somewhat higher (p = 0.08) in the anterior Q wave group (18.1%) than in the other two groups (inferoposterior Q wave 11.7%; non-Q wave 15.6%). Survivorship analyses extending over 3 years revealed that electrocardiographic classification of the type of first infarction and Q wave location did not make significant independent contributions to the risk of postinfarction cardiac death or first recurrent cardiac event, either before or after adjustment for baseline clinical variables.

Adult↗
PubMed1990

Prognostic significance of nonfatal myocardial reinfarction. Multicenter Diltiazem Postinfarction Trial Research Group.

In most risk stratification and intervention postinfarction trials, cardiac mortality is used as the major outcome end point either alone or in combination with nonfatal reinfarction. However, the independent risk carried by nonfatal reinfarction for subsequent cardiac death has not been quantified. The prognostic significance of nonfatal reinfarction was determined from the multicenter diltiazem trial data base of 1,234 patients treated with placebo followed up for 1 to 4 years after acute myocardial infarction. One hundred sixteen patients had at least one nonfatal reinfarction, 14 (12%) of whom subsequently experienced cardiac death. Of the remaining 1,118 patients without nonfatal reinfarction, 110 (9.8%) experienced cardiac death. Compared with event-free patients, patients with nonfatal reinfarction were more likely (p less than 0.05) to be women, to have had an infarction before their index event and to have had prior cardiac-related symptoms. Cox survivorship analyses, using pertinent baseline clinical variables along with nonfatal reinfarction as a time-dependent predictor variable, revealed that nonfatal reinfarction carried a significant and independent risk for subsequent cardiac mortality (hazard ratio 3.0, p = 0.002), which was greater than that carried by other significant predictor variables (New York Heart Association functional class, pulmonary congestion on chest radiograph, blood urea nitrogen level, predischarge Holter-recorded ventricular premature complexes and radionuclide ejection fraction). The cardiac mortality risk associated with nonfatal reinfarction was further increased in patients whose index event was their first infarction (hazard ratio 5.4, p = 0.0006). Thus, nonfatal reinfarction carries a strong, significant and independent risk for subsequent cardiac death in patients surviving an acute myocardial infarction.

Adult↗
PubMed1990

Long QT syndrome. New electrocardiographic characteristics.

The long QT syndrome is electrocardiographically characterized by a prolonged QT interval and by several other, more subtle, ST-T-U wave abnormalities, most of which have not been quantified. To determine the possible usefulness of several new electrocardiographic characteristics in identifying patients with known long QT syndrome, logistic regression models were applied to a data base of seven new, relatively independent, electrocardiographic repolarization variables. These were measured on digitized 12-lead electrocardiograms of 315 normal subjects and 37 patients with the long QT syndrome (members of well-identified long QT syndrome families, QTc greater than 0.44 second, 27% symptomatic), who ranged in age from 17 to 60 years. Electrocardiographic variables that independently differentiated (p less than 0.001) patients with long QT syndrome from normal subjects included quantitative measures of repolarization: early duration, rate, T wave symmetry, late phenomena, and heterogeneity. All selected repolarization variables except the early duration variable were essentially independent of the QTc (r2 less than 0.15), and all contributed significantly to the identification of patients with long QT syndrome. A classification model of five electrocardiographic predictor variables resulted in an estimated sensitivity (95% confidence interval) of 92.6% (81.6-100%) and an estimated specificity (95% confidence interval) of 95.8% (93.6-98.1%). This model performed significantly better than an alternative classification model that was based on the early duration variable as a single predictor variable. The symptomatic status of patients with long QT syndrome could not be predicted by any combination of the electrocardiographic variables in the investigated model.

Adolescent↗
PubMed1990

Tumor cell drug resistance and its reversal.

Tumors that formerly were uniformly fatal can now be cured by cancer chemotherapy. However, successful anticancer therapy is faced by many obstacles, such as excessive normal tissue toxicity and drug resistance. Tumor drug resistance may be either intrinsic or acquired. The multidrug resistance (MDR) is a unique phenomenon and is characterized by tumor resistance to various structurally unrelated drugs. Known mechanisms for MDR include overexpression of a membrane P-glycoprotein 170 and elevated cellular levels of reducing agents, such as glutathione (GSH). Currently available strategies for overcoming drug resistance include competitive inhibitors of the P-glycoprotein 170, inhibitors of GSH synthesis, and adjuvant therapy with hyperthermia. Development of drug resistance is analogous to a physiological detoxification mechanism and may continue to limit the effectiveness of cancer chemotherapy in the near future.

Antineoplastic Agents↗
PubMed1989

Characterization of a cisplatin-resistant subline of murine RIF-1 cells and reversal of drug resistance by hyperthermia.

The development of tumor cell drug resistance is a major obstacle which often leads to failure of cancer chemotherapy. Therefore, reversing the cell drug resistance would have important implications in cancer treatment. We have developed a cisplatin-resistant mouse tumor cell line from the radiation induced fibrosarcoma (RIF-1) parental line; this line is named RIF/ptr1 versus the parental line RIF/pts1. It is shown that the formation of cisplatin-DNA interstrand cross-links is the same for both cell lines although the intracellular cisplatin concentrations of resistant line is significantly lower. The cytosolic activities of glutathione reductase, glutathione peroxidase, and DT-diaphorase were the same in two cell lines. However, the concentration of glutathione was significantly higher in the resistant line. The resistant line was shown to be more sensitive to the cytotoxicity of heat (43 degrees C) but the combination of heat and drug had the same tumoricidal effect for both cell lines. The addition of verapamil also had a similar effect on both cell lines. We conclude that the major difference between these two lines was the glutathione-related detoxification of platinum. Regardless of drug resistance, the combination of drug and heat can effectively kill both cell lines. Elevated glutathione in RIF/ptr1 cells may be associated both with enhanced heat sensitivity and drug resistance such that combined treatments with drug and heat were equally effective in killing cells of either line.

Animals↗
PubMed1989

Electrocardiographic quantitation of ventricular repolarization.

Quantification of the electrocardiographic ventricular repolarization involving the T-U wave complex is usually performed with reference to the axis of the T wave and the QT interval duration. A novel quantitative approach to improve the description of ventricular repolarization was applied to the digitized electrocardiograms of 423 normal subjects. Six electrocardiographic repolarization characteristics were identified: duration, rate, area, symmetry, late phenomena, and interlead heterogeneity. A computer algorithm was designed to automatically interpret the electrocardiographic repolarization segment and measure 11 variables that quantified these repolarization characteristics. The application of redundancy-reduction techniques selected a final set of seven variables that were used in the statistical analysis. The QT interval, which was included in the initial group of variables, was replaced by the time interval between S wave offset and T wave maximum. All selected electrocardiographic variables were independent of age (r2 less than 0.11) and body surface area (r2 less than 0.03); all except the early duration variable were heart rate- and QT interval-independent (r2 less than 0.2, r2 less than 0.13, respectively; and most were uncorrelated to each other. A comparison of repolarization characteristics by gender revealed that repolarization duration was significantly more prolonged (p less than 0.0001) in women than in men. This multidimensional quantitative approach conveys a new and more complete description of the repolarization process and provides an electrocardiographic repolarization database in normal subjects as a reference standard for identifying patients with disordered repolarization.

Adult↗
PubMed1989

The interaction between diltiazem and left ventricular function after myocardial infarction. Multicenter Diltiazem Post-Infarction Research Group.

The interactions between diltiazem and three parameters of left ventricular function using cardiac death as the end point were investigated in 2,466 patients, aged 25-75 years, who were involved in the long-term diltiazem postinfarction trial. Indexes of left ventricular function included pulmonary congestion on chest x-ray, acute anterolateral Q wave myocardial infarction on electrocardiogram, and radionuclide ejection fraction. Pulmonary congestion and acute anterolateral infarction had significant (p less than 0.01) interactions with treatment allocation, and the third variable, ejection fraction, showed a similar trend (p less than 0.1). There was a diltiazem-related reduction in cardiac death (Cox hazard ratio, 0.76-0.86) for each of the parameters reflecting good ventricular function, and a significant diltiazem-related increase in cardiac death (Cox hazard ratio, 1.52-1.85) for each of the parameters associated with impaired function. Three-factor interactions highlighted the extremes of the favorable and adverse effects of diltiazem in subsets with unimpaired and impaired left ventricular function. These findings permit more appropriate selection of patients for the safe and effective administration of diltiazem to postinfarction patients.

Adult↗