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1.
Case Rep Ophthalmol ; 15(1): 225-229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38500543

RESUMEN

Introduction: Conjunctival nevi are benign tumors that are commonly located at the nasal or temporal limbus and rarely in the fornix or tarsus. We report a case of a patient presenting with a solitary compound cystic nevus of the conjunctival fornix in the background of bilateral complexion-associated melanosis. Case Presentation: A 71-year-old African-American female was referred for evaluation of an incidentally noted melanocytic lesion of the right conjunctival fornix. The patient underwent an excisional biopsy, revealing histological features consistent with a compound cystic nevus. Conclusion: This finding is noteworthy due to the rarity of conjunctival nevi originating in the fornix. The case underscores the importance of excisional biopsy in evaluating conjunctival forniceal melanocytic lesions to exclude malignant melanoma, a critical consideration for prognosis.

2.
Taiwan J Ophthalmol ; 12(3): 325-329, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36248076

RESUMEN

PURPOSE: To examine changes in intraocular pressure (IOP) in patients with thyroid eye disease (TED) following teprotumumab. MATERIALS AND METHODS: A retrospective review of 17 patients with TED who received teprotumumab between January 2020 and September 2021 was conducted. IOP, extent of proptosis, and clinical activity score were reviewed at baseline and at 6 weeks, 12 weeks, and 24 weeks for patients undergoing teprotumumab treatment. The primary outcome measure was change in IOP, while secondary outcome measures included changes in proptosis and clinical activity score. RESULTS: Of the 17 patients (34 eyes) with TED who were treated with teprotumumab, the mean age was 50.5 years, and 15 (88%) were female. The mean baseline IOP was 20 mm Hg (range 13-28), and the mean baseline clinical activity score was 3.8 (range 0-6). Of the 34 eyes examined at baseline, examinations were repeated in 16 at 6 weeks, 26 at 12 weeks, and 8 at 24 weeks. At week 6 of treatment, mean IOP decreased by 4.9 mm Hg (P < 0.0001). At week 12 of treatment, mean IOP decreased by 4.6 mm Hg (P < 0.0001). Mean IOP was decreased at last record of follow-up by 4.9 mm Hg (P < 0.0001). CONCLUSION: Among patients with TED, teprotumumab treatment was associated with a reduction in IOP.

4.
Obstet Gynecol ; 139(5): 821-831, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35576341

RESUMEN

OBJECTIVE: To characterize gynecology clinical trials over time, compare gynecology subspecialties, and analyze factors associated with early discontinuation, results reporting, and publication. METHODS: We conducted a cross-sectional analysis of all gynecology trials registered on ClinicalTrials.gov between 2007 and 2020 and their resulting publications. Trials were analyzed with descriptive, multivariable logistic, and Cox regression analyses. Primary exposure variables were trial funding and subspecialty. The three primary outcomes included early discontinuation, results reporting to ClinicalTrials.gov, and publication in a peer-reviewed journal indexed on PubMed. RESULTS: Of 223,690 trials registered on ClinicalTrials.gov between October 2007 and March 2020, only 3.7% focused on gynecology (n=8,174, approximately 3,759,086 participants). Subspecialties included reproductive endocrinology and infertility (n=1,428, 17.5%), gynecologic oncology (n=2,063, 25.2%), urogynecology (n=1,118, 13.7%), family planning (n=648, 7.9%), and other benign gynecology (n=2,917, 35.7%). Only 42.0% of completed trials disseminated results through results reporting and publication. Of all funding types, industry-funded trials were the most likely to be discontinued early (P<.001). Academic-funded trials were the least likely to report results (adjusted odds ratio [aOR] 0.38, 95% CI 0.30-0.50) but the most likely to publish (aOR 1.62, 95% CI 1.24-2.12). The number of reproductive endocrinology and infertility trials increased the most of any subspecialty between 2007 and 2020 (6.4% growth rate). Reproductive endocrinology and infertility and family planning trials were the most likely to be stopped early (reproductive endocrinology and infertility: adjusted hazard ratio [aHR] 2.08, 95% CI 1.59-2.71; family planning: aHR 1.55 95% CI 1.06-2.25). When completed, reproductive endocrinology and infertility trials were the least likely to report results (aOR 0.58, 95% CI 0.38-0.88). No significant differences were seen between subspecialties with respect to publication. CONCLUSION: Gynecology trials comprise only 3.7% of all clinical trials. The paucity of gynecology clinical trials aligns with decades of female underrepresentation in research. When completed, gynecology trials have poor dissemination. Our findings raise concern about bias in the performance, reporting, and publication of gynecology clinical trials.


Asunto(s)
Ginecología , Infertilidad , Estudios Transversales , Femenino , Humanos , Oportunidad Relativa , Informe de Investigación
5.
J Glaucoma ; 31(4): 218-223, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35131983

RESUMEN

PRCIS: In primary angle closure suspects (PACS), self-identified Black race was a risk factor for intraocular pressure (IOP) elevation and iritis following laser peripheral iridotomy (LPI). Laser type was not associated with either immediate post-LPI IOP elevation or iritis in multivariate analysis. PURPOSE: The aim was to determine the impact of laser type and patient characteristics on the incidence of IOP elevation and iritis after LPI in PACS. MATERIALS AND METHODS: The electronic medical records of 1485 PACS (2407 eyes) who underwent either neodymium-doped yttrium-aluminum-garnet or sequential argon and neodymium-doped yttrium-aluminum-garnet LPI at the University of Pennsylvania between 2010 and 2018 were retrospectively reviewed. Average IOP within 30 days before LPI (baseline IOP), post-LPI IOP within 1 hour, laser type, laser energy, and the incidence of new iritis within 30 days following the procedure were collected. Multivariate logistic regression accounting for intereye correlation was used to assess factors associated with incidence of post-LPI IOP elevation and iritis, adjusted by age, sex, surgeon, and histories of autoimmune disease, diabetes, and hypertension. RESULTS: The incidence of post-LPI IOP elevation and iritis were 9.3% (95% confidence interval: 8.1%-10.5%) and 2.6% (95% CI: 1.9%-3.2%), respectively. In multivariate analysis, self-identified Black race was a risk factor for both IOP elevation [odds ratio (OR): 2.08 compared with White; P=0.002] and iritis (OR: 5.07; P<0.001). Higher baseline IOP was associated with increased risk for post-LPI IOP elevation (OR: 1.19; P<0.001). Laser type and energy were not associated with either post-LPI IOP elevation or iritis (P>0.11 for all). CONCLUSIONS: The incidence of immediate IOP elevation and iritis following prophylactic LPI was higher in Black patients independent of laser type and energy. Heightened vigilance and increased medication management before and after the procedure are suggested to help mitigate these risks.


Asunto(s)
Glaucoma de Ángulo Cerrado , Iritis , Terapia por Láser , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/cirugía , Humanos , Presión Intraocular , Iridectomía/métodos , Iris/cirugía , Iritis/cirugía , Terapia por Láser/métodos , Estudios Retrospectivos , Factores de Riesgo
6.
Orbit ; 40(6): 461-469, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32900269

RESUMEN

Purpose: To review the clinical features and treatment-associated outcomes of primary orbital melanoma among cases reported in the literature and to present a case treated with orbital exenteration and post-operative radiotherapy.Methods: Case reports and case series on primary orbital melanoma published in the literature between 1980 and 2020 were reviewed. Data collected included patient demographics, presenting ocular symptoms, diagnostic imaging, histology, management, and outcomes.Results: Eighty-eight cases of primary orbital melanoma were reviewed. The average age at presentation was 45 years and 58% of patients were male. The most common presenting symptoms and signs were proptosis (73%), decreased visual acuity (32%), pain (14%), diplopia (15%), and palpable mass (9%). Imaging frequently showed a well-circumscribed enhancing lesion. Diagnosis was made by histology in all cases, and orbital blue nevus was identified in 42%. In the majority of cases, treatment consisted of orbital exenteration (54%) or excision (38%). Adjuvant radiotherapy was given in 47% of cases. For the 72 patients with reported outcomes, 36% had metastases, 15% had local recurrence, and 32% died of metastatic disease. Patients who received surgery and radiotherapy had improved survival compared to those who received surgery alone (p = .01). There was no difference in survival between those who underwent orbital exenteration or excision (p = .16).Conclusions: Primary orbital melanoma is a rare malignancy and should be considered in patients with a history of unilateral proptosis and a well-defined orbital mass on imaging. Surgery remains the mainstay of treatment. Adjuvant radiotherapy may improve patient survival.


Asunto(s)
Melanoma , Nevo Azul , Neoplasias Orbitales , Neoplasias Cutáneas , Humanos , Masculino , Melanoma/radioterapia , Melanoma/cirugía , Evisceración Orbitaria , Neoplasias Orbitales/cirugía , Estudios Retrospectivos
7.
Cell Rep ; 33(5): 108271, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33147455

RESUMEN

Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells (RGCs). Recent studies have implicated pro-inflammatory microglia, macrophages, and A1 astrocytes in the pathogenesis of neurodegenerative diseases. The role of pro-inflammatory, neurotoxic A1 astrocytes in glaucoma is just beginning to be explored. Using a mouse model of glaucoma, we demonstrate that ocular hypertension is sufficient to trigger production of C1q, interleukin-1α (IL-1α), and tumor necrosis factor α (TNF-α), three cytokines necessary and sufficient to drive the formation of A1 astrocytes. Upregulation of these cytokines occurs first in CD11b+ CD11c+ cells followed by CD11b+ CD11c- cells. Ablation of this pathway, by either genetic deletions of C1qa, IL-1α, and TNF-α, or treatment with glucagon-like peptide-1 receptor agonist NLY01, reduces A1 astrocyte transformation and RGC death. Together, these results highlight a neuroinflammatory mechanism of glaucomatous neurodegeneration that can be therapeutically targeted by NLY01 administration.


Asunto(s)
Receptor del Péptido 1 Similar al Glucagón/agonistas , Inflamación/patología , Hipertensión Ocular/complicaciones , Neuronas Retinianas/patología , Animales , Astrocitos/patología , Antígeno CD11b/metabolismo , Muerte Celular , Complemento C1q/metabolismo , Femenino , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Interleucina-1alfa/metabolismo , Presión Intraocular , Masculino , Ratones Endogámicos C57BL , Hipertensión Ocular/fisiopatología , Células Ganglionares de la Retina/patología , Factor de Necrosis Tumoral alfa/metabolismo
8.
PLoS One ; 14(4): e0215598, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30998802

RESUMEN

Coffee leaf rust caused by the fungus Hemileia vastatrix is one of the most important leaf diseases of coffee plantations worldwide. Current knowledge of the H. vastatrix genome is limited and only a small fraction of the total fungal secretome has been identified. In order to obtain a more comprehensive understanding of its secretome, we aimed to sequence and assemble the entire H. vastatrix genome using two next-generation sequencing platforms and a hybrid assembly strategy. This resulted in a 547 Mb genome of H. vastatrix race XXXIII (Hv33), with 13,364 predicted genes that encode 13,034 putative proteins with transcriptomic support. Based on this proteome, 615 proteins contain putative secretion peptides, and lack transmembrane domains. From this putative secretome, 111 proteins were identified as candidate effectors (EHv33) unique to H. vastatrix, and a subset consisting of 17 EHv33 genes was selected for a temporal gene expression analysis during infection. Five genes were significantly induced early during an incompatible interaction, indicating their potential role as pre-haustorial effectors possibly recognized by the resistant coffee genotype. Another nine genes were significantly induced after haustorium formation in the compatible interaction. Overall, we suggest that this fungus is able to selectively mount its survival strategy with effectors that depend on the host genotype involved in the infection process.


Asunto(s)
Basidiomycota/fisiología , Coffea/microbiología , Perfilación de la Expresión Génica , Regulación Fúngica de la Expresión Génica , Genoma Fúngico , Interacciones Huésped-Patógeno , Enfermedades de las Plantas/microbiología , Secuenciación Completa del Genoma
9.
Invest Ophthalmol Vis Sci ; 58(11): 4703-4711, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28910446

RESUMEN

Purpose: Our previous experiments demonstrated that intravitreal injection of platelet-derived growth factor-AA (PDGF-AA) provides retinal ganglion cell (RGC) neuroprotection in a rodent model of glaucoma. Here we used PDGFRα-enhanced green fluorescent protein (EGFP) mice to identify retinal cells that may be essential for RGC protection by PDGF-AA. Methods: PDGFRα-EGFP mice expressing nuclear-targeted EGFP under the control of the PDGFRα promoter were used. Localization of PDGFRα in the neural retina was investigated by confocal imaging of EGFP fluorescence and immunofluorescent labeling with a panel of antibodies recognizing different retinal cell types. Primary cultures of mouse RGCs were produced by immunopanning. Neurobiotin injection of amacrine cells in a flat-mounted retina was used for the identification of EGFP-positive amacrine cells in the inner nuclear layer. Results: In the mouse neural retina, PDGFRα was preferentially localized in the ganglion cell and inner nuclear layers. Immunostaining of the retina demonstrated that astrocytes in the ganglion cell layer and a subpopulation of amacrine cells in the inner nuclear layer express PDGFRα, whereas RGCs (in vivo or in vitro) did not. PDGFRα-positive amacrine cells are likely to be Type 45 gamma-aminobutyric acidergic (GABAergic) wide-field amacrine cells. Conclusions: These data indicate that the neuroprotective effect of PDGF-AA in a rodent model of glaucoma could be mediated by astrocytes and/or a subpopulation of amacrine cells. We suggest that after intravitreal injection of PDGF-AA, these cells secrete factors protecting RGCs.


Asunto(s)
Células Amacrinas/metabolismo , Astrocitos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Animales , Biotina/análogos & derivados , Biotina/farmacología , Western Blotting , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Colina O-Acetiltransferasa/metabolismo , Modelos Animales de Enfermedad , Proteínas Fluorescentes Verdes/metabolismo , Ratones , Ratones Transgénicos , Microscopía Confocal , Microscopía Fluorescente , Neuroprotección , Fármacos Neuroprotectores , Células Ganglionares de la Retina/metabolismo , Ácido gamma-Aminobutírico/metabolismo
10.
J Bacteriol ; 199(20)2017 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-28760846

RESUMEN

Most integral outer membrane proteins (OMPs) of Gram-negative bacteria, such as Escherichia coli, assume a ß-barrel structure. The ß-barrel assembly machine (Bam), a five-member complex composed of ß-barrel OMP BamA and four associated lipoproteins, BamB, BamC, BamD, and BamE, folds and inserts OMPs into the outer membrane. The two essential proteins BamA and BamD interact to stabilize two subcomplexes, BamAB and BamCDE, and genetic and structural evidence suggests that interactions between BamA and BamD occur via an electrostatic interaction between a conserved aspartate residue in a periplasmic domain of BamA and a conserved arginine in BamD. In this work, we characterize charge-change mutations at these key BamA and BamD residues and nearby charged residues in BamA with respect to OMP assembly and Bam complex stability. We show that Bam complex stability does not correlate with function, that BamA and BamD must adopt at least two active conformational states during OMP assembly, and that these charged residues are not required for function. Rather, these charged residues are important for coordinating the activities of BamA and BamD to allow efficient OMP assembly. We present a model of OMP assembly wherein recognition and binding of unfolded OMP substrate by BamA and BamD induce a signaling interaction between the two proteins, causing conformational changes necessary for the assembly reaction to proceed. By analogy to signal sequence recognition by SecYEG, we believe these BamA-BamD interactions ensure that both substrate and complex are competent for OMP assembly before the assembly reaction commences.IMPORTANCE Conformational changes in the proteins of the ß-barrel assembly machine (Bam complex) are associated with the folding and assembly of outer membrane proteins (OMPs) in Gram-negative bacteria. We show that electrostatic interactions between the two essential proteins BamA and BamD coordinate conformational changes upon binding of unfolded substrate that allow the assembly reaction to proceed. Mutations affecting this interaction are lethal not because they destabilize the Bam complex but rather because they disrupt this coordination. Our model of BamA-BamD interactions regulating conformation in response to proper substrate interaction is reminiscent of conformational changes the secretory (Sec) machinery undergoes after signal sequence recognition that ensure protein quality control.


Asunto(s)
Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/química , Escherichia coli/metabolismo , Multimerización de Proteína , Proteínas de la Membrana Bacteriana Externa/química , Proteínas de la Membrana Bacteriana Externa/genética , Análisis Mutacional de ADN , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Modelos Biológicos , Modelos Moleculares , Conformación Proteica
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