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1.
BMJ Case Rep ; 17(3)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38442982

RESUMO

Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of antiphospholipid syndrome characterised by diffuse arterial and venous thrombosis, in the presence of positive antiphospholipid antibodies. The multiple sites of thrombosis in small, medium and large vessels progress to multiorgan failure, accounting for the high mortality rate associated with CAPS. Unregulated complement activation is increasingly recognised as critical to the pathogenesis of CAPS. Early diagnosis is essential to initiate prompt life-saving treatment with the triple therapy of anticoagulation, immunosuppression and either plasmapheresis or intravenous immunoglobulin. Among other immunosuppressive agents, eculizumab, a complement inhibitor has demonstrated efficacy in treatment-resistant cases.We report an instructive case of a woman presenting with both clinical and laboratory findings consistent with primary CAPS, resistant to initial treatment and responsive to eculizumab, with emphasis on genetic testing and implications for future therapy.


Assuntos
Síndrome Antifosfolipídica , Feminino , Humanos , Síndrome Antifosfolipídica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Antifosfolipídeos , Plasmaferese
2.
Front Neurosci ; 16: 1012133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36478876

RESUMO

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease. Despite therapeutic advances, a significant proportion of RA patients are resistant to pharmacological treatment. Stimulation of the cervical vagus nerve is a promising alternative bioelectric neuromodulation therapeutic approach. However, recent clinical trials show cervical vagus nerve stimulation (VNS) was not effective in a significant proportion of drug resistant RA patients. Here we aim to assess if abdominal vagus nerve stimulation reduces disease severity in a collagen-induced arthritis (CIA) rat model. The abdominal vagus nerve of female Dark Agouti rats was implanted and CIA induced using collagen type II injection. VNS (1.6 mA, 200 µs pulse width, 50 µs interphase gap, 27 Hz frequency) was applied to awake freely moving rats for 3 h/day (days 11-17). At 17 days following the collagen injection, unstimulated CIA rats (n = 8) had significantly worse disease activity index, tumor necrosis factor-alpha (TNF-α) and receptor activator of NFκB ligand (RANKL) levels, synovitis and cartilage damage than normal rats (n = 8, Kruskal-Wallis: P < 0.05). However, stimulated CIA rats (n = 5-6) had significantly decreased inflammatory scores and ankle swelling (Kruskal-Wallis: P < 0.05) compared to unstimulated CIA rats (n = 8). Levels of tumor necrosis factor-alpha (TNF-α) remained at undetectable levels in stimulated CIA rats while levels of receptor activator of NFκB ligand (RANKL) were significantly less in stimulated CIA rats compared to unstimulated CIA rats (P < 0.05). Histopathological score of inflammation and cartilage loss in stimulated CIA rats were no different from that of normal (P > 0.05). In conclusion, abdominal VNS alleviates CIA and could be a promising therapy for patients with RA.

3.
Oxf Med Case Reports ; 2019(2): omy131, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30800327

RESUMO

A 64-year-old gentleman initially presented with nephrotic syndrome and membranous nephropathy with positive staining for C1q, which was suspicious for lupus membranous nephritis. Investigation led to the simultaneous diagnosis of colorectal cancer (CRC). The CRC was surgically excised and the patient's nephrotic syndrome resolved. The patient subsequently presented with classic systemic lupus erythematosus (SLE) including positive serological markers, mouth-ulcers and a photosensitive maculopapular rash. Two months later the patient represented with an SLE flare encompassing the full-hand of renal-pulmonary syndrome and vasculitic-neuropathy, importantly at this presentation occult recurrence of CRC was proven with tissue biopsy. Major histocompatibility class II haplotyping demonstrated HLA-DRB1*03, a known predisposition for SLE. This case depicts the scenario of tumour transformation triggering SLE development in a predisposed individual after an initial paraneoplastic manifestation in the form of membranous nephropathy (plus C1q). This supports the potential role of tumourgenesis in the development of SLE in a primed individual.

4.
Int J Rheum Dis ; 22(1): 55-61, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28205411

RESUMO

AIM: The aim of this qualitative study was to report the findings of the Defining rheumatoid arthritis progression using Doppler Ultrasound in Clinical practice (DEDUCE) Medical Practice Activity, which was developed to facilitate the utilization of Doppler ultrasound (DUS) by Australian rheumatologists in the treatment of patients with rheumatoid arthritis (RA). METHOD: Twenty-one rheumatologists recruited a total of 80 patients with RA in Disease Activity Score of 28 joints (DAS28) remission for DUS assessment and completed a pre- and post-activity questionnaire assessing their experience with DUS, as well as a 6-month follow-up questionnaire. Rheumatologists discussed DUS results with patients using visual aids. Patients completed a pre- and post-DUS assessment questionnaire. Data were summarized using descriptive statistics. RESULTS: Following completion of the activity, 95% of rheumatologists (20/21) believed DUS was a useful assessment tool for patients with RA. The majority found the DUS results useful and more than half thought the DUS assessment fit well into their consultation. A majority of rheumatologists indicated they would use DUS imaging in patients with low disease activity and remission, and for disease activity assessment to inform in therapeutic decision-making. All patients who responded found the visual aids useful and most felt that discussing DUS results improved understanding of their disease and would help with medication adherence. CONCLUSION: Incorporation of DUS imaging into routine clinical practice is feasible, encourages rheumatologists to utilize and expand their clinical application of DUS imaging in patients with RA, and may improve patient understanding of their disease and adherence to medication.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Atitude do Pessoal de Saúde , Recursos Audiovisuais , Articulações/diagnóstico por imagem , Educação de Pacientes como Assunto/métodos , Reumatologistas/psicologia , Ultrassonografia Doppler , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/psicologia , Austrália , Compreensão , Estudos de Viabilidade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Articulações/efeitos dos fármacos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Satisfação do Paciente , Valor Preditivo dos Testes , Pesquisa Qualitativa , Índice de Gravidade de Doença , Inquéritos e Questionários
5.
Arthritis Res Ther ; 17: 328, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26577945

RESUMO

A small peptide, OP3-4, blocks receptor activator of NF-κB from binding to its ligand, receptor activator of NF-κB ligand (RANKL), and was reported recently to inhibit bone resorption, promote bone formation and protect cartilage in a preclinical rheumatoid arthritis model. The latter effects may result from inhibition of RANKL reverse signalling in osteoblasts and chondrocytes. Whether other RANKL inhibitors, such as denosumab, share this action is not known, but OP3-4 at least has potential to provide anabolic treatment for both systemic and focal bone loss in inflammatory arthritis.


Assuntos
Antirreumáticos/farmacologia , Artrite Reumatoide/tratamento farmacológico , Reabsorção Óssea/tratamento farmacológico , Oligopeptídeos/farmacologia , Osteogênese/efeitos dos fármacos , Ligante RANK/antagonistas & inibidores , Animais , Artrite Reumatoide/patologia , Denosumab/farmacologia , Humanos
6.
Cytokine ; 68(2): 101-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24767864

RESUMO

OBJECTIVE: To identify how the gp130-signaling cytokine oncostatin M (OSM), acting alone or in concert with IL-1ß or TNFα, affects synovial fibroblast expression of genes relevant to inflammation and bone erosion in inflammatory arthritis. METHODS: Synovial fibroblasts (SFs) were isolated from non-arthritic wild type (WT) or OSM receptor deficient (OSMR(-/-)) mice and stimulated with OSM, IL-1ß or TNFα and their combinations. Cytokine gene expression was assessed by quantitative RT-PCR. ELISA, flow cytometry and immunohistochemistry identified protein expression. Gene expression patterns were confirmed in SFs isolated from patients with osteoarthritis (OASFs) and rheumatoid arthritis (RASFs). RESULTS: Expression of OSM and its receptors, gp130, OSMR and LIFR, was increased in synovial tissue from the mouse antigen-induced arthritis model. In isolated WT mouse synovial fibroblasts OSM alone, or in synergy with IL-1ß, or together with TNFα, potently induced expression of the pro-inflammatory cytokine IL-6. OSM also induced a sustained increase in mRNA levels of the pro-osteoclastic cytokine RANKL. Combining OSM with IL-1ß, but not with TNFα, further increased RANKL expression. Importantly these effects of OSM were all dependent on the expression of OSMR. Furthermore, OSM also increased expression of its own receptors, gp130 and OSMR and the IL-1 receptor, IL1-R1; the latter effects were also observed in both human OASFs and RASFs. CONCLUSION: Together our data suggests that OSM signaling via OSMR in SFs has the potential to contribute significantly to joint destruction in inflammatory arthritis. It not only induces expression of pro-inflammatory and pro-osteoclastic cytokines but can also augment its own actions and that of IL-1 by inducing expression of OSMR and IL-1R1.


Assuntos
Fibroblastos/metabolismo , Interleucina-1beta/metabolismo , Oncostatina M/metabolismo , Receptores de Oncostatina M/metabolismo , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/patologia , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Camundongos Endogâmicos C57BL , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina-1/metabolismo , Receptores de Oncostatina M/deficiência
7.
Int J Rheum Dis ; 16(6): 637-51, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24131599

RESUMO

AIM: To develop Australian and New Zealand (ANZ) recommendations for the investigation and follow-up of undifferentiated peripheral inflammatory arthritis (UPIA) using an evidence-based approach. METHODS: Ten questions pertaining to the investigation and follow-up of patients with UPIA in daily rheumatological practice were defined by clinicians using a modified Delphi approach. A systematic literature search was conducted for each of the final questions. The results were presented to a workshop of 54 ANZ rheumatologists in May 2009. Discussions were held to develop consensus statements for each question, based on published evidence and clinical experience/expertise. RESULTS: Ten recommendations were made on diagnostic value of clinical features in the patient's history and examination, predictors of poor prognosis and persistence, synovial fluid analysis, serology, imaging and human leukocyte antigen B27 testing. The lack of specific research to inform recommendations presented a challenge. Dynamic discussion groups outlined individual experience in areas without good quality clinical trial evidence. The median strength of support for the final set of recommendations was 7/10 (interquartile range 6-8), ranging from 6 to 9 for individual statements. CONCLUSION: Ten ANZ recommendations for the investigation and follow-up of UPIA were formulated, based on available evidence and extensive clinical experience. The systematic literature review was of limited value while animated discussion of individual experience, with subsequent information exchange, highlighted the importance of merging clinical expertise with published literature to establish practical recommendations that can improve quality of care in rheumatology.


Assuntos
Artrite/diagnóstico , Artrite/terapia , Medicina Baseada em Evidências/normas , Reumatologia/normas , Artrite/classificação , Austrália , Consenso , Técnica Delphi , Humanos , Nova Zelândia , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do Tratamento
9.
Clin Biochem ; 43(3): 278-86, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19857478

RESUMO

OBJECTIVES: Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified. DESIGN, METHODS, AND RESULTS: Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (+/-SD) ThT fluorescence did not differ significantly between groups (controls 0.97+/-0.26, RA 1.12+/-0.45, and SLE 0.74+/-0.23), the combined data set showed significant inverse correlation (p=0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum. CONCLUSIONS: We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk.


Assuntos
Doenças Cardiovasculares/sangue , Fluorescência , Tiazóis/sangue , Adulto , Peptídeos beta-Amiloides/metabolismo , Animais , Benzotiazóis , Biomarcadores/sangue , Bovinos , Humanos , Masculino , Pessoa de Meia-Idade , Aldeído Pirúvico/metabolismo , Fatores de Risco , Albumina Sérica/metabolismo
10.
Aust Fam Physician ; 38(3): 113-4, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19283250

RESUMO

The presentation of haemochromatosis is typified by abdominal pain, arthralgia and fatigue or weakness. Arthropathy may be the major presenting feature. The detection of an osteoarthritis-like process involving the metacarpophalangeal (MCP) and wrist joints in middle aged men should signal the possibility of under lying haemochromatosis. Other joints such as the shoulder, hip,knee or ankle may be affected. However, the preferential involvement of the second and third MCP joints is striking and may provide the opportunity for early identification of iron overload disease. The "iron salut" can be an efficient screening tool for this MCP joint arthropathy but it is not well known by clinicians.


Assuntos
Hemocromatose/diagnóstico , Ferro/metabolismo , Articulação Metacarpofalângica/patologia , Adulto , Hemocromatose/complicações , Hemocromatose/fisiopatologia , Humanos , Masculino , Fatores de Risco , Síndrome
11.
Rheum Dis Clin North Am ; 32(4): 759-73, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17288976

RESUMO

Inflammatory synovitis induces profound bone loss and OCLs are the instrument of this destruction. TNF blockers have an established role in the prevention of inflammatory bone loss in RA; however, not all patients respond to anti-TNF therapy and side effects may prevent long-term treatment in others. The B-cell--depleting antibody rituximab and the T-cell costimulation blocker abatacept are emerging as major treatment options for patients who are resistant to anti-TNF [96,97]. Proof-of-concept studies demonstrate that targeting RANK-mediated osteoclastogenesis prevents inflammatory bone loss and clinical application has only just begun. The efficacy of RANKL inhibition has been witnessed in trials of Denosumab, and RANKL-neutralizing antibodies are likely to become the treatment of choice for blocking RANKL in RA [77,78]. A major limitation of RANKL antagonism is that it does not treat synovitis. Therefore, anti-RANKL therapy most likely will be used in the context of MTX therapy. There is uncertainty about the possible extraskeletal adverse effects of long-term effects of long-term RANKL blockade. In particular, anti-RANKL therapy could jeopardize dendritic cell function or survival. The demonstrable role of OCLs in inflammation-induced bone loss also invites a reconsideration of the new BPs for bone protection [98]. Studies of ZA in preclinical models indicate that bone protection is comparable to that afforded by OPG. One possible caveat is that intravenous BPs are linked to jaw osteonecrosis [99], although the incidence is confined mainly to intensive treatment in the oncology setting. Although pulsed PTH stimulated bone formation in arthritic models, it has yet to be proven clinically in the context of powerful OCL inhibition with TNF or RANKL antagonists. With strategies that normalize OCL numbers, clinicians are poised to accomplish effective prevention of inflammation-induced bone loss.


Assuntos
Artrite Reumatoide/complicações , Reabsorção Óssea/prevenção & controle , Osteoporose/etiologia , Osteoporose/prevenção & controle , Artrite Reumatoide/fisiopatologia , Reabsorção Óssea/etiologia , Difosfonatos/uso terapêutico , Humanos , Inflamação/fisiopatologia , Osteoclastos/fisiologia , Linfócitos T/fisiologia , Fator de Necrose Tumoral alfa/fisiologia
12.
Arthritis Rheum ; 48(1): 81-9, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12528107

RESUMO

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation. METHODS: Arterial elasticity was assessed by pulse wave analysis in RA patients with (n = 15) and without (n = 38) CAD, and in controls matched 1:1 for age, sex, and CAD status. Vascular risk factors, including high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), and serum amyloid A (SAA) levels, were assessed. RESULTS: SAE and LAE were significantly lower and SVR was significantly higher in RA patients than in controls. RA patients also had higher levels of hsCRP, SAA, and sVCAM-1. SAE and LAE values were inversely correlated with markers of inflammation. Associations of SAE and LAE with RA were independent of conventional risk factors, but were dependent on markers of inflammation. CONCLUSION: Vascular function is abnormal in RA, with reduced SAE and LAE and increased SVR relative to controls. Arterial elasticity is inversely associated with measures of inflammation. These measures may be clinically useful in the detection and monitoring of vascular disease in RA.


Assuntos
Artrite Reumatoide/epidemiologia , Artrite Reumatoide/patologia , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/patologia , Idoso , Artrite Reumatoide/imunologia , Biomarcadores , Doença da Artéria Coronariana/imunologia , Estudos Transversais , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resistência Vascular , Vasculite/epidemiologia , Vasculite/imunologia , Vasculite/patologia
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