Tratamiento del asma severo con omalizumab: experiencia pediátrica en Chile y revisión de la literatura / Omalizumab treatment on severe asthma patients: pediatric experience in Chile and literature review

This paper presents clinical experience with Omalizumab treatment in 8 pediatric patients in Chile. All children presented difficult to control asthma despite receiving high intensity treatment, with low quality of life. All patients were studied in order to discard errors in asthma diagnosis and to evaluate asthma treatment adherence and inhalation technique. After evaluation, patients proven to have severe therapy resistant asthma were indicated treatment with Omalizumab. Significant clinical improvement was observed, with reduced asthma symptoms and number of exacerbations, as well as an improved quality of life. Omalizumab showed a good safety profile with mild and transient adverse reactions in 6 administrations of a total of 122.

Se presenta la experiencia clínica con el uso de Omalizumab en 8 pacientes pediátricos en nuestro país. Todos los pacientes presentaban asma sin control a pesar de recibir terapia de alta intensidad, asociado a una muy deficiente calidad de vida. La totalidad de los pacientes fueron sometidos en cada centro a un estudio exhaustivo para poder descartar error en el diagnóstico y se evaluó la adherencia y la técnica inhalada. Al comprobarse que estos pacientes tenían asma severo resistente a tratamiento se indicó Omalizumab, el cual produjo una mejoría clínica significativa. Se observó una reducción de las exacerbaciones y de los síntomas de asma acompañado de una mejoría de la calidad de vida, asociado a un buen perfil de seguridad. Se observaron reacciones adversas leves y transitorias en 6 administraciones de un total de 122.

Green tea polyphenol extract in vivo attenuates inflammatory features of neutrophils from obese rats.

PURPOSE: Our study aimed to evaluate whether obesity induced by cafeteria diet changes the neutrophil effector/inflammatory function and whether treatment with green tea extract (GT) can improve neutrophil function. METHODS: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight), and obesity was induced by cafeteria diet (8 weeks). Neutrophils were obtained from the peritoneal cavity (injection of oyster glycogen). The following analyses were performed: phagocytic capacity, chemotaxis, myeloperoxidase activity (MPO), hypochlorous acid (HOCl), superoxide anion (O 2 (·-) ), hydrogen peroxide (H2O2), IL-1ß, IL-6 and TNFα, mRNA levels of inflammatory genes, calcium mobilisation, activities of antioxidant enzymes, hexokinase and G6PDH. RESULTS: Neutrophils from obese rats showed a significant decrease in migration capacity, H2O2 and HOCl production, MPO activity and O 2 (·-) production. Phagocytosis and CD11b mRNA levels were increased, while inflammatory cytokines release remained unmodified. mRNA levels of TLR4 and IκK were enhanced. Treatment of obese rats with GT increased neutrophil migration, MPO activity, H2O2, HOCl and O 2 (·-) production, whereas TNF-α and IL-6 were decreased (versus obese). Similar reductions in TLR4, IκK and CD11b mRNA were observed. Catalase and hexokinase were increased by obesity, while SOD and G6PDH were decreased. Treatment with GT reduced catalase and increased the GSH/GSSG ratio. CONCLUSION: In response to a cafeteria diet, we found a decreased chemotaxis, H2O2 release, MPO activity and HOCl production. We also showed a significant immunomodulatory effect of GT on the obese condition recovering some of these factors such H2O2 and HOCl production, also reducing the levels of inflammatory cytokines.

Green tea catechins alone or in combination alter functional parameters of human neutrophils via suppressing the activation of TLR-4/NFκB p65 signal pathway.

The purpose of this study was to evaluate the potential of a mixture containing the four main catechins found in green tea, as well it separately, as modulators of the functional parameters of human neutrophils. The cells were obtained from peripheral blood of healthy individuals isolated and cultured with a mix: 30 µM of EGCG, 3 µM of EGC, 2 µM of ECG and 1.4 µM of EC, as well as each one alone. We evaluated the cytotoxicity of catechins, production of several reactive oxygen species (ROS), antioxidant enzymes (SOD, CAT, GPx and GR), Nrf2, TLR4/IKK/NFκB, CD11b mRNA levels, intracellular calcium release, chemotactic and phagocytic capacity, myeloperoxidase (MPO), and G6PDH activities, hypochlorous acid (HOCl) and pro-inflammatory cytokines release, protein levels of TLR4, p38 MAPK, iNOS and p-65 NFκB. The actions of the catechins were evidenced by the reduction in inflammatory parameters, including the suppression of TLR4, NFκB and iNOS protein expression, decreased release of TNF-α, IL-1ß and IL-6, migration capacity, MPO activity and HOCl production and the suppression of ROS, nitric oxide and peroxynitrite production, while inducing antioxidant enzyme activities and Nrf2 mRNA levels, phagocytic capacity and calcium release. Our results demonstrate that catechins present marked immunomodulatory actions, either alone or in combination.

Inmunodeficiencias y su relación con enfermedades autoinmunes / Immunodeficiencies and their relation with autoinmune diseases

Aunque pueda parecer paradójico, las inmunodeficiencias primarias y la secundaria a infección por VIH frecuentemente se complican con enfermedades autoinmunes. Esto debido a la desregulación del sistema inmune y a la activación policlonal debida a infecciones recurrentes. Se revisan diversas enfermedades autoinmunes y autoanticuerpos asociados con ambos tipos de inmunodeficiencias. Las enfermedades autoinmunes pueden ser la primera manifestación de una inmunodeficiencia, por lo que deben estudiarse especialmente si la enfermedad autoinmune es atípica. Las patologías más frecuentemente asociadas son las citopenias autoinmunes y los enfermedades reumatológicas. Debe realizarse una exclusión completa de las infecciones coincidentes o posiblemente causantes de complicaciones autoinmunes antes de iniciar tratamientos específicos para ellas.

Although it may seem paradoxical, primary immunodeficiencies and HIV immunodeficiency are frecuently complicated by autoimmune conditions. This is because of the immune system disregulation and polyclonal activation due to recurrent infections. We review various autoimmune diseases and autoantibodies associated with both types of immunodeficiencies. Autoimmune diseases my be the first manifestation of an immunodeficiency, so we should screen for it, specially if this autoimmune disease is atypical. The most frecuent disease associated with immunodeficiencies are autoimmune cytopenias and rheumatologic disorders. A through exclusion of infections coincident with or possibly causative of autoimmune complication should be undertaken before initiating specific treatments for autoimmune disease in this patients.

Inmunopatogenia de la arteritis de la temporal / Immunopathogenesis of temporal arteritis

La arteritis de la temporal, clasificada como una vasculitis que compromete vasos de gran y mediano calibre, debe ser considerada como una emergencia médica, dado el potencial de causar ceguera y accidentes vasculares. La lesión típica corresponde a granulomas en la pared vascular, los que están constituidos por macrófagos y célulasT CD4+. Éstos se activan en la adventicia, luego de interactuar con las células dendríticas nativas. La injuria tisular es mediada por diversos subtipos de macrófagos, los que ejercen las diferentes funciones efectoras. El daño que domina en la capa media resulta del estrés oxidativo y determina la apoptosis de las células musculares lisas y la nitración de las endoteliales. Por otro lado, factores de crecimiento derivados de macrófagos determinan la hiperplasia intimal y la consecuente oclusión luminal. Las manifestaciones clínicas se relacionan estrechamente con el sitio isquémico. El tratamiento de elección son los corticoides sistémicos, los cuales pueden asociarse a inmunosupresores como también con agentes biológicos.

Temporal arthritis, which is classified as a large-and medium-caliber vessel vasculitis, should be considered as a medical emergency, given its potential to cause blindness and strokes. The injury typically corresponds to granulomas in the vascular wall, which are composed of macrophages and CD4+ T cells. They are activated in the adventitia, after interacting with native dendritic cells. Immunopathological mechanisms involve different subtypes of macrophaesges, which exert different effector functions. Damage that prevails within the median layer is secondary to oxidative stress and triggers apoptosis of smooth muscle cells and nitration of endothelial cells. On the other hand, growth factors derived from macrophages determine intimal hyperplasia and subsequent luminal occlusion. Clinical manifestations are closely related to the ischemic site. The treatment of choice is systemic corticosteroids, which can be associated with immunosuppressive drugs as well as biological agents.

Inmunoterapia con veneno de himenópteros: presentación de diez casos clínicos / Immunotherapy against hymenoptera venom: Report of ten patients

Background: Immunotherapy can be used to treat allergic reactions to insect stings, specially bees and wasps. Aim: To report the experience with immunotherapy with aqueous extracts of hymenoptera venoms (bees and wasps). Material and methods: Ten patients aged 6 to 58 years were treated in an allergy center of a University Clinical Hospital. The medical indication for this treatment was, in all patients, anaphylactic reactions after hymenoptera stings. Immunotherapy was carried out using standardized vaccines (Aqueous extracts Venomvac LETI, Spain), applied in a traditional protocol, with subcutaneous injections. This protocol had two phases: a buildup phase (between weeks 1 and 13) and a monthly maintenance phase, from the 13th week. The monthly maintenance dose was 100 fig of hymenoptera specific venom extract. Results: Six patients had adverse reactions of different severity, during the treatment protocols and all had a good response to immediate therapeutic measures. After these events, they followed the protocol without problems. Two patients, treated with bee vaccines, suffered an accidental bee sting during the maintenance phase and they developed only local reactions. Conclusions: The lack of adverse reactions to bee stings in these two patients indicates the acquisition of clinical tolerance.

[Immunotherapy against hymenoptera venom: report of ten patients]. / Inmunoterapia con veneno de himenópteros: presentación de diez casos clínicos.

BACKGROUND: Immunotherapy can be used to treat allergic reactions to insect stings, specially bees and wasps. AIM: To report the experience with immunotherapy with aqueous extracts of hymenoptera venoms (bees and wasps). MATERIAL AND METHODS: Ten patients aged 6 to 58 years were treated in an allergy center of a University Clinical Hospital. The medical indication for this treatment was, in all patients, anaphylactic reactions after hymenoptera stings. Immunotherapy was carried out using standardized vaccines (Aqueous extracts Venomvac LETI, Spain), applied in a traditional protocol, with subcutaneous injections. This protocol had two phases: a buildup phase (between weeks 1 and 13) and a monthly maintenance phase, from the 13th week. The monthly maintenance dose was 100 fig of hymenoptera specific venom extract. RESULTS: Six patients had adverse reactions of different severity, during the treatment protocols and all had a good response to immediate therapeutic measures. After these events, they followed the protocol without problems. Two patients, treated with bee vaccines, suffered an accidental bee sting during the maintenance phase and they developed only local reactions. CONCLUSIONS: The lack of adverse reactions to bee stings in these two patients indicates the acquisition of clinical tolerance.

[Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis associated to the use of propylthiouracil. Report of four cases]. / Vasculitis ANCA-positivo en pacientes hipertiroideos usuarios de propiltiouracilo: Report of four cases.

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is an uncommon complication of the use of propylthiouracil. When it occurs, it affects multiple organs as any systemic vasculitis. We report three females and one male, aged 30, 40, 43 and 41 years respectively, that after a lapse of 12 to 28 months of propylthiouracil use, presented clinical signs of vasculitis. All had high titers of ANCA against myeloperoxidase. In three patients, a skin biopsy confirmed the diagnosis. The condition subsided when propylthiouracil was discontinued, but one female patient required the use of prednisone.

Vasculitis ANCA-positivo en pacientes hipertiroideos usuarios de propiltiouracilo: Report of four cases / Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis associated to the use of propylthiouracil

Antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis is an uncommon complication of the use of propylthiouracil. When it occurs, it affects multiple organs as any systemic vasculitis. We report three females and one male, aged 30, 40, 43 and 41 years respectively, that after a lapse of 12 to 28 months of propylthiouracil use, presented clinical signs of vasculitis. All had high titers of ANCA against myeloperoxidase. In three patients, a skin biopsy confirmed the diagnosis. The condition subsided when propylthiouracil was discontinued, but one female patient required the use of prednisone.

Manifestaciones clínicas de la granulomatosis de Wegener y la poliangeítis microscópica en Santiago-Chile, 1990-2001 / Clinical features of Wegener granulomatosis and microscopic polyangiitis in Chilean patients

Background: Systemic vasculitis are a group of heterogeneous diseases characterized by inflammation and necrosis of blood vessel walls. The etiology is not known, but geographic and environmental factors are implicated. Aim: To describe the clinical features of microscopic polyangiitis (MPA) and Wegener's granulomatosis (WG) in a Chilean cohort of patients. Patients and methods: Retrospective review of the medical records of 123 patients with the diagnosis of systemic vasculitis (65 MPA and 58 WG), seen from 1990 to 2001. The diagnosis were made based on the American College of Rheumatology and Chapel Hill criteria. Results: The mean follow-up for MPA was 15 months (1-120) and for WG, 20 months (1-120). The median age (years) at diagnosis for MPA was 61 (19-82) and WG 50 (20-82). Gender distribution was similar in both groups (male: 68percent and 57percent respectively).The main clinical features in the MPA group were renal involvement (68percent), peripheral nervous system involvement (57percent), pulmonary hemorrhage (28percent), and skin disease (32percent). In the WG group were alveolar hemorrhage (62percent), renal involvement (78percent), paranasal sinus involvement (57percent), and ocular disease (26percent). In both, creatinine levels above 2.0 mg/dl were associated with a higher mortality (p< 0.01). ANCA by immunofluorescence was performed in 56 MPA patients (75percent had pANCA, 4percent had cANCA and 21percent were ANCA negative) and in 55 WG patients (17percent had pANCA, 79percent had cANCA and 4percent were ANCA negative). Global mortality was 18percent and 17percent respectively, and the most common causes of death were infections. Conclusions: The clinical features of our patients are similar to other published data. In our WG and MPA patients the main predictor for death was a serum creatinine above 2 mg/dl.

Síndrome de hiper-IgM asociado a colangitis esclerosante y neoplasia vesicular: caso clínico / X-linked hyper-IGM syndrome associated to sclerosing cholangitis and gallbladder cancer

We report a 11 years old male diagnosed as a X-linked hyper-IgM syndrome that presented with recurrent infections and sclerosing cholangitis and later developed a gallbladder cancer. Immunological evaluation showed decreased levels of serum IgG and IgA with elevated levels of IgM. Study of CD40 ligand expression on mitogen activated peripheral blood mononuclear cells revealed total absence of this marker on T lymphocytes. Molecular analysis detected, in the patient and his mother, a nonsense mutation in exon 1 of the transmembrane segment of the CD40 ligand. He also presented elevation of alkaline phosphatases and mild elevation of liver enzymes. Liver biopsy demonstrated the presence of idiopathic sclerosing cholangitis. The patient was started on monthly IVIG therapy at 400 mg/kg, as well as ursodeoxycholic acid and vitamin E, with normalization of his IgG and IgM levels a decrease in the incidence of infections and normalization of liver function. Three years after diagnosis, we detected the presence of polyps inside the gallbladder that were reported at biopsy as adenocarcinoma. He underwent hepatic bisegmentectomy (VI B-V) and local lymphadenectomy

[Characteristics of hospitalization of patients with rheumatic diseases admitted to a tertiary care hospital]. / Características de la hospitalización reumatológica en un hospital de nivel terciario.

BACKGROUND: The diagnostic profile of patients with rheumatic diseases admitted to a general hospital is variable. AIM: To report the epidemiological profile of patients with rheumatic diseases admitted to a tertiary care hospital. MATERIAL AND METHODS: All admissions to a Medicine ward of a general hospital and seen by the Rheumatology team were prospectively registered during one year in 1999. Patients were classified as primarily admitted for a rheumatic disease or admitted for other cause that required a consultation with the Rheumatology team. RESULTS: One hundred forty five admissions due to rheumatic diseases were registered. Of these, 82 were due to primary rheumatic diseases. Systemic lupus erythematosus, rheumatoid arthritis and vasculitis were the main diagnoses and the mean hospital stay was 18.5 days. Sixty three patients required a consultation with the Rheumatology team specially due to osteoarthritis and crystal induced diseases. CONCLUSIONS: Admissions due to rheumatic diseases are prolonged, correspond to 0.46% of all admissions and the main responsible disease is systemic lupus erythematosus.

Características de la hospitalización reumatológica en un hospital de nivel terciario / Features of patients with rheumatic diseases admitted to a tertiary care hospital

Background: The diagnostic profile of patients with rheumatic diseases admitted to a general hospital is variable. Aim: To report the epidemiological profile of patients with rheumatic diseases admitted to a tertiary care hospital. Material and methods: All admissions to a Medicine ward of a general hospital and seen by the Rheumatology team were prospectively registered during one year in 1999. Patients were classified as primarily admitted for a rheumatic disease or admitted for other cause that required a consultation with the Rheumatology team. Results: One hundred forty five admissions due to rheumatic diseases were registered. Of these, 82 were due to primary rheumatic diseases. Systemic lupus erythematosus, rheumatoid arthritis and vasculitis were the main diagnoses and the mean hospital stay was 18.5 days. Sixty three patients required a consultation with the Rheumatology team specially due to osteoarthritis and crystal induced diseases. Conclusions: Admissions due to rheumatic diseases are prolonged, correspond to 0.46 per cent of all admissions and the main responsible disease is systemic lupus erythematosus

[Immune modulating effect of intravenous gamma globulin in a patient with overlapping syndrome]. / Efecto inmunomodulador de gamaglobulina endovenosa en un caso de síndrome de sobreposición.

We report a 46 years old woman with a diagnosis of systemic lupus erythematosus and scleroderma overlapping syndrome. During treatment with steroids and azathioprine, the appearance of paresthesias and a progressive invalidating proximal weakness was interpreted as a steroidal myopathy. Steroidal treatment was progressively discontinued, but lupic activity and esophageal involvement exacerbated. Therefore, the use of immune modulating doses of intravenous gamma globulin (2 g/kg/total dose) was decided. The patient received this dose in two consecutive days and, 48 hours later, a notable improvement in esophageal function and general condition was verified. After six months of follow up, the disease remains inactive.

Atención por traumatismos y envenenamientos infantiles en un servicio de urgencia urbano / Attention for children's traumatisms and poisoning in an urban emergency service

El presente estudio se emprendió con el propósito de describir las características clínicas y epidemiológicas de los consultantes por accientes, menores de 15 años, en un Servicio de Urgencia Urbano. La información se obtuvo de una muestra de consultas de 10 días elegidos al azar, dentro del período comprendido entre el 1- de septiembre de 1988 al 31 de agosto de 1989. Se obtuvo así un total de 3.941 consultas de las cuales el 17% correspondieron a accidentes. Se observó un predominio del sexo masculino (59%), así como el hecho que la menor proporción de accidentes se encuentra en el grupo de menores de un año. El lugar de la ocurrencia del accidente no se consignó en el 91%. Las lesiones más frecuentes en todos los grupos de edad fueron las contusiones. Las fracturas y mordeduras fueron más comunes en los hombres, en tanto que las contusiones lo fueron en las mujeres. Las lesiones fueron de pronóstico leve, en el 60% de los casos y el 90% de los pacientes pudieron retornar a sus domicilios sin necesidad de ser hospitalizados. Se destaca la importancia de las medidas preventivas, como así mismo la necesidad de mejorar la calidad de la atención de urgencia en los Servicios de Salud estatales que benefician un porcentaje importante de la población del país