It is well established that interleukin-6 (IL-6) is an essential growth factor for multiple myeloma (MM) and patients with increased IL-6 levels have a poor prognosis. In healthy subjects, the presence of the C allele at a polymorphic site (-174 G/C) of the IL-6 gene is related to low IL-6 levels. In view of the potential association of this particular polymorphism with IL-6 concentration, and the relevance of IL-6 in MM pathogenesis, the objective of the present study was to investigate the prevalence of IL-6 (-174 G/C) promoter polymorphism and its association with development of MM in Brazilian individuals. We investigated the prevalence of these alleles in 52 patients and 60 healthy subjects (matched by age, sex, and race) of a Brazilian population. Thirty patients were male (42.4%), 24 (46.2%) were white and the median age at diagnosis was 58.5 years (range: 28 to 84 years). To determine the IL-6 (-174 G/C) polymorphism, molecular analysis was performed by polymerase chain reaction followed by endonuclease restriction digestion. The genotype distributions observed in the group of patients were 4% CC, 42% GC and 54% GG. The C allele frequency was 0.25. These results were similar to the control group, suggesting no impact of this polymorphism on the susceptibility to MM.

The biologic basis of the negative prognosis of plasmablastic myeloma is not fully understood. To determine whether histologically aggressive multiple myeloma (MM) is associated with a more angiogenic marrow environment, bone marrow samples from 50 recently diagnosed MM patients were evaluated. Twelve percent (6/50) of patients presented plasmablastic MM, and this feature correlated with moderate/strong intensity of vascular endothelial growth factor staining of plasma cells (P = 0.036). Although plasmablastic MM was not associated with increasing of microvessel density, this new evidence of increased expression of vascular endothelial growth factor on plasmablasts suggests that the adverse prognosis conferred by plasmablastic disease may be due, at least in part, to secretion of this angiogenic cytokine, also suggesting that the subset of MM patients with plasmablastic features may derive particular benefit from antiangiogenic therapies.

Patients with sickle cell anemia (Hb SS) or sickle cell trait (Hb AS) may present several types of renal dysfunction; however, comparison of the prevalence of these abnormalities between these two groups and correlation with the duration of disease in a large number of patients have not been thoroughly investigated. In a cross-sectional study using immunoenzymometric assays to measure tubular proteinuria, microalbuminuria, measurement of creatinine clearance, urinary osmolality and analysis of urine sediment, we evaluated glomerular and tubular renal function in 106 adults and children with Hb SS (N = 66) or Hb AS (N = 40) with no renal failure (glomerular filtration rate (GFR) >85 ml/min). The percentage of individuals with microalbuminuria was higher among Hb SS than among Hb AS patients (30 vs 8%, P<0.0001). The prevalence of microhematuria was similar in both groups (26 vs 30%, respectively). Increased urinary levels of retinol-binding protein or ß2-microglobulin were detected in only 3 Hb SS and 2 Hb AS patients. Urinary osmolality was reduced in patients with Hb SS or with Hb AS; however, it was particularly evident in Hb SS patients older than 15 years (median = 393 mOsm/kg, range = 366-469) compared with Hb AS patients (median = 541 mOsm/kg, range = 406-722). Thus, in addition to the frequently reported early reduction of urinary osmolality and increased GFR, nondysmorphic hematuria was found in 26 and 30% of patients with Hb SS or Hb AS, respectively. Microalbuminuria is an important marker of glomerular injury in patients with Hb SS and may also be demonstrated in some Hb AS individuals. Significant proximal tubular dysfunction is not a common feature in Hb SS and Hb AS population at this stage of the disease (i.e., GFR >85 ml/min).

O teste manual direto do Polybrene<FONT FACE="Symbol">Ò</FONT> (TDP) e o teste de Coombs direto (TCD) foram utilizados para a detecção de IgG na superfície de hemácias de pacientes com diagnóstico clínico e laboratorial de anemia hemolítica auto-imune (AHAI). OBJETIVO: Comparar a sensibilidade e especificidade do TPD e do TCD no diagnóstico da AHAI. MÉTODO: Foram estudados 18 pacientes com diagnóstico clínico-laboratorial de AHAI. Como indivíduos controles, foram testados 20 doadores de sangue assintomáticos e 20 pacientes com anemia falciforme. RESULTADOS: O TCD foi positivo em 14 pacientes e negativo em quatro indivíduos, enquanto o TDP foi positivo em 17 pacientes e negativo em um indivíduo que apresentava TCD positivo devido a fixação de complemento (C3d) nas hemácias. Todos os eluatos positivos realizados com a técnica de diclorometano revelaram anticorpos quentes com especificidade "anti-Rh". A sensibilidade do TDP (94%) para detectar fixação de IgG in vivo foi significantemente maior (p<0,05) que a do TCD (78%), enquanto os dois testes apresentaram a mesma especificidade (100%). CONCLUSÃO: O presente estudo permite concluir que, além de apresentar maior sensibilidade que o TCD, o TDP é um método rápido e de baixo custo, sendo, dessa forma, um teste auxiliar útil no diagnóstico de AHAI, especialmente nos pacientes com TCD negativo.

The direct manual PolybreneTM test (DPT) and the direct antiglobulin tests (DAT) were employed to detect antibody sensitizing red blood cell (RCB) in patients with clinical and laboratorial findings of autoimmune hemolytic anemia (AIHA). PURPOSE: To compare the sensitivity and specificity of DPT and DAT in the diagnosis of AIHA. METHODS: Eighteen consecutive patients with diagnosis of AIHA were evaluated. The control group consisted of 20 normal volunteers blood donors and 20 patients with sickle cell anemia. All patients and controls were submitted to DPT and DAT. All DAT positive samples were further tested using monospecific reagents ( anti-IgG heavy chain and anti-C3d). Positive samples for either DPT or DAT were evaluated by eluate technique using. The dichloromethane (DCM). RESULTS: The DAT was positive in 14 patients and negative in 4 subjects, while the DPT was positive in 17 patients and negative in 1 individual who had a positive DAT owing to complement (C3d). All positive eluates performed with DCM showed RBC autoantibodies with presumed "anti-Rh" specifity. The sensitivity rate of the DPT (94%) was significantly (p<0.05) higher than the sensitivity rate of DAT (78%) to determine whether IgG was bound in vivo, but no difference was found regarding the specificity of the two tests. CONCLUSION: 1) The DPT is more sensitive than the DAT in detecting IgG autoantibody on the RBCs of patients with AIHA; 2) because of its simplicity and rapidity, the DPT is a useful additional screening test for the investigation of Coombs-negative AIHA.

A presença de leucócitos nos produtos hemoterápicos alogênicos transfundidos tem sido associada à ocorrência de determinadas reações transfusionais, tais como a reação transfusional febril não-hemolítica, a aloimunização e refratariedade à transfusão de plaquetas, a doença enxerto-versus-hospedeiro, e a efeitos imunomodulatórios. Além disso, os leucócitos podem ser vetores de transmissão de agentes infecciosos, tais como o CMV, o HTLV-I/II e o EBV. Tem sido postulado que a remoção dos leucócitos em hemocomponentes mediante uso de filtros leucocitários pode prevenir a ocorrência dessas reações. Entretanto, a eficácia clínica da desleucotização permanece sem definição. Tem sido sugerido que a remoção de 1 log10 de leucócitos previne a reação transfusional não-hemolítica, a remoção de 2 log10 pode prevenir a transmissão de viroses, enquanto que a remoção de > ou = 3 log10 pode ser necessária para a prevenção de aloimunização plaquetária. Entretanto, devido à carência de estudos que analisem apropriadamente as vantagens do uso clínico rotineiro dos filtros, permanecem sem completa definição quais são as reais indicações clínicas para o uso de hemocomponentes desleucotizados; quais são os graus de desleucotização necessários para prevenir as diferentes reações; e se a remoção dos leucócitos deve ser realizada antes ou após o armazenamento do hemocomponente. Dessa maneira, somente estudos clínicos prospectivos poderão definir o custo-benefício da aplicação clínica de filtros leucocitários em hemoterapia.

Leukocytes present in allogeneic blood components have been associated with adverse effects to the recipient. These include the development of febrile transfusion reactions, alloimmunization to human leukocyte antigens, graft-versus-host disease, and immunomodulatory effects. In addition, such leukocytes may be the vector of infectious agents such as CMV, HTLV-I/II, and EBV. It has been postulated that the use of white blood cell filters to reduce the leukocyte content in allogeneic blood products may minimize the occurrence of these biological adverse effects associated with leukocytes present in transfused blood products. However, it is still to be determined the clinical effectiveness of leukodepletion. It has been suggested that 1 log10 leukocyte reduction prevents febrile non-hemolytic transfusion reactions; that a 2 log10 reduction may prevent the transmission of viroses; and that a > or = 3 log10 reduction may be necessary to prevent platelet alloimmunization. However, because there are no data available as guidelines for the use of leukodepleted blood products for most clinical indications, the use of white cell filters should be restricted to selected patients for whom such data exist. Properly designed prospective clinical trials are necessary to provide data to help to define the cost-benefit of the clinical application of leukodepletion.