Drug Levels and Antibodies Against TNF-blockers in Spondyloarthritis and Rheumatoid Arthritis are Associated with the Activity but they do Not Predict it.

BACKGROUND: Many patients may have resistance to TNF-blockers. These drugs may induce neutralizing antibodies. The determination of the drug levels of TNF-blockers and Anti-Drug Antibodies (ADAs) against TNF-blockers may help to make clinical decisions. OBJECTIVES: The objective of this study was to associate and predict the drug levels of TNFblockers and ADAs in relation to disease activity in patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA). METHODS: Cross-sectional study including patients fulfilling ASAS classification criteria for SpA and 2010 ACR-EULAR classification criteria for RA. These patients were treated with Adalimumab (ADA), Infliximab (IFX), and Etanercept (ETN). A bivariate analysis and the chi-square test were performed to evaluate the association of ADAs and drug levels with activity measures for SpA and RA. Five regression models analyzing drug levels, ADAs and disease activity measures using a multiple linear regression were performed in order to evaluate the prediction of ADAs and drug levels in relation to disease activity. RESULTS: In SpA, IFX levels were associated with BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (p=0.034). In RA, total drug levels were associated with DAS28-ESR (28 joint Disease activity Score-erythrocyte sedimentation rate), (p=0.008), DAS28-CRP (p=0.042), CDAI (Clinical Disease Activity Index) (p=0.047) and SDAI (Simple Disease activity index), (p=0.017). ADA levels had association with CDAI (p=0.002) and SDAI (p=0.002). IFX levels were associated with a DAS28-ESR (p=0.044), DAS28-CRP (p=0.022) and SDAI (p=0.022). ADAs were associated in SpA with BASDAI (p=0.027). Drug levels and ADAs did not predict disease activity in patients with SpA or RA. CONCLUSION: ADAs and drug levels of anti-TNF are associated with disease activity measures in patients with SpA and RA. However, they cannot predict clinical activity in these conditions.

Area contact networks and the spatio-temporal spread of infectious salmon anemia virus (ISAV) in Chile.

Area management, the coordination of production and biosecurity practices across neighboring farms, is an important disease control strategy in aquaculture. Area management in aquaculture escalated in prominence in response to outbreaks of infectious salmon anemia (ISA) internationally. Successes in disease control have been attributed to the separation achieved through area-level synchronized stocking, fallowing, movement restrictions, and fomite or pest control. Area management, however, is costly; often demanding extra biosecurity, lengthy or inconveniently timed fallows, and localization of equipment, personnel, and services. Yet, this higher-order organizational structure has received limited epidemiologic attention. Chile's National Fisheries and Aquaculture Service instigated area management practices in response to the 2007 emergence of ISA virus (ISAV). Longitudinal data simultaneously collected allowed retrospective evaluation of the impact of component tenets on virus control. Spatiotemporal analyses identified hydrographic linkages, shared ports, and fish transfers from areas with recent occurrence of ISAV as the strongest predictors of virus spread between areas, though specifics varied by ISAV type (here categorized as HPR0 for the non-virulent genotypes, and HPRv otherwise). Hydrographic linkages were most predictive in the period before implementation of enhanced biosecurity and fallowing regulations, suggesting that viral load can impact spread dynamics. HPR0 arose late in the study period, so few HPRv events were available by which to explore the hypothesis of HPR0 as progenitor of outbreaks. However, spatiotemporal patterns in HPRv occurrence were predictive of subsequent patterns in HPR0 detection, suggesting a parallel, or dependent, means of spread. Better data precision, breadth and consistency, common challenges for retrospective studies, could improve model fit; and, for HPR0, specification of diagnostic test accuracy would improve interpretation.

Vemurafenib-induced toxic epidermal necrolysis: possible cross-reactivity with other sulfonamide compounds.

Vemurafenib is a newly licensed target-directed medication. It has been proven to improve the survival of patients with metastatic melanoma and the BRAF(V600E) mutation; however, adverse cutaneous reactions are frequent. Few cases of life-threatening severe cutaneous adverse reactions (SCARs) induced by vemurafenib have been reported. Dabrafenib, another selective BRAF inhibitor, has been licensed recently as an alternative drug with the same indications. From a molecular point of view, both vemurafenib and dabrafenib contain a sulfonamide group; cross-reactivity to sulfonamide compounds has been reported in allergic patients. We report on a patient with vemurafenib-induced toxic epidermal necrolysis (TEN). In vitro analysis of lymphocyte reactivity to vemurafenib showed positive results, confirming drug causality. In addition, lymphocytes from the patient reacted to dabrafenib and to the antibiotic sulfonamide drug sulfamethoxazole. Moreover, lymphocytes from two patients with cutaneous adverse reactions to sulfamethoxazole also reacted to vemurafenib and dabrafenib in vitro. These data strongly suggest that there might be clinical cross-reactivity between BRAF inhibitors and sulfonamides in some patients. Thus, precautions should be taken to avoid sulfonamide drugs as much as possible in patients showing serious hypersensitivity reactions to vemurafenib and vice versa.

Risk factors perceived predictive of ISA spread in Chile: applications to decision support.

Aquaculture is anticipated to be a critical element in future solutions to global food shortage. However, diseases can impede industry efficiency and sustainability. Consequently, diseases can and have led to dramatic re-structuring in industry or regulatory practices. The emergence of infectious salmon anemia (ISA) in Chile is one such example. As in other countries, many mitigations were instituted universally, and many incurred considerable costs as they introduced a new layer of coordination of farming activities of marine sites within common geographic areas (termed 'neighborhoods' or 'barrios'). The aggregate response led to a strong reduction in ISA incidence and impact. However, the relative value of individual mitigations is less clear, especially where response policies were universally applied and retrospective analyses are missing 'controls' (i.e., areas where a mitigation was not applied). Further, re-focusing policies around disease prevention following resolution of an outbreak is important to renew sustainable production; though, again, field data to guide this shift in purpose are often lacking. Expert panels can offer timely decision support in the absence of empirical data. We convened a panel of fish health experts to weight risk factors predictive of ISA virus (ISAV) introduction or spread between Atlantic salmon barrios in Chile. Barrios, rather than sites, were the unit of interest because many of the new mitigations operate at this level and few available studies examine their efficacy. Panelists identified barrio processing plant biosecurity, fallowing strategies, adult live fish transfers, fish and site density, smolt quality, hydrographic connection with other neighborhoods, presence of sea lice (Caligus rogercresseyi), and harvest vessel biosecurity as factors with the greatest predictive strength for ISAV virulent genotype ('HPR-deleted') occurrence. Fewer factors were considered predictive of ISAV HPR0 genotype ('HPR0') occurrence, with greatest strengths assigned to fish and site density, adult live fish transfers, and smolt facility HPR0 status. Field validation based on ISAV and risk factor occurrence after panel completion generally supports expert estimates, and highlights a few factors (e.g., broodstock HPR0 status) less conclusive in the original study. Results inform legislation, industry best management practices and surveillance design.

Indicaciones y utilidad de la inmunoglobulina por vía intravenosa en el manejo de polimiositis refractaria: reporte de caso y revisión de la literatura / Indications and utility of intravenous immunoglobulin in the treatment of refractory polymyositis: a case report and literature review / Indicações e utilidade da imunoglobulina intravenosa na abordagem de polimiosite refratário: relato de caso e revisão da literatura

Las miopatías inflamatorias corresponden a un grupo heterogéneo de enfermedades adquiridas que comprometen el sistema muscular. Tienen en común la presencia de debilidad como síntoma predominante asociado a inflamación muscular. La polimiositis (PM) es una entidad subaguda que afecta principalmente adultos y compromete estructuras musculares proximales. En este artículo se presenta el caso de un paciente de 19 años de edad con diagnóstico confirmado de PM por clínica (compromiso muscular proximal, disfagia), por los resultados de las pruebas bioquímicas (elevación sérica de la creatina kinasa o CK), por estudio de la ultraestructura por microscopia óptica de alta resolución y por los resultados de la resonancia magnética nuclear (RMN) de músculo, quien fue refractario al manejo inicial con corticoesteroides, azatioprina y ciclofosfamida. Con la administración de inmunoglobulina por vía intravenosa se observa una respuesta clínica favorable con aumento progresivo de la fuerza muscular. A pesar de que los esteroides constituyen el tratamiento de elección, en los casos refractarios se usan los agentes inmunosupresores, y la recomendación para su utilización depende de la experiencia médica o conocimiento empírico y de los resultados de los estudios de análisis de seguridad y eficacia. La inmunoglobulina por vía IV es ampliamente usada en el tratamiento de varias enfermedades autoinmunes y su eficacia radica en el efecto inmunomodulador. Sin embargo, es necesario realizar estudios clínicos controlados adicionales, que evalúen su eficacia y seguridad en pacientes con PM...

Inflammatory myopathies belong to a heterogeneous group of acquired diseases involving the muscular system. The predominant symptom is weakness associated with muscle soreness. Polymyositis (PM) is a disorder that primarily affects adults and involves proximal muscle structures. Here, a case report of a 19-year-old patient diagnosed with PM is presented as confirmed by clinical evidence (involving proximal muscle, dysphagia), biochemical findings (elevated serum CK), high-resolution optical microscopy, and ultra structure and nuclear magnetic resonance of muscle. The patient was refractory to initial treatment with corticosteroids, azathioprine and cyclophosphamide. With the administration of intravenous immunoglobulin a good clinical response was observed with progressive increase in muscle strength. Although steroids constitute the main treatment, in refractory cases the use of immunosuppressive agents is recommended, base on medical experience or empirical knowledge together with the analysis of safety and efficacy. Intravenous immunoglobulin is widely used in the treatment of various autoimmune diseases and its effectiveness relies on immunomodulatory effect. Controlled clinical studies are needed to evaluate further its efficacy and safety in patients with PM...

As miopatias inflamatórias pertencem a um grupo heterogêneo de doenças adquiridas, envolvendo o sistema muscular. Têm em comum a presença de fraqueza como sintoma predominante associada a inflamação musculares. A polimiosite (PM) é uma entidade subaguda que afeta principalmente adultos e envolve estruturas musculares proximais. Este artigo apresenta o caso de um doente de 19 anos com diagnóstico confirmado de PM por clínica (envolvendo a musculatura proximal, disfagia), pelos resultados de testes bioquímicos (níveis séricos elevados de creatinoquinase ou CK), para o estudo da ultra-estrutura por microscopia óptica de alta resolução y por los resultados de la resonancia magnética nuclear (RMN) de músculo, que era refratária ao tratamento inicial com corticóides, azatioprina e ciclofosfamida. Com a administração de imunoglobulina intravenosa há uma resposta clínica favorável com aumento progressivo da força muscular. Embora os esteróides são o tratamento de escolha, em casos refratários, são utilizados os imunossupressores, e a recomendação para o uso depende da experiência médica ou conhecimento empírico e os resultados dos estudos de análise de segurança e eficácia. A imunoglobulina intravenosa é amplamente utilizado no tratamento de várias doenças auto-imunes e sua eficácia está no efeito imunomodulador. No entanto, é necessário realizar mais estudos clínicos controlados que avaliem sua eficácia e segurança em pacientes com PM...

Farmacoeconomía de la terapia biológica de las espondiloartropatías: [revisión] / Biological therapy pharmacoeconomics of the spondyloarthropathies: [review]

Las espondiloartropatías (EAS) son un grupo de enfermedades reumatológicas crónicas e inflamatorias. El diagnóstico de estas patologías frecuentemente es tardío; su curso evolutivo es progresivo, con el consecuente deterioro funcional y discapacidad, con compromiso articular que conlleva a la disminución en la calidad de vida con un alto impacto socioeconómico. La mayoría de los estudios farmacoeconómicos se enfocan en los aspectos de la sociedad o del proveedor de los servicios de salud, y sólo una minoría toma en cuenta la perspectiva del paciente, de donde se pueden estimar los recursos médicos directos e indirectos que el paciente y su familia destinan al tratamiento de la enfermedad. La terapia biológica ha demostrado control de todos los aspectos de la actividad de la enfermedad, incluyendo reactantes de fase aguda, dolor y rigidez, capacidad funcional, movilidad espinal, artritis periférica y entesitis.

Miopatía por cuerpos de inclusión. Caso clínico y revisión de la literatura / Miopatia por corpos de inclusão. Relato de caso e revisão da literatura / Inclusion body myopathy. Case report and literature review

La miositis por cuerpos de inclusión (MCI) es una patología poco común que se presenta en individuos mayores de 50 años y con mayor frecuencia en hombres; sin embargo, los síntomas pueden empezar 20 años antes de su diagnóstico. Hasta un 30% de los casos de miopatías inflamatorias pueden ser de MCI y su prevalencia varía en los diferentes países y grupos étnicos. Clínicamente se manifiesta como debilidad lentamente progresiva proximal y distal. En este artículo se presenta un caso de una paciente de 78 años con antecedentes previos de diabetes mellitus tipo 2, hipertensión arterial, e hipotiroidismo, con cuadro de 18 meses de evolución consistente en debilidad de miembros inferiores, incapacidad para subir y bajar escaleras, limitación en la marcha, acompañado de disestesias. Se realizó la medición de la creatin quinasa (CK) y su valor inicial fue 7820, la electromiografía y neuroconducciones mostraron polineuropatia axonal motora en las cuatro extremidades y miopatía inflamatoria. Se trató con glucorticoides a dosis de 1 mg/kg y después de seis meses de tratamiento no se observó mejoría. Se decide tomar biopsia muscular que mostró miopatía por cuerpos de inclusión, lo que explicó la falla terapéutica inicial. Este caso es interesante desde el punto de vista clínico, ya que no es frecuente la elevación de la CK en los niveles que presentó la paciente y por las múltiples comorbilidades asociadas...

Inclusion body myositis (IBM) is an infrequent disease in people over 50 years of age, affecting more frequently males; however the symptoms may begin 20 years before its diagnosis. Up to 30% of all inflammatory myopathies can be IBM and its prevalence varies among different countries and ethnical groups. IBM manifest clinically by slowly progressive proximal and distal weakness. In this article a report of case is presented: A female patient 78 years old with previous history of type 2 diabetes mellitus, hypertension and hypothyroidism; with 18 months history of weakness in lower limbs, inability to climb stairs, limited to walk, associated with dysesthesias. The initial CK was 7820 mg/dl, the electromyography and nerve conductions reported a motor axonal polyneuropathy of four limbs and inflammatory myopathy. She was treated with steroids at doses of 1mg/kg without improvement, after 6 months of treatment. It was decided to take a muscle biopsy that showed an inclusion body myopathy, explaining the initial treatment failure. This case is interesting from a clinical point of view, since it is not frequent elevated CK levels as it was presented by the patient and for the numerous associated co-morbidities...

A miosite por corpo de inclusão (MCI) é uma doença rara que apresenta-se em indivíduos acima de 50 anos, atingindo 30% das miopatias inflamatória; orém os sintomas podem começar 20 anos antes. Sua prevalência varia entre países e grupos étnicos. Clínicamente manifesta-se como uma fraqueza lentamente progressiva proximal e distal mais frecuentemente nos homens. Nós relatamos um caso de uma paciente de 78 anos com antecedentes de diabetes mellitus tipo 2, hipertensão e hipotireoidismo. Com quadro clínico de 18 meses de evolução consistindo em fraqueza nos membros inferiores, incapacidade de subir escadas, a limitação para a marcha, acompanhados de disestesias. Foi feito a prova de CK dando um valor inicial de 7820 e com eletromiografia e neurocondução que informaram polineuropatia axonal motora de quatro membros e miopatia inflamatória. Foi tratado com corticóides em doses de 1 mg / kg sem melhora após 6 meses de tratamento, razão pela qual foi decidido fazer uma biópsia do músculo que mostrou miopatía do corpo de inclusão, explicando a falha do tratamento inicial. Este caso é interessante do ponto de vista clínico, uma vez que não é frequente a elevação da CK nos niveis apresentados pela paciente e pelas múltiplas comorbidades associadas...

[Pulmonary artery aneurism in a patient with Behçet disease. Report of one case]. / Aneurisma de la arteria pulmonar en Enfermedad de Behçet.

Behçet disease is a systemic disease with diverse clinical symptoms which vary according to the organs and systems involved. Typically, patients have oral and genital ulcers and episodic ocular involvement with periods of clinical improvement. We report an 18-year-old mole presenting with chest pain and hemoptysis and a history of ulcers in the oral cavity and scrotum. A chest CAT scan showed a mass located adjacent to the heart that a pulmonary arteriography defined as a left pulmonary artery aneurism. The patient was operated, excising left inferior pulmonary lobe. Due to skin and ocular involvement, the patient complied with criteria for Behçet disease. Immunosuppressive treatment with prednisone and azathioprine was started and the patient was discharged from the hospital.

Aneurisma de la arteria pulmonar en Enfermedad de Behçet / Pulmonary artery aneurism in a patient with Behçet disease. Report of one case

Behçet disease is a systemic disease with diverse clinical symptoms which vary according to the organs and systems involved. Typically, patients have oral and genital ulcers and episodic ocular involvement with periods of clinical improvement. We report an 18-year-old mole presenting with chest pain and hemoptysis and a history of ulcers in the oral cavity and scrotum. A chest CAT scan showed a mass located adjacent to the heart that a pulmonary arteriography defined as a left pulmonary artery aneurism. The patient was operated, excising left inferior pulmonary lobe. Due to skin and ocular involvement, the patient complied with criteria for Behçet disease. Immunosuppressive treatment with prednisone and azathioprine was started and the patient was discharged from the hospital.

Tratamiento de la gota aguda / Treatment of acute gout / Tratamento da gota aguda

La gota es una patología ampliamente descrita a lo largo de la evolución de la historia de la medicina. Desde los tiempos de Galeno hasta nuestros días, continúa siendo un problema de salud pública que genera morbilidad e incapacidad en quien la padece. Aunque la terapéutica no ha cambiado mucho en los últimos años, se hace necesaria una actualización de la información existente en la literatura, ya que se siguen presentando errores en su manejo, no solo en cuanto a la indicación de un medicamento en una situación clínica específica, sino también en el cuidado atento que amerita el posible desarrollo de efectos secundarios a los fármacos tradicionalmente empleados para su manejo...

Gout has been amply described from the times of Galen and it continues to be a public health problem that causes important morbidity in the world population. The treatment of acute gout has not changed in the last years, but a current review and actualization of the medical literature is necessary since there are continuous flaws in the management of this illness, not only in the actual indication of specific drugs, but also in the attentive care required due to the potential development of side effects from the traditional medications used in the treatment...

A gota é uma patologia amplamente descrita ao longo da evolução da história da medicina. Desde os tempos de Galeno até nossos dias, continua sendo um problema de saúde pública que gera morbilidade e incapacidade em quem a padece. Ainda que a terapêutica não mudasse muito nos últimos anos, faz-se necessária uma atualização da informação existente na literatura, devido a que se continuam apresentando erros em seu manejo, não só quanto à indicação de um medicamento numa situação clínica específica, como também no cuidado atencioso que merece o possível desenvolvimento de efeitos secundários aos fármacos tradicionalmente empregados para seu manejo...

Cambio en la capacidad funcional, calidad de vida y actividad de la enfermedad, en un grupo de pacientes colombianos con artritis reumatoide refractaria al tratamiento convencional, que recibieron terapia con infliximab como medicamento de rescate / Changes in the functional capacity, quality of life and activity of the disease in a group of colombian patients with rheumatoid arthritis refractory to the conventional treatments, who were treated with infliximab as rescue therapy / Mudança na capacidade funcional, qualidade de vida e atividade da doença, num grupo de pacientes colombianos com artrites reumatoide refratária ao tratamento convencional, que receberam terapia com infliximab como medicamento de resgate

Rheumatoid arthritis is a chronic inflammatory process that effects mostly the joints leading to destruction of the joint, deformity, incapacity and deterioration of the quality of life. As a result of technologic advances and the better knowledge of the pathophisiology of the disease, there are new therapeutic options with biologic agents. There are no reports from Colombia about the experience with Infliximab in patients with rheumatoid arthritis. The objective of this study was to quantify the changes in quality of life, functional capacity, signs and symptoms related to the inflammatory activity and the therapeutic efficacy, in a group of Colombian patients with long term rheumatoid arthritis (13±10 years) refractory to conventional treatments. A total of 31 patients, 22 women and 9 men, aged 51±12 years and an average evolution of disease of 13.2±10.4 years, who had active disease in spite of having received Methrotexate or Leflunomide in combination with other agents, such as low doses of glucocorticoids, analgesics and antiinflammatories, received infusions of Infliximab at doses of 3mg/kg during weeks 0, 2, 6, 14, and 22, following the guidelines of the Colombian Rheumatology Association. It was determined that the median functional capacity measured by HAQ-DI went from 1,2±0,54 to 0,29±0.28, that the quality of life measured by Spanish-AIMS improved globally from 48,4±14.4 to 29,4±8.2 in each of its eight components. There was also improvement in the components of SF-12 since the physical health went from 39,9±13,7 to 55,5±24,1 and mental health from 57,0±24,2 to 74,6±17,0. Although 71% of the patients had some type of side effect, they were minor and the medication was not stopped. These findings agree with the international reports that the administration on Infliximab induces a significative improvement in those patients with refractory rheumatoid arthritis. Taking into account the potential side effects and the real risk of tuberculosis in our country, the administration of Infliximab must be carried out in specialized units with well trained personnel and under the strict supervision of a rheumatologist.

La artritis reumatoide (AR) es una enfermedad inflamatoria crónica que afecta principalmente las articulaciones, produciendo destrucción articular, deformidad, discapacidad y deterioro de la calidad de vida. Como nuevas opciones de tratamiento, producto del avance tecnológico y del conocimiento de la fisiopatología de la enfermedad, han aparecido recientemente en el mercado los denominados agentes biológicos. Teniendo en cuenta que no hay reportes colombianos sobre la experiencia con infliximab en pacientes con AR, el objetivo de este estudio fue cuantificar en un grupo de pacientes colombianos con AR de larga evolución (13±10 años) y refractarios al tratamiento convencional, el cambio en la calidad de vida, la capacidad funcional, en los síntomas y signos relacionados con la actividad inflamatoria y en la seguridad terapéutica producidos por infliximab. Un total de 31 pacientes, 22 mujeres y 9 hombres, con edades de 51±12 años y un promedio de evolución de enfermedad de 13,2±10,4 años, que permanecieron activos a pesar de recibir metotrexate o leflunomida en combinación con otros agentes modificadores de la enfermedad, bajas dosis de glucocorticoides, analgésicos y antiinflamatorios, recibieron infusiones de infliximab de tres mg/kg dosis durante 22 semanas, siguiendo las recomendaciones de la Asociación Colombiana de Reumatología, en las semanas 0, 2, 6, 14 y 22. Se encontró que la capacidad funcional medida por HAQ-DI pasó de 1,2±0,54 a 0,29±0.28, que la calidad de vida medida por Spanish-AIMS mejoró en su calificación global de 48,4±14.4 a 29,4±8.2 y en cada uno de sus ocho componentes. Hubo también mejoría en los componentes del SF-12, pues la salud física pasó de 39,9±13,7 a 55,5±24,1 y la salud mental de 57,0±24,2 a 74,6±17,0. Aunque el 71% refirió algún evento adverso durante el seguimiento, estos fueron menores y no obligaron a la suspensión del medicamento. Sólo tres pacientes fueron retirados, uno por hipotensión repetitiva al inicio de la infusión, otro por reacción anafiláctica que requirió reanimación y el otro por tuberculosis pleural luego de dos meses de iniciado el medicamento. Se encontró entonces que de acuerdo con los reportes internacionales, la administración de infliximab conlleva a una mejoría significativa en los enfermos con AR refractaria a los tratamientos comunes, evidenciada en los signos y síntomas relacionados con la actividad de la AR, así como en la calidad de vida y en la capacidad funcional. Teniendo en cuenta la posibilidad las reacciones adversas durante la aplicación y que en nuestro país la tuberculosis es un riesgo real, la administración del infliximab debe hacerse en unidades especializadas con personal entrenado y bajo la supervisión estricta del reumatólogo...

A artrite reumatóide (AR) é uma doença inflamatória crônica que afeta principalmente as articulações, produzindo destruição articular, deformidade, incapacidade e deterioração da qualidade de vida. Como novas opções de tratamento, produto do avanço tecnológico e do conhecimento da fisiopatologia da doença, apareceram recentemente no mercado os denominados agentes biológicos. Tendo em conta que não há reportes colombianos sobre a experiência com infliximab em pacientes com AR, o objetivo deste estudo foi quantificar num grupo de pacientes colombianos com AR de longa evolução (13±10 anos) e refratários ao tratamento convencional, a mudança na qualidade de vida, a capacidade funcional, nos sintomas e signos relacionados com a atividade inflamatória e na segurança terapêutica produzidos por infliximab. Um total de 31 pacientes, 22 mulheres e 9 homens, com idades de 51±12 anos e uma média de evolução de doença de 13,2±10,4 anos, que permaneceram ativos apesar de receber metotrexate ou leflunomida em combinação com outros agentes modificadores da doença, baixas doses de glucocorticoides, analgésicos e antiinflamatórios, receberam infusões de infliximab de três mg/kg dose durante 22 semanas, seguindo as recomendações da Associação Colombiana de Reumatologia, nas semanas 0, 2, 6, 14 e 22. Encontrou-se que a capacidade funcional medida por HAQ-DEI passou de 1,2±0,54 a 0,29±0.28, que a qualidade de vida medida por Spanish-AIMS melhorou em sua qualificação global de 48,4±14.4 a 29,4±8.2 e em cada um de seus oito componentes. Teve também melhoria nos componentes do SF-12, pois a saúde física passou de 39,9±13,7 a 55,5±24,1 e a saúde mental de 57,0±24,2 a 74,6±17,0. Ainda que o 71% referiu algum evento adverso durante o seguimento, estes foram menores e não obrigaram à suspensão do medicamento. Só três pacientes foram retirados, um por hipotensão repetitiva ao início da infusão, outro por reação anafilática que requereu reanimação e o outro por tuberculose pleural depois de dois meses de iniciado o medicamento. Encontrou-se então que de acordo com os reportes internacionais, a administração de infliximab implica uma melhoria significativa nos enfermos com AR refratária aos tratamentos comuns, evidenciada nos signos e sintomas relacionados com a atividade da AR, bem como na qualidade de vida e na capacidade funcional. Tendo em conta a possibilidade às reações adversas durante a aplicação e que em nosso país a tuberculose é um risco real, a administração do infliximab deve fazer-se em unidades especializadas com pessoal treinado e sob a supervisão estrita do reumatólogista...

¿Música en la sala de espera? Estudio sobre la aplicación y efectos de la música en la sala de espera de una unidad de salud mental / No disponible

La música se ha utilizado en la historia como un elementoterapéutico y también para ayudar a centrarnosen la vivencia del presente. El estudio realizado mide elpadecimiento de los pacientes de una sala de espera desalud Mental, a los que se expone música especialmentediseñada para rememorar emociones, ideas, relajar,tranquilizar y fomentar la asociación de ideas.Los resultados del estudio denotan la eficacia de lamúsicacomo elemento amortiguador del estrés del tiempo deespera y predisponen positivamente al paciente a su visita

The music has been used as a therapeutic element inhistory. Nowadays, it helps the costumers to focuse inthe present life experiences. Research efectued measuresthe way of thinking on patients at the MentalHealth waiting room. It has exposed specially musicdesigned to remember emotions, relaxation, calm andpromote the association ideas.The research results indicated that the music effectivenessas a pacify element of waiting time stress andpredispose them, in a positive way, to the consultation

Activity of caspofungin and voriconazole against clinical isolates of Candida and other medically important yeasts by the CLSI M-44A disk diffusion method with Neo-Sensitabs tablets.

In vitro activity of caspofungin and voriconazole against 184 clinical isolates of Candida and other medically important yeasts in comparison with that of fluconazole, ketoconazole, itraconazole and amphotericin B was determined by using a disk diffusion method (Neo-Sensitabs) standardized according to the recommendations of the CLSI documents M44-A and M44-S1 (same medium: Mueller-Hinton plus methylene blue; inoculum and minimal inhibitory concentration/zone breakpoints). Seventy-two percent of clinical isolates were susceptible to caspofungin, 23.6% showed an intermediate susceptibility (most of them were Candida parapsilosis) and 4.3% were resistant (values for Candida spp. were 71.2, 23.8 and 5%, respectively). For voriconazole, 96.7% of clinical isolates were susceptible and 3.3% were resistant (Candida spp.: 96 and 3.8%, respectively). Both caspofungin and voriconazole showed high activity against a wide variety of clinically important yeasts.

In vitro activity of voriconazole against dermatophytes, Scopulariopsis brevicaulis and other opportunistic fungi as agents of onychomycosis.

Using a reference microdilution method, we studied the antifungal susceptibility to voriconazole and fluconazole of 304 clinical isolates from four species of onychomycosis-causing dermatophytes, 196 isolates of dermatophytes not related to nail infection as well as Scopulariopsis brevicaulis, Fusarium spp. and Scytalidium dimidiatum. Results showed a high antifungal activity of voriconazole against dermatophytes (geometric mean minimal inhibitory concentration (MIC)=1.14 microg/mL; MIC for 50% of the organisms (MIC(50))=0.062 miccrog/mL; MIC for 90% of the organisms (MIC(90))=0.25 microg/mL). For S. brevicaulis, the in vitro activity of voriconazole was considerably lower (geometric mean MIC=8.52 microg/mL; MIC(50) and MIC(90)=16 microg/mL). Although voriconazole is not among the drugs recommended for the management of onychomycosis, it can be a useful alternative for recalcitrant infections.

Capacidad de las células Hep-2, Hep-2000® Inmunofluorescencia y Hep-2000® Colorzyme, en la determinación de ANAS y SSA/Ro en la evaluación inicial en pacientes con Enfermedad del Tejido Conectivo no Diferenciada / Capacity of cells Hep-2, Hep-2000® Immunofluorescence and Hep-2000® Colorzyme, in the determination of ANAS and SSA/Ro, in the initial evaluation of patients with Undifferentiated Connective Tissue Disease

Introducción: la presencia de anticuerpos antinucleares (ANAS) ha sido tradicionalmente asociada a enfermedades del tejido conectivo; su determinación se constituye en una importante herramienta en el diagnóstico de estas entidades. Para su evaluación, se han utilizado métodos de inmunofluoresencia (IFI) que emplean como sustrato las células Hep-2. En los últimos años, se han generado nuevos sustratos celulares a partir de la manipulación genética de las iniciales denominados Hep-2000®. Estas permiten la identificación del antígeno Ro de manera simultánea. La incorporación reciente de métodos enzimáticos para la lectura de la prueba, ha generado una nueva técnica llamada Colorzyme que permite el uso del microscopio de luz, constituyéndose en una alternativa económica y funcional en comparación con la IFI convencional. Objetivo: el presente estudio pretende establecer la capacidad para detectar ANAS en los sustratos: Hep-2 y Hep-2000® por las técnicas de IFI y Colorzyme, en un grupo de pacientes con Enfermedad del Tejido Conectivo no Diferenciada (ETCND). Adicionalmente comparó la detección del antígeno Ro en los sustratos Hep-2000® con los resultados obtenidos por la técnica de ENAS ELISA tradicional. Materiales y métodos: se analizaron 26 pacientes con ETCND a quienes se les determinó ANAS por las técnicas: Hep-2 IFI; Hep-2000® IFI; Hep-2000 Colorzyme y ENAS por ELISA Screening (con especificidad para los autoantígenos Sm, RNP, SS-A/Ro, SS-B/La, Scl-70 y Jo-1). Resultados: los resultados encontrados por las técnicas revelan un mayor rendimiento diagnóstico (ANAS positivos) en las células Hep-2000®: 23 (88%) por IFI y 21 (81%) Colorzyme, comparadas con 20 (76%) del sustrato Hep-2 IFI. Todos los patrones “clásicos” IFI estuvieron representados en la técnica de Hep-2 IFI; en la técnica de Hep-2000® IFI no se observó el patrón homogéneo, por Colorzyme no se observaron los patrones nucleolar ni el citoplasmático. En todas las técnicas la forma predominante de presentación fue el patrón moteado fino: 50% Colorzyme, 42,9 % para Hep-2000® IFI y 34,6% para Hep-2 IFI. En general se obtuvieron buenas correlaciones en los resultados entre las técnicas Hep-2000® IFI y la enzimática (r=0,74 p<0,000) con una concordancia 0,71 (Cohen K, p<0,000), mas no así con Hep-2 que fue de 0,21 (p<0,03). Las correlaciones entre los patrones de IFI (r=0,6 p<0,000) y las diluciones (r=0,75 p<0,000) fueron mejores entre los sustratos Hep-2000®, comparadas con las células Hep-2 (r=0,5 p<0,003). Para establecer la capacidad de identificación del autoantígeno Ro de las técnicas Hep-2000®, se compararon los resultados obtenidos con los de la técnica específica de ELISA para SSA-Ro. Las células Hep-2000® mostraron una sensibilidad del 66% por IFI y del 33% Colorzyme. Conclusiones: la utilización de células Hep-2 sigue siendo una buena alternativa para la determinación de ANAS. Sin embargo, las células Hep- 2000® pueden considerarse un sustrato útil y confiable en nuestro medio, tanto por color como IFI. La técnica por color facilita su realización al abolir el uso de IFI, recurso tecnológico escaso en muchas instituciones. Los resultados negativos para Ro deben ser interpretados con cautela pacientes con ETCND, en algunos de estos casos es posible se requiera de la confirmación por otros métodos.

Introduction: The presence of antinuclear antibodies (ANAS) has been traditionally associated to conective tissue diseases. and their determination is an important tool in the diagnose of these entities. In the last years the Cells Hep-2 has been used .in the Inmunofluoresencia technique (IFI),. New cellular sustratos has been generated by genetic manipulation, denominated Hep-2000®. These allow the identification of the antigen Ro in the same procedure. The recent incorporation of enzymatic methods for the reading of the test, has generated a new technique called Colorzyme, This allows the use of the microscope of light that become the procedure in an economical and functional alternative in comparison with the conventional IFI. Objective: The present study pretend to establish the capacity of detection of ANAS in sustratos: Hep-2 and Hep-2000® for IFI and Colorzyme, in a group of patients with No Differentiated Conective Tissue Disease (NDCTD). Additionally compares the detection of the antigen Ro in Hep-2000® cells and confront the results obtained by the ENAS-ELISA technique . Materials and methods: The presence of ANAS were analyzed in the serum of 26 patients with NDCTD by the techniques: Hep-2 IFI; Hep-2000® IFI; Hep-2000 Colorzyme® and ENAS for ELISA Screening (with specificity for the auto antigens Sm, RNP, SS-A/Ro, SS-B/La, Scl-70 and Jo-1). Results: Hep-2000®: demonstrated a better capacity in order to found ANAS: 23 (88%) for IFI and 21 (81%) for Colorzyme, compared with 20 (76%) of Hep-2 IFI. All the patterns «classic¼ IFI was represented in the Hep-2 cells IFI; Hep-2000 IFI the homogeneous pattern was not observed. In Colozyme tecnique the nucleolar and citoplasmic patron was not observed. In all the techniques the predominant form of presentation was the speckle-fine pattern: 50% Colorzyme, 42.9% for Hep-2000® IFI and 34.6% for Hep-2 IFI Good correlations were obtained in the results among the technique Hep-2000® IFI and the Colorzyme (r=0.74 p <0.000) but not in the Hep-2 IFI substrate: 0.21 (p <0.03). The correlations among the patterns of IFI (r=0.6 p <0.000) and the dilutions (r=0.75 p <0.000) were better among the Hep-2000® substrates, compared with the Hep-2 cells (r=0.5

In vitro antifungal susceptibility testing of filamentous fungi with Sensititre Yeast One.

Sensititre is a colorimetric microdilution method for in vitro antifungal susceptibility testing based on the M27-A document (National Committee for Clinical Laboratory Standards) for yeasts. Difference between both methods is the presence of Alamar-blue and RPMI 1640 (glucose 2%) as culture medium. Antifungal susceptibility to amphotericin B, fluconazole, itraconazole, ketoconazole and flucytosine, 100 opportunistic filamentous fungi (Aspergillus spp., Fusarium spp., Scedosporium spp.) obtained from pathological samples was determined by the Sensititre method. Induction to conidium and sporangiospore formation at 35 degrees C was used to get inoculum and plates were covered by 1 ml of saline and suspensions were made by gently probing by a sterile loop. Optical densities of the conidial suspensions were adjusted to 80-82% transmittance for Aspergillus spp. and 68-70% for the rest of strains tested. Final inoculum concentration size was 0.4 x 10(4)-5 x 10(4) CFU ml(-1). Readings were made at 72 h of incubation at 35 degrees C; amphotericin B and itraconazole was active against Aspergillus fumigatus with CMI90 1 and 0.5 microg ml(-1), respectively, opposite to Scedosporium prolificans and Scedosporium apiospermum. As it was expected, a CMI90 of 256 microg ml(-1) for fluconazole and CMI90 for flucytosine amounting to 64 g ml(-1) were obtained. Sensititre Yeast One is a useful method and an alternative to reference methods to determine antifungal susceptibility of filamentous fungi for clinical laboratory routine. Correlation with microdilution results is studied. New triazole derivatives should be included as soon as their clinical use will be feasible.

In vitro antifungal activity of sertaconazole compared with nine other drugs against 250 clinical isolates of dermatophytes and Scopulariopsis brevicaulis.

We have tested 250 strains belonging to 15 species of clinically important dermatophytes and Scopulariopsis against ten antifungal drugs using an agar diffusion method (NeoSensitabstrade mark, Rosco, Taastrup, Denmark). Some of the experimental factors were adapted to dermatophyte development, such as temperature (28 vs. 35 degrees C) and time of incubation (2-5 days vs. 21-74 h). The antifungals used are itraconazole, ketoconazole, miconazole, clotrimazole, sertaconazole, terbinafine, tioconazole, fluconazole, isoconazole and econazole. Except for fluconazole, all the drugs tested have shown to be highly effective, especially sertaconazole and terbinafine. Percentages of susceptibility ranged between 94% for terbinafine, 87.6% for sertaconazole and 86.4% clotrimazole; 81.6% econazole; 42.8% fluconazole; 57.2% isoconazole; 78.4% itraconazole; 74.4% ketoconazole; 73.3% miconazole, and 85.2% for tioconazole. Percentages of resistance were similar between sertaconazole and terbinafine (4%) but in contrast to the 48% obtained for fluconazole.