bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of anti-CD4 antibodies on the release of IL-6 and TNF-α in whole blood samples from patients with systemic lupus erythematosus
Authors: Brink I , Thiele B , Burmester G-R , Trebeljahr G , Emmrich F , Hiepe F 
Published: November 2003

Anti-CD4 antibodies have been recently introduced into the therapy of various autoimmune diseases, among them systemic lupus erythematosus (SLE). Their modes of action are not yet fully understood. Interference with cytokine release may be one possible mechanism. Therefore, the effects of anti-CD4 antibodies on the cytokine release of IL-6 (interleukin-6) and TNF-a (tumor necrosis factor alpha) were investigated in a whole blood culture system. Basal and phytohemagglutin/lipopolysaccharide (PHA/LPS)-stimulated cytokine patterns were compared to cytokine release after the addition of anti-CD4 antibodies (MAX. 166H5) or methylprednisolone in short time whole blood cell culture systems from 12 patients with active SLE, 23 patients with inactive SLE and 12 healthy volunteers. TNF-oc and IL-6 concentrations were determined in the supernatants by ELISA. High disease activity correlated with an increased production of proinflammatory cytokines. Cell cultures of patients with inactive SLE showed a diminished capacity to respond to mitogenic stimulation. Anti-CD4 antibodies added in vitro suppressed significantly the unstimulated production of IL-6 (P < 0.02) in the cell cultures of patients with active SLE and in the PHA/LPS-stimulated cell cultures from both groups of SLE patients (both P < 0.001) and healthy volunteers (P < 0.01). However, MAX.16H5 did not affect the release of TNF-a. In control samples methylprednisolone considerably reduced stimulated and unstimulated IL-6 and TNF-ca production in all SLE patients, irrespective of the disease state, and in all healthy controls. These data indicate that the proinflammatory cytokines are involved in the pathogenesis of SLE. It is assumed that anti-CD4 antibodies, which can be effective in the treatment of highly active lupus patients, may act via their influence on cytokine release. The decrease of the proinflammatory cytokines IL-6 under therapy with MAX. 16H5 could explain the observations of clinical trials and animal studies which showed a reduction of inflammatory parameters and diminished production of autoantibodies following treatment with anti-CD4 antibodies.
Chronic or recurrent headache in patients with systemic lupus erythematosus: a case control study
Authors: Fernández-Nebro A , Palacios-Muñoz R , Gordillo J , Abarca-Costalago M , De Haro-Liger M , Rodríguez-Andreu J , González-Santos P 
Published: November 2003

Controversy exists concerning the prevalence of headache in systemic lupus erythematosus (SLE) and its importance as a neuropsychiatric manifestation, especially when it occurs independently of disease activity and with the typical characteristics of primary chronic headache. Most reports to date have either studied both types of headache, whether or not related to systemic lupus erythematosus, or have not used adequate controls. This study determines the prevalence and types of chronic primary headache in patients with systemic lupus erythematosus in a case-control study which we performed in a tertiary care hospital. We studied 71 consecutive patients with systemic lupus erythematosus and 71 healthy unrelated subjects matched for age and sex from the same geographical area. Clinical evaluation using a specific standard protocol for the presence and characteristics of headache according to the operative classification criteria of the International Headache Society. The overall prevalence of headache, tension-type headache, and migraine was similar among patients and controls [33 (46.5%), 17 (23.9%) and 16 (22.5%) vs 31 (43.7%), 17 (23.9%) and 13 (18.3%), respectively]. The mean age of onset of headache was higher in the patients (28.7–14.3 vs 18.5–5.6 y; P = 0.001) and the subjective response to analgesics was lower than in the controls [19 (63%) vs 28 (93.3%); P = 0.004]. There were no differences in the presence of precipitating factors or family history of headache. There were no relevant clinical or immunological differences among the patients regarding the presence or absence of tension-type headache or migraine. Patients with systemic lupus erythematosus do not differ from healthy controls for the presence and type of chronic or recurrent headache.
Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like illnesses: MS or APS?
Authors: IJdo J W , Conti-Kelly A M , Greco P , Abedi M , Amos M , Provenzale J M , Greco T P 
Published: November 2003

Objective: To describe the frequency, clinical, and laboratory features of patients diagnosed with multiple sclerosis (MS) or MS-like illnesses (MSL) among a large, prospectively followed cohort of anti-phospholipid antibody (aPL)-positive patients. Methods: Between 1990 and 1995 patients referred to a university-affiliated rheumatology clinic were prospectively evaluated for aPL based on questionnaires designed to detect aPL-related symptoms and/or a family history of aPL-related illnesses. Magnetic resonance imaging (MRI) was performed when significant neurological features were present. A subgroup of all patients diagnosed with MS or MSL was identified and their clinical, laboratory, and imaging findings were reviewed. Results: Of 322 patients evaluated for aPL-related symptoms or events, 189 (59%) were positive for at least one class of aPL. Twenty-six of 322 patients (8%) carried a diagnosis of MS or MSL, either at the initial evaluation or during the study period. Twenty-three of the 26 individuals (88%) tested positive for aPL, while the remaining 3 (11%) tested repeatedly negative. Eighteen of the 23 patients (78%) had either more than one class of aPL or had multiple positive titers. IgM aCL was noted in 18 of the 23 patients (78%). Oligoclonal bands were noted in five patients. Antinuclear antibodies (ANA) and low complement levels were frequently observed. Blinded MRI readings showed lesions consistent with MS in the majority of cases. Clinically, 7 patients had transverse myelitis (TM), while optic neuritis (ON) was present in 8 patients. Most patients had either occult symptoms of rheumatic disease or contributory family histories. None had a defined underlying connective-tissue disease. Conclusion: A substantial number of aPL-positive patients have a concurrent diagnosis of MS or MSL, frequently presenting with elevated IgM aCL, optic neuritis, and transverse myelitis. The anti-phospholipid syndrome (APS) should be strongly considered as an alternative diagnosis to MS in these patients.
β2 glycoprotein I containing immune-complexes in lupus patients: association with thrombocytopenia and lipoprotein (a) levels
Authors: George J , Gilburd B , Langevitz P , Levy Y , Nezlin R , Harats D , Shoenfeld Y 
Published: November 2003

In this study we determined the prevalence and clinical associations of immune-complexescontaining beta-2-glycoprotein I (b2GPI) in randomly selected SLE patients. We studied 38 consecutive SLE patients attending the Rheumatology Unit. Previous arterial or venous-thrombosis were documented by the appropriate diagnostic test. Lipid profile including total cholesterol, LDL, VLDL, HDL and Lp(a) levels were determined from the sera of the fasting patients. Antibodies to cardiolipin, oxidized LDL and b2GPI were detected employing ELISA. b2GPI containing IgG immune-complexes were assayed by using a dot-blot assay. Fourteen SLE patients (36.8%) were found to be positive for the presence of IgG anti-b2GPI antibodies. Ten of the SLE patients (26.3%) were found to have high levels of b2GPI containing immune-complexes. There was a positive correlation between b2GPI-IC levels and the occurrence of thrombocytopenia in the patients (P < 0.05). Furthermore, patients with SLE and venous thrombosis had higher levels of b2GPI-IC when compared with thrombosis-free patients or with healthy controls (P < 0.05). Patients with higher Lp(a) levels (> 50 mg/dl) possessed higher levels of b2GPI-IC as compared with patients with lower Lp(a) concentration (< 20 mg/dl) (P < 0.05). These results suggest that IC-containing b2GPI can help in defining a subpopulation of SLE patients with increased risk of thrombocytopenia and further aid in resolving mechanisms of immune-mediated tissue damage.
Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus
Authors: Tjernström F , Hellmer G , Nived O , Truedsson L , Sturfelt G 
Published: November 2003

We investigated whether IL1RN alleles separately or in combination with MHC class II variants, contribute to susceptibility to SLE and to analysed if IL1RN alleles are markers of disease severity. We investigated 81 patients from a defined area in southern Sweden diagnosed between 1981–1992 and 10 consecutive Caucasian families with multiple cases of SLE. As control group 189 healthy blood donors was used. PCR amplification of defined gene sequences was used in determining the IL1RN polymorphism as well as the MHC class II variants. The IL-1RA levels were measured by an immunoassay. We found an increased frequency of IL1RN*2 in both the epidemiological cohort and in the multicase families (P < 0.01). Alone IL1RN*2 and MHC class II (DR17,DQ2) separately increased the SLE risk moderately. The occurrence of IL1RN*2 and MHC class II variants DR17 and DQ2 together increased the risk to develop SLE by a sevenfold. The IL-1RA gene polymorphism did not correlate with disease severity or with renal involvement. We found an association between IL1RN*1 and arthritis (P < 0.001). Serum level of IL-1RA did not correspond to any specific IL1RN allele. An increased frequency of IL1RN*2 suggests the presence of a gene, implemented in SLE-susceptibility, in the IL1RN region of chromosome 2. IL1RN*2 and specific variants of MHC class II act in synergy to increase disease susceptibility. IL1RN*1 may be a marker of risk for development of arthritis.
Chilblain lupus erythematosus is associated with antibodies to SSA/Ro
Authors: Franceschini F , Calzavara-Pinton P , Quinzanini M , Cavazzana I , Bettoni L , Zane C , Facchetti F , Airò P , McCauliffe D P , Cattaneo R 
Published: November 2003

Chilblain lupus erythematosus (CL) of Hutchinson is a subtype of lupus erythematosus (LE) characterized by erythematous lesions induced by cold, damp climates. A number of patients affected by CL eventually develop features of systemic lupus erythematosus (SLE).We report here 9 patients with chilblain cutaneous lesions, 6 of them were affected by SLE and 2 by SCLE. The onset of CL preceded the diagnosis of LE, from 1 to 10 years in 3 cases, it was concurrent in one case and was subsequent in the remaining 4 cases. Raynaud's phenomenon and photosensitivity were other prominent clinical features in patients with CL. Nailfold capillaroscopy revealed pathological changes in every patient examined. ANA and anti-SSA/Ro antibodies were detected in all nine patients. Anti-SSB/La were detected in 2 cases, anti-Sm in one case, and anti Sm and anti-RNP in a one case. Antibodies to dsDNA and complement consumption were found in the six patients with SLE. The fine specificity of anti-SSA/Ro was determined by immunoblotting: anti-60kD and anti-52 kD were detected in three sera, anti-60kD alone in 5 sera, while one serum did not blot. In conclusion, the present study suggests that chilblain LE is associated with SSA/Ro autoantibodies, as is SCLE, hypergammaglobulinemic purpura and neonatal lupus erythematosus.
Systemic lupus erythematosus in three ethnic groups: III A comparison of characteristics early in the natural history of the LUMINA cohort
Authors: Alarcón G S , Friedman A W , Straaton K V , Moulds J M , Lisse J , Bastian H M , McGwin G , Bartolucci A A , Roseman J M , Reveille J D 
Published: November 2003

Aim: To determine and contrast the socioeconomic-demographic and clinical features of patients with recent onset (5 y) systemic lupus erythematosus (SLE) from three ethnic groups, Hispanic, African-American and Caucasian (H, AA, C). Subjects and methods: SLE cases (American College of Rheumatology criteria) (incident (n ‘ 56), prevalent (n ‘ 173)), were enrolled in a longitudinal study at The University of Alabama at Birmingham, The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston. Socioeconomic-demographic, clinical, immunological, behavioral and psychological data were obtained using validated instruments and standard laboratory techniques, and compared. Results: 70 H, 88 AA and 71 C SLE patients constitutethis cohort. H and AA patients were younger and of lower socioeconomic-demographic status. They also had evidence of more frequent organ system involvement (renal, cardiovascular), more auto-antibodies, more active disease (after adjusting for discrepant socioeconomic-demographic features), lower levels of social support and more abnormal illness-related behaviors (more in H than in AA). H also were more likely to have an abrupt disease onset; C were more likely to be on antimalarials but less likely to be on corticosteroids. H, AA, and C used health care resources comparably. They had similar levels of pain and physical and mental functioning after adjusting for age, disease duration, income, education, social support, illness-related behaviors, and Systemic Lupus Activity Measure or SLAM scores. Conclusions: H and AA patients have more active SLE, at an earlier age of onset, and a less favorable socioeconomic-demographic structure (worse among the H than AA) which predispose them to a less favorable natural history.
Seasonal variations in activity of systemic lupus erythematosus in a subarctic region
Authors: Haga H-J , Brun J G , Rekvig O P , Wetterberg L 
Published: November 2003

Photosensitivity is one of the major clinical features of Systemic Lupus Erythematosus (SLE), and is considered to be implicated in the disease pathogenesis. We studied seasonal variations of SLE disease activity at latitude 70 North where there is no sunlight in the winter time, in contrast to 24 h daily sunlight in the summer (midnight sun). The associations between the level of plasma melatonin in June and December with disease manifestations were also studied. Twenty-one SLE patients were examined each month for 1 y, and disease activity was assessed by laboratory parameters as well as clinical disease activity parameters SLEDAI and doctor's global assessment. Melatonin levels were quantified by a RIA-assay. There was no significant change of clinical measures or laboratory parameters of disease activity from one month to the next during the one year, except photosensitive rashes. January was the only month without SLE-flares or arthritis, in contrast to rest of the year. The levels of plasma melatonin were highest in December for seven patients and highest in June for one patient (P < 0.005). Plasma melatonin levels did not correlate with measures of clinical disease activity. At a latitude of 70 North there were no major seasonal variations in SLE disease activity during the one year. There was an accumulation of photosensitivity in the summer months, but no indications of worsening of the disease in the winter months. In contrast to the rest of the year, there was no flare in January which had only 5.6 h of sunshine. The level of p-melatonin did not correlate with measures of disease activity.
Methodological issues of corticosteroid use in SLE clinical trials
Authors: Corzillius M , Bae S-C 
Published: November 2003

Objective: To describe and analyze how investigators handled concurrent steroid intake in SLE clinical trials; to identify remaining methodological problems and to discuss potential solutions. Methods: A review of the literature was performed in Medline to identify randomized controlled trials (RCT) in lupus published during the past decade. A set of criteria was defined a priori to analyze these trials covering different aspects of steroid use in RCTs with regard to eligibility, randomization, post-randomization steroid use, analysis and reporting. Results: Seventeen trials met the inclusion criteria and were analyzed. Median sample size was 30, ranging from 10–71. In three trials corticosteroid application was the study intervention. Three reports did not address steroid use among study subjects at all. In seven trials steroid use was part of the eligibility criteria in some way. Of the trials that allowed concurrent steroid use, seven checked for equal distribution of baseline steroids. In some cases clinically relevant differences did not reach statistical significance as sample sizes were very small. In only one study was randomization stratified for steroid use. Instructions for post-randomization steroid use were specified in only 3 of 14 trials where steroids were not part of the intervention. In 11 RCTs concurrent steroid use was free or no information was provided. Steroid dosing during the intervention was reported as a secondary outcome measure in four trials. Conclusions: As sample sizes are often small, simple randomization is not reliable to avoid relevant between-group differences in baseline steroids. The power of statistical testing for group differences is limited for the same reason. Stratified randomization is rarely used. Free concurrent steroid use during the intervention is frequently allowed in lupus RCTs despite the risk of bias. Better data and accepted standards for a priori specified steroid regimens in RCTs are highly warranted.
Responsiveness and sensitivity to change of SLE disease activity measures
Authors: Corzillius M , Fortin P , Stucki G 
Published: November 2003

The ability of outcome measures to detect change over time is critical for their usefulness in clinical trials. Two concepts are applied in the assessment of evaluative instruments: We endorse the recommendation that a distinction be made between sensitivity and responsiveness. Sensitivity to change refers to the capacity of instruments to measure change statistically. Sensitivity statistics relate the magnitude of observed change to some measure of variablity and are essentially signal-to-noise ratios. Responsiveness addresses the detection of clinically relevant change. The methodology is still evolving but a common approach has been to correlate the observed change in scores with external standards that are believed to indicate clinical relevance (e.g., physician-or patient-based transition scales). Sensitivity to change and responsiveness of SLE activity indices have been addressed in a small number of studies. These indicate that the most widely used systems (SLEDAI. SLAM, BILAG) are sensitive to change although the available evidence does not allow preference for one instrument over the others. Little research has been done on the responsiveness of these measures. This article reviews the methodological concepts in measuringclinical change and summarizes reports on sensitivity and responsiveness of lupus activity scores.
World Wide Web: Opportunities, challenges, and threats
Authors: Edworthy S M 
Published: November 2003

The Internet provides new opportunities to gather information on the population and may provide alternatives to the traditional methods of conducting clinical trials in systemic lupus erythematosus. The ‘world wide web-www’ has grown extensively in the past decade and it is estimated that there will be over 1 billion individuals on the net by the year 2005. Notifying, recruiting and assessing patients using Internet technology are already potential uses of this electronic medium. However, total reliance on the Internet could lead to biased sampling of patients with lupus. Women with low incomes or who are unemployed are less likely to have access to the Internet. Individuals with neurological deficits may have trouble using the Internet effectively. Data collected on the web may not have high reliability and much work needs to be completed to determine the psychometric properties of information derived from this source. One of the greatest threats to contend with is protecting the confidentiality of patient information when using electronic communication. Safeguards against inadvertent or unintended release of information must receive high priority in any attempt to use the Internet for clinical trials. Particular attention should be paid to email messages, which have the potential to be intercepted or sent to individuals without clearance to see patient information. Nevertheless, the costs to systems performance caused by security measures must also be considered and balanced against the need for access by those with appropriate authority. A number of websites already exist for the benefit of patients and providers. Clinicians and scientists interested in the field of lupus research will need to keep up to date on the rapidly proliferating information that is becoming available. This article lists sites which can be visited now.
Methods of reducing loss of efficiency due to discreteness of distributions
Authors: Cohen A , Sackrowitz H B 
Published: November 2003

All models of this paper involve R × C contingency tables in which the total frequency is fixed (full multinomial model), or in which the row totals are fixed (product multinomial model). For the most part, we assume that the column categories are ordered. For the full multinomial model the null hypothesis of interest is independence, i.e., the ( ij)th cell probability is the product of the marginal probabilities of the ith row and jth column. In the product multinomial model the null hypothesis is that the R multinomial distributions have the same vector of cell probabilities.Our review includes (1) a careful listing of two-sided and one-sided alternatives, and (2) methodology to reduce the loss of efficiency of tests because of the discreteness of the model (The methodologies discussed are efficient in several senses. Tests are exact. Tests have very favorable and robust power properties. Tests make use of back-up statistics, thereby providing a finer grid of p-values. In some special cases, e.g., a 2 × C table and a one-sided alternative, conditional p-values are found, within seconds, simply by entering row frequencies into a given website. Thus, computational efficiency is exceptional.), and (3) a critique of some exact linear permutation tests (that are conditional on row and column margins) for both two-sided and some one-sided alternatives. Furthermore, recommendations as to which tests to use for specific alternatives are made.