RESUMO
Atherosclerotic cardiovascular mortality is increased in rheumatoid arthritis (RA) patients. We evaluated the association of inflammatory response with platelet, endothelial, coagulation activation parameters; and subclinical atherosclerosis in RA patients. We included 27 RA patients (21 female; six male) and 19 healthy subjects (14 female; five male). Disease activity score (DAS28) in RA patients was calculated; and patients were divided into two groups as active and inactive. Flow cytometry was used to determine platelet CD62P expression, platelet microparticles (PMP), platelet-monocyte (PMC) and platelet-neutrophil complexes (PNC). Plasma E-selectin, thrombin-antithrombin (TAT) complex, and serum sCD40L levels were determined by ELISA. The intima-media thickness (IMT) of carotid arteries was determined by B-mode ultrasonography. In RA patients, platelet CD62P expression (p < 0.001), PMC (p = 0.037) and sCD40L (p < 0.001) levels were increased when compared to the control group. PNC (p = 0.07) and TAT levels (p = 0.1) were non-significantly higher, and PMP level (p = 0.075) was nonsignificantly lower in RA patients. Soluble E-selectin level was significantly higher in the active RA group than in the inactive RA group (p = 0.009). There was no correlation between carotid IMT and activity markers, the evaluated parameters (p > 0.05).The increase in markers of active platelets, CD62P and sCD40L, and PMC levels might be associated with the increased cardiovascular mortality in RA. Nevertheless, none of these parameters were associated with carotid IMT: this suggests that one cross-sectional value might not be a good marker for atherosclerosis
Assuntos
Artrite Reumatoide/metabolismo , Aterosclerose/metabolismo , Ativação Plaquetária , Antitrombinas/metabolismo , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Aterosclerose/sangue , Aterosclerose/complicações , Biomarcadores/sangue , Biomarcadores/metabolismo , Coagulação Sanguínea , Ligante de CD40/sangue , Ligante de CD40/metabolismo , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Selectina E/sangue , Selectina E/metabolismo , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/fisiologia , Neutrófilos/fisiologia , Selectina-P/sangue , Selectina-P/metabolismo , Trombina/metabolismo , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , UltrassonografiaRESUMO
We explored the relationship between the cytogenetic/biologic characteristics of B-chronic lymphocytic leukemia (B-CLL) cells and their tendency to undergo spontaneous or fludarabine-induced apoptosis in vitro. B cells from 36 B-CLL patients were incubated with or without fludarabine for 48 h. Apoptosis was determined by two assays: annexin V staining and DNA staining. Fluorescence in situ hybridization was used for detection of trisomy 12, 11q deletion, and 17p deletion. Bcl-2 and CD38 expressions were determined by flow cytometry. Five patients had 17p deletion, 6 had trisomy 12, and another 6 had 11q deletion. B-CLL cells with 17p deletion had significant resistance to apoptosis induced by fludarabine and a slight spontaneous resistance to apoptosis. Bcl-2 and CD38 were not associated with in vitro spontaneous and fludarabine-induced apoptosis. In conclusion, 17p deletion, which causes loss of p53 gene, is associated with resistance to fludarabine-induced apoptosis in vitro. New treatment modalities should be tried in B-CLL patients with 17p deletion.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Leucemia Linfocítica Crônica de Células B/genética , Vidarabina/análogos & derivados , ADP-Ribosil Ciclase 1/metabolismo , Idoso , Idoso de 80 Anos ou mais , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Feminino , Citometria de Fluxo , Humanos , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Vidarabina/farmacologiaRESUMO
Platelet activation and circulating platelet-leucocyte complexes increase in vascular ischemic events and autoimmune inflammatory diseases. Platelet activation markers and platelet-leucocyte complexes were evaluated in primary Raynaud's phenomenon (RP) and in RP secondary to systemic sclerosis (SSc). Whole-blood flow cytometry was utilized to quantify CD62P, platelet microparticles (PMP), platelet-monocyte complexes (PMC) and platelet-neutrophil complexes (PNC) in primary RP and in SSc patients with secondary RP. SSc patients with secondary RP had significantly higher platelet CD62P expression than primary RP patients and controls (P = 0.017 and 0.004, respectively). Primary and secondary RP patients had higher mean PMC and PNC levels than controls (all P < or = 0.001). PMP level in SSc patients with pulmonary hypertension was significantly higher than in others (P = 0.048). All parameters were similar in SSc patients with and without digital ulcers, aspirin-users and nonusers (P > 0.05). CD62P level decreased significantly after iloprost administration in four patients with digital ulcers (16.1 +/- 17.4 vs 7.4 +/- 3.8%, P = 0.03). Our results suggest there is platelet-leucocyte complex formation in RP, and, despite antithrombotic therapy, platelet activation and platelet-leucocyte interaction are ongoing in SSc. This is important as it might have potential therapeutic implications with respect to using antiplatelet drugs in SSc.
Assuntos
Selectina-P/metabolismo , Ativação Plaquetária/fisiologia , Doença de Raynaud/sangue , Escleroderma Sistêmico/sangue , Adulto , Feminino , Citometria de Fluxo , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/complicações , Doença de Raynaud/fisiopatologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/fisiopatologiaRESUMO
The frequency of antiheparin-platelet factor 4 antibodies by means of antigenic and functional assays ((14) C-serotonin release assay and citrated plasma platelet aggregation) was determined in 115 Turkish patients undergoing cardiac surgery. Blood samples were taken immediately before surgery and on days 5 and 10 +/- 2. Platelet counts were recorded and thrombotic events were determined by clinical methods. Antibody generation measured by enzyme-linked immunosorbent assay before surgery (n = 44) and on days 5 (n = 44) and 10 (n = 115) was 15.9%, 34.1%, and 65.2%, respectively. Positive samples from functional assays were 4.4% on day 0 and 7.0% on day 10. All positive samples had been negative on day 0. A high frequency of antiheparin-platelet factor 4 antibody generation and a low frequency of clinical heparin-induced thrombocytopenia were determined in these patients. These results obtained for Turkish patients are similar to those of other studies of heparin-induced thrombocytopenia.
Assuntos
Anticorpos/análise , Procedimentos Cirúrgicos Cardíacos , Fator Plaquetário 4/imunologia , Trombocitopenia/epidemiologia , Adulto , Idoso , Anticoagulantes/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Feminino , Heparina/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária , Estudos Prospectivos , Trombocitopenia/induzido quimicamente , Turquia/epidemiologiaRESUMO
The coagulation system is activated and coagulation activation markers are elevated in acute ischemic stroke with nonvalvular atrial fibrillation (NVAF). The etiology, severity, and prognosis of the ischemic stroke might be estimated with the level of the activation of the coagulation system. In this study, prothrombin F1+2 (F1+2), D-dimer, and fibrinogen levels were measured in patients with acute ischemic stroke with and without NVAF, and stroke severity was compared with these hemostatic parameters. Of 55 patients, 29 had sinus rhythm (group I), 26 had NVAF (group II); 20 healthy subjects (group III) were included in the study. Subtypes of cerebral infarction were classified. The patients underwent stroke severity, electrocardiography, echocardiography, cranial computed tomography, cervical duplex ultrasonography, and hemostatic parameter studies. In group II, F1+2 level (2.83+/-0.89) was significantly higher than in group I (2.33+/-0.80) and III (1.94+/-0.64) (p values: group I-II, 0.036; groups II-III, 0.001; groups I-III, 0.104). In group III, fibrinogen level (251.64+/-60.96) was significantly lower than that in groups I (347.97+/-111.49) and II (364.04+/-86.20) (p=0.001). D-dimer was not significantly different between groups. In group I, lacunar syndrome (LACS), and in group II, partial and total anterior circulation syndrome (PACS+TACS) were more common (p=0.013, p=0.001, respectively). In group II, Scandinavian Stroke Scale scores were lower than those in group I (group I=45.2+/-14, group II=35.4+/-18.9, p=0.02). In conclusion, activation of coagulation, demonstrated by increment F1+2, is more abundant in the stroke patients with NVAF than in the stroke patients with sinus rhythm. Our results also showed that activation of the hemostatic system might be related to stroke subtype and stroke severity. It is suggested that the oral anticoagulation treatment as prophylaxis is important in the prevention of stroke in patients with NVAF.
Assuntos
Fibrilação Atrial/sangue , Acidente Vascular Cerebral/sangue , Trombofilia/complicações , Idoso , Fibrilação Atrial/etiologia , Estudos de Casos e Controles , Avaliação de Medicamentos , Feminino , Fibrinogênio/análise , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Protrombina , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologiaRESUMO
Patients with type 2 diabetes mellitus (DM) are at risk for the development of cardiovascular diseases, which can in part be explained by disturbances in the hemostatic and fibrinolytic systems. The effects of rosiglitazone treatment on the fibrinolytic system and insulin sensitivity in patients with type 2 DM were assessed. Twenty-four patients with type 2 DM and 28 healthy subjects were enrolled in the study. Plasma global fibrinolytic capacity (GFC), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) levels were measured. Insulin resistance was calculated by hoemostasis model assessment. Patients with type 2 DM then were placed on rosiglitazone (4 mg/day, for 12 weeks) in addition coexistent medication, and baseline tests were repeated. There was no difference between mean t-PA levels of the two groups. PAI-1 levels were higher in diabetic patients than control subjects (p < 0.01). Diabetic patients had lower GFC and t-PA/PAI-1 levels than control subjects (p < 0.05, p < 0.05). PAI-1 levels were positively correlated with waist circumference in diabetic group (r = 0.4, p < 0.05). After rosiglitazone treatment, there was no difference in mean plasma levels of GFC, t-PA, PAI-1 and t-PA/PAI-1 in diabetics. Insulin sensitivity significantly improved after the addition of rosiglitazone treatment in diabetic patients (p < 0.01). The short-term and low-dose treatment with rosiglitazone in type 2 diabetic patients has no effects on the fibrinolytic system, although it improves insulin sensitivity.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Fibrinólise/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Adulto , Diabetes Mellitus Tipo 2/sangue , Feminino , Homeostase/efeitos dos fármacos , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/sangue , Rosiglitazona , Tiazolidinedionas/administração & dosagem , Ativador de Plasminogênio Tecidual/sangueRESUMO
We evaluated the effects of pentoxifylline and indomethacin and heparin in a rabbit model of disseminated intravascular coagulation (DIC) induced by infusion of 100 µg/kg/hour of Escherichia coli endotoxin lipoplysaccharide (LPS) for 6 hour. Heparin, indomethacin, pentoxifylline or saline were administered simultaneously with LPS. In addition, a control group was formed which was administered only saline. Hemostatic markers at 0, 1/2, 2, and 6 hour as well as histopathologic changes in the organs and the mortality at 24 hour were determined. The infusion of LPS caused a severe impairment in hemostasis and fibrin accumulation in the pulmonary vasculature. Heparin significantly improved hemostatic impairment and reduced the fibrin accumulation in the pulmonary vasculature. Pentoxifylline and indomethacin had no significant effect on DIC, except that pentoxifylline prevented the decrement in platelet count slightly (p< 0.05). None of the drugs, including heparin, had any effect on mortality. As a result, the prevention of the synthesis of only one cytokine or autocoid is not considered enough to control the results of endotoxemia.
RESUMO
The case of a 42-year-old woman with aleukemic Bence Jones-type multiple myeloma who developed ocular abnormalities is described. Extramedullary plasmocytomas, either as solitary lesions or as manifestations of multiple myeloma, rarely involve the orbit and dural structures. Early detection of such lesions indicates an aggressive clinical course. In this paper we describe the magnetic resonance imaging findings of ocular and dural myelomatous involvement.
Assuntos
Neoplasias Meníngeas/patologia , Mieloma Múltiplo/patologia , Invasividade Neoplásica , Neoplasias Orbitárias/patologia , Adulto , Dura-Máter/patologia , Feminino , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Pulmonary alveolar proteinosis (PAP) is the intra-alveolar accumulation of periodic-acid schiff (PAS) positive material. PAP is one of the underrecognized causes of pulmonary infiltrates in patients with hematologic malignancies. Here, we present a patient with acute lymphoid leukemia (ALL) in first remission that developed fever and diffuse pulmonary infiltrates during the neutropenic stage of consolidation chemotherapy. The histopathologic examination of bronchoalveolar lavage (BAL) fluid and transbronchial biopsy specimen demonstrated the presence of PAS-positive eosinophilic material. Empirical antibiotherapy and granulocyte-colony stimulating factor (G-CSF) were given. After the correction of neutropenia with G-CSF, the patient's fever disappeared, acute phase reactants decreased, pulmonary infiltrates resolved. We present this case because it was the first patient in whom the correction of neutropenia with G-CSF was followed by resolution of PAP.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Proteinose Alveolar Pulmonar/tratamento farmacológico , Feminino , Humanos , Infiltração Leucêmica , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/etiologia , Indução de RemissãoRESUMO
Essential thrombocythemia (ET) rarely causes obstruction of coronary arteries or acute myocardial infarction. Treatment of acute myocardial infarction in patients with ET may be a problem due to the important role of platelets in the pathogenesis of infarction. There is no reported case of acute myocardial infarction with essential thrombocythemia treated with a glycoprotein IIb/IIIa inhibitor. In this report, a 49-year-old woman with essential thrombocythemia, admitted with a diagnosis of acute inferolateral myocardial infarction, was treated with tirofiban, a glycoprotein IIb/IIIa receptor blocker.
Assuntos
Infarto do Miocárdio/etiologia , Trombocitemia Essencial/complicações , Trombocitemia Essencial/tratamento farmacológico , Tirosina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Tirofibana , Resultado do Tratamento , Tirosina/uso terapêuticoRESUMO
Activated protein C (APC) resistance has been found to be an important cause of venous thrombosis. The prevalence of F V Leiden (FVL) in general population is variable according to the region and the ethnic group. The aim of this study was to determine the prevalence of APC resistance and FVL in healthy population in Edirne as a representative sample of province of Edirne. Total 467 healthy subjects were studied. There were 238 males (50.96%) and 229 females (49.04%). APC resistance was studied by functional and DNA methods. There were a total 22/476 subjects (4.7%) were APC resistance. There were 20/476 subjects (4.28%) who had FVL by DNA test. Of these, there were 18 heterozygous and 2 homozygous FVL and other two subjects have no FVL mutation but have the high levels of FVIII to explain acquired APC resistance. The coexistence of FVL and the deficiencies of protein C (1/22), protein S (2/22) and antithrombin (1/22) were also studied. No one of subjects had prothrombin gene mutation. The data showed that the prevalence of APC resitance and FVL in healthy Turkish population were similar to the previously reported publications in Turkey and Europe. One thing is a keeping in mind to be the coexistence of FVL and the other known thrombophilic risk factors.
Assuntos
Anemia Aplástica/epidemiologia , Imunossupressores/efeitos adversos , Sarcoma de Kaposi/epidemiologia , Neoplasias Cutâneas/epidemiologia , Anemia Aplástica/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Ciclosporina/efeitos adversos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Vincristina/uso terapêuticoRESUMO
We aimed to evaluate the prevalences of self-reported anxiety and depression symptoms in hematological malignancy patients and to determine the association between the presence of these disorders and the results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30). One hundred and forty patients with a diagnosis of a hematological malignancy completed the Hospital Anxiety and Depression Scale (HADS) and the General Health Questionnaire. Patients with higher anxiety scores were more frequently inpatients, had higher EORTC general symptom scores, and they had lower cognitive, emotional, social functioning and global quality of life (QoL) scores (all p values <0.05). Patients with higher depression scores had more frequently active disease and were inpatients; they had higher mean Eastern Cooperative Oncology Group performance scores, EORTC gastrointestinal system and general symptom scores, and significantly lower physical, role, emotional, social and cognitive functioning and global QoL scores (all p values <0.01). During follow-up, it was observed that survival curves of patients with active disease who had higher HADS depression scores tended to be shorter than those with lower scores (p = 0.1). Anxiety and depression are frequent in hematological malignancy patients and associated with poor QoL and performance status. In addition, the presence of self-reported depression might have a predictive value for poor prognosis.
Assuntos
Depressão/epidemiologia , Neoplasias Hematológicas/psicologia , Qualidade de Vida , Adulto , Idoso , Ansiedade , Cognição , Emoções , Feminino , Nível de Saúde , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/fisiopatologia , Neoplasias Hematológicas/radioterapia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Comportamento Social , Inquéritos e Questionários , Análise de Sobrevida , Sobreviventes , TurquiaRESUMO
It is reported that the incidence of thromboembolism is increased in ulcerative colitis (UC), and hypercoagulability persists even when patients are in remission. We evaluated the association of inflammatory response parameters with UC activity, and activation parameters of the platelets, endothelium, and the coagulation system in UC. Eighteen UC patients and 19 healthy subjects were included in the study. The patients' clinical features were recorded down; whole blood counts and acute phase parameters were evaluated. UC patients were divided into two as active (9 patients) and inactive (9 patients) according to combined clinical activity index (CAI) and endoscopic activity index (EAI) scores. In all subjects, platelet CD62P expression, platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC), and platelet microparticles (PMP) were determined by flow cytometry. E-selectin, thrombin-antithrombin complex (TAT) levels in plasma, and sCD40L levels in serum were determined by ELISA. In both active and inactive UC patients, platelet CD62P expression, the percentages of PMC, and PNC were significantly higher than those in the control group (P< 0.01). PMP level was higher in the control group than in inactive UC patients (P = 0.001). sCD40L level was significantly higher in active UC group than in the control group (P < 0.01). EAI score correlated significantly with PMP (r = 0.5, P = 0.04) and sCD40L (r = 0.48, P = 0.044); CAI score had a negative correlation (r = -0.68, P = 0.002) with sE-selectin level. In addition to increased CD62P expression and sCD40L, increased formation of PMC and PNC suggests a role for platelet-leukocyte complex formation together with platelet activation in thromboembolic events observed in UC.
Assuntos
Plaquetas/imunologia , Colite Ulcerativa/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Ativação Plaquetária/imunologia , Adolescente , Adulto , Idoso , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Endoscopia Gastrointestinal/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The most frequent autoimmune complication in chronic lymphocytic leukemia (CLL) is autoimmune hemolytic anemia (AIHA). There are various treatment modalities; however, there is not much experience with the use of the chimeric anti-CD20 monoclonal antibody rituximab in the autoimmune complications of CLL. Here, we present our patient with CLL and AIHA whose AIHA was unresponsive to various treatment modalities. The administration of 375 mg/m(2)/day rituximab weekly for four cycles halted hemolysis and resulted in resolution of the patient's anemia. One year after therapy, the patient is well with a normal blood count. Rituximab might be preferred over other treatment modalities in the autoimmune complications of CLL because it is effective and has fewer side effects than other therapies.
Assuntos
Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Leucemia Linfocítica Crônica de Células B/complicações , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Anticorpos Monoclonais Murinos , Seguimentos , Humanos , Masculino , Rituximab , Resultado do TratamentoRESUMO
Cyclooxygenases (COX) are key enzymes in the conversion of arachidonic acid to prostaglandins. Several studies have shown a relation between angiogenesis and COX-2 expression. Elevated expression of cyclooxygenase-2 (COX-2), however, has not been reported in multiple myeloma (MM) in the literature. The aim of this study is to investigate COX-2 expression in MM as well as its correlation with prognostic factors and estimated survival rates. Immunohistochemical staining of the paraffin-embedded bone marrow biopsy tissues (n = 51) was performed using isoform-specific COX-2 polyclonal antisera (Santa Cruz Biotechnology, Santa Cruz, CA). Results were correlated with recognized clinical parameters, which were retrospectively obtained from patients' files. There were 15, 19, and 17 bone marrow biopsy specimens with negative, weak-moderate, and strong COX-2 immunostaining, respectively. According to univariate analysis, beta2-microglobulin, age, stage, COX-2 expression, and serum lactate dehydrogenase levels were significant prognostic factors for survival in patients with multiple myeloma. COX-2 expression, age, and serum lactate dehydrogenase levels (greater than 1x normal level) were significant prognostic factors by multivariate analysis. Kaplan-Meier overall survival estimate of those patients with negative or weak-moderate COX-2 immunoreactivity in myeloma cells was significantly better than that of patients with strong COX-2 immunoreactivity (log-rank chi(2) = 21,43, P < 0.001). COX-2 overexpression was associated with reduced estimated survival. Poor prognostic factors such as LDH, age, and beta2-microglobulin were also correlated with COX-2 expression. Potent, specific COX-2 inhibitors showing evident antiangiogenic and antitumor effects on cancers could provide new therapeutic strategies in the treatment of MM.