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Biomedical subjects

J D Cohen

Publications and source records attributed to J D Cohen.

At least 19 recordsLinked to original sources
PubMed1992

Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group.

OBJECTIVE: To evaluate the contribution of mild to moderate hypertension to progressive loss of renal function by analysis of renal function data from the Multiple Risk Factor Intervention Trial. DESIGN: The cohort of men with mild to moderate hypertension (baseline diastolic blood pressure > or = 90 mm Hg), randomized to a special intervention (SI) group or usual care (UC) group, were examined for change in renal function based on individual reciprocal creatinine slopes over an average of 7 years' follow-up as the outcome measure. Contribution of blood pressure control during follow-up, age, race, and blood pressure at entry were assessed. PARTICIPANTS: The cohort of 5524 (463 black, 5061 nonblack) hypertensive men receiving no therapy at entry provided the data for the present analysis. RESULTS: Blood pressure control was similar for black and white participants, but significant decline in reciprocal creatinine slope was found for black men (mean slope, -0.0090 +/- 0.0013 dL/mg/y) compared with white men (+0.0018 +/- 0.0004 dL/mg/y) (P < .001 for difference between blacks and whites). Decline in renal function was also greater among individuals with elevated systolic (P < .001) as well as diastolic blood pressure (P < .001), and older individuals (P < .001). No difference between the SI and UC groups was seen in reciprocal creatinine slopes, but in both groups combined, treatment that maintained diastolic blood pressure below an average value of 95 mm Hg was associated with stable or improving renal function, whereas participants whose blood pressure remained 95 mm Hg or greater continued to decline at -0.0013 +/- 0.0009 dL/mg/y (P = .007 for difference). Separate examination of the subset of black men (n = 463) failed to show such a difference. CONCLUSIONS: Effective blood pressure control was associated with stable or improving renal function in nonblacks but not in blacks. These findings emphasize the importance of blood pressure control to maintain adequate renal function in hypertensive white men and raise important questions about the relationship of pressure reduction and renal function change in blacks.

Adult↗
PubMed1992

Abnormal electrocardiograms and cardiovascular risk: role of silent myocardial ischemia. Evidence from MRFIT.

The Multiple Risk Factor Intervention Trial (MRFIT) was designed as a primary prevention study to test the effect of multifactorial intervention on long-term outcome in men with a combination of risk factors that placed them in the top 10-15 percentiles of risk for coronary artery disease. Of the 12,866 patients in this study, the 3,600 men (about 28%) with abnormalities in the baseline electrocardiogram were prospectively identified. They were expected to be at increased risk for coronary events compared with those without electrocardiographic abnormalities. Analysis of cumulative mortality data following antihypertensive regimens that included high dosages of diuretics revealed an association between electrocardiographic abnormalities at rest and diuretic treatment that related to adverse outcome. When the dosages of the diuretic were lowered, this trend was reversed. It is proposed that diuretic-related hypokalemia may predispose patients who may have silent myocardial ischemia to potentially fatal arrhythmias and that use of potassium-sparing antihypertensive regimens be considered in high-risk hypertensive patients.

Adult↗
PubMed1992

Outcome of urgent percutaneous transluminal coronary angioplasty in acute myocardial infarction: comparison of single-vessel versus multivessel coronary artery disease.

Despite recent clinical trials of percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction, specific groups of patients that may benefit from adjunctive or alternative therapy have yet to be adequately characterized. The in-hospital outcome of 151 consecutive patients treated for acute myocardial infarction with urgent PTCA of the infarct-related artery was studied to identify a subgroup of patients at high risk. Patients were divided into two groups based on the angiographic presence of either single-vessel (n = 86) or multivessel (n = 65) coronary artery disease. Despite PTCA of only the infarct-related artery and similar baseline clinical characteristics such as age, peak serum creatine kinase concentration, left ventricular ejection fraction, and time from the onset of chest pain to arrival at the hospital, the group with multivessel disease had a lower rate of successful angioplasty (75% vs 92%, p < 0.005), with higher incidences of persistent total occlusion of the infarct-related artery (14% vs 3%, p < 0.02) and procedural complications during PTCA (28% vs 13%, p < or = 0.02), and were more likely to have multiple complications (12% vs 1%, p < 0.004). In addition, the group with multivessel disease had a higher rate of urgent (< or = 24 hours) coronary artery bypass graft surgery (13% vs 2%, p < 0.05) and a trend toward a higher in-hospital mortality rate (6% vs 1%, p < or = 0.17). By stepwise logistic regression, only the presence of single-vessel versus multivessel disease was predictive of PTCA success (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia.

Connectionist models are used to explore the relationship between cognitive deficits and biological abnormalities in schizophrenia. Schizophrenic deficits in tasks that tap attention and language processing are reviewed, as are biological disturbances involving prefrontal cortex and the mesocortical dopamine system. Three computer models are then presented that simulate normal and schizophrenic performance in the Stroop task, the continuous performance test, and a lexical disambiguation task. They demonstrate that a disturbance in the internal representation of contextual information can provide a common explanation for schizophrenic deficits in several attention- and language-related tasks. The models also show that these behavioral deficits may arise from a disturbance in a model parameter (gain) corresponding to the neuromodulatory effects of dopamine, in a model component corresponding to the function of prefrontal cortex.

Computer Simulation↗
PubMed1992

Smoking is a risk factor for coronary spasm in young women.

BACKGROUND: Risk factors for pure coronary spasm are not known. Clinical observations have pointed to cigarette smoking, a known risk factor for obstructive coronary artery disease. METHODS AND RESULTS: We conducted a case-neighborhood control study of premenopausal women, a population segment with the lowest prevalence of obstructive coronary artery disease. The cases were 21 premenopausal women (age range, 36-41 years) with angiographically proven coronary spasm. All coronary arteriograms were analyzed by two independent experienced cardiologists on two occasions. There were no differences between analyses; all cases had normal baseline coronary angiogram except for two, who had less than 20% coronary luminal stenosis in segments other than the site of the focal vasospasm. All cases had normal hemodynamics at rest, normal left ventricular function, and were in sinus rhythm. Ascertainment of the cases was done by angiographic demonstration of focal coronary spasm spontaneously or by ergonovine provocation. Six cases developed spontaneous coronary spasm before catheter engagement, and in 15, coronary spasm was induced by ergonovine provocation. Each case was asked to name as many as possible female neighborhood acquaintances of similar age and racial background who were willing to answer the same standardized questionnaire. The same standardized questionnaire was completed for each case and each control (n = 63). The standardized questionnaire was designed to obtain information on health characteristics, habits, socioeconomic status, and education. Only cigarette smoking was significantly more prevalent among coronary spasm cases. Cigarette smokers were 13 cases (62%) and 11 controls (17.5%) (p less than 0.001). The odds ratio was 7.7, with a 95% confidence interval of 2.6-23.1. CONCLUSIONS: These findings suggest that there is a very strong association between cigarette smoking and pure coronary spasm in young women.

Adult↗
PubMed1992

A parallel distributed processing approach to automaticity.

We consider how a particular set of information processing principles, developed within the parallel distributed processing (PDP) framework, can address issues concerning automaticity. These principles include graded, activation-based processing that is subject to attentional modulation; incremental, connection-based learning; and interactivity and competition in processing. We show how simulation models, based on these principles, can account for the major phenomena associated with automaticity, as well as many of those that have been troublesome for more traditional theories. In particular, we show how the PDP framework provides an alternative to the usual dichotomy between automatic and controlled processing and can explain the relative nature of automaticity as well as the fact that seemingly automatic processes can be influenced by attention. We also discuss how this framework can provide insight into the role that bidirectional influences play in processing: that is, how attention can influence processing at the same time that processing influences attention. Simulation models of the Stroop color-word task and the Eriksen response-competition task are described that help illustrate the application of the principles to performance in specific behavioral tasks.

Association Learning↗
PubMed1991

Effect of hyperthermia in vitro and in vivo on adenine and pyridine nucleotide pools in human peripheral lymphocytes.

Hyperthermia has been shown in vitro and in vivo to potentiate the effects of ionizing irradiation. Previous studies found that hyperthermia alters the metabolism of adenosine diphosphate (ADP)-ribose polymers required for recovery from DNA damage and that poly(ADP-ribose) polymerase activity is very sensitive to cellular nicotinamide-adenine dinucleotide (NAD) levels. Thus, the effect of 41.8 degrees C hyperthermia in vitro and in vivo on NAD and adenosine triphosphate (ATP) levels was studied in human peripheral lymphocytes. In vitro studies showed significant decreases in oxidized NAD (NAD+) and ATP levels after heating that simulated a clinical whole-body hyperthermia (WBH) treatment. This nucleotide depletion could not be attributed to nucleotide leakage or increased enzymatic NAD+ consumption. As the reduction of NAD observed was sufficient to decrease poly(ADP-ribose)polymerase activity by 50%, the studies were extended to clinica cases. Cellular NAD+ and ATP were measured in previously stored lymphocytes obtained from four patients before and after WBH; a statistically significant decrease in NAD+ was observed after WBH which quantitatively agreed with the in vitro results. Based on these results a prospective study was done in three patients; NAD+ was extracted immediately on sample collection, and the kinetics of WBH-induced NAD depletion were studied. These data, which agree quantitatively with the laboratory results, are presented.

Adenosine Triphosphate↗
PubMed1991

Managing the whole patient with hypertension: practical applications in a clinical setting.

Physicians are aware of the value of treating hypertension. Complications such as stroke and congestive heart failure are less likely to occur in the well-controlled patient. In our quest to add coronary heart disease to this list, we must go beyond simple reduction of blood pressure. We must consider other risk factors such as hypercholesterolemia, cigarette smoking, diabetes mellitus, and family history. The presence of one or more of these may indicate a more aggressive treatment approach. Similarly the presence of left ventricular hypertrophy, coronary disease, or renal disease may indicate specific pharmacotherapy. On the other hand, the low-risk patient with no other problems or conditions may be treated with only nonpharmacologic therapy such as weight loss, dietary sodium reduction, and/or alcohol restriction. Every patient has a different constellation of findings. Every patient should be treated individually. It is no longer sufficient just to lower blood pressure; we need to manage the whole patient with hypertension; keeping in mind that most antihypertensive agents are equally effective, the side effect profile is often the decisive factor in choosing an antihypertensive agent.

Adult↗
PubMed1991

Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents.

This open, multicenter phase III study was designed to assess the efficacy and long-term safety of terazosin (1 to 40 mg/day), alone or in combination with other antihypertensive drugs, in 364 patients with mild to moderate essential hypertension. Compared with baseline values, long-term terazosin monotherapy or combination therapy resulted in consistent decreases in both systolic and diastolic blood pressures, with a mean reduction in supine diastolic pressure of 12 to 14 mm Hg. The numbers of patients with controlled blood pressure at the last evaluable visit of each therapy period were as follows: terazosin alone, 106 of 245 (43%); terazosin with added diuretic, 70 of 112 (63%); diuretic with added terazosin, 47 of 88 (53%); and terazosin plus diuretic with added beta-blocker, 22 of 32 (69%). Most adverse events were mild or moderate in severity. Only pain in extremities had a higher incidence during long-term treatment (6%, 181 to 360-day period) than during initial short-term treatment (5%, 1 to 90-day period). Three of six syncopal events occurred during the initial 180 days of treatment; this 0.8% (3/364) incidence was comparable with that reported previously for short-term studies. Only one case of syncope occurred during terazosin monotherapy. Terazosin was judged to be a safe and effective long-term medication for the treatment of hypertension.

Adrenergic alpha-Antagonists↗
PubMed1991

Thymidine-cisplatin vs thymidine-carboplatin interactions in human T-cell acute leukemia.

Thymidine is shown to sensitize JM human T-cell acute leukemia cells to cisplatin killing in vitro with dose modifying factors of 1.72, 1.62, and 1.76 at 200, 500, and 1000 micrograms thymidine/ml x 24 h. The magnitude of thymidine-cisplatin sensitization increases with longer thymidine exposures (500 micrograms/ml) up to 16 h but is not further increased at 24 h. For a 25 h thymidine exposure, enhancement is greater for cisplatin (3 micrograms/ml x 1 h) starting 12-24 h into the thymidine exposure vs starting at 0-8 h (p less than or equal to 0.0004). Results are precisely the same for simultaneous studies using carboplatin except that (1) thymidine enhances carboplatin cytotoxicity more than cisplatin killing, (2) enhancement of carboplatin killing varies little with the timing of carboplatin administration during a 25 h thymidine exposure. These findings are discussed relative to their clinical applicability.

Carboplatin↗
PubMed1991

Trials of hypertension prevention. Phase I design.

Phase I of the Trials of Hypertension Prevention (TOHP) was a National Heart, Lung, and Blood Institute-sponsored, 3-year, national, multicenter, randomized, controlled trial designed to test the feasibility and efficacy of three life-style (weight loss, sodium restriction, and stress management) and four nutrition supplement (calcium, magnesium, fish oil, and potassium) interventions aimed at lowering diastolic blood pressure in those whose blood pressure was initially in the high normal range (80 to 89 mm Hg). A total of 2182 volunteers were recruited and allocated to the various treatment arms, such that each hypothesis was tested with a power of 85% or higher to detect a diastolic blood pressure treatment effect of 2 mm Hg. The four nutrition supplement interventions were delivered in a double-blinded fashion and the three life-style interventions, single (observed) -blinded. Phase I was designed to provide a rigorous test of short-term lowering of blood pressure for each of the seven treatments chosen and provides the basis for planning of a subsequent long-term trial of hypertension prevention.

Adult↗
PubMed1991

Echocardiographic evaluation of cardiac structure and function in elderly subjects with isolated systolic hypertension.

One hundred four participants in the Systolic Hypertension in the Elderly Program (SHEP) trial (mean age 71 +/- 6 years) were examined by Doppler echocardiography to gain information on the cardiac structural and functional alterations in isolated systolic hypertension. Participants had a systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg and were compared with 55 age-matched normotensive control subjects. Left ventricular mass index was significantly higher in the participants than in the normotensive subjects (103 +/- 28 versus 87 +/- 23 g/m2, p = 0.0014) and 26% of the participants met echocardiographic criteria for left ventricular hypertrophy compared with 10% of normotensive subjects. Left atrial index was also greater in participants than in normotensive subjects (2.26 +/- 0.32 versus 2.11 +/- 0.24 cm/m2, p = 0.005) and 51% of participants had left atrial enlargement. Doppler measures of diastolic filling were significantly different between the two groups, with peak atrial velocity higher (76 +/- 17 versus 69 +/- 17 cm/s, p = 0.02) and ratio of peak early to atrial velocity lower (0.76 +/- 0.23 versus 0.86 +/- 0.22, p = 0.0124) in participants. There was no correlation between left ventricular mass index and Doppler measures of diastolic function, but relative wall thickness correlated significantly with peak atrial velocity (r = 0.22, p = 0.016) and peak early to peak atrial velocity ratio (r = 0.24, p = 0.007). There was no difference in M-mode ejection phase indexes of systolic performance (shortening fraction and peak velocity of circumferential fiber shortening) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Events in the Cardiac Arrhythmia Suppression Trial (CAST): mortality in patients surviving open label titration but not randomized to double-blind therapy.

The patient characteristics and outcomes were studied in the 318 patients who survived open label drug titration in the Cardiac Arrhythmia Suppression Trial (CAST) and who were not randomized to double-blind therapy and in 942 patients, who were randomized to double-blind placebo therapy. The patients randomized to placebo therapy had a lower total mortality or resuscitated cardiac arrest rate (4% vs. 8.5%). However, at baseline, nonrandomized patients were dissimilar from patients randomized to placebo in the following ways: older; lower left ventricular ejection fraction; greater use of digitalis, diuretic drugs and antihypertensive agents; lesser use of beta-adrenoceptor blocking agents and more frequent prior cardiac problems, including runs of ventricular tachycardia and left bundle branch block. A matched comparison that took these inequities into account showed no significant differences in mortality or rate of resuscitation from cardiac arrest between nonrandomized patients and clinically equivalent patients randomized to placebo. Cox regression analysis indicated that two factors significantly increased the hazard ratio for arrhythmic death or resuscitated cardiac arrest in the nonrandomized patients: female gender (4.7, p less than 0.05) and electrocardiographic events (ventricular tachycardia, proarrhythmia, widened QRS complex, heart block, bradycardia) during open label titration (7.0, p less than 0.005). However, some potentially important differences between men and women were not included in the Cox regression model. Of the nonrandomized patients, approximately 70% were not randomized because of lack of suppression of ventricular premature depolarizations or adverse events, or both, and the remaining 30% because of patient or private physician request with no indication of another reason.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1991

Systolic Hypertension of the Elderly Program (SHEP). Part 10: Analysis.

The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses. The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death. The sample size achieved (4,736 participants) should be adequate to address the proposed questions. Monitoring procedures have been described and established. A data and safety monitoring board that uses these procedures is closely following the data from the trial. The board will periodically examine the data to determine whether termination of the study is warranted.

Health Services for the Aged↗
PubMed1991

Facilitation of mechanical ventilation in status asthmaticus with continuous intravenous thiopental.

Mechanical ventilation in status asthmaticus is associated with a significant mortality and morbidity. To facilitate intermittent positive pressure ventilation (IPPV), we have used continuous IV thiopental (thiopentone) together with traditional ventilatory techniques. With this policy, we were able to achieve rapid correction of arterial blood gas tensions in a group of 20 severe asthmatics requiring IPPV. By 1 hour, peak airway pressure (PAP) had fallen from 58.6 +/- 15.7 to 30.2 +/- 10.9 cm H2O (p less than 0.001). During the same period, PaCO2 fell from 51.3 +/- 15.3 to 40.17 +/- 8.2 mm Hg (p less than 0.05) and pH rose from 7.25 +/- 0.1 to 7.33 +/- 0.1 (p less than 0.001). Morbidity was low and in particular, no episode of barotrauma was noted. All patients survived the acute attack and were successfully liberated from the ventilator. We conclude that these results are largely attributable to our use of early and continuous IV anesthesia induced by thiopental.

Adult↗