bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic lupus erythematosus and the risk of malignancy
Authors: Cibere J , Sibley J , Haga M 
Published: November 2003

The objective of this study was to determine the relative risks of malignancy and of site-specific malignancies in patients with systemic lupus erythematosus (SLE). A cohort of 297 patients (91% Caucasian) with SLE were seen between 1975 and 1994 and followed for a mean of 12 years at the University of Saskatchewan Rheumatic Disease Unit. Expected cancer incidence rates were determined based on Province of Saskatchewan population statistics matched to each study patient for age, sex and calendar year of follow-up. Standardized incidence ratios (SIRs) of observed to expected cancers and 95% confidence intervals (95% CI) were calculated. A total of 27 cases of cancer were observed, whereas only 16.9 were expected (SIR 1.59 (95% CI 1.05–2.32)). For site-specific malignancies, an excess of cancer of the cervix (SIR 8.15 (95% CI 1.63–23.81)) as well as hemopoietic malignancy (SIR 4.9 (95% CI 1.57–11.43)) was found. The hemopoietic cancers were predominantly non-Hodgkin's lymphoma (SIR 7.01 (95% CI 1.88–17.96)). We did not find an association of malignancy with known risk factors, including use of cytotoxic agents. Increased risk of malignancy, notably non-Hodgkin's lymphoma and perhaps cervical cancer, should be regarded as a complication of SLE.
Reliability and validity of systemic lupus activity measure-revised (SLAM-R) for measuring clinical disease activity in systemic lupus erythematosus
Authors: Bae S-C , Koh H-K , Chang D-K , Kim M-H , Park J-K , Kim S Y 
Published: November 2003

New clinical scales for semiquantitating disease activity in systemic lupus erythematosus (SLE) are widely used in research. They are reliable and valid measures. One of the original scales, the Systemic Lupus Activity Measure (SLAM), has been modified based on experience with it in multiobserver studies and training of individuals in its use. We tested the psychometric properties of the revised SLAM (SLAM-R). SLAM-R was tested on 30 SLE patients, who fulfilled 1997 revised ACR criteria and were selected to represent a range of disease activity. The patients were evaluated independently by two physicians, who studied the instruction booklet and who had never used SLAM-R, on two occasions 2–4 weeks apart. At the first visit, the physician's global assessment of activity using visual analog scale, anti-dsDNA Ab, C3 and C4 were checked for construct validity. The psychometric properties were analyzed with nested analysis of variance and Pearson's correlation coefficient using SAS. All patients were female, the median age was 31 (15–52) y, and the mean score of SLAM-R was 10.5±5.3 (3–26). Estimates of reliability were 0.78 of inter-rater, 0.61 of inter-visit, 0.76 of physician 1 between visits, and 0.56 of physician 2 between visits. Among subcategories except ‘Eye,’ the ‘Gastrointestinal’ category had the highest (0.96) and the ‘Neuromotor’ category had the lowest inter-rater reliability (0.50). With respect to construct validity, the correlation of SLAM-R scores with the disease activity variables except C4 was high and statistically significant. In conclusion, the SLAM-R is reliable and valid for measuring clinical disease activity in SLE.
Significance of isolated hematuria and isolated pyuria in systemic lupus erythematosus
Authors: Rahman P , Gladman D D , Ibanez D , Urowitz M B 
Published: November 2003

Hematuria or sterile pyuria as isolated urinary findings present a clinical dilemma for the treating physician. Our objective was to determine whether isolated hematuria and isolated sterile pyuria are associated with active systemic lupus erythematosus (SLE) with respect to renal and non-renal disease activity. This is a descriptive study from a large SLE cohort followed prospectively at the University of Toronto Lupus Clinic. All episodes of isolated hematuria and isolated pyuria between 1970 and 2000 were identified from our database. Isolated hematuria was defined as >5 red blood cells per high power field; isolated sterile pyuria was defined as >5 white blood cells per high power field in the absence of urinary infection and other renal manifestations. Non-renal disease activity (defined as nrSLEDAI >1) was determined at first episode of isolated hematuria and pyuria. Renal disease activity was assessed by scoring renal biopsies within 3 months of detecting isolated hematuria or sterile pyuria. Thirty-four percent (323=946) of our cohort had at least one episode of isolated hematuria. Seventy-seven percent of these patients had concurrent non-renal disease activity. Of the 22 biopsies scored with isolated hematuria, 96% were abnormal (WHO >class I), including 52% with active nephritis. Twenty-three percent (215=946) had at least one episode of isolated sterile pyuria. Seventy-eight percent of these patients had concurrent non-renal disease activity. All 12 biopsies scored with isolated pyuria were abnormal (WHO Class >1), including 75% with active nephritis. The appearance of isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. An ongoing debate has emerged regarding the significance of isolated hematuria and isolated pyuria with respect to SLE disease activity. The results of this study suggest that isolated hematuria and isolated pyuria is associated with active renal and non-renal disease activity. Thus isolated hematuria and isolated sterile pyuria should be considered manifestations of active SLE.
In vitro ultraviolet irradiation induces pro-inflammatory responses in cells from premorbid SLE mice
Authors: Foltyn V N , Golan T D 
Published: November 2003

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease, in which sunlight (especiallyits ultraviolet radiation (UVR)) is known to induce exacerbation of cutaneous lesions as well as systemic manifestations of the disease. The aim of this in vitro study was toinvestigate whether UVR (UVA, UVB) amplifies pro-inflammatory factors in cultured dermal fibroblasts (DF) or lymph node cells derived from premorbid or morbid mice from the murine SLE strains (MRL-1pr=1pr, (NZB/NZW)F1), in comparison to cells derived from normalmice from the non-SLE strains (C57BL=6, BALB/c). Our results demonstrate the following. Dermal fibroblast of premorbid SLE mice showed increased susceptibility toUVA and UVB irradiation, determined by viability assay, incomparison to those of normal mice. UVB irradiation inducedan enhanced expression of ICAM-1 in such SLE derived cells,in comparison to cells of normal mice. UVA and UVB increased functional activity of LFA-1 in lymph node cells of premorbid SLE mice and not in normal controls. UVB irradiation induced increased production and secretion of pro-inflammaory cytokines (IL-1, IL-6, TNF-a) in DF o premorbid SLE mice, in comparison to normal controls. Theenhanced pro-inflammatory responses to UVR werealsoobserved in experiments conducted with cells derivedfrom morbid SLE mice. In conclusion, the pro-inflammatory pronenessdetected in the premorbid stage of murine SLE could be ofmajor importance in SLE pathogenesis. Furthermore, it suggests that the autoimmine inflammatory process in vivo, triggered initially by immune complex deposition, could be further amplified by UVR.
Polymorphisms of the CTLA-4 exon 1 and promoter gene in systemic lupus erythematosus
Authors: Lee Y H , Kim Y R , Ji J D , Sohn J , Song G G 
Published: November 2003

The objective of this study was to determine whether the polymorphisms of the CTLA-4 exon 1 (/49) and promoter (7318) are associated with susceptibility to systemic lupus erythematosus (SLE) and its clinical features. Polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the CTLA-4 exon 1 (/49) and promoter (7318) in 80 SLE patients and 86 healthy control subjects. The genotype distribution of the CTLA-4 exon 1 (/49) differed between SLE patients and controls (w2 = 6.74, 2 degrees of freedom (d.f.), P = 0.03). The CTLA-4 AG genotype occurred more frequently in patients with SLE (46.3% vs 33.7% controls). On the other hand, the CTLA-4 AA genotype as well as the CTLA-4 GG genotype was less frequent among SLE patients than among control subjects (1.3% vs 9.3% and 52.5% vs 57.0%, respectively). The genotype distribution of the CTLA-4 promoter (-318) different between SLE patients and control subjects (CT, TT, CC; genotype 27.5%, 0%, 72.5% vs 16.3%, 4.7%, 79.1% controls respectively, w2 = 6.36 2 d.f., P = 0.04). However, Fisher's exact or w2 P-values for each genotypes of the CTLA-4 exon l (+49) and promoter (-318) between SLE and control group < 0.05. Clinically, in the lupus patients there was no significant difference according to the CTLA-4 polymorphism. In conclusion, no correlation was found between CTLA-4 exon 1 (+49) and promoter (-318) polymorphisms and SLE in our study.
AVEMAR (a new benzoquinone-containing natural product) administration interferes with the Th2 response in experimental SLE and promotes amelioration of the disease
Authors: Ehrenfeld M , Blank M , Shoenfeld Y , Hidvegi M 
Published: November 2003

The potential of oral treatment with AVEMAR (AVEMAR), a new benzoquinone-containing fermentation product of wheat germ, on features of experimental systemic lupus erythematosus (SLE) in naive mice, induced by idiotypic manipulation, was studied. We assessed the effect of AVEMAR on the profile of autoantibody production and the response of Th1=Th2 related cytokines as well as the clinical picture of experimental SLE in the SLE-induced mice. When the product was given in the pre-immunization period, down-regulation of autoantibody production (anti-dsDNA, mouse 16=6 Id, and anti-histones) following treatment with AVEMAR was noted (eg anti-dsDNA decreased from 0.898 0.097 OD at 405 nm to 0.519 0.103 OD following treatment). This effect was sustained for at least 4 weeks after discontinuation of the therapy. Serological manifestations associated with a delay in Th2 response (IL-4 and IL-10) were recorded (eg IL-4 decreased from 91.7 8.11 to 59.55 7.78 ng =ml in splenocyte condition media). The mice showed normal ESR, WBC and less than 100 mg/dl of protein in the urine in comparison to > 300 mg/dl protein in the SLE non-treated mice. In conclusion, oral intake of AVEMAR can ameliorate the clinical manifestations of experimental SLE, via affecting the Th1=Th2 network inhibiting Th2 response.
Geographical variation in mortality from systemic lupus erythematosus in the United States
Authors: Walsh S J , Dechello L M 
Published: November 2003

The aim was to identify demographic and environmental factors that affect the incidence and course of systemic lupus erythematosus (SLE) by studying geographical variation in mortality from the disease. Counts of SLE deaths during a 10-y period were determined for each of the 3111 counties in the United States. The counts were subjected to statistical techniques for detecting spatial clusters with significantly higher or lower mortality than expected. Census data were used to compare attributes of the resulting clusters. Four clusters with significantly elevated SLE mortality were identified. They were centered in Alabama, Arkansas, Louisiana and New Mexico and had 41–65% more SLE deaths than expected. Four other clusters with significantly low mortality were centered in Minnesota, Vermont, Virginia and Washington and had 32 ± 44% fewer deaths than expected. Comparison of SLE mortality rates between the New Mexico and Vermont clusters yielded relative risks of 3.2, 3.4 and 5.9 for white, black and other race women, respectively, and of 2.1, 5.2 and ‘undefined’ for white, black and other race men. Census data showed that the clusters with elevated mortality had higher poverty rates and/or greater concentrations of ethnic Hispanics than those with lower mortality. SLE mortality rates show great regional variation within the United States. The variation appears to reflect, in part, geographical patterns in socioeconomic status and in the distribution of persons of Hispanic origin.
Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity
Authors: Jacobi A M , Rohde W , Ventz M , Riemekasten G , Burmester G-R , Hiepe F 
Published: November 2003

Recent accumulated evidence suggests that prolactin (PRL) is an important immunomodulator and plays a part in the pathogenesis of systemic lupus erythematosus (SLE). The current study assessed the frequency of hyperprolactinaemia in patients with SLE and its association with defined clinical manifestations or serological abnormalities. PRL levels were analysed in 60 patients with SLE including a follow-up of 20 patients, 18 patients with rheumatic autoimmune diseases other than SLE (AID) and in 47 normal healthy subjects (NHS) using ELISA. Clinical manifestations and disease activity (ECLAM) were recorded. Autoantibodies (anti-dsDNA, anti-CL) were determined by standard techniques. In all, 28.3% of the patients with SLE had raised serum PRL. Their PRL levels (17.4 15.1 ng =ml, P < 0.0001) and those of patients with AID (13.1 10.3 ng/ml, P < 0.001) were significantly higher compared to NHS (6.3 3.2 ng =ml). Anti-dsDNA (rs=0.3, P=0.04) and anti-CL antibody titres (IgG; rs=0.3, P=0.03) correlated with PRL level. Furthermore, elevated erythrocyte sedimentation rate (ESR), anaemia, decrease in C3, fatigue, fever and renal involvement were associated with hyperprolactinaemia. These results were confirmed by follow-up examinations. Moderate hyperprolactinaemia is present in a subset of patients with SLE and serum PRL correlates with clinical and serological disease activity.
Prolactin in human systemic lupus erythematosus
Authors: Jara L J , Vera-Lastra O , Miranda J M , Alcala M , Alvarez-Nemegyci J 
Published: November 2003

In the last decade, evidence has accumulated to support the hypothesis that both mild and moderate elevations of serum prolactin (PRL) participate in the clinical expression and pathogenesis of systemic lupus erythematosus (SLE). Hyperprolactinemia (HPRL) has been found in 20–30% of patients with SLE. HPRL seems to be associated with clinical activity of SLE during pregnancy. Although the relationship between HPRL and active SLE in non-pregnant patients is controversial, recent clinical and experimental studies support the potential role of prolactin (PRL) as a promoter of clinical activity and severity of SLE. Mild elevations of serum PRL secondary to microadenoma could trigger the onset of SLE in a subset of patients. Elevated PRL and interleukin (IL)-6 have been found in the urine of patients with active lupus nephritis and in cerebrospinal fluid (CSF) of patients with active central nervous system (CNS) SLE. PRL may therefore participate in the pathogenesis of lupus nephritis and cerebritis, and the presence of PRL may reflect an abnormal communication between the immune system and the neuroendocrine system in active SLE. Lymphocytes from patients with active SLE produce increased amounts of PRL, and this extrapituitary PRL may participate in aberrant immune processes in SLE. There is exciting new evidence that HPRL in SLE may be explained by stimulation of pituitary PRL secretion by cytokines. In addition, defects in peptidergic modulators and dopamine metabolism have been described in patients with SLE. The interactions between PRL, cytoquines, autoantibodies and organ involvement suggest that PRL participates in local and generalized immune and inflammatory processes and acts as a bridge between the neuroendocrine and immune systems in SLE. Understanding the interactions between these systems in SLE will help us to understand and treat this important autoimmune disease.
Analysis of anti-prolactin autoantibodies in systemic lupus erythematosus
Authors: Blanco-Favela F , Chavez-Rueda K , Leaños-Miranda A 
Published: November 2003

Evidence has shown that prolactin is an essential component of an effective immune response. In systemic lupus erythematosus, clinical trials have produced controversial information about the role of PRL. Some results find association between serum PRL levels and disease activity. In contrast, other authors did not find this. Recently, autoantibodies against prolactin in SLE patients have been described. One hundred percent of SLE patients with anti-PRL autoantibodies had hyperprolactinemia (hPRL) and 31.7% of the SLE patients classified with idiopathic hPRL had anti-prolactin antibodies. A similar result was found in 103 pediatric SLE patients. The patients with idiopathic hyperprolactinemia and anti-PRL autoantibodies had less clinical and serological lupus activity than the SLE patients with idiopathic hyperprolactinemia, but without anti-PRL autoantibodies. This evidence suggests that anti-PRL autoantibodies or the complex with any other molecule, like macroprolactinemia (big-big PRL) could have attenuated biological activity and this could explain why some clinical studies did not find any association between serum PRL levels and disease activity in SLE patients. However, studies in vitro have shown normal or elevated biological activity in Nb2 cell lines using PRL from serum with anti-PRL autoantibodies from patients with or without autoimmune diseases. Several conclusions could be drawn. One is that while a set of hyperprolactinemic SLE patients display autoantibodies against PRL, it is not clear what role these autoantibodies play in the whole system. However, until now, we knew that the patients with antibodies to PRL lacked the clinical symptoms of hyperprolactinemia such as menstrual disturbances and/or galactorrhea and show less clinical and serological lupus activity.
Left-sided heart valve abnormalities and risk of ischemic cerebrovascular accidents in patients with systemic lupus erythematosus
Authors: Morelli S , Bernardo M L , Viganego F , Sgreccia A , De Marzio P , Conti F , Priori R , Valesini G 
Published: November 2003

The aim of the study was to assess the relationship between ischemic cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or stroke, and left-sided heart valve abnormalities (LHVAs) in patients with systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were studied.At baseline, history, clinical and laboratoryevaluations, as well as trans-thoracic echocardiography (TTE) were performed. From the original population, so patients were followed up for a mean time of 5.80 + 1.53 years. After a mean period of 5.39 + 1.42 years; 40 patients underwent a repeat TTE. Previous ICVA history was present at baseline in 16 patients (22.5%). Of these, 13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly associated to diagnosis of secondary anti-phospholipid syndrome (SAPS), positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were not more commonly observed in patients with SAPS compared to patients without SAPS. At the end of follow-up, irrespective of any differences in antithrombotic treatment, ICVAs had occurred in 13 patients.During follow-up, ICVAs had recurredin seven patients, while a first eventTIA occurredin one patient. Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a trend towards a positive correlation of the former with SAPS. This study demonstratesthat LHVAs represent a compelling risk factor for the development of ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated with ICVAs, did not clearly correlate with LHVAs in our study. These results provide insight on the pathogenesis of ICVAs and may give clues on the potential efficacy of preventive/therapeutic strategies in different SLE subpopulations.
A Long-Term Study of Hydroxychloroquine Withdrawal on Exacerbations in Systemic Lupus Erythematosus
Authors:   The Canadian Hydroxychloroquine Study Group, Tsakonas E , Joseph L , Esdaile J M , Choquette D , Senécal J-L , Cividino A , Danoff D , Osterland C K , Yeadon C , Smith C D 
Published: November 2003

The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).
High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus
Authors: Perniok A , Wedekind F , Herrmann M , Specker C , Schneider M 
Published: November 2003

Increased in vitro apoptosis and altered expression of apoptosis-related molecules have been reported in systemic lupus erythematosus (SLE). It was speculated that autoantigens released from apoptizing cells may contribute to the etiopathogenesis of SLE by both activation of autoreactive lymphocytes and the formation of immune complexes. Conflicting data about the level of cellular apoptosis from animal models for SLE and human SLE indicate different pathomechanisms. In the present study we analysed the count of circulating early apoptotic cells and its correlation with the clinical activity in SLE compared with the amount in primary systemic vasculitis (PSV). The percentage of early apoptotic cells determined by Annexin V-FITC binding cells was significantly increased in peripheral blood of SLE patients compared with normal healthy donors (NHD) and PSV (NHD 5.62%, SLE 13.68%, PSV 8.69%). Analysis of lymphocytes revealed significantly increased counts in the T cell populations (NHD 5.15%, SLE 12.22%, PSV 10.01%), whereas the increase in B cells did not reach significance level (NHD 9.20%, SLE 18.95%, PSV 16.59%). Apoptotic cell count revealed no correlation to SLAM-Score or to immunosuppressive therapy, corticosteroid-dosage or absolute lymphocyte count. The general increase of circulating apoptotic cells may indicate an impaired clearance in SLE patients, independent of clinical activity or therapeutic interventions. Autoantigens from apoptotic cells may contribute to both activation of autoreactive lymphocytes and formation of immune complexes.