RESUMEN
Thrombosis is common in Behçet's Syndrome (BS), and there is a need for better biomarkers for risk assessment. As microparticles expressing Tissue Factor (TF) can contribute to thrombosis in preclinical models, we investigated whether plasma microparticles expressing Tissue Factor (TF) are increased in BS. We compared blood plasma from 72 healthy controls with that from 88 BS patients (21 with a history of thrombosis (Th+) and 67 without (Th-). Using flow cytometry, we found that the total plasma MP numbers were increased in BS compared to HC, as were MPs expressing TF and Tissue Factor Pathway Inhibitor (TFPI) (all p < 0.0001). Amongst BS patients, the Th+ group had increased total and TF positive MP numbers (both p ≤ 0.0002) compared to the Th- group, but had a lower proportion of TFPI positive MPs (p < 0.05). Consequently, the ratio of TFPI positive to TF positive MP counts (TFPI/TF) was significantly lower in Th+ versus Th- BS patients (p = 0.0002), and no patient with a TFPI/TF MP ratio >0.7 had a history of clinical thrombosis. We conclude that TF-expressing MP are increased in BS and that an imbalance between microparticulate TF and TFPI may predispose to thrombosis.
Asunto(s)
Síndrome de Behçet/metabolismo , Micropartículas Derivadas de Células/metabolismo , Tromboplastina/metabolismo , Trombosis/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo/métodos , Adulto JovenRESUMEN
Falls are an important health issue. They cause significant morbidity and mortality particularly in older people, and also have marked psychological effects on the individual. The literature focuses particularly on older adults, an age group in which both visual impairment and falls are more prevalent, as is the associated morbidity. In this review, we summarise the current literature and point to further studies which need to be undertaken. The consequences of falls are well recognised, and there has been considerable work into identifying risk factors. Changes in visual components such as visual field, acuity, contrast sensitivity and stereopsis all have a part and the co-existence of other sensory impairments certainly increases the risk of falls. However there remain considerable gaps in our knowledge of the relationship between visual loss and falls, for example in patients with diabetic eye disease. Furthermore, there is also conflicting data as to the importance of different visual components. Various interventions, such as programmed inter-disciplinary involvement, have shown promise, however these need further confirmation of their efficacy and cost effectiveness. An added confounder may be that an intervention (eg, cataract extraction) paradoxically affects an individual's future activity level and behaviour, thereby increasing the risk of falling. With an ageing population the importance of this topic is likely to increase, as will the potential benefits of optimising our assessment and management of these patients.
Asunto(s)
Accidentes por Caídas , Trastornos de la Visión/complicaciones , Accidentes por Caídas/prevención & control , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Reino Unido/epidemiología , Trastornos de la Visión/epidemiologíaRESUMEN
AIM: There is little information on the demographic and clinical characteristics of Behçet's disease in children in different parts of the world. We sought to provide this information through a questionnaire survey of specialist eye centres. METHODS: Descriptive questionnaires were collected from 25 eye centres in 14 countries. The questionnaire surveyed details of juvenile-onset Behçet's disease with uveitis. Ethnic groups, clinical features, treatments and prognosis of paediatric-age Behçet's disease were examined on a worldwide scale. RESULTS: The clinical data of 135 juvenile-onset and 1227 adult-onset patients with uveitis were collected. The average age of disease diagnosis in the children was 11.7 years old. Of the ethnic groups identified 54% were from Middle East, 43% from Europe, but only 2% from East/South Asian countries. By contrast, 19.2% of adult patients were from East or South Asia. The frequency of genital ulcers in juvenile patients was 38.7%, which was significantly lower than in adult cases (53.5%; p<0.01). CONCLUSIONS: Behçet's disease with uveitis was less common in children than in adults in East/South Asia. Although the clinical features of the systemic disease were similar in children and adults, there was a lower frequency of genital ulceration in children.
Asunto(s)
Síndrome de Behçet/etnología , Adulto , Edad de Inicio , Asia Sudoriental/etnología , Síndrome de Behçet/epidemiología , Niño , Europa (Continente)/etnología , Asia Oriental/etnología , Femenino , Humanos , Masculino , Medio Oriente/etnología , PrevalenciaRESUMEN
The current treatment of ocular toxoplasmosis is controversial. The mainstay of treatment has been pyrimethamine and sulphonamides with or without systemic corticosteroids, but the actual evidence that antibiotics have a beneficial effect in recurrent toxoplasmic retinochoroiditis is unsupported by randomised placebo controlled trials. Thus far there have only been three studies looking at the efficacy of antibiotic treatment, all of which were methodologically weak and two of which were perfomed more than 30 years ago. All studies reported adverse effects from treatment. There is an urgent need for further randomised, double blind, placebo controlled studies for lesions in all parts of the retina and to test the efficacy of adjunctive corticosteroid treatment.
Asunto(s)
Corticoesteroides/uso terapéutico , Antiprotozoarios/uso terapéutico , Medicina Basada en la Evidencia , Toxoplasmosis Ocular/tratamiento farmacológico , Coriorretinitis/prevención & control , Ensayos Clínicos como Asunto , HumanosRESUMEN
OBJECTIVES: To present and analyse the literature sources regarding the management of Behçet disease (BD) identified during the systematic literature research, which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD. METHODS: Problem areas and related keywords regarding the management of BD were determined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A systematic literature research was performed using MedLine and Cochrane Library resources through to December 2006. Meta-analyses, systematic reviews, randomised controlled trials (RCTs), open studies, observational studies, case control studies and case series' involving > or = 5 patients were included. For each intervention the effect size and number needed to treat were calculated for efficacy. Odds ratios and numbers needed to harm were calculated for safety issues of different treatment modalities where possible. RESULTS: The literature research yielded 137 articles that met the inclusion criteria; 20 of these were RCTs. There was good evidence supporting the use of azathioprine and cyclosporin A in eye involvement and interferon (IFN)alpha in mucocutaneous involvement. There were no RCTs with IFNalpha or tumour necrosis factor (TNF)alpha antagonists in eye involvement. Similarly controlled data for the management of vascular, gastrointestinal and neurological involvement is lacking. CONCLUSION: Properly designed, controlled studies (new and confirmatory) are still needed to guide us in managing BD.
Asunto(s)
Antirreumáticos/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Medicina Basada en la Evidencia/métodos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
OBJECTIVES: Behçet's disease (BD) is a multisystem inflammatory disease characterised by recurrent orogenital ulceration, ocular inflammation and skin lesions whose aetiology is currently unknown. We hypothesized that levels of cytokines in the serum might provide either diagnostic or activity markers for the disease. METHODS: Levels of 10 cytokines were analysed in a multiplex bead analysis system as well as IL-15 by ELISA, in 79 serum samples from 52 patients with BD. The same cytokines were also measured in serum samples from 20 patients with recurrent aphthous stomatitis (RAS), as disease controls, and 15 healthy volunteers. The results were correlated with disease activity and current drug therapy. RESULTS: CXCL8 and TNF were the most abundant cytokines and were significantly raised compared to both patients with RAS and healthy controls. IL-15 was present in all samples and was significantly raised in both patients with BD and RAS compared to healthy controls. By comparison, cytokines associated with an adaptive immune response such as IFNgamma and IL-2 were found in few samples, while IL-4 and IL-10 were not detected in any sample. Levels of cytokines correlated with each other suggesting a response to the same stimulus, however, there was no association with either disease activity or treatment. CONCLUSION: Cytokines related to activity of the innate immune response were most prominent in this study and showed good correlation with each other. In particular, it was shown that IL-15 was raised in BD. However, there was no pattern of cytokine expression relating to disease activity or treatment.
Asunto(s)
Síndrome de Behçet/diagnóstico , Síndrome de Behçet/inmunología , Citocinas/sangre , Interleucina-15/sangre , Síndrome de Behçet/sangre , Biomarcadores/sangre , Femenino , Humanos , Masculino , Estomatitis Aftosa/sangre , Estomatitis Aftosa/inmunologíaRESUMEN
AIMS: To describe the clinical and radiological features of orbital apex syndromes caused by presumed tuberculosis (TB). METHODS: A review of the discharge summaries of all patients seen in the Medical Eye Unit (MEU), St Thomas' Hospital between 1975 and 2006 identified seven patients with a diagnosis of orbital apex syndrome or optic neuropathy attributable to TB. Case notes and radiology were reviewed retrospectively for each patient. RESULTS: All of the patients were born outside the UK and were HIV-negative. Four presented during 2005-6. Six of the seven patients presented with a visual acuity (VA) of less than counting fingers (CF), but all achieved a VA of 6/9 or better after a median 3 weeks of treatment with antituberculous treatment and systemic corticosteroids. All patients had constitutional symptoms. Chest x ray and CSF were normal in each case, but MRI was abnormal in six. CONCLUSIONS: We report a recent cluster of tuberculous orbital apex syndromes, in the context of an increasing incidence of TB in the UK. The condition is difficult to diagnose, but the combination of high-dose corticosteroids and anti-TB medication was rapidly effective and achieved a good outcome in all cases.
Asunto(s)
Enfermedades del Nervio Óptico/etiología , Tuberculosis Ocular/complicaciones , Corticoesteroides/uso terapéutico , Adulto , Antituberculosos/uso terapéutico , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Estudios Retrospectivos , Síndrome , Resultado del Tratamiento , Tuberculosis Ocular/diagnóstico , Tuberculosis Ocular/tratamiento farmacológicoRESUMEN
Toxoplasma infection accounts for up to 50% of all cases of posterior uveitis worldwide. In this review the control of Toxoplasma infection generally, and specific in the eye, by the immune system is discussed.
Asunto(s)
Coriorretinitis/inmunología , Toxoplasma/inmunología , Toxoplasmosis Ocular/inmunología , Animales , Bovinos , Citocinas/inmunología , Humanos , Inmunidad/inmunología , Redes y Vías Metabólicas/inmunología , Ratones , Óxido Nítrico/inmunologíaRESUMEN
Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is regarded with other molecules such as HLA, PTPN22 and CARD15 as genetic master switches of autoimmunity. Single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with autoimmune conditions. We analysed the SNPs -318C/T and 49A/G in CTLA-4 in patients with Behcet's disease (BD), patients with intermediate uveitis and appropriate controls. Blood was collected from 236 patients with BD from the UK and the Middle East (ME), all fulfilling the International Study Group criteria for the diagnosis of BD, and 143 patients with idiopathic intermediate uveitis were recruited from the Medical Eye Unit at St Thomas' Hospital. Samples from healthy individuals from each geographical centre were used as controls. DNA was prepared by standard methods, and SNPs -318 and 49 in CTLA-4 were detected by a polymerase chain reaction-sequence specific primers (PCR-SSP) assay using primer mixes. The results showed that there was no association with either polymorphism in patients with BD from the UK or the ME. Similarly, there was no association in patients with intermediate uveitis. Moreover, there was no association with SNP in CTLA-4 and disease manifestations in BD or outcome in patients with intermediate uveitis. Both BD and intermediate uveitis have HLA associations, but there is no difference in distribution of CTLA-4 polymorphisms that are associated with other autoimmune diseases. The lack of association with polymorphisms in CTLA-4 and other master controlling genes of autoimmunity suggests that mechanisms that mediate such a description for BD and intermediate uveitis have still to be elucidated.
Asunto(s)
Antígenos CD/genética , Síndrome de Behçet/genética , Polimorfismo de Nucleótido Simple , Uveítis Intermedia/genética , Síndrome de Behçet/patología , Antígeno CTLA-4 , Estudios de Casos y Controles , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVES: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion. METHODS: The multidisciplinary expert committee, a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), consisted of nine rheumatologists (one who was also a clinical epidemiologist and one also a Rehabilitation Medicine doctor), three ophthalmologists, one internist, one dermatologist and one neurologist, representing six European countries plus Tunisia and Korea. A patient representative was also present. Problem areas and related keywords for systematic literature research were identified. Systematic literature research was performed using Medline and the Cochrane Library databases from 1966 through to December 2006. A total of 40 initial statements were generated based on the systematic literature research. These yielded the final recommendations developed from two blind Delphi rounds of voting. RESULTS: Nine recommendations were developed for the management of different aspects of BD. The strength of each recommendation was determined by the level of evidence and the experts' opinions. The level of agreement for each recommendation was determined using a visual analogue scale for the whole committee and for each individual aspect by the subgroups, who consider themselves experts in that field of BD. There was excellent concordance between the level of agreement of the whole group and the "experts in the field". CONCLUSION: Recommendations related to the eye, skin-mucosa disease and arthritis are mainly evidence based, but recommendations on vascular disease, neurological and gastrointestinal involvement are based largely on expert opinion and uncontrolled evidence from open trials and observational studies. The need for further properly designed controlled clinical trials is apparent.
Asunto(s)
Síndrome de Behçet/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Artritis/tratamiento farmacológico , Ciclosporina/efectos adversos , Medicina Basada en la Evidencia , Enfermedades Gastrointestinales/terapia , Humanos , Cooperación Internacional , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades de la Piel/tratamiento farmacológico , Uveítis/tratamiento farmacológico , Enfermedades Vasculares/tratamiento farmacológicoRESUMEN
OBJECTIVE: To systematically review the strength of evidence that supports the premise that there are different expressions in the clinical phenotype of Behcet's disease (BD) in different ethnic groups. METHODS: The hierarchy of evidence and inclusion criteria were decided prior to the search for relevant literature. We searched Medline and Embase databases between 1966 and March 2005 for publications related to epidemiology of Behcet's disease or syndrome. Relevant papers were extracted in hard copy and the references of all these papers were then hand searched for further articles. RESULTS: Four population-based studies, of which two were from Turkey, and seven non-population-based comparative studies were found. The majority of literature identified were case series and were not included in the review. There were insufficient cross-sectional studies from different populations to be able to compare phenotypic differences. None of the comparative studies found evidence of a difference in the clinical expression of BD between ethnic groups. CONCLUSIONS: There is insufficient evidence to support the premise that there are different expressions in the clinical phenotype of BD in different ethnic groups. Population-based, cross-sectional surveys or case-control studies using standardized criteria and clear ethnic definitions are suggested to investigate this hypothesis further.
Asunto(s)
Síndrome de Behçet/etnología , Humanos , Fenotipo , Proyectos de InvestigaciónRESUMEN
Behçet's disease (BD) is a chronic relapsing-remitting inflammatory disorder of unknown origin, affecting multiple organs. Neurological involvement is one of the most devastating manifestations of BD and may be fatal. We report a 36-year-old woman with neuro-Behçet who was treated with low-dose pulse cyclophosphamide (St. Thomas' protocol) and methylprednisolone, with almost complete clinical remission.
Asunto(s)
Síndrome de Behçet/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Vasculitis del Sistema Nervioso Central/tratamiento farmacológico , Adulto , Síndrome de Behçet/complicaciones , Población Negra , Femenino , Humanos , Inyecciones Intravenosas , Inducción de Remisión , Vasculitis del Sistema Nervioso Central/complicaciones , Vasculitis del Sistema Nervioso Central/etiologíaRESUMEN
PURPOSE: To investigate changes in immune response genes following Toxoplasma gondii infection of Müller cells. METHODS: Human Müller cells were infected or mock infected with two strains of T. gondii (RH and Prugniaud). RNA and supernatants were collected from infected and uninfected cells at 2 and 24 h. RNA from the two time points were compared using a custom made DNA microarray. Real time PCR or human cytokine antibody array was used to confirm up-regulation of immune molecules. RESULTS: Gene expression in infected cells showed up-regulation of CCL2, IL-6, CXCL8, and CXCL2. CCL2 and CXCL2 gene expression was confirmed by real time PCR. IL-6 and CXCL8 protein production was confirmed by a cytokine antibody array. IL-4 production was observed by cytokine antibody array but not by DNA microarray. In contrast, infection with T. gondii did not induce interferon-gamma (IFNgamma) and IL-12 expression, molecules conventionally associated with the inter-conversion of tachyzoite to bradyzoite. CONCLUSION: These results indicate that while in vitro infected Müller cells may be capable of inducing an immune response by attracting blood-borne leucocytes, they do not appear able to directly control the proliferation of T. gondii.
Asunto(s)
Expresión Génica/inmunología , Genes MHC Clase II/fisiología , Toxoplasmosis/inmunología , Animales , Línea Celular , Citocinas/metabolismo , Perfilación de la Expresión Génica , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Toxoplasma/inmunologíaRESUMEN
AIM: To compare the clinical findings in children with symptomatic toxoplasmic ocular lesions attributable to infection acquired before or after birth. METHODS: Cases were prospectively ascertained for 24 months through national surveillance units and reference laboratories in the British Isles. Age and presenting symptoms, site of lesion and visual impairment in children who were classified as acquiring infection either before or after birth on the basis of clinical and serological findings were compared. RESULTS: 31 children had toxoplasmic retinochoroiditis, 15 had congenital infection and all but three of these presented before the age of 4 years. The remaining 16 children acquired toxoplasmosis postnatally, and 14 of 16 presented after the age of 10 years. A further four children had retinochoroiditis due to other causes. The presence of bilateral, multiple or posterior pole lesions did not distinguish between the two groups, but most children (16/19; 84%) presenting with acute ocular symptoms had postnatally acquired infection. Unilateral visual impairment (Snellen < or =6/18) was equally prevalent in the two groups (4/9 before birth v 7/16 after birth; p>0.5). Only two children had bilateral visual impairment, both of whom had congenital infection. No child was blind. CONCLUSIONS: About 50% of children with ocular lesions due to toxoplasmosis had postnatal infection. Retinochoroidal lesions due to infection before and after birth were indistinguishable. The prognosis for bilateral visual function was good, regardless of when infection was acquired.
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Coriorretinitis/parasitología , Complicaciones Parasitarias del Embarazo , Toxoplasmosis Ocular/transmisión , Trastornos de la Visión/parasitología , Adolescente , Edad de Inicio , Niño , Preescolar , Coriorretinitis/patología , Femenino , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Pronóstico , Estudios Prospectivos , Toxoplasmosis Ocular/complicaciones , Toxoplasmosis Ocular/congénito , Toxoplasmosis Ocular/patologíaAsunto(s)
ADN Bacteriano/análisis , Infecciones Bacterianas del Ojo/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sífilis/diagnóstico , Treponema pallidum/genética , Cuerpo Vítreo/microbiología , Adulto , Infecciones Bacterianas del Ojo/microbiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To establish the role of intravitreal triamcinalone acetonide (TA) in the long term management of refractory uveitic cystoid macular oedema (CMO) and to determine the long term visual outcome in these patients. METHOD: This is a retrospective observational case series. All patients had resistant CMO and active inflammation. The primary outcome measure was complete resolution of CMO on ocular coherence tomography. Visual acuity and intraocular pressure were also monitored. Twelve eyes of twelve patients received 2 (n = 10) to 4 (n = 2) mg of intravitreal TA. All had previously been unresponsive to orbital floor steroids. Fluorescein angiography was performed where indicated. RESULTS: There was complete resolution of CMO in all patients. Nine patients had improvement in acuity at there final follow up (mean follow up 40.5 months). Seven had improved by 2 lines (58%). In 3 patients there was no visual improvement. These 3 failed to respond to re-treatment. Five other patients were re-treated because of recurring CMO and deteriorating VA (median time to re-treatment 4 mths). The mean number of re-treatments for this group with orbital floor TA was three. 41.6% of patients developed ocular hypertension (33.8 mhg mean). One required a trabeculectomy. CONCLUSIONS: 2 mg of intravitreal TA is effective even in cases of resistant uveitic CMO. Although re-treatment is often required, the initial response to treatment can be maintained by subsequent orbital floor steroid injections.
Asunto(s)
Glucocorticoides/uso terapéutico , Edema Macular/tratamiento farmacológico , Triamcinolona Acetonida/uso terapéutico , Uveítis/tratamiento farmacológico , Agudeza Visual/fisiología , Adulto , Femenino , Angiografía con Fluoresceína , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Inyecciones , Presión Intraocular , Edema Macular/fisiopatología , Masculino , Persona de Mediana Edad , Recurrencia , Retratamiento , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Triamcinolona Acetonida/administración & dosificación , Triamcinolona Acetonida/efectos adversos , Uveítis/fisiopatología , Cuerpo VítreoRESUMEN
HLA-B*51 is known to be associated with Behcet's disease (BD) in many ethnic groups. The pathogenic gene, however, may lie close to the HLA-B locus and therefore be in linkage disequilibrium with HLA-B*51. On the basis of the proximity of MIC genes to HLA-B, their expression pattern and their affinity for the activating NKG2D receptor on natural killer (NK) cells and gammadelta T cells, these molecules have been postulated as susceptibility factors in BD. DNA from 56 western European Caucasians with BD and 90 Caucasian controls were analysed by polymerase chain reaction using allele-specific primers for MICA and MICB alleles. An increased allele frequency of MICA*009 was found in the BD patient group (25.0%) when compared with the controls (7.2%). This was associated with a corresponding decrease in MICA*008 in the BD patients (36.6%) compared with the controls (46.7%), which was not significant. MICA*009 was strongly associated with the presence of HLA-B*51 in patients and controls. No significant difference in frequency of MICB alleles was found between patients and controls. Both HLA-B*51 and MICA*009 are strongly associated with BD in a pure Caucasian BD patient group, and the two alleles are in linkage disequilibrium. No MICB allele was found to associate significantly with the disease, an unexpected finding considering the close proximity of the MICA and MICB loci. Our results suggest that while MICB does not influence the development of BD, polymorphisms in MICA may be pathogenic, perhaps through the interaction with NK and gammadelta T cells.