Epidemiology of biopsy-proven giant cell arteritis in South Australia.

BACKGROUND/AIM: To determine the epidemiology and clinical features of biopsy-proven giant cell arteritis (GCA) in South Australia (SA). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Survival in scleroderma: results from the population-based South Australian Register.

AIM: To ascertain the mortality risk and investigate clinical and serological factors influencing survival of patients listed on the South Australian Scleroderma Register (SASR). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Engaging medical students in occupational and environmental medicine--a new approach.

BACKGROUND: For a number of reasons, engaging the interest of medical students in the discipline of occupational and environmental medicine (OEM) can be challenging. AIMS: To renew a curriculum in OEM within a graduate medical programme with an emphasis on student involvement to maximize their interest in the topic. METHODS: A second year student cohort of a 4 year graduate medical programme was surveyed as to their preferences for the content of a short course of OEM embedded in their medical course. The course was extensively rewritten as a result of the student survey, with a number of topics deleted from the old course and new topics added. In order to validate the content of the new course, local occupational physicians (OPs) were also surveyed as to their opinion of an appropriate curriculum in OEM for medical students. The new course was taught to the subsequent cohort of second year medical students. The students' ratings of the course pre- and post-revision were compared. RESULTS: The student satisfaction rates of the course significantly improved as a result of the changes. The content of the student-led curriculum was strikingly similar to the course proposed by the local OP with a few key exceptions. CONCLUSIONS: Student involvement in curriculum design in OEM is entirely feasible. It can result in a curriculum similar to that designed by expert opinion but has the advantage of strongly engaging student interest.

The role of diet in the management of gout: a comparison of knowledge and attitudes to current evidence.

BACKGROUND: Evidence supports dietary modifications in the management of gout. Despite this, the degree of implementation of this evidence by nutrition professionals and rheumatologists and those affected by gout is unknown. The present study aimed to compare usual dietary practices of patients with gout to evidence for dietary management of gout and to investigate whether the knowledge and attitudes of nutrition professionals and rheumatologists reflects current evidence. METHODS: A food frequency questionnaire was used to determine usual dietary intake of patients with gout, a separate questionnaire examined gout-related dietary modifications (n = 29). Online questionnaires to examine attitudes towards dietary management of gout were completed by nutrition professionals and rheumatologists. RESULTS: Proportions of participants whose reported intakes were inconsistent with current evidence for the dietary management of gout were: alcohol, n = 14 (48%); beer, n = 18 (62%); seafood, n = 29 (100%); meat, n = 7 (24%); beef/pork/lamb, n = 24 (83%); dairy products, n = 12 (41%); vitamin C supplementation, n = 29 (100%). Of the 61 rheumatologists and 231 nutrition professionals who completed the online survey, the majority considered that weight loss and decreased alcohol intake were important or very important outcomes. Proportions were lower for decreased purine intake. Thirty-four (56%) rheumatologists do not refer patients with gout to dietetic services and, of those who do, the majority refer less than half. CONCLUSIONS: Overall, patients with gout in the present study were not implementing evidence for dietary management of their condition and complex dietary issues were evident.

Effect of intra-articular infliximab on synovial membrane pathology in a patient with a seronegative spondyloarthropathy.

OBJECTIVE: To demonstrate the efficacy of intra-articular infliximab in a patient with a persistent monarthritis who had previously had two arthroscopic synovectomies with limited success, and to determine the effect of intra-articular infliximab on synovial membrane pathology METHOD: Arthroscopic synovial biopsy specimens were collected before and after treatment with intra-articular infliximab. The synovial tissue was stained for a range of inflammatory cell subsets, cell adhesion molecules and cytokines using immunohistochemical techniques and quantified using digital image analysis and a semiquantitative scoring method. RESULTS: Clinical improvement in the knee synovitis was seen after the first two intra-articular infliximab treatments, with a sustained clinical remission lasting for more than 12 months after the third treatment. Significant changes in cellular infiltration and expression of cytokines and cell adhesion molecules occurred as a result of treatment with intra-articular infliximab, with a reduction in some but not all cells in the inflammatory infiltrate, as well as a reduction in the expression of cell adhesion molecules (intercellular adhesion molecule-1 and vascular adhesion molecule-1) and production of cytokines (interleukin 1beta and tumour necrosis factor alpha). CONCLUSION: Intra-articular infliximab administration is a viable treatment for a persistent monarthritis resistant to other treatment options and can successfully modulate the inflammatory milieu within the synovial membrane.

Influence of rheumatoid arthritis on work participation in Australia.

BACKGROUND: The aim of the study was to determine the prevalence of work disability in a cohort of Australians with rheumatoid arthritis. METHODS: A cross-sectional study of a sample of 497 individuals aged 18-65 years with rheumatoid arthritis in Adelaide, South Australia, was carried out. RESULTS: Of those employed, 130 (51%) were in full-time employment (> or= 35 h per week) work and 124 (49%) were in part-time employment (average 20 h per week). Overall, the observed/expected numbers working were 254/316 (relative risk 0.8 (0.69-0.91)). Using a comparator adjusted by removing those on the disability support pension, the relative risk of the working was 0.74. The observed/expected numbers working part time in the study group were 124/89 (relative risk 1.4 (1.25-1.65)). Those who continued to work had lower Health Assessment Questionnaire scores, less morning stiffness, superior scores for patient assessed level of function, lower pain scores, lower joint counts, a lower C-reactive protein, better measures of 'patient global assessment' and higher levels of education compared with the group who had ceased work. Overall, of those working at the time of diagnosis, 20% had ceased work within 5 years and approximately 40% had ceased work by 20 years. Of those who ceased work, the mean duration from time of diagnosis to work cessation was 7 years with half the subjects who ceased work doing so within 4 years of diagnosis. CONCLUSION: Work disability associated with rheumatoid arthritis in Australia is very significant and costly. Work disability occurs relatively early in the disease and is associated with several identifiable variables, many of which may be amenable to intervention strategies.

Wegener's granulomatosis: epidemiological and clinical features in a South Australian study.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The effect of rheumatoid arthritis on personal income in Australia.

BACKGROUND: The aim of this study was to estimate the effect of rheumatoid arthritis (RA) on the personal income of a cohort of individuals with RA in Australia. METHODS: A cross-sectional study of a sample of 497 working age people with RA in Adelaide, South Australia was carried out. RESULTS: The average personal income of an individual with RA in our cohort in 2003-2004 was $A22 400 compared with the Australian mean annual income of $A38 000. When standardized, the income of our cohort was 66% that of the average income of the Australian population. Overall one-third of the RA cohort relied principally on the social security system for their income and more than 75% of the cohort estimated they had lost greater than $A10 000 per annum in personal income as a result of their disease. Individuals with RA who were not working had annual incomes on average of more than $A20 000 less than those who continued to work. CONCLUSION: The personal income loss associated with RA in Australia is of enormous significance. It reduces a large population of individuals to relative financial poverty and potentially limits their access to a range of services including private health services.

Scleroderma in South Australia: further epidemiological observations supporting a stochastic explanation.

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.

The effect of lead on the metabolic and energetic status of the Yabby, Cherax destructor, during environmental hypoxia.

The concomitant effects of Pb and hypoxia on respiration and muscle energy status were examined in the freshwater crayfish Cherax destructor to determine if Pb intoxication exacerbated the effects of hypoxia. C. destructor, either intoxicated for 14 days with 0.5 mgL(-1)Pb, or from Pb-free control conditions, were subjected to progressive hypoxia at -2.7 kPah(-1) to a O2 partial pressure in the water (PwO2) of 1.33 kPa. This hypoxia was then sustained for 3 h. Pb-exposure reduced O2-uptake (MO2) at all PwO2 above 1.33 kPa but without any saving in ventilation, implying that Pb either unlinked ventilation from actual O2 requirements or rendered O2 transfer across the gill less efficient. Hypoxia alone induced no change in the adenylate energy charge (AEC), total adenylate (TAN), ATP/ADP ratio or in the equilibrium constant for adenylate kinase K'(ADEN), apparently due to protection of ATP levels by arginine phosphate. Under maximal hypoxia (PwO2=1.33 kPa) the Pb-exposed crayfish increased muscle ADP by 73% (tail) and 158% (chelae) but without any change in AMP, ATP or TAN. Thus, AEC declined (chelae AEC=0.71; tail AEC=0.85), as did the ATP/ADP ratio and K'(ADEN). L-Lactate increased in the muscle tissues of control but not Pb-exposed crayfish, consistent with a lowered O2 requirement in the Pb-exposed animals. The Pb intoxication slowed respiration and probably glycolysis, possibly altering the [ATP]:[ADP] equilibrium concentrations for adenylate kinase K'(AK). Lowered MO2 during severe hypoxia slows oxidative phosphorylation and ADP accumulation could occur as non-utilised substrate and may reflect a transient disequilibrium. During this time ATP levels were protected by arginine phosphate. AEC is sensitive to Pb in hypoxic crayfish but the changes have low importance for the energetic competence of the crayfish. During sustained hypoxia the crayfish recovered their energy status regardless of the Pb-exposure and this was, therefore, not a feature of Pb intoxication. Consequently, the ADP was recovered into the ATP pool of the hypoxic crayfish, and demand on arginine phosphate relieved. The Pb exposure did not otherwise exacerbate the effect of sustained hypoxia and C. destructor appeared to cope well with Pb intoxication, apparently by a specific Pb-induced hypometabolism separate from hypoxic response. Lowered metabolism as a survival response has limitations in the longer term and the implications for crustaceans generally warrant further study.

The Felty syndrome: a case-matched study of clinical manifestations and outcome, serologic features, and immunogenetic associations.

Thirty-two patients with the Felty syndrome, defined by the presence of rheumatoid arthritis, splenomegaly, and neutropenia, have been studied in comparison with 32 patients with rheumatoid arthritis matched for age, sex, and disease duration, and 9 patients with rheumatoid arthritis and idiopathic neutropenia. Patients with the Felty syndrome had severe destructive arthritis, which progressed during follow-up despite little evidence of objective synovitis, and a higher frequency of extra-articular manifestations, including vasculitis. Bacterial infection tended to occur in patients with the lowest neutrophil count but continued to occur in some despite normalization of the WBC. Prognosis was poor and 8 deaths occurred, predominantly from sepsis. Serologic features were prominent. High titers of IgG rheumatoid factor and circulating immune complexes characterized patients with persistent neutropenia. A family history of rheumatoid arthritis was more common in patients with the Felty syndrome. The association with HLA DR4 was very strong; in addition there was an increased frequency of the DQw3 variant, 3b, suggesting that HLA Class II genes in linkage with DR4 may contribute to disease expression.

T cell activation in the elderly: evidence for specific deficiencies in T cell/accessory cell interactions.

We studied T cell activation in the healthy aged (greater than 70 years) by examining lymphocyte proliferative responses to various mitogenic stimuli in accessory cell (AC)-dependent and AC-independent systems. Results show that despite a near normal response to the anti-CD3 monoclonal antibody (mAb) OKT3, peripheral blood mononuclear cells (PBM) from the elderly exhibit a profound reduction in phytohaemagglutinin (PHA)-responsiveness (approximately 30% of young adults). This deficit becomes even more severe at suboptimal doses of PHA. Adding exogenous interleukin-2 (IL-2) or pretreating the AC population with gamma interferon (IFN-gamma) returns the level of proliferation to that seen with young adults. Furthermore, replacing "old" AC with AC from young adults or with U937 (a monocytic cell line) in T cell/AC cell-mixing experiments restores PHA-responsiveness in 70% of cases. On the other hand, AC from the aged fully support PHA responses in T cells from young adults. In AC-depleted cultures, purified T cells from the aged respond normally to the co-mitogenic stimuli, PHA + PMA. Taken together, these results suggest that the age-associated diminution in PHA-responsiveness is due, at least in part, to specific deficiencies in T cell/AC communication.

Effects of ex vivo manipulation on the expression of cell adhesion molecules on neutrophils.

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.

Central nervous system toxoplasmosis in homosexual men.

Many opportunistic infections have been associated with an acquired immunodeficiency state in which cellular immune status has been altered. Two homosexual patients are described who presented with fever, peripheral eosinophilia, and a travel history to Haiti and were found to have central nervous system toxoplasmosis. Despite definitive diagnosis and appropriate therapy, both died. Techniques for diagnosis of central nervous system toxoplasmosis are discussed, and the importance of brain biopsy in this clinical situation is stressed. Eosinophilia may serve as an early diagnostic marker for disseminated toxoplasmosis in homosexual patients.

Cytomegaloviral infection presenting as a solitary pulmonary nodule.

Cytomegaloviral infection presenting in an immunologically compromised host as a solitary pulmonary nodule has not previously been reported. A patient with a renal transplant and with no pulmonary symptoms was noted to have a single nodule on a chest roentgenogram. At autopsy, this proved to be secondary to cytomegaloviral infection. Differential diagnostic considerations in the immunosuppressed patient are discussed.

Factors regulating osteoclast formation in human tissues adjacent to peri-implant bone loss: expression of receptor activator NFkappaB, RANK ligand and osteoprotegerin.

Aseptic bone loss adjacent to orthopedic joint implants is a common cause of joint implant failure in humans. This study investigates the expression of key regulators of osteoclast formation, receptor activator NFkappaB (RANK), Receptor activator of NFkappaB ligand (RANKL) and osteoprotegerin (OPG), in the peri-implant tissues of patients with osteolysis compared with levels in synovial tissues from osteoarthritic and healthy subjects. Immunohistochemical studies demonstrated that significantly higher levels of RANKL protein (p<0.05) were found in the peri-implant tissues of patients with implant failure than in similar tissues from osteoarthritic and healthy subjects. In contrast, OPG protein levels were similar in all tissues. RANKL, expressed as mRNA and protein, was predominantly associated with cells containing wear particles. Dual labeling studies showed that the cells expressing RANKL protein were macrophages. In situ hybridization studies confirmed that mRNA encoding for these proteins is also expressed by cells in the peri-implant tissues. In addition, RANK mRNA was expressed in cells that contained wear particles. These findings show that abnormally high levels of RANKL are expressed in peri-implant tissues of patients with prosthetic loosening and that these abnormal levels of RANKL may significantly contribute to aseptic implant loosening.

Comparative evaluation of CD5 B cells in patients with rheumatoid arthritis and essential mixed cryoimmunoglobulinemia using FACS analyzer and FACSCAN flow cytometer.

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).