ORCID Profile
0000-0002-4330-6398
Current Organisation
Flinders University
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Publisher: Wiley
Date: 02-2012
DOI: 10.1111/J.1445-5994.2010.02406.X
Abstract: There is a paucity of literature on the patterns and predictors of mortality in idiopathic inflammatory myopathies (IIM). To determine the patterns and predictors of mortality in a South Australian cohort of patients with biopsy-proven IIM. The living/deceased status (and for deceased patients the causes of death) of patients with histologically determined IIM was determined from the Births, Deaths and Marriages Registry. Standardised mortality ratios (SMR) were generated compared with the age/gender matched South Australian population. The effect of presence/absence of the components of the Bohan and Peter criteria on risk ratios (RR) for mortality was determined. The effect of comorbidities and autoantibodies on mortality was investigated. The SMR for mortality in IIM was 1.75 and was significantly increased in all disease subgroups, being highest in patients with dermatomyositis (2.40). Dominant causes of death were cardiovascular disease (31%), infections (22%) and malignancy (11%). Risk factors for death were age at time of biopsy (hazard ratio 1.05), ischaemic heart disease (RR 2.97, P < 0.0001), proximal weakness at diagnosis (RR 1.8, P= 0.03), definite diagnosis of IIM per the Bohan and Peter criteria (RR 2.14, P < 0.0001), and the absence of autoantibodies (RR 1.9, P < 0.001). Patients with IIM are at 75% increased risk for mortality, and cardiovascular diseases account for the commonest causes of death. This study suggests a thorough cardiovascular evaluation of these patients is indicated, and raises the possibility that targeted interventions such as the use of aspirin or statins may improve outcomes in IIM.
Publisher: BMJ
Date: 1988
DOI: 10.1136/ARD.47.1.28
Abstract: Pulse methylprednisolone therapy has dramatic effects on clinical and immunological parameters of disease activity in patients with rheumatoid arthritis. Previous studies of this treatment have all used the intravenous route and methylprednisolone succinate. This study addresses the question of whether oral prednisolone in equivalent doses can substitute for intravenous methylprednisolone in pulse therapy in a double blind parallel study. It is shown that oral prednisolone has clinical and immunological effects equivalent to those of intravenous methylprednisolone, making it possible to administer pulse therapy to patients with rheumatoid arthritis as outpatients without the inconvenience and inherent dangers of intravenous administration.
Publisher: Wiley
Date: 10-1998
DOI: 10.1002/1529-0131(199810)41:10<1783::AID-ART10>3.0.CO;2-W
Publisher: Oxford University Press (OUP)
Date: 03-1990
DOI: 10.1111/J.1365-2249.1990.TB08091.X
Abstract: The molecular size of serum IgG, IgA and IgM in patients with a variety of monoclonal and polyclonal immune disorders has been determined by a sensitive immunoblotting technique. IgM, IgA and IgG3 paraproteins from patients with B cell lymphoproliferative disorders frequently polymerize with IgA paraproteins demonstrating two polymeric series, the basic unit of the more dominant series being monomeric IgA, and the second consists of a basic unit having a molecular mass of approximately 70 kD heavier than monomeric IgA. The molecular nature of this heavier IgA moiety was shown to be IgA covalently bound with a single moleculeof serum albumin or alpha anti-trypsin and this moiety was also observed in small quantities in sera from healthy subjects. IgM paraproteins, particularly from patients with malignant Iymphoproliferativc disorders, consisted of varying proportions of decamers, pentamers and monomers together with other low molecular weight IgM oligomers. Paraproteins from patients with benign conditions showed less tendency to exist in multiple molecular weight forms. Serum immunoglobulins from patients with polyclonal immune disorder also showed molecular sized heterogeneity. Significantly increased levels of dimeric IgA were observed in patients with alcoholic cirrhosis and Felty's syndrome, while low molecular weight IgM was commonly seen in patients with autoimmune disorders. In these latter disorders monomeric IgM correlated significantly with the serum IgM level suggesting a disorder of assembly of the IgM subunits during an ongoing IgM immune response. We have demonstrated considerable molecular size heterogeneity of serum immunoglobulins both in health and disease and have indicated some possible clinical associations.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1981
DOI: 10.1097/00004424-198103000-00014
Abstract: Radiologic contrast materials activate complement by both the classical and alternative pathways. This activation is time, dose, and temperature dependent and is able to proceed with equal facility in either the presence or absence of Ca++ or Mg++ chelating reagents (EGTA, EDTA). All the components examined (C1, C4, C2, Factor B, C3, and C5) were consumed during complement activation. Immune complexes are produced during interaction of serum with contrast materials. The activation of complement by contrast materials appears to be principally initiated by the activation of plasminogen to plasmin. Inhibition of plasminogen activators by epsilon-aminocaproic acid affects complement activation markedly.
Publisher: Wiley
Date: 04-1984
DOI: 10.1111/J.1445-5994.1984.TB04273.X
Abstract: Circulating low molecular weight (LMW) IgM was demonstrated in five of 38 patients with B cell lymphoproliferative disorders. These five patients all had malignant disease and could be sub ided into two groups. In the first group were three patients, each with an associated serum IgM paraprotein two had Waldenström's macroglobulinemia, and one lymphocytic lymphoma. The two patients of the second group did not have IgM paraproteins one had lymphocytic lymphoma and one chronic lymphocytic leukemia. Both these patients also had acquired C1 esterase inhibitor deficiency, a previously recognised association with circulating LMW IgM. None of the 16 patients with benign IgM macroglobulinemia had circulating LMW IgM. In those positive sera with LMW IgM this moiety contributed between 10.5% and 37.5% of the total IgM. There was no apparent association between LMW IgM and total IgM levels, kappa/lambda typing or the presence of Bence Jones proteinuria, but rheumatoid factor, immune complexes and cryoglobulins occurred in many of the sera which contained LMW IgM. Pokeweed mitogen stimulated peripheral blood mononuclear cells from two patients with circulating LMW IgM secreted considerable quantities of this moiety in vitro but this did not occur in two patients with benign IgM macroglobulinemia. We conclude that LMW IgM is found in the malignant but not the benign forms of B cell lymphoproliferative disorders and is frequently associated with other serological abnormalities. The basic abnormality causing defective IgM polymerisation in these disorders is obscure.
Publisher: Georg Thieme Verlag KG
Date: 08-05-2012
Abstract: Over 30 years since it was first described as a discrete clinical entity, the antiphospholipid antibody syndrome (APS) remains a challenge for both laboratory workers and clinicians in a wide range of specialties. In addition to the presence of appropriate clinical features, the diagnosis of APS also fundamentally requires the finding of positive antiphospholipid antibody (aPL) test result(s), which comprise clot-based assays for the identification of lupus anticoagulant (LA) and immunologic ("solid-phase") assays such as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI). This article is the first of two that review the process for, and provides recommendations to improve, internal quality control (IQC) and external quality assurance (EQA or proficiency testing) for aPL assays. These processes are critical for ensuring the quality of laboratory test results and thence the appropriate clinical diagnosis and management of APS. This article covers aCL and aβ2GPI testing. In brief, IQC is a process that helps control the quality of laboratory test results on a test-by-test basis IQC should include s les that provide values around the assay critical cut-off values, and there is added value in the inclusion of non-kit assay controls. EQA is a process that helps laboratories assess their performance against those of their peers. For aCL and aβ2GPI testing, we provide some updated findings from the Royal College of Pathologists of Australasia Immunology Quality Assurance Program, and covering testing for the past 3 years (2009 to 2011 inclusive). Findings show similar trends to past years, indicating limited improvement in cross-laboratory test results and interpretations. In summary: (1) EQA participants reported greatly varying numerical test data for both aCL and aβ2GPI, with interlaboratory coefficients of variation > 50% with most test challenges (2) there was considerable overlap in the interpretation (negative, positive, low positive, moderate positive, strong positive) that different participants ascribed to identical numerical test results and (3) there was limited consensus among participants as to whether test results for in idual EQA specimens were either positive or negative for aCL and/or aβ2GPI.
Publisher: Wiley
Date: 04-1999
DOI: 10.1111/J.1445-5994.1999.TB00689.X
Abstract: A genetic component is thought to contribute to 30-40% of the expression of rheumatoid arthritis (RA) with the HLA-DR4, w4 (B1*0401), w14 (B1*0404) genes (and associated shared rheumatoid epitope) constituting a substantial portion of this risk. Our objective was to determine the presence of these risk factors in a group of patients with RA and to correlate presence with disease outcome. Forty-three RA patients who had been regularly assessed up to a ten year period since their initial entry into two gold treatment trials were studied. DR4, w4, w14 and shared rheumatoid epitope were determined on peripheral blood lymphocytes using flow cytometry and specific monoclonal antibodies. Disease outcome was measured by Health Assessment Questionnaire (HAQ) score and C-Reactive Protein (CRP) as a serological measure of joint inflammation. To confirm accuracy of the flow cytometric technique, DR typing and epitope status was compared with results obtained by genotyping in a subset of 14 patients. There was complete concordance between these two techniques for the rheumatoid epitope. However, concordance was not complete (both false positives and false negatives) for DR4, w4 and w14. Hence the presence of rheumatoid epitope was only evaluated further in the larger group. The presence of the shared rheumatoid epitope correlated positively with poorer outcome on serological assessment (p < 0.05). No significant correlation between HAQ score and rheumatoid epitope status was observed although a weak trend was noted. These studies suggest that determination of rheumatoid epitope status by flow cytometry may provide useful data concerning the long term outcome of patients with RA.
Publisher: Wiley
Date: 1986
Abstract: Paired s les of synovial fluid (SF) and blood were obtained prior to and at 4 and 24 hours following high-dose methylprednisolone infusion therapy in a group of patients with refractory rheumatoid arthritis. After therapy there was a significant decrease in numbers of polymorphonuclear leukocytes, lymphocytes, immune complexes, and C-reactive protein in the SF. Measurement of lymphocyte subsets, using monoclonal antibodies, revealed that at 4 hours postinfusion, there was a disproportionate decrease in the percentage of SF lymphocytes expressing class II antigens (HLA-DR or Ia-like). These data suggest that glucocorticoids induce rapid changes in SF indices of disease activity and may directly influence T cell activation within the rheumatoid joint.
Publisher: BMJ
Date: 25-05-2006
Publisher: Elsevier BV
Date: 10-2019
Publisher: Wiley
Date: 08-1997
Abstract: To establish whether the clinical efficacy of pulse methylprednisolone (MP 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments. Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin-1beta (IL-1beta), IL-8, and tumor necrosis factor alpha (TNFalpha) were measured by enzyme-linked immunosorbent assay and biologic assays prostaglandin E2 (PGE2) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFalpha, IL-8, IL-1beta, and the IL-1 receptor antagonist protein (IL-1Ra). MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFalpha in the lining and sublining regions of the synovial membrane, as well as substantial decreases in the levels of TNFalpha in serum and synovial fluid. There was also reduced IL-8 expression in the synovial lining, as well as reduced synovial fluid IL-8 levels. No effect on synovial membrane IL-1beta and IL-1Ra or synovial fluid IL-1beta and PGE2 was found. MP therapy rapidly reduces IL-8 and TNFalpha levels in the synovial compartment, with cytokine changes in the serum and synovial fluid reflecting the changes in the synovial membrane. Alterations in TNFalpha expression in the synovial membrane correlated with clinical response to, and subsequent relapse after, MP therapy.
Publisher: Georg Thieme Verlag KG
Date: 02-2005
Abstract: We evaluated the performance of anticardiolipin (aCL) and beta2-glycoprotein I (beta2-GPI) antibody assays through a large external quality assurance program. Data from the 2002 cycle of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP) were analyzed for variation in reported numerical values and semiquantitative results or interpretations according to method type or group and in conjunction with available clinical data. High interlaboratory variation in numerical results and notable method-based variation, combined with a general lack of consensus in semiquantitative reporting, continues to be observed. Numerical results from cross-laboratory testing of 12 serum s les (for immunoglobulin G [IgG]-aCL, IgM-aCL, and IgG-beta2-GPI) yielded interlaboratory coefficients of variation (CVs) that were higher than 50% in six of 12 (50%) specimens for IgG-aCL, and 12 of 12 (100%) specimens for IgM-aCL and IgG-beta2-GPI. Semiquantitative reporting also varied considerably, with total (100%) consensus occurring in only four of 36 (11%) occasions. General consensus (where > 90% of participating laboratories agreed that a given serum s le gave a result of either negative or positive) was only obtained on 13 of 36 (36%) occasions. Variation in results between different method types or groups were also present, resulting in potential biasing of the RCPA QAP-defined target results by the large number of laboratories using the dominant aCL assays. Finally, laboratory findings frequently did not agree with the available clinical information. In conclusion, in a large proportion of specimens from the 2002 RCPA QAP cycle, laboratories could not agree on whether a serum s le tested was aCL-positive or aCL-negative, or beta2-GPI-positive or beta2-GPI-negative. Despite prior attempts to improve the standardization of testing and reporting practices, laboratory testing for aCL and anti-beta2-GPI still demonstrates significant interlaboratory and intermethod variation, which needs to be taken into account for the clinical interpretation of test results, especially those from different laboratories.
Publisher: BMJ
Date: 02-1989
DOI: 10.1136/ARD.48.2.108
Abstract: A prospective 24 week study of 31 patients with active rheumatoid arthritis (18 women, 13 men) was undertaken to determine whether weekly intramuscular sodium aurothiomalate (gold) would influence delayed type cutaneous hypersensitivity (DTH) and other indices of cell mediated immunity. DTH to seven recall antigens was measured by Multitest on three occasions during the study. Twenty five patients completed the study. At entry 13 patients (12 female) were anergic, and no significant correlations were found between DTH and other clinical and immunological indices. Women showed a significantly greater depression of DTH than men. At week 24 only three of the patients were anergic with significant increase in mean DTH score being noted particularly to tuberculin, candida, and streptococcus. Improvement in DTH was observed in both gold responders and non-responders. In conclusion, patients with active rheumatoid arthritis show impairment of DTH, which is reversed by chrysotherapy. This effect is most apparent in women and appears to be relatively independent of the clinical response.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2008
Publisher: Oxford University Press (OUP)
Date: 06-2003
Publisher: Wiley
Date: 03-2012
DOI: 10.1111/J.1445-5994.2011.02706.X
Abstract: We review the aetiology of scleroderma from an epidemiological perspective examining genetic, environmental and stochastic risk factors. The presence of familial clustering (but with low twin concordance) suggests a genetic contribution, and this has been confirmed with recent candidate gene and genome-wide association screening demonstrating both major histocompatibility complex and non-major histocompatibility complex genetic linkage. In contrast, environmental associations are weak or inconsistent. An examination of the age-adjusted incidence curve of scleroderma is consistent with a stochastic process involving five to eight random events. In pathogenesis, scleroderma is best considered as an autoimmune disorder where genetic and environmental factors are both important variables, but random events are also likely to play a pivotal role. We suggest that these random events might result in acquired somatic mutations or epigenetic alterations involving genes coding for immune receptors, tolerogenic gates or proteins involved in immune regulation, inflammation and/or repair that, over time, might summate to form a requisite cassette (of genetic changes), which allows the initiation and progression of the autoimmune process.
Publisher: Wiley
Date: 05-1992
DOI: 10.1111/J.1749-6632.1992.TB24673.X
Abstract: In this study, using both a FACSCAN flow cytometer and the FACS analyzer, and two-color fluorescence, CD5 B cells have been enumerated in the peripheral blood (PB) of normal controls (NC) and patients with rheumatoid arthritis (RA) or essential mixed cryoimmunoglobulinemia (EMC). Using a FACSCAN flow cytometer, no significant difference was observed between the percentage of CD5 B cells in the NC (21.24% +/- 3.71) and RA (24.83% +/- 3.85), or EMC (21.03% +/- 6.38). Using the FACS analyzer, however, there was significant difference between the NC (9.14% +/- 3.82) and EMC (2.84% +/- 2.58) (p less than 0.05), but no significant difference between the NC and RA (7.17% +/- 2.55). Further analysis of 10,000 B cells selected by live gating showed that there were three populations of B cells, with the majority of B cells unstained, a small number of cells brightly stained for CD5 in the NC (3.78% +/- 1.09) or RA (2.80% +/- 0.96), and about 6.45% to 9.43% with intermediate staining in patients with RA and the NC, respectively. In addition, serum low molecular weight IgM (LMW IgM) from patients with RA was detected by an enhanced chemiluminescence detection system combined with a modified immunoblot technique. A significant linear correlation was observed between the percentage of CD5 B cells and the height of LMW IgM peak (r = 0.69, p less than 0.05).
Publisher: Wiley
Date: 12-1996
Abstract: To investigate the effects of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP) on cell adhesion molecule expression on the synovial vascular endothelium in patients with rheumatoid arthritis (RA). Sequential arthroscopic biopsy s les were taken before and 24 hours after MP administration (10 patients) and at the time of RA flare (2 patients) and after retreatment with MP (1 patient). Immunoperoxidase staining for E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1 CD54) and platelet-endothelial cell adhesion molecule (PECAM CD31) was performed, and the staining was quantified by color video image analysis. MP caused a rapid (within 24 hours) and substantial decrease in the expression of E-selectin on the synovial vascular endothelium, with a smaller reduction in ICAM-1 expression on synovial vascular endothelium and the synovial lining. There were no similar effects on synovial membrane P-selectin or PECAM expression. A potential mechanism by which MP impairs neutrophil trafficking into inflamed RA joints might be by reducing E-selectin, and possibly, ICAM-1, expression in the synovial membrane.
Publisher: BMJ
Date: 02-1990
DOI: 10.1136/ARD.49.2.81
Publisher: Wiley
Date: 15-05-2007
Publisher: Elsevier BV
Date: 06-2005
DOI: 10.1080/00313020500033262
Abstract: To investigate the histological, ultrastructural and immunohistochemical features of the vascular lining of dermal telangiectasia, a characteristic clinical finding in scleroderma. Standard histological, electron microscopic and immunohistological techniques were used to examine dermal telangiectasias in five patients with limited scleroderma, the most common scleroderma variant in Caucasian populations. The telangiectasias were dilated postcapillary venules located in the papillary and superficial reticular dermis. The vessel walls consisted of non-fenestrated endothelial cells surrounded by a variable number of pericytes and smooth muscle cells. There were no unique ultrastructural features. Thickened collagen fibres in the reticular or deep dermis were seen in all but one patient, although in variable and generally minimal quantities. Surrounding infiltrating inflammatory cells were scarce. No enhanced endothelial staining was obtained with antibodies directed against endoglin, endothelin, E-selectin and ICAM-1 suggesting a resting or inactivated state. The immunohistological and ultrastructural features of the lining endothelium of established telangiectasias in long-standing, limited scleroderma appear benign. It would be of interest to examine telangiectasias in the early phase of their formation. Alternatively, other explanations need to be explored in understanding the aetiopathogenesis of telangiectasia in scleroderma.
Publisher: Elsevier BV
Date: 1992
DOI: 10.1016/0022-1759(92)90233-J
Abstract: An enhanced chemiluminescence detection system combined with a modified immunoblot technique is described for the detection of low molecular weight IgM (LMW IgM) in human sera and cell culture supernatants at levels down to 2 pg/ml. This detection system is reliable, specific and more sensitive than the previously described chromogenic detection system. Importantly, this method has, for the first time, revealed LMW IgM in the sera from all 34 healthy adults and 26 neonatal cord bloods tested. A significant linear correlation was observed between the LMW IgM and the total circulating IgM in both the healthy adult sera (r = 0.88, p less than 0.001) and cord blood sera (r = 0.98, p less than 0.001).
Publisher: Wiley
Date: 08-1986
DOI: 10.1111/J.1445-5994.1986.TB02024.X
Abstract: The clinical manifestations and laboratory findings of two patients with a presumptive diagnosis of coxsackie B4 virus infection are described. A striking feature was the similarity with adult onset Still's disease, with spiking fever, evanescent macular rash, and severe polyarthritis. This latter feature persisted for many weeks and required steroids to control the symptoms. Review of the literature has supported the proposition that many cases of adult onset Still's disease may be due to coxsackie B4 or other viral infection and it is suggested that these agents should be actively sought in future cases.
Publisher: Wiley
Date: 05-1976
DOI: 10.1111/J.1365-2141.1976.TB00978.X
Abstract: The clinical manifestation fo IgA multiple myeloma are usually not considered distinguishable from those of IgG myeloma despite the fact that IgA differs from IgG in several characteristics, particularly molecular size heterogeneity. The clinical and laboratory features of 25 patients with IgA myeloma seen during a 5 year period are presented. The degree of paraprotein polymerization was observed to vary greatly in these patients but remained chronologically constant in six in iduals studied on several occasions over this period. The patients were ided into two groups on the basis of the degree of paraprotein polymerization. The first group comprised those patients in whom the IgA paraprotein was greater than 50% polymerized, whilst in the second group the paraprotein was predominantly monomeric. No clinical or pathological differences were seen between the 'polymeric' and 'monomeric' groups of myeloma apart from that directly attributable to the physicochemical effect of the paraprotein polymerization. Thus, five patients out of 11 of the 'polymeric' group had developed the hyperviscosity syndrome, whilst no patients in the 'monomeric' group had developed this complication. The concentration of the paraprotein during the course of the disease was comparable in both groups. This syndrome is considered to be relatively common in IgA myeloma and adds to the morbidity and mortality of the disease. Its anticipation and treatment may improve the quality and survival of patients likely to develop this complication.
Publisher: Wiley
Date: 10-2008
DOI: 10.1111/J.1445-5994.2008.01694.X
Abstract: The epidemiology of Wegener's granulomatosis (WG) has shown a latitude-dependent predisposition in Northern Hemisphere and in New Zealand. There are no studies describing epidemiology or long-term follow up of WG reported from Australia. The aims of this study were to describe the epidemiological and clinical features of WG in South Australia (SA). The 5-year incidence of WG in SA over the period 2001-2005 was determined using the International Classification of Diseases classification (M313) of the discharge diagnosis using the Integrated South Australian Activity Collection. A retrospective case record analysis of 30 patients fulfilling the American College of Rheumatology criteria for WG and managed at two regional hospitals over a 20-year period (1985-2004) was carried out. The 5-year incidence of WG in SA was 56 per 10(6) (95% confidence interval 44.1-68.4 per 10(6)). There were no regional or seasonal variations in disease occurrence. The demographic, clinical and serological features in the clinical study were similar to previously published studies. Significant treatment-related morbidity was noted with 50% of patients having atherosclerotic vascular complications. The median survival was 12 years. There were two important periods with greater risk of dying -- in the first 5 years and after 10 years. The 5-year incidence of WG in SA is higher than that in the same latitudinal region in New Zealand ( approximately 34 degrees S). Atherosclerotic vascular disease was a major long-term morbidity. There is increased incidence of early mortality, warranting the need for earlier diagnosis and better therapies. Further studies from Southern Hemisphere are required for better epidemiological description of this disease.
Publisher: Elsevier BV
Date: 11-1996
DOI: 10.1016/S0198-8859(96)00152-8
Abstract: Circulating LMW IgM was detected in a group of 100 healthy adults, but in very low or trace concentrations. A significant correlation was observed between total IgM and LMW IgM (r = 0.81, p < 0.01), which suggests that the presence of LMW IgM may be due to the "overspill" of LMW IgM during IgM synthesis and secretion. Significantly higher levels of LMW IgM and total IgM were found in females as compared with males. Furthermore, a weak association between A1, B8, DR3 and elevated IgM was also found. However the precise significance of this association is unclear.
Publisher: BMJ
Date: 12-1976
Abstract: A description has been given of cerebrospinal fluid (CSF) immunoglobulins in 355 patients with demyelinating, infectious, neuropathic, and other neurological disorders. An increase in the CSF IgG/albumin quotient was observed in 19/36 (53%) cases of definite multiple sclerosis (MS), in 13/47 (28%) cases of probable or possible MS, in 6/9 (67%) cases of proven herpes simplex viral encephalitis (HSVE), in 3/4 (75%) cases of neurosyphilis, in 1/1 case of subacute sclerosing panencephalitis (SSPE), in 2/9 )22%) cases of other central nervous system infections, and in 2/12 (17%) cases of polyneuritis when compared with a group of 236 patients having other neurological disorders. In constrast, a relative increase in the CSF IgA of IgM was seen only in some of the patients with central nervous system infections. It was also found that the quotient CSF/serum IgG, expressed as a percentage of the CSF/serum albumin, was better in distinguishing patients with definite or suspected MS from those with other neurological disorders than the quotients IgG/albumin or IgG/total protein. The CSF K/lambda ratio and the CSF and serum complement-fixing antibody titre to measles and herpes simplex virus were measured in many of the patients. In general, abnormalities of these measurements were associated with raised IgG/albumin quotients. However, in eight patients with definite or suspected MS, a normal IgG/albumin quotient was found with abnormal CSF K/lambda ratios (6 cases) or abnormal CSF titres of measles antibody (7 cases). In addition, two patients, with HSVE had normal IgG/albumin ratios but detectable herpes antibody in the CSF. These findings suggest that the measurement of the relative concentration of CSF immunoglobulin in combination with the K/lambda ratio and antibody titre to various viruses may supplement each other in the endeavour to detect central nervous system immunglobulin sysnthesis in neurological diseases.
Publisher: Springer Science and Business Media LLC
Date: 13-06-2007
Publisher: BMJ
Date: 12-1990
Abstract: Antibodies to nuclear antigens were assessed in 23 children with juvenile chronic arthritis (JCA) and 66 of their first degree relatives. Serum s les from 16 patients with JCA (70%) and nine relatives (14%) had antinuclear antibodies by indirect immunofluorescence. Antibodies against nuclear antigens in rabbit thymus extract or an erythroblastoid cell line (K562) were detected by countercurrent immunoelectrophoresis and immunoblotting in 16 patients (70%) and 39 family relatives (59%). Immunoblotting did not show any banding patterns common to all patients with JCA, though bands in the 43-45 kD range were detected in 5/23 patients. Anticardiolipin antibodies were found in 7/23 patients. In total, 18/20 families (90%) had members other than the probands with detectable autoantibodies. In five families immunoblotting showed common banding patterns between the probands and other members. This suggests that there might be an inherited trend towards autoimmune responses in some families of patients with JCA.
Publisher: Springer Science and Business Media LLC
Date: 02-12-2010
DOI: 10.1007/S00296-010-1637-5
Abstract: The aim of this study was to determine the HLA and autoantibody associations of patients with histologically confirmed idiopathic inflammatory myositis (IIM). Serum and DNA were archived from South Australian patients with biopsy-proven dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM). HLA typing for Class I and II alleles was performed by serology and DNA-based technology, respectively, for 133 myositis patients and 166 Caucasian population-based controls. Myositis-specific and myositis-associated autoantibodies were detected by line immunoblot. All alleles of the 8.1AH were associated with myositis susceptibility. The B8-DR3 haplotype fragment conferred the strongest susceptibility (OR 2.9, 95% CI 1.8-4.6), and the B-DR region of other ancestral haplotypes was associated with myositis subgroups. Autoantibodies were present in 42/130 (32%) IIM patients and were more frequent in DM (11/17, 65%) than PM (23/70, 33%) or IBM (8/43, 19%), P = 0.002. Autoantibodies were associated with DRB1 03 (P = 0.0005) but also with DRB1 04 (P = 0.004). The frequency of autoantibodies in the three myositis subgroups mirrored the frequency of DR4. Polyarthralgia (±synovitis) was more common in DM/PM (30/76, 39%) than IBM (3/32, 9%), P = 0.004, and there was a strong ordinal association between the prevalence of autoantibodies and polyarthralgia ± synovitis (proportional OR = 5.5, 95% CI 2.3-13.7, P = 0.0004). The central MHC region confers the strongest susceptibility for IIM and also modulates disease phenotype. Our findings reveal a novel association of autoantibodies with DR4 and with arthralgia/synovitis in IIM and raise the possibility of a genetically (DR4) determined citrullination of myositis autoantigens expressed in muscle and synovium.
Publisher: Oxford University Press (OUP)
Date: 10-02-2010
DOI: 10.1093/RHEUMATOLOGY/KEP467
Abstract: RA is characterized at the synovial tissue level by synovial lining hyperplasia, angiogenesis and mononuclear cell infiltrates. A failure of apoptotic pathways may explain these pathological changes in RA synovial tissue. This study aims to demonstrate the presence of initiators and inhibitors of apoptosis in RA synovial tissue and the effect of treatment with DMARDs on apoptotic pathways in RA. Synovial biopsy specimens were obtained at arthroscopy from 16 RA patients before and at 3- or 6-month intervals after commencing treatment with a DMARD. Apoptosis (by the terminal deoxynucleotidyl transferase mediated dUTP nick end labelling method and polyADP-ribose polymerase staining), proteins regulating apoptosis [Fas, FADD-like IL1b converting enzyme inhibitory protein (FLIP), Bcl-2, Survivin and X-linked inhibitor of apoptosis protein (XIAP)] and the presence of activated caspases (caspases 3 and 8) were detected by immunohistochemistry and quantified using image analysis and semiquantitative techniques. Fifteen patients responded to treatment, with an ACR response of > or =20%, 13 achieving an ACR response of > or =50% and 3 achieving an ACR remission. There was a significant reduction in SM macrophages and memory T cells, with an increase in fibroblast-like synovial lining cells following DMARD treatment. Apoptosis was not detected in the inflamed synovial tissue of RA patients before starting treatment, despite evidence of caspase activation, but was detectable after successful treatment with DMARDs. Inhibitors of activated caspases (FLIP, Survivin and XIAP) were detected in RA synovial tissue and were down-modulated with successful DMARD treatment. Apoptotic pathways are defective in RA synovial tissue from patients with active disease, despite the presence of activated caspases, possibly due to the abundant expression of inhibitors of the caspase pathway in RA synovial tissue. DMARD treatment can modulate apoptosis in the RA SM, which may lead to restoration of the SM architecture towards that of normal synovial tissue.
Publisher: Wiley
Date: 20-02-2008
DOI: 10.1111/J.1445-5994.2007.01525.X
Abstract: The aim of the study was to investigate: (i) familial scleroderma (FS) risk factors, (ii) subtype concordance and (iii) relationship between dates (DSO) and ages (ASO) at scleroderma onset. Forty-seven cases (23 families 25 FS pairs) were identified. Scleroderma disease onset was defined by (i) Raynaud's onset, (ii) first symptom onset (1SxO), (iii) second symptom onset (2SxO) and (iv) scleroderma diagnosis (SDx). Female : male and limited : diffuse (L : D) ratios were 8.4:1 and 3.3:1. The Raynaud's onset - SDx interval was longer in limited disease (L : D = 14.6:3.1 years P = 0.01). Raynaud's first occurred in 36% women > or =50 years. The median differences in ASO between affected family members were 10-12 years. Disease subtype concordance exceeded discordance (16:9 clusters (P = 0.32) 16:7 families (P = 0.17)). The observed/expected LL : LD : DD ratios were 14: 8:1/11:7:1 (P = 0.66). FS affected 34% (95% confidence interval 19-50) sister-sister and 44% (95% confidence interval 27-75) mother-daughter pairs. The second family member's SDx was made at the same (9%) or a younger age (80%) than the first family member. In 14 LL disease families ASO was closer between sisters than mothers-daughters (P = 0.07). There was a trend towards closer ages - than dates - at Raynaud's and 1SxO in scleroderma-affected family members (P = 0.054) and closer dates - than ages - at 2SxO (P = 0.02) and SDx. FS showed female predominance, relatively late onset Raynaud's, subtype ratios similar to idiopathic scleroderma and earlier SDx in younger family members. Familial L scleroderma has a longer prediagnostic latency than familial D scleroderma. FS is likely under-ascertained. In LL scleroderma, Raynaud's/1SxO is possibly more genetically determined and 2SxO/SDx more environmentally determined.
Publisher: Springer Science and Business Media LLC
Date: 16-12-1999
Abstract: The shared rheumatoid epitope (SRE) on the MHC class II antigen-presenting molecule constitutes a probable genetic risk factor for the occurrence of rheumatoid arthritis (RA) and may also determine disease severity. We have used a novel flow cytometric technique to determine the SRE in over 500 predominantly Caucasian patients attending a general rheumatology clinic. This technique has been validated against a polymerase chain reaction (PCR)/SSO molecular method. The SRE was observed in 90% of patients with Felty's syndrome (n = 10) and 75% of patients with RA (n = 178) as compared with 39% of patients with osteoarthritis or non-inflammatory rheumatic disorders (n = 73). Thus, the SRE determined by this method has a sensitivity for RA of 0.75, a specificity of 0.62 and an estimated positive predictive value of 0.02. In our RA cohort, there was no correlation between the functional outcome (health assessment questionnaire score) and SRE status. In conclusion, the determination of the SRE status by a flow cytometric method was found to have only modest sensitivity and specificity for RA furthermore, the SRE did not correlate with functional outcomes. The clinical utility of the SRE assay is yet to be defined.
Publisher: Wiley
Date: 07-07-2006
DOI: 10.1111/J.1445-5994.2006.01138.X
Abstract: Progress in the understanding of the aetiopathogenesis of scleroderma (systemic sclerosis) has been painfully slow and this has greatly impeded the application of specific disease modifying treatments. This article provides a brief historical overview of scleroderma (including the important Australian contribution of Dr Alfred Barnett and colleagues--see accompanying article in this issue on pages 513-18), highlights some recent pathogenic developments and summarises some exciting new therapies. Cautious optimism can now be offered to scleroderma sufferers.
Publisher: BMJ
Date: 09-04-1983
DOI: 10.1136/BMJ.286.6372.1171
Abstract: Monoclonal antibodies specific for lymphocyte subsets were used to examine circulating lymphocytes obtained at frequent intervals from healthy subjects. A diurnal rhythm was found in the total numbers of lymphocytes, T cells, inducer/helper cells, suppressor/cytotoxic cells, Ia positive cells, and B cells. The lowest levels of all subsets were seen at 0900 hours and the highest levels at 2100. In some subjects the ratio of helper to suppressor cells varied considerably during the s le period, though the ratio was relatively constant for the group as a whole.
Publisher: Wiley
Date: 29-11-2013
Publisher: Springer Science and Business Media LLC
Date: 04-1998
Publisher: AMPCo
Date: 10-1981
Publisher: Wiley
Date: 04-1996
DOI: 10.1111/J.1445-5994.1996.TB00879.X
Abstract: The clinical associations of anti-lamin autoantibodies were first described in 1973. Since then a number of in idual case reports and two small series have been published. These have suggested an association with connective tissue disorders and autoimmune liver disease. To identify the clinical and laboratory associations of anti-lamin autoantibodies in an Australian population. Retrospective review of routine antinuclear antibody testing between 1990-1994 for characteristics linear staining of nuclear envelope on indirect immunofluorescence on HEp-2 cells with clinical status defined by retrospective review of case records. Twenty-eight patients were identified and the clinical status of 27 patients defined. Eleven patients had associated IgG anti-cardiolipin antibodies anti-phospholipid syndrome was present in nine. Seven further patients had liver disease five had autoimmune liver disease, with associated autoantibodies. The remaining nine patients had a erse group of diseases. There was no correlation between the titre of the autoantibody and clinical status. An association with anti-cardiolipin antibodies was found although the cause remains obscure. Anti-lamin autoantibodies, as identified by indirect immunofluorescence, are associated with a erse group of diseases but particularly with anti-phospholipid syndrome and liver disease. Testing for anti-phospholipid antibodies and more specific markers of systemic lupus erythematosus and autoimmune disease, for ex le anti-dsDNA antibodies, anti-smooth muscle antibodies and anti-mitochondrial antibodies should be pursued when anti-lamin autoantibodies are detected.
Publisher: Wiley
Date: 10-1999
DOI: 10.1111/J.1445-5994.1999.TB01620.X
Abstract: The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell ision. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control group of consecutive ANA positive, anti-MSA negative in iduals had anti-thyroid antibodies measured. Statistical comparison used chi2 test. Fifty-five subjects (43F) were identified with mean age 59.8 (range 17-91) 39 had specific diagnoses, with 16 identified as part of non-specific investigations. 'Arthritis' broadly accounted for the largest group, transient inflammatory arthritis n=7, degenerative joint disease n=6, rheumatoid arthritis n=5. Adenocarcinoma and mesothelioma accounted for one case each. Thirty-two subjects had anti-thyroid antibodies tested, with ten of 21 and two of 11 positive among the groups with anti-MSA titre >1:80 and <1:40 respectively, chi2=2.7, p=0.1. Anti-thyroid antibodies were detected more frequently among the high titre anti-MSA group (ten of 21) compared with high titre positive ANA, negative anti-MSA group (two of 11), RRisk 4.4, chi2=5.34, p=0.02. This study confirmed the relative rarity of anti-MSA and that its association is primarily with rheumatic diseases. The coincidence of mesothelioma is novel with only two previous reports of malignancy and anti-MSA. The co-association of high titre anti-MSA and thyroid autoantibodies suggest that the latter should be a follow up investigation if the former is identified as part of an investigative screen.
Publisher: Wiley
Date: 2001
DOI: 10.1002/1529-0131(200101)44:1<245::AID-ANR38>3.0.CO;2-D
Publisher: Elsevier BV
Date: 1992
DOI: 10.3109/00313029209063615
Abstract: Rheumatoid Arthritis (RA) synovial membranes were examined by single and dual immunohistological techniques with a number of monoclonal antibodies against lymphocyte and macrophage related antigens. CD4 positive T lymphocytes frequently expressed MHC Class II antigens and were found in sublining collections in close association with activated macrophages as well as B lymphocytes. CD8 positive T cells surrounded these collections as well as being scattered throughout the membrane and also frequently expressed MHC Class II antigens. IL2 receptor (IL2r) expression on T cells and CD5 expression on B cells were rarely seen in these synovial membranes. Similar immunohistological architecture was found in synovial membranes from patients with psoriatic arthritis (PA) and Reiter's Syndrome (RS). Normal synovium contained few T cells, with few cells expressing MHC Class II antigens. Synovium from osteoarthritis (OA) patients also demonstrated similar immunohistological changes to those found in inflammatory arthritides, suggesting that there are only quantitative rather than qualitative differences between the synovial membrane immunohistological architecture from patients with inflammatory and noninflammatory arthritides.
Publisher: Wiley
Date: 1985
Abstract: Recently, innovative statistical tools have been used to model patterns of change in psychological treatments. These tools can detect patterns of change in patient progress early in treatment and allow for the prediction of treatment outcomes and treatment length. We used growth mixture modeling to identify different latent classes of early change in patients with panic disorder (N = 326) who underwent a manualized cognitive-behavioral treatment. Four latent subgroups were identified, showing clusters of change trajectories over the first 5 sessions. One of the subgroups consisted of patients whose symptoms rapidly decreased and also showed the best outcomes. This information improved treatment prediction by 16.1% over patient intake characteristics. Early change patterns also significantly predicted patients' early treatment termination. Patient intake characteristics that significantly predicted class membership included functional impairment and separation anxiety. These findings suggest that early treatment changes are uniquely predictive of treatment outcome.
Publisher: BMJ
Date: 05-1999
DOI: 10.1136/ARD.58.5.266
Abstract: To document the frequency and disease phenotype of various rheumatic diseases in the Australian Aborigine. A comprehensive review was performed of the archaeological, ethnohistorical, and contemporary literature relating to rheumatic diseases in these indigenous people. No evidence was found to suggest that rheumatoid arthritis (RA), ankylosing spondylitis (AS), or gout occurred in Aborigines before or during the early stages of white settlement of Australia. Part of the explanation for the absence of these disorders in this indigenous group may relate to the scarcity of predisposing genetic elements, for ex le, shared rheumatoid epitope for RA, B27 antigen for AS. In contrast, osteoarthritis appeared to be common particularly involving the temporomandibular joint, right elbow and knees and, most probably, was related to excessive joint loading in their hunter gatherer lifestyle. Since white settlement, high frequency rates for rheumatic fever, systemic lupus erythematosus, and pyogenic arthritis have been observed and there are now scanty reports of the emergence of RA and gout in these original Australians. The occurrence and phenotype of various rheumatic disorders in Australian Aborigines is distinctive but with recent changes in diet, lifestyle, and continuing genetic admixture may be undergoing change. An examination of rheumatic diseases in Australian Aborigines and its changing phenotype may lead to a greater understanding of the aetiopathogenesis of these disorders.
Publisher: Wiley
Date: 05-1999
DOI: 10.1002/1529-0131(199905)42:5<1067::AID-ANR32>3.0.CO;2-S
Publisher: Elsevier BV
Date: 02-2022
Publisher: Elsevier BV
Date: 2015
Publisher: Wiley
Date: 27-11-2023
DOI: 10.1111/IMJ.15966
Abstract: Nailfold capillaroscopy (NFC) is a simple noninvasive microscopic technique used to identify characteristic morphological abnormalities in the nailfold capillaries. The presence of this microvasculopathy appears to be of fundamental importance in the pathological processes that underlie the scleroderma spectrum disorders (including dermatomyositis and antisynthetase myositis). This review discusses the different methodologies and techniques in performing NFC and stresses the diagnostic utility achieved with simple ‘bedside’ techniques utilising the ophthalmoscope, dermatoscope or smart phone. Recent advances in reporting abnormal microvascular patterns and vascular metrics (e.g. capillary density and dropout) are discussed. The aetiopathogenesis of the microvasculopathy is currently unknown but its close association with Raynaud Phenomena and specific autoantibodies together with recent observations from sequential NFC allows speculations on its possible mechanism. Finally, future developments in the use of NFC as a possible biomarker in the management of the scleroderma spectrum disorders are discussed, with a recommendation that NFC becomes more widely available, particularly in rheumatological, immunological and dermatological practice. NFC provides a clinically accessible window on the pathologic process fundamental to scleroderma‐related disease.
Publisher: Springer Science and Business Media LLC
Date: 09-1995
DOI: 10.1007/BF00302125
Publisher: Springer Science and Business Media LLC
Date: 12-1987
DOI: 10.1007/BF00270525
Abstract: Here we consider a reaction diffusion system of three plankton populations, a zooplankton feeding on two phytoplankton populations, in two different settings. Firstly, the two phytoplanktons are both non-toxic and both enhance the growth of the grazing zooplankton. Secondly, we assume that one of the phytoplankton releases toxin and thereby inhibits the growth of the zooplankton. Our analytic and numerical study shows that the spatiotemporal distribution of the plankton species is uniform when both phytoplankton populations are non-toxic. However, in the presence of toxin-producing phytoplankton, the biomass distribution of all the plankton populations becomes inhomogeneous.
Publisher: Springer Science and Business Media LLC
Date: 16-02-2008
DOI: 10.1007/S00296-008-0540-9
Abstract: Previous studies have demonstrated an increased risk of breast cancer among patients with systemic sclerosis (scleroderma). To describe the clinical characteristics of 21 patients with both systemic sclerosis and breast cancer, and compare their risk factors to female scleroderma patients without breast cancer, in a population-based cohort study of South Australia. Subjects with scleroderma and breast cancer were identified from the South Australian Scleroderma Register with cross-linking to the South Australian Cancer Registry, last updated to the end of December 2005. Clinical information was obtained from standardised self-administered questionnaires and case note reviews. Odds ratios for the risk factors for breast cancer in scleroderma were determined, and clinical variables were analysed using chi square, Fisher's exact, Mann-Whitney and t tests. At the end of December 2005 there were a total of 389 female patients with scleroderma. Of these, 21 (5.4%) had been diagnosed with breast cancer. The mean age of onset of scleroderma was 43.5 years, and the mean age of breast cancer was 60.5 years in those with scleroderma and breast cancer. The majority (71.4%) had limited scleroderma, with anti-centromere antibody being the most prevalent serological abnormality. In 16 (76%) patients the diagnosis of breast cancer occurred on an average of 22.3 years after the onset of their first scleroderma symptom. When compared to 48 controls, scleroderma patients with breast cancer were found to have a higher incidence of a positive family history of breast cancer (Fisher's exact test, p = 0.04) and a lower incidence of hormone-replacement therapy use (Fisher's exact test, p = 0.0026). This population-based cohort study provides evidence that the majority of patients with scleroderma and breast cancer have limited scleroderma and anti-centromere antibody. Given the increased incidence of solid tumours in systemic sclerosis, we suggest regular screening of female patients for breast cancer, especially in those with a family history.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2014
DOI: 10.1007/S10067-014-2512-7
Abstract: Myopathy associated with anti-signal recognition particle (SRP) antibodies is a rare form of myopathy, which is thought to be distinct from classic polymyositis. We sought to determine the demographic, clinical and histopathological features of patients with anti-SRP antibodies. Hence we undertook an audit of patients with histologically-confirmed myositis who had anti-SRP antibodies. Of 144 patients with inflammatory myositis tested for myositis-specific and myositis-associated antibodies between 2007 and 2011 inclusive, five with anti-SRP antibodies were identified. All five were male, four had severe proximal weakness, one was asymptomatic and three had dysphagia. None had cardiovascular involvement. All patients showed isolated anti-SRP positivity and absence of antinuclear antibodies. Muscle histopathology showed variable myofibre necrosis, and most had an inflammatory infiltrate. Majority showed a favorable response to combination immunosuppressive therapy. Myopathy associated with anti-SRP antibodies is clinically heterogeneous in presentation. Muscle histopathology shows a mixture of necrotic and inflammatory features.
Publisher: Wiley
Date: 2014
DOI: 10.1111/IMJ.12293
Abstract: To determine the epidemiology and clinical features of biopsy-proven giant cell arteritis (GCA) in South Australia (SA). Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies at SA Pathology laboratories, from 1 January 1992, to 31 July 2011. Epidemiological data were collected through patient questionnaires and standardised case note reviews. Incidence was estimated using Australian Bureau of Statistics population data for SA. Seasonality was analysed by Cosinor analysis, and time-to- event analysis was performed for the duration of steroid use. There were 314 cases of biopsy-proven GCA (72% female). The mean age at diagnosis of GCA was 78 years (interquartile range 72-82). The estimated population incidence for people over 50 was 3.2 per 100,000 person years. The female : male incidence ratio was 2.3 (P < 0.001), and incidence increased with each age decade. There was evidence of seasonal variation (P = 0.015), with higher rates observed in the summer months. Clinical data were available for 163 patients (68% female, median age 78 years). The most common presenting clinical features were temporal headache (74%), visual disturbance (68.4%), jaw claudication (59.3%) and symptoms of polymyalgia rheumatica (56%). The median initial steroid dose was 60 mg, with median duration of steroid use 4.5 years. Corticosteroid side-effects were common, affecting 89%, with 34% reporting five or more. This is the first epidemiological study of Australian biopsy-proven GCA patients. Age at onset and gender associations were similar to other Western populations. There was a high burden of steroid use in these patients.
Publisher: Informa UK Limited
Date: 14-04-2021
Publisher: AMPCo
Date: 10-1996
DOI: 10.5694/J.1326-5377.1996.TB138603.X
Abstract: Cleavage and polyadenylation specific factor 6 (CPSF6) has been documented as an oncoprotein in different types of cancer. However, functions of CPSF6 have not been investigated yet in esophageal squamous cell carcinoma (ESCC). Here, we aimed to investigate the potential clinical values and biological functions of CPSF6 in ESCC. For determining the expression level of CPSF6 in ESCC patients, we analyzed published data, performed quantitative real-time polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. Kaplan-Meier curves and log-rank tests were used for survival analyses. GO and KEGG analyses were done for CPSF6-related genes. Cell proliferation, colony formation and xenograft assays were conducted to verify the effects of CPSF6 on ESCC. In addition, cell cycle and apoptosis assays were also performed to manifest the functions of CPSF6 and circCPSF6. RNA pulldown and radioimmunoprecipitation (RIP) assays were used for confirming the interaction between circCPSF6 (hsa_circ_0000417) and CPSF6 protein. The regulatory relationship between CPSF6 protein and circCPSF6 was determined by RT-qPCR. We found that CPSF6 was upregulated in ESCC tissues and overexpression of cytoplasmic CPSF6 was associated with poor prognosis. GO and KEGG analyses suggested that CPSF6 could mainly affect cell ision in ESCC. Further experiments manifested that CPSF6 promoted cell proliferation and colony formation These findings gave us insight that overexpression of cytoplasmic CPSF6 protein is associated with poor prognosis in ESCC and CPSF6 may function as an oncoprotein, at least in part, through regulating circCPSF6 expression.
Publisher: BMJ
Date: 06-1985
DOI: 10.1136/ARD.44.6.379
Abstract: In a cross-sectional study of over 3000 consecutive serum specimens the levels of rheumatoid factor (RF) measured by rate nephelometry (Beckman ICS II) were compared with values obtained by the more traditional methods of sheep cell agglutination (Rose-Waaler) and latex agglutination. Similar values for sensitivity and specificity were found for all three methods for rheumatoid arthritis, with nephelometry giving slightly higher levels of sensitivity for other rheumatic disorders. A significant correlation (r = 0.46, p less than 0.01) was found between the nephelometric and Rose-Waaler method for 147 consecutive seropositive specimens. Of interest, however, several disparate results were observed, and explanations for these were sought. Longitudinal studies of RF were performed in 49 seropositive patients over a two-year period. The nephelometric method was considered superior compared with the other techniques because of its ability to detect changes in absolute levels at earlier stages and its low interassay coefficient of variance (11%). We conclude that the nephelometric technique appears suitable for routine diagnostic use, offers several advantages compared with more traditional methods, and is no more expensive per test specimen than the Rose-Waaler technique.
Publisher: Springer Science and Business Media LLC
Date: 06-1992
DOI: 10.1007/BF00300978
Abstract: Plasma concentrations of propranolol and practolol were measured in patients with coeliac disease and normal subjects. The mean plasma propranolol concentration in the coeliac patients was higher throughout the period of study, the differences being significant at one, six, and eight hours. The plasma concentration profile of practolol in the coeliacs followed a similar pattern but lagged behind that of the normal subjects. A possible reason for these differences is an alteration in the rate of drug diffusion across the atrophic mucosa of the upper jejunum in coeliac disease. Analysis of the results of the propranolol study suggests that an increase in the rate of absorption combined with saturation of first pass extraction may account for the increased plasma concentrations of unchanged propranolol found in coeliac disease. These abnormalities of drug absorption do not appear to be related to the duration of treatment with a gluten free diet.
Publisher: BMJ
Date: 14-05-2019
Publisher: AMPCo
Date: 1998
Publisher: Wiley
Date: 03-2009
DOI: 10.1111/J.1445-5994.2008.01822.X
Abstract: The idiopathic inflammatory myopathies are a group of systemic autoimmune syndromes characterized by striated muscle inflammation. Here, we discuss the clinical features of this group of conditions and review the recent developments in the understanding of the pathogenesis and immunogenetics of the idiopathic inflammatory myopathies. The role of myositis-specific autoantibodies and their clinical significance and an overview of management are also provided.
Publisher: Wiley
Date: 2005
DOI: 10.1111/J.1445-5994.2004.00646.X
Abstract: Isolated pulmonary hypertension (PHT) is now the most frequent cause of disease-related death in limited cutaneous scleroderma, the commonest disease variant of this disabling connective tissue disorder. Endothelin-1 receptor antagonists provide symptomatic benefit but to date have not been shown to prolong survival. To determine the frequency, disease characteristics and survival of symptomatic patients with isolated PHT in our cohort of scleroderma patients. Systematic review of the clinical course of all patients registered on the South Australian Scleroderma Register, a population-based register of 374 living and 234 deceased patients with scleroderma. Thirty-four patients were identified with isolated PHT, the majority with limited scleroderma. From our deceased register, we estimate that >11% of patients with this limited variant will develop this complication. Isolated PHT occurs as a late-stage complication approximately 20 years after the first symptoms of scleroderma. Patients with isolated PHT were characterized by the presence of multiple telangiectasia, reduced nailfold capillary density, digital ulceration, gross reduction of diffusing capacity for carbon monoxide and echocardiographic evidence of elevated pulmonary artery pressure. Survival was significantly shortened as compared with those patients without this complication (P=0.002), with a mean survival of 2.5 years from symptomatic onset of PHT. Isolated PHT occurs as a late-stage complication in > or =11% of patients with limited cutaneous scleroderma and leads to rapid death from right heart failure. The early use of endothelin-1 receptor antagonists may change the natural history of this fatal complication.
Publisher: Springer Science and Business Media LLC
Date: 05-1990
DOI: 10.1007/BF02274821
Publisher: Wiley
Date: 12-2008
DOI: 10.1111/J.1445-5994.2008.01636.X
Abstract: The presence of sicca symptoms is a frequent finding in patients with systemic sclerosis (SSc). The aim of this study was to examine the prevalence of sicca symptoms in a South Australian cohort of SSc patients and correlate this to a number of parameters, including autoantibody status, use of anticholinergic medication, age and the presence of functional anti-muscarinic-3 receptor (M3R)-blocking antibodies. A screening questionnaire was sent out to all patients on the South Australian Scleroderma Register from the years 1998-2006 to determine the prevalence of sicca symptoms. A subset of patients on the register had ocular sicca symptoms tested by use of Schirmer's strips to validate the accuracy of the questionnaire. Eight patients were tested for anti-M3R-blocking antibodies using a functional physiological assay. One hundred and ninety-three SSc patients took part in this study. Sicca symptoms were present in 59% of patients with the limited form of SSc, compared with 49% of patients with the diffuse form and 40% of patients with the overlap syndrome. The use of anticholinergic medication or thyroxine was associated with higher sicca scores in SSc patients. SS-A and SS-B autoantibodies (seen in Sjögren's syndrome) were detected in eight patients in this study. The detection of anti-M3R-blocking antibodies correlated well to presence of sicca. This study confirmed that sicca symptoms are found in a high proportion of patients with SSc, especially those with the limited variant. Further testing of larger numbers of SSc patients with sicca for anti-M3R-blocking antibodies will be needed before more definitive conclusions can be drawn. Physicians should be made aware that sicca symptoms are a frequent cause of morbidity for SSc patients*.
Publisher: Springer Science and Business Media LLC
Date: 05-1990
DOI: 10.1007/BF02274822
Publisher: Oxford University Press (OUP)
Date: 03-2007
Publisher: Springer Science and Business Media LLC
Date: 05-1990
DOI: 10.1007/BF02274825
Publisher: Elsevier BV
Date: 04-1986
DOI: 10.1016/0022-1759(86)90056-6
Abstract: Two techniques for the definitive identification of low molecular weight (LMW) IgM have been compared, namely, filtration chromatography combined with nephelometry and a modified immunoblotting assay. The results indicate that the latter is a more sensitive and reliable technique. Furthermore the resolution of immunoblotting is such that it can distinguish additional oligomeric forms of IgM as well as monomeric IgM suggesting a disorder of polymerization of pentameric IgM. As the presence of LMW IgM in the sera of patients with various disorders is of prognostic significance the immunoblot technique merits consideration as a useful screening assay to detect this moiety.
Publisher: Wiley
Date: 05-2010
Publisher: BMJ
Date: 1988
DOI: 10.1136/ARD.47.1.15
Abstract: In a prospective 24 week study of 25 patients with rheumatoid arthritis (RA) weekly intramuscular (IM) sodium aurothiomalate resulted in a small but significant reduction in the circulating lymphocyte count. Analysis of absolute levels of pan T cells, T4 helper cells, T8 suppressor cells, T4/8 ratio, B cells, and major histocompatibility complex (MHC) class II positive cells showed reductions in these subsets, though these changes did not reach significance. At entry there was no association between circulating lymphocyte counts and subsets and clinical and laboratory indices which reflected disease activity, and during the study gold responders could not be differentiated from non-responders with regard to changes in lymphocyte counts and subsets. Thus this study suggests that weekly IM gold leads to a modest reduction in circulating lymphocyte numbers which involves most subsets. This effect appears to be independent of the clinical efficacy of this drug.
Publisher: Wiley
Date: 14-09-2007
DOI: 10.1111/J.1440-1673.2007.01693.X
Abstract: Skeletal muscle metastases from pancreatic carcinoma are exceedingly rare with only a few cases reported in the published work. The case of a 59-year-old man with bilateral, symmetric gluteal muscle metastases from pancreatic carcinoma is presented. This case was clinically challenging as until skeletal muscle biopsy was carried out, the working diagnosis was that of paraneoplastic polymyositis. A brief review of the published work is also presented.
Publisher: Oxford University Press (OUP)
Date: 02-2010
Abstract: To determine the prevalence and diagnostic utility of monospecific anti-Ro52 (defined as an immune response against Ro-52 antigen in the absence of reactivity to Ro-60 antigen) reactivity in selected autoimmune diseases. Stored diagnostic non-consecutive serum s les obtained from patients with systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS), systemic sclerosis, idiopathic inflammatory myopathies (IIM), rheumatoid arthritis, primary biliary cirrhosis and mixed essential cryoglobulinaemia were analysed by line immunoassay to detect the presence of anti-Ro52 and other autoantibodies. Monospecific anti-Ro52 reactivity was found in 51 (12.7%) of the 402 s les tested. Anti-Ro52 was the most common serological marker in patients with IIM (35/147, 23.8%) and co-occurred with anti-Jo1 (10/18, 55.6% p=0.02). The prevalence of anti-Ro52 reactivity was significantly more than anti-Ro60 reactivity in patients with IIM, systemic sclerosis, primary biliary cirrhosis, mixed essential cryoglobulinemia and pSS. The mean signal intensity of anti-Ro52 reactivity was significantly higher in pSS than SLE and associated with rheumatoid factor positivity. The mean signal intensity of anti-Ro52 correlated with anti-Ro60 and anti-La in pSS and SLE. Monospecific anti-Ro52 reactivity is not disease specific but may be of importance in patients with IIM. Furthermore, as anti-Ro52 reactivity is more prevalent than anti-Ro60 reactivity in certain autoimmune conditions, specific testing for their distinction in clinical practice is recommended.
Publisher: Informa UK Limited
Date: 1993
DOI: 10.3109/01913129309027800
Abstract: The ultrastructural appearances of corneal crystalloidal deposits are described in two patients with an IgG-kappa paraproteinemia of uncertain pathogenesis. The crystalloids in one patient were overwhelmingly intracellular and were found mainly in stromal keratocytes, but also in basal corneal epithelial cells and the limbal vascular endothelium. Four types of crystalloid or immunoprotein-containing granules were recognizable in this case: 1) fibrillary crystalloids with a curvilinear filamentous substructure 2) angulated geometric crystalloids that often had a linear filamentous substructure and transverse or oblique periodicity 3) cordlike crystalloids and 4) lysosomelike granules with amorphous contents. Immunoelectron microscopy demonstrated that all of these structures labeled for kappa-light chains, and rectangular type 2 crystalloids showed approximately a twofold greater concentration of the colloidal gold probe than the type 1 fibrillary crystalloids. The evidence suggested development of the crystalloids within lysosomes, with a progression from the granules containing amorphous material, through fibrillary crystalloids, to the geometric structures. The circumferential distribution of the corneal deposits, as well as the presence of vascular endothelial crystalloids and reduplication of external laminae around limbal blood vessels, suggests that the crystalloids originated predominantly or entirely from the blood, with transport of immunoprotein across damaged limbal microvasculature. The abnormal vasculature may also have contributed to corneal edema, which in turn may have exacerbated corneal opacification. The crystalloidal deposits in the other case were exclusively extracellular they were located beneath and between corneal basal epithelial cells, and predominantly as a mantle around in idual keratocytes. The crystalloids in this case consisted overwhelmingly of thick-walled tubules about 40 nm in diameter that labeled for both kappa-light chains and gamma chains with the colloidal gold immunoprobe. In addition, lucent vesicles within keratocytes were found only in sections labeled for kappa-light chains and were positive. The factors that might contribute to the formation of corneal crystalloidal deposits in immunoproliferative disorders are discussed, and include: 1) an inherent propensity for crystallization of some immunoglobulins or kappa-light chains, perhaps because of abnormal molecular structure and 2) local factors in the cornea that might promote deposition and crystallization of immunoprotein, such as temperature, pH, the water content, and extracellular matrix components.
Publisher: Elsevier BV
Date: 10-1995
DOI: 10.1016/0022-1759(95)00146-2
Abstract: In vitro studies of neutrophil adhesion generally utilise purified populations and are often performed at 37 degrees C. This study determines the effects of temperature changes and neutrophil separation procedures on the expression of cell adhesion molecules on neutrophils. We found that neutrophil separation procedures involving erythrocyte sedimentation and hypotonic lysis are associated with a significant increase in the expression of both a structural and functional epitope of the beta 2 integrin CD11b, an increase in the expression of sialyl Lewisx (CD15s) and the hyaluronate receptor (CD44) as well as a significant decrease in L-selectin (CD62L) expression. Separated neutrophils are also more resistant than unseparated neutrophils to PMA induced upregulation of a functional epitope of CD11b. Incubating neutrophils at 37 degrees C is associated with increases in the expression of structural and functional epitopes of CD11b. Neutrophil separation is also associated with increases in the expression of both structural and functional epitopes of CD11b which is greater when neutrophil separation is performed at room temperature compared with neutrophil separation at 0-4 degrees C. However, this difference is lost when the latter are incubated at 37 degrees C. Furthermore, neutrophil separation at both 0-4 degrees C and room temperature is associated with a significant increase in CD15s expression. This increase is less when separation is performed at room temperature. These findings suggest that neutrophil separation should be performed at room temperature unless the cells are going to be used at 0-4 degrees C. Researchers using purified neutrophil populations need to be aware of these significant structural and functional changes when extrapolating in vitro results to in vivo situations.
Publisher: Elsevier BV
Date: 1991
DOI: 10.3109/00313029109060810
Abstract: A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) in Clinical Immunology, involving 128 laboratories over a 1 yr period, revealed the following: successful participation in the program by 16 overseas laboratories (distant from Australia) only 30% of laboratories succeeded in returning their results by the scheduled date on every occasion quantitation of urinary total protein and Bence Jones protein was poor and varied over a log scale immunofixation was more successful in characterizing urinary paraprotein than immunoelectrophoresis densitometry of protein electrophoresis appeared the method of choice in quantitating serum paraproteins accurately nephelometric techniques gave better concordance between laboratories than turbidometric, radial immunodiffusion or agglutination techniques poor concordance between laboratories in detecting weakly positive antinuclear antibodies (ANA) some laboratories had difficulties in identifying ANA patterns (only 60% of laboratories correctly identified the anticentromere pattern) few laboratories could correctly identify antibodies to extractable nuclear antigens (ENA) flow cytometry gave a smaller dispersion of lymphocyte subpopulation percentages than microscopy. A method was established to rank laboratory performance of selected tests over the 1 yr period. Such a comparative ranking scheme may alert laboratories in identifying specific or generalized deficiencies in performance.
Publisher: Wiley
Date: 10-2003
DOI: 10.1046/J.1440-1711.2003.01181.X
Abstract: A systematic review has been undertaken of antinuclear antibody testing over a 6-year period in a regional immunotherapy laboratory servicing a population of 400 000. Twenty-eight per cent of the 20 205 antinuclear antibody tests performed on a hyperexpressing Ro transfected cellular substrate were positive (titre >/= 1 : 80) with the most common immunofluorescent patterns being homogeneous (39%), speckled (20%), mixed (17%), nucleolar (8%), Ro (7%) and centromere (4%). Ro antibody as detected by immunofluorescence was strongly concordant with anti-Ro detected by counter immunoelectrophoresis precipitation of 261 anti-Ro counter immunoelectrophoresis precipitation positive patients surveyed, only 15 were missed and 20 masked (with homogenous pattern) by immunofluorescence. Ro antibodies were found in patients with a variety of immune disorders, particularly connective tissue disorders, whilst a clinical survey of the anticentromere sera revealed that 67% were derived from patients with limited scleroderma. Extractable nuclear antibodies and their characterization was performed on 10 939 occasions with 12.9% being positive with anti-Ro constituting 30.2%, anti-Ro/La 25.7%, unidentified precipitin line 17.8%, anti-ribo nuclear protein 12.5%, respectively, with anti-Scl70, anti-Jo-1 and anti-Sm and various combinations making up the remainder. Unidentified precipitin lines were particular prominent in patients with connective tissue disorders. DNA quantification was performed on 12 068 occasions with 11% giving elevated values, the majority from patients with systemic lupus erythematosus. Of these positive sera 44% also demonstrated one or more extractable nuclear antibodies and 25% anticardiolipin antibodies. Regular participation in a Quality Assurance Program revealed accurate and consistent performance of antinuclear antibody testing. In conclusion antinuclear antibody detection and characterization for systemic immune disorders can provide the clinician with useful diagnostic and prognostic information it is important that the laboratory results are relevant, timely, accurate and precise. Systematic reviews as demonstrated in this report, can provide such evidence.
Publisher: BMJ
Date: 06-1985
DOI: 10.1136/ARD.44.6.384
Abstract: Gout and classical rheumatoid arthritis rarely coexist. We report a patient with strong evidence for both these diseases. Possible reasons for the negative correlation between these diseases are summarised. One hypothesis suggests inhibition of surface activity of monosodium urate crystals (MSU) by binding of rheumatoid factor (RF). This was studied with a purified monoclonal rheumatoid factor (mRF) with specificity for IgG. The mRF bound preferentially to MSU coated with IgG in contrast with the IgM control. Inhibition of the neutrophil chemiluminescence (CL) response to IgG-coated MSU was observed at concentrations of mRF that had no effect on the CL response to uncoated crystals. Neutrophil activation was not altered by coating crystals with an IgM control at the same concentration. These data suggest that RF may bind to antigenic determinants on exposed Fc of adsorbed IgG and block the interaction of crystal-bound IgG with Fc receptors. Although crystal coating by RF may modify the expression of gouty arthritis, it is unlikely to be the sole explanation for the dissociation between gout and RA.
Publisher: AMPCo
Date: 02-1984
DOI: 10.5694/J.1326-5377.1984.TB103996.X
Abstract: Death as a result of a bee sting is uncommon in Australia. During the 22 years from 1960 to 1981, 25 in iduals have been recorded by the Australian Bureau of Statistics as having died shortly after a bee sting. This gives a mortality incidence of 0.086/1 000 000 population per year, but may be an underestimate, as we report two additional fatalities that did not appear in the records of the Bureau of Statistics. South Australia has the highest mortality rate from bee stings of all the Australian States, with a recorded fatality rate of 0.26/1 000 000 population per year. As in other surveys, fatalities occur predominantly in men over 40 years of age, which suggests that there may be other contributory risk factors, for ex le, coronary atherosclerosis. No deaths were reported in in iduals aged from six to 19 years, the age group in which bee-sting anaphylaxis is particularly common. It thus appears that the prevention of death per se is not a strong rationale for routine bee-venom immunotherapy in schoolchildren and young adults.
Publisher: BMJ
Date: 02-1990
DOI: 10.1136/ARD.49.2.103
Abstract: Phenotypic and genotypic characteristics of the peripheral blood mononuclear cells in nine patients with Felty's syndrome have been examined. One patient had an increased number and percentage of peripheral blood mononuclear cells with the phenotype CD3+ Leu-7+ CD16+ and showed a clonal rearrangement of the T cell receptor B chain gene. The remaining eight patients all showed a germline configuration of the T cell receptor B chain gene. In two patients an increased proportion of CD3+ Leu-7+ CD16- peripheral blood mononuclear cells (45 (SD 11)% of peripheral blood mononuclear cells) were found, while the remaining six patients had proportions of CD3+ Leu-7+ cells similar to those of patients with uncomplicated rheumatoid arthritis. These data confirm that patients with Felty's syndrome are heterogeneous, with at least three different peripheral blood mononuclear cell phenotypic subsets. One subset is characterised by a clonal expansion of an unusual lymphocyte subpopulation, another by polyclonal expansion, and the third subset has the same proportions of peripheral blood mononuclear cells as patients with uncomplicated rheumatoid arthritis.
Publisher: Oxford University Press (OUP)
Date: 11-2000
Publisher: BMJ
Date: 12-1988
Abstract: Low molecular weight IgM, the monomeric subunit of pentameric IgM, was clearly detected by immunoblotting and filtration chromatographic techniques in six patients with juvenile chronic arthritis and in trace quantities in a further eight of 24 patients studied. This low molecular weight IgM moiety contributed up to 33% of the total circulating IgM and was strongly associated with raised serum concentrations of IgM and the presence of antinuclear antibodies, extractable antinuclear antibodies, and rheumatoid factor. Immunoblot analysis of positive serum s les showed small quantities of other low molecular weight oligomers of IgM in addition to monomeric IgM. It is postulated that the presence of low molecular weight IgM in the serum of patients with juvenile chronic arthritis reflects a disorder of the intracellular assembly of IgM subunits during a stimulated IgM immune response. The pathogenetic role of low molecular weight IgM remains uncertain.
Publisher: Springer Science and Business Media LLC
Date: 1992
DOI: 10.1007/BF00314925
Abstract: The effects of prednisolone azathioprine and 6-mercaptopurine on polymorphonuclear neutrophil chemotaxis, phagocytosis, and killing of Staphylococcus aureus and Candida albicans have been studied. In twenty patients with a functioning kidney graft, taking both azathioprine 2.5 mg/kg/day and prednisolone (mean dose 0.59 mg/kg/day range 0.30-1.0 mg/kg/day), the polymorphonuclear function did not significantly differ from that in either twenty-two normal or eighteen uraemic controls. Addition of prednisolone, 1.2 X 10(-5) M, azathioprine, 2.1 X 10(-5) M, and 6-mercaptopurine, 2.1 X 10(-5) M, using each drug alone, to normal human polymorphonuclear cells in vitro did not significantly alter their function. It is concluded that prednisolone and azathioprine together in vivo and that both these drugs and 6-mercaptopurine singly in vitro have no significant deleterious effect on polymorphonuclear function and do not contribute, in this way, to the increased susceptibility of patients receiving these drugs to infection.
Publisher: BMJ
Date: 02-2006
Publisher: BMJ
Date: 12-01-2007
Publisher: Wiley
Date: 06-1981
Abstract: Low molecular weight (LMW) IgM was measured in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and other rheumatic diseases. High levels were seen in RA, particularly in rheumatoid vasculitis and Felty's syndrome, and significant correlations occurred between LMW IgM and the rheumatoid factor (RF) level and other indices that reflected active or severe disease. LMW IgM-RF, measured by radioimmunoassay in those column fractions containing LMW IgM, correlated significantly with LMW IgM (P less than 0.005) preliminary experiments suggested that in some sera, a considerable proportion of the LMW IgM consisted of LMW IgM-RF. We conclude that LMW IgM and LMW IgM-RF may have important implications in the immunopathogenesis of RA and other rheumatic diseases.
Publisher: Oxford University Press (OUP)
Date: 10-2000
DOI: 10.1093/RHEUMATOLOGY/39.10.1067
Abstract: To investigate the effects of a 1000 mg i.v. pulse of methylprednisolone succinate (pulse therapy) on the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the synovial membrane of the knee in patients with rheumatoid arthritis (RA). Sequential arthroscopic biopsies of the knee were taken before and 24 h after pulse therapy (11 patients), at disease relapse (three patients) and after retreatment with pulse therapy (one patient). Immunoperoxidase staining for MMP-1 (interstitial collagenase), MMP-3 (stromelysin-1) and TIMP-1 was performed and the immunoreactive staining quantified by colour video image analysis. In the synovial lining layer, MMP-1 and TIMP-1 immunostaining was reduced by a mean of 47% (P = 0.02) and 72% (P = 0.05), respectively, 24 h after pulse methylprednisolone therapy. In the synovial sublining layer, MMP-1 was reduced by a mean of 51% (P = 0.08) and TIMP-1 by a mean of 73% (P = 0.02) 24 h after pulse methylprednisolone therapy. There was no change in MMP-3 staining in the synovial lining or sublining layer. High-dose pulse methylprednisolone therapy is associated with a rapid (within 24 h) and substantial decrease in the expression of MMP-1 and TIMP-1 but not MMP-3 in the synovial membrane in RA.
Publisher: BMJ
Date: 02-1984
DOI: 10.1136/ARD.43.1.34
Abstract: Membrane activation of human neutrophils by preformed immune complexes and heat aggregated human gammaglobulins was studied by chemiluminescence. Strong neutrophil activation was found with human-albumin rabbit-antialbumin complexes prepared at equivalence, with maximal activation occurring in slight antigen excess. Furthermore different preparations of heat aggregated gammaglobulin which were of large size also showed similar activity. In contrast, heat aggregates of small size were inactive and blocked the chemiluminescent response found with larger active aggregates. A purified monoclonal rheumatoid factor with specificity for IgG modulated these responses when preincubated with preformed complexes or aggregates. Both enhancement of the neutrophil chemiluminescence response with inactive preparations and suppression of the response with highly active preparations were observed. Kinetic studies of the neutrophil chemiluminescent response varied with respect to the activating preparation, but were generally biphasic. This observation suggested an initial direct membrane activation followed by a more delayed response reflecting phagocytosis of complexes. We have demonstrated the direct activation of neutrophil chemiluminescence by laboratory preparations of immune complexes. The chemiluminescent responses observed were influenced by both the size and immunochemical properties of the activating complexes and by the presence of rheumatoid factor. These observations may have important implications in the immunopathogenesis of immune-complex-mediated diseases.
Publisher: Wiley
Date: 02-1984
DOI: 10.1111/J.1445-5994.1984.TB03588.X
Abstract: We report the complication of cardiac t onade occurring secondary to a pericardial effusion in a patient with persistently seronegative rheumatoid arthritis. The frequency and presenting features of this potentially life threatening complication of rheumatoid arthritis are reviewed and management of this complication is discussed.
Publisher: AMPCo
Date: 09-1984
DOI: 10.5694/J.1326-5377.1984.TB133034.X
Abstract: Urticaria and angio-oedema are a symptom complex covering a wide range of clinical disorders. Specific types are now well described, and it appears that many cases of idiopathic chronic urticaria which make up the vast majority of patients referred for assessment are due to intolerance to natural salicylates, preservatives and colouring agents. There is, therefore, an urgent need for legislation to enforce the clear identification of these chemicals in processed food and drugs.
Publisher: Wiley
Date: 2001
DOI: 10.1002/1529-0131(200102)44:2<343::AID-ANR52>3.0.CO;2-Q
Publisher: Wiley
Date: 02-2021
DOI: 10.1111/IMJ.14772
Publisher: BMJ
Date: 04-1983
DOI: 10.1136/ARD.42.2.158
Abstract: The majority of paired sera and synovial fluids from 21 patients with rheumatoid arthritis produced a rapid chemiluminescent response when incubated with human neutrophils. Synovial fluid gave considerably higher responses than the paired serum specimen. In contrast little or no response was found with paired sera and joint fluid taken from patients with gout, psoriasis, and osteoarthritis and with sera from healthy donors. A similar chemiluminescent response was observed when neutrophils were preincubated with large aggregates of heated human gammaglobulin (HAGG), which were used as a model of immune complexes. Smaller nonreactive aggregates of gammaglobulin became reactive after preincubation with a purified monoclonal rheumatoid factor (mRF) which had a high avidity for aggregated IgG. The addition of this monoclonal rheumatoid factor also caused enhancement of chemiluminescence by rheumatoid sera. Further evidence suggesting that the active material found in these rheumatoid specimens contained complexed immunoglobulin was obtained by indirect immunofluorescence. Neutrophils developed intracellular immunoglobulin inclusions after preincubation in reactive rheumatoid sera but not with nonreactive or normal sera. However, activation of neutrophil chemiluminescence by rheumatoid specimens did not correlate significantly with levels of rheumatoid factor or immune complexes suggesting that the activating complexes were of a particular type. In conclusion we have shown the direct activation of neutrophil chemiluminescence by rheumatoid sera synovial fluid and suggest that the activation is caused by large IgG-containing immune complexes. It is possible that this activation may have important implications in the immunopathogenesis of the rheumatoid inflammatory process.
Publisher: Wiley
Date: 05-2003
DOI: 10.1046/J.1445-5994.2003.00358.X
Abstract: Background : Scleroderma renal crisis (SRC) is a rare but feared complication of scleroderma. Angiotensin‐converting enzyme (ACE) inhibition has significantly improved survival, but it is unknown whether prophylactic ACE inhibitors will prevent this complication. Aims : To determine: (i) the frequency of SRC in our cohort of well‐characterized scleroderma patients resident in South Australia, (ii) any predisposing clinical and serological features, (iii) median disease duration at which SRC occurs, (iv) possible precipitants, (v) disease outcome, and (vi) whether patients were taking ACE inhibitors prior to onset of SRC. Methods : Systematic review of the clinical course of all patients registered on the South Australian Scleroderma Register. Results : SRC occurred in 16 patients. This constituted 2.8% of a total scleroderma cohort and 15% of the diffuse scleroderma cohort identified in South Australia. All 16 patients had diffuse cutaneous scleroderma. SRC occurred at a median disease duration of 15 months (range 1 week− 11 years). Disease outcome was poor (five deaths, three requiring long‐term dialysis and only two patients regaining a normal creatinine) despite aggressive antihypertensive treatment (including ACE inhibitors) in an intensive care or specialized renal unit. Two patients were later able to discontinue dialysis. Only two patients were taking small doses of ACE inhibitors prior to the onset of their SRC. The frequency of Scl‐70 was decreased in the SRC group ( P = 0.003). Conclusion : SRC is a rare event occurring in a small proportion of patients with diffuse scleroderma. The outcome of SRC was poor despite aggressive antihypertensive treatment. It is hypothesized that prophylactic ACE inhibition in susceptible patients might prevent or ameliorate this complication. (Intern Med J 2003 33: 216−220)
Publisher: BMJ
Date: 06-1990
DOI: 10.1136/ARD.49.6.370
Abstract: To test the hypothesis that early steroid pulsing augments the efficacy and decreases the toxicity of chrysotherapy 40 patients with rheumatoid arthritis were studied in a double blind, placebo controlled study. During the first three months of gold treatment group 1 received monthly intravenous methylprednisolone pulsing (steroid group) while group 2 received placebo (placebo group). All patients were assessed clinically and serologically over a 24 week period. Twelve patients were withdrawn before completion of the study and all but one of the remaining 28 patients reported clinical and serological improvements. Two patients in the steroid group were withdrawn owing to gold induced side effects while four were withdrawn in the placebo group. These small numbers were not significantly different. Minor side effects occurred more commonly in the placebo group. The clinical response was clearly better in the steroid group with statistical significance almost being achieved. In an endeavour to obtain a significant conclusion further patients will now be entered into this study.
Publisher: Wiley
Date: 24-01-2013
Publisher: Elsevier
Date: 1976
Publisher: Wiley
Date: 31-05-2011
DOI: 10.1002/ART.30352
Publisher: BMJ
Date: 1990
DOI: 10.1136/GUT.31.1.88
Abstract: Low molecular weight IgM is the monomeric subunit of pentameric IgM and is not generally found in the blood of healthy in iduals. Using a sensitive immunoblotting technique, low molecular weight IgM was detected in all 17 patients with primary biliary cirrhosis and constituted up to 5% of the total circulating IgM. This low molecular weight IgM moiety correlated significantly with total IgM (p less than 0.01) but not with the specific biliary cirrhosis mitochondrial autoantibody anti-M2. Furthermore it was not possible to show that a partially purified s le of low molecular weight IgM contained M2 binding activity. Mitogen stimulated peripheral blood mononuclear cells from two of four patients were observed to secrete low molecular weight IgM in vitro, a finding seen in only one of six healthy subjects. Immunoblot analysis of patients sera revealed the presence of other oligomers of IgM in addition to low molecular weight IgM. In conclusion this study suggests that during the enhanced IgM synthesis observed in primary biliary cirrhosis a defect occurs in the assembly of the IgM pentamer with release of monomeric and oligomeric IgM into the circulation. The pathogenic significance of these circulating low molecular weight IgM species is unknown.
Publisher: Oxford University Press (OUP)
Date: 09-2001
DOI: 10.1093/RHEUMATOLOGY/40.9.965
Abstract: To investigate the change in synovial membrane cytokine content and cell adhesion molecule expression in sequential biopsies from the same knee joint of patients with rheumatoid arthritis, before and following anti-rheumatic drug treatment and to assess the relationship of these changes with clinical responses to the drug treatment. A selected group of patients with rheumatoid arthritis, some of whom had achieved a disease remission based on American College of Rheumatology (ACR) criteria, were included in this study. Sequential synovial biopsies obtained before and throughout the treatment period were studied by immunohistochemical labelling techniques for the cellular content, production of a range of pro- and anti-inflammatory cytokines and the expression of cell adhesion molecules. The staining was quantitated using computer-assisted digital image analysis. There was a decrease in tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) production in the synovial membrane lining and sublining of all patients who responded to treatment. The changes in IL-1 receptor antagonist production were variable. Paradoxically, there was a trend to decreased synovial membrane production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGFbeta), while IL-4 was not detectable in any of the synovial membrane biopsies. A significant reduction in the density and total amount of E-selectin expression in the synovial membrane was seen. Similarly, intercellular adhesion molecule-1 (ICAM-1) expression in the lining and sublining was decreased in those patients who had a significant clinical response to drug treatment or attained disease remission. There were no consistent or significant changes seen in the expression of other cell adhesion molecules in the synovial membranes of these patients. Successful drug treatment of rheumatoid arthritis patients is characterized at the synovial membrane level by a decrease in TNFalpha, IL-10 and TGFbeta production. Some (E-selectin and ICAM-1) but not all (P-selectin, VCAM-1, PECAM-1) cell adhesion molecules are modulated in patients who respond clinically to drug treatment. E-selectin and ICAM-1 may be important targets for the development of future drug treatments for rheumatoid arthritis.
Publisher: Wiley
Date: 08-2018
DOI: 10.1111/IMJ.13799
Abstract: Scleroderma is a rare connective tissue disorder characterised by inflammation, vasculopathy and excessive fibrosis. Patients with scleroderma are known to have decreased life expectancy. To investigate changes in life expectancy in patients with scleroderma over a 30-year period. Utilising the South Australian Scleroderma Register, deceased patients were identified. We examined changes in age of death and duration of disease in these patients over three time periods: 1985-1994, 1995-2004 and 2005-2015. Analyses of scleroderma subtypes were performed, and comparisons were made to the general South Australian population. A total of 413 deceased patients was identified. Females were overrepresented 315 to 98 265 had limited scleroderma, 90 diffuse and 22 overlap disease. Over 30 years, the mean age of death improved from 66.4 to 74.5 years (P < 0.001). Duration of disease improved from 12.1 to 22.9 years (P < 0.001). Improvement in survival was seen in limited (P = 0.001), diffuse (P = 0.04) and overlap (P = 0.04) subgroups. The increase in survival was only seen for female (9.8 ± 4.2 years) but not male (1.4 ± 6.7 years) patients. Over the last 30 years, survival has significantly improved for female but not male patients. As no disease-modifying drugs have consistently been shown to alter disease course, this improvement is likely attributable to general improvements in medical care, including that of scleroderma-related complications. While the life expectancy for limited disease is now close to that of the general population, patients with diffuse and overlap disease continue to suffer from significant early mortality.
Publisher: Wiley
Date: 2005
DOI: 10.1111/J.1445-5994.2004.00729.X
Abstract: Scleroderma (systemic sclerosis) has not been reported before in Australian Aborigines. We describe in detail a community middle-aged Aboriginal woman whose diffuse scleroderma terminated fatally with a renal crisis. Moreover, we have identified a further five Aboriginal patients on the South Australian Scleroderma Register (two with diffuse, two with limited and one with overlap scleroderma), a number consistent with that expected from the 2001 census data for our state. However, an analysis of all antinuclear antibody (ANA) requests from the Top End of Australia over a 6-year period revealed only two Aborigines with low titre anticentromere antibody (despite frequent occurrence of ANA with other specificities). Neither of these Aborigines had features of scleroderma. In conclusion, scleroderma does occur in indigenous Australians but further studies are needed to confirm the apparent infrequency of centromere-associated limited scleroderma (which is the commonest form of scleroderma in our Caucasian population).
Publisher: AMPCo
Date: 2012
DOI: 10.5694/MJA11.10821
Abstract: Mackay and Burnet's Autoimmune diseases, published in 1962, marked the beginning of autoimmunity as a clinical science and led to the future acceptance of the existence of autoimmunity. While there is still controversy regarding the mechanisms of autoimmunity, the authors' insightful hypothesis based on clonal selection theory and the emergence of "forbidden clones", due to somatic mutations, is still current, with recent evidence giving further credence to this hypothesis. We salute Mackay and Burnet on the 50th anniversary of this seminal publication. It is particularly pleasing that it has an iconic Australian origin.
Publisher: Wiley
Date: 12-2007
Publisher: Wiley
Date: 20-05-2001
DOI: 10.1046/J.1445-5994.2001.00048.X
Abstract: Scleroderma is an autoimmune disorder of unknown cause. Previous epidemiological studies have suggested some regional clustering and associations with occupations involving exposure to silica dusts and hydrocarbons. To determine: (i) prevalence and incidence of scleroderma in South Australia (SA), a state with a stable population living in well-defined urban, rural and industrial regions, (ii) hospital separation rates, (iii) cumulative survival rates, (iv) gender and disease subclassification, (v) geographical residency and occupations, (vi) familial associations and (vii) age at onset versus age-specific incidence rate. Creation of the South Australian Scleroderma Register (SASR) to identify demographics and clinical and serological features of all scleroderma patients resident in SA. Scleroderma occurs in South Australia with a point prevalence of 23 per 10(5) and an incidence of approximately 1/15th of this. However, this prevalence is high compared with other regional world studies. Scleroderma is predominantly a female disease, with most patients having the limited form of scleroderma characterized by the presence of the anticentromere antibody and a mean survival of 27.6 years. In contrast, diffuse scleroderma is a less benign disease occurring at an early age of onset and has a mean survival of 9.6 years. Scleroderma occurs throughout SA without regional localization. Weak associations are seen in males, but not females, with occupations involving possible environmental exposure to silica or hydrocarbons. Scleroderma rarely occurs in families. No strong genetic or environmental influences were found to account for the relatively common occurrence of scleroderma in SA. The age at onset versus age-specific incidence curve suggests that scleroderma can be considered as a stochastic illness involving a number of random events occurring in a predisposed population. These random events may involve mutations of pivotal somatic genes.
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
DOI: 10.1038/S41377-020-00357-W
Abstract: Based on a developed theory, we show that introducing a meta-grid of sub-wavelength-sized plasmonic nanoparticles (NPs) into existing semiconductor light-emitting-devices (LEDs) can lead to enhanced transmission of light across the LED-chip/encapsulant interface. This results from destructive interference between light reflected from the chip/encapsulant interface and light reflected by the NP meta-grid, which conspicuously increase the efficiency of light extraction from LEDs. The “meta-grid”, should be inserted on top of a conventional LED chip within its usual encapsulating packaging. As described by the theory, the nanoparticle composition, size, interparticle spacing, and distance from the LED-chip surface can be tailored to facilitate maximal transmission of light emitted from the chip into its encapsulating layer by reducing the Fresnel loss. The analysis shows that transmission across a typical LED-chip/encapsulant interface at the peak emission wavelength can be boosted up to ~99%, which is otherwise mere ~84% at normal incidence. The scheme could provide improved transmission within the photon escape cone over the entire emission spectrum of an LED. This would benefit energy saving, in addition to increasing the lifetime of LEDs by reducing heating. Potentially, the scheme will be easy to implement and adopt into existing semiconductor-device technologies, and it can be used separately or in conjunction with other methods for mitigating the critical angle loss in LEDs.
Publisher: Elsevier BV
Date: 10-1984
Publisher: Wiley
Date: 25-11-2015
DOI: 10.1002/ART.39316
Abstract: To determine the relationships between systemic sclerosis (SSc)-related autoantibodies, as well as their clinical associations, in a well-characterized Australian patient cohort. Serum from 505 Australian SSc patients were analyzed with a commercial line immunoassay (EuroLine Euroimmun) for autoantibodies to centromere proteins CENP-A and CENP-B, RNA polymerase III (RNAP III epitopes 11 and 155), the 90-kd nucleolar protein NOR-90, fibrillarin, Th/To, PM/Scl-75, PM/Scl-100, Ku, topoisomerase I (topo I), tripartite motif-containing protein 21/Ro 52, and platelet-derived growth factor receptor. Patient subgroups were identified by hierarchical clustering of the first 2 dimensions of a principal components analysis of quantitative autoantibody scores. Results were compared with detailed clinical data. A total of 449 of the 505 patients were positive for at least 1 autoantibody by immunoblotting. Heatmap visualization of autoantibody scores, along with principal components analysis clustering, demonstrated strong, mutually exclusive relationships between CENP, RNAP III, and topo I. Five patient clusters were identified: CENP, RNAP III strong, RNAP III weak, topo I, and other. Clinical features associated with CENP, RNAP III, and topo I were consistent with previously published reports concerning limited cutaneous and diffuse cutaneous SSc. A novel finding was the statistical separation of RNAP III into 2 clusters. Patients in the RNAP III strong cluster had an increased risk of gastric antral vascular ectasia, but a lower risk of esophageal dysmotility. Patients in the other cluster were more likely to be male and to have a history of smoking and a history of malignancy, but were less likely to have telangiectasia, Raynaud's phenomenon, and joint contractures. Five major autoantibody clusters with specific clinical and serologic associations were identified in Australian SSc patients. Subclassification and disease stratification using autoantibodies may have clinical utility, particularly in early disease.
Publisher: BMJ
Date: 02-1988
DOI: 10.1136/ARD.47.2.105
Abstract: Low molecular weight (LMW) IgM is the monomeric subunit of pentameric IgM. It was not found in the sera of 20 healthy subjects but was detected in all six patients with mixed cryoglobulinaemia with a mean value of 1.4 g/l, representing 34% of the total IgM. In three of four patients studied LMW IgM was monoclonal and of the same light chain type (kappa) as the pentameric monoclonal IgM rheumatoid factor (RF) observed in the cryoprecipitate. LMW IgM was proportionately under-represented, however, in the cryoprecipitate compared with the corresponding serum, possibly because of the lower valency of the LMW molecule. Immunoblot analysis of sera showed the presence of other oligomers of IgM in addition to monomeric IgM, suggesting that a disorder of IgM assembly was responsible for its occurrence, and this was supported by the secretion of large proportions of LMW IgM in vitro by peripheral blood mononuclear cells (PBMC) from one patient with this disorder but not from healthy controls. In conclusion, the occurrence of large quantities of monoclonal LMW IgM in mixed cryoglobulinaemia was observed, and it is suggested that this is unlikely to have a direct pathogenic significance. It is postulated that its presence reflects a disturbance of assembly of the monomeric IgM subunits that occurs during the polymerization of the pentameric molecule.
Publisher: Oxford University Press (OUP)
Date: 2003
DOI: 10.1093/RHEUMATOLOGY/KEG047
Abstract: To demonstrate the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in synovial tissue from rheumatoid arthritis (RA) patients, establish the cell lineage expressing OPG and compare the expression of OPG in RA, spondyloarthropathies, osteoarthritis and normal synovial tissue. Synovial biopsy specimens were obtained at arthroscopy from 16 RA and 12 spondyloarthropathy patients with active synovitis of a knee joint, six RA patients with no evidence of active synovitis, 10 patients with osteoarthritis and 18 normal subjects. Immunohistological analysis was performed using monoclonal antibodies (mAb) to detect OPG and RANKL expression. In addition, dual immunohistochemical evaluation was performed with lineage-specific monoclonal antibodies (macrophages, fibroblasts and endothelial cells) and OPG to determine the cell lineages expressing OPG. The sections were evaluated by computer-assisted image analysis and semiquantitative analysis. Two patterns of OPG expression were seen, one exclusively in endothelial cells and one expressed predominantly in macrophages in the synovial lining layer. Both patterns of OPG staining could be blocked with excess recombinant OPG. Endothelial and synovial lining expression of OPG was seen in all synovial tissues except those from patients with active RA. In contrast, RANKL expression was seen predominantly in synovial tissue from patients with active disease, mainly in sublining regions, particularly within areas of lymphocyte infiltration. OPG expression on macrophage type synovial lining cells as well as endothelial cells is deficient in RA patients with active synovitis, in contrast to that seen in spondyloarthropathy patients with active synovitis. This deficiency in OPG expression in the inflamed joint of RA patients may be important in the development of radiologically defined joint erosions.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2007
DOI: 10.1007/S10067-007-0762-3
Abstract: We present a case of antisynthetase syndrome manifesting with interstitial lung disease, mechanic's hands, nailfold abnormalities, and subclinical myositis, in the presence of antibodies to the aminoacyl tRNA synthetase PL-12 and also to Ro52. Antibodies to Ro52 have been recently associated with idiopathic inflammatory myositis, but there have only been occasional reports of this antibody occurring in association with aminoacyl tRNA synthetases, including PL-12. Our case adds to the descriptions of the concurrence of antibodies to PL-12 and Ro52. The mechanism for the coupling of antibody response remains elusive but is likely to play a fundamental role in disease pathogenesis.
Publisher: Wiley
Date: 30-11-2011
Publisher: Wiley
Date: 02-1996
Abstract: To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP). Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium-99 hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled from indium-111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time. Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on the modified Health Assessment Questionnaire (P<0.05), tender joints (P<0.005), VAS for pain (p<0.005), and generalized stiffness (P<0.005), as well as a decrease in the C-reactive protein level (P<0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis. Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.
Publisher: Wiley
Date: 24-06-2008
DOI: 10.1002/ART.23818
Abstract: To demonstrate the effect of treatment with disease-modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet. Synovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration <12 months) before and at 3-6-month intervals after starting treatment with a disease-modifying agent. Immunohistologic analysis was performed using monoclonal antibodies to detect OPG and RANKL expression, with staining quantitated using computer-assisted image analysis and semiquantitative analysis techniques. Serial radiographs of the hands and feet were analyzed independently by 2 radiologists and a rheumatologist using the van der Heide modification of the Sharp scoring method. Thirteen patients achieved a low disease state as defined by a disease activity score 20% after disease-modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet. Successful treatment-induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.
Publisher: Wiley
Date: 12-1995
DOI: 10.1111/J.1445-5994.1995.TB02854.X
Abstract: Scleroderma is a systemic rheumatic disorder seen in a wide range of clinical specialties. To establish the prevalence and mortality rates of scleroderma in South Australia (SA), to determine the relative frequency and characteristics of the three principal subsets (diffuse, limited and overlap), and to examine the role of nailfold capillaroscopy in subset identification and implied prognosis. Outpatient and discharge diagnostic indexes from five major teaching hospitals in SA were reviewed between February 1987 and November 1993. A total of 215 patients with scleroderma were identified. Case notes of 115 of these patients were reviewed in order to validate scleroderma diagnosis, and subset characteristics such as sex, mean age at diagnosis, extent of skin involvement, internal organ involvement and serology were analysed. Fifty-two of these patients were then examined prospectively to confirm positive discharge diagnosis, and nailfold capillaroscopy was performed on these patients. The point prevalence of scleroderma in SA for 1993 was estimated to be 208/10 This figure is a conservative estimate and is higher than most other reported series. The female to male ratio was 4:1. The majority of patients had limited disease with a ratio of 6:1:1.6 limited vs diffuse vs overlap. Systemic involvement excluding the oesophageal components limited disease was found predominantly in the diffuse group. Autoimmune serology was positive in 90% of patients, with Scl-70 being more common in diffuse scleroderma, anti-centromere antibody (ACA) in the limited form and anti-ribonucleoprotein (RNP) in the overlap form. Nailfold capillaroscopy was useful in predicting disease-subtype as capillary dilatation was observed predominantly in limited disease, capillary dropout in diffuse disease. Scleroderma is more common in SA than previously recognised. Limited disease is more common than diffuse or overlap disease, carries a better prognosis and in associated with ACA. Nailfold capillaroscopy is a useful tool in disease assessment and may provide useful diagnostic and prognostic information.
Publisher: Wiley
Date: 13-10-2011
Publisher: Elsevier BV
Date: 1998
DOI: 10.1080/00313029800169676
Abstract: The demographic, clinical, pathological and serological features of 123 decreased patients with systemic sclerosis have been analysed. These patients consisted of all identified patients dying with this disease in South Australia between 1983 and 1996 inclusive. There were 85 females and 38 males, with the ratio of limited:diffuse:overlap disease subset being 9:5:1. Disease characteristics revealed that patients with the limited disease tended to be female with high frequencies of the centromere autoantibody, while patients with the diffuse disease had equal gender representation with the frequent presence of nucleolar, speckled or homogeneous antinuclear antibody. Mean duration of disease and mean age of death for the limited:diffuse:overlap subsets differed significantly between groups (p < 0.05) and were 16.5, 9.3 and 10.9 years and 71.9, 57.8 and 52.8 years respectively. Cumulative survival curves for the subsets differed highly significantly, with patients with the limited diseases dying more commonly from right heart failure (documented terminally in 25% of the centromere positive limited subset), cardiovascular disease or cancer, while patients with the diffuse subset died from respiratory failure, renal failure or cardiovascular disease. In conclusion, this retrospective analysis has revealed that scleroderma is a relatively common but clinically heterogeneous disorder. There are important clinical and prognostic implications in defining limited versus diffuse versus overlap disease.
Publisher: BMJ
Date: 08-2003
DOI: 10.1136/ARD.62.8.728
Abstract: Previous studies have suggested an increased risk of cancer among patients with scleroderma. To study a population based cohort of patients with scleroderma in South Australia. Subjects with scleroderma were identified from the South Australian Scleroderma Registry established in 1993. All subjects on the scleroderma registry were linked to the South Australian Cancer Registry to identify all cases of cancer until 31 December 2000. Standardised incidence ratios (SIRs) for cancer for subjects with scleroderma were determined using the age- and sex-specific rates for South Australia. In 441 patients with scleroderma, 90 cases of cancer were identified, 47 of which developed after inclusion on the scleroderma registry. The SIRs for all cancers among these patients were significantly increased (SIR=1.99 95% confidence interval (95% CI) 1.46 to 2.65) compared with the cancer incidence rates for South Australia. The SIRs for lung cancer (SIR=5.9 95% CI 3.05 to 10.31) were also significantly increased. The SIRs for all cancers among the subgroups with diffuse scleroderma (SIR=2.73 95% CI 1.31 to 5.02) and limited scleroderma (SIR=1.85 95% CI 1.23 to 2.68) were significantly increased. This population based cohort study provides evidence that scleroderma is associated with cancer, and in particular, lung cancer. In addition, both diffuse and limited forms of scleroderma are associated with a similarly increased risk of cancer.
Publisher: Oxford University Press (OUP)
Date: 27-04-2009
Publisher: Elsevier BV
Date: 10-1974
DOI: 10.1016/S0140-6736(74)91154-4
Abstract: Domain-specific physical activities may have different correlates and health effects, but few large studies have examined these questions, especially their separate associations with adiposity. We analysed cross-sectional data of 466 605 adults without any prior chronic diseases, enrolled during 2004-8, from 10 erse localities across China. Physical activity level in each of 4 domains (occupation, commuting, household, and active-recreation), calculated as metabolic equivalent (MET)-hr/day, was related to social-demographic factors and measures of adiposity (body mass index [BMI], waist circumference [WC], and bio-impedance derived percentage body fat), using multivariable linear and logistic regression models. The overall mean age was 50.8 years. The mean total physical activity was 21.7 MET-hr/day, mainly from occupation (62%) and household chores (26%), but little from active-recreation (4%), with women having a much higher household activity than men. Older participants had a lower level of occupational activity but a higher level of household and active-recreational activity, particularly after retirement. There was no linear association of occupational activity with adiposity, but working women tended to have a lower adiposity (e.g. 1.0 cm WC) than non-working women. In men, there was an inverse and apparently linear association between adiposity and levels of both commuting-related and household activities, with 3 MET-hr/day associated with -0.11 and -0.13 kg/m(2) BMI, -0.42 and -0.62 cm WC, and -0.28 and -0.33 percentage points of body fat, respectively. In women, only household activity showed a linear, but weaker, association with adiposity. A higher adiposity was observed among men and women with higher levels of active-recreational activity. In Chinese adults, physical activity mainly involves occupation and housework, with little from active-recreational activity. Domain-specific physical activities varied by socio-demographic factors and had different associations with adiposity.
Publisher: Elsevier BV
Date: 08-1987
DOI: 10.1016/0165-0378(87)90067-2
Abstract: Thirty cord blood sera from healthy neonates and five sera from still-born infants (two with suspected infections and high IgM) were assessed for the presence of low molecular weight (LMW) IgM using two independent sensitive techniques, viz. filtration chromatography and immunoblotting. The first technique revealed this LMW moiety in 4 of 22 sera, all from healthy full-term infants, and it constituted 4-25% of the total IgM. LMW IgM was not found in any of the 30 sera using the immunoblotting technique or in 15 healthy adult sera, but was found consistently in rheumatoid sera used as positive controls.
Publisher: Wiley
Date: 11-11-2005
Publisher: Wiley
Date: 05-2018
DOI: 10.1111/IMJ.13745
Abstract: Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log-rank χ Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality.
Publisher: Informa UK Limited
Date: 1991
Publisher: Wiley
Date: 12-01-2012
DOI: 10.1002/MUS.22279
Abstract: Necrotizing myopathy (NM) is distinguished from idiopathic inflammatory myositis (IIM) by dominance of myofiber necrosis, lack of mononuclear inflammatory infiltrates, and presence of antibodies to signal recognition particle (SRP). The clinical features of 64 cases of NM were determined. Measurement of autoantibodies was undertaken on stored sera from 23 patients with NM. The incidence of malignancy was determined from the South Australian Cancer Registry. NM patients showed male predominance (61%), more frequent myalgias, and higher creatine kinase (CK) levels compared with IIM patients. Patients with NM had a high incidence of systemic lupus erythematosus (SLE) (21%), hypertension (11 of 17, 65%), and diabetes mellitus (3 of 13, 23%). No patient had antibodies to SRP. NM patients showed no altered risk for malignancy compared with the South Australian population (P = 0.86). NM is associated with SLE, hypertension, and diabetes mellitus. Comprehensive assessment of cardiovascular risk is indicated in NM, which raises the possibility of targeted interventions.
Publisher: Springer Science and Business Media LLC
Date: 1982
DOI: 10.1007/BF00541265
Publisher: Wiley
Date: 05-2011
DOI: 10.1111/J.1445-5994.2010.02281.X
Abstract: To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR). The SASR is a population-based register, which was commenced in 1993 and has actively sought to recruit all scleroderma patients diagnosed in SA over a 15-year period. Clinical and serological details have been accessed from questionnaires or from clinical and laboratory files. Standardized mortality ratio (SMR) was calculated and survival analyses performed on all living and deceased patients listed on this SASR (n = 786). Patients with scleroderma had increased mortality compared with the general SA population (SMR 1.46 (95% confidence interval (CI) 1.28-1.69)). Factors that adversely altered survival included older age at onset, male gender, diffuse skin involvement, presence of scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer and anti-topoisomerase (Scl-70) and anti-U1 RNP antibodies, while a trend was observed with increased nailfold capillary dropout. Mean age of death for patients with limited scleroderma was 74.1 years (95% CI 72.5-75.7), diffuse scleroderma 62.9 years (95% CI 59.4-66.4) and overlap disease 57.8 years (95% CI 48.7-66.9). Survival improved over the 15-year study period. Scleroderma substantially reduces life expectancy. Survival is influenced by age at onset, gender, diffuse involvement of skin fibrosis, visceral involvement, development of cancer, extent of microvascular capillary damage and by the presence of scleroderma-associated antibodies, Scl-70 and RNP. Scleroderma renal crisis continues to carry high mortality. Survival improved over the 15-year study period.
Publisher: BMJ
Date: 19-09-2006
Publisher: Oxford University Press (OUP)
Date: 1975
Abstract: A patient is described who had myeloma of the polymeric IgA variety, together with a striking hyperlipidaemia and xanthomatosis. Investigations into the protein and lipid abnormality failed to demonstrate any mechanism for the hyperlipidaemia. A review of the literature, however, validates this clinical entity and some of the suggested explanations are discussed.
Publisher: Wiley
Date: 09-1986
Abstract: The development of high-performance transparent conducting oxides is critical to many technologies from transparent electronics to solar cells. Whereas n-type transparent conducting oxides are present in many devices, their p-type counterparts are not largely commercialized, as they exhibit much lower carrier mobilities due to the large hole effective masses of most oxides. Here we conduct a high-throughput computational search on thousands of binary and ternary oxides and identify several highly promising compounds displaying exceptionally low hole effective masses (up to an order of magnitude lower than state-of-the-art p-type transparent conducting oxides), as well as wide band gaps. In addition to the discovery of specific compounds, the chemical rationalization of our findings opens new directions, beyond current Cu-based chemistries, for the design and development of future p-type transparent conducting oxides.
Publisher: Oxford University Press (OUP)
Date: 06-2008
DOI: 10.1111/J.1365-2133.2008.08541.X
Abstract: Crusted scabies is a rare and severely debilitating disease characterized by infestation of the skin with up to millions of Sarcoptes scabiei mites, high total IgG levels, extremely high total IgE levels, and the development of hyperkeratotic skin crusts that may be loose, scaly and flaky or thick and adherent. To describe crusted scabies skin pathogenesis and identify markers associated with an inappropriate immune response leading to disease progression. Serial sections from skin biopsies obtained from two patients with severe crusted scabies were examined by immunohistochemistry for cell surface markers and inflammatory and regulatory cytokines. Concurrent levels of total B- and T-cell subsets and IgE, IgA, IgM, IgG and IgG subclasses were analysed in the blood. In addition antibody levels were recorded in a further 33 patients with crusted scabies and 14 patients with ordinary scabies. A predomination of infiltrating CD8+ T lymphocytes in the dermis was observed compared with minimal helper T lymphocytes (CD4+) and the absence of any B cells. The proportion of T and B lymphocytes and T-cell subsets in the blood of these patients were within normal ranges, indicating a selective movement of CD8+ T cells into the dermis. Furthermore, strong staining for the inflammatory cytokine interleukin-1 beta and anti-inflammatory cytokine transforming growth factor-beta1 was observed. Elevated levels of IgE, IgG, IgG1, IgG3 and IgG4 were recorded. Skin-homing cytotoxic T cells contribute to an imbalanced inflammatory response in the dermis of crusted scabies lesional skin. This, in combination with the lack of B cells, is contributing to the failure of the skin immune system to mount an effective response resulting in uncontrolled growth of the parasite.
Publisher: Wiley
Date: 12-1986
DOI: 10.1111/J.1445-5994.1986.TB00032A.X
Abstract: In a retrospective study of 39 patients with infective endocarditis (IE) all had elevated concentrations of C reactive protein (CRP) at presentation, patients with the acute variety having significantly higher values than patients with the subacute variety. In addition, the majority of patients with subacute bacterial endocarditis had elevated concentrations of circulating immune complexes (CICs) and rheumatoid factor (RF), both of which were absent in all but one of nine patients with acute bacterial endocarditis. Two patients with subacute and one with acute bacterial endocarditis had low values of C3 and C4. Measurement of CRP, CICs, and RF did not distinguish between patients with and without extracardiac manifestations. Sequential analysis of patients revealed that a successful response to antimicrobial treatment was indicated by a striking and rapid decline in CRP, with less striking declines in CICs, RF, and IgM. Antibiotic failure was indicated by the persistence of high concentrations of CRP and CICs. We conclude that the measurement of C reactive protein is of some value in the diagnosis and management of infective endocarditis. A normal CRP concentration excludes this diagnosis. The measurement of CRP alone appears sufficient for monitoring most cases of infective endocarditis with the sequential measurement of rheumatoid factor and circulating immune complexes adding no useful information except where the CRP remains elevated despite treatment. In this latter instance, persisting high levels of CRP and circulating immune complexes together herald an ominous course.
Publisher: Wiley
Date: 09-2002
DOI: 10.1002/ART.10640
Publisher: Oxford University Press (OUP)
Date: 27-06-2003
Publisher: Wiley
Date: 07-07-2006
DOI: 10.1111/J.1445-5994.2006.01125.X
Abstract: The aim of this study was to determine the incidence, prevalence, survival and selective demographic characteristics of scleroderma occurring in South Australia over the 10-year period 1993-2002. Analysis of the database of the South Australian Scleroderma Register: a population-based register established in 1993. Patients with scleroderma resident in South Australia (n = 353 at 2002) were ascertained from multiple sources and clinical and demographic data were obtained from mailed questionnaire and from review of computerized hospital databases, case notes or referring letters. Time-space cluster analysis was carried out according to the Knox method. Control data were obtained from the Australian Bureau of Statistics census. The mean prevalence was 21.4 per 10(5) (95% confidence interval 20.2-22.6) and the mean cumulative incidence of 1.5 per 10(5) (95% confidence interval 1.32-1.73) with no significant change in incidence over the study period (P = 0.13). Cumulative survival improved over the study period, with patients with diffuse disease having significantly reduced survival (as compared with limited disease, P < 0.001). The proportion with diffuse disease ( approximately 22%) remained steady. There was a small but significant predisposition in patients with a continental European birthplace (P < 0.001). A family history of scleroderma was noted in 1.6% with lambda1 (familial risk) of 14.3 (95% confidence interval 5.9-34.5). However, a family history of systemic autoimmunity (especially rheumatoid arthritis) was more common (6%). No socioeconomic stratification, temporal clustering nor spatio-temporal clustering was observed either at time of initial symptom or at 10 years before disease onset. Scleroderma occurs relatively infrequently in South Australia with no significant change in incidence observed over the 10-year study period. However, cumulative survival has improved. Identified risk factors include family history of scleroderma (risk approximately 14-fold), female sex (risk approximately 5-fold) and European birthplace (risk approximately 2.5-fold) however, the majority of the disease variance appears unexplained. A stochastic explanation based on genetic instability is favoured to explain this paradox.
Publisher: Elsevier BV
Date: 04-1984
DOI: 10.1016/0022-1759(84)90325-9
Abstract: The central regulatory system that generates biological rhythms is regulated by circadian clock genes expressed by cells in the suprachiasmatic nucleus. Signals from this system are converted to adrenocortical hormones through the sympathetic nervous system and transmitted to peripheral organs. Another system releases glucocorticoids (GCs) in response to stress through the HPA-axis. Here we investigated the second messenger GC, which is shared by these systems and influences the expression of circadian clock genes of cells of the musculoskeletal system and in viable bone tissue. We used mouse-derived cell lines, which differentiate into osteoblasts (MC3T3-E1, C2C12, and 10T1/2) as well as primary cultures of mouse osteoblasts to determine the expression levels of circadian clock genes that respond to GC. Mice (mPer2 The expression of major circadian clock genes was detected in each cell line, and their responsiveness to GC was confirmed. We focused on Our investigations of the mechanisms that regulate circadian rhythm function in tissues of the musculoskeletal system that respond to the stress hormone GC, reveal that
Publisher: Oxford University Press (OUP)
Date: 20-01-2010
DOI: 10.1093/RHEUMATOLOGY/KEP409
Abstract: Results of previous studies investigating the association between GCA and malignancy are conflicting. We performed a study of the risk of cancer in patients with biopsy-proven GCA. Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies from the major pathology laboratories in South Australia (SA). All subjects with biopsy-proven GCA were linked to the SA Cancer Registry to identify cases of cancer until 31 December 2006. Standardized incidence ratios (SIRs) for cancer were determined using the age- and gender-specific rates for SA. There were 226 cases of biopsy-proven GCA (163 females and 63 males). Thirty-one cases were diagnosed with cancer, following the diagnosis of biopsy-proven GCA. There was no increased risk of cancer among those with biopsy-proven GCA, following the diagnosis of GCA compared with the general population (SIR 1.2 95% CI 0.8, 1.6). This cohort study did not demonstrate any increased risk for malignancy in subjects with biopsy-proven GCA.
Publisher: Portico
Date: 1999
DOI: 10.1358/DOT.1999.35.2.527968
Abstract: This paper reviews the cytokine profiles and various cell adhesion molecules expressed in the more common inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis, the spondyloarthropathies (Reiter's syndrome, ankylosing spondylitis), as well as systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, giant cell arteritis and polymyositis. Knowledge of the broad range of cytokines produced in these conditions and the expression of cell adhesion molecules that result from cytokine production will assist in the understanding of the pathogenesis of these conditions and may lead to new therapeutic interventions.
Publisher: BMJ
Date: 10-1980
DOI: 10.1136/ARD.39.5.438
Abstract: The C1q binding assay and the nephelometric monoclonal rheumatoid factor assay were able to discriminate 79% and 57% respectively of rheumatoid arthritis (RA) patients from healthy blood donors. In addition these assays could distinguish those patients with active arthritis from those with inactive disease, and the C1q binding assay correlated significantly with other laboratory indices of the rheumatoid process, including the erythrocyte sedimentation rate, low molecular weight or 7S IgM, and the rheumatoid factor titre. High levels of C1q binding were also seen in rheumatoid vasculitis. Both assays gave higher mean values in synovial fluid compared with the corresponding serum, but it appeared from ultracentrifugal analysis and from a lack of a consistent correlation between these assays that each assay was measuring different forms of immunecomplex-like material which may be involved in the immunopathogenesis of this disease. The C1q binding assay is of some value in the laboratory assessment of rheumatoid arthritis and appears to offer greater advantages than the monoclonal rheumatoid factor assay, although the usefulness of this latter assay may be very dependent on the monoclonal rheumatoid factor used.
Publisher: BMJ
Date: 08-1980
DOI: 10.1136/ARD.39.4.349
Abstract: Laser nephelometric estimation of IgM in the eluate fractions following Sepharose 6B chromatography has enabled the calculation of the proportion of low molecular weight IgM (7S IgM) in normal and pathological sera. This figure has then been used to determine the absolute amount of 7S IgM. Twenty-seven of 36 (75%) patients with rheumatoid arthritis had 7S IgM with a mean value of 17 mg/100 ml (170 mg/l) (range 2.5-59 mg/100 ml). No sera from 10 healthy controls were found to contain 7S IgM. Patients with active rheumatoid arthritis had significantly more 7S IgM than those with inactive disease, but there was no significant difference between those patients with and without rheumatoid vasculitis. Significant correlations occurred between 7S IgM and the absolute IgM level (P < 0.01), the Rose-Waaler titre (P < 0.01), and the erythrocyte sedimentation rate (P = 0.01). However, there was no significant correlation with the age of the patient, the duration of the disease, or the level of circulating immune complexes as measured by the Clq binding assay. It is concluded that 7S IgM commonly occurs in rheumatoid arthritis, and it is postulated that a common immunological stimulus is responsible for the production of 7S IgM and rheumatoid factors, serological abnormalities that characterise this disease.
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1080/00313020500058268
Abstract: To develop a technique for homogeneity testing of serum aliquot s les suitable for use in the Quality Assurance Program in Clinical Immunology (QAP Pty Ltd). Albumin was selected as the surrogate protein marker for the product to be tested and the coefficient of dispersion (COD) calculated as the measure of homogeneity. To detect changes in the average level of homogeneity, cumulative sum control (cusum) charts were used. The COD(%) for each triplicate reading of albumin obtained from 34 specimens was normally distributed with a mean of 0.49% and a standard deviation of 0.25%. In industrial quality control schemes the action line is generally set at the upper 99% confidence limits, hence any triplicate s le would be considered to have acceptable homogeneity if the COD was < or = 1.08%. Cusum charts were created to monitor albumin homogeneity over time. The use of albumin measurement as the surrogate appears statistically suitable for homogeneity testing in QAP programs for immunodiagnostic testing. CUSUM charts are particularly useful to monitor such homogeneity testing.
Publisher: BMJ
Date: 11-1987
Abstract: The discovery and de-discovery of the xenotropic murine leukemia virus-related virus (XMRV) has been a tumultuous roller-coaster ride for scientists and patients. The initial associations of XMRV with chronic fatigue syndrome and prostate cancer, while providing much hope and optimism, have now been discredited and/or retracted following overwhelming evidence that (1) numerous patient cohorts from around the world are XMRV-negative, (2) the initial reports of XMRV-positive patients were due to contamination with mouse DNA, XMRV plasmid DNA, or virus from the 22Rv1 cell line and (3) XMRV is a laboratory-derived virus generated in the mid 1990s through recombination during passage of a prostate tumor xenograft in immuno-compromised mice. While these developments are disappointing to scientists and patients, they provide a valuable road map of potential pitfalls to the would-be microbe hunters.
Publisher: BMJ
Date: 08-1986
DOI: 10.1136/ARD.45.8.673
Abstract: The effect of coating monosodium urate crystals (MSU) with low density lipoprotein (LDL), postulated previously as a major regulator of gouty inflammation, was studied in a neutrophil chemiluminescence (CL) assay and an air pouch model of inflammation induced by MSU. LDL crystalline coating abrogated the neutrophil CL response but, in contrast, had no inhibitory effect on leucocyte accumulation, levels of the prostaglandin (PG) metabolite 6-keto-PGF1 alpha, and exudation of plasma proteins in the in vivo model. This latter observation raises doubts about the postulated physiological role of LDL in terminating the acute gouty attack.
Publisher: Wiley
Date: 03-1998
DOI: 10.1002/1529-0131(199803)41:3<564::AID-ART27>3.0.CO;2-C
Abstract: It is common to find that some of the lactose in dairy powders and pharmaceutical tablets is present in the unstable amorphous state. Therefore, their crystallization thermodynamics in different solvents are particularly important. In this paper, the solubility of α-lactose monohydrate (α-LM) in 15 mono-solvents such as ethanol, isopropanol, methanol, 1-propanol, 1-butanol, 2-butanol, isobutanol, 1-pentanol, isoamylol, 1-hexanol, 1-heptanol, 1-octanol, propanoic acid, acetonitrile, and cyclohexanone was evaluated by using the gravimetric method in the temperature ranges from 274.05 K to 323.05 K at constant pressure (1 atm). In the given temperature range, the solubility of α-LM in these solvents increased with the rising of temperature, the highest solubility of α-LM was found in methanol (2.37 × 10
Publisher: BMJ
Date: 04-1995
DOI: 10.1136/ARD.54.4.245
Abstract: To determine if there are specific patterns of illness behaviour in patients with arthritis, and if abnormal patterns of illness behaviour are associated with withdrawal from trials of anti-inflammatory drugs, and to examine which aspects of illness behaviour are perceived by rheumatologist to be related to the disease process. The illness behaviour questionnaire (IBQ) was administered to 211 patients with rheumatoid arthritis (RA) and 107 patients with osteoarthritis (OA) participating in five drug trials of NSAIDs at the beginning of the studies, and was commented upon by 17 clinical rheumatologists. Factor analysis of 211 patients with RA produced a unique factor solution. RA patients were more preoccupied with their illness and its effects and worried more about their health than patients with OA. Patients who withdrew from drug trials showed behaviour patterns similar to those of chronic pain patients, and different from those of patients who completed the studies. When asked to account for a rheumatoid patient's response to the IBQ, rheumatologists focused on physical symptoms and did not recognise some of the psychological issues which patients saw as being relevant. We have demonstrated differences in illness behaviour between patients with OA and with RA. Patients withdrawing from drug trials of NSAIDs showed differences in illness behaviour compared with those successfully completing the trials. Rheumatologists underestimated the impact of the disease on their RA patients' psychological well being.
Publisher: Wiley
Date: 15-05-2007
Publisher: AMPCo
Date: 06-1985
Publisher: Wiley
Date: 09-2011
DOI: 10.1111/J.1445-5994.2010.02164.X
Abstract: To determine the clinical, serological and prognostic features of patients with autoantibodies against three aminoacyl-transfer RNA synthetases (ARS), namely Jo-1 (histidyl-tRNA synthetase), PL-7 (threonyl-tRNA synthetase) and PL-12 (alanyl-tRNA synthetase) in South Australia. Patients with autoantibodies against ARS detected by line immunoassay (anti-Jo1, anti-PL7, anti-PL12) or enzyme-linked immunosorbent assay (anti-Jo1) were identified from existing laboratory databases for the period 1994-2009. Demographic, clinical and serological data were obtained by retrospective review of patients' medical records and laboratory databases. Forty-two patients with autoantibodies were identified (anti-Jo1 = 37, anti-PL7 = 4, anti-PL12 = 1). Females were more commonly affected than males (M : F = 12:30). Twenty-one patients had polymyositis (anti-Jo1 = 17, anti-PL7 = 4), seven dermatomyositis (anti-Jo1 = 6, anti-PL12 = 1), 10 overlap syndrome (anti-Jo1 = 10 lupus = 4, scleroderma = 3, Sjögren's syndrome = 2 and rheumatoid arthritis = 2) and four had interstitial lung disease (ILD) only (anti-Jo1 = 4). ILD was present in 69%, polyarthritis in 59% and positive anti-nuclear antibody (ANA) in 43% of patients. Concurrence of autoantibodies against Ro-52 with Jo-1 was seen in 12 patients. The mean follow-up period was 8.3 years (95% CI 5.8-10.8) with 12 deaths. Poor prognostic indicators were age of onset >60 years (P= 0.001), cancer (P= 0.002), negative ANA (P= 0.006) and negative autoantibodies to extractable nuclear antigens (P= 0.02). Patients with autoantibodies against ARS present with varied clinical features and occasionally with isolated lung involvement (amyopathic ILD). Older age of onset, malignancy and negative immunologic tests are predictors of poor prognosis. Concurrence of autoantibodies against Jo-1 and Ro-52 may reflect a coupling effect during generation of autoimmunity.
Publisher: Wiley
Date: 05-2010
Publisher: Oxford University Press (OUP)
Date: 04-2001
Publisher: The Journal of Rheumatology
Date: 15-08-2011
Abstract: To compare mortality rates and cause of death in patients with biopsy-proven giant cell arteritis (GCA) with those in the general population. Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies in South Australia, from January 1, 1992, to December 31, 2006. All patients with biopsy-proven GCA were linked to the South Australian Births, Death and Marriage Registry to identify deaths until December 31, 2006. Standardized mortality ratios and relative survival (ratio of observed survival in GCA group to expected survival of general South Australian population, matched by age, sex, and calendar time) were calculated. The cause of death recorded on the death certificate was also documented. There were 225 cases of biopsy-proven GCA (163 women and 62 men). The mean age at diagnosis of GCA was 78.2 years. The mean followup period was 66.2 months (SD 47.1 mo). During the followup period, there were 71 deaths in the GCA group (50 women, 21 men). The standardized mortality ratio was 0.99 (95% CI 0.77–1.25). The relative survival for different followup periods demonstrates that patients with GCA experienced similar mortality to the general population (age-matched and sex-matched). Death from cardiovascular causes (45%) was the most common, followed by infection (17%) and cancer (17%). Infection was a significantly more common cause of death in the first year (chi-squared, p = 0.0002). Our population-based cohort study did not demonstrate any increased mortality risk for patients diagnosed with biopsy-proven GCA. The risk of death from infection early in the disease may be increased.
Publisher: BMJ
Date: 08-1976
DOI: 10.1136/ARD.35.4.314
Abstract: Evidence has been presented suggesting that circulating immune complexes occur in over half of the sera of patients with rheumatoid arthritis. These IgG-containing complexes were small, eluting between IgG and IgM on gel filtration on Sepharose 6B and were not seen in the sera of healthy control subjects. These complexes were detected in the sera of both seronegative and seropositive patients and their quantity did not correlate with IgM rheumatoid factor titre. The quantity of complexed IgG was estimated from a ratio derived from the IgG profile obtained by gel filtration of the serum. This quantity correlated significantly with the degree of inhibition by the rheumatoid sera of cytolysis in vitro of IgG sensitized target cells by K cells from human peripheral blood. A significant inverse correlation was observed between the quantity of serum complexes and the chemotactic index of the circulating polymorphonuclear leucocytes obtained from the same rheumatoid patient. It is suggested that ingestion of these complexes may be implicated in the reduction in chemotaxis observed in patients with rheumatoid arthritis. There was no correlation between the quantity of the complexes in the sera and the clinica, haematological, and biochemical measurements.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2012
DOI: 10.1007/S00296-012-2489-Y
Abstract: The South Australian (SA) myositis database has registered all patients with biopsy-proven inflammatory myositis in SA from 1980 to 2009. We determined the incidence and associations of malignancy in myositis by linking this database with the SA cancer registry. Standardized incidence ratios (SIR) for malignancy were determined using the total SA population over the same time period, stratified by age and gender. The SIR for cancer in the myositis population (n = 373) was 1.39, p = 0.047. There was a trend towards an increased SIR in dermatomyositis but no increased risk of malignancy in polymyositis or inclusion body myositis. Malignancies of the lung and prostate were the commonest and 28 % of malignancies occurred within one year of IIM diagnosis. The odds of developing cancer were significantly raised in the presence of a shawl sign, male gender, and in patients with overlap syndrome or rheumatoid arthritis whilst myalgia was a significant protective factor. HLA-A28 allele was overrepresented in patients with malignancy (11 vs 2 %, p = 0.006). Patients in SA with myositis are at modestly increased risk for malignancy. We report clinical and genetic risk factors allowing the identification of patients at greatest risk for malignancy.
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/IMJ.13052
Publisher: BMJ
Date: 06-1994
DOI: 10.1136/ARD.53.6.383
Abstract: To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (RA) and to explore the possibility that LMW IgM is derived selectively from this subset of B cells. LMW IgM in sera and culture supernatants was detected by a sensitive immunoblot technique with an enhanced chemiluminescence detection system. CD5 B cells were determined by FACScan cytometry. In vitro studies were established in culture plates containing pokeweed mitogen with or without 2-mercaptoethanol (2-ME). Supernatants were obtained from CD5 positive hybridomas and CD5 negative hybridomas. Other immunological indices were measured by laser nephelometry. Circulating LMW IgM was detected in all rheumatoid patients with significantly higher levels being observed in sero-positive patients. LMW IgM correlated significantly with total IgM and RF. Peripheral blood mononuclear cells (PBMC) from the majority of the patients with RA secreted LMW IgM in vitro as did mononuclear cells from a synovial fluid s le. The addition of low concentrations of 2-ME to the culture medium enhanced the proportions of secreted monomeric IgM. In contrast, PBMC from healthy subjects secreted only trace quantities of LMW IgM. In RA no significant correlations were observed between CD5 B cells and LMW IgM and RF. LMW IgM could be detected in the supernatants from both CD5+ and CD5- B cell lines. Finally, CD5 B cells were not significantly elevated in RA and levels remained constant over time. LMW IgM exists in high concentrations in RA sera and synovial fluid. Serum level correlates with RF and IgM. In vitro studies have suggested that the occurrence of LMW IgM may be due to an intrinsic defect(s) in the assembly of the IgM pentameric molecule. LMW IgM is unlikely to be derived solely from CD5 B cells.
Publisher: Springer Science and Business Media LLC
Date: 06-1986
DOI: 10.1007/BF01965007
Abstract: An acute overdosage of 30 mg of pizotifen causing a pyrexial illness is reported. The clinical features suggest that the effects of overdosage are principally due to the anticholinergic activity of this drug. Resolution of symptoms occurred after 10 hours, without specific therapy.
Publisher: Elsevier BV
Date: 2002
DOI: 10.1080/003130202760120535
Abstract: To review the disease associations and laboratory features occurring in IgM paraproteinaemia. Systematic review of all new serum IgM paraproteins detected over a 6-year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses were ascertained from a computerised laboratory database or clinical notes, whilst associated laboratory features were obtained from the same sources. The 125 IgM paraproteins detected constitute 19.7% of all new paraproteins observed over the period of study. IgM paraproteinaemia occurred more commonly in males and its frequency increased with age. Approximately 30% were associated with B cell lymphoproliferative disorders (Waldenstrom's macroglobulinaemia, non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, amyloid, etc.) with the remainder being labelled as monoclonal IgM gammopathies of uncertain significance (four having a peripheral neuropathy). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of IgM, beta2-microglobulin, the presence of free urinary light chains and demonstrated molecular size heterogenicity of the paraprotein (presence of decamers, oligomers and monomers in addition to the pentamer) but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients. IgM paraproteinaemia was most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of paraprotein (>15 g/l) elevated levels of beta2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen, regular monitoring of paraprotein levels is considered mandatory in the management of these patients.
Publisher: The Journal of Rheumatology
Date: 29-12-2009
Publisher: Springer Science and Business Media LLC
Date: 21-11-2006
Publisher: No publisher found
Date: 2001
DOI: 10.1002/1529-0131(200102)44:2%3C343::AID-ANR52%3E3.0.CO;2-Q
Publisher: Springer Science and Business Media LLC
Date: 20-10-2006
DOI: 10.1007/S00296-005-0058-3
Abstract: To determine the "hand anatomic index" (HAI--a quantitative measure of hand deformity) in systemic sclerosis (scleroderma) and to compare it with the other measures of hand deformity and functional impairment. The HAI (measure of open hand span minus closed hand span/lateral height of hand) was determined in 30 patients with scleroderma and compared with hand deformity (as assessed by two independent rheumatologists) and with the Health Assessment Questionnaire (mHAQ), hand strength and prehensile gripability data. The HAI was confirmed as a reliable measure which clearly distinguished patients with increasing hand deformity and separated patients with diffuse scleroderma (n=12) from limited scleroderma (n=18), P=0.005. The HAI correlated significantly with measures of global functional impairment (as measured by the mHAQ) r=-0.46, P=0.01, hand strength r=0.51, P=0.0001 and prehensile gripability, r=-0.37, P=0.05 but neither with disease duration r=-0.16, P=NS nor age at disease onset r=0.20, P=NS. It was estimated that the HAI accounts for ~25% of the total global disability (as measured by HAQ). Measurement of the HAI in scleroderma provides a reliable and objective measure reflecting variable degrees of hand deformity and functional impairment and might provide a valid clinical outcome measure in patients with this disabling disorder.
No related grants have been discovered for peter roberts-thomson.