Posted by rob on July 23, 2005 under Uncategorized | 
Orenstein JM, Russo P, Didier ES, Bowers C, Bunin N, Teachey DT
Ultrastruct Pathol. 2005 May-Aug ; 29(3): 269-76
Microsporidia are ubiquitous obligate eukaryotic intracellular parasites that are now felt to be more akin to degenerate fungi than to protozoa. Microsporidia can be highly pathogenic, causing a broad range of symptoms in humans, especially individuals who are immunocompromised. The vast majority of human cases of microsporidiosis have been reported during the past 20 years, in patients with HIV/AIDS, while only relatively rare cases have been described in immunocompetent individuals. However, microsporidia infections are being increasingly reported in patients following solid-organ transplanation, where the main symptom has been diarrhea. The authors report the first case of pulmonary microsporidial infection in an allogeneic bone marrow transplant recipient in the United States and only the second case in the world. The patient, with a history of Hodgkin disease followed by acute myelogenous leukemia received a T-cell-depleted graft, but succumbed to respiratory failure 63 days post transplantation. An open lung biopsy, taken just before death, was originally thought to show toxoplasmosis. The correct diagnosis of microsporidiosis was made postmortem by light and electron microscopy. DNA polymerase chain reaction analysis confirmed the diagnosis and furthermore revealed it to be the dog strain of the microsporidia species Encephalitozoon cuniculi. Although to date rarely diagnosed, microsporidial infection should also be considered in the differential diagnosis of, e.g., unexplained pulmonary infection in bone marrow transplant patients.
Fatal Pulmonary Microsporidiosis Due to Encephalitozoon cuniculi Following Allogeneic Bone Marrow Transplantation for Acute Myelogenous Leukemia.
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Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S, Beran M, Estey E, Kantarjian HM, Issa JP
Blood. 2005 Jul 21;
An activating 1849G>T mutation of JAK2 tyrosine kinase was recently described in chronic myeloproliferative disorders (MPD). Its role in other hematological neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematological neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5/14 patients or 36%). JAK2 mutation was also detected in 3/16 (19%) patients with Philadelphia-chromosome (Ph)-negative chronic myelogenous leukemia (CML), 2/11 (18%) patients with megakaryocytic AML, 7/52 (13%) patients with chronic myelomonocytic leukemia, and in 1/68 (1%) patients with myelodysplastic syndromes. No mutation was found in Ph-positive CML (99 patients), AML M0-M6 (28 patients) and acute lymphoblastic leukemia (20 patients). We conclude that JAK2 1849G>T mutation is common in Ph-negative MPD but not critical for transformation to the acute phase of these diseases, and generally rare in aggressive leukemias.
JAK2 mutation 1849G >T is rare in acute leukemias but can be found in CMML, Philadelphia-chromosome negative CML and megakaryocytic leukemia.
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Manoharan A
IDrugs. 2000 Dec ; 3(12): 1525-33
Decitabine, a potent DNA methyltransferase inhibitor, which was originally under development by Pharmachemie, is being developed by SuperGen [341375]. Pharmachemie had been studying decitabine in phase II clinical trials for several leukemia indications in Europe and the US [328658,218338]. Preliminary results indicated that the compound was active in the treatment of myelodysplasia, relapsed leukemia, acute myeloid leukemia and postallogeneic progenitor cell transplant relapse [240549]. The compound is in phase II clinical trials with phase III trials scheduled to begin shortly [389367]. Decitabine has been used to treat myelodysplastic syndrome in a total of 125 patients, with an overall response rate of 49%. In a study using decitabine to treat chronic myelogenous leukemia in 81 patients, a response rate of 62% among patients in chronic phase of the disease was achieved [388947]. In a phase I/II trial designed to establish safety and efficacy in the treatment of sickle cell anemias treatment with decitabine generated a response in 100% of the patients tested: a total of eight patients were enrolled, each experienced elevated levels of fetal hemaglobin. Side effects were minimal and the drug was well tolerated. Plans for additional clinical studies of decitabine as a treatment for sickle cell anemia are underway [388307]. A phase II trial using a low dose of decitabine in patients with myelodysplastic syndrome has been completed. Of 66 patients entered, 62 were evaluable. The response rate was 48%, with a median response duration of 40 weeks. The mean survival from the start of therapy was 13 months [309098]. In a study with 37 CML patients, a 25% overall response rate was seen in those patients in the blastic phase of the disease, and a 52% response rate was observed in the accelerated phase patients. The most significant side effect was prolonged myelosuppression [278488]. The drug suppresses cellular growth in seven human tumor cell lines, possibly by reactivation of certain growth suppressor genes [278485].
Decitabine (SuperGen).
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The full moon rises behind the ancient temple of Posseidon, in Sounio.
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Crossman LC, Druker BJ, Deininger MW, Pirmohamed M, Wang L, Clark RE
Blood. 2005 Aug 1; 106(3): 1133-4
hOCT 1 and resistance to imatinib.
