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1.
J Cancer Res Ther ; 14(5): 1075-1078, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30197351

RESUMO

OBJECTIVE: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin lymphoma (NHL) patients. We also determined the effect of this polymorphism on clinical features and outcome of NHL. METHODS: We included 90 NHL patients (54 males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related rs18011157 polymorphism was determined by polymerase chain reaction. RESULTS: rs18011157 polymorphism was significantly more frequent in NHL patients with GA genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%) and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor prognostic factors in univariate analysis were the presence of B symptoms, initially high International Prognostic Index (IPI), splenomegaly, nonresponse to first-line therapy, the presence of early relapse, and carrying A allele (GA plus AA genotypes). The independent prognostic factors in multivariate analysis were only early relapse and an initially high IPI score. DISCUSSION: CXCL12 rs1801157 polymorphism which was found to be associated with extranodal involvement and increased LDH in NHL might be a marker of poor prognosis in patients with GA and AA genotypes. CONCLUSIONS: CXCL12-related rs18011517 polymorphism was more frequent in NHL patients: it might be associated with NHL pathogenesis and outcome.


Assuntos
Quimiocina CXCL12/genética , Predisposição Genética para Doença , Linfoma não Hodgkin/genética , Prognóstico , Adulto , Idoso , Alelos , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
2.
Clin Rheumatol ; 36(1): 103-109, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27864698

RESUMO

We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values <0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.


Assuntos
Genótipo , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Quinases da Família src/genética , Adulto , Complexo CD3/genética , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Variação Genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Quinase Syk/genética , Resultado do Tratamento , Turquia
3.
Arch Rheumatol ; 32(1): 39-45, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30375526

RESUMO

OBJECTIVES: This study aims to evaluate the mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR) in gouty arthritis (GA) and rheumatoid arthritis (RA) patients, as well as their relationship with atherosclerotic cardiovascular mortality (ACVM). PATIENTS AND METHODS: The study included 122 GA patients (96 males, 26 females; mean age 64.6±13.4 years; range 34 to 82 years), 82 RA patients (40 males, 42 females; mean age 62.1±12.1 years; range 29 to 83 years), and 61 healthy controls (34 males, 27 females; mean age 65.3±4.8 years; range 33 to 80 years). Clinical and ACVM data were obtained from medical charts. Erythrocyte sedimentation rate, C-reactive protein, MPV, and NLR were recorded at the time of diagnosis and one month after therapy. RESULTS: Mean platelet volume in GA (8.49±1.5) and RA (7.98±0.99) groups were significantly lower than in healthy controls (9.8±15) (p<0.001). NLR in healthy controls (1.9±0.74) was significantly lower than in GA (3.6±2.3) and RA (3.7±2.5) groups (p<0.001). After treatment, MPV did not change significantly in GA and RA groups (p values >0.05); however, NLR decreased in both groups (p<0.001). Nine GA and 12 RA patients died from ACVM during follow-up. GA patients with ACVM were older and had more frequent hypertension, higher MPV, and higher intercritical CRP level. In multivariate analysis, MPV was an independent poor prognostic factor for ACVM in GA patients. CONCLUSION: Gouty arthritis and RA patients had significantly lower MPV and significantly higher NLR than controls. MPV might be used as a potential biomarker for the development of ACVM in GA.

4.
Cancer Biomark ; 17(4): 391-396, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27689615

RESUMO

BACKGROUND: Apelin/APJ system regulates angiogenesis and is overexpressed in some malignancies. Apelin can induce lymphangiogenesis and lymph node metastasis. OBJECTIVE: We evaluated apelin levels in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL); and analyzed the association between apelin levels and clinical findings. METHODS: We included consecutive 29 MM, 31 NHL patients, and 19 healthy controls. Patients' demographic and clinical features, treatment modalities, and responses were recorded from hospital records. Plasma apelin was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: MM patients had significantly higher plasma apelin level than NHL and healthy control groups (p< 0.001). Apelin level in NHL group was similar to controls (p> 0.05). ROC curve analysis showed that the area under the curve value for apelin level in MM was 0.842 ng/ml (95%CI: 0.739-0.945, p< 0.001). Plasma apelin level ≥ 0.827 ng/ml had 76% sensitivity and 86% specificity for the diagnosis of MM. Multivariate Cox regression analysis showed that MM patients with high apelin level had better prognosis and patients with advanced stage of disease (ISS-3) had significantly poor prognosis when compared to others. In the MM group, apelin level correlated negatively with LDH (r = -0.39, p= 0.038). CONCLUSIONS: In MM, plasma apelin level was significantly higher than in NHL and control groups. Apelin could be playing a role in MM pathogenesis; and apelin level could be used as a diagnostic and prognostic biomarker in MM.


Assuntos
Biomarcadores Tumorais/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Mieloma Múltiplo/sangue , Apelina , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Prognóstico , Taxa de Sobrevida
5.
Indian J Hematol Blood Transfus ; 32(3): 262-7, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27429517

RESUMO

The most common genetic disorder in Philadelphia negative chronic myeloproliferative neoplasms is the JAK2-V617F mutation. In the present study, we aimed to determine risk factors for thrombosis in patients with essential thrombocytosis and polycythemia vera. We screened the medical records of 101 patients. Risk factors which may predict thrombosis were recorded. Venous thrombosis (VT) before diagnosis was significantly higher in JAK2 positive patients. VT after diagnosis was similar in JAK2 positive and negative groups, and was significantly higher in elderly patients. Treatment places importance on the JAK2 mutation under unmodifiable cardiovascular risk factors such as advanced age after diagnosis.

6.
Rheumatol Int ; 36(7): 945-53, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27221456

RESUMO

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.


Assuntos
Amiloidose/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Amiloidose/diagnóstico , Amiloidose/epidemiologia , Amiloidose/imunologia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Produtos Biológicos/efeitos adversos , Progressão da Doença , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/induzido quimicamente , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/imunologia , Prevalência , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/imunologia , Fatores de Tempo , Resultado do Tratamento , Tuberculose/induzido quimicamente , Tuberculose/epidemiologia , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/imunologia , Turquia/epidemiologia
7.
Clin Rheumatol ; 35(4): 919-25, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26960450

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of autoantibodies and the involvement of multiple organ systems. Systemic sclerosis (SSc) is another autoimmune disease that causes fibrosis. We will aim to analyse the role of killer cell immunoglobulin-like receptor (KIR) genotypes and their existence with the respective HLA ligands in patients with SLE and SSc. Forty-five SLE, 25 SSc and 40 healthy controls were included. We examined the presence/absence of KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1 and their known HLA ligands. In the SLE group, the KIR2DL5, KIR2DL5B and KIR2DS3 genes were significantly more frequent, and KIR2DL3 gene was significantly less than in controls (p values <0.05). In SSc patients, the KIR2DS3 gene was more frequent than in controls (p = 0.032). The KIR2DL3 gene was detected more frequently in controls while KIR2DS3 gene was more frequent in the patient group when SLE and SSc patients were combined (p values < 0.05). The KIR2DS2/HLA-C and KIR2DS2/HLA-C combinations were significantly more in both SLE and SSc groups than in controls. The KIR2DL2 and KIR2DL5B genes were protective from neurologic involvement in SLE patients (p values <0.05). The variations of some KIR genes such as KIR2DL5, KIR2DL5B, KIR2DS3 and KIR2DL3 may have a role in the pathogenesis of SLE and SSc. Also, the presence of KIR2DL2 and KIR2DL5B may cause major organ involvement, like neurologic involvement, in SLE.


Assuntos
Genótipo , Lúpus Eritematoso Sistêmico/genética , Receptores KIR/genética , Escleroderma Sistêmico/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Antígenos HLA-C/genética , Haplótipos , Humanos , Ligantes , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Receptores KIR2DL2/genética , Receptores KIR2DL3/genética , Receptores KIR2DL5/genética , Escleroderma Sistêmico/imunologia
8.
Clin Rheumatol ; 35(8): 2063-2071, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26992904

RESUMO

Epidemiological data about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is very limited. Until now, there has been no study about the epidemiology of AAV in Turkey. In this study, we evaluated the frequency of AAV in the northeastern part of Turkey. The general clinical features of patients diagnosed with AAV at our center within the last 10 years (2004-2014) were retrospectively recorded down. The incidence rates and the prevalence per 1,000,000 population aged ≥16 years were calculated. In addition, we evaluated the clinical features and survival rates of AAV patients. There were 30 patients with granulomatous polyangiitis (GPA), 15 with microscopic polyangiitis (MPA), and 5 with eosinophilic polyangiitis (EGPA). The overall prevalence of AAV in our region was 69.3/1,000,000 in individuals ≥16 years. Males had a similar prevalence (73.2/1,000,000) with females (65.4/1,000,000). The mean annual incidence rate was 8.1/million for all AAV. The annual incidence of AAV in females was 6.9/million; in males, it was 9.2/million. The annual incidence for GPA was calculated as 4.8/1,000,000, the incidence for MPA was 2.4/1,000,000, and the incidence for CSS was 0.8/1,000,000. Ten-year survival of patients with AAV was 65.3 %. The only independent poor prognostic factor in Cox's multivariate analysis was advanced age at the time of diagnosis (OR 7.5, 95 % CI 10.6-526, p = 0.043). The frequency of all AAV in northwestern Turkey was similar to that in southern Europe; however, it was lower than the frequency in Northern Europe.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Adulto , Distribuição por Idade , Idoso , Anticorpos Anticitoplasma de Neutrófilos/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Distribuição por Sexo , Taxa de Sobrevida , Turquia/epidemiologia , Adulto Jovem
9.
Hematol Oncol Stem Cell Ther ; 9(2): 41-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26806462

RESUMO

OBJECTIVE/BACKGROUND: Myelodysplastic syndromes (MDSs) are a group of monoclonal hematopoietic diseases consisting of a number of various entities. The presence of differences in chromosomal content of cells within the same individual is known as chromosomal mosaicism. The impact of mosaic pattern on the prognosis of MDS has been unclear. In this study, we aimed to determine the impact of mosaic pattern on the survival of patients with MDS. METHODS: We retrospectively evaluated 119 patients diagnosed with MDS at the Trakya University Faculty of Medicine, Department of Hematology. Giemsa-Trypsin-Giemsa banding was used to evaluate chromosomal abnormality. The effect of chromosomal abnormality mosaicism on overall survival and transformation to acute leukemia was evaluated by Kaplan-Meier survival analysis. RESULTS: The mean age at diagnosis was 66.3years, and the mean disease duration was 24.2months. Chromosomal abnormality was observed in 32.5% of patients. Patients with chromosomal abnormalities comprising at least 50% metaphases had significantly lower overall survival than patients with abnormality comprising up to 50% of all abnormal metaphases (p=.003). There were no differences in transformation to acute leukemia among patients with higher and lower chromosomal mosaicism (p=.056). CONCLUSION: The most important outcome of this study was to demonstrate worse overall survival rates in MDS patients with higher abnormal chromosomal mosaicism than patients with lesser abnormal chromosomal mosaicism. Higher levels of abnormal chromosomal mosaicism did not predict transformation to acute leukemia. The cause of worse outcomes of patients with higher abnormal chromosomal mosaicism may be related to clonal mass.


Assuntos
Aberrações Cromossômicas , Mosaicismo , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Demografia , Feminino , Humanos , Cariotipagem , Masculino , Metáfase , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Análise de Sobrevida , Organização Mundial da Saúde
10.
Wien Klin Wochenschr ; 128(Suppl 8): 576-580, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25854909

RESUMO

BACKGROUND: In this study, we determined the frequency of migraine headache in iron-deficiency anemia (IDA) patients and whether it was related to anxiety, depression, and somatization. METHODS: We included 127 consecutive IDA patients into the study. All patients were asked validated questions about headache and migraine face-to-face. They were administered validated questionnaires for anxiety-depression The Hospital Anxiety and Depression Scale and somatization. The quality of life (QoL) disturbance associated with headache was marked on a 0-10 VAS. RESULTS: Of all IDA patients, 79.5 % defined headache at any time of their life. In addition, 36.2 % of all IDA patients defined the criteria for migraine. IDA patients with migraine were more frequently smokers and had significantly lower hemoglobin and mean corpuscular volume values (p values < 0.05). The IDA group with migraine had significantly higher mean anxiety score (p = 0.046) and headache-related QoL disturbance score (p = 0.021) than the IDA group without migraine. Migraine patients with aura had lower hemoglobin values (p = 0.02), higher depression scores (p = 0.005), and higher migraine-related QoL disturbance scores than others. CONCLUSIONS: IDA patients have a high frequency of migraine headache. The presence of anxiety and depression have great influence on the presence of migraine in IDA patients.


Assuntos
Anemia Ferropriva/epidemiologia , Ansiedade/epidemiologia , Depressão/epidemiologia , Transtornos de Enxaqueca/epidemiologia , Transtornos Somatoformes/epidemiologia , Saúde da Mulher/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/diagnóstico , Anemia Ferropriva/psicologia , Ansiedade/diagnóstico , Ansiedade/psicologia , Causalidade , Comorbidade , Depressão/diagnóstico , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/psicologia , Fatores de Risco , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/psicologia , Turquia/epidemiologia , Adulto Jovem
11.
Int J Rheum Dis ; 19(12): 1304-1309, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25292400

RESUMO

AIM: There is significant autoantibody production in systemic lupus erythematosus (SLE) and scleroderma (SSc); microchimerism is also thought to play a role in pathogenesis. We determined the frequency of anti-HLA antibodies in SLE and SSc patients and evaluated associated clinical factors. METHODS: We included 77 SLE patients, 46 SSc patients and 53 healthy controls into the study. Clinical data about the patients were obtained from hospital records. Anti-human leukocyte (anti-HLA) antigen antibody analysis of sera was performed by applying Lifecodes anti-HLA Class I and Class II Screening kits based on xMAP technology. RESULTS: The frequencies of class I and II anti-HLA antibodies were significantly higher in SLE (27.3% and 41.6%) and SSc (26.1% and 41.3%) groups than in healthy controls (1.9% and 5.7%) (all P < 0.001). Frequencies of thrombocytopenia (P = 0.021), anti-ribonucleoprotein (P = 0.037) and anti-Ro (P = 0.027) were significantly higher in the class I antibody-positive SLE group; however, pericarditis was less frequent (P = 0.05). On the other hand, the class II antibody-positive SLE group had more frequent anti-ribosomal P antibody (P = 0.038), but less frequent active disease (P = 0.038). In the SSc group, class I antibody-positive patients had more frequent digital ulcers (P = 0.048) and anti-centromere antibodies (P = 0.01). There was no association of anti-HLA antibodies with pulmonary hypertension and interstitial fibrosis in SSc patients. CONCLUSIONS: Both class I and class II antibodies were found to be significantly increased in SLE and SSc. Rather than major organ involvement, anti-HLA antibodies were associated with the presence of other antibodies in both diseases.


Assuntos
Autoanticorpos/sangue , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Escleroderma Sistêmico/imunologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/sangue , Escleroderma Sistêmico/diagnóstico , Testes Sorológicos , Regulação para Cima
13.
Ann Saudi Med ; 35(1): 31-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26142935

RESUMO

BACKGROUND AND OBJECTIVES: Until now, very few studies evaluated the association between gastrointestinal and psychiatric symptoms in iron deficiency anemia (IDA). The study investigated the frequency of functional dyspepsia (FD) in IDA patients and determined its association with depression and somatization. DESIGN AND SETTINGS: The study was conducted at the Hematology Department of Trakya University Medical Faculty, which is a tertiary referral center in northwestern Turkey. It was a case-control study. MATERIALS AND METHODS: A total of 125 consecutive IDA patients and 57 healthy control subjects were included. Patients and controls were questioned about the severity of their gastrointestinal system (GIS)-related symptoms and the presence of constipation and associated symptoms using a visual analog scale. In addition, IDA patients were administered a validated depression scale (Beck Depression Inventory, BDI) and somatization symptoms checklist. RESULTS: IDA patients had more frequent self-reported constipation compared with controls (56% vs 22.8%, P < .001). The mean scores of bloating, dyspepsia, and constipation-related quality of life (QoL) disturbance were significantly higher in the IDA group than in the control group (all P values.


Assuntos
Anemia Ferropriva/psicologia , Depressão/complicações , Dispepsia/psicologia , Adulto , Estudos de Casos e Controles , Constipação Intestinal/epidemiologia , Constipação Intestinal/etiologia , Constipação Intestinal/psicologia , Dispepsia/epidemiologia , Dispepsia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Inquéritos e Questionários , Turquia , Escala Visual Analógica
14.
Clin Exp Rheumatol ; 33(4 Suppl 91): S15-22, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26148346

RESUMO

OBJECTIVES: The pathogenesis of fibrosis in scleroderma (SSc) is unknown. TGF-ß and platelet-derived growth factor are important in the development of fibrosis and tyrosine kinases are involved in these pathways. The possible antifibrotic effects of various kinase inhibitors in SSc have been studied before. Spleen tyro-sine kinase (Syk) is a protein tyrosine kinase which activates intracellular signal transduction pathways; and has been claimed to be involved in the pathogenesis of systemic autoimmune diseases. Inhibition of Syk suppresses IgE- and IgG-associated FcR signal activation in various cell types; and suppresses experimental arthritis and skin and kidney disease in lupus-prone mice. We investigated the ability of a small drug, the Syk inhibitor, fostamatinib, to protect mice from bleomycin-induced SSc. METHODS: Four study groups of BALB/c mice were included into this study: control, bleomycin (administered subcutaneously to BALB/c mice for 21 days), bleomycin and fostamatinib (mice fed with chow containing a Syk inhibitor for 21 days), and fostamatinib alone groups. Skin and lung tissue specimens were obtained and evaluated histologically. RESULTS: Treatment with fostamatinib significantly reduced skin thickness and fibrosis. Mice treated with fostamatinib also displayed less fibrosis and inflammation in the lung tissue. Following fostamatinib treatment, Syk, phospho-Syk, and TGF-ß expression decreased in both skin and lung tissues. CONCLUSIONS: The Syk inhibitor fostamatinib prevented bleomycin-induced fibrosis and inflammation in the skin and in the lung. The anti-fibrotic effect of fostamatinib is linked to reduced Syk phosphorylation and TGF-ß expression. The Syk pathway appears as a potential molecular target for therapeutic intervention in SSc.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Pulmão/efeitos dos fármacos , Oxazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Fibrose Pulmonar/prevenção & controle , Piridinas/farmacologia , Escleroderma Sistêmico/prevenção & controle , Pele/efeitos dos fármacos , Aminopiridinas , Animais , Bleomicina , Citoproteção , Modelos Animais de Doenças , Imunoglobulina E/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Pulmão/enzimologia , Pulmão/imunologia , Pulmão/patologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos Endogâmicos C57BL , Morfolinas , Fosforilação , Proteínas Tirosina Quinases/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Pirimidinas , Receptores Fc/metabolismo , Escleroderma Sistêmico/induzido quimicamente , Escleroderma Sistêmico/enzimologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Transdução de Sinais/efeitos dos fármacos , Pele/enzimologia , Pele/imunologia , Pele/patologia , Quinase Syk , Fator de Crescimento Transformador beta/metabolismo
15.
Leuk Lymphoma ; 56(10): 2902-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25699652

RESUMO

Natural killer (NK) cell killer immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of many diseases. We determined the association between polymorphisms of KIR and their ligands and susceptibility to non-Hodgkin lymphoma (NHL), clinical features and prognosis. We included 90 patients with NHL and 94 controls. In the NHL group, KIR2DS1, HLA-Bw4 (Thr80) and HLA-Bw4 (Thr80)+/Bw4 (Iso80)- ligands were significantly more frequent. Patients with early-stage NHL had more frequent KIR2DL5 and KIR2DL5B than patients with advanced-stage NHL. During a median follow-up of 27 months, 26 patients with NHL died. Poor prognostic factors in univariate analysis were KIR2DL5A, KIR2DS1 and KIR3DS1 genotypes. In multivariate Cox regression analysis, advanced age and early relapse were poor prognostic factors. KIR genes and ligands had no significant effect on survival. The activating KIR2DS1 gene might activate NK cells, contributing to the production of more lymphoma cells. In addition, KIR2DS1, KIR2DL5A and KIR3DS1 might also be associated with a poor prognosis in NHL.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Linfoma não Hodgkin/genética , Polimorfismo Genético , Receptores KIR/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Antígenos HLA/genética , Humanos , Ligantes , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Prognóstico
16.
Ann Hematol ; 94(3): 459-66, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25238800

RESUMO

We evaluated the clinical features, treatment modalities, treatment responses, and prognosis of our patients with immune thrombocytopenia (ITP). Furthermore, we estimated the frequency of ITP in the Thrace region of Turkey. Two hundred sixteen patients diagnosed with ITP between 2000 and 2012 at our center were retrospectively evaluated. Patients' clinical features, treatments, and responses to treatment modalities were recorded. The mean annual incidence of ITP was 2.92/100,000 (95%CI: 1.57-4.27). The overall prevalence of ITP was 35.1/100,000 (95%CI: 30.3-39.8). The administration of first-line therapy resulted in complete remission (CR) in 76.5 % of patients and partial remission (PR) in 13.6 %. After 5 years, 33 % of patients who were responsive to first-line therapy were still in relapse-free remission. Of patients who were given second-line therapy, CR was obtained in 71.3 % and PR in 14.9 %. The duration of relapse-free remission was longer with splenectomy than with steroids (p < 0.001). Five years after splenectomy, 62 % of patients were in relapse-free remission; contrarily, this was lower with steroids (36 % at 5 years). The annual incidence and prevalence of ITP in northwestern Turkey was similar to data from western countries-at the lower limit for some countries. Effective treatment strategies seem to be steroids as first-line therapy and splenectomy in refractory cases.


Assuntos
Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
17.
Hematology ; 20(5): 267-71, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25271869

RESUMO

Aims We determined plasma levels of dickkopf-1 (DKK-1) and osteopontin (OPN) which have roles in the Wnt pathway in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) patients and in healthy controls. We also tested whether DKK-1 and OPN levels could be of clinical or prognostic significance in CLL and NHL. Methods We included 36 CLL, 24 NHL patients, and 21 healthy controls. Patients' clinical and demographic features, treatment modalities, and response to treatment were recorded. DKK-1 and OPN levels in plasma obtained at initial diagnosis were determined with enzyme-linked immunosorbent assay. Results CLL patients had significantly lower DKK-1 levels than NHL and control groups (P levels, respectively, 0.048 and 0.017). OPN level was significantly higher in NHL group than in CLL and control groups (P values, 0.017 and <0.001). CLL patients with early and late Rai stages of disease had similar DKK-1 and OPN levels. After a median follow-up of 48 months, 13 CLL patients died. Univariate analysis showed that advanced Rai stages and older age were significantly poor prognostic factors. DKK-1 level in CLL patients who have died was significantly lower than those who were alive (P = 0.035). NHL patients with extranodal involvement had significantly higher OPN levels than those with no involvement (P = 0.04). Conclusions Our results demonstrated that the Wnt pathway inhibitor DKK-1 was decreased in CLL. OPN was increased in NHL and associated with extranodal involvement. In order to reveal the pathogenic and clinical roles of DKK-1 and OPN in CLL and NHL, larger studies need to be conducted.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/sangue , Leucemia Linfocítica Crônica de Células B/sangue , Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico , Osteopontina/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Curva ROC , Análise de Sobrevida
18.
Australas J Dermatol ; 56(2): 116-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25367408

RESUMO

BACKGROUND/OBJECTIVES: We evaluated the clinical characteristics of patients with haematological malignancies at our centre who were diagnosed with leukaemia cutis (LC). In addition, we describe the spectrum of other skin lesions, including, secondary skin malignancies and nonspecific benign skin lesions in haematological malignancy patients. METHODS: We defined 58 skin lesions that developed in 54 inpatients hospitalised in the Department of Haematology, Trakya University Medical Faculty, Turkey. All skin lesions that developed in inpatients between 2006 and 2012 had been evaluated by a dermatologist. The patients' clinical features, skin biopsy results and therapies were obtained from hospital files. The diagnosis of LC was based on clinical features and histopathological examinations of the skin biopsy. RESULTS: There were 11 patients with LC. Six (54.5%) had acute myeloblastic leukaemia. In nine patients (82%), LC was present at the initial presentation. Secondary skin malignancy was detected in 11 patients (five basal cell carcinoma, four Kaposi's sarcoma, one squamous cell carcinoma, one malignant melanoma); and malignancy was present in two patients (18%) at the initial presentation. Nonspecific benign skin lesions, the most frequent of which were drug eruptions, were determined in 32 of our patients. LC had a significantly higher likelihood of being present at initial presentation than other skin lesions (P < 0.01). The median survival in LC patients was quite short (4.5 months). CONCLUSIONS: LC was usually diagnosed at the initial presentation of the patient or during the early course of the disease. Having LC was a poor prognostic factor.


Assuntos
Toxidermias , Neoplasias Hematológicas/patologia , Infiltração Leucêmica/patologia , Segunda Neoplasia Primária/patologia , Neoplasias Cutâneas/patologia , Pele/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Toxidermias/etiologia , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatopatias/etiologia , Dermatopatias/patologia , Neoplasias Cutâneas/induzido quimicamente
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