Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
1.
Curr Alzheimer Res ; 20(11): 802-810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38409714

RESUMO

BACKGROUND: Cannabis consumption has rapidly increased in the United States due to more states legalizing non-medical and medical use. There is limited research, however, investigating whether cannabis may be associated with cognitive function, particularly across multiple dimensions of cannabis use. OBJECTIVE: The objective of this study was to examine whether cannabis consumption reason, frequency, and method are associated with subjective cognitive decline (SCD). METHODS: Data were obtained from 4,744 U.S. adults aged 45 and older in the 2021 Behavioral Risk Factor Surveillance System (BRFSS). SCD was a self-reported increase in confusion or memory loss in the past year. Odds of SCD by cannabis use reason, frequency, and methods (e.g., smoke, eat, vaporize) were examined using multiple logistic regression after imputing missing data, applying sampling weights, and adjusting for sociodemographic, health, and substance use covariates. RESULTS: Compared to non-users, non-medical cannabis use was significantly associated with 96% decreased odds of SCD (aOR=0.04, 95% CI=0.01-0.44, p<.01). Medical (aOR=0.46, 95% CI=0.06-3.61, p=.46) and dual medical and non-medical use (aOR=0.30, 95% CI=0.03-2.92, p=.30) were also associated with decreased odds of SCD, although not significant. Cannabis consumption frequency and method were not significantly associated with SCD. CONCLUSION: The reason for cannabis use, but not frequency and method, is associated with SCD. Further research is needed to investigate the mechanisms that may contribute to the observed associations between non-medical cannabis use and decreased odds of SCD.


Assuntos
Sistema de Vigilância de Fator de Risco Comportamental , Disfunção Cognitiva , Uso da Maconha , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Disfunção Cognitiva/epidemiologia , Idoso , Estados Unidos/epidemiologia , Uso da Maconha/epidemiologia , Autorrelato , Fumar Maconha/epidemiologia
2.
Retina ; 43(3): 520-522, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412945

RESUMO

PURPOSE: To investigate the effectiveness of an intraoperative surgical technique to reduce the incidence of immediate postoperative cavity hemorrhage in patients undergoing vitrectomy for complications of proliferative diabetic retinopathy. METHODS: A single-center, prospective study of 20 consecutive patients who underwent vitrectomy for proliferative diabetic retinopathy-related complications. A standard 3-port pars plana vitrectomy with either 23 g or 25 g was performed. At the end of surgery, the infusion was switched off to create transient hypotony and endolaser photocoagulation with long-duration burns were applied to actively leaking blood vessel. RESULTS: The average age was 56.2 + 12.8 years. Eleven eyes had actively bleeding vessels at the end of surgery and received endolaser photocoagulation. No patients were found to have hypotony at Day 1 postoperative. Preoperative median visual acuity was 20/1,600 improving to 20/40 at a median of 2.3 weeks post-op (range 0.4-8.5 weeks). Two eyes (10%) had a small postoperative cavity hemorrhage with 20/40 vision, which did not require further intervention. CONCLUSION: The described technique was found to be effective in reducing the incidence of postoperative cavity hemorrhage from up to 75% reported in literature to 10% in our pilot study. Further study with a larger number of patients is required.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Retinopatia Diabética/complicações , Estudos Prospectivos , Projetos Piloto , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/etiologia , Fotocoagulação a Laser , Vitrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Hemorragia Vítrea/cirurgia , Estudos Retrospectivos
3.
Ophthalmologica ; 246(1): 32-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36566742

RESUMO

INTRODUCTION: Postoperative steroid/antibiotic drop regimens are known to effectively suppress inflammation and infection following pars plana vitrectomy (PPV), but the steroid frequently induces ocular hypertension (OHT). The aim of this contemporaneous cohort-control study was to assess safety and efficacy of a novel post-PPV drop regimen conceived to address this problem. METHODS: Electronic case notes of consecutive eyes undergoing PPV between December 2020 and April 2021 at St. Thomas' Hospital, London, UK, were reviewed retrospectively. Postoperative drops in the intervention cohort consisted of 1-week g. dexamethasone 0.1%/antibiotic QDS and 1-month g. ketorolac TDS. Standard care controls received 1-month g. dexamethasone 0.1%/antibiotic QDS. RESULTS: Fifty-eight patients were in the intervention cohort, and 151 received standard care. The primary outcome measure was IOP ≥30 mm Hg 2 weeks postoperatively. This occurred in none of the intervention group but in 14% of controls (p = 0.01). Secondary outcomes of rates of anterior uveitis and cystoid macular edema did not differ significantly between the groups, but those in the intervention cohort had fewer hospital visits (p = 0.0004). CONCLUSION: A post-PPV drop regimen of 1-week dexamethasone 0.1%/antibiotic and 1-month ketorolac may be as effective as an anti-inflammatory but safer in terms of OHT incidence than standard care 1-month dexamethasone 0.1%.


Assuntos
Hipertensão Ocular , Vitrectomia , Humanos , Vitrectomia/efeitos adversos , Estudos Retrospectivos , Cetorolaco , Hipertensão Ocular/etiologia , Hipertensão Ocular/prevenção & controle , Dexametasona , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle
6.
Eye (Lond) ; 35(9): 2601-2606, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33219339

RESUMO

BACKGROUND/OBJECTIVES: Postoperative endophthalmitis is a rare, but serious complication of pars plana vitrectomy (PPV). Subconjunctival cefuroxime injection has been the traditional choice for post vitrectomy endophthalmitis prophylaxis. Its effectiveness and safety in this context are however poorly understood and cases of retinal toxicity have been reported. The traditional standard subconjunctival antibiotic prophylaxis has been superceded in cataract surgery by intracameral antibiotic prophylaxis. SUBJECTS/METHODS: The primary aim of this three centre non-randomised retrospective database cohort study of 7,532 PPV procedures was to identify the rate of endophthalmitis in cohorts of patients treated with intracameral or subconjunctival cefuroxime. A secondary aim was to estimate the achieved intraocular antibiotic concentrations of cefuroxime in eyes with intracameral versus subconjunctival administration using mathematical modelling. RESULTS: The overall incidence of postoperative endophthalmitis was 0.07% (5/7532). There were no cases of endophthalmitis in eyes receiving intracameral cefuroxime alone or in combination with subconjunctival cefuroxime (0/5586). Patients receiving subconjunctival cefuroxime alone had a higher incidence of endophthalmitis (0.22%, 4/1835), and there was one case of endophthalmitis in eyes not receiving any perioperative antibiotics (0.9%, 1/111). No cases of cefuroxime toxicity were identified. With subconjunctival cefuroxime, in the presence of a sclerotomy leak, we estimated the vitreous drug concentration to be higher than that for intracameral cefuroxime and potentially toxic. CONCLUSIONS: Intracameral cefuroxime appears to be a safe and efficient choice for prophylaxis against endophthalmitis after PPV. Small eyes with intraocular tamponade seem to be at particular risk of drug toxicity if cefuroxime is administered via the subconjunctival route.


Assuntos
Extração de Catarata , Endoftalmite , Infecções Oculares Bacterianas , Câmara Anterior , Antibacterianos/efeitos adversos , Cefuroxima/efeitos adversos , Estudos de Coortes , Endoftalmite/epidemiologia , Endoftalmite/etiologia , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/prevenção & controle , Humanos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Vitrectomia
7.
J Labelled Comp Radiopharm ; 63(12): 502-516, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32812275

RESUMO

One of the main challenges in targeted alpha therapy is assuring delivery of the α-particle dose to the targeted cells. Thus, it is critical to identify ligands for α-emitting radiometals that will form complexes that are very stable, both in vitro and in vivo. In this investigation, thorium-227 (t1/2 = 18.70 days) chelation of ligands containing hydroxypyridinonate (HOPO) or picolinic acid (pa) moieties and the stability of the resultant complexes were studied. Chelation reactions were followed by reversed-phased HPLC and gamma spectroscopy. Studies revealed that high 227 Th chelation yields could be obtained within 2.5 h or less with ligands containing four Me-3,2-HOPO moieties, 1 (83%) and 2 (65%), and also with ligands containing pa moieties, H4 octapa 3 (65%) and H4 py4pa 6 (87%). No reaction occurred with H4 neunpa-p-Bn-NO2 4, and the chelation reaction with another pa ligand H4 pypa 5 gave inconsistent yields with a very broad radio-HPLC peak. The ligands spermine-(Me-3,2-HOPO)4 1, H4 octapa 3, and H4 py4pa 6 had high stability (i.e., 87% of 227 Th still bound to the ligand) in phosphate-buffered saline at room temperature over a 6-day period. Preliminary studies with ligand 6 demonstrated efficient chelation of thorium-226 (t1/2 = 30.57 min) when heated to 80°C for 5 min.


Assuntos
Partículas alfa/uso terapêutico , Quelantes/química , Tório/química , Tório/uso terapêutico
8.
J Nucl Med ; 61(9): 1300-1306, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32169919

RESUMO

We reviewed 111In-DOTA-anti-CD45 antibody (BC8) imaging and bone marrow biopsy measurements to ascertain the biodistribution and biokinetics of the radiolabeled antibody and to investigate differences based on type of hematologic malignancy. Methods: Serial whole-body scintigraphic images (4 time points) were obtained after infusion of the 111In-DOTA-BC8 (176-406 MBq) into 52 adult patients with hematologic malignancies (lymphoma, multiple myeloma, acute myeloid leukemia, and myelodysplastic syndrome). Counts were obtained for the regions of interest for spleen, liver, kidneys, testicles (in men), and 2 marrow sites (acetabulum and sacrum), and correction for attenuation and background was made. Bone marrow biopsies were obtained 14-24 h after infusion, and the percentage of administered activity was determined. Absorbed radiation doses were calculated. Results: Initial uptake in liver averaged 32% ± 8.4% (SD) of administered activity (52 patients), which cleared monoexponentially with a biologic half-time of 293 ± 157 h (33 patients) or did not clear (19 patients). Initial uptake in spleen averaged 22% ± 12% and cleared with a biologic half-time of 271 ± 185 h (36 patients) or longer (6 patients). Initial uptake in kidney averaged 2.4% ± 2.0% and cleared with a biologic half-time of 243 ± 144 h (27 patients) or longer (9 patients). Initial uptake in red marrow averaged 23% ± 11% and cleared with a biologic half-time of 215 ± 107 h (43 patients) or longer (5 patients). Whole-body retention half-time averaged 198 ± 75 h. Splenic uptake was higher in the AML/MDS group than in the lymphoma group (P ≤ 0.05) or the multiple myeloma group (P ≤ 0.10). Liver represented the dose-limiting organ. For liver uptake, no significant differences were observed among the 3 malignancy groups. Average calculated radiation absorbed doses per unit of administered activity for a therapy infusion of 90Y-DOTA-BC8 were 0.35 ± 0.20 cGy/MBq for red marrow, 0.80 ± 0.24 cGy/MBq for liver, 3.0 ± 1.4 cGy/MBq for spleen, 0.055 ± 0.014 cGy/MBq for total body, 0.21 ± 0.15 cGy/MBq for osteogenic cells, and 0.17 ± 0.15 cGy/MBq for kidneys. Conclusion:111In-DOTA-BC8 had a long retention time in liver, spleen, kidneys, and red marrow, and the highest absorbed doses were in spleen and liver. Few differences were observed by malignancy type. The exception was greater splenic uptake in the leukemia/MDS group than in the lymphoma or multiple myeloma group.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Neoplasias Hematológicas/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Feminino , Compostos Heterocíclicos com 1 Anel/química , Humanos , Radioisótopos de Índio/química , Marcação por Isótopo , Cinética , Antígenos Comuns de Leucócito/imunologia , Masculino , Pessoa de Meia-Idade , Radiometria , Distribuição Tecidual
9.
Acta Ophthalmol ; 98(8): e960-e967, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31674134

RESUMO

PURPOSE: To determine the feasibility of a definitive study of intravitreal ranibizumab to promote the clearance of persistent diabetic vitreous haemorrhage and thereby avoid vitrectomy. METHODS: This randomised, double-masked, placebo-controlled feasibility study recruited 24 participants with persistent diabetic vitreous haemorrhage listed for pars plana vitrectomy. Participants were randomised to a single 0.5-mg intravitreal ranibizumab injection or a single subconjunctival saline injection. The primary outcome measure was the number of participants requiring pars plana vitrectomy at week 7. RESULTS: Eight of 12 participants (66.7%) in the ranibizumab group required vitrectomy at week 7 versus 12 of 12 (100%) in the placebo group (absolute risk reduction 33.3%, 95% confidence interval 2.1-70.7%; p = 0.09). One additional eye in the ranibizumab group required vitrectomy by 12 months. Mean visual acuity letter score at 12 months was 72.7 ± 12.3 in the ranibizumab group and 75.1 ± 10.1 in the placebo group. Safety was similar across groups. CONCLUSION: Intravitreal ranibizumab may reduce the likelihood of proceeding to vitrectomy in patients with persistent, dense diabetic vitreous haemorrhage. Further studies appear feasible and justified.


Assuntos
Bevacizumab/administração & dosagem , Retinopatia Diabética/complicações , Ranibizumab/administração & dosagem , Acuidade Visual , Hemorragia Vítrea/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio Vascular , Estudos Retrospectivos , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/etiologia
10.
Eye (Lond) ; 34(8): 1386-1391, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31685970

RESUMO

BACKGROUND: To evaluate the spontaneous change in size over the time of idiopathic full-thickness macular holes (IFTMHs) using optical coherence tomography (OCT). METHODS: This retrospective observational study included 24 eyes of 24 consecutive patients waiting for IFTMH surgery. On OCT horizontal B-scan passing through the center of the fovea, the minimum linear diameter (MLD), the basal diameter (BD), and the presence of vitreomacular adhesion (VMA) were evaluated. The mean total and daily MLD and BD variations were calculated as both absolute and percentage values. RESULTS: The MLD and BD size increase was statistically significant (P < 0.0001). The MLD size increase was significantly greater for small (<250 µm) versus both medium (≥250 to ≤400 µm) and large (>400 µm) IFTMHs in all analysis: the total absolute (P = 0.0248), the daily absolute (P = 0.0186), the total percentage (P = 0.0020), and the daily percentage (P = 0.0008) variations. For the BD, the significance between the same groups was achieved only in the daily percentage change (P = 0.0220). The presence of VMA did not influence the amount of MLD and BD increase. The rate of increase was dependent on the size of hole at presentation (MLD: small: 1.67 microns per day; medium: 0.61 microns per day; large: 0.44 microns per day). CONCLUSIONS: Both MLD and BD increase over the time in IFTMHs. There is a significantly greater rate of increase in hole size in smaller holes compared with larger. Therefore, prioritisation for small IFTMH may be justified.


Assuntos
Perfurações Retinianas , Humanos , Retina , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual
11.
Eye (Lond) ; 33(12): 1884-1889, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31270465

RESUMO

BACKGROUND/AIMS: Poor visual outcomes have recently been reported in black patients undergoing vitrectomy and delamination surgery for complications of proliferative diabetic retinopathy. We therefore investigated the outcome of surgery on a similar cohort of black patients and examined for potential predictors of visual success. METHODS: A single-centre retrospective case review of consecutive black patients who underwent vitrectomy and delamination surgery for complications of PDR between July 2010 and September 2017. The primary outcome measure was change in visual acuity (VA) at 6 months post-operatively. Multiple linear regression analysis was performed to evaluate determinants of change in VA. RESULTS: A total of 44 eyes of 44 patients were included. Mean age was 53.7 (range: 24.3-75.8) years. In all, 43% were male. A total of 52% had adjunctive pre-operative anti-VEGF therapy. Mean pre-operative VA was 1.49 logMAR ± 0.73 (range 0.18 to 2.6 logMAR). Mean change in VA at 6 months was a gain of 0.59 ± 0.94 logMAR (range 1.9 logMAR acuity loss to 2.5 logMAR acuity gain). Four cases required further surgery to treat rhegmatogenous detachment. The acuity of 68% improved by 0.3 or more logMAR. Silicone oil was used as primary tamponade in 7%. Pre-operative VA and use of silicone oil significantly predicted VA decline at 6 months (p = 0.001 and p = 0.007). CONCLUSIONS: The majority of our cohort derived visual benefit from vitrectomy and delamination for PDR-related complications. Improvement in VA was comparable to outcomes from the UK National Ophthalmic Database report. Silicone oil should be avoided these patients if possible.


Assuntos
População Negra , Retinopatia Diabética/fisiopatologia , Acuidade Visual , Vitrectomia/métodos , Adulto , Idoso , Retinopatia Diabética/etnologia , Retinopatia Diabética/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia , Adulto Jovem
12.
PLoS One ; 13(10): e0205135, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30335787

RESUMO

The objective of this study was to translate reaction conditions and quality control methods used for production of an astatine-211(211At)-labeled anti-CD45 monoclonal antibody (MAb) conjugate, 211At-BC8-B10, from the laboratory setting to cGMP production. Five separate materials were produced in the preparation of 211At-BC8-B10: (1) p-isothiocyanato-phenethyl-closo-decaborate(2-) (B10-NCS), (2) anti-CD45 MAb, BC8, (3) BC8-B10 MAb conjugate, (4) [211At]NaAt, and (5) 211At-BC8-B10. The 211At-labeling reagent, B10-NCS, was synthesized as previously reported. BC8 was produced, then conjugated with B10-NCS under cGMP conditions to form BC8-B10. [211At]NaAt was produced by α-irradiation of Bi targets, followed by isolation of the 211At using a "wet chemistry" method. The clinical product, 211At-BC8-B10, was prepared by reacting [211At]NaAt with BC8-B10 in NH4OAc buffer (pH 5.5) for 2 min at room temperature, followed by size-exclusion chromatography purification. Quality control tests conducted on the 211At-BC8-B10 included evaluations for purity and identity, as well as pyrogen and sterility tests. Stability of the 211At-BC8-B10 in 25 mg/mL sodium ascorbate solution was evaluated at 1, 2, 4, 6 and 21 h post isolation. For qualification, three consecutive 211At-BC8-B10 clinical preparations were successfully conducted in the cGMP suite, and an additional cGMP clinical preparation was carried out to validate each step required to deliver 211At-BC8-B10 to a patient. These cGMP preparations provided 0.80-1.28 Gbq (21.5-34.5 mCi) of 211At-BC8-B10 with radiochemical purity of >97%. The preparations were found to be sterile and have a pyrogen level <0.50 EU/mL. Cell binding was retained by the 211At-BC8-B10. 211At-BC8-B10 in ascorbic acid solution demonstrated a radiochemical stability of >95% for up to 21 h at room temperature. The experiments conducted have defined conditions for translation of 211At-BC8-B10 production from the laboratory to cGMP suite. This study has allowed the initiation of a phase I/II clinical trial using 211At-BC8-B10 (NCT03128034).


Assuntos
Anticorpos Monoclonais/biossíntese , Indústria Farmacêutica/métodos , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Antígenos Comuns de Leucócito/imunologia , Células Alógenas , Astato , Ensaios Clínicos como Assunto , Indústria Farmacêutica/normas , Humanos , Controle de Qualidade , Transplante Homólogo
13.
Blood Adv ; 2(14): 1664-1679, 2018 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-30012585

RESUMO

Fumagillin is an antiangiogenic and antineoplastic fungal natural product, and TNP-470 is one of its most potent analogs. Decades of studies revealed that TNP-470 has potent anticancer activities via destruction of neovasculature. In stark contrast, TNP-470 has been reported to suppress lymphocyte proliferation, thereby limiting its clinical potentials. In an attempt to investigate whether the similar or opposite immunomodulatory effect of TNP-470 could act on myeloid cells, we found that TNP-470 potentiates the immunogenicity of dendritic cells (DCs) toward a phenotype with T helper cell type 1 (Th1)-stimulatory features. Using DC vaccine on a murine melanoma cancer model, the TNP-470-treated DC vaccine could significantly induce tumor-specific immunogenicity and substantially enhance tumor eradication when compared with vehicle-treated DC vaccine in a prophylactic setting. Enhanced tumor-specific immunogenicity and delayed tumor progression were observed in a therapeutic setting upon the TNP-470-treated DC vaccine. Our data showed that TNP-470 potentiates Toll-like receptor signaling, including NF-κB activation, in DCs to transcriptionally activate interleukin-12 production, thus inducing a Th1-immune response. Our current study uncovers a novel immune function of TNP-470 in DCs and redefines its role as a novel class of small molecule immune adjuvant in DC-based cancer vaccine given potentiation of DC immunogenicity is a major roadblock in DC vaccine development. Our study not only provides a novel adjuvant for ex vivo-cultured patient-specific DC vaccines for cancer treatment but also discovers the distinct immunostimulatory function of TNP-470 in DCs of myeloid lineage that differs from its immunosuppressive function in lymphoid cells.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vacinas Anticâncer/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Dendríticas/imunologia , O-(Cloroacetilcarbamoil)fumagilol/farmacologia , Células Th1/imunologia , Animais , Diferenciação Celular/imunologia , Células Dendríticas/patologia , Masculino , Melanoma/imunologia , Melanoma/patologia , Melanoma/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Células Th1/patologia
14.
Oncotarget ; 9(32): 22301-22315, 2018 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-29854279

RESUMO

Triptolide (TL) is a potent anti-tumor, anti-inflammatory and immunosuppressive natural compound. Mechanistic studies revealed that TL inhibits tumor growth and triggers programmed cell death. Studies further suggested that TL inhibits heat shock response in cancer cells to induce apoptosis. HSP90ß is the major component of heat shock response and is overexpressed in different types of cancers. Given almost all identified HSP90ß inhibitors are either N or C-terminal inhibitors, small molecules attacking cysteine(s) in the middle domain might represent a new class of inhibitors. In the current study, we showed that TL inhibits HSP90ß in triple manner. Characterization suggests that TL inhibits ATPase activity by preventing ATP binding thus blunts the chaperone activity. TL disrupts HSP90ß-CDC37 (co-chaperone) complex through middle domain Cys366 of HSP90ß and causes kinase client protein degradation. At the cellular level, the TL-mediated decrease in CDK4 protein levels in HeLa cells causes reduced phosphorylation of Rb resulting in cell cycle arrest at the G1 phase. Furthermore, our results demonstrated that TL triggers programmed cell death in an HSP90ß-dependent manner as knockdown of HSP90ß further sensitized TL-mediated cell cycle arrest and apoptotic effect. Surprisingly, our data showed that TL is the first drug to be reported to induce site-specific phosphorylation of HSP90ß to drive apoptosome formation in the early phase of the treatment. In summary, our study established that TL is a novel middle domain HSP90ß inhibitor with bi-phasic multi-mechanistic inhibition. The unique regulatory mechanism of TL on HSP90ß makes it an effective inhibitor.

15.
Indian J Ophthalmol ; 66(5): 681-686, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29676315

RESUMO

Purpose: To determine the long-term incidence of fellow-eye surgical involvement in patients who have undergone first-eye vitreoretinal (VR) surgery for a variety of indications. This was a single-institution retrospective, consecutive series. Methods: Eighteen years of electronic surgical data were reviewed at our institution. All patients having surgery for the following indications were included: rhegmatogenous retinal detachment (RRD), macular hole (MH), epiretinal membrane (ERM), proliferative diabetic retinopathy (PDR), vitritis, and dropped nucleus. Primary outcome was the cumulative incidence of fellow-eye surgery at 10 years by Kaplan-Meier analysis. Results: Total follow-up was 29,629 patient-years. Cumulative incidence (± standard error) of fellow-eye surgery at 10 years was 7.2% ± 0.6% for RRD, 9.1% ± 1.3% for ERM, 7.5% ± 1.8% for MH, 30.6% ± 1.9% for PDR, 13.7% ± 2.9% for vitritis, and 2.8% ± 1.6% for dropped nuclei. The hazard for second-eye surgery was greatest in the early postoperative period after first-eye surgery for all indications. For RRD, the hazard was 2.7% ± 0.3% at year 1, 1.1% ± 0.2% at year 2, and 0.5% ± 0.2% at year 5. Risk factors for fellow-eye involvement for RRD were younger age (P < 0.001) and male gender (P < 0.01). Conclusion: We report the long-term risk of fellow-eye involvement in various VR pathologies, which is important in counseling patients regarding their risks as well as planning service provision.


Assuntos
Previsões , Complicações Pós-Operatórias/epidemiologia , Doenças Retinianas/cirurgia , Medição de Risco , Centros de Atenção Terciária/estatística & dados numéricos , Cirurgia Vitreorretiniana/efeitos adversos , Idoso , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Complicações Pós-Operatórias/etiologia , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/etiologia , Doenças Retinianas/epidemiologia , Estudos Retrospectivos , Fatores de Risco
16.
Retina ; 38(9): 1865-1872, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29324594

RESUMO

PURPOSE: The aim of this study was to report the intraoperative and postoperative complications of phacovitrectomy for epiretinal membrane (ERM) and macular hole (MH). METHODS: This was a retrospective audit of 1,052 phacovitrectomy operations (410 for ERM and 642 for MH) by the same surgical team between 1998 and 2017. Outcome measures included rates of intraoperative anterior segment and posterior segment complications such as posterior capsule rupture and retinal breaks. A subgroup analysis of 189 procedures in which postoperative complications were rigorously recorded was also undertaken. RESULTS: The rate of posterior capsule rupture was 2.2%, with no difference between ERM and MH (1.7 vs. 2.5%; P = 0.40). Iatrogenic retinal tears were more common in MH than in ERM surgery (15.6 vs. 6.8%; P < 0.001). The chance of one or more anterior segment or posterior segment intraoperative complications occurring (excluding iatrogenic retinal breaks) was not associated with: indication for surgery, grade of surgeon, gauge of surgery, surgical machine, diabetic status, patient sex, or patient age. Subgroup analysis showed postoperative events as follows: posterior capsular opacification 10.6% (20/189), posterior synechiae 4.2% (8/189), uveitis 2.1% (4/189), angle closure glaucoma 1.6% (3/189), and rhegmatogenous retinal detachment 1.1% (2/189). CONCLUSION: Phacovitrectomy seems to be safe in phakic patients with ERM or MH, performed either by fellows or consultants. It avoids the requirement for repeat surgery and is more cost and resource efficient.


Assuntos
Membrana Epirretiniana/cirurgia , Complicações Intraoperatórias/epidemiologia , Facoemulsificação/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Perfurações Retinianas/cirurgia , Vitrectomia/efeitos adversos , Idoso , Membrana Epirretiniana/complicações , Feminino , Humanos , Incidência , Masculino , Perfurações Retinianas/complicações , Estudos Retrospectivos , Reino Unido/epidemiologia
17.
Eur J Ophthalmol ; 27(3): 367-371, 2017 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-27791248

RESUMO

PURPOSE: The true prevalence of retinal detachment and other vitreoretinal disorders in different ethnic groups is not well-established. Understanding differences in vitreoretinal disease prevalence is important to appropriately allocate resources to meet demand where ethnic variation in the community exists. The aim of this study is to provide hospital-based data on the proportion of people with vitreoretinal disorders in the 3 main ethnic groups in the United Kingdom: Caucasian, Afro-Caribbean, and South Asian. METHODS: A retrospective study was performed on 3,262 patients undergoing vitreoretinal procedures for various indications between 2001 and 2014 from a single center in London, UK. RESULTS: The majority of patients with known ethnicity were Caucasian (80.19%) followed by Afro-Caribbean (12.31%) and Asian (5.20%). The mean age of the study population was 59.64 ± 15.75 years, with 57.28% males. Rhegmatogenous retinal detachment (RRD) was the common indication for surgery across all ethnic groups (54.83%). Caucasians were older, on average, compared to other ethnic groups at the time of surgery for RRD (p<0.05) and achieved higher success rates after primary surgery and were less likely to require silicone oil as primary tamponade. Macular hole was more common in the ethnic minorities with similar closure rates. Surgery for complications of diabetic retinopathy was more common in Afro-Caribbeans and Asians compared to Caucasians (28.07%, 24.02%, and 9.40%, p<0.05). CONCLUSIONS: This study presents a large population-based data analysis on ethnic variation in vitreoretinal disorders. This may assist in predicting the requirement of vitreoretinal service provision depending on local ethnic variation.


Assuntos
Etnicidade , Descolamento Retiniano/cirurgia , Cirurgia Vitreorretiniana/métodos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Descolamento Retiniano/etnologia , Estudos Retrospectivos , Fatores de Tempo , Reino Unido/epidemiologia
18.
Int J Ophthalmol ; 9(1): 108-10, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26949619

RESUMO

AIM: To evaluate the functional outcome after removal of silicone oil (ROSO) in patients undergoing retinectomy for complex retinal detachment. METHODS: We performed a retrospective case note review of patients who underwent ROSO after retinectomy for complex retinal detachment. Patients with less than 6mo follow up and recurrent retinal detachment following ROSO were excluded. RESULTS: Thirty-six patients were included. The mean best corrected visual acuity (BCVA) pre-ROSO was 1.13 logMAR (SD 0.5). The mean BCVA 3mo following ROSO was 1.16 logMAR (SD 0.53), 6mo following ROSO 1.13 (SD 0.63), and 12mo following ROSO 1.18 (SD 0.69). At 12mo after ROSO, the BCVA improved in 38.9% of patients, remained unchanged in 25%, and deteriorated in 36.1%, although there was no statistical significant difference in BCVA after ROSO at 3, 6 and 12mo (P=0.93). The size of retinectomy ranged from 15° to 270° (SD 53) and did not influence the visual outcome (P=0.11). CONCLUSION: There was no statistically significanT difference in BCVA between pre- and post- ROSO following retinectomy for complex retinal detachment. There was no statistical difference in visual outcome related to the size of the retinectomy.

19.
Taiwan J Ophthalmol ; 6(4): 199-200, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29018742

RESUMO

This manuscript describes a case of successful reattachment of a macular-off retinal detachment following optical coherence tomography-guided internal drainage of retained subretinal fluid following a nondrain method. To date, there has not been any documented treatment option for this common phenomenon. This novel technique describes a method to remove such fluid and successfully appose the retina to the retinal pigment epithelial layer.

20.
Lima; s.n; 2014. 45 p. tab.
Tese em Espanhol | LILACS, LIPECS | ID: biblio-1114010

RESUMO

Objetivo: Determinar la prevalencia de Helicobacter pylori en pacientes sintomáticos gástricos que acuden a la Consulta externa del Hospital I Octavio Mongrut Muñoz, a través de la prueba del Test de aliento. Planteamiento del Problema: La Organización Mundial de la Salud ha considerado al Helicobacter pylori como carcinógeno Tipo 1. Esto no significa que esta bacteria produzca sustancias carcinogénicas o mutagénicas, sino que como consecuencia de una inflamación crónica y progresiva de la mucosa gástrica, lleva a la gastritis atrófica, entidad considerada como una condición precancerosa. Material y Métodos: Se diseñó un estudio Observacional, Descriptivo y Longitudinal. El estudio se llevó a cabo en el Hospital I Octavio Mongrut Muñoz (HIOMM) que pertenece a la Red Asistencial Sabogal (RAS) de (EsSALUD); en pacientes a los cuales se les solicitó la prueba del Test de Aliento en el período comprendido entre enero a diciembre de los años 2007 al 2010. Resultados: La prevalencia de la infección por Hp., fue de 63.7 por ciento, 61.89 por ciento, 59.68 por ciento y 69.26 por ciento entre los años 2007 al 2010 respectivamente. Conclusión: La prevalencia encontrada se encuentra por encima de países desarrollados y en concordancia con la prevalencia en Latinoamérica. No encontrándose diferencias estadísticas significativas en relación al grupo etario y sexo con los estudios a nivel de Latinoamérica.


Assuntos
Masculino , Feminino , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Helicobacter pylori , Infecções por Helicobacter/epidemiologia , Sinais e Sintomas Digestórios , Estudos Longitudinais , Estudos Observacionais como Assunto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA