Different effects of anti-TNF-alpha biologic drugs on the small bowel macroscopic inflammation in patients with ankylosing spondylitis.

BACKGROUND & AIMS: Considering the ability of anti-TNF alpha drugs to lower the burden intestinal inflammation in patients with inflammatory bowel disease (IBD), and the similarity between IBD and ankylosing spondylitis (AS) regarding inflammatory intestinal involvement, we aimed to investigate the impact of anti-TNF alpha biologic therapy on subclinical intestinal inflammation in AS patients. METHODS: Between January 2008 and December 2013, 38 AS patients and 23 controls were enrolled in the study and investigated with small bowel videocapsule endoscopy examination and ileocolonoscopy. Each tertile of the small bowel (proximal, mid and distal) was assessed by calculating the Lewis score based on the image stream. RESULTS: The Lewis scores were significantly higher in the AS group compared to controls (580.9 ± 818 vs. 81 ± 121, p<0.001). 16 patients (42.1%) were on anti-TNF alpha therapy (Adalimumab (n = 5), Infliximab (n = 5) or Etanercept (n = 6)).31.3% of them used NSAIDs simultaneously, compared with 77.3% of the other patients (p<0.01). Their Lewis scores were lower compared to the other patients for the entire small bowel (306 ± 164 vs. 790 ± 1038, p = 0.015), its proximal and distal tertiles (238 ± 154 vs. 560 ± 543, p = 0.021, and 140 ± 189 vs. 300 ± 220, p = 0.027, respectively). The Lewis score was also lower in patients receiving Adalimumab/Infliximab compared to those on Etanercept for the entire bowel and its distal tertile (262 ± 165 vs. 380 ± 148, p = 0.069 and 62 ± 101 vs. 273 ± 236, p = 0.060, respectively). CONCLUSION: Anti-TNF alpha therapy in patients with AS reduces the subclinical intestinal inflammation, but the magnitude seems to depend upon the class anti-TNF alpha agent used (Clinical Trials. gov NCT00768950).

IL-17, IL-6 and IFN-γ in Systemic Sclerosis Patients.

BACKGROUND: Systemic sclerosis (Ssc) is an autoimmune disease characterized by cutaneous and visceral fibrosis and its pathogenesis is incompletely understood. T helper cells are key regulators of the immune response and they seem to be involved in Ssc clinical manifestations. The aim of the study is to determine key cytokines secreted by Th1 (IFN-γ), Th2 (IL-6) and Th17 (IL-17) in Ssc patients and correlate them with specific manifestations of Ssc patients. MATERIAL AND METHODS: 35 consecutive Ssc patients and 20 age and sex matched controls were recruited. Serum IL-17, IFN-γ and IL-6 were determined using ELISA method. RESULTS: Serum IL-17 and IL-6 levels were not significantly different in Ssc patients and controls. Serum IFN-γ levels were higher in Ssc patients when compared to controls. Higher serum IFN-γ levels associated with pulmonary hypertension. After adjusting for gender and age, IL-17 levels remained independently associated with some clinical manifestations of Ssc patients (telangiectasia and high activity score of Ssc). CONCLUSION: Th17 and Th1 cell responses are active in Ssc patients as their cytokines associated with higher disease activity scores and pulmonary manifestations. Th17 and Th1 specific activity and homing within Ssc patients still needs to be defined and determined in order to target them as potential future therapeutic targets in Ssc patients.

Study of chemotactic activity developed by neutrophils from rheumatoid arthritis patients.

Neutrophils are the predominant cells accumulated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Accumulation of neutrophils may be regarded as a possible way by which neutrophils exert cytotoxic functions. The aim of the present study was to analyze the chemotactic response of neutrophils (PMNs) isolated from the peripheral blood or SF of patients with RA by performing the chemotaxis assay, in which N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as chemotactic agent. Our results showed that FMLP induced response of peripheral blood neutrophils from 12 patients with RA was similar with the response of 15 healthy controls. A decreased chemotactic response to FMLP was, however, observed in PMNs isolated from the SF of RA patients as comlipared with peripheral blood cells. Therefore, this defective chemotactic ability of neutrophil, was inversely correlated with the number of infiltrating cells in SF. These results indicate that chemotactic ability of neutrophils may be reduced after migration to the SF. Because PMNs chemotaxis in vivo has likely occurred in the presence of serum or SF, we tried to simulate the same conditions in vitro. Therefore, we analyzed the effect of serum or SF on the RA-PMNs chemotaxis. Heat-inactivated serum produced a marked reduction of chemotactic activity developed by PMNs isolated from patients with RA. Notably, a significant increase of chemotactic activity was observed when FMLP and serum stimuli were used together, as compared with the same stimuli used alone. The results suggested that complement activation might interfere with neutrophils chemotaxis. SF amplifies the chemotactic activity of PMNs isolated from peripheral blood of RA patients, but does not affect the chemotaxis developed by PMNs isolated from SF. The data might suggest that several components of SF (IL-8, leukotrien B4, thrombin, platelet-activating factor, etc.) could serve as a potent stimulus for recruitment of neutrophils from periphery into the RA joint. In conclusion, serum or SF components seem to contribute to chemotaxis of neutrophils and play a role in differential killing of PMNs and incidence of infection.

Small bowel inflammatory involvement in Behçet's disease associated spondyloarthritis is different from other spondyloarthritides. A prospective cohort study.

BACKGROUND & AIMS: Behçet's disease presents some similar clinical features with seronegative spondyloarthritides (SpA), raising the question whether a subgroup of patients with Behçet's disease belong in fact to the latter. As the already known inflammatory involvement at the level of the small bowel in SpA patients could not be extrapolated for patients with Behçet's disease associated SpA (BehSpA), the present study aims to investigate and compare it in these diseases. METHODS: 54 consecutive patients with a form of SpA, and 7 patients with BehSpA were enrolled and submitted to videocapsule endoscopy (VCE) examination. After reviewing the VCE findings, calculation of the score of small bowel mucosal inflammatory change (Lewis) was performed for each patient. The comparison was made with a control group, sex and age-matched to the patients in the study groups. RESULTS: The Lewis score differed in the groups considered for analysis (mean of 439, 179 and 81 in the SpA, BehSpA and the control group, respectively, with p = 0.04 for the comparison SpA vs. BehSpA and 0.05 for the comparison BehSpA vs. controls). C reactive protein (CRP) level was markedly reduced in the BehSpA group vs. the other SpA group (2.08 and 14.02 mg/L, respectively; p = 0.053). CONCLUSION: The significant difference in intestinal inflammatory involvement in BehSpA versus the other SpAs, as well as the significantly lower serum levels of CRP, as revealed by the present study, clearly draw a line between the two disease entities.

Th17 and IL-17 immunity in chronic hepatitis C infection.

Hepatitis C virus (HCV) is one of the most important etiologic agents of postransfusional hepatitis and a common cause of chronic hepatitis, cirrhosis and hepatocarcinoma. T helper (Th)17 cells are a newly discovered Th cell subset with implications in both host defense and autoimmunity. Th17 implications in chronic HCV infection are not well characterized. Given the important role in multiple other immune and inflammatory conditions, they are of obvious interest. Specific HCV-Th17 cells are implicated in immune response modulation, correlated with fibrosis severity and intrahepatic inflammatory status. Serum IL-17 levels are higher in chronic HCV infected patients and Th17 cytokines are modulated within the therapeutic response at anti-viral treatment. However, novel intriguing data indicate that Th17 boost could be associated with spontaneous HCV clearance. It is possible that Th17 could play a dual role (both beneficial and harmful) and that an unbalance of regulating factors (chemokines, transcription factors, receptor expression, etc.) rather than the lymphocyte itself could tip the Th17 immune response one way or another. The role of Th17 cells in host anti HCV defense is beginning to emerge and one has to focus upon its potential beneficial aspects and not only on its destructive potential.

Hepatitis C virus-mixed cryoglobulinemia-lymphoma relationship.

HCV (hepatitis C virus) chronic hepatitis has become one the most expensive diseases for public health systems all over the world in the past 10-20 years, a real epidemic, the second most frequent, after hepatitis B virus infection. Due to the complex manifestations, one may consider HCV infection as a "systemic" disease. Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of HCV infection, but cryoglobulinemic vasculitis (CV) is considered to be relatively sparse although prevalence studies are needed. Presence of serum cryoglobulins is essential for MC diagnosis, but serum levels do not correlate with the disease activity or prognosis. MC can be defined as a B lymphocyte proliferation disease being characterized by polyclonal activation and antibody synthesis. Evolution to lymphoma should be considered continuous but also other infectious, environmental or genetic factors could be involved. The t (14.18) translocation and Bcl-2 activation in B lymphocytes, B cell-activating factor (BAFF), E2-CD81 interaction, immunoregulatory T CD4+CD25(high) + lymphocytes and type III IFNs might play an important role in MC and lymphoma evolution in HCV patients.

Neuromyelitis optica--complication or comorbidity in primary Sjögren's syndrome?

We report two cases of neuromyelitis optica (NMO) associated with primary Sjögren's syndrome (pSS), comparing the clinical and laboratory features of these predominant neurological patients and reporting their different outcome. NMO - a severe demyelinating disorder of the central nervous system - primarily affects the spinal cord and optic nerves, resulting in longitudinally extensive transverse myelitis and/or optic neuritis. Our patients had a late pSS diagnosis, due to the absence of sicca syndrome and specific Sjögren serology in the early stages of their diseases, when the neurological symptoms prevailed. Many NMO patients have an accompanying autoimmune disease, most commonly Sjögren syndrome and systemic lupus erythematosus or a related profile of non-organ-specific autoantibodies. Neurologic involvement occurs in approximately 20% of patients with pSS, usually preceding the diagnosis (in 75-80% of the cases) [1,2]. The frequency of both neurologic manifestations (revealing pSS) and negative autoimmune serology, especially in the event of CNS involvement, could explain why underlying pSS is misdiagnosed [3,4]. Screening for pSS should be systematically performed in cases of acute or chronic myelopathy and/or cranial nerve involvement, mainly because these patients have a severe outcome. The presence of the anti-aquaporin4 antibodies, besides anti-Ro and anti-La, in both reported cases, is intriguing and raises the question of whether we are facing two distinct diseases or the NMO is just complicating an unusually less expressive Sjögren's syndrome subtype.

NSAID-induced deleterious effects on the proximal and mid small bowel in seronegative spondyloarthropathy patients.

AIM: To investigate the small bowel of seronegative spondyloarthropathy (SpA) patients in order to ascertain the presence of mucosal lesions. METHODS: Between January 2008 and June 2010, 54 consecutive patients were enrolled and submitted to a video capsule endoscopy (VCE) examination. History and demographic data were taken, as well as the history of non-steroidal anti-inflammatory drug (NSAID) consumption. After reading each VCE recording, a capsule endoscopy scoring index for small bowel mucosal inflammatory change (Lewis score) was calculated. Statistical analysis of the data was performed. RESULTS: The Lewis score for the whole cohort was 397.73. It was higher in the NSAID consumption subgroup (P = 0.036). The difference in Lewis score between NSAID users and non-users was reproduced for the first and second proximal tertiles of the small bowel, but not for its distal third (P values of 0.036, 0.001 and 0.18, respectively). There was no statistical significant difference between the groups with regard to age or sex of the patients. CONCLUSION: The intestinal inflammatory involvement of SpA patients is more prominent in NSAID users for the proximal/mid small bowel, but not for its distal part.

T helper 17 cell population in lupus erythematosus.

UNLABELLED: Lupus erythematosus (LE) is an autoimmune inflammatory disease that involves many organs and systems. Immunological factors seem to play a key-role in LE pathogenesis. LE patients have T lymphocytes dysfunctions.Th17 is implicated in the pathogenesis of various autoimmune diseases like psoriasis, multiple sclerosis or rheumatoid arthritis. The purpose of this study was to evaluate the circulating Th17 cell population in LE patients. MATERIAL AND METHODS: A total of 15 LE patients were recruited and divided into three groups: systemic lupus erythematosus (SLE), discoid lupus (DLE) and subacute lupus (SCLE). Serum IL-17A, IL-17F and IL-23 were detected. Th17 circulating cells were evaluated by flow cytometry. RESULTS: Serum IL-17A and IL-17F levels were higher in SLE, DLE and SCLE patients compared to healthy controls. The number of Th17 cells were higher in SLE and DLE patients (p<0.05). the number of CD3+IL-17+ cells were higher in SLE, DLE and SCLE patients (p<0.05). CONCLUSION: Th17 lymphocytes are implicated in LE pathogenesis. Our findings suggest that IL-17 is implicated not only in SLE but also in DLE and SCLE immunopathogenesis.

Ankylosing spondylitis or Crohn's disease? Case report and review of the literature.

A 27-year-old male with a 2 year history of ankylosing spondylitis (AS) was investigated for intermittent episodes of diarrhea and found to have granulomatous ileitis. Differential diagnosis, discussions regarding similarities in immune alterations in both AS and Crohn's disease and therapeutic options are presented in this paper.

Central pontine and extrapontine myelinolysis.

At the crossover of specialties, the osmotic demyelination syndromes are under-diagnosed clinical entities. Even if the knowledge and the management of these entities have evolved in the latest years, many issues are still unsolved. Initially described as diseases affecting alcoholics and malnourished and considered affecting solely the pons, it is now known that osmotic demyelination can produce extrapontine lesions (extrapontine myelinolysis). Rapid correction of sodium in hyponatremic patients is pathogenically involved in the genesis of central pontine and extrapontine myelinolysis. The aim of this review is to focus on the main characteristics of the disease, which can represent a challenge for the clinicians in respect to its recognition and treatment.

An immunological approach to cerebral ischemia (I). Immune cells and adhesion molecules.

Ischemic stoke is a major cause of death and an important source of disability in industrialized countries. Since there is no ideal treatment for cerebral ischemia, any approach aiming to limit the devastating consequences of the ischemic process is justified. Concerning immune responses, it has become clear in the latest years that actors of the immune system are involved in multiple and various neurobiological processes such as cerebral ischemia, neurodegeneration, neuroprotection and neuroregeneration. An immunological approach to cerebral ischemia can distinguish, besides the implication of inflammation in the developing of atherothrombosis thus leading to stroke, the clear involvement of immune cells and mediators in processes continuing the initial stage of ischemia, having consequences on recovery or lesion extent. Cerebral infarctions develop within minutes to hours of cessation of the cerebral blood flow, but may expand over subsequent days. There is increasing evidence that leukocytes, cytokines, cell adhesion molecules, and other immune mediators contribute to secondary infarction growth, but inflammatory cytokines are also involved in signaling pathways leading to neuroprotection related to ischemic pre-conditioning. The aim of this review is to show some aspects concerning the complex and diverse functions of immune modifications occurring in cerebral ischemia. This first part will focus on the involvement of immune cells, adhesion molecules and immunological transcription factors in the development of ischemic lesion.

Antiphospholipid antibodies and migraine: a retrospective study of 428 patients with inflammatory connective tissue diseases.

The antiphospholipid syndrome (APS) is defined by the presence of antiphospholipid antibodies (aPL), associated with thrombosis or recurrent spontaneous abortions. APS can occur alone or secondary to other conditions, especially associated to inflammatory systemic autoimmune diseases. Among the neurological manifestations associated with aPL, only ischemic stroke is recognized by the actual classification criteria for APS. Other neurological manifestations have been, however, repeatedly reported in case studies of APS patients. Headache, and especially migraine, was commonly reported in APS patients and is one of the classical features described by Hughes as related to aPL, but studies failed to confirm this association. We studied retrospectively the association between headache syndromes and aPL in 428 patients with inflammatory connective tissue diseases admitted in the Neurology and Internal Medicine Departments of Colentina Hospital-Bucharest. We found that migraine alone, not headache of all types, is significantly associated with aPL in patients with systemic immune disease. We studied the presence of cerebral ischemia in patients with headache and aPL. In SLE patients, headache (all types) is significantly associated with positive titers of aPL, and cerebral ischemic lesions are significantly encountered. Even if both migraine and aPL are conditions with high frequency in patients with immune systemic disease and their association may be coincidental, the presence of ischemic lesions in patients showing this association suggests the need to define a sub-group at risk, for whom headache can be a marker and anticoagulants can be discussed.

Anticardiolipin antibodies, recurrent stroke and vascular events: a prospective study on 210 patients.

The presence of anticadiolipin antibodies (aCL) has been associated with vascular occlusive events. However, the role of aCL in predicting ischemic events, particularly ischemic stroke, is controversial. In order to determine if aCL is either associated with thrombotic disease or with an increased risk of recurrent stroke or thrombotic events, we performed a prospective study on a cohort of Romanian patients with stroke that were tested for aCL. We studied the prevalence of cardiovascular risk factors in the two subgroups (aCL positive or aCL negative) considering the age of patients and the medical evolution in the first 12 months after the index stroke. Globally, neither the antecedents of thrombotic events or abortions, nor the clinical or biological profile or the recurrence of vascular events showed any significant difference between the group with or without aCL. Only in two patients the criteria for antiphospholipid syndrome were fulfilled. In 37% of cases, there was a variability of aCL positive titers at 8 weeks after the index event. This raised the necessity to isolate a subpopulation with higher risk of ischemia in the presence of aCL, and the need of more specific subtypes of antiphospholipid antibodies as a marker of thrombophilia.

Lupus-like disease with anticardiolipin antibodies and lupus anticoagulant as a cause for atypical Eaton-Lambert syndrome and peripheral nerve disease: a case report.

In the practice of neurology, the type of clinical involvement suggests the site of the lesion and the mechanism beneath. Sometimes, the symptoms can be delusive, turning the diagnostic approach to a wrong path and raising the necessity of an algorithm considering the less probable entities. Dysimmunity as mechanism of neurological disease involving both the neuromuscular junction and peripheral nerves is frequently insidious and difficult to suspect on clinical basis alone. We report the case of a 67-year-old male with atypical Eaton-Lambert syndrome and mononeuropathy probably in relation with lupus-like entity. The patient has also high titers of anticardiolipin antibodies and lupus anticoagulant. We are considering the diagnostic algorithm before an isolated and atypical neurological presentation and reviewing the main neurological manifestations in lupus-like and autoimmune systemic disease. We raise the difficulty to classify an inflammatory connective tissue disease in the absence of other pathologic features than autoantibodies and isolated neurological symptoms and discussing the main therapeutic issues.

[Bronchoalveolar lavage findings in the pulmonary impairment related to systemic sclerosis]. / Evaluarea prin lavaj bronhiolo-alveolar a afectarii pulmonare din scleroza sistemica.

UNLABELLED: The main objective of the study was to evaluate the relationship between the findings of the bronchoalveolar lavage (BAL) and the lung function in patients with systemic sclerosis and subsequent pulmonary impairment. The study was retrospective and included 17 cases with systemic sclerosis and pulmonary involvement investigated at "Marius Nasta" Institute. Bucharest, between January 1999-August 2001. Lung function assessment found the following: VC (% of predicted) = 82.5 +/- 14; DLCO (% of predicted) = 67.5 +/- 23.2. Cell count in BAL fluid showed: total number of cells x 10(6) = 11.5 +/- 6; lymphocytes (%) = 22.9 +/- 15.4; neutrophils (%) = 15.2 +/- 13.4; eosinophils (%) = 1.9 +/- 0.9; macrophages (%) = 58.1 +/- 19.8. We also compared the cell pattern according to DLCO value: the patients with DLCO > 80% had increased levels of eosinophils (5.2 +/- 4.9 vs 0.9 +/- 0.2, p = 0.007) while the group with DLCO < 80% presented significantly higher levels of neutrophils (16.1 +/- 15.5 vs 12.6 +/- 2.8, p = 0.003) compared to the group with normal lung function. CONCLUSIONS: Patients with systemic sclerosis and normal lung function present an increased level of eosinophils in BAL fluid, suggesting a transitory alveolitis. In change, those with DLCO < 80% have a higher level of neutrophils, usually associated to pulmonary fibrosis. The investigation by BAL appears to be a reliable tool for the assessment of the pulmonary impairment related to systemic sclerosis.

Avaliação preliminar da escala de desempenho em informática educacional com professores / Preliminar evaluation of educational informatics performance scale

É indiscutível o uso da tecnologia como ferramenta básica no cotidiano educacional. Faz-se necessário um instrumento de avaliação que possibilite a identificação do padrão de desempenho dos professores em informática educacional. Objetivou-se verificar a eficácia da Escala de Desempenho em Informática Educacional, em formato eletrônico, através de um estudo piloto para identificar as evidências de validação. Participaram da pesquisa 82 professores de escolas públicas e privadas de ensino fundamental. A Escala de Desempenho em Informática Educacional, respondida via Internet, tem 51 itens com quatro alternativas de resposta a fim de determinar o perfil do professor. Verificou-se que a Escala de Desempenho em Informática Educacional apresenta uma boa consistência interna (αCronbach =0,9678) e uma correlação média entre os itens de 0,3792. A precisão interna do instrumento, verificada pelo método das metades, revelou homogeneidade dos itens. A análise fatorial indicou a necessidade apenas da reorganização de alguns itens nos níveis propostos. A análise das qualidades psicométricas do instrumento associada à fatorial revelou que há possibilidade de validação da Escala de Desempenho em Informática Educacional.

The information technology is an education elementary tool. An instrument able to analyze teachers performance using this technology as an educational tool is very important. This research purpose was to evaluate the psychometrics characteristics of the Educational Informatics Performance Scale through an online pilot study. 82 elementary teachers from public and private schools were the subjects of this study. Educational Informatics Performance Scale, which was answered online, was composed by 51 items with 4 answer choices each one in order to define every teacher's profile. The results has presented a good internal consistency (αCronbach =0,9678) and a 0,3792 average items correlation. The instrument internal precision has identified the items homogeneity, and it was verified by the split-half method. The factorial analysis has suggested some items rearranges according to the scale definitions. The psychometrics qualities added to the results of factorial analysis has revealed the Educational Informatics Performance Scale effectiveness validity.

Avaliação de compreensão em leitura usando cloze na 4ªsérie / Evaluation of the reading comprehension using cloze on the fourth grade of the fundamental school

O presente estudo teve por objetivos caracterizar o desempenho em compreensão em leitura e verificar as qualidades psicométricas da Prova de Compreensão em Leitura. Participaram desta pesquisa 511 alunos, com idade entre 9 e 14 anos (M = 9,80; DP = 8,4), sendo 53% do gênero masculino, cursando regularmente a quarta serie do ensino fundamental de escolas publicas e particulares do interior de São Paulo. A Prova de Compreensão em Leitura e composta por um trecho da historia na qual foi aplicada a Técnica de Cloze. Os resultados revelaram que 66% dos participantes tem dificuldade para compreender o que tem, e 22% podem ser considerados competentes. A Prova de Compreensão em Leitura apresentou evidencias de validade de critico quanto a idade e possibilita discriminar os leitores hábeis dos que apresentam dificuldades em leitura. Quanto a fidedignidade do instrumento, o coeficiente Alpha de Cronbach indicou precisão de 0,95.

The present study aims at characterizing reading comprehension performance and analyzing the psychometric qualities of the Reading Comprehension Test. 511 students took part in this research; their age ranged from 9 to 14 years of age (M = 9.80: SD = 8.4), 534 were male, and all of them was attending the fourth grade of funamental school, both public and private. The Reading Comprehension Test is comprised of a text in which Cloze Technique was applied. The results revealed that 68% of the participants have difficulties of under-standing what they read, and 22% could be considered competent. The Reading Comprehension Test showed evidences of age criteria validity, and it discriminates the competent readers from those who show difficulties in reading. The Cronbach Alpha coefficient indicated a precision of 0,95.