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61.
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63.
Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia 总被引:3,自引:4,他引:3
Five patients with sickle cell anemia were treated with hydroxyurea (HU), in hopes of augmenting their production of fetal hemoglobin. Laboratory responses in two patients treated for more than 2 years were encouraging and there were suggestions of clinical improvement. Long- term HU therapy should be considered for severely affected adults with sickle cell anemia who are willing to accept what is probably a small risk of carcinogenesis. Preliminary chromosomal analysis and knowledge of the clastogenic properties of HU suggest that conception and pregnancy should be avoided. Pharmacokinetic studies will probably be necessary to adjust individual dosage schedules so that cytotoxicity is avoided. F cell responses can be seen in 2 to 3 weeks if the HU dose is optimal, but establishment of a large number of F cells in the circulation may take a month or longer. 相似文献
64.
Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
65.
Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity 总被引:1,自引:5,他引:1
Broxterman HJ; Sonneveld P; Feller N; Ossenkoppele GJ; Wahrer DC; Eekman CA; Schoester M; Lankelma J; Pinedo HM; Lowenberg B; Schuurhuis GJ 《Blood》1996,87(11):4809-4816
We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies. 相似文献
66.
Jones Gareth T. Mallawaarachchi Bhadra Shim Joanna Lock Jonathan Macfarlane Gary J. 《Rheumatology international》2020,40(10):1581-1591
Rheumatology International - Comorbid fibromyalgia, in axial spondyloarthritis (axSpA) has been shown to influence disease activity and function, and quality of life. Although several papers exist,... 相似文献
67.
Hany Elmariah Yvette L. Kasamon Marianna Zahurak Karen W. Macfarlane Noah Tucker Gary L. Rosner Javier Bolaños-Meade Ephraim J. Fuchs Nina Wagner-Johnston Lode J. Swinnen Carol Ann Huff William H. Matsui Douglas E. Gladstone Shannon R. McCurdy Ivan Borrello Christian B. Gocke Satish Shanbhag Kenneth R. Cooke Richard F. Ambinder 《Biology of blood and marrow transplantation》2018,24(5):1099-1102
Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non–first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age, 56 years) with hematologic malignancies who underwent NMA haplo T cell–replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24% (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival 64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1-year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to 79%). NMA haplo BMT with PTCy from non–first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first-degree relatives. 相似文献
68.
A national confidential enquiry into community acquired pneumonia deaths in young adults in England and Wales. British Thoracic Society Research Committee and Public Health Laboratory Service
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BACKGROUND: The aim of this study was to describe the frequency, causal pathogens, management, and outcome of a population of young adults who died from community acquired pneumonia (CAP). METHODS: Pneumonia deaths in England and Wales in adults aged 15-44 were identified between September 1995 and August 1996. Patients with underlying chronic illness including HIV infection were excluded. Clinical details for each case were collected from the hospital and general practitioner records. RESULTS: Death from CAP was identified in 27 previously well young adults (1.2 per million population per year). Twenty were known to have consulted a GP for this illness. Nine received antibiotics before hospital admission. A causative pathogen was identified in 17 cases (Streptococcus pneumoniae in eight). Bacteraemia was present in seven. All patients who reached a hospital ward received antibiotics (69% within two hours of admission). The British Thoracic Society antibiotic guidelines for severe CAP were followed in only 10 cases. Cardiac arrest at home or on arrival at hospital occurred in six cases, one of whom was successfully resuscitated. Of the remaining 21 patients, 71% had two or more markers of severe CAP. All 22 who were admitted reached an intensive care unit, but 11 of these required transfer to another hospital for some aspect of intensive care. One third of patients died within 24 hours of presenting to the hospital. CONCLUSIONS: Death from CAP in previously fit young adults still occurs. While some deaths might be preventable by better patient management, most are unlikely to be preventable by current management practices. 相似文献
69.
70.
Li Voon Chong JS Lecky BR Macfarlane IA 《International journal of clinical practice》2000,54(9):621-622
Seizures or encephalopathy associated with thyrotoxicosis are very rare. A 30-year-old man with thyrotoxicosis and strongly positive thyroid antibodies presented with generalised seizures preceded by an encephalopathic illness of a few days duration. CSF protein was raised and EEG showed bilateral slowing of activity. Antithyroid drug treatment rendered him biochemically euthyroid, his cognitive state returned to normal and his seizures stopped. Subsequently he had a recurrence of both encephalopathy and seizures on two occasions, coinciding with relapses of the thyrotoxicosis. This supports the view that the hyperthyroid state caused this serious neurological condition. Treatment with 131I caused hypothyroidism and he has remained seizure free and well for six years on thyroxine replacement. Corticosteroids may have been helpful in the management of his encephalopathy. 相似文献