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Biomedical subjects

R J Cohen

Publications and source records attributed to R J Cohen.

At least 73 records · Page 4Linked to original sources

Detection of chaotic determinism in time series from randomly forced maps.

Time series from biological system often display fluctuations in the measured variables. Much effort has been directed at determining whether this variability reflects deterministic chaos, or whether it is merely "noise". Despite this effort, it has been difficult to establish the presence of chaos in time series from biological sytems. The output from a biological system is probably the result of both its internal dynamics, and the input to the system from the surroundings. This implies that the system should be viewed as a mixed system with both stochastic and deterministic components. We present a method that appears to be useful in deciding whether determinism is present in a time series, and if this determinism has chaotic attributes, i.e., a positive characteristic exponent that leads to sensitivity to initial conditions. The method relies on fitting a nonlinear autoregressive model to the time series followed by an estimation of the characteristic exponents of the model over the observed probability distribution of states for the system. The method is tested by computer simulations, and applied to heart rate variability data.

Algorithms↗

Clinical utility of T-wave alternans.

Electrical alternans represents a variation in the morphology of electrocardiographic complexes on an every-other-beat basis in an ABABAB... pattern. Apparent electrical alternans associated with pericardial effusion results from rotation of the heart in the pericardial sac, and not true alternation in electrical conduction patterns. In contrast, true electrical alternans results from an alternation in electrical conduction patterns in the heart itself. Repolarization alternans is true electrical alternans associated with the ST segment and T wave of the electrocardiogram (ECG). Here we will focus on T-wave alternans (TWA) and its association with susceptibility to ventricular tachyarrhythmias. Electrical alternans was reported in the literature as early as 1909. Historically, electrical alternans has been regarded as a fairly rare electrocardiographic abnormality. Case reports of electrical alternans have been associated with a variety of disease states, including acute ischemia, Prinzmetal's angina, a variety of electrolyte abnormalities, and the long QT syndrome. Interestingly, patients born with the prolonged QT syndrome have a very high incidence of sudden cardiac death at an early age. Schwartz and Malliani showed that patients with the prolonged QT syndrome who do not demonstrate alternans at rest, may evidence alternans during stress such as emotional excitement. Thus, over the years electrical alternans has been associated anecdotally with conditions associated with an increased risk of ventricular arrhythmias. In 1948, Kalter reviewed the world literature on electrical alternans and found a total of 41 reported cases. In addition, he reviewed clinical ectrocardiograms from 6059 patients and found five new cases (incidence of less than 1 in 1000 patients). Interestingly, he found a very high mortality, 62%, associated with this condition. Despite the clinical associations reported in the literature, the consensus view of electrical alternans until recent years has been that alternans is an electrocardiographic curiosity rarely encountered in clinical practice which, when identified, does not have specific clinical significance.

Animals↗

Effects of age at introduction of complementary foods to breast-fed infants on duration of lactational amenorrhea in Honduran women.

Lactational amenorrhea (LA) is associated with postpartum infertility and is known to be related to breast-feeding frequency and duration, but the exact role of complementary feeding of the infant has not been clearly defined. Data on LA were collected during and after a 2-mo intervention trial in which low-income Honduran women who had breast-fed fully for 4 mo were randomly assigned to one of three groups: continued full breast-feeding until 6 mo (FBF, n = 50), introduction of complementary foods at 4 mo with ad libitum breast-feeding from 4 to 6 mo (SF, n = 47), or introduction of complementary foods at 4 mo with maintenance of baseline breast-feeding frequency from 4 to 6 mo (SF-M, n = 44). Women were followed up until the infant was 12 mo of age, or later if menses had not occurred by then. All but six of the women continued to breast-feed for > or = 12 mo. With the exclusion of those whose menses returned before 18 wk postpartum (which could not have been due to the intervention), the proportion of women who were amenorrheic at 6 mo was 64.5% in the SF group, 80.0% in the FBF group, and 85.7% in the SF-M group (chi-square test = 4.13, P = 0.02; one-tailed test with the latter two groups combined). The total duration of LA did not differ significantly among groups. The most significant determinant of LA was time spent breast-feeding (min/d), which was in turn negatively associated (P = 0.06) with the infant's energy intake from complementary foods in regression analyses. These results indicate that there is a significant effect of introducing foods at 4 mo on the likelihood of amenorrhea at 6 mo postpartum, but not thereafter, and that this effect is not seen in mothers who maintain breast-feeding frequency.

Adolescent↗

Correspondence between discrete and continuous models of excitable media: trigger waves.

We present a theoretical framework for relating continuous partial differential equation (PDE) models of excitable media to discrete cellular automata (CA) models on a randomized lattice. These relations establish a quantitative link between the CA model and the specific physical system under study. We derive expressions for the CA model's plane wave speed, critical curvature, and effective diffusion constant in terms of the model's internal parameters (the interaction radius, excitation threshold, and time step). We then equate these expressions to the corresponding quantities obtained from solution of the PDEs (for a fixed excitability). This yields a set of coupled equations with a unique solution for the required CA parameter values. Here we restrict our analysis to "trigger" wave solutions obtained in the limiting case of a two-dimensional excitable medium with no recovery processes. We tested the correspondence between our CA model and two PDE models (the FitzHugh-Nagumo medium and a medium with a "sawtooth" nonlinear reaction source) and found good agreement with the numerical solutions of the PDEs. Our results suggest that the behavior of trigger waves is actually controlled by a small number of parameters.

Animals↗

Linear and nonlinear ARMA model parameter estimation using an artificial neural network.

This paper addresses parametric system identification of linear and nonlinear dynamic systems by analysis of the input and output signals. Specifically, we investigate the relationship between estimation of the system using a feedforward neural network model and estimation of the system by use of linear and nonlinear autoregressive moving-average (ARMA) models. By utilizing a neural network model incorporating a polynomial activation function, we show the equivalence of the artificial neural network to the linear and nonlinear ARMA models. We compare the parameterization of the estimated system using the neural network and ARMA approaches by utilizing data generated by means of computer simulations. Specifically, we show that the parameters of a simulated ARMA system can be obtained from the neural network analysis of the simulated data or by conventional least squares ARMA analysis. The feasibility of applying neural networks with polynomial activation functions to the analysis of experimental data is explored by application to measurements of heart rate (HR) and instantaneous lung volume (ILV) fluctuations.

Computer Simulation↗

Prostate cancer mortality in New Zealand: the past and projections for the future.

BACKGROUND: Ageing male populations and improved diagnosis of early stage disease have contributed to the increasing incidence of prostate cancer observed in many Western countries. The clinical significance of these diagnosed cancers is, however, currently unclear. The aim of this study is to examine trends over time in prostate cancer mortality as an indicative measure of clinically significant disease during a 29-year period (1965-93) which preceded the extensive use of early cancer diagnostic techniques or radical therapy protocols. METHODS: Age-specific and age-standardized rates were calculated for each year during the study period, using routinely collected mortality and demographic data. A Poisson regression model was used to describe trends in the age-specific rates over time to predict numbers of prostate cancer deaths and the lifetime risk of death over the next 20 years. RESULTS: Significant annual increases ranging from 1 to 2.6% were found for age-specific prostate cancer mortality rates over the 29-year time period, with the largest increases experienced in the younger age groups at risk. Based on projected population ageing and growth alone, annual numbers of prostate cancer deaths are predicted to increase from 487 in 1993 to 664 by the year 2006 and then to 833 by the year 2016. Continuation of the observed increases in age-specific mortality rates would result in a predicted 797 deaths by the year 2006, while an expected 1115 deaths is calculated for the year 2016. This would correspond with an increase in the lifetime risk of death from prostate cancer from a present 3.7 to 4.5% in 10 years and 6.2% in 20 years. CONCLUSIONS: The changing pattern of prostate cancer mortality described in this study is likely to represent a significant increase in the incidence of clinically significant disease. This will have a significant impact on the ageing New Zealand male population, and important implications for the provision of effective treatment and preventive strategies.

Age Distribution↗

T wave alternans during exercise and atrial pacing in humans.

INTRODUCTION: Evidence is accumulating that microvolt T wave alternans (TWA) is a marker of increased risk for ventricular tachyarrhythmias. Initially, atrial pacing was used to elevate heart rate and elicit TWA. More recently, a noninvasive approach has been developed that elevates heart rate using exercise. METHODS AND RESULTS: In 30 consecutive patients with a history of ventricular tachyarrhythmias, the spectral method was used to detect TWA during both atrial pacing and submaximal exercise testing. The concordance rate for the presence or absence of TWA using the two measurement methods was 84%. There was a patient-specific heart rate threshold for the detection of TWA that averaged 100 +/- 14 beats/min during exercise compared with 97 +/- 9 beats/min during right atrial pacing (P = NS). Beyond this threshold, there was a significant and comparable increase in level of TWA with decreasing pacing cycle length and increasing exercise heart rates. CONCLUSIONS: The present study is the first to demonstrate that microvolt TWA can be assessed reliably and noninvasively during exercise stress. There is a patient-specific heart rate threshold beyond which TWA continues to increase with increasing heart rates. Heart rate thresholds for the onset of TWA measured during atrial pacing and exercise stress were comparable, indicating that heart rate alone appears to be the main factor of determining the onset of TWA during submaximal exercise stress.

Adult↗

Effect of low-dose scopolamine on autonomic control of the heart.

BACKGROUND: In low doses, scopolamine paradoxically enhances parasympathetic outflow to the heart. The mechanisms which mediate this action are not fully understood. Moreover, there are conflicting data regarding the potential role of sympathetic activity. This study in 17 healthy individuals was designed to characterize the influence of low dose transdermal scopolamine on the gain of the baroreflex and respiratory heart rate reflex and to determine the role of sympathetic activity. METHODS: The effect of scopolamine was analyzed in the time and frequency domain by computing heart rate variability indices. The gains of the respiratory heart rate reflex and the baroreflex were estimated simultaneously by means of a cardiovascular system identification approach using an optimized autoregressive moving average algorithm. Measurements were repeated in the upright posture to assess the influence of enhanced sympathetic activity. In six subjects ambulatory ECGs were recorded to determine whether there are diurnal variations of the effect of scopolamine. RESULTS: Scopolamine enhances vagal modulation of heart rate through both the respiratory-heart rate reflex and the baroreflex, as the gains of both were augmented by the drug in the supine and in the upright postures. CONCLUSIONS: Scopolamine increases parasympathetic cardiac control by augmenting the gain of the respiratory-heart rate and baroreflex. This action is not attenuated in the upright posture when sympathetic tone is increased.

Administration, Cutaneous↗

System identification of closed-loop cardiovascular control: effects of posture and autonomic blockade.

We applied system identification to the analysis of fluctuations in heart rate (HR), arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize quantitatively the physiological mechanisms responsible for the couplings between these variables. We characterized two autonomically mediated coupling mechanisms [the heart rate baroreflex (HR baroreflex) and respiratory sinus arrhythmia (ILV-HR)] and two mechanically mediated coupling mechanisms [the blood pressure wavelet generated with each cardiac contraction (circulatory mechanics) and the direct mechanical effects of respiration on blood pressure (ILV-->ABP)]. We evaluated the method in humans studied in the supine and standing postures under control conditions and under conditions of beta-sympathetic and parasympathetic pharmacological blockades. Combined beta-sympathetic and parasympathetic blockade abolished the autonomically mediated couplings while preserving the mechanically mediated coupling. Selective autonomic blockade and postural changes also altered the couplings in a manner consistent with known physiological mechanisms. System identification is an "inverse-modeling" technique that provides a means for creating a closed-loop model of cardiovascular regulation for an individual subject without altering the underlying physiological control mechanisms.

Adult↗

Nonlinear pattern analysis of ventricular premature beats by mutual information.

The frequency of ventricular premature beats (VPBs) has been related to the risk of mortality. However, little is known about the temporal pattern of occurrence of VPBs and its relationship to autonomic activity. Hence, we applied a general correlation measure, mutual information, to quantify how VPBs are generated over time. We also used mutual information to determine the correlation between VPB production and heart rate in order to evaluate effects of autonomic activity on VPB production. We examined twenty subjects with more than 3000 VPBs/day and simulated random time series of VPB occurrence. We found that mutual information values could be used to characterize quantitatively the temporal patterns of VPB generation. Our data suggest that VPB production is not random and VPBs generated with a higher value of mutual information may be more greatly affected by autonomic activity.

Adult↗

Detection of "noisy" chaos in a time series.

Time series from biological system often displays fluctuations in the measured variables. Much effort has been directed at determining whether this variability reflects deterministic chaos, or whether it is merely "noise". The output from most biological systems is probably the result of both the internal dynamics of the systems, and the input to the system from the surroundings. This implies that the system should be viewed as a mixed system with both stochastic and deterministic components. We present a method that appears to be useful in deciding whether determinism is present in a time series, and if this determinism has chaotic attributes. The method relies on fitting a nonlinear autoregressive model to the time series followed by an estimation of the characteristic exponents of the model over the observed probability distribution of states for the system. The method is tested by computer simulations, and applied to heart rate variability data.

Algorithms↗

Power law behavior of RR-interval variability in healthy middle-aged persons, patients with recent acute myocardial infarction, and patients with heart transplants.

BACKGROUND: The purposes of the present study were (1) to establish normal values for the regression of log(power) on log(frequency) for, RR-interval fluctuations in healthy middle-aged persons, (2) to determine the effects of myocardial infarction on the regression of log(power) on log(frequency), (3) to determine the effect of cardiac denervation on the regression of log(power) on log(frequency), and (4) to assess the ability of power law regression parameters to predict death after myocardial infarction. METHODS AND RESULTS: We studied three groups: (1) 715 patients with recent myocardial infarction; (2) 274 healthy persons age and sex matched to the infarct sample; and (3) 19 patients with heart transplants. Twenty-four-hour RR-interval power spectra were computed using fast Fourier transforms and log(power) was regressed on log(frequency) between 10(-4) and 10(-2) Hz. There was a power law relation between log(power) and log(frequency). That is, the function described a descending straight line that had a slope of approximately -1 in healthy subjects. For the myocardial infarction group, the regression line for log(power) on log(frequency) was shifted downward and had a steeper negative slope (-1.15). The transplant (denervated) group showed a larger downward shift in the regression line and a much steeper negative slope (-2.08). The correlation between traditional power spectral bands and slope was weak, and that with log(power) at 10(-4) Hz was only moderate. Slope and log(power) at 10(-4) Hz were used to predict mortality and were compared with the predictive value of traditional power spectral bands. Slope and log(power) at 10(-4) Hz were excellent predictors of all-cause mortality or arrhythmic death. To optimize the prediction of death, we calculated a log(power) intercept that was uncorrelated with the slope of the power law regression line. We found that the combination of slope and zero-correlation log(power) was an outstanding predictor, with a relative risk of > 10, and was better than any combination of the traditional power spectral bands. The combination of slope and log(power) at 10(-4) Hz also was an excellent predictor of death after myocardial infarction. CONCLUSIONS: Myocardial infarction or denervation of the heart causes a steeper slope and decreased height of the power law regression relation between log(power) and log(frequency) of RR-interval fluctuations. Individually and, especially, combined, the power law regression parameters are excellent predictors of death of any cause or arrhythmic death and predict these outcomes better than the traditional power spectral bands.

Adult↗

Exercise recordings for the detection of T wave alternans. Promises and pitfalls.

Despite significant advances in the treatment of sudden cardiac death, many individuals still go untreated because routine clinical tests do not identify them to be at risk. Recently, a study to identify individuals at risk has shown that the presence of T wave alternans (TWA), a fluctuation in T wave morphology occurring on an every-other-beat basis, is an accurate predictor of subsequent ventricular tachyarrhythmic events. T wave alternans as low as a few microvolts was found to be significant in predicting risk. Since TWA is often detectable only at elevated heart rates, the study used atrial pacing to increase the heart rate to approximately 100 beats/min. To make TWA measurement more broadly applicable, the authors have developed a methodology that uses noninvasive physiologic stress to raise the heart rate. A particular challenge was the measurement of TWA during exercise, since the levels of noise during exercise can far exceed the levels of TWA. However, by using special multisegment Hi-Res electrodes (Cambridge Heart, Bedford, MA), noise reduction software, and a spectral method of alternans analysis, the authors have been able to reduce noise and reliably measure microvolt-level alternans. This study presents an overview of the methodology for recording and analyzing microvolt-level TWA during ergometer exercise.

Adolescent↗

Assessment of invasive growth pattern and lymphocytic infiltration in colorectal cancer.

A total of 122 specimens of colorectal cancer were re-assessed in relation to the reporting of invasive growth pattern (expanding vs. infiltrating) and presence or absence of peritumoral lymphocytic infiltrate as used in the Jass prognostic classification. Jass agreed with 69% of cases reported as infiltrating and 90% of reported as expanding. This parameter was distributed similarly amongst Dukes B and C cases in the original assessment (P = 0.27), whereas in the reviewed data infiltrating cases were more likely to be staged as Dukes C (P = 0.04). Jass agreed with 44% of lymphocyte present and 94% of lymphocyte absent assessments. The original lymphocyte assessments showed no significant differences in distribution between Dukes A and B cases (P = 0.12) or B and C cases (P = 0.75), whereas the reviewed data showed significant differences for A vs. B (P = 0.015) and B vs. C cases (P = 0.0025). Criteria for assessment were circulated to eight observers who revisited 20 of the cases in which there was disagreement. Consensus agreement with Jass was achieved in nine of 10 cases for invasive growth pattern and seven of 10 cases for lymphocyte infiltration (with two being evenly split). Most observers showed at least fair levels of agreement with Jass and some achieved excellent levels of agreement. This study indicates that assessment of criteria used in the Jass prognostic system for colorectal cancer is less than optimal in routine practice, but is improved through the provision of simple guidelines.

Colorectal Neoplasms↗

Prostatic adenocarcinoma labelled with a monoclonal antibody and polyclonal serum: a quantitative assessment.

OBJECTIVE: To investigate the detection of tissue prostate-specific antigen (PSA) using a monoclonal antibody or polyclonal serum in patients with localized prostate cancer. PATIENTS AND METHODS: Fifteen samples of prostatic tissue from patients with localized prostate cancer were assessed for PSA using monoclonal antibodies and polyclonal serum. The intensity and area of chromogen precipitation in several microscopic fields was determined using image analysis. RESULTS: There were significant differences in the intensity and distribution of PSA labelling in the tumour between the methods; polyclonal serum was more sensitive in detecting PSA in tissue sections. Notably, there was a focal "possible clonal' pattern of negative labelling with the monoclonal antibody, which contrasted with the positivity of the polyclonal marker. CONCLUSIONS: The loss of PSA expression in some poorly differentiated cancers may represent the loss of specific epitopes rather than loss of the entire protein.

Adenocarcinoma↗

Development of collagenous colitis in a cecoplasty of a patient with interstitial cystitis.

We present the case of a 45-yr-old female patient with a 23 yr history of interstitial cystitis that multiple surgical procedures, including a ceco-cystoplasty, were unable to cure. After a cystectomy was performed, histological examination of the bladder showed the development of collagenous colitis. Although the etiology of both interstitial cystitis and collagenous colitis is unknown, this report postulates an association between these two conditions.

Colectomy↗

An efficient approach to ARMA modeling of biological systems with multiple inputs and delays.

This paper presents a new approach to AutoRegressive Moving Average (ARMA or ARX) modeling which automatically seeks the best model order to represent investigated linear, time invariant systems using their input/output data. The algorithm seeks the ARMA parameterization which accounts for variability in the output of the system due to input activity and contains the fewest number of parameters required to do so. The unique characteristics of the proposed system identification algorithm are its simplicity and efficiency in handling systems with delays and multiple inputs. We present results of applying the algorithm to simulated data and experimental biological data In addition, a technique for assessing the error associated with the impulse responses calculated from estimated ARMA parameterizations is presented. The mapping from ARMA coefficients to impulse response estimates is nonlinear, which complicates any effort to construct confidence bounds for the obtained impulse responses. Here a method for obtaining a linearization of this mapping is derived, which leads to a simple procedure to approximate the confidence bounds.

Algorithms↗