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Biomedical subjects

L Glass

Publications and source records attributed to L Glass.

At least 19 recordsLinked to original sources
PubMed1992

Phase resetting and fixed-delay stimulation of a simple model of respiratory rhythm generation.

In a previous study (Lewis et al., 1990), the response of the respiratory rhythm to a perturbing stimulus was investigated using two different stimulus protocols: phase resetting and fixed-delay stimulation. The first protocol consists of measuring the effects of perturbing an oscillator at different phases of the cycle on the duration of the perturbed cycle. The resulting phase response curves (PRCs) can be used to characterize the properties of the oscillator (Winfree, 1980). A second protocol, fixed-delay stimulation, involves perturbing an oscillator at a fixed latency from the onset of the cycle, repeated every n-th cycle. If a single stimulus produces an effect that lasts longer than a single cycle, complicated responses can be expected from fixed-delay stimulation (Lewis et al., 1987). A simple three-phase model for respiratory rhythm generation based on a hypothesis by Richter and coworkers (1982, 1983, 1986) was investigated in the context of these experimental studies. Phase resetting and fixed-delay stimulation protocols were simulated in the model. PRCs of the model resemble those obtained experimentally: a phase-dependent prolongation or shortening of the inspiratory phase depending on the stimulus magnitude, and a slight prolongation of the expiratory phase. Stimuli delivered to the model repetitively during successive inspiratory periods at a fixed-delay produced various combinations of shortened and prolonged cycles, similar to those observed in the experiments. However, the marked increases in cycle duration observed in the experiments during, as well as after, stimulation were not evident in the model. These comparisons suggest that (1) PRCs may not be an adequate way to evaluate certain models of rhythmogenesis, and (2) to improve the present simplified formulation of the three-phase model of the respiratory oscillator, time-varying stimulus dependent effects should be incorporated.

Animals↗
PubMed1992

The topology of phase response curves induced by single and paired stimuli in spontaneously oscillating chick heart cell aggregates.

The topological properties of the phase resetting of biological oscillators by an isolated stimulus delivered at various phases of the cycle depend on whether the stimulus is "weak" or "strong." When multiple stimuli are delivered to the oscillator, the response to stimulation also depends on the time between the stimuli, and the rate at which the oscillator returns to an underlying limit cycle attractor. If the time between two consecutive "weak" stimuli is sufficiently short, the effects produced by the pair of stimuli may be characteristic of a single "strong" stimulus. These results are demonstrated in a model experimental system, spontaneously beating aggregates of cells derived from embryonic chick heart, and are illustrated by consideration of a simple theoretical model of nonlinear oscillators, the Poincaré oscillator.

Animals↗
PubMed1992

Possible trazodone potentiation of fluoxetine: a case series.

BACKGROUND: Fluoxetine is an effective serotonin reuptake inhibitor antidepressant that can fail to alleviate either insomnia or major depression in a substantial minority of depressed patients. Trazodone has been reported to be both an effective nonbenzodiazepine hypnotic for antidepressant-associated insomnia and a possible serotonergic antidepressant adjunct. We present a case series of patients with variable responses when trazodone was added to fluoxetine. METHOD: Eight consecutive depressed (DSM-III-R) patients taking fluoxetine were given trazodone either for sleep or as a possible antidepressant potentiator. RESULTS: Three (37.5%) of the eight patients (confidence interval = 4.0%-71.0%) had improvements in both sleep and depression. The remaining five patients either were unaffected by the addition of trazodone to fluoxetine or had intolerable adverse drug reactions. CONCLUSION: Trazodone may be an effective hypnotic and antidepressant potentiator when combined with fluoxetine for some patients, but its use may be limited by adverse effects.

Adult↗
PubMed1992

Predictors of cocaine use in pregnancy.

Several hundred thousand infants are exposed to cocaine in utero every year in the United States. In an attempt to provide services for women abusing drugs, various programs have been proposed for prenatal drug testing. This study was conducted to assess the sensitivity, specificity, and predictive values of screening programs based on a variety of clinical and historical factors. Between October 1988 and March 1989, 1111 parturients who delivered at an inner-city hospital had urine samples and data collected. The urine, linked by code number to the data, which contained no identifiers, was tested anonymously for illicit drugs. We then assessed the associations of a variety of historical and clinical variables with positive toxicologies. An acknowledged history of drug use or a combination of no prenatal care and cigarette use provided the most valid prediction of cocaine use, with a 59.8% sensitivity, 97.5% specificity, 70% positive predictive value, and 94.9% negative predictive value for positive urine toxicologic examinations. The addition of clinical data such as low birth weight did not improve predictive values significantly. Although the use of easily available historical data allowed correct identification of 60% of parturients who used cocaine, no combination of factors could detect all users. If it is considered beneficial to identify all users at a given point, then urine toxicology screening would be more appropriate than sole reliance on patient history.

Cocaine↗
PubMed1991

The biologic and social consequences of perinatal cocaine use in an inner-city population: results of an anonymous cross-sectional study.

Cocaine use among pregnant women and reports of its adverse perinatal consequences have increased substantially over the past 10 years. However, most researchers have studied patients registered at drug treatment centers or have relied on voluntary participation by patients, either of which introduces the possibility of selection bias. To determine the frequency and consequences of prenatal cocaine use among an unselected inner-city obstetric population, we collected urine samples from parturient women at a municipal hospital and anonymously tested these specimens for metabolites of cocaine, marijuana, opiates, and methadone. Urine specimens, with linked obstetric data sheets, were available from a study population of 1111 patients, and pediatric data sheets were available for 846 mother-infant pairs. Cocaine metabolites were found in 11.5% of the urine samples collected, whereas metabolites of marijuana, opiates, and methadone, respectively, were present in 1.1%, 1.2%, and 0.3% of the specimens. Cocaine users were more likely than nonusers to have had no prenatal care (51% vs 8.8%; p less than 0.0001), to be American-born rather than Caribbean-born (71% vs 33%; p less than 0.001), and to have a higher parity (1.83 vs 1.14; p less than 0.0001). Infants of cocaine users had a lower mean gestational age (-0.93 weeks; p less than 0.01), a lower mean birth weight (2560 +/- 788 vs 3151 +/- 699 gm; p less than 0.001), and an increased probability of having an Apgar score of less than 7 at 5 minutes (12.5% vs 3.2%; p less than 0.0001). Multiple linear regression analysis that isolated confounding variables such as the presence or absence of prenatal care, maternal age and parity, and the use of cigarettes and alcohol did not substantially affect the differences described above. The effect of cigarette smoking on reducing fetal size was cumulative. In conclusion, cocaine is the most commonly used illicit drug among parturients in this community and is strongly associated with underutilization of prenatal care services. Infants of cocaine users are more likely to be preterm and depressed at birth and to have a low birth weight. Cocaine use, through the above-noted effects, increases the need for prenatal care while simultaneously decreasing the likelihood that it will be obtained.

Adult↗
PubMed1991

A unified model of atrioventricular nodal conduction predicts dynamic changes in Wenckebach periodicity.

The atrioventricular (AV) node responds in a complex fashion to changes in activation rate. A variety of approaches have been used to explain these dynamic AV nodal responses, but none has been able to account fully for AV nodal behavior. Three specific rate-dependent properties of the AV node have been described: 1) time-dependent recovery after excitation, 2) an effect of short cycles to advance recovery ("facilitation"), and 3) a gradual slowing of conduction in response to sustained, high-frequency activation ("fatigue"). We hypothesized that a model incorporating quantitative descriptors of all three processes might be able to account for a wide variety of AV nodal behaviors. Quantitative descriptors of AV nodal recovery, facilitation, and fatigue were developed based on AV nodal conduction changes during selective pacing protocols in seven autonomically blocked dogs. These descriptors were incorporated into a set of mathematical equations that define AV nodal conduction of any beat based on activation history. The equations were then applied to predict pacing-induced Wenckebach periodicity in each dog. Experimental data were obtained after nine to 19 step decreases in atrial cycle length into the Wenckebach zone in each animal. Observed behaviors included complex patterns of block, a progressive increase in the level of block over 5 minutes of rapid pacing, and periods of alternating patterns of block. The model accurately predicted the onset of AV block at each cycle length, the relation between conduction ratio and cycle length as a function of time, and the changing patterns of Wenckebach periodicity during sustained atrial pacing. All three terms of the model equation (describing recovery, facilitation, and fatigue) were essential to account fully for the observed behaviors. Elimination of AV nodal fatigue from the model resulted in failure to account for time-dependent changes in Wenckebach patterns, whereas exclusion of facilitation led to consistent overestimation of the degree of AV block at each cycle length. We conclude that a mathematical model incorporating terms to describe recovery, facilitation, and fatigue accurately predicts a wide range of Wenckebach-type behavior and that complex conduction patterns of the AV node can be fully accounted for by simple functional AV nodal properties.

Animals↗
PubMed1991

Evolution of rhythms during periodic stimulation of embryonic chick heart cell aggregates.

During periodic stimulation of spontaneously beating chick heart cell aggregates, there is often an evolution of coupling patterns between the stimulator and the aggregate action potential. For example, at rapid stimulation frequencies, a rhythm that is initially 1:1 (stimulus frequency:aggregate frequency) can evolve to other rhythms such as 5:4 and 4:3. Time-dependent effects generated during periodic stimulation are characterized by three types of experiments to determine 1) the effect of periodic stimulation on the intrinsic cardiac beat rate (overdrive suppression), 2) the effect of periodic stimulation on the phase resetting properties of the aggregate, and 3) the time-dependent changes in the coupling patterns between the stimulator and the aggregate during periodic stimulation. The protocols involved variations in the duration and rate of periodic stimulation. A mathematical model is developed in the form of a two-dimensional finite difference equation based on the data from experiments 1 and 2. The model is used to predict the data generated by experiment 3. There is good correspondence with the experiments in that the theory reproduces complex transitions between various rhythms and displays irregular rhythms similar to those observed experimentally. These results have implications for the evolution of cardiac arrhythmias such as atrioventricular heart block and modulated parasystole.

Animals↗
PubMed1990

The effects of superior laryngeal nerve stimulation on the respiratory rhythm: phase-resetting and aftereffects.

The effect of brief superior laryngeal nerve stimulation on the respiratory rhythm was investigated in midcollicular decerebrate, unanesthetized, artificially ventilated, paralysed, vagotomized and debuffered cats. Stimulus trains (50 ms, 200 Hz) delivered during inspiration (I) with intensities exceeding a threshold value, that was inversely related to the phase of the cycle, terminated I and shortened the following expiration (E) (irreversible I termination). Stimulus trains given during I with intensities just below this threshold value produced a transient suppression of I followed by resumption of activity, resulting in a slight prolongation of both I and the following E (reversible I termination). Stimulation during E produced a phase-dependent prolongation of E, but did not affect the next I. Phase-resetting curves were constructed by measuring the changes in respiratory cycle duration produced by stimuli given at phases throughout the cycle. A single stimulus produced aftereffects that lasted several cycles. The aftereffects were investigated by delivering stimuli at a fixed delay from cycle onset every n cycles (n is an integer). Certain combinations of delay, stimulus intensity, and n, resulted in (1) a variable combination of reversible and irreversible I terminations, rather than a consistent response, and (2) an increase in cycle duration. The stimulus aftereffects, that can last up to 9 cycles, may account for previously described unpredictability in the response of the respiratory oscillator to a given stimulus.

Animals↗
PubMed1990

Delayed visual feedback and movement control in Parkinson's disease.

The dependence of movement on visual information was compared for healthy individuals and Stage II-III patients with Parkinson's disease (PD). A time delay (0-1400 ms) was introduced into a visually guided motor tracking task which required the subject to maintain constant index finger position relative to a stationary baseline on an oscilloscope. For healthy individuals, delayed visual feedback induced complex oscillations in finger displacement. Similar results were obtained for four of eight patients with PD. However, oscillations were not induced in four of eight patients with PD because of reduced gain and/or a higher tremor amplitude at zero delay which obscured the tracking error. These results suggest that some patients with PD are able to utilize visual information for controlling tracking in this motor task in the same manner as healthy individuals.

Adult↗
PubMed1990

NASPE young investigator awardee-1990. Complex rhythms resulting from overdrive suppression in electrically stimulated heart cell aggregates.

Spontaneously beating embryonic chick heart cell aggregates were stimulated with current pulses delivered either as periodic trains, or at a fixed delay after each action potential. Following stimulation at fixed rates faster than the intrinsic rate, there was a transient slowing of the spontaneous rhythm. This response, called overdrive suppression, can lead to a complex evolution of rhythms. During periodic stimulation there is a continuum of dropped beat patterns, and during fixed delay stimulation bursting activity appears. This study provides a conceptual basis for understanding analogous rhythms in the intact heart.

Action Potentials↗
PubMed1979

Structure and dynamics of neural network oscillators.

Techniques are given to represent oscillating neural networks by asynchronous logical switching networks, and to analyze the oscillating networks using a directed graph called a state transition diagram. Consideration is restricted to network oscillators containing no rhythm determining pacemaker neurons, and no neurons exhibiting self-limiting properties such as post-inhibitory rebound or accumulating refractoriness. In the state transition diagrams, stable oscillations are associated with a particular geometric configuration called a cyclic attractor (the heavy cycle in Fig. 2). We show that given the network connectivity it is possible to predict autonomous dynamic behaviour, as well as behaviour following hyperpolarizing or depolarizing inputs to neurons of the network. Conversely, given information about patterns of firing activity during cycles and transients of neural networks, the network connectivity can be predicted. The theoretical techniques can be used to generate a census of network structures capable of generating stable oscillations. Several representative network oscillators are discussed in the context of previous theoretical and experimental studies of the structure of neural network oscillators. Although the number of theoretically possile network oscillators capable of generating sustained oscillations is very large, the techniques which are given should be useful in the design of experiments capable of distinguishing between equally plausible hypotheses.

Action Potentials↗
PubMed1979

A simple model for phase locking of biological oscillators.

A mathematical model is presented for phase locking of a biological oscillator to a sinusoidal stimulus. Analytical, numerical and topological considerations are used to discuss the patterns of phase locking as a function of amplitude of the sinusoidal stimulus and the relative frequencies of the osillator and the sinusoidal stimulus. The sorts of experimental data which are needed to make comparisons between theory and experiment are discussed.

Biological Clocks↗
PubMed1979

The speech-language pathologist's role in understanding the genetics of Van der Woude syndrome.

A family report of three generations of Van der Woude syndrome (cleft lip or palate and lip pits) is presented to show that the speech-language pathologist may play an important role in identifying patients with this defect. Understanding the genetic basis of this syndrome and documentation of family history through pedigree analysis can be instrumental in identifying other family members potentially affected with speech disorders. Because the diagnosis of Van der Woude syndrome was made in one member of the family in the pedigree, three other family members who had never received previous diagnosis or treatment of their speech disorders were identified. Other family members were referred for genetic counseling. The concepts of autosomal dominant transmission, variable expression, incomplete penetrance, and the pedigree technique for recording family history are also presented.

Child, Preschool↗