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R J Cohen

Publications and source records attributed to R J Cohen.

At least 91 records · Page 5Linked to original sources
PubMed1996

A dual-input nonlinear system analysis of autonomic modulation of heart rate.

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

Adult↗
PubMed1996

Predicting sudden cardiac death from T wave alternans of the surface electrocardiogram: promise and pitfalls.

Sudden cardiac death remains a preeminent public health problem. Despite advances in preventative treatment for patients known to be at risk, to date we have been able to identify, and thus treat, only a small minority of these patients. Therefore, there is a major need to develop noninvasive diagnostic technologies to identify patients at risk. Recent studies have demonstrated that measurement of microvolt-level T wave alternans is a promising technique for the accurate identification of patients at risk for ventricular arrhythmias and sudden cardiac death. In this article, we review the clinical data establishing the relationship between microvolt T wave alternans and susceptibility to ventricular arrhythmias. We also review the methods and technology that have been developed to measure microvolt levels of T wave alternans noninvasively in broad populations of ambulatory patients. In particular, we examine techniques that permit the accurate measurement of T wave alternans during exercise stress testing.

Artifacts↗
PubMed1996

Changes in autonomic activity preceding onset of nonsustained ventricular tachycardia.

BACKGROUND: The triggering role of the autonomic nervous system in the initiation of ventricular tachycardia has not been established. To investigate the relationship between changes in autonomic activity and the occurrence of nonsustained ventricular tachycardia (NSVT) we examined heart rate variability (HRV) during the 2-hour period preceding spontaneous episodes of NSVT. Twenty-four subjects were identified retrospectively as having had one episode of NSVT during 24-hour Holter ECC recording. METHODS: We measured the mean interval between normal heats (meanRR), the standard deviation of the intervals between beats (SD), the percentage of counts of sequential intervals between normal beats with a change of >50 ms (%RR50), the logarithms of low- and high-frequency spectral components (lnLF, lnHF) of HRV for sequential 10-minute segments preceding NSVT. The correlation dimension (CDim) of HRV was calculated similarly for sequential 20-minute segments. We assessed the significance of the time-course change of each marker over the 120-minute period prior to NSVT onset. RESULTS: MeanRR (P < 0.05), lnLF (P < 0.0001), lnHF (P < 0.0001), the natural logarithm of the ratio of LF to HF (ln[LF/HF]; P < 0.05), and CDim (P < 0.05) showed significant time-course changes during that period, while SD and %RR50 did not. MeanRR, lnLF, lnHF, and CDim all decreased prior to the onset of NSVT, whereas ln(LF/HF) increased. We divided the subjects into two groups: one consisting of 12 patients with coronary artery disease; and the second group of 12 patients without known coronary artery disease. Both groups showed significant changes (P < 0.05) of CDim, lnLF, and lnHF preceding the episodes of NSVT. CONCLUSIONS: Changes in the pattern of HRV prior to the onset of episodes of NSVT suggest that changes in autonomic activity may commonly play a role in the triggering of spontaneous episodes of NSVT in susceptible patients. The measured changes suggest a reduction in parasympathetic activity, perhaps in conjunction with an increase in sympathetic activity, may trigger NSVT.

Adult↗
PubMed1996

Elevation of cGMP with normal expression and activity of rod cGMP-PDE in photoreceptor degenerate labrador retrievers.

Cyclic guanosine 3',5'-monophosphate (cGMP) levels were determined in retinas from a strain of Labrador Retrievers with inherited retinal dystrophy manifesting at early stages of retinal differentiation. The cGMP contents of dystrophic retinas of dogs from 1 to 4 months of age (n = 7) were significantly higher (p = 0.001) than in age-matched controls of the same breed (n = 11). Ultrastructure along the vertical retinal meridian was studied in developing retinas and findings were related to those of age-matched wild-type controls of the same breed. Slow central to peripheral progression of degeneration was observed in affected dogs. No differences were found in total cGMP-phosphodiesterase (PDE) activity, in PDE subunit composition as determined by Western blotting of 2-month-old homozygote affected retinas, or in the amino acid sequence deduced from the nucleotide sequence of the PDE beta-subunit as compared to controls. This model of photoreceptor degeneration thus is the first case of an apparent abnormality of cGMP metabolism that is not associated with a defect in the PDE catalytic subunits, and it is also the first reported model not associated with severe developmental abnormalities and rapid degeneration.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1996

Do exclusively breast-fed infants require extra protein?

It has been argued that the growth rate of exclusively breast-fed infants may be limited by their protein intake. This issue was examined using data from an intervention study in Honduras in which infants were randomly assigned to be exclusively breast-fed for the first 6 mo (EBF; n = 50), or to receive preprepared solid foods (including egg yolk) in addition to breast milk beginning at 4 mo (n = 91). Neither weight gain nor length gain from 4 to 6 mo differed between groups despite a 20% higher protein intake (as well as significantly higher intakes of iron, zinc, calcium, vitamin A, and riboflavine) in the latter group. The 20 infants with the highest protein intakes in that group were matched to 20 EBF infants on the basis of energy intake; protein intake was 1.46 +/- 0.09 versus 1.10 +/- 0.17 g/kg/d, respectively (p < 0.001), but growth rate did not differ between groups. Similarly, the 20 infants with the lowest protein intakes in the EBF group were matched (by energy intake) to 20 infants given solid foods; protein intake was very low in the former compared with the latter (0.81 +/- 0.13 versus 1.04 +/- 0.20 g/kg/d; p < 0.001), yet there was still no difference in growth. Infant morbidity was relatively low and did not influence the results. These analyses indicate that protein intake is not likely to be a limiting factor with regard to growth of breast-fed infants from 4 to 6 mo of age.

Body Height↗
PubMed1995

The law of mass action governs antigen-stimulated cytolytic activity of CD8+ cytotoxic T lymphocytes.

An analysis of the initial antigen-recognition step in the destruction of target cells by CD8+ cytolytic T lymphocytes (CTLs) shows that a relationship in the form of the law of mass action can be used to describe interactions between antigen-specific receptors on T cells (TCRs) and their natural ligands on target cells (peptide-major histocompatibility protein complexes, termed pepMHC complexes), even though these reactants are confined to their respective cell membranes. For a designated level of lysis and receptor affinities below about 5 X 10(6) M-1, the product of the required number of pepMHC complexes per target cell ("epitope density") and TCR affinity for pepMHC complexes is constant; therefore, over this range TCR affinities can be predicted from epitope densities (or vice versa). At higher receptor affinities ("affinity ceiling") the epitope density required for half-maximal lysis reaches a lower limit of less than 10 complexes per target cell.

Amino Acid Sequence↗
PubMed1995

Transfer function analysis of respiratory sinus arrhythmia: a measure of autonomic function in diabetic neuropathy.

Standard techniques measuring heart rate (HR) variability do not account for its dependence on the rate and depth of respiration or measure the time relationship between changes in lung volume and HR. We used transfer function analysis to determine the magnitude and time relationship of the HR response to a known change in lung volume in controls and diabetics. This technique demonstrated significant differences between controls and diabetics with varying degrees of autonomic dysfunction. Specifically, reduced supine vagal and increased supine sympathetic HR modulation was found with progression of the autonomic neuropathy. In response to postural change the normal diabetics displayed impaired sympathetic HR modulation. Transfer function analysis yields new insight into the sequence of changes that occur with diabetic autonomic neuropathy and provides an accurate, easily comprehensible measurement of respiratory induced HR variability.

Adult↗
PubMed1995

Maternal activity budgets: feasibility of exclusive breastfeeding for six months among urban women in Honduras.

Although exclusive breastfeeding for 6 months is likely to be beneficial for infant health, mothers often cite time pressures as a reason to introduce other foods. Using 12-hr in-home observations at 19 and 24 wk postpartum, we compared maternal activity budgets and time spent breastfeeding among low-income, urban mothers not employed outside the home who exclusively breastfed (EBF) or gave other foods in addition to breast milk (BF+SF). Breastfeeding time was similar between groups (averaging approx 75 min/12 hr) except that multiparous EBF mothers at 24 wk spent more time breastfeeding their infants than did BF+SF mothers. However, total time devoted to infant feeding (including preparation and feeding of solids in the BF+SF group) was significantly greater in the BF+SF group than in the EBF group (except among multiparous women at 24 wk). Feeding frequency per 12-hr averaged 6.7-8.9 in the EBF group and 5.4-8.1 BF + 1.8 meals in the BF+SF group. Both EBF and BF+SF mothers had considerable 'free' time; they spent, on average, 2-3 hr during each 12-hr period resting, chatting or watching TV. Primiparous women tended to spend less time at household chores and child care than multiparous women. Of the BF+SF mothers, 60% said that breastfeeding was 'somewhat' or 'very' time-demanding (vs 15% of EBF mothers), 49% said that it interfered with other activities (vs 6% of EBF mothers), and 26% said that they gave other foods to extend the time between breastfeeds. Although many of the BF+SF mothers knew that giving foods may increase infant illness, there were cultural pressures not to exclusively breastfeed. For example, many introduced solids to their infants prior to 6 months because they believed that infants should 'learn' how to eat other foods, to 'acclimate' the stomach and learn to differentiate flavors. We conclude that time constraints are not a barrier to exclusive breastfeeding in this population, although they may be perceived as a barrier.

Activities of Daily Living↗
PubMed1995

Immunohistochemical detection of oncogene proteins and neuroendocrine differentiation in different stages of prostate cancer.

The progression of prostatic adenocarcinoma from localized disease to metastatic carcinoma appears to be a multi-step sequence. The expression of common oncogenes/oncosuppressor genes and the mediating effect of neuroendocrine tumor cells may play a role in this progression. The expression of the more frequently investigated oncogenes/oncosuppressor genes (p53, c-myc, c-erbB-2, bcl-2) and the presence of neuroendocrine cells were assessed in prostatic cancer tissue from patients with localized and metastatic cancer. These oncogenes/oncosuppressor genes were evaluated according to tumor stage and grade and their relationship to one another. Grade was not related to any of the oncogene markers or to the presence of neuroendocrine cells. Advancing stage was associated with a significant increase in p53 expression, while other markers remained constant in all stages. Neuroendocrine cells, p53, c-myc, c-erbB-2 and bcl-2 were rarely co-expressed at any stage of prostate cancer.

Carcinoma↗
PubMed1995

Schistosomiasis and prostate cancer.

In endemic geographical areas schistosomiasis has been implicated as an etiological agent in the pathogenesis of bladder, colorectal and renal carcinoma. In particular bladder cancer commonly occurs in such geographic locations almost 2 decades earlier than in non-endemic areas. A relationship between prostate cancer and bilharzial infestation is not established. This is a report of 3 cases of co-existent schistosomiasis and prostatic adenocarcinoma occurring in unusually young patients.

Adenocarcinoma↗
PubMed1995

Maternal anthropometric status and lactation performance in a low-income Honduran population: evidence for the role of infants.

As part of a study on the optimal timing of complementary feeding in Honduras, we assessed breast milk volume and composition at 4, 5, and 6 mo in 141 low-income women who were randomly assigned to exclusively breast-feed for the first 6 mo or to complement breast milk with prepared solid foods beginning at 4 mo. Milk volume averaged 797 +/- 139 g/d at 4 mo. Maternal body mass index was positively associated with infant birth weight and milk energy density. In multivariate analyses in which group assignment was controlled for, milk volume was positively associated with birth weight but negatively associated with milk energy density. Infant breast milk energy intake was positively associated with birth weight and milk energy density. Maternal anthropometric status was not a significant predictor of milk volume or infant energy intake when birth weight and milk energy density were included in the models. These results indicate that infant characteristics, such as birth weight and the ability to self-regulate intake in response to milk energy density, mediate the relationship between maternal anthropometric status and lactation performance.

Anthropometry↗
PubMed1995

Delaying the introduction of complementary food until 6 months does not affect appetite or mother's report of food acceptance of breast-fed infants from 6 to 12 months in a low income, Honduran population.

Low income, primiparous mothers who had exclusively breast-fed for 4 mo were randomly assigned to one of three groups: 1) continued exclusive breast-feeding to 6 mo (EBF), 2) introduction of complementary foods at 4 mo, with ad libitum nursing 4-6 mo (SF), and 3) introduction of complementary foods at 4 mo, with maintenance of base-line nursing frequency 4-6 mo (SF-M). After the intervention phase (4-6 mo; n= 141), home visits were conducted for a subsample at 9 (n = 60) and 12 (n = 123) mo. At each visit, an observer recorded infant food intake at the midday meal and interviewed the mother regarding usual feeding patterns and the infant's acceptance of 20 common food items. All but two infants (1.5%) were breast-fed to 9 mo and all but eight (6%) to 12 mo. There were no significant differences among groups in breast-feeding frequency, amount or number of foods consumed at the midday meal, percentage of food offered that was consumed, usual daily number of meals and snacks, number of food groups consumed, or overall food acceptance score. Frequency of consumption of foods from eight different food groups (dairy, meats, eggs, grains, beans, fruits, vegetables, tubers) was not significantly different among groups except that, at 9 mo only, the SF group (but not the SF-M group) consumed more vegetables than did the EBF group. These results indicate that delaying the introduction of complementary foods until 6 mo does not adversely affect appetite or food acceptance among breast-fed infants.

Adolescent↗
PubMed1995

An equivalent body surface charge model representing three-dimensional bioelectrical activity.

A new surface-source model has been developed to account for the bioelectrical potential on the body surface. A single-layer surface-charge model on the body surface has been developed to equivalently represent bioelectrical sources inside the body. The boundary conditions on the body surface are discussed in relation to the surface-charge in a half-space conductive medium. The equivalent body surface-charge is shown to be proportional to the normal component of the electric field on the body surface just outside the body. The spatial resolution of the equivalent surface-charge distribution appears intermediate between those of the body surface potential distribution and the body surface Laplacian distribution. An analytic relationship between the equivalent surface-charge and the surface Laplacian of the potential was found for a half-space conductive medium. The effects of finite spatial sampling and noise on the reconstruction of the equivalent surface-charge were evaluated by computer simulations. It was found through computer simulations that the reconstruction of the equivalent body surface-charge from the body surface Laplacian distribution is very stable against noise and finite spatial sampling. The present results suggest that the equivalent body surface-charge model may provide an additional insight to our understanding of bioelectric phenomena.

Body Surface Potential Mapping↗
PubMed1995

Kinetics of cycle length dependence of ventricular repolarization: effect of autonomic blockade.

INTRODUCTION: Beat-to-beat adaptation of ventricular repolarization duration to cardiac cycle length and autonomic activity has not been previously characterized in the spontaneously beating human heart. METHODS AND RESULTS: The ECG of 14 healthy subjects was recorded from the supine and upright positions. Autonomic blockade was accomplished by atropine and propranolol. RR and RT intervals were measured by a computer algorithm, and the impulse response (h) from RR to RT computed. In the supine position the maximal adjustment of the RT interval occurred in the first beat following a change in cycle length (hpeak = 17.8 +/- 1.6 msec/sec), but continued to be detectable for 3.8 seconds (2.9-4.7 sec). Propranolol attenuated the peak impulse response to 15.8 +/- 4.0 msec/sec (P = NS). In the standing position the peak impulse response was increased to 25.2 +/- 5.0 msec/sec (P = 0.004 vs supine), and the impulse response duration (hdur) shortened to 1.4 seconds (1.3-1.6). This was reversed by beta blockade (hpeak = 10.7 +/- 3.6 [P = 0.005 vs standing]; hdur = 5.5 sec [4.8-6.1]). Parasympathetic and combined autonomic blockade resulted in too little residual heart rate variability to estimate the impulse response accurately. The slope of the regression of delta RT and delta RR in the supine position was 0.0177 +/- 0.0016, which was closely correlated with the peak impulse response (r = 0.91). CONCLUSIONS: System identification techniques can assist in characterizing the cycle dependence of ventricular repolarization and may provide new insights into conditions associated with abnormal repolarization.

Adult↗
PubMed1995

Colonic cell proliferation in two different ethnic groups with contrasting incidence of colon cancer: is there a difference in carcinogenesis?

Most studies on colorectal carcinogenesis suggest a field defect, preceding overt development of cancer. The low incidence of adenomatous polyps in the African population, however, suggests that there may be an alternative route for cancer development. The aim of the study was to discover if the difference in incidence of colorectal cancer in Africans compared with the white population is reflected in a different pattern of cell proliferation. Histological normal mucosa from 30 patients (15 white South African (W), 15 South African Africans (A)) with confirmed colon cancer were examined. Proliferating cells were detected using the Ki-67 antigen. In addition, cell proliferation data were obtained, from 30 age matched controls (15 Africans, 15 white South Africans), without colorectal disease. The African controls were significantly younger (mean (SD) (A: 42 (20), W: 66 (13), p < 0.05)) than the white controls. The second control group had a significantly higher mean (SD) total labelling index (W: 11 (3), A: 6 (4), p < 0.05). In addition the proliferative pattern of the white group without evidence of colorectal cancer showed a comparatively large amount of dividing cells in compartment 2, compared with African controls (mean (SD) (W: 21 (8), A: 9 (8), p < 0.05)). Mucosa from Africans with cancer showed a proliferative pattern with the same increased total labelling index (A: 15 (5), W: 16 (6), p = NS, phase II proliferative lesion) and an even more pronounced upward expansion (phase I proliferative lesion) compared with white cancer patients. This suggests that the mechanism of colorectal carcinogenesis is similar in Africans and the white population. The lack of clinical evidence of the adenoma-carcinoma sequence, and the incidence of cancer at a comparatively young age in Africans may be explained by the fact that colorectal cancer in this ethnic group behaves more aggressively and that adenomatous polyps are rapidly converted into overt cancer before detection.

Adenoma↗
PubMed1995

Respiratory sinus arrhythmia: time domain characterization using autoregressive moving average analysis.

Fourier-based techniques are mathematically noncausal and are therefore limited in their application to feedback-containing systems, such as the cardiovascular system. In this study, a mathematically causal time domain technique, autoregressive moving average (ARMA) analysis, was used to parameterize the relations of respiration and arterial blood pressure to heart rate in eight humans before and during total cardiac autonomic blockade. Impulse-response curves thus generated showed the relation of respiration to heart rate to be characterized by an immediate increase in heart rate of 9.1 +/- 1.8 beats.min-1.l-1, followed by a transient mild decrease in heart rate to -1.2 +/- 0.5 beats.min-1.l-1 below baseline. The relation of blood pressure to heart rate was characterized by a slower decrease in heart rate of -0.5 +/- 0.1 beats.min-1.mmHg-1, followed by a gradual return to baseline. Both of these relations nearly disappeared after autonomic blockade, indicating autonomic mediation. Maximum values obtained from the respiration to heart rate impulse responses were also well correlated with frequency domain measures of high-frequency "vagal" heart rate control (r = 0.88). ARMA analysis may be useful as a time domain representation of autonomic heart rate control for cardiovascular modeling.

Adult↗