Gastrointestinal Symptoms and Elevated Levels of Anti-Saccharomyces cerevisiae Antibodies Are Associated with Higher Disease Activity in Colombian Patients with Spondyloarthritis.

BACKGROUND: Spondyloarthritis (SpA) is a group of articular inflammatory rheumatic diseases that their gastrointestinal manifestations are around 10% of their extra-articular symptoms, supporting that the inflammatory response of the intestinal mucosa could be associated with the clinical status. OBJECTIVES: To investigate the association between gastrointestinal symptoms and autoantibodies and disease activity between SpA patients, healthy subjects (HS), and patients with inflammatory bowel disease (IBD). METHODS: 102 SpA patients, 29 IBD patients, and 117 HS were included. Autoantibodies as ASCA, ANCA, anti-tTG, anti-DGP, ANA, and IgA were measured. The patients were assessed to evaluate clinical and gastrointestinal symptoms. An association analysis was performed using Chi square test and a logistic regression. RESULTS: Significant differences were found for ASCA levels in SpA (28.2%) compared to IBD (14.2%) and HS (6.0%) (p = 0.029), as well as for ANAS in SpA (49.5%) and IBD (37.9%) (p < 0.001) and abdominal pain (p = 0.012) between SpA (54.3%) and IBD (27.5%). Significant associations were found between BASDAI > 4 and gastrointestinal symptoms (p < 0.05) and IgA (p = 0.007). The association for abdominal bloating was maintained (OR: 3.93, CI-95%, 1.14-13.56; p = 0.030). CONCLUSIONS: Gastrointestinal symptoms, ASCA, ANAS, and IgA levels were associated with high disease activity in SpA compared with IBD and HS.

Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condition in Patients with Rheumatoid Arthritis?

BACKGROUND AND OBJECTIVE: Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. MATERIALS AND METHODS: One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). RESULTS: Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). CONCLUSION: Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

MÉTODOS PARA LA IDENTIFICACIÓN DEL ANTÍGENO DE HISTOCOMPATIBILIDAD HLA-B27: COMPARACIÓN DE CUATRO PROTOCOLOS TÉCNICOS / METHODS FOR IDENTIFICATION OF ANTIGEN HLA-B27 HISTOCOMPATIBILITY: FOUR TECHNICAL COMPARISONS OF PROTOCOLS / MÉTODOS PARA A IDENTIFICAÇÃO DO ANTIGÉNIO DE HISTOCOMPATIBILIDADE HLA-B27: CAMPARAÇAO DE QUATRO PROTOCOLOS TÉCNICOS

Introducción: La asociación del HLA-B27 y las Espondiloartritis, ha hecho evidente que la tipificación del HLA-B27 sea considerada como un apoyo en el diagnóstico de estas enfermedades. Los métodos más empleados para la determinación del antígeno HLA-B27 en los laboratorios clínicos y en investigación son: la microlinfocitotoxicidad (MCTX), la citometría de flujo digital (CMFd), la citometría de flujo análoga (CMFa) y la reacción en cadena de la polimerasa con primers de secuencia específicos (PCR-SSP). Objetivo: Comparar MCTX con la CMFd, la CMFa con la CMFd, y la técnica de CMFd frente a PCR-SSP. Métodos: Se analizaron 4109 solicitudes de HLA-B27 en población con manifestaciones sugestivas de EAS remitidas entre 2009 y 2012 al Hospital Militar Central y al Instituto de Referencia Andino. Se evaluaron las frecuencias obtenidas por Chi cuadrado (X2); para estimar la concordancia metodológica se utilizó el Coeficiente de Correlación Intraclase (CCI). Los análisis se realizaron con el paquete estadístico SPSS V18. Resultados: Al evaluar 467 datos por la técnica de CMFa frente a PCR-SSP, la CMFa mostró 239 resultados entre positivos y en rango indeterminado, de los cuales, luego de ser confirmados PCRSSP, solo 213 demostraron la expresión de HLA-B27 (p<0.05). Se obtuvieron 208 resultados realizados por CMFd y PCR-SSP simultáneamente, observándose una alta correspondencia entre estas técnicas (p<0.05). Para evaluar la concordancia entre la MCTX y CMFd se analizaron 34 datos, revelando un 100% de correspondencia entre esta dos metodologías (CCI=1,p<0.05). Conclusión: La citometría de flujo digital es un método rápido que presenta un desempeño altamente confiable para la identificación de HLA-B27, resultados que se recomiendan confirmar por PCR SSP.

Introduction: The association between HLA-B27 and spondyloarthritis has made clear the fact that identification of HLA-B27 antigen is considered as a support in the diagnosis of these diseases. The most commonly used methods for determination of the HLA-B27 antigen in clinical laboratories as well as in their research, are microlymphocytotoxicity (MCTX), digital flow cytometry (CMFd), analogous flow cytometry (CMFa) and the Single Specific Primer-Polymerase Chain Reaction (PCRSSP). Objective: compare the CMFd against MCTX, CMFa against CMFd and CMFd against PCR-SSP. Methods: 4109 requests for HLA-B27 were analyzed with manifestations suggestive of SpA submitted between 2009 and 2012 at Hospital Militar Central and Instituto de Referencia Andino. To analyze the frequencies Chi square (X2) was evaluated; to estimate the methodological concordance the intraclass correlation coefficient (ICC) was used. All proposed analyzes were performed with SPSS V18. Results: 467 data obtained by CMFa versus PCR-SSP evaluated the CMFA showed 239 results between positive and indeterminate range, which, after being confirmed by molecular biology (PCRSSP), only 213 showed the expression of HLA-B27 (p <0.05). PCR-SSP and CMFd performed 208 results simultaneously, showing a high correlation between these techniques (p <0.05). To evaluate the correlation between CMFd and MCTX, 34 data were analyzed, revealing a 100% match on the positive results from these two methodologies (ICC = 1, p <0.05). Conclusion: The digital flow cytometry is a rapid method that presents a highly reliable for the initial identification of HLA-B27; results confirmed by PCR SSP recommend performance.

Introdução: a associação do HLA-B27 e as Espondilartrite, evidenciou que a tipificação do HLAB27 seja considerada como um suporte no diagnóstico dessas doenças. Os métodos mais usados para a determinação do antígeno HLA-B27 nos laboratórios clínicos e no investigação são: a microlinphocitotoxicity (MCTX), a citometria de fluxo digital (CMFd), a citometria de fluxo análoga (CMFa) e a reação em cadeia de a polimerasa com primers de sequência específicos (PCR-SSP). Objetivo: Comparar MCTX com a CMFd, a CMFa com a CMFd, e a técnica de CMFd com PCRSSP. Métodos: 4109 solicitudes de HLA-B27 em população com manifestações sugestivas de EAS remitidas entre 2009 e 2012 ao Hospital Militar e ao Instituto de Referencia Andino, foram analisadas. Avaliaram-se as frequências obtidas por Chi quadrado (X2); para estimar a concordância metodológica foi utilizado o Coeficiente de Correlação Intraclasse (CCI). Os análises estão feitos com o paquete estadístico SPSS V18. Resultados: A CMFa mostrou 239 resultados entre positivos e em rango indeterminado quando avaliou-se 467 dados com a técnica de CMFa com PCR-SSP. Só 213 deles demostraram a expressão de HLA-27 (p<0.05), depois de ser confirmados PCR-SSP. Foram obtidos 208 resultados por CMFd y PCR-SSP em simultâneo, com uma alta correspondência entre estas técnicas (p<0.05). Para avaliar a concordância entre MCTX y CMFd analisaram-se 34 dados, revelando um 100% de correspondência entre as duas metodologias (CCI=, p<0.05). Conclusão: A citometria de fluxo é um método rápido que tem um desempeno muito confiável para a identificação de HLA-B27, resultados recomendados para confirmar por PCR SSP.

Association of tumor necrosis factor alpha-308 promoter polymorphism with spondyloarthritides patients in Colombia.

The pathogenesis of SpA is considered to be a complex and multi-factorial process and, similar to other autoimmune diseases, includes the activity of proinflammatory cytokines such as TNF alpha. Our study compared the -308 promoter polymorphism of TNF alpha with TNF alpha levels, HLA-B27 status, age at the onset of symptoms, SpA subtype and the clinical degree of activity in Colombian SpA patients and healthy subjects (HS). Comparisons of the TNF alpha-308A genotype among HS and SpA patients (P = 0.004), uSpA patients (P = 0.040), ReA patients (P = 0.001), were significantly different and AS patients (P = 0.110), as were alleles for SpAs (P = 0.007) between patients with SpAs and controls. Initial exploratory analyses demonstrated that the TNF alpha-308 SNP genotype frequencies were different among SpA patients and HS in the Colombian population studied. Furthermore, there was no significant correlation with activity and functional clinical index, serum TNF alpha level or HLA B27 status. Allele frequencies, on the other hand, were correlated with the activity clinical index.

Association between Th-17 cytokine profile and clinical features in patients with spondyloarthritis.

OBJECTIVES: In recent years, a substantial amount of information has become available on the relationship between cytokines associated with the Th-17 profile and the development of spondyloarthritis (SpA). The purpose of this study was to evaluate inflammation markers in serum and synovial fluid (SF) and levels of cytokines related to the Th-17 profile in patients with different subtypes of SpA and healthy subjects. METHODS: We evaluated this cytokine profile in light of the clinical activity of the disease in 62 patients. Serum cytokine levels (IL-17, IL-6, IL-1 alpha, TNF alpha, IFN-gamma) were measured by flow cytometry. IL-23, serum amyloid (SAA) and metalloproteinase 3 (MMP-3) were measured with ELISA. In all patients, clinical evaluation was performed using the activity and function indexes of the disease. RESULTS: A comparison showed that IL-17, IL-23, IL-1 alpha, IL-6, and TNF-alpha levels were significantly higher in the serum of SpA patients than healthy subjects (HS), and there were no differences among SpA subtypes. In SF we found higher concentrations of cytokines, but only IL-23 showed significant differences (p<0.05). We found a relationship between enthesitis and peripheral involvement and serum IL-17 levels (9 to 63 pg / ml). There was a correlation between levels above 63 pg/ml and a history of infection. Higher levels of IL-23 in synovial fluid could suggest local amplification of the Th-17 cytokine profile. CONCLUSIONS: These results suggest a possible relationship between IL-17 and enthesis involvement in SpA.

The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general.

OBJECTIVE: To evaluate new classification criteria for peripheral spondyloarthritis (SpA) in patients with SpA with peripheral manifestations only. METHODS: In this Assessment of SpondyloArthritis international Society (ASAS) study, two prespecified sets of criteria were compared against the European Spondylarthropathy Study Group (ESSG) and Amor criteria in newly referred consecutive patients with undiagnosed peripheral arthritis, and/or enthesitis, and/or dactylitis that usually began before 45 years of age. The clinical diagnosis (SpA vs no SpA) made by the ASAS rheumatologist served as reference standard. RESULTS: In all, 24 ASAS centres included 266 patients, with a final diagnosis of SpA being made in 66.2%. After adjustments a final set of criteria showed the best balance between sensitivity (77.8%) and specificity (82.9%): arthritis and/or enthesitis and/or dactylitis plus (A) one or more of the following parameters: psoriasis, inflammatory bowel disease, preceding infection, human leucocyte antigen B27, uveitis, sacroiliitis on imaging, or (B) two or more other parameters: arthritis, enthesitis, dactylitis, inflammatory back pain in the past, family history of SpA. The new criteria performed better than modified versions of the ESSG (sensitivity 62.5%, specificity 81.1%) and the Amor criteria (sensitivity 39.8%, specificity 97.8%), particularly regarding sensitivity. In the entire ASAS population of 975 patients the combined use of ASAS criteria for axial SpA and ASAS criteria for peripheral SpA also had a better balance (sensitivity 79.5%, specificity 83.3%) than the modified ESSG (sensitivity 79.1%, specificity 68.8%) and Amor criteria (sensitivity 67.5%, specificity 86.7%), respectively. CONCLUSIONS: The new ASAS classification criteria for peripheral SpA performed well in patients presenting with peripheral arthritis, enthesitis and/or dactylitis.

Remodelación ósea en espondiloartritis / Bone remodeling in spondyloarthritis

Las espondiloartropatías (EAS) corresponden a un grupo de patologías inflamatorias crónicas caracterizadas por proliferación ósea que progresivamente conduce a anquilosis y discapacidad funcional. Las alteraciones radiológicas observadas en dichos pacientes revelan cambios erosivos y sobrecrecimiento de estructuras óseas conocidas como sindesmofitos. Teniendo en cuenta la entesis como órgano primario de la enfermedad, varios procesos tienen lugar en este sitio anatómico: inflamación, destrucción ósea y finalmente nueva formación ósea. El proceso inflamatorio tiene como resultado un exceso de formación ósea, y el impacto neto depende de la localización, tipo celular, citoquinas y factores presentes en el micro ambiente local. Varias moléculas que actúan ya sea como moduladores inmunológicos o reguladores de la homeostasis del hueso, han sido implicadas en la mediación del imbalance entre reabsorción y formación que finalmente resulta en degeneración a nivel de la zona de entesis y/o articular. Modelos animales sugieren que la anquilosis articular que puede llegar a producirse puede ser independiente del Factor de Necrosis Tumoral Alfa; por lo tanto, el proceso de neoformación tisular puede ser considerado un blanco terapéutico adicional. La vía de señalización Wnt, considerada el principal regulador de osteoblastogénesis (Familia de glicoproteína Wnt), teniendo en cuenta su papel en cuanto a regulación del imbalance entre formación y resorción ósea, ha constituido un nuevo campo de investigación de gran interés durante los últimos años.

Spondyloarthritis are a group of chronic inflammatory diseases characterized by progressive new bone formation leading to ankylosis and functional disability. The radiographic changes in these patients may show erosive changes and overgrowth of bony structures called syndesmophytes. Given the enthesis as the primary organ of the disease, several processes take place: inflammation, bone destruction and finally new bone formation. The inflammatory process results in excess of bone formation and the impact depends on the location, cell type, cytokines and factors in the local microenvironment. Several molecules that act either as immune modulators or regulators of bone homeostasis have been implicated in mediating the imbalance between resorption and formation that ultimately results in joint degeneration. Animal models suggest that joint ankylosis may be independent of TNF alfa; therefore the process of new tissue formation can be an additional therapeutic target. The Wnt signaling pathway, considered the primary regulator of osteoblastogenesis and its role in terms of regulating the imbalance between bone formation and resorption, is a new research field of great interest in recent years.

Nuevo paradigma en espondiloartritis: Linfocitos Th-17 / New paradigm in spondyloarthritis: Lymphocytes Th-17

Las espondiloartritis son un grupo heterogéneo de enfermedades asociadas principalmente al complejo mayor de histocompatibilidad alelo HLA- B 27, y factores ambientales. La evidencia de esos desórdenes reflejan un origen autoinmune mediado por el sistema inmune adaptativo, en donde la composición de las lesiones inflamatorias está representada principalmente por macrófagos activados, linfocitos B y linfocitos T. El fenotipo y naturaleza de esas células T aún no están bien establecidos. Recientes estudios han demostrado que el clásico modelo de las células T CD4 efectoras Th-1/Th-2 en estas patologías debe ser reevaluado y darle espacio a las células Th-17 dentro de las patogenias inflamatorias articulares. Estudios preliminares dirigen la investigación hacia el eje IL-23/IL-17 en espondiloartropatías como una nueva propuesta. Considerar el bloqueo de las moléculas involucradas en esta vía podría ser interesante como nuevos blancos terapéuticos.

Spondyloarthritides are a heterogeneous group of diseases which are mainly associated with HLA B 27 and environmental factors. The evidence for these disorders reflects an adaptive immune system-mediated autoimmune origin where inflammatory lesion composition is mainly represented by activated macrophages, B lymphocytes and T lymphocytes. These T-cells phenotype and nature has not been well established. Recent studies have shown that the classical CD4+ Th-1/Th-2 effector-cell model should be reevaluated and Th-17 cells should be introduced in inflammatory joint pathogenesis. Preliminary studies have directed research towards the IL-23/IL-17 axis in spondyloarthropathies as a new proposal. The intervention of the molecules involved in this pathway might be interesting as new therapeutic targets.

The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection.

OBJECTIVE: To validate and refine two sets of candidate criteria for the classification/diagnosis of axial spondyloarthritis (SpA). METHODS: All Assessment of SpondyloArthritis international Society (ASAS) members were invited to include consecutively new patients with chronic (> or =3 months) back pain of unknown origin that began before 45 years of age. The candidate criteria were first tested in the entire cohort of 649 patients from 25 centres, and then refined in a random selection of 40% of cases and thereafter validated in the remaining 60%. RESULTS: Upon diagnostic work-up, axial SpA was diagnosed in 60.2% of the cohort. Of these, 70% did not fulfil modified New York criteria and, therefore, were classified as having "non-radiographic" axial SpA. Refinement of the candidate criteria resulted in new ASAS classification criteria that are defined as: the presence of sacroiliitis by radiography or by magnetic resonance imaging (MRI) plus at least one SpA feature ("imaging arm") or the presence of HLA-B27 plus at least two SpA features ("clinical arm"). The sensitivity and specificity of the entire set of the new criteria were 82.9% and 84.4%, and for the imaging arm alone 66.2% and 97.3%, respectively. The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI (sensitivity 85.1%, specificity 65.1%) and slightly better than that of the modified Amor criteria (sensitivity 82.9, specificity 77.5%). CONCLUSION: The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain. TRIAL REGISTRATION NUMBER: NCT00328068.

Prostatectomía radical laparoscópica: experiencia inicial / Laparoscopic radical prostatectomy: initial experience

La prostatectomía radical es el tratamiento de elección en tumores confinados a la glándula. Desde las publicaciones de Guilleneau y Vallancien, el abordaje laparoscópico ha sido un tema de controversia. Entre mayo de 2000 y abril de 2001 se seleccionaron 18 pacientes para prostatectomía radical laparoscópica. Todos los pacientes eran portadores de un adenocarcinoma prostático localizado, en estadíos clínicos T1 y T2. La edad promedio fue de 65 años y el estadío clínico fue <= T2a. El APE promedio fue de 11 ng/ml y el score de Gleason estuvo entre 5 y 8. El tiempo operatorio fue en promedio de 260 minutos (rango de 155 a 450 minutos). El sangrado promedio fue de 344 ml. Fue necesaria la conversión en 2 de los primeros pacientes. La complicación más frecuente fue la lesión de recto en 3 pacientes, reconocida intraoperatoriamente. Nos encontramos en el inicio de la curva de aprendizaje de la técnica, por lo que se deberá esperar una serie mayor de pacientes para poder realizar conclusiones más acertadas.

[Laparoscopic lumboaortic retroperitoneal lymphadenectomy in testicular neoplasm]. / Linfadenectomía retroperitoneal lumboaórtica laparoscópica en cáncer de testículo.

Lumboaortic lymphadenectomy is a therapeutic alternative for patients with nonseminomatous testis tumors and its principal untoward effect is the loss of ejaculation. The anatomic knowledge of lymph node metastasis allows lower limit definition of aortic dissection, maintaining the diagnostic sensitivity and ejaculation. We report three patients with nonseminomatous testis tumors subjected to a reduced video-laparoscopic lumboaortic lymphadenectomy. An adequate amount of tissue was obtained in all and lymph node metastasis found in two. No complications occurred and patients were discharged 48 hours later. It is concluded that this technique is an alternative staging technique with low morbidity that allows a rapid patient discharge.

[Laparoscopic nephrectomy: report of 2 cases]. / Nefrectomia laparoscópica: comunicación de 2 casos.

Laparoscopic surgery has become very popular in general surgery. Its most significant advantages for patients are a better postoperative comfort and fast return to work. We report two young female patients with a gynecologic cancer in whom a laparoscopic nephrectomy was performed. The surgical procedure and the post operative recovery were uneventful. These promising results show that laparoscopic surgery is applicable in traditional urologic procedures.

Short term diet of precooked corn meal almost lacking in tryptophan and interspecific rat-mouse aggressive behaviour.

The content of tryptophan in a precooked corn meal and in 4 types of selected corn seeds: Zea mays indurata, identata, opaque/2 and Marano synth., has been determined by three different methods: ion-exchange chromatography, spectrofluorometry and spectrophotometry. This content is very low, less than 0.080% d.w. Alimentation for 4 d with a diet composed of precooked corn meal with a tryptophan content less than 0.025% induced the appearance of aggressive-cidal or aggressive non-cidal behaviour towards the mouse in more than half of Wistar rats bred in a room constantly lighted by a sodium steam light. The appearance of this behaviour is probably connected with a decrease in brain serotonin.

[Effect of a short-term diet based on precooked corn flour on the muricidal behavior of male SM Wistar rats]. / Effetti di una dieta "short term" a base di farina di mais precotta sul comportamento muricida (mouse killing behaviour) di ratti maschi Wistar SM.

The aim of this research is to observe if the lack of cerebral serotonin, obtained by a diet almost devoid of tryptophan (precooked yellow corn meal) is able to trigger the muricide behaviour in male Rats naturally non-muricide. To determine the tryptophan content in the food used and in 4 types of selected maize flour (Zea mays: indurata, indentata, opaque/2 and synt. marano), 3 different methods have been used (ion-exchange chromatography, spectrofluorometry, spectrophotometry). The muricide behaviour, or the interspecific attack, has been tested by comparison Rat-Mouse. The results show that the feeding with a diet "short term" (4 days), composed of precooked corn meal, with a very low content of tryptophan, induces the appearance of muricide or aggressive behaviour towards the Mouse in more than half of the Wistar Rats, bred in a room constantly lighted by sodium steam light. The appearance of the above-mentioned behaviour is connected with the decrease in cerebral serotonin.

[Effects of a short-term diet of precooked corn flour on the vaginal cycle, in rats placed in various conditions of environmental illumination]. / Effetti di una dieta "short term" con farina di mais precotta sul ciclo vaginale, in ratte poste in diverse condizioni di illuminazione ambientale.

The aim of this research is to study the effects of a diet almost devoid of tryptophan, which is given by a feeding with precooked yellow corn meal (corn mush), on the alterations of the estrous cycle of animals in several conditions of environmental lighting. Indeed, it is known that cerebral serotonin influences the releasing of LH and consequently the ovulation. The different types of environmental lighting are: 1) Natural (alternating Day-Night = L/D). 2) Continuous dark (D/D). 3) Continuous light by sodium steams (L/L sodium). 4) Continuous light by fluorescent neon tubes (L/L neon). The muricide behaviour is studied by comparison rat-mouse. The feeding with precooked yellow corn meal (diet lacking of tryptophan) unchains in the 100% of the observations the CEA (Constant Estrous Anovulatory), and significantly shrinks the estral cycle in the female Wistar Rat in several conditions of environmental lighting.