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.

Full 3-D OCT-based pseudophakic custom computer eye model.

We compared measured wave aberrations in pseudophakic eyes implanted with aspheric intraocular lenses (IOLs) with simulated aberrations from numerical ray tracing on customized computer eye models, built using quantitative 3-D OCT-based patient-specific ocular geometry. Experimental and simulated aberrations show high correlation (R = 0.93; p<0.0001) and similarity (RMS for high order aberrations discrepancies within 23.58%). This study shows that full OCT-based pseudophakic custom computer eye models allow understanding the relative contribution of optical geometrical and surgically-related factors to image quality, and are an excellent tool for characterizing and improving cataract surgery.

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...

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...

[Severe acute ethylene glycol poisoning: diagnostic utility of osmolar gap monitoring]. / Intoxicación aguda grave por etilenglicol: valor de la monitorización del gap osmolar en su diagnóstico.

Ethylene glycol intake is a rare cause of alcohol poisoning in our practice setting. Most cases are voluntary, representing suicide attempts. Because delayed treatment leads to serious morbidity and high mortality (up to 50%), early diagnosis is essential for preventing harmful consequences and even death. Diagnosis is based on clinical suspicion and laboratory findings. Given that most hospitals do not have the means to measure the specific toxin in plasma, osmolar gap monitoring usually serves as a rapid diagnostic test for detecting the presence of osmotically active substances like ethylene glycol in plasma. We report a case of voluntary poisoning after the patient swallowed antifreeze. Successful treatment began early, with monitoring of the osmolar gap and plasma level correspondence. We also comment on the range of therapeutic options, emphasizing antidotes such as ethanol and fomepizole which provide the basis for treatment.

Proteolytic cleavage of chemokines by Trypanosoma cruzi's cruzipain inhibits chemokine functions by promoting the generation of antagonists.

Chagas disease is a chronic inflammatory disease caused by infection with Trypanosoma cruzi. Although it had a decline in recent years, it still affects millions of people in Latin America. The host immune response against this parasite is complex and relies on the development of an efficient T cell-mediated response; however, T. cruzi displays a number of evasion mechanisms allowing it to remain undetected even for years. One of these is the secretion of anti-inflammatory molecules such as proteases and the modulation of biological functions of chemokines. Our objective was to analyze the effect of a major cysteine protease, cruzipain, on a number of critical functions of several CC chemokines, both in vitro and in vivo. Initially, using a murine model of T. cruzi infection, we demonstrated that CCL-2 and CCL-12 chemokines are highly expressed at different stages and correlated with an increase in the expression of cruzipain. In addition, we demonstrated that cruzipain is capable of differentially cleaving CCL-2 and CCL-12 chemokines, as well as CCL-13. Analysis of the proteolysed products identified unique cleavage sites in these chemokines. These cruzipain-modified chemokine products were tested in chemotaxis assays using monocytic cells. We found that cruzipain treated-CCL-2 maintained its biological activity, in contrast to the closely related CCL-12 and CCL-13 chemokines, which showed little or null agonist activity after treatment. Furthermore, based on this analysis, a 14-mer cruzipain-derived chemokine peptide (CDCP-1) was chemically synthesized and tested for agonist activity using in vitro chemotaxis assays. Interestingly, CDCP-1 showed antagonist activity affecting in vitro migration of monocytic cells and calcium flux release. In conclusion, our results demonstrate that cruzipain modulates biological functions of chemokines through proteolytic cleavage, by generating chemokine-derived peptides with antagonist activities. This event could play a role during the latest phases of Chagas disease, when the parasite may differentially modulate chemokine-mediated inflammatory responses.

CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation.

Airway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides.

Pilot study of expedited HIV-1 testing of women in labor at an inner-city hospital in New York City.

To evaluate the feasibility of offering voluntary counseling and expedited human immunodeficiency virus (HIV) testing to women in labor, and to assess the characteristics of two rapid HIV assays compared with results from an expedited standard enzyme immunoassay (EIA), with Western blot confirmation, as indicated, we undertook a pilot study immediately prior to enactment of New York State regulations (August 1999) requiring expedited testing of laboring women (or newborns) with undocumented HIV status. From June 9, 1999 through July 2, 1999, we offered HIV counseling and testing (C&T) to all medically stable women in active labor, 106 of 125 (85%) of whom accepted. One woman was confirmed HIV-1 seropositive. Rapid assay sensitivity and specificity were: SUDS 100 and 98%, and Multispot 100 and 100%, respectively in comparison with 100 and 99% for the standard EIA. The positive predictive values (PPV) were SUDS 33%; Multispot 100%; and EIA 50%. While our sample size was small, it appears that the accuracy of rapid and expedited HIV assays may be improved by requiring two different reactive assays before informing women of HIV-seropositive results or initiating antiretroviral treatment.

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.

Pseudo-Meigs' Syndrome.

Meigs' syndrome is defined as a hydrothorax with ascites and a pelvic tumor, both of which resolve on removal of the tumor. Pseudo-Meigs' is a variant not possessing the original tumor cell types described by Meigs. Both these syndromes should be considered in otherwise healthy women who present with either new or recurrent hydrothorax and ascites. This case concerns a 21-year-old woman who presented to the emergency department (ED) with a recurrent hydrothorax. After performing a pelvic examination that was suspicious for a pelvic mass, further evaluation by ultrasonography showed ascites and a pelvic tumor. Surgeons from the Obstetrics and Gynecology Department performed an exploratory laparotomy with removal of the tumor. Subsequently, there was no recurrence of the ascites and hydrothorax. The tumor was diagnosed histologically as a benign mature teratoma. The literature of Meigs' and Pseudo-Meigs' is reviewed, focusing on the history, pathology, and clinical characteristics. The clinical significance for the emergency physician is discussed.

Congenital medullary tubular stenosis. A case of Caffey-Kenny syndrome.

We report a case of congenital medullary stenosis of the tubular bones, or Caffey-Kenny syndrome. The patient was referred to our department with retarded psychomotor development and contractures.

Resuscitative thoracotomy for patients with traumatic injury.

The clinical course and final outcome were determined for 63 trauma victims who underwent resuscitative thoracotomy (RT) for hypovolemic cardiac arrest in the Department of Emergency Medicine during a 24-month period. The objectives of the study were to determine the efficacy of and indications for RT and to define the prognostic signs for survival. Of 63 patients, six were successfully resuscitated (9.5%), and five of these were discharged from the hospital (7.9%). The presence of pupillary reactions was an extremely reliable indicator of successful outcome (P = 0.0009), as was the presence of some respiratory effort (P = 0.025). None of the victims of blunt trauma (n = 6) or severe head injury (n = 13) survived. Three of 17 patients (17.6%) with stab wounds and two of 36 (5.6%) with gunshot wounds survived the procedure. RT was beneficial in 13.6% of patients who had isolated organ system injuries, but no patient with injuries to more than two organ systems survived. Victims of isolated penetrating thoracic trauma had an 11.8% survival rate, as opposed to a 0% survival rate for those with abdominal trauma. The best prognosis was in victims with penetrating cardiac injuries, who had a 22.7% survival rate. The cost of RT averaged $1660 per patient, exclusive of physician charges. In our experience, RT is most beneficial for victims of penetrating thoracic trauma, especially those with cardiac injuries. However, routine use of this high cost/low benefit procedure cannot be recommended for patients who have cardiac arrest secondary to blunt trauma or severe head injuries. Also, it is not recommended for patients whose pupillary reflexes and respiratory movements are absent.

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