Parker Ja

Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion

Data from a non-randomised study have hinted that in patients with acute pulmonary embolism (PE), thrombolysis followed by heparin more rapidly reverses right-ventricular dysfunction and restores pulmonary tissue perfusion than does heparin alone. We have pursued this idea in a randomised protocol. 46 haemodynamically stable patients were randomised to recombinant tissue plasminogen activator (alteplase, rt-PA) 100 mg over 2 h followed by intravenous heparin and 55 to heparin alone. Right-ventricular wall motion was assessed qualitatively, and right-ventricular end diastolic area was estimated by planimetry from echocardiograms at baseline and at 3 and 24 hours. Pulmonary perfusion scans were obtained at baseline and 24 hours. In 39% of rt-PA patients but in only 17% of heparin alone patients right-ventricular wall motion at 24 hours had improved from baseline and in 2% and 17%, respectively, it worsened (p = 0.005). rt-PA patients also had a significant decrease in right-ventricular end-diastolic area during the 24 hours after randomisation and a significant absolute improvement in pulmonary perfusion (14.6% vs 1.5%). No clinical episodes of recurrent PE were noted among rt-PA patients, but there were 2 fatal and 3 non-fatal clinically suspected recurrent PEs within 14 days in patients randomised to heparin alone. rt-PA rapidly improves right-ventricular function and pulmonary perfusion among patients with PE and may lead to a lower rate of adverse clinical outcomes.

Evaluation of a New Bipyridine Inotropic Agent — Milrinone — in Patients with Severe Congestive Heart Failure

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.

Myocardial Salvage after Intracoronary Thrombolysis with Streptokinase in Acute Myocardial Infarction

Nine patients with acute myocardial infarction had cardiac catheterization and intracoronary infusions of streptokinase 2.3 to 4.3 hours (mean, 3.5) after the onset of symptoms. Occluded coronary arteries were opened within approximately 20 minutes in all patients, but reocclusion occurred in one patient. The immediate effect of thrombolysis on myocardial salvage was assessed with the intracoronary injection of thallium-201. Improved regional perfusion, indicating myocardial salvage after recanalization, was observed in seven of the nine patients. One patient, who had also sustained a nontransmural infarction one week before, had no change after thrombolysis. In the ninth patient, recanalization of a coronary artery was followed by reocclusion and worsening of the myocardial-perfusion defect. Intracoronary thallium-201 studies two weeks and three months after streptokinase infusion in two patients were unchanged in comparison with scintiscans performed 1.5 hours after thrombolysis. These short-term observations suggest that recanalization of obstructed coronary arteries after intracoronary thrombolysis can salvage jeopardized myocardium, However, evaluation of the long-term effects of this procedure on survival and myocardial function will require controlled clinical trials.

Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial

Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism.

Early reversal of right ventricular dysfunction in patients with acute pulmonary embolism after treatment with intravenous tissue plasminogen activator

To assess abnormalities of right heart function and their reversal with thrombolysis in pulmonary embolism, serial imaging and Doppler echocardiographic studies were performed before and after a 6 hour intravenous infusion of 80 to 90 mg of recombinant tissue-type plasminogen activator (rt-PA) in seven patients with segmental or lobar acute pulmonary embolism. None of the five men and two women had known prior pulmonary hypertension. Substantial clot lysis and improvement in pulmonary blood flow, as determined by serial pulmonary angiography and perfusion lung scanning, were achieved in all. Coincident with clot lysis, pulmonary artery systolic pressure decreased (from 42 +/- 11 to 26 +/- 7 mm Hg, p less than 0.005), right ventricular diameter decreased (from 3.9 +/- 1.0 to 2.0 +/- 0.5 cm, p less than 0.005) and left ventricular diameter increased (from 3.7 +/- 0.9 to 4.4 +/- 0.6 cm, p less than 0.01). Right ventricular wall movement, initially mildly, moderately or severely hypokinetic in one, two and four patients, respectively, normalized in five and improved to mild hypokinesia in two. Tricuspid regurgitation was present before lytic therapy in six patients. In five, flow velocity in the tricuspid regurgitant jets indicated a peak systolic right ventricular minus right atrial pressure gradient of 25 to 52 mm Hg. Tricuspid regurgitation was detected early after lytic therapy in only two patients. Systolic septal flattening was noted before but not after lysis. These findings confirm that pulmonary emboli may result in appreciable right ventricular dysfunction and dilation, resultant tricuspid regurgitation, abnormal septal position and decreased left ventricular size.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional ejection fraction: a quantative radionuclide index of regional left ventricular performance.

Radionuclide measurements of regional left ventricular ejection fraction were evaluated as a quantitative index of regional left ventricular function. Left ventricular regional ejection fractions were derived from background-corrected, time-activity curves in 43 patients assessed by both gated equilibrium radionuclide angiocardiography left ventricular contrast angiography. From a single, modified left anterior oblique projection, the regional change in background corrected counts was determined in each of three anatomic regions. The normal range for regional radionuclide ejection fraction was determined in 10 patients with normal contrast ventriculograms without obstructive coronary artery disease at coronary arteriography. Regional ejection fraction was compared with percent segmental axis shortening extent of akinetic segments in corresponding regions of thecontrast ventriculogram. Radionuclide roentgenographic methods were in agreement as to the presence or absence of abnormal wall motion in 83 of 99 left ventricular regions (84%) in 33 patients evaluated prospectively. Comparison of regional ejection fraction demonstrated significant differences between regions with roentgenographically determined normokinesis (75 ± 3%, mean ± SEM), hypokinesis (44 ± 3%, p ≤ 0.0005) akinesis (24 ± 5%, p ≤ 0.005). We conclude that the left ventricular regional ejection fraction provides a reliable quantitative assessment of regional left ventricular performance.

The SNMMI Practice Guideline for Therapy of Thyroid Disease with 131I 3.0

1UC Health University Hospital, Cincinnati, Ohio; 2Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; 3Beaumont Health System, Royal Oak, Michigan; 4Guy’s Hospital, London, United Kingdom; 5Columbia University Medical Center, New York, New York; 6Cincinnati Children’s Medical Center, Cincinnati, Ohio; 7New York–Presbyterian/Weill Cornell Medical Center, New York, New York; 8University of Southern California, Los Angeles, California; 9University of California at Los Angeles, Los Angeles, California; 10Vanderbilt University Medical Center, Nashville, Tennessee; 11Beth Israel Deaconess Medical Center, Boston, Massachusetts; 12Mallinckrodt Institute of Radiology, St. Louis, Missouri; 13Jacobi Medical Center, Bronx, New York; 14Vanderbilt University, Nashville, Tennessee; and 15Cedars-Sinai Medical Center, Los Angeles, California

An Evaluation of 99mTc-Labeled Red Blood Cell Scintigraphy for the Detection and Localization of Gastrointestinal Bleeding Sites

99mTechnetium-labeled red blood cell scintigraphy was performed upon 39 patients with clinical evidence for acute lower gastrointestinal bleeding from an unknown source. Seventeen of 39 patients (44%) had a scan became positive 6 or more h after injection, consistent with intermittent bleeding, in 8 of 17 patients (47%). In the 11 patients in whom the bleeding site was definitely identified by arteriography, surgery, or colonoscopy, scintigraphy correctly localized the bleeding site in 10 of 11 patients (91%). Four of 11 patients (36%) had an active bleeding site identified by arteriography. Ten of 17 patients (58%) with a positive scan required either gelfoam embolization (4 patients) or surgery (6 patients) to control the bleeding, whereas only 1 of 22 patients (5%) required surgery when the scan was negative. Six deaths occurred in the scan-positive patients compared with no deaths in the scan-negative patients. None of the 8 patients who had arteriography and no active bleeding site by scintigraphy had arteriographically demonstrable active bleeding. Scintigraphy provides a reliable noninvasive test to screen patients in whom arteriography is being considered to localize active bleeding sites. If the arteriogram is negative, the scintigraphic findings alone may guide the surgical or arteriographic intervention. In addition, scintigraphy identifies two patient populations which have considerably different morbidity and mortality.

Role of single photon emission computed tomography/computed tomography in localization of ectopic parathyroid adenoma: a pictorial case series and review of the current literature.

The parathyroid glands are located posterior to the upper and lower poles of the thyroid and are derived from the third and fourth pharyngeal pouches. Usually there are only 2 superior glands, whereas only 40% of patients have their inferior glands located near the inferior thyroid poles. Ectopic locations include the carotid sheath, anterior mediastinum, retropharynx, or intrathyroidal locations. Single photon emission computed tomography/computed tomography (SPECT/CT) offers the advantage of combining function and anatomy for exact localization of ectopic parathyroid adenomas. In this pictorial review, we present 4 cases of hyperparathyroidism caused by ectopic parathyroid adenomas and review the literature on the additional value of their localization with SPECT/CT. Combined SPECT/CT scanners permit more reliable localization of ectopic adenomas. The additional information can aid in exact preoperative localization. In one study of 16 patients, SPECT/CT identified 39% more lesions compared with SPECT imaging alone. In other comparisons of planar, SPECT and SPECT/CT imaging modalities, SPECT/CT permitted the highest reader confidence in localization, especially for mediastinal adenomas. Larger studies are needed to establish the role and cost-effectiveness of SPECT/CT.

Role of BRAFV600E in the First Preclinical Model of Multifocal Infiltrating Myopericytoma Development and Microenvironment

Myopericytoma (MPC) is a rare tumor with perivascular proliferation of pluripotent stem-cell-like pericytes. Although indolent, MPC may be locally aggressive with recurrent disease. The pathogenesis and diagnostic biomarkers of MPC are poorly understood. We discovered that 15% of benign MPCs (thyroid, skin; 3 of 20 samples) harbored BRAF(WT/V600E); 33.3% (1 of 3 samples) of BRAF(WT/V600E)-MPCs were multifocal/infiltrative/recurrent. Patient-MPC and primary MPC cells harbored BRAF(WT/V600E), were clonal and expressed pericytic-differentiation biomarkers crucial for its microenvironment. BRAF(WT/V600E)-positive thyroid MPC primary cells triggered in vitro (8.8-fold increase) and in vivo (3.6-fold increase) angiogenesis. Anti-BRAF(V600E) therapy with vemurafenib disrupted angiogenic and metabolic properties (~3-fold decrease) with down-regulation (~2.2-fold decrease) of some extracellular-matrix (ECM) factors and ECM-associated long non-coding RNA (LincRNA) expression, with no effects in BRAF(WT)-pericytes. Vemurafenib also inhibited (~3-fold decrease) cell viability in vitro and in BRAF(WT/V600E)-positive thyroid MPC patient-derived xenograft (PDX) mice (n = 5 mice per group). We established the first BRAF(WT/V600E)-dependent thyroid MPC cell culture. Our findings identify BRAF(WT/V600E) as a novel genetic aberration in MPC pathogenesis and MPC-associated biomarkers and imply that anti-BRAF(V600E) agents may be useful adjuvant therapy in BRAF(WT/V600E)-MPC patients. Patients with BRAF(WT/V600E)-MPC should be closely followed because of the risk for multifocality/recurrence.