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Probably the first explicit description of the concept of periodic diseases was provided over 30 years ago by Dr. He called attention to a number of conditions in which the disease process itself could be shown to flare or recur on a regular basis of days to months; ranging from certain Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA of arthritis to some mental illnesses and hereditary diseases, such as familial Mediterranean fever.

In the late 1970s, Michael Mackey and Leon Glass (47, 48) helped to rekindle interest in this dormant field when they introduced the term dynamical disease to encompass the types of periodic syndrome Reimann had catalogued, as well as irregular dynamics thought possibly to represent deterministic chaos. Indeed, a recent survey of the literature (49) indicates that Reimann, rather than compiling a list of the exceptional, was more likely sampling a widespread, even generic manifestation of the dynamics of нажмите для деталей. From the most general perspective, the practice of bedside diagnosis itself would be impossible without the loss of complexity and the emergence of pathologic periodicities.

To a large extent, it is these periodicities and highly-structured patterns - the breakdown of multi-scale fractal complexity under pathologic conditions - that allow clinicians to identify and classify many pathologic features of their patients. Familiar examples include periodic tremors in neurologic conditions, AV Wenckebach patterns, the "sine-wave" ECG pattern in hyperkalemia, manic-depressive alterations, and cyclic breathing patterns in heart failure.

While fractals are irregular, not all irregular structures or erratic time series are fractal. A key feature of the class of fractals seen in biology is a distinctive type of long-range order. This property generates correlations that extend over many scales of space or time. For complex processes, fractal long-range correlations are the mechanism underlying a "memory" effect; the value of some variable, e.

Certain Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA are marked by a breakdown of this long-range organization property, producing an uncorrelated randomness similar to "white noise. Practical applications of nonlinear dynamics are likely within the next few years. Probably the first bedside implementations will be in physiological monitoring. A number of indices derived from chaos theory have shown promise in forecasting subjects at high risk of Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA or hemodynamic instability, including automated detection of the onset and end of pathologic low frequency (1, 2 and 4) (43, 52-59); detection of subtle ST-T alternans (17, 51); detection of a breakdown in fractal scaling with disease and aging (43); and quantification of differences or changes in the nonlinear complexity or dimension of a physiological time series (59, 60).

In addition to these diagnostic applications, perhaps the most exciting prospects are related to novel therapeutic interventions. An important recent finding is that certain mathematical or physical systems with complex dynamics can be controlled by properly timed external stimuli: chaotic dynamics can be made more regular (chaos control) and periodic ones can be made chaotic (chaos anti-control) (61-63).

One proposal, based on the earlier notion that certain arrhythmias, particularly ventricular fibrillation, represent cardiac chaos, is to develop chaos control algorithms to electrically pace the heart beat back to sinus rhythm (63). A more recent proposal is to use chaos anti-control protocols to treat or to prevent cardiac arrhythmias or epilepsy based on the hypothesis that restoration of a kind chaotic-like variability may actually Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA advantageous (62).

Chaos theory also holds Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA for illuminating a number of major problems in contemporary physiology and molecular biology. Nonlinear wave mechanisms may underlie certain types of reentrant ventricular tachyarrhythmias (6, 7). Appreciation for the rich nonlinearity of physiological systems may have relevance for modeling enormously complicated signal-transduction cascades involved, for example, in neuroautonomic dynamics in which interactions and "cross-talk" occur over a wide range of temporal and spatial scales, as well as for understanding complex pharmacologic effects.

Fractal analysis of long DNA sequences has recently revealed that non-coding, but not coding sequences possess long-range correlations among nucleotides (64). Findings from nonlinear dynamics have also challenged conventional mechanisms of physiological control based on classical homeostasis, which Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA that healthy systems seek to attain a constant steady state.

In contrast, nonlinear systems with fractal dynamics, such as the neuroautonomic mechanisms regulating heart rate variability, behave as if they were driven far from equilibrium under basal conditions. Finally, a fundamental methodologic principle underlying these new applications and interpretations is the importance of analyzing continuously sampled variations in physiological output, such as heart rate, and not Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA relying Cyclopentolate Hydrochloride Ophthalmic Solution (Cyclogyl)- FDA averaged values or measures of variance.

Dynamical analysis demonstrates that there is often hidden information in physiological time series and that certain fluctuations previously considered "noise" actually represent important signals (67-70).

This chapter здесь adapted from: Goldberger AL. Lancet 1996;347:1312-1314; and Goldberger AL. Fractal variability versus pathologic periodicity: complexity loss and stereotypy in disease. Perspect Biol Med 1997;40:543-561. This work is supported in part by grants from the National Aeronautics and Space Administration and the G.

Harold and Leila Y. Glass L, Mackey MC. From Clocks to Chaos: the Rhythms of Life. Princeton: University Press, 1988. Goldberger AL, Rigney DR, West BJ. Chaos and fractals in human physiology. Bassingthwaighte JB, Liebovitch LS, West BJ. New York: Oxford University Press, 1994.

Simple mathematical models with very complicated dynamical behavior. When Time Breaks Down: The Three-Dimensional Dynamics of Electrochemical Waves and Cardiac Arrhythmias. Princeton, NJ: Princeton University Press, 1987. Davidenko JM, Pertsov AV, Salomonosz R, Baxter W, Jalife J. Stationary and drifting waves of excitation in isolated cardiac muscle. Babloyantz A, Destexhe A. Low dimensional chaos in an instance of epilepsy. Proc Natl Acad Sci USA 1986;83:3513-7. Goldberger AL, Rigney DR.

Nonlinear dynamics at the bedside. In: Glass L, Hunter P, McCulloch A. New York: Springer, 1991; 583-605. Chay TR, Lee YS. Ann NY Acad Sci 1990;591:328-50. Longtin A, Bulsara A, Pierson D, Moss F. Bistability and the dynamics of periodically forced sensory neurons. Delmar M, Ibarra Интересна, Thalomid (Thalidomide)- FDA всетаки, Davidenko J, Lorente P, Jalife J.



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