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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
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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
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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]
Lupus treatment has evolved considerably with spectacular advances that can be summarized in 10 points. Hydroxychloroquine and cyclophosphamide are still standard drugs, provided their use is optimized. Contraception and postmenopausal hormone replacement therapy have finally been tested in randomized studies with fairly reassuring results, although prudence remains essential in patients with severe lupus and above all in those with thrombotic complications (antiphospholipid syndrome). Mycophenolic acid has been shown to be useful in the treatment of lupus nephropathies, but its specific place in the therapeutic strategy remains to be defined. Other drugs (sirolimus, abatacept) are currently being evaluated. Anti-lymphocyte B therapies are growing in popularity. Rituximab and other drugs (anti-BAFF, TACI-Fc) are also being evaluated and their results appear very interesting. Interferon alpha (type I) inhibition is an attractive therapeutic approach in lupus but its use in humans is still premature. Peptide vaccination with fragments of autoantibodies or autoantigens is an elegant strategy, and preliminary results justify further studies. Anti-TNF molecules may be beneficial in lupus. Complement inhibition can be useful in lupus and antiphospholipid syndrome but drugs usable in humans (anti-C5) must be developed. Atheromatosis in lupus is the principal cause of morbidity and mortality and must be managed. Smoking cessation is essential, but other approaches (statins) should also be discussed. Many futuristic types of immune manipulation may be envisioned (proteasome inhibition, modulation of Fc gammaRIIB, and modulation of cell signaling (PI3kgamma)). Hence the perspectives are numerous. We will soon be able to optimize the treatment of our patients. Nevertheless, rigorous evaluation of the risk/benefit ratio of new drugs and of their most appropriate place in the therapeutic strategy against systemic lupus is indispensable.
MIB Abstract ID Number: 14878
PreMedline Identifier: 18242045
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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 ***
About La Jolla Pharmaceutical Company
La Jolla Pharmaceutical Company is dedicated to improving and preserving human life by developing innovative pharmaceutical products. The Company's leading product in development is Riquent(R), which is designed to treat lupus renal disease by preventing or delaying renal flares. Lupus renal disease is a leading cause of sickness and death in patients with lupus. The Company has also developed potential small molecule drug candidates to treat various other autoimmune and inflammatory conditions. The Company's common stock is traded on The NASDAQ Global Market under the symbol LJPC. More information about the Company is available on its Web site: http://www.ljpc.com.
This press release and the presentations may contain forward-looking statements within the meaning of the federal securities laws. When used, the words "anticipate," "assume," "believe," "estimate," "expect," "intend," "may," "plan," "project," "result," "should," "will" and similar expressions that do not relate solely to historical matters identify forward-looking statements. Forward-looking statements are subject to risks and uncertainties, both known and unknown and often beyond the Company's control, and are not guarantees of future performance insofar as actual events or results may vary materially from those anticipated. Factors that may cause such a variance consist of, among others, those discussed from time to time in the Company's filings with the Securities and Exchange Commission, including the risks described in "Risk Factors" in the Company's Annual Report on Form 10-K for the year ended December 31, 2006, and specifically the Company's ability to: demonstrate sufficiently Riquent's efficacy and safety in clinical trials; manufacture Riquent on an adequate scale for clinical use; or develop further and commercialize Riquent successfully, either on its own or with a partner. The Company expressly disclaims any responsibility to update forward-looking statements.
La Jolla Pharmaceutical Company
Andrew Wiseman, Ph.D., Sr. Director of Investor Relations
858-646-6615
andrew.wiseman@ljpc.com
or
The Communications Strategy Group
Edward Agne, President
781-631-3117
edagne@comstratgroup.com
Logo: http://ljpc.com/index.html
MIB Abstract ID Number: 14893
Proquest Identifier: 1436684821
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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
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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 ***
Novo Nordisk is conducting four clinical trials of Interleukin 21 in patients with various types of cancer, while ZymoGenetics is conducting three separate clinical trials of the drug. The two companies share data. Interleukin 31, designed to treat inflammatory disease, is in preclinical research.
In a statement that accompanied its fourth-quarter results in late January, Novo Nordisk said it planned to out-license Interleukin 21 to another company, as part of a strategy to terminate its research on oncology and focus instead on inflammatory disease. The company holds rights to the drug outside North America. Novo Nordisk did not explain why it was curtailing its partnership on Interleukin 31. The company will transfer its rights to that drug outside North America to Merck Serono, which also was developing the drug, according to a ZymoGenetics filing with the Securities and Exchange Commission.
Susan Specht, a spokeswoman for ZymoGenetics, downplayed Novo Nordisk's decision to out-license work on Interleukin 21.
"We're excited because it means that we'll have a partner with expertise in oncology," she said. She referred questions about Interleukin 31 to Novo Nordisk. A spokesman for Novo Nordisk, Sean Clements, wrote in an e-mail that he did not have information on Interleukin 31 and added that the company did not typically comment on preclinical compounds.
But Kevin DeGeeter, an analyst at Oppenheimer & Co. who also has questioned the prospects of Recothrom, said that the loss of the two partnerships was a blow to ZymoGenetics.
"Just because Novo says it wants to out-license the program doesn't mean it's going to find a partner with the expertise and financial resources that Novo brought to the table," he said.
"There has been a considerable amount of money to get to this point in development," he said. "It's not exactly a vote of confidence for the work that Zymo is doing. It looks a lot to me that Novo did what every drug company does. They looked at the data, (and) drew some conclusions (that) putting more of their own money into it was not the best decision for them."
He said that Novo Nordisk's oncology program included five clinical trials, four of which involved Interleukin 21. Thus, he said in a research report, "Novo's plan to exit oncology drug development reflects, at least in part, a tepid view of the prospects of Interleukin 21."
Novo Nordisk spun off ZymoGenetics in 2000. As part of the spinoff, DeGeeter said, Novo Nordisk licensed seven ZymoGenetics compounds, including Interleukin 21 and Interleukin 31. The company has now returned four of the seven compounds to ZymoGenetics, including Interleukin 31.
Two other compounds are "mired in preclinical development," DeGeeter wrote in a research report, while Novo Nordisk is now out-licensing Interleukin 21.
"It raises a little bit of a red flag. Where is the next success going to come from?" he said in an interview.
In addition to Interleukin 21 and Interleukin 31, ZymoGenetics is developing Atacicept to treat rheumatoid arthritis and multiple sclerosis.
In a bid to concentrate on a smaller number of programs, ZymoGenetics said Feb. 13 it would eliminate 80 positions through a combination of layoffs, attrition and the elimination of unfilled positions by scaling back some early-stage research programs. In its filing with the Securities and Exchange Commission on Friday, ZymoGenetics said it had laid off 40 employees.
MIB Abstract ID Number: 14735
Proquest Identifier: 1441633301
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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
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Systemic lupus erythematosus.
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
<<No Abstract Available>>
MIB Abstract ID Number: 14926
PreMedline Identifier: 18227111
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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
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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
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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
Comment in:
Ann Rheum Dis. 2008 Mar;67(3):281-2.
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
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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
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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 ***
According to the Epilepsy Foundation, for example, seizures are twice as common in Hispanics as they are in non-Hispanics and lupus is twice as prevalent among Hispanic women as it is among Caucasian women. The Alzheimer's Foundation has found that Hispanics are at greater risk to develop dementia than the rest of the population, and the number of Hispanics with Alzheimer's disease is expected to grow dramatically in the coming years. Additionally, stroke has been found to be the fourth leading cause of death among Hispanics, according to the American Stroke Association.
"The medicines now in the research pipeline will add to the substantial progress made in the last five years by biopharmaceutical companies in developing new and more effective neurological treatments," said PhRMA President and CEO Billy Tauzin. "The growing number of older Americans nationwide, who are susceptible to conditions such as Alzheimer's and Parkinson's disease, will especially benefit from these new medicines. This strong commitment to research is a product of the determination of the men and women working for America's pharmaceutical research companies to develop new medicines that will enable patients to live longer, healthier, and more productive lives."
The neurological medicines in development include 82 for Alzheimer's disease, 26 for epilepsy, 23 for stroke, 30 for Parkinson's disease, 58 for brain tumors, 46 for multiple sclerosis, 29 for migraine and other headaches, 35 for sleep disorders, and 171 for several types of pain. Other medicines in development target brain injuries, Huntington's disease, spinal cord injuries, cerebral palsy and restless legs syndrome.
These neurological conditions cost hundreds of billions of dollars in care, lost workdays, and reduced productivity annually, with the cost of Alzheimer's alone tallying more than $148 billion.
"Researchers are making exciting progress in the search for new cures and treatments for neurological disorders. But these efforts are wasted if the medicines we develop aren't accessible to patients who need them," said Johnson.
Help is available to patients in need through the Partnership for Prescription Assistance, a program sponsored by America's pharmaceutical research companies. To date, the PPA has helped nearly 5 million patients nationwide, including more than 365,000 people in Texas. Since its launch in April 2005, the PPA bus tour has visited all 50 states and more than 1,500 cities to educate people about patient assistance programs. Just last month, the bus made its ninth trip through Texas and visited more than 30 cities.
The "Help is Here Express" is staffed by trained specialists able to quickly help uninsured patients in need access information on more than 475 patient assistance programs, including nearly 200 programs offered by pharmaceutical companies. When the "Help is Here Express" moves on, patients can visit PPA's easy-to-use Web site (www.pparx.org) or call the toll-free phone number (1-888-4PPA-NOW).
To read the Medicines in Development for Neurological Disorders 2008 on the PhRMA Web site, click on the following link: http://www.phrma.org/
The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country's leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $43 billion in 2006 in discovering and developing new medicines. Industry wide research and investment reached a record $55.2 billion in 2006.
PhRMA Internet Address: http://phrma.org
For information on stories of hope and survival, visit: http://sharingmiracles.com/
For information on how innovative medicines save lives, visit: http://innovation.org
For information on the Partnership for Prescription Assistance, visit: http://pparx.org
For information on the danger of imported drugs, visit: http://buysafedrugs.info
SOURCE Pharmaceutical Research and Manufacturers of America
Credit: Pharmaceutical Research and Manufacturers of America
MIB Abstract ID Number: 14793
Proquest Identifier: 1440005071
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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
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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 ***
"The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice," wrote J.L. Lamoureux and colleagues.
The researchers concluded: "Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity.'."
Lamoureux and colleagues published their study in the Journal of Experimental Medicine (Reduced receptor editing in lupus-prone MRL/1pr mice. Journal of Experimental Medicine, 2007;204(12):2853-2864).
For additional information, contact A.J. Feeney, Scripps Research Institute, Dept. of Immunology, 10666 N Torrey Pines Rd., La Jolla, CA 92037, USA.
Publisher contact information for the Journal of Experimental Medicine is: Rockefeller University Press, 1114 First Avenue, 4TH FL, New York, NY 10021, USA.
MIB Abstract ID Number: 14896
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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
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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
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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
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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:
- N Engl J Med. 2008 Feb 28;358(9):956-61.
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 stratificat | |
