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1.
Intern Med J ; 54(7): 1097-1105, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38323357

RESUMEN

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare autoimmune disease which is managed by a range of specialities. There are limited data on treatment practices in Australia and New Zealand. AIMS: To understand current patterns of acute AAV treatment in Australia and New Zealand. METHODS: An online survey was conducted between July and October 2022 investigating physicians' views on the management of AAV, focusing on induction therapy. The survey contained questions pertaining to access to treatment and responses to clinical management scenarios. Eosinophilic granulomatosis with polyangiitis was not included. A chi-squared test of independence was performed for statistical analysis. RESULTS: From a total of 55 responses, plasma exchange was difficult to access for 44% of respondents, more so in rural centres, and they also had difficulty accessing infusion centres. New Zealand clinicians had more difficulty accessing rituximab, with only 44% reporting easy access compared with Australian clinicians (93%). With clinical management scenarios, there was variation in the dosing regimen of glucocorticoids and initiation of plasma exchange, with 42% of respondents prescribing a glucocorticoid regimen different from the standard of care, the 'reduced-dose' arm of the Plasma Exchange and Glucocorticoids for the Treatment of ANCA-Associated Vasculitis trial. The choice of cyclophosphamide or rituximab for induction therapy was based on patient characteristics and medical history. CONCLUSIONS: There is substantial variation in approaches to the acute management of AAV in Australia and New Zealand, including differences in resource availability. This variation in care demonstrates the need to implement current practice guidelines and institute contemporary monitoring of AAV management, to achieve best patient outcomes.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glucocorticoides , Intercambio Plasmático , Rituximab , Humanos , Intercambio Plasmático/métodos , Nueva Zelanda , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Australia , Rituximab/uso terapéutico , Glucocorticoides/uso terapéutico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encuestas y Cuestionarios , Masculino , Factores Inmunológicos/uso terapéutico
2.
Diabetologia ; 57(9): 1977-85, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24957662

RESUMEN

AIMS/HYPOTHESIS: The AGEs and the receptor for AGEs (RAGE) are known contributors to diabetic complications. RAGE also has a physiological role in innate and adaptive immunity and is expressed on immune cells. The aim of this study was to determine whether deletion of RAGE from bone-marrow-derived cells influences the pathogenesis of experimental diabetic nephropathy. METHODS: Groups (n = 8/group) of lethally irradiated 8 week old wild-type (WT) mice were reconstituted with bone marrow from WT (WT → WT) or RAGE-deficient (RG) mice (RG → WT). Diabetes was induced using multiple low doses of streptozotocin after 8 weeks of bone marrow reconstitution and mice were followed for a further 24 weeks. RESULTS: Compared with diabetic WT mice reconstituted with WT bone marrow, diabetic WT mice reconstituted with RG bone marrow had lower urinary albumin excretion and podocyte loss, more normal creatinine clearance and less tubulo-interstitial injury and fibrosis. However, glomerular collagen IV deposition, glomerulosclerosis and cortical levels of TGF-ß were not different among diabetic mouse groups. The renal tubulo-interstitium of diabetic RG → WT mice also contained fewer infiltrating CD68(+) macrophages that were activated. Diabetic RG → WT mice had lower renal cortical concentrations of CC chemokine ligand 2 (CCL2), macrophage inhibitory factor (MIF) and IL-6 than diabetic WT → WT mice. Renal cortical RAGE ligands S100 calgranulin (S100A)8/9 and AGEs, but not high mobility box protein B-1 (HMGB-1) were also decreased in diabetic RG → WT compared with diabetic WT → WT mice. In vitro, bone-marrow-derived macrophages from WT but not RG mice stimulated collagen IV production in cultured proximal tubule cells. CONCLUSIONS/INTERPRETATION: These studies suggest that RAGE expression on haemopoietically derived immune cells contributes to the functional changes seen in diabetic nephropathy by promoting macrophage infiltration and renal tubulo-interstitial damage.


Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Riñón/metabolismo , Receptores Inmunológicos/metabolismo , Animales , Diabetes Mellitus Experimental/genética , Macrófagos/metabolismo , Masculino , Ratones , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/genética
3.
Int J Rheum Dis ; 24(7): 904-911, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34019342

RESUMEN

AIM: Although antineutrophil cytoplasmic antibody-associated vasculitis (AAV) most commonly affects older individuals, many patients develop the disease during their most productive working years. The aim of this study was to examine the effects of AAV on employment and work disability in a cohort of Australian patients of working age. METHODS: Patients attending a vasculitis clinic located in Melbourne, Australia, completed an employment questionnaire in addition to the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem. RESULTS: The average age of the 47 respondents was 47.8 ± 11.9 years (range 22-63 years), with a median disease duration of 60 months (range 10.2-318.5 months). There were 68.1% who were currently employed, but 20.6% of respondents employed at the time of diagnosis were no longer working and 10.6% had experienced a significant reduction in work hours since their diagnosis. There were 12.7% who were dependent on the disability support pension. The rate of work disability was 23.4%. Many participants considered themselves work impaired (41.9%), with 10.1% having missed work in the previous week. Furthermore, 44.7% of respondents reported that their financial stability had been negatively impacted by their vasculitis diagnosis. Fatigue was commonly reported. Work disabled patients were significantly more likely to be obese and less likely to have completed a tertiary education. Work disabled patients tended to be older, myeloperoxidase-antineutrophil cytoplasmic antibody positive, and have renal involvement and lung involvement. CONCLUSION: A proportion of people living with AAV in Australia experience a decline in employment and an increase in work disability when living with this condition.


Asunto(s)
Absentismo , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Costo de Enfermedad , Eficiencia , Empleo , Calidad de Vida , Adulto , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/psicología , Australia/epidemiología , Estudios de Cohortes , Evaluación de la Discapacidad , Fatiga/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios , Evaluación de Capacidad de Trabajo
4.
Nat Commun ; 10(1): 2201, 2019 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-31101814

RESUMEN

Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Predisposición Genética a la Enfermedad , Lupus Eritematoso Sistémico/genética , Proteínas de la Membrana/genética , Familia-src Quinasas/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adolescente , Adulto , Animales , Linfocitos B/citología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Estudios de Casos y Controles , Línea Celular , Núcleo Celular/inmunología , Núcleo Celular/metabolismo , Niño , Modelos Animales de Enfermedad , Femenino , Frecuencia de los Genes , Células HEK293 , Voluntarios Sanos , Humanos , Factores Reguladores del Interferón/inmunología , Factores Reguladores del Interferón/metabolismo , Interferón Tipo I/inmunología , Interferón Tipo I/metabolismo , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación Missense , Secuenciación del Exoma , Familia-src Quinasas/metabolismo
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