111In platelet scintigraphy for the noninvasive detection of carotid plaque thrombosis.

BACKGROUND AND PURPOSE: Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. METHODS: We compared the performance of (111)In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. RESULTS: Positivity at (111)In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. CONCLUSIONS: Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.

Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer.

PURPOSE: Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity. PATIENTS AND METHODS: One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units. RESULTS: One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms. CONCLUSION: Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.

Alteration in regulation of myocardial blood flow in one-vessel coronary artery disease determined by positron emission tomography.

The behavior of myocardial blood flow (MBF) regulation in territories supplied by angiographically normal vessels of patients with coronary artery disease (CAD) has been poorly investigated. Resting MBF and coronary reserve were evaluated in 32 patients with stable angina, no previous myocardial infarction, and isolated left anterior descending or left circumflex coronary artery stenosis (> or = 50% diameter narrowing). MBF was measured, in the absence of any medical therapy, by means of dynamic positron emission tomography and 13N-ammonia. MBF measurements at baseline and after intravenous dipyridamole (0.56 mg/kg administered over 4 minutes), were obtained both in the stenosis-related regions and in contralateral territories. As a control group, 14 normal subjects were evaluated according to the same protocol. At rest, the 32 patients with CAD had similar MBF values in the stenotic and remote regions (0.76 +/- 0.21 and 0.77 +/- 0.19 ml/min/g, respectively, p = NS); both these values were significantly (p < 0.01) reduced with respect to mean MBF in normal subjects (1.03 +/- 0.25 ml/min/g). The dipyridamole study was completed in 30 patients; these patients had lower values of maximal MBF in the stenotic than in the remote regions (1.52 +/- 0.65 vs 1.76 +/- 0.68 ml/min/g, p < 0.05); however, both these values were significantly reduced (p < 0.01) with respect to mean dipyridamole MBF in normal subjects (3.66 +/- 0.92 ml/min/g). Thus, in patients with CAD, resting and maximal MBF can be reduced not only in myocardial territories supplied by stenotic arteries, but also in territories supplied by angiographically normal arteries.

Scintigraphic evaluation of biliary leakage following laparoscopic cholecystectomy.

Three patients with biliary leakage following coelioscopic cholecystectomy after percutaneous drainage of abdominal collection underwent 99m Tc TRIMETHYL-BROMO IDA biliary scintigraphy. In all cases, scintigraphy showed the site of the leak with a good dynamic evaluation of tracer confirming the adequacy of percutaneous drainage. Two patients were treated conservatively; one underwent surgical repair of a common bile duct lesion because of the high output of bile despite nasobiliary drainage. Biliary scintigraphy provides useful information in case of suspicious biliary leakage after coelioscopic cholecystectomy.

Intrapleural fluid movements described by a porous flow model.

We injected technetium-labeled albumin (at a concentration similar to that of the pleural fluid) in the costal region of anesthetized dogs (n = 13) either breathing spontaneously or apneic. The decay rate of labeled activity at the injection site was studied with a gamma camera placed either in the anteroposterior (AP) or laterolateral (LL) projection. In breathing animals (respiratory frequency approximately 10 cycles/min), 10 min after the injection the activity decreased by approximately 50% on AP and approximately 20% on LL imaging; in apneic animals the corresponding decrease in activity was reduced to approximately 15 and approximately 3%, respectively. We considered label translocation from AP and LL imaging as a result of bulk flows of liquid along the costomediastinal and gravity-dependent direction, respectively. We related intrapleural flows to the hydraulic pressure gradients existing along these two directions and to the geometry of the pleural space. The pleural space was considered as a porous medium partially occupied by the mesh of microvilli protruding from mesothelial cells. Solution of the Kozeny-Carman equation for the observed flow velocities and pressure gradients yielded a mean hydraulic radius of the pathways followed by the liquid ranging from 2 to 4 microns. The hydraulic resistivity of the pleural space was estimated at approximately 8.5 x 10(5) dyn.s.cm-4, five orders of magnitude lower than that of interstitial tissue.

Coronary vasodilation is impaired in both hypertrophied and nonhypertrophied myocardium of patients with hypertrophic cardiomyopathy: a study with nitrogen-13 ammonia and positron emission tomography.

To assess regional coronary reserve in hypertrophic cardiomyopathy, regional myocardial blood flow was measured in 23 patients with hypertrophic cardiomyopathy and 12 control subjects by means of nitrogen-13 ammonia and dynamic positron emission tomography. In patients with hypertrophic cardiomyopathy at baseline study, regional myocardial blood flow was 1.14 +/- 0.43 ml/min per g in the hypertrophied (20 +/- 3 mm) interventricular septum and 0.90 +/- 0.35 ml/min per g (p less than 0.05 versus septal flow) in the nonhypertrophied (10 +/- 2 mm) left ventricular free wall. These were not statistically different from the corresponding values in control subjects (1.04 +/- 0.25 and 0.91 +/- 0.21 ml/min per g, respectively, p = NS). After pharmacologically induced coronary vasodilation (dipyridamole, 0.56 mg/kg intravenously over 4 min), regional myocardial blood flow in patients with hypertrophic cardiomyopathy increased significantly less than in control subjects both in the septum (1.63 +/- 0.58 versus 2.99 +/- 1.06 ml/min per g, p less than 0.001) and in the free wall (1.47 +/- 0.58 versus 2.44 +/- 0.82 ml/min per g, p less than 0.001). In addition, patients with hypertrophic cardiomyopathy who had a history of chest pain had more pronounced impairment of coronary vasodilator reserve than did those without a history of chest pain. After dipyridamole, coronary resistance in the septum decreased by 38% in patients without a history of chest pain, but decreased by only 14% in those with such a history (p less than 0.05). Coronary resistance in the free wall decreased by 45% in patients without and by 27% in those with a history of chest pain (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics of the intrapleural distribution of a radioactive bolus.

Through the use of a gamma-camera placed horizontally over the chest of 5 supine, anesthetized and spontaneously breathing dogs we studied the kinetics of the intrapleural spreading of 1 ml saline containing 2 mg of 99mTc labelled albumin (250 microCi/kg) injected at various points on the costal side. From the postinjection sequence of gamma-camera images, we defined, along the intrapleural spreading pathways, some regions of interest (ROI) displaying a preferential label accumulation. In all the animals the ROI roughly corresponded to the apical, mediastinal and latero-diaphragmatic regions. The kinetics of the intrapleural label distribution, estimated from the time course of the activity under the ROI, displayed an initial rapid phase, lasting a few minutes, followed by a marked slowing down of the exchange processes. At 30 min regional counts reached an apparent steady state, the activity values greatly varying (even by 10 fold) among the animals, for the ROI corresponding to the same anatomical region, independently on the site of injection. The mathematical modelling of the regional activity curves required the assumption of a progressive decrease in the exchange coefficients to account for a marked slowing down of the exchange processes with increasing time.

Regional protein absorption rates from the pleural cavity in dogs.

In five supine spontaneously breathing anesthetized dogs we injected into the pleural space 0.5-1 ml of saline solution containing 2 mg/ml albumin labeled with technetium-99m. By use of a gamma camera placed horizontally over the chest, we followed, up to 120 min, the activity over the whole lung and over the preferential accumulation areas of the label (regions of interest, ROI) that corresponded to the apical, mediastinal, and laterodiaphragmatic regions. Activities were corrected for the decay rate of the isotope used. On the average, the activity over the whole lung decreased by 27% up to 120 min. The overall activity over the ROI amounted to 44.3% after the injection and decreased to 24% of total at 120 min, thus accounting for 75% of the total decrease in activity. At 10 min, the activity per unit surface of the gamma camera image (As) was from 2.2- to 5.7-fold higher over the ROI than for the rest of the lung image. The decrease of As at 120 min was 18-, 13-, and 5-fold greater for mediastinal, diaphragmatic, and apical regions, respectively, compared with the rest of the lung image. The time course of the changes in As are discussed in terms of regional albumin egress rate based on the functional interaction between the Starling and the lymphatic mechanisms.