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Biomedical subjects

S Sherry

Publications and source records attributed to S Sherry.

At least 19 recordsLinked to original sources
PubMed1991

Creation of the recombinant tissue plasminogen activator (rt-PA) image and its influence on practice habits.

American physicians have commonly practiced thrombolytic therapy for acute myocardial infarction with the recombinant form of tissue plasminogen activator (rt-PA), although its cost is much higher than that of streptokinase. The greater popularity of rt-PA is based on the belief that it is a more effective and a safer drug for achieving myocardial salvage and mortality reduction. However, a series of studies testing this assumption have not substantiated its greater efficacy or safety with respect to not only streptokinase but also urokinase and anisoylated plasminogen-streptokinase activator complex (APSAC). This editorial reviews the sequence of events that led to the creation of the rt-PA image, the mistaken premises on which it was based and the questions that need to be addressed if we are to strengthen the scientific method for evaluating similar types of drugs and its influence on practice habits including the costs to the health system.

Anistreplase↗
PubMed1991

Streptokinase and recombinant tissue plasminogen activator (rt-PA) are equally effective in treating acute myocardial infarction.

In recent trials, patients with myocardial infarction who received either recombinant tissue-type plasminogen activator (rt-PA) or streptokinase showed essentially no difference in the amount of myocardial salvage, in mortality reduction, or in the incidence of bleeding complications. These findings thus failed to fulfill the expectation that rt-PA would be twice as effective as streptokinase as a thrombolytic agent. The basis for this mistaken prediction was an unfortunate overemphasis on an inadequate surrogate endpoint, namely, the patency or reperfusion rate at 90 minutes after the start of therapy. Using the 90-minute patency or reperfusion rate as an endpoint has several serious limitations. First, it is an observation made at only one point in time during a dynamic process that may change even during the infusion proper. Second, a single view at 90 minutes completely disregards the possibility of subsequent reocclusion which often occurs within 1 hour after treatment. Third, an image at 90 minutes is more a reflection of the speed of thrombolysis than of whether lysis will eventually occur; the pace of clot lysis depends on both the agent used and the age of the thrombus. Fourth, lysis at 90 minutes is of minimal relevance for myocardial salvage unless observed within the time frame when infarction size can be limited significantly, which is generally less than 4 hours between symptom onset and the time that reperfusion is accomplished. Fifth, a stable state of vessel patency is meaningful for mortality reduction even if stabilization occurs after completion of the infarction. Such "late," but lasting, patency is a critical component of the "open vessel" principle and explains, at least in part, the survival benefit that accrues to patients treated even 24 hours after the onset of symptoms. There is currently no evidence that rt-PA has a more beneficial effect on survival or function than does streptokinase or any other plasminogen activator used in treating acute myocardial infarction; nor is there any evidence that patients who receive rt-PA therapy show a decreased incidence of bleeding complications compared with those who receive streptokinase, despite the relative fibrinogen-sparing attribute of rt-PA. Given the poor predictive value of the 90-minute angiogram for ultimate clinical advantage of one agent over another, studies that are limited to this endpoint are of marginal use in evaluating treatment regimens used in mortality studies. The best evidence to date indicates that streptokinase and rt-PA are of equivalent value for survival after acute myocardial infarction, a conclusion that can be justifiably challenged only with a valid mortality study.

Clinical Trials as Topic↗
PubMed1991

Thrombolytic therapy for noncoronary diseases.

Thrombolytic therapy has been used fairly extensively in the management of acute proximal deep-vein thrombophlebitis of the extremities, acute pulmonary embolism, and acute peripheral arterial thrombosis and embolism in addition to acute thrombotic coronary events. In the presence of acceptable indications and a favorable benefit to risk ratio, this form of therapy, when successful, has served as a useful adjunct in the management of these disorders. In deep-vein thrombophlebitis, lysis of the thrombus before permanent pathological changes (eg, organization, scarring) have occurred can prevent venous valvular dysfunction and postural venous hypertension and its complications, especially the postphlebitic syndrome. In the more severe forms of acute pulmonary embolism, thrombolytic therapy, when applied early after symptom onset, decreases morbidity and is likely to prevent a chronic increase in pulmonary vascular resistance and persistent pulmonary hypertension. In peripheral arterial thrombo-occlusive events, early restoration of flow through thrombolysis has been shown to limit ischemic damage and serve as a useful supplement to angioplasty or surgery. Thrombolytic therapy has been used less extensively in acute strokes. Here the danger of reperfusion causing bleeding into a softened area of brain undergoing infarction has slowed its evaluation for this disorder; its application to stroke remains experimental.

Acute Disease↗
PubMed1990

Pharmacology of anistreplase.

Eminase (anistreplase), or anisoylated plasminogen streptokinase activator complex (APSAC), is a reversibly inactivated lys-plasminogen-streptokinase activator complex that is given rapidly over a period of 2-5 minutes, and has a half-life in the circulation of 90-105 min. Eminase represents a significant advance in drug design for therapeutic thrombolysis based on convenience in administration, high gradient (especially initially) for diffusion into thrombus, improved fibrin binding, ability to lyse fibrin rapidly, improved stability in the circulation, long duration of action, and production of an antithrombotic state.

Anistreplase↗
PubMed1989

The origin of thrombolytic therapy.

The origin of thrombolytic therapy is briefly reviewed. It began 40 years ago with the demonstration that the injection into patients of a partially purified activator of the native plasminogen-plasmin enzyme system was capable of dissolving clotted blood and fibrinous loculations in the chest. However, the application of this form of therapy for the dissolution of intravascular thrombi had to await a series of further developments, including extensive purification of the thrombolytic agents, evidence that plasminogen activators would be more appropriate than plasmin for thrombolysis and proof, first in animals and then in humans, that thrombi could be dissolved by the systemic administration of plasminogen activators. The first study of thrombolytic therapy in acute myocardial infarction was reported in 1958. However, despite many studies conducted during the next 20 years, with encouraging reductions in mortality, thrombolytic therapy for acute myocardial infarction became established only when angiography provided visual evidence of the presence of a thrombus obstructing an infarct-related artery and of the achievement of prompt lysis with the administration of thrombolytic agents.

Coronary Disease↗
PubMed1988

Unresolved clinical pharmacologic questions in thrombolytic therapy for acute myocardial infarction.

Thrombolytic therapy has now become established as a useful therapeutic measure for the immediate treatment of an acute evolving transmural infarction. Nevertheless, several important and fundamental aspects of a pharmacologic nature remain to be resolved. Prominent among these is whether or not fibrin specificity of a thrombolytic agent provides important benefits, and whether heparin therapy as commonly employed to prevent rethrombosis has been effective. Review of the available data raises serious questions as to the validity of current views and the appropriateness of prevailing trends.

Fibrin↗
PubMed1988

Anxiety, depression, and menstrual symptoms among freshman medical students.

Based on data from a larger longitudinal study of medical students and physicians, this study establishes the incidence of some menstrual symptoms in a nonclinical population of 82 healthy, female, first-year medical students and investigates the correlation of self-reported anxiety and depression scores with these symptoms. Findings show that nearly half reported the frequent occurrence of at least one menstrual symptom that appeared to cause discomfort but did not interfere with performance. The data suggest an association between anxiety and depression scores and certain self-reported menstrual symptoms in this population. The study suggests the need for further investigation of the nature of the relationship between dysphoric moods and menstrual symptoms in healthy women.

Adult↗