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1.
Cornea ; 43(8): 1053-1057, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38294898

RESUMO

PURPOSE: The aim of this study was to report 2 cases of levamisole-adulterated cocaine-induced mucous membrane pemphigoid. METHODS: This study is a review of case reports and literature. RESULTS: Two patients presented with bilateral severe purulent conjunctivitis, corneal ulceration, and rapidly progressive forniceal shortening. Both patients were active cocaine users. A complete blood analysis showed a positive antineutrophil cytoplasmic antibody immunofluorescence with a mixed perinuclear antineutrophil cytoplasmic antibody and cytoplasmic-staining antineutrophil cytoplasmic antibody pattern. Direct immunofluorescence examination of conjunctival tissue showed linear deposition of component 3 and immunoglobulins at the basal membrane. A diagnosis of levamisole-adulterated cocaine-induced mucous membrane pemphigoid was made. In case 1, this suspicion was confirmed by investigating remnants of cocaine on the patient's debit card using mass spectrometry, which contained traces of levamisole. In both cases, aggressive immunosuppressive therapy combining systemic corticosteroids and rituximab was able to control the disease. However, by the time these therapies were initiated, significant corneal injury had occurred requiring corneal grafts in both patients. CONCLUSIONS: Given the rising abuse of cocaine, it is important that ophthalmologists are made aware of its association with severe atypical cicatricial conjunctivitis. To the best of our knowledge, we present the first case proving the causal relationship between levamisole and ocular cicatricial pemphigoid.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Levamisol , Penfigoide Mucomembranoso Benigno , Humanos , Levamisol/efeitos adversos , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Penfigoide Mucomembranoso Benigno/induzido quimicamente , Masculino , Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína/efeitos adversos , Pessoa de Meia-Idade , Contaminação de Medicamentos , Feminino , Adulto , Glucocorticoides/uso terapêutico
2.
BMJ Case Rep ; 16(1)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707098

RESUMO

We present a case of bilateral interstitial keratitis leading to perforation in a woman with hidradenitis suppurativa (HS). A woman in her mid-20s with a history of HS and Grave's disease was referred to the corneal service with loss of vision and pain in both eyes since childhood. She was found to have circumferential thinning and steepening affecting her peripheral cornea bilaterally. Corrected distance visual acuity with spectacles was in the right eye 6/7.5, and in the left 6/30, with local thinnest area of 209 and 217 µm in the right and left eyes, respectively. She experienced recurring episodes of redness and irritation, and perforation occurred. The corneal perforation was managed with cyanoacrylate glueing, followed by a local conjunctival flap. Systemic immunosuppression with mycophenolate mofetil and adalimumab was commenced, with improvement after 18 months of treatment. Dermatologists and ophthalmologists should be aware of this association given its potential severity.


Assuntos
Perfuração da Córnea , Hidradenite Supurativa , Ceratite , Feminino , Humanos , Criança , Hidradenite Supurativa/complicações , Ceratite/complicações , Ceratite/cirurgia , Córnea/cirurgia , Perfuração da Córnea/etiologia , Perfuração da Córnea/terapia , Adalimumab
3.
Telemed J E Health ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426741

RESUMO

Introduction: During the COVID-19 pandemic, keratoconus patient care moved from in-person clinics to virtual care. We surveyed patient satisfaction with the new virtual clinic model. Methods: We assessed the views of keratoconus patients enrolled in the novel virtual service between June 1 and July 31, 2020, in individual structured telephone interviews using Likert questions. Results: Of the 88 patients enrolled, the opinions of 69 patients could be evaluated (78.4%). Compared with previous in-person visits, mean waiting times for diagnostic examinations dropped from 43 (±32) min to 4 (±3) min (p < 0.001). The majority of patients (68; 99%) were satisfied or very satisfied with the overall service irrespective of the communication channel (telephone or video). A majority also indicated a desire to continue attending the virtual keratoconus clinic after the pandemic and supported the idea of decentralized sites for future diagnostic measurements. Discussion: A novel virtual service to monitor keratoconus progression was well received and was associated with shorter waiting times. There was a strong interest on the part of patients to further develop the virtual keratoconus clinic. Conclusions: This study demonstrates that keratoconus patients managed very well the conversion from in-person to virtual care. A solid majority of keratoconus patients also supported further expansion of the virtual consultations to a completely decentralized telemedicine model.

4.
Cornea ; 41(4): 456-461, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35244626

RESUMO

PURPOSE: The purpose of this study was to assess an intellectual disability (ID) cohort with keratoconus (KC) regarding ophthalmic (visual acuity and corneal tomography) and systemic characteristics and to describe an appropriate clinical algorithm for investigation and management of KC in this setting. METHODS: This was the retrospective cohort study of patients with ID (Down syndrome, autism, and other) in the cornea department of a tertiary referral ophthalmic hospital in Dublin, Ireland. Retrospective chart review was conducted on people with ID undergoing examination under anesthesia or crosslinking under general anesthetic. Key outcome data included corneal examination findings, corneal tomography, visual acuity, and examination findings (eg, type of ID, general anesthetic, and cardiac status). RESULTS: Mean age of the 24 patients was 31.9 years (66.7% male). ID type was Down syndrome (66.7%), autism (25%), and other (8.3%). KC was diagnosed in 98% of eyes, with 45.8% having untreatable advanced disease (57.1% of these bilateral), 39.6% amenable to corneal collagen crosslinking (35.7% of these bilateral), and 6.3% having corneal transplantation. Congenital heart defects were present in 37.5% of the Down syndrome group. There were no serious ocular or systemic adverse events. CONCLUSIONS: KC is strikingly prevalent in the ID population. Ireland has the highest rate of Down syndrome in Europe (26.3:10,000 live births). This group is rarely suitable for corneal transplantation, and corneal collagen crosslinking is an effective intervention to prevent progression to advanced KC in this already socially restricted group. We propose an algorithm for investigation/treatment and also recommend uniform pediatric KC screening/treatment in ID populations.


Assuntos
Transtorno do Espectro Autista/complicações , Transplante de Córnea , Reagentes de Ligações Cruzadas/uso terapêutico , Síndrome de Down/complicações , Deficiência Intelectual/complicações , Ceratocone/terapia , Adolescente , Adulto , Criança , Colágeno/metabolismo , Substância Própria/efeitos dos fármacos , Substância Própria/metabolismo , Topografia da Córnea , Feminino , Seguimentos , Humanos , Ceratocone/tratamento farmacológico , Ceratocone/fisiopatologia , Ceratocone/cirurgia , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Riboflavina/uso terapêutico , Raios Ultravioleta , Acuidade Visual/fisiologia , Adulto Jovem
5.
J Ophthalmol ; 2021: 5514055, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150337

RESUMO

OBJECTIVES: To compare presentation of infectious keratitis during COVID-19 lockdown with previous years, assess relative severity, and compare outcomes between COVID-19 and pre-COVID-19 era groups. METHODS: Acute presentations of infectious keratitis during a strict government-mandated COVID-19 lockdown period were analysed retrospectively (March-May 2020). Data were compared with the same periods in 2018-2019. The clinical notes of patients undergoing corneal scrapes were reviewed, and data were collected on treatment, culture growth, surgical interventions, visual outcomes, admission rates, and risk factors. RESULTS: There were 37% fewer presentations of infectious keratitis to the ED in 2020 (N = 29, 47, and 45, respectively). Risk factor profiles and microbial data were similar across all periods. Admission rates and use of fortified antibiotics were lower in 2020. COVID-19 era cases recovered less vision (LogMAR 0.26, 0.67, and 0.45, respectively; p = 0.04) and were more likely to require surgical intervention (10%, 4%, and 2%, respectively; OR 3.4 (CI 0.7-17.9, p = 0.1)). CONCLUSION: A concerning fall in presentations of infectious keratitis to ED during the pandemic lockdown was observed. Though societal behaviour changed during the lockdown, our data suggest it is unlikely that the incidence of infectious keratitis fell significantly. It is unclear how and where these patients were treated. We postulate that lower levels of visual recovery and higher rates of surgical intervention may have been caused by delays in accessing care. To minimise avoidable ocular morbidity as COVID-19 resurges, we must communicate clearly with patients and health professionals on how to access available emergency eye care services.

6.
Ir J Med Sci ; 190(2): 825-834, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32886296

RESUMO

BACKGROUND: First Irish National Corneal Transplant Registry report. AIM: To report about current corneal transplantation practices in Ireland including patient demographics, indications and types of transplant performed and to compare the findings with other developed countries. METHODS: Nationwide retrospective review of the corneal transplants performed in Ireland between 2016 and 2019. RESULTS: Overall, 536 keratoplasties were carried out: 256 (47.8%) Penetrating Keratoplasties (PK), 212 (39.6%) Descemet Stripping Automated Endothelial Keratoplasties (DSAEK), 30 (5.6%) Descemet Membrane Endothelial Keratoplasties (DMEK), and 25 (4.7%) Deep Anterior Lamellar Keratoplasties (DALK). The most common indication was Keratoconus (KC, 19%), followed by Fuchs endothelial dystrophy (FED, 18.8%), and Pseudophakic bullous keratopathy (PBK, 17%). KC (34%) and re-grafting (17%) were the leading indications for PK, whereas FED and PBK were the major indications for DSAEK (38% and 33%) and DMEK (67% and 20%), respectively. During the period studied, the number of transplants increased from 11.3 to 14 grafts per month. The number of PKs remained stable, whereas Endothelial Keratoplasties, DSAEK and DMEK, increased (3.8 to 5.6 and 0.2 to 1.6 per month, respectively), becoming the most commonly performed grafts since 2018. Only a small number of DALK were performed. CONCLUSIONS: Corneal transplantation in Ireland is following international trends as endothelial procedures have become the most common approach since 2018. However, a low overall number of transplants is performed in Ireland compared with other countries suggesting that care pathways should be implemented to improve access to corneal transplantation.


Assuntos
Transplante de Córnea/métodos , Idoso , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Cornea ; 39(2): e5, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31764286
8.
Cornea ; 38(8): 955-958, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31276459

RESUMO

PURPOSE: To describe the clinical features, risk factors, and treatment outcomes after supratarsal injection of triamcinolone for vernal keratoconjunctivitis (VKC). METHODS: A retrospective review of all patients treated with supratarsal triamcinolone for VKC between February 2002 and May 2017 at the Royal Victoria Eye and Ear Hospital and Our Lady's Children Hospital Crumlin, Dublin, Ireland, was performed. RESULTS: Twenty-five patients, 46 eyes, and 145 injections were included for analysis. The mean age at first injection was 9.1 ± 5.7 years. Ninety-six percent of the patients were male. A seasonal variation was noted, with 59 injections (41%) of triamcinolone administered for acute and refractive cases of VKC in the summer compared with 35 (24%), 35 (24%), and 16 (11%) in the spring, autumn, and winter months, respectively. The most common presenting complaint was red eye, which was seen in all cases. Hay fever (64%) was the most common associated systemic disease. Each eye required, on average, 3.2 injections (range 1-9 injections), and the mean duration from the onset of symptoms to final treatment was 3.03 years (range 0-7.9 years). The mean presenting and final visual acuities were 0.33 and 0.11 logarithm of the minimum angle of resolution, respectively (P < 0.0001). During our study period, no patient experienced intraocular pressure rise requiring treatment, development of lenticular opacity, or ptosis after supratarsal injection of triamcinolone. CONCLUSIONS: In this case series, supratarsal triamcinolone was used in cases of VKC in which topical medications had failed to control the disease process. All patients reported improvement after treatment. There were no cases of intraocular pressure rise, lenticular opacity, or ptosis development after treatment.


Assuntos
Conjuntivite Alérgica/tratamento farmacológico , Pálpebras/efeitos dos fármacos , Glucocorticoides/uso terapêutico , Triancinolona Acetonida/uso terapêutico , Adolescente , Criança , Pré-Escolar , Conjuntivite Alérgica/fisiopatologia , Feminino , Glucocorticoides/efeitos adversos , Humanos , Lactente , Injeções , Irlanda , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos , Acuidade Visual/fisiologia , Adulto Jovem
9.
Open Ophthalmol J ; 12: 273-280, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30369992

RESUMO

OBJECTIVE: To assess the impact of the magnitude of preoperative and postoperative corneal astigmatism on refractive outcomes in patients undergoing cataract surgery or lens exchange with an extended depth of focus intraocular lens. To compare visual outcomes of steep and temporal on-axis corneal incisions. SETTING: Department of Ophthalmology, Blackrock Clinic, Dublin, Ireland. DESIGN: Prospective cohort analysis. METHODS: Fifty-three consecutive adult patients (94 eyes) undergoing routine phacoemulsification with Symfony IOL implantation were analysed. Exclusion criteria: targets for mini-monovision, incomplete data, other ocular pathology. Data were prospectively collected on pre- and postoperative refraction, keratometry, distance vision, near vision, surgical wound site and Surgically Induced Astigmatism (SIA). RESULTS: The average postoperative monocular Uncorrected Distance and Near visual acuities (UDVA and UNVA) were 0.12 LogMAR (± 0.1) (6/7.5+1) and 0.34 LogMAR (± 0.09) respectively. The average binocular UDVA and UNVA were 0.05 (± 0.07) and 0.29 LogMAR (± 0.06) respectively. Low levels of preoperative corneal astigmatism (0-0.99 D) were associated with better LogMAR UDVA and UNVA when compared with higher levels (> 0.99 D): 0.11 (CI 0.103-0.107) vs. 0.206 (CI 0.122-0.290) (p =0.015, CI 95%) and 0.33 (CI 0.316 - 0.356) vs. 0.39 (CI 0.34-0.43) (p =0.034, CI 95%) respectively. When patients with steep on-axis corneal incisions were compared with temporal on-axis corneal incisions, no difference was detected in visual outcome or SIA. CONCLUSION: The Symfony IOL is an effective surgical means of addressing presbyopia and reducing postoperative spectacle dependence. We stress caution when offering potential spectacle independence for patients with over 1D of preoperative corneal astigmatism as these patients achieve statistically significantly inferior and less predictable visual results.

10.
Int J Ophthalmol ; 11(7): 1129-1131, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30046528

RESUMO

AIM: To evaluate the outcomes of alcohol delamination (ALD) of the corneal epithelium for the treatment of recurrent corneal erosion syndrome (RCES) and to implement a standardized treatment protocol for this condition utilizing evidence based practice and the findings of an internal audit. METHODS: A retrospective analysis of 42 eyes of 40 patients diagnosed with RCES who were treated with ALD between January 2006 and March 2016 was conducted. Patients had 20% alcohol applied to the cornea with the use of a well for 40s. Patients were reviewed one week later in the Outpatient Department. Outcome criteria were established based on standards from other studies in the medical literature. These included, a treatment success rate of at least 72% (defined as complete resolution of symptoms one month after treatment), a postoperative complication a rate of <5% (mainly infective keratitis, and subepithelial haze), and the absence of any detrimental effect on visual acuity in ≥95% of patients. RESULTS: The mean age at the time of ALD was 41.17±13.44y. Patients were followed for an average of 12.8±15.65mo. The majority were female (52.5%, n=21) and the majority of eyes treated with ALD were left eyes (62.9%, n=26). Trauma was the primary aetiology in our study population. Treatment was successful in 73.8% (n=31) of eyes and in 75% (n=30) of patients. Recurrence occurred in 26.2% of eyes at a mean of 10.41±12.63mo post treatment. CONCLUSION: ALD is an efficacious and cost-effective primary surgical intervention for RCES.

11.
Science ; 356(6334)2017 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-28336563

RESUMO

On 14 November 2016, northeastern South Island of New Zealand was struck by a major moment magnitude (Mw) 7.8 earthquake. Field observations, in conjunction with interferometric synthetic aperture radar, Global Positioning System, and seismology data, reveal this to be one of the most complex earthquakes ever recorded. The rupture propagated northward for more than 170 kilometers along both mapped and unmapped faults before continuing offshore at the island's northeastern extent. Geodetic and field observations reveal surface ruptures along at least 12 major faults, including possible slip along the southern Hikurangi subduction interface; extensive uplift along much of the coastline; and widespread anelastic deformation, including the ~8-meter uplift of a fault-bounded block. This complex earthquake defies many conventional assumptions about the degree to which earthquake ruptures are controlled by fault segmentation and should motivate reevaluation of these issues in seismic hazard models.

12.
J Refract Surg ; 32(6): 379-84, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27304601

RESUMO

PURPOSE: To evaluate the long-term effectiveness and safety of combined LASIK and small-aperture intracorneal inlay implantation (KAMRA; AcuFocus, Irvine, CA) for the surgical compensation of presbyopia and refractive errors. METHODS: Retrospective chart review of all ametropic, presbyopic patients who underwent combined LASIK and KAMRA inlay implantation at a single clinic. Demographic data and preoperative uncorrected and corrected monocular and binocular near and distance visual acuity (UNVA, UDVA, and CDVA) with manifest refractive spherical equivalent (MRSE) were collected and analyzed. All perioperative adverse events were recorded. RESULTS: In total, 132 patients were available (median age: 56 years; interquartile range (IQR) ± 5; range: 44 to 68 years). Median preoperative MRSE was +1.37± 1.20 diopters (D). The majority (113; 85%) were hypermetropic. Preoperative median UNVA improved from N24 (J13) ±6 to N6 (J5) ±1 by day 1 postoperatively, remaining stable throughout follow-up. At last follow-up, 97% of patients achieved UNVA of N5 (J3) or better. Median UDVA (implanted eye) improved from 20/40 (0.50 ± 0.41 on the decimal chart) preoperatively to 20/25 (0.80 ± 0.13) at month 12. Binocular UDVA was 20/20 in 88%, with CDVA unchanged for 84% at 12 months. No patient lost more than one line of CDVA. MRSE was also stable, albeit +0.25 D off-target refraction (-0.75 D). Two inlays were explanted due to suboptimal adaptation/corneal haze. CONCLUSIONS: The results of this follow-up study show that combined insertion of a small-aperture corneal inlay with LASIK in presbyopic patients improves near vision with a slight compromise in distance vision in the implanted eye. Overall, it appears to be a safe, effective procedure for the treatment of presbyopia. [J Refract Surg. 2016;32(6):379-384.].


Assuntos
Substância Própria/cirurgia , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Lasers de Excimer/uso terapêutico , Polivinil , Presbiopia/cirurgia , Próteses e Implantes , Implantação de Prótese , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Presbiopia/fisiopatologia , Refração Ocular/fisiologia , Estudos Retrospectivos , Acuidade Visual/fisiologia
14.
Br J Ophthalmol ; 100(2): 269-73, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26124460

RESUMO

BACKGROUND/AIMS: To report five cases of infectious keratitis following corneal inlay implantation for the surgical correction of presbyopia. METHODS: This was a retrospective, observational case series. Five eyes of five patients were identified consecutively in two emergency departments during a 1-year period, from November 2013 to November 2014. Patients' demographics, clinical features, treatment and outcomes are described. RESULTS: There were four female patients and one male, aged 52-64 years. Three patients had the KAMRA inlay (AcuFocus) and two had the Flexivue Microlens inlay (Presbia Coöperatief U.A.) inserted for the treatment of presbyopia and they presented from 6 days to 4 months postoperatively. Presenting uncorrected vision ranged from 6/38 to counting fingers. One patient's corneal scrapings were positive for a putatively causative organism, Corynebacterium pseudodiphtheriticum, and all patients responded to broad-spectrum fortified topical antibiotics. All patients lost vision with final uncorrected visual acuity ranging from 6/12 to 6/60 and best-corrected vision ranging from 6/7.5 to 6/12. Two patients' corneal inlays were explanted and three remained in situ at last follow-up. CONCLUSIONS: Infectious keratitis can occur at an early or late stage following corneal inlay implantation. Final visual acuity can be limited by stromal scarring; in the cases where the infiltrate was small and off the visual axis at the time of presentation, the final visual acuity was better than those patients who presented with larger lesions affecting the visual axis. Though infection may necessitate removal of the inlay, early positive response to treatment may enable the inlay to be left in situ.


Assuntos
Substância Própria/cirurgia , Úlcera da Córnea/etiologia , Infecções por Corynebacterium/etiologia , Infecções Oculares Bacterianas/etiologia , Presbiopia/cirurgia , Implantação de Prótese/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Resinas Acrílicas , Antibacterianos/uso terapêutico , Materiais Biocompatíveis , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Corynebacterium/isolamento & purificação , Infecções por Corynebacterium/diagnóstico , Infecções por Corynebacterium/tratamento farmacológico , Quimioterapia Combinada , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Feminino , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ , Lasers de Excimer/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polivinil , Presbiopia/fisiopatologia , Próteses e Implantes , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/tratamento farmacológico , Estudos Retrospectivos
15.
Invest Ophthalmol Vis Sci ; 55(9): 5795-805, 2014 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-25125605

RESUMO

PURPOSE: The improved surgical outcomes associated with transplantation of cultivated amniotic membrane expanded limbal epithelium (AMLE) compared to traditional donor methods has led to substantial adoption of this technique for treatment of limbal stem cell deficiency. METHODS: The mRNA expression profiles of AMLE and CE were assayed using microarrays. Transcripts with a 1.5-fold change in either direction in addition to a Bonferroni adjusted P value < 0.05 were considered to be differentially expressed. Expression changes detected by microarray profiling and important corneal-limbal markers were assessed using quantitative real-time PCR (qRT-PCR) and immunofluorescence staining. RESULTS: A total of 487 probe sets (319 upregulated and 168 downregulated) were found to be differentially expressed between AMLE and CE. Enrichment analysis revealed significant overrepresentation of multiple biological processes (e.g., response to wounding, wound healing, and regulation of cell morphogenesis) within the differentially expressed gene list. The expression of a number of genes that were upregulated (ABCG2, S100A9, ITGA5, TIMP2, FGF5, PDGFC, SEMA3A) and downregulated (KLF4, P63α) in AMLE was confirmed using qRT-PCR. Immunofluorescence confirmed that AMLE cultures were P63α, ABCG2, CK3, CK12, and E-cadherin (E-cad) positive. CONCLUSIONS: In this study, we have shown that genes associated with wound healing processes are upregulated in AMLE. These gene expression changes may contribute to corneal restoration and the positive outcomes associated with transplantation.


Assuntos
Epitélio Corneano/metabolismo , Limbo da Córnea/metabolismo , Cicatrização/fisiologia , Âmnio/citologia , Biomarcadores/metabolismo , Cadáver , Células Cultivadas , Transplante de Córnea , Perfilação da Expressão Gênica , Humanos , Fator 4 Semelhante a Kruppel , Análise em Microsséries , RNA/metabolismo , RNA Mitocondrial
17.
J Phys Chem A ; 114(10): 3457-65, 2010 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-20155963

RESUMO

The conversion of soluble proteins to insoluble amyloid fibrils is associated with numerous human diseases. The peptide GNNQQNY is a short segment of the yeast prion protein Sup35 that previously has been found to form amyloid fibrils in a similar manner to the protein itself. The approach taken in this work was to attach this peptide sequence to an insoluble polymer matrix through solid phase peptide synthesis and give it the internal freedom to fold into its local conformation in an organic solvent. Observation of its monomeric structure, free from the effects of aggregation, entropic solvent effects, and neighboring molecules, was possible by two-dimensional high-resolution magic angle spinning (1)H NMR spectroscopy. Analysis of the through-bond correlations and through-space interactions observed in the spectra, combined with global energy minimization via computational studies, led to the observation that the peptide chain adopts a compact beta-like turn at the central hydrophilic residues. The technique of peptide attachment to a polymer resin and observation by NMR may allow for future study of single peptide fragments prone to aggregation.


Assuntos
Amiloide/química , Oligopeptídeos/química , Fragmentos de Peptídeos/química , Fatores de Terminação de Peptídeos/química , Príons/química , Resinas Sintéticas/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae , Sequência de Aminoácidos , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/metabolismo , Ligação Proteica , Conformação Proteica , Solventes/química , Tirosina
18.
J Phys Chem A ; 114(1): 324-35, 2010 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-19919076

RESUMO

We report the results of our solid-state (67)Zn NMR study of the various zinc sites in four zinc-amino acid coordination complexes: bis(glycinato)zinc(II) monohydrate; bis(l-alaninato)zinc(II); bis(l-histidinato)zinc(II) dihydrate; and sodium bis(l-cysteinato)zincate(II) hexahydrate; as well as a related complex, bis(imidazole)zinc(II) chloride. We demonstrate the advantages of using high (21.1 T) applied magnetic fields for detecting (67)Zn directly at ambient temperatures using the quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) pulse sequence. The stepped-frequency technique was employed in cases where the central-transition (CT) (67)Zn NMR spectra were too broad to be uniformly excited. The parameters of the anisotropic zinc tensors were extracted by iterative simulations of the experimental spectra. In all cases, the quadrupolar interaction is found to dominate the central-transition (67)Zn NMR spectra; no convincing effects from chemical shift anisotropy (CSA) on the NMR spectra of the five complexes could be reliably detected at this field strength. Analyses of the experimental NMR spectra reveal that the (67)Zn quadrupolar coupling constants (C(Q)) range from 7.05 to 26.4 MHz, the isotropic chemical shifts (delta(iso)) range from 140 to 265 ppm, and the quadrupolar asymmetry parameters (eta(Q)) range from 0.20 to 0.95. The first report of the NMR spectral features of pentacoordinated zinc sites is included for two complexes. Quantum chemical calculations of the electric field gradient (EFG) and magnetic shielding tensors reproduced the experimental results to a reasonable extent. Moreover, the computationally determined orientations of both tensors permit correlations between NMR tensor properties and zinc local environments to be understood.


Assuntos
Aminoácidos/química , Compostos Organometálicos/química , Zinco/química , Espectroscopia de Ressonância Magnética , Padrões de Referência , Isótopos de Zinco
19.
Cornea ; 28(3): 285-92, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19387229

RESUMO

AIM: To identify the risk factors for, and to report the microbiological findings and clinical outcomes of, severe microbial keratitis (MK). METHODS: This was a retrospective study of all cases of presumed MK admitted to a tertiary referral center over a 2-year period (September 2001 to August 2003). Data recorded included demographic data, details relating to possible risk factors, results of microbiological studies, clinical findings at presentation, and clinical and visual outcomes. RESULTS: Ninety patients were admitted with a diagnosis of presumed MK during the study period. The mean age of patients was 45 +/- 32 years, and the male to female ratio was 47:43 (52.2%:47.7%). Predisposing risk factors for MK included contact lens wear (37; 41.1%), anterior segment disease (19; 21.1%), ocular trauma (13; 14.4%), systemic disease (5; 5.6%), and previous ocular surgery (1; 1.1%). Cultured organisms included gram-negative bacteria (17; 51.5%), gram-positive bacteria (11, 33.3%), acanthamoeba (2; 6.1%), and fungi (1; 3%). Visual acuity improved significantly after treatment [mean best-corrected visual acuity (+/-standard deviation) at presentation: 0.76 (+/-0.11); mean best-corrected visual acuity at last follow-up: 0.24 (+/-0.07); P < 0.001]. Secondary surgical procedures were required in 18 (20%) cases, and these included punctal cautery (1; 1.1%), tissue glue repair of corneal perforation (2; 2.2%), tarsorrhaphy (9; 9.9%), Botulinum toxin-induced ptosis (1; 1.1%), penetrating keratoplasty (3; 3.3%), and evisceration (2; 2.2%). CONCLUSIONS: Contact lens wear remains a significant risk factor for severe MK. MK remains a threat to vision and to the eye, but the majority of cases respond to prompt and appropriate antimicrobial therapy.


Assuntos
Ceratite por Acanthamoeba/parasitologia , Úlcera da Córnea/microbiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Fúngicas/microbiologia , Ceratite por Acanthamoeba/diagnóstico , Ceratite por Acanthamoeba/terapia , Adolescente , Adulto , Antibacterianos/uso terapêutico , Antiprotozoários/uso terapêutico , Criança , Pré-Escolar , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/terapia , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/terapia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/terapia , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Oftalmológicos , Admissão do Paciente , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Acuidade Visual
20.
Magn Reson Chem ; 46(1): 30-5, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18098229

RESUMO

The growing importance of solid-phase peptide synthesis (SPPS) has necessitated the development of spectroscopic experiments that can be used to obtain structural and conformational information on resin-bound peptides. Despite the utility of two-dimensional high-resolution magic angle spinning (HRMAS) NMR experiments that provide homonuclear shift correlations, experiments that provide heteronuclear shift correlations are necessary for complex conformational and structural elucidatory problems. Here we report the optimization and implementation of non-gradient inverse NMR experiments for acquiring the 1H-13C shift correlations of resin-bound peptides. The use of non-gradient experiments is advantageous as many magic angle spinning (MAS) probes do not possess gradient coils. An HRMAS BIRD-HMQC experiment with a reduced 1JCH constant has proven very suitable for obtaining one-bond correlations. Long-range correlations can be interpolated by using a non-gradient HRMAS CT-HMBC-1 experiment where the resulting data is processed with forward linear prediction. It has been shown that removing the effects of 1H-1H J-modulation is crucial in order to view cross peaks that correspond to long-range correlations. Additionally, both experiments prove extremely useful over routine one-dimensional 13C HRMAS experiments for extracting carbon chemical shift data. The non-gradient HRMAS BIRD-HMQC and CT-HMBC-1 experiments can be used to assist in conformational analysis and to identify and deconvolute situations where accidental equivalence and seemingly correlated isochronous signals arise.


Assuntos
Ressonância Magnética Nuclear Biomolecular/métodos , Oligopeptídeos/síntese química , Carbono , Hidrogênio , Oligopeptídeos/química , Transição de Fase , Conformação Proteica
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