Effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on rat vascular smooth muscle in vitro--the role of the endothelium.

Hypotension is a frequent side effect of the antidepressant treatment. It is controversial whether this effect is attributable to interactions within the central nervous or the cardiovascular system. We examined often used antidepressants for their vasoactive properties in vitro in rat aortal rings with and without endothelium. The influence of pre-incubation with the antidepressants (0.5 µM) on adrenergic elicited smooth muscle contraction and the effects of cumulative concentrations (0.05 µM-500 µM) of the antidepressants on isometric tension were measured. In addition, conceivable modulation of the NO-cGMP, adrenergic and potassium channel pathways were examined. Amitriptyline and fluoxetine inhibited, whereas tranylcypromine enhanced adrenergic elicited responses of smooth muscle contraction. The antidepressants amitriptyline, fluoxetine and tranylcypromine showed, to a different extent, vasorelaxing properties in the preparations pre-contracted with phenylephrine 0.1 µM; the pEC50, (means and S.E.M.) in descending order of potency: amitriptyline 6.98 (0.13), fluoxetine 6.11 (0.05), tranylcypromine 5.33 (0.05) (n=8 each, preparations with endothelium); or after pre-contraction with KCl 20 mM: fluoxetine 6.00 (0.06), tranylcypromine 4.99 (0.30), amitriptyline, 4.89 (0.11), (n=7 each, preparations with endothelium). Venlafaxine did not relax the aortal rings and even lead to further contraction of the endothelium intact preparations. The observed effects were partially endothelium dependent via activation of the NO-cGMP pathway and some probably mediated through K+ channel activation. Amitriptyline, fluoxetine and tranylcypromine relax rat aorta in vitro. They partially delay vascular smooth muscle reactions to adrenergic agonists and can lead to sustained hypotension episodes despite administration of sympathomimetic drugs.

Primary extranodal lymphomas of gastrointestinal localizations: a single institution 5-yr experience.

This study is aimed at comparison of patients with extranodal lymphomas based on pathohistological findings differences (MALT vs non-MALT) as well as regarding gastric and non-gastric localization, and determining the significance of clinical-laboratory parameters with respect to therapeutic response and length of survival. A total of 56 patients with extranodal non-Hodgkin's lymphomas of the gastrointestinal tract were evaluated over a 5-yr period. Regarding the localization of the disease, the stomach was most frequently affected, 39 patients (70%); followed by small and large intestines, 17 patients. As for the pathohistological findings, MALT lymphoma accounted for 70%, DLBCL 25%, while other subtypes accounted for 5%. Patients' distribution was analyzed according to CS based on both Ann Arbor and Lugano systems; however, the difference obtained between the groups was not statistically significant in both staging types of patients. Statistically significant difference in patients' distribution was not found with respect to IPI index, bone marrow infiltration, anemia, hypoalbuminemia, or histological subtype and localization. Difference in survival between patients according to the pathohistological type was not statistically significant also according to the type of the affected gastrointestinal tract organ. Statistical significance of difference according to survival probability was obtained based on age (survival is longer in patients over 55 yr of age); according to CS and according to Ann Arbor and Lugano classifications (the patients with lower CS live significantly longer); according to IPI index (the survival is significantly longer in patients with lower probability: IPI-0,1, and 2), as well as patients free of bone marrow infiltration whose survival is also significantly longer.

Ki-67 proliferative marker in lymph node aspirates of patients with non-Hodgkin's lymphoma.

Proliferative activity of lymphoma cells was tested by immunocytochemical staining with Ki-67 monoclonal antibody in 63 aspirates of peripheral lymph nodes sampled from patients suffering from non-Hodgkin's lymphoma. Referring to the dominant cell population in nodal aspirates, a rising trend of Ki-67 proliferative marker was noted from the small cells (X = 13.20) and small cells with notched nucleus (X = 43.52) and large cells (X = 79.47) with histopathologic equivalents corresponding to aggressive lymphoma. Statistical testing of the difference in the Ki-67 proliferative marker against demographic and clinical-laboratory characteristics of the studied patients revealed the levels of significance for the performance status, bone marrow infiltration, and albumin serum value. Correlation of cytomorphological and immunocytochemical results was tested against International Prognostic Index (IPI). Statistically significant correlation of Ki-67 with cytomorphology and REAL-immunocytochemical classification of lymphoma was confirmed, but not with the IPI index. In order to determine the prognostic importance of Ki-67 marker, the patients were classified into those with low Ki-67 (<20% of proliferating cells), mean proliferation index Ki-67 (range 20-59%), and high proliferative index Ki-67 (positive in over 60% of lymphoma cells). Testing Ki-67 with survival we have found that the low proliferative index was associated with the longest survival, median about 36 mo; for proliferative marker values ranging between 20 and 59%, the median survival was 30.4 mo; and survival of patients with the high proliferative index was only 12.9 mo.

[Acute megakarioblastic leukemia: de novo and transformation of chronic myeloid leukemia]. / Prikaz bolesnika s akutnom megakarioblastnom leukemijom.

Acute megakarioblastic leukemia (AMKL) is a rare myeloproliferative syndrome with a fulminant clinical course characterized by progressive pancytopenia, palior, weakness and severe haemorrhage. Two cases of AMKL are presented: a 18-year old male with pancytopenia and massive haemorrhage, lymphadenopathy, organomegaly and mediastinal tumour. The diagnosis of AMKL was established by cytological and immunocytochemical analyses of peripherial blood cells (blasts were GPIIIa and GPIb postitive), by histological analysis or the bone marrow and lymph node, and immunohistochemical analysis of lymph node. The second case had megakarioblastic transformation of HGL which was confirmed by cytomorphological and immunophenotypical analyses. In spite of therapy, the patients died soon after the first signs of the disease.