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| Immunology Example 1: Systemic Lupus Erythematosus |
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| Archived Abstracts |
| Biogen Idec Inc. | ||||
Biogen Idec Prices $1.0 Billion Senior Unsecured Notes Offering Lead Author: [none given] Additional Authors: Business Wire. New York, 2008-02-29 Biogen Idec Inc. (NASDAQ: BIIB) announced today that it has priced a public offering of $1.0 billion principal amount of senior unsecured notes. The offering of senior unsecured notes includes $450 million in aggregate principal amount of 6.0% notes due 2013 and $550 million in aggregate principal amount of 6.875% notes due 2018. The sale of the notes is expected to close on March 4, 2008, subject to customary closing conditions. Biogen Idec plans to use the net proceeds from this offering, together with cash on hand, to repay indebtedness under its $1.5 billion bridge facility, the proceeds of which were used to repurchase shares of Biogen Idec's common stock in a $3.0 billion "Dutch Auction" tender offer settled on July 2, 2007. Goldman, Sachs & Co. and Merrill Lynch & Co. are the book-running managers for the offering. The offering of these securities is being made only by means of a prospectus and related prospectus supplement. Electronic copies of the prospectus and related prospectus supplement may be requested from Goldman, Sachs & Co. by mail at Goldman, Sachs & Co., Attention: Prospectus Department, 85 Broad Street, New York, NY 10004, by fax at (212) 902-9316 or by email at prospectus-ny@ny.email.gs.com or by Merrill Lynch, Pierce, Fenner & Smith Incorporated at 4 World Financial Center, New York, New York 10080, Attention: Prospectus Department, 866-500-5408. About Biogen Idec Biogen Idec creates new standards of care in therapeutic areas with high unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the discovery, development, manufacturing, and commercialization of innovative therapies. Patients in more than 90 countries benefit from Biogen Idec's significant products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis. For product labeling, press releases and additional information about the company, please visit www.biogenidec.com. MIB Abstract ID Number: 14712 Proquest Identifier: 1438345021 * To access this Proquest article the user must create an account. |
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| Rituxan OR Rituximab & Biogen | ||||
Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Lead Author: Kavanaugh A Additional Authors: Rosengren S, Lee SJ, Hammaker D, Firestein GS, Kalunian K, Wei N, Boyle DL. Ann Rheum Dis., 2008-03-01, 67(3):402-8. Epub 2007 Jul 20. University of California, San Diego, Division of Rheumatology, Allergy, and Immunology, 9500 Gilman Drive, Mail Code 0943, La Jolla, CA 92093-0943, USA. akavanaugh@ucsd.edu OBJECTIVE: Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab is effective in rheumatoid arthritis (RA). Marked depletion of circulating B cells, seen in almost all patients, does not correlate with efficacy. The potential synovial immunomodulatory effects of rituximab have not been fully defined. METHODS: The ARISE trial is an open label, serial synovial biopsy (pre-treatment and 8 weeks) study of rituximab, given 1 g intravenously on days 0 and 14 without peri-infusional steroids, in active RA patients on concomitant methotrexate (MTX). Synovial tissue was analysed by immunohistochemistry with digital image analysis and gene expression by real-time PCR. RESULTS: The mean (SD) baseline DAS28 score was 6.5 (0.4), and mean MTX dose 17.3 mg/week. Of 13 patients, 11 had failed prior tumour necrosis factor (TNF) inhibitor therapy. With treatment, all patients experienced near complete depletion of circulating B cell numbers. During the 6 months after treatment, 7/13 patients achieved an American College of Rheumatology (ACR) 20% improvement (ACR20) response, 3/13 an ACR50 response and 2/13 an ACR70 response. There was a significant decrease in synovial B cells after treatment, but only a small trend towards greater reduction among clinical responders. Among the three patients with ACR50 responses there was a significant decrease in synovial immunoglobulin synthesis. CONCLUSIONS: These data suggest that unlike those in circulation, synovial B cells are decreased but are not eliminated by rituximab therapy. Patients with higher levels of response may have more consistent depletion of synovial B cells, and may also have an alteration in synovial B cell function, as indicated by decreases in synovial immunoglobulin synthesis. Thus, effects on synovial B cells may be necessary but not sufficient for inducing clinical efficacy. Other effects, such as on primary lymph organ B cell antigen presentation or cytokine production, may be operative. MIB Abstract ID Number: 14717 PreMedline Identifier: 17644541 *To access this PubMed use the PreMedline Identifier in the PubMed search field |
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[Systemic lupus erythematosus: news and therapeutic perspectives] Lead Author: Sibilia J Additional Authors: Pasquali JL. Presse Med., 2008-03-01, 37(3 Pt 2):444-59. Epub 2008 Jan 31. Centre national de référence des maladies auto-immunes, Service de rhumatologie, CHU de Strasbourg, F-67098 Strasbourg Cedex, France. jean.sibilia@wanadoo.fr [Article in French] MIB Abstract ID Number: 14878 PreMedline Identifier: 18242045 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Bristol-Myers Squibb Co. | ||||
| Orencia OR Abatacept & Bristol-Myers | ||||
| Fred Hutch | ||||
| Genentech Inc. | ||||
| Ocrelizumab & Genentech | ||||
| Rituxan OR Rituximab & Genentech | ||||
| GlaxoSmithKline | ||||
| LymphoStat-B & GlaxoSmithKline | ||||
| Human Genome Sciences | ||||
| LymphoStat-B & Human Genome Sciences | ||||
| Immunomedics Inc. | ||||
| Epratuzumab & Immunomedics Inc. | ||||
| La Jolla Pharmaceuticals | ||||
La Jolla Pharmaceutical Company to Present at Susquehanna Financial Group Healthcare Conference Lead Author: [none given] Business Wire. New York, 2008-02-28 La Jolla Pharmaceutical Company (Nasdaq: LJPC) today announced that Niv E. Caviar, Executive Vice President, Chief Business and Financial Officer, will present on Tuesday, March 4, at 9:00 am Eastern Time during the Susquehanna Financial Group Second Annual SIGnificant Options in Healthcare Conference. On Wednesday, March 5, at 1:00 pm, at the conference, Matthew Linnik, Ph.D., Executive Vice President and Chief Scientific Officer, will participate in a panel discussion entitled: "Lupus: Crossing the Finish Line, New Therapies for SLE." The conference will take place at The W Hotel in New York City. *** Click Here to view the full text of this abstract *** MIB Abstract ID Number: 14893 Proquest Identifier: 1436684821 * To access this Proquest article the user must create an account.
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| Riquent OR Abetimus & La Jolla | ||||
| Trubion Pharmaceuticals | ||||
| TRU-015 & Trubion Pharmaceuticals | ||||
| Roche Pharmaceuticals | ||||
| CellCept & Roche | ||||
Novel therapies of lupus nephritis. Lead Author: Schieppati A Additional Authors: Remuzzi G. Curr Opin Nephrol Hypertens., 2008-03-01, 17(2):156-61. Mario Negri Institute for Pharmacological Research, Italy, Unit of Nephrology and Dialysis, Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy. PURPOSE OF REVIEW: To review the results of the current therapy of lupus nephritis, highlighting successes and pitfalls, and summarizing the evidence available on the new agents RECENT FINDINGS: The established treatment of lupus nephritis with aggressive immunosuppression, based on cyclophosphamide and steroids, has improved the outcome of lupus nephritis, but is burdened with significant adverse effects. The search for alternative, less toxic, therapeutic strategies has prompted a number of clinical studies, mycophenolate mofetil being the agent most studied. Results of trials showed that this drug is equally effective with fewer toxic complications than standard therapy, but its long-term efficacy is not yet known. During the last few years experimental studies in the pathogenesis of lupus nephritis have provided an enormous improvement in our knowledge and have offered the possibility to attempt targeting the disease with a more selective approach. The evidence for the role of these new therapies is reviewed. SUMMARY: While the current alternative to standard therapy, i.e. mycophenolate mofetil, still needs to be confirmed with well designed, properly powered studies, new therapeutic agents, targeted to the pathogenetic mechanism of the disease, are promising improved efficacy with less toxicity.MIB Abstract ID Number: 14900 PreMedline Identifier: 18277148 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| VLST | ||||
| ZymoGenetics | ||||
NOVO NORDISK TO END 2 DRUG PARTNERSHIPS WITH SPINOFF; ZYMOGENETICS DOWNPLAYS MOVE Lead Author: JOSEPH TARTAKOFF Seattle Post - Intelligencer., 2008-03-05, pg. E.1 Novo Nordisk, the Danish health care company that spun off ZymoGenetics eight years ago, plans to pull out of two partnerships to develop drugs with the Seattle company - moves that ZymoGenetics downplayed but that one analyst said raised questions about the viability of the company's product pipeline. Earlier this year, the Food and Drug Administration approved ZymoGenetics' first product, Recothrom, which is used to control bleeding during surgery. But the two drugs being developed with Novo Nordisk - Interleukin 21 and Interleukin 31 - are among five that ZymoGenetics considers to be candidates for future products. *** Click Here to view the full text of this abstract *** MIB Abstract ID Number: 14735 Proquest Identifier: 1441633301 * To access this Proquest article the user must create an account. |
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| Atacicept & ZymoGenetics | ||||
| Generic Drugs | ||||
| Anti-malarials & Generic Drugs | ||||
Lupus nephritis and Raynaud's phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies. Lead Author: Choojitarom K Additional Authors: Verasertniyom O, Totemchokchyakarn K, Nantiruj K, Sumethkul V, Janwityanujit S. Clin Rheumatol., 2008-03-01, 27(3):345-51. Epub 2007 Sep 2. Division of Allergy-Immunology-Rheumatology, Department of Medicine, Ramathibodi Hospital, 270 Rama6 Road, Bangkok, 10400, Thailand. This study is aimed to determine the predictors of nongravid vascular thrombosis in systemic lupus erythematosus (SLE) patients with positive antiphospholipid antibodies (SLE-aPL). A cohort of 67 SLE-aPL patients who had at least one positive test for lupus anticoagulant (LA), anticardiolipin (aCL), or anti-beta2glycoprotein-1(B2) was examined. Main outcome was the presence of vascular thrombosis. Association between thrombosis and risk factors was examined by contingency table. The odds ratio (OR) of significant predictors was determined by logistic regression. Three percent of patients were LA(+), 6% were aCL(+), 31% were B2(+), 3% were aCL(+)LA(+), 35.8% were aCL(+)B2(+), 7.5% were LA(+)B2(+), and 13.4% were positive for all tests. As for clinical manifestations, 79% had lymphopenia, 76% had lupus nephritis (LN), 41.8% had autoimmune hemolytic anemia, 34.3% had thrombocytopenia, 20.9% had abortion, and 19.4% had Raynaud's phenomenon (RP). Thrombosis occurred in 26 patients. The prevalence of thrombosis for SLE-aPL was 38.8%. Thrombosis was observed more frequently in patients with LA(+) (12 of 18) than the others (14 of 49; p = 0.01). Two-by-two table showed that oral contraceptive and LN were significantly associated with increased risk of thrombosis, while lymphopenia and antimalarials were significantly associated with decreased risk of thrombosis. Multivariate analysis confirmed that LN and RP were associated with increased risk of thrombosis (OR = 6.2 and 3.2; p = 0.005 and 0.008), while lymphopenia and antimalarials were associated with decreased risk of thrombosis (OR = 0.86 and 0.18; p = 0.02 and 0.034). LA is the strongest test to determine the risk of thrombosis in SLE-aPL. The presence of LN and RP strongly predicts thrombosis, while lymphopenia and antimalarials are protective. These findings help to identify patients who may benefit from prophylactic therapy. MIB Abstract ID Number: 14906 PreMedline Identifier: 17805483 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Chemotherapy & Generic Drugs | ||||
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Lead Author: Rahman A Additional Authors: Isenberg DA. N Engl J Med., 2008-02-28, 358(9):929-39. Centre for Rheumatology Research, Division of Medicine, University College London, London, United Kingdom.
<<No Abstract Available>> MIB Abstract ID Number: 14907 PreMedline Identifier: 18305268 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Neuropsychiatric lupus and reversible posterior leucoencephalopathy syndrome: a challenging clinical dilemma. Lead Author: Mak A Additional Authors: Chan BP, Yeh IB, Ho RC, Boey ML, Feng PH, Koh DR, Ong BK. Rheumatology (Oxford)., 2008-03-01, 47(3):256-62. Epub 2007 Dec 15. Division of Rheumatology, Department of Medicine, National University Hospital, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074. mdcam@nus.edu.sg Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS. MIB Abstract ID Number: 14909 PreMedline Identifier: 18084001 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Lead Author: Jónsdóttir T Additional Authors: Gunnarsson I, Risselada A, Henriksson EW, Klareskog L, van Vollenhoven RF. Ann Rheum Dis., 2008-03-01, 67(3):330-4. Epub 2007 Sep 7. Department of Rheumatology, Karolinska University Hospital, Solna, S-171 76 Stockholm, Sweden. OBJECTIVE: To evaluate efficacy, serological responses, and predictors of response in patients with severe and refractory systemic lupus erythematosus (SLE) treated with rituximab plus cyclophosphamide. METHODS: 16 patients entered a treatment protocol using rituximab plus cyclophosphamide. Disease activity was assessed by the SLE disease activity index (SLEDAI) and by the British Isles Lupus Assessment Group (BILAG) index. RESULTS: At six months follow up, mean SLEDAI values decreased significantly from (mean (SD)) 12.1 (2.2) to 4.7 (1.1). Clinical improvement (50% reduction in SLEDAI) occurred in all but three patients. All but one patient responded according to BILAG. Remission defined as SLEDAI <3 was achieved in nine of 16 patients. Isotype analysis of anti-dsDNA antibodies revealed preferential decreases of IgG and IgA, but not IgM. Higher absolute numbers of CD19+ cells at baseline were correlated with shorter depletion time (r = -0.6). CONCLUSIONS: The majority of patients improved following rituximab plus cyclophosphamide. The differential downregulation of anti-DNA of the IgG and IgA but not the IgM isotypes supports the hypothesis that cells producing pathogenic autoantibodies are preferentially targeted by the treatment. The fact that greater absolute numbers of CD19+ cells at baseline predict a less impressive clinical and serological response suggests that more flexible dosing could be advantageous. MIB Abstract ID Number: 14910 PreMedline Identifier: 17827182 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Corticosteroids & Generic Drugs | ||||
Bleeding and thrombosis in a patient with secondary antiphospholipid syndrome. Lead Author: Kaaroud H Additional Authors: Beji S, Guermazi S, Moussa FB, Hamida FB, Ezzine S, Abdallah TB, El Younsi F, Kheder A. Saudi J Kidney Dis Transpl., 2008-03-01, 19(2):227-31. Departments of Nephrology, Internal Medicine, Charles Nicolle Hospital, Tunis, Tunisia. hayet.kaarout@rns.tn. Antiphospholipid antibodies have been associated with occurrence of arterial and venous thrombotic events and fetal loss, which together constitute the antiphospholipid syndrome (APS). However, bleeding is rare in this syndrome. We report a case of systemic lupus erythematosus (SLE) with APS complicated simultaneously by thrombotic and hemorrhagic events. A 34-year-old woman was a known case of diffuse proliferative lupus nephritis associated with APS, on treatment with corticosteroids, cyclophosphamide and anticoagulants. She presented in February 2004 with severe anemia, menorrhagia, gingival bleeding and acute loss of vision in the left eye. Investigations revealed a hematoma in the psoas muscle with thrombosis of the inferior vena cava and occlusion of the retinal vein. Blood tests revealed a strongly positive lupus anticoagulant, factor XI deficiency (35%) and decrease of free protein S (44%). Factor XI inhibitor, anti-prothrombin, and anti-protein S antibodies were absent. The patient was treated with corticosteroids and six pulses of cyclophosphamide, which resulted in a rapid disappearance of bleeding, reduction of hematoma and normalization of hematological abnormalities. She was maintained on corticosteroids, azathioprine and anticoagulant agents were introduced. After a follow-up of 28 months, there was no recurrence of bleeding, the thrombosis had resolved, and there was a decrease in the levels of circulating anticoagulant as well as anticardiolipin antibodies.MIB Abstract ID Number: 14911 PreMedline Identifier: 18310872 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Chronic intestinal pseudo-obstruction in patients with systemic lupus erythematosus: report of four cases. Lead Author: Ceccato F Additional Authors: Salas A, Góngora V, Ruta S, Roverano S, Marcos JC, Garcìa M, Paira S. Clin Rheumatol., 2008-03-01, 27(3):399-402. Epub 2007 Oct 16. Rheumatology Section, Hospital JM Cullen, Santa Fe, Argentina. Chronic intestinal pseudo-obstruction (CIPO), a recently recognized manifestation of systemic lupus erythematosus (SLE) with only 23 cases reported in the English literature, may appear as a complication or as the initial presentation of SLE and usually occurs during the setting of an active lupus. The pathogenic mechanism in SLE is unknown. We describe four additional cases with clinical, radiological, and manometric features of CIPO. As SLE-related CIPO usually responds to treatment with high doses of corticosteroids and/or immunosuppressive and prokinetic agents, a high level of awareness of this complication is needed to avoid unnecessary surgical intervention. MIB Abstract ID Number: 14914 PreMedline Identifier: 17938989 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Brief and long maternal separations decrease corticosterone secretion in a lupus-prone strain: dissociation from disease-related parameters. Lead Author: Catallani B Additional Authors: Palma BD, Gil FZ, Suchecki D. Brain Behav Immun., 2008-03-01, 22(3):367-74. Epub 2007 Oct 24. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), Rua Napoleão de Barros, 925, 04024-002 Vila Clementino, São Paulo, SP, Brazil. Neonatal manipulations are known to alter the activity of the immune system and the hypothalamus-pituitary-adrenal (HPA) axis. This study was performed in order to examine whether brief and long maternal separations (BMS and LMS, respectively) interfere with the onset and development of murine lupus in NZB/NZWF1 females, and to determine whether the pattern of corticosterone (CORT) secretion throughout life is associated to the expression of the disease. Maternal separation was performed daily during postnatal days 1-14, lasting 15 min in the BMS group and 3h in the LMS group. Blood was sampled from the retro-orbital plexus on the 9th week, and every other week, from 10th to 34th weeks of life, for detection of anti-nuclear antibodies (ANA) and anti-double-strand DNA (anti-dsDNA) antibodies, and for determination of CORT serum levels. Urine samples were collected on the 21st, 27th, 33rd and 37th weeks of life. There were no group differences in regard to disease-related parameters, but LMS females presented a tendency for late onset of anti-dsDNA antibodies. BMS and LMS mice exhibited reduced CORT levels compared to non-manipulated (NM) animals. There was a strong negative correlation between total mean CORT concentration and onset of ANA, and a strong positive correlation between total mean CORT concentration and life span only in the NM group. Neonatal manipulations appeared to eliminate these correlations; hence, both BMS and LMS modified basal CORT secretion and the association between glucocorticoids and immune activity in the NZB/NZWF1 mouse strain. MIB Abstract ID Number: 14915 PreMedline Identifier: 17920241 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Cyclophosphamide & Generic Drugs | ||||
Predictors of premature gonadal failure in patients with systemic lupus erythematosus. Results from LUMINA, a multiethnic US cohort (LUMINA LVIII). Lead Author: González LA Additional Authors: McGwin G Jr, Durán S, Pons-Estel GJ, Apte M, Vilá LM, Reveille JD, Alarcón GS. Ann Rheum Dis., 2008-02-28, [Epub ahead of print] The University of Alabama at Birmingham, United States. OBJECTIVE: To examine the predictors of time-to-premature gonadal failure (PGF) in SLE patients from LUMINA, a multiethnic US cohort. METHODS: PGF was defined as per the SLICC Damage Index (SDI). Factors associated with time-to-PGF occurrence were examined by univariable and multivariable [three models according to cyclophosphamide use, at T0 (model 1), over time (model 2) and the total number of intravenous pulses (model 3)] Cox proportional hazards regression analyses. RESULTS: Thirty-seven of 316 women (11.7%) developed PGF (19 Hispanic-Texans, 14 African Americans, four Caucasians and no Hispanic-Puerto Ricans). By multivariable analyses, older age at T0 (HR=1.10 to 1.14; 95% CI 1.02 to 1.05-1.19 to 1.23) and disease activity (SLAM-R) in all models (HR=1.22 to 1.24; 95% CI 1.10 to 1.12-1.35 to 1.37), Hispanic-Texan ethnicity in models 2 and 3 (HR=4.06 to 5.07; 95% CI 1.03 to 1.25-15.94 to 20.47) and cyclophosphamide use in models 1 and 3 (1-6 pulses) (HR=4.01 to 4.65; 95% CI 1.55 to 1.68-9.56 to 13.94) were predictors of a shorter time-to-PGF. CONCLUSIONS: Disease activity and Texan-Hispanic ethnicity emerged as predictors of a shorter time-to-PGF while the associations with cyclophosphamide use and older age were confirmed. Furthermore, cyclophosphamide induction therapy emerged as an important determinant of PGF. MIB Abstract ID Number: 14916 PreMedline Identifier: 18299303 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Health-related quality of life in patients with systemic lupus erythematosus and its relationship with cyclophosphamide pulse therapy. Lead Author: Medeiros MM Additional Authors: Menezes AP, Silveira VA, Ferreira FN, Lima GR, Ciconelli RM. Eur J Intern Med., 2008-03-01, 19(2):122-8. Epub 2007 Dec 26. Adjunct Professor of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Federal University of Ceara, Fortaleza, Brazil. OBJECTIVES: To examine health-related quality of life in Brazilian patients with systemic lupus erythematosus (SLE) and compare patients using cyclophosphamide (CP) pulse therapy with those who do not use it. METHODS: Patients with SLE using or not CP completed the SF-36 and SRQ-20 (psychological morbidity) questionnaire. The Lupus Activity Criteria Count (LAAC) assessed SLE disease activity. RESULTS: We studied 102 patients with SLE. The presence of psychological morbidity was associated with all the scores from SF-36. The physical component summary (PCS) of the SF-36 was significantly lower in patients with activity disease and the mental component summary (MCS) was significantly lower in the patients with psychological morbidity. Comparing patients using or not CP, it was not observed in a statistical significant difference in the 8 domains of the SF-36, nor in the PCS and MCS between the two groups. The prevalence of psychological morbidity evaluated by the SRQ-20 has not presented a statistical significant difference between the patients using or not CP. In the multivariate analysis, using the PCS and MCS as separate dependent variables, the most important variable associated with them was psychological morbidity. CONCLUSION: Cyclophosphamide pulse therapy does not worse health-related quality of life in patients with SLE. The presence of psychological distress is an important factor associated with worse quality of life. MIB Abstract ID Number: 14918 PreMedline Identifier: 18249308 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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The difference between lupus nephritis class IV-G and IV-S in Koreans: focus on the response to cyclophosphamide induction treatment. Lead Author: Kim YG Additional Authors: Kim HW, Cho YM, Oh JS, Nah SS, Lee CK, Yoo B. Rheumatology (Oxford). , 2008-03-01, 47(3):311-4. Epub 2008 Jan 19. Division of Rheumatology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea. OBJECTIVES: To evaluate the response to induction therapy with intravenous (i.v.) cyclophosphamide (CYC) in Korean patients with class IV-G (diffuse global proliferative glomerulonephritis) and class IV-S (diffuse segmental proliferative glomerulonephritis) lupus nephritis (LN) according to the classification system of the International Society of Nephrology/Renal Pathology Society (ISN/RPS). METHODS: Of the 52 patients with biopsy-proven diffuse proliferative LN, who had been treated with i.v. CYC over a 10-yr period, 42 had been treated with i.v. CYC (equal to or more than 500 mg) for 6 consecutive months and had biopsy specimens containing more than nine glomeruli. The renal pathology of these 42 patients was reclassified according to the International Society of Nephrology and the Renal Pathology Society 2003 classification, and their renal response rates and laboratory indices after induction therapy were analysed. RESULTS: Of the 42 patients assessed, 30 (71%) had IV-G and 12 (29%) had IV-S. Pre-treatment 24 h urinary protein was significantly higher and pre-treatment concentration of anti-dsDNA antibody was significantly lower in IV-G than in IV-S patients. Following induction therapy, complete remission rates were significantly higher in patients with IV-S (67%, 8/12) than in patients with IV-G (33%, 10/30) LN. CONCLUSIONS: Class IV-G LN responded more poorly to induction therapy with i.v. CYC pulse than class IV-S LN. MIB Abstract ID Number: 14919 PreMedline Identifier: 18204087 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Effect of lower dose intravenous cyclophosphamide on remission induction in Korean patients with lupus nephritis. Lead Author: [none given] Additional Authors: Seong SS, Choi CB, Yun HR, Kim YJ, Sung YK, Bae SC. Rheumatol Int., 2008-03-01, 28(5):453-8. Epub 2007 Oct 9. Department of Internal Medicine, Konyang University Hospital, Daejeon, 302-718, Republic of Korea. This study retrospectively investigated the efficacy and adverse events of applying a lower dose (0.5 g/m(2)) of monthly intravenous (IV) cyclophosphamide (CYC) for lupus nephritis in Korean patients. Adverse events occurred in 64 patients (61.5%) of 104 lupus nephritis patients who were treated with IV CYC, with the most common being those related to the gastrointestinal system, followed by infection, symptoms related to the hematopoietic system, skin and its appendages, reproductive system, and urinary system. Lower-dose IV CYC therapy resulted in renal remission or response in 76 patients (73.1%), which was as effective as the reported outcomes of higher-dose (0.75-1.0 g/m(2)) IV CYC regimens. Adverse events were more likely (with borderline statistical significance, p = 0.055) in those who achieved renal remission or response than in nonresponders. MIB Abstract ID Number: 14921 PreMedline Identifier: 17924111 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Hydroxychloroquine & Generic Drugs | ||||
THROMBOSIS; Researchers from St. Thomas' Hospital describe findings in thrombosis Lead Author: M.A. Khamashta Drug Law Weekly, 2008-03-04, EXPANDED REPORTING; Pg. 2026 St. Thomas Hospital, Rayne Institute, Lupus Arthritis Research Unit, London SE1 7EH, UK. According to recent research from London, the United Kingdom, "The antiphospholipid syndrome (APS) is characterized by a wide variability in clinical manifestations. Recommendations for therapy are conditioned by the lack of appropriate studies, due either to methodological limitations or excessive selection of patients." "There is consensus in treating patients with APS and first venous thrombosis with warfarin to a target international normalized ratio (INR) of 2.3-3.0. However, a recent systematic review including observational studies found patients with APS and stroke to be at a high risk of recurrent events. We thus recommend a target INR > 3.0 in this group. Likewise, the optimal approach for women with obstetric manifestations of APS is not completely defined; some authors recommend universal aspirin plus heparin whereas others consider aspirin in monotherapy useful for women with recurrent early miscarriage only. Correction of vascular risk factors and a high-risk management of pregnancy, including Doppler studies of the uterine and umbilical vessels, are warranted," wrote G. Ruizlrastorza and colleagues, St. Thomas' Hospital. The researchers concluded: "Hydroxychloroquine and statins are likely to become important in the future.'." Ruizlrastorza and colleagues published their study in Best Practice & Research in Clinical Rheumatology (The treatment of antiphospholipid syndrome: A harmonic contrast. Best Practice & Research in Clinical Rheumatology, 2007;21(6):1079-1092). For additional information, contact M.A. Khamashta, St. Thomas Hospital, Rayne Institute, Lupus Arthritis Research Unit, London SE1 7EH, UK. Publisher contact information for the journal Best Practice & Research in Clinical Rheumatology is: Bailliere Tindall, 24-28 Oval Rd., London NW1 7DX, England. MIB Abstract ID Number: 14925 *To access this Lexis-Nexis article the user must create an account. |
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| Mycophenolate mofetil & Generic Drugs | ||||
| Antilipemic Agents | ||||
| Antimetabolites | ||||
| Antinuclear Antibody Titer (AAT) | ||||
| Atorvastatin | ||||
Comment on: Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 week controlled trial. Lead Author: Kotyla PJ. Rheumatology (Oxford)., 2008-03-01, 47(3):381-2; author reply 382-3. Epub 2008 Jan 28. MIB Abstract ID Number: 14926 PreMedline Identifier: 18227111 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Comment on: Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial: reply. Lead Author: Ferreira GA Additional Authors: Andrade LE, Sato EI. Rheumatology (Oxford)., 2008-03-01, 47(3):382-383. Epub 2008 Jan 7. Rua Botucatu 740, CEP 040 23-900, São Paulo, Brazil. emiliasato@reumato.epm.br.
<<No Abstract Available>> MIB Abstract ID Number: 14927 PreMedline Identifier: 18180248 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Autoimmune Diseases | ||||
Treatment choices, preferences and decision-making by patients with rheumatoid arthritis. Lead Author: Chilton F Additional Authors: Collett RA. Musculoskeletal Care., 2008-03-01, 6(1):1-14. Rheumatology Department, South Warwickshire NHS Trust Hospital, Warwick, UK. Objectives: To explore rheumatoid arthritis (RA) patient treatment preferences, their decision-making and the treatment choices they would make when faced with three anti-tumour necrosis factor-alpha (TNF-alpha) therapy options.Methods: Two methods of enquiry were used: postal questionnaire and one-to-one interviews. RA patients not taking anti-TNF-alpha medications were asked to complete a questionnaire after reading a written scenario, which involved choosing and identifying factors that influenced their treatment choice from three anti-TNF-alpha therapies: etanercept (Enbrel), adalimumab (Humira) and infliximab (Remicade). Patients who had tried more than one anti-TNF-alpha medication were asked at one-to-one interviews for their treatment preferences and how their current treatment had been decided.Results: Both interviewees and questionnaire respondents chose adalimumab as their preferred treatment. Interviewees identified lack of control, convenience and technical issues as influencing treatment choice. Questionnaire respondents were less likely than interviewees to want to participate in making decisions about the selection of anti-TNF-alpha therapy. There were few gender differences. Patients younger than 61 years old were more confident about self-administering treatment, and preferred subcutaneous (sc) over intravenous (iv) medication, as this reduced regular hospital attendance. Older patients preferred health care staff to administer treatment and more readily identified 'contact with other patients/meeting others' and 'staff availability if problems arise' as factors influencing choice.Conclusions: RA patients demonstrate a clear treatment preference. Different factors influence patients who choose sc compared with iv medications. Many RA patients either wished to share in treatment decisions or relinquish responsibility to the health professional when choosing anti-TNF-alpha therapy. Patients require reassurance and continuing dialogue with clinicians to manage their condition optimally. Copyright (c) 2007 John Wiley & Sons, Ltd. MIB Abstract ID Number: 14702 PreMedline Identifier: 17726671 *To access this PubMed use the PreMedline Identifier in the PubMed search field |
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Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Lead Author: Lequerré T Additional Authors: Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J; Société Francophone pour la Rhumatologie et les Maladies Inflammatoires en Pédiatrie (SOFREMIP); Club Rhumatismes et Inflammation (CRI). Ann Rheum Dis., 2008-03-01, 67(3):302-8. Epub 2007 Oct 18. Rheumatology Department, Rouen University Hospital & Inserm 905, 76031 Rouen, France. thierry.lequerre@univ-rouen.fr BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement. MIB Abstract ID Number: 14707 PreMedline Identifier: 17947302 *To access this PubMed use the PreMedline Identifier in the PubMed search field |
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Clinical Outcome and Imaging Changes After Intraarticular (IA) Application of Etanercept or Methylprednisolone in Rheumatoid Arthritis: Magnetic Resonance Imaging and Ultrasound-Doppler Show No Effect of IA Injections in the Wrist After 4 Weeks. Lead Author: Boesen M Additional Authors: Boesen L, Jensen KE, Cimmino MA, Torp-Pedersen S, Terslev L, Koenig M, Danneskiold-Samsøe B, Røgind H, Bliddal H. J Rheumatol., 2008-03-01, [Epub ahead of print] From The Parker Institute Frederiksberg Hospital; Rigshospitalet, Department of Radiology, MRI Section, Copenhagen, Denmark; and Rheumatologic Clinic, Department of Internal Medicine, University of Genoa, Genoa, Italy. OBJECTIVE: To assess the magnetic resonance imaging (MRI) and ultrasound (US) changes in the wrist of patients with rheumatoid arthritis (RA) 4 weeks after an US guided intraarticular (IA) injection. METHODS: Contrast enhanced MRI and US-Doppler were performed at baseline and 4 weeks after IA injection of either 40 mg methylprednisolone (n = 12) or 25 mg etanercept (n = 13) in 25 patients with RA taking disease modifying antirheumatic drugs with a therapy-resistant wrist joint. All injections were US guided. RESULTS: There was an improvement in swollen target joint score (p < 0.001), tender target joint score (p < 0.002), and physician visual analog scale score (p < 0.001) after 4 weeks. Baseline MRI synovitis score was mean 5.08 (range 3-9) and was unchanged at followup in the whole group (p = 0.52) and between treatment groups (p = 0.43). MRI edema score (mean 4.46, range 0-29) in the total group was unchanged after 4 weeks (p = 0.13), whereas MRI erosion score increased in the total group from baseline, 17.88 (range 7-40), to 4 weeks, 18.25 (range 7-40) (p < 0.001). Neither US-Doppler color fraction (0.07) nor Resistive Index (RI) (p = 0.36) changed from baseline to 4 week followup. CONCLUSION: In contrast to the clinical evaluation, imaging measures of relevance for the estimation of inflammation, US-Doppler, US RI, MRI synovitis, and bone-marrow edema did not change 4 weeks after a single IA injection of either methylprednisolone or etanercept in the wrist. Within the same period, erosive progression in some patients suggested that joints with active disease may deteriorate within as little as 1 month, and that this development is not arrested by 1 injection. Given the small sample size of our study further studies are required to confirm our results.MIB Abstract ID Number: 14743 PreMedline Identifier: 18322991 *To access this PubMed use the PreMedline Identifier in the PubMed search field |
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Report on 547 New Medicines in Development for Neurological Disorders Released in San Antonio Lead Author: [none given] PR Newswire. New York, 2008-03-05 Pharmaceutical Research and Manufacturers of America The Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for neurological diseases. The report found America's pharmaceutical research companies are testing 547 new medicines to help treat neurological diseases. "We released this report in San Antonio because of its particular relevance to the health of this city's population and to the population in Texas," said PhRMA Senior Vice President Ken Johnson. The report was unveiled at the University Center for Community Health. "Over half of San Antonio's population is Hispanic, and Texas has the second largest Hispanic population in the country. Some of the diseases highlighted in the report, including epilepsy, stroke, Alzheimer's disease and lupus, are among the diseases that disproportionately affect Hispanic Americans." *** Click Here to view the full text of this abstract *** MIB Abstract ID Number: 14793 Proquest Identifier: 1440005071 * To access this Proquest article the user must create an account. |
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Macrophage activation syndrome: A frequent but under-diagnosed complication associated with rheumatic diseases. Lead Author: Tristano AG. Additional Authors: Med Sci Monit., 2008-03-01, 14(3):RA27-36. Department of Internal Medicine, Dr. Domingo Luciani Hospital, Caracas, Venezuela and Department pf Pharmaceutical and Administrative Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, U.S.A. Macrophage activation syndrome (MAS) or hemophagocytic syndrome is a severe complication of chronic rheumatic diseases especially in systemic-onset juvenile rheumatoid arthritis (JRA). Although the cause of MAS is unknown, dysregulation of macrophage-lymphocyte interactions with subsequent increases in the levels of both T cell-derived and macrophage-derived cytokines could be involved in this syndrome, leading to an intense systemic inflammatory reaction, which accounts for the main clinical picture. Patients usually present with an acute febrile illness, hepatosplenomegaly, lymphadenopathy, cutaneous and mucosal bleeding, pancytopenia, and central nervous system, cardiac, and renal involvement. Treatment of MAS in patients with rheumatic diseases has not been standardized yet, but it commonly includes a variety of agents such as high-dose corticosteroids, cyclosporine, cyclophosphamide, etoposide, and intravenous immunoglobulin (IVIG). This article reviews the current literature about the pathogenesis, clinical manifestation, diagnosis, and treatment of this severe complication associated with rheumatic diseases.MIB Abstract ID Number: 14877 PreMedline Identifier: 18301366 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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LUPUS; Research from J.L. Lamoureux and co-authors provides new data about lupus Lead Author: A.J. Feeney Biotech Week, 2008-03-05, EXPANDED REPORTING; Pg. 1307 Scripps Research Institute, Dept. of Immunology, 10666 N Torrey Pines Rd., La Jolla, CA 92037, USA. According to recent research from the United States, "Journal of Experimental Medicine The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity." *** Click Here to view the full text of this abstract *** MIB Abstract ID Number: 14896 *To access this Lexis-Nexis article the user must create an account. |
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Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties. Lead Author: Wielosz E Additional Authors: Majdan M, Zychowska I, Jeleniewicz R. Rheumatol Int., 2008-03-05, [Epub ahead of print] Department of Rheumatology and Connective Tissue Diseases, Medical University of Lublin, Jaczewskiego 8 Street, 20-090, Lublin, Poland, ewaw1973@op.pl. We report the case of coexistence of five autoimmune diseases in a 36-year-old woman, who initially developed psoriasis. Several years later, the patient was diagnosed with a mixed connective tissue disease and primary biliary cirrhosis (PBC). On admission to the Department of Rheumatology and Connective Tissue Diseases, the patient fulfilled classification criteria of an overlap syndrome systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome/systemic sclerosis (SSc)/Sjogren's syndrome (SS) with coexisting PBC and psoriasis. The SLE symptoms included discoid lupus erythematosus, arthritis, pancytopenia, antinuclear antibodies and anticardiolipin antibodies. Moreover, the patient met the criteria of antiphospholipid syndrome diagnosed based on preterm delivery before week 34, and high values of anticardiolipin antibodies were found at repeated determinations. The SSc symptoms included sclerodactyly, pulmonary fibrosis with pulmonary hypertension and esophageal dysfunction. The SS syndrome involved xerostomia, xerophthalmia, the positive Schirmer's test and presence of anti-SS antibodies. The literature reports overlap syndromes in various combinations; however, the coexistence of five autoimmune diseases is extremely rare. MIB Abstract ID Number: 14929 PreMedline Identifier: 18320193 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Autoimmune disease in individuals and close family members and susceptibility to non-Hodgkin's lymphoma. Lead Author: Mellemkjaer L Additional Authors: Pfeiffer RM, Engels EA, Gridley G, Wheeler W, Hemminki K, Olsen JH, Dreyer L, Linet MS, Goldin LR, Landgren O. Arthritis Rheum., 2008-02-29, 58(3):657-666 [Epub ahead of print] Danish Cancer Society, Copenhagen, Denmark. OBJECTIVE: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome have been consistently associated with an increased risk of non-Hodgkin's lymphoma (NHL). This study was initiated to evaluate the risks of NHL associated with a personal or family history of a wide range of autoimmune diseases. METHODS: A population-based case-control study was conducted that included 24,728 NHL patients in Denmark (years 1977-1997) and Sweden (years 1964-1998) and 55,632 controls. Using univariate logistic and hierarchical regression models, we determined odds ratios (ORs) of NHL associated with a personal history of hospital-diagnosed autoimmune conditions. Risks of NHL associated with a family history of the same autoimmune conditions were assessed by similar regression analyses that included 25,941 NHL patients and 58,551 controls. RESULTS: A personal history of systemic autoimmune diseases (RA, SLE, Sjögren's syndrome, systemic sclerosis) was clearly linked with NHL risk, both for individual conditions (hierarchical odds ratios [OR(h)] ranged from 1.6 to 5.4) and as a group (OR(h) 2.64 [95% confidence interval (95% CI) 1.72-4.07]). In contrast, a family history of systemic autoimmune diseases was modestly and nonsignificantly associated with NHL (OR(h) 1.31 [95% CI 0.85-2.03]). An increased risk of NHL was found for a personal history of 5 nonsystemic autoimmune conditions (autoimmune hemolytic anemia, Hashimoto thyroiditis, Crohn's disease, psoriasis, and sarcoidosis) (OR(h) ranged from 1.5 to 2.6) of 27 conditions examined. CONCLUSION: Overall, our results demonstrate a strong relationship of personal history of systemic autoimmune diseases with NHL risk and suggest that shared susceptibility may explain a very small fraction of this increase, at best. Positive associations were found for a personal history of some, though far from all, nonsystemic autoimmune conditions. MIB Abstract ID Number: 14930 PreMedline Identifier: 18311836 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Increase in the level of macrophage colony-stimulating factor in patients with systemic lupus erythematosus. Lead Author: Yang PT Additional Authors: Xiao WG, Zhao LJ, Lu J, He LM, Kasai H, Ito M. Ann Rheum Dis., 2008-03-01, 67(3):429-30.
<<No Abstract Available>> MIB Abstract ID Number: 14931 PreMedline Identifier: 18292107 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. Lead Author: Hom G Additional Authors: Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, Lee AT, Chung SA, Ferreira RC, Pant PV, Ballinger DG, Kosoy R, Demirci FY, Kamboh MI, Kao AH, Tian C, Gunnarsson I, Bengtsson AA, Rantapää-Dahlqvist S, Petri M, Manzi S, Seldin MF, Rönnblom L, Syvänen AC, Criswell LA, Gregersen PK, Behrens TW. N Engl J Med. , 2008-02-28, 358(9):900-9. Epub 2008 Jan 20. Genentech, South San Francisco, CA 94080, USA. Comment in: BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4 are established susceptibility genes; there is strong evidence for the existence of additional risk loci. METHODS: We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden. RESULTS: Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case-control series (rs13277113; odds ratio, 1.39; P=1x10(-10)) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3x10(-11)). CONCLUSIONS: We identified and then confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region. Copyright 2008 Massachusetts Medical Society. MIB Abstract ID Number: 14935 PreMedline Identifier: 18204098 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Connective Tissue Diseases | ||||
Serum levels of sex steroid hormones and matrix metalloproteinases after intra-articular glucocorticoid treatment in female patients with rheumatoid arthritis. Lead Author: Weitoft T Additional Authors: Larsson A, Rönnblom L. Ann Rheum Dis., 2008-03-01, 67(3):422-4. Epub 2007 Sep 18. Department of Research and Development, County Council of Gävleborg/Uppsala University, Section of Rheumatology, Gävle Hospital, Sweden. tomas.weitoft@lg.se OBJECTIVES: To study metalloproteinase activity and sex steroid hormone production in serum after intra-articular glucocorticoid treatment for knee synovitis. METHODS: 18 female patients with rheumatoid arthritis and synovitis of the knee with need for intra-articular glucocorticoid treatment were included in this study. Serum samples of matrix metalloproteinases (MMP-1/TIMP complex and MMP-3), dehydroepiandrosterone sulphate, testosterone, oestradiol, steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone were collected before injection with 20 mg triamcinolone hexacetonide, and 24 h, 48 h, 1 week and 2 weeks after injection, respectively. RESULTS: Serum levels of MMP-3 were significantly decreased, but MMP-1/TIMP complex was unaffected. Dehydroepiandrosterone sulphate, testosterone and oestradiol levels all decreased and tended to return to baseline levels during the observation period. Steroid hormone binding globulin, follicle stimulating hormone and luteinising hormone levels were unchanged. CONCLUSIONS: Intra-articular glucocorticoid treatment causes a temporary, but considerable suppression of sex steroid hormone secretion. The reduction of MMP-3 indicates an inhibition of the inflammatory, but probably also the cartilage destructive processes within the treated joint. MIB Abstract ID Number: 14838 PreMedline Identifier: 17878211 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Anti-p53 Autoantibody in Systemic Sclerosis: Association with Limited Cutaneous Systemic Sclerosis. Lead Author: Hara T Additional Authors: Ogawa F, Muroi E, Komura K, Takenaka M, Hasegawa M, Fujimoto M, Sato S. J Rheumatol., 2008-03-01, 35(3):451-7. Epub 2008 Jan 15. From the Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki; and Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. OBJECTIVE: To determine the prevalence and clinical significance of anti-p53 antibody in patients with systemic sclerosis (SSc). METHODS: Anti-p53 antibody was examined by ELISA and immunoblotting. Findings were correlated with clinical features of disease and other autoantibodies and compared with other connective tissue diseases as well as normal controls. p53 activity to bind target DNA was evaluated by ELISA using a plate coated with oligonucleotide containing the consensus binding site for p53. RESULTS: IgG anti-p53 antibody levels were elevated in patients with SSc compared to patients with systemic lupus erythematosus (n = 20; p < 0.05), dermatomyositis (n = 21; p < 0.005), atopic dermatitis (n = 17; p < 0.0005), or bullous pemphigoid (n = 10; p < 0.0005) and normal controls (n = 21; p < 0.0005). Remarkably, anti-p53 antibody levels were higher in patients with limited cutaneous SSc (lSSc; n = 30) than those found in patients with diffuse cutaneous SSc (dSSc; n = 40; p < 0.05). IgG or IgM anti-p53 antibody levels did not correlate with the presence or levels of other autoantibodies. IgG anti-p53 antibody was associated with longer disease duration (p < 0.05) and decreased percentage vital capacity (p < 0.05), and correlated negatively with modified Rodnan total skin thickness score (r = -0.352, p < 0.01). Immunoblotting analysis confirmed the presence of IgG anti-p53 antibody in selected patients with SSc. IgG isolated from sera of selected patients with SSc that contained IgG anti-p53 antibody inhibited the p53 activity relative to normal controls. CONCLUSION: IgG anti-p53 antibody was detected in lSSc and dSSc, and was more prominent in lSSc, indicating that IgG anti-p53 antibody is a novel autoantibody associated with lSSc, a milder form of SSc. MIB Abstract ID Number: 14937 PreMedline Identifier: 18203319 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus. Lead Author: Lee CS Additional Authors: Hu CY, Tsai HF, Wu CS, Hsieh SL, Liu LC, Hsu PN Clin Exp Immunol. , 2008-03-01, 151(3):383-90. Epub 2008 Jan 8. Department of Internal Medicine, McKay Memorial Hospital and MacKay Medicine, Nursing and Management College, Taipei, Taiwan. Decoy receptor 3 (DcR3/TR6) is a decoy receptor for the Fas ligand (FasL) and can inhibit FasL-induced apoptosis. It has been reported recently that DcR3 can induce T cell activation via co-stimulation of T cells, suggesting that DcR3 may be involved in the pathophysiology of autoimmune diseases. This study aims to analyse the serum DcR3 in patients with systemic lupus erythematosus (SLE) and to investigate the role of DcR3 in the pathogenesis of SLE. Significantly elevated serum DcR3 was observed in SLE patients, and the mean serum DcR3 level was significantly higher for those with active disease [SLE disease activity index (SLEDAI) >/= 10] compared with that in patients with inactive disease (SLEDAI < 10). In addition to reducing activation-induced cell death in activated T cells via neutralization of the FasL, soluble DcR3-Fc enhanced T cell proliferation and increased interleukin-2 and interferon-gamma production via co-stimulation of T cells. Moreover, enhanced T cell reactivity to DcR3-induced co-stimulation was demonstrated in lymphocytes from patients with SLE, suggesting the elevated serum DcR3 may associate with enhanced T cell activation in vivo. These findings are the first to demonstrate that serum DcR3 concentrations are increased in SLE patients, and this may imply a possible role of DcR3 in the pathogenesis of SLE via enhanced T cell hyperreactivity and reduced apoptosis in activated T cells. MIB Abstract ID Number: 14938 PreMedline Identifier: 18190609 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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B cell depletion therapy for patients with systemic lupus erythematosus results in a significant drop in anticardiolipin antibody titres. Lead Author: Ioannou Y Additional Authors: Lambrianides A, Cambridge G, Leandro MJ, Edwards JC, Isenberg DA. Ann Rheum Dis., 2008-03-01, 67(3):425-6. Epub 2007 Sep 28. Centre for Rheumatology, Department of Medicine, University College London, 250 Euston Road, , London NW1 2PG, UK. j.ioannou@ich.ucl.ac.uk BACKGROUND: B cell depletion therapy (BCDT) has recently been used with success to treat patients with rheumatoid arthritis and systemic lupus erythematosus (SLE). As antiphospholipid antibodies have been implicated in the pathogenesis of the antiphospholipid syndrome (APS), we asked the question whether BCDT affects levels of IgG anticardiolipin antibodies (aCL) in our cohort of 32 SLE patients given this treatment. METHODS: We identified seven SLE patients who had undergone BCDT and had had at least two moderate positive aCL titres at least 12 weeks apart. Of these only one patient had APS. IgG aCL were measured at time 0 and 6-9 months post BCDT. RESULTS: At time 0, the mean IgG aCL level was 20.6 standardized IgG antiphospholipid units (GPLU) (range (SD) 10-32, (10.1), normal level <5). At 6-9 months post depletion the IgG aCL levels in six of the seven patients was undetectable and in the other patient the level reduced from 25 GPLU to 15 GPLU (p<0.005, two-tailed paired t test). At baseline, only one patient had a mildly positive anti-beta(2)-glycoprotein I (beta(2)GPI) antibody level at 30% (compared to an in-house standard), which fell to 5% post-BCDT. CONCLUSIONS: This small observational study in patients with SLE is the first to demonstrate that BCDT results in a significant reduction in levels of IgG aCL. MIB Abstract ID Number: 14940 PreMedline Identifier: 17905784 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Glomerulonephritis | ||||
Estrogen receptor-alpha deficiency attenuates autoimmune disease in (NZB x NZW)F1 mice. Lead Author: Bynoté KK Additional Authors: Hackenberg JM, Korach KS, Lubahn DB, Lane PH, Gould KA. Genes Immun., 2008-03-01, 9(2):137-52. Epub 2008 Jan 17. Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-5805, USA. Estrogens promote lupus in humans and some mouse models of this disease. Nonetheless, little is known about the role of estrogen receptors in lupus pathogenesis. Here, we report that in females on the lupus-prone (NZB x NZW)F(1) background, disruption of estrogen receptor-alpha (ER alpha or Esr1) attenuated glomerulonephritis and increased survival. ER alpha deficiency also retarded development of anti-histone/DNA antibodies, suggesting that ER alpha promotes loss of immunologic tolerance. Furthermore, ER alpha deficiency in (NZB x NZW)F(1) females attenuated the subsequent development of anti-double-stranded DNA (dsDNA) IgG antibodies, which are associated with glomerulonephritis in this model. We provide evidence that ER alpha may promote lupus, at least in part, by inducing interferon-gamma, an estrogen-regulated cytokine that impacts this disease. ER alpha deficiency in (NZB x NZW)F(1) males increased survival and reduced anti-dsDNA antibodies, suggesting that ER alpha also modulates lupus in males. These studies demonstrate that ER alpha, rather than ER beta, plays a major role in regulating autoimmunity in (NZB x NZW)F(1) mice. Furthermore, our results suggest for the first time that ER alpha promotes lupus, at least in part, by impacting the initial loss of tolerance. These data suggest that targeted therapy disrupting ER alpha, most likely within the immune system, may be effective in the prevention and/or treatment of lupus. MIB Abstract ID Number: 14944 PreMedline Identifier: 18200028 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Expression of mRNA for functional molecules in urinary sediment in glomerulonephritis. Lead Author: Tsugawa K Additional Authors: Oki E, Suzuki K, Imaizumi T, Ito E, Tanaka H. Pediatr Nephrol., 2008-03-01, 23(3):395-401. Epub 2007 Dec 19. Department of Pediatrics, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan, kojituga@royal.ocn.ne.jp. Recent studies have suggested that gene expression studies using urinary sediment might be a non-invasive approach to assessing activity and pathogenesis in glomerulonephritis. However, little information is available regarding the mRNA expression patterns of functional molecules, such as T-bet, GATA-3, FOXP3, and retinoic acid-inducible gene-I (RIG-I), in urinary sediment, from patients with immunocomplex-mediated glomerulonephritis. Fourteen lupus nephritis (LN) patients, 13 IgA nephropathy (IgAN) patients, and 12 healthy controls were enrolled in the study. The mRNA expressions of T-bet, GATA-3, FOXP3 and RIG-I in urinary sediment were measured using real time quantitative polymerase chain reaction. We also studied the expression of RIG-I in kidney tissue specimens obtained from LN and IgAN patients. Significant differences in the expression patterns of GATA-3, FOXP3 and RIG-I, and marginal differences in T-bet expression, were observed between the three study groups. Immunofluorescent staining for RIG-I was observed in the tissue specimens from the LN patients, but not in those from the IgAN patients. The mRNA expression patterns of T-bet, GATA-3, FOXP3 and RIG-I in urinary sediment differ according to diagnostic category. These results suggest that the measurement of these target gene expressions might be a useful, non-invasive method for clinical monitoring and studying of pathogenesis in glomerulonephritis. MIB Abstract ID Number: 14945 PreMedline Identifier: 18095005 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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CDK/GSK-3 inhibitors as therapeutic agents for parenchymal renal diseases. Lead Author: Obligado SH Additional Authors: Ibraghimov-Beskrovnaya O, Zuk A, Meijer L, Nelson PJ. Kidney Int., 2008-03-01, 73(6):684-90. Epub 2007 Dec 19. Division of Nephrology, New York University School of Medicine, New York, New York 10016, USA. Drug discovery to lessen the burden of chronic renal failure and end-stage renal disease remains a principle goal of translational research in nephrology. In this review, we provide an overview of the current development of small molecule cyclin-dependent kinase (CDK)/glycogen synthase kinase-3 (GSK-3) inhibitors as therapeutic agents for parenchymal renal diseases. The emergence of this drug family has resulted from the recognition that CDKs and GSK-3s play critical roles in the progression and regression of many kidney diseases. CDK/GSK-3 inhibitors suppress pathogenic proliferation, apoptosis, and inflammation, and promote regeneration of injured tissue. Preclinical efficacy has now been demonstrated in mesangial proliferative glomerulonephritis, crescentic glomerulonephritis, collapsing glomerulopathy, proliferative lupus nephritis, polycystic kidney diseases, diabetic nephropathy, and several forms of acute kidney injury. Novel biomarkers of therapy are aiding the process of drug development. This review will highlight these advancements in renal therapeutics. MIB Abstract ID Number: 14946 PreMedline Identifier: 18094678 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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C1q nephropathy in two young sisters. Lead Author: Kari JA Additional Authors: Jalalah SM. Pediatr Nephrol., 2008-03-01, 23(3):487-90. Epub 2007 Oct 21. Pediatrics Department, King AbdulAziz University Hospital, P.O. Box 80215, Jeddah, 21589, Saudi Arabia, jkari@doctors.org.uk. C1q nephropathy (C1qNP) is a controversial and uncommon form of glomerulonephritis, characterized by mesangial immunoglobulin and complement deposits, predominantly C1q, with no evidence of systemic lupus erythematosus. Clinically, it may present as nephrotic syndrome and non-nephrotic proteinuria per se or associated with microhematuria, hypertension, or renal insufficiency. We describe two sisters with C1qNP, who presented with steroid-resistant nephrotic syndrome. Both sisters presented before the age of 2 years, and they showed a poor response to other immunosuppressive therapy. Both girls had normal serum complement levels, negative antinuclear antibodies (ANAs) and negative hepatitis B antigen. Renal biopsy in both patients showed histological features of mesangioproliferative glomerulonephritis, with diffuse "full-house" positive immunofluorescence reaction in the mesangial area. The immunofluorescence reaction for C1q was most intense and co-dominant with IgG in both patients. Correspondingly, electron microscopy demonstrated dense deposits mainly in the mesangial areas too. We report on two young sisters with the characteristic features of C1qNP presented in early childhood. To the best of our knowledge, this is the first report of C1qNP in siblings. MIB Abstract ID Number: 14947 PreMedline Identifier: 17952693 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Gram-Positive Bacterial Infections | ||||
| Hyperlipidemia | ||||
| Immunosuppressants | ||||
| Lupus Nephritis | ||||
Current therapy of lupus nephritis. Which is the best option? Lead Author: Silva-Fernández L Additional Authors: Andreu-Sánchez JL, Ginzler EM. Rev Clin Esp. , 2008-03-01, 208(3):138-41. Servicio de Reumatología. Hospital Universitario Puerta de Hierro, Madrid. Spain. lsilvaf.hpth@salud.madrid.org. Renal involvement in systemic lupus erythematosus (SLE) is an important cause of morbidity and mortality, reaching a prevalence of 39% during the course of the disease. Currently, the therapy for severe lupus nephritis is based on the use of high-dose corticosteroids and immunosuppressive drugs, being traditionally cyclophosphamide the most frequently used agent. Recent studies have demonstrated the efficacy of mycophenolate mofetil as induction therapy for lupus nephritis. Azathioprine, a safe drug during pregnancy, has not been demonstrated to be as effective as mycophenolate or cyclophosphamide as induction therapy, although it is an effective drug for maintenance of remission. MIB Abstract ID Number: 14901 PreMedline Identifier: 18275768 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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Sickle cell nephropathy with diffuse proliferative lupus nephritis: a case reports. Lead Author: Kanodia KV Additional Authors: Vanikar AV, Goplani KR, Gupta SB, Trivedi HL. Diagn Pathol., 2008-02-28, 3(1):9 [Epub ahead of print] ABSTRACT: BACKGROUND: Sickle cell nephropathy (SCN) is an important cause of mortality in patients with sickle cell disease. SCA with systemic lupus erythematosus (SLE) is known in children and less common in adults, however diffuse proliferative lupus nephritis (DPLN) with SCN has rarely been reported in adults. It requires early diagnosis and aggressive management. CASE PRESENTATION: We present here a 35 years old lady with sickle cell disease who presented with edema, dyspnoea on exertion, pyuria and had raised s. creatinine of 7 mg %. Her biopsy revealed SCN with DPLN. She is on maintenance hemodialysis after 2 months of diagnosis. CONCLUSION: DPLN with SCN is a rare entity with poor prognosis, which may be overlooked and needs aggressive management. MIB Abstract ID Number: 14948 PreMedline Identifier: 18307766 *To access this PubMed use the PreMedline Identifier in the PubMed search field. |
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| Multisystem inflammatory disease (MID) | ||||
| Misdiagno* Lupus | ||||
| Mycobacterium Infections | ||||
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