Surapon Worapongpaiboon

Pulmonary arterial hypertension in previously splenectomized patients with β-thalassemic disorders

Our aim was to study the cause and describe the clinical features of pulmonary arterial hypertension (PHT) in splenectomized β-thalassemia (β-Thal) patients. Ten splenectomized β-Thal patients with systolic pulmonary artery (PA) pressure >30 mm Hg were evaluated by echocardiography, right-heart catheterization, and pulmonary angiography. Five of these patients later underwent hemodynamic studies. Echocardiography and pulmonary angiography on the 10 patients showed normal values of left ventricular systolic function and no findings of acute or chronic pulmonary embolism. Hemodynamic evaluation showed very high PA pressures associated with markedly increased pulmonary vascular resistance indices (PVRIs). Hematological evaluation of the 10 patients showed marked anemia, markedly increased numbers of nucleated red blood cells (nRBCs), and serum ferritin. Mean platelet count, plasma β2 thromboglobulin, and thrombin—antithrombin III complex levels were significantly increased. It was concluded that PHT can be found in splenectomized β-Thal patients. Features associated with PHT were female sex, hemoglobin E/β-Thal, status many years postsplenectomy, marked anemia, markedly increased nRBC count, thrombocytosis, and very high serum ferritin levels. PHT was not due to pulmonary emboli. Our findings suggested that severe PHT was due to increased PVRI from thrombotic pulmonary arteriopathy, likely from chronic low-grade hypercoagulability and platelet activation after splenectomy.

Generation of CD3+CD56+ cytokine-induced killer cells and their in vitro cytotoxicity against pediatric cancer cells

A certain number of pédiatrie cancer patients still succumb to relapse following conventional treatment of their malignancies. One of the mechanisms of relapse is escape from immunity. Adoptive cellular immunotherapy with effector cells has the potential to overcome this escape. In adults, the CD3+CD56+ cell, a cytokine-induced killer (CIK) cell, appears to be a promising effector cell type with the greatest cytotoxicity. This effector cell type may work in children as well. No similar studies with children have been published. We speculated that expanded CD3+CD56* cells obtained from pédiatrie cancer patients during remission would act similarly against various pédiatrie tumor cell lines; therefore, we undertook the present study to find support for our speculation. This study was undertaken to generate and expand CD3’CD56’ CIK cells from normal peripheral blood mononuclear cells (PBL) obtained from 6 children with cancer (2 with acute lymphoblastic leukemia, 2 with large cell lymphoma, and 2 with osteosarcoma) in remission after intensive chemotherapy and to study the cytotoxic activities of these cells against chronic myeloid leukemia cell line K562 t(9:22), 4 pédiatrie tumor cell lines [infant acute lymphoblastic leukemia RS4 t(4;ll), THL/AML acute lymphoblastic leukemia REH t(12:21), alveolar rhabdomyosarcoma Rh-Cr t(2;13), and Ewing sarcoma EW-Le t(11;22)], and 2 pédiatrie glioblastoma multiforme cultured cell lines (G74 and G77). CIK cells were generated and expanded in culture medium to which interferon y, monoclonal antibody against CD3, and interleukin 2 were added at appropriate times. Cells were counted by flow cytometry. Net lactate dehydrogenase release from target cells incubated with CIK cells was used as an index of CIK cell cytotoxicity against various pédiatrie tumor cell lines. Ihe results show that after 21 days in culture CD3*CD56+ CIK cells derived from the 6 pédiatrie patients accounted for a median of 28.3% of the entire culture (range, 10.7%-36.4%). Before expansion no such cells were found in any of the 6 children. Median lytic activity rates of CIK cells were 45.5% to 64.5%, rates that contrasted drastically to the lytic activity rates of PBL, which were only 8% to 12%. The findings of the present study are encouraging. They provide information for developing adoptive immunotherapy for future clinical trials with pédiatrie cancer patients, particularly those patients with minimal residual disease after intensive chemotherapy or stem cell transplantation (especially nonmyeloablative transplantation procedures).

Definite Ocular Sarcoidosis Using Endobronchial Ultrasonography with Transbronchial Needle Aspiration

Purpose. To introduce a minimally invasive procedure, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), to obtain a pathologic evidence of a definite ocular sarcoidosis in a patient who initially presented with presumed ocular sarcoidosis with pulmonary involvement. Methods. An EBUS-TBNA procedure was performed at perihilar lymph nodes, subcarina, and right paratrachea of the patient and specimen obtained was sent for histocytopathological studies. Result. Histocytopathological findings revealed aggregates of epithelioid histiocytes forming a noncaseous granuloma, a hallmark of sarcoidosis. Conclusion. EBUS-TBNA should be considered an alternative procedure to provide cytohistopathology proven diagnosis of definite ocular sarcoidosis.