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961.
Lymphoblastic lymphoma: an immunophenotype study of 26 cases with comparison to T cell acute lymphoblastic leukemia 总被引:4,自引:1,他引:4
A series of 26 lymphoblastic lymphomas (LLs) and 13 T cell acute lymphoblastic leukemias (ALLs) were investigated using a battery of monoclonal antibodies applied to tissue frozen sections. Twenty-one of the LLs were of T lineage. All but one of the T cell LLs were of immature thymic phenotype, mostly corresponding to stage II cortical thymocyte development. The T cell LLs expressed Leu-1 in 100%, Leu-4 and Leu-9 in 95%, and Leu-5 in 85% of the cases. The high percentage of Leu-4 expression in this series is probably due to detection of cytoplasmic antigen with our methods. One LL was of pre-B or B cell and two cases were of common ALL phenotype. Two cases were of undefined phenotype, expressing markers of both B and T cell differentiation. Pediatric cases showed a greater tendency toward T cell phenotype than did adult cases. The cases of T cell ALL were immunophenotypically similar to the cases of T cell LL but showed a tendency toward a more immature phenotype. 相似文献
962.
Predictors of death from chronic graft-versus-host disease after bone marrow transplantation 总被引:4,自引:9,他引:4
Wingard JR; Piantadosi S; Vogelsang GB; Farmer ER; Jabs DA; Levin LS; Beschorner WE; Cahill RA; Miller DF; Harrison D 《Blood》1989,74(4):1428-1435
Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) in 85 patients were reviewed to determine which were risk factors for death. In a multivariate proportional hazards analysis, three baseline factors emerged as independent predictors of death: progressive presentation (chronic GVHD following acute GVHD without resolution of acute GVHD; hazard ratio of 4.1, 95% Cl = 2.1 to 7.8), lichenoid changes on skin histology (hazard ratio of 2.2, 95% Cl = 1.1 to 4.3), and elevation of serum bilirubin greater than 1.2 mg/dL (hazard ratio = 2.1, 95% Cl = 1.1 to 4.1). Actuarial survival of 23 chronic GVHD patients with none of these risk factors was 70% at 6 years (95% Cl = 38%, 88%). Thirty-eight patients with one of these risk factors had a projected 6-year survival of 43% (95% Cl = 21%, 63%). The 29 patients with any combination of two or more of these factors had a projected 6-year survival of only 20% (95% Cl = 8%, 37%). Identification of baseline risk factors should facilitate design of trials of chronic GVHD therapies and assignment of high-risk patients to more aggressive innovative therapeutic regimens. 相似文献
963.
Dr. S. Runge C. Warnke Dr. P. Abel Dr. S. Friesecke Prof. Dr. S. Felix 《Intensivmedizin und Notfallmedizin》2005,42(2):172-176
Zusammenfassung
Metformin wird als Therapie der Wahl bei Patienten mit Diabetes-mellitus-Typ-II und Übergewicht empfohlen. Bedeutende Nachteile des Metformin sind die hohe Anzahl von Kontraindikationen und die schwere Laktazidose als seltene, aber mit einer hohen Letalität assoziierten Komplikation.
Fallvorstellung
Der 74-jährige Patient wurde beatmet, mit dem Verdacht auf kardiogenen Schock, aus einem Krankenhaus der Primärversorgung verlegt. Anamnestisch klagte der Patient seit dem Vormittag des Aufnahmetages über progrediente Dyspnoe und Sehstörungen. Der Diabetes-mellitus-Typ-II war Metformin therapiert. Bei Aufnahme sahen wir einen komatösen Patienten im schweren Schock mit Kussmaulatmung, Anurie und Hypothermie. Labor und Blutgasanalyse ergaben eine Laktazidose. Ein schwerer Volumenmangel und eine schwere kardiale Dysfunktion als Schockursache konnten ausgeschlossen werden. Es fand sich ein vasogener Schock, eine Sepsis oder gar ein septischer Schock bestand jedoch nicht. Somit mussten wir von einer Metformin-assoziierten Laktazidose bei progredienter Niereninsuffizienz ausgehen.Mit der Hämodialyse wurde unverzüglich begonnen.40 Stunden nach Aufnahme verstarb unser Patient trotz maximaler intensivmedizinischer Maßnahmen im Kreislaufschock und Multiorganversagen.
Fazit
Bei unserem Patienten entwickelte sich unter der Therapie mit Metformin unerkannt eine progrediente Nierenfunktionsstörung. In der Folge kam es zur tödlichen Laktazidose. Symptome wie Hyperventilation, gastrointestinale Beschwerden, Verwirrtheit, Hypotonie und Oligoanurie bei einem Typ II Diabetiker sollten, differentialdiagnostisch auch den Verdacht auf eine Metformin-assoziierte Laktazidose lenken. Nach unserer Erfahrung tritt die Metformin assoziierte Laktazidose, allein durch Akkumulation bei Niereninsuffizienz ohne Gewebshypoxie, häufiger auf als in der Literatur beschrieben. 相似文献
964.
A quality of life scale was developed to measure the subjective fear of falling in nursing home residents. We assessed the dimensions fear of falling, daily living and social life within a randomized controlled trial of hip protector use. The Nottingham Health Profile (NHP) was used for validation. Statistical analysis covered factor analysis, internal consistency of subscales, construct and discriminant validity. Factor analysis revealed three reliable components (Cronbach's Alpha): fear of falling (0.92), social restriction due to limited mobility (0.74) and restriction by clothes due to the hip protector (0.72). The subscales fear of falling and social restriction were significantly intercorrelated with all subscales of the NHP. The new tool is a reliable and valid measure of fear of falling in nursing home residents. However, generalizability and applicability are limited by the small proportion of subjects able to complete the tests. 相似文献
965.
Loss of all or part of the long arm of human chromosome 5 is a recurrent abnormality in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), especially after chemotherapy for a prior malignancy. It is one of the worst prognostic indicators in AML, associated with chemotherapy resistance and short survival. These deletions center at band 5q31, which has thus been proposed as the location of a tumor suppressor gene; this site is to be distinguished from that observed in 5q- syndrome, centering at 5q32. To define the molecular extent and the clinical prevalence of 5q31 deletions, we collected a series of AML and MDS cases of mixed karyotype, taking care to exclude MDS cases with 5q- syndrome. The samples were analyzed for loss of heterozygosity (LOH) using a panel polymerase chain reaction (PCR)-based microsatellite markers from 5q, comparing malignant cells with normal tissue derived from lymphoblastoid cell lines or buccal mucosa scrapings. Losses were detected in seven of 29 matched samples, including four of 17 with MDS, and three of 12 with AML; six of these seven also had a cytogenetically-visible del(5q) or -5. The one case without a cytogenetic deletion showed molecular loss of three contiguous markers, with retention of flanking markers interleukin-9 (IL-9) and D5S414, and thus contained a small deletion that is below cytogenetic resolution. PCR failed to detect 5q loss in two cases with large cytogenetic deletions, but both had been treated and contained low percentages of malignant cells in the samples. This study thus led to the identification of a case with a minimal deletion for the 5q31 tumor suppressor gene, specified by IL-9-D5S414, that is approximately 1 Mb (2 cM) in extent. Additionally, we demonstrate that PCR-based allelotyping is a reliable method for the detection of chromosomal deletion in myeloid malignancy, providing the specimens contain a high proportion of malignant cells. These studies will help to identify the tumor-suppressor gene at 5q31, and will help to develop molecular methods for diagnosis and monitoring of these disorders. 相似文献
966.
Jackson CW; Hutson NK; Steward SA; Ashmun RA; Davis DS; Edwards HH; Rehg JE; Dockter ME 《Blood》1988,71(6):1676-1686
The mechanisms that determine and regulate platelet size are unknown. By phase microscopy, we observed that Wistar Furth (WF) rats had macrothrombocytopenia. In this study, we have characterized and compared platelets and megakaryocytes of WF rats with those of Wistar, Long-Evans hooded (LE), and Sprague-Dawley rats. In addition, we have examined the mode of inheritance of this WF rat platelet abnormality. The average platelet count of WF rats was only one-third that of the other three rat strains. In contrast, the mean platelet volume (MPV) of adult WF rats was twice that of the other rat strains; however, the average megakaryocyte diameter and DNA content distribution of WF rats were not significantly different from those of LE rats. The average megakaryocyte concentration was 30% lower in the WF strain compared with that of LE rats. Mazelike membrane formations were observed in WF platelets and megakaryocytes by electron microscopy. Reciprocal crosses of WF and LE rats resulted in offspring with MPVs and platelet counts like those of LE rats, indicating that the macrothrombocytopenic trait is recessive in its inheritance. Reciprocal marrow transplants between the WF and LE strains resulted in MPVs like those of the donor strain, demonstrating that the macrothrombocytopenia is an intrinsic marrow abnormality of the WF strain. Splenectomy did not alter the MPV of WF rats. The response of WF megakaryocytes and platelets to severe, acute thrombocytopenia was similar to that of LE rats except that the shift to higher megakaryocyte DNA contents was muted and platelet recovery was slower in the WF rats. In summary, the WF rat has a hereditary macrothrombocytopenia that is recessive in nature and not due to differences in megakaryocyte size or DNA content. These results suggest that the macrothrombocytopenia of WF rats results from the formation of fewer platelets per megakaryocyte, possibly resulting from a qualitative or quantitative defect in some component necessary for proper subdivision of megakaryocyte cytoplasm into platelets. 相似文献
967.
Studies on B lymphoid tumors treated with monoclonal anti-idiotype antibodies: correlation with clinical responses 总被引:4,自引:0,他引:4
J N Lowder T C Meeker M Campbell C F Garcia J Gralow R A Miller R Warnke R Levy 《Blood》1987,69(1):199-210
Monoclonal anti-idiotype antibodies can be made which are exquisitely specific for B lymphocytic malignancies. We have conducted a clinical trial in which some patients' tumors regressed after infusion of such antibodies. Here, we evaluated characteristics of the antibodies, the tumors, and the patients to determine which features best correlated with the clinical response. Neither the isotype of the murine antibodies, nor their avidity were predictive of clinical outcome. The specific epitope to which the antibodies bound was characterized by immunochemical techniques. Reactivity with a heavy-light chain combinatorial determinant correlated somewhat with clinical effect. Variations in the characteristics of the individual tumors such as antigen sites per cell and ability to modulate the surface immunoglobulin were not predictive of response. In one patient with prolymphocytic leukemia the anti-idiotype antibody had a direct antiproliferative effect on tumor cells in vitro. This patient's tumor response was explainable by such a direct mechanism. In the other patients, who had lymphomas, therapeutic outcome correlated with the number of host nontumor cells infiltrating the tumor. The vast majority of these nontumor cells were mature T lymphocytes of the Leu 4, Leu 3 (T3, T4) phenotype. Thus, a preexistent host-tumor interaction seems to be important in the in vivo effect of anti-idiotype antibodies in B cell tumors. 相似文献
968.
A human thymus-leukemia antigen defined by hybridoma monoclonal antibodies. 总被引:16,自引:6,他引:16 下载免费PDF全文
R Levy J Dilley R I Fox R Warnke 《Proceedings of the National Academy of Sciences of the United States of America》1979,76(12):6552-6556
A series of mouse hybridomas producing monoclonal antibodies against human acute lymphocytic leukemia (ALL) cells was generated and screened for tumor specificity. Among 1200 primary cultures, 60 produced an antibody that could distinguish between the immunizing leukemia cells and an isologous B lymphoblastoid cell line. Of these, two produced an antibody that detects an antigen expressed preferentially on ALL cells and on a subpopulation of normal cells found in the cortex of the thymus. Other normal human lymphoid cells from lymph nodes, spleen, bone marrow, and peripheral blood express only low levels of this antigen. High levels of this "thymus-leukemia" antigen were found on T-ALL cells, T-ALL-derived cell lines, and some "null" ALL cells. By contrast, B-cell leukemias, B lymphoblastoid cell lines, and normal and malignant myeloid cells contain either low or undetectable amounts of this antigen. The thymus-leukemia antigen has been isolated from the membranes of leukemia cells by detergent solubilization and subsequent immunoprecipitation with the monoclonal antibody. Preliminary biochemical characterization shows the antigen to be associated with a polypeptide of Mr approximately 28,000. 相似文献
969.
McSweeney PA; Rouleau KA; Storb R; Bolles L; Wallace PM; Beauchamp M; Krizanac-Bengez L; Moore P; Sale G; Sandmaier B; de Revel T; Appelbaum FR; Nash RA 《Blood》1996,88(6):1992-2003
Increasingly, enriched populations of hematopoietic progenitors are used in experimental and clinical transplantation studies. The separation of progenitors is based on the expression of CD34, a marker preferentially expressed on progenitor cells. The dog model has been important for preclinical transplant studies, because it has proven predictive for outcomes in human hematopoietic stem cell transplantation. To identify and isolate canine hematopoietic progenitors, we have cloned a cDNA encoding a CD34 homologue from a canine myelomonocytic leukemia cell line, ML2. The CD34 homologue cDNA predicts an amino acid sequence that is highly conserved with human and murine CD34 in the cytoplasmic domain, transmembrane domain, and C- terminal end of the extracellular domain, but shows considerable divergence from these sequences at the amino-terminal end of the protein. In Western blotting studies, canine CD34 homologue (caCD34) appears to be a heavily and variably glycosylated protein with a molecular weight of approximately 100 kD and shows some tissue-specific differences in protein mass. To evaluate the expression of caCD34 protein, the extracellular domain of caCD34 was expressed as an Ig fusion protein and used as an immunogen to generate a rabbit polyclonal antiserum. The antiserum reacted against the fusion protein, against vascular endothelium, and with three leukemic cell lines. Approximately 1% of canine bone marrow cells stained brightly with antibodies to caCD34 and this population was 25- to 50-fold enriched for colony- forming units-granulocyte-macrophage as compared to unfractionated marrow mononuclear cells. These findings suggest that the canine CD34 homologue is expressed on bone marrow progenitor cells and, thus, that this molecule should be a valuable marker for identifying and isolating canine hematopoietic progenitors for experimental hematopoiesis and stem cell transplantation. 相似文献
970.
Super HJ; McCabe NR; Thirman MJ; Larson RA; Le Beau MM; Pedersen-Bjergaard J; Philip P; Diaz MO; Rowley JD 《Blood》1993,82(12):3705-3711
Chromosome band 11q23 is frequently involved in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) de novo, as well as in myelodysplastic syndromes (MDS) and lymphoma. Five percent to 15% of patients treated with chemotherapy for a primary neoplasm develop therapy-related AML (t-AML) that may show rearrangements, usually translocations involving band 11q23 or, less often, 21q22. These leukemias develop after a relatively short latent period and often follow the use of drugs that inhibit the activity of DNA-topoisomerase II (topo II). We previously identified a gene, MLL (myeloid-lymphoid leukemia or mixed-lineage leukemia), at 11q23 that is involved in the de novo leukemias. We have studied 17 patients with t-MDS/t-AML, 12 of whom had cytogenetically detectable 11q23 rearrangements. Ten of the 12 t-AML patients had received topo II inhibitors and 9 of these, all with balanced translocations of 11q23, had MLL rearrangements on Southern blot analysis. None of the patients who had not received topo II inhibitors showed an MLL rearrangement. Of the 5 patients lacking 11q23 rearrangements, some of whom had monoblastic features, none had an MLL rearrangement, although 4 had received topo II inhibitors. Our study indicates that the MLL gene rearrangements are similar both in AML that develops de novo and in t-AML. The association of exposure to topo II- reactive chemotherapy with 11q23 rearrangements involving the MLL gene in t-AML suggests that topo II may play a role in the aberrant recombination events that occur in this region both in AML de novo and in t-AML. 相似文献