Biomedical subjects

J D Cohen

Publications and source records attributed to J D Cohen.

At least 55 records · Page 3Linked to original sources

PubMed1999

Low hot pain threshold predicts shorter time to exercise-induced angina: results from the psychophysiological investigations of myocardial ischemia (PIMI) study.

OBJECTIVES: The purpose of this study was to test whether cutaneous thermal pain thresholds are related to anginal pain perception. BACKGROUND: Few ischemic episodes are associated with angina; symptoms have been related to pain perception thresholds. METHODS: A total of 196 patients with documented coronary artery disease underwent bicycle exercise testing and thermal pain testing. The Marstock test of cutaneous sensory perception was administered at baseline after 30 min of rest on two days and after exercise and mental stress. Resting hot pain thresholds (HPTs) were averaged for the two baseline visits and divided into two groups: 1) average HPT <41 degrees C, and 2) average HPT > or =41 degrees C, to be clearly indicative of abnormal hypersensitivity to noxious heat. RESULTS: Patients with HPT <41 degrees C had significantly shorter time to angina onset on exercise testing than patients with HPT > or =41 degrees C (p < 0.04, log-rank test). Heart rates, systolic blood pressure and rate-pressure product at peak exercise were not different for the two groups. Resting plasma beta-endorphin levels were significantly higher in the HPT <41 degrees C group (5.9+/-3.7 pmol/liter vs. 4.7+/-2.8 pmol/liter, p = 0.02). Using a Cox proportional hazards model, patients with HPT <41 degrees C had an increased risk of angina (p = 0.03, rate ratio = 2.0). These differences persisted after adjustment for age, gender, depression, anxiety and history of diabetes or hypertension (p < 0.01). CONCLUSIONS: Occurrence of angina and timing of angina onset on an exercise test are related to overall hot pain sensory perception. The mechanism of this relationship requires further study.

Adult↗

PubMed1999

Context-processing deficits in schizophrenia: converging evidence from three theoretically motivated cognitive tasks.

To test the hypothesis that the ability to actively represent and maintain context information in a central function of working memory and that a disturbance in this function contributes to cognitive deficits in schizophrenia, the authors modified 3 tasks--the AX version of the Continuous Performance Test, Stroop, and a lexical disambiguation task--and administered them to patients with schizophrenia as well as to depressed and healthy controls. The results suggest an accentuation of deficits in patients with schizophrenia in context-sensitive conditions and cross-task correlations of performance in these conditions. However, the results do not definitively eliminate the possibility of a generalized deficit. The significance of these findings is discussed with regard to the specificity of deficits in schizophrenia and the hypothesis concerning the neural and cognitive mechanisms that underlie these deficits.

Adult↗

PubMed1999

Gastric emptying after elective abdominal aortic aneurysm surgery: the case for early postoperative enteral feeding.

OBJECTIVE: To assess gastric emptying with a view to early postoperative enteral nutrition after elective abdominal aortic aneurysm (AAA) surgery. METHODS: The paracetamol absorption test was used to assess gastric emptying in 13 consecutive patients at 6, 18 and 32 h following elective AAA surgery. All patients received postoperative analgesia with marcaine given via an epidural catheter during the first 48 postoperative hours. Normal emptying was defined as an area under the plasma paracetamol concentration curve at 60 min (AUC-60) of > 600 mg/min/l. RESULTS: The median time to normal gastric emptying was 18 +/- 7.7 h. One patient (7.6%) had normal emptying at 6 h, nine (69%) at 18 h and 12 (92%) at 32 h. The nasogastric tubes were removed at a median of 3.2 days after surgery, and enteral feeding was commenced on day 4. CONCLUSIONS: Gastric emptying was normal 18 h post-AAA surgery as assessed by the paracetamol absorption test. In view of the importance of maintaining an intact gastrointestinal mucosa, enteral nutrition may be commenced on the second postoperative day.

Absorption↗

PubMed1999

The "benefits" of distractibility: mechanisms underlying increased Stroop effects in schizophrenia.

Recent studies of selective attention in schizophrenia patients suggest a particular pattern of single-trial Stroop performance: increased facilitation but not interference in reaction times (RTs), combined with increased error interference. Our Stroop task analysis suggests that this pattern can be explained by a selective attention deficit if one accounts for (1) performance in the congruent condition; (2) the nature of the neutral stimulus; (3) the relationship between accuracy and RT; and (4) response set effects. To test these hypotheses, we examined Stroop performance in 40 DSM-IV schizophrenia patients and 20 healthy control subjects, using a range of neutral stimuli (color patches, noncolor words, color words not in the response set). The findings confirmed several of our predictions and the results were consistent with the hypothesis that abnormal Stroop performance in schizophrenia reflects a failure to adequately attend to the task-appropriate stimulus dimension (color). This inattention affects both the congruent and incongruent conditions and multiple points in the information processing pathway.

Adult↗

PubMed1999

Phase I trial of intravenous thymidine and carboplatin in patients with advanced cancer.

PURPOSE: To evaluate the biologic interactions and toxicities of carboplatin combined with a 24-hour infusion of thymidine 75 mg/m(2) in a phase I trial. PATIENTS AND METHODS: Thirty-two patients with cancer refractory to conventional therapy were treated. The first set of patients (n = 7) received thymidine alone 4 weeks before subsequent planned courses of thymidine combined with carboplatin followed (4 weeks) by carboplatin alone. Carboplatin was administered over 20 minutes at hour 20 of the 24-hour thymidine infusion. The carboplatin dose was escalated in patient groups: 200 mg/m(2) (n = 3); 300 mg/m(2) (n = 7); 350 mg/m(2) (n = 4); 400 mg/m(2) (n = 3); 480 mg/m(2) (n = 10); and 576 mg/m(2) (n = 5). At the maximum-tolerated dose (480 mg/m(2)), five patients received combined therapy first and carboplatin alone second, and five patients received carboplatin first and combined therapy second. Maintenance therapy for stable or responding patients was combined therapy. RESULTS: Evaluation demonstrated a trend toward thymidine protection of carboplatin-induced treatment-limiting thrombocytopenia. Neutropenia with carboplatin alone or in combination was negligible. Thymidine alone had no myelosuppressive effects and produced reversible grade 1 or 2 nausea and vomiting (57%), headache (25%), and grade 1 neurotoxicity (22%). Thymidine did not enhance expected carboplatin toxicities. There was no therapy-related infection or bleeding. Analysis of platinum in plasma ultrafiltrate and urine showed no effect by thymidine. Similarly, thymidine pharmacokinetics was not affected by carboplatin. As predicted, nicotinamide adenine dinucleotide levels in peripheral lymphocytes were increased during exposure to carboplatin and/or thymidine but were decreased by carboplatin alone. In three patients with high-grade glioma, responses included one complete remission (21 months) and one partial remission (14 months) at the 480-mg/m(2)-dose level, and disease stabilization (7 months) at the 400-mg/m(2-dose) level. A minor response was observed in a patient with metastatic colon cancer (5 months) at the 480-mg/m(2)-dose level. CONCLUSION: The combination of carboplatin and thymidine as described is well tolerated. The data presented have resulted in a phase II study by the North American Brain Tumor Consortium.

Adult↗

PubMed1999

The contribution of the anterior cingulate cortex to executive processes in cognition.

The anterior cingulate cortex (ACC), on the medial surface of the frontal lobes, has frequently been hypothesized to make critical contributions to the function of neural systems involved in the executive control of cognition. Three principal theories have been developed to account for this role. The first, 'motivated attention', emphasizes the limbic identity of the ACC and the effects of lesions to this area of the brain. The second, 'attention allocation', emphasizes the fact that during functional neuroimaging studies activation of the ACC is seen during tasks that elicit incompatible response tendencies that must be resolved for correct performance. The third theory, 'error detection', reflects the observation of a negative scalp potential occurring during incorrect responses which appears to have a medial frontal generator. The first and last theories suggest evaluative functions by the ACC in the service of control, while attention allocation suggests a strategic function. We have proposed that the data supporting all three theories can be reconciled if the ACC were detecting conflicting processes during task performance that might be associated with errors. In support of this hypothesis we describe results using event-related fMRI which confirm that the ACC does show error related activity but that the same region of the brain also shows increased response related activity during correct responses associated with response competition. This suggests a re-conceptualization of the contribution of the ACC to executive processes that support an evaluative role, specifically the on-line detection of processing conflicts that may be associated with deteriorating performance. Unresolved questions related to the contribution of this region to executive processes and potential future directions for research on the function of this region of the brain are discussed.

Animals↗

PubMed1999

Cardiovascular disease: tomorrow is the reason for today's therapeutics. An interview with Jerome D. Chen.

The prevalence and magnitude of cardiovascular disease in the United States make it the leading cause of mortality, far surpassing deaths from all cancers. More than 900,000 Americans die each year from cardiovascular causes, including stroke, hypertension, congestive heart failure, atherosclerosis, and congenital heart defects, according to American Heart Association estimates. Coronary heart disease alone accounts for 50% of all cardiovascular deaths. A host of agents designed to help manage cardiovascular disorders and related conditions (eg, hypertension, diabetes, and hypercholesterolemia) are available to physicians who treat patients at high risk. In this interview, Jerome D. Cohen, MD, explains why more aggressive use of these drug treatments today could significantly improve older patients' quality of life and reduce the risk of a disabling or fatal cardiovascular event in the next millennium.

Aged↗

PubMed1999

Auxin metabolism in mosses and liverworts.

The plant hormone auxin (indole-3-acetic acid, IAA) is involved in the control of many phenomena during plant development. By characterizing steady-state free and conjugated IAA levels using a stable isotope dilution method coupled with gas chromatography- selected ion monitoring- mass spectrometry, this paper provides a detailed characterization of IAA metabolism in five liverworts, four mosses, and two tracheophytes. Long-term IAA conjugation patterns were monitored by incubating actively growing tissue with (14)C-IAA and then analyzing the de novo synthesis of IAA conjugates with radioimaging techniques. The liverworts, mosses, and tracheophytes can be differentiated by the total amount of IAA metabolites, the proportion of free and conjugated IAA, the chemical nature of their IAA conjugates, and the rates of IAA conjugation. Our tentative conclusion is that the liverworts appear to employ a biosynthesis-degradation strategy for the regulation of free IAA levels, in contrast to the conjugation-hydrolysis strategy apparently used by the mosses and tracheophytes. Such alternative metabolic strategies may have profound implications for macroevolutionary processes in these plant groups.

Journal Article↗

PubMed1998

Heterogeneity among cardiac ischemic and anginal responses to exercise, mental stress, and daily life.

The objectives of this study were to compare and contrast indicators of ischemia in a well-characterized group of 196 patients with coronary artery disease, documented angiographically or by verified history of myocardial infarction, and a positive exercise test result. Myocardial ischemia occurs frequently in response to everyday stressors in patients with coronary artery disease. The Psychophysiological Interventions in Myocardial Ischemia study provides a unique opportunity to study neuroendocrine and psychological manifestations of ischemia. Patients with exercise-induced ischemia underwent exercise radionuclide ventriculography and electrocardiographic monitoring and 2 laboratory mental stressors (Speech and Stroop) after being withdrawn from cardiac medications. In addition, 48-hour ambulatory electrocardiograms were recorded during routine daily activities. Patients with a history of angina within the past 3 months reported angina during the bicycle or treadmill test with a much higher frequency than patients without such an anginal history (77% vs 26%). Ejection fraction (EF) responses to the Stroop test were abnormal in 48% of patients with an abnormal EF response to the Speech task, versus 17% in patients with a normal EF response (p <0.01). Seventy-six percent of patients had an abnormal EF response to bicycle exercise. Three indicators of ischemia (ST-segment depression, wall motion abnormality, and EF response) were compared during the same laboratory stressor and across different types of stress tests. Presence of the 3 indicators was only moderately associated during exercise, and only weak or nonsignificant associations occurred among the presence of the 3 ischemic markers during mental stress. Occurrence of the same ischemic markers was moderately associated between the 2 mental stress tasks, but few associations were found between the occurrence of the same ischemic marker during exercise and mental stress. There is a marked heterogeneity of responses to psychological and exercise stress testing using electrocardiography, ambulatory electrocardiography, or radionuclide criteria for ischemia during stress. The heterogeneity may be related to differences in the magnitude or types of physiologic responses provoked and to differences in the sensitivity and specificity of the different tests used to identify ischemia.

Aged↗

PubMed1998

Dopamine and the mechanisms of cognition: Part I. A neural network model predicting dopamine effects on selective attention.

BACKGROUND: Dopamine affects neural information processing, cognition, and behavior; however, the mechanisms through which these three levels of function are affected have remained unspecified. We present a parallel-distributed processing model of dopamine effects on neural ensembles that accounts for effects on human performance in a selective attention task. METHODS: Task performance is stimulated using principles and mechanisms that capture salient aspects of information processing in neural ensembles. Dopamine effects are simulated as a change in gain of neural assemblies in the area of release. RESULTS: The model leads to different predictions as a function of the hypothesized location of dopamine effects. Motor system effects are simulated as a change in gain over the response layer of the model. This induces speeding of reaction times but an impairment of accuracy. Cognitive attentional effects are simulated as a change in gain over the attention layer. This induces a speeding of reaction times and an improvement of accuracy, especially at very fast reaction times and when processing of the stimulus requires selective attention. CONCLUSIONS: A computer simulation using widely accepted principles of processing in neural ensembles can account for reaction time distributions and time-accuracy curves in a selective attention task. The simulation can be used to generate predictions about the effects of dopamine agonists on performance. An empirical study evaluating these predictions is described in a companion paper.

Attention↗

PubMed1998

Dopamine and the mechanisms of cognition: Part II. D-amphetamine effects in human subjects performing a selective attention task.

BACKGROUND: A neural network computer model described in a companion paper predicted the effects of increased dopamine transmission on selective attention under two different hypotheses. METHODS: To evaluate these predictions we conducted an empirical study in human subjects of D-amphetamine effects on performance of the Eriksen response competition task. Ten healthy volunteers were tested before and after placebo or D-amphetamine in a double-blind cross-over design. RESULTS: D-amphetamine induced a speeding of reaction time overall and an improvement of accuracy at fast reaction times but only in the task condition requiring selective attention. CONCLUSIONS: This pattern of results conforms to the prediction of the model under the hypothesis that D-amphetamine primarily affects dopamine transmission in cognitive rather than motor networks. This suggests that the principles embodied in parallel distributed processing models of task performance may be sufficient to predict and explain specific behavioral effects of some drug actions in the central nervous system.

Administration, Oral↗

PubMed1998

Anterior cingulate cortex, error detection, and the online monitoring of performance.

An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.

Brain Mapping↗

PubMed1998

Effect of treatment of isolated systolic hypertension on left ventricular mass.

CONTEXT: Left ventricular (LV) hypertrophy is a common problem among elderly patients with isolated systolic hypertension (ISH), but the effect of treatment of ISH on LV mass is not known. OBJECTIVE: To assess the ability of antihypertensive drug treatment to reduce LV mass in ISH. DESIGN: Echocardiographic Substudy of the Systolic Hypertension in the Elderly Program (SHEP). PATIENTS: A total of 104 participants at the St Louis SHEP site who had interpretable baseline echocardiograms, 94 of whom had 3-year follow-up echocardiograms. INTERVENTION: The SHEP participants were randomized to placebo or active treatment with chlorthalidone (12.5-25 mg/d), with atenolol (25-50 mg/d) added if necessary to maintain goal blood pressure. MAIN OUTCOME MEASURE: Change in LV mass assessed by echocardiography. RESULTS: Minimum follow-up was 3 years. In the active treatment group, 91% and 80% of subjects were receiving treatment with chlorthalidone alone by the end of years 1 and 3, respectively. The LV mass index was 93 g/m2 in the active treatment group and 100 g/m2 in the placebo group (P<.001). The LV mass index declined by 13% (95% confidence interval, - 3% to - 23%) in the active treatment group compared with a 6% increase (95% confidence interval, - 3% to + 16%) in the placebo group over 3 years (P=.01). CONCLUSION: Treatment of ISH with a diuretic-based regimen reduces LV mass.

Aged↗

PubMed1998

Reproducibility of fMRI results across four institutions using a spatial working memory task.

Four U.S. sites formed a consortium to conduct a multisite study of fMRI methods. The primary purpose of this consortium was to examine the reliability and reproducibility of fMRI results. FMRI data were collected on healthy adults during performance of a spatial working memory task at four different institutions. Two sets of data from each institution were made available. First, data from two subjects were made available from each site and were processed and analyzed as a pooled data set. Second, statistical maps from five to eight subjects per site were made available. These images were aligned in stereotactic space and common regions of activation were examined to address the reproducibility of fMRI results when both image acquisition and analysis vary as a function of site. Our grouped and individual data analyses showed reliable patterns of activation in dorsolateral prefrontal cortex and posterior parietal cortex during performance of the working memory task across all four sites. This multisite study, the first of its kind using fMRI data, demonstrates highly consistent findings across sites.

Adult↗

PubMed1998

Outcome after elective infrarenal aortic aneurysm surgery.

We conducted a prospective case series study to investigate the causes of and factors influencing morbidity and mortality in 102 consecutive patients after elective infrarenal abdominal aneurysm (AAA) surgery between 1992 and 1995. Preoperative factors (demographics, risk factor indexes, electrocardiographic findings, ejection fraction, and stress imaging scans were indicated) and intraoperative factors (duration of surgery, size of aneurysm, complications, units of blood transfused, and additional procedures performed) were recorded. Patients were admitted to the intensive care unit (ICU) for at least 24 hours and followed for 30 days postoperatively. The mortality rate was 4.9%, due in all cases to multiorgan dysfunction syndrome (MODS). Death was preceded by colon ischemia (two patients), intraabdominal bleeding (two patients), or sepsis (one patient). Only the preoperative blood urea nitrogen correlated with mortality (p = 0.042). Complications occurred in 59% of patients in the ICU and involved the cardiovascular system in 83% of them (heart rate > 90 bpm in 49%). On multivariate analysis, only duration of surgery was associated with ICU complications (p = 0.018). No complication resulted in mortality. Ward complications occurred in 13%, and 5% of these patients required readmission to the ICU. Although cardiac complications are considered the major cause of mortality after infrarenal AAA surgery, all five deaths in the present series were due to MODS. Preoperative screening should be more selective, and intraoperative and postoperative care should be stressed.

Aged↗

PubMed1998

A microtechnique for the analysis of free and conjugated indole-3-acetic acid in milligram amounts of plant tissue using a benchtop gas chromatograph-mass spectrometer.

A microtechnique was developed for the quantification of indole-3-acetic acid (IAA) in plant samples of one milligram fresh weight or less. The method permitted quantification of both free and conjugated IAA using a benchtop gas chromatograph-mass spectrometer. New methods for sample purification with high recovery at microscale levels, together with simple changes that result in enhanced sensitivity of the instrumentation, allowed for a significant reduction in the amount of plant material required for analysis. Single oat (Avena sativa L.) coleoptile tips could be studied with this method and were found to contain free and total IAA levels of 137 and 399 pg.mg-1 fresh weight, respectively. A single 5-d-old Arabidopsis thaliana (L.) Heynh. seedling was shown to contain 61 pg.mg-1 fresh weight free IAA and 7850 pg.mg-1 fresh weight of total IAA following basic hydrolysis. This microtechnique provides a way to accurately measure IAA levels in very small structures and individual seedlings, thus making it a valuable research tool for elucidating the role and distribution of auxin in relation to growth and development.

Arabidopsis↗

PubMed1998

The gene for indole-3-acetyl-L-aspartic acid hydrolase from Enterobacter agglomerans: molecular cloning, nucleotide sequence, and expression in Escherichia coli.

A 5.5-kb DNA fragment containing the indole-3-acetyl-aspartic acid (IAA-asp) hydrolase gene (iaaspH) was isolated from Enterobacter agglomerans strain GK12 using a hybridization probe based on the N-terminal amino acid sequence of the protein. The DNA sequence of a 2.4-kb region of this fragment was determined and revealed a 1311-nucleotide ORF large enough to encode the 45-kDa IAA-asp hydrolase. A 1.5-kb DNA fragment containing iaaspH was subcloned into the Escherichia coli expression plasmid pTTQ8 to yield plasmid pJCC2. Extracts of IPTG-induced E. coli cultures containing the pJCC2 recombinant plasmid showed IAA-asp hydrolase levels 5 to 10-fold higher than those in E. agglomerans extracts. Homology searches revealed that the IAA-asp hydrolase was similar to a variety of amidohydrolases. In addition, IAA-asp hydrolase showed 70% sequence identity to a putative thermostable carboxypeptidase of E. coli.

Amidohydrolases↗

PubMed1998

Protection of leukemic cells by deoxycytidine: in vitro measures of protection against cytosine arabinoside.

Plasma deoxycytidine levels can be very high in leukemia patients. Such levels strongly protected leukemia cell lines against cytosine arabinoside (araC), fludarabine and 2-chlorodeoxyadenosine when using clonogenic survival as the endpoint. This endpoint is not easily used when studying protection in clinical leukemia cell samples. Therefore, we tested other ways to quantify protection based on biochemical measures of viability or drug metabolism. The estimates of the strength of protection based on rates of DNA synthesis, cellular araC uptake and incorporation of araC into DNA were much lower than the estimates using clonogenic survival. The MTT viability assay gave excellent estimates and appears promising for studying protection in primary leukemia cell samples.

Cell Survival↗