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1.
Artigo em Inglês | MEDLINE | ID: mdl-38917392

RESUMO

BACKGROUND AND OBJECTIVE: The Food and Drug Administration recently approved treatments of geographic atrophy (GA). Our study aims to quantify the time for a lesion to reach the central fovea based on reduction of GA growth rates from therapeutics compared to the natural history. PATIENTS AND METHODS: A previously published study calculates local border expansion rate of GA lesions at varying retinal eccentricities. In this study, we use these rates to model GA expansion toward the fovea and the effects of treatments that reduce growth in GA area by 15% to 45% on lesions of varying sizes with posterior margin 250, 500, 750, 1000, 1250, 1500, and 3000 µm from the fovea. RESULTS: Lesions with an area 8 mm2 and posterior edge 500 µm from the fovea will reach the fovea in 5.08 years with no treatment, but the same lesions will reach the fovea in 5.85, 6.52, 7.36, and 8.46 years with a treatment that reduces growth in GA area by 15%, 25%, 35%, and 45%, respectively. CONCLUSIONS: Distance of the posterior edge of the lesion was the primary factor in GA growth toward the fovea, and lesion size only minimally affects growth rates of GA. Based on the efficacy of current and future therapeutics and distance of GA to the fovea, our study provides the marginal time benefit of treatment to guide patients and clinicians, placing both the natural history of GA and the effects of current and future treatments into clinical context. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

2.
Int J Ophthalmol ; 17(3): 564-569, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721505

RESUMO

AIM: To evaluate the efficacy of pneumatic retinopexy (PR) in patients undergoing PR as primary treatment for rhegmatogenous retinal detachment (RRD) and analyze the factors associated with success and failure in the studied population. METHODS: A retrospective chart review was done of patients with RRD treated with PR as primary management method treated at New York Eye and Ear Infirmary of Mount Sinai between January 2017 and December 2021. Primary outcome measured success or failure of PR. Secondary outcome measured best corrected visual acuity (BCVA) after PR. A separate risk analysis was done to identify and stratify risks associated with success and failure of PR. RESULTS: A total of 179 eyes from 179 patients were included for final analysis. The 83 patients (46.37%) achieved anatomical reattachment of the retina after primary PR with no need for additional surgery. The 96 patients (53.63%) had a failed primary PR and required a PPV and 6 of them required pars plana vitrectomy (PPV) with scleral buckle (SB). In total, 19 cases (10.61%) were done as temporizing pneumatics, 18 (94.74%) underwent PPV, and 1 (5.26%) did not require further intervention. The visual acuities at postoperative month 1 (POM1) for patients who underwent primary PR successfully and for those that underwent PPV after, were 0.58 (20/80) and 1.03 (20/200) respectively. Patients who met Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) criteria had a statistically significant decreased risk of primary PR failing (hazard ratio 0.29, P=0.00). Majority of missed or new breaks were found superotemporally. CONCLUSION: PR is a good treatment option for treating RRDs in patients that meet PIVOT criteria and can be conducted as a temporizing measure. PIVOT criteria and fovea on status decrease the risk of PR failure.

3.
Retina ; 44(6): 954-964, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271674

RESUMO

PURPOSE: To determine how often ChatGPT is able to provide accurate and comprehensive information regarding clinical vitreoretinal scenarios. To assess the types of sources ChatGPT primarily uses and to determine whether they are hallucinated. METHODS: This was a retrospective cross-sectional study. The authors designed 40 open-ended clinical scenarios across four main topics in vitreoretinal disease. Responses were graded on correctness and comprehensiveness by three blinded retina specialists. The primary outcome was the number of clinical scenarios that ChatGPT answered correctly and comprehensively. Secondary outcomes included theoretical harm to patients, the distribution of the type of references used by the chatbot, and the frequency of hallucinated references. RESULTS: In June 2023, ChatGPT answered 83% of clinical scenarios (33/40) correctly but provided a comprehensive answer in only 52.5% of cases (21/40). Subgroup analysis demonstrated an average correct score of 86.7% in neovascular age-related macular degeneration, 100% in diabetic retinopathy, 76.7% in retinal vascular disease, and 70% in the surgical domain. There were six incorrect responses with one case (16.7%) of no harm, three cases (50%) of possible harm, and two cases (33.3%) of definitive harm. CONCLUSION: ChatGPT correctly answered more than 80% of complex open-ended vitreoretinal clinical scenarios, with a reduced capability to provide a comprehensive response.


Assuntos
Inteligência Artificial , Doenças Retinianas , Cirurgia Vitreorretiniana , Humanos , Estudos Transversais , Estudos Retrospectivos , Doenças Retinianas/cirurgia
4.
J Vitreoretin Dis ; 7(4): 329-332, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37927316

RESUMO

Purpose: To report a new modification of an illuminated endolaser to facilitate safe endophotocoagulation during chandelier-assisted scleral buckling surgery. Methods: This case series comprised phakic patients with rhegmatogenous retinal detachments (RRDs) who had primary scleral buckling with chandelier endoillumination, external drainage, and endophotocoagulation using the modified endolaser instrument. Results: All 6 patients had successful outcomes after primary scleral buckling for RD repair without significant intraoperative or postoperative complications. Conclusions: The new modified endolaser instrument can be safely used in a nonvitrectomized eye during chandelier scleral buckling.

5.
Ophthalmic Surg Lasers Imaging Retina ; 54(4): 218-222, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36884243

RESUMO

BACKGROUND AND OBJECTIVE: This study reports a case series of patients with persistent macular holes (MHs) who underwent human amniotic membrane subretinal placement to achieve successful anatomic MH closure. PATIENTS AND METHODS: This was a retrospective case series of patients with persistently open full-thickness MHs who underwent human amniotic membrane placement. Patients were observed up to 6 months postoperatively. RESULTS: Ten patients were included. The mean preoperative best-corrected visual acuity was 1.6 logMAR (20/800). Postoperatively, mean best-corrected visual acuity improved to 1.3 logMAR (20/400) at 1 month and 1.1 logMAR (20/250) by the 3- and 6-month visits. In all cases, the MH appeared closed at the 1-week visit and remained closed at their last follow-up. Optical coherence tomography showed closure in all cases. No adverse events were reported. CONCLUSIONS: Human amniotic membrane sub-retinal placement may serve as a useful surgical technique to assist in the closure of recalcitrant macular holes. [Ophthalmic Surg Lasers Imaging Retina 2023;54:218-222.].


Assuntos
Perfurações Retinianas , Humanos , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Âmnio , Vitrectomia/métodos , Acuidade Visual , Tamponamento Interno/métodos , Tomografia de Coerência Óptica , Membrana Basal/cirurgia
6.
BMJ Case Rep ; 15(12)2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36593595

RESUMO

A woman in her 70s experienced painless vision loss in the right eye for 1 month. Acute retinal necrosis-induced panuveitis was the referral diagnosis. With dense vitreous haze, a vitrectomy was performed for vitreous biopsy followed by multimodal imaging. Vitreous biopsy yielded negative PCR results for herpes viruses and only inflammatory cells. Post-vitrectomy imaging showed involuted but pervasive pigmentary foci in the outer retina and the retinal pigment epithelium. Concurrently, peripheral blood showed pancytosis with giant platelets and a Janus kinase 2 (JAK2) mutation, which prompted a haematological evaluation. CT and MRI revealed a right frontal lobe intra-axial mass, diagnosed as diffuse large B cell lymphoma (DLBCL). Subsequently, bone marrow aspirate confirmed the pathogenic V617F JAK2 mutation. Following chemotherapy, the patient achieved lymphoma regression and uveitic quiescence. This is the first case report of acute unilateral panuveitis in a patient with JAK2 mutation and DLBCL but without evidence of intraocular involvement.


Assuntos
Linfoma Difuso de Grandes Células B , Pan-Uveíte , Feminino , Humanos , Janus Quinase 2/genética , Pan-Uveíte/diagnóstico , Retina , Vitrectomia , Linfoma Difuso de Grandes Células B/diagnóstico , Mutação
7.
Eur J Ophthalmol ; 32(5): NP37-NP41, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33757333

RESUMO

BACKGROUND: Some patients with diabetic macular edema (DME) fail to completely respond to anti-vascular endothelial growth factor (VEGF) therapy. These patients have a high treatment burden in the absence of significant improvement. We investigate the role of intravitreal dexamethasone insert (IDI) in eyes with super-refractory DME. METHODS: A non-randomized interventional study was performed among eyes with super-refractory DME refractory to anti-VEGF therapy. Eyes were treated with IDI after failing clinical response to anti-VEGF, with a minimum of 15 prior. Failure to respond was defined as failure of vision to improve at least one line on Snellen Acuity chart, central subfield thickness (CST) greater than 320 µm, or failure of CST to improve by 10% or more. Eyes with glaucoma or prior uncontrolled steroid-responsive ocular hypertension were excluded. Patient outcomes were analyzed at weeks 6, 12, 24, and year 1. RESULTS: Six eyes of four patients were identified. All patients had failed aflibercept. The mean number of prior anti-VEGF injections was 34.5. Eyes received an average of 2.92 dexamethasone injections per person-year (PY) and required breakthrough anti-VEGF injection at 1.95/PY. Mean pre-treatment visual acuity was 0.475 LogMAR, improving to 0.342 at week 6, and 0.375 at 1 year. Mean CST pre-injection was 386.5 mm, improving to 315 mm at 1 year. No glaucoma developed. CONCLUSIONS: Intravitreal dexamethasone insert appears effective in eyes with super-refractory DME. IDI resulted in excellent anatomic improvement on SD-OCT as well as modest visual improvement. Injection burden was reduced in those who may otherwise receive years of monthly treatments.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Dexametasona , Diabetes Mellitus/tratamento farmacológico , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Fatores de Crescimento Endotelial/uso terapêutico , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular
9.
BMJ Open Ophthalmol ; 5(1): e000394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32201733

RESUMO

OBJECTIVE: Fovea-involving subretinal haemorrhage is challenging to manage with uncertain visual outcomes. We reviewed outcomes of patients with fovea-involving macular haemorrhage treated with pars plana vitrectomy (PPV) and subretinal tissue plasminogen activator (tPA) with pneumatic displacement. METHODS AND ANALYSIS: This is a retrospective interventional case series. All patients with submacular haemorrhage who underwent PPV with subretinal tPA injection were included. Reasons for exclusion encompassed patients who underwent intravitreal tPA injection in the office without surgery, insufficient follow-up or documentation. Primary outcomes of interest were postoperative visual acuity (VA) at month 1 and 3. Secondary outcomes were median VA at month 3 by location of haemorrhage and underlying diagnosis. RESULTS: Thirty-seven total patients were included. The mean age was 68.2 years, with 54.1% (20/37) females. The most common aetiology was exudative macular degeneration (43.2%), followed by undifferentiated choroidal neovascularisation (CNV) (18.9%), polypoidal choroidal vasculopathy (18.9%), traumatic CNV (10.8%), macroaneurysm (5.4%) and proliferative diabetic retinopathy (2.7%). Median preoperative VA was 20/2000, postoperative month 1 was 20/347 (p<0.01), improving to 20/152 (p<0.01) at month 3. Proportion of patients gaining vision 3+ lines in vision was 15/36 (42%). Mean preoperative central subfield thickness on optical coherence tomography was 512.2 µm for sub-retinal pigment epithelium haemorrhage and 648.2 µm for subretinal haemorrhage (p=0.48). Difference in VA by diagnosis was not significant (p=0.60). CONCLUSIONS: PPV with subretinal tPA injection and pneumatic displacement of submacular haemorrhage offers modest visual recovery for a diverse group of patients. Location of haemorrhage or specific diagnosis may not predict outcome.

10.
Am J Ophthalmol ; 214: 32-39, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31926887

RESUMO

PURPOSE: To assess the factors influencing the Medicare collections disparity between male and female ophthalmologists. DESIGN: Retrospective cohort study. METHODS: The Medicare Provider Utilization and Payment Data from 2012-2015 were combined with the 2015 Physician Compare National Downloadable file and US Census data. Three complementary regression models were generated for number of patients seen, number of services performed per patient, and the amount collected per service. Predictor variables included gender, calendar year, geography, years since medical school graduation, and subspecialty. RESULTS: After adjusting for age, geography, and subspecialty, women ophthalmologists collected 42% less as compared to male ophthalmologists, with the median male ophthalmologist out-earning the 75th-percentile female ophthalmologist across almost all age groups, practice categories, and geographic regions. Although women are entering more lucrative subspecialties (cataract and retina) at a higher rate than before, the percentage of women pursuing these subspecialties remains lower than that of men. CONCLUSIONS: Compared with men, women ophthalmologists see fewer patients and have lower Medicare collections. The observed gender gap in collections was highly persistent across years in practice, subspecialty, and geographic region. Future studies are warranted to examine whether the observed gender collections gap results from structural inequities, social circumstances, or personal choices.


Assuntos
Reembolso de Seguro de Saúde/economia , Medicare/economia , Oftalmologistas/tendências , Oftalmologia/economia , Médicas/tendências , Padrões de Prática Médica/economia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Estados Unidos
11.
Ophthalmic Surg Lasers Imaging Retina ; 47(6): 563-9, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27327286

RESUMO

BACKGROUND AND OBJECTIVE: To identify the clinical features, organisms, and treatment outcomes in patients with endophthalmitis associated with glaucoma drainage implants. PATIENTS AND METHODS: A retrospective noncomparative case series. RESULTS: Of the 13 patients, exposure occurred in eight eyes, including exposure of the tube in four eyes, exposure of the patch graft in three eyes, and exposure of the plate in one eye. In the remaining five eyes, either recent implant placement or conjunctival revision occurred. The most common organism was Staphylococcus epidermidis (five eyes). Intravitreal antibiotics were administered in all eyes, with the exception of one eye (primary evisceration). Removal of the implant was performed in six eyes and evisceration or enucleation was performed in three eyes. Median pre-infection visual acuity was 20/80 (range: 20/30 to hand motion). Visual acuity at last follow-up was no light perception (five eyes), light perception (two eyes), hand motion (one eye), and better than or equal to 20/200 (five eyes). CONCLUSION: Clinical features associated with endophthalmitis include implant exposure and a history of recent surgery. Staphylococcus epidermidis was the most common isolate. Although removal of the implant was performed in many patients, successful treatment was accomplished in some patients without removal. Visual outcomes were generally poor. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:563-569.].


Assuntos
Endoftalmite/etiologia , Infecções Oculares Bacterianas/etiologia , Implantes para Drenagem de Glaucoma/efeitos adversos , Glaucoma/cirurgia , Infecções Estafilocócicas/terapia , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Remoção de Dispositivo , Endoftalmite/diagnóstico , Endoftalmite/terapia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/etiologia , Staphylococcus epidermidis/isolamento & purificação , Acuidade Visual , Vitrectomia/métodos
12.
Ophthalmic Surg Lasers Imaging Retina ; 46(3): 391-2, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25835309

RESUMO

The objective of this report is to demonstrate that individuals with dome-shaped macula can develop persistent subretinal fluid due to abrupt changes in the thickness of the choroid, making it unlikely to be reported. Additionally, these patients often have pigment epithelial detachments, suggestive of possible choroidal neo-vascularization. These two qualities can often lead to persistent subretinal fluid that is refractory to treatment.


Assuntos
Corioide/patologia , Macula Lutea/patologia , Miopia Degenerativa/diagnóstico , Descolamento Retiniano/diagnóstico , Líquido Sub-Retiniano , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Acuidade Visual
13.
Retina ; 34(11): 2161-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25072648

RESUMO

PURPOSE: To assess for change in intraocular pressure (IOP) in neovascular age-related macular degeneration patients switched to aflibercept after receiving previous treatments of intravitreal bevacizumab or ranibizumab. METHODS: This is a retrospective chart review of the first 53 patients (53 eyes) treated with at least 2 injections of 2 mg in 0.05 mL of aflibercept by March 6, 2013, after at least 2 previous injections of 0.5 mg in 0.05 mL of ranibizumab with or without previous injections of 1.25 mg in 0.05 mL of bevacizumab. The analysis was restricted to the first such sequence within each patient. The last previous anti-vascular endothelial growth factor injection before the switch to aflibercept was ranibizumab in all cases included in the study. Each person served as his or her own control. The pre-aflibercept IOP in the before state (treatment with bevacizumab or ranibizumab) was the preinjection IOP measure before dilation at the visit of the first aflibercept injection. Statistical analysis was performed using Microsoft Excel. RESULTS: There were 41 patients who were first treated with ranibizumab followed by aflibercept and 12 patients treated with ranibizumab and bevacizumab followed by aflibercept. For each of these sequences, IOP in the treated eye during treatment with aflibercept (the after state) was computed in 3 different ways: the first IOP, the last IOP, and the mean IOP for the period when treated with aflibercept. The pooled data showed a mean pre-aflibercept (the before state) IOP of 14.87 that decreased to a mean first IOP of 14.57, mean last IOP of 13.79, and a mean IOP of 14.14 during aflibercept treatment. The inference is based on the pooled analysis. The 95% confidence interval for the differences (after minus before) were -0.30 (-1.12 to 0.52), -1.08 (-1.83 to -0.32), and -0.73 (-1.30 to -0.17) for the first, last, and mean IOPs, respectively. The corresponding P values were 0.46 for the first, 0.006 for the last, 0.01 for the mean IOP during the aflibercept treatment period. CONCLUSION: Intraocular pressure was found to be significantly lower in patients switched to aflibercept after previous treatments with ranibizumab and/or bevacizumab. Aflibercept may have a more favorable IOP safety profile in patients previously on other anti-vascular endothelial growth factor treatments.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Degeneração Macular , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Bevacizumab , Substituição de Medicamentos , Feminino , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/fisiopatologia , Masculino , Ranibizumab , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
14.
Ophthalmology ; 115(9): 1517-24, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18378315

RESUMO

PURPOSE: To compile a survey of complications during and after Descemet's stripping with automated endothelial keratoplasty (DSAEK) in 118 eyes conducted by cornea subspecialists at a single academic center. DESIGN: Retrospective case series. PARTICIPANTS: One hundred eighteen eyes undergoing DSAEK in 99 patients. METHODS: Outcomes of DSAEK performed in 118 eyes by 10 surgeons were reviewed retrospectively. Sixty-four eyes had pseudophakic bullous keratopathy. Forty-one had Fuchs' endothelial dystrophy and cataract. Three had aphakic bullous keratopathy. In 10 eyes, previous DSAEK performed at the same institution failed. Complications of DSAEK were noted from the intraoperative and postoperative periods. Detached DSAEK grafts were repositioned, rebubbled, or both immediately after diagnosis of this complication. MAIN OUTCOME MEASURES: Intraoperative and postoperative complications of DSAEK. RESULTS: Graft detachment was the most common type of complication encountered. In 27 (23%) of 118 eyes, graft detachments were observed. Twenty-five eyes with detached grafts successfully were repositioned or rebubbled after surgery, or both. In 1 eye, a previously detached graft reattached spontaneously. In 1 aphakic eye, the graft detached into the vitreous cavity. In 17 eyes, successful reattachment of the cornea occurred (68%). Twenty-one of the 118 eyes were considered to have failed DSAEK, meaning that persistent edema was present after DSAEK. Seven (6%) demonstrated graft rejection. In 5 eyes (4%), retinal detachment (RD) developed. In 6 (5%), cystoid macular edema developed. In 1 aphakic patient, an air bubble could not be maintained during surgery, and sulfur hexafluoride was injected into the anterior chamber. In 1 eye (1%), epithelial ingrowth developed. One eye (1%) demonstrated blood in the graft interface. In 1 eye (1%), a limited intraoperative suprachoroidal hemorrhage occurred. Two eyes (2%) had pupillary block after surgery that resolved with removal of the air bubble. CONCLUSIONS: Descemet's stripping with automated endothelial keratoplasty has become a popular and effective treatment for corneal endothelial dysfunction, but complications resulting from DSAEK do occur. Graft detachment is the most common complication, but postoperative repositioning or rebubbling, or both, allow for graft reattachment in most cases. Other complications found in this series were graft failure, graft rejection, cystoid macular edema, RD, suprachoroidal hemorrhage, and pupillary block. Retained Descemet's membrane and epithelial ingrowth, are potential causes of dislocation.


Assuntos
Transplante de Córnea , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano/transplante , Complicações Intraoperatórias , Complicações Pós-Operatórias , Câmara Anterior/patologia , Doenças da Córnea/cirurgia , Lâmina Limitante Posterior/patologia , Endotélio Corneano/patologia , Feminino , Sobrevivência de Enxerto , Inquéritos Epidemiológicos , Humanos , Implante de Lente Intraocular , Masculino , Facoemulsificação , Estudos Retrospectivos , Óleos de Silicone/administração & dosagem , Hexafluoreto de Enxofre/administração & dosagem , Tomografia de Coerência Óptica
16.
Int J Hematol ; 80(2): 146-54, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15481443

RESUMO

The bone marrow of patients with myelodysplastic syndromes (MDS) shows excessive intramedullary apoptosis, particularly in S-phase cells. In the light of previous reports that showed a link between experimental overexpression of the E2F1 transcription factor and apoptosis in the S phase, we compared the status of E2F1 protein in bone marrow mononuclear cells of MDS patients with that of healthy donors. Nearly 67% of MDS marrow samples showed higher expression of E2F1 transcription factor than in healthy donors. The retinoblastoma gene product, Rb, is a major negative regulator of E2F1 activity; however, Rb protein levels were found to be normal in MDS marrow samples. Amplification of genomic DNA by the polymerase chain reaction (PCR) showed no E2F1 gene amplification or mutation in the Rb-binding region of E2F1 in MDS patients, nor was transcriptional up-regulation noted when E2F1 messenger RNA (mRNA) levels were estimated with real-time reverse transcriptase-PCR. Furthermore, the overexpression of E2F1 was paralleled by its increased transcriptional activity, as reflected by the increased mRNA levels for one of its target genes, dihydrofolate reductase. Importantly, in a subset of the studied MDS patients for whom a simultaneous measurement of apoptosis in S-phase cells was possible, the E2F1 protein levels showed a significant positive correlation with this phenomenon. Previously, increased E2F1 activity in human disease had been found primarily as a consequence of Rb derailment. Hence, the observation in MDS of increased E2F1 activity in the presence of normal Rb levels is novel and unique, and E2F1 activity in association with apoptosis in S-phase cells may thus have significant therapeutic implications.


Assuntos
Células da Medula Óssea/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Síndromes Mielodisplásicas/patologia , Fatores de Transcrição/genética , Idoso , Células da Medula Óssea/metabolismo , Fatores de Transcrição E2F , Fator de Transcrição E2F1 , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Valores de Referência , Proteína do Retinoblastoma/genética , Fase S , Tetra-Hidrofolato Desidrogenase/genética , Transcrição Gênica/genética
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