text: content Lupus ABSTRACTS Alexander NJ., 1987. The type of dietary fat affects the severity of autoimmune disease in NZB/NZW mice. Araghi-Niknam M., 1997. Cytokine dysregulation and increased oxidation is prevented by dehydroepiandrosterone in mice infected with murine leukemia retrovirus. Belmont M., 1998. Lupus Clinical Overview Berk L., 1994. The laughter-immune connection. An interview with J.R. Dunn. Bottiglieri T., 1994. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Breban M., 1999. Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis. Callegari PE ., 1995. Laboratory tests for rheumatic diseases. When are they useful? Clark WF., 2001. Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study. Cohen N., 1994. Pavlovian conditioning of the immune system. Cooke HM., 1985. Dietary intervention in systemic lupus erythematosus: 4 cases of clinical remission and reversal of abnormal pathology. Corman LC., 1985. The role of diet in animal models of systemic lupus erythematosus: possible implications for human lupus. Cuadrado MJ., 2001. Thalidomide: Efficacy and Safety in 30 Patients with Lupus and Skin Involvement . DeHoratius R., 1997. Genetics and lupus. Gourley MF., 1996. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Jiang S., 1998. Dehydroepiandrosterone synergizes with antioxidant supplements for immune restoration in old as well as retrovirus-infected mice. Kakuda T., 2000. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Kanda N., 1996. Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Keisler LW., 1995. Aberrant hormone balance in fetal autoimmune NZB/W mice following prenatal exposure to testosterone excess or the androgen blocker flutamide. Kelly V., 1985. A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus is MRL-mice. Lakshminarayanan S., 2001. Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. Leiba A., 200.1 Diet and lupus. Lupus Alert., 1988. Lupus: Support and Survival: Vitamins and Nutritional Management of Lupus Pisetsky DS., 1993. Systemic lupus erythematous. Rahman P., 1997. Cytotoxic therapy in systemic lupus erythematosus. Experience from a single center. Rider V., 2001. Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. Robinson DR., 1985. The protective effect of dietary fish oil on murine lupus. Schroeder JO., 1997. Plasmapheresis and subsequent pulse cyclophosphamide in severe systemic lupus erythematosus. Preliminary results of the LPSG-Trial. Sotolongo JR Jr., 1984. Successful treatment of lupus erythematosus cystitis with DMSO. Suzuki T., 1995. Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). Trentham DE., 1993. Effects of oral administration of type II collagen on rheumatoid arthritis. Tsao BP., 1997. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. van Vollenhoven RF., 2000. Dehydroepiandrosterone in systemic lupus erythematosus. Wallace D., 1995. The Lupus Book Yang BC., 1998. Exogenous dehydroepiandrosterone modified the expression of T helper-related cytokines in NZB/NZW F1 mice. Yokogoshi H., 1998. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. The type of dietary fat affects the severity of autoimmune disease in NZB/NZW mice. Alexander NJ, Smythe NL, Jokinen MP Am J Pathol 1987 Apr;127(1):106-21 The type of dietary fat dramatically affects the onset of autoimmune disease in lupus-prone female New Zealand Black/New Zealand White F1 (B/W) mice. Disease development was strikingly slowed in mice fed a diet containing quantities of omega-3 fatty acids (fish oil, FO). By 10 months of age, 94% of the FO mice were still living, whereas all the mice fed a saturated fat diet (lard,L) were dead. Those mice fed a corn oil (CO) diet were intermediate with 35% alive at the 10-month time evaluation. Long after the L and CO groups had succumbed to glomerulonephritis, the FO group had negligible proteinuria. Both B and T cell function, particularly antibody production and resultant circulating immune complex (CIC) levels, were modified by the type of dietary fat. FO mice exhibited lower levels of anti-ds-DNA and lower levels of CICs than L or CO mice. B/W antibody response to a T-independent antigen (DNP-dextran) was enhanced at 8 months of age in FO mice, whereas it was suppressed in L mice. T-dependent (sheep red blood cell) responses at that time period were reduced in all the diet groups, a reflection of the reduced numbers of accessory T cells as determined by FACS analysis. The natural killer (NK) response to YAC-1 cells decreased in the L group from 5 to 9 months of age but remained unchanged in the CO and FO groups. Severe glomerulonephritis was the most common histopathologic finding in the L and CO groups. Arteritis was found in the spleens of nearly all the L and CO mice. Arteritis of the heart, colon and intestine, stomach, kidney, and liver were also seen principally in the L mice. In contrast, most FO mice had minimal to mild glomerulonephritis and no or minimal arteritis in the spleen. It is likely omega-3 fatty acids of fish oil reduce immune-complex-induced glomerulonephritis through production of prostaglandin metabolites with attenuated activity and/or through altering cell membrane structure and fluidity, which may, in turn, affect the responsiveness of immune cells. Cytokine dysregulation and increased oxidation is prevented by dehydroepiandrosterone in mice infected with murine leukemia retrovirus. Araghi-Niknam M, Zhang Z, Jiang S, Call O, Eskelson CD, Watson RR Arizona Prevention Center, University of Arizona, Tucson 85724, USA. Proc Soc Exp Biol Med 1997 Dec;216(3):386-91 The effects of murine leukemia retrovirus infection on production of cytokines was investigated in mice fed different doses of dehydroepiandrosterone (DHEA). Young C57BL/6 female mice were injected with LP-BM5 murine retrovirus or were kept as uninfected controls. Two weeks later, each group was divided into subgroups: fed unsupplemented AIN 93 diet as the control, or diets supplemented with 0.02% DHEA (0.9 mg/mouse/day) or 0.06% DHEA (2.7 mg/mouse/day). The uninfected mice supplemented with 0.06% DHEA showed a significant (P < 0.05) increase in interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) production, and hepatic vitamin E levels. Retroviral infection induced severe oxidative stress that was reduced by DHEAS supplementation in retrovirally infected mice. DHEA supplementation prevented the retrovirus-induced loss of cytokines (IL-2 and IFN-gamma) secretion by mitogen stimulated spleen cells. DHEA also suppressed the production of cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) by T helper 2 (Th2) cells which were otherwise stimulated by retrovirus infection. Thus, immune dysfunction and increased oxidation induced by murine retrovirus infection were largely prevented by DHEA. Lupus Clinical Overview 1998. Belmont, M. Dr. Belmont's Homepage (www.cerebel.com/lupus). The laughter-immune connection. An interview with J.R. Dunn. Berk, L., Tan, S. Humor and Health Letter 1994 Nov-Dec; 3(6): 1-8. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Bottiglieri T, Hyland K, Reynolds EH. Metabolic Disease Center, Baylor Research Institute, Dallas, Texas. Drugs. 1994 Aug;48(2):137-52. This review focuses on the biochemical and clinical aspects of methylation in neuropsychiatric disorders and the clinical potential of their treatment with ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders. Efficacy of thalidomide in the treatment of refractory ankylosing spondylitis. Breban M, Gombert B, Amor B, Dougados M Hopital Cochin, Universite Rene Descartes, Paris, France. Arthritis Rheum 1999 Mar;42(3):580-1 No abstract. Laboratory tests for rheumatic diseases. When are they useful? Callegari PE, Williams WV. Division of Rheumatology, University of Pennsylvania School of Medicine, Philadelphia, USA. Postgrad Med. 1995 Apr;97(4):65-8, 71-4. Because negative tests often do not exclude a rheumatic disease and positive tests do not always diagnose it, judicious use of laboratory testing in patients with suspected rheumatic disease is essential. The final diagnosis must be made clinically. However, when the tests are used in conjunction with clinical manifestations, they may help differentiate the numerous rheumatic disorders, and they may also be of value in monitoring activity of the disease. Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study. Clark WF, Kortas C, Heidenheim AP, Garland J, Spanner E, Parbtani A. London Health Sciences Centre, The University of Western Ontario, Canada. firstname.lastname@example.com J Am Coll Nutr 2001 Apr;20(2 Suppl):143-8 OBJECTIVE: The objective of this study was to determine the renoprotective effects of ground flaxseed in patients with lupus nephritis. METHODS: Forty patients with lupus nephritis were asked to participate in a randomized crossover trial of flaxseed. Twenty-three agreed and were randomized to receive 30 grams of ground flaxseed daily or control (no placebo) for one year, followed by a twelve-week washout period and the reverse treatment for one year. At baseline and six month intervals, serum phospholipids, flaxseed sachet counts, serum creatinine, 12-hour urine albumin excretion and urine albumin to creatinine ratios, serum viscosity and plasma lipids were measured. RESULTS: There were eight drop-outs and of the 15 remaining subjects flaxseed sachet count and serum phospholipid levels indicated only nine were adherent to the flaxseed diet. Plasma lipids and serum viscosity were unaltered by the flaxseed supplementation whereas serum creatinine in the compliant patients during flaxseed administration declined from a mean of 0.97+/-0.31 mg/dL to a mean of 0.94+/-0.30 mg/dL and rose in the control phase to a mean of 1.03+/-0.28 mg/dL [p value <0.08]. Of the fifteen patients who completed the study, similar changes were noted [p value <0.1]. The nine compliant patients had lower serum creatinines at the end of the two-year study than the 17 patients who refused to participate [p<0.05]. Microalbumin at baseline declined in both control and flaxseed time periods, but there was a trend for a greater decline during flaxseed administration [p<0.2]. CONCLUSIONS: Flaxseed appears to be renoprotective in lupus nephritis, but this interpretation is affected by under powering due to poor adherence and potential Hawthorne effects. Pavlovian conditioning of the immune system. Cohen N, Moynihan JA, Ader R Department of Microbiology and Immunology, University of Rochester Medical Center, N.Y. 14642. Int Arch Allergy Immunol 1994 Oct;105(2):101-6 In the classical Pavlovian conditioning paradigm, a stimulus that unconditionally elicits a physiological response is repeatedly paired with a neutral stimulus that does not elicit that same response. Eventually, the neutral stimulus becomes a conditioned stimulus in that it elicits the physiological response in the absence of an unconditioned stimulus. Here we summarize experiments in which Pavlovian conditioning has revealed an intimate relationship between the central nervous system and the immune system. Dietary intervention in systemic lupus erythematosus: 4 cases of clinical remission and reversal of abnormal pathology. Cooke, H.M., Reading, C.M. Int. Clin. Nutr. Rev. 1985; 5(4): 166-76. No abstract found The role of diet in animal models of systemic lupus erythematosus: possible implications for human lupus. Corman LC Semin Arthritis Rheum 1985 Aug;15(1):61-9 Studies of diet in the mouse model of SLE have established the beneficial effects of a low calorie, low fat diet in these animals as well as the importance of the specific source of dietary fat. The role of zinc in murine and human SLE is less clear. The reported improvement of patients with SLE and other related diseases on a low phenylalanine and tyrosine diet high in fish content, and the lupus inducing capacity of a nonphysiologic amino acid present in alfalfa are also reviewed. The need for carefully controlled prospective studies of diet in patients with SLE is noted, and a diet of potential therapeutic benefit is described. Thalidomide: Efficacy and Safety in 30 Patients with Lupus and Skin Involvement 2001. Cuadrado, M.J., Smith, E., Gordon, P. et al. Presented at the 65th Annual Meeting of the American College of Rheumatology, San Francisco, California, November 10-15, 2001. Genetics and lupus. DeHoratius, R. Learning About Lupus: A User Friendly Guide 1997. Moore, M., McGrory, C., Rosenthal, R., Eds. Ardmore, PA: Lupus Foundation of Delaware Valley. Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis. A randomized, controlled trial. Gourley MF, Austin HA 3rd, Scott D, Yarboro CH, Vaughan EM, Muir J, Boumpas DT, Klippel JH, Balow JE, Steinberg AD National Institutes of Health, Bethesda, Maryland, USA. Ann Intern Med 1996 Oct 1;125(7):549-57 BACKGROUND: Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis. OBJECTIVE: To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone. DESIGN: Randomized, controlled trial with at least 5 years of follow-up. SETTING: Government referral-based research hospital. PATIENTS: 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (> 1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis. INTERVENTIONS: Bolus therapy with methylprednisolone (1 g/m2 body surface area), given monthly for at least 1 year; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m2 body surface area), given monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide. MEASUREMENTS: 1) Renal remission (defined as < 10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of < 1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis. RESULTS: Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methylprednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group. 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes zoster (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group. 32% of the combination therapy group, and 7.4% of the methylprednisolone group). CONCLUSIONS: Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen. Dehydroepiandrosterone synergizes with antioxidant supplements for immune restoration in old as well as retrovirus-infected mice. Jiang, S., Lee, J., Zang, Z. et al. J. Nutr. Biochem. 1998; 9(7): 362-9. Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat. Kakuda T, Nozawa A, Unno T, Okamura N, Okai O. Central Research Institute, Itoen Ltd., Shizuoka, Japan. email@example.com Biosci Biotechnol Biochem. 2000 Feb;64(2):287-93. In this study, the inhibiting action of theanine on the excitation by caffeine at the concentration regularly associated with drinking tea was investigated using electroencephalography (EEG) in rats. First, the stimulatory action by caffeine i.v. administration at a level higher than 5 micromol/kg (0.970 mg/kg) b.w. was shown by means of brain wave analysis, and this level was suggested as the minimum dose of caffeine as a stimulant. Next, the stimulatory effects of caffeine were inhibited by an i.v. administration of theanine at a level higher than 5 micromol/kg (0.781 mg/kg) b.w., and the results suggested that theanine has an antagonistic effect on caffeine's stimulatory action at an almost equivalent molar concentration. On the other hand, the excitatory effects were shown in the rat i.v. administered 1 and 2 micromol/kg (0.174 and 0.348 mg/kg) b.w. of theanine alone. These results suggested two effects of theanine, depending on its concentration. Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Kanda N, Tsuchida T, Tamaki K Department of Dermatology, Faculty of Medicine, University of Tokyo, Japan. Clin Exp Immunol 1996 Nov;106(2):410-5 We studied the in vitro effect of testosterone on spontaneous immunoglobulin production by human peripheral blood mononuclear cells (PBMC). Testosterone inhibited IgG and IgM production by PBMC both from males and females. The inhibitory effect of testosterone was revealed at doses more than 1 nM, increased dose-dependently, and reached a plateau at 100 nM. At doses < 1000 nM, testosterone did not reduce cell viability. Testosterone treatment reduced IgG production by 59.0% and that of IgM by 61.3% compared with control. Immunoglobulin production by B cells was also suppressed by testosterone, though the magnitude of the suppressive effect on B cells was lower than that on whole PBMC; testosterone-induced decrease of IgG production compared with control was 26.9% and that of IgM was 24.9%. Exogenous IL-6 partially restored the impaired immunoglobulin production of testosterone-treated PBMC; IgG production in testosterone culture was increased by IL-6 from 35.6% to 66.5% of control and that of IgM was also increased from 38.9% to 71.2%, respectively. Testosterone treatment reduced IL-6 production of monocytes by 78.4% compared with control, but neither affected that of T cells or B cells. These results suggest that testosterone may suppress immunoglobulin production of human PBMC directly by inhibiting B cell activity and indirectly by reducing IL-6 production of monocytes. It is thus indicated that this hormone may have protective and therapeutic effects on human autoimmune diseases. Aberrant hormone balance in fetal autoimmune NZB/W mice following prenatal exposure to testosterone excess or the androgen blocker flutamide. Keisler LW, vom Saal FS, Keisler DH, Rudeen PK, Walker SE Department of Veterans Affairs Medical Center, Columbia, Missouri. Biol Reprod 1995 Nov;53(5):1190-7 F1 hybrid New Zealand Black (NZB) x New Zealand White (NZW) (NZB/W) mice are hormone-sensitive models of the human disease systemic lupus erythematosus. In this study, NZB/W fetuses produced by pregnant NZB mice were compared with F1 C57BL/6 x DBA/2 (C57/DBA2) hybrid fetuses produced by nonautoimmune C57BL/6 females. Dams of both strains were treated with testosterone or the androgen blocker flutamide to alter the hormonal environment in late gestation. Hormonal changes in male fetuses carried by treated dams were of interest because hormonal manipulation using either testosterone or flutamide has been shown to increase longevity in male NZB/W offspring. Testosterone-implanted NZB dams developed the expected elevations in circulating maternal testosterone, whereas C57BL/6 dams treated with either testosterone or flutamide had elevated maternal serum testosterone concentrations. The treatment-induced changes in circulating testosterone in NZB dams and C57BL/6 dams were not reflected in serum from 18-day NZB/W or C57/DBA2 fetuses. Male NZB/W offspring from untreated control NZB dams had unexpectedly high levels of serum estradiol and alpha fetoprotein and relatively low extractable testicular testosterone, compared with nonautoimmune male control fetuses. Maternal testosterone treatments produced a significant decrease in serum estradiol in NZB/W male fetuses, and placental testosterone content was also reduced. Our findings suggest that placental androgen control is regulated differently in the autoimmune NZB-NZB/W vs. the nonautoimmune C57BL/6-C57/DBA2 maternal-placental-fetal unit. A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus is MRL-mice. Kelly, V. et al. J. Immunol. 1985 Mar; 134(3): l914-9. No abstract available. Factors associated with low bone mineral density in female patients with systemic lupus erythematosus. Lakshminarayanan S, Walsh S, Mohanraj M, Rothfield N. Department of Medicine, University of Connecticut Health Center, Farmington 06030-1310, USA. J Rheumatol 2001 Jan;28(1):102-8 OBJECTIVE: To study risk factors for low bone mineral density (BMD, g/cm) in patients with systemic lupus erythematosus (SLE). METHODS: Ninety-two consecutive patients with SLE followed by rheumatology faculty between 1997 and 1999 completed a questionnaire regarding lifestyle during the clinic visit, a chart review was performed, and data were collected for the time of the first dual energy x-ray absorptiometry (DXA) examination. Univariate and multivariate statistical analyses were used to assess relationships between various risk factors and BMD. RESULTS: Ninety-eight percent of patients had received prednisone, 51% were postmenopausal (9 of whom received hormone replacement therapy), 68% had received hydroxychloroquine, and 15% were osteoporotic. The following factors were found to be significantly related to lower BMD by univariate analysis: Caucasian race, older age at diagnosis, higher age at the time of the first DXA, longer disease duration, higher cumulative corticosteroid dose, higher SLE Damage Index score, and postmenopausal status. In the multivariate analysis only the following factors were significant: Caucasian race, increased number of pregnancies, postmenopausal status, higher SLE Damage Index, and higher cumulative corticosteroid dose. An unexpected finding was that taking hydroxychloroquine was the only factor associated with higher BMD of the hip and spine in the univariate analysis, and it remained predictive of higher BMD of the hip and spine in the multivariate analysis. CONCLUSION: Hydroxychloroquine appears to protect against low BMD in corticosteroid treated patients with SLE. Diet and lupus. Leiba A, Amital H, Gershwin ME, Shoenfeld Y. Research Unit of Autoimmune Diseases, Department of Medicine B Chaim Sheba Medical Center, Tel Hashomer, Israel. Lupus. 2001;10(3):246-8. The effect of dietary modifications has been extensively studied in lupus animal models. Calorie, protein, and especially fat restriction, caused a significant reduction in immune-complex deposition in the kidney, reduced proteinuria and prolongation of the mice's life span. The addition of polyunsaturated fatty acids (PUFAs), such as fish oil or linseed oil, was also related to decreased mice morbidity and mortality in animal models of lupus and of antiphospholipid syndrome. PUFAs such as eicosapetaenoic acid (EPA) and docosahexaenoic acid (DHA) competitively inhibit arachidonic acid with a resultant decrease in inflammatory eicosanoids and cytokines. Human studies support the effect of a PUFAs-enriched diet, both scrologically and clinically. Large scale clinical studies are needed to confirm the primary results. Lupus: Support and Survival: Vitamins and Nutritional Management of Lupus 1988. Lupus Alert. Rockville, MD: Lupus Foundation of America (www.lupus.org). Systemic lupus erythematous. Pisetsky, D.S. Primer on the Rheumatic Diseases, Tenth Edition 1993, pp. 100-5. Schumacher, H.R., Klippel, J.H., Koopman, W.J., Eds. Atlanta: The Arthritis Foundation. Cytotoxic therapy in systemic lupus erythematosus. Experience from a single center. Rahman P, Humphrey-Murto S, Gladman DD, Urowitz MB Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Hospital, Ontario, Canada. Medicine (Baltimore) 1997 Nov;76(6):432-7 The present survey of cytotoxic therapy from a single large lupus clinic has shown that approximately 33% of the patients have received cytotoxic therapy at some point in their course. These agents were initiated for a variety of manifestations, with renal manifestations being the major indication, accounting for 28.2% of the cytotoxic agents used. Other common indications for initiation of cytotoxic therapy included steroid sparing (18.4%), global flare (12.5%), neurologic manifestations (11.4%), and musculoskeletal (8.6%). Azathioprine, methotrexate, and cyclophosphamide accounted for 98% of all cytotoxic agents used. Azathioprine was the most frequently used cytotoxic drug (70%), followed by methotrexate (21.5%) and cyclophosphamide (9.4%). Cytotoxic agents were used sequentially in 12.5% of patients and in combination in 4.2% of the patients. Overall, the use of cytotoxic therapy appears to be beneficial in reducing global disease activity, as the mean SLEDAI fell by 2.59 (33%) over 6 months of cytotoxic therapy, and the mean steroid dose was reduced by 37% over the same time period. There was also an improvement in most organ-specific indications with the use of cytotoxic agents. Overall the cytotoxic agents were well tolerated, with 17% of the courses being discontinued due to a side effect. Cytopenia was the most common side effect necessitating discontinuation of cytotoxic agents. Estrogen increases CD40 ligand expression in T cells from women with systemic lupus erythematosus. Rider V, Jones S, Evans M, Bassiri H, Afsar Z, Abdou NI. School of Biological Sciences, University of Missouri-Kansas City, USA. email@example.com J Rheumatol. 2001 Dec;28(12):2644-9. OBJECTIVE: To examine the in vitro effects of estrogen on CD40 ligand (CD40L) expression in peripheral blood T cells isolated from patients with systemic lupus erythematosus (SLE) and normal controls. METHODS: T cells from female patients with SLE and controls were cultured in serum-free medium without and with 2-fluoroestradiol. Some T cells were activated by further culture on anti-CD3 coated plates. Calcineurin was activated in some T cells by culture in ionomycin. Cell surface CD40L was quantitated by FACS analysis. mRNA expression was measured using semiquantitative PCR. RESULTS: Lupus T cells cultured in medium containing 2-fluoroestradiol showed a significant (p = 0.04) increase in the amount of CD40L on the cell surface, but not in the number of positive cells, compared to the same T cells cultured without estradiol. Estradiol did not significantly change CD40L expression on the surface of T cells from normal women. In addition, the difference in cell surface CD40L between T cells cultured without and with estradiol was significantly greater (p = 0.048) on SLE than on normal T cells. Culture of SLE T cells in medium containing 2-fluoroestradiol followed by T cell receptor (TCR) activation for 2 h using anti-CD3 resulted in a significant (p = 0.04) estrogen dependent increase in CD40L mRNA. The estrogen dependent increases in SLE T cell CD40L mRNA and cell surface protein were blocked by the estrogen receptor antagonist ICI 182,780. SLE and normal T cells pretreated with estradiol and cultured with ionomycin for 2 h to activate calcineurin showed no significant differences in CD40L mRNA. CONCLUSION: These results suggest that estradiol, working through the estrogen receptor, stimulates the expression of CD40L in unstimulated and activated SLE T cells. Estradiol effects may be exerted on multiple regulatory steps that control CD40L expression. The estrogen dependent increase in CD40L expression could hyperstimulate SLE T cells and thereby contribute to the pathogenesis of SLE. The protective effect of dietary fish oil on murine lupus. Robinson DR, Prickett JD, Polisson R, Steinberg AD, Levine L Prostaglandins 1985 Jul;30(1):51-75 Dietary marine lipids markedly reduce the severity of glomerulonephritis and its associated mortality in inbred strains of mice developing autoimmune disease, a model for human systemic lupus erythematosus. We report here the influence of varying the dose of menhaden oil and the timing of its administration on the mortality of female (NZB x NZW) F1 mice. After ingesting 25 wt% menhaden oil (MO) for periods of 1.5 weeks to 12 months, there was a stable content of tissue n-3 fatty acids, with total n-3 fatty acids of 28% and 35% in spleen and liver, respectively. The extent of protection from mortality was dependent on the dose of MO with marked protection at doses of 11 to 25%, marginal protection at 5.5% and no protection at 2.5% MO. Delay in the institution of MO until ages 5 or 7 months still resulted in large reductions of mortality. Conversely, institution of a MO diet from 6 weeks until ages 5 to 7 months followed by a change to beef tallow resulted in little protection. Serum levels of 4 cyclooxygenase products were reduced ranging from 26 to 76% in mice fed MO diets, compared to mice fed beef tallow, based on radioimmunoassay. The degree of reduction of mortality on different doses of MO was correlated best with tissue levels of C22:5, and levels of C20:5 and C22:6 were similar at high and low doses of MO, suggesting that levels of 22:5 may be related to the protective effects of marine lipids on autoimmune disease. Plasmapheresis and subsequent pulse cyclophosphamide in severe systemic lupus erythematosus. Preliminary results of the LPSG-Trial. Schroeder, J.O., Schwab, U., Zeuner, R. et al. Arthritis Rheum. 1997 Sep; 40(9, Suppl.): S325. No abstract available. Successful treatment of lupus erythematosus cystitis with DMSO. Sotolongo JR Jr, Swerdlow F, Schiff HI, Schapira HE Urology 1984 Feb;23(2):125-7 Systemic lupus erythematosus patients sometimes present with pathologically confirmed lupus interstitial cystitis. Treatment with prednisone has not been observed to be successful. Two patients are presented who were successfully treated with intravesical dimethyl sulfoxide (DMSO). Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). Suzuki T, Suzuki N, Engleman EG, Mizushima Y, Sakane T Department of Immunology, St. Marianna University School of Medicine, Kanagawa, Japan. Clin Exp Immunol 1995 Feb;99(2):251-5 The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum. Effects of oral administration of type II collagen on rheumatoid arthritis. Trentham DE, Dynesius-Trentham RA, Orav EJ, Combitchi D, Lorenzo C, Sewell KL, Hafler DA, Weiner HL Department of Medicine, Beth Israel Hospital, Boston, MA. as reported by The Arthritis Foundation (www.arthritis.org). Science 1993 Sep 24;261(5129):1727-30 Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis. Evidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus. Tsao BP, Cantor RM, Kalunian KC, Chen CJ, Badsha H, Singh R, Wallace DJ, Kitridou RC, Chen SL, Shen N, Song YW, Isenberg DA, Yu CL, Hahn BH, Rotter JI.University of California, Los Angeles, USA. firstname.lastname@example.com J Clin Invest 1997 Feb 15;99(4):725-31 Genetic susceptibility confers significant risk for systemic lupus erythematosus (SLE). The MHC region and other polymorphic loci have been associated with SLE. Because more compelling evidence for an involvement of a genetic locus includes linkage, we tested a candidate region homologous to a murine SLE susceptibility region in 52 SLE-affected sibpairs from three ethnic groups. We analyzed seven microsatellite markers from the human chromosome 1q31-q42 region corresponding to the telomeric end of mouse chromosome 1, the region where specific manifestations of murine lupus, including glomerulonephritis and IgG antichromatin, have been mapped. Comparing the mean allele sharing in affected sibpairs of each of these seven markers to their expected values of 0.50, only the five markers located at 1q41-q42 showed evidence for linkage (P = 0.0005-0.08). Serum levels of IgG antichromatin also showed evidence for linkage to two of these five markers (P = 0.04), suggesting that this phenotype is conserved between mice and humans. Compared to the expected random distribution, the trend of increased sharing of haplotypes was observed in affected sibpairs from three ethnic groups (P < 0.01). We concluded that this candidate 1q41-q42 region probably contains a susceptibility gene(s) that confers risk for SLE in multiple ethnic groups. Dehydroepiandrosterone in systemic lupus erythematosus. van Vollenhoven RF. Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden. firstname.lastname@example.com Rheum Dis Clin North Am. 2000 May;26(2):349-62. DHEA has shown promise for the treatment of SLE in three controlled and several uncontrolled clinical trials, including one large multicenter study comprising nearly 200 patients. The main benefits of DHEA seem to be a decrease in corticosteroid requirements and improved overall symptomatology. Intriguing aspects of DHEA treatment in SLE that require further study are a possible bone protective effect and improvements in cognitive function. The most frequent side effect is mild acneiform dermatitis, and long-term concerns include lowered HDL cholesterol. The Lupus Book 1995. Wallace, D. New York: Oxford University Press. Exogenous dehydroepiandrosterone modified the expression of T helper-related cytokines in NZB/NZW F1 mice. Yang BC, Liu CW, Chen YC, Yu CK Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. email@example.com Immunol Invest 1998 Jul-Sep;27(4-5):291-302 The onset of lupus-like disease in NZB/NZW F1 mice was correlated with the expression of IL-10 at 4 m of age, and with a sequential enhanced expression of IFN-gamma and IL-6 between 6 to 8 m of age. The expression of IFN-gamma and IL-6 was associated with exacerbation of disease symptom, production of anti-DNA antibody, and increase in total serum IgG1. Exogenous dehydroepiandrosterone (DHEA) given in animal diet significantly prolonged survival, and delayed formation of autoantibody of NZB/NZW F1 mice as compared to mice fed on control diet. The effect of DHEA paralleled a delay in the expression of IL-10 and IL-6 and an earlier detection of IL-12 transcripts. Moreover, DHEA-fed mice had higher serum IgG2a level than control diet-fed mice. Collectively, DHEA may modify the activation of distinct subset of T helper cells in NZB/NZW F1 mice at different phases of disease progression. Effect of theanine, r-glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Yokogoshi H, Kobayashi M, Mochizuki M, Terashima T. School of Food and Nutritional Sciences, The University of Shizuoka, Yada, Shizuoka, Japan. email@example.com Neurochem Res. 1998 May;23(5):667-73. Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.


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20% Off Nursery Bedding
When you buy $75 or more nursery bedding
Use Coupon Code: BSND20
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Phone: (601) 362-7257
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The DaVinci Parker 4-in-1 Convertible Crib is engineered for years of comfort and style. With a discreet drawer for easy storage, the Parker crib is just what baby needs. Crib converts into toddler bed, daybed and full sized bed.(with separate purchase of conversion kit).
Maximum Weights: Stop using when child begins to climb or reaches 35" Toddler Bed: 50 lbs. Full Size Bed: 165 lbs.
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Book your room at The Central Palace
Double Room, Jetted TubMax Occupancy: 3 guests (up to 2 children, 2 infants)
Signature Room, 2 Single Beds, Jetted TubMax Occupancy: 3 guests (up to 2 children, 2 infants)
Triple Room, Jetted TubMax Occupancy: 3 guests (up to 2 children, 2 infants)
Junior Suite, Jetted TubMax Occupancy: 4 guests (up to 2 children, 2 infants)
Suite, 1 King Bed with Sofabed, Jetted TubMax Occupancy: 4 guests (up to 3 children, 2 infants)
Bosphorus SuiteMax Occupancy: 3 guests (up to 2 children, 2 infants)
Standard Single Room, 1 Queen BedMax Occupancy: 2 guests (up to 1 child, 1 infant)
4-star Beaux Arts hotel in Istanbul (Taksim) near Taksim Square
This hotel is located in Istanbul (Taksim), close to Taksim Square, Dolmabahce Palace, and Galata Tower. Also nearby are Maiden's Tower and Spice Bazaar.
Hotel Features
In addition to a restaurant, The Central Palace features a health club. Other amenities include complimentary wireless Internet access and complimentary high-speed (wired) Internet access.
Room Amenities
All guestrooms feature jetted bathtubs, complimentary wireless Internet access, and sofa beds. Other amenities include air conditioning and safes.Information missing or incorrect? Tell us!
At your hotel
At your hotel
The Central Palace features a health club and a sauna. The hotel offers a restaurant. A complimentary breakfast is offered. High-speed wired and wireless Internet access is complimentary.
Business-related amenities at this 4-star property consist of a business center and meeting rooms. Event facilities measure 646 square feet (60 square meters). This Beaux Arts hotel also offers tour/ticket assistance, multilingual staff, and a fireplace in the lobby. For a surcharge, a roundtrip airport shuttle (available on request) is offered to guests.
The Central Palace is a smoke-free property.
- 24-hour front desk
- Babysitting or childcare (surcharge)
- Airport transportation (surcharge)
- Total number of rooms - 107
- Number of floors - 12
- Business center
- Free breakfast
- Dry cleaning/laundry service
- Elevator/lift
- Express check-out
- Fireplace in lobby
- Health club
- Tours/ticket assistance
- Free Wi-Fi
- Free wired high-speed Internet
- Laundry facilities
- Meeting rooms
- Multilingual staff
- Porter/bellhop
- Restaurant
- Room service (24 hours)
- Safe-deposit box at front desk
- Year Built 2004
- Conference space size (feet) - 646
- Conference space size (meters) - 60
- Number of meeting rooms - 4
- Free parking nearby
- Sauna
- Smoke-free property
- Number of buildings/towers - 1
- Television in lobby
Stay connected
Available in all rooms: Free Wi-Fi
Available in some public areas: Free Wi-Fi , Free wired high-speed Internet
Park your car
Free parking nearby
In your room
- Premium TV channels
- Balcony
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- Phone
- Minibar
- Coffee/tea maker
- Hair dryer
- Jetted bathtub
- Bathtub only
- Desk
- In-room safe
- Sofa bed
- Free Wi-Fi
- Connecting/adjoining rooms available
- Cribs/infant beds (complimentary)
Eat and drink
Guests are offered a complimentary buffet breakfast.
The Central Palace has a restaurant on site.
24-hour room service is available.
Recreational amenities at the hotel include a health club and a sauna.
The fine print for The Central Palace
When you arrive
Check-in time starts at 2 PM
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Check-out time is noon
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Accepted at this hotel: Diners Club, MasterCard, Visa, American Express
You need to know
Extra-person charges may apply and vary depending on hotel policy.
Government-issued photo identification and a credit card or cash deposit are required at check-in for incidental charges.
Special requests are subject to availability upon check-in and may incur additional charges. Special requests cannot be guaranteed.
- No onsite parking is available.
No pets or service animals allowed
- Airport shuttle fee: TRY 106 per vehicle (one way)
We should mention
The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation. No pets and no service animals are allowed at this property.


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Having a strong federal Species at Risk Act is essential to protect our most vulnerable plants and animals, and the habitat they need to survive and recover on federal lands. It also enables the federal government to step in where needed to protect species at risk on provincial and territorial lands, acting as a critical safety net for endangered species, regardless of where they live in Canada.
Over 650 species are at risk of disappearing forever. Speak up now for a strong federal Species at Risk Act!
* If you've already signed on to help protect Canada's species at risk, write a letter now to the Minister of Environment to explain why this is important to you!


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While many Chicagoans are getting ready for fireworks and barbecues this Fourth of July, one family is coping with the sad anniversary of a train derailment and bridge collapse, which killed two beloved parents.
Two brothers, Matt and Rob Lindner, stood in a chilly rain Tuesday, next to the overpass where their parents were killed a year ago this week. The setting was very different from a year ago, when sizzling heat contributed to a derailment, and the death of their parents.
Last Fourth of July, Burt and Zorine Lindner, were beneath an overpass in Glenview when a coal train derailed, causing the viaduct to collapse and kill them. Their sons have never discussed the accident or their love for their parents publicly, until now.
"It's been a year," Rob Lindner says. "We still don't know what happened."
"We just use them as an example, and say how they would respond to whatever," Matt Lindner says of coping. "If it's as simple as eating dinner, if it is bubby's noodle dish for dinner, which is as simple as it can be, but one that my mom made for the kids all the time."
Railroad executives say hot temperatures caused a kink in the rails and that an inspector was on his way when the train derailed. The Lindners say railroad workers knew of the problem beforehand.
"What happened to us was a completely preventable thing," Rob says. "The problem was known and yet they did nothing about it. They did nothing to stop the trains from running."
"The early investigation revealed that the railroad knew on July 4th that their were kinks in that line before the train hit the bridge," Lindner's attorney Bob Clifford explains.
The Federal Railroad Administration is still investigating. After a year, the Lindners expected more.
"When you hear them say, oh well, it was a hot day, well listen to the news now! Everywhere in America we're talking about how we're having record hot days," Rob says.
The two brothers thank everyone who have offered condolences and remind everyone that the Fourth of July should be a time for celebration, regardless of the pain which sometimes comes with it.
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Photos and Videos
The actor and the rest of the cast talk about the fifth installment of the hit franchise at the film's world premiere in Rio de Janeiro. For more exclusive videos go to AccessHollywood.com
Vin Diesel and Paul Walker are back together for "one last job" (isn't that always the way?), but this time they've got to deal with a lawman named Hobbs (Dwayne "The Rock" Johnson) leading a special unit to stop them. This is gonna be the fastest and most furious sequel ever! Comes out April 29.
Nobody--not even the suits at Universal--anticipated that "Fast 5" would be so successful, not just commercially, but critically. So it's no wonder that the studio is eager to squeeze out as many installments as quickly as possible.
Shooting multiple films from a franchise consecutively is a time-tested way to maximize the economy and speed with which films get into theaters, and so the studio is considered having director Justin Lin and screenwriter Chris Morgan get to work on both "Fast" 6 and 7, reported 24 Frames. It's the same approach Paramount is considering for "Transformers."
"Fast 5" has taken in more than $600 million, and, we never thought we'd say this, it is awesome. Don't believe us (cuz we work for NBC Universal)? Check out Rotten Tomatoes--all sorts of folks liked it.
As we've said before, are our complaint about all this "Fast"-ness is that it appears to have prevented Lin from taking over the "Terminator" franchise. Just think what he could do with only one bad actor to shoot around...


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The GrandifloraHome.com team is busy meeting with makers and scouring markets to find just the right beautiful modern objects for your home.
We're getting closer, but it's still a few weeks before we're ready to introduce you to the new, improved, vastly expanded Grandiflora Home online. To be the first to know about our launch and get first dibs on the treasures we'll have on display, please sign up for our mailing list.


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University Holidays and Summer Schedule
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PS1 Maintenance
|Date: Wednesday, July 24th, 2013
PS1 levels 4 and 5 will be closed for cleaning on Thursday, July 25th. Levels 6 and 7 have already been cleaned and we request those levels be used for parking.
Level 3 will be closed for cleaning on Friday, July 26th after 12:30 pm.
Cleaning is expected to take 2 hours per floor.
Thank you for your patience while we complete our annual maintenance projects. If you have specific questions or concerns, please e-mail email@example.com or call (270) 745-2361.
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This week only (Sept 1-5)
Sept 3rd
How does one ditch a dependence on soda? Here are five tips for kicking your soda habit for good.
Are artificial sweeteners used in soft drinks and foods safe? Will they make us fat? How much is too much? Science doesn't have all the answers yet, but researchers have some clues.
Speed Limit Reduced on Normal and State Streets


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Find an Internship or Volunteer in Sheffield Lake, Ohio ( OH )
If you're looking for internships or volunteer work in Sheffield Lake, Ohio or even to get a summer job, you've come to the right place! With over 30,000 around the county, chances are that GrooveJob.com has the right job for you and wants to be your only source for finding internships and volunteer positions in Sheffield Lake, Ohio.
We've got plenty of intern and volunteer work in Sheffield Lake, Ohio. Check out the list of employers below who have positions in Sheffield Lake. Remember to check back with Groovejob.com on a regular basis. We add new internships and volunteer jobs listings to our database every week, so you'll find new opportunities every time you check back with us.
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Intern , Technician Internship Program (TIP)
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Cleveland, OH
Marketing Intern
…of Marketing, Marketing Brand Management interns are assigned several projects during their internship program. These projects immerse...
Westlake, OH
Intern - Entertainment and Media Industry Opportunity
…on the semester. Required Qualifications Must be currently registered in an internship for academic credit with your...
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Tax Consultant ( Intern ) Summer 2015 (Cleveland) John Carroll University
…with another Deloitte Tax service line and/or another Deloitte function-specific subsidiary. Internship Program The Deloitte Tax LLP...
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Intern - Ballpark Operations - Entertainment - Stage
…maintain efficiencies and cost effectiveness and ensure a safe environment This internship is from March thru end of baseball season....
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Early Learning Family Advocate Assistant Intern (Fall 2014- Dec 2014)
Early Learning Family Advocate Intern Fall 2014- Dec 2014) -- 18 hours per week -- Non- paid Summary THE CENTERS is an organization...
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Prototype Development Intern
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Supply Chain Intern
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Visiting Team
Water, ice, ice bags and emergency equipment (AED, long board, splints, and crutches) will be provided at all home events.
The training room will be open 2 hours prior to the start of all home events. If you need access to the training room earlier than the time allotted, please call a day ahead and we will be happy to accommodate you.
A certified athletic trainer and/or EMT will be provided for all home events.


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Activision Sues To Stop Brutal Legend ReleaseBy Alice O'Connor, Jun 04, 2009 7:19pm PDT Update 2: Further AP details reveal more of Activision's complaint. The publisher claims Double Fine was paid $15 million to develop Brutal Legend but missed a key deadline last year, allegedly stating that another nine months and $7 million were needed.
While no agreement to get Brutal Legend back on course was ever reached, Activision contests it never gave up publishing rights and as such Double Fine could not take the game to EA. Activision bemoans the loss of its investment not only in Brutal Legend itself, but the ability to sell seemingly lucrative Legend-based downloadable content.
Update: The official Brutal Legend Twitter received a simple update, since removed:
Re: today's bummer news...in the words of the inimitable Ms. Beyonce Knowles, "If you liked it you shoulda put a ring on it".
Original story: Activision is suing Double Fine Productions to stop the release of Brutal Legend, The Associated Press reported, claiming it still holds a valid contract to publish the heavy metal fantasy and has invested roughly $15 million in it.
The dispute stems from Brutal Legend's troubled history. Activision declined to acquire the game's publishing rights from Vivendi when the two merged in July 2008. EA picked up Brutal Legend that December, and planned to release it on October 13 this year.
Reports emerged in February that Activision believed it was still in negotiations over Brutal Legend when EA picked up the title, and was considering suing. An EA representative responded at the time that it would "be like a husband abandoning his family and then suing after his wife meets a better looking guy."
EA and Double Fine Productions have yet to comment, but we'll keep you updated.
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By: mittense x Show Full PostThat is absurd, but the EA quote is pretty great.Jun 04, 2009 10:59am PDT
By: smacknca x Show Full PostThis is what happened to our beloved game industry when it became a monstrous beast of profit. i genuinely wish it hadnt overtaken movies in profits....every god damn decision these days is just about making the maximum amount of money. the quantity of lawsuits is just getting insane now, sue sue sue sue its practically a staple of our daily news at this point.Jun 04, 2009 12:11pm PDTThis is what happened to our beloved game industry when it became a monstrous beast of profit. i genuine... : smacknca
Thread Truncated. Click to see all 34 replies.
Welcome to corporate America. : OxygenGraffiti
yup. on the bright side ea isnt going to take this laying down. since they arent a small developer witho... : smacknca
youre aware that its a corporation's OBLIGATION to make every last nickle of profit possible, right? that... : radio_babylon
This is largely a bullshit argument with very little basis in reality. It only really has any effect when... : FlatlineDixay
the officers of a corportation are obligated to act in the best interests of their stakeholders. this is ... : radio_babylon
No, he's right, it's a bullshit argument that reduces things to absurdities. For example, here in the ... : Conan
i think thats pretty unlikely, yeah... however, i can damn near GUARANTEE that if there were a shareholde... : radio_babylon
*their : radio_babylon
You think it's unlikely that small developers would be hesitant to work with a publisher with a history o... : Conan
sorry i wasnt clear, i was kind of responding to both your posts at once. i meant that not going after do... : radio_babylon
Man, I'm glad you're not actually in charge of any business I'm invested in. Despite your comments, th... : Conan
sure, but youre just as ethical as you have to be, and no more. rampaging evil exposes shareholders to ri... : radio_babylon
We have no idea who's wrong and who's right in this case. So there is no need to imply that Activision ac... : [7]kami
They'll be on the block for letting rights languish while somebody else bought them; I doubt the fact tha... : FlatlineDixay
its better than letting the rights languish and then NOT trying to recover what they could. look, i ge... : radio_babylon
making the maximum amount of money EVERYTHING (well almost) is a business, everything is about getting... : Big Luke
I agree. The game industry is really starting to suck.. : Lord Skellington
By: scener x Show Full PostAll this drama for a game that will bomb at retail.Jun 05, 2009 3:01am PDT
By: asdiop x Show Full PostI wish they'd both go fuck themselves. You expect that kinda horseshit from EA but I guess Activision is gearing up to be the next big douche bag in video game history.Jun 04, 2009 11:44am PDTI wish they'd both go fuck themselves. You expect that kinda horseshit from EA but I guess Activision is... : asdiop
Thread Truncated. Click to see all 7 replies.
gearing up : jake2000
definitely. : Sgt_Boomstick
And they've definitely been earning it from me : dancingpolkabear
I love news like this. You begin to get a feel who the real scumbags of the gaming Industry are. Too bad ... : YummiGummi
By: Lord Skellington x Show Full PostPublishers in this state need to die.
Look at Valve. They publish their own stuff right? And If I understand correctly they also get involved in other peoples games games. Same with §DR when they existed, with Max Payne, Prey etc.
Those guys were developers themselves. A game developer is the only thing that should be allowed to publish a game.
I've completely lost what I was trying to say..but I'm sure you understand the gist of it. If not, then I will simply say..Monkey Tennis.Jun 05, 2009 1:20am PDTPublishers in this state need to die. Look at Valve. They publish their own stuff right? And If I unde... : Lord Skellington
Thread Truncated. Click to see all 7 replies.
3d realms did the first max payne.. alot of companies get so gross in number they just expand under a ... : ekuriox
By: Schnapple x Show Full PostDevil's Advocate: could Activision be in the right here?
Could this be what happened?
1. Double Fine signs publishing rights for Brutal Legend to Activision
2. Activision gives Double Fine $15M, sets a deadline. Double Fine presumably agrees
3. Double Fine misses deadline, says they need nine more months and $9M
4. Activision doesn't give Double Fine more money, wants to negotiate
5. Double Fine, during negotiations, sells the publishing rights to EA
6. EA gives Double Fine the $9M they need. Perhaps they figure it's Double Fine's problem to pay back Activision?
7. Activision says that they still own the publishing rights, that they're not Double Fine's to sell, and threatens to sue
8. Double Fine ignores Activision
9. Activision sues Double Fine
It's not like there's some sort of "publishing rights police" that can prevent this sort of thing from happening - Activision suing because they believe they've been wronged and that Double Fine illegally sold the publishing rights is how these things get handled.
And the reason Activision wants to block the release of the game is because if they're right then EA doesn't have the right to put the game out in the first place.
Granted, this is me pulling this all out of my ass, guessing the above scenario based off of taking Activision at face value. I love Double Fine, I bought Psychonauts, and I want this game to succeed (release a PC version please) but really, maybe Double Fine is in the wrong here? We want to believe that they're the spunky rebel of the game developing world but could they have pulled a dick move of their own here?Jun 04, 2009 8:03pm PDTDevil's Advocate: could Activision be in the right here? Could this be what happened? 1. Double Fin : Schnapple
Thread Truncated. Click to see all 13 replies.
First of all, Double Fine signed the publishing rights to Vivendi, not Activision. When Activision and Vi... : evildanish
That 15 million was paid to double Fine so I imagine they have/had some kind of contract in place. : cell9song
By: Cygnus X-1 x Show Full PostThis reminds of people watching their neighbors fight through their window and making all kinds of uninformed judgments.Jun 05, 2009 4:46pm PDT
By: kungfusquirrel x Show Full PostActivision bemoans the loss of its investment not only in Brutal Legend itself, but the ability to sell seemingly lucrative Legend-based downloadable content.
Read: Guitar Hero unlocksJun 05, 2009 6:18am PDTActivision bemoans the loss of its investment not only in Brutal Legend itself, but the ability to sell s : kungfusquirrel
By: baron calamity x Show Full PostI guess this will be just like the Watchmen movie. The game will be published, we will see it and play it, but EA and Actard will have to split the profits. Also like the Watchmen movie it won't be a huge hit and both publishers will take a loss.Jun 05, 2009 7:55am PDTI guess this will be just like the Watchmen movie. The game will be published, we will see it and play it... : baron calamity
By: nudel x Show Full PostTHANK YOU ACTIVISION for trying to prevent more media containing Jack Black from seeing release. Godspeed.Jun 05, 2009 6:51am PDTTHANK YOU ACTIVISION for trying to prevent more media containing Jack Black from seeing release. Godspeed... : nudel
By: Dave-A x Show Full PostDoes $22 million seem like a m-m-m-monster budget for this game, or is this fairly normal these days? I had hopes that Brütal Legend would turn out awesome and sell well, but it never occurred to me that it would be a leader in the sales department.Jun 04, 2009 7:29pm PDTDoes $22 million seem like a m-m-m-monster budget for this game, or is this fairly normal these days? I h... : Dave-A
By: the archvile x Show Full PostWe need a cage match. Kotick vs. Riccitiello. Winner take all. FIGHT!Jun 04, 2009 8:57pm PDT
Thread Truncated. Click to see all 3 replies.
JR goes running a lot... : Sturm08
Ricci hands down. : Sgt_Boomstick
By: melt_core x Show Full PostTo put things in perspective;
This game has cost more than DNF!
I don't believe it tells us much about Brutal Legend actually, but a lot about DNF. It's cost wasn't as craaaazy high as we first thought it was... oh welp..Jun 05, 2009 12:59am PDTTo put things in perspective; This game has cost more than DNF! I don't believe it tells us much ab... : melt_core
Thread Truncated. Click to see all 13 replies.
They claim to have put 20 million.. : melt_core
Who claims it? : uncle slappy
3dRealms : melt_core
I'm having trouble believing that figure. : GreatGooglyMoogly
Yea but 3drealms is also publishing and developing their own game.. Double Fine has a crappy ass game ... : ekuriox
By: Schnapple x Show Full PostSolution: Let Activision publish the PC version.
And also, make a PC version.
PC VERSION DAMMITJun 04, 2009 11:05am PDTSolution: Let Activision publish the PC version. And also, make a PC version. PC VERSION DAMMIT : Schnapple
Thread Truncated. Click to see all 9 replies.
This! PC version please please please. : Esquilax1138
Great, we're half way there, now they just need to say there WILL be a PC version. : Esquilax1138
living on a prayer... : j0nchan
Lol! 12345 : Lord Skellington
By: Physick1 x Show Full PostActivision is turning into a giant pile of bullfuck.Jun 04, 2009 11:07am PDT
Thread Truncated. Click to see all 16 replies.
Turning? They've BEEN one for a while now. When it comes to being a corporate dickhole, EA = Old an... : carbontree
Remember 2005 when they increased the prices saying: "Our games better"? I lost all my respect to them ri... : anal justice
Carmack. Enjo-oy. : holaareola
the BJs will be too, probably. : duffman03
you could just buy all their games used : dancingpolkabear
Isn't the lead character named BJ? lol. : phil_mckraken
By: gibbo x Show Full Postmaybe i'm crazy, but the easy solution here is that activision receive 2/3 of the publishers profits and EA receives the other 1/3. they should receive commiserations respective to their investment in the product.
if they don't like it they can fund things to completion. of course EA should re-coup any costs of manufacture and distribution and advertising before activision sees a dime.Jun 05, 2009 1:53am PDTmaybe i'm crazy, but the easy solution here is that activision receive 2/3 of the publishers profits and ... : gibbo
By: italiano3d x Show Full Postno more activision games for me. Publishers have to learn that these types of actions need to not be happening. This 15 million they seek for themselves dumping the title and then waiting till after ea invests a fuck ton in the game is rediculous. And its a practice publishers need to stop doing. Stop trying to kill off titles so you can swallow their IP. Stop it. Your killing creativity.Jun 05, 2009 12:57am PDT
By: deathofrats x Show Full PostFreaking greedy whores. This is why I don't buy Activision products. They are complete bastards.Jun 04, 2009 9:57pm PDTFreaking greedy whores. This is why I don't buy Activision products. They are complete bastards. : deathofrats
Thread Truncated. Click to see all 2 replies.
Indeed. : XSilencedXDream
By: silentbobuk x Show Full Post/"be like a husband abandoning his family and then suing after his wife meets a better looking guy"/
lolJun 04, 2009 11:05pm PDT/"be like a husband abandoning his family and then suing after his wife meets a better looking guy"/ l... : silentbobuk
By: araczynski x Show Full Posti can't see this not be a clear cut case. presumably all game publishers/developers are so fucking lawyer/legal heavy handed when they set up contracts for work that i can't imagine that phrases like "ownership of all related/derivate works directly related to said funded project belong to us until some section X paragraph Y"
it should be in black and white, and whoever is stupid here will hopefully get assraped all nice and proper.Jun 04, 2009 9:48pm PDT
By: freakynipples69 x Show Full PostUgh. I hate reading this stories; they are becoming more and more common. Video game producers and managers, please stop this from ever happening.Jun 04, 2009 9:15pm PDT
By: D-OveRMinD x Show Full PostThe tweet "If you liked it you shoulda put a ring on it" pretty much hit the nail on the head. Activision seems to not ever give a shit about writing off the money losers...but as soon as they gain popularity and look like they may be blockbusters, here they come a-suin. It's like they hate being screwed, but are all about letting someone else invest for a while so they can come back and screw them in the 11th hour.Jun 04, 2009 9:08pm PDT
By: qsylvr x Show Full PostI'm sure it's complicated and involves a lot of lawyers poring over contract clauses. I have to believe that neither Double Fine nor Activision would be stupid enough to do something blatantly in violation of contract. And of course EA would never get involved with a publishing contract without some background checks first.
So, it's probably going to come down to finger-pointing and nit-picking over tiny random details. And then eventually there will be some private out-of-court settlement agreement and everyone will move on after agreeing to disagree over the contract interpretation.Jun 04, 2009 8:31pm PDT
By: mexpak x Show Full PostAn EA representative responded that it would "be like a husband abandoning his family and then suing after his wife meets a better looking guy."
Did everyone gloss over this? That's hilariousJun 04, 2009 12:06pm PDTAn EA representative responded that it would "be like a husband abandoning his family and then suing afte... : mexpak
By: uncle slappy x Show Full PostI'm just glad they're suing over this general and not a game Im actually looking forward to.Jun 04, 2009 6:23pm PDT
By: pigvomit x Show Full Post$15 million dollars?Jun 04, 2009 11:16am PDT$15 million dollars? : pigvomit
By: dancingpolkabear x Show Full PostRight when EA stops being a bitch, Activision takes its place and fucks with us even more. Just you wait Activision, Tim will get you, and your children!Jun 04, 2009 4:13pm PDT
By: avatar_58 x Show Full PostHere I was thinking VUgames couldn't get any worse. Then they got bought up by Activision, Maximum douchbaggery now.Jun 04, 2009 2:14pm PDT
By: Fuzzmatang x Show Full PostThis sounds like what happened with Watchmen (Fox vs. Warner Bros).
What a douchebag move Activision...both in timing (announcing this during E3) and doing it to begin with.Jun 04, 2009 2:05pm PDT
By: italiano3d x Show Full Postea is going to eat their lawyers alive and bleed 10+ million out of activision for lawyer expenses. hahaJun 04, 2009 2:01pm PDT
By: binaryc x Show Full PostI predict this being settled out of court for around $10 million.Jun 04, 2009 1:16pm PDT
By: voodooraze x Show Full PostOh this is just lame, activision better not fuck with this. I want this game worse than I want to get rid of these herpes.Jun 04, 2009 1:15pm PDT
By: Deathlove x Show Full PostActivision, die in a fucking fire. Until you release something that I want, then you can do that, then die again.Jun 04, 2009 11:12am PDTActivision, die in a fucking fire. Until you release something that I want, then you can do that, then di... : Deathlove
By: CoreContingency x Show Full PostThat $15 million has gotta be some BS extrapolated figure they had the bean counters whip from the Vivendi holdings in order to add validity to this otherwise nonsense lawsuit. Activision declined to acquire rights after the merge. End of story. Hopefully common sense will prevail in the courtroom and the judge will slap Activision with the bill for this one along with legal fee's for the Defense.Jun 04, 2009 12:31pm PDT
By: shotgun1 x Show Full PostI'm sure Tim wasn't desperate to get a publisher at the time and just forgot about activision. /sarcasm
What a load of shit, activision probably didn't want it because they thought it would be a critically acclaimed financial flop and now they're shitting themselves because it might be a hit. GUITAR HERO IS DOING AWESOME, THIS GAME ROCKS OMG OMG OMG /sueJun 04, 2009 12:18pm PDT
By: Cihte x Show Full PostAn EA representative responded that it would "be like a husband abandoning his family and then suing after his wife meets a better looking guy."
That's awesome. lol.Jun 04, 2009 12:14pm PDT
By: sammyl x Show Full PostTotal dick move here folks.Jun 04, 2009 12:07pm PDT
By: freshyk x Show Full PostThis better not fuck with ROCKTOBER.Jun 04, 2009 11:28am PDT
By: Dexter111 x Show Full PostHahaha, anyone remember what they said in Interviews after the Activision/Vivendi-Merger and the Dick-Move of dropping Ghostbusters / Brutal Legend?
"When asked about the Vivendi Games franchises that were tossed aside when Activision consumed the company (e.g. 50 Cent, Ghostbusters and Brutal Legend) during yesterday's conference call (transcript via Seeking Alpha), the Big Kahuna said, "With respect to the franchises that don't have the potential to be exploited every year across every platform with clear sequel potential that can meet our objectives of over time becoming $100 million plus franchises, that's a strategy that has worked very well for us.""
Anyway, fuck them both, gimme a PC versions or both go to hell :PJun 04, 2009 12:04pm PDT
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LAKE DELTON, WI (WTAQ) - Four people have been arrested in Lake Delton, after they allegedly invaded a home near Edgerton and stole 30 guns, cash, and a pick-up truck.
Rock County authorities said two men entered the home late Friday night, held a man and a woman at gunpoint, and demanded that a safe be opened. The amount of cash taken was not disclosed.
The homeowner's truck was found abandoned in Janesville on Saturday.
Monday, two men and two men – all in their 20's – were arrested. Authorities said they were in a stolen car that was spotted in the Wisconsin Dells area.
Police said four people ran out of the moving vehicle as it was about to come to a stop. Two were arrested immediately, and it took an hour-and-a-half to nab the other two.
Meanwhile, Rock County officers said they were working with investigators in Walworth County to determine if the suspects were involved in burglaries in that county recently.


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Our Mission
The mission of the Program in Personalized and Genomic Medicine is to facilitate the pace of discovery in Personalized and Genomic Medicine; to accelerate the translation of these new discoveries to improve patient care; and to enhance the training and education of future generations of physicians and scientists in personalized medicine and genome science.
The unveiling of the complete sequence of the human genome is providing exciting new insights into human biology and disease. Coupled with advances occurring in areas such as high throughput technologies and computing, exceptional opportunities now exist to uncover the molecular bases of many medical conditions, from rare monogenic diseases to common diseases of complex inheritance - discoveries that will translate into exciting new strategies for prevention and treatment.
The Program in Personalized and Genomic Medicine is an inter-departmental program that emphasizes a multidisciplinary team approach to research training and discovery. Faculty have expertise across a wide range of disciplines including clinical investigation, molecular genetics, cytogenetics, cancer genetics, biochemical genetics, functional genomics, molecular and cell biology, genetic epidemiology, statistical genetics, and bioinformatics.
The program offers opportunities for students at all stages including undergraduate, graduate, and post-graduate. The graduate program grants both master's and doctoral level degrees.Graduate training for students interested in genetics and genomics is supported by the Graduate Program in Life Sciences, including the Program in Epidemiology and Human Genetics and the Program in Molecular Medicine. In addition, there is the American Board of Genetic Counseling (ABGC) nationally accredited Master's in Genetic Counseling training program. Positions are also available for post-doctoral fellows in genetics/genomics as well as M.D. fellows.


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by WRETHAOFFGRID on OCTOBER 3, 2012 - 28 Comments in FOOD, OFF-GRID 101, WRETHA
Living off grid, I get questions from time to time, mainly about how we live, some even think we must live in a cave and eat dirt and wear skins… I said I live off grid, but we don't live that primitively! :) I do enjoy some of the modern conveniences of life, including having a place to keep perishable foods, aka a refrigerator.
When we first moved off grid, in Dec '07, we brought with us a small, dorm sized fridge, but honestly we didn't use it much, only plugging it up on the occasions when I brought home a gallon of milk or a pound of ground beef, once the perishable food was gone, we unplugged the fridge. What I quickly found out was the standard type of fridge used up a LOT of power and they tend to be very inefficient. (more…)


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Revolutionary Road
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Summary: Leonardo DiCaprio and Kate Winslet reteam for the first time since Titanic in this critically acclaimed drama about a young couple's crumbling marriage. It's 1955 and Frank and April Wheeler (DiCaprio, Winslet) are a popular, good-looking suburbanite couple with two children. But their picture-perfect life hides a dark underbelly of unhappiness and infidelity that leads their marriage down an increasingly perilous road. Michael Shannon was nominated for a Best Supporting Actor Oscar(R) with his "breakthrough performance" (The L.A. Times) as an insightful mental patient. Kathryn Hahn, David Harbour and Kathy Bates star. Directed by Sam Mendes, based on a novel by Richard Yates, screenplay by Justin Haythe. (R) (AC,AL,BN,MV)
PRODUCER : John Hart,Scott Rudin,Sam Mendes,Bobby Cohen,Marion Rosenberg,David M. Thompson,Henry Fernaine
CAST : Leonardo DiCaprio,Kate Winslet,Michael Shannon,Kathryn Hahn,David Harbour,Kathy Bates
WRITER : Justin Haythe,Richard Yates
DIRECTOR : Sam Mendes
Genre : Drama
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Vista® Hair Release Tab, Left Hand
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Slumberdown Summer Cool Duvet - 4.5 Tog and 10.5 Tog Ratings
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2 reviews
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Slumberdown Summer Cool Duvet in Single, Double and King sizes; 4.5 and 10.5 tog rating
Have a fantastic night's sleep even when the weather is hot and sticky with the Summer Cool duvet from Slumberdown.
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It's machine washable too, so it'll be easy to keep fresh and hygienic.
Matching pillows are available separately (see item number 3WKVY).
Useful info:
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- Machine washable
- Matching pillows available separately
Slumberdown Winterfill Hollowfibre Duvet - 13.5 and 15 Tog
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Slumberdown Winterfill provides outstanding warmth and comfort, filled with Hollowfibre. Complimented by a great value pillow pair that provides firm support.Cotton. Machine washable.


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Three treatment goals
When considering how to treat your relapsing MS; your doctor likely has 3 key treatment goals in mind:
- Slowing disability progression
- Reducing the frequency of relapses
- Reducing the development of new brain lesions as seen on MRI
Once on an MS therapy, your doctor will continue to monitor the 3 key MS treatment goals as well as any side effects you experience in order to assess how well your treatment is working. In general, your doctor will want to know if:
- You are experiencing any new symptoms and/or worsening symptoms
- You have had any relapses—how many, the duration and severity
- There any changes in your neurological exam; particularly if it suggests disability progression
- There are any changes on your MRI; such as new lesion development
Enhance your conversation with your health care provider about the disease-modifying therapy that's right for you using the Treatment Journal. The Treatment Journal helps you identify preferences for your treatment routine, including dosing, administration and product features, and allows you to create a report that you can take with you to your next appointment.
Enhance your conversation with your health care provider about the disease-modifying therapy that's right for you. The Treatment Journal will help you identify preferences for your treatment routine, including dosing, administration and product features.
Did you know? Rebif® (interferon beta-1a) is the only self-injected relapsing MS therapy proven to meet all 3 treatment goals in MS:
- Slows disability progression
- Reduces relapse rates
- Reduces active brain lesions on the studied MRI measures*†
The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.
* Refers to new lesions and total lesion burden or area as defined in the AAN and MS Council guidelines.
† New or enlarging lesions detected with PD/T2-weighted MRI.
Rebif® (interferon beta-1a) is used to treat relapsing forms of MS to decrease the frequency of relapses and delay the occurrence of some of the physical disability that is common in people with MS. Rebif is not approved for treatment of chronic progressive MS.
Important safety information
What is the most important information I should know about Rebif?
Rebif will not cure multiple sclerosis (MS) but it has been shown to decrease the number of flare-ups and slow the occurrence of some of the physical disability that is common in people with MS. Rebif can cause serious side effects, so before you start taking Rebif, you should talk with your doctor about the possible benefits of Rebif and its possible side effects to decide if Rebif is right for you. Potential serious side effects include:
- Depression. Some patients treated with interferons, including Rebif, have become seriously depressed (feeling sad). Some patients have thought about killing themselves and a few have committed suicide. Depression (a sinking of spirits or sadness) is not uncommon in people with multiple sclerosis. However, if you are feeling noticeably sadder or helpless, or feel like hurting yourself or others, you should tell a family member or friend right away and call your doctor as soon as possible. Your doctor may ask that you stop using Rebif. You should also tell your doctor if you have ever had any mental illness, including depression, and if you take any medications for depression
- Liver problems. Your liver may be affected by taking Rebif and a few patients have developed severe liver injury. Your health care provider may ask you to have regular blood tests to make sure that your liver is working properly. If your skin or the whites of your eyes become yellow or if you are bruising easily you should call your doctor right away
- Risk to pregnancy. If you become pregnant while taking Rebif you should call your doctor right away. Rebif may cause you to lose your baby (miscarry) or may cause harm to your unborn child. You and your doctor will need to decide whether the potential benefit of taking Rebif is greater than the risks are to your unborn child
- Allergic reactions. Some patients taking Rebif have had severe allergic reactions leading to difficulty breathing and loss of consciousness. Allergic reactions can happen after your first dose or may not happen until after you have taken Rebif many times. Less severe allergic reactions, such as itching, flushing or skin bumps, can also happen at any time. If you think you are having an allergic reaction, stop using Rebif immediately and call your doctor
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Who should not take Rebif?
Do not take Rebif if you:
- Have had an allergic reaction, such as difficulty breathing, flushing, or hives, to another interferon beta or to human albumin
If you have any of the following conditions or serious medical problems, you should tell your doctor before taking Rebif:
- Depression (a sinking feeling or sadness), anxiety (feeling uneasy or fearful for no reason), or trouble sleeping
- Liver diseases
- Problems with your thyroid gland
- Blood problems, such as bleeding or bruising easily, and anemia (low red blood cells) or low white blood cells
- Epilepsy
- Are planning to become pregnant
Tell your doctor about all medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Rebif and other medicines may affect each other, causing serious side effects. Talk to your doctor before you take any new medicines.
What are the possible side effects of Rebif?
- Flu-like symptoms (fever, chills, sweating, muscle aches and tiredness)
- Skin reactions. Soreness, redness, pain, bruising, or swelling may occur at the place of injection
- Depression and anxiety. Some patients taking interferons have become very depressed and/or anxious
- Liver problems
- Abdominal pain
- Blood problems. You may have a drop in the levels of infection-fighting blood cells, red blood cells or cells that help to form blood clots. If the drop in levels is severe, it can lessen your ability to fight infections, make you feel tired or sluggish or cause you to bruise or bleed easily
- Thyroid problems. Your thyroid function may change. Symptoms of changes in the function of your thyroid include feeling cold or hot all the time, change in your weight (gain or loss) without a change in your diet or amount of exercise you are getting
- Severe allergic reactions. Allergic reactions are rare and may be associated with difficulty in breathing and loss of consciousness, which require immediate medical attention
Let your doctor know if you have any of these symptoms or feel sad, tired, hot or cold, or experience hives, rashes, bruising, yellowing of the skin, or a change in body weight (gain or loss).
Refer to the Instructions for Use that comes with the Rebif® Rebidose® (interferon beta-1a) autoinjector.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit
or call
This information is not intended to replace discussions with your doctor. For additional information about Rebif, please consult the Prescribing Information and Medication Guide and talk to your doctor. You can also visit www.rebif.com or call toll-free 1-877-447-3243. Rebif is available by prescription only.
MS LifeLines is an educational support service for people living with MS and their families. Speakers and MS LifeLines Ambassadors who participate in Talk MS or in live events are sponsored by EMD Serono, Inc. and Pfizer Inc. Rebif, Rebif Rebidose, Rebiject II, MS LifeLines, and the Rebif logo are registered trademarks of EMD Serono, Inc. or its affiliates.
Brought to you by EMD Serono, Inc. and Pfizer Inc, the co-marketers of Rebif in the US.
This information is intended only for residents of the United States.


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Content tagged with 'Maserati Quattroporte'
Seven Notes: Gilles Peterson's top 10
It's fitting that one of London's favourite adopted DJ's, Gilles Peterson, DJ'ed at the final Seven Notes show in Clerkenwell. From his Talkin' Loud and Acid Jazz labels to his… Read more
Posted on: Wednesday, 17 Jul 2013
Categories: Music
Tags: Arthur Blythe, B&W, Big John Patton, bowers & wilkins, Earth Wind and Fire, Gilles Peterson, Gonzales, James Blake, Laura Mvula, Maserati Quattroporte, Neil Young, Nuyorican Soul, Portishead, The JBs, Top 10 playlists
Seven Notes: DJ Harvey's top 10 tracks to listen to in a Maserati
Rolling Stone magazine placed DJ Harvey at number 10 in their 25 DJs That Rule The Earth list, writing "if Keith Richards was a DJ, he'd totally be Harvey" Harvey… Read more
Posted on: Thursday, 6 Jun 2013
Categories: Music
Tags: David Bowie Nick Cave and the Bad Sees, DJ Harvey, ELO, Gustav Holst, Jimi Hendrix, Locussolus, Map of Africa, Maserati Quattroporte, pink floyd, Seven Notes, Steely Dan, Wendy Carlos
Seven Notes: KZA's top 10
KZA DJed at the fourth Seven Notes event in Japan. KZA is one half of a DJ/ production team Force of Nature, and pursues their own individualistic style in underground… Read more
Posted on: Friday, 24 May 2013
Categories: Music, Top 10 playlists
Tags: Alphabet City, Cosmic Kids, Eddie C, Harway Bros, Howie B, KZA, Margot, Mario Basanov, Maserati Quattroporte, Reverso 68, Seven Notes, Spirit Catcher, The Juan Maclean, Top 10 playlists, Tornado Wallace
Seven Notes: Perfection of Design
Seven Notes Creative Director Mat Cook and Musician/Producer Howie B discuss the concept behind the tour and why the two brands work together so well. Seven Notes, a touring exhibition… Read more
Posted on: Wednesday, 24 Apr 2013
Categories: Car audio, Events and shows
Tags: Howie B, Maserati Quattroporte, Seven Notes
Watch the Maserati Quattroporte audio system in action
The full-blooded roar of a Maserati V8 has always been a thing of beauty. Now, thanks to a combination of careful speaker placement and fine-tuning, the Quattroporte's Bowers & Wilkins… Read more
Posted on: Wednesday, 6 Mar 2013
Categories: Car audio, New products, Speakers
Tags: Abbey Road studios, Bowers & Wilkins 800 series, Car audio, Maserati Quattroporte, Maserati V8
GQ takes the new Bowers & Wilkins equipped Maserati Quattroporte for a test drive
Definitive men's magazine GQ took the new Bowers & Wilkins equipped Maserati Quattroporte for a test drive, and loved every minute of it. The magazine took the car on a… Read more
Posted on: Thursday, 21 Feb 2013
Categories: Car audio, New products, News
Tags: GQ Magazine, in car audio, Maserati Quattroporte