Rheumatoid arthritis is characterized by progressive synovial inflammation and joint destruction. While matrix metalloproteinases (MMPs) are implicated in the erosion of unmineralized cartilage, bone destruction involves osteoclasts, the specialized cells that resorb calcified bone matrix. RANK ligand (RANKL) expressed by stromal cells and T cells, and its cognate receptor, RANK, were identified as a critical ligand-receptor pair for osteoclast differentiation and survival. A decoy receptor for RANKL, osteoprotegerin, (OPG) impinges on this system and regulates osteoclast numbers and actiyity. RANKL is also expressed in collagen-induced arthritis (CIA) in which focal collections of osteoclasts are prominent at sites of bone destruction. To determine the role of RANK signaling events in the effector phase of CIA, we investigated effects of Fc-osteoprotegerin fusion protein (Fc-OPG) in CIA. After induction of CIA in Dark Agouti rats, test animals were treated with or without Fc-OPG (3 mg/kg/day) subcutaneously for 5 days, beginning at the onset of disease. Paraffin-embedded joints were then analyzed histologically and the adjacent bone assessed by histomorphometry. Osteoclasts were identified using TRAP staining and expression of the mRNA for OPG and RANKL was identified by in situ hybridization. The results indicated that short-term Fc-OPG effectively prevented joint destruction, even though it had no impact on the inflammatory aspects of CIA. In arthritic joints, Fc-OPG depleted osteoclast numbers by over 75% and diminished bone erosion scores by over 60%. Although cartilage loss was also reduced by Fc-OPG, the effects on cartilage were less striking than those on,bone. in arthritic joints OPG mRNA was highly expressed and co-localized with mRNA. These data demonstrate that short term Fc-OPG treatment has powerful anti-erosive effects, principally on bone, even though synovitis is not affected. These findings indicate the potential utility of disrupting RANK signaling to preserve skeletal integrity in inflammatory arthritis.

Many investigators worldwide are currently exploring the role of peripheral blood stem cell transplantation (PBSCT) in managing autoimmune diseases. We report the case of a woman with systemic lupus erythematosus (SLE) with mucocutaneous and renal involvement, who underwent PBSCT for stage IVB Hodgkin's disease. Following the development of the lymphoma, she has had a prolonged clinical and serologic remission of the SLE. The potential effects of lymphoproliferative disorders and PBSCT on the course of SLE are considered.

Inflammatory vasculopathy and thrombotic thrombocytopenic purpura (TTP) are rare complications of scleroderma. We report a 54-year-old woman with limited cutaneous scleroderma who developed medium size and small vessel vasculitis. Inflammatory changes of medium size muscular arteries presented as ovarian vasculitis and mononeuritis multiplex, while arteriolar involvement presented as TTP with associated central nervous system involvement. In addition, possible noninflammatory involvement of small muscular arteries was expressed as Raynaud's phenomenon.

Medical Journal of AustraliaVolume 165, Issue 6 p. 352-352 Letter Arthritis in Australia: an emerging public health problem Catherine Finocchiaro, Catherine Finocchiaro Senior Lecturers Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VICSearch for more papers by this authorMichael J Abramson, Michael J Abramson Senior Lecturers Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VICSearch for more papers by this authorPeter F J Ryant, Peter F J Ryant Clinical Associate Professor Department of Medicine, Monash University, Melbourne, VICSearch for more papers by this author Catherine Finocchiaro, Catherine Finocchiaro Senior Lecturers Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VICSearch for more papers by this authorMichael J Abramson, Michael J Abramson Senior Lecturers Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VICSearch for more papers by this authorPeter F J Ryant, Peter F J Ryant Clinical Associate Professor Department of Medicine, Monash University, Melbourne, VICSearch for more papers by this author First published: 01 September 1996 https://doi.org/10.5694/j.1326-5377.1996.tb125010.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume165, Issue6September 1996Pages 352-352 RelatedInformation

Between 1987 and 1991 we performed Yttrium-90 (Y-90) silicate radionuclide synovectomies on 40 joints of 20 haemophiliac patients with haemophilic arthropathy. All were male, their mean age was 31 yr and 15 of the 20 (75%) were HIV antibody positive. The number of joint bleeds and amount of factor (VIII and IX) replacement given in the 6 months pre- and 6 and 12 months post-radionuclide synovectomy was compared. Y-90 silicate synovectomy was shown significantly to reduce both the number of joint bleeds (P < 0.001) and factor usage (P < 0.001) in the 6 months after the procedure, a result maintained up to 12 months. Depot methyl prednisolone was co-administered with Y-90 but thought unlikely to contribute to joint response beyond 6 months. The reduction of joint bleeds and factor usage was even more dramatic in the 6- to 12-month period post-synovectomy although this was not reflected by the P value (P < 0.001). The reduction of joint bleeds and factor consumption post-synovectomy was most obvious in elbow joints, although the other joints as a group showed a significant reduction. Patients who were HIV antibody positive showed considerable improvement up to 12 months post-treatment, both in reduction of joint bleeds and as a consequence factor consumption. This improvement was seen to a lesser extent in the smaller HIV-negative group.

The clinical and histological findings of a patient with mixed essential cryoglobulinemia (MECG) who developed post partum renal failure and the nephrotic syndrome are described. The renal insufficiency responded dramatically to intensive plasma exchange and longer term immunosuppression with associated resolution of the renal histological changes. To our knowledge deterioration of renal function in the post partum period has not been previously described in the syndrome of MECG.

The kinetics of radiolabelled heat damaged red cell (HDRBC) distribution have been studied in humans using a gamma camera, and compared with the kinetics of other blood cells. Liver uptake of 111In labelled HDRBC was completed within about 10 min of injection; splenic uptake was biphasic with a half time of about 5 min over the first 20 min following injection, and a later half time much longer than this. Activity initially present in the lung fields cleared within 24 h. The rate constants of liver uptake of 99mTc labelled HDRBC and of 111In labelled platelets were very similar; the rate constants of splenic uptake of these 2 particles were also very similar up to about 20 min following injection when the splenic platelet levels became constant and the HDRBC level continued to slowly rise. Splenic uptake and blood clearance of red cells coated with IgG (IgG‐RBC), in contrast to HDRBC, were monoexponential.It was concluded that: (1) the blood clearance of HDRBC was due to pooling within, and to irreversible extraction by, the spleen; (2) liver uptake of HDRBC, which was irreversible, was completed within 10 min of injection; (3) IgG‐RBC clearance was due to irreversible extraction by the spleen; (4) HDRBC uptake in the lung was unrelated to reticuloendothelial function, and represented prolonged transit through the lung microvasculature.

Functional hyposplenism, a clinical entity which has only recently been recognised, is usually assessed quantitatively by the rate of clearance of radiolabelled heat damaged erythrocytes (HDE) from the circulation. Based on recent observations on the kinetics of HDE, we have developed a 3 compartmental model of HDE distribution between the spleen and blood, and calculated, in a large series of clearance curves, splenic blood flow, HDE intrasplenic transit time and splenic HDE extraction ratio. Transit time (about 15 min) was of the same order as platelet transit time and extraction ratio (about 35%) was similar to that recorded in animals. Thr relationships between blood flow, transit time and extraction ratio provided evidence in support of 2 separate functional compartments, of which only one was engaged in phagocytosis, present within the spleen.

Salmonellosis was diagnosed in 4 patients with systemic lupus erythematosus (SLE). Three patients were taking prednisolone, and 3 had evidence of nephritis. All patients were febrile with clinical evidence of lupus activity at the time of diagnosis. Two patients had evidence of hyposplenism during the infection. Because salmonellosis manifests clinical symptoms like those of active SLE, the diagnosis of the salmonella infection was delayed. In 3 patients, the salmonella infection localized to a site of clinical SLE involvement and in all 4 patients, it occurred simultaneously with other bacterial infections. Multiple factors, including impaired mononuclear phagocytic system function, may predispose SLE patients to bacterial infections, especially intracellular parasites such as salmonella.

The rate of clearance from the blood of heat-damaged erythrocytes (HDE) is used routinely as a quantitative assessment of splenic function. The time taken for the value at 3 min to fall by 50% (t0.5)is usually taken as the index of function. The clearance of HDE is dependent on three processes: splenic blood flow, splenic HDE extraction ratio and intrasplenic transit time of "unextracted' HDE, returning to the circulation. Exponential analysis of the clearance curve can resolve these three functions. Simple methods of analysis, however, such as t0.5, which are applied directly to the curve, may be weighted in favour of any one of them. In this paper, a large number of clearance curves have been analysed and the components of splenic function resolved. The t0.5, the percentage fall in HDE between 8 and 28 min (C20), the rate constant at 8 min (K8) and the rate constant of the tail of the curve (alpha 2) have been correlated with these components. K8 showed a close correlation with splenic blood flow, and alpha 2 with the rate of HDE phagocytosis. In general, the correlation between the various components of splenic function was better with C20 than with t0.5. This is explained predominantly by the fact that the t0.5 includes liver clearance. The t0.5 should therefore be used with caution as an estimate of splenic function, which can be usefully assessed by applying alternative simple methods of analysis described.

Australian and New Zealand Journal of MedicineVolume 11, Issue 4 p. 545-549 Systemic Lupus Erythematosus—Some Aspects of Management* G. R. V. Hughes, Corresponding Author G. R. V. Hughes Rheumatology Unit, Royal Postgraduate Medical School and Hammersmith Hospital, London †Consultant Physician and Senior Lecturer in Medicine.Rheumatology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS, EnglandSearch for more papers by this authorP. F. J. Ryan, P. F. J. Ryan Rheumatology Unit, Royal Postgraduate Medical School and Hammersmith Hospital, London ‡Honorary Senior Registrar and Research Fellow.Search for more papers by this author G. R. V. Hughes, Corresponding Author G. R. V. Hughes Rheumatology Unit, Royal Postgraduate Medical School and Hammersmith Hospital, London †Consultant Physician and Senior Lecturer in Medicine.Rheumatology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London W12 OHS, EnglandSearch for more papers by this authorP. F. J. Ryan, P. F. J. Ryan Rheumatology Unit, Royal Postgraduate Medical School and Hammersmith Hospital, London ‡Honorary Senior Registrar and Research Fellow.Search for more papers by this author First published: August 1981 https://doi.org/10.1111/j.1445-5994.1981.tb04629.xCitations: 3 † *Based on a lecture given to the meeting of the ARA/NZRA combined annual scientific meeting, 27th October, 1980, Adelaide. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Hughes GRV. Systemic lupus erythematosus. Treatment and prognosis. Brit Med J 1979; 2: 1019–21. 2 Hughes GRV. The treatment of systemic lupus erythematosus: the case for conservative management Clin Rheum Dis 1979; 5: 641–7. 3 Fessei WJ. SLE in the community. Arch Intern Med 1974; 134: 1027–35. 4 Wilson W., Hughes GRV. Rheumatic disease in Jamaica. A 3 year study Am Rheum Dis 1979; 38: 320–3. 5 Miller KB, Schwarti RS. Familial abnormalities of suppressor cell function in SLE. N Engl J Med 1979; 301: 803. 6 Inman RD. Current comment: Immunologic sex differences and the female predominance in systemic iupus erythematosus. Arthritis Rheum 1978; 21: 849–50. 7 Travers R. Hughes GRV. Oral contraseptive therapy and SLE J Rheumatol 1978; 5; 448–9. 8 Lahita RG, Bradlow HL, Kunkel HG, J. Fishman Alterations of oestrogen metabolism in SLE. Arthritis Rheum 1979; 22: 1195–7. 9 Roubiniam JR, Papoian R., N. Tabal Androgenic hormones mosulate autoantibody responses and improve survival in murine lupus. J Clin invest 1977; 59: 1066–9. 10 Batchelor JR, Mansilla R., Hughes GRV et al Hydralazine-induced SLE. The influnce of HLA-DR and sex upon susceptibility Lancer: 1980; 1: 1461–3. 11 Tan EM. Ultraviolet Eight and SLE In: GRV Hughes ed. Modern lopies in rheumatology London : Heinemann Medical. 1976. 12 Pinching AJ, Travers RL, Hughes GKV. T. Jones, Moss S. Detection of cerebra: involvement in SLE using 15–oxygen brain scanning. Lancet 1978; 1: 898–901. 13 Bresmihan B., Oliver M. Hughes GRV. An antineuronal antibody associated with neuropsychratric disease in SLE. Arthritis Rheum 1979; 22: 313–20. 14 Hughes GRV. Central nervous system lupus—diagnosis and treatment. J Rheumatol 1980; 3: 405–11. 15 Cameron JS, Turner DR. Ogg CS et al. SLE with nephritis: A long-term study Q J Med 1979; 189: 1–24. 16 Dubois EL Antimalarials in the management of discoid and systemic lupus erythematosus. Semin Arthritis Rheum 1978; 8: 33–51. Citing Literature Volume11, Issue4August 1981Pages 545-549 ReferencesRelatedInformation

Arthritis & RheumatismVolume 24, Issue 8 p. 1070-1073 ArticleFree to Read The heterogeneity of serologic findings and predisposing host factors in drug-induced lupus erythematosus G. R. V. Hughes MD, Corresponding Author G. R. V. Hughes MD Royal Postgraduate Medical School, Hammersmith Hospital, London W12, EnglandRoyal Postgraduate Medical School, Hammersmith Hospital, London W12, EnglandSearch for more papers by this authorR. I. Rynes, R. I. RynesSearch for more papers by this authorA. Gharavi, A. GharaviSearch for more papers by this authorP. F. J. Ryan, P. F. J. RyanSearch for more papers by this authorJ. Sewell, J. SewellSearch for more papers by this authorR. Mansilla, R. MansillaSearch for more papers by this author G. R. V. Hughes MD, Corresponding Author G. R. V. Hughes MD Royal Postgraduate Medical School, Hammersmith Hospital, London W12, EnglandRoyal Postgraduate Medical School, Hammersmith Hospital, London W12, EnglandSearch for more papers by this authorR. I. Rynes, R. I. RynesSearch for more papers by this authorA. Gharavi, A. GharaviSearch for more papers by this authorP. F. J. Ryan, P. F. J. RyanSearch for more papers by this authorJ. Sewell, J. SewellSearch for more papers by this authorR. Mansilla, R. MansillaSearch for more papers by this author First published: August 1981 https://doi.org/10.1002/art.1780240814Citations: 24AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume24, Issue8August 1981Pages 1070-1073 RelatedInformation