摘要:

Hydroxyurea (HU) and recombinant human erythropoietin (rHuEpo) have been used in several studies to elevate Hb F level in sickle cell disease (SCD) patients and hence to ameliorate the clinical presentations of the disease. The treatment protocol and doses have varied in the different studies. We studied the effects of HU + rHuEpo combination therapy in sickle cell anaemia (SCA patients) to investigate the Hb F manipulation and hence treatment of SCA. Six patients with severe SCA were selected for treatment with HU (20-25 mg/kg body weight) and rHuEpo (400-800 U/kg body weight) combination therapy for 4 weeks followed by HU (20-25 mg/kg body weight) maintenance therapy for 6 months to 1 year. Iron and folic acid were administered during HU + rHuEpo treatment. Signs, symptoms and complications were recorded to obtain the severity index. Only patients with a severity index ≥ 6 were included in the study. Haematological and biochemical parameter values, Hb A2, Hb F, Hb F distribution, Hb F cells, bilirubin level and reticulocyte count were assessed at least on 2-3 occasions prior to initiation of the therapy protocol to establish baseline values. During the treatment period, the clinical presentations were monitored and the estimation of the laboratory parameters was carried out every 4-8 weeks. The results of these parameters during HU and rHuEpo combination therapy and HU maintenance therapy were compared with baseline values using paired t test. The elevation in the level of Hb F, Hb F cells, total haemoglobin, red cell count and MCV were significant (p < 0.005), while reticulocyte count and total bilirubin were significantly decreased (p < 0.05). Each patient showed an individual pattern of Hb F elevation. The increase in Hb F level was correlated with the haematological and biochemical parameters using the General Linear Model Programme of Statistical Analysis System. In general, the clinical presentation improved as Hb F level increased in each patient. In addition, the positive correlation with the haematological parameters and negative correlation with reticulocytes and total bilirubin confirmed the beneficial effect of elevated Hb F level on reducing red cell haemolysis. No correlation could be demonstrated between the pretreatment Hb F level and the increase in Hb F during the treatment period. Daily doses of HU with a single intravenous rHuEpo and iron supplementation elevate Hb F and Hb F cells in SCA patients. The Hb F level can be maintained high on HU therapy alone. This treatment regime may prove to be useful to elevate Hb F rapidly and to maintain a high level particularly in those SCD patients who do not respond to HU alone (non-responders).

ISSN:0001-5792    

DOI:10.1159/000204112

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We have cloned and characterized the human thymopoietin (TP) coding region and studied the mRNA expression of this gene in different hematopoietic cell lines. The 150-bp PCR fragment that encodes the 49-amino-acid human TP peptide was isolated from genomic placental DNA. Its colinearity with the cDNA sequence suggests lack of introns within the coding region. TP mRNA expression was demonstrated in lymphocytes from all the differentiation stages investigated, as well as in a myeloid cell line (K-562). These findings suggest a further expansion of the proposed TP functions.

ISSN:0001-5792    

DOI:10.1159/000204113

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We studied the effects of interleukin-1 (IL-1) and tumor necrosis factor (TNF) on mouse megakaryocytopoiesis to evaluate the role of these cytokines in reactive thrombocytosis associated with inflammation. Injections of IL·l or TNF to mice induced a significant increase in the megakaryocyte progenitor cell (CFU-Meg) count in the spleen. When IL·l and TNF were injected simultaneously, the splenic CFU-Meg count was remarkably increased compared with mice injected with either IL·l (p < 0.003) or TNF (p < 0.001) alone. On the other hand, neither IL·l nor TNF showed any megakaryocyte-potentiating or -stimulating effects in vitro. In the sera obtained 4 h after administration of IL·l, TNF or both, high megakaryocyte potentiating activities were found. Furthermore, an extremely high level of IL·6 was detected in the serum after administration of both IL·l and TNF. These results strongly suggest that IL·l and TNF stimulate megakaryocytopoiesis indirectly via other cytokine(s) induced from accessory cells, and that increased levels of IL·l and TNF play important roles in the development of reactive thrombocytosis caused by inflammation.

ISSN:0001-5792    

DOI:10.1159/000204114

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The effect of methylprednisolone on fresh cells from patients with chronic lymphocytic leukaemia (CLL) has been studied using the differential staining cytotoxicity (DiSC) assay resulting in LC90S of < 0.2 to 2,000 μg/ml. Cells from previously treated patients were, on average, significantly more sensitive to methylprednisolone than those from untreated patients (mean LC90 = 5.7 μg/ ml, n = 61 vs 31.0 μg/ml, n = 17, respectively; p < 0.05). Twelve patients with advanced disease were given high-dose methylprednisolone (1 g/m2/day i.v. × 5 days). In 7 cases, > 3 courses were given; 3 patients did not respond (2 achieved palliation) and 4 (57%) achieved a good partial response. These latter 4 patients were all clinically resistant to chlorambucil and anthracyclines and 2 were resistant to fludarabine. In 5 cases, 1 or 2 courses were given but no patients responded. The 8 nonresponders survived a median of 3.5 months whilst the responders have survived a median of 28.5+ months (3 of 4 still alive). This work suggests a rationale for why CLL patients resistant to standard chemotherapy may benefit from high-dose methylprednisolone therapy. Due to cost and toxicity associated with therapy, the decision to treat would be best made on the basis of a DiSC assay result. This pilot study requires confirmation with a well-designed controlled clinical trial.

ISSN:0001-5792    

DOI:10.1159/000204115

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

From a group of 118 patients with chronic idiopathic thrombocytopenic purpura (ITP), 43 were older than 60 years at diagnosis. In this report, we describe the clinical evolution and therapeutic response in young and old patients. The overal rate of hemorrhagic manifestations was similar in the two age groups, but a greater risk for severe bleeding was observed in elderly patients. There were no significant differences between old and young patients in response to steroids. In none of our patients was mortality associated with bleeding or side effects of the treatment. In conclusion, we have observed a more benign clinical course in elderly patients with chronic ITP as compared to previous reports.

ISSN:0001-5792    

DOI:10.1159/000204116

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

CD34+ progenitor cells were harvested from bone marrow and peripheral blood from 10 healthy donors by immunomagnetic isolation and enrichment procedures. The CD34+ cell population was investigated using a battery of enzyme reactions and monoclonal antibodies on cytospin preparations. Additionally, morphometric measurements were carried out and also liquid suspension culture studies were performed to ascertain vitality and stem cell character. More than 95% of the total yield of medullary CD34 progenitors expressed CD45 (LCA), CD43 (MT1) and β-glucuronidase. Reactivity with CD33 (My9), CD15 (LeuMl), CD38 (Leul7), CD20 (L26) and Ret40f (glyco-phorin C) was assumed to be in keeping with a transition into more differentiated elements of the various hemopoietic lineages. Morphometric analysis revealed conspicuous heterogeneity of the CD34+ cell population considering size measurements. This finding was in line with the diversities of antigen expression, indicating the more committed nature of CD34+ stem cells derived from the bone marrow in comparison with those progenitors isolated from the peripheral blood. Moreover, proliferation marker staining by PCNA disclosed a positivity in a considerable number of progenitors in contrast to the findings in CD34+ cells that are found in the peripheral blood.

ISSN:0001-5792    

DOI:10.1159/000204117

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We performed long-term follow-up studies of 5 patients with paroxysmal nocturnal hemoglobinuria (PNH). The percentages of decay-accelerating-factor (DAF)-defïcient erythrocytes were almost stable or slowly increased during the 2-4 years’ observation periods when the effects of treatment with drugs or blood transfusion and pregnancy were excluded. However, a tendency of increase in the percentages of DAF-deficient erythrocytes was observed along with the duration of the disease. Our findings suggest that the growth advantage of PNH clones beyond the normal hematopoiesis may be different from the other clonal stem cell disorders.

ISSN:0001-5792    

DOI:10.1159/000204118

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We describe two patients with non-Hodgkin’s lymphoma (NHL) who suffered cytomegalovirus (CMV)-related small intestinal perforations during the course of chemotherapy. Surgical specimens from both patients revealed his-tologic evidence of occlusive vasculitis and tissue destruction caused by CMV-affected cells in the submucosa and muscular walls, that may have played an important role in the pathogenesis of these perforations. Although such intestinal perforations are rare complications in NHL patients, CMV infection should be recognized as a primary etiological factor in acute abdominal crises when treating NHL patients with pharmaceutical agents including steroids. Emergency surgery and the anti-CMV agent, ganciclovir, would improve the prognoses of such patients.

ISSN:0001-5792    

DOI:10.1159/000204119

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Rare cases of low-grade lymphomas have been described in patients with human immunodeficiency virus (HIV) infection. However, this is the first reported case of mantle-cell lymphoma, a type of low-grade lymphoma, in a patient who also had HIV infection. Salient clinical features included lymphocytosis, lymphadenopathy, splenomegaly, and involvement of the bone marrow and meninges. The disease proved to be unusually aggressive and response to chemotherapy was insignificant. The patient survived only 4 months.

ISSN:0001-5792    

DOI:10.1159/000204120

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We report the identification of an Hb S homozygosity in a 29-year-old multiple-transfused patient with severe kidney disease using a new reverse-transcription polymerase chain reaction (RT-PCR) technique with mRNA as starting template. The procedure requires considerably less time than sequencing of genomic DNA and is recommended for use in the diagnosis of Hb S and other hemoglobinopathies.

ISSN:0001-5792    

DOI:10.1159/000204121

出版商:S. Karger AG    

年代:1995

数据来源: Karger