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Biomedical subjects

G V Sharma

Publications and source records attributed to G V Sharma.

At least 37 records · Page 2Linked to original sources
PubMed1991

Coronary bypass surgery improves survival in high-risk unstable angina. Results of a Veterans Administration Cooperative study with an 8-year follow-up. Veterans Administration Unstable Angina Cooperative Study Group.

To identify high-risk subgroups, 468 patients with unstable angina were prospectively stratified according to the clinical presentation of unstable angina (type I or type II) and left ventricular function (normal or abnormal) and were randomized to conventional medical therapy or surgical treatment with coronary bypass surgery. Type I patients (n = 374) were those who had progressive effort angina or recent angina at rest. Type II patients (n = 94) were those who had severe rest angina associated with ST-T changes on the electrocardiogram. Follow-up for 8 years showed that the cumulative mortality rates for type II patients with abnormal left ventricular function were significantly lower in the surgical patients compared with the medical cohorts (13% versus 46%, p less than 0.04). In the other subgroups, cumulative medical and surgical mortality rates were not different. Thus, type II patients with abnormal left ventricular function appear to be the subgroup of patients who are at the highest risk with medical therapy. Coronary bypass surgery significantly reduces the mortality in this high-risk subgroup of patients with unstable angina.

Angina, Unstable↗
PubMed1990

Internal mammary artery and saphenous vein graft patency. Effects of aspirin.

As part of two Department of Veterans Affairs Cooperative Trials, we obtained angiographic patency data for internal mammary artery (IMA) and saphenous vein grafts to the left anterior descending (LAD) coronary artery at 1 year after coronary artery bypass surgery. Patients received either aspirin 325 mg q.d., aspirin 325 mg t.i.d., aspirin 325 mg and dipyridamole 75 mg t.i.d., or placebo. Aspirin was initiated either 12 hours before or 6 hours after operation. Patients were stratified preoperatively for extent of disease and randomized to the therapies outlined above. There was no randomization to IMA versus saphenous vein grafts to the LAD. When the patients taking placebo were compared with those taking aspirin, there were no differences in the IMA (100.0% versus 92.1%, p = 0.385) or vein graft (88.8% versus 90.4%, p = 0.675) patency rates. The patency rate, irrespective of treatment, for all IMA grafts was 92.8% (220 of 237) versus 90.1% (345 of 383) for all vein grafts to the LAD (p = 0.309). Thus, both the IMA and vein grafts had excellent patency rates at 1 year. Aspirin did not alter this at 1 year, and there were no differences between IMA and vein graft patency to the LAD.

Aspirin↗
PubMed1989

Medical compared with surgical management of unstable angina. 5-year mortality and morbidity in the Veterans Administration Study.

We evaluated medical in comparison to surgical plus medical (surgical) treatment of unstable angina using a prospective randomized protocol that stratified patients by clinical presentation and by invasive evaluation of left ventricular (LV) function. Clinical presentations were as follows--type 1: progressive or new onset angina relieved by medication; type 2: prolonged bouts of angina poorly or incompletely relieved by medication. Abnormal LV function was arbitrarily defined as ejection fraction less than 0.50 or LV end-diastolic pressure 16 mm Hg or more. Of 468 patients, 237 were assigned to medical and 231 to surgical therapy. There were 374 type 1 and 94 type 2 patients. LV function was normal in 334 and abnormal in 134 patients. Compared with results at 24 months, this 60-month follow-up study showed important differences in survival for patients with three-vessel disease: 75% for medical and 89% for surgical patients (p less than 0.02). The cumulative 5-year rate of repeat hospitalizations for cardiac reasons was less with surgical patients for either clinical presentation. For type 1, medical patients had a 56% rate, and surgical patients had a 42% rate (p = 0.004). For type 2, medical patients had a 62% rate, and surgical patients had a 43% rate (p = 0.05). Overall mortality did not differ between the two treatments, and this remained true in type 1 versus type 2 patients and in those with normal versus abnormal LV function. However, regression analysis of medical and surgical groups with ejection fraction as a continuous variable showed that mortality of medical patients depended on ejection fraction (p = 0.004), whereas the mortality of surgical patients did not (p = 0.76), and survival in the surgical group was higher in the lowest ejection fraction tercile-73% for medical and 86% for surgical patients, p = 0.03. We conclude that surgery improves survival in patients with three-vessel disease and leads to fewer subsequent hospitalizations for cardiac reasons. An impaired ejection fraction had an adverse impact on survival of medical patients but not on surgical patients, and mortality in surgical patients was improved compared with medical patients in the lowest ejection fraction tercile.

Angina Pectoris↗
PubMed1988

Randomised controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism.

The effect of intravenous recombinant human tissue-type plasminogen activator (rt-PA) was compared with that of urokinase in 45 patients with angiographically documented pulmonary embolism (PE) in a randomised controlled trial. The two principal end-points were clot lysis at 2 h, as assessed by angiography, and pulmonary reperfusion at 24 h, as assessed by perfusion lung scanning. All patients received the full dose of rt-PA but urokinase infusions were terminated prematurely (on average after 18 h) in 9 patients because of allergy in 1 and uncontrollable bleeding in 8. By 2 h, 82% of rt-PA-treated patients showed clot lysis, compared with 48% of urokinase-treated patients (p = 0.008; 95% CI for the difference = 10-58%). Improvement in lung scan reperfusion at 24 h was identical in the two treatment groups. The reduction in fibrinogen did not differ significantly between the rt-PA and urokinase groups (45% vs 39% at 2 h and 34% vs 40% at 24 h). The results indicate that in the dose regimens employed, rt-PA acts more rapidly and is safer than urokinase in the treatment of acute PE.

Acute Disease↗
PubMed1988

Tissue plasminogen activator and acute pulmonary embolism.

We assessed the efficacy and safety of peripheral intravenous recombinant human tissue-type plasminogen activator (rt-PA) in 47 patients with angiographically documented pulmonary embolism (PE). We administered 50 mg/2 h and, if necessary, an additional 40 mg/4 h. By 6 hours, 94% of the patients had angiographic evidence of clot lysis that was slight in 5, moderate in 12, and marked in 27 patients. Among the 34 patients with pulmonary hypertension prior to treatment, average pulmonary artery pressure decreased from 43/17 (27) to 31/13 (19) mm Hg (P less than 0.0001). The average lung scan perfusion defect decreased from 37% before therapy to 16% (P less than 0.01) after therapy among the 19 patients who had pre- and post-treatment lung scans. Of 7 patients with pre- and post-treatment imaging and Doppler echocardiograms, hypokinetic right ventricular wall movement (mild in 1, moderate in 2, and severe in 4) normalized in 5 and improved to mild hypokinesis in 2. Right ventricular diameter decreased from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm (P less than 0.005). Fibrinogen decreased 33% from baseline at 2 h and 42% from baseline at 6 h. However, patients with the greatest degree of angiographic clot lysis at 2 h had a preponderance of fibrinogenolysis over fibrinolysis, demonstrated by a lower ratio of cross-linked fibrin degradation products to fibrin(ogen) degradation products (0.14 +/- 0.09 vs. 0.54 +/- 0.82) (P less than 0.04). Among selected patients, peripheral intravenous rt-PA is associated with rapid lysis of PE, improved pulmonary perfusion, and improved right ventricular function.

Biomarkers↗
PubMed1987

Historical overview of antithrombotic and thrombolytic therapy.

Early attempts to treat thromboembolic disorders focused on the prevention of thrombus formation, along with the prevention of extension and/or embolization of an existing thrombus. Antithrombotic therapy for these conditions included intravenous and oral anticoagulants and later antiplatelet agents, all of which remain in use today. Subsequent research sought a thrombolytic agent that could lyse a clot directly. Intravenously administered streptokinase and urokinase were found to act on the inactive proenzyme plasminogen to produce the active enzyme plasmin that could safely and effectively lyse fresh fibrin clots. These agents have proved effective for the treatment of myocardial infarction and pulmonary embolism, as well as peripheral arterial and venous thromboembolic conditions. Recent efforts have been directed toward a search for clot-specific agents that would avoid the systemic lytic state associated with the use of urokinase and streptokinase. Three clot-specific plasminogen activators are currently being evaluated: recombinant tissue-specific plasminogen activator, anisoylated streptokinase plasminogen activator complex, and pro-urokinase.

Anticoagulants↗
PubMed1987

Thrombolytic therapy of acute pulmonary embolism: current status and future potential.

Recombinant human tissue-type plasminogen activator (rt-PA), a relatively clot-specific fibrinolytic agent, represents a novel and promising approach to thrombolytic therapy of pulmonary embolism. Therefore, the efficacy and safety of peripheral intravenous rt-PA therapy were assessed in 47 patients with angiographically documented pulmonary embolism. The drug regimen was 50 mg over 2 hours followed by repeat angiography and, if necessary, an additional 40 mg over 4 hours. By 6 hours, 44 of the 47 patients had angiographic evidence of clot lysis that was slight (n = 5), moderate (n = 12) or marked (n = 27). Among the 34 patients with pulmonary hypertension before treatment (mean pulmonary artery pressure exceeding 17 mm Hg), the pressure decreased from 43/17 (mean 27) to 31/13 (mean 19) mm Hg (p less than 0.0001). Fibrinogen decreased 33% from baseline at 2 hours and 42% from baseline at 6 hours. There were two major complications that required surgical control of bleeding: hemorrhage from a pelvic tumor and mediastinal tamponade in a patient 8 days after coronary artery bypass surgery. The initial results demonstrate that, among selected patients, peripheral intravenous rt-PA can rapidly and, for the most part, safely lyse pulmonary embolism within 6 hours.

Acute Disease↗
PubMed1986

Acute pulmonary embolism treated with tissue plasminogen activator.

Recombinant human tissue-type plasminogen activator (rt-PA) was given via a peripheral vein to 36 patients with angiographically documented pulmonary embolism. The regimen was 50 mg/2 h followed by repeat angiography and, if necessary, an additional 40 mg/4 h. By 6 h, 34 of 36 patients had angiographic evidence of clot lysis, slight in 4, moderate in 6, and marked in 24. The quantitative score improved 21% by 2 h and 49% by 6 h. Fibrinogen decreased 30% from baseline at 2 h and 38% from baseline at 6 h. 2 patients had major complications: in one, bleeding from a pelvic tumour required surgery; in the other, who had had coronary artery bypass surgery eight days earlier, pericardial tamponade developed. These initial results in selected patients make a case for expanded investigational use of peripheral intravenous rt-PA in pulmonary embolism.

Acute Disease↗
PubMed1986

Intraoperative assessment of the physiologic significance of coronary stenosis in humans.

Coronary angiography is generally considered the gold standard in assessing the significance of coronary stenosis. The inadequacy of coronary angiography has frequently been demonstrated by intraoperative findings that differ from those projected by the catheterization report. To better assess the physiologic significance of coronary stenosis, we measured intramyocardial pH intraoperatively in 50 myocardial segments supplied by stenotic coronary arteries before and after revascularization in 42 patients undergoing coronary artery bypass grafting. The hemodynamic, electrocardiographic, and pH responses to atrial pacing were recorded intraoperatively before and after revascularization. The coronary angiograms, performed within 3 months before bypass grafting, were reviewed by a single independent observer. Preoperative and postoperative radionuclide ventriculograms were performed and also reviewed by an independent observer. In response to atrial pacing, a fall exceeding 0.02 pH units was considered to represent ischemia and was observed in 28 segments. Patients exhibiting this response comprised Group I. Twenty-two segments demonstrated a fall of less than 0.02 pH units or a rise in pH in response to atrial pacing. Patients having this response comprised Group II. Segments in Group I responded dramatically to revascularization, with the pH during atrial pacing rising from -0.09 +/- 0.01 to -0.02 +/- 0.01 (p less than 0.001). Nine patients demonstrated ischemic S-T changes during atrial pacing, all in Group I. Pre-pacing hemodynamic parameters were similar in both groups. Group I patients, however, demonstrated a significant fall in mean arterial pressure during atrial pacing, from 92.0 +/- 3.0 to 78.4 +/- 3.3 mm Hg (p less than 0.001) whereas Group II patients did not. Twelve segments that angiograms indicated were supplied by critically stenotic vessels (greater than 75%) failed to demonstrate a significant fall in their pH during atrial pacing. In these segments, intraoperative findings and postoperative results corroborated the metabolic findings. Coronary angiography, therefore, was only 45% specific in assessing physiologically significant obstructions. The degree of segmental wall motion abnormalities likewise correlated poorly with the pH changes. Unlike coronary angiography, the response of intramyocardial pH to pacing is an accurate metabolic tool to assess myocardial ischemia in humans.

Angina, Unstable↗
PubMed1984

Clinical and hemodynamic correlates in pulmonary embolism.

The clinical presentation of pulmonary embolism may be dominated by manifestations of pulmonary infarction or by the signs and symptoms of an acute hemodynamic disturbance. Most often, some manifestation is present along with hemodynamic abnormalities, which may range from shock or cardiac arrest to tachycardia.

Blood Pressure↗
PubMed1984

Pulmonary embolism.

It is estimated that 600,000 or more symptomatic episodes of pulmonary embolism occur each year in the United States, and this diagnosis is one that may often be missed. This article provides an appraisal of currently used diagnostic procedures, including laboratory tests, arterial oxygen tension, chest radiography, electrocardiography, lung scanning, and selective pulmonary angiography, and examines the available therapeutic options and their indications.

Angiography↗
PubMed1984

Is streptokinase safe during menses?

We used intravenous streptokinase to treat a young woman with deep venous thrombosis manifested during her menses. There was no increase in menstrual bleeding, and she was symptom free six months later. Because menstrual endothelium after the first day of menses relies on arteriolar constriction for hemostasis rather than the formation of fibrin, we think that streptokinase may not be contraindicated in thrombotic disorders that occur during menses after the first day.

Adult↗