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1.
Herz ; 47(4): 354-365, 2022 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-34554285

RESUMO

The "fat hypothesis of coronary heart disease", according to which saturated fatty acids (SFA) increase the concentration of low-density lipoprotein-cholesterol (LDL-C) and consequently increase the risk for cardiovascular diseases, influenced the nutritional recommendations over the last 60 years, initially in the USA and later also in Europe. Over the years there accumulated a growing body of evidence from epidemiology and controlled clinical studies that the consumption of SFA per se was not associated with an increased cardiovascular risk and the limitation of consumption of SFA did not show a preventive effect. The focus on the SFA content negated the biologically heterogeneous and sometimes biologically favorable effects of various SFAs. In addition, it was neglected that SFAs in foodstuffs are bound in a variety of complex matrices, which are composed of dozens of nutrients with different structures and concomitant substances and therefore each triggers different biological responses and metabolic effects. Accordingly, such nutrient-based recommendations are principally not very productive and also difficult to realize. In addition, LDL­C is not a suitable marker to assess the effect of lifestyle interventions, such as nutrition or physical activity, on the global cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Ácidos Graxos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol , Gorduras na Dieta/metabolismo , Ácidos Graxos/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Fatores de Risco
3.
Strategies Trauma Limb Reconstr ; 12(2): 77-89, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28444580

RESUMO

The purpose of this study was to summarize and evaluate results of three-dimensional (3D-) planned corrective osteotomies of malunited distal radius fractures. 3D-planning techniques provide the possibility to address 3D-deformity that conventional planning methods might not address. We systematically searched PubMed, EMBASE and the Cochrane library for studies that performed a 3D-planned corrective osteotomy on patients with a malunited distal radius fracture. Fifteen studies with a total of 68 patients were included in the analysis. In 96% of cases, the preoperatively present palmar tilt, radial inclination and ulnar variance showed statistically significant improvement postoperatively with restoration to within 5° or 2 mm of their normal values. Mean flexion-extension, pro-supination and grip strength showed statistically significant improvement (p < 0.05). Complications were reported in 11 out of 68 patients (16%). With the current advances in 3D printing technology, 3D-planned corrective osteotomies seem a promising technique in the treatment of complex distal radius malunions. Level of evidence IV Systematic review of case series, Level IV.

4.
Eur J Clin Nutr ; 69(12): 1369-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26373963

RESUMO

We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in-patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone.


Assuntos
Preparações de Ação Retardada/uso terapêutico , Hipoglicemia/dietoterapia , Amido/uso terapêutico , Zea mays/química , Idoso de 80 Anos ou mais , Peptídeo C/sangue , Preparações de Ação Retardada/química , Doença de Depósito de Glicogênio Tipo I/sangue , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Doença de Depósito de Glicogênio Tipo I/dietoterapia , Humanos , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Insulina/sangue , Anticorpos Anti-Insulina/sangue , Masculino , Amido/química
5.
Thromb Res ; 134(5): 980-4, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25201005

RESUMO

INTRODUCTION: Splenic marginal zone lymphoma (SMZL) is a rare low-malignant Non-Hodgkin lymphoma (NHL), in which immune mediated paraneoplastic phenomena such as autoimmune hemolytic anemia (AIHA), autoimmune thrombocytopenia (ITP) and C1 esterase inhibitor deficiency are relatively common. MATERIALS AND METHODS: We performed a multicenter retrospective study in 70 patients on the prevalence and clinical features of antiphospholipid antibodies (aPLA) in SMZL. RESULTS AND CONCLUSIONS: Nine patients (13%) had the diagnosis of a lupus anticoagulant (LA). The occurrence of venous thromboembolic events was significantly higher in LA positive patients compared to LA negative patients (4/9 [44%] vs 5/61 [8%], p = 0.002), especially within 12 months after splenectomy (3/6 [50%] vs 2/28 [7%], p = 0.007). None of the patients with LA had a persistent complete remission of LA after splenectomy, but complete remission of LA was achieved in 2/2 patients after rituximab-bendamustine immuno-chemotherapy. In conclusion, our data show a relatively high prevalence of aPLA in SMZL and an increased risk of postsplenectomy thrombosis in these patients. The fact that rituximab-bendamustine was effective for eradicating LA may be considered as an argument for using immuno-chemotherapy as first line therapy in SMZL patients with LA.


Assuntos
Inibidor de Coagulação do Lúpus/análise , Linfoma de Zona Marginal Tipo Células B/complicações , Neoplasias Esplênicas/complicações , Trombose/complicações , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Antineoplásicos/uso terapêutico , Feminino , Humanos , Imunoterapia , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab , Baço/patologia , Esplenectomia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Resultado do Tratamento
6.
Haemophilia ; 17(5): e889-94, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21457407

RESUMO

Paraneoplastic FVIII antibodies may occur concurrent with the diagnosis or at various times after diagnosis and treatment of cancer. Between 2002 and 2009, we observed two patients with acquired haemophilia A due to an FVIII auto-antibody, which appeared 4 and 5 months after uncomplicated cancer surgery. We aimed to evaluate if such an association of cancer surgery and FVIII antibody formation has been observed previously. We retrieved all published case reports of cancer-associated FVIII auto-antibodies from PubMed for the period 1950-2010. The search in the literature revealed 13 patients in whom a FVIII inhibitor developed after uncomplicated surgery for cancer and a bleeding-free time interval of up to 6 months; 11/15 patients had abdominal cancers (five colon cancer, four pancreatic cancer, gastric cancer and choledochus carcinoma one each). The median time period between surgery and antibody detection was 3 months (1 week-6 months). In most cases, the antibody titre was low (median: 14 BU mL⁻¹, range: 1.7-64 BU mL⁻¹). Immunosuppressive treatment was successful in most of the cases - nine of the treated patients reached a sustained CR of the antibody after a median time of 3 months. Postoperative paraneoplastic FVIII inhibitors may be regarded as a special, not yet recognized subgroup of acquired FVIII antibodies. They share some characteristics with postpartum FVIII inhibitors with regard to the latency period between the triggering event and the appearance of the antibody, and between the usually low antibody titres and their good response to immunosuppressive treatment.


Assuntos
Autoanticorpos/imunologia , Fator VIII/imunologia , Hemofilia A/imunologia , Neoplasias/imunologia , Síndromes Paraneoplásicas/imunologia , Complicações Pós-Operatórias/imunologia , Idoso , Feminino , Hemofilia A/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/cirurgia , Síndromes Paraneoplásicas/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico
7.
Haemophilia ; 15(4): 888-93, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19473415

RESUMO

Survival of patients with haemophilia is still a relevant issue of great interest. A survival analysis was conducted among 226 patients with haemophilia A and B (128 severe haemophiliacs), who were treated at the haemophilia care centre in Vienna. Information on mortality in our patient cohort was obtained from the Austrian Central Death Register. Overall, 96 of a total of 226 patients (42.5%) died between 1983 and 2006; 37 patients (38.5%) died due to HIV-infection, 15 due to HCV infection, 15 due to bleeding (15.6%, respectively) and 29 (30.2%) due to various other causes. The mortality of HIV-positive patients was 74.3% (n = 55) and that of HCV-positive patients was 40.4% (n = 55) in the analysed period. The patient mortality rates were compared with those of the general Austrian male population following adjustment for age and calendar period. We found that the cumulative relative survival of all patients was 0.694 (95% CI 0.614-0.767). The cumulative relative survival of patients with severe haemophilia (FVIII or IX level < or =1%) was 0.489 (0.394-0.579), but was normal (0.986; 95% CI 0.858-1.082) for patients with mild or moderate haemophilia (FVIII or IX level 2-50%). The survival rate was lowest in HIV-positive patients (0.287; 95% CI 0.186-0.398), but was also decreased to 0.874 (0.776-0.951) in HIV-negative patients. It can, therefore, be concluded that the survival of patients with severe haemophilia is still decreased compared to those with non-severe haemophilia and the general male population, regardless of HIV-infection.


Assuntos
HIV-1 , Hemofilia A/mortalidade , Hemofilia B/mortalidade , Hepatite C/mortalidade , Adolescente , Adulto , Idoso , Áustria , Criança , Pré-Escolar , Infecções por HIV/mortalidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
8.
Surg Endosc ; 22(4): 821-48, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18293036

RESUMO

BACKGROUND: Although laparoscopic splenectomy (LS) has become the standard approach for most splenectomy cases, some areas still remain controversial. To date, the indications that preclude laparoscopic splenectomy are not clearly defined. In view of this, the European Association for Endoscopic Surgery (EAES) has developed clinical practice guidelines for LS. METHODS: An international expert panel was invited to appraise the current literature and to develop evidence-based recommendations. A consensus development conference using a nominal group process convened in May 2007. Its recommendations were presented at the annual EAES congress in Athens, Greece, on 5 July 2007 for discussion and further input. After a further Delphi process between the experts, the final recommendations were agreed upon. RESULTS: Laparoscopic splenectomy is indicated for most benign and malignant hematologic diseases independently of the patient's age and body weight. Preoperative investigation is recommended for obtaining information on spleen size and volume as well as the presence of accessory splenic tissue. Preoperative vaccination against meningococcal, pneumococcal, and Haemophilus influenzae type B infections is recommended in elective cases. Perioperative anticoagulant prophylaxis with subcutaneous heparin should be administered to all patients and prolonged anticoagulant prophylaxis to high-risk patients. The choice of approach (supine [anterior], semilateral or lateral) is left to the surgeon's preference and concomitant conditions. In cases of massive splenomegaly, the hand-assisted technique should be considered to avoid conversion to open surgery and to reduce complication rates. The expert panel still considered portal hypertension and major medical comorbidities as contraindications to LS. CONCLUSION: Despite a lack of level 1 evidence, LS is a safe and advantageous procedure in experienced hands that has displaced open surgery for almost all indications. To support the clinical evidence, further randomized controlled trials on different issues are mandatory.


Assuntos
Laparoscopia , Esplenectomia/métodos , Esplenopatias/cirurgia , Europa (Continente) , Humanos
9.
Ann Hematol ; 86(10): 705-10, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17503045

RESUMO

We report on four cases (three women, one man, age at diagnosis 26-61 years) with severe autoimmune thrombocytopenia (AITP) who were refractory to initial steroid therapy (n = 4), to subsequent splenectomy (n = 2), azathioprine (n = 1), and cyclosporine (n = 1). Over years they received low-dose continuous or intermittent steroid therapy. After 6 to 31 years these patients achieved a "spontaneous" complete remission (CR) (n = 3) or partial remission (PR) (n = 1) unrelated to any specific second or third line treatment; CR/PR are sustained for 0.5+ to 9+ years. These data indicate that spontaneous remissions may occur in AITP even after a long duration of the disease.


Assuntos
Púrpura Trombocitopênica Idiopática , Remissão Espontânea , Corticosteroides/administração & dosagem , Adulto , Idoso , Azatioprina/administração & dosagem , Estudos de Coortes , Ciclosporina/administração & dosagem , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/terapia , Esplenectomia , Fatores de Tempo
10.
Leukemia ; 20(3): 404-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16424872

RESUMO

We previously reported the results of a double-blind, placebo-controlled study of Filgrastim in patients with de novo AML undergoing induction and consolidation chemotherapy. The study demonstrated that Filgrastim was effective and well tolerated and had no impact on complete remission or survival. We now report follow-up data on these patients, assessing long-term effects with emphasis on prognostic indicators. After a median follow-up of 7 years, 434 (83%) patients were dead, 73 (14%) were alive, and 14 (3%) were lost to follow-up. The proportions of deaths were similar in the Filgrastim (83%) and placebo (84%) groups. No differences in median time to death (1.04 years Filgrastim, 1.13 years placebo; P = 0.97) or median disease-free survival (0.86 years Filgrastim, 0.79 years placebo; P = 0.52) were evident. Proportional hazard modeling identified age, performance status, and French-American-British subtype as independent predictors for survival (P < 0.001, P = 0.005, and P = 0.036, respectively), whereas cytogenetic status was not (P = 0.118). Filgrastim had no effect on overall survival in any of these subgroup analyses as none of the treatment comparisons were statistically significant. These findings indicate that Filgrastim can be effectively used to support patients with AML undergoing induction and consolidation chemotherapy without worsening long-term disease outcome.


Assuntos
Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adulto , Antineoplásicos/efeitos adversos , Feminino , Filgrastim , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteínas Recombinantes , Análise de Sobrevida
11.
Hamostaseologie ; 26(1): 5-6, 8-12, 2006 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-16444316

RESUMO

The Deutsche Arbeitsgemeinschaft für Blutgerinnungsforschung (DAB) (German Working Party on Blood Coagulation) was founded in 1956 by a few German specialists in haemostasis. In 1982, the DAB was replaced by the Society on Thrombosis and Haemostasis (GTH), which was multinational, with emphasis on German speaking countries. Since I started in this field there was steady progress in the diagnosis and treatment of haemorrhagic and thrombotic disorders. Milestones were the production of effective and safe factor VIII and IX concentrates for haemophilia treatment, the diagnosis of venous thromboembolic disorders by non-invasive methods, the definition of thrombophilic states by laboratory methods and the diagnosis and treatment of immune coagulopathies. In other fields, progress was less impressive. During the last decades attempts have been made to optimize and standardize diagnosis and treatment in the thrombosis and haemostasis field (evidence based medicine). Despite guidelines and consensus statements the clinical problems in individual patients are still frequent and considerable. Therefore, physicians with a special expertise in the field of thrombosis and haemostasis are needed.


Assuntos
Hemostasia , Técnicas Hemostáticas/tendências , Trombose , Transtornos da Coagulação Sanguínea/diagnóstico , Alemanha , Humanos , Tromboembolia/diagnóstico
12.
J Thromb Haemost ; 3(5): 949-54, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15869590

RESUMO

BACKGROUND: Limited data exist on the risk of pregnancy-associated venous thromboembolism (VTE) in women with a history of VTE. OBJECTIVE: To evaluate the risk of recurrent pregnancy-associated thrombosis in women with previous VTE in a large retrospective cohort study. PATIENTS AND METHODS: One hundred and fifty-nine women with at least one pregnancy (293 pregnancies in total) after a VTE were included into the study. The patients underwent a standardized interview on their history of thrombosis and pregnancy-associated complications. RESULTS: Eight recurrent events occurred during 197 pregnancies without thrombosis prophylaxis. The probability of VTE during pregnancy without thrombosis prophylaxis was 6.2% (95% confidence interval 1.6-10.9%). The risk was constant over the whole period of pregnancy. Of the eight women with VTE during pregnancy four had heterozygous FV:R506Q, two in combination with hyperhomocysteinemia. No VTE occurred during 87 pregnancies with thrombosis prophylaxis. In the postpartum period 15 VTEs occurred, two of 83 (2.4%) after pregnancy termination, one of 53 (1.9%) after miscarriage, three of 10 (30%) after stillbirth and nine of 138 (6.5%) after live birth. CONCLUSIONS: Without thrombosis prophylaxis the risk for recurrent symptomatic VTE is substantial during the whole period of pregnancy in women with previous VTE. The majority of events occurred after delivery, reflecting the very high risk during the postpartum period. Prospective and comparative trials to ascertain efficacy and safety of prophylactic heparin are urgently needed.


Assuntos
Complicações Cardiovasculares na Gravidez , Tromboembolia/diagnóstico , Tromboembolia/prevenção & controle , Trombose Venosa/diagnóstico , Trombose Venosa/prevenção & controle , Adolescente , Adulto , Testes de Coagulação Sanguínea , Estudos de Coortes , Fator V/genética , Feminino , Heparina/farmacologia , Heparina de Baixo Peso Molecular/farmacologia , Heterozigoto , Humanos , Hiper-Homocisteinemia/genética , Modelos Biológicos , Gravidez , Resultado da Gravidez , Risco , Fatores de Risco , Fatores de Tempo
13.
Bone Marrow Transplant ; 35(1): 57-62, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15531903

RESUMO

There is consensus that matching of unrelated donors (URD) and patients for HLA class II alleles improves the outcome of hematopoietic stem cell transplantation (HSCT). However, the significance of HLA class I allelic mismatches for transplant outcome is under discussion and reports on long-term effects like chronic graft-versus-host disease (GVHD) are rare. Thus, we investigated the association of human leukocyte antigen (HLA) class I allele mismatches and outcome in 144 patients given HSCT from URD who were matched for HLA-DRB1, DRB3/4/5, and DQB1 alleles. The risk of chronic GVHD was significantly increased in patients with class I mismatched donors, the mismatch either detected by low- or high-resolution typing. A single HLA class I allele mismatch significantly increased the risk of chronic GVHD in multivariate analysis. Overall survival was significantly reduced in patient/donor pairs with more than one-allele class I mismatch. Thus, selection of unrelated donors for transplantation should be based on high-resolution HLA class I typing.


Assuntos
Doença Enxerto-Hospedeiro , Antígenos HLA/biossíntese , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Adulto , Idoso , Alelos , Doadores de Sangue , Incompatibilidade de Grupos Sanguíneos , Feminino , Genes MHC Classe I , Genes MHC da Classe II , Sobrevivência de Enxerto , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Células-Tronco Hematopoéticas/imunologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
14.
Leukemia ; 18(6): 1102-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15085149

RESUMO

The prognostic value of the detection of peripheral blood (PB) and/or bone marrow (BM) involvement by polymerase chain reaction (PCR) amplification of rearranged immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (Igkappa) genes was evaluated in 155 patients with diffuse large B-cell lymphomas (DLBCL). Immunoglobulin gene rearrangements (IgR) were detected in 35/155 (23%) patients. The presence of IgR in PB/BM was related to clinical stage (CS I-III vs CS IV; P<0.001), histopathological detection of BM involvement (P<0.001), and the International Prognostic Index (P<0.001). IgR-positive cases had a significantly lower complete remission (CR) rate (18/35, 51%) than IgR-negative patients (85/120, 71%; P=0.042), and a significantly poorer overall survival (OAS) at 5 years (25 vs 66%; P<0.001). There was a significant difference in the estimated OAS at 5 years between patients with negative BM histology and negative PCR results (66%), patients with negative BM histology but positive IgR (37%), and patients with positive BM histology (12%). Our results indicate that molecular methods improve the accuracy of staging in patients with DLBCL and define a group of patients with normal bone marrow histology who have a significantly poorer OAS due to molecular detection of PB/BM involvement.


Assuntos
Rearranjo Gênico do Linfócito B , Linfoma de Células B/genética , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Medula Óssea/patologia , Células Clonais , DNA de Neoplasias/análise , Humanos , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Reação em Cadeia da Polimerase , Prognóstico , Análise de Sobrevida
15.
Ann Hematol ; 83(1): 9-13, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-13680175

RESUMO

We have originally shown that spontaneous granulocyte/macrophage colony (CFU-GM) formation in semisolid medium is a characteristic in vitro feature of chronic myelomonocytic leukemia (CMML). However, the clinical significance of spontaneous CFU-GM growth in CMML is unknown so far. CFU-GM growth characteristics were studied in semisolid cultures in the absence of exogenous cytokines using peripheral blood mononuclear cells in 30 patients with CMML at first presentation. The median number of CFU-GM/10(5) MNC of all patients was 48.5 (range 0-622) with 18 patients having colony numbers below 100 (low CFU-GM growth) and 12 patients above 100 (high CFU-GM growth). Kaplan-Meier analysis revealed that patients with high CFU-GM growth had a significantly shorter survival than patients with low CFU-GM growth (median 6.5 vs. 44.5 months, p<0.00002). The probability of survival after 2 years was 60.5% for patients with low colony growth but 0% in those with high colony formation. Patients with CFU-GM >100 had a significantly higher WBC count, a higher LDH, and a higher number of blast cells in blood and bone marrow than patients with low colony growth. Moreover, patients with high colony growth had more often splenomegaly and lower platelet counts. In seven patients, in whom semisolid in vitro cultures were performed after transformation into RAEBT/AML, spontaneous colony growth was significantly increased as compared to CFU-GM growth in patients before transformation (median number/10(5) MNC 533, range 212-4553, p<0.005). This study demonstrates that high (>100) spontaneous CFU-GM formation in CMML at presentation correlates with increased disease activity and represents a novel and important prognostic factor predicting for short survival of CMML patients.


Assuntos
Granulócitos/patologia , Leucemia Mielomonocítica Crônica/patologia , Macrófagos/patologia , Células-Tronco Neoplásicas/patologia , Idoso , Idoso de 80 Anos ou mais , Ensaio de Unidades Formadoras de Colônias , Feminino , Humanos , Leucemia Mielomonocítica Crônica/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Risco , Análise de Sobrevida
16.
Leukemia ; 18(1): 146-55, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14603341

RESUMO

To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.


Assuntos
Genes p53/genética , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/classificação , Linfoma Difuso de Grandes Células B/patologia , Plasmócitos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/análise , Feminino , Seguimentos , Genes de Imunoglobulinas , Centro Germinativo/imunologia , Herpesvirus Humano 4/genética , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Linfoma de Células B/classificação , Linfoma de Células B/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Imunoblástico de Células Grandes/classificação , Linfoma Imunoblástico de Células Grandes/mortalidade , Linfoma Imunoblástico de Células Grandes/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Viral/genética , Deleção de Sequência , Taxa de Sobrevida , Resultado do Tratamento
17.
Leukemia ; 18(2): 293-302, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14671635

RESUMO

Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.


Assuntos
Análise Citogenética , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/genética , Doença Aguda , Classificação , Feminino , Seguimentos , Humanos , Cariotipagem , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Recidiva , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms
18.
Ann Hematol ; 82(5): 271-7, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12739063

RESUMO

The growth characteristics and the prognostic value of cytokine-stimulated myeloid colony formation from peripheral blood mononuclear cells (PBMC) of patients with myelodysplastic syndromes (MDS) are largely unknown. In this study we have determined the number of myeloid colony-forming units (mCFUs) in semisolid medium from 112 MDS patients and correlated them with French-American-British (FAB) type, the international prognostic scoring system (IPSS), karyotype, peripheral blood (PB) and bone marrow (BM) blast cells, cytopenias, lactate dehydrogenase (LDH), and survival data. Concerning the FAB classification, lower median mCFUs were found in patients with refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) compared to refractory anemia with excess of blast cells (RAEB) and refractory anemia with excess of blasts cells in transformation (RAEB-T). In vitro growth in MDS clearly correlated with the cytogenetic risk groups defined by the IPSS (30.5/10(5) PBMCs with favorable karyotypes, 191 in the intermediate prognostic group, 677 with unfavorable cytogenetics, p=0.015 favorable vs unfavorable). BM blast cells >5% (60.5 vs 255 colonies, p=0.032) as well as LDH levels above the normal limit (64.5 vs 425 colonies, p=0.045) were also associated with higher colony formation. Patients were stratified according to the number of circulating mCFUs into a low growth, intermediate growth and high growth group. Median survival was 343 days in the high growth, 1119 days in the low growth, and 2341 days in the intermediate growth group ( p=0.0002). Multivariate analyses revealed colony growth ( p=0.0056), PB blast cells ( p=0.0069), cytogenetic risk group ( p=0.024), and platelet count ( p=0.018) to predict survival in our patients. After inclusion of the IPSS risk categories, mCFU levels remained a highly predictive parameter for survival ( p=0.0056) and acute myeloblastic leukemia (AML) transformation ( p=0.0003).


Assuntos
Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/mortalidade , Células Progenitoras Mieloides/citologia , Células Sanguíneas , Técnicas de Cultura de Células , Divisão Celular , Análise Citogenética , Feminino , Humanos , Leucócitos Mononucleares/citologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndromes Mielodisplásicas/classificação , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
19.
Ann Hematol ; 82(5): 290-4, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12739064

RESUMO

For patients with adult chronic immune thrombocytopenia (ITP) splenectomy (SE) is a highly effective treatment, but there are still uncertainties regarding the long-term efficacy and safety. We evaluated the long-term efficacy and safety of SE in 48 consecutive adult patients with chronic ITP (26 women, 22 men) who underwent SE between 1990 and 2001 at the General Hospital in Vienna, Austria. All patients had no remission after steroid treatment and were steroid dependent. The median age at the time of SE was 44 years (range: 16-77 years). Of 48 patients, 37 achieved a complete remission (CR, platelet count >100 x 10(9)/l), 8 a partial remission (PR) (platelet count 30-100 x 10(9)/l), and 2 had no response (NR). The probability of the overall survival was 98% at a median postsplenectomy observation time of 3.5 years. Seven patients with CR and four patients with PR relapsed. There were no relapses after 1 year. The probability of continuous complete remission (CCR) at 10 years was 79%. The probability of having a platelet count of >100 x 10(9)/l or >30 x 10(9)/l was 61% and 67%, respectively, at 5 and 10 years after splenectomy. Of the 11 relapsed patients, 5 had a second CR ( n=3) or PR ( n=2). The postoperative platelet count was the best predictor for a long-term remission. All patients with postoperative platelet counts >250 x 10(9)/l remained in CR. Patients aged >45 years had a similar success rate as compared with younger patients. Three patients had infections (one pneumonia and two fever of unknown origin) requiring hospitalization, but none had overwhelming septicemia.


Assuntos
Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia , Adolescente , Adulto , Idoso , Doença Crônica , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Recidiva , Indução de Remissão , Trombocitopenia/imunologia , Trombocitopenia/cirurgia , Resultado do Tratamento
20.
Ann Hematol ; 82(5): 295-8, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12679886

RESUMO

We report on a 35-year-old woman who underwent allogeneic stem cell transplantation (SCT) in second complete remission (CR) of acute myeloid leukemia (AML) after reduced-intensity conditioning with fludarabine and 2 Gy of total body irradiation. For graft-versus-host disease (GVHD) prophylaxis, cyclosporin A (CsA) and mycophenolate mofetil (MMF) were given. On day 27 after SCT complete hematological remission and donor chimerism was documented. However, in CD34(+) bone marrow cells 28% of recipient hematopoiesis persisted. On day +59 leukemic relapse occurred. After discontinuation of CsA and onset of GVHD, complete donor chimerism and hematological CR were achieved which has been maintained for 14 months.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Imunoterapia , Leucemia Mieloide/terapia , Condicionamento Pré-Transplante/métodos , Doença Aguda , Adulto , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Recidiva , Indução de Remissão , Transplante Homólogo
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