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Biomedical subjects

A L Goldberger

Publications and source records attributed to A L Goldberger.

At least 19 recordsLinked to original sources

Loss of 'complexity' and aging. Potential applications of fractals and chaos theory to senescence.

The concept of "complexity," derived from the field of nonlinear dynamics, can be adapted to measure the output of physiologic processes that generate highly variable fluctuations resembling "chaos." We review data suggesting that physiologic aging is associated with a generalized loss of such complexity in the dynamics of healthy organ system function and hypothesize that such loss of complexity leads to an impaired ability to adapt to physiologic stress. This hypothesis is supported by observations showing an age-related loss of complex variability in multiple physiologic processes including cardiovascular control, pulsatile hormone release, and electroencephalographic potentials. If further research supports this hypothesis, measures of complexity based on chaos theory and the related geometric concept of fractals may provide new ways to monitor senescence and test the efficacy of specific interventions to modify the age-related decline in adaptive capacity.

Aging

Long-range correlations in nucleotide sequences.

DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.

Animals

Spectral analysis of heart rate dynamics in elderly persons with postprandial hypotension.

Prior studies suggest that postprandial hypotension in elderly persons may be due to defective sympathetic nervous system activation. We examined autonomic control of heart rate (HR) after a meal using spectral analysis of HR data in 13 old (89 +/- 6 years) and 7 young (24 +/- 4 years) subjects. Total spectral power, an index of overall HR variability, was calculated for the frequency band between 0.01 and 0.40 Hz. Relatively low-frequency power, associated with sympathetic nervous system and baroreflex activation, was calculated for the 0.01 to 0.15 Hz band. High-frequency power, representing parasympathetic influences on HR, was calculated for the 0.15 to 0.40 Hz band. Mean arterial blood pressure declined 27 +/- 8 mm Hg by 60 minutes after the meal in elderly subjects, compared with 9 +/- 8 mm Hg in young subjects (p less than or equal to 0.0001, young vs old). The mean change in low-frequency HR power from 30 to 50 minutes after the meal was +19.4 +/- 25.3 U in young subjects versus -0.1 +/- 1.5 U in old subjects (p less than or equal to 0.02). Mean change in total power was also greater in young (19.0 +/- 26.6 U) subjects compared with old subjects (0.0 +/- 1.6 U, p greater than or equal to 0.02). Mean ratio of low:high-frequency power increased 3.1 +/- 3.3 U in young subjects vs 0.5 +/- 2.7 U in old subjects (p less than or equal to 0.01). The increase in low-frequency HR power and in the low:high frequency band ratio in young subjects is consistent with sympathetic activation in the postprandial period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature.

A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement.

Adult

Aging and the complexity of cardiovascular dynamics.

Biomedical signals often vary in a complex and irregular manner. Analysis of variability in such signals generally does not address directly their complexity, and so may miss potentially useful information. We analyze the complexity of heart rate and beat-to-beat blood pressure using two methods motivated by nonlinear dynamics (chaos theory). A comparison of a group of healthy elderly subjects with healthy young adults indicates that the complexity of cardiovascular dynamics is reduced with aging. This suggests that complexity of variability may be a useful physiological marker.

Adult

Reperfusion arrhythmias after thrombolysis. Electrophysiologic tempest, or much ado about nothing.

Arrhythmias that may accompany myocardial reperfusion have generated significant clinical interest. First, there were concerns, based on animal studies, that high-grade ventricular tachyarrhythmias would pose a serious threat following thrombolytic therapy to treat an evolving myocardial infarction. Second, lower-grade arrhythmias, such as accelerated idioventricular rhythm, were cited as useful, noninvasive markers of successful reperfusion. Critical review of the current data, however, indicates that arrhythmias following thrombolytic therapy for acute myocardial infarction are usually neither dangerous clinical events nor consistent markers of reperfusion.

Animals

The fractal lung: universal and species-related scaling patterns.

The mammalian lung exhibits features of a fractal tree: heterogeneity, self-similarity and the absence of a characteristic scale. The finite nature of the lung ultimately limits the range over which self-similarity scaling characteristics are applicable. However, generalization based on the scaling features of fractals, provides unique insight into geometric organization of anatomic structures. Furthermore, the mathematical theory of renormalization groups provides a description of the harmonically-modulated inverse power-law scaling observed for bronchial tree dimensions observed in different species. Compared to several mammalian species (dog, rat, hamster), the human lung shows marked differences in the phase of the harmonic modulation for both length and diameter measurements. These inter-species scaling differences suggest that evolutionary factors modify certain universal features of morphogenesis.

Anatomy, Comparative

Spectral characteristics of heart rate variability before and during postural tilt. Relations to aging and risk of syncope.

Fourier analysis of heart rate (HR) may be used to characterize overall HR variability as well as low- and high-frequency components attributable to sympathetic and vagal influences, respectively. We analyzed HR spectral characteristics of 12 healthy young (18-35 years) and 10 healthy old (71-94 years) subjects before and during 60 degrees head-up tilt. Total spectral power in the 0.01-0.40-Hz frequency range and low-frequency (0.06-0.10 Hz) and high-frequency (0.15-0.40 Hz) components of the HR power spectrum were significantly lower in old than in young subjects in supine and upright positions. To characterize and compare overall HR variability in young and old subjects, we computed the regression lines relating the log amplitude to the log frequency of the supine HR spectra (l/fx plots). The regression lines for old subjects were lower and steeper (mean slope, -0.78 [5%, 95% confidence limits (CL), -0.73, -0.83]) than in young (mean slope, -0.67 [CL, -0.62, -0.72]), indicating not only reduced overall spectral amplitude but also relatively greater attenuation of high-frequency HR components in the old subjects. This finding illustrates a novel way to quantify the loss of autonomic influences on HR regulation as a function of age. During postural tilt, HR variability was unchanged in the old subjects. For the entire group of young subjects, total HR variability increased during tilt. Six young subjects developed vasovagal syncope during tilt, enabling us to examine differences in the HR spectra of these subjects while they were asymptomatic before syncope.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cardiac chaos.

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Animals

Beyond pure parasystole: promises and problems in modeling complex arrhythmias.

The dynamics of pure parasystole, a cardiac arrhythmia in which two competing pacemakers fire independently, have recently been fully characterized. This model is now extended in an attempt to account for the more complex dynamics occurring with modulated parasystole, in which there exists nonlinear interaction between the sinus node and the ectopic ventricular focus. Theoretical analysis of modulated parasystole reveals three types of dynamics: entrainment, quasiperiodicity, and chaos. Rhythms associated with quasiperiodicity obey a set of rules derived from pure parasystole. This model is applied to the interpretation of continuous electrocardiographic data sets from three patients with complicated patterns of ventricular ectopic activity. We describe several new statistical properties of these records, related to the number of intervening sinus beats between ectopic events, that are essential in characterizing the dynamics and testing mathematical models. Detailed comparison between data and theory in these cases show substantial areas of agreement as well as potentially important discrepancies. These findings have implications for understanding the dynamics of the heartbeat in normal and pathological conditions.

Animals

Nonlinear mechanics of the heart's swinging during pericardial effusion.

When excessive fluid accumulates in the pericardial space, the heart, suspended by the great vessels, is then free to swing as a pendulum. The swinging may occur at either the same frequency as the heart rate (1:1 oscillation) or at half the heart rate (2:1 oscillation), the latter frequency often arising during cardiac tamponade. We show that these two frequencies of oscillation may be explained by the nonlinearity of Newton's equation of motion as applied to the heart. Terms in the equation correspond to gravitational and buoyancy forces, forces due to ejection of blood into the great vessels, and damping forces. A transition between the 1:1 and 2:1 swinging is found to occur when particular parameters of the model are changed, notably when there is an increase of heart rate. This finding is compatible with previous clinical reports.

Heart

Instrumentation and practice standards for electrocardiographic monitoring in special care units. A report for health professionals by a Task Force of the Council on Clinical Cardiology, American Heart Association.

The proposed recommendations for continuous electrocardiographic monitoring systems represent goals for future development. Description of a technique in the report does not constitute an endorsement of its clinical use. Lead systems for ECG monitoring must adequately sense the cardiac electrical field and the leads should be standardized. Future monitors should be capable of simultaneously displaying and analyzing multiple leads. Recommendations for electrode placement and position of patient are made. Important parameters in each category of standards for instrumentation published in 1983 in the American National Standard for Cardiac Monitors, Heart Rate Meters, and Alarms are listed. Selected procedures proposed by the Association for the Advancement of Medical Instrumentation to inform users of minimally acceptable accuracy of computerized systems in a standardized manner are presented. Emphasis is placed on the importance of nursing and medical staff capabilities. Personnel qualifications and training as well as systems to assure and maintain quality of immediate ECG diagnosis are highlighted.

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