Ultra-short celiac disease exhibits differential genetic and immunophenotypic features compared to conventional celiac disease / La enfermedad celiaca ultra corta presenta una expresión genética e inmunológica distinta a la de la enfermedad celiaca convencional

Background: Ultra-short coeliac disease (USCD) is a novel celiac disease (CD) subtype limited to the duodenal bulb (D1). HLA haplotypes and flow cytometry have not been assessed yet. Aims: To compare genetic, clinical, serologic, histopathologic and inmmunophenotypic parameters between USCD and conventional celiac disease (CCD) patients. Methods: Prospective single-center study in children and adult patients undergoing duodenal biopsies on a gluten-containing diet. Biopsies for histology and flow cytometry were taken separately from D1 and distal duodenum. Biopsies in seronegative patients with celiac lymphogram were repeated after 2 years on a gluten-free diet. Results: Among 505 included patients, 127 were diagnosed with CD, of whom 7 (5.5%) showed USCD. HLADQ2 was significantly less common in USCD compared to CCD (71% vs. 95%, p 0.003). Likewise, USCD patients showed more frequent non-significant seronegativity (28% vs. 8%, p 0.07) and significantly lower titrations (7–15IU/ml) of tissue transglutaminase antibodies (tTG-IgA) (60% vs. 13%, p<0.001). Biopsies from D1 revealed significant less NK cells down-expression in USCD patients (1.4 vs. 5, p 0.04). Conclusions: Up to 5.5% of CD patients showed USCD. A lower frequency of HLADQ2, along with less serum tTG-IgA titration and duodenal NK cell suppression, were differential features of USCD.(AU)

Antecedentes: La enfermedad celiaca ultracorta (ECUC) es un nuevo fenotipo de la enfermedad celiaca, que afecta exclusivamente al bulbo duodenal (D1), cuyas características genéticas e inmunológicas no han sido descritas. Objetivos: Comparar las características genéticas, clínicas, serológicas, histológicas e inmunológicas entre ECUC y enfermedad celiaca convencional (ECC). Métodos: Estudio prospectivo, unicéntrico, en el que se realizaron biopsias duodenales a pacientes adultos y pediátricos que seguían una dieta con gluten. Se realizó análisis histológico y por citometría de flujo por separado de duodeno distal y D1. En pacientes seronegativos con histología o linfograma concordante con EC, se repitió la biopsia tras 2 años con dieta sin gluten. Resultados: Se incluyeron 505 pacientes, siendo diagnosticados 127 de enfermedad celiaca, de los cuales 7 (5,5%) tenían ECUC. Los pacientes con ECUC expresaron el haplotipo DQ2 con menor frecuencia que en la ECC (71% vs. 95%, p 0,003) y presentaron mayor seronegatividad (28% vs. 8%, p 0,07) y, de manera significativa, titulaciones bajas de anticuerpos antitransglutaminasa (7-15IU/ml) (60% vs. 13%, p < 0,001). Comparado con la ECC, la citometría de flujo en las biopsias bulbares reveló una reducción atenuada significativa de células NK (1,4 vs. 5, p 0,04) en pacientes con ECUC. Conclusiones: Un 5,5% de los pacientes celiacos presentaron ECUC. Comparada con la ECC, las características diferenciales de la ECUC son menor expresión de HLADQ2, títulos más bajos de anticuerpos antitranglutaminasa y menor supresión de células NK a nivel bulbar.(AU)

Ultra-short celiac disease exhibits differential genetic and immunophenotypic features compared to conventional celiac disease.

BACKGROUND: Ultra-short coeliac disease (USCD) is a novel celiac disease (CD) subtype limited to the duodenal bulb (D1). HLA haplotypes and flow cytometry have not been assessed yet. AIMS: To compare genetic, clinical, serologic, histopathologic and inmmunophenotypic parameters between USCD and conventional celiac disease (CCD) patients. METHODS: Prospective single-center study in children and adult patients undergoing duodenal biopsies on a gluten-containing diet. Biopsies for histology and flow cytometry were taken separately from D1 and distal duodenum. Biopsies in seronegative patients with celiac lymphogram were repeated after 2 years on a gluten-free diet. RESULTS: Among 505 included patients, 127 were diagnosed with CD, of whom 7 (5.5%) showed USCD. HLADQ2 was significantly less common in USCD compared to CCD (71% vs. 95%, p 0.003). Likewise, USCD patients showed more frequent non-significant seronegativity (28% vs. 8%, p 0.07) and significantly lower titrations (7-15IU/ml) of tissue transglutaminase antibodies (tTG-IgA) (60% vs. 13%, p<0.001). Biopsies from D1 revealed significant less NK cells down-expression in USCD patients (1.4 vs. 5, p 0.04). CONCLUSIONS: Up to 5.5% of CD patients showed USCD. A lower frequency of HLADQ2, along with less serum tTG-IgA titration and duodenal NK cell suppression, were differential features of USCD.

First Description of Late-Onset Autoinflammatory Disease Due to Somatic NLRC4 Mosaicism.

OBJECTIVE: Autoinflammatory diseases are inherited disorders of innate immunity that usually start during childhood. However, several recent reports have described an increasing number of patients with autoinflammatory disease starting in adulthood. This study was undertaken to investigate the underlying cause of a case of late-onset uncharacterized autoinflammatory disease. METHODS: Genetics studies were performed using Sanger sequencing and next-generation sequencing (NGS) methods. In silico, in vitro, and ex vivo analyses were performed to determine the functional consequences of the detected variant. RESULTS: We studied a 57-year-old woman who at the age of 47 years began to have recurrent episodes of fever, myalgias, arthralgias, diffuse abdominal pain, diarrhea, adenopathies, and systemic inflammation, which were relatively well controlled with anti-interleukin-1 (anti-IL-1) drugs. NGS analyses did not detect germline variants in any of the known autoinflammatory disease-associated genes, but they identified the p.Ser171Phe NLRC4 variant in unfractionated blood, with an allele fraction (2-4%) compatible with gene mosaicism. Structural modeling analyses suggested that this missense variant might favor the open, active conformation of the NLRC4 protein, and in vitro and ex vivo analyses confirmed its propensity to oligomerize and activate the NLRC4 inflammasome, with subsequent overproduction of IL-18. CONCLUSION: Our findings indicate that the postzygotic p.Ser171Phe NLRC4 variant is a plausible cause of the disease in the enrolled patient. Functional and structural studies clearly support, for the first time, its gain-of-function behavior, consistent with previously reported NLRC4 pathogenic variants. These novel findings should be considered in the diagnostic evaluation of patients with adult-onset uncharacterized autoinflammatory disease.

Rare immunofluorescence patterns of autoantibodies on HEp-2 cells defined by ICAP identify different autoimmune diseases in the absence of associated specificities: a Spanish multicentre study.

OBJECTIVES: ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. METHODS: We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. RESULTS: Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). CONCLUSION: Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.

The Immunomodulatory Signature of Extracellular Vesicles From Cardiosphere-Derived Cells: A Proteomic and miRNA Profiling.

Experimental data demonstrated that the regenerative potential and immunomodulatory capacity of cardiosphere-derived cells (CDCs) is mediated by paracrine mechanisms. In this process, extracellular vesicles derived from CDCs (EV-CDCs) are key mediators of their therapeutic effect. Considering the future applicability of these vesicles in human diseases, an accurate preclinical-to-clinical translation is needed, as well as an exhaustive molecular characterization of animal-derived therapeutic products. Based on that, the main goal of this study was to perform a comprehensive characterization of proteins and miRNAs in extracellular vesicles from porcine CDCs as a clinically relevant animal model. The analysis was performed by identification and quantification of proteins and miRNA expression profiles. Our results revealed the presence of clusters of immune-related and cardiac-related molecular biomarkers in EV-CDCs. Additionally, considering that priming stem cells with inflammatory stimuli may increase the therapeutic potential of released vesicles, here we studied the dynamic changes that occur in the extracellular vesicles from IFNγ-primed CDCs. These analyses detected statistically significant changes in several miRNAs and proteins. Notably, the increase in interleukin 6 (IL6) protein, as well as the increase in mir-125b (that targets IL6 receptor) was especially relevant. These results suggest a potential involvement of EV-CDCs in the regulation of the IL6/IL6R axis, with implications in inflammatory-mediated diseases.

Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies.

The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.

Metodología en autoinmunidad y algoritmos de trabajo: anticuerpos antinucleares y sus especificidades / No disponible

No disponible

A Case of Immediate Hypersensitivity Reaction to Maltitol.

BACKGROUND: Maltitol is a sugar alcohol that is frequently used as a noncaloric sweetener, although it is also used as an excipient, a plasticizer in gelatin capsules, and an emollient. It has not been previously described as an agent involved in immediate hypersensitivity reactions. METHODS: We report on an anaphylactoid reaction with pharyngeal occlusion suffered by a 60-year-old man after ingestion of a candy containing maltitol syrup. A prick-to-prick test was performed with the candy and maltitol powder. Other allergens were excluded as causative agents of the adverse reaction, although the patient refused to undergo an oral challenge test with the candy. A basophil activation test (BAT) was performed with maltitol powder, and a dose-response curve was generated. The test was also performed in 3 healthy controls. RESULTS: Both prick-to-prick tests were negative. The result of the BAT was positive at all the concentrations tested in the patient's blood and negative in all the controls. CONCLUSIONS: The BAT can help to clarify the agents implicated in an adverse reaction and can reduce the risk involved in diagnosis. The BAT can also prove useful in the study of reactions caused by low-molecular-weight antigens, for which routine diagnostic tests are not feasible.

Short-, Intermediate-, and Long-Term Changes in Basophil Reactivity Induced by Venom Immunotherapy.

PURPOSE: The basophil activation test (BAT) has been used to monitor venom immunotherapy (VIT) due to its high specificity. A previous study has reported a good correlation between a significant decrease in basophil activation during 5 years of VIT and clinical protection assessed by sting challenge. The following prospective study was performed to examine changes in basophil reactivity over a complete VIT period of 5 years. METHODS: BAT in a dose-response curve was studied prospectively in 10 hymenoptera venom-allergic patients over 5 years of VIT. BAT was performed at the time of diagnosis, 1 month after finishing the VIT build-up phase, and 3, 6, 12, 24, and 60 months after beginning treatment. The repeated measures ANOVA was applied to evaluate basophil activation changes throughout VIT. A cross-sectional study was also performed in 6 patients who received treatment for more than 3 years, and in another 12 patients who followed immunotherapy for at least 5 years. RESULTS: An early activation decrease was observed during the first 3 months of treatment, compared to pre-treatment values. This activation decrease was not maintained 6 to 18 months after treatment, but was observed again after 2 years of treatment, and maintained until the completion of the 5-year immunotherapy period. In cross-sectional analysis, the 6 patients who received treatment for 3 years, and 9 of the 12 patients who received treatment for 5 years, had negative BAT results. Three patients in this last group had positive BAT results and 2 patients had systemic reactions after field stings. CONCLUSIONS: BAT appears to be an optimal non-invasive test for close monitoring of VIT.

Very low doses of direct intravenous iron in each session as maintenance therapy in hemodialysis patients.

BACKGROUND: Intravenous (IV) iron supplementation is widely used in hemodialysis (HD) patients to treat their periodic losses. However, the ideal dose and frequency is unknown. The goal of the study is to see if a 20 mg dose of iron IV at the end of each session of HD as iron maintenance is better than the iron prior therapy. We analyze the erythropoiesis activity (EA) and functional iron (FI) after four weeks of treatment. METHODS: In 36 patients, we measure reticulocyte count and content of hemoglobin reticulocyte (CHr) as EA and FI markers, respectively, before and after the treatment. Before the study, 23 patients received another different therapy with IV iron as maintenance therapy. RESULTS: Reticulocyte count: 49.7 ± 23.8 × 10(3) before and 47.2 ± 17.2 × 10(3) after the treatment (p= 0.51). The CHr: 34.8 ± 3.7 pg and 34.4 ± 3.5 pg, respectively, (p= 0.35), showing an excellent correlation with the other FI markers (serum iron r = 0.6; p = 0.001; saturation transferrin r = 0.49; p = 0.004); that is not shown with the serum ferritin (r = 0.23; p = 0.192) or the hepcidin levels (r = 0.22; p = 0.251). There was not a correlation between the C-Reactive Protein, reticulocyte count, and CHr. The 13 patients who did not receive the iron prior to the study showed high FI levels, but not an increased of the serum ferritin or the serum hepcidin levels. CONCLUSIONS: The administration of a small quantity of iron at the end of every HD session keeps the EA and the FI levels and allows reducing the iron overload administered and/or decreasing the iron stores markers in some patients.

Atorvastatina, anticuerpos LDL oxidada y su relación con la edad / Atorvastatin and oxidized low density lipoprotein antibody. Relationship to age

Fundamento y objetivos: En pacientes hipercolesterolémicos, estudiamos las relaciones de los valores plasmáticos de anticuerpos anti lipoproteínas de baja densidad (LDL) oxidadas con diferentes variables de interés cardiovascular y sus cambios tras el tratamiento con atorvastatina. Pacientes y método: En 48 pacientes se determinaron los valores de anticuerpos anti-LDL oxidadas, biomarcadores lipídicos, de estrés oxidativo e inflamatorios, a la entrada del estudio y tras 24 semanas de tratamiento con 20mg de atorvastatina. Resultados: Los valores basales de anticuerpos anti-LDL oxidadas se correlacionaron con la edad (r=0,41, p=0,03), cintura (r=0,38, p=0,04) y la proteína C reactiva ultrasensible (PCRs) (r=0,46, p=0,02), pero no con el resto de variables. El tratamiento con atorvastatina no disminuyó los valores de anticuerpos anti-LDL oxidadas (valor basal medio [intervalo de confianza del 95%] de 413 mUI/ml [187-1196] y a las 24 semanas de 349 mUI/ml [101-1559]). El porcentaje de cambio de anticuerpos anti-LDL oxidadas en la semana 24 se correlacionó negativamente con la edad (r=−0,37, p=0,03), pero no con cambios en el resto de las variables. Conclusiones: En sujetos con hipercolesterolemia, los valores plasmáticos de anticuerpos anti-LDL oxidadas se relacionaron positivamente con la edad, cintura y PCRs. No se observaron cambios de los valores plasmáticos de anticuerpos anti-LDL oxidadas tras el tratamiento con atorvastatina, pero su variación se relacionó con la edad, lo que sugiere que las acciones inmunomoduladoras de las estatinas pueden depender de ésta (AU)

Background and objectives: In hypercholesterolemic patients, we studied the relationships of plasma levels of LDLoxab with cardiovascular variables and its changes after treatment with atorvastatin. Patients and methods: We studied, in 48 patients, the levels of LDLoxab, as well as lipid, oxidative stress and inflammatory biomarkers, at baseline and 24 weeks after treatment with 20mg of atorvastatin. Results: Baseline: a correlation was observed between LDLoxab and age (r= 0.41, P=.03), waist (r=0.38, P=.04) and C reactive protein (r= 0.46, P=.02), but not with other variables. Atorvastatin treatment did not decrease LDLoxab;(mU/mL, median [CI 95%]: baseline: 413 [187-1,196] and 24 weeks: 349 [101-1559]). The percentage change at week 24, was negatively correlated with age (r=−0.37, P=.03) but not with other variables. Conclusion: In hypercholesterolemic subjects plasma LDLoxab levels were positively corelated with age, waist and C reactive protein. There were no changes in plasma levels of LDLoxab after treatment with atorvastatin, but the variation was associated with age, suggesting that the immunomodulatory actions may depend of this (AU)

[Atorvastatin and oxidized low density lipoprotein antibody. Relationship to age]. / Atorvastatina, anticuerpos LDL oxidada y su relación con la edad.

BACKGROUND AND OBJECTIVES: In hypercholesterolemic patients, we studied the relationships of plasma levels of LDLoxab with cardiovascular variables and its changes after treatment with atorvastatin. PATIENTS AND METHODS: We studied, in 48 patients, the levels of LDLoxab, as well as lipid, oxidative stress and inflammatory biomarkers, at baseline and 24 weeks after treatment with 20mg of atorvastatin. RESULTS: Baseline: a correlation was observed between LDLoxab and age (r= 0.41, P=.03), waist (r=0.38, P=.04) and C reactive protein (r= 0.46, P=.02), but not with other variables. Atorvastatin treatment did not decrease LDLoxab;(mU/mL, median [CI 95%]: baseline: 413 [187-1,196] and 24 weeks: 349 [101-1559]). The percentage change at week 24, was negatively correlated with age (r=-0.37, P=.03) but not with other variables. CONCLUSION: In hypercholesterolemic subjects plasma LDLoxab levels were positively corelated with age, waist and C reactive protein. There were no changes in plasma levels of LDLoxab after treatment with atorvastatin, but the variation was associated with age, suggesting that the immunomodulatory actions may depend of this.

Large Evaluation of Anti-Cardiolipin and anti-Beta2Glycoprotein I Assays: Results from the AutoimmunityWorkshop of the Spanish Society of Immunology

Despite their clinical utility and the importance that laboratory testshave in APS diagnosis, probably the most important drawback of suchtests is the elevated intra- and inter-laboratory variation. The aim of thepresent work was to assess the multilaboratory performance of aCL (..) (AU)

A pesar de la indudable utilidad clínica y de la importancia de laspruebas de laboratorio en el diagnóstico del síndrome antifosfolípido(APS), probablemente el mayor defecto de dichas pruebas es su elevadavariabilidad intra- e inter-laboratorio. El objetivo del presente trabajo fueevaluar el comportamiento de los ensayos (..) (AU)

Basophil activation test for the in vitro diagnosis of nonsteroidal anti-inflammatory drug hypersensitivity.

There is need for an in vitro diagnostic test for hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). The purpose of this study was to assess the reliability of one such diagnostic, the basophil activation test. Forty-three drug hypersensitive patients referring several immediate reactions (anaphylaxis, urticaria, angioedema, asthma, and rhinoconjunctivitis) to one or more NSAIDs and 29 controls participated. Using the Basotest commercial kit, 63 determinations were performed with the drugs implicated in the adverse reactions (ASA, ibuprofen, metamizol, diclofenac, paracetamol, and ketorolac). In 16 patients additional determinations were made with other chemically unrelated NSAIDs. Forty-two determinations were made for controls. The analysis was performed by flow colorimetric cytometry and double staining with the monoclonal antibodies anti-IgE and anti-CD63. A Basophil Activation Index (percentage of activated basophils after allergen stimulation/percentage of basally activated basophils) of two or more was considered a positive result. Specificity of 100% and sensitivity of 42.85% were achieved. The positive predictive value was 100%, and the negative predictive value was 53.84%. In 35.29% of intolerant patients there was a positive reaction to at least two drugs implicated in adverse reactions, and in 27.27% of these patients there was a positive reaction to other chemically unrelated NSAIDs. The basophil activation test is useful for the in vitro diagnosis of NSAID hypersensitivity, providing good specificity and positive predictive value and diagnostic reliability in the assessment of NSAID intolerance.

[Effects of atorvastatin in N-terminal pro-brain natriuretic peptide plasma levels in hypercholesterolemic patients with or without hypertension]. / Efecto de la atorvastatina sobre los valores del propéptido natriurético cerebral N-terminal en pacientes con hipercolesterolemia con hipertensión arterial y sin ella.

BACKGROUND AND OBJECTIVE: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful predictor of cardiovascular events in patients without clinical evidence of cardiovascular disease. It is unknown if the cardiovascular risk factors control can modify these levels. We studied if atorvastatin treatment decrease NT-proBNP levels in hypercholesterolemic subjects, with and without hypertension. PATIENTS AND METHOD: It was an open, prospective study in 39 patients with hypercholesterolemia without clinical evidence of cardiovascular disease. 15 (38.5%) had hypertension. Blood samples were collected initially and 12 and 24 weeks after beginning treatment with 20 mg of atorvastatin. RESULTS: The median age was 54 years, and 41% were males. NT-proBNP (pg/ml) values were: 193 (294) at baseline; 141 (211) (p < 0.05) after 12 weeks therapy, and 89 (130) (p < 0.01) at 24 weeks. In hypertensive patients value changed from: 275 (388) at baseline, 196 (290) (p < 0.05) and 112 (124) (p < 0.001) after 12 and 24 weeks treatment. And the levels in normotensives patients were: 137 (198) at baseline, 103 (129) (p = NS), and 74 (135) (p < 0.001) at 12 and 24 weeks after treatment with atorvastatin. We didn't find any correlations between the percentage decrease in NT-proBNP levels, and change of total cholesterol, systolic blood pressure, C reactive protein, or nitrites/nitrates blood levels, at 12, and 24 weeks compared to baseline levels. CONCLUSIONS: In middle-aged hypercholesterolemic patients, without evidence of cardiovascular disease, atorvastatin therapy decrease NT-proBNP blood levels, in both hypertensive and normotensives subjects.

Efecto de la atorvastatina sobre los valores del propéptido natriurético cerebral N-terminal en pacientes con hipercolesterolemia con hipertensión arterial y sin ella / Effects of atorvatatin in N-terminal pro-brain natriuretic peptide plasma levels in hypercholesterolemic patients with or without hypertension

Fundamento y objetivo: La concentración plasmática del propéptido natriurético cerebral N-terminal (NT-proBNP) es útil como predictor de acontecimientos cardiovasculares en la población asintomática. Se desconoce si el control de los factores de riesgo cardiovascular puede modificar dichos valores. Hemos estudiado si el tratamiento con atorvastatina disminuye los valores del NT-proBNP en pacientes hipercolesterolémicos, con hipertensión y sin ella. Pacientes y método: Realizamos un estudio prospectivo y abierto en 39 pacientes con hipercolesterolemia que se hallaban asintomáticos; 15 de ellos (38,5%) eran hipertensos. Se les realizaron extracciones de sangre basal y a las 12 y 24 semanas de tratamiento con 20 mg de atorvastatina. Resultados: La mediana de la edad fue de 54 años y un 41% eran varones. Para el conjunto de la población, los valores medios (desviación estándar) del NT-proBNP (pg/ml) fueron: basal, 193 (294); a las 12 semanas de tratamiento, 141 (211) (p < 0,05), y a las 24 semanas, 89 (130) (p < 0,01). En los pacientes hipertensos, dichos valores fueron: basal, 275 (388); a las 12 semanas, 196 (290) (p < 0,05), y las 24 semanas, 112 (124) (p < 0,001); y en los normotensos: basal, 137 (198); a las 12 semanas, 103 (129) (p = no significativo), y a las 24 semanas, 74 (135) (p < 0,001). No se encontró relación entre el porcentaje de descenso del NT-proBNP y las variaciones del colesterol total, presión arterial sistólica, proteína C reactiva y valores de nitritos/nitratos sanguíneos entre las 12 y 24 semanas respecto a los valores basales. Conclusiones: El tratamiento con atorvastatina en pacientes asintomáticos de mediana edad con hipercolesterolemia disminuye los valores sanguíneos del NT-proBNP tanto en sujetos hipertensos como normotensos

Background and objective: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful predictor of cardiovascular events in patients without clinical evidence of cardiovascular disease. It is unknown if the cardiovascular risk factors control can modify these levels. We studied if atorvastatin treatment decrease NT-proBNP levels in hypercholesterolemic subjects, with and without hypertension. Patients and method: It was an open, prospective study in 39 patients with hypercholesterolemia without clinical evidence of cardiovascular disease. 15 (38.5%) had hypertension. Blood samples were collected initially and 12 and 24 weeks after beginning treatment with 20 mg of atorvastatin. Results: The median age was 54 years, and 41% were males. NT-proBNP (pg/ml) values were: 193 (294) at baseline; 141 (211) (p < 0.05) after 12 weeks therapy, and 89 (130) (p < 0.01) at 24 weeks. In hypertensive patients value changed from: 275 (388) at baseline, 196 (290) (p < 0.05) and 112 (124) (p < 0.001) after 12 and 24 weeks treatment. And the levels in normotensives patients were: 137 (198) at baseline, 103 (129) (p = NS), and 74 (135) (p < 0.001) at 12 and 24 weeks after treatment with atorvastatin. We didn't find any correlations between the percentage decrease in NT-proBNP levels, and change of total cholesterol, systolic blood pressure, C reactive protein, or nitrics/nitrates blood levels, at 12, and 24 weeks compared to baseline levels. Conclusions: In middle-aged hypercholesterolemic patients, without evidence of cardiovascular disease, atorvastatin therapy decrease NT-proBNP blood levels, in both hypertensive and normotensives subjects

Anaphylaxis caused by cloxacillin: diagnosis with seriated analysis by way of basophil activation test.

We report a case of anaphylaxis caused by cloxacillin in a 13-year-old patient. The basophil activation test, performed 25 days after the anaphylactic reaction, was positive to cloxacillin, amoxicillin, and penicillin G and negative to ibuprofen, tolerated by the patient. The analysis was performed 17 days after the reaction was not conclusive because 74% of the basophil population was activated in basal conditions. The abnormally high activation was similar to that found in an analysis before the reaction, exactly 4 days after finishing a well-tolerated treatment with amoxicillin. This first analysis was available because a patient's sample was taken from the emergency laboratory as a blind control for a study to assess the basophil activation test reliability in diagnosis of hypersensitivity to NSAIDs. The high number of activated basophils in basal conditions after treatment with amoxicillin and before the anaphylactic reaction to cloxacillin probably reflects the beginning of the sensitization. Until now, no cases of hypersensitivity to cloxacillin have been diagnosed by means of the basophil activation test.