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Biomedical subjects

S Greenberg

Publications and source records attributed to S Greenberg.

At least 19 recordsLinked to original sources

Efficacy and risks of moricizine in inducible sustained ventricular tachycardia.

OBJECTIVE: To assess the efficacy and toxicity of moricizine in treating patients with serious ventricular arrhythmias and inducible sustained ventricular tachycardia. DESIGN: Uncontrolled clinical trial. SETTING: The intensive care and telemetry units of Northwestern Memorial Hospital, St. Francis Hospital and Medical Center, and Lenox Hill Hospital. PATIENTS: Twenty-six patients with sustained ventricular arrhythmias or hemodynamically significant nonsustained ventricular tachycardia, most of whom failed therapy with at least one class I antiarrhythmic agent. INTERVENTION: Patients were treated with moricizine, 400 to 1000 mg/d. MEASUREMENT: Efficacy was assessed by the results of programmed ventricular stimulation done during moricizine therapy. MAIN RESULTS: Seven of the 26 patients (27%) developed life-threatening ventricular proarrhythmia during moricizine loading. Three patients had incessant sustained ventricular tachycardia, two had incessant nonsustained ventricular tachycardia, one had new sustained ventricular tachycardia, and one had new cardiac arrest. One of these patients died of intractable ventricular fibrillation. No clinical or electrophysiologic variables clearly identified those at risk for proarrhythmia. Only 3 of 26 patients (12%) became noninducible on moricizine. CONCLUSION: Moricizine has a low rate of efficacy and carries a considerable risk for life-threatening proarrhythmia in patients with serious ventricular arrhythmias and inducible ventricular tachycardia who have failed therapy with other class I antiarrhythmic agents.

Adult

Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study of elderly subjects: a report from the Bronx Longitudinal Aging Study.

This report is from a 10-year cohort study of community-dwelling elderly men and women. Mean age at the time of entry into the study was 79 years. Annual chest x-ray studies were performed, and data are presented regarding prevalence, incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a transverse diameter of the cardiac silhouette greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio). At the time of entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of the subjects with cardiomegaly at baseline died compared with 33% of the subjects without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively; p = 0.014). Cardiovascular disease incidence was also higher for those with preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p = 0.0001). According to the Cox proportional hazards regression analysis, age, cardiomegaly, diabetes, and prior evidence of myocardial infarction were independent predictors for death in this cohort. Similarly, the best predictive variables for cardiovascular disease were age, diabetes, prior evidence of myocardial infarction, and cigarette smoking. Of the 359 subjects without cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and their risk of cardiovascular disease was 1.8 times that of subjects whose test results were negative for cardiomegaly throughout the study (p = 0.003). Thus cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films, irrespective of cause, is associated with a poor prognosis in very elderly men and women.

Aged

Strongyloides stercoralis hyperinfection in a carrier of HTLV-I virus with evidence of selective immunosuppression.

A patient with near fatal Strongyloides hyperinfection syndrome is briefly described. Investigation for possible risk factors for this parasitic infection disclosed that he was a carrier of human T-cell leukemia virus type I (HTLV-I), but without evidence of disease due to this retrovirus. Over the next few years, the patient's serum antibody levels of IgG to S. stercoralis larvae declined and became undetectable despite continued infection with the parasite. Repeated courses of appropriate treatment cleared the parasitic infection only temporarily. The patient was also found to have undetectable total serum IgE and a negative immediate hypersensitivity skin test to S. stercoralis antigens. Five of six other patients with HTLV-I-associated disease and with or without strongyloidiasis were also found to have very low total serum IgE levels. It is postulated that HTLV-I infection in certain individuals may selectively impair immune responses that are critical in controlling strongyloidiasis.

Antibodies, Helminth

Environmentally contaminated families: therapeutic considerations.

The unique stress for families of exposure to environmental toxins is discussed in terms of the physical characteristics of such contaminants and resultant adaptational dilemmas, the agent or cause of the injury, and institutional responses to the contamination. Recommendations for mental health professionals working with contaminated families are presented.

Adaptation, Psychological

Hypertension: cardiovascular implications in a cohort of old old.

OBJECTIVE: To examine the prevalence and cardiovascular implications of hypertension in advanced age. DESIGN: Prospective non-interventional study of a fixed cohort of very elderly subjects. PARTICIPANTS AND SETTING: The subjects were 488 community-dwelling volunteers. Mean age at entry was 79 years (range 75-85). All subjects were ambulatory, non-demented, and free of terminal illness at baseline. Participants were evaluated at the gerontology department of an urban medical school. MAIN OUTCOME MEASURES: Cardiovascular morbid and mortal events that were followed included fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, and death. Prevalence of unrecognized myocardial infarction defined by electrocardiographic changes was also assessed. RESULTS: When hypertension was defined by history, current use of medications, or measured elevations in blood pressure, 78% of the subjects could be considered hypertensive. Univariate analysis showed an increased incidence of strokes in subjects with measured hypertension (P = 0.04). Subjects with elevated blood pressure (untreated) were more likely to develop clinically unrecognized myocardial infarction (P = 0.017). Multivariate survival analysis showed hypertension to be a modest predictor of overall cardiovascular disease (P = 0.067) but not of all-cause mortality. Left ventricular hypertrophy was a predictor of cardiovascular disease (P = 0.013) and all-cause mortality (P = 0.008). Age remained a significant risk factor for these endpoints, even in the very old. Isolated systolic hypertension was analyzed separately and in univariate analysis was a risk factor for stroke but not other cardiovascular morbidity. CONCLUSIONS: Hypertension at advanced age remains a modestly important risk factor in the development of cardiovascular disease.

Age Factors

B-cell activation and differentiation by HIV-1 antigens among volunteers vaccinated with VaxSyn HIV-1.

The generation of memory B cells in response to vaccination with a baculovirus-derived recombinant gp160 candidate AIDS vaccine, VaxSyn HIV-1, was investigated in 12 healthy human volunteers who were immunized with VaxSyn HIV-1, hepatitis B vaccine, or alum adjuvant alone on days 1, 28, 180, and 540. Peripheral blood mononuclear cells were collected pre- and post-immunization and cultured unstimulated or with pokeweed mitogen (PWM), VaxSyn HIV-1 (rgp160), or HIV-1 lysate (iHIV-1) for 7 days before polyclonal and HIV-1-specific IgG production in culture supernatants (SNs) were measured. No differences were seen in the spontaneous or PWM-induced IgG production in SN from vaccinees and controls. Only vaccinee SN contained higher-than-normal levels of polyclonal IgG after stimulation with either rgp160 or iHIV-1, especially after the second and third booster immunizations on days 180 and 540, respectively. There were also contemporaneous increases in HIV-1-specific antibody in SN of all vaccinees, albeit at different time points throughout the study. We conclude that VaxSyn HIV-1 induces antigen-specific B-cell responses with the generation of memory B cells in vivo that can be reactivated in vitro to deliver an anamnestic response.

AIDS Vaccines

Clinical and angiographic characteristics and outcome of patients with rest-unstable angina occurring during regular aspirin use.

Today many patients admitted with an acute coronary syndrome are already taking aspirin. Because they have symptoms despite antithrombotic therapy, these patients are presumed to be at higher risk for subsequent clinical events. In a pilot trial of antithrombotic therapy in patients with unstable angina at rest or non-Q wave infarction, 93 patients admitted within 48 h of pain were prospectively followed up for 12 weeks. On admission, 29 patients (31%) were already taking daily aspirin; 64 (68%) were receiving no antiplatelet agent. After enrollment all patients received antithrombotic therapy with either aspirin or heparin according to protocol regardless of prior aspirin use. The two groups (prior users versus nonusers of aspirin) were similar with regard to age, gender, coronary risk factors, prior antianginal medication, duration of symptomatic coronary disease, presentation with non-Q wave infarction and extent of electrocardiographic changes on admission. Quantitative analysis of coronary arteriograms (on a 0 to 10 scale) showed similar myocardium-in-jeopardy scores (JS). Follow-up events (recurrent ischemia [Isch], infarction [MI] and revascularization [Revasc]) were: (formula: see text) Aspirin users experiencing rest angina are similar to other patients with ischemic rest pain. The "resistant to aspirin" group does not constitute a subgroup that is at higher risk for cardiac events or revascularization.

Adult

Usefulness of ST-segment changes in greater than or equal to 2 leads on the emergency room electrocardiogram in either unstable angina pectoris or non-Q-wave myocardial infarction in predicting outcome.

To determine the reliability of the admission electrocardiogram in predicting outcome in patients hospitalized for chest pain at rest, 90 patients were randomized into a trial of aspirin versus heparin in unstable angina or non-Q-wave myocardial infarction, and prospectively followed for 3 months. The emergency room admission electrocardiogram was analyzed for ST-segment deviation greater than or equal to 1 mm/lead and T-wave changes. Unfavorable outcomes were recurrent ischemic pain, myocardial infarction and coronary revascularization with angioplasty or surgery. In patients who underwent coronary arteriography, a myocardium in jeopardy score ranging from 0 to 10 was assigned, based on the number of vessels with a diameter stenosis greater than or equal to 70% and the location of the stenoses. Considering all 90 patients, an admission electrocardiogram with ST-segment deviation in greater than or equal to 2 leads had a positive predictive value for adverse clinical events of 79% and a negative predictive value of 64%. In the subset of patients without left ventricular hypertrophy and whose admission electrocardiograms were recorded during chest pain (62 of 90), the positive predictive value of ST deviation in greater than or equal to 2 leads improved to 89% and the negative value to 72%. Of the 62 patients, 53 underwent coronary arteriography. There was a positive linear correlation between the total number of leads with ST-segment deviation and the myocardium in jeopardy score (r = 0.80, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

A fluorescence technique to distinguish attached from ingested erythrocytes and zymosan particles in phagocytosing macrophages.

While investigating the role of [Ca2+]i in Fc receptor-mediated phagocytosis, we found that clamping the [Ca2+]i to low levels by a variety of methods often led to increased plasma membrane permeability, rendering the hypotonic lysis method for calculating the phagocytosis index unreliable. To overcome this difficulty we developed a method for calculating the phagocytosis index of IgG-coated RBC that does not depend on hypotonic lysis. It depends on the ability of ingested RBC to create dark-appearing phagocytic vacuoles when the cytoplasm of murine macrophages is stained with acridine orange. Uningested or partially ingested RBC do not change the appearance of the otherwise uniformly stained cytoplasm of the macrophages. Since this method does not rely on hypotonic lysis to distinguish attached from ingested RBC, it can be used in situations when macrophages are unusually sensitive to hypotonic treatment (e.g. after clamping the macrophage [Ca2+]i to low levels). It can also be applied to the study of phagocytosis of particles that are not susceptible to hypotonic lysis (e.g., zymosan).

Acridine Orange

Comparison of celiprolol and propranolol in stable angina pectoris. Celiprolol International Angina Study Group.

The comparative antianginal effects and safety of propranolol and celiprolol, a highly beta 1-selective adrenoceptor blocker with selective partial beta 2-adrenoceptor agonist activity, were assessed in an international multicenter, placebo run-in, active control, double-blind, randomized, titration-to-effect study of 140 patients with stable, exercise-induced angina pectoris. At baseline, all patients received placebo for 2 weeks, then titrated doses of once-daily celiprolol (200, 400, 600 mg) or twice-daily propranolol (total daily dose 80, 160, 320 mg) over 4 weeks, followed by a 2-week maintenance period. Heart rate and blood pressure, at rest and with exercise, weekly anginal attack frequency, nitroglycerin consumption and symptom-limited treadmill exercise times (modified Bruce protocol) were assessed. Compared with their respective baselines, both celiprolol and propranolol reduced anginal attack and nitroglycerin consumption rates to a comparable degree, while improving exercise tolerance (p less than 0.05). Treatment with propranolol compared with celiprolol, however, was associated with a significantly lower heart rate at rest (p less than 0.01). The double-product at the conclusion of exercise testing was significantly reduced by both drugs. Celiprolol and propranolol had similar effects on blood pressure, and were well tolerated. More symptomatic bradycardia occurred with propranolol. Despite the differences in their hemodynamic actions, once-daily celiprolol is as effective as twice-daily propranolol in the treatment of patients with stable angina pectoris.

Adrenergic beta-Antagonists

Sustained ventricular tachycardia associated with sarcoidosis: assessment of the underlying cardiac anatomy and the prospective utility of programmed ventricular stimulation, drug therapy and an implantable antitachycardia device.

The presentation, cardiac anatomy and utility of programmed ventricular stimulation in seven patients with sustained ventricular tachycardia associated with sarcoidosis are described. The mean patient age was 38 +/- 8 years. Pulmonary involvement was apparent in three patients and no systemic manifestations of sarcoidosis were present in one patient. All patients had electrocardiographic abnormalities at rest and six had a left ventricular ejection fraction less than 45%. All seven patients had left ventricular wall motion abnormalities and five had mitral valve dysfunction. Sustained ventricular tachycardia was easily induced in all patients. Spontaneous sustained ventricular tachycardia was not prevented with corticosteroid administration. Despite antiarrhythmic drug therapy, two patients had sudden cardiac death and an additional four had recurrence of ventricular tachycardia. Four patients had an automatic cardioverter-defibrillator implanted and received drug therapy; all four received appropriate shocks. This report represents the largest descriptive series of consecutive patients with sustained ventricular tachycardia associated with sarcoidosis. Antiarrhythmic drug therapy of ventricular tachycardia in patients with sarcoidosis, even when guided with programmed ventricular stimulation, is associated with a high rate of arrhythmia recurrence or sudden death, or both. Thus, implantation of an automatic antitachycardia device (cardioverter-defibrillator) should be considered as primary therapy in such patients. Furthermore, sarcoidosis should be excluded, with Kveim skin testing if necessary, in any patient with sustained ventricular tachycardia of unknown origin.

Adult

Ca(2+)-independent F-actin assembly and disassembly during Fc receptor-mediated phagocytosis in mouse macrophages.

Phagocytosis of IgG-coated particles by macrophages is presumed to involve the actin-based cytoskeleton since F-actin accumulates beneath forming phagosomes, and particle engulfment is blocked by cytochalasins, drugs that inhibit actin filament assembly. However, it is unknown whether Fc receptor ligation affects the rate or extent of F-actin assembly during phagocytosis of IgG-coated particles. To examine this question we have used a quantitative spectrofluorometric method to examine F-actin dynamics during a synchronous wave of phagocytosis of IgG-coated red blood cells by inflammatory mouse macrophages. We observed a biphasic rise in macrophage F-actin content during particle engulfment, with maxima at 1 and 5 min after the initiation of phagocytosis. F-actin declined to resting levels by 30 min, by which time particle engulfment was completed. These quantitative increases in macrophage F-actin were reflected in localized changes in F-actin distribution. Previous work showed that the number of IgG-coated particles engulfed by macrophages is unaffected by buffering extracellular calcium or by clamping cytosolic free calcium concentration ([Ca2+]i) to very low levels (Di Virgilio, F., B. C. Meyer, S. Greenberg, and S. C. Silverstein. 1988. J. Cell Biol. 106: 657-666). To determine whether clamping [Ca2+]i in macrophages affects the rate of particle engulfment, or the assembly or disassembly of F-actin during phagocytosis, we examined these parameters in macrophages whose [Ca2+]i had been clamped to approximately less than 3 nM with fura 2/AM and acetoxymethyl ester of EGTA. We found that the initial rate of phagocytosis, and the quantities of F-actin assembled and disassembled were similar in Ca(2+)-replete and Ca(2+)-depleted macrophages. We conclude that Fc receptor-mediated phagocytosis in mouse macrophages is accompanied by an ordered sequence of assembly and disassembly of F-actin that is insensitive to [Ca2+]i.

Actin Cytoskeleton

Angiotensin converting enzyme inhibitors as initial monotherapy in severe hypertension. Quinapril and captopril.

This 6-week, double-blind, parallel-group study compared the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitors quinapril and captopril as initial monotherapies in patients with severe hypertension (diastolic blood pressure [DBP] greater than or equal to 115 and less than or equal to 130 mm Hg). A total of 97 patients, aged between 18 and 70 years, were randomized to 5 mg oral quinapril twice daily or 25 mg captopril twice daily with maximum titration to 20 mg quinapril twice daily or 100 mg captopril twice daily. With the morning dose 25 mg hydrochlorothiazide (HCTZ) could be added at week 4 of the double-blind phase or earlier if required for safety considerations. For the monotherapy phase, mean reductions in DBP of 12.1 mm Hg were achieved with both treatments. Clinical response rates (reduction in DBP greater than or equal to 10 mm Hg) were 58% for quinapril and 44% for captopril. At the end of therapy, with optional HCTZ, mean reductions in DBP were 19.0 mm Hg for the quinapril-treated group and 16.2 mm Hg for the captopril-treated group. None of the differences achieved statistical significance. Headache was the most frequently reported adverse event in both treatment groups with 8 reports each. No clinically significant changes in laboratory data were observed in any parameter for either treatment group. Quinapril and captopril provide comparable efficacy and safety in treatment of severe hypertension when used as initial monotherapy and with the addition of optional HCTZ.

Administration, Oral

Hemodynamic and myocardial energetic effects of CK-3197, a selective positive inotropic agent.

CK-3197 was developed as a selective positive inotropic agent for the treatment of congestive heart failure. We compared the hemodynamic and myocardial energetic effects of CK-3197 to ouabain in the pentobarbital-anesthetized dog. Fifteen minutes after intravenous (i.v.) administration of CK-3197 (0.1, 0.3, and 1.0 mg/kg) to five dogs, mean left ventricular (LV) dP/dt increased by 24, 68, and 109% and mean arterial pressure (MAP) decreased by 4, 9, and 18%, respectively, from basal values. CK-3197 was 11 times more potent as a positive inotropic agent than as a vasodilator. Heart rate (HR) increased by 5, 14, and 24% after these doses of CK-3197, whereas LV end diastolic pressure (LVEDP) decreased by 4 mm Hg after the highest dose of compound. LV oxygen consumption (MVO2) and stroke MVO2 increased by 9, 25, and 102% and 1, 8, and 58%, respectively, at the peak of the increases in LV dP/dt. Ouabain (0.02 and 0.03 mg/kg, i.v.) increased MAP (12 and 22%), HR (2 and 20%), and LV dP/dt (19 and 36%), with a 14 and 16% increase in LV MVO2 and a 12 and -6% change in stroke MVO2. Thus, CK-3197 is a selective, positive inotropic agent with preload reducing activity in the dog. CK-3197, similar to ouabain, produced energy-efficient positive inotropic responses with either no increase in MVO2 or increases in myocardial oxygen consumption that were less than the expected 1:1 ratio with LV dP/dt. Therefore, CK-3197 may have significant utility in the clinical treatment of congestive heart failure.

Animals

A composite model of the auditory periphery for the processing of speech based on the filter response functions of single auditory-nerve fibers.

A composite model of the auditory periphery, based upon a unique analysis technique for deriving filter response characteristics from cat auditory-nerve fibers, is presented. The model is distinctive in its ability to capture a significant broadening of auditory-nerve fiber frequency selectivity as a function of increasing sound-pressure level within a computationally tractable time-invariant structure. The output of the model shows the tonotopic distribution of synchrony activity of single fibers in response to the steady-state vowel [e] presented over a 40-dB range of sound-pressure levels and is compared with the population-response data of Young and Sachs (1979). The model, while limited by its time invariance, accurately captures most of the place-synchrony response patterns reported by the Johns Hopkins group. In both the physiology and in the model, auditory-nerve fibers spanning a broad tonotopic range synchronize to the first formant (F1), with the proportion of units phase-locked to F1 increasing appreciably at moderate to high sound-pressure levels. A smaller proportion of fibers maintain phase locking to the second and third formants across the same intensity range. At sound-pressure levels of 60 dB and above, the vast majority of fibers with characteristic frequencies greater than 3 kHz synchronize to F1 (512 Hz), rather than to frequencies in the most sensitive portion of their response range. On the basis of these response patterns it is suggested that neural synchrony is the dominant auditory-nerve representation of formant information under "normal" listening conditions in which speech signals occur across a wide range of intensities and against a background of unpredictable and frequently intense acoustic interference.

Animals

Resolution of ventricular tachycardia and endocardial tuberculoma following antituberculosis therapy.

A 23-year-old woman presented with sustained ventricular tachycardia and was found to have an endocardial mass by echocardiography and by magnetic resonance imaging. The diagnosis of cardiac endocardial tuberculoma was made, and she was treated with antituberculous therapy and an antiarrhythmic drug for one year. After a year, the mass was no longer present, and with all antiarrhythmic medications stopped, ventricular tachycardia could no longer be induced by electrophysiologic study. There has been no clinical recurrence.

Adult

Treatment of superior vena cava thrombosis with recombinant tissue type plasminogen activator.

Thrombotic occlusion of the superior vena cava is an uncommon but serious complication of chronic indwelling venous catheters. Several reports have shown thrombolytic therapy with intravenous streptokinase or urokinase to be effective in the treatment of this condition. We report a case of superior vena cava thrombosis in a 53-year-old woman receiving chemotherapy for breast carcinoma through a subcutaneously implanted venous access catheter who was successfully treated with peripheral infusion of recombinant tissue type plasminogen activator (rtPA).

Antineoplastic Combined Chemotherapy Protocols