Carcinoma, a fibrolamellar variant--immunohistochemical analysis of 4 cases

BACKGROUND/AIMS: To analyze, by means of immunocytochemistry, the cases of fibrolamellar variant of hepatocellular carcinoma (FLC), diagnosed in our Department. METHODOLOGY: The material comprised 4 FLC cases of tumors resected surgically. Besides the routine morphological assessment, we used a panel of immunohistochemical stainings including: hepatocellular cytokeratin, CK7, CK19, Ki67, PCNA, chromogranin A, synaptophysin, NSE, insulin, calcitonin, parathormon, CD34, EBV (LMP), Bcl2, cyclin D1. RESULTS: In 3 out of 4 cases, we observed co-expression of CK7 with hepatocellular CK. In addition, there was positive staining with some endocrine markers in the majority of patients. In one case, we found strong cyclin D1 immunoreactivity which correlated with EBV (LMP) immunoreactivity, in the same patient. The score of PCNA positivity varied between 15 and 90%. In all cases Ki67 was negative. CONCLUSIONS: The incidence of FLC, among all hepatocellular carcinomas diagnosed in our Department was 5.1%. In accordance with other reports, all our FLC cases were young patients without underlying liver disease. We were unable to find a correlation between FLC cellular immunophenotype, and histological and clinical markers of malignancy. In addition, it appears that PCNA is a better marker of cell-proliferation in FLC than Ki67. The significance of EBV infection in FLC requires further study.     

Serum level of beta-chemokine RANTES in patients with coronary artery disease

Chronic inflammatory process plays an important, as still not clear, role in pathophysiology of coronary artery disease (CAD), especially in acute coronary syndromes. Chemokines are present in atherosclerotic plaques and are essential factors in the recruitment of leukocytes and stabilization of atherosclerotic lesions. The aim of the study was the evaluation of RANTES serum level in patients with stabile CAD and seeking for correlations between RANTES serum level and progression of atherosclerotic lesions. The study included 83 patients from 22 to 87 years old, 41 women (mean age 61,2 +/- 12,5) and 42 men (mean age 58,8 +/- 15,4), who were admitted to the Cardiology Department for coronarography. After coronarography the patients were separated in 4 groups according to the presence of atherosclerotic lesions. Patients with atherosclerotic lesions were also divided depending on the severity of anginal pains to CCS II or CCS III classes. Blood samples for the measurement of RANTES serum level were taken at baseline conditions on the day after the admittance to the hospital. RANTES serum level was measured by enzyme-linked immunoabsorbent assay (ELISA) kit system (Endogen, MA, USA). There was not statistically significant differance in RANTES serum level between patients with CAD and subjects without atherosclerotic lesions in coronary arteries with or without arterial hypertension. Significantly higher levels of RANTES were observed in patients with atherosclerotic lesions in coronary arteries and anginal pains in CCS II class, than in patients with atherosclerotic lesions in coronary arteries and anginal pains in CCS II class, as well as in subjects without atherosclerotic lesions (respectively 58.5 vs 42.1 pg/ml and 54.5 vs 41.9 pg/ml, p<0.01). Significant positive corellations were found in patients with CAD between RANTES serum level and systolic blood pressure (r Pearson 0,291, p<0.05), and cholesterol (R Spearman 0.289, p<0.05). In all patients analysis of regression found significant correlation between RANTES serum level and systolic blood pressure (p 0.296, B 0.391, p<0.007). These results may indicate the active implication of chemokines in the pathophysiology of atherosclerotic lesions.     

Effects of SolCD39, a Novel Inhibitor of Platelet Aggregation,on Platelet Deposition and Aggregation after PTCA in a Porcine Model

Introduction: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP.Methods and Results: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5–7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by > 90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7 ± 1.4 versus 11.7 ± 3.4) and fibrin (3.5 ± 0.4 versus 4.2 ± 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAP_SFLLRN) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel.Conclusions: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study.Abbreviated Abstract. E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5–7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.Supported in part by a Merit Review grant from the Department of Veterans Affairs (A.J.M., M.J.B.), and by National Institutes of Health grants HL 47073, HL 46403, and NS 41462 (A.J.M., M.J.B.) and by Immunex Corp., Seattle, WA.     

Concomitant recovery of atrial mechanical and endocrine function after cardioversion in patients with persistent atrial fibrillation

OBJECTIVES: The purpose of this study was to evaluate left atrial mechanical function recovery and plasma atrial natriuretic peptide (ANP) release following successful cardioversion of persistent atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is characterized by functional deterioration, loss of atrial contraction, and elevation of plasma ANP levels. The response of ANP release toward atrial mechanical function after cardioversion of AF has not been fully examined. METHODS: We examined 29 patients with successfully cardioverted persistent AF in whom sinus rhythm was maintained for at least 30 days after cardioversion. We assessed mechanical function of the left atrium at 24 h and 7 and 30 days after cardioversion and evaluated plasma ANP level at the same time. Atrial mechanical function was assessed during echocardiographic examination by means of the peak velocity of the transmitral A-wave, early transmitral to atrial flow velocity ratio, and atrial filling fraction (AFF). The plasma ANP level was determined by the radioimmunoassay method. RESULTS: Plasma ANP levels were significantly reduced from 59.4 +/- 16.6 pg/ml to 31.1 +/- 9.2 pg/ml at 24 h after successful cardioversion. Within 30 days, we noted progressive improvement of atrial systolic function (increase in AFF from 21% to 31%, p < 0.05). At the same time, plasma ANP levels gradually increased from 31.1 +/- 9.2 pg/ml at 24 h to 36.9 +/- 12.8 pg/ml on day 30 following cardioversion (p < 0.05). CONCLUSIONS: Plasma ANP levels significantly decreased in patients with persistent AF after successful cardioversion. In the 30 days after cardioversion, gradual elevation of plasma ANP concentration was observed concomitantly with an increase of AFF. Plasma ANP release after successful cardioversion of persistent AF might be due to recovery of atrial mechanical function.