Experimental Annealing of Zircon: Influence of Inclusions on Stability, Intracrystalline Melt Migration, Common Lead Leaching, and Permeability to Fluids.

Zircon derived from crustal rocks can survive dissolution into hot basalts during magma hybridization and rock assimilation if it is shielded as an inclusion phase in early-formed phenocrysts or in minerals from non-disaggregated xenoliths. Under these conditions, zircon can be thermally shocked, triggering recrystallization of metamict domains and reaction with its hosted mineral inclusions. This work simulates this process by performing thermal annealing experiments on zircon grains with variable degrees of metamictization. These were embedded in cristobalite powder under a N2 atmosphere at 1 bar and 1300 °C. The thermal annealing produces recrystallization of metamict domains, melting of multi-phase mineral inclusions, nanopore formation, and microcrack propagation by thermo-elastic stress. The porosity enhances intracrystalline melt mobility, leaching out trace-element and mineral impurities. Baddeleyite was formed at temperatures below the thermal decomposition of pure zircon by two mechanisms: (i) recrystallization of metamict domains assisted by silica migration from the reaction site and (ii) incongruent zircon dissolution into molten mineral inclusions with a high CaO/SiO2 ratio. Highly metamict zircons with elevated common Pb and radiogenic Pb loss, which were impossible to date with SHRIMP, lost all their common Pb and some radiogenic Pb upon annealing, producing well-fitted discordias with a significant upper intercept age.

Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL / Effect of antimalarials on the different domains of the SLICC damage index in patients of the GLADEL cohort

Objetivos: Estimar el efecto de los antimaláricos (AM) sobre los diferentes dominios del índice de daño SLICC (SDI). Métodos: Se estudiaron pacientes con diagnóstico clínico reciente (≤2 años) de lupus eritematoso sistémico (LES) de la cohorte GLADEL. Variable de estudio: aumento en los dominios del SDI desde el ingreso a la cohorte. Variables independientes: características sociodemográficas, clínicas, laboratorio y tratamientos. El efecto de los AM, como variable dependiente del tiempo, sobre los dominios más frecuentes del SDI (ajustado por factores de confusión) fue examinado con un modelo de regresión de Cox multivariado. Resultados: De 1466 pacientes estudiados, 1049 (72%) recibieron AM con un tiempo medio de exposición de 30 meses (Q1-Q3: 11-57) y 665 pacientes (45%) presentaron daño durante un seguimiento medio de 24 meses (Q1-Q3: 8-55); 301 eventos fueron cutáneos, 208 renales, 149 neuropsiquiátricos, 98 musculoesqueléticos, 88 cardiovasculares y 230 otros. Después de ajustar por factores de confusión, el uso de AM se asoció a un menor riesgo de daño renal (HR 0,652; IC 95%: 0,472-0,901) y en el límite de la significancia estadística (HR 0,701, IC 95%: 0,481-1,024) para el dominio neuropsiquiátrico. Conclusión: En GLADEL, el uso de AM se asoció independientemente a un menor riesgo de daño acumulado renal.

Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.

Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.

Schwann cells and oligodendrocytes are the myelinating cells of the peripheral and central nervous system, respectively. Despite having different myelin components and different transcription factors driving their terminal differentiation there are shared molecular mechanisms between the two. Sox10 is one common transcription factor required for several steps in development of myelinating glia. However, other factors are divergent as Schwann cells need the transcription factor early growth response 2/Krox20 and oligodendrocytes require Myrf. Likewise, some signaling pathways, like the Erk1/2 kinases, are necessary in both cell types for proper myelination. Nonetheless, the molecular mechanisms that control this shared signaling pathway in myelinating cells remain only partially characterized. The hypothesis of this study is that signaling pathways that are similarly regulated in both Schwann cells and oligodendrocytes play central roles in coordinating the differentiation of myelinating glia. To address this hypothesis, we have used genome-wide binding data to identify a relatively small set of genes that are similarly regulated by Sox10 in myelinating glia. We chose one such gene encoding Dual specificity phosphatase 15 (Dusp15) for further analysis in Schwann cell signaling. RNA interference and gene deletion by genome editing in cultured RT4 and primary Schwann cells showed Dusp15 is necessary for full activation of Erk1/2 phosphorylation. In addition, we show that Dusp15 represses expression of several myelin genes, including myelin basic protein. The data shown here support a mechanism by which early growth response 2 activates myelin genes, but also induces a negative feedback loop through Dusp15 to limit over-expression of myelin genes.

Stringent comparative sequence analysis reveals SOX10 as a putative inhibitor of glial cell differentiation.

BACKGROUND: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor. As such, the identification of genes regulated by SOX10 will provide insight into Schwann cell biology and related diseases. While genome-wide studies have successfully revealed SOX10 target genes, these efforts mainly focused on myelinating stages of Schwann cell development. We propose that less-biased approaches will reveal novel functions of SOX10 outside of myelination. RESULTS: We developed a stringent, computational-based screen for genome-wide identification of SOX10 response elements. Experimental validation of a pilot set of predicted binding sites in multiple systems revealed that SOX10 directly regulates a previously unreported alternative promoter at SOX6, which encodes a transcription factor that inhibits glial cell differentiation. We further explored the utility of our computational approach by combining it with DNase-seq analysis in cultured Schwann cells and previously published SOX10 ChIP-seq data from rat sciatic nerve. Remarkably, this analysis enriched for genomic segments that map to loci involved in the negative regulation of gliogenesis including SOX5, SOX6, NOTCH1, HMGA2, HES1, MYCN, ID4, and ID2. Functional studies in Schwann cells revealed that: (1) all eight loci are expressed prior to myelination and down-regulated subsequent to myelination; (2) seven of the eight loci harbor validated SOX10 binding sites; and (3) seven of the eight loci are down-regulated upon repressing SOX10 function. CONCLUSIONS: Our computational strategy revealed a putative novel function for SOX10 in Schwann cells, which suggests a model where SOX10 activates the expression of genes that inhibit myelination during non-myelinating stages of Schwann cell development. Importantly, the computational and functional datasets we present here will be valuable for the study of transcriptional regulation, SOX protein function, and glial cell biology.

PANLAR Consensus Recommendations for the Management in Osteoarthritis of Hand, Hip, and Knee.

OBJECTIVE: The objective of this consensus is to update the recommendations for the treatment of hand, hip, and knee osteoarthritis (OA) by agreeing on key propositions relating to the management of hand, hip, and knee OA, by identifying and critically appraising research evidence for the effectiveness of the treatments and by generating recommendations based on a combination of the available evidence and expert opinion of 18 countries of America. METHODS: Recommendations were developed by a group of 48 specialists of rheumatologists, members of other medical disciplines (orthopedics and physiatrists), and three patients, one for each location of OA. A systematic review of existing articles, meta-analyses, and guidelines for the management of hand, hip, and knee OA published between 2008 and January 2014 was undertaken. The scores for Level of Evidence and Grade of Recommendation were proposed and fully consented within the committee based on The American Heart Association Evidence-Based Scoring System. The level of agreement was established through a variation of Delphi technique. RESULTS: Both "strong" and "conditional" recommendations are given for management of hand, hip, and knee OA and nonpharmacological, pharmacological, and surgical modalities of treatment are presented according to the different levels of agreement. CONCLUSIONS: These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.

SOX10 regulates an alternative promoter at the Charcot-Marie-Tooth disease locus MTMR2.

Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function. Loss-of-function mutations in the gene encoding myotubularin-related protein 2 (MTMR2) cause Charcot-Marie-Tooth disease type 4B1 (CMT4B1), a severe demyelinating peripheral neuropathy characterized by myelin outfoldings along peripheral nerves. Previous reports indicate that MTMR2 is ubiquitously expressed making it unclear how loss of this gene causes a Schwann cell-specific phenotype. To address this, we performed computational and functional analyses at MTMR2 to identify transcriptional regulatory elements important for Schwann cell expression. Through these efforts, we identified an alternative, SOX10-responsive promoter at MTMR2 that displays strong regulatory activity in immortalized rat Schwann (S16) cells. This promoter directs transcription of a previously unidentified MTMR2 transcript that is enriched in mouse Schwann cells compared to immortalized mouse motor neurons (MN-1), and is predicted to encode an N-terminally truncated protein isoform. The expression of the endogenous transcript is induced in a heterologous cell line by ectopically expressing SOX10, and is nearly ablated in Schwann cells by impairing SOX10 function. Intriguingly, overexpressing the two MTMR2 protein isoforms in HeLa cells revealed that both localize to nuclear puncta and the shorter isoform displays higher nuclear localization compared to the longer isoform. Combined, our data warrant further investigation of the truncated MTMR2 protein isoform in Schwann cells and in CMT4B1 pathogenesis.

A Proteoglycan-Like Molecule Offers Insights Into Ground Substance Changes During Holothurian Intestinal Regeneration.

Extracellular matrix remodeling is an essential component of regenerative processes in metazoans. Among these animals, holothurians (sea cucumbers) are distinguished by their great regenerative capacities. We have previously shown that fibrous collagen as well as other fibrous components disappear from the connective tissue (CT) early during intestinal regeneration, and later return as the organ primordia form. We now report on changes of the nonfibrous component of the CT. We have used Alcian Blue staining and an antibody, Proteoglycan Like-1 (PGL-1), that recognizes a proteoglycan-like antigen to identify the presence of proteoglycans in normal and regenerating intestines. Our results show that early in regeneration, the ground substance resembles that of the mesentery, the structure from where the new intestine originates. As regeneration proceeds, Alcian Blue staining and PGL-1 labeling reorganize, so that by 4 weeks the normal intestinal CT pattern is achieved. Together with our previous findings, the data suggest that CT components that might be detrimental to regeneration disappear early on, while those that might be beneficial to regeneration, such as proteoglycans, are present throughout the regenerative process.

Osteoarthritis in Latin America: Study of Demographic and Clinical Characteristics in 3040 Patients.

BACKGROUND: Latin America is a heterogeneous region made up of different populations, cultures, latitudes, altitudes, and immigrants from different areas and ethnic groups. OBJECTIVE: The purpose of this study is to describe the clinical and demographic profile of patients with osteoarthritis (OA) evaluated by a selected group of rheumatologists in 13 Latin American countries. METHODS: A descriptive, observational, cross-sectional study was conducted in 13 Latin American countries of patients with symptomatic OA. Data were collected over a 3-month period using an ad hoc questionnaire to evaluate the clinical and demographic features of OA seen by rheumatologists. RESULTS: Among the 3040 patients, their average age was 62.5 years, and female-to-male ratio was 4.8:1. Patients with body mass index of greater than 30 kg/m or obesity was found in 38.2%. Approximately 88% had primary OA. Joints with OA were as follows: knee 31.2%, hand 9.5%, hand and knee 22.9%, proximal and distal interphalangeal joints (erosive OA) 6.5%, axial 6.6%, and hip 1.3%. Approximately 88.5% had radiographic severity of grade 2 or 3 on Kellgren-Lawrence scale (0-4). Nonsteroidal anti-inflammatory drugs were the predominant OA treatment included in combinations with glucosamine sulfate/chondroitin and viscosupplementation. Associated comorbidities included hypertension (39%), obesity (36.3%), diabetes mellitus (12%), and without comorbidity (12.7%). CONCLUSIONS: This is 1 of the largest population studies that evaluated the characteristics of OA in 3040 patients evaluated by rheumatologists in 13 Latin American countries. This study provides important data for each Latin American country to develop new health care planning in management of OA.

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...

Active comparator trial of teriparatide vs alendronate for treating glucocorticoid-induced osteoporosis: results from the Hispanic and non-Hispanic cohorts.

Glucocorticoid use is a leading cause of secondary osteoporosis. This post hoc analysis compared teriparatide vs alendronate on bone mineral density (BMD) in Hispanic and non-Hispanic patients with glucocorticoid-induced osteoporosis. The 18-mo results from all patients (N=428) in a double-blind trial of teriparatide (20 microg/d) and alendronate (10 mg/d) who had taken glucocorticoids for >or=3 mo were reported (Saag et al. N Engl J Med 2007). The present study analyzed results from the Hispanic (n=61) and non-Hispanic (n=367) cohorts. The BMD was measured by dual-energy X-ray absorptiometry (DXA). In the Hispanic cohort at 18 mo, there were significantly greater increases from baseline in the teriparatide vs alendronate group in lumbar spine BMD (9.8%+/-1.7% vs 4.2%+/-1.4%; p<0.001; mean+/-SE) and total hip BMD (5.9%+/-1.6% vs 1.3%+/-1.3%, p<0.001), with no significant difference between groups at the femoral neck (4.3%+/-2.2% vs 2.0%+/-1.8%, p=0.228). Within each treatment group, the BMD responses were not significantly different in the Hispanic vs non-Hispanic cohort. The number of patients reporting >or=1 adverse event was not significantly different between treatments in either cohort, with more patients reporting nausea in the teriparatide group. In summary, teriparatide was more efficacious than alendronate in increasing BMD in Hispanic and non-Hispanic patients with glucocorticoid-induced osteoporosis. Both treatments were generally well tolerated.

Environmental management and firm performance: a case study.

This study has as its aim to help to clarify the relationship between environmental management and economic performance by integrating it into a wider framework that includes the relationship between environmental strategy and firm performance, the latter being understood as the combination of environmental performance, competitive advantage and economic performance. A case study of the COATO farming cooperative showed us that its environmental management, focused on prevention logic, has had a positive net effect on its environmental performance. Besides, the order in which these practices were adopted favoured the development of new organisational capabilities that have contributed to the appearance of advantages derived from the greater accumulated experience of employees in creating new projects that are designed to reduce residues and pollution. COATO has also obtained a competitive advantage in differentiation thanks to an improved brand image and to its increased credibility in business relationships. Finally, a positive correlation exists between the pioneering proactive strategy adopted by this cooperative and the improvement of its firm performance with respect to the other firms in its sector.

Normatización para la administración y el seguimiento de los agentes bilógicos y de quimioterapia usados en reumatología / Guidelines for use of biologic agents and quimiotherapy in Rheumatology

El desarrollo de las ciencias básicas como la inmunología, la genética y la biología molecular ha permitido implementar nuevas alternativas de tratamiento en enfermedades que tradicionalmente contaban con pocas opciones terapéuticas. La reumatología en los últimos años ha adoptado y extendido el uso de agentes biológicos y la quimioterapia en la mayoría de las enfermedades reumáticas. Para ello es necesario establecer guías para la utilización de estos agentes. El uso inapropiado de estos agentes puede llevar a consecuencias catastróficas. Los nuevos medicamentos deben ser usados sólo por personas expertas en el tratamiento de las enfermedades reumáticas y su administración debería realizarse en condiciones ideales para minimizar el riesgo. La Asociación Colombiana de Reumatología pretende con este documento establecer las guías locales para utilizar estos agentes

Th1/Th2 cytokines in patients with systemic lupus erythematosus: is tumor necrosis factor alpha protective?

OBJECTIVES: To determine the circulating levels of Th1 and Th2 cytokines in patients with systemic lupus erythematosus (SLE) and to elucidate their association with disease activity and autoimmune response. METHODS: We included 52 patients and 25 healthy controls. Serum levels of tumor necrosis factor (TNF) alpha, interferon (IFN) gamma, interleukin (IL)-12p70, IL-10, and IL-4, as well as anti-DNA, -Ro, -La, -RNP, and -Sm antibodies were determined by enzyme-linked immunosorbent assay. Disease activity was recorded according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and classified as very active (SLEDAI > or = 13), moderately active (SLEDAI: 3-12), or inactive (SLEDAI < or = 2). RESULTS: The mean age of the patients was 34.2 +/- 12.6 years, and the mean duration of disease was 4.9 +/- 7.6 years. Twelve patients (23%), 20 patients (34.5%), and 20 patients (34.5%) had highly, moderately, and inactive SLE, respectively. Levels of IFN-gamma, TNF-alpha, and IL-12 were significantly higher in patients than in healthy controls (P <.03), as well as the IL-12/IL-10, IL-12/IL-4, IFN/IL-10, IFN/IL-4, TNF/IL-10, and TNF/IL-4 ratios (P <.01), suggesting a major participation of Th1 over Th2 cytokines. Nevertheless, a direct correlation between Th1 (IFN-gamma and TNF-alpha) and Th2 (IL-4 and IL-10) cytokines was observed in patients (r >.5, P <.01), indicating a mutual Th1-Th2 participation. TNF-alpha levels and the TNF/IL-10 ratio were higher in patients with inactive disease compared with patients with very active disease and controls (P <.04). IL-12 levels and IL-12/IL-4, as well as IL-12/IL-10, ratios were higher in patients with very active disease than in those with inactive SLE and controls (P <.01). IL-10 levels were associated with anti-DNA, anti-Ro, and anti-La response (P <.01). CONCLUSION: Our results suggest that TNF-alpha could be a protective factor in SLE patients, whereas IL-12p70 participates in disease activity and IL-10 influences the autoimmune response (autoantibody production).

Factores de riesgo relacionados con la osteoporosis en una poblacion latinoamericana / Risk factors and osteoporosis in latinoamerican population

La osteoporosis (OP) es una alteración sistémica del esqueleto, la cual afecta principalmente a mujeres de mayor edad. La presente investigación fue diseñada para el estudio de algunos factores de riesgo para OP, en una población específica. En un estudio de casos y controles se incluyeron 367 mujeres con edades entre 30 y 80 años, mientras acudían para tamizaje de OP mediante DEXA-DMO. De ellas, 193 tenían diagnóstico de OP y 174 tenían DEXA normal. Para calcular la probabilidad de tener OP, se diseñó un modelo estadístico, el cual incluía edad, años en menopausia e índice de Masa Corporal (IMC). Se encontró que las mujeres con OP tenían mayor edad, más años en menopausia y menor IMC. Los antecedentes familiares para OP, el hábito de fumar, el ejercicio, la ingesta de calcio y el uso de TRH, no fueron significantes. Se concluye que existen factores de riesgo con mayor impacto sobre el desarrollo de la OP. Se necesitan mayores estudios de población para definir la validez de estos hallazgos

Clinical and immunological factors associated with lupus nephritis in patients from northwestern Colombia.

A cross-sectional and multicenter study was undertaken to analyze the clinical and immunological characteristics at diagnosis associated with nephritis in northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty-nine patients with lupus nephritis were included and were compared to 100 SLE patients without nephritis. A multivariate analysis was performed. The patients who developed nephritis had a higher frequency of oral ulcers (41% vs. 21%, OR = 3.1, 95% CI: 1.3-7.5 p = 0.01) and malar erythema (77% vs. 45%, OR = 4.4, 95% CI: 1.8-10.8 p = 0.001). Lupus nephritis was observed in 77% of cases during the first year of the disease. The frequency of anti-DNA antibodies was higher in patients with nephritis, however, differences were not statistically significant (83% vs 64%, OR = 2.6, 95% CI: 1.03-6.41, p = 0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remained unchanged throughout the evolution of the disease. Patients with lupus nephritis had a higher prevalence of arterial hypertension (60% vs 10%, OR = 13.7, 95% IC: 5-37, p = 0.00001) and hyperlipidemia (30% vs 7%, OR = 8.1, 95% IC: 2.5-27, p = 0.0006) at onset. Finally, patients with lupus nephritis required more hospitalizations (> 1) over the course of disease (89% vs 60%, OR = 7.8, 95% CI: 2.1-29, p = 0.002). In conclusion, lupus nephritis appears early during the course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of disease are associated factors. Lupus nephritis is a major risk factor leading to repeated hospitalizations. This study may help to assist in public health policies in our population in order to improve patient outcomes while simultaneously reducing disease costs.

Clinical an immunological factors associated with lupus nephritis in patients from northwestern Colombia / Factores clínicos y epidemiológicos asociados con nefritis lúpica en pacientes del noroccidente colombiano

A cross-sectional and multicenter study was undertaken to analyze the clinical and immunological characteristics at diagnosis associated with nephritis in northwestern Colombian patients with systemic lupus erythematosus (SLE). Thirty nine patients with lupus nephritis were included and were compared to 100 SLE patients without nephritis. A multivariate analysis was performed. The patients who developed nephritis had a higher frequency of oral ulcers (41 percent vs. 21 percent, OR3.1, 95 percent CI: 1.3-7.5 p 0.01) and malar erythema (77 percent vs. 45 percent, OR4.4, 95 percent CI: 1.8-10.8 p0.001). Lupus nephritis was observed in 77 percent of cases during the first year of the disease. The frequency of anti-DNA antibodies was higher in patients with nephritis, however, differences were not statistically significant (83 percent vs 64 percent, OR2.6, 95 percent CI: 1.03-6.41, p0.06). The presence of other autoantibodies (anti-Ro, anti-La, anti-RNP, anti-Sm and anticardiolipin) at diagnosis was similar in both groups. This autoantibody profile remained unchanged throughout the evolution of the disease. Patients with lupus nephritis had a higher prevalence of arterial hypertension (60 percent vs 10 percent, OR13.7, 95 percent IC: 5-37, 0.00001) and hyperlipidemia (30 percent vs 7 percent, OR8.1, 95 percent IC: 2.5-27, p0.0006) at onset. Finally, patients with lupus nephritis required more hospitalizations (1) over the course of disease (89 percent vs 60 percent, OR7.8, 95 percent IC: 2.1-29, p0.002). In conclusion, lupus nephritis appears early during the course of SLE. Malar erythema, oral ulcers, hypertension and hyperlipidemia at onset of disease are associated factors. Lupus nephritis is a major risk factor leading to repeated hospitalizations. This study may help to assist in public health policies in our population in order to improve patient outcomes while simultaneously reducing disease costs.

Manifestaciones cardiacas de las enfermedades reumaticas / Cardiac manifestations of rheumatic diseases

Las enfermedades reumáticas son un complejo de entidades que afectan principalmente articulaciones, músculos y estructuras del tejido conectivo, pero también comprometen de una forma u otra el corazón y sus estructuras vasculares. La afectación cardiovascular es dada principalmente por entidades como la artritis reumatoide, el lupus eritemato-so sistémico o el síndrome antifosfolípido, no sólo por fenómenos autoinmunes y vasculíticos, sino tam-bién por la reciente asociación entre la enfermedad ateroesclerótica acelerada y dichas patologías. La siguiente revisión hace énfasis en las manifestaciones cardiacas de las enfermedades reumáticas excluyendo las producidas por la fiebre reumática

Central nervous system compromise in primary Sjögren's syndrome.

Central nervous system (CNS) involvement in primary Sjögren's syndrome (SS) is poorly understood, and its frequency as well as its manifestations are subjects of controversy. The current study was undertaken to determine the prevalence and the clinical and immunogenetic characteristics of CNS compromise in a well defined group of patients with primary SS. In this retrospective study, patients fulfilled the European classification criteria. Among 120 patients with primary SS, 3 (2.5%) had CNS compromise (multiple sclerosis-like illness, complicated migraine, and optic neuritis with epilepsy). The CNS involvement coincided with the onset of sicca symptoms in 1 case. All 3 patients carried the human leukocyte antigen (HLA) DQB1*0303 allele and tested positive for anti-Ro antibodies, but not for anti-cardiolipin antibodies. Although rare, CNS compromise in primary SS can be the presenting manifestation of the disease in a few cases, and may be severe and varied.