RESUMO
Sortase-assembled pili contribute to virulence in many Gram-positive bacteria. In Enterococcus faecalis, the endocarditis and biofilm-associated pilus (Ebp) is polymerized on the membrane by sortase C (SrtC) and attached to the cell wall by sortase A (SrtA). In the absence of SrtA, polymerized pili remain anchored to the membrane (i.e. off-pathway). Here we show that the high temperature requirement A (HtrA) bifunctional chaperone/protease of E. faecalis is a quality control system that clears aberrant off-pathway pili from the cell membrane. In the absence of HtrA and SrtA, accumulation of membrane-bound pili leads to cell envelope stress and partially induces the regulon of the ceftriaxone resistance-associated CroRS two-component system, which in turn causes hyper-piliation and cell morphology alterations. Inactivation of croR in the OG1RF ΔsrtAΔhtrA background partially restores the observed defects of the ΔsrtAΔhtrA strain, supporting a role for CroRS in the response to membrane perturbations. Moreover, absence of SrtA and HtrA decreases basal resistance of E. faecalis against cephalosporins and daptomycin. The link between HtrA, pilus biogenesis and the CroRS two-component system provides new insights into the E. faecalis response to endogenous membrane perturbations.
Assuntos
Aminoaciltransferases , Proteínas de Bactérias , Biofilmes , Cisteína Endopeptidases , Enterococcus faecalis , Fímbrias Bacterianas , Chaperonas Moleculares , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/metabolismo , Aminoaciltransferases/genética , Aminoaciltransferases/metabolismo , Enterococcus faecalis/genética , Cisteína Endopeptidases/genética , Cisteína Endopeptidases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Biofilmes/crescimento & desenvolvimento , Membrana Celular/metabolismo , Regulação Bacteriana da Expressão Gênica , Virulência/genética , Antibacterianos/farmacologia , Ceftriaxona/farmacologiaRESUMO
Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition.
Assuntos
Infecções por Escherichia coli , Proteínas de Escherichia coli , Proteínas de Membrana , Fosfotransferases , Policetídeos , Staphylococcus aureus , Fatores de Transcrição , Animais , Antibacterianos/metabolismo , Carbono/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Mutagênicos/metabolismo , N-Metilaspartato/metabolismo , Peptídeos , Fosfotransferases/genética , Policetídeos/metabolismo , Staphylococcus/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Fatores de Transcrição/metabolismo , Infecção dos Ferimentos/microbiologiaRESUMO
Enterococcus faecalis is a frequent opportunistic pathogen of wounds, whose infections are associated with biofilm formation, persistence, and recalcitrance toward treatment. We have previously shown that E. faecalis wound infection persists for at least 7 days. Here we report that viable E. faecalis are present within both immune and non-immune cells at the wound site up to 5 days after infection, raising the prospect that intracellular persistence contributes to chronic E. faecalis infection. Using in vitro keratinocyte and macrophage infection models, we show that E. faecalis becomes internalized and a subpopulation of bacteria can survive and replicate intracellularly. E. faecalis are internalized into keratinocytes primarily via macropinocytosis into single membrane-bound compartments and can persist in late endosomes up to 24 h after infection in the absence of colocalization with the lysosomal protease Cathepsin D or apparent fusion with the lysosome, suggesting that E. faecalis blocks endosomal maturation. Indeed, intracellular E. faecalis infection results in heterotypic intracellular trafficking with partial or absent labelling of E. faecalis-containing compartments with Rab5 and Rab7, small GTPases required for the endosome-lysosome trafficking. In addition, E. faecalis infection results in marked reduction of Rab5 and Rab7 protein levels which may also contribute to attenuated Rab incorporation into E. faecalis-containing compartments. Finally, we demonstrate that intracellular E. faecalis derived from infected keratinocytes are significantly more efficient in reinfecting new keratinocytes. Together, these data suggest that intracellular proliferation of E. faecalis may contribute to its persistence in the face of a robust immune response, providing a primed reservoir of bacteria for subsequent reinfection.
Assuntos
Enterococcus faecalis , Proteínas rab de Ligação ao GTP , Animais , Endossomos/metabolismo , Enterococcus faecalis/metabolismo , Lisossomos/metabolismo , Mamíferos , Proteínas rab de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7RESUMO
PURPOSE: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients. METHODS: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging. RESULTS: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05). CONCLUSION: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words).
Assuntos
Síndromes do Olho Seco , Glândulas Tarsais , Humanos , Glândulas Tarsais/diagnóstico por imagem , Estudos Transversais , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Piscadela , LágrimasRESUMO
INTRODUCTION: To compare intrasession agreement and repeatability of wavefront aberration measurements from three different aberrometers obtained using Hartmann-Shack, ray tracing and automated retinoscopy methods, as well as their interdevice agreement. METHODS: Three consecutive measurements were obtained using the Pentacam AXL Wave, the iTrace and the OPD-Scan III in 47 eyes of 47 patients. Wavefront refractions, root mean square of total aberrations (RMS total), RMS of higher-order aberrations (HOA) and second-, third- and fourth-order HOAs were exported for 4-mm pupils. Wavefront refractions were converted into vector components: M, J0 and J45 . Intrasession agreement and repeatability were evaluated using intraclass correlation coefficients (ICCs) and repeatability coefficients (RCs); interdevice agreement was assessed using the Bland-Altman method. RESULTS: The intrasession agreement and repeatability of RMS HOA were comparable between the three devices; both the Pentacam AXL Wave and the OPD-Scan III had better intrasession agreement and repeatability for the RMS total than the iTrace (p ≤ 0.02). Intrasession repeatability for the majority of second- and third-order aberrations was better on the Pentacam AXL Wave than on the iTrace (p ≤ 0.01) and OPD-Scan III (p ≤ 0.04), although their agreement and repeatability in spherical aberration were comparable (p ≥ 0.24). Significant systematic differences and proportional bias were detected for almost all refraction power vectors and Zernike coefficients among the three devices. CONCLUSIONS: In this study, all three devices provided good-to-excellent agreement for aberration measurements. Most of the individual Zernike's components were not exchangeable between different aberrometers. Their relative intrasession performance in agreement and repeatability varied significantly across different ocular aberration parameters.
Assuntos
Aberrações de Frente de Onda da Córnea , Humanos , Aberrometria/métodos , Refração Ocular , Reprodutibilidade dos Testes , RetinoscopiaRESUMO
BACKGROUND: We investigated the ocular surface disturbances in COVID-19 patients discharged from the hospital. METHODS: One hundred and seventy-nine eyes of 109 healthy participants and 456 eyes of 228 post-COVID-19 patients received comprehensive eye examinations; the latter were interviewed with questionnaires on ocular symptoms before and after COVID-19 diagnosis. Associations of ocular surface manifestations with virological and ophthalmic parameters were evaluated by multivariable mixed linear or logistic regression models. RESULTS: Mean interval between COVID-19 diagnosis and ophthalmic evaluation was 52.23 ± 16.12 days. The severity of meibomian gland dysfunction (MGD) based on clinical staging was higher in post-COVID-19 than healthy eyes (1.14 ± 0.67 vs. 0.92 ± 0.68, p = 0.002) and so was ocular surface staining score (0.60 ± 0.69 vs. 0.49 ± 0.68, p = 0.044). Patients requiring supplementary oxygen during hospitalisation had shorter tear break-up time (ß -1.63, 95% CI -2.61 to -0.65). Cycle threshold (Ct) value from upper respiratory samples (inversely correlated with viral load) at diagnosis had an OR = 0.91 (95% CI 0.84-0.98) with new ocular surface symptoms 4 weeks after diagnosis. The presence of ocular surface symptoms 1 week prior to COVID-19 diagnosis showed an OR of 20.89 (95% CI 6.35-68.66) of persistent or new ocular symptoms 4 weeks afterward. CONCLUSIONS: MGD and ocular surface staining are more common and severe in post-COVID-19 patients. Patients with higher viral loads have greater risks of ocular surface symptoms. Patients requiring supplementary oxygen are more likely to show tear film instability. Ocular surface evaluation should be considered 1-3 months following hospital discharge for any COVID-19 patient.
Assuntos
COVID-19 , Síndromes do Olho Seco , Doenças Palpebrais , Disfunção da Glândula Tarsal , COVID-19/epidemiologia , Teste para COVID-19 , Síndromes do Olho Seco/diagnóstico , Humanos , Glândulas Tarsais , Oxigênio , LágrimasRESUMO
PURPOSE: To describe a reproducible and easily available goat socket model for training of various oculoplastic operations, and to evaluate trainees' perception of this training model in terms of their learning progress and satisfaction. METHODS: Goat sockets including orbital rim and eye with eyelids were harvested in form of a split-head model. Ophthalmology residents underwent individual surgical training using the goat socket model, supervised by an oculoplastic attending. Participants completed a questionnaire in form of a 5-point Likert Scale to evaluate their learning progress and satisfaction. OUTCOME MEASURES: Types of oculoplastic operations performed using the goat socket models, and participants' rating of their learning progress and satisfaction were reported. RESULTS: A wide range of oculoplastic operations including both eyelid and orbital operations could be simulated because of similarities of the goat eye model to the human eye anatomy. Fifteen ophthalmic trainees participated in surgical training using the goat eye model. All (100%) participants agreed that surgical simulation using the goat socket model increased their skills in surgical instrumentation and carrying out surgical steps, and their confidence in operating on patients. Most (87%) agreed the model resembled reasonably well compared to surgeries in human, and 93% would recommend training with the model to fellow resident ophthalmologists before operating on human patients. CONCLUSIONS: Oculoplastic surgical training using goat sockets is simple, readily available, and inexpensive. Trainee users showed promising feedback and positive learning progress using the goat socket model.
Assuntos
Pálpebras , Cabras , Animais , Competência Clínica , Pálpebras/cirurgia , Humanos , Procedimentos Cirúrgicos Oftalmológicos , Órbita/cirurgiaRESUMO
BACKGROUND: Standard epithelium-off collagen cross-linking using Dresden protocol (S-CXL) is the standard of care for progressive keratoconus. Despite its efficacy, epithelial debridement is associated with pain, delayed visual rehabilitation, stromal oedema and haze. Minimising these complications while achieving a comparable efficacy remains an unmet need. METHODS: Comparative studies between transepithelial iontophoresis-assisted CXL (I-CXL) and S-CXL reporting the outcomes of visual, refractive, topographic, aberrometry, demarcation line, endothelial cell density, confocal microscopy or complications were identified from databases. Assessments of publication bias, meta-analyses, sensitivity analysis, subgroup analysis, and meta-regressions were performed. RESULTS: In this meta-analysis, 586 eyes from three randomised controlled trials and seven comparative studies were analysed. No differences were found in the change in uncorrected/corrected distance visual acuities, mean/maximum keratometry, central corneal thickness, higher order aberration, spherical aberration, coma, subbasal nerve/anterior stromal keratocyte density and demarcation line depth in both CXL protocols (P ≥ .052). However, I-CXL resulted in less thinning at the minimum pachymetry (standardised mean difference 0.25; 95% confidence interval [CI] 0.06-0.44). More importantly, there was a significant reduction in complications following I-CXL (odds ratio 0.30; 95% CI 0.12-0.75). Meta-regression analyses on demarcation line depth and complication suggested that I-CXL was more effective than S-CXL when baseline maximum keratometry was >55.2 D and the risk of complication was independent of other baseline covariates. CONCLUSION: I-CXL has a more favourable safety profile, as evidenced by the available literature, with less thinning at the minimum pachymetry and reduced risk of complications while achieving comparable effects on visual, refractive, topographic, aberrometry, and morphological outcomes as S-CXL.
Assuntos
Ceratocone , Fotoquimioterapia , Colágeno , Topografia da Córnea , Reagentes de Ligações Cruzadas , Humanos , Iontoforese , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Metanálise como Assunto , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Raios UltravioletaRESUMO
IMPORTANCE: To investigate the choroidal thickness (CT) in patients with thyroid-associated orbitopathy (TAO). BACKGROUND: To compare CT of TAO patients and healthy subjects. DESIGN: Prospective cross-sectional study in a public hospital. PARTICIPANTS: One hundred and four eyes of 52 TAO patients and 52 eyes of 26 healthy subjects. METHODS: CT was measured with enhanced-depth imaging optical coherence tomography (EDI-OCT) at the subfoveal, macular and peripapillary regions. Multivariate linear regression was used to evaluate the associations of subfoveal CT with systemic and ocular variables among TAO eyes. MAIN OUTCOME MEASURES: CT of both groups. RESULTS: CT of eyes with TAO was significantly increased at the subfoveal region, 1 and 2 mm from the fovea nasally, temporally and superiorly, and 1 mm inferior to the fovea (all P < .05). No significant difference was found in CT at 2 mm inferior to the fovea (P = .094) and all four quadrants of the peripapillary region (superior, P = .096; nasal, P = .732; inferior, P = .179; temporal, P = .052). Among TAO eyes, thinner subfoveal choroid was associated with worsening exophthalmos (P = .043), poorer visual acuity (P = .017), increasing age (P = .040) and axial length (P < .001). There was no association between CT and clinical activity score (P = .239). CONCLUSIONS AND RELEVANCE: TAO patients showed thicker choroid than controls over the macula, but not the peripapillary regions. Thinner subfoveal choroid was associated with worsening exophthalmos and poorer vision. EDI-OCT can monitor choroidal vascular changes associated with TAO and its complications.
Assuntos
Corioide/patologia , Oftalmopatia de Graves/patologia , Adulto , Corioide/diagnóstico por imagem , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Tomografia de Coerência Óptica , Acuidade VisualRESUMO
New strategies are urgently needed to target MRSA, a major global health problem and the leading cause of mortality from antibiotic-resistant infections in many countries. Here, we report a general approach to this problem exemplified by the design and synthesis of a vancomycin-d-octaarginine conjugate (V-r8) and investigation of its efficacy in addressing antibiotic-insensitive bacterial populations. V-r8 eradicated MRSA biofilm and persister cells in vitro, outperforming vancomycin by orders of magnitude. It also eliminated 97% of biofilm-associated MRSA in a murine wound infection model and displayed no acute dermal toxicity. This new dual-function conjugate displays enhanced cellular accumulation and membrane perturbation as compared to vancomycin. Based on its rapid and potent activity against biofilm and persister cells, V-r8 is a promising agent against clinical MRSA infections.
Assuntos
Antibacterianos/uso terapêutico , Biofilmes/efeitos dos fármacos , Peptídeos Penetradores de Células/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/fisiologia , Vancomicina/análogos & derivados , Vancomicina/uso terapêutico , Animais , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Linhagem Celular , Peptídeos Penetradores de Células/síntese química , Peptídeos Penetradores de Células/farmacologia , Peptídeos Penetradores de Células/toxicidade , Desenho de Fármacos , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Oligopeptídeos/síntese química , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Oligopeptídeos/toxicidade , Vancomicina/farmacologia , Vancomicina/toxicidade , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Enterococos Resistentes à Vancomicina/fisiologiaRESUMO
Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. A thin 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) film is layered onto the peptide-impregnated PCL as a diffusion barrier, to modulate and enhance release kinetics. The impregnated peptides are eventually released in a controlled fashion. The use of 2,2,2-trifluoroethanol (TFE), as polymerization and solvation medium, induces the impregnated peptides to adopt highly stable turned conformation, conserving peptide integrity, and functionality during both encapsulation and subsequent release processes. The dual layer coating showed sustained antibacterial functionality, lasting for 14 days. In vivo assessment using an experimental mouse wounding model demonstrated good biocompatibility and significant antimicrobial efficacy of the coating under physiological conditions. The coating was translated onto silicone urinary catheters and showed promising antibacterial efficacy, even outperforming commercial silver-based Dover cather. This anhydrous polymer-based platform holds immense potential as an effective antibacterial coating to prevent clinical device-associated infections. The simplicity of the coating process enhances its industrial viability.
Assuntos
Anti-Infecciosos/farmacocinética , Peptídeos Catiônicos Antimicrobianos/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos , Poliésteres/administração & dosagem , Animais , Anti-Infecciosos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Modelos Animais de Doenças , Camundongos , Infecções Urinárias/prevenção & controle , Infecção dos Ferimentos/prevenção & controleAssuntos
Oftalmopatia de Graves , Ácido Micofenólico , Humanos , Ácido Micofenólico/uso terapêutico , Sirolimo , Estudos Prospectivos , Diplopia/tratamento farmacológico , Oftalmopatia de Graves/tratamento farmacológico , Imunossupressores/uso terapêutico , Terapia de Imunossupressão , Rejeição de Enxerto , Quimioterapia CombinadaRESUMO
PURPOSE: To determine the reliability of 3 scales for assessing soft tissue inflammatory and congestive signs associated with thyroid eye disease. METHODS: This was a multicentered prospective observational study, recruiting 55 adults with thyroid eye disease from 9 international centers. Six thyroid eye disease soft tissue features were measured; each sign graded using 3 scales (presence/absence [0-1], 3-point scale [0-2], and percentage [0-100]). Each eye was graded twice by 2 independent raters. Accuracy (fraction of agreement) was calculated between the 2 trials for each rater (intrarater reliability) and between raters for all trials (interrater reliability) to determine the most sensitive scale for each feature that maintained a threshold of agreement greater than 0.70. Trial, intrarater reliability, and interrater reliability were determined by accuracy measurement of agreement for each inflammatory/congestive feature. RESULTS: Fifty-five patients had 218 assessments for 6 thyroid eye disease metrics. The intrarater reliability for each feature was consistently better than the interrater reliabilities. Using an agreement of 0.70 or better, for the interrater tests, conjunctival and eyelid edema could be reliably measured using the 0-1 or 0-2 scale while conjunctival and eyelid redness could only be reliably measured with the binary 0-1 scale. Caruncular edema and superior conjunctival redness could not be measured reliably between 2 raters with any scale. The percentage scale had poor agreement unless slippage intervals of >20% were allowed on either side of the measurements. CONCLUSIONS: Of the specific periocular soft tissue inflammatory features measured between raters in the Clinical Activity Score and Vision, Inflammation, Strabismus, Appearance scales, edema of the eyelids and conjunctiva could reliably be measured by both 0-1 and 0-2 scales, erythema of the eyelid and bulbar conjunctiva could reliably be measured only by the 0-1 scale, and the other parameters of superior bulbar erythema and caruncular edema were not reliably measured by any scale.
Assuntos
Oftalmopatia de Graves/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Túnica Conjuntiva/patologia , Edema/patologia , Pálpebras/patologia , Feminino , Oftalmopatia de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemAssuntos
Doença Relacionada a Imunoglobulina G4/diagnóstico por imagem , Nervo Oculomotor/diagnóstico por imagem , Doenças do Nervo Óptico/diagnóstico por imagem , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Imunoglobulina G/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition with diffuse thickening of the dura mater, which may cause a compressive effect or vascular compromise. We report on a 28-year-old Chinese woman with a history of granulomatous mastitis 7 years previously and oligomenorrhoea, headache, blurred vision, and raised prolactin level 2 years previously, that was diagnosed as prolactinoma and treated conservatively with bromocriptine. However, she had recurrent bilateral vision loss when the bromocriptine was stopped. Her symptoms were resolved by high-dose steroid injection but remained steroid-dependent. Serial magnetic resonance imaging scan showed progressive diffuse thickening of the pachymeningitis with disappearance of pituitary apoplexy. Lumbar puncture showed lymphocytosis with no organisms. Open biopsy of the meninges was performed and histology showed features of inflammatory infiltrates and vasculitis. This is an unusual presentation of a rare condition in this age-group, with co-existing granulomatous mastitis and chronic otitis media, and is a diagnostic challenge mimicking pituitary macroadenoma and meningioma in initial magnetic resonance imaging scans.
Assuntos
Meningite/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Prolactinoma/diagnóstico , Adulto , Bromocriptina/uso terapêutico , Diagnóstico Diferencial , Feminino , Antagonistas de Hormônios/uso terapêutico , Humanos , Meningite/patologia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/tratamento farmacológico , Prolactinoma/complicações , Prolactinoma/tratamento farmacológico , Transtornos da Visão/etiologiaRESUMO
STUDY OBJECTIVES: This study aimed to explore the relationship between post-illumination pupillary response (PIPR) with sleep and circadian measures in a community sample of healthy older adults. METHODS: Eligible participants were invited to complete a one-week sleep diary, actigraphy and provide an overnight urine sample to measure urinary 6-sulfatoxymelatonin (aMT6s). PIPR was defined as the as the pupil constriction at 6s post-stimulus (PIPR-6s), and ii) for 30s beginning 10s after stimulus (PIPR-30s) normalized as a percentage to the baseline pupil diameter, after 1s of blue and 1s of red-light stimulus, respectively. The Net-PIPRs were reported by subtracting the PIPR to red stimulus from the PIPR to blue stimulus. The relationship between PIPR metrics to aMT6s and actigraphic rest-activity rhythm parameters was examined by generalized linear models. RESULTS: A total of 48 participants were recruited (Mean age: 62.6 ± 7.1 years, Male: 44%). Both Net PIPR-6s and Net PIPR-30s were significantly associated with actigraphic rest-activity amplitude (B=0.03, p=0.001 and B=0.03, p=0.01, respectively), and actigraphic rest-activity mesor (B=0.02, p=0.001 and B=0.03, p=0.004, respectively). Additionally, the Net PIPR-30s were positively associated with overnight aMT6s level (B=0.04, p=0.03), and negatively associated with actigraphic rest-activity acrophase (B=-0.01, p=0.004) in the fully adjusted models. CONCLUSION: Attenuated PIPR is associated with a reduced actigraphic amplitude and mesor. The reduced retinal light responsivity may be a potential pathway contributing to impaired photic input to the circadian clock and resulted in the age-related circadian changes in older adults.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Retinopatia Diabética/diagnóstico por imagem , Taxa de Filtração Glomerular/fisiologia , Tomografia de Coerência Óptica/métodos , Capilares/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia/métodos , Humanos , Testes de Função Renal , Modelos Logísticos , Masculino , Prognóstico , Índice de Gravidade de DoençaRESUMO
PURPOSE: To study the effect of bicanalicular silicone intubation on endonasal endoscopic mechanical dacryocystorhinostomy (EEM-DCR) for primary acquired nasolacrimal duct obstruction (PANDO). DESIGN: Randomized clinical trial. PARTICIPANTS: A total of 120 consecutive adults (103 females) with a presenting age of 64 ± 13.7 years (range, 39-92 years) underwent EEM-DCR for PANDO from November 2005 to May 2009 in a lacrimal referral center. METHODS: The EEM-DCR was performed by 2 lacrimal surgeons using standard techniques. Patients were randomly assigned to receive or not receive bicanalicular silicone intubation for 8 weeks. No antimetabolite was used. All patients received a course of oral antibiotics during nonabsorbable nasal packing for flaps tamponade, which was removed at the first postoperative visit. Patients were assessed at 1, 3, 6, 12, 26, and 52 weeks after the operation. MAIN OUTCOME MEASURES: Surgical success was defined by symptomatic relief of epiphora, reestablishment of nasolacrimal drainage confirmed by irrigation by 1 masked observer, and positive functional endoscopic dye test by the operative surgeon at 12 months postoperatively. Intraoperative and postoperative complications were recorded. RESULTS: A total of 118 of the 120 randomized cases completed 12 months of follow-up. Two patients died of unrelated medical illnesses during follow-up. At 12 months postoperatively, there was no statistical difference in the success rate between patients with (96.3%) and without (95.3%) intubation (P=0.79). The odds ratio of failure without silicone intubation was 1.28 (95% confidence interval, 0.21-7.95). There was no difference in the incidence (P=0.97) or the time to develop (P=0.12) granulation tissue between the 2 groups. No significant difference was found between successful and failed cases in terms of age (P=0.21), sex (P=0.37), laterality (P=0.46), mode of anesthesia (P=0.14), surgeon (P=0.26), use of stent (P=0.79), or presence of granulation tissue postoperatively (P=0.39). CONCLUSIONS: The current study design provided 90% statistical power to detect more than 21% difference in surgical outcome, and no such difference was found whether intubation was used or not used in EEM-DCR for PANDO at the 12-month follow-up. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Assuntos
Dacriocistorinostomia , Dacriocistorinostomia/instrumentação , Intubação/instrumentação , Ducto Nasolacrimal/cirurgia , Elastômeros de Silicone , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Dacriocistorinostomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To describe the clinicopathological characteristics of patients with eyelid tumours in Hong Kong. DESIGN: Retrospective case series. SETTING: A tertiary eye centre in Hong Kong. PATIENTS: A computerised retrieval system was used to identify all patients who underwent eyelid mass excisions with histological reports, encountered in the period 2000 to 2009, in a tertiary eye centre. The demographics (age, gender), clinical features (laterality, tumour topography), and the pathological diagnosis of each patient were documented. Descriptive statistical tabulation and analyses were performed on the data. RESULTS: In all, 198 patients were identified; all were Chinese. Their mean age was 54 years for benign lesions and 68 years for malignant ones. Women were more commonly affected. Benign tumourous lesions occurred more commonly on the upper (n=91; 54%) than lower eyelid (n=79; 47%), whereas malignant lesions more often affected the lower (n=17, 61%) than upper (n=11, 39%) eyelid. The distribution of left and right eye involvement was similar (103 vs 101, respectively). In six patients, there were bilateral benign lesion. Regarding benign masses, 45 (27%) were intradermal neavi, 38 (22%) were squamous papillomas, 25 (15%) were seborrhoeic keratosis lesions, 14 (8%) were epidermoid cysts, and 7 (4%) were compound naevi. Regarding malignant eyelid tumours, the most common was basal cell carcinomas (n=12, 43%), 5 (18%) were squamous cell carcinomas, 3 (11%) were actinic keratosis lesions, and 2 (7%) each were sebaceous gland carcinomas and melanomas. CONCLUSION: Benign lesions constituted the majority of these eyelid tumours. Among the malignant lesions, basal cell carcinoma was the commonest type, with lower lid involvement in majority. Sebaceous gland carcinoma is not rare, which is in contrast to Caucasian populations. The relative frequencies of the most common malignant tumours in Hong Kong differed substantially from those reported in other Asian studies.