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1.
Lupus ; 25(12): 1385-94, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27055520

RESUMO

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need.


Assuntos
Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/economia , Adulto , Autoanticorpos/imunologia , Feminino , Grécia , Custos de Cuidados de Saúde , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
2.
Access Microbiol ; 5(9)2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841100

RESUMO

Bacillus Calmette-Guérin (BCG), is administered intravesically as an adjuvant immunotherapy for the treatment of non-muscle invasive bladder cancer. While mild non-infectious problems can occur in up to 85 % of cases, significant local and systemic complications have been reported in 1-5 % of cases. We report the case of a patient with superficial bladder cancer who developed multiorgan failure after intravesical BCG instillation including the kidney and liver with subsequent haemophagocytic lymphohistiocytosis. Our case illustrates the first reported combination of secondary haemophagocytic lymphohistiocytosis with severe renal and liver failure after BCG immunotherapy for bladder carcinoma. Treatment strategy is discussed.

3.
J Gen Virol ; 92(Pt 6): 1343-1351, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21307221

RESUMO

The core region of the hepatitis C virus (HCV) genome possesses an overlapping ORF that has been shown to encode a protein, known as the alternate reading frame protein (ARFP), F or core+1. The biological role of this protein remains elusive, as it appears to be non-essential for virus replication. However, a number of independent studies have shown that the ARFP/F/core+1 protein elicits humoral and cellular immune responses in HCV-infected individuals and interacts with important cellular proteins. To assess the significance of the core+1 humoral response in HCV-infected patients, we examined the prevalence of anti-core+1 antibodies in sera from patients with hepatocellular carcinoma (HCC) in comparison with chronically HCV-infected individuals without HCC. We produced two HCV core+1 histidine-tagged recombinant proteins for genotypes 1a (aa 11-160) and 1b (aa 11-144), as well as a non-tagged highly purified recombinant core+1/S protein (aa 85-144) of HCV-1b. Using an in-house ELISA, we tested the prevalence of core+1 antibodies in 45 patients with HCC in comparison with 47 chronically HCV-infected patients without HCC and 77 negative-control sera. More than 50 % of the serum samples from HCC patients reacted with all core+1 antigens, whereas <26 % of the sera from the non-HCC HCV-infected individuals tested positive. No core+1-specific reactivity was detected in any of the control samples. In conclusion, the high occurrence of anti-core+1 antibodies in the serum of HCC patients suggests a role for the ARFP/F/core+1 protein in the pathogenesis of HCC.


Assuntos
Carcinoma Hepatocelular/imunologia , Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/imunologia , Neoplasias Hepáticas/imunologia , Proteínas do Core Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus/genética , Anticorpos Anti-Hepatite C/sangue , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Proteínas do Core Viral/genética
4.
Clin Genet ; 80(6): 586-90, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21166788

RESUMO

A large scale genetic and epidemiological study of Huntington's disease (HD) was carried out in Greece from January 1995 to December 2008. Diagnostic testing was carried out in 461 symptomatic individuals, while 256 were tested for presymptomatic purposes. The diagnosis of HD with a CAG expansion ≥ 36 was confirmed in 278 symptomatic individuals. The prevalence of HD in Greece was estimated at approximately 2.5 to 5.4:100,000, while the mean minimum incidence was estimated at 2.2 to 4.4 per million per year. The molecular diagnosis of HD was confirmed in the majority of patients (84.4%) sent for confirmation. The false-positive cases 15.6% were characterized by the absence of a family history of HD and the presence of an atypical clinical picture. The uptake of predictive testing for HD was 8.6%. A prenatal test was requested in six pregnancies. The findings of our study do not differ significantly from those of similar studies from other European countries despite the relative genetic isolation of Greece. Of interest is the identification of clusters of HD in Greece. The presence or absence of a family history of HD should be interpreted cautiously, during the diagnostic process.


Assuntos
Predisposição Genética para Doença , Doença de Huntington/diagnóstico , Doença de Huntington/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Testes Genéticos/estatística & dados numéricos , Grécia/epidemiologia , Humanos , Doença de Huntington/epidemiologia , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Linhagem , Gravidez , Diagnóstico Pré-Natal , Prevalência , Estudos Prospectivos , Adulto Jovem
5.
Clin Neuropathol ; 30(1): 11-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21176712

RESUMO

OBJECTIVE: The purpose of this study was to investigate the clinical, electrophysiological and pathological features of Churg Strauss syndrome (CSS) neuropathy. METHODS: Biopsies were selected from over 700 sural nerve biopsies. The diagnosis of vasculitis was based on established clinicopathological criteria. Complete laboratory, clinical, electrophysiological and pathological studies were performed in all cases. RESULTS: Nerve biopsies of 9 patients were diagnosed as Churg-Strauss syndrome. The pathological features were vasculitis with predominant axonal degeneration and a varying pattern of myelinated fiber loss. The vasculitic changes were found mainly in small epineural blood vessels. Mononeuritis multiplex and distal symmetrical and asymmetrical sensorimotor neuropathy, were equally frequent. CONCLUSION: We conclude that, Churg-Strauss syndrome complicated frequently with polyneuropathy, and as remission depends on immunosuppressive therapy, it is important to recognize it in the early stage. The diagnosis of polyneuropathy is based on clinical and electrophysiologic studies, but precise histology, immunolohistochemistry and morphometric study of the peripheral nerve biopsy may be decisive in establishing the diagnosis.


Assuntos
Síndrome de Churg-Strauss/complicações , Síndrome de Churg-Strauss/patologia , Polineuropatias/etiologia , Polineuropatias/patologia , Adulto , Idoso , Biópsia , Síndrome de Churg-Strauss/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polineuropatias/tratamento farmacológico , Nervo Sural/patologia
6.
Semin Arthritis Rheum ; 51(1): 137-143, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33383289

RESUMO

OBJECTIVE: To assess the efficacy and safety of the IL-1b inhibitor canakinumab in all adults with refractory Still's disease identified from the National Organization For Medicines for off-label drug use. METHODS: In a retrospective longitudinal multicenter cohort of 50 patients (median age 39 years) with active Still's disease despite treatment with corticosteroids (n = 11), conventional and synthetic (n = 34) and/or biologic disease modifying anti-rheumatic drugs (n = 30), we assessed the efficacy of canakinumab 150-300 mg administered every 4 (n = 47) or 8 weeks (n = 3) as combination therapy or monotherapy (n = 7) during a median follow-up of 27 (3-84) months. RESULTS: Α complete response was initially observed in 78% of patients within 3 months (median), irrespective of age at disease onset. A partial response was evident in 20%. One patient had resistant disease. Treatment de-escalation was attempted in 15 of 39 complete responders and a complete drug discontinuation in 21 patients for 8 months (median). Eleven patients (22%) relapsed during treatment, one during de-escalation process, and 11 after treatment discontinuation. Overall, 9 of 11 relapses were successfully treated with canakinumab treatment intensification or re-introduction. At last visit, 18% of patients were off treatment due to remission and 26% due to disease activity. Canakinumab had a significant corticosteroid sparing effect allowing weaning in 21 of 41 cases. Infections (20%, severe 4%) and leucopenia (6%) led to treatment cessation in one patient. CONCLUSION: High rates of sustained remission were observed in this, largest so far, real-life cohort of adult patients with refractory Still's disease treated with canakinumab.


Assuntos
Antirreumáticos , Produtos Biológicos , Doença de Still de Início Tardio , Adulto , Anticorpos Monoclonais Humanizados , Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Humanos , Uso Off-Label , Estudos Retrospectivos , Doença de Still de Início Tardio/tratamento farmacológico , Resultado do Tratamento
7.
Ann Rheum Dis ; 69(7): 1352-5, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20472596

RESUMO

OBJECTIVES: The aim of this prospective study was to examine the safety of anti-tumour necrosis factor (TNF) therapy in patients with rheumatic disease and hepatitis B virus (HBV) infection. METHODS: 14 patients with chronic HBV infection, 19 HBV-vaccinated patients and 19 patients with resolved HBV infection were included in the study. All HBV-infected patients received combination therapy with oral antivirals and anti-TNF agents. During treatment the levels of hepatitis B surface antibodies (anti-HBs) in HBV-vaccinated patients and of serum HBV DNA in patients with chronic or resolved HBV infection were monitored. RESULTS: No viral reactivation was observed in patients with resolved HBV infection while anti-HBs titres decreased during anti-TNF treatment in vaccinated patients, similarly to patients treated with methotrexate alone. None of the HBV-infected patients developed liver decompensation or a significant increase in alanine aminotransferase levels. One patient (7%) treated with lamivudine and etanercept showed viral reactivation due to the emergence of a lamivudine-resistant mutant strain. CONCLUSIONS: Anti-TNF agents represent a safe option for patients with chronic HBV infection when combined with antiviral therapy, as well as in patients previously exposed to HBV receiving no HBV prophylaxis. Resistant HBV strains may arise in patients with chronic hepatitis B, necessitating the initial use of anti-HBV agents with a low risk of resistance.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Hepatite B Crônica/complicações , Espondiloartropatias/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Artrite Reumatoide/complicações , Farmacorresistência Viral , Feminino , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/prevenção & controle , Humanos , Lamivudina/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espondiloartropatias/complicações , Ativação Viral/efeitos dos fármacos
9.
Eur Neurol ; 63(6): 350-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20530965

RESUMO

BACKGROUND/AIMS: The onset of multiple sclerosis (MS) in Greece has not been systematically studied. We sought to provide data on the onset of MS in Greece with detailed information regarding initial symptoms, and to confirm the prognostic significance of demographic and clinical factors at onset. METHODS: We studied 1,034 consecutive patients with MS and independently assessed 265 patients 'seen at onset'. We used the MS severity score and survival analysis (time to reach an Expanded Disability Status Scale score of 4.0) to evaluate the prognostic significance of factors at onset. RESULTS: Female-to-male ratio was 1.9:1 and mean age at onset was 30.7 +/- 9.9 years. MS was primary progressive in 9.6%. Initial symptoms were optic neuritis in 20.1%, brainstem dysfunction in 14.7%, dysfunction of long tracts in 49.3%, cerebral dysfunction in 1% and a combination of symptoms in 14.9%. In 'seen at onset' patients, detailed data on initial symptoms are presented. Female gender, earlier age at onset, 'bout onset' and onset with optic neuritis were associated with less severe disease and longer time to disability. CONCLUSION: The onset of MS in Greece is similar to Western populations. Initial symptoms are within the expected spectrum. Prognostic significance of factors at onset is as previously identified.


Assuntos
Esclerose Múltipla , Adulto , Idade de Início , Feminino , Grécia/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Adulto Jovem
10.
Arthritis Res Ther ; 22(1): 56, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32293545

RESUMO

BACKGROUND: European data indicate that systemic sclerosis (SSc)-related death rates are increasing, thus raising concerns about SSc's optimal management. Herein, we describe current treatment modalities and drug survival in a real-life SSc cohort. METHODS: Details on immunosuppressive/antiproliferative (methotrexate, mycophenolate, cyclophosphamide, azathioprine, rituximab, tocilizumab) and vasoactive agent [(endothelin receptor antagonists (ERAs), sildenafil, iloprost, and calcium channel blockers (CCB)] administration during the disease course (11.8 ± 8.4 years, mean + SD) of 497 consecutive patients examined between 2016 and 2018 were retrospectively recorded. Drug survival was assessed by Kaplan-Meier analysis. RESULTS: Methotrexate was the most frequently administered immunosuppressive/antiproliferative agent (53% of patients), followed by cyclophosphamide (26%), mycophenolate (12%), and azathioprine (11%). Regarding vasoactive agents, CCB had been ever administered in 68%, ERAs in 38%, iloprost in 7%, and sildenafil in 7% of patients; 23% of patients with pulmonary fibrosis had never received immunosuppressive/antiproliferative agents, 33% of those with digital ulcers had never received ERAs, iloprost, or sildenafil, whereas 19% of all patients had never received either immunosuppressive/antiproliferative or other than CCB vasoactive agents. Survival rates of methotrexate, cyclophosphamide, and mycophenolate differed significantly, being 84/75%, 59/43%, and 74/63% at 12/24 months, respectively, with inefficacy being the most frequent discontinuation cause. Conversely, CCB, ERAs, and sildenafil had high and comparable retention rates of 97/91%, 88/86%, and 80/80%, respectively. CONCLUSIONS: Existing therapeutic limitations indicate that more evidence-based treatment is warranted for successful management of SSc. Vasculopathy seems to be managed more rigorously, but the low retention rates of immunosuppressive/antiproliferative drugs suggest that effective and targeted disease-modifying agents are warranted.


Assuntos
Preparações Farmacêuticas/administração & dosagem , Escleroderma Sistêmico/tratamento farmacológico , Adulto , Idoso , Azatioprina/uso terapêutico , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas/classificação , Estudos Retrospectivos , Vasoconstritores/uso terapêutico
11.
Eur J Neurol ; 16(2): 205-11, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19146641

RESUMO

BACKGROUND AND PURPOSE: The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (tau(T)) or hyperphosphorylated at threonin-181(tau(P-181)) form and beta amyloid peptide 1-42 (A beta 42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD. METHODS: The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls. RESULTS: Alzheimer's disease and MD showed increased levels of tau(T), tau(P) and reduced levels of A beta 42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying >or=85% of patients, either in the form of a discriminant function or in the form of the tau(T) x tau(P-181)/A beta 42 formula. CONCLUSIONS: Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Demência Vascular/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Demência/diagnóstico , Demência Vascular/diagnóstico , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino
12.
Clin Exp Rheumatol ; 27(3): 409-15, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19604432

RESUMO

BACKGROUND: The frequency of primary systemic small vessel vasculitides (PSV) varies among different geographic regions and age categories. We studied PSV in patients from middle-eastern Crete (Greece), and compared clinical characteristics in younger (<65 years) versus older (> or = 65 years) adult patients. METHODS: The records of 67 patients (33 younger, 34 older adults) diagnosed with PSV during 1995-2003 who were referred to a mixed secondary/tertiary care University Hospital in Crete were reviewed. Data on clinical manifestations, diagnosis, therapy, and adverse outcomes (end stage renal disease, death) during a median follow-up of 6 (range 0-12) years were recorded. Multivariate regression analysis was applied to identify independent predictors for adverse outcomes. RESULTS: The overall annual incidence of PSV was 19.5/million (95% confidence interval [CI] 15.7-23.4), 48.9/million (95% CI 33.8-63.9) in older and 12.4/million (95% CI 7.7-17) in younger adults. Microscopic polyangiitis was more prevalent in older patients (65%) and Wegener's Granulomatosis in younger patients (52%). Thirty-one percent of older patients developed end-stage renal disease as compared to 11% of younger patients (p=0.103). Mortality rates were 60% in older patients and 19% in younger patients (p=0.001). In multivariate regression analysis age (Beta=0.33 per 1-year, p=0.005), serum creatinine (Beta=0.29 per 1-mg/dL, p=0.011), and lung involvement (Beta=0.36, p=0.002) at the time of diagnosis were independent predictors for end stage renal disease and/or death. CONCLUSION: This study documents increased frequency and significant mortality of PSV among older people in Crete, with MPA being the most prevalent type. Age, serum creatinine, and lung involvement are important predictors for adverse outcome in these patients.


Assuntos
Microvasos/patologia , Vasculite/epidemiologia , Vasculite/patologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Seguimentos , Granulomatose com Poliangiite/epidemiologia , Granulomatose com Poliangiite/mortalidade , Granulomatose com Poliangiite/patologia , Grécia/epidemiologia , Humanos , Vasculite por IgA/epidemiologia , Vasculite por IgA/mortalidade , Vasculite por IgA/patologia , Incidência , Estimativa de Kaplan-Meier , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Vasculite/mortalidade , Adulto Jovem
13.
Acta Neurol Scand ; 119(5): 332-7, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18976327

RESUMO

BACKGROUND: Interleukin (IL)-12 is a heterodimeric cytokine produced by activated blood monocytes, macrophages and glial cells. It enhances differentiation and proliferation of T cells and increases production of proinflammatory cytokines. IL-10 is a pleiotropic cytokine produced by both lymphocytes and mononuclear phagocytes including microglia. Recent studies demonstrated the neuroprotective effect of IL-10. There is little information about the involvement of IL-12 or IL-10 in the pathophysiology of Parkinson's disease (PD). OBJECTIVES: The objective of our study was to assess the role of IL-12 as a potential marker of immune reactions in patients with PD and to investigate whether IL-10, an immunosuppressive cytokine, may have a neuroprotective effect in the pathogenesis of PD. PATIENTS AND METHODS: We measured using immunoassay serum IL-12 and IL-10 levels in 41 patients with PD in comparison with serum levels in 19 healthy subjects (controls) age and sex matched. IL-12 and IL-10 levels were tested for correlation with sex, age, disease duration, Hoehn and Yahr stage and the UPDRS III score. RESULTS: The PD group presented with significantly increased IL-10 levels when compared with the control group (P = 0.02). The increase observed was not affected by the treatment status. A strong and significant correlation between IL-10 and IL-12 levels was observed in patients with PD (R(S) = 0.7, P < 0.000001). CONCLUSIONS: Our findings suggest that IL-10 may be involved in the pathogenetic mechanisms of PD. The elevation of IL-10 and the significant correlation between IL-10 and IL-12, a proinflammatory cytokine, may suggest that immunological disturbances and neuroprotective mechanisms are involved in patients with PD.


Assuntos
Citoproteção/imunologia , Tolerância Imunológica/imunologia , Interleucina-10/sangue , Interleucina-12/sangue , Doença de Parkinson/sangue , Doença de Parkinson/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores/sangue , Quimiotaxia de Leucócito/imunologia , Encefalite/sangue , Encefalite/imunologia , Encefalite/fisiopatologia , Feminino , Gliose/sangue , Gliose/imunologia , Gliose/fisiopatologia , Humanos , Interleucina-10/análise , Interleucina-12/análise , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Fagócitos/imunologia , Valor Preditivo dos Testes , Regulação para Cima/imunologia
14.
Neurol Sci ; 30(5): 409-11, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19585078

RESUMO

This case attempts to explicit the importance of clinical examination in the differential diagnosis of two similar clinical entities namely astereognosia and stereoanesthesia. The patient presented below involves a multiple sclerosis patient whose symptoms were considered at first to be a case of astereognosia since she mainly complained of an inability to recognize and name the form and nature of objects by touch. However, a thorough clinical examination and the results of neurophysiological and neuroimaging testing demonstrated that it involved a case of stereoanesthesia due to a demyelinating lesion at the cervical region of the spinal cord.


Assuntos
Agnosia/diagnóstico , Transtornos de Sensação/diagnóstico , Tato/fisiologia , Adulto , Feminino , Humanos , Vibração
15.
J Viral Hepat ; 15(11): 817-26, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18554242

RESUMO

The immunopathogenesis of hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) virus (HBV) infection has not been adequately investigated. We studied the cellular immune responses of peripheral lymphocytes using proliferating assays, intracellular cytokine staining (ICS) and ELISPOT interferon-gamma (IFN-gamma) assays after non-specific and specific stimulation with whole HBV proteins and synthetic peptides. Thirty patients with HBeAg negative CHB, eleven HBsAg inactive carriers, nine patients with acute hepatitis B and 22 healthy controls were included in the study. Patients with HBeAg negative CHB demonstrated an increased number of peripheral CD8+ T cells while their peripheral blood mononuclear cells showed increased proliferation after in vitro stimulation with overlapping hepatitis B core derived peptides and an envelope derived epitope (HBs 182-191 aa), similar to those observed in acute hepatitis B. Using ICS, we found an expanded population of IFN-gamma producing T lymphocytes, CD4+ and CD8+, after non-specific stimulation, in HBeAg negative CHB compared to all other groups. HBeAg negative CHB and acute hepatitis B patients had a similarly increased number of core specific T cells measured by the IFN-gamma assays. Inactive HBsAg carriers showed minimal proliferative responses overall while they exhibited an increased number of envelope specific effector T cells (measured by ICS). In conclusion, we showed that overall CD4+ T cell responses from patients with HBeAg negative CHB were comparable to those of acute hepatitis B, while inactive HBsAg carriers despite their limited proliferative capacity the effector activity of their peripheral T cells was maintained.


Assuntos
Proliferação de Células , Citocinas/biossíntese , Antígenos da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Leucócitos Mononucleares/imunologia , Adulto , Células Cultivadas , Feminino , Antígenos E da Hepatite B/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia
16.
Clin Exp Rheumatol ; 26(5): 784-92, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19032809

RESUMO

OBJECTIVE: The 3E (Evidence, Experts and Exchange) Initiative is a multi-national effort that involves a large number of experts and practicing rheumatologists addressing specific questions relevant to everyday clinical practice, concerning the management of Ankylosing Spondylitis. Within this multinational group, the Hellenic working group, addressed specific issues complementary to the international ones, and formulated evidence-based recommendations, in order to improve everyday clinical practice for patients with Ankylosing Spondylitis. METHODS: A scientific committee of rheumatologists specializing in AS formulated a set of 7 questions in three domains: diagnosis, monitoring and treatment. Literature search in MedLine for papers published up to August 2006 was conducted. The evidence to support each proposition was evaluated and scored. To avoid any conflict of interest with the sponsor issues related to the use of biologics were not discussed. After extensive discussion among 50 rheumatologists and one Delphi round of votes, the final recommendations were formulated. RESULTS: A literature search resulted in a total of 320 relevant papers of which 29 were evaluated. A total of seven recommendations were formulated: two concerning diagnosis (role of HLA-B27 and MRI) and prognosis, one concerning monitoring for extra-articular manifestations and four concerning treatment (analgesics, disease modifying agents and physical therapy) were made. The level of evidence and the strength of recommendation were reported. The compiled agreement among experts ranged from 90% up to 100%. CONCLUSION: Recommendations for the management of AS were developed using an evidence-based approach followed by physicians' consensus with high level of agreement. These are complementary to existing ones, and address specific domains of everyday clinical practice.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Medicina Baseada em Evidências , Metotrexato/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Grécia , Humanos , Espondilite Anquilosante/diagnóstico
17.
Int J Neurosci ; 118(9): 1251-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18698508

RESUMO

Aim of the report was the study of the clinical features of neurosyphilis in the last 40 years (1965-2005). The investigation was based on the retrospective review of patients with neurosyphilis hospitalized in our hospital from 1965 to 2005 (period A: 1965-1984 and B: 1985-2005). Eighty one patients with neurosyphilis were studied. Typical forms represent 68.6% of cases of neurosyphilis in period A. In period B, 85.7% of the cases are presented with atypical clinical patterns. Typical forms of the disease were no longer common, while atypical and masked clinical patterns prevailed. Neuropsychiatric symptoms were the most common manifestations of the disease.


Assuntos
Neurossífilis/diagnóstico , Neurossífilis/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neurossífilis/patologia , Estudos Retrospectivos
18.
Clin Rheumatol ; 37(2): 515-526, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28484887

RESUMO

Patients with rheumatoid arthritis (RA) have higher aortic stiffness and cardiovascular risk. Tumor necrosis factor alpha (TNF-a) antagonists reduce inflammation in RA and are indicated for the treatment of patients with severe active rheumatoid disease. However, it is debatable if they have favorable effects on cardiovascular health. The present meta-analysis evaluates the effect of TNF-a antagonists on aortic stiffness and wave reflections, predictors of cardiovascular events and mortality, in RA patients. A search of PubMed, Cohrane, and Embase databases was conducted to identify studies into the effect of TNF-a antagonists on aortic stiffness in RA patients. Aortic stiffness and wave reflections were assessed by aortic (carotid-femoral [cf]) pulse wave velocity (PWV) and augmentation index (AIx), respectively. cfPWV significantly improved following TNF-a antagonist treatment (mean change: -0.53 m/s, 95% CI: -0.833 to -0.218, p = 0.001), independently of age and clinical response to treatment. A more prominent reduction in cfPWV was associated with etanercept/adalimumab (mean difference: -0.62 m/s, 95% CI: -0.968 to -0.272 m/s, p < 0.001) versus infliximab (mean difference: -0.193 m/s, 95% CI: -0.847 to 0.462 m/s, p = 0.564). TNF-a antagonist treatment induced a significant improvement in AIx (mean change: -1.48%, 95% CI: -2.89 to -0.078%, p = 0.039), but this reduction was influenced by age and clinical response to treatment. The balance of evidence suggests that TNF-a antagonists may have a beneficial effect on aortic stiffness and, therefore, on cardiovascular risk. However, larger, longitudinal studies are warranted to confirm such findings.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Rigidez Vascular/efeitos dos fármacos , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/fisiopatologia , Etanercepte/administração & dosagem , Etanercepte/uso terapêutico , Humanos , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Análise de Onda de Pulso
19.
Eur J Neurol ; 14(2): 168-73, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17250725

RESUMO

The aim of the present study was the quantitation of total tau protein (tau(T)), tau phosphorylated at threonine 181 (tau(P-181)) and beta-amyloid(1-42) (Abeta42) in the cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD) and controls. Double sandwich ELISAs (Innogenetics) were used for the measurements. Total tau was significantly increased in iNPH and highly increased in AD as compared with the control group, whilst Abeta42 was decreased in both diseases. CSF tau(P-181) levels were significantly increased only in AD, but not in iNPH as compared with the controls. A cut-off level for tau(T) at 300 pg/ml, successfully discriminated AD from normal aging with a 95.8% specificity and 91% sensitivity; whilst the tau(P-181)/tau(T) ratio (cut-off value 0.169) was more specific (100%) but less sensitive (92.5%). For the discrimination of iNPH from AD tau(T) achieved low specificity (77.8%) but high sensitivity (92.5%), whilst tau(P-181) (cut-off value 47.4) was both sensitive and specific (88.7% and 86.7% respectively) for the discrimination of these disorders. The present study, despite being clinical, supports the notion that CSF tau(P-181) alone or in combination with tau(T) may be a useful marker in the discrimination of iNPH from AD.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/diagnóstico , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosfoproteínas/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Idoso , Envelhecimento/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/metabolismo , Fosforilação , Sensibilidade e Especificidade , Treonina , Proteínas tau/metabolismo
20.
Dement Geriatr Cogn Disord ; 24(6): 434-40, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17971664

RESUMO

BACKGROUND: An early and accurate diagnosis of Alzheimer's disease (AD) is important in order to initiate symptomatic treatment with currently approved drugs and will be of even greater importance with the advent of disease-modifying compounds. METHODS: Protein profiles of human cerebrospinal fluid samples from patients with AD (n = 85), frontotemporal dementia (n = 20), and healthy controls (n = 32) were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to verify previously discovered biomarkers. RESULTS: We verified 15 protein biomarkers that were able to differentiate between AD and controls, and 7 of these 15 markers also differentiated AD from FTD. CONCLUSION: A panel of cerebrospinal fluid protein markers was verified by a proteomics technology which may potentially improve the accuracy of the AD diagnosis.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer , Demência/diagnóstico , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Biomarcadores , Cromogranina A/líquido cefalorraquidiano , Cistatina C , Cistatinas/líquido cefalorraquidiano , Diagnóstico Diferencial , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Ribonuclease Pancreático/líquido cefalorraquidiano
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