Long-term Outcome of Lupus Nephritis Class II in Argentine Patients: An Open Retrospective Analysis.

BACKGROUND: There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. METHODS: A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. RESULTS: Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1-35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11-305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0-4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0-1.7 g/d]) (P = 0.0133).In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). CONCLUSIONS: This series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect.

Long-term follow-up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to JAK2/CALR/MPL mutational status.

BACKGROUND: Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial. AIM: To assess the impact of mutational status in response rates and development of adverse events during long-term use of anagrelide. METHODS: We retrospectively evaluated 67 patients with essential thrombocythemia treated with anagrelide during 68 (4-176) months. RESULTS: Mutational frequencies were 46.3%, 28.3%, and 1.5% for JAK2V617F, CALR and MPL mutations. Anagrelide yielded a high rate of hematologic responses, which were complete in 49.25% and partial in 46.25%, without differences among molecular subsets. The rate of thrombosis during treatment was one per 100 patient-years, without excess bleeding. Anemia was the major adverse event, 30.3% at 5-yr follow-up, being more frequent in CALR(+) (P < 0.05). Myelofibrotic transformation developed in 14.9% (12.9%, 21%, and 12.5% in JAK2V617F(+), CALR(+), and triple-negative patients, respectively, P = NS) and those treated >60 months were at higher risk, OR (95% CI) 9.32 (1.1-78.5), P < 0.01, indicating the need for bone marrow monitoring during prolonged treatment. CONCLUSION: Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.

Association between the presence of anti-C1q antibodies and active nephritis in patients with systemic lupus erythematosus.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). A retrospective analysis was carried out on a group of 24 patients with SLE to evaluate whether the presence of anti-C1q antibodies (anti-C1q) is related to renal involvement and to explore the behaviour of anti-C1q with respect to LN during a four-year follow-up period. A first serum sample stored at the serum bank, taken not more than three years after SLE diagnosis and one serum sample per year for the subsequent four years were used to detect anti-C1q. Lupus clinical manifestations and serological markers of activity corresponding to the date of each serum sample selected were collected from medical records. In the first serum sample, anti-C1q were found in 8 active SLE. LN was confirmed by histology in 5/8 patients who were positive for anti-C1q and in 1/16 patients who were negative for these autoantibodies (p = 0.0069). Three patients (3/8) had anti-C1q without renal involvement but with lupus skin manifestation. Anti-C1q levels decreased in 3/5 patients with LN who responded to treatment and remained higher in 2/5 patients who needed a new renal biopsy which showed severe renal disease. The 15 patients without severe kidney disease and anti-C1q negative at diagnosis did not develop LN and anti-C1q remained negative in the 4 years of follow up. Anti-C1q were found in SLE patients with active renal involvement or with lupus skin disease. The absence of anti-C1q seemed to be linked to low probabilities of renal involvement.

Association between the presence of anti-c1q antibodies and active nephritis in patients with systemic lupus erythematosus

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE). A retrospective analysis was carried out on a group of 24 patients with SLE to evaluate whether the presence of anti-C1q antibodies (anti-C1q) is related to renal involvement and to explore the behaviour of anti-C1q with respect to LN during a four-year follow-up period. A first serum sample stored at the serum bank, taken not more than three years after SLE diagnosis and one serum sample per year for the subsequent four years were used to detect anti-C1q. Lupus clinical manifestations and serological markers of activity corresponding to the date of each serum sample selected were collected from medical records. In the first serum sample, anti-C1q were found in 8 active SLE. LN was confirmed by histology in 5/8 patients who were positive for anti-C1q and in 1/16 patients who were negative for these autoantibodies (p = 0.0069). Three patients (3/8) had anti-C1q without renal involvement but with lupus skin manifestation. Anti-C1q levels decreased in 3/5 patients with LN who responded to treatment and remained higher in 2/5 patients who needed a new renal biopsy which showed severe renal disease. The 15 patients without severe kidney disease and anti-C1q negative at diagnosis did not develop LN and anti-C1q remained negative in the 4 years of follow up. Anti-C1q were found in SLE patients with active renal involvement or with lupus skin disease. The absence of anti-C1q seemed to be linked to low probabilities of renal involvement.

La nefritis lúpica (NL) es una complicación grave del Lupus Eritematoso Sistémico (LES). Se analizó retrospectivamente en 24 pacientes con LES si la presencia del anticuerpo anti-C1q (anti-C1q) se asociaba con NL y el comportamiento del anti-C1q respecto a la NL en un período de seguimiento de cuatro años. El anti-C1q se determinó en una primera muestra de suero no distante en más de tres años del diagnóstico de LES y en una muestra por año en los siguientes cuatro años. Se obtuvo información de las historias clínicas, sobre manifestaciones clínicas de LES y marcadores serológicos de actividad para las fechas de selección de cada suero. En la primera muestra de suero se detectó anti-C1q en 8 pacientes con LES activo. NL fue confirmada por histología en 5 de ellos y en uno de 16 pacientes con anti-C1q negativos (p = 0.0069); 3 de 8 pacientes fueron anti-C1q positivos sin NL y con lesiones en piel. Los niveles de anti-C1q disminuyeron en 3/5 pacientes con NL que respondieron al tratamiento y se mantuvieron aumentados en 2/5 que necesitaron una nueva biopsia, que evidenció compromiso renal grave. Los 15 pacientes sin enfermedad renal grave y con anti-C1q negativo al diagnóstico no desarrollaron NL y el anti-C1q se mantuvo negativo en los 4 años de seguimiento. El anti-C1q se asoció en pacientes con LES a NL activa o con compromiso en piel. La ausencia del anti-C1q parecería relacionarse a un menor riesgo de desarrollar nefropatía lúpica.

[Inflammatory myopathy with initial respiratory muscles involvement and rheumatoid arthritis]. / Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea.

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.

Miopatía inflamatoria con compromiso inicial de músculos respiratorios y artritis reumatoidea

Las miopatías inflamatorias constituyen un grupo heterogéneo de enfermedades musculares adquiridas de presentación subaguda, crónica y a veces aguda. Las entidades clínicas más frecuentes son la dermatomiositis, la polimiositis, la miositis necrotizante autoinmune y la miositis por cuerpos de inclusión. Suelen presentarse con debilidad muscular con predominio proximal y simétrica, pero rara vez comprometen los músculos respiratorios. Presentamos el caso de una mujer de 39 años con miopatía inflamatoria inespecífica que presentó insuficiencia respiratoria secundaria a hipoventilación alveolar por debilidad muscular y requirió asistencia respiratoria mecánica. Respondió favorablemente y de forma rápida tras el tratamiento instaurado con inmunosupresores (corticoides y metotrexato) e inmunoglobulina humana endovenosa. Se utilizó ventilación no invasiva como alternativa a la intubación orotraqueal con adecuada tolerancia.

Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.

Functional characterization of residues involved in redox modulation of maize photosynthetic NADP-malic enzyme activity.

Two highly similar plastidic NADP-malic enzymes (NADP-MEs) are found in the C(4) species maize (Zea mays); one exclusively expressed in the bundle sheath cells (BSCs) and involved in C(4) photosynthesis (ZmC(4)-NADP-ME); and the other (ZmnonC(4)-NADP-ME) with housekeeping roles. In the present work, these two NADP-MEs were analyzed regarding their redox-dependent activity modulation. The results clearly show that ZmC(4)-NADP-ME is the only one modulated by redox status, and that its oxidation produces a conformational change limiting the catalytic process, although inducing higher affinity binding of the substrates. The reversal of ZmC(4)-NADP-ME oxidation by chemical reductants suggests the presence of thiol groups able to form disulfide bonds. In order to identify the cysteine residues involved in the activity modulation, site-directed mutagenesis and MALDI-TOF (matrix-assisted laser desorption ionization-time of flight) analysis of ZmC(4)-NADP-ME were performed. The results obtained allowed the identification of Cys192, Cys246 (not conserved in ZmnonC(4)-NADP-ME), Cys270 and Cys410 as directly or indirectly implicated in ZmC(4)-NADP-ME redox modulation. These residues may be involved in forming disulfide bridge(s) or in the modulation of the oxidation of critical residues. Overall, the results indicate that, besides having acquired a high level of expression and localization in BSCs, ZmC(4)-NADP-ME displays a particular redox modulation, which may be required to accomplish the C(4) photosynthetic metabolism. Therefore, the present work could provide new insights into the regulatory mechanisms potentially involved in the recruitment of genes for the C(4) pathway during evolution.

Pulmón del soldador de arco / Arc welder's lung

La siderosis del soldador o neumoconiosis siderótica fue descripta por Doig y McLaughlin en 1936 como una enfermedad pulmonar causada por la inhalación crónica de polvo de hierro en soldadores de arco eléctrico. Presentamos un caso de siderosis del soldador asociada a aumento de los niveles de ferritina, sin hallazgo de depósito de hierro en otros órganos y sin causas evidentes de hemosiderosis secundaria.

Pneumoconiosis of electric arc welder or siderotic pneumoconiosis was described by Doig and McLaughlin in 1936 as a lung disease caused by chronic inhalation of iron fumes in electric arc welders. We present a case report of electric arc welder siderosis associated with high levels of ferritin, without findings of iron deposit in any other organ.

Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia.

This study investigated the involvement of chemokines including stromal derived factor 1 (SDF-1), interleukin 8 (IL-8), growth-related oncogene alpha (GRO-alpha) and their receptors, CXCR4, CXCR2 and CXCR1 in essential thrombocythemia (ET), a chronic myeloproliferative disease characterized by megakaryocytic hyperplasia and high platelet count. Fifty-three ET patients were studied. Plasma levels of SDF-1, IL-8 and GRO-alpha, evaluated by enzyme-linked immunosorbent assay, and flow cytometric analysis of CXCR1 and CXCR2 on the platelet membrane, were found to be normal in ET patients. CXCR4 expression on platelet surface as well as platelet CXCR4 mRNA detected by real-time reverse transcription polymerase chain reaction, were decreased. Platelet CXCR4 internalization rate was normal while SDF-1-induced platelet aggregation was delayed, decreased or absent. Immunohistochemical staining revealed that megakaryocytes were also affected. CXCR4 decrease was not observed either in peripheral white blood cells or in circulating CD34(+) precursors. These results show that CXCR4 is decreased in the megakaryocytic lineage in ET, mainly due to a reduced CXCR4 production, and an abnormal platelet response to SDF-1. This report is the first to describe platelet and megakaryocytic CXCR4 deficiency in a human disease and the presence of this abnormality in a megakaryocytic-related illness highlights the important role of SDF-1/CXCR4 axis in platelet development.

Enfermedad cardiaca grave en la esclerosis sistemica / Severe cardiac disease in scleroderma

Uma mujer de 36 años de edad con diagnóstico de esclerosis sistémica (ES) desarrolló un cuadro agudo de miositis esquelética e insuficiencia cardíaca grave. Evolucionó con shock cardiogénico y a pesar del tratamiento con drogas inotrópicas y altas dosis de corticoides falleció a los cinco días de haber ingresado. La autopsia reveló áreas de necrosis coagulativa miocárdicas con miocitolisis y necrosis en banda de contracción. Son muy pocos los casos comunicados de insuficiencia cardíaca grave asociada a la ES.

Lesion quistica adrenal: hallazgo incidental / Cystic adrenal lesion. Incidental finding

Se presenta el hallazgo de una mesa adrenal quística unilateral no funcionante encontrada incidentalmente en una ecografía durante la evaluación de síntomas abdominales inespecíficos. Según la clasificación de quistes adrenales coresponde a un pseudoquiste multilocular con fibrosis y calcificación e la pared. La presencia de Factor VIII en el revestimiento de los quistes inidicaría un origen vascular de los mismos.

Sindrome antifosfolipidico catastrofico. Comunicacion de dos formas de presentación / Catastrophic antiphopholipidid syndrome. Communication of two forms of presentation

El síndrome antifosfolipídico (SAFL) se caracteriza por la presencia de abortos espontáneos, trombosis arteriales y venosas, trombocitopenia y el hallazgo de anticuerpos antifosfolipídicos en sangre. En una minoría de los casos tiene un curso rápidamente fatal. Presentamos dos pacientes jóvenes con lupus eritematoso sistémico (LES) y anticuerpos antifosfolipídicos, que desarrollaron un cuadro agudo que rápidamente les provocó la muerte. Si bien el cuadro clínico y de laboratorio fue distinto - en una paciente había predominantemente microtrombosis con anemia hemolítica microangiopática, similar a la púrpura trombótica trombocitopénica (PTT), mientras que en la otra se evidenció trombosis de vasos pequeños y medianos, sin hemólisis-, en la autopsia de ambas pacientes se encontraron trombosis en múltiples órganos, configurando el cuadro de SAFL catastrófico. No hay casos descriptos de este síndrome desencadenado por neumonía por Pneumocistis carinii como se observó en una de nuestras pacientes.

Necrosis cortical renal: estudio clínico y anatomopatológico / Kidney cortex necrosis: clinical and anatomopathological study

En un período de 35 años, 1964 pacientes fueron derivados al Instituto de Investigaciones Médicas para ser dializados por una IRA. De ellos, 30 casos (2 por ciento) presentaron una Necrosis Cortical Renal. Las causas obstétricas fueron responsables del 80 por ciento de las NCR, y en este grupo el 70 por ciento correspondió a complicaciones durante el 3º trimestre de embarazo y el 30 por ciento a abortos sépticos del 1º y 2º trimestre. De las causas no obstétricas, w casos fueron sepsis, 1 gran quemado, 1 hemorragia masiva post-traumática, 1 deshidratación en paciente diábetico y un Lupues Eritematoso Sistémico. Sepsis (93 por ciento), shock (60 por ciento) y Coagulación Intravascular Diseminada (5o por ciento), fueron el común denominador de los causales de las graves alteraciones de la microcirculación evidenciadas en las autopsias. La anuria total fue la presentación habitual del cuadro, y la prolongada duración de la oligoanuria (36 días), fueron el rasgo distintivo de la IRA. La sospecha clínica y la PBR realizada a los 30 días de inicio del cuadro fueron los elementos diagnósticos utilizados, aunque la TC renal es de gran ayuda para establecer diagnósticos tempranos. Hubo una mortalidad del 77 por ciento y de los 7 sobrevivientes todos quedaron con una severa disminución de la función renal, debiendo ingresar a plan de hemodiálisis crónica dentro de los primeros 36 meses de alta. La histología renal reveló 12 casos de NCR parcelar, 6 sobrevivieron y 18 NCR masiva bilateral con un solo sobreviviente.

Rol del calcio intracelular en la nefrotoxicidad por gentamicina / Role of increased intracellular calcium in the nephrotoxicity produced by gentamicin

Recientemente se ha llamado la atención sobre el rol que tendría el aumento del calcio intracelular en el mecanismo de la injuria celular isquémica y de otras formas de injurias. Para evaluar ésta hipótesis utilizamos el modelo de daño renal tubular tóxico producido por la gentamicina. Nosotros tratamos ratas con verapamil (V) (Bloqueante de los canales de calcio), antes y después de provocarle una nefrotoxicidad por gentamicina (G) y no encontramos protección de la nefrotoxicidad observándose una disminución similar del Clearance de Creatinina (G: 0,47 ñ 0,09; G + V: 0,59 ñ 0,05 ml/min/100 g peso corporal), un incremento semejante de la excreción fraccional de sodio (G: 1,68 ñ 0,50; G + V: 1,23 ñ 0,1%) y el mismo grado de daño tubular histológico (G: 3 ñ 0,23; G + V: 2,7 ñ 0,19). El aumento de la disponibilidad de calcio extracelular, producido por la hipercalcemia inducida por vitamina D, (H), durante la producción de toxicidad renal por gentamicina, no exacerbó la injuria tubular renal como lo demuestran la misma disminución de Clearance de creatinina (G: 0,18 ñ 0,2; G + H: 0,6 ñ 0,1 ml/min/100 g peso corporal), el mismo aumento de la excreción fraccional de sodio (G: 1,25 ñ 0,2; G + H: 1,5 ñ 0,3%) y el mismo grado de daño tubular histológico (G: 1,85 ñ 0,26; G + H: 2 ñ 0,37). Nuestros resultados no apoyan la hipótesis que propone el aumento de calcio intracelular como mediador de la injuria nefrotóxica

Rabdomiolisis alcohólica con compromiso miocárdico / Alcoholic rhabdomyolysis with myocardial involvement

Presentamos un paciente de 32 años con antecedentes de alcoholismo, que refirió disnea de esfuerzo desde 8 meses antes, con peoría en los días previos a su internación. En otro hospital se diagnosticó tromboembolismo pulmonar masivo. Ingresó al Instituto en colapso circulatorio. La radiografía de tórax mostró cardiomegalia. Se lo ventiló artificialmente y se efectuó monitoreo hemodinámico, corrigiéndose los parámetros anormales. La evolución se complicó con colecistitis gangrenosa y bronconeumonia falleciendo a los 13 días de internado. La necropsia mostró rabdomiolisis esquelética y cardíaca, estigmas anatómicos de alcoholismo, peritonitis y bronconeumonia. El interés de esta presentación reside en la comprobación anatómica de rabdomiolisis cardíaca, hecho previamente supuesto

Selective experimental transvenous catheter ablation of the right bundle branch

La ablación transvenosa o fulguración selectiva de la rama derecha del haz de His puede ser de utilidad para la producción de bloqueo de rama derecha, tanto con fines experimentales como para el tratamiento de arritmias reentrantes que incluyan la rama derecha en su circuito. En el presente trabajo se describe la técnica experimental para lograr la ablación selectiva de la rama derecha del haz de His. Fueron estudiados siete perros mestizos a quenes, previa anestesia general, se les intodujo un catéter bipolar USCI 6 o 7 French a través de la vena femoral, manibrándolo convenientemente dentro del corazón, hasta obtener los potenciales correspondientes a la depolarización de la rama derecha del haz de His (Fig. 1). Se emplearon los siguientes criterios: 1) distancia electrograma de la rama derecha-onda A de baja amplitud, y 2) electrograma de la rama derecha distinto del electrograma del haz de His. A continuación se conectaron las dos terminales del electrodo bipolar a la paleta catódica de un desfibrilador convencional y a la paleta anódica restante se la ubicó sobre el dorso del animal. Seguidamente se efectuó un choque eléctrico con una energía equivalente a 9-10,5 Joules/Kg siendo necesario en dos perros de rama derecha (Tabla 1). En todos los animales se obtuvo BCRD (Fig. 2), en 4 de ellos se lo documentó vectocardiográficamente (Fig.3). Luego del choque un bloqueo AV completo transitorio fue observado en todos los casos. La anatomía patológica comprobó la indemnidad del septum interventricular alto y la válvula tricúspide (Fig. 4), así como del nódulo AB (Fig. 5). Lesiones significativas fueron halladas sobre la rama derecha del haz de His (Fig. 6) y la pared libre del ventrículo deecho; este último hallazgo se efectó en dos animaes (28,5%) y debe interpretarse que no tuvo par alos animales traducción clínica alguna