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Biomedical subjects

R I Levin

Publications and source records attributed to R I Levin.

At least 37 records · Page 2Linked to original sources
PubMed1988

Quantitation of transient myocardial ischemia by digital, ambulatory electrocardiography.

Transient myocardial ischemia is more frequently silent than accompanied by angina. The frequency of ischemia varies markedly from day to day, so that in order to accurately define the total ischemic burden, it may be necessary to quantitate ischemic episodes for periods longer than 24 hours. Therefore, a programmable, digital device was developed for long-term, interactive, ambulatory monitoring of the electrocardiogram, which uses variations in a time-averaged ST level as an indicator of myocardial ischemia. The electrocardiographic signal is digitized at 256 Hz and analyzed by an algorithm. If ST depression is planar or downsloping and persists for more than 40 seconds, and if the ST depression is equal to or more than a user-programmed threshold, the device marks the onset of an ischemic event and times it. The algorithm has been validated by comparison of its analysis of the ST segment to human and computerized analyses of frequency-modulated Holter recordings and stress tests. To assess the feasibility and utility of long-term monitoring, patients with documented coronary artery disease were monitored continuously for 14-day periods. Of 26 patients enrolled, 8 completed a protocol for individualization of anti-ischemic therapy using transdermal nitroglycerin. Over 90% of ischemic episodes in this group of patients, all of whom had had a previous myocardial infarction, were silent. Treatment with 10 mg of transdermal nitroglycerin reduced the number of ischemic episodes by 59% and the duration of ischemia by 60% (p less than 0.001); there was no diminution in the effectiveness of treatment from week 1 to week 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1988

The effect of aspirin on the hemodynamic response to nitroglycerin.

The role of prostaglandins in mediating the hemodynamic response to nitroglycerin in vivo is controversial. To determine the effect of inhibiting prostaglandin production on the response to nitroglycerin, either placebo or aspirin (650 mg) was administered 1 hour prior to the administration of nitroglycerin (432 micrograms) sublingually to 40 healthy volunteers in a double-blind, randomized, cross-over study. Prior to nitroglycerin administration, blood pressure and pulse rate were determined noninvasively every 2 minutes until stable conditions were reached, and then after nitroglycerin administration determinations were made every 1 minute for the first 10 minutes, every 2 minutes for the next 10 minutes, and every 5 minutes until 30 minutes had elapsed. At peak response in the placebo study, nitroglycerin lowered systolic pressure from 117 +/- 10 to 111 +/- 10 mm Hg (p less than 0.0001). Unexpectedly, nitroglycerin increased diastolic pressure from 75 +/- 8 to 80 +/- 7 mm Hg (p less than 0.005), thus reducing pulse pressure significantly. Pulse rate after nitroglycerin increased from 72 +/- 11 to 85 +/- 14 (p less than 0.001). Aspirin slightly modified the pattern of response at 1 minute but altered neither the peak hemodynamic responses nor the areas under the time-pressure and time-pulse curves. Thus nitroglycerin-induced prostaglandin production does not play a major role in the systemic hemodynamic response to nitroglycerin in vivo.

Adolescent↗
PubMed1987

Non-steroidal anti-inflammatory drugs: how do they work?

Current dogma holds that non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (for example, indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli such as C5-derived peptides and leukotriene B4 even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and Quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the post-stimulation rise in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil enhance intracellular levels of cyclic AMP.

Adult↗
PubMed1986

Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells.

Since adenosine and its analogue 2-chloroadenosine prevent neutrophils from generating superoxide anion in response to chemoattractants, we sought to determine whether these agents could inhibit neutrophil-mediated injury of endothelial cells. The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP, 0.1 microM) enhanced the adherence of neutrophils to endothelial cells twofold (18 +/- 2% vs. 39 +/- 3% adherence, P less than 0.001) and caused substantial neutrophil-mediated injury to endothelial cells (2 +/- 2% vs. 39 +/- 4% cytotoxicity, P less than 0.001). 2-Chloroadenosine (10 microM) not only inhibited the adherence of stimulated neutrophils by 60% (24 +/- 2% adherence, P less than 0.001) but also diminished the cytotoxicity by 51% (20 +/- 4% cytotoxicity, P less than 0.002). Furthermore, depletion of endogenously released adenosine from the medium by adenosine deaminase-enhanced injury to endothelial cells by stimulated neutrophils (from 39 +/- 4% to 69 +/- 3% cytotoxicity, P less than 0.001). Indeed, in the presence of adenosine deaminase, even unstimulated neutrophils injured endothelial cells (19 +/- 4% vs. 2 +/- 2% cytotoxicity, P less than 0.001). These data indicate that engagement of adenosine receptors prevents both the adhesion of neutrophils and the injury they cause to endothelial cells. Adenosine inhibits injury provoked not only by cells that have been stimulated by chemoattractants but also by unstimulated cells. Based on this model of acute vascular damage we suggest that adenosine is not only a potent vasodilator, but plays the additional role of protecting vascular endothelium from damage by neutrophils.

2-Chloroadenosine↗
PubMed1986

Potential for real-time processing of the continuously monitored electrocardiogram in the detection, quantitation, and intervention of silent myocardial ischemia.

Current technology for monitoring and analyzing the ST segment allows for accurate description of ST-segment deviation, which in most cases is a valid measure of myocardial ischemia. In this article, the authors describe a new method that utilizes microprocessor analysis of the electrocardiogram to detect ST-segment deviation in ambulatory subjects. This technique results in the ability to characterize the total ischemic burden over long periods of time and to intervene acutely in order to treat myocardial ischemia and possibly to prevent complications of coronary artery disease.

Algorithms↗
PubMed1985

Physician choices in the treatment of angina pectoris.

Uncertainty about optimal treatment for many diseases results in heterogeneous management by definition. It was hypothesized that identifiable characteristics in a physician's background would influence the management of any such condition and thereby explain some of this heterogeneity. A vignette describing a patient with new-onset angina and a questionnaire ascertaining individual physician characteristics and management preferences were sent to attending physicians and house staff in the Department of Medicine at New York University School of Medicine. Although physicians believed very strongly that the patient had angina on the basis of the history, there was no consensus about managing the hypothetic patient. The age of the physician was the single most important predictor of management, with the younger half of the sample more likely to hospitalize (p less than 0.001), less likely to prescribe nitroglycerin as a sole therapy (p less than 0.005), and more likely to prescribe beta blockers (p less than 0.005). The era in which a physician trains may determine practices that persist for a lifetime. These findings may have important implications for medical education and the quality and cost of medical care.

Age Factors↗
PubMed1985

Activator headgear therapy.

A method of treatment is described using an activator and cervical headgear simultaneously to correct malocclusions of the Class II, Division 1 type. The case reports of ten treated patients are used to demonstrate the effects of the application of this technique. Changes in the dentition and facial skeleton were analyzed and the significance of the different responses to the application of the same appliances assessed. The hypothesis proposing that a simultaneous application of both appliances may result in a number of desirable effects greater than that induced by each individual appliance is examined. The hypothetical basis for the application of this technique is partially substantiated by the clinical observations. Within a period of about 1 year, correction of the Class II molar occlusion to a Class I molar occlusion is obtained, with a simultaneous reduction of overbite and overjet. Skeletal changes were found to be variable and related to facial type and the rate of facial growth. Brachyfacial and mesofacial types responded most favorably to treatment. The most favorable effects were observed when there was a large quantitative mandibular growth and brachyfacial or mesofacial growth pattern. In dolichofacial types with a slow mandibular growth rate, mandibular rotation was found to be clockwise; cervical traction appears contraindicated, and a combination of activator with occipital medium to high pull is considered more appropriate.

Activator Appliances↗
PubMed1985

Modes of action of aspirin-like drugs.

Current dogma holds that nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (e.g., indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli, such as C5-derived peptides and leukotriene B4, even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3 mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the poststimulation increase in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil activation as reflected by their capacity to inhibit movements of Ca and to enhance intracellular levels of cyclic AMP.

Anti-Inflammatory Agents↗
PubMed1985

Human neutrophil elastase modulates platelet function by limited proteolysis of membrane glycoproteins.

During blood coagulation human polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/liter. We therefore studied the effect of elastase on platelet structure and function. Physiologic concentrations of elastase specifically inhibited thrombin-induced platelet aggregation and ristocetin-induced agglutination of washed platelets in a time- and dose-dependent manner. This was associated with a decrease in the number of high affinity thrombin binding sites on the platelet surface (analysis by "Ligand" program) from 31 per platelet to 12 per platelet (P less than 0.05). As analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, treatment of 3H-labeled platelets with elastase resulted in a decrease in the percent glycoprotein at 130,000-150,000 Mr = and an increase in the percent protein at Mr = 102,000. The supernatant from elastase-treated platelets contained a Mr = 88,000 glycoprotein not found in the supernatant from untreated platelets. Immunoprecipitation studies with monoclonal antiglycoprotein Ib demonstrated that treatment of whole platelets with physiologic concentrations of elastase resulted in proteolytic cleavage of glycoprotein Ib. Elastase treatment of glycoprotein immunoisolated with monoclonal antiglycoprotein Ib antibody resulted in formation of a glycopeptide with the same electrophoretic mobility as the Mr = 102,000 membrane-related glycopeptide. In contrast, analysis by Western blot technique using antiglycoprotein IIb and IIIa antibodies demonstrated that elastase did not degrade glycoproteins IIb or IIIa. We conclude that elastase inhibition of thrombin-induced platelet stimulation is accompanied by (a) a reduction in the number of thrombin binding sites per platelet and (b) proteolysis of glycoprotein Ib.

Blood Platelets↗
PubMed1984

Aspirin inhibits vascular plasminogen activator activity in vivo. Studies utilizing a new assay to quantify plasminogen activator activity.

Vascular or tissue-type plasminogen activator (TPA) is a key enzyme in physiologic fibrinolysis. To study the role of prostaglandins in modulating the synthesis and release of TPA in vivo, we prospectively studied the effect of aspirin (650 mg/d X 2) on TPA activity in 13 human subjects before and after 10 min of forearm venous occlusion. TPA activity was quantified by a newly developed enzyme-linked immunosorbent assay that both measures and differentiates between TPA and urokinase (UK)-like plasminogen activator activity. This assay is based on the observation that the concentration of alpha 2-plasmin inhibitor-plasmin complexes in Reptilase-clotted plasma increases linearly in proportion to the amount of activator added. Resting TPA activity was higher in women than in men (0.56 +/- 0.59 vs. 0.15 +/- 0.11 U/ml, P = 0.049). Venous occlusion induced an eightfold rise in TPA activity in women (to 4.5 U/ml, P = 0.006) and a 15-fold rise in men (to 2.28 U/ml, P = 0.004), whereas UK activity was not detected. Aspirin inhibited the rise in TPA activity after venous occlusion by 69% in men (P = 0.004) and 70% in women (P = 0.014). In contrast, aspirin had no effect on pre- or post-occlusion hematocrits or Factor VIII-related antigen levels. There was no correlation between plasma salicylate level and percentage inhibition of TPA. Neither exogenous aspirin (0-1 microgram/ml) nor salicylate (0-70 micrograms/ml) inhibited the generation of alpha 2-plasmin inhibitor-plasmin complexes by exogenous TPA or interfered with the assay system. We conclude that aspirin may have an antifibrinolytic effect in man that has not been previously described.

Aspirin↗
PubMed1982

The urban emergency department: the issue of professional responsibility.

The urban emergency department is routinely asked to manage not only medical emergencies, but also a great variety of social emergencies. This situation is caused in part by budgetary constraints which prevent other agencies from providing 24-hour coverage. In an age of instant access to computerized information, these conditions often result in ethical and legal problems of extreme complexity. A case is presented which raises the issues of confidentiality and liberty in the fiduciary relationship between doctor and patient. The concept of personal care is found to be paramount.

Adult↗
PubMed1982

The interaction of sodium nitroprusside with human endothelial cells and platelets: nitroprusside and prostacyclin synergistically inhibit platelet function.

Sodium nitroprusside (NP) is a potent vasodilator that also inhibits platelet aggregation. To test the hypothesis that NP causes both of these effects by altering the balance between prostacyclin (PGI2) produced by endothelial cells and thromboxane A2 (TXA2) produced by platelets, we incubated each of these cell types with NP for 5 minutes and assayed the PGI2 and TXA2 produced. NP at pharmacologically achieved doses (0.01--30 micrograms/ml) inhibited platelet aggregation and resultant TXA2 synthesis in a dose- and time-dependent manner (p less than 0.001). The inhibition was not dependent on cAMP production, external calcium concentration, or suppression of TXA2 synthesis. NP did not alter the production of PGI2 by cultured human endothelial cells as measured by radioimmunoassay for 6-Keto-PGF1 alpha, the stable hydrolysis product of PGI2. However, supernates of NP-treated endothelial cells containing low, noninhibitory concentrations of NP unexpectedly inhibited platelet aggregation. This inhibition of platelet aggregation was due to synergy between PGI2 (0.1--3 nM) and NP (p interaction less than 0.03). The synergistic inhibition by NP and PGI2 of platelet aggregation and TXA2 synthesis in vivo may explain some of the beneficial actions of NP in the treatment of hypertension and congestive heart failure.

Calcium↗
PubMed1981

Nitroglycerin stimulates synthesis of prostacyclin by cultured human endothelial cells.

Nitroglycerin (NTG), the agent most commonly used to treat acute angina pectoris, is a vasodilator whose mechanism of action remains unknown. We hypothesized that NTG might induce endothelial cells to synthesize prostacyclin (PGI(2)), a known vasodilator and inhibitor of platelet aggregation. Therefore, cultured human endothelial cells were incubated with NTG at various concentrations for 1-3 min. PGI(2) biologic activity in the endothelial cell supernates was assayed by inhibition of platelet aggregation in vitro. The concentration of 6-keto-PGF(1alpha), the stable hydrolysis product of PGI(2), was measured by specific radioimmunoassay.NTG alone significantly inhibited platelet aggregation and thromboxane A(2) synthesis only at suprapharmacologic concentrations (>/=1 mug/ml). However, when NTG at clinically attainable concentrations (0.1-10 ng/ml) was incubated with endothelial cells, the endothelial cell supernates inhibited platelet aggregation in a dose-dependent manner. The inhibitor was heat labile. Radioimmunoassay of the endothelial cell supernates for 6-keto-PGF(1alpha) demonstrated that NTG elicited dose-dependent increments in the synthesis of PGI(2) by endothelial cells, ranging from 13% at NTG 10 pg/ml to 63% at NTG 10 ng/ml (P < 0.01, n = 10). Pretreatment of endothelial cells with either aspirin (50 muM for 120 min) or the prostacyclin synthetase inhibitor 15-hydroperoxyarachidonic acid (20 mug/ml for 15 min) abolished production of the platelet inhibitory substance. Synergy between NTG and PGI(2) in the inhibition of platelet aggregation was not present at clinically attainable concentrations of NTG.Thus, NTG at clinically attainable concentrations causes a dose-dependent increase in PGI(2) synthesis by endothelial cells. If this phenomenon occurs in vivo, the PGI(2) produced could ameliorate myocardial ischemia by causing peripheral vasodilation and decreasing cardiac work, inhibiting platelet aggregation and thromboxane A(2) synthesis, and possibly reversing coronary artery vasospasm.

Cells, Cultured↗