Autologous peripheral blood stem cell transplantation for adults with B-lineage acute lymphoblastic leukemia: a pilot study.

We conducted a pilot study on autologous peripheral blood stem cell transplantation (PBSCT) for 11 adults with B-lineage acute lymphoblastic leukemia (ALL) in first complete remission (CR) or even in those with more advanced stages. All patients achieved CR by induction therapy, of whom 10 were treated with anthracycline, vincristine and prednisolone-based regimens. After consolidation therapy, all patients except one received high-dose cytarabine followed by granulocyte colony-stimulating factor (G-CSF) administration to collect PBSCs. Ten patients received busulfan 4 mg/kg for 4 days, etoposide 20 mg/kg for 3 days and ranimustine 200 mg/m2 for 2 days as a conditioning regimen. One received a regimen consisting of etoposide, cyclophosphamide and total body irradiation. From day 1, G-CSF was given intravenously, and no additional chemotherapy was administered. At the median follow-up time of 30.8 months, four of six patients with standard-risk B-lineage ALL survived within the range of 19.7 to 85.4 months without relapse. In contrast, only one of five with high-risk B-lineage ALL survived for 36.3 months without relapse. Autologous PBSCT as post-remission therapy may prolong CR in adults with standard-risk B-lineage ALL.

Sequential synthesis and secretion of pectinases by Penicillium frequentans.

Penicillium frequentans synthesized eleven polygalacturonases and three pectinesterases when grown in the presence of pectin, sodium polypectate or monogalacturonic acid. When glucose was the sole carbohydrate source in the medium two of these polygalacturonases and one pectinesterase were produced. The enzymes produced under any of these conditions degraded pectic substrates to monogalacturonic acid, suggesting that this monosaccharide or its metabolites should induce the pectinolytic complex. All pectinesterases and most of the extracellular polygalacturonases were synthesized after the 2nd hour of incubation. The pectinases produced by Penicillium frequentans were not secreted at the same time but after 5 hours of incubation all of them could be detected outside the cell those detected only inside the cell were probably membrane-associated or unglycosylated forms of the extracellular pectinases.

Cytomegalovirus pneumonitis, activated prothrombin time prolongation and subacute thyroiditis after unrelated allogeneic bone marrow transplantation.

A 22-year-old female with acute myeloid leukemia (AML) in complete remission received a conditioning regimen containing antithymocyte globulin for an unrelated bone marrow transplant (BMT). After BMT, the patient suffered from cytomegalovirus (CMV) pneumonitis with markedly high levels of CMV antigenemia, activated prothrombin time (APTT) prolongation, and subacute thyroiditis. Recovery of CD4+ cells was delayed as long as 1 year after BMT. An association between these three episodes and viral infection due to the delayed recovery of CD4+ cells is suggested.

Comparative study of intracellular and extracellular pectinases produced by Penicillium frequentans.

The filamentous fungus Penicillium frequentans synthesized eleven polygalacturonases (PGs) and two pectinesterases (PEs) when grown in liquid culture supplemented with pectin. Seven PGs and the two PEs were secreted in the medium, whereas four PGs were not secreted. Among the secreted PGs, the endo-PG (band 10) and exo-PGs (band 5) were the enzymes secreted at the highest levels. All secreted PGs bound to lectin and their secretion and/or enzymic activities were inhibited by tunicamycin (TM), except for the constitutive and inducible endo-PG (band 10). Studies on the affinity for concanavalin A (ConA) and the effect of TM suggested that the secreted endo-PG and exo-PG differed in level and process of glycosylation. The exo-PG was characterized as a N-glycoprotein, whereas the endo-PG is probably an O-glycoprotein. The PGs (bands 3 and 4) were neither bound to ConA nor secreted and their enzymic activities were inhibited by TM, suggesting that they are probably N-glycoproteins with complex oligosaccharides of type three and tetra-antennary structure. The other PGs (bands 6 and 8) that were not secreted and did not bind to ConA were not inhibited by TM. These enzymes presented chromatographic characteristics and effects with TM that were similar to endo-PG (band 10), because these PGs might be unglycosylated or/and aggregate forms of the endo-PG (band 10).

Analysis of C-KIT, TIE and HTK expression on leukemic cells using flow cytometry: a preliminary report.

C-KIT, TIE and HKT expression on leukemic cells from patients were simultaneously analyzed using flow cytometry. Consistent with previous reports, leukemic cells from most patients with de novo acute myeloid leukemia (AML) were C-KIT-positive (28/35), while those from patients with B-lineage acute lymphoid leukemia (B-ALL) were C-KIT-negative (0/9). In the B-ALL patients, leukemic cells trom seven patients had one or more myeloid antigen such as CD13, CD15 and CD33. In contrast to C-KIT expression, leukemic cells from only one patient with acute monocytic leukemia were TIE-positive. Similarly, leukemic cells from only two patients (one, B-ALL with t(4;11)(q21;q23) and one, essential thrombocythemia in myeloblastic transformation (ET-MBT)) were HTK-positive. These results suggest that among the three receptor tyrosine kinases, C-KIT is the most useful marker for identifying AML.

[Retrospective analysis of elderly patients > or = 60 years of age with acute leukemia].

A retrospective analysis was performed on 76 consecutive elderly patients with acute leukemia aged 60 years or more (48 men, 28 women). Forty patients were 60-69 years old, 28 were 70-79 years old and 8 were > or = 80 years old. There were 55 patients with acute myelogenous leukemia (AML), 13 acute lymphoblastic leukemia (ALL) and 8 AML from myelodysplastic syndrome (MDS/AML). Patients were treated with the JALSG protocol, CAG regimen, or low-dose Ara-C regimen for AML, and DVP/M-CHOP protocol for ALL. The complete remission (CR) rates were 52.7% (29 of 55) in AML, 61.5% (8 of 13) in ALL, and 0% in MDS/AML. The median CR durations were 226, 85, 0 days, and the median survivals were 204, 177, 99 days, respectively. CR rates were 65.3% for the JALSG protocol, 62.5% for the CAG regimen and 25.0% for low-dose Ara-C regimen. According to age, CR was obtained 62.5% in patients aged 60-69 years and 33.3% in patients over 70 years old. Our results indicated that patients aged 60-69 years should be treated with intensive chemotherapy.

Activation of inwardly rectifying K+ channels by GABA-B receptors expressed in Xenopus oocytes.

In Xenopus oocytes coinjected with poly(A)+ RNA derived from the rat cerebellum and cRNAs for the cloned G protein-gated inwardly rectifying K+ channel (GIRK), GIRK1 and GIRK2, the GABA-B agonist baclofen elicited inwardly rectifying K+ currents. The inward K+ currents elicited by baclofen were inhibited by the selective GABA-B antagonists 2-OH saclofen and CGP 35348, and by the GIRK inhibitor Ba2+. In contrast, baclofen caused no currents in oocytes injected with the cerebellar poly(A)+ RNA alone, the poly(A)+ RNA and cRNA for GIRK1 or GIRK2, or only cRNAs for GIRK1 and GIRK2. These findings indicate that GABA-B receptors in the rat cerebellum were functionally expressed in Xenopus oocytes and activated the cloned GIRKs composed of GIRK1 and GIRK2 as heteromultimers.

[Acute myeloid leukemia with monosomy 7 accompanied by central diabetes insipidus].

A 27-year-old female was diagnosed as having atypical aplastic anemia in 1979 because of hypercellular bone marrow with abnormal erythroblasts and megakaryocytes. Afterward the diagnosis was corrected to myelodysplastic syndrome (RA) due to the reevaluation of the bone marrow smears. In March, 1995, thirst and polyurea occurred. In April, 1995, bone marrow aspiration biopsy showed the proliferation of atypical blasts (28%), and two months later, the number of the blasts increased (30%) and leukemic progression was noticed. Only 0.5 percent of the blasts showed weak peroxidase activity, and most of the blasts had CD13, CD33 and several adhesion molecules as CD11a, CD11b, CD44, CD54 and CD56. Karyotype of the bone marrow cells was 45, XX, -7. Her polyurea was caused by central diabetes insipidus. She was also complicated by pleuritis, colon ulcer, sinusitis and hypothalamic dysfunction. The etiology of these signs was due to the leukemic cell infiltration. She died despite of receiving multi-drug chemotherapy.

[Thrombotic complication in the course of aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome; possible involvement of dysplasminogenemia (plasminogen Tochigi) in the pathogenesis of thrombosis].

A 44-year-old Japanese man having aplastic anemia (AA)-paroxyamal nocturnal hemoglobinuria (PNH) syndrome was referred to our hospital because of purpuras due to thrombocytopenia in July 1994. He suffered from pneumonia after admission, complicated with cerebral, splenic, and left renal infarction. Pulmonary infaction was also confirmed by perfusion lung scan. He had a plasma plasminogen (PLG) functional activity of 54.4% with a normal level of PLG antigen. The gel isoelectrofocusing pattern of the plasminogen derived from the patient showed 10 normal bands and 10 additional doublet bands with slightly higher isoelectric points than the normal components. Abnormal PLG is converted by urokinase to an inactive two-chain plasmin molecule. These findings were similar to those of a case with dysplasminogenemia (PLG Tochigi) reported by Aoki et al. He was given warfarin for the prevention of thrombosis in December 1994. As of October 1995, these was no recurrence of thrombosis. The cause of thrombosis in the present case have been the association with PNH, predisposition to PLG Tochigi, or the complication of pneumonia. This is the first report of AA/PNH syndrome associated with dysplasminogenemia.

Seminário Redes Integradas de Atenção à Saúde - Renato Tasca

Apresentação com o título 'A atenção à Saúde coordenada pela APS: construindo as Redes de Atenção no SUS - Documento de posição da OPAS Brasil' realizada por Renato Tasca, coordenador do Grupo de Redes da Opas/OMS. Arquivo disponível para leitura e/ou download no ícone ao lado.