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M Malik

Publications and source records attributed to M Malik.

At least 19 recordsLinked to original sources
PubMed1992

Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: not an invariant correlation with metastasis.

Numerous studies have reported a correlation between production of 72-kDa (MMP-2) and 92-kDa (MMP-9) type-IV collagenases/gelatinases and the metastatic potential of cancer cells. An abrogating effect of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) on metastases has also been noted. In this report we have used sensitive enzyme-linked immunoassays to measure MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in eight human lung-cancer cell lines which were characterized for biological behavior in nude mice. We demonstrated that the Calu-6 and A549 cell lines with the highest metastatic, invasive and tumorigenic potential secreted the highest levels of MMP-2. MMP-9 and TIMP-1 secretions were comparatively low in all cell lines. TIMP-2 secretion, which exceeded MMP-2 secretion for all cell lines, did not correlate with metastatic potential. To further explore these correlations, the metastatic Calu-6 cell line was transfected with a K-rev-1 cDNA expression construct. The K-rev revertant cell lines demonstrated a more differentiated phenotype and were less tumorigenic, invasive and metastatic in nude mice. Nonetheless, the Calu-6 revertant cell lines secreted higher levels of MMP-2 than the parent cell line. In conclusion, invasion and metastasis by lung-cancer cells requires not only enhanced MMP production, but also other less well-understood tumorigenic characteristics. The multiplicity of factors required by cancer cells for dissemination helps to explain the minute fraction of cancer cells from a primary tumor that ever develop into a metastasis.

Animals↗
PubMed1992

Effect of thrombolytic therapy on the predictive value of signal-averaged electrocardiography after acute myocardial infarction.

Standard time domain variables from signal-averaged electrocardiography were examined in a population of 331 survivors of acute myocardial infarction. Of these subjects, 130 received early (less than 24 hours) thrombolytic therapy. During a follow-up of greater than or equal to 10 months, there were 17 arrhythmic events (8.5%) (sudden death or sustained symptomatic ventricular tachycardia) in the group without thrombolysis and 8 (6.2%) in those with thrombolysis. Statistically, highly significant differences between the signal-averaged electrocardiographic variables of patients with and without arrhythmic events were found in the group without thrombolysis, whereas only root-mean-square voltage of the terminal 40 ms of the signal-averaged QRS complex was statistically associated with outcome (the differences in the other 2 indexes being not significant) in patients with thrombolysis. When using 2 previously published categoric criteria for the diagnosis of abnormal signal-averaged electrocardiography, the performance of these criteria in predicting arrhythmic events was substantially better in the group without thrombolysis than in those with thrombolysis (positive predictive accuracy greater than 3 times lower). Retrospectively adjusted receiver-operator characteristics showed that for a sensitivity of 30%, the maximum achievable positive predictive accuracy of signal-averaged electrocardiography for arrhythmic events was 100% in the group without thrombolysis, but only 27% in those with thrombolysis. It is concluded that standard signal-averaged electrocardiography after acute myocardial infarction is less informative in patients who receive thrombolytic treatment.

Adult↗
PubMed1992

Differences between predictive characteristics of signal-averaged electrocardiographic variables for postinfarction sudden death and ventricular tachycardia.

Several studies indicate that the electrophysiologic substrate for sustained ventricular tachycardia differs from that of ventricular fibrillation. This prospective study examined whether there were clinically relevant differences between the predictive values of the standard time-domain signal-averaged (SA) electrocardiographic (ECG) variables for ventricular tachycardia and sudden death after myocardial infarction. Predischarge SA electrocardiograms were recorded in 332 patients after infarction. During a follow-up period of greater than or equal to 6 months, there were 12 sudden deaths (3.6%), 14 patients (4.2%) developed spontaneous sustained ventricular tachycardia and 20 patients (6%) died of circulatory failure. The sensitivity, specificity and positive predictive accuracy of the numerical values of the time-domain SA electrocardiographic variables for predicting sudden death and ventricular tachycardia were compared. The optimal criteria for predicting ventricular tachycardia required the positivity of greater than or equal to 2 of the standard time-domain SA variables, whereas the optimal criteria for predicting sudden death required the positivity of all 3 variables. A high specificity was sustained over a wider range of sensitivity for sudden death than it was for ventricular tachycardia and the values of the variables which provided the same sensitivity for sudden death and ventricular tachycardia were different. For a sensitivity of 70%, the positive predictive accuracy was 31% for predicting sudden death and 13% for predicting ventricular tachycardia. The study concludes that differences in the predictive characteristics of variables for ventricular tachycardia and sudden death may be used to refine postinfarction risk stratification.

Adult↗
PubMed1992

Frequency versus time domain analysis of signal-averaged electrocardiograms. I. Reproducibility of the results.

Three repeated signal-averaged electrocardiographic (ECG) recordings were made in 40 subjects (15 healthy volunteers, 10 patients with ventricular tachycardia without apparent heart disease and 15 patients with ventricular tachycardia after myocardial infarction). In each subject, the three recordings were made within 25 min. The recordings were subsequently analyzed by 1) the conventional time domain method of signal-averaged ECG analysis with use of filter settings of 25 to 250 Hz and 40 to 250 Hz, 2) a spectral analysis method computing the energy area within the spectral boundaries of 40 to 140 Hz and the ratio between the energies of areas within the boundaries 40 to 140 Hz and 0 to 40 Hz, and 3) spectral temporal mapping computing the "normality factor." The study compared the reproducibility of these three approaches to the analysis of signal-averaged ECGs. First, the reproducibility of the diagnostic conclusions (that is, of the diagnosis of late potentials) was compared for the time domain method and for spectral temporal mapping. Second, the reproducibility of the numeric values of individual indexes provided by different methods was compared for all methods by computing the ratios between standard deviations of measurements in individual patients and standard deviation of all measurements. The reproducibility of diagnostic conclusions was significantly higher for the time domain method than for spectral temporal mapping (p less than 0.05, sign test). The numeric reproducibility of the normality factors produced by spectral temporal mapping was significantly lower than the numeric reproducibility of the values of all indexes provided by time domain, spectral area and spectral area ratio methods (p less than 0.05 to 0.00005, Wilcoxon tests). Spectral temporal mapping was the least reproducible method for the analysis of signal-averaged ECGs.

Adult↗
PubMed1992

Frequency versus time domain analysis of signal-averaged electrocardiograms. II. Identification of patients with ventricular tachycardia after myocardial infarction.

Late potentials detected by the time domain signal-averaged electrocardiogram (ECG) are a well established marker for ventricular tachycardia in patients after a myocardial infarction, but the value of frequency domain analysis of the signal-averaged ECG in identifying these patients remains controversial. This study compared the results of time domain, frequency domain and spectral temporal mapping analyses of the signal-averaged ECG in 30 postinfarction patients with spontaneous sustained ventricular tachycardia and in 30 postinfarction patients without ventricular tachycardia matched for age, gender and infarct site. No patient with bundle branch block was included. Time domain signal-averaged ECG indexes were significantly different in patients with and without ventricular tachycardia (p less than 0.001). Frequency domain results were not consistently different between these groups. The values of the normality factor of spectral temporal mapping were significantly lower in patients with ventricular tachycardia (p less than 0.04). Results of the time domain signal-averaged ECG were abnormal in 22 patients with ventricular tachycardia (73%) but in only 3 control patients (10%) (p less than 0.001). Spectral temporal mapping results were abnormal in 21 patients with ventricular tachycardia (70%) compared with 12 control patients (40%) (p less than 0.04). When the optimal numeric values of dichotomy points were computed for patient stratification at different sensitivity levels, time domain analysis identified patients with ventricular tachycardia with significantly fewer false positive results than were obtained with either frequency analysis or spectral temporal mapping. It is concluded that frequency domain analysis and spectral temporal mapping of the signal-averaged ECG did not improve the identification of postinfarction patients with ventricular tachycardia and without bundle branch block.

Aged↗
PubMed1992

Frequency versus time domain analysis of signal-averaged electrocardiograms. III. Stratification of postinfarction patients for arrhythmic events.

The predictive characteristics of spectral temporal analysis and time domain analysis of the signal-averaged electrocardiogram (ECG) for postinfarction arrhythmic events were compared in 257 patients. During a 6-month follow-up period, 7 patients (2.7%) died suddenly and 9 (3.5%) developed spontaneous sustained ventricular tachycardia. The mean numeric values of the standard time domain signal-averaged ECG variables in patients without arrhythmic events differed significantly from those in patients with arrhythmic events. The mean values of the spectral temporal signal-averaged ECG variables did not differ between the two patient groups. A strategy requiring positivity in any two time domain signal-averaged ECG variables provided the optimal receiver operating characteristic curves for predicting arrhythmic events. With spectral temporal analysis, a strategy using the Hanning window and diagnosing a positive signal-averaged ECG when two variables were abnormal provided the optimal curve for predicting arrhythmic events. Receiver operating characteristic curves showed that over a wide range of sensitivity, time domain variables had higher specificity for predicting arrhythmic events than did spectral temporal variables. Time domain analysis also provided significantly fewer false positive results than did spectral temporal analysis up to sensitivity values of 70%. It is concluded that time domain analysis of the signal-averaged ECG is superior to spectral temporal analysis for predicting arrhythmic events after myocardial infarction.

Adult↗
PubMed1992

Effects of myocardial electrotonic interaction on the sequence of excitation and repolarisation and on T wave polarity. Computer modelling experiments.

A computer model of a 3-dimensional rectangular block of myocardial tissue (3969 cells) has been used to investigate the influence on excitation and repolarisation sequences and on the modelled electrocardiographic T wave of (a) electrotonic interaction, (b) intrinsic distribution of refractoriness, and (c) the speed of repolarisation of action potentials. The model allowed electrotonic interactions to be investigated separately during the depolarisation and repolarisation phases. Scales of 14 values of the strength of electrotonic interaction during the depolarisation phase, 14 values of the strength of electrotonic interaction during the repolarisation phase, 3 shapes of action potential, and 5 distributions of tissue refractoriness were selected and all 2940 combinations were examined. In each experiment, the tissue model was artificially excited and the resulting excitation and repolarisation sequences were simulated. The results of the study suggested that electrotonic interactions between excited cells can cause non-uniform speed of propagation which, by means of the phase shifts of action potentials, contributes to the inversion of the repolarisation sequence and to the physiologic orientation of T waves. Experiments with this model did not support the hypothesis that simple electrotonic smoothing of the differences in repolarisation phases due to the excitation phase shift of action potentials reverses the repolarisation sequence and explains T wave polarity.

Action Potentials↗
PubMed1992

Late potentials after acute myocardial infarction. Performance of different criteria for the prediction of arrhythmic complications.

In order to compare different criteria for the definition of late potentials in patients after myocardial infarction, three signal averaged ECG variables, duration of the signal-averaged QRS complex (QRS), root-mean-square voltage of the terminal 40 ms (RMS-40), and the duration of low amplitude signals less than 40 microV (LASD-40), were assessed in 332 survivors of acute myocardial infarction who were followed-up for at least 6 months, during which 12 patients died suddenly and 14 suffered symptomatic sustained ventricular tachycardia. The associations of the three variables with arrhythmic events were analysed in the total population, in infarct site and age-specific subgroups. The sensitivity and specificity for the prediction of arrhythmic events was computed (for all dichotomy points) and compared with nine published criteria for late potentials based on the same three variables. Analysis showed that (a) the total signal averaged QRS duration was a better predictor of arrhythmic events than the other two variables, (b) for arrhythmic events in cases of anterior infarctions, higher RMS-40 dichotomy limits and lower QRS and LASD-40 dichotomy limits were needed for cases of inferior infarction, (c) a multivariate stratification of arrhythmic events based on all three variables performed better in the anterior infarction population than in the inferior infarction population, (d) the strategy defining late potentials, which requires that two variables reach critical values, is better than the strategies that require that any one or all three variables reach critical values, (e) all the definitions of late potentials performed differently in the populations with anterior as compared to inferior infarctions; to identify groups at similar risk of arrhythmic events, different criteria defining late potentials should be used in these subpopulations.

Action Potentials↗
PubMed1992

Operating systems.

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Computer Systems↗
PubMed1992

Prediction of antiarrhythmic efficacy of class I and III agents in patients with ventricular tachycardia by signal-averaged ECG analysis.

The effects of procainamide and dofetilide (pure Class III antiarrhythmic agent) on the signal-averaged ECG (SAECG) were examined in relation to the results of programmed ventricular stimulation studies in 25 patients with inducible sustained monomorphic ventricular tachycardia. Procainamide prolonged significantly the total QRS and low amplitude signal durations (140 +/- 31 msec vs 166 +/- 48 msec, P < 0.0001; 50 +/- 25 msec vs 65 +/- 38 msec, P < 0.002, respectively) whereas the root mean square voltage of the last 40 msec of the QRS complex was significantly reduced (22 +/- 21 microV vs 13 +/- 12 microV, P < 0.006). Procainamide was effective (prevention of the inducibility of sustained ventricular tachycardia or prolongation of the cycle length of ventricular tachycardia by > 100 msec) in 15 of 27 drug trials. Of the procainamide induced SAECG changes, the fractional prolongation of the total QRS duration was the best parameter that identified effectively treated patients (24% +/- 16% in responders vs 10% +/- 11% in nonresponders, P < 0.014). A fractional prolongation of the total QRS duration by > 15% identified effectively treated patients with a sensitivity of 87%, specificity of 81%, and an overall predictive accuracy of 84%. Dofetilide did not change the SAECG, and no SAECG parameter predicted the results of programmed ventricular stimulation. The effects of both drugs on the spectral analysis (area ratios) and on the spectral temporal mapping (the values of normality factor) of the SAECG were not consistent. In conclusion, antiarrhythmic efficacy of procainamide can be predicted by the degree of drug induced prolongation of the signal-averaged QRS complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1992

Prognostic value of baroreflex sensitivity testing after acute myocardial infarction.

BACKGROUND: Disturbances of autonomic function are recognised in both the acute and convalescent phases of myocardial infarction. Recent studies have suggested that disordered autonomic function, particularly the loss of protective vagal reflexes, is associated with an increased incidence of arrhythmic deaths. The purpose of this study was to compare the value of differing prognostic indicators with measures of autonomic function and to assess the safety of arterial baroreflex testing early after infarction. METHODS: As part of a prospective trial of risk stratification in post-infarction patients arterial baroreflex sensitivity, heart rate variability, long term electrocardiographic recordings, exercise stress testing, and ejection fraction were recorded between days 7 and 10 in 122 patients with acute myocardial infarction. RESULTS: During a one year follow up period there were 10 arrhythmic events. Baroreflex sensitivity was appreciably reduced in these patients suffering arrhythmic events (1.73 SD (1.49) v 7.83 (4.5) ms/mm hg, 95% confidence interval (CI) 4.8 to 7.3, p = 0.0001). Significant correlations were noted with age (r = -0.68, p less than 0.001) but not left ventricular function. When baroreflex sensitivity was adjusted for the effects of age and ventricular function baroreflex sensitivity was still considerably reduced in the arrhythmic group (2.1 v 7.57 ms/mm Hg, p less than 0.0001). Depressed baroreflex sensitivity carried the highest relative risk for arrhythmic events (23.1, 95% CI 7.7 to 69.2) and was superior to other prognostic variables including left ventricular function (10.4, 95% CI 3.3 to 32.6) and heart rate variability (10.1, 95% CI 5.6 to 18.1). No major complications were noted with baroreflex testing and in particular no patients developed ischaemic or arrhythmic symptoms during the procedure. CONCLUSIONS: Disordered autonomic function as measured by depressed baroreflex sensitivity or reduced heart rate variability was associated with an increase incidence of arrhythmic events in post-infarction patients. Baroreflex testing can be safely performed in the immediate post-infarction period.

Adult↗
PubMed1992

Influence of age on the relation between heart rate variability, left ventricular ejection fraction, frequency of ventricular extrasystoles, and sudden death after myocardial infarction.

AIMS: To examine the influence of age on the prediction of sudden death after acute myocardial infarction based on heart rate variability (HRv), left ventricular ejection fraction (LVEF), and the frequency of ventricular extrasystoles. BACKGROUND: Autonomic and left ventricular function and the frequency of ventricular extrasystoles change with age but the influence of age on the prediction of sudden death from these variables has not been examined. METHODS: The 477 patients who had been through an early postinfarction risk stratification protocol and followed up for a mean of 790 days were dichotomised at 60 years of age. RESULTS: Sudden deaths occurred with similar frequency in both age groups (12 (4.7%) of the 256 patients aged < 60 years and seven (3.2%) of the 221 older patients). Sudden death, however, accounted for 52% of all deaths in the young group but only 18.4% of all deaths in the older group (p < 0.01). An HRv index of < 20 units combined with an average of more than 10 ventricular extrasystoles an hour on Holter monitoring (VE10) had a sensitivity of 50%, a positive predictive accuracy of 33%, and a risk ratio of 18 in the young group (p < 0.001) but was not significantly predictive in older patients. The situation was similar when the combination of an LVEF < 40% with VE10 was considered. This combination had a sensitivity of 44%, positive predictive accuracy of 36.4%, and a risk ratio of 16.1 in young patients (p < 0.001), but was not significantly predictive in older patients. The combination of VE10 with either LVEF < 40% or HRv < 20 units gave a sensitivity of 75%, positive predictive accuracy of 30%, and a risk ratio of 30 in young patients (p < 0.001), but the relation between this combination and sudden death in older patients was not statistically significant. CONCLUSION: In postinfarction patients aged < 60 sudden death was a more predominant mode of death and was more reliably predicted from a depressed HRv index, an LVEF < 40%, and VE10 than in older postinfarction patients. These findings may have important implications for post-infarction risk stratification and management.

Age Factors↗
PubMed1991

Comparison of the predictive characteristics of heart rate variability index and left ventricular ejection fraction for all-cause mortality, arrhythmic events and sudden death after acute myocardial infarction.

Heart rate (HR) variability index and left ventricular ejection fraction (EF) were compared for the prediction of all-cause mortality, arrhythmic events and sudden death in 385 survivors of acute myocardial infarction. For arrhythmic events, where, for a sensitivity of 75%, HR variability index had a specificity of 76%, EF had a specificity of only 45%. An EF of less than or equal to 40% had a sensitivity of 42% and a specificity of 75% for arrhythmic events; for the same sensitivity an HR variability index of 20 U had a specificity of 92%. An EF less than or equal to 40% had a sensitivity of 40% and a specificity of 73% for sudden death; HR variability index had a specificity of 83% for the same sensitivity. For all cause mortality, where, for a sensitivity of 75%, HR variability index had a specificity of 52%, EF had a specificity of 40%. It is concluded that HR variability index appears a better predictor of important postinfarction arrhythmic complications than left ventricular EF, but both indexes perform equally well in predicting all-cause mortality.

Adult↗
PubMed1991

Age-related normal values of signal-averaged electrocardiographic variables after acute myocardial infarction.

The study examined standard time domain variables of a signal-averaged electrocardiogram (SAECG) in 328 survivors of acute myocardial infarction. The correlation of these variables with age and the influence of age on the prediction of postinfarction arrhythmic complication (sudden death [n = 12] or sustained ventricular tachycardia, or both [n = 14]) from the SAECG were investigated. Statistically highly significant correlations (p less than or equal to 0.00002) between age and SAECG variables were found. Compared with patients aged less than 60 years, the SAECG-based stratification of arrhythmic complications after myocardial infarction in patients greater than 60 years had lower sensitivity for the same values of specificity and lower specificity for the same values of sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Computer simulation of electronic interactions during excitation and repolarisation of myocardial tissue.

A three-dimensional model of myocardial tissue has been developed which incorporates electrotonic interactions between neighbouring myocytes. The algorithms of the model are based on asynchronous planning of discrete events. Each cellular element is described in a logical way and traces a predefined action potential which is dynamically modified depending on the electrotonic interactions. The model has a low computational complexity and has been implemented on personal workstations even for experiments investigating arrhythmogenic processes and simulating several tens of cycles in blocks composed of several thousand elements. The paper describes the algorithmic implementation of the model and presents three series of experiments examining the dependence of the accuracy of the model on the size of the modelled tissue, changes of the shape of simulated T-waves due to electrotonic interactions and arrhythmogenic processes caused by lowering the threshold of the electric flow which excites individual cells.

Algorithms↗