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Biomedical subjects

M Malik

Publications and source records attributed to M Malik.

At least 163 records · Page 9Linked to original sources
PubMed1996

Fluoroquinolone action in mycobacteria: similarity with effects in Escherichia coli and detection by cell lysate viscosity.

Fluoroquinolones are potent antibacterial agents that are being used as therapeutic agents for the treatment of multidrug-resistant tuberculosis. To better understand fluoroquinolone action in mycobacteria, the effects of ciprofloxacin were examined. DNA synthesis was inhibited rapidly in Mycobacterium smegmatis, DNA cleavage was readily observed by an empirical assay of cell lysate viscosity, and cell growth was blocked. These data are explained by the formation of gyrase-DNA-ciprofloxacin complexes that block replication fork movement. The bactericidal action of ciprofloxacin against M. smegmatis, Mycobacterium bovis BCG, and Escherichia coli occurred more slowly in cells with longer doubling times. The bactericidal effect against M. bovis BCG was partially blocked by pretreatment with chloramphenicol, an inhibitor of protein synthesis, and by very high concentrations of ciprofloxacin itself. Similar responses occur when E. coli is treated with ciprofloxacin. These similarities between E. coli and mycobacteria indicate that results from extensive fluoroquinolone studies with E. coli can be applied to mycobacteria. A simple viscometric assay of DNA cleavage is described. The assay is expected to be useful for screening new fluoroquinolone derivatives for increased effectiveness against clinically important bacteria.

Anti-Infective Agents↗
PubMed1996

[Reproducibility of signal-averaged electrocardiography].

The reproducibility of the parameters defining the presence of late potentials on the signal-averaged electrocardiogram is one of the limiting factors of the method. The authors studied the coefficients of correlation and reproducibility of these parameters in patients with coronary artery disease. In addition, they tried to determine which parameter was most often responsible for changing a diagnostic conclusion (i.e., presence or absence of late potentials). Two signal-averaged ECGs were recorded one after the other in 127 patients. The presence of late potentials was defined as the presence of a least two of the following criteria: total amplified and averaged QRS duration (tQRS) > 114 ms: duration of the last signal of under 40 microV (LAS) > 38 ms, and root mean square of the amplitude of the last 40 ms (RMS) < 20 microV. The correlation coefficients were 0.98, 0.96 and 0.94 for the duration of tQRS, LAS and RMS respectively (p < 0.0001). The coefficients of reproducibility were 7.0 ms. 7.0 ms and 16.1 microV respectively. Late potentials were present in 22% of patients. A change in diagnosis between the first and second recording was observed in 10 subjects (8% of the population). A combined change in LAS and RMS was responsible for 6 of these revised diagnoses, a change in LAS alone in 2 cases, of the RMS alone in 1 case and the tQRS alone in 1 case. In patients with coronary artery disease, the immediate reproducibility of the diagnosis of late potentials is affected by changes in LAS and RMS. The tQRS is only rarely responsible for a change in diagnosis. This study suggests that the result of the signal-averaged ECG should be interpreted with caution when the LAS or RMS are near their threshold values.

Action Potentials↗
PubMed1996

[Influence of the duration of recording in the reproducibility of the signal averaged electrocardiogram].

The authors studied the possibility of improving the reproducibility of the signal averaged ECG by increasing the number of averaged QRS complexes. One hundred patients were included in the study. In each cases, 400 QRS complexes were recorded on twice, consecutively, in strictly identical conditions. During each recording, the total duration of the amplified and averaged QRS complex (tQRS), the duration of the terminal signal below 40 microV (LAS) and the root mean square of the amplitude of the last 40 ms (RMS) were determined for 100, 200, 300 and 400 recorded QRS complexes. The presence of late potentials was defined as the positivity of two of the following criteria: tQRS > 114 ms, LAS > 38 ms, RMS < 20 microV. The number of contradictory diagnostic conclusions between two successive recordings of the same duration decreased progressively with the number of averaged QRS complexes: 10 for 100 QRS, 10 for 200 QRS, 9 for 300 QRS and 6 for 400 QRS complexes, but this improvement was not statistically significant. The absolute differences of tQRS and RMS between two successive recordings of the same duration were statistically different for the four durations of recording (p = 0.05) and there was a tendency towards statistical significance for LAS (p = 0.09). The best quantitative reproducibility of the 3 parameters was obtained with the recording of 300 QRS complexes. In conclusion, the reproducibility of the signal averaged ECG is improved when the number of average QRS complexes is increased. The authors' results suggests that reproducibility this is optimal with the amplification and averaging of 300 QRS complexes.

Action Potentials↗
PubMed1996

[Risk of mortality after myocardial infarction: value of heart rate, its variability and left ventricular ejection fraction].

Heart rate variability is a useful parameter for risk stratification after myocardial infarction. However, the relationship between heart rate itself and its variability has not been adequately studied. The authors compared the average RR interval of 24 hours recorded by Holter monitoring with the variability of heart rate and of left ventricular ejection fraction to assess the risk of death after myocardial infarction. A total of 579 patients was followed up for 2 years after acute myocardial infarction. During this period, there were 54 deaths, 42 of cardiac origin, 26 being classified as sudden death. The positive predictive value of left ventricular ejection fraction was lower than those of mean RR interval and the variability of heart rate for overall mortality, cardiac mortality and sudden death. The three indices were essentially equivalent for the prediction of non-sudden cardiac death. The positive predictive value of heart rate variability was better than the mean RR interval for sensitivities < 40%, for all cause mortality. However, for sensitivities > 40%, the two parameters were equivalent or slightly in favour of the mean heart rate over 24 hours. The authors conclude that the mean RR interval over 24 hours is an important prognostic index after myocardial infarction. This index is more powerful than left ventricular ejection fraction and comparable to heart rate variability.

Aged↗
PubMed1995

DNA supercoiling in a thermotolerant mutant of Escherichia coli.

A spontaneously occurring, nalidixic acid-resistant (NalR), thermotolerant (T/r) mutant of Escherichia coli was isolated. Bacteriophage P1-mediated transduction showed that NalR mapped at or near gyr A, one of the two genes encoding DNA gyrase. Expression of gyrA+ from a plasmid rendered the mutant sensitive to nalidixic acid and to high temperature, the result expected for alleles mapping in gyrA. Plasmid linking number measurements, made with DNA from cells grown at 37 degrees C or shifted to 48 degrees C, revealed that supercoiling was about 12% less negative in the T/r mutant than in the parental strain. Each strain preferentially expressed two different proteins at 48 degrees C. The genetic and supercoiling data indicate that thermotolerance can arise from an alteration in DNA gyrase that lowers supercoiling. This eubacterial study, when coupled with those of archaebacteria, suggests that DNA relaxation is a general aspect of thermotolerance.

Chromosome Mapping↗
PubMed1995

Day-to-day reproducibility of time-domain measures of heart rate variability in survivors of acute myocardial infarction.

We conclude that in clinically unchanged conditions, the time-domain HR variability measures derived from 24-hour ambulatory recordings of AMI survivors are stable during the early convalescent phase, and the day-to-day differences have only little effect on the result. The only exception appears to be the pNN50 parameter, the use of which should be favorably substituted by the rMSSD measurement. Geometric estimates of HR variability are highly and consistently correlated with statistical measures of overall HR variability, and may be used as substitutes for each other.

Adult↗
PubMed1995

Influence of the infarct site on the identification of patients with ventricular tachycardia after myocardial infarction based on the time-domain and spectral turbulence analysis of the signal-averaged electrocardiogram.

In a significant proportion of patients with sustained ventricular tachycardia (VT) following anterior myocardial infarction, the areas of slow conduction are activated early during cardiac depolarization. Therefore, they may not be detected by the standard time-domain analysis of the signal-averaged electrocardiogram (SAECG) which is limited to the terminal part of the QRS complex. Spectral turbulence analysis of the SAECG is a new frequency domain technique which examines the whole QRS complex and may improve identification of patients with sustained VT following anterior infarction. We compared the results of time-domain and spectral turbulence analyses of the SAECG in 53 postinfarction patients with sustained VT and in 53 age-, gender- and infarct site-matched patients without VT. The receiver operator characteristic curves have shown that the time-domain analysis resulted in better identification of patients with VT following inferior than following anterior infarction (e.g., at the sensitivity level of 90%, the corresponding values of specificity were 96 and 90%, respectively), whereas the spectral turbulence analysis performed better in the anterior site of infarction. When both time-domain and spectral turbulence analyses were combined, the accuracy of the SAECG for identification of patients with VT following anterior infarction improved, reaching a specificity of 97% at the sensitivity level of 90%. In conclusion (1) spectral turbulence analysis of the SAECG results in better identification of patients with VT following anterior than following inferior infarction, and (2) the combination of time-domain and spectral turbulence analyses of the SAECG may improve identification of patients with VT following anterior infarction.

Aged↗
PubMed1995

Effects of passive tilt and submaximal exercise on spectral heart rate variability in ventricular fibrillation patients without significant structural heart disease.

It has been shown that tilt and exercise elicit significant changes in autonomic activity in normal subjects and that submaximal exercise causes a greater reduction in heart rate variability (HRV) in animals susceptible to ventricular fibrillation (VF). Whether there is an abnormal HRV response to tilt and exercise in patients at risk of sudden cardiac death (SCD) remains unknown. Short-term HRV before and during passive tilt and exercise was studied in 12 survivors of out-of-hospital cardiac arrest with documented VF and compared with 12 age- and sex-matched normal controls. No patient had significant structural heart disease or left ventricular dysfunction. HRV was computed as total-frequency (TF, 0.01 to 1.00 Hz), low-frequency (LF, 0.04 to 0.15 Hz) and high-frequency (HF, 0.15 to 0.40 Hz) components. There was no significant difference between normal controls and SCD survivors in HRV before or during tilt or submaximal exercise testing. The HF component was significantly decreased during tilt compared with that in the supine position in both normal controls (5.85 +/- 0.61 vs 5.08 +/- 0.95 In(msec2), p = 0.005) and patients (5.58 +/- 1.49 versus 4.74 +/- 1.18 In(msec2), p = 0.003). There was again no significant change in the TF or LF components during tilt in either patients or controls. All frequency components were significantly decreased during submaximal exercise testing in both patients and controls. However, there was no significant difference in any of these tilt- and exercise-induced changes in HRV between normal controls and SCD survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.

Adolescent↗
PubMed1995

Numeric processing of Lorenz plots of R-R intervals from long-term ECGs. Comparison with time-domain measures of heart rate variability for risk stratification after myocardial infarction.

The so-called "Lorenz plots" are scatterplots that show the R-R interval as a function of the preceding R-R intervals. Repeatedly, it has been proposed that these plots might be used for visualizing the variability of the heart rate and that the assessment of heart rate variability (HRV) from these plots might be superior to conventional measures of HRV. However, a precise numeric evaluation of the images of Lorenz plots have never been suggested. To classify the images of Lorenz plots, a computer package that measures their density was developed. For each rectangular area of the plot, the relative number of R1/R2 samples in that area is established and a function is created that assigns the maximum relative number of samples (i.e., the maximum density) to each size of an area of the plot. Plots that are very compact result in a sharply falling density function, while plots that are more diffuse lead to a flat density function. The distinction between such types of density function may be expressed as a logarithmic integral of the density function to express the "compactness" of the plot numerically. As the computational demands of this approach are intensive, an approximate method that restricts the measurement of the density to the area around the peak of the plot was also developed. The results of this approximate method correlate strongly with the full results (r = .98), and approximate measurement of one plot requires less than 1 minute of computer time. The approximate method has been applied to a set of 24-hour Holter records obtained from 637 survivors of acute myocardial infarction. For each record, the SDNN and SDANN values were also calculated as conventional measures of HRV. Both the density of the Lorenz plots and the conventional measures of HRV were used to investigate the differences among 48 patients who suffered an arrhythmic event (sudden death or sustained symptomatic ventricular tachycardia) during a 2-year follow-up period and the remaining 589 patients without arrhythmic postinfarction complications. At a sensitivity of 30%, the Lorenz plot density distinguished the patients with events with a positive predictive accuracy of 58%, while the SDNN and SDANN led to a positive predictive accuracy of only 23 and 18%, respectively. Thus, a detailed analysis of Lorenz plots is feasible and more clinically useful than the conventional measures of HRV.

Adult↗
PubMed1995

Computer files.

From what has been said, several recommendations can be made for users of small personal computers regardless of which operating system they use. If your computer has a large hard disk not specially required by any single application, organize the disk into a small number of volumes. You will then be using the computer as if it had several smaller disks, which will help you to create a logical file structure. The size of individual volumes has to be selected carefully with respect to the files kept in each volume. Otherwise, it may be that you will have too much space in one volume and not enough in another. In each volume, organize the structure of directories and subdirectories logically so that they correspond to the logic of your file content. Be aware of the fact that the directories suggested as default when installing new software are often not the optimum. For instance, it is better to put different graphics packages under a common subdirectory rather than to install them at the same level as all other packages including statistics, text processors, etc. Create a special directory for each task you use the computer. Note that it is a bad practice to keep many different and logically unsorted files in the root directory of any of your volumes. Only system and important service files should be kept there. Although any file may be written all over the disk, access to it will be faster if it is written over the minimum number of cylinders. From time to time, use special programs that reorganize your files in this way.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Storage Devices↗
PubMed1995

Algebraic decomposition of the TU wave morphology patterns.

In principle, the T wave results from the differences in durations of action potentials (AP) of different ventricular regions. Based on this concept, a mathematical model has been developed that represents the TU wave morphology as a summation of four AP-like functions: TU = S1 - S2 + L1 - L2. The sigmoidal shape of AP-like curves is produced by Hill's equation V(t) = a . tn/(bn + tn). Each of the decomposition functions is characterized by two parameters: the amplitude at the beginning of QRS (Amax), and the duration at 5% of Amax (D95). The set of four decomposition functions leads to eight parameters that provide detailed characteristics of the TU wave morphology. The model was validated using 170 TU wave complexes recorded digitally in leads V2-V6 from 22 normal subjects and 12 patients with abnormal TU wave morphologies (negative, biphasic, and notched T waves). The electrocardiographic signals were sampled at 100 Hz and a best-fit procedure was used to obtain the decomposition. In all cases the coefficients of correlation between original TU patterns and their mathematical models were > or = 0.99. The mean absolute difference between the observed and modeled values of the TU patterns was similar in cases with normal and abnormal TU wave morphologies (4.65 +/- 0.41 microV vs 5.19 +/- 0.48 microV respectively) demonstrating that the model is capable of describing and categorizing various TU patterns by a set of eight numerical parameters.

Cardiomyopathy, Hypertrophic↗
PubMed1995

Identification of atrial fibrillation episodes in ambulatory electrocardiographic recordings: validation of a method for obtaining labeled R-R interval files.

Current systems for analyzing ambulatory electrocardiograms (ECGs) are unable to distinguish precisely between sinus rhythm and atrial fibrillation (AF) episodes, and are unable to produce RR interval listings that distinguish AF from sinus rhythm on a beat-to-beat basis. We describe a method for obtaining such a computerized listing ("Composite Rhythm" file) from ambulatory recordings containing episodes of AF. The file lists the rhythm of each beat, its real time, and the QRS complex morphology. A visual inspection is made of a full printout of the recording to identify the precise time of onset and termination of each episode of AF. These times are entered into a computer and identified with the corresponding beats on a conventional RR interval file generated by Holter analysis. The method was validated using 1-hour segments from 20 ambulatory ECGs containing 145 episodes of AF. These were visually identified by four independent observers with a mean sensitivity of 99.1%. The first beat of AF was identified concordantly in 96% of episodes, with a discrepancy of < or = 3 beats in the other episodes. The times of 200 selected QRS complexes were then entered into the computer by each observer; 91.1% of these complexes were identified exactly and 100% were identified to within one beat. The Composite Rhythm files have several potential applications for testing AF detection algorithms and studying the mode of onset of AF.

Algorithms↗
PubMed1995

Risk stratification and prediction of sudden death following myocardial infarction.

Accurate and reliable identification of those survivors of acute myocardial infarction who are at high risk of sudden death remain an important and challenging problem. This review summarises the current state-of-the-art of the risk stratification techniques and lists achievements in this field. The review comments in detail on individual factors used in risk stratification. Residual ischemia may be considered as one of the main triggering factors of post-infarction arrhythmia. Depressed left ventricular ejection fraction indicates deterioration of ventricular function. Electrical instability of the myocardium reflects the potential substrate of arrhythmia. Frequent ventricular ectopic activity provides triggers of ventricular tachycardia and/or fibrillation when acting on a suitable substrate. Impaired autonomic status of the heart may lead to the loss of vagal antiarrhythmic protection. Further, the tests used for risk stratification are discussed. Ventriculography provides estimates of left ventricular ejection fraction. Holter monitoring is used for the assessment of ventricular ectopic activity and heart rate variability. Exercise testing is used to address residual ischemia. Programmed ventricular stimulation and the analysis of signal averaged electrocardiograms estimate electrical instability of the myocardium. Baroreflex sensitivity is a measure of cardiac parasympathetic reflexes. The design and results of different experimental and clinical studies which utilised these tests are also discussed.

Autonomic Nervous System↗
PubMed1995

Time course of Fos-like immunoreactivity associated with cholinergically induced REM sleep.

Now that the pharmacology and neuronal connectivity underlying REM sleep is beginning to be understood, it is important to begin investigations that elucidate the transcriptional response related to the REM sleep process. The present study focuses on determining the temporal development of Fos-like immunoreactivity (Fos-LI) in the dorsolateral pons following cholinergically induced, sustained rapid eye movement (REMc) sleep in cats. Microinjections (0.25 microliter) of vehicle (n = 3) or carbachol (0.2-4.0 micrograms/0.25 microliters) were made into the medial pontine reticular formation. Carbachol produced a state with all the signs of natural REM sleep, and with durations from 0 min to 120 min. Animals were killed either immediately or at various intervals after the end of REMc. Compared to vehicle- and carbachol-treated animals without REMc, the animals with REMc showed a significantly higher number of Fos-LI cells in pontine regions that have been implicated in REM sleep generation. Regions with REMc-associated Fos-LI increases included the lateral dorsal tegmental (LDT) and pedunculopontine tegmental (PPT) nuclei; the locus coeruleus; the dorsal raphe; and the medial pontine reticular formation. More Fos-LI cells were found with longer REMc bouts than with shorter-duration REMc bouts. However, with 2 hr long REMc bouts the number of Fos-LI cells returned to control levels, suggesting that the c-fos transcriptional cascade is turned off once a threshold of REMc has been reached. These findings indicate that pontine neuronal populations implicated in REM sleep express more c-fos in the course of REMc, and that the extent of expression is related to the duration of the state.

Animals↗
PubMed1994

Change of autonomic influence on the heart immediately before the onset of spontaneous idiopathic ventricular tachycardia.

OBJECTIVES: This study aimed to assess heart rate variability immediately before the onset of episodes of spontaneous ventricular tachycardia. BACKGROUND: It has been shown that decreased heart rate variability may be associated with a propensity to ventricular tachyarrhythmias. However, it is still disputed whether there is an abrupt change in heart rate variability immediately before the onset of these arrhythmias. METHODS: Twenty-three patients with idiopathic ventricular tachycardia underwent two-channel 24-h Holter monitoring in a drug-free state. Spectral heart rate variability was computed as low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components at 2-min intervals over a 1-h period immediately before the onset of ventricular tachycardia. Average values of heart rate variability were also computed for the entire 24-h recordings. The low/high frequency component ratio was calculated as an index of the autonomic balance of the heart. RESULTS: Seventy-one episodes of ventricular tachycardia from the 23 recordings formed this study. There was an increased low/high ratio during 6- to 8-min periods immediately before the onset of ventricular tachycardia episodes compared with the average values for the entire 24 h. This increase in the low/high ratio resulted largely from a decrease in the high frequency component value (4.70 +/- 1.15 vs. 5.10 +/- 1.06 ln[ms2] [mean +/- SD], p = 0.001) because there was no significant change in the low frequency component value (6.37 +/- 1.20 vs. 6.34 +/- 0.91 ln[ms2], p = 0.786, 95% confidence interval -0.25 to 0.19 ln[ms2], type II error < 0.0001 for change of 7.8%). In contrast, there were no significant differences in the low or high frequency components or low/high ratio between 6-min salvo-free periods 40 min before the onset of ventricular tachycardia and the average 24-h values (type II error < 0.0001, < 0.038 and < 0.1841, respectively, for change of 7.8%). The low/high ratio was also significantly higher during the 6 min immediately before the onset of ventricular tachycardia compared with that during the 6-min salvo-free periods 40 min before the onset of ventricular tachycardia. A significant increase in mean heart rate immediately before the onset of ventricular tachycardia was also noted. CONCLUSIONS: There is a significant change in autonomic influence on the heart during the last few minutes preceding the onset of episodes of idiopathic ventricular tachycardia. This seems to result mainly from decreased vagal activity rather than enhanced sympathetic input to the heart.

Adolescent↗