Next generation sequencing characterizes the extent of HLA diversity in an Argentinian registry population.

Next generation DNA sequencing is used to determine the HLA-A, -B, -C, -DRB1, and -DQB1 assignments of 1472 unrelated volunteers for the unrelated donor registry in Argentina. The analysis characterized all HLA exons and introns for class I alleles; at least exons 2, 3 for HLA-DRB1; and exons 2 to 6 for HLA-DQB1. Of the distinct alleles present, there are 330 class I and 98 class II. The majority (~98%) of the cumulative allele frequency at each locus is contributed by alleles that appear at a frequency of at least 1 in 1000. Fourteen (18.2%) of the 77 novel class I and II alleles carry nonsynonymous variation within their exons; 52 (75.4%) class I novel alleles carry only single, apparently random, nucleotide variation within their introns/untranslated regions. Alleles encoding protein variation not usually detected by typing focused only on the exons encoding the antigen recognition domain are 1.0% of the class I assignments and 7.3% of the class II assignments (predominantly DQB1*02:02:01, DQB1*03:19:01, and DRB1*14:54:01). Updates to the common and well documented list of alleles include 10 alleles previously thought to be uncommon but that are found at least 30 times. Five locus haplotypes estimated using the expectation-maximization algorithm as present 3 or more times total 187. While the known HLA diversity continues to increase, the conservation of known allele sequences is remarkable. Overall, the HLA diversity observed in the Argentinian population reflects its European and Native American ancestry.

A CCL chemokine-derived peptide (CDIP-2) exerts anti-inflammatory activity via CCR1, CCR2 and CCR3 chemokine receptors: Implications as a potential therapeutic treatment of asthma.

Allergic asthma is a chronic inflammatory disease characterized by the accumulation of eosinophils, Th2 cells and mononuclear cells in the airways, leading to changes in lung architecture and subsequently reduced respiratory function. We have previously demonstrated that CDIP-2, a chemokine derived peptide, reduced in vitro chemotaxis and decreased cellular infiltration in a murine model of allergic airway inflammation. However, the mechanisms involved in this process have not been identified yet. Now, we found that CDIP-2 reduces chemokine-mediated functions via interactions with CCR1, CCR2 and CCR3. Moreover, using bone marrow-derived eosinophils, we demonstrated that CDIP-2 modifies the calcium fluxes induced by CCL11 and down-modulated CCR3 expression. Finally, CDIP-2 treatment in a murine model of OVA-induced allergic airway inflammation reduced leukocyte recruitment and decreases production of cytokines. These data suggest that chemokine-derived peptides represent new therapeutic tools to generate more effective antiinflammatory drugs.

Optimización del uso de las imágenes en la patología suprarrenal (parte 2)q

Objetivos de aprendizaje: El objetivo de este trabajo es proponer un algoritmo de estudio por imágenes de las lesiones suprarrenales que permita arribar a un diagnóstico correcto en el menor tiempo posible. Esto favorece la adopción de la conducta terapéutica más apropiada para cada patología y puede modifi car en forma sustancial el tratamiento. Aunque las características estructurales de las lesiones generalmente son inespecífi cas, es posible, a través de las técnicas de imágenes actuales, diferenciar las lesiones compatibles con procesos benignos de las compatibles con procesos malignos y, con la colaboración del endocrinólogo y el laboratorio, también se pueden distinguir las lesiones funcionantes de las no funcionantes. Revisión de tema: Se evaluaron en forma retrospectiva, entre mayo del 2009 y diciembre del 2011, 157 pacientes con patología suprarrenal. En total, eran 95 mujeres y 61 hombres, de 33 a 78 años (media: 55 años). El protocolo de estudio consistió en una tomografía computada (TC) sin contraste intravenoso (IV), con toma de la densidad de la lesión, seguida de una tomografía computada con contraste intravenoso y tiempo de lavado con toma de densidad de la lesión en tiempo portal y tardío a los 15 minutos (tiempo de lavado o wash-out). Las mediciones y cálculos realizados fueron: tamaño de la lesión suprarrenal, densidad media de la misma durante las tres fases estudiadas y porcentajes de lavado relativo y absoluto. Se realizó resonancia magnética (RM) y tomografía computada por emisión de positrones con 18F-fl uorodesoxiglucosa (FDG-PET/TC) sólo en aquellos pacientes que así lo requirieron. Además, se compararon los resultados con los de la literatura actualizada sobre el tema. Hallazgos en imágenes: La conjunción de los datos clínicos, de laboratorio y las imágenes con el algoritmo propuesto permitió identifi car 59 adenomas no funcionantes (49 unilaterales y 10 bilaterales), 29 adenomas funcionantes, 9 hiperplasias bilaterales, 4 mielolipomas (2 de ellos en una paciente con hiperplasia suprarrenal congénita virilizante simple), 2 quistes, 2 hematomas, 3 linfomas (2 secundarios y 1 primario bilateral), 30 metástasis, 5 carcinomas adrenocorticales, 12 feocromocitomas, 1 feocromocitoma maligno y 1 ganglioneuroma. Conclusión: La utilización de un algoritmo de estudio adecuado, con las herramientas diagnósticas más apropiadas y accesibles, permite la correcta caracterización de las lesiones suprarrenales. A su vez, evita la pérdida de tiempo, el diagnóstico incorrecto, la irradiación excesiva del paciente y la mala utilización de los recursos.

Training Objectives: The aim of this study is to propose an algorithm for the evaluation of adrenal lesions in order to arrive at the correct diagnosis in the shortest possible time. This method would be suitable for the most appropriate therapeutic procedures for each pathology, and may substantially modify a given treatment. In spite of the fact that the structural features of lesions are generally non-specifi c, with imaging techniques, it is possible to establish features which could help us differentiate benign from malignant lesions and with the contribution of the endocrinologist and the laboratory, to distinguish functional from non-functional ones. Topic review: A retrospective evaluation from May 2009 to December 2011 has been carried out on 157 patients with adrenal diseases, including 95 females and 61 males, from 33 to 78 years of age (mean age 55). The study protocol consisted in non-contrasted intravenous computed tomography, with lesion density measurement, followed by contrasted intravenous computed tomography and wash out time with lesion density determination in portal time and delayed after 15 minutes wash out. Measurements and calculations were: adrenal lesion size, medium density and absolute and relative wash-out percentiles. Magnetic resonance and 18F-fl uorodeoxyglucose positron emission tomography was only performed on those patients that required these techniques. A comparison of the present results with those in the literature is included. Imaging fi ndings: Fifty-nine patients with a non-functional adenoma were identifi ed (49 unilateral and 10 bilateral), 29 functional adenomas, 9 with bilateral hyperplasia, 4 myelolipomas (2 in a female patient with simple virilizing congenital adrenal hyperplasia), 2 cysts, 2 hematomas, 3 lymphomas (2 secondary and 1 primary bilateral), 30 metastases, 5 adrenocortical carcinomas, 12 pheochromocytoma,1 malignant pheochromocytoma and 1 ganglioneuroma. Conclusion: The use of an appropriate study algorithm, with proper diagnostic tools, enables adrenal lesions to be correctly differentiated. Moreover, this approach prevents loss of time, a wrong diagnosis, excessive irradiation of the patient, and incorrect use of resources.

Optimización del uso de las imágenes en la patología suprarrenal (parte 1) / Optimization of the use of imaging in adrenal pathology (part 1)

Objetivos de aprendizaje: El objetivo de este trabajo es proponer un algoritmo de estudio por imágenes de las lesiones suprarrenales que permita arribar a un diagnóstico correcto en el menor tiempo posible. Esto favorece la adopción de la conducta terapéutica más apropiada para cada patología y puede modificar en forma sustancial un tratamiento. Aunque las características estructurales de las lesiones generalmente son inespecíficas, es posible, a través de las técnicas de imágenes actuales, diferenciar las lesiones compatibles con procesos benignos de las compatibles con procesos malignos y, con la colaboración del endocrinólogo y el laboratorio, también se pueden distinguir las lesiones funcionantes de las no funcionantes. Revisión de tema: Se evaluaron en forma retrospectiva, entre mayo del 2009 y diciembre del 2011, 157 pacientes con patología suprarrenal. En total, eran 95 mujeres y 61 hombres, de 33 a 78 años (media: 55 años). El protocolo de estudio consistió en una tomografía computada (TC) sin contraste intravenoso (IV), con toma de la densidad de la lesión, seguida de una tomografía computada con contraste intravenoso y tiempo de lavado con toma de densidad de la lesión en tiempo portal y tardío a los 15 minutos (tiempo de lavado o wash-out). Las mediciones y cálculos realizados fueron: tamaño de la lesión suprarrenal, densidad media de la misma durante las tres fases estudiadas y porcentajes de lavado relativo y absoluto. Se realizó resonancia magnética (RM) y tomografía computada por emisión de positrones con 18F-fluorodesoxiglucosa (FDG-PET/TC) sólo en aquellos pacientes que así lo requirieron. Además, se compararon los resultados con los de la literatura actualizada sobre el tema. Hallazgos en imágenes: La conjunción de los datos clínicos, de laboratorio y las imágenes con el algoritmo propuesto permitió identificar 59 adenomas no funcionantes (49 unilaterales y 10 bilaterales), 29 adenomas funcionantes, 9 hiperplasias bilaterales, 4 mielolipomas (2 de ellos en una paciente con hiperplasia suprarrenal congénita virilizante simple), 2 quistes, 2 hematomas, 3 linfomas (2 secundarios y 1 primario bilateral), 30 metástasis, 5 carcinomas adrenocorticales, 12 feocromocitomas, 1 feocromocitoma maligno y 1 ganglioneuroma. Conclusión: La utilización de un algoritmo de estudio adecuado, con las herramientas diagnósticas más apropiadas y accesibles, permite la correcta caracterización de las lesiones suprarrenales. A su vez, evita la pérdida de tiempo, el diagnóstico incorrecto, la irradiación excesiva del paciente y la mala utilización de los recursos.(AU)

Objectives of training: The aim of this study is to propose an algorithm for the evaluation of adrenal lesions in order to arrive at the correct diagnosis in the shortest possible time. This method would favor the most appropriate therapeutic procedures for each pathology and may substantially modifi ed a given treatment. In spite of the fact that the structural features of lesions are generally non-specifi c, it is possible with imaging techniques, to establish compatible features which could help us differentiate benign from malignant lesions and with the contribution of the endocrinologist and the laboratory, to distinguish functional from non-functional ones. Topic revision: A retrospective evaluation was carried out from May 2009 to December 2011 on 157 patients with adrenal diseases, including 95 females and 61 males, from 33 to 78 years of age (mean age 55). The study protocol consisted of non-contrasted intravenous computed tomography, with lesion density measurement, followed by contrasted intravenous computed tomography and wash out time with lesion density determination in portal time and later at 15’ during wash out. Measurements and calculations were: adrenal lesion size, medium density and absolute and relative washing percentiles. Magnetic resonance and 18F-fl uorodesoxyglucose positron emission tomography was only performed on those patients who required these techniques. A comparison of the present results with those in the literature is included. Imaging fi ndings: Fifty-nine patients with non-functional adenoma were identifi ed (49 unilateral and 10 bilateral), 29 functional adenomas, 9 with bilateral hyperplasia, 4 myelolipomas (2 in a female patient with simple virilizing congenital adrenal hyperplasia), 2 cysts, 2 hematomas, 3 lymphomas (2 secondary and 1 primary bilateral), 30 metastases, 5 adrenocortical carcinomas, 12 pheochromocytomas,1 malignant pheochromocytoma, and 1 ganglioneuroma. Conclusion: The use of an appropriate study algorithm, with proper diagnostic tools, allows the correct characterization of adrenal lesions. Moreover, this approach prevents loss of time, a wrong diagnosis, excessive irradiation of the patient, and incorrect use of resources.(AU)

Optimización del uso de las imágenes en la patología suprarrenal (parte 1) / Optimization of the use of imaging in adrenal pathology (part 1)

Objetivos de aprendizaje: El objetivo de este trabajo es proponer un algoritmo de estudio por imágenes de las lesiones suprarrenales que permita arribar a un diagnóstico correcto en el menor tiempo posible. Esto favorece la adopción de la conducta terapéutica más apropiada para cada patología y puede modificar en forma sustancial un tratamiento. Aunque las características estructurales de las lesiones generalmente son inespecíficas, es posible, a través de las técnicas de imágenes actuales, diferenciar las lesiones compatibles con procesos benignos de las compatibles con procesos malignos y, con la colaboración del endocrinólogo y el laboratorio, también se pueden distinguir las lesiones funcionantes de las no funcionantes. Revisión de tema: Se evaluaron en forma retrospectiva, entre mayo del 2009 y diciembre del 2011, 157 pacientes con patología suprarrenal. En total, eran 95 mujeres y 61 hombres, de 33 a 78 años (media: 55 años). El protocolo de estudio consistió en una tomografía computada (TC) sin contraste intravenoso (IV), con toma de la densidad de la lesión, seguida de una tomografía computada con contraste intravenoso y tiempo de lavado con toma de densidad de la lesión en tiempo portal y tardío a los 15 minutos (tiempo de lavado o wash-out). Las mediciones y cálculos realizados fueron: tamaño de la lesión suprarrenal, densidad media de la misma durante las tres fases estudiadas y porcentajes de lavado relativo y absoluto. Se realizó resonancia magnética (RM) y tomografía computada por emisión de positrones con 18F-fluorodesoxiglucosa (FDG-PET/TC) sólo en aquellos pacientes que así lo requirieron. Además, se compararon los resultados con los de la literatura actualizada sobre el tema. Hallazgos en imágenes: La conjunción de los datos clínicos, de laboratorio y las imágenes con el algoritmo propuesto permitió identificar 59 adenomas no funcionantes (49 unilaterales y 10 bilaterales), 29 adenomas funcionantes, 9 hiperplasias bilaterales, 4...

Objectives of training: The aim of this study is to propose an algorithm for the evaluation of adrenal lesions in order to arrive at the correct diagnosis in the shortest possible time.This method would favor the most appropriate therapeutic procedures for each pathology and may substantially modifi ed a given treatment. In spite of the fact that the structural features of lesions are generally non-specifi c, it is possible with imaging techniques, to establish compatible features which could help us differentiate benign from malignant lesions and with the contribution of the endocrinologist and the laboratory, to distinguish functional from non-functional ones.Topic revision: A retrospective evaluation was carried out from May 2009 to December 2011 on 157 patients with adrenal diseases, including 95 females and 61 males, from 33 to 78 years of age (mean age 55). The study protocol consisted of non-contrasted intravenous computed tomography, with lesion density measurement, followed by contrasted intravenous computed tomography and wash out time with lesion density determination in portal time and later at 15’ during wash out.Measurements and calculations were: adrenal lesion size, medium density and absolute and relative washing percentiles. Magnetic resonance and 18F-fl uorodesoxyglucose positron emission tomography was only performed on those patients who required these techniques. A comparison of the present results with those in the literature is included.Imaging fi ndings: Fifty-nine patients with non-functional adenoma were identifi ed (49 unilateral and 10 bilateral), 29 functional adenomas, 9 with bilateral hyperplasia, 4 myelolipomas (2 in a female patient with simple virilizing congenital adrenal hyperplasia), 2 cysts, 2 hematomas, 3 lymphomas (2 secondary and 1 primary bilateral), 30 metastases, 5 adrenocortical carcinomas, 12 pheochromocytomas,1 malignant pheochromocytoma, and 1 ganglioneuroma...

Quality of life improvement in Latin American patients suffering from chronic venous disorder using a combination of Ruscus aculeatus and hesperidin methyl-chalcone and ascorbic acid (quality study).

AIM: The present study assessed the effect of Ruscus aculeatus, hesperidin methyl-chalcone and ascorbic acid (HMC-AA), in the treatment of chronic venous disorders (CVD) in Latin American patients. METHODS: This study is an observational, single arm, multicentric and prospective trial. Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological (CEAP) classes were included. Patient profiles, risk factors, clinical symptomatology and quality of life (QoL) assessed by SF-12 and CIVIQ questionnaires were evaluated at inclusion and after 12-week treatment. RESULTS: The main factors influencing the previous management of patients were age, gender, body mass index (BMI), familial history, physical activity, exposure to heat, heavy loads lifting, profession and clinical characteristics. All clinical symptoms significantly improved with treatment and, as BMI and CEAP classes increased. Ankle circumferences decreased over time, correlating with BMI and CEAP classes. The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class. The CIVIQ score significantly improved over time, correlating with age and CEAP classes. CONCLUSION: A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD.

[Ergotism caused by automedication]. / Ergotismo por automedicación.

The authors report 7 cases of gangrenous ergotism (six women and one man) secondary to an overdose of ergotamine ingested in order to relieve migraine crisis. In all cases, patients presented symptoms and signs of severe arterial constriction confirmed by echography and angiography. Hallucinations were absent. Ergotamine ingestion was discontinued and treatment was based on vasodilators and sympathectomy. After treatment, all seven patients showed clinical improvement with disappearance of the vasospastic symptoms and signs, and an increase in the plethysmographic index of blood perfusion, measured by Doppler echography. These changes were observed even in a patient who lost two toes of the right foot. Although, none of the patients presented hallucinations, the authors made reference to the historical first use of the ergot in magic and religious rites that took place in Eleusis, at the time of classic Greece, as well as the more recent mystic use of ergot in Salem, New England, in 1692. Migraine is indeed a serious disease, frequently causing despair to the patient, who attempts to alleviate the migraneous crisis with an overdose of ergotamine. Accordingly, physicians must be aware of prophylactic vasodilating drugs, reducing the risk of ergotism.

Slender versus threatening angiodysplasias: observe, operate or obturate? A delusive decision.

Beside the immediate success of surgery and of embolization of angiodysplasias, certain number of patients return to medical consultation, because recanalization of the arteriovenous fistulae after their resection or obturation. From the presentation of two clinical cases of thoracic angiodysplasia: one of them slender, and threatening the other, the authors point out the complications and recurrence after surgical resection or arterial embolization. The recurrence takes place even when only one artery remains permeable after resection or embolization of the fistula. There are cases where the affected limb has to be amputated. However, angiodysplasia shows itself in the stump of the amputee limb. Uncontrolled angio-genesis is the natural history or postoperatory evolution of angiodysplasias, probably originated by an erroneous genetic program, which persist in spite of resection of the vascular malformation, causing a therapeutic failure.

Sindrome del X fragil: discusion del primer caso confirmado citogeneticamente en Chile. / Fragile X syndrome: report of the 1st case confirmed cytogenetically in Chile

Se describe un escolar de 10 11/12 anos referido para evaluacion genetica por presentar RM de causa desconocida, problemas conductuales, asimetria testicular y otras caracteristicas fenotipicas sugerentes de una afeccion genetica. Las caracteristicas clinicas hicieron sospechar un sindrome del X fragil. Este diagnostico fue confirmado a traves del estudio cromosomico en medio deficiente en acido folico (TC 199 + 2%FCS). El estudio posterior con una nueva tecnica que facilita la expresion del sitio fragil (TC 199 + 5% FCS + FUdR 0.05 microgramoM) aumento su frecuencia de 2.46% a 7%. Se discuten algunos aspectos clinicos, psicologicos y citogeneticos de este sindrome