A simple, rapid liquid chromatography/tandem mass spectrometric (LC–MS/MS) assay was developed and validated for the quantification of both unbound and total paclitaxel in plasma following treatment with Abraxane (ABI-007) or Taxol. Accurate and reproducible analysis of ABI-007, an albumin nanoparticle formulation of paclitaxel could not be achieved using previously published methodology designed for Taxol. The final validated method involved protein precipitation followed by vacuum filtration, in a 96-well format for rapid processing. The 4 min run employed gradient elution on a Waters SymmetryShield C8 (2.1 mm × 50 mm, 3.5 μm) column, followed by tandem mass spectrometric detection, in electrospray positive mode. Calibrator samples were prepared daily with paclitaxel and analyzed with both ABI-007 and paclitaxel quality control samples. To measure unbound drug, sample preparation was preceded by ultrafiltration. The assay was linear over the range of 10–2500 ng/mL, with dilution providing measurement up to 50,000 ng/mL. Within-run and between-run precision for all QC samples was less than 5.0% and 10.4%, respectively. Accuracy was high, with deviation of less than 6.1% for all QCs. Measurement of unbound paclitaxel was precise (BRP and WRP <10%).

In Dilated Cardiomiopathy (DCM), frequent apical thrombosis could be explained by modifications of the Left Ventricular (LV) shape and haemodynamic perturbations of apical flow.

Histological examination of pulmonary vessels is very important to estimate the reversibility degree of the pulmonary vascular modifications, which correlates with the evolution of many heart diseases and the results of surgical treatment. The aim of our study was to elaborate a repeatable method for prelevating pulmonary tissue, without the risks and the complications of the methods used in present. Our method was experimented on 35 dogs and 20 corpses, using a biopsy catheter specially created by us for this purpose. During right cardiac catheterization, after fixing the catheter in a pulmonary artery ram, 2-3 mm pulmonary tissue fragments were prelevated, and their macro and microscopical examination revealed no significant injuries at the puncture site. In conclusion, endovascular pulmonary biopsy can be a repeatable method, without risks, useful to follow the modifications of pulmonary circulation.

OBJECTIVE:It is well known that in the evolution of cardiac diseases, thromboembolic accidents are quite frequent. In patients with acute peripheral ischaemia, surgical treatment is usually the procedure of choice, but in some circumstances some of these patients cannot benefit from the surgical treatment. Conservative treatment rarely leads to satisfactory results. An alternative of therapy is the thrombolysis, but administration of Streptokinase in systemic dose can lead to serious thromboembolic accidents and hemorrhage. Intra-arterial administration of the drug, in small doses, can eliminate this risk. The aim of this study was to demonstrate the efficacy of intra-arterial thrombolysis in patients with cardiac diseases complicated with peripheral arterial emboli.METHOD:In the period 1984-1997, we performed a number of 84 intra-arterial thrombolyses. Sixty-one of them were performed in case of chronic or acute arterial obstruction of the inferior limbs, occurring in the evolution of chronic arterial disease, 14 in the patients with acute obstruction caused by emboli from cardiac cavities, and 9 in the patients with arterial embolism of other origin. We applied this procedure infusing Streptokinase intraarterially, continuously, directly and progressively in the thrombus, with a rate of 2-4000 unit/min, and a total dose more than 100,000-120,000 units. All patients had been consulted previously in a surgical unit and for different reasons surgical treatment was not indicated.RESULTS:We succeeded to repermeabilise the entire arterial route at all the patients (fact demonstrated by the clinical and Doppler examinations). We obtained complete primary repermeabilisation in 79% cases (11 cases), and repermeabilisation at 24 hours in all cases. We did not record major complications during this procedure.CONCLUSIONS:At the cases we studied (a small number), this method seems to be an alternative of therapy with good results in the restoration of obstructed arterial circulation. Intra-arterial administration of Streptokinase, in small doses, can eliminate the haemorrhagic and thromboembolic risks that appear in case of systemic administration of the drug.

In the past years, diagnosis of myocardial diseases became less difficult. A major contribution in this direction has the recent development of diagnosis methods. One of the most recent diagnosis procedures is the endomyocardial biopsy, which manages directly through the histologic examination to establish a clear diagnosis in myocardial diseases. This method provides faithful morphological data about the pathological changes in the myocardium. The aim of our study was to underline the importance of endomyocardial biopsy in an accurate diagnosis of different cardiomyopathies. In the period of 12 years (1986-1998), in the Cardiovascular Department of the First Medical Clinic Târgu-Mureş, Romania, were admitted 137 patients suffering from different cardiomyopathies. We performed a number of more than 100 endomyocardial biopsies on 25 of them, obtaining in each case 3 to 5 samples of endomyocardial tissue from the right ventricle. In all cases the Cordis bioptome was introduced in the right ventricle via femoralis vein. The complications were minor: ventricular extrasystoles. In all cases, we succeeded to obtain enough tissue for the histopathological examination, from different areas of RV. Histologic examination showed in all cases characteristic aspects of different cardiomyopathies. helping to clarify the diagnosis. After performing Endomyocardial Biopsy, we record an important increase of dilated cardiomyopathy percentage of diagnosis, from 40% to 72%. In patients with dilated cardiomyopathy, we observed a good correlation between hemodynamical data (Ejection Fraction, Left Ventricle End-Diastolic Pressure, etc.) and the index of myocardial damage, especially the degree of interstitial fibrosis. Using this method it is possible to distinguish different types of cardiomyopathies, such as: primary dilated cardiomyopathy, eosinophilic cardiomyopathy, myocarditis, idiopathic hypertrophic cardiomyopathy. Because the complications of this procedure are insignificant, and because of its important benefit for an accurate diagnosis, we recommend to apply this method for different cardiomyopathies.

It is well known in the literature that myocardial tissue is present in different degrees in pulmonary veins, but the eventual role of this myocardial tissue in pulmonary veins is not very clear at this moment. We presumed that one of the compensatory mechanisms in heart failure could be represented by the development of this myocardial tissue in the pulmonary veins. We studied the extension of this myocardial tissue in patients with dilated cardiomyopathy (DCM). We performed a histologic examination of the myocardial tissue from the pulmonary veins, in patients with heart failure in advanced stages. These patients died in the hospital and we obtained the pulmonary tissue for examinations during the autopsy. At the border between the media and the adventitia of the pulmonary vein, the myocardial tissue is present and is well developed. Some of the fibers have a sinuous course, others present a longitudinal aspect, especially in the external layers. In some sections bundles and bands of muscle fibers are present. In the sections where no myocardial tissue was shown, the smooth muscular fibers were very numerous. The necroptic histologic studies showed different degrees of hypertrophy of the myocardial tissue in the pulmonary veins, in the patients with heart failure in advanced stages. We observed that dilatation degree of cardiac cavities and decrease of the ejection fraction correlates with hypertrophy degree of the myocardial tissue in the pulmonary veins. This can be an argument for the compensatory role of this hypertrophy.