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ÍtemSolo MetadatosATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure(2019) Delcour C.; Amazit L.; Patino L.C.; Magnin F.; Fagart J.; Delemer B.; Young J.; Laissue P.; Binart N.; Beau I.Purpose: Primary ovarian insufficiency (POI) is a frequent disorder that affects ~1% of women under 40 years of age. POI, which is characterized by the premature depletion of ovarian follicles and elevated plasma levels of follicle-stimulating hormone (FSH), leads to infertility. Although various etiological factors have been described, including chromosomal abnormalities and gene variants, most cases remain idiopathic. The aim of the present study was to identify and validate functionally new sequence variants in ATG (autophagy-related genes) leading to POI. Methods: We have reanalyzed, in silico, the exome sequencing data from a previously reported work performed in 69 unrelated POI women. Functional experiments using a classical hallmark of autophagy, the microtubule-associated protein 1 light chain 3? (LC3), were then used to link these genes to this lysosomal degradation pathway. Results: We venture a functional link between ATG7 and ATG9A variants and POI. We demonstrated that variant ATG7 and ATG9A led to a decrease in autophagosome biosynthesis and consequently to an impairment of autophagy, a key biological process implicated in the preservation of the primordial follicles forming the ovarian reserve. Conclusion: Our results unveil that impaired autophagy is a novel pathophysiological mechanism involved in human POI. © 2018, American College of Medical Genetics and Genomics.- ÍtemSolo MetadatosThe putative protective role of hepatitis B virus (HBV) infection from autoimmune disorders(2008) Ram, Maya; Anaya, Juan-Manuel; Barzilai, Ori; Izhaky, David; Katz, Bat-sheva Porat; Blank, Miri; Shoenfeld, YehudaBackground: The etiology of autoimmune diseases is not fully clarified and the mechanisms underlying their initiation and progression are still obscure. It is becoming clear that in a genetic susceptible individual an environmental trigger such as infectious agent in general and viruses in particular could initiate the development of an autoimmune disease. Hepatitis B virus (HBV) is notorious in its association with diverse autoimmune diseases. Therefore, we aimed to determine the presence of hepatitis B core antibody (HBcAb), a seromarker for past or present infection with HBV, in a large number of sera collected from patients with different autoimmune diseases. Methods: A cohort of 675 sera samples of 5 different autoimmune diseases and healthy donors were screened for evidence of a prior infection with HBV. All samples were tested for hepatitis B core antibody (IgG) using the Monolisa anti-HBc PLUS commercial kit (Bio-Rad, Hercules, San Francisco, USA). Results: Lower percentage of HBcAb was found in sera of the autoimmune diseases when compared to normal controls. Fifteen (10.7%) from 140 normal controls were found positive for the presence of HBcAb. Two (2%) out of 98 multiple sclerosis (MS) sera were positive for the presence of HBcAb (OR: 0.17, 95%CI: 0.03-0.77, p = 0.01), 3 (2.5%) out of 117 systemic lupus erythematosus (SLE) sera (OR: 0.2, 95%CI: 0.06-0.77, p = 0.01), 4 (4.5%) out of 89 type 1 diabetes (T1D), 5 (6.1%) from 82 Sjogren's syndrome (SS) sera and 12 (8%) from 149 rheumatoid arthritis (RA) sera were positive for the presence of HBcAb. Conclusions: Our data divulge an unexpected low percentage of antibodies to HBcAg in patients with SLE, MS and T1D in comparison to healthy matched donors. This finding may raise a protective role to HBV in some autoimmune diseases i.e. hygiene theory. © 2008 Elsevier B.V. All rights reserved.
- ÍtemSolo MetadatosPlasma exchange therapy for a severe relapse of Devic's disease in a pregnant woman: A case report and concise review(2016) Tabares, Jonathan Rubio; Gonzalez, Pablo Felipe AmayaNeuromyelitis optica (NMO) or Devic's disease is an autoimmune inflammatory demyelinating condition affecting the central nervous system (CNS). It was initially believed to be a variant of multiple sclerosis (MS). However, the discovery of NMO-IgG anti-AQP4 antibodies marked an objective distinction between these conditions. Treatment of acute attacks is generally based on pulsed steroids, followed by long-term immunosuppression with azathioprine, oral steroids, and rituximab as first-line therapies. Plasma exchange therapy is indicated for steroid-resistant relapses. We describe a case report of a pregnant woman with a severe relapse of Devic's disease, initially misdiagnosed as MS, unresponsive to pulsed steroids, and who underwent plasma exchange therapy safely, with excellent clinical response and with no adverse outcome for the fetus. © 2016 Elsevier B.V.
- ÍtemSolo MetadatosLong-term Visual Outcomes of Intravitreal Bevacizumab in Inflammatory Ocular Neovascularization(2009-08) Mansour, Ahmad M.; Arevalo, J. Fernando; Ziemssen, Focke; Mehio-Sibai, Abla; Mackensen, Friederike; Adan, Alfredo; Chan, Wai-Man; Ness, Thomas; Banker, Alay S.; Dodwell, David; Tran, Thi Ha Chau; Fardeau, Christine; LeHoang, Phuc; Mahendradas, Padmamalini; Berrocal, Maria; Tabbarah, Zuheir; Hrisomalos, Nicholas; Hrisomalos, Frank; Al-Salem, Khalil; Guthoff, RainerPurpose To assess the long-term role of bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in inflammatory ocular neovascularization. Design Retrospective multicenter consecutive case series of inflammatory ocular neovascularization. Methods settings: Multicenter institutional and private practices. study population: Patients with inflammatory ocular neovascularization in one or both eyes of varying etiologies who failed standard therapy. intervention: Intravitreal injection of bevacizumab. main outcome measures: Improvement of best-corrected visual acuity (BCVA) expressed as logarithm of minimal angle of resolution (logMAR), and decrease in central foveal thickness as measured by optical coherence tomography at 6, 12, 18, and 24 months of follow-up. Results Mean logMAR BCVA (central foveal thickness) following intravitreal bevacizumab was as follows: baseline, 0.65 (6/27 or 20/90) (338 ?m; 99 eyes of 96 patients); 6 months, 0.42 (6/16 or 20/53) (239 ?m; 2.0 injections; 81 eyes); 12 months, 0.39 (6/15 or 20/49) (241 ?m; 2.3 injections; 95 eyes); 18 months, 0.40 (6/15 or 20/50) (261 ?m; 3.0 injections; 46 eyes); and 24 months, 0.34 (6/13 or 20/44) (265 ?m; 3.6 injections; 27 eyes). Paired comparisons revealed significant visual improvement at 6 months of 2.4 lines (P = .000), at 12 months of 2.5 lines (P = .000), at 18 months of 2.5 lines (P = .001), and at 24 months of 2.2 lines (P = .013). Paired comparisons revealed significant central foveal flattening at 6 months of 78 ?m (P = .000), at 12 months of 85 ?m (P = .000), at 18 months of 90 ?m (P = .003), and at 24 months of 77 ?m (P = .022). Three eyes developed submacular fibrosis and 1 eye submacular hemorrhage. Conclusion Intravitreal bevacizumab led in the long-term to significant mean visual improvement of ?2.2 lines and significant foveal flattening in a wide variety of inflammatory ocular diseases without major complications. Choroidal neovascularization (CNV) and neovascularization of the disc or elsewhere (NVD/E) in the retina can be an occasionally late sequela of inflammatory chorioretinal diseases,1 and rarely an early manifestation.2 Our group has previously reported the 3-month results of intravitreal bevacizumab (Avastin; Genentech Inc, South San Francisco, California, USA) in inflammatory ocular neovascularization in 84 eyes. Intravitreal bevacizumab led to short-term significant visual improvement and regression of inflammatory ocular neovascularization in a wide variety of inflammatory ocular diseases.3 The long-term safety profile of bevacizumab, and visual prognosis in inflammatory ocular neovascularization, may be jeopardized by submacular fibrosis,4, 5 cystoid macular edema (CME),6, 7, 8 or spread of chorioretinal atrophy. The objective of this report is to assess the long-term safety and efficacy of intravitreal bevacizumab in a retrospective collaborative case series study of inflammatory ocular neovascularization. Methods Consecutive cases of inflammatory ocular neovascularization resistant to corticosteroid with or without antimicrobial therapy and/or immunosuppression treated with intravitreal bevacizumab and followed for more than 6 months were included in the present analysis. The cases were contributed by members of the American Society of Retina Specialists and the American Uveitis Society as detailed elsewhere.3 Intravitreal bevacizumab was injected using a 30-gauge needle in a sterile manner after topical anesthesia and povidone instillation in the lower cul-de-sac. Bevacizumab aliquots were prepared in the hospital pharmacies of the corresponding institution. A standardized spreadsheet was used to collect the clinical data. Cases with prior CME, diabetes mellitus, or age-related macular degeneration were excluded. Most of the patients had initially been treated in a stepwise fashion with high-doses of oral corticosteroid, with or without intraocular or sub-Tenon corticosteroid or immunosuppressive therapy (as monitored by a rheumatologist). All patients signed an informed consent after detailed information about the limited experience, potential side effects, and the off-label usage of the drug. Best-corrected visual acuity (BCVA) was assessed using either Early Treatment Diabetic Retinopathy Study (ETDRS) or Snellen charts (half-and-half) and listed as logarithm of minimal angle of resolution (logMAR) equivalents. Retreatment was done when there was recurrent activity evaluated by funduscopy, fluorescein angiography (leakage, growth of CNV), or optical coherence tomography examination. Differences between final and initial BCVA or central foveal thickness (CFT) were tested using paired Student t test. For small sample size comparisons, nonparametric tests were used. Further associations were performed using one-way analysis of variance (ANOVA) or ?2 test for continuous and categorical variables, respectively. All analysis was conducted using SPSS 13.0 statistical package (SPSS Inc, Chicago, Illinois, USA), and a P value less than .05 was considered significant. Results Ninety-nine consecutive eyes of 96 patients, 33 male and 63 female (78 White, 9 Asian, 8 Hispanic, and 1 Black) with a mean age of 39 years, were examined at baseline and followed up between 6 months and 24 months (TABLE 1, TABLE 2). The right eye was involved in 55 subjects and the left in 44 subjects (3 patients having bilateral disease). Uveitis was active in 26 eyes at the time of ocular neovascularization. Forty-one patients (44 eyes) were taking oral, periocular, or intraocular corticosteroids or other immunosuppressive agents. Thirty-three eyes received 0.1 ml (2.5 mg) of intravitreal bevacizumab and 66 eyes received 0.05 ml (1.25 mg). The diagnosis was punctate inner choroidopathy (23), multifocal choroiditis with panuveitis (19), ocular histoplasmosis (13), idiopathic (12), serpiginous choroiditis (9), Vogt-Koyanagi-Harada disease (6), ocular toxoplasmosis (5), Eales disease (4), sarcoidosis (2), sympathetic ophthalmia (2), tuberculosis (2), acute placoid pigment epitheliopathy (1), and birdshot choroiditis (1).
- ÍtemSolo MetadatosDid Mozart Suffer from Gilles de la Tourette Syndrome?(2017) Palacios Sánchez, Leonardo; Botero Meneses, Juan Sebastián; Vergara-Méndez L.D.; Pachón N.; Martínez A.; Ramírez Clavijo, Sandra RocíoThe personal and private lives of great men and women in history, like writers, painters and musicians, have been the subject of great interest for many years. A clear example of this is the vast scrutiny is cast over the famous composer, Wolfgang Amadeus Mozart. What may have started as curiosity, rapidly evolved into extensive research, as the answers about the musician's legendary talent may lie in the details of his life (his childhood, his relationships, his quirks and his mannerisms). It is usually up to historians, anthropologists or philosophers to delve into the pages of old books, trying to grasp answers and clues. However, for some time, Physicians have sought their own part in solving the puzzle. The long told hypothesis regarding Mozart's diagnosis of Gilles de la Tourette syndrome will be examined. Could all of the peculiarities and oddities of the genius be caused by a neurological disorder? Or was this musical genius just an eccentric brilliant man?. © 2016 Asociación Colombiana de Psiquiatría
- ÍtemSolo MetadatosHistidine-tryptophan-ketoglutarate solution versus blood cardioplegia in cardiac surgery: A propensity-score matched analysis(2018) Pizano, Alejandro; Montes, Felix Ramon; Carreño, Marisol; Echeverri, Dario; Umaña, Juan PabloBackground: Choosing a cardioplegic solution is a significant issue in modern cardiac surgery. Although different options are available, the optimal strategy for myocardial protection has not been established. The aim of this study was to compare intraoperative and postoperative effects of histidine–tryptophan–ketoglutarate (HTK) solution with those of standard blood cardioplegia with St Thomas No 2 solution. The study was conducted using a large cohort of adult patients undergoing complex cardiac surgery. Methods: This study was a single center retrospective review of prospectively collected data. Between January 2008 and December 2015, 4480 patients underwent cardiac surgery using cardiopulmonary bypass (CPB) and cardioplegic arrest. Patients were divided into a blood cardioplegia group (n = 3852) and an HTK solution group (n = 628). Propensity score matching was used to adjust for differences between the two groups, and 292 matched pairs were identified. The primary end point was Intensive Care Unit (ICU) length of stay (LOS). Secondary end points included intraoperative changes in serum sodium concentration, readmission to ICU, transfusion of blood products, 30-day hospital readmission, 30-day mortality, and the incidence of major postoperative complications. Results: No significant differences were found between the matched groups with regard to baseline characteristics. Aortic cross-clamp and CPB times were longer for the blood cardioplegia (147.4 versus 132.8 min; P less than .001). Administration of HTK solution was associated with acute and transient hyponatremia (141 versus 130 mmol/L; P less than .001). ICU LOS was comparable between the groups (5.4 versus 5.4 days; P = .585). No significant differences were noted in any other secondary end point. Conclusions: During complex cardiac surgery, both cardioplegia techniques were equivalent in terms of early clinical outcomes. © 2018 Forum Multimedia Publishing, LLC.
- ÍtemSolo MetadatosTemozolomide down-regulates P-glycoprotein in human blood-brain barrier cells by disrupting Wnt3 signaling(2014) Riganti, Chiara; Salaroglio, Iris C.; Pinzòn-Daza, Martha L.; Caldera, Valentina; Campia, Ivana; Kopecka, Joanna; Mellai, Marta; Annovazzi, Laura; Couraud, Pierre-Olivier; Bosia, Amalia; Ghigo, Dario; Schiffer, DavideLow delivery of many anticancer drugs across the blood-brain barrier (BBB) is a limitation to the success of chemotherapy in glioblastoma. This is because of the high levels of ATP-binding cassette transporters like P-glycoprotein (Pgp/ABCB1), which effluxes drugs back to the bloodstream. Temozolomide is one of the few agents able to cross the BBB; its effects on BBB cells permeability and Pgp activity are not known. We found that temozolomide, at therapeutic concentration, increased the transport of Pgp substrates across human brain microvascular endothelial cells and decreased the expression of Pgp. By methylating the promoter of Wnt3 gene, temozolomide lowers the endogenous synthesis of Wnt3 in BBB cells, disrupts the Wnt3/glycogen synthase kinase 3/?-catenin signaling, and reduces the binding of ?-catenin on the promoter of mdr1 gene, which encodes for Pgp. In co-culture models of BBB cells and human glioblastoma cells, pre-treatment with temozolomide increases the delivery, cytotoxicity, and antiproliferative effects of doxorubicin, vinblastine, and topotecan, three substrates of Pgp that are usually poorly delivered across BBB. Our work suggests that temozolomide increases the BBB permeability of drugs that are normally effluxed by Pgp back to the bloodstream. These findings may pave the way to new combinatorial chemotherapy schemes in glioblastoma. © 2013 Springer Basel.
- ÍtemSolo MetadatosVirus-Induced Anterior Uveitis (VIAU) in Immunocompromised Patients(2018) de-la-Torre, AlejandraPurpose: To describe the clinical characteristics, diagnosis, and treatment of VIAU in immunocompromised patients. Methods: A critical review of literature was performed. Results: Diagnosis and treatment of VIAU in immunocompromised patients may be a challenge due to atypical clinical-courses, severe presentations, and more frequent recurrences. A conclusive diagnosis can be made by aqueous-humour PCR-analysis. Visual prognosis depends on early diagnosis and prompt treatment. Frequent ocular examinations are recommended in HIV patients with CD-4-counts below 100 in order to rule out opportunistic ocular coinfections. It is essential to bear in mind the potential side-effects of therapeutic interventions and consider the possibility of Immune Recovery Uveitis (IRU) in eyes with treated viral retinitis after the initiation of HAART. Conclusions: Early diagnosis and treatment of VIAU in immunocompromised patients can be achieved with high suspicion, recognizing clinical features, and obtaining specimens for molecular diagnostic testing in order to avoid usually severe ocular morbidity. ©, © Taylor and Francis Group, LLC.
- ÍtemSolo MetadatosPrevalence of delayed neurodevelopment in children from Bogotá, Colombia, South America(2007) Vélez van Meerbeke, Alberto Francisco; Talero Gutiérrez, Claudia; González Reyes, Rodrigo EstebanBackground: Undiagnosed children with neurodevelopment delay disorders (NDD) frequently experience school difficulties, leading to school desertion or academic failure with subsequent familial, social and work-related problems. Methods: In 2004-2005, we conducted a cross-sectional study to determine the prevalence of developmental delay among preschoolers in Bogotá (Colombia); convenience samples in several socioeconomic areas of the city were screened to define the prevalence of NDD. Parents and teachers were interviewed to identify children with possible NDD. Selected children were evaluated with a neurodevelopmental abbreviated scale (EAD-1). Results: We screened 2,043 preschool children aged less than 60 months; 288 suspected cases were examined individually using the EAD-1 scale. One or more abnormal items (alert category) were found in 67 (23.3%) children, for an estimated prevalence of 32.8‰ children less than 5 years of age, including deficits in gross motor function (9.3‰), personal-social interactions (9.8‰), fine motor skills (10.3‰), auditory language delay (18.6‰) and overall delay (10.8‰). Conclusions: There is limited information regarding the prevalence of neurodevelopmental delay in nonindustrialized countries. The prevalence obtained in Bogotá, Colombia, is within the expected range; however, we identified NDD among apparently healthy children from nurseries and kindergartens, who had previously been undiagnosed and untreated. Lack of evaluation of developmental milestones in children in Colombia is a substantial public health problem that will require effective intervention. Copyright © 2007 S. Karger AG.
- ÍtemSolo MetadatosCalidad de vida y percepción de apoyo social en personas con HIV en Bogotá, Colombia(2018-03-22) Moreno-Montoya, Jose; Barragán González, Ana María; Martínez Matheus, Margin del Socorro; Rodríguez, Amanda; González, Ángela CarmelaEn estudios llevados a cabo en paises desarrollados se ha establecido que las personas con HIV/sida refieren tener una menos calidad de vida y menor apoyo social.Objetivo. Explorar la asociacion entre la percepcion del apoyo social afectivo o de personas de confianza y cada dimension de la calidad de vida relacionada con la salud en personas con HIV/sida en Bogota.Materiales y metodos. Se hizo un estudio de corte transversal en personas con HIV/sida seleccionadas por conveniencia, en el marco de un programa de atencion en una red hospitalaria de Bogota. Se utilizaron los cuestionarios de calidad de vida relacionada con la salud SF36 y el cuestionario generico de apoyo social funcional Duke-UNC-11. Se utilizaron modelos de regresion lineal en el analisis.Resultados. Se evidencio una relacion directa entre la dimension del bienestar emocional de la calidad de vida, el apoyo social afectivo (SS=7,36; IC95% 1,04-13,68) y el de personas de confianza (SS=11,63; IC95% 5,30-17,96), asi como entre las dimensiones de la funcion fisica, el desempeno emocional y el dolor corporal y la percepcion del apoyo social de tipo afectivo, y entre el apoyo social de personas de confianza y las dimensiones de la vitalidad y la funcion social. Se encontro una relacion inversa entre los promedios de los puntajes de las dimensiones de desempeno emocional, desempeno fisico y salud general y la percepcion del apoyo social de tipo afectivo con la primera dimension y el de personas de confianza con las dos ultimas.Conclusiones. Los sujetos con una mejor percepcion del apoyo social reportaron una mejor calidad de vida relacionada con la salud, lo cual puede servir de base para la planeacion, el diseno y la implementacion de planes de atencion medica que incorporen variables clinicas, paraclinicas y del entorno del paciente.
