Depression and anxiety in patients with multiple sclerosis treated with interferon-beta or fingolimod: Role of indoleamine 2,3-dioxygenase and pro-inflammatory cytokines.

Depression/anxiety (D/A) occurs in up to 50% of multiple sclerosis (MS) patients. Proinflammatory cytokines induce classical symptoms of depression. Activation of the inflammatory response also triggers production of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, the amino acid precursor of serotonin and melatonin. It has been suggested that IDO is the link between the immune and serotonergic systems. This study aimed to quantify the levels of IDO and pro-inflammatory and anti-inflammatory cytokines in patients with MS and depression, according to treatment with interferon-beta (IFN-ß) or fingolimod. The study inclusion criteria were age 18-60 years and a clinical and radiological diagnosis of MS. One hundred and thirty-two patients diagnosed by McDonald's criteria and followed up at Brasília District Hospital, Brazil, with relapsing-remitting MS were identified as potential study participants. Thirty-five of these patients were identified to be receiving treatment with fingolimod or IFN-ß and to have a diagnosis of D/A. IDO and pro-inflammatory and anti-inflammatory cytokine levels were compared between these 35 patients and 18 healthy controls. The level of IL-10 (an anti-inflammatory cytokine) was lower in both the fingolimod-treated (P â€‹< â€‹0.001) and IFN-ß-treated (P â€‹< â€‹0.01) patient groups than in the control group. IFN-ß-treated patients showed increased IDO expression and decreased inflammatory cytokine levels. In contrast, fingolimod-treated patients showed significantly decreased expression of IDO and significantly increased levels of proinflammatory cytokines produced by innate immune cells, including tumor necrosis factor-alpha and interleukin-6. The agents used to treat MS maintain symptoms of D/A in patients with MS via different mechanisms.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis.

Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

From Charcot's descriptions to the current understanding of neuropsychiatric symptoms in multiple sclerosis / Das descrições de Charcot à compreensão atual dos sintomas neuropsiquiátricos na esclerose múltipla

ABSTRACT Neuropsychiatric disorders in multiple sclerosis have been known since the original clinicopathological description by Charcot in the late nineteenth century. Charcot, in the last decades of his life, became involved in the field of neuropsychiatry. This produced a battle between rival schools in the era that still echoes to this day. Charcot's intuition, including the line of thought of Babinski, one of his most famous disciples, was that there was a connection between mood disorders and many of the diseases of the nervous system. Medicine's concern with establishing a relationship between mood disorders and disease stems from the ancient and middle ages with references found in the Hippocratic doctrine. However, it was only in the second half of the nineteenth and early twentieth century, with Charcot's discoveries, that this discussion was established in a structured way, laying the foundations of neuropsychiatry.

RESUMO Os distúrbios neuropsiquiátricos na esclerose múltipla são conhecidos desde a descrição clínico-patológica original de Charcot no final do século XIX. Charcot nas últimas décadas de sua vida se envolveu no campo da neuropsiquiatria. Isso produziu uma batalha de escolas rivais na época que ainda ecoa até hoje. A intuição de Charcot, incluindo a linha de pensamento de Babinski, um de seus discípulos mais famosos, foi a teoria correta da conexão entre os transtornos do humor e muitas das doenças do sistema nervoso. A preocupação da Medicina em estabelecer uma relação entre transtornos do humor e doenças vem das idades antiga e média, com referências encontradas na doutrina hipocrática. No entanto, foi apenas na segunda metade do século XIX e início do século XX que, com as descobertas de Charcot essa discussão foi realizada de maneira estruturada, estabelecendo os fundamentos da neuropsiquiatria.

Adele Bloch-Bauer (1881-1925): Possible diagnoses for Gustav Klimt's Lady in Gold.

One of the most famous works by the Austrian symbolist painter Gustav Klimt and one of the most widely reproduced works of art worldwide, Adele Bloch-Bauer I which portrays the beautiful wife of Austrian magnate Ferdinand Bloch-Bauer. Adele was the only woman painted by Klimt on more than one occasion. Apart from the beauty and value of the painting, the daring sea of gold that surrounds Adele and the gentle intimacy with which her fragile figure is portrayed have shrouded the history of this painting in mystery. Beyond speculation as to a special bond between artist and model, observation of the painting with a keener, clinical gaze yields evidence of potential illness in the model: facial erythema which, if not produced artificially by makeup, could represent a malar rash; pallor or cyanosis of the hands; and her draped fingers, which seemingly attempt to hide a deformity. This paper seeks to provide a biographical review both of the painter, Gustav Klimt, and of the subject, Adele Bloch-Bauer; to analyse Klimt's two portrayals of her in a search for evidence of a potential intimate relationship between artist and muse and, finally, to compile clinical evidence of possible diagnoses for the Lady in Gold.

Exercise and fatigue in rheumatoid arthritis.

Fatigue, the enduring sensation of weakness, lack of energy, tiredness or exhaustion, is described by 40%-80% of patients with rheumatoid arthritis as their most disabling symptom with wide-ranging consequences for quality of life. Little attention has been paid to its multidimensional nature or to its reliability as a measure to evaluate progression of the disease. Low impact aerobic exercise affects the level of fatigue, and this same level of fatigue influences the exercise itself. We searched Medline, Cochrane Collaboration Register of Controlled Trials (CCRCT), Lilacs, PubMed and Scopus databases for randomized controlled trials (with appropriate description of methods, materials and results) on the assessment of fatigue and exercise. Review articles, case reports, letters to the editor and editorials were excluded. Of 121 references initially identified, 4 randomized controlled trials met the inclusion criteria. Two studies used the MAF scale (Multidimensional Assessment of Fatigue), one used the MAC (Mental Adjustment to Cancer) fatigue scale, and all trials used POMS (Profile of Mood States) to assess fatigue. All four trials conducted a 12 week program of two to three times/ week and different periods of follow-up. Two studies used low impact aerobic exercise, one used dance-based exercise, and another study followed a home cardiopulmonary conditioning program using a stationary bicycle. While fatigue appears to be a reliable outcome measure in the clinical management of RA, especially when related to exercise prescription, further research is needed to evaluate the correlation between exercise, fatigue and quality of life, using fatigue scales validated to explore the different components of fatigue and its wide-ranging consequences.

Validade dos esfigmomanômetros utilizados por profissionais de saúde do hospital universitário da Universidade de Brasília / Validity of the sphygmomanometers used by health care professionals at the university hospital of the University of Brasilia

Objetivo: Determinar a precisão dos esfigmomanômetros aneróides, utilizados no Hospital Universitário da Universidade de Brasília. Material e métodos: Foram avaliados 57 aparelhos em relação a defeitos físicos e à precisão. Em novembro de 1997, dois técnicos do Instituto Nacional de Metrologia, Normalização e Qualidade Industrial (Inmetro) aferiram os esfigmomanômetros aneróides portáteis de médicos, enfermeiros e alunos do Hospital Universitário da Universidade de Brasília, utilizando-se o equipamento Onneken-Calibrator, modelo OM 631.000 S (Alemanha). Resultados: O defeito mais encontrado, na avaliação de 12 equipamentos, foi a perda do batente limitador (7/12). Outros defeitos foram vazamento de ar (2/12) e visor estragado (3/12). Esses aparelhos foram reprovados na aferição. Pelos critérios do Inmetro, 35 aparelhos foram aprovados e receberam o selo de validade, e 10 aparelhos foram reprovados. Se considerarmos os critérios do National Bureau of Standards e os da Association for the Advancement of Medical Instrumentation, 15 aparelhos teriam sido reprovados, dos quais nove superestimaram a medida da pressão sanguínea arterial e seis a subestimaram. Dos 57 aparelhos, 55 (96,5 por cento) estavam em uso. Conclusão: Constatou-se que 22 (38,5 por cento) de todos os manômetros avaliados, segundo os critérios do Inmetro, apresentaram-se inadequados à pratica clínica, 12 (21 por cento) por defeitos físicos e 10 (17,5 por cento) por imprecisão. Esses números estão de acordo com os descritos na literatura. Se considerarmos os critérios mais rígidos do National Bureau Standards da Association for the Advancement of Medical Instrumentation, essa porcentagem subirá para 47 por cento.

Cytokines and dysregulation of the immune response in human malaria

The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-I (IL-1) in malaria are lacking. We found that only 2 out of 35 subjectswith acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T- lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 ñ 2,900) and P. vivax malaria (13,000 ñ 3,300), as compared to that of healthy individuals (27,000 ñ 3,000). Addition of IL-1 partially reserved depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2