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Biomedical subjects

R J Cohen

Publications and source records attributed to R J Cohen.

At least 19 recordsLinked to original sources
PubMed1999

Age of introduction of complementary foods and growth of term, low-birth-weight, breast-fed infants: a randomized intervention study in Honduras.

BACKGROUND: The optimal age at which to introduce complementary foods is a topic of considerable debate. OBJECTIVE: This study was designed to evaluate this issue in a nutritionally vulnerable population in Honduras. DESIGN: Mothers of low-birth-weight (1500-2500 g) term (ie, small-for-gestational-age) infants were recruited in the hospital and assisted with exclusive breast-feeding during the first 4 mo. At 4 mo, mothers were randomly assigned to either continue exclusive breast-feeding to 6 mo (EBF; n = 59) or to feed complementary solid foods (jarred rice cereal, chicken, and fruit and vegetables) twice daily from 4 to 6 mo while continuing to breast-feed at their initial frequency (SF; n = 60). At 4 and 6 mo, breast milk and total energy intake were measured for a nonrandom subsample (those who could stay overnight in a central unit: 32 EBF and 31 SF). RESULTS: At 4 mo, breast milk intake in the subsample was not significantly different between groups (EBF: 729 +/- 135 g/d; SF: 683 +/- 151 g/d: P >0.2); from 4 to 6 mo it increased (by 28 g/d) in the EBF group but decreased (by 39 g/d) in the SF group (P < 0.005). Nonetheless, total energy intake (including solid foods) increased more from 4 to 6 mo in the SF than in the EBF group. However, there were no significant differences between groups in weight or length gain during the intervention or subsequently (6-12 mo). CONCLUSION: There was no growth advantage of complementary feeding of small-for-gestational-age, breast-fed infants between 4 and 6 mo of age.

Adult↗
PubMed1999

Precision, accuracy, and reliability of hemoglobin assessment with use of capillary blood.

BACKGROUND: Previous research has suggested that there may be significant within-subject variability, both site-to-site and over time, in hemoglobin concentrations in capillary blood. OBJECTIVE: This study examined the reliability of the portable hemoglobinometer (PHM) system with use of capillary blood and the implications of errors of the magnitude found for the classification of anemia status in individuals and population groups. The precision and accuracy of the method with use of venous blood were also tested. DESIGN: Three empirical data sets were used to measure reliability, precision, and accuracy of the PHM system [2 from Honduras (n = 87 and 141); 1 from Bangladesh (n = 73)]. Simulation data were used to assess the implications of errors for screening individuals for anemia and to estimate anemia prevalence. RESULTS: High within-subject variability (unreliability) was identified when capillary blood from the left hand was compared with that from the right hand (CV: 6.3%) and when measurements were taken on 4 consecutive days (CV: 7.0%). Reliability was only 69% and 50%, respectively. Precision and accuracy, however, were very high (concordance coefficients of 0.99 and 0.98 and CV < 1%). CONCLUSIONS: The simulation data showed that errors of the magnitude found due to unreliability can lead to misclassification of anemia status in individuals and small biases in anemia prevalence estimates. We recommend replicate sampling to reduce the influence of unreliability in the use of the PHM system with capillary blood.

Adolescent↗
PubMed1999

Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies.

The objective of this study was to establish a three-dimensional (3-D) in vitro model system of cardiac muscle for electrophysiological studies. Primary neonatal rat ventricular cells containing lower or higher fractions of cardiac myocytes were cultured on polymeric scaffolds in bioreactors to form regular or enriched cardiac muscle constructs, respectively. After 1 wk, all constructs contained a peripheral tissue-like region (50-70 micrometer thick) in which differentiated cardiac myocytes were organized in multiple layers in a 3-D configuration. Indexes of cell size (protein/DNA) and metabolic activity (tetrazolium conversion/DNA) were similar for constructs and neonatal rat ventricles. Electrophysiological studies conducted using a linear array of extracellular electrodes showed that the peripheral region of constructs exhibited relatively homogeneous electrical properties and sustained macroscopically continuous impulse propagation on a centimeter-size scale. Electrophysiological properties of enriched constructs were superior to those of regular constructs but inferior to those of native ventricles. These results demonstrate that 3-D cardiac muscle constructs can be engineered with cardiac-specific structural and electrophysiological properties and used for in vitro impulse propagation studies.

Aging↗
PubMed1999

System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy.

We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.

Adult↗
PubMed1998

Characterization of cytoplasmic secretory granules (PSG), in prostatic epithelium and their transformation-induced loss in dysplasia and adenocarcinoma.

Cytoplasmic clarity is a histological feature of normal prostatic secretory cells, but in this study, tissue fixation in strong (>2.5%) glutaraldehyde dramatically altered cytological staining. Secretory cytoplasm appeared red and granular on routine stains because of myriad intensely staining eosinophilic granules (PSG). Immunostaining for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) showed their exclusive localization to the PSG. Electron microscopy confirmed these findings and also showed that after fixation in many agents, including formaldehyde, PSG appeared empty, accounting for the artefactual "clear cell" appearance on light microscopy. PSG were most densely concentrated apically in a bud-shaped luminal compartment in which cytokeratin was selectively absent. Normal exocrine secretion was visualized as detachment of apocrine buds or their in situ disintegration. Distinctively in dysplasia and almost all carcinomas, PSG were rare to absent, and proteases were free in the cytoplasm, often concentrated beneath the apical membrane. The apocrine compartment was absent, with no observed secretory mechanism. Tumor cells had dark amphiphilic cytoplasm after all fixatives. This provided a reliable method of distinguishing malignant from benign glands in tissues fixed in strong glutaraldehyde. Clear cell carcinomas, whose cytoplasm mimicked routinely fixed normal secretory cells, surprisingly had almost no PSG. Instead, their "granules" were lipid-filled vacuoles reflecting a secretory pathway not seen in normal cells, dysplasia, or the common "dark cell" carcinomas. These observations may define two distinctive biological pathways of prostate cancer evolution and may facilitate diagnostic decisions on needle biopsy samples.

Acid Phosphatase↗
PubMed1998

Prediction of pathological stage and clinical outcome in prostate cancer: an improved pre-operative model incorporating biopsy-determined intraductal carcinoma.

OBJECTIVE: To relate the predictive value of serum prostate specific antigen (PSA) levels, histological grade and intraductal carcinoma (IDC-P, a possible marker of poor prognosis) to pathological stage and subsequent clinical outcome, and thus derive an improved predictive model to aid the decision to initiate potentially curative therapy in localized prostate cancer. MATERIALS AND METHODS: Fifty-nine radical prostatectomy specimens were histologically graded, allocated a pathological stage and the tumour volume determined by image analysis. Pre-operative (needle biopsy) tumour grade, the presence or absence of IDC-P, and serum PSA levels were correlated with the pathological stage. This was used to define the sequence and values that would be incorporated into a predictive model for pathological stage and clinical outcome. RESULTS: There were close correlations between cancer volume and tumour grade (P = 0.004) and between cancer volume and serum PSA level (P = 0.003). However, in tumours with IDC-P, serum PSA level did not correlate with tumour volume of IDC-P (P > 0.9). IDC-P was an independent variable that significantly improved the prediction of pathological stage and tumour volume, and furthermore, was closely related to (r = 0.53, P = 0.001) and accurately predicted treatment failure. CONCLUSION: The model which best predicted pathological stage and clinical outcome involved first identifying those cancers with IDC-P as having the poorest outcome. Cancers without IDC-P were then separated into low- and high-risk groups on the basis of serum PSA levels below and above 10 ng/mL, and those in the high-risk group further stratified using Gleason grading. Furthermore, the use of a sequential consideration of pre-operative variables including IDC-P allowed cases to be grouped which, after radical surgery, closely correlated with clinical outcome.

Biopsy, Needle↗
PubMed1998

Intraductal carcinoma of the prostate metastatic to the penile urethra: a rare demonstration of two morphologic patterns of tumor growth.

Penile metastases from prostate cancer are rare and are usually a manifestation of wide-spread cancer dissemination. Isolated urethral metastases form a small fraction of these cases, have a longer survival rate and may represent spread by implantation following instrumentation. We report a case of prostatic carcinoma presenting with an isolated metastasis to the penile urethra after catheterisation and transurethral prostatectomy. The primary tumor had a prominent intraductal component whose architectural features were mimicked in the metastasis. The possible mechanisms of spread and the diverse appearances of cancer associated with an intraductal component are discussed.

Aged↗
PubMed1998

Effects of age of introduction of complementary foods on iron status of breast-fed infants in Honduras.

To evaluate the effect of introducing complementary foods before 6 mo of age, we randomly assigned 164 infants who had been exclusively breast-fed for 4 mo to continue being exclusively breast-fed until 6 mo (EBF group) or to receive iron-fortified foods in addition to breast milk from 4 to 6 mo (BF+SF group). At 6 mo, the BF+SF group had higher mean iron intake (4 mg/d compared with 0.2 mg/d in EBF infants) and higher hemoglobin, hematocrit, and ferritin values than the EBF group (P < 0.05). The percentage with low hemoglobin (< 103 g/L) did not differ significantly between groups, but fewer infants in the BF+SF group had a low hematocrit (< 0.33; 21.4% compared with 32.0%, respectively; P < 0.05). The percentage of infants with ferritin concentrations < 12 microg/L at 6 mo was lower than the percentage with low hemoglobin or hematocrit, raising questions about the validity of the cutoffs at this age. Infants at greatest risk for anemia and low ferritin were those with birth weights < 2500 g; no infant with a birth weight > 3000 g had a low ferritin value at 6 mo. We conclude that the risk of iron deficiency is low among infants with birth weights > 3000 g who are exclusively breast-fed for 6 mo. Iron drops are recommended for low-birth-weight infants; for breast-fed infants with birth weights between 2500 and 3000 g, further research is needed to determine whether iron drops are more effective than complementary foods for preventing iron deficiency before 6 mo.

Age Factors↗
PubMed1998

Effect of the Advanced Trauma Life Support program on medical students' performance in simulated trauma patient management.

BACKGROUND: Part of the senior medical students' examination at the University of Toronto involves testing with simulated patient management. We compared the performance in these simulations of senior medical students who received Advanced Trauma Life Support (ATLS) training with those who did not receive ATLS training. METHODS: Thirty-two students (group I) completed a standard ATLS course, 12 students (group II) audited the ATLS course, and their performance in the trauma simulations was compared with 44 matched control students (group III) from the same class. Performance in the nontrauma patient simulation stations was also analyzed. The score on each station was standardized to a maximum of 20. The students were also graded on overall Approach (scale of 1 to 5) and pass status. RESULTS: The mean scores (+/-SD, *p < 0.05 compared with other groups) were as follows: Trauma Station, 17.5 +/- 1.02* for group I, 11.76 +/- 0.72* for group II, and 14.67 +/- 0.54* for group III; Nontrauma Station, 13.05 +/- 0.95 for group I, 12.25 +/- 0.72 for group II, and 11.88 +/- 0.80 for group III; Approach, 4.45 +/- 0.50* for group I, 2.09 +/- 0.60* for group II, 3.50 +/- 0.67* for group III. The ATLS-trained and ATLS-audit students had higher scores in the trauma stations than the control group, with the highest scores being in the ATLS-trained group. All ATLS-trained students passed with 62.5% honors and 37.5% passing grades. The ATLS-audit group had 33.3% honors and 66.6% passing grades, compared with the control group who had 84.09% pass, 9.09% borderline, and 6.82% failure in the trauma stations. CONCLUSIONS: The ATLS course, both complete and audit status, prepares students more appropriately for managing trauma patients as judged by trauma simulation scenarios. Consideration should be given for including ATLS as an integral part of the senior medical student curriculum.

Canada↗
PubMed1998

T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers.

INTRODUCTION: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low- or moderate-risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high-risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms. METHODS AND RESULTS: Ninety-five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal-averaged ECG, analysis of 24-hour Holter monitoring, and QT dispersion from the 12-lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram-documented ventricular fibrillation or tachycardia during follow-up. Kaplan-Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor. CONCLUSIONS: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low- or moderate-risk patients, and needs to be prospectively evaluated in such populations.

Adult↗
PubMed1998

Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival.

OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

Arrhythmias, Cardiac↗
PubMed1997

Electrical alternans during rest and exercise as predictors of vulnerability to ventricular arrhythmias.

This investigation was performed to evaluate the feasibility of detecting repolarization alternans with the heart rate elevated with a bicycle exercise protocol. Sensitive spectral signal-processing techniques are able to detect beat-to-beat alternation of the amplitude of the T wave, which is not visible on standard electrocardiogram. Previous animal and human investigations using atrial or ventricular pacing have demonstrated that T-wave alternans is a marker of vulnerability to ventricular arrhythmias. Using a spectral analysis technique incorporating noise reduction signal-processing software, we evaluated electrical alternans at rest and with the heart rate elevated during a bicycle exercise protocol. In this study we defined optimal criteria for electrical alternans to separate patients from those without inducible arrhythmias. Alternans and signal-averaged electrocardiographic results were compared with the results of vulnerability to ventricular arrhythmias as defined by induction of sustained ventricular tachycardia or fibrillation at electrophysiologic evaluation. In 27 patients alternans recorded at rest and with exercise had a sensitivity of 89%, specificity of 75%, and overall clinical accuracy of 80% (p <0.003). In this patient population the signal-averaged electrocardiogram was not a significant predictor of arrhythmia vulnerability. This is the first study to report that repolarization alternans can be detected with heart rate elevated with a bicycle exercise protocol. Alternans measured using this technique is an accurate predictor of arrhythmia inducibility.

Adolescent↗
PubMed1997

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↗
PubMed1997

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↗