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Prospective evaluation of chronic organ damage in adult sickle cell patients: A seven‐year follow‐up study
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Charlotte F. J. van Tuijn Marein Schimmel Eduard J. van Beers Erfan Nur Bart J. Biemond 《American journal of hematology》2017,92(10):E584-E590
Organ damage in sickle cell disease (SCD) is a crucial determinant for disease severity and prognosis. In a previous study, we analyzed the prevalence of SCD‐related organ damage and complications in adult sickle cell patients. We now describe a seven‐year follow‐up of this cohort.All patients from the primary analysis in 2006 (n = 104), were included for follow‐up. Patients were screened for SCD‐related organ damage and complications (microalbuminuria, renal failure, elevated tricuspid regurgitation flow velocity (TRV) (≥2.5 m/seconds), retinopathy, iron overload, cholelithiasis, avascular osteonecrosis, leg ulcers, acute chest syndrome (ACS), stroke, priapism and admissions for vaso‐occlusive crises (VOC) biannually. Upon 7 years of follow‐up, progression in the prevalence of avascular osteonecrosis (from 12.5% to 20.4%), renal failure (from 6.7% to 23.4%), retinopathy (from 39.7% to 53.8%) was observed in the whole group. In HbSS/HbSβ0‐thal patients also progression in microalbuminuria (from 34% to 45%) and elevated TRV (from 40% to 48%) was observed while hardly any progression in the prevalence of cholelithiasis, priapism, stroke or chronic ulcers was seen. The proportion of patients with at least one episode of ACS increased in the group of HbSS/HbSβ0‐thal patients from 32% to 49.1%. In conclusion, 62% of the sickle cell patients in this prospective cohort study developed a new SCD‐related complication in a comprehensive care setting within 7 years of follow‐up. Although the hospital admission rate for VOC remained stable, multiple forms of organ damage increased substantially. These observations underline the need for continued screening for organ damage in all adult patients with SCD. 相似文献
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Factors that affect human hemopoiesis are produced by T-cell growth factor dependent and independent cultured T-cell leukemia-lymphoma cells 总被引:3,自引:0,他引:3
Some laboratory results and clinical situations suggest that human T cells may be important in the regulation of growth of hematopoietic cells. Since the discovery of T-cell growth factor (TCGF), systems are now available for the long-term specific in vitro propagation of mature normal or neoplastic human T cells, providing an opportunity to study the influence of T cells on hematopoiesis. Recently, 24 cell lines from patients with cutaneous T-cell lymphoma (CTCL) and T-cell acute lymphoblastic leukemia (T-ALL) were grown with TCGF and then assessed for release of humoral factors that affect hematopoiesis. Conditioned media (CM) from these cell lines were tested for erythroid burst- promoting activity (BPA) and granulocyte colony-stimulating activity (CSA). BPA was detected in CM from 3/6 cultures of T-ALL patients and 4/6 CTCL cultures. CSA was found in the CM from 6/8 cultures of T-ALL patients, 7/12 CTCL cultures, and 3/4 CTCL cell lines that become independent of exogenous TCGF for growth. The CSA from several of the neoplastic T-cell cultures stimulated high levels of eosinophil colonies, a possible source of the eosinophilia seen in these patients. The ability of continuously proliferating human T lymphocytes, which retain functional specificity and responsiveness to normal humoral regulation, to produce factors that directly or indirectly stimulate myeloid and erythroid colony formation lends further credence to the role of T lymphocytes in regulating hematopoiesis. 相似文献
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High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy 总被引:2,自引:1,他引:2
Brown RA; Herzig RH; Wolff SN; Frei-Lahr D; Pineiro L; Bolwell BJ; Lowder JN; Harden EA; Hande KR; Herzig GP 《Blood》1990,76(3):473-479
Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens. 相似文献
26.
The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect. 相似文献
27.
We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma. 相似文献
28.
BJ Ferguson MD 《International forum of allergy & rhinology》2014,4(5):345-346
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We examined all available data on HLA-A and -B antigen distributions in patients with Crohn's disease and ulcerative colitis. The risk of Crohn's disease was significantly increased in individuals with HLA-A2, having a relative risk of 1.25, in 730 pooled Caucasoid patients compared with 10 863 pooled controls, and decreased in individuals with HLA-A11, having a relative risk of 0.62. The risk of ulcerative colitis was also significantly increased in individuals with HLA-B27 and -Bw35, having a relative risk of 1.81 and 1.41 respectively, in 560 pooled Caucasoid patients compared with 6151 pooled controls, whilst in 144 pooled Japanese patients who were compared with 442 pooled controls, the risk of colitis was increased in individuals with HLA-B5 with a relative risk of 2.79. All differences remained significant after correction for the number of antigens examined. The bases for these genetic associations are unclear. 相似文献