Síndrome de Alagille. Experiencia clínica y sobrevida de un caso

Paciente masculino de 7 años de edad, padres y hermana de 11 años sanos. A los 15 días de nacido inicia con vómitos, ictericia y acolia. Al examen mostró rasgos particulares: frente ancha, puente nasal deprimido, mentón puntiagudo cara triangular y ojos profundos. Escleras y piel con tinte ictérico-verdoso, xantomas faciales. Soplo cardíaco sistólico III/VI en foco pulmonar. Hígado 4 cm debajo del reborde costal derecho. Perfil bioquímico: colestasis, hiperamonemia e hiperlipidemia. Radiografía de columna: hemivertebras. Ultrasonido: sin dilatación de vías biliares intrahepáticas, vesícula biliar atrófica. Ecocardiograma: estenosis de la arteria pulmonar y persistencia del conducto arterioso. Biopsia hepática: ductopenia, fibrosis leve. Los criterios de colestasis, facies peculiar, cardiopatía congénita y hemivertebras con ductopenia sustentan el diagnóstico de Síndrome de Alagille. Su evolución 7 años después demuestra que cursa con enfermedad renal estadio II, acidosis tubular renal, hipertensión arterial, hiperparatiroidismo secundario, anemia microcítica-hipocrómica, detención del crecimiento y retraso psicomotriz; complicaciones compensadas con el tratamiento médico, que le permite llevar una calidad de vida satisfactoria. El síndrome es una alteración autosómica dominante con expresión variable y el pronóstico de sobrevida depende del grado de compromiso y malformación de órganos y sistemas; la literatura reporta que la esperanza de vida a 20 años es entre 75-80%. Es importante reconocer este síndrome (incidencia mundial 1/100,000 nacidos vivos) dentro del diagnóstico diferencial de colestasis infantil para identificarlo y determinar su frecuencia

The Open Global Glacier Model (OGGM) v1.1

Despite their importance for sea-level rise, seasonal water availability, and as a source of geohazards, mountain glaciers are one of the few remaining subsystems of the global climate system for which no globally applicable, open source, community-driven model exists. Here we present the Open Global Glacier Model (OGGM), developed to provide a modular and open-source numerical model framework for simulating past and future change of any glacier in the world. The modeling chain comprises data downloading tools (glacier outlines, topography, climate, validation data), a preprocessing module, a mass-balance model, a distributed ice thickness estimation model, and an ice-flow model. The monthly mass balance is obtained from gridded climate data and a temperature index melt model. To our knowledge, OGGM is the first global model to explicitly simulate glacier dynamics: the model relies on the shallow-ice approximation to compute the depth-integrated flux of ice along multiple connected flow lines. In this paper, we describe and illustrate each processing step by applying the model to a selection of glaciers before running global simulations under idealized climate forcings. Even without an in-depth calibration, the model shows very realistic behavior. We are able to reproduce earlier estimates of global glacier volume by varying the ice dynamical parameters within a range of plausible values. At the same time, the increased complexity of OGGM compared to other prevalent global glacier models comes at a reasonable computational cost: several dozen glaciers can be simulated on a personal computer, whereas global simulations realized in a supercomputing environment take up to a few hours per century. Thanks to the modular framework, modules of various complexity can be added to the code base, which allows for new kinds of model intercomparison studies in a controlled environment. Future developments will add new physical processes to the model as well as automated calibration tools. Extensions or alternative parameterizations can be easily added by the community thanks to comprehensive documentation. OGGM spans a wide range of applications, from ice–climate interaction studies at millennial timescales to estimates of the contribution of glaciers to past and future sea-level change. It has the potential to become a self-sustained community-driven model for global and regional glacier evolution.</p

The Endoscopic Endonasal Approach to the Hypoglossal Canal: The Role of the Eustachian Tube as a Landmark for Dissection

IMPORTANCE: Improvements in endoscopic technology and reconstructive techniques have made the endoscopic endonasal approach (EEA) a viable option to approach ventromedial lesions in the region of the hypoglossal canal. Prior to contemplating this surgical corridor, a thorough understanding of anatomic relationships and landmarks is essential to safely approach this region of the posterior skull base through an EEA. OBJECTIVE: To describe the surgical technique and anatomic landmarks in the EEA to the hypoglossal canal through referencing nasopharyngeal and posterior skull base anatomy. DESIGN, SETTING, AND PARTICIPANTS: Study of latex-injected cadaveric heads at the North Carolina Eye Bank Multidisciplinary Surgical Skills Laboratory at the University of North Carolina. INTERVENTIONS: An EEA to the hypoglossal canal was carried out bilaterally in 5 embalmed, latex-injected cadaver heads. MAIN OUTCOMES AND MEASURES: Cadaveric measurements of anatomic landmarks and relationships in the approach were obtained using a 10-cm surgical ruler and were reported as mean distances. Additionally, high-quality endoscopic images demonstrating the operative technique and anatomic relationships were obtained. RESULTS: The distance between the lacerum segment of the internal carotid arteries, the superolateral boundary, was 23.6 mm (SD, 11.8 mm). The distance between the anterolateral edge of the occipital condyles, the inferolateral boundary, was 19 mm (SD, 0.80 mm). The supracondylar groove was identified in the same anteroposterior plane as the nasopharyngeal orifice of the eustachian tube, and the anterior-most edge of the occipital condyle was 14 mm (SD, 0.82 mm) from the posterosuperior edge of the salpingopharyngeal fold. Additionally, the transtubercular corridor was on the same plane as the superior edge of the torus tubarius in the anteroposterior axis. The distance to the hypoglossal canal from midline was 10 mm, which was found after completing drilling in the transcondylar and transtubercular corridors. Last, the hypoglossal nerve rootlets were identified entering the canal 6 mm inferiorly and 8 mm laterally from the vertebrobasilar junction. CONCLUSIONS AND RELEVANCE: The eustachian tube and other elements of nasopharyngeal anatomy are fixed landmarks that provide important points of reference when approaching the hypoglossal canal through an EEA. A thorough understanding of these anatomic relationships is vital in safely navigating this direct, surgical corridor to the posterior fossa

Extensive Mucocutaneous Histiocytic Sarcoma raised from an Acute B Lymphocytic Leukemia: A Case Report at Hospital Mexico, Costa Rica

Histiocytic sarcomas are rare neoplasms with poor prognosis originating from histiocytic or dendritic cell clones and associated with haematological malignancies such as acute or chronic leukemias and lymphomas. We describe a case of a patient who developed a disseminated and extensive mucocutaneous histiocytic sarcoma during remission.UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

Extragenital Müllerian adenosarcoma with pouch of Douglas location

Background: Of all female genital tract tumors, 1-3% are stromal malignancies. In 8-10% of cases, these are represented by Mullerian adenosarcoma an extremely rare tumor characterized by a stromal component of usually low-grade malignancy and by a benign glandular epithelial component. Variant that arises in the pouch of Douglas is scarcely mentioned in the medical literature.Case Presentation: A 49-year-old para-0 woman, was seen at our OB/GYN-UNIT because she complained vaguely of pelvic pain. She had a mass of undefined nature in the pouch of Douglas. A simple excision of the mass showed low-grade Mullerian adenosarcoma with areas of stromal overgrowth. One and a half year after surgery, at another hospital, a mass was detected in the patient's posterior vaginal fornix and removed surgically. Six months later she came back to our observation with vaginal bleeding and mass in the vaginal fornix. We performed radical surgery. The pathological examination showed recurrent adenosarcoma. Surgical treatment was supplemented by radiation therapy.Conclusions: The case of Mullerian adenosarcoma reported here is the third known so far in the literature that was located in the pouch of Douglas. To date, only two other such cases have been reported, including one resulting from neoplastic degeneration of an endometriotic cyst

Onchocerciasis in San Vicente Pacaya, Guatemala

An epidemiological survey for onchocerciasis was carried out in the San Vicente Pacaya area of Guatemala. A total of 2,153 inhabitants were examined by a single skin snip, and 664 (30.8%) were positive for microfilariae. Slit lamp examination of the anterior chamber of the eye revealed microfilariae in 6.2%; the positive rate for microfilariae in the anterior chamber was proportional to the microfilarial density in the skin. The altitude-dependent character of onchocercal infection was shown in this mountainous area, suggesting that transmission occurs principally between 600 and 1,300 m. Of 1,217 persons examined simultaneously by skin snip and by palpation for nodules, 587 were positive by one or both methods; 101 infections were detected by onchocercal nodules only and these were usually in children or persons living in areas of low endemicity. It was concluded that both the skin snip and a search for nodules are required for accurately determining the prevalence of onchocerciasis in Guatemala

A human brainstem glioma xenograft model enabled for bioluminescence imaging

Despite the use of radiation and chemotherapy, the prognosis for children with diffuse brainstem gliomas is extremely poor. There is a need for relevant brainstem tumor models that can be used to test new therapeutic agents and delivery systems in pre-clinical studies. We report the development of a brainstem-tumor model in rats and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to therapy as part of this model. Luciferase-modified human glioblastoma cells from five different tumor cell sources (either cell lines or serially-passaged xenografts) were implanted into the pontine tegmentum of athymic rats using an implantable guide-screw system. Tumor growth was monitored by BLI and tumor volume was calculated by three-dimensional measurements from serial histopathologic sections. To evaluate if this model would allow detection of therapeutic response, rats bearing brainstem U-87 MG or GS2 glioblastoma xenografts were treated with the DNA methylating agent temozolomide (TMZ). For each of the tumor cell sources tested, BLI monitoring revealed progressive tumor growth in all animals, and symptoms caused by tumor burden were evident 26–29 days after implantation of U-87 MG, U-251 MG, GBM6, and GBM14 cells, and 37–47 days after implantation of GS2 cells. Histopathologic analysis revealed tumor growth within the pons in all rats and BLI correlated quantitatively with tumor volume. Variable infiltration was evident among the different tumors, with GS2 tumor cells exhibiting the greatest degree of infiltration. TMZ treatment groups were included for experiments involving U-87 MG and GS2 cells, and in each case TMZ delayed tumor growth, as indicated by BLI monitoring, and significantly extended survival of animal subjects. Our results demonstrate the development of a brainstem tumor model in athymic rats, in which tumor growth and response to therapy can be accurately monitored by BLI. This model is well suited for pre-clinical testing of therapeutics that are being considered for treatment of patients with brainstem tumors

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Unravelling the genome-wide contributions of specific 2-alkyl-4-quinolones and PqsE to quorum sensing in Pseudomonas aeruginosa

The pqs quorum sensing (QS) system is crucial for Pseudomonas aeruginosa virulence both in vitro and in animal models of infection and is considered an ideal target for the development of anti-virulence agents. However, the precise role played by each individual component of this complex QS circuit in the control of virulence remains to be elucidated. Key components of the pqs QS system are 2-heptyl-4-hydroxyquinoline (HHQ), 2-heptyl-3-hydroxy-4-quinolone (PQS), 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), the transcriptional regulator PqsR and the PQS-effector element PqsE. To define the individual contribution of each of these components to QS-mediated regulation, transcriptomic analyses were performed and validated on engineered P. aeruginosa strains in which the biosynthesis of 2-alkyl 4-quinolones (AQs) and expression of pqsE and pqsR have been uncoupled, facilitating the identification of the genes controlled by individual pqs system components. The results obtained demonstrate that i) the PQS biosynthetic precursor HHQ triggers a PqsR-dependent positive feedback loop that leads to the increased expression of only the pqsABCDE operon, ii) PqsE is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development, iii) PQS promotes AQ biosynthesis, the expression of genes involved in the iron-starvation response and virulence factor production via PqsR-dependent and PqsR-independent pathways, and iv) HQNO does not influence transcription and hence does not function as a QS signal molecule. Overall this work has facilitated identification of the specific regulons controlled by individual pqs system components and uncovered the ability of PQS to contribute to gene regulation independent of both its ability to activate PqsR and to induce the iron-starvation response