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1.
Vis Neurosci ; 41: E002, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38725382

RESUMO

Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.


Assuntos
Células Fotorreceptoras Retinianas Cones , Degeneração Retiniana , Sciuridae , Tomografia de Coerência Óptica , Animais , Degeneração Retiniana/induzido quimicamente , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Cones/patologia , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Modelos Animais de Doenças , Injeções Intravítreas , Oftalmoscopia , Nitroprussiato/farmacologia , Feminino , Masculino
2.
J Burn Care Res ; 45(3): 655-659, 2024 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-38520289

RESUMO

While most friction burns are adequately managed in an outpatient setting, many may require hospital admission, operative excision, and extended care. To this day, there is a wide variance in friction burn management. Our goal is to review the etiology, management, and outcomes of such burns warranting hospitalization. We conducted a retrospective review of all friction burns admitted to a single, American Burn Association-verified burn center from January 1, 2016 to December 31, 2020. A total of 28 (34%) patients required surgery for their friction burns and 15 (18%) ultimately required a split-thickness skin graft. The mean number of operations was 2.4 (95% CI 1.6-3.1). Overall, the operative group was younger (29.9 vs 38.3 years, P = .026), more likely to have a concomitant traumatic brain injury (25% vs 7%, P = .027), and had a longer hospital length of stay (17.5 vs 3.9 days, P < .001). Both groups had a similar overall TBSA (8.5% vs 10.0%, P = .35), but the operative group had a larger surface area comprised of third-degree burns (3.05% vs 0.2%, P < .001). Overall, friction burns resulting in hospital admission are associated with high-energy traumatic mechanisms and concomitant injuries. Patients who need operative intervention for their burns typically require multiple procedures often culminating in a split-thickness skin graft. While non-operative management of friction burns with topical agents has been found to be successful, patients with higher injury severity scores should be monitored very closely as they may require surgical excision.


Assuntos
Queimaduras , Fricção , Transplante de Pele , Humanos , Queimaduras/terapia , Masculino , Estudos Retrospectivos , Adulto , Feminino , Tempo de Internação/estatística & dados numéricos , Alta do Paciente , Unidades de Queimados , Pessoa de Meia-Idade , Hospitalização
3.
Stem Cell Reports ; 19(3): 331-342, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38335965

RESUMO

Several retinal degenerations affect the human central retina, which is primarily comprised of cones and is essential for high acuity and color vision. Transplanting cone photoreceptors is a promising strategy to replace degenerated cones in this region. Although this approach has been investigated in a handful of animal models, commonly used rodent models lack a cone-rich region and larger models can be expensive and inaccessible, impeding the translation of therapies. Here, we transplanted dissociated GFP-expressing photoreceptors from retinal organoids differentiated from human induced pluripotent stem cells into the subretinal space of damaged and undamaged cone-dominant 13-lined ground squirrel eyes. Transplanted cell survival was documented via noninvasive high-resolution imaging and immunohistochemistry to confirm the presence of human donor photoreceptors for up to 4 months posttransplantation. These results demonstrate the utility of a cone-dominant rodent model for advancing the clinical translation of cell replacement therapies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Degeneração Retiniana , Animais , Humanos , Células Fotorreceptoras Retinianas Cones/transplante , Células-Tronco Pluripotentes Induzidas/transplante , Retina , Degeneração Retiniana/terapia , Sciuridae
4.
Chest ; 164(3): e61-e63, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37689474

RESUMO

Venous bullet embolism is an exceedingly rare trauma diagnosis that presents diagnostic and therapeutic challenges. We present the case of a 32-year-old man who sustained multiple gunshot wounds with a venous bullet embolism to the right pulmonary artery. Imaging at first demonstrated a bullet lodged within the right lower lobe. The patient underwent multiple bronchoscopies and ultimately was found to have a bullet embolus in the right pulmonary artery. Repeat endovascular attempts failed at removal, and during a right thoracotomy, the bullet migrated to the left pulmonary artery. Coil embolization of the left lower lobe pulmonary artery was performed, and the patient was found to be asymptomatic at the 1-year follow-up. To our knowledge, this is the first case to demonstrate coil embolization of the pulmonary artery as a method of endovascular treatment for a venous bullet embolus. We present this case report to emphasize the difficulty in diagnosis, localization, and management of a migratory bullet within the pulmonary circulation.


Assuntos
Traumatismo Múltiplo , Ferimentos por Arma de Fogo , Masculino , Humanos , Adulto , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/diagnóstico , Artéria Pulmonar/diagnóstico por imagem , Prótese Vascular , Broncoscopia
5.
J Trauma Acute Care Surg ; 93(1): 130-134, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35727592

RESUMO

BACKGROUND: This study examines the rates of pediatric auto versus pedestrian collision (APCs) and determined ages and periods of greatest risk. We hypothesized that the rate of APC in children would be higher on school days and in the timeframes correlating with travel to and from school. METHODS: Retrospective case-control study of APC on school and nonschool days for patients younger than 18 years at an urban Level II pediatric trauma center from January 2011 to November 2019. Frequency of APC by hour of the day was plotted overall, for school versus nonschool days and for age groups: 0 year to 4 years, 5 years to 9 years, 10 years to 13 years, and 14 years to 17 years. t Test was used with a p value less than 0.05, which was considered significant. RESULTS: There were 441 pediatric APC in the study period. Frequency of all APC was greater on school days (0.174 vs. 0.101; relative risk [RR], 1.72, p < 0.001), and APC with Injury Severity Score greater than 15 (0.039 vs. 0.024; p = 0.014; RR, 1.67; 95% confidence interval, 1.10-2.56). Comparing school day with nonschool day, the 0-year to 4-year group had no significant difference in APC frequency (0.021 vs. 0.014; p = 0.129), APC frequency was higher on school days in all other age groups: 5 years to 9 years (0.036 vs. 0.019; RR, 1.89; p = 0.0134), 10 years to 13 years (0.055 vs. 0.024; RR, 2.29; p < 0.001), and 14 years to 17 years (0.061 vs. 0.044; RR, 1.39; p = 0.045). The greatest increase in APC on school days was in the 10-year to 13-year age group. DISCUSSION: All school age children are at higher risk of APC on school days. The data support our hypothesis that children are at higher risk of APC during transit to and from school. The age 10-year to 13-year group had a 129% increase in APC frequency on school days. This age group should be a focus of injury prevention efforts. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.


Assuntos
Acidentes de Trânsito , Pedestres , Acidentes de Trânsito/prevenção & controle , Estudos de Casos e Controles , Criança , Pré-Escolar , Humanos , Recém-Nascido , Escala de Gravidade do Ferimento , Estudos Retrospectivos
6.
Am J Prev Med ; 62(2): 203-210, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34649735

RESUMO

INTRODUCTION: Colorectal cancer is the second leading cause of cancer deaths in Latinos in the U.S., but it is unclear, from previous research, whether Latinos have differing rates of colorectal cancer screening methods from those of non-Hispanic Whites. METHODS: This study used electronic health records from 686 community health centers across 21 states in the Accelerating Data Value Across a National Community Health Center of the National Patient-Centered Clinical Research Network. Records from English-preferring Latinos, Spanish-preferring Latinos, and non-Hispanic Whites aged 50-75 years were included. A total of 5 outcomes were compared between 2012 and 2017 to provide a comprehensive view of colorectal cancer screening: (1) any colorectal cancer screening, (2) stool-based screening, (3) annual rates of stool testing, (4) any referral for lower gastrointestinal endoscopy, and (5) endoscopy referral among patients with a positive stool-based screening. RESULTS: In this study (N=204,243), Spanish-preferring Latinos had higher odds of any colorectal cancer screening (OR=1.44, 95% CI=1.23, 1.68) and stool-based testing (OR=1.82, 95% CI=1.55, 2.13) than non-Hispanic Whites. English- and Spanish-preferring Latinos had lower odds of having ever had a referral for endoscopy in the study period than non-Hispanic Whites (English: OR=0.23, 95% CI=0.15, 0.34; Spanish: OR=0.55, 95% CI=0.40, 0.74), even with a positive stool-based screening (English: OR=0.14, 95% CI=0.06, 0.33; Spanish: OR=0.33, 95% CI=0.19, 0.57). CONCLUSIONS: In a multistate network of community health centers, Latino patients aged >50 years were more likely to receive stool-based screening tests for colorectal cancer than non-Hispanic Whites but were less likely to receive endoscopy referrals than non-Hispanic Whites, even when experiencing a positive stool-based screening test. Initiatives to improve Latino colorectal cancer outcomes should encourage indicated referrals for lower gastrointestinal endoscopy.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Disparidades em Assistência à Saúde , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etnologia , Hispânico ou Latino , Programas de Rastreamento , Brancos , Estados Unidos , Disparidades em Assistência à Saúde/etnologia
7.
Mol Ther Methods Clin Dev ; 22: 96-106, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34485598

RESUMO

Intravitreal injection is the most widely used injection technique for ocular gene delivery. However, vector diffusion is attenuated by physical barriers and neutralizing antibodies in the vitreous. The 13-lined ground squirrel (13-LGS), as in humans, has a larger relative vitreous body volume than the more common rodent models such as rats and mice, which would further reduce transduction efficiency with the intravitreal injection route. We report here a "pre-retinal" injection approach that leads to detachment of the posterior hyaloid membrane and delivers vector into the space between vitreous and inner retina. Vectors carrying a ubiquitously expressing mCherry reporter were injected into the deep vitreous or pre-retinal space in adult wild-type 13-LGSs. Then, adeno-associated virus (AAV)-mediated mCherry expression was evaluated with non-invasive imaging, immunofluorescence, and flow cytometry. Compared to deep vitreous delivery, pre-retinal administration achieved pan-retinal gene expression with a lower vector dose volume and significantly increased the number of transduced cone photoreceptors. These results suggest that pre-retinal injection is a promising tool in the development of gene therapy strategies in animal models and is a potential approach for use in human research, particularly in younger individuals with an intact posterior hyaloid membrane and stable vitreous.

8.
J Burn Care Res ; 42(6): 1254-1260, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34143185

RESUMO

Electronic cigarettes are advertised as safer alternatives to traditional cigarettes yet cause serious injury. U.S. burn centers have witnessed a rise in both inpatient and outpatient visits to treat thermal injuries related to their use. A multicenter retrospective chart review of American Burn Association burn registry data from five large burn centers was performed from January 2015 to July 2019 to identify patients with electronic cigarette-related injuries. A total of 127 patients were identified. Most sustained less than 10% total body surface area burns (mean 3.8%). Sixty-six percent sustained second-degree burns. Most patients (78%) were injured while using their device. Eighteen percent of patients reported spontaneous device combustion. Two patients were injured while changing their device battery, and two were injured modifying their device. Three percent were injured by secondhand mechanism. Burn injury was the most common injury pattern (100%), followed by blast injury (3.93%). Flame burns were the most common (70%) type of thermal injury; however, most patients sustained a combination-type injury secondary to multiple burn mechanisms. The most injured body region was the extremities. Silver sulfadiazine was the most common agent used in the initial management of thermal injuries. Sixty-three percent of patients did not require surgery. Of the 36% requiring surgery, 43.4% required skin grafting. Multiple surgeries were uncommon. Our data recognize electronic cigarette use as a public health problem with the potential to cause thermal injury and secondary trauma. Most patients are treated on an inpatient basis although most patients treated on an outpatient basis have good outcomes.


Assuntos
Traumatismos por Explosões/complicações , Traumatismos por Explosões/diagnóstico , Queimaduras/diagnóstico , Queimaduras/etiologia , Escala de Gravidade do Ferimento , Adulto , Álcalis/efeitos adversos , Queimaduras Químicas/etiologia , Sistemas Eletrônicos de Liberação de Nicotina , Traumatismos Faciais/etiologia , Feminino , Traumatismos da Mão/etiologia , Humanos , Masculino , Estudos Retrospectivos , Medição de Risco
9.
J Grad Med Educ ; 13(1): 113-118, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33680310

RESUMO

BACKGROUND: Surgical residency training has an extended tradition of long hours. Residency programs use a variety of call schedules to combat resident fatigue and sleep deprivation while maintaining adherence to duty hour restrictions. Nonetheless, there is a paucity of data regarding objective measurements of sleep during the different call schedules included in general surgery training. OBJECTIVE: The primary objective of this study was to compare the quantity of sleep in 24-hour time frames across all types of shifts worked by general surgery residents at our institution. The secondary objective was to measure activity level in total steps during various time frames. METHODS: This prospective observational study was performed between April 4 and August 26, 2018, with general surgery residents. Each resident was assigned a Fitbit Charge 2 to wear during all rotations, including general surgery and subspecialty services. RESULTS: Twenty-six out of 31 residents voluntarily participated in the study (84%). In-house call (IHC) had significantly less sleep in a 24-hour time frame than home call and night float (144 vs 283 vs 246 minutes, P < .001 and P < .028). IHC had significantly more steps than home call (11 245 vs 8756 steps, P = .039). The smallest number of steps was obtained when residents were not working (7904 steps). CONCLUSIONS: Our data demonstrate that surgical residents on IHC have significantly less sleep compared to all other types of on-call time frames. Residents on IHC have the most steps across all time frames.


Assuntos
Internato e Residência , Exercício Físico , Fadiga , Humanos , Admissão e Escalonamento de Pessoal , Sono , Privação do Sono , Tolerância ao Trabalho Programado , Carga de Trabalho
10.
Vasc Endovascular Surg ; 55(2): 105-111, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33063647

RESUMO

OBJECTIVES: The most widely accepted grading system for blunt traumatic aortic injury (BTAI) by the Society of Vascular Surgery (SVS) recommends endovascular repair for grade 2 and greater. Non-operative management in grade 2 injuries has been shown to be reasonable in certain circumstances. The natural history of low-grade injuries (1, 2) when managed non-operatively is not well defined. METHODS: Utilizing our trauma registry, patients from 2013 to 2016 with blunt traumatic injury who underwent initial computed tomography were identified. Aortic pathology was graded and grouped by SVS classification. Clinical courses were reviewed for timing of interventions, repeat imaging, concurrent injuries, and outcomes. Analysis of variance and Chi-square tests of significance were utilized to compare between groups. RESULTS: Out of 10,178 patients, we identified 32 with BTAI (grade: 1 (n = 13), 2 (n = 5), 3 (n = 3), 4 (n = 11)). High-grade injuries (3, 4) resulted only from motor vehicle, motorcycle, and pedestrian mechanisms. Initially, 9 patients (28%) required intervention, 5 (16%) were treated non-operatively, and 18 (56%) underwent repeat imaging. On repeat imaging, injuries that did not resolve remained stable and no injuries were found to progress. Of these patients, 9 (50%) required delayed intervention and 9 (50%) successfully underwent non-operative management. Patients with low-grade injuries were more likely to have successful non-operative management than those with high-grade injuries (72% vs 7%; p < 0.01). CONCLUSIONS: While low-grade injuries generally have good outcomes, some ultimately do require delayed intervention, and short-term imaging is not reliable in identifying these cases.


Assuntos
Aorta/cirurgia , Procedimentos Endovasculares , Centros de Traumatologia , Procedimentos Cirúrgicos Vasculares , Lesões do Sistema Vascular/terapia , Ferimentos não Penetrantes/terapia , Adolescente , Adulto , Aorta/diagnóstico por imagem , Aorta/lesões , Aortografia , Criança , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Lesões do Sistema Vascular/diagnóstico por imagem , Ferimentos não Penetrantes/diagnóstico por imagem , Adulto Jovem
11.
Sci Rep ; 10(1): 20382, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230161

RESUMO

Photobiomodulation (PBM) by far-red (FR) to near-infrared (NIR) light has been demonstrated to restore the function of damaged mitochondria, increase the production of cytoprotective factors and prevent cell death. Our laboratory has shown that FR PBM improves functional and structural outcomes in animal models of retinal injury and retinal degenerative disease. The current study tested the hypothesis that a brief course of NIR (830 nm) PBM would preserve mitochondrial metabolic state and attenuate photoreceptor loss in a model of retinitis pigmentosa, the P23H transgenic rat. P23H rat pups were treated with 830 nm light (180 s; 25 mW/cm2; 4.5 J/cm2) using a light-emitting diode array (Quantum Devices, Barneveld, WI) from postnatal day (p) 10 to p25. Sham-treated rats were restrained, but not treated with 830 nm light. Retinal metabolic state, function and morphology were assessed at p30 by measurement of mitochondrial redox (NADH/FAD) state by 3D optical cryo-imaging, electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), and histomorphometry. PBM preserved retinal metabolic state, retinal function, and retinal morphology in PBM-treated animals compared to the sham-treated group. PBM protected against the disruption of the oxidation state of the mitochondrial respiratory chain observed in sham-treated animals. Scotopic ERG responses over a range of flash intensities were significantly greater in PBM-treated rats compared to sham controls. SD-OCT studies and histological assessment showed that PBM preserved the structural integrity of the retina. These findings demonstrate for the first time a direct effect of NIR PBM on retinal mitochondrial redox status in a well-established model of retinal disease. They show that chronic proteotoxic stress disrupts retinal bioenergetics resulting in mitochondrial dysfunction, and retinal degeneration and that therapies normalizing mitochondrial metabolism have considerable potential for the treatment of retinal degenerative disease.


Assuntos
Metabolismo Energético/efeitos da radiação , Terapia com Luz de Baixa Intensidade/métodos , Mitocôndrias/efeitos da radiação , Degeneração Retiniana/radioterapia , Retinose Pigmentar/radioterapia , Animais , Modelos Animais de Doenças , Eletrorretinografia , Flavina-Adenina Dinucleotídeo/metabolismo , Raios Infravermelhos , Mitocôndrias/metabolismo , NAD/metabolismo , Oxirredução , Ratos , Ratos Transgênicos , Degeneração Retiniana/diagnóstico por imagem , Degeneração Retiniana/metabolismo , Degeneração Retiniana/patologia , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/patologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos da radiação , Retinose Pigmentar/diagnóstico por imagem , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologia , Tomografia de Coerência Óptica , Resultado do Tratamento
12.
J Trauma Acute Care Surg ; 89(4): 691-697, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32590561

RESUMO

BACKGROUND: Traumatic esophageal perforation is rare and associated with significant morbidity and mortality. There is substantial variability in diagnosis and treatment. Esophageal stents have been increasingly used for nontraumatic perforation; however, stenting for traumatic perforation is not yet standard of care. The purpose of this study was to evaluate current management of traumatic esophageal perforation to assess the frequency of and complications associated with esophageal stenting. METHODS: This was an Eastern Association for the Surgery of Trauma multi-institutional retrospective study from 2011 to 2016 of patients with traumatic cervical or thoracic esophageal injury admitted to one of 11 participating trauma centers. Data were collected and sent to a single institution where it was analyzed. Patient demographics, injury characteristics, initial management, complications, and patient mortality were collected. Primary outcome was mortality; secondary outcomes were initial treatment, esophageal leak, and associated complications. RESULTS: Fifty-one patients were analyzed. Esophageal injuries were cervical in 69% and thoracic in 31%. Most patients were initially managed with operative primary repair (61%), followed by no intervention (19%), esophageal stenting (10%), and wide local drainage (10%). Compared with patients who underwent operative primary repair, patients managed with esophageal stenting had an increased rate of esophageal leak (22.6% vs. 80.0%, p = 0.02). Complication rates were higher in blunt compared with penetrating mechanisms (100% vs. 31.8%, p = 0.03) despite similar Injury Severity Score and neck/chest/abdomen Abbreviated Injury Scale. Overall mortality was 9.8% and did not vary based on location of injury, mechanism of injury, or initial management. CONCLUSION: Most patients with traumatic esophageal injuries still undergo operative primary repair; this is associated with lower rates of postoperative leaks as compared with esophageal stenting. Patients who have traumatic esophageal injury may be best managed by direct repair and not esophageal stenting, although further study is needed. LEVEL OF EVIDENCE: Therapeutic, level IV.


Assuntos
Perfuração Esofágica/cirurgia , Lesões do Pescoço/complicações , Traumatismos Torácicos/complicações , Centros de Traumatologia , Adulto , Drenagem/efeitos adversos , Perfuração Esofágica/etiologia , Perfuração Esofágica/mortalidade , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Stents/efeitos adversos , Estados Unidos , Adulto Jovem
13.
Invest Ophthalmol Vis Sci ; 61(6): 48, 2020 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-32574351

RESUMO

Purpose: To image retinal macrophages at the vitreoretinal interface in the living human retina using a clinical optical coherence tomography (OCT) device. Methods: Eighteen healthy controls and three patients with retinopathies were imaged using a clinical spectral-domain OCT. In controls, 10 sequential scans were collected at three different locations: (1) ∼9 degrees temporal to the fovea, (2) the macula, and (3) the optic nerve head (ONH). Intervisit repeatability was evaluated by imaging the temporal retina twice on the same day and 3 days later. Only 10 scans at the temporal retina were obtained from each patient. A 3-µm OCT reflectance (OCT-R) slab located above the inner limiting membrane (ILM) surface was averaged. Results: In controls, ramified macrophage-like cells with regular spatial separation were visualized in the temporal and ONH OCT-R images; however, cell structures were not resolvable at the macula. Interim changes in cell position suggestive of cell translocation were observed between images collected on the same day and those collected 3 days later. There was considerable variation in cell density and nearest-neighbor distance (NND) across controls. Mean ± SD cell densities measured at the temporal and ONH were 78 ± 23 cells/mm2 and 57 ± 16 cells/mm2, respectively. Similarly, mean ± SD NNDs measured at the temporal and ONH were 74.3 ± 13.3 µm and 93.3 ± 20.0 µm, respectively. Nonuniform spatial distribution and altered morphology of the cells were identified in patients with retinopathies. Conclusions: Our findings showed regular spatial separation and ramified morphology of macrophage-like cells on the ILM surface with cell translocation over time in controls. Their distribution and morphology suggest an origin of macrophage-like cells such as microglia or hyalocytes.


Assuntos
Macrófagos/patologia , Disco Óptico/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Adulto , Feminino , Humanos , Masculino , Fibras Nervosas/patologia , Adulto Jovem
14.
Am J Ophthalmol ; 219: 87-100, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32446738

RESUMO

PURPOSE: To report baseline visual fields in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study. DESIGN: Cross-sectional study within a natural history study. METHODS: Setting: multicenter, international. STUDY POPULATION: Usher syndrome type 2 (USH2) (n = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) (n = 47) associated with biallelic disease-causing sequence variants in USH2A. OBSERVATION PROCEDURES: Repeatability of full-field static perimetry (SP) and between-eye symmetry of kinetic perimetry (KP) were evaluated with intraclass correlation coefficients (ICCs). The association of demographic and clinical characteristics with total hill of vision (VTOT) was assessed with general linear models. Associations between VTOT and other functional and morphologic measures were assessed using Spearman correlation coefficients and t tests. MAIN OUTCOME MEASURES: VTOT (SP) and III4e isopter area (KP). RESULTS: USH2 participants had more severe visual field loss than ARRP participants (P < .001, adjusting for disease duration, age of enrollment). Mean VTOT measures among 3 repeat tests were 32.7 ± 24.1, 31.2 ± 23.4, and 31.7 ± 23.9 decibel-steradians (intraclass correlation coefficient [ICC] = 0.96). Better VA, greater photopic ERG 30-Hz flicker amplitudes, higher mean microperimetry sensitivity, higher central subfield thickness, absence of macular cysts, and higher III4e seeing area were associated with higher VTOT (all r > .48; P < .05). Mean III4e isopter areas for left (4561 ± 4426 squared degrees) and right eyes (4215 ± 4300 squared degrees) were concordant (ICC = 0.94). CONCLUSIONS: USH2 participants had more visual field loss than participants with USH2A-related ARRP, adjusting for duration of disease and age of enrollment. VTOT was repeatable and correlated with other functional and structural metrics, suggesting it may be a good summary measure of disease severity in patients with USH2A-related retinal degeneration.


Assuntos
Proteínas da Matriz Extracelular/genética , Retinose Pigmentar/diagnóstico , Síndromes de Usher/diagnóstico , Transtornos da Visão/diagnóstico , Campos Visuais/fisiologia , Adulto , Estudos Transversais , Progressão da Doença , Eletrorretinografia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Retina/fisiopatologia , Retinose Pigmentar/genética , Retinose Pigmentar/fisiopatologia , Índice de Gravidade de Doença , Síndromes de Usher/genética , Síndromes de Usher/fisiopatologia , Transtornos da Visão/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo Visual
15.
Am J Pathol ; 189(2): 320-338, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30472209

RESUMO

Farber disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene, resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classic cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus. That said, the full effect of ACDase deficiency on the visual system has not been studied in detail. We previously developed a mouse model that is orthologous for a known patient mutation in Asah1 that recapitulates human FD. Herein, we report evidence of a severe ocular pathology in Asah1P361R/P361R mice. Asah1P361R/P361R mice exhibit progressive retinal and optic nerve pathology. Through noninvasive ocular imaging and histopathological analyses of these Asah1P361R/P361R animals, we revealed progressive inflammation, the presence of retinal dysplasia, and significant storage pathology in various cell types in both the retina and optic nerves. Lipidomic analyses of retinal tissues revealed an abnormal accumulation of ceramides and other sphingolipids. Electroretinograms and behavioral tests showed decreased retinal and visual responses. Taken together, these data suggest that ACDase deficiency leads to sphingolipid imbalance, inflammation, dysmorphic retinal and optic nerve pathology, and severe visual impairment.


Assuntos
Ceramidase Ácida/genética , Lipogranulomatose de Farber , Mutação de Sentido Incorreto , Nervo Óptico , Retina , Transtornos da Visão , Ceramidase Ácida/metabolismo , Substituição de Aminoácidos , Animais , Ceramidas/genética , Ceramidas/metabolismo , Modelos Animais de Doenças , Lipogranulomatose de Farber/enzimologia , Lipogranulomatose de Farber/genética , Lipogranulomatose de Farber/patologia , Inflamação/enzimologia , Inflamação/genética , Inflamação/patologia , Camundongos , Camundongos Mutantes , Nervo Óptico/enzimologia , Nervo Óptico/patologia , Retina/enzimologia , Retina/patologia , Esfingolipídeos/genética , Esfingolipídeos/metabolismo , Transtornos da Visão/enzimologia , Transtornos da Visão/genética , Transtornos da Visão/patologia
16.
Nature ; 562(7728): 526-531, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30333627

RESUMO

The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Genoma Humano/genética , Genômica , Leucemia Mieloide Aguda/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , DNA (Citosina-5-)-Metiltransferases/genética , DNA Metiltransferase 3A , Conjuntos de Dados como Assunto , Exoma/genética , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Masculino , Terapia de Alvo Molecular , Proteínas Nucleares/genética , Nucleofosmina , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Análise de Sequência de RNA , Fatores de Processamento de Serina-Arginina/genética
17.
Opt Lett ; 43(11): 2470-2473, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29856406

RESUMO

Indocyanine green (ICG) is routinely used during surgery to stain the inner limiting membrane (ILM) and provide contrast on white light surgical microscopy. While translation of optical coherence tomography (OCT) for intraoperative imaging during ophthalmic surgery has enhanced visualization, the ILM remains difficult to distinguish from underlying retinal structures and ICG does not provide additional OCT contrast. We present photothermal OCT (PT-OCT) for high-specificity detection of ICG on retinal OCT images. We demonstrate our technique by performing an ILM peel in ex vivo eyes using low ICG concentrations and laser powers. These results establish the feasibility of PT-OCT for intraoperative guidance during retinal surgery.


Assuntos
Membrana Basal/diagnóstico por imagem , Corantes/administração & dosagem , Membrana Epirretiniana/diagnóstico por imagem , Verde de Indocianina/administração & dosagem , Tomografia de Coerência Óptica/métodos , Animais , Retina/diagnóstico por imagem , Suínos
18.
Am J Surg ; 215(3): 498-501, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29198854

RESUMO

BACKGROUND: The purpose of this study was to compare patient outcomes for thoracic epidural anesthesia (TEA) with transversus abdominis plane (TAP) blocks. METHODS: A prospective, randomized trial was performed for patients undergoing abdominal oncologic surgeries. RESULTS: There were 32 TAP and 35 TEA subjects. The TEA group demonstrated increased episodes of hypotension in the first 24 h (3 v 0.6, p = 0.02). There was no difference in 24-48 h fluid balance between the groups. Overall parenteral morphine equivalents of opioids administered for the TEA group were higher for each postoperative day (p < 0.05). The post-operative survey did not demonstrate any difference in subjective pain between the TAP and TEA groups (6 v 6 p = 0.35). There was no attributable morbidity associated with either technique. CONCLUSIONS: TAP block use was associated with lower parenteral morphine equivalent usage and decreased incidence of hypotension in the early post-operative period compared to TEA.


Assuntos
Músculos Abdominais/inervação , Neoplasias Abdominais/cirurgia , Anestesia Epidural , Hipotensão/etiologia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Abdome/inervação , Abdome/cirurgia , Adulto , Idoso , Feminino , Hidratação , Humanos , Hipotensão/prevenção & controle , Hipotensão/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vértebras Torácicas , Resultado do Tratamento
19.
Ophthalmology ; 125(3): 444-452, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29103792

RESUMO

PURPOSE: To characterize and quantify early foveal development in preterm infants and to compare this development between eyes treated with intravitreal bevacizumab or laser photocoagulation (LPC) and untreated eyes. DESIGN: Observational case series. PARTICIPANTS: One hundred thirty-one preterm infants undergoing retinopathy of prematurity (ROP) screenings. METHODS: Handheld OCT imaging was performed longitudinally on all patients. Thickness measurements of the inner and outer retinal layers were obtained at the foveal center and the nasal and temporal foveal rims. Comparisons between treated and untreated eyes were adjusted for age and other confounding variables. MAIN OUTCOME MEASURES: Weekly change in inner and outer retinal thickness and presence of inner retinal layers, ellipsoid zone (EZ), and cystoid macular changes (CMCs). RESULTS: Outer retinal thickness at the foveal center increased by 3.1 µm/week in untreated eyes and 7.2 µm/week in bevacizumab-treated eyes (P = 0.038). Eyes treated with LPC had a lower probability of having all inner retinal layers present at the foveal center (odds ratio, 0.04; P = 0.001) and a lower probability of having the EZ present at the foveal center (odds ratio, 0.07; P = 0.024) compared with untreated eyes. Cystoid macular changes were found in 53% of patients and 22% of imaging sessions. The age-adjusted incidence of CMCs was not correlated with bevacizumab or LPC treatment. CONCLUSIONS: Intravitreal bevacizumab therapy for ROP is associated with more rapid outer retinal thickening at the foveal center, whereas LPC is associated with earlier extrusion of the inner retinal layers and delayed development of the EZ at the foveal center. Long-term follow-up is needed to determine the visual significance of these findings.


Assuntos
Bevacizumab/administração & dosagem , Fóvea Central/patologia , Recém-Nascido Prematuro , Fotocoagulação a Laser/métodos , Retinopatia da Prematuridade/terapia , Acuidade Visual/fisiologia , Inibidores da Angiogênese/administração & dosagem , Progressão da Doença , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Injeções Intravítreas , Masculino , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/fisiopatologia , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento
20.
Vision Res ; 132: 3-33, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28212982

RESUMO

Adaptive optics is a relatively new field, yet it is spreading rapidly and allows new questions to be asked about how the visual system is organized. The editors of this feature issue have posed a series of question to scientists involved in using adaptive optics in vision science. The questions are focused on three main areas. In the first we investigate the use of adaptive optics for psychophysical measurements of visual system function and for improving the optics of the eye. In the second, we look at the applications and impact of adaptive optics on retinal imaging and its promise for basic and applied research. In the third, we explore how adaptive optics is being used to improve our understanding of the neurophysiology of the visual system.


Assuntos
Fenômenos Fisiológicos Oculares , Óptica e Fotônica , Retina/fisiologia , Transtornos da Visão/reabilitação , Percepção Visual/fisiologia , Animais , Humanos , Psicofísica , Transtornos da Visão/fisiopatologia , Visão Ocular/fisiologia
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