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Biomedical subjects

M Malik

Publications and source records attributed to M Malik.

At least 127 records · Page 7Linked to original sources
PubMed1997

Selection of dichotomy limits for multifactorial prediction of arrhythmic events and mortality in survivors of acute myocardial infarction.

AIMS: To evaluate the predictive value and optimum dichotomy limits for different combinations of prognostic indicators for the prediction of arrhythmic events and cardiac mortality in post-infarction patients. BACKGROUND: Studies of new interventions based on risk stratification after myocardial infarction have often used a single variable as a predictor of risk. However, whether the dichotomy limits of these single variables, derived from univariate analyses, should be altered when such variables are combined for the prediction of risk after myocardial infarction has not been examined. METHODS: Left ventricular ejection fraction, signal-averaged electrocardiography, heart rate variability index, mean heart rate and ventricular extrasystole frequency were recorded pre-discharge in 439 survivors of their first myocardial infarction. Arrhythmic events and cardiac mortality were recorded during 1 year (range 1-6 years) follow-up. RESULTS: During follow-up for at least 1 year, there were 25 cardiac deaths and 23 arrhythmic events. Different optimum dichotomy limits were obtained for the prediction of cardiac mortality vs arrhythmic events, for different combinations of variables, for different selected levels of sensitivity and for different numbers of variables abnormal before identification of those at risk. The dichotomy limit of the heart rate variability index for the prediction of events appeared to be the least affected by the inclusion of other variables. For example, when predicting arrhythmic events using combinations of left ventricular ejection fraction and/or heart rate variability, the optimum dichotomy limits when each variable was used alone was 32% and 18 units respectively; 43% and 18 units when either left ventricular ejection fraction or heart rate variability are required to be abnormal, and 52% and 19 units when both are required to be abnormal before identification of those at risk of arrhythmic events. CONCLUSIONS: Dichotomy limits derived from univariate analyses do not optimally predict events when used in the multivariate setting. Risk stratification can be improved by using several variables in combination and is further improved by using dichotomy limits of these variables which are different from those used in or derived from univariate analyses.

Aged↗
PubMed1997

Heart rate variability: origins, methods, and interpretive caveats.

Components of heart rate variability have attracted considerable attention in psychology and medicine and have become important dependent measures in psychophysiology and behavioral medicine. Quantification and interpretation of heart rate variability, however, remain complex issues and are fraught with pitfalls. The present report (a) examines the physiological origins and mechanisms of heart rate variability, (b) considers quantitative approaches to measurement, and (c) highlights important caveats in the interpretation of heart rate variability. Summary guidelines for research in this area are outlined, and suggestions and prospects for future developments are considered.

Animals↗
PubMed1997

Computation modes of multivariate positive predictive characteristics.

Multivariate receiver operator characteristics (ROCs) and positive predictive characteristics (PPCs), based on a combination of two or more clinical variables, are usually computed by varying dichotomy limits for each variable independently. This approach has a similar number of degrees of freedom (i.e., uses the same number of programmable parameters) as the approach which defines test positive cases based on a linear combination of all the clinical variables involved. Either approach can be implemented without any assumption about the underlying probability distributions by using an exhaustive computer search. Both approaches were compared in a demonstration study of predicting 2-year all cause mortality after acute myocardial infarction, based on applying various time- and spectral-domain indices of signal-averaged ECGs from a research survey. The results showed that the optimum mode for the computation of ROCs and PPCs depends on the character of the particular data used. Therefore, in order to increase the precision of the retrospective multifactoral studies, both approaches to ROC and PPC computation should be used and compared in each individual investigation.

Algorithms↗
PubMed1997

Graphical representation of complex data--diurnal patterns of initiations of atrial fibrillation episodes.

A construction of a purpose designed graphical display is demonstrated in a study investigating the circadian distribution of patterns of RR interval sequences preceding episodes of paroxysmal atrial fibrillation (PAF). Based on a comparison with a (80%, 120%) range around the median of preceding 10 RR intervals, each RR interval is classified as normal, short, or long. Classifications of RR intervals in n-tuplets (n = 1, ...,5) preceding PAF episodes are used to compute probabilities of individual types of sequences occurring within 4-hour periods of the day (between 1 am, 5 am, 9 am, 1 pm, 5 pm, and 9 pm). Graphical representation of the data is proposed using a hierarchy of bar graphs. The graphical system has been filled with data of 327 atrial fibrillation episodes recorded in 46 24-hour ECGs in PAF patients. The graphical analysis supports a link between PAF initiation and cardiac autonomic status.

Anti-Arrhythmia Agents↗
PubMed1997

Performance of basic ventricular tachycardia detection algorithms in implantable cardioverter defibrillators: implications for device programming.

Around 20% of patients with third generation implantable cardioverter defibrillators receive inappropriate therapy, usually triggered by atrial fibrillation. This is because the criteria used for ventricular tachycardia detection by current implantable cardioverter defibrillators are based on the analysis of a sequence of RR intervals and may be inappropriately satisfied by supraventricular tachyarrhythmias. Algorithms for ventricular tachycardia detection were challenged against the full RR interval sequences from 482 spontaneous episodes of atrial fibrillation and 260 spontaneous episodes of ventricular tachycardia to determine their ability to discriminate between the arrhythmias. The sensitivities and specificities of the algorithms were calculated over a wide range of programmable parameters. For a given window length and detection interval, the most stringent algorithms, that required all beats to be classified as "fast", were more specific than those allowing a proportion of "normal" intervals, even after adjustment for differing sensitivity. These differences were less marked for faster tachycardias. Specificity increased with the detection window length to a limit of approximately 18 beats. We conclude that ventricular tachycardia is detected with the highest specificity if all beats in an analyzed sequence are required to be "fast," even after lengthening of the tachycardia detection interval to maintain sensitivity. Further improvement in algorithm performance may require the incorporation of criteria such as tachycardia onset and stability.

Algorithms↗
PubMed1997

Analysis of clinical follow-up databases: risk stratification studies and prospective trial design.

Design of new prospective studies should utilize detailed retrospective evaluations of clinical data. For this purpose, clinical data are needed containing both prospectively recorded values of risk factors and follow-up events. A concept of a new trial can then be modeled within the existing data-set. The development of such a model consists of the following steps: (a) the distribution of values of risk factors has to be investigated in the whole recorded population and the statistical association of the risk factors with follow-up events has to be established; (b) the stratification characteristics (sensitivity, specificity, and predictive accuracies) have to be evaluated for individual risk factors and for their multivariate combinations; (c) the stratification characteristics have to be converted into estimates of mortality reduction expected within the high risk group and used for the optimum trial design in terms of screened and randomized patient numbers. In this review, the strategy of designing a new trial is demonstrated using data of 644 survivors of acute myocardial infarction with available 3-year follow-up during which 74 patients died. A model of a new trial is considered involving reduced left ventricular ejection fraction, increased 24-hour mean heart rate, and depressed 24-hour heart rate variability as risk stratifiers.

Arrhythmias, Cardiac↗
PubMed1997

QT interval dispersion and its clinical utility.

QT dispersion as a measure of interlead variations of QT interval duration in the surface 12-lead ECG is believed to reflect regional differences in repolarization heterogeneity and thus, may provide an indirect marker of arrhythmogenicity. Methodology for determining QT dispersion and reproducibility of this parameter vary significantly between studies and, together with some other unresolved problems with QT dispersion assessment, often lead to contradictory suggestions about potential clinical utility of this parameter. The results of our own study in 213 survivors of myocardial infarction, together with a comprehensive review of the literature, suggest that most of these inconsistencies reflect incomplete understanding of electrocardiographic correlates of both normal and abnormal ventricular repolarization. The application of more objective techniques, such as spectral analysis or combined assessment of different parameters (e.g., area beneath the T wave and its symmetricity) may add a new dimension to the noninvasive assessment of ventricular repolarization.

Arrhythmias, Cardiac↗
PubMed1997

Holter, loop recorder, and event counter capabilities of implanted devices.

The current generation of cardiac pacemakers and implantable cardioverter defibrillators almost all have some capabilities to store data regarding device activity and patient events for future retrieval. This information may provide valuable information regarding device function and whether this is proving valuable in patient management. Examples include "pace-sense" counters, which can reveal under sensing of patient events, and serial lead impedance measurements, which are able to demonstrate trends not seen on isolated measurements. Holter capabilities become vital in more advanced devices for documenting the utility of, and fine tuning the programming of features such as antitachycardia pacing, rate-responsiveness, and mode-switching. Finally, the ability to store patient events as marker channels and even intracardiac electrograms adds a diagnostic capability not available through external monitoring. This role has now been advanced by the development of a purely diagnostic implantable loop recorder.

Defibrillators, Implantable↗
PubMed1997

Heart rate variability in idiopathic dilated cardiomyopathy: relation to disease severity and prognosis.

OBJECTIVE: To assess the clinical importance of heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (DCM). PATIENTS AND METHODS: Time domain analysis of 24 hour HRV was performed in 64 patients with DCM, 19 of their relatives with left ventricular enlargement (possible early DCM), and 33 healthy control subjects. RESULTS: Measures of HRV were reduced in patients with DCM compared with controls (P < 0.05). HRV parameters were similar in relatives and controls. Measures of HRV were lower in DCM patients in whom progressive heart failure developed (n = 28) than in those who remained clinically stable (n = 36) during a follow up of 24 (20) months (P = 0.0001). Reduced HRV was associated with NYHA functional class, left ventricular end diastolic dimension, reduced left ventricular ejection fraction, and peak exercise oxygen consumption (P < 0.05) in all patients. DCM patients with standard deviation of normal to normal RR intervals calculated over the 24 hour period (SDNN) < 50 ms had a significantly lower survival rate free of progressive heart failure than those with SDNN > 50 ms (P = 0.0002, at 12 months; P = 0.0001, during overall follow up). Stepwise multiple regression analysis showed that SDNN < 50 ms identified, independently of other clinical variables, patients who were at increased risk of developing progressive heart failure (P = 0.0004). CONCLUSIONS: HRV is reduced in patients with DCM and related to disease severity. HRV is clinically useful as an early non-invasive marker of DCM deterioration.

Adolescent↗
PubMed1997

Autonomic modulation of ventricular rate in atrial fibrillation.

This study investigated the changes in R-R interval in 23 patients (11 men and 12 women; mean age 61 yr) with persistent atrial fibrillation in response to several provocative maneuvers including active postural change, Valsalva maneuver, handgrip, and rhythm-controlled respiration. Averaged R-R intervals were shortened immediately after postural change (from 797 +/- 35 ms supine to 677 +/- 27 ms standing; P < 0.01) and recovered to the 90% level within 100 s. During Valsalva strain and handgrip, mean R-R intervals were significantly shortened (from 737 +/- 37 ms sitting to 697 +/- 38 ms in Valsalva and from 773 +/- 68 ms sitting to 701 +/- 58 ms in handgrip; both P < 0.01). During rhythm-controlled respiration, only two cases (10.5%) showed power peaks in spectrograms of moving-window-averaged R-R intervals at the frequency corresponding to respiration rhythm. The ventricular response to atrial fibrillation is influenced by an increase in sympathetic tone and a decrease in parasympathetic tone but is not necessarily influenced by the increase in parasympathetic dominance. These results suggest that even in atrial fibrillation patients, the autonomic nervous system modulates the ventricular rate via the atrioventricular node and atrial tissue.

Adult↗
PubMed1996

Refinement of the Van der Woude gene location and construction of a 3.5-Mb YAC contig and STS map spanning the critical region in 1q32-q41.

Van der Woude syndrome (VWS) is the most frequent form of syndromic clefting. Linkage analysis has localized the gene between D1S245 and D1S414, an interval of 4.1 cM with the following order of loci: centromere-D1S245/D1S471-D1S491-D1S205-D1S414 -telomere. A microdeletion around D1S205 aided in narrowing the critical region to D1S491-D1S414 by heterozygosity testing. In this study, the location was refined by detection of a recombinant with D1S205 in a new family, indicating that VWS lies between D1S491 and D1S205, a 1.6-cM interval. A roughly 3.5-Mb YAC contig was built from D1S245 through D1S414, encompassing the interval D1S491-D1S205 in level 1 or level 2 paths. Clones were assembled by sequence tagged site (STS) content using the five polymorphic markers from above, four novel STSs identified from YAC ends, and a new STS derived from probe CRI-L461 (D1S70). D1S70 was assigned to the critical region. One single YAC, yCEPH785B2, contains both flanking STSs (D1S491, D1S205). STS content mapping suggests neither chimerism nor deletion of yCEPH785B2 but does suggest that the maximum size of the critical region is approximately 850 kb. All STSs were tested for their presence on a somatic cell hybrid containing the microdeleted chromosome 1 as the sole human chromosome 1 component. Both the proximal and distal ends of the microdeletion mapped to the 850-kb YAC, yCEPH785B2. Therefore, the microdeletion overlapped the critical region, confirming the genetic recombinant data.

Chromosome Mapping↗
PubMed1996

Arterial baroreflex sensitivity assessed from phase IV of the Valsalva maneuver.

To assess the feasibility of 2 noninvasive methods for arterial baroreflex sensitivity testing based on phase IV of the Valsalva maneuver, the performance of a simple arterial baroreflex sensitivity index compared with a slope method and reproducibility of repeated measurements of either parameter were evaluated in 36 subjects without structural heart disease. The study showed feasibility and reproducibility of both these methods for arterial baroreflex sensitivity assessment and demonstrated the importance of an appropriate rest period between repeated Valsalva maneuvers, giving a basis for prospective testing of noninvasive determination of arterial baroreflex sensitivity together with phenylephrine method in survivors of myocardial infarction.

Adolescent↗
PubMed1996

DNA gyrase and topoisomerase IV on the bacterial chromosome: quinolone-induced DNA cleavage.

DNA gyrase, the bacterial enzyme that supercoils DNA, is trapped on chromosomal DNA by the 4-quinolone compounds, as drug-gyrase complexes that contain DNA breaks. Examination of chromosomal DNA extracted from Escherichia coli indicated that bacteriostatic concentrations of oxolinic acid trap gyrase and block DNA synthesis without releasing broken DNA from gyrase-DNA complexes. Release, detected as free rotation of DNA in the presence of an intercalating dye, occurred only at high, bactericidal oxolinic acid concentrations. Release of DNA breaks and cell death were both blocked by chloramphenicol, an inhibitor of protein synthesis, suggesting that synthesis of additional protein activity is required to free the DNA ends. Ciprofloxacin, a more potent quinolone, released DNA breaks and killed cells even in the presence of chloramphenicol. It is proposed that this second, chloramphenicol-insensitive mode for release of DNA breaks and cell killing arises from dissociation of gyrase subunits. Ciprofloxacin also killed a gyrase (gyrA) mutant resistant to the prototype of quinolone, nalidixic acid, and created complexes on DNA detected by DNA fragmentation. This lethal effect of ciprofloxacin was eliminated by additional mutations mapping in parC, one of the two genes encoding topoisomerase IV. Thus, the fluoroquinolone compounds have two intracellular targets. In the absence of the gyrA mutation, the parC (CipR) allele did not by itself confer resistance to ciprofloxacin, indicating that gyrase is the major quinolone target in E. coli. These findings provide a molecular explanation for quinolone action in bacteria and a new way to study topoisomerase IV-chromosome interactions.

Anti-Infective Agents↗
PubMed1996

Short- and long-term assessment of heart rate variability for risk stratification after acute myocardial infarction.

Depressed heart rate variability (HRV) has been shown to be a powerful and independent risk factor in patients following acute myocardial infarction (AMI). A detailed comparison of the predictive values between short- and long-term HRV has not been made. The predictive value of short-term HRV for 1-year total cardiac mortality was studied in 700 consecutive patients after AMI. All patients underwent 24-hour Holter monitoring before discharge from the hospital (5 to 8 days after AMI) and were followed up for 1 year. Short-term HRV was computed as the standard deviation of all normal RR intervals (SDNN) from a 5-minute stationary period selected from 24-hour Holter electrocardiographic recordings. Long-term HRV was computed as an HRV index over the entire 24 hours. There was a significant but relatively poor correlation between SDNN and HRV index (r = 0.51, p <0.001). The positive predictive accuracy of SDNN for 1-year mortality (13% to 18%) was lower than the HRV index (17% to 43%) over a range of sensitivity of 25% to 75%. Assessment of HRV index in > or = 35% of the patients preselected by the lowest SDNN was able to achieve predictive power similar to that of HRV index assessed in all the patients. These data suggest that lower predischarge short-term HRV is associated with increased 1-year total cardiac mortality in patients after AMI. Analysis of long-term HRV for postinfarction risk stratification can safely be limited to patients preselected by depressed short-term HRV measures.

Analysis of Variance↗
PubMed1996

Histone-like protein HU and bacterial DNA topology: suppression of an HU deficiency by gyrase mutations.

The abundant bacterial protein called HU has the ability to wrap and bend DNA in vitro, and thus it has long been thought to play a role in DNA supercoiling. In the absence of HU, Escherichia coli formed tiny colonies on agar, rapidly accumulated suppressor mutations, and was hypersensitive to novobiocin. Three types of evidence implicated gyrase in the suppression of an HU deficiency. First, spontaneous suppressors that restored normal growth and reduced sensitivity to novobiocin mapped in gyrB, one of the genes encoding DNA gyrase. Second, a pair of known gyrB mutations (gyrB-203 Ts gyrB-221 NovR) allowed normal growth at permissive (30 degrees C) but not at intermediate (37 degrees C) conditions. Third, introduction of a gyrB-expressing plasmid restored normal colony size. DNA supercoiling comparisons showed that chromosomal supercoiling decreased in the absence of HU and increased toward wild-type levels in the presence of a spontaneous gyrB suppressor. Taken together, these data establish that HU has a physiological role in chromosomal DNA topology, probably by facilitating the action of gyrase.

Alleles↗