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1.
Eur J Surg Oncol ; 48(11): 2308-2314, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36184421

RESUMO

Pelvic exenteration, first described in 1948 and subsequently refined, may be offered as a last hope of cure to patients with recurrent or locally advanced pelvic tumours, where radiotherapy is not an option. It is a complex, morbid, ultra-radical procedure involving en-bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid. This article discusses the evolution of and current indications for pelvic exenteration in gynaecologic oncology as well as the reasons for its decline: primary and secondary prevention of cervical cancer (the recurrence of which is the most common indication for exenteration); improvements in treatment of cervical, endometrial, vaginal and vulvar cancer in the primary and recurrent setting; and the advent of novel therapies.


Assuntos
Neoplasias dos Genitais Femininos , Exenteração Pélvica , Radioterapia (Especialidade) , Neoplasias do Colo do Útero , Neoplasias Vulvares , Humanos , Feminino , Neoplasias dos Genitais Femininos/radioterapia , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Neoplasias Vulvares/radioterapia , Neoplasias Vulvares/cirurgia , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos
2.
Clin Oncol (R Coll Radiol) ; 34(3): 198-204, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34903431

RESUMO

AIMS: Quality assurance in radiotherapy (QART) is essential to ensure the scientific integrity of a clinical trial. This paper reports the findings of the retrospective QART assessment for all centres that participated in PORTEC-3; a randomised controlled trial that compared pelvic radiotherapy with concurrent chemoradiotherapy to the pelvis followed by adjuvant chemotherapy. The trial showed an overall survival benefit for the addition of the chemotherapy in the management of women with high-risk endometrial cancer. MATERIALS AND METHODS: Clinicians were invited to upload a randomly selected case/s treated at each of the participating sites. Panel reviewers analysed the contours to certify that the target volumes and organ at risk structures were contoured according to guidelines. The results were categorised into acceptable, minor variation, major variation or unevaluable. The radiotherapy plans were dosimetrically evaluated using the well-established Trans-Tasman Radiation Oncology Group (TROG) protocol. RESULTS: Between August 2010 and January 2018, data from 146 patients of 686 consecutively treated patients were retrospectively reviewed. All 16 Australia and New Zealand and 71 of 77 international centres uploaded data for evaluation. In total, 3514 dosimetric and contour variables were reviewed. Of these, 3136 variables were deemed acceptable (89.2%), with 335 minor (9.6%) and 43 major variations (1.2%). Major contour variations included the clinical target volume vaginal vault, clinical target volume parametria and differential planning target volume vault expansion. CONCLUSION: The results of the QART assessment confirmed high uniformity and low rates of both minor and major deviations in contouring and dosimetry in all sites. This supports the safe introduction of the PORTEC-3 treatment protocol into routine clinical practice.


Assuntos
Radioterapia (Especialidade) , Quimiorradioterapia , Quimioterapia Adjuvante , Feminino , Humanos , Pelve , Estudos Retrospectivos
3.
Prog Retin Eye Res ; 85: 100970, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33930561

RESUMO

Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Müller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision. Müller glial cells, which are the major structural cells of the retina, play a very important role in retinal homeostasis during health and disease. They are responsible for the spontaneous retinal regeneration observed in zebrafish and lower vertebrates during early postnatal life, and despite the presence of Müller glia with stem cell characteristics in the adult mammalian retina, there is no evidence that they promote regeneration in humans. Like many other stem cells and neurons derived from pluripotent stem cells, Müller glia with stem cell potential do not differentiate into retinal neurons or integrate into the retina when transplanted into the vitreous of experimental animals with retinal degeneration. However, despite their lack of integration, grafted Müller glia have been shown to induce partial restoration of visual function in spontaneous or induced experimental models of photoreceptor or retinal ganglion cell damage. This improvement in visual function observed after Müller cell transplantation has been ascribed to the release of neuroprotective factors that promote the repair and survival of damaged neurons. Due to the development and availability of pluripotent stem cell lines for therapeutic uses, derivation of Müller cells from retinal organoids formed by iPSC and ESC has provided more realistic prospects for the application of these cells to retinal therapies. Several opportunities for research in the regenerative field have also been unlocked in recent years due to a better understanding of the genomic and proteomic profiles of the developing and regenerating retina in zebrafish, providing the basis for further studies of the human retina. In addition, the increased interest on the nature and function of cellular organelle release and the characterization of molecular components of exosomes released by Müller glia, may help us to design new approaches that could be applied to the development of more effective treatments for retinal degenerative diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas , Peixe-Zebra , Animais , Células Ependimogliais , Humanos , Neuroglia , Proteômica , Retina , Células Ganglionares da Retina
4.
Clin Oncol (R Coll Radiol) ; 33(9): e403-e411, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33715936

RESUMO

Radiotherapy and brachytherapy are the definitive treatments for locally advanced cervix cancer. The use of soft-tissue imaging, particularly magnetic resonance imaging, has enhanced their effectiveness and improved clinical outcomes. However, the use of magnetic resonance imaging is largely restricted to well-resourced centres in both the first and developing world and remains elusive to many less advantaged centres, particularly those in areas with a high burden of cervix cancer. Ultrasound is an accessible, affordable and accurate imaging modality that can be used throughout the brachytherapy procedure. Ultrasound is primarily used to ensure safe insertion of the applicator but can also be used to guide planning. The methods used to utilise ultrasound images for planning are described. Ultrasound is particularly useful as a verification aid to confirm applicator placement after patients are moved and transferred around the radiotherapy department. It can also be used to verify the dimensions of treatment volumes over the course of brachytherapy. There is a crucial unmet need for an accessible economical soft-tissue imaging modality in cervical brachytherapy. Ultrasound has the potential to meet this need.


Assuntos
Braquiterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Ultrassonografia , Ultrassonografia de Intervenção , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
5.
Eye (Lond) ; 31(6): 856-864, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28128793

RESUMO

PurposeChildren with cataract and their families face intensive medical and surgical management, with numerous hospital attendances, topical medications, and surgical procedures, as well as uncertainty about the child's future visual ability, education, and independence. Little is known about the impact on functional visual ability, vision-, and health-related quality of life (VR-, HR-QoL).Patients and methodsSeventy two children aged 2-16 years (mean 8.45, SD 4.1) treated for developmental or secondary cataract and their parents/carers completed three validated instruments measuring functional visual ability, VR-, and HR-QoL: the Cardiff Visual Ability Questionnaire for Children (CVAQC), Impact of Vision Impairment for Children (IVI-C), and PedsQL V 4.0.ResultsAll scores are markedly reduced: median (interquartile range (IQR)) CVAQC score -1.42 (-2.28 to -0.03), mean (SD) IVI-C score 65.67 (16.91), median (IQR) PedsQL family impact score 75 (56.94-88.19), parent report 71.74 (51.98-88.5), self-report 76.09 (61.96-89.13). Psychosocial PedsQL subscores are lower than physical subscores. Parent-completed tools (PedsQL family and parent report) state greater impact on HR-QoL than tools completed by children/young people, particularly in teenagers. Older children/young people have higher functional visual ability scores than younger children.ConclusionsCataract has a marked a long-term impact on functional visual ability and quality of life of children and young people, with HR-QoL affected to degrees reported in children with severe congenital cardiac defects or liver transplants.


Assuntos
Catarata/psicologia , Gerenciamento Clínico , Nível de Saúde , Qualidade de Vida , Acuidade Visual , Adolescente , Catarata/fisiopatologia , Catarata/terapia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Autorrelato , Inquéritos e Questionários
6.
Biomater Sci ; 4(6): 943-7, 2016 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-27127811

RESUMO

The Fc-fusion mimetic RpR 2[combining low line] was prepared by disulfide bridging conjugation using PEG in the place of the Fc. RpR 2[combining low line] displayed higher affinity for VEGF than aflibercept. This is caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics.


Assuntos
Receptores de Fatores de Crescimento do Endotélio Vascular/química , Receptores de Fatores de Crescimento do Endotélio Vascular/imunologia , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/imunologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Dissulfetos/química , Humanos , Fragmentos Fab das Imunoglobulinas/química , Fragmentos Fab das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Peso Molecular , Polietilenoglicóis/química , Ligação Proteica/imunologia , Multimerização Proteica
7.
Glia ; 64(4): 495-506, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26556395

RESUMO

Retinal gliosis is characterized by biochemical and physiological changes that often lead to Müller glia proliferation and hypertrophy and is a feature of many neuro-degenerative and inflammatory diseases such as proliferative vitreoretinopathy (PVR). Although Müller glia are known to release inflammatory factors and cytokines, it is not clear whether cytokine production by these cells mirrors the pattern of factors present in the gliotic retina. Lysates from normal cadaveric retina and gliotic retinal specimens from patients undergoing retinectomy for treatment of PVR, the Müller cell line MIO-M1 and four human Müller glial cell preparations isolated from normal retina were examined for their expression of cytokines and inflammatory factors using semi-quantitative dot blot antibody arrays and quantitative arrays. Comparative analysis of the expression of inflammatory factors showed that in comparison with normal retina, gliotic retina exhibited greater than twofold increase in 24/102 factors examined by semiquantitative arrays, and a significant increase in 19 out of 27 factors assessed by quantitative methods (P < 0.05 to P < 0.001). It was observed that with the exception of some chemotactic factors, the majority of cytokines and inflammatory factors were produced by Müller glia in vitro and included G-CSF, MCP-1, PDGF-bb, RANTES, VEGF, and TGFß2. These results showed that a large number of inflammatory factors expressed by Müller glia in vitro are upregulated in the gliotic retina, suggesting that targeting the production of inflammatory factors by Müller glia may constitute a valid approach to prevent neural damage during retinal gliosis and this merits further investigations.


Assuntos
Citocinas/metabolismo , Células Ependimogliais/imunologia , Retina/imunologia , Vitreorretinopatia Proliferativa/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular , Humanos , Immunoblotting , Pessoa de Meia-Idade , Retina/cirurgia , Vitreorretinopatia Proliferativa/cirurgia
8.
Eye (Lond) ; 29(10): 1360-7, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26315700

RESUMO

PURPOSE: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the U.K. Biobank. METHODS: Biobank is a study of U.K. residents aged 40-69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112,690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined. RESULTS: In all, 1916 (1.7%) people in U.K. Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs. 56.7 years, P<0.001) and male (2.1% vs. 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18 mm Hg both eyes, P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001) compared with those without (16 mm Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was -0.72 for those reporting glaucoma and -0.95 for those without (P<0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (<£18,000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P<0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect. CONCLUSIONS: In a large U.K. cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions.


Assuntos
Glaucoma/epidemiologia , Classe Social , Adulto , Distribuição por Idade , Idoso , Córnea/fisiologia , Estudos Transversais , Elasticidade/fisiologia , Feminino , Glaucoma/diagnóstico , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Fatores de Risco , Autorrelato , Distribuição por Sexo , Inquéritos e Questionários , Reino Unido/epidemiologia , Acuidade Visual/fisiologia
9.
Eye (Lond) ; 29(6): 820-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25853399

RESUMO

PURPOSE: To compare and examine the storage stability of compounded bevacizumab in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC syringes have been used in a recent clinical study and bevacizumab stability has not been reported for this type of syringe. METHODS: Repackaged bevacizumab was obtained from Moorfields Pharmaceuticals in PC and PP syringes. Bevacizumab from the stored syringes was analysed at monthly time points for a 6-month period and compared with bevacizumab from a freshly opened vial at each time point. SDS-PAGE electrophoresis and size-exclusion chromatography (SEC) was used to observe aggregation and degradation. Dynamic light scattering (DLS) provided information about the hydrodynamic size and particle size distribution of bevacizumab in solution. VEGF binding and the active concentration of bevacizumab was determined by surface plasmon resonance (SPR) using Biacore. RESULTS: SDS-PAGE and SEC analysis did not show any changes in the presence of higher molecular weight species (HMWS) or degradation products in PC and PP syringes from T0 to T6 compared with bevacizumab sampled from a freshly opened vial. The hydrodynamic diameter of bevacizumab in the PC syringe after 6 months of storage was not significantly different to bevacizumab taken from a freshly opened vial. Using SPR, the VEGF binding activity of bevacizumab in the PC syringe was comparable to bevacizumab taken from a freshly opened vial. CONCLUSION: No significant difference over a 6-month period was observed in the quality of bevacizumab repackaged into prefilled polycarbonate and polypropylene syringes when compared with bevacizumab that is supplied from the vial.


Assuntos
Inibidores da Angiogênese/análise , Bevacizumab/análise , Polímeros , Polipropilenos , Seringas , Inibidores da Angiogênese/química , Bevacizumab/química , Composição de Medicamentos , Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Polímeros/química , Polipropilenos/química , Multimerização Proteica , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
10.
Eye (Lond) ; 28(8): 931-43, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24924446

RESUMO

Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma.


Assuntos
Glaucoma/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Criança , Pré-Escolar , Humanos
11.
Eye (Lond) ; 24(7): 1127-34; quiz 1135, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20539317

RESUMO

PURPOSE: To determine whether prophylactic laser peripheral iridotomy (LPI) for primary angle closure (PAC) is associated with cataract progression. METHODS: In 1999, Mongolian volunteers aged>or=50 years were invited to participate in a longitudinal study. Glaucoma was excluded in all participants and 712 of them were selected to undergo a full ophthalmic examination as part of the study protocol. Lenses were graded and PAC diagnosed using international classification systems. In 2005, all traced participants underwent a similar dilated examination. Diagnosis of cataract progression was based on the inter-observer variation +2 standard deviations. The association between LPI at baseline and cataract progression was assessed using chi2-test and logistic regression. RESULTS: Of 712 participants, 158 were diagnosed with occludable angles and treated with LPI. In 2005, 137 participants (19.2%) had died, 315 (315/575=54.8%) were traced, and dilated examination was performed on 276 (48%) of them. Progression of nuclear opacity (NO), cortical, and posterior subcapsular (PSC) opacities were evident in 40 (14.5%, 95% confidence interval (CI)=10.6-19.2%), 89 (32.2%, 95% CI=26.8-38.1%), and 11 participants (4.0%, 95% CI=2.0-7.0%), respectively. Although NO was more likely to progress in those with LPI in a crude analysis (odds ratio (OR)=2.02, 95% CI=1.00-4.11, P=0.05), no evidence of an independent association was detected in multivariate analysis adjusting for age, sex, and baseline Schaffer grading (adjusted OR=1.24, 0.41-3.75, P=0.7). There was no evidence of an association between LPI and progression of PSC or cortical opacities. CONCLUSIONS: There is no evidence that prophylactic LPI is independently associated with cataract progression in this study.


Assuntos
Catarata/etiologia , Glaucoma de Ângulo Fechado/cirurgia , Iridectomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Catarata/classificação , Catarata/fisiopatologia , Progressão da Doença , Feminino , Glaucoma de Ângulo Fechado/complicações , Humanos , Iridectomia/métodos , Terapia a Laser , Cristalino/patologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mongólia , Fatores de Risco
12.
Drug Discov Today ; 15(7-8): 287-99, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20197108

RESUMO

Glaucoma is the most common age-related optic nerve disease and also the most common neuropathy, affecting approximately 60 million people worldwide in its most common forms. This figure is expected to rise to 80 million by 2020. Glaucoma is a neurodegenerative disease in which various triggers induce cascades of secondary events, which ultimately lead to apoptotic retinal ganglion cell (RGC) death. The main risk factor for glaucomatous nerve damage is raised pressure in the eye. Understanding the cascades mediating optic nerve damage enables the development of new, neuroprotective treatment strategies that might not only target the initial insult but also prevent or delay secondary neurodegeneration. Furthermore, neuroregeneration and repopulation of the visual pathway by stem or neural precursor cells is becoming possible. Increasing understanding of the pathways involved in directed axon growth and manipulation of stem and progenitor cells towards an RGC fate have facilitated first successes in animal models of glaucoma.


Assuntos
Glaucoma/patologia , Glaucoma/terapia , Regeneração Nervosa/fisiologia , Doenças do Nervo Óptico/patologia , Doenças do Nervo Óptico/terapia , Nervo Óptico/patologia , Animais , Glaucoma/genética , Humanos , Pressão Intraocular/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Nervo Óptico/irrigação sanguínea , Doenças do Nervo Óptico/genética , Fluxo Sanguíneo Regional/fisiologia , Vias Visuais/patologia , Proteína bcl-X/biossíntese , Proteína bcl-X/genética
13.
Exp Eye Res ; 90(2): 308-15, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19961848

RESUMO

Retinal ganglion cell (RGC) death in glaucoma models is associated with accumulation of activated microglia, a sign of neural degeneration which has been shown to constitute a barrier for transplant cell survival and migration. This study investigated the use of triamcinolone (TA) to control macrophage/microglia accumulation in a model of RGC depletion to create a permissive environment for stem cell grafting. Intravitreal NMDA alone or in combination with TA was used to induce rapid onset of RGC death in 3-4 week old Lister hooded (LH) rat eyes prior to Müller stem cell transplantation into the vitreoretinal space. The effect of NMDA on RGC death and microglial accumulation was assessed immuno-histochemically, whilst electroretinography (ERG) was used to assess RGC function. Post transplantation, survival of grafted cells and their association with microglia were also examined by immunohistochemical methods. Intravitreal injection of NMDA alone resulted in severe macrophage/microglia accumulation associated with extensive RGC death 4-7 days post-treatment. Combination of NMDA with TA significantly reduced microglial numbers in the RGC when compared to NMDA only treated eyes while still depleting the retina of RGC. At the same time, NMDA/TA treatment also caused functional RGC loss as demonstrated by reduction of the scotopic threshold response. Upon transplantation with Müller stem cells, NMDA/TA treatment caused significant reduction in the number of transplant associated macrophage/microglia compared to eyes treated with NMDA alone. On this basis it is proposed that intravitreal injection of TA may be useful as an effective anti-inflammatory agent to control macrophage/microglia accumulation induced by RGC death, thereby creating a retinal environment permissive to cell transplantation studies.


Assuntos
Anti-Inflamatórios/farmacologia , Sobrevivência de Enxerto/fisiologia , Macrófagos/metabolismo , Microglia/metabolismo , N-Metilaspartato/toxicidade , Células Ganglionares da Retina/patologia , Transplante de Células-Tronco , Triancinolona Acetonida/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Sobrevivência Celular , Eletrorretinografia , Técnica Indireta de Fluorescência para Anticorpo , Hibridização in Situ Fluorescente , Marcação In Situ das Extremidades Cortadas , Injeções , Microglia/citologia , Ratos , Células Ganglionares da Retina/metabolismo , Corpo Vítreo
14.
J Hand Surg Eur Vol ; 34(6): 783-7, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19786408

RESUMO

Mechanical tension and contracture are two related facets of tissue biology. This study assessed the effect of ilomastat, a broad-spectrum matrix metalloprotease (MMP) inhibitor, on generation of tension by Dupuytren's disease fibroblasts. Nodule and cord-derived fibroblasts were isolated from five patients with Dupuytren's disease; flexor retinaculum acted as the control. A culture force monitor (CFM) provided an in vitro model of tissue organization to assess development of mechanical tension, lattice contraction and spatial remodelling by fibroblasts. Responses to ilomastat were compared to treatment with a control peptide. Nodule and cord-derived fibroblasts exhibited a two-fold increase in tension compared with flexor retinaculum. Ilomastat significantly inhibited development of tension by nodule and cord but not flexor retinaculum derived fibroblasts at 100 microM. These results imply that MMP activity mediates regulation of tensile strength by Dupuytren's disease fibroblasts and may be an important therapeutic target in patients with Dupuytren's disease.


Assuntos
Contratura de Dupuytren/patologia , Inibidores Enzimáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Indóis/farmacologia , Inibidores de Metaloproteinases de Matriz , Células Cultivadas , Citocalasina D/farmacologia , Humanos , Ácidos Hidroxâmicos , Inibidores da Síntese de Ácido Nucleico/farmacologia
15.
Eye (Lond) ; 23(9): 1775-80, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19136925

RESUMO

BACKGROUND: Adult height is independently related to ocular dimensions and shorter people have shorter globes and shallower anterior chambers. We investigated the relationship between adult height and angle dimensions to explore measuring height as a possible screening test for angle closure. METHODS: A population-based, cross-sectional survey of adult Chinese living in the Tanjong Pagar district, Singapore was conducted. Anterior chamber depth, gonioscopic angle width and height were assessed using standardized protocols. RESULTS: Data were available for 996 persons. Shorter people had shallower anterior chamber depth (2.35 mm for persons <144 cm vs 2.72 mm for persons >170 cm, P=0.008) and smaller gonioscopic angles (22 degrees for <144 cm vs 30 degrees for >170 cm, P=0.079). After controlling for age and gender, adult height was significantly related to anterior chamber depth (P=0.008) but not significantly related to gonioscopic angle width (P=0.079). Female sex and age > or = 50 years used together correctly identified 45/66 (68.2%) individuals with an occludable angle (sensitivity 68.2%, specificity 61.3%). Fewer people, 41/66 (62.1%), were correctly identified when height <160 cm was added to female sex and age 50 > or = years (sensitivity was 62.1% and specificity was 64.7%). CONCLUSIONS: Shorter adult height is significantly associated with a shallower anterior chamber depth, but the addition of height contributed little to demographics (age and gender) as the preliminary screening criteria to identify individuals at risk of an occludable angle.


Assuntos
Câmara Anterior/patologia , Estatura , Glaucoma de Ângulo Fechado/diagnóstico , Adulto , Idoso , Estudos Transversais , Feminino , Glaucoma de Ângulo Fechado/fisiopatologia , Humanos , Pressão Intraocular , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Singapura , Malha Trabecular/patologia
16.
Eye (Lond) ; 23(9): 1859-65, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18949008

RESUMO

PURPOSE: Inflammation is a risk factor for scarring after trabeculectomy surgery. Mast cells are important mediators of inflammation and scarring in allergic eye disease. This exploratory project investigated the presence of mast cells in the conjunctiva of glaucoma patients having trabeculectomy surgery. METHODS: Conjunctival biopsies from glaucoma patients belonging to specific groups: medically treated glaucoma (M, n=6), repeat glaucoma surgery (S, n=8), and uveitic glaucoma (U, n=7). The control group (C, n=8) was retinal detachment patients undergoing repair surgery for the first time. Immunohistochemistry techniques stained for the presence of the intracellular mast cell enzyme tryptase. RESULTS: The median mast cell tryptase-positive counts for all glaucoma groups (M, S, and U) ranged from 0.102-0.113 cells/mm2 compared to 0.064 cells/mm2 for group C. This was statistically significant comparing group S to group C (P=0.0063), but not when comparing groups U or M to group C. The mast cell tryptase-positive counts did not significantly differ among the groups. CONCLUSIONS: Mast cell numbers were significantly increased in glaucoma patients who have previously undergone surgery (group S). Mast cell activity may contribute to the scarring process and the increased risk of excessive conjunctival scarring after trabeculectomy surgery. Further investigation needs to be performed to evaluate this potential role.


Assuntos
Túnica Conjuntiva/patologia , Glaucoma/patologia , Inflamação/patologia , Mastócitos/patologia , Uveíte/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Proliferação de Células , Cicatriz/etiologia , Túnica Conjuntiva/enzimologia , Feminino , Glaucoma/enzimologia , Humanos , Imuno-Histoquímica , Inflamação/complicações , Inflamação/enzimologia , Masculino , Mastócitos/enzimologia , Pessoa de Meia-Idade , Trabeculectomia , Triptases/análise , Uveíte/complicações , Uveíte/enzimologia , Adulto Jovem
17.
Neurosci Lett ; 440(3): 251-4, 2008 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-18572317

RESUMO

A mixture of olfactory ensheathing cells and fibroblasts cultured from the adult rat olfactory mucosa was transplanted through a scleral incision into the retina. A major stream of transplanted cells migrated through the stratum opticum and penetrated for up to about 0.5mm into the optic nerve head. This stream of transplanted cells consisted of a mixture of bipolar olfactory ensheathing cells with long processes which give rise to a non-myelinating ensheathment of single retinal ganglion cell axons, and olfactory nerve fibroblasts embedded in a dense fibronectin-positive extracellular matrix. A second stream of ovoid olfactory ensheathing cells with tufted processes and unaccompanied by fibroblasts or matrix migrate into the internal plexiform layer. The incorporation of olfactory ensheathing cells in the optic nerve head may suggest future possibilities for protection of the axons in this vulnerable region from mechanical damage, as in the raised intraocular pressure of glaucoma.


Assuntos
Axônios/fisiologia , Transplante de Células/métodos , Mucosa Olfatória/citologia , Disco Óptico/citologia , Retina/cirurgia , Células Ganglionares da Retina/citologia , Animais , Movimento Celular/fisiologia , Células Cultivadas , Feminino , Fibroblastos/fisiologia , Fibronectinas/metabolismo , Proteínas de Neurofilamentos/metabolismo , Ratos
18.
Br J Ophthalmol ; 92(3): 303-9, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18303151

RESUMO

BACKGROUND/AIMS: To investigate the correlation between optic disc parameters and their association with demographic variables in a Chinese population. METHODS: Disc data were obtained from 929 subjects aged > or = 40 years from the Tanjong Pagar glaucoma survey of Singapore, using a novel planimetric method of sequential stereo-photographs. Biometric data (refractive error, keratometry, axial length, anterior chamber depth, lens thickness) were used to calculate ocular magnification. Camera magnification was quantified with a model eye. A "normal" dataset of 622 subjects was generated by exclusion of subjects with abnormal results on psychophysical testing, an occludable angle or an intraocular pressure > 97.5th percentile in either eye. RESULTS: Median disc area (DA), cup area (CA), and rim area (RA) were 2.09 (range 1.28-4.01) mm2, 0.69 (0.01-1.90) mm2 and 1.38 (0.82-2.50) mm2, respectively. There was strong evidence of an association between DA and RA (Spearman's rho 0.624, p<0.001). DA and RA were significantly greater in men (median DA = 2.20; range 1.30-3.56; median RA, 1.45; range 0.85-2.30) than women (median DA, 2.00; range 1.28-4.01; median RA, 1.36; range 0.82-2.49, p<0.001). DA increased with age (Spearman's rho 0.115, p = 0.004), while RA was unrelated (rho -0.041; p = 0.308). CONCLUSIONS: The morphometric characteristics of optic discs in Chinese Singaporeans are very similar to those described in other groups, with the temporal sector rim having the smallest area. Disc and rim areas vary with sex (men > women). Disc area (but not that of the rim) increases with age.


Assuntos
Povo Asiático/estatística & dados numéricos , Disco Óptico/anatomia & histologia , Adulto , Idoso , Envelhecimento/patologia , Biometria/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valores de Referência , Caracteres Sexuais , Singapura
19.
Br J Ophthalmol ; 92(3): 310-4, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18303152

RESUMO

BACKGROUND/AIMS: To investigate the association of biometric and systemic variables with optic disc characteristics in Chinese Singaporean adults. METHODS: Ocular, biometric and medical data including intraocular pressure, refractive error, keratometry, axial length (AL), anterior chamber depth, corneal and lens thickness as well as optic disc data (using planimetry of stereo-photographs) were obtained from 622 normal subjects aged > or = 40 years from the Tanjong Pagar glaucoma survey of Singapore. RESULTS: Disc area (DA) was positively associated with AL and height but was unrelated to corneal thickness. Following adjustment for IOP and sex, DA remained positively associated with AL, height and age. Neuroretinal rim area (RA) was also significantly and positively associated with AL and also with height. RA was negatively associated with IOP and was unrelated to blood pressure, history of diabetes, myocardial infarction, stroke or migraine. CONCLUSIONS: These data on a Chinese Singaporean population identify height and axial length of the globe as significantly associated with rim area of the disc. These features should be taken into account in statistical assessments of optic nerve head morphometry. This may improve the discriminative ability of image analysis to detect glaucomatous changes. In addition, we identified a statistically significant but small inverse association between rim area and IOP within the normal statistical range.


Assuntos
Povo Asiático/estatística & dados numéricos , Disco Óptico/anatomia & histologia , Adulto , Idoso , Envelhecimento/patologia , Biometria/métodos , Estatura , Topografia da Córnea/métodos , Estudos Transversais , Olho/anatomia & histologia , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Valores de Referência , Erros de Refração/patologia , Singapura
20.
Br J Ophthalmol ; 92(1): 30-3, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18156373

RESUMO

BACKGROUND: Primary angle closure glaucoma (PACG) accounts for nearly 50% of global glaucoma blindness. There are currently no public health strategies to deal with this problem. Screening and prophylactic treatment of primary angle closure suspects (PACS) with laser peripheral iridotomy (LPI) may form a feasible population-level intervention. However, more information about the natural history of PACS is required before such an approach could be considered. METHODS: Six hundred and forty-four participants aged 50 years with a central anterior chamber depth (cACD) of <2.53 mm underwent a full slit-lamp examination in 1999. Of these, 160 participants diagnosed as having occludable angles by gonioscopy (ISGEO classification) were excluded from all further analysis, leaving 484 for follow-up. Six years later, 95/484 (19.6%) had died. A total of 201 of 389 participants traced (51.7%) were re-examined. The potential risk factors for the development of an occludable angle were assessed using the chi squared test, t test and the Wilcoxon rank sum test. RESULTS: At follow-up, 41 participants (20.4%, 95% CI: 14.8 to 25.7) were diagnosed as having incident PACS. Narrower angles, identified by grading of limbal chamber depth and gonioscopy at baseline, were strongly associated with incident occludable angles (p = 0.01 and p<0.01, respectively). There was weak evidence of an association with change in cACD (p = 0.05), and no evidence of an association with age, gender, and baseline cACD for the development of occludable angles. CONCLUSIONS: Narrower angles as determined by limbal chamber depth grading and gonioscopy at baseline were the main risk factors identified for the development of occludable angles.


Assuntos
Glaucoma de Ângulo Fechado/epidemiologia , Idoso , Câmara Anterior/patologia , Progressão da Doença , Métodos Epidemiológicos , Feminino , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/patologia , Gonioscopia , Humanos , Limbo da Córnea/patologia , Masculino , Pessoa de Meia-Idade , Mongólia/epidemiologia , Prognóstico
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