Increased erythrocyte aggregation as an indicator for an aggressive clinical course in Behçet's disease: a prospective study

OBJECTIVE—Changes in blood rheology, especially increased erythrocyte aggregation (EA) might play an important part in the development of arterial and venous thrombotic lesions. A prospective study was designed to evaluate EA in patients with Behçet's disease (BD) and to see if this parameter is predictive for the future development of vascular complications, such as deep vein thrombosis of various organ systems and uveitis.
METHODS—EA was measured by a photometric Myrenne aggregometer in 38 patients with BD at the time of initial diagnosis and in 40 age and sex matched healthy controls (HC).
RESULTS—During a median follow up period of 13.5 months, 13 patients developed vascular-ocular complications (eight deep vein thrombosis, nine uveitis, and four both deep vein thrombosis and uveitis). Patients were further divided into two groups: BD-a with mucocutaneous symptoms and arthritis only; BD-b with associated vascular-ocular complications. EA values at high shear rate (M) and at low shear rate (M1) were compared among the groups.
CONCLUSION—EA values at M and M1 were significantly higher in BD-b than BD-a and HC (p<0.001). These results suggest that determination of EA rates might be useful to identify subgroups who are likely candidates for developing vascular-ocular complications in BD and management of factors known to affect blood rheology might be beneficial.

Keywords: erythrocyte aggregation; Behcet's syndrome     

Angiotensin-converting enzyme expression of the lymphoma-associated macrophages in the lymph nodes of Hodgkin's disease

OBJECTIVE: Angiotensin-converting enzyme (ACE) is involved in the control of cellular proliferation. Tumor-associated macrophages promote lymphoma pathogenesis via affecting tumor cell growth and associated survival factors. We assessed ACE expression in the neoplastic lymph node microenvironment of Hodgkin's lymphoma (HL), particularly in macrophages and in nonneoplastic lymphoid tissue. METHODS: Paraffin sections of the lymph nodes from randomly selected 20 HL cases with nodular sclerosing and 20 mixed cellular types were included into the study. Five normal tonsils and five lymph nodes showing reactive lymphoid hyperplasia were used as controls. Immunohistochemistry of lymph node biopsies had been performed with monoclonal antibody against human ACE. Sections were evaluated by two pathologists. RESULTS: ACE-expressing histiocytes were observed in lymph nodes of HL. ACE staining was also observed in the vascular endothelium in all the tissues evaluated. Neoplastic lymphoid tissues and control tissues did not express ACE. CONCLUSION: ACE expression of the lymphoma-associated macrophages in the lymph nodes of HL may represent the point of cross-talk between renin-angiotensin system (RAS) and lymphomagenesis. ACE could serve in the pathobiological function of the tissue-based macrophages in tumorigenesis of HL.     

HIV感染者/AIDS患者血清基质金属蛋白酶-9表达与T细胞亚群的相关性研究

目的：了解艾滋病病毒(HIV)感染者及艾滋病(AIDS)患者血清中基质金属蛋白酶—9(MMP—9)水平表达及与T细胞亚群的相关性。方法：用酶联免疫吸附试验(ELISA)和流式细胞分析法，检测了18例HIV感染者和24例AIDS患者血清中MMP—9水平和淋巴细胞中CD3^ 、CD4^ 、CD9^ 的表达及绝对数。结果：HIV感染者组和AIDS患者组MMP—9水平较对照组明显升高(P＜0．05，P＜0.01)。AIDS患者组CD3^ 细胞数较对照组显著减少(P＜0．05)。HIV感染者组和AIDS患者组CD4^ 计数降低非常明显(P＜0．001)，CD8^ 计数非常明显升高(P＜0．00l，P＜0．01)，CD4^ ／CD8^ 的比值倒置。AIDS患者组MMP—9水平、CD3^ ，CD4^ 、CD8^ 的表达较HIV感染者组均有明显差异。HIV感染者组和AIDS患者组MMP—9表达与CD4^ 细胞数呈负相关(P＜0．05，P＜0．01)，AIDS患者组MMP—9水平与CD8^ 细胞数明显相关(P＜0．05)。结论:感染HIV后，MMP—9的水平随病情发展而增加，CD3^ 、CD4^ 细胞数逐渐减少，可作为判断AIDS患者疾病严重程度的指标。     

Overt gastrointestinal bleeding in haematologic neoplasms

BACKGROUND AND AIM: Patients with acute leukaemia suffer from various haemorrhages, most frequently due to thrombocytopenia. We could not reach any information regarding the frequency of gastrointestinal bleeding in acute leukaemia and decided to search this complication in patients with acute and chronic leukaemias and myeloproliferative disorders, retrospectively. PATIENTS AND METHODS: During a 6-year period, 291 patients with acute leukaemia, 52 patients with chronic leukaemia and 108 patients with myeloproliferative disorders had been followed. Thirty-two cases of overt gastrointestinal haemorrhage episodes (25 upper, 7 lower) were observed during the mentioned period. RESULTS: The frequency of bleeding episodes was 7.1% (32/451) in haematologic malignancies as a whole, 5.8% (17/291) for acute leukaemia, 1.9% (1/52) for chronic leukaemia and 13% (14/108) for myeloproliferative disorders. If the patients with myeloproliferative disorders in blastic phase were analysed separately, the ratio was 30% (6/20). Oesophagogastroduodenoscopy, which could be performed in 8 of 25 upper gastrointestinal haemorrhage episodes, revealed erosive gastritis in five patients and duodenal ulcers in three patients. Neutropenic enterocolitis was the underlying cause in all of the seven patients with lower gastrointestinal haemorhage. Five out of the seven patients had acute leukaemia. In 7 bleeding attacks, out of 32, the ultimate result was death. Generally, the haemorrhage was only a contributing cause of mortality. All of the mortality cases were patients with acute leukaemia. CONCLUSION: Especially, the patients with myeloproliferative disorders are prone to develop gastrointestinal haemorrhage. The manifestation is generally as upper gastrointestinal bleeding due to gastric erosions and duodenal ulcers. Lower gastrointestinal bleeding is frequently a problem of the patients with acute leukaemia. It is commonly a sign of neutropenic enterocolitis.     

Plasma basic fibroblast growth factor and bone marrow fibrosis in clonal myeloproliferative disorders

Basic fibroblast growth factor (bFGF) is an important growth factor involved in clonal hematopoietic expansion, neoangiogenesis, and bone marrow fibrosis, all of which are important pathobiologic features of clonal chronic myeloproliferative disorders (CMPD) and myelodysplastic syndromes (MDS). The aim of this study was to assess circulating bFGF concentrations in patients with CMPD and MDS with respect to the presence of bone marrow fibrosis in histopathologic examination. The study group comprised 18 patients with CMPD (six female, 12 male; median age 50 years), seven patients with MDS (one female, six male; median age 66 years) and 10 healthy adults as controls (four female, six male; median age 29 years). CMPD group included six chronic myelogenous leukemia (CML), seven essential thrombocythemia (ET), three polycythemia vera (PV), two agnogenic myeloid metaplasia (AMM). All seven MDS patients were the FAB subtype of refractory anemia (RA). Bone marrow biopsy sections stained with hematoxylin and eosin (H & E) and for reticulin were examined for the presence of fibrosis. The median plasma bFGF level was 18.2 pg/ml (interquartile range, IQR: 15.2-26.7) in patients with CMPD, 18.0 pg/ml (IQR: 15.8-26.4) in patients with MDS, 13.6 pg/ml (IQR: 9.9-20.0) in the control group. The bFGF levels were significantly higher in patients with CMPD in comparison with the healthy control group (P = 0.031). Circulating bFGF tended to be significantly lower in relation to the development of marrow fibrosis (P = 0.028). The complicated interactions of bFGF and fibrosis in the context of CMPD may be either 'cause' or 'effect'. The bFGF might represent an important link between angiogenesis, fibrosis, and clonal neoplastic hematopoiesis during the development of CMPD.     

Plasma thrombopoietin in patients with cavernous transformation of the portal vein

Thrombopoietin (TPO), the primary regulator of thrombopoiesis, is produced mainly in the liver. Previous studies investigating blood TPO in chronic liver diseases revealed conflicting results. It has been suggested that hepatic TPO production is regulated by the portal blood supply to the liver. However, the role of TPO in the pathobiological basis of idiopathic portal vein thrombosis (PVT) and cavernous transformation of the portal vein (CTPV) has not been elucidated. The objective of this study is to assess plasma TPO concentrations in patients with CTPV. Eleven patients (4 men and 7 women, aged 38+/-12 years) with CTPV were studied. Sixteen healthy adults served as the control group (8 men and 8 women, aged 34+/-12 years). Median plasma TPO concentration was 326 pg/mL (range, 15-1402 pg/mL) in the patients with CTPV and 62.65 pg/mL (range, 38.5-102 pg/mL) in the control group (P = .003). In this study, we found significantly higher TPO concentrations in the plasma of patients with CTPV. The higher concentrations could be a result of the altered portal hemodynamics due to thrombosis. Moreover, TPO release by activated platelets might lead to the subsequent propagation of thrombosis in PVT.     

Development of day-8 colony-forming unit-spleen hematopoietic progenitors during early murine embryogenesis: spatial and temporal mapping

The ontogeny of the hematopoietic system in mammalian embryos occurs during the yolk sac (YS) and the fetal liver (FL) stages. Events leading to the establishment of hematopoiesis in the FL remain obscure. The appearance of colony-forming units-spleen (CFU-S) in the FL is preceded by a gradual increase of CFU-S in the YS and a more rapid increase in the AGM region (area comprising dorsal aorta, gonads, and mesonephros) during day 10 of development (Medvinsky et al, Nature 364:64, 1993). By this time, the AGM CFU-S attain a high frequency equivalent to that found in the adult bone marrow. The analogous area gives rise to adult hematopoiesis in amphibians and probably in birds. We present here a more complete picture of CFU-S development during transition from the pre-liver to liver stage of hematopoiesis. (1) Dissectional analysis of the mouse AGM region shows the presence of CFU- S both around the dorsal aorta and in the uro-genital ridges. (2) The embryonic gut also shows low but distinctive CFU-S activity. This initial intrabody pattern of CFU-S distribution in murine embryogenesis parallels that found for primordial germ cells. (3) The beginning of definitive liver hematopoiesis is accompanied by wide dissemination of CFU-S in the embryonic tissues. (4) Comparison of spleen colonies arising from the AGM and YS has shown morphologic differences. In contrast to simple erythroid constitution of the YS colonies, a broader variety of cells are found within the AGM-derived colonies that are similar to those derived from 11-day FL. These data suggest a lineage relationship for hematopoietic progenitors between the AGM region and the FL.     

The predictability of factor V Leiden (FV:Q(506)) gene mutation via clotting-based diagnosis of activated protein C resistance.

After the discovery of activated protein C resistance (APCR) due to factor V Leiden mutation and the causal relationship of the phenomenon with clinical thromboembolism, a wide variety of functional clotting-based assays were developed for testing of APCR in relation to the specific DNA-based analysis of FV:Q(506) Leiden. The aim of this study is to assess a clotting-based APCR assay using procoagulant crotalidae snake venom with respect to the sensitivity, specificity, and predictability for the presence of the factor V Leiden mutation. APCR testing and factor V DNA analyses have been performed concurrently on 319 patient specimens. APCR values of the patients with homozygous factor V Leiden mutation (70.4+/-13.5 s) were significantly lower (p<0.001) in comparison to the subjects with the heterozygous mutation (87.6+/-13.4 s). The assay is highly sensitive (98.7%) and specific (91.9%) for the screening of factor V Leiden mutation. The sensitivity and specificity of the APCR testing reached to 100% below the cut-off value of 120 s among the patients with homozygous factor V Leiden mutation. Therefore, this method could help the desired effective optimal screening strategy for the laboratory search of hereditary thrombophilia focusing on the diagnosis of APCR due to FV:Q(506).