bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematological, hemostatic and clinical chemistry disturbances induced by Crotalus durissus terrificus snake venom in dogs
Authors: de sousa-e-Silva M CC , Tomy S C , Tavares F L , Navajas L , Larsson M HMA , Lucas S RR , Kogika M M , Sano-Martins I S
Published: November 2003

The aim of this study was to investigate the hematological, hemostatic and biochemical disturbances induced by the injection of Crotalus durissus terrificus venom in dogs under controlled conditions. For this purpose three groups of animals were used: an experimental group (E), which was injected i.m. with C. durissus terrificusvenom (1 mg/kg); and two control groups / antivenom / which were injected i.m. with 150 mM NaCl. Groups E and AV were treated i.v. withCrotalus antivenom 2 hours after the first injection. Serum levels of alkaline phosphatase and alanine aminotransferase were increased in groups E and AV at 24 and 48 hours after serumtherapy, respectively. The increased serum levels of myoglobin, creatine kinase and aspartate aminotransferase demonstrated that animals developed rhabdomyolysis. A persistent neutrophilic leukocytosis was already noticeable at 2 hours after envenomation and lasted even after serumtherapy. The animals of groups E and AV presented eosinopenia 24 hours after serumtherapy, and collagen-induced platelet hypoaggregation was observed without thrombocytopenia. Increased levels of fibrinogen/fibrin degradation products (FnDP/FgDP), hypofibrinogenemia, and a2-antiplasmin consumption were observed at 2 hours after envenomation, indicating secondary activation of fibrinolysis. Our data suggest that the biochemical and hemostatic disturbances induced by C. durissus terrificus venom in dogs are related to its myotoxic and thrombin-like activities.
Validation of a Chinese version of the Medical Outcomes Study Family and Marital Functioning Measures in patients with SLE
Authors: Thumboo J , Feng P-H , Soh C-H , Boey M-L , Thio S-t , Fong K-Y
Published: November 2003

The objective was to validate a Chinese translation of the Medical Outcomes Study Family and Marital Functioning Measures (FFM and MFM) in patients with systemic lupus erythematosus (SLE).

Chinese-speaking SLE patients (n ‘ 69) completed a self-administered questionnaire containing the FFM and MFM and assessing demographic and socio-economic status twice within a 2 week period. SLE activity, disease-related damage and quality of life were assessed using the BILAG, SLICC/ACR Damage Index and SF-36 Health Survey, respectively. Scale psychometric properties were assessed through factor analysis, Cronbach's alpha, quantifying test ± retest differences and known-groups construct validity.

Factor analysis identified 1 factor corresponding to the FFM and 2 factors corresponding to the MFM. Internal consistency for the FFM was excellent (a ‘ 0.92) while that for the MFM was acceptable (a ‘ 0.62). Mean (s.d.) test ± retest differences were 0.06 (1.54) points for the FFM and 0.03 (2.08) points for the MFM. 11 and 10 of 13 a priori hypotheses relating the FFM and MFM, respectively, to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales.

The Chinese FFM and MFM are valid and reliable measures of family and marital functioning in Chinese-speaking SLE patients, with psychometric properties very similar to the source English version.
Maculopapular lupus rash in a young woman with systemic involvement
Authors: Cardinali C , Giomi B , Caproni M , Fabbri P
Published: November 2003

We describe a 23-y-old woman with known systemic lupus erythematosus (SLE) who presented to us with the characteristic maculopapular lupus rash. Although well-known among the LE-specific skin lesions, this acute cutaneous manifestation is rarely reported.
Vascular events in hypertensive patients with systemic lupus erythematosus
Authors: Rahman P , Aguero S , Gladman D D , Hallett D , Urowitz M B
Published: November 2003

Our purpose was to examine prospectively the relationship between systemic hypertension and vascular events in patients with SLE.

SLE patients followed in the University of Toronto Lupus Clinic presenting between 1980 and 1988 and within one year of their diagnosis of SLE were identified. Standard definitions were used for hypertension and for all vascular events (MI, angina, CVA, PVD). The presence of traditional CAD risk factors, along with disease- and therapy-related risk factors for the development of vascular disease, were compared in the hypertensive and normotensive group. A multivariate logistic regression was performed to determine the best predictor of a vascular event.

One hundred and fifty patients were identified in our inception cohort [75 hypertensive (50%) and 75 (50%) normotensive]. Seventeen hypertensive patients (22.7%) had at least one vascular event as compared to six (8.0%) normotensive patients (P = 0.022). The vascular events included 7 with CAD, 5 with CVA, and 5 with PVD in the hypertensive group while in the normotensive group 3 patients developed CAD, 2 CVA and 1 PVD. Fifteen deaths were recorded in the hypertensive group as compared to eight deaths in the non-hypertensive groups (P = 0.09). The groups were comparable with respect to associated risk factors, except for higher frequency of hypercholesterolemia (P = 0.003), azotemia (P = 0.001) and corticosteroid use (P = 0.038) in the hypertension group. In a multivariate analysis the best predictor of a vascular event was hypercholesterolemia (OR 6.9, 95% CI 2.4–24.8, P < 0.001).

We conclude that systemic hypertension is associated with an increased frequency of vascular events in SLE. This is best explained by its association with hypercholesterolemia.
The rating scale preference measure as an evaluative measure in systemic lupus erythematosus
Authors: Ward M M , Marx A S , Barry N N
Published: November 2003

Preference measures may be useful tools to assess patients' overall health-related quality of life. We studied the validity and sensitivity to change of the rating scale preference measure in patients with systemic lupus erythematosus (SLE), and compared its properties with those of the patient global assessment of SLE activity, in a prospective longitudinal observational study of changes in the symptoms and clinical disease activity of 23 patients. Patients were assessed every two weeks for up to 40 weeks. Construct validity was assessed by the strength of correlations between changes over time in the rating scale preference measure and patient global assessment and changes in the physician global assessment, Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measure (ECLAM), the British Isles Lupus Assessment Group index (BILAG), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Changes in the rating scale were more highly correlated with changes in each of these standards than were changes in the patient global assessment, demonstrating the construct validity of this measure. Sensitivity to change was measured using the two-week interval of greatest change in either the physician global assessment or the SLE activity measures as standards. The rating scale preference measure was less sensitive to change than the patient global assessment when tested against four different standards. The sensitivity to change of the rating scale was less than one-half that of the patient global assessment when either the SLAM or ECLAM was used as the standard. Although these results support the validity of the rating scale as a measure of health-related quality of life in patients with SLE, its limited sensitivity to change may make it less attractive as an endpoint measure in clinical trials.
From BILAG to BLIPS—disease activity assessment in lupus past, present and future
Authors: Isenberg D A , Gordon C
Published: November 2003

During the past 16 years, members of the British Isles Lupus Assessment Group (BILAG) have met on a regular basis and have been instrumental in devising a comprehensive disease activity index and, in association with others in the international rheumatological community, devising and/or testing damage and patients self-assessment indices. The history of what the BILAG group has achieved is set out here and the latest attempts at computerisation and improvements in the Disease Activity Index itself are described.
Safety profile and causes of withdrawal due to adverse events in systemic lupus erythematosus patients treated long-term with cyclosporine A
Authors: Conti F , Priori R , Alessandri C , Spinelli F R , Medda E , Valesini G
Published: November 2003

Several case reports and uncontrolled trials have established the use of cyclosporine A (CsA) in systemic lupus erythematosus (SLE) but some concerns have been raised because of its kidney damaging effects. We here report the results of a retrospective follow-up study designed to assess the safety profile and causes of discontinuation due to adverse events in SLE patients treated with CsA.

We treated 56 SLE patients with oral CsA at doses of 3 ± 5 mg/kg for an average of 26 months. Adverse events not leading to the discontinuation of therapy were observed in 62.5% of the patients, the most frequent being hypertrichosis. CsA was stopped because of the occurrence of side effects in 9=56 (16%) of the patients. The most common were nephrotoxicity (3=9) and the occurrence of tremors (3=9). These effects were always reversible within three months of CsA withdrawal. The patients who were older than 40 y had a significant slightly increased risk of stopping CsA therapy for any adverse events (RR 1.08; CI 95% 1.03 ± 1.14).

In comparison with previous studies, this study involved a larger cohort of SLE patients who were evaluated for a longer period of follow-up, and confirmed the good tolerability of CsA in these subjects.
Systemic lupus erythematosus presenting with a reticular erythematous mucinosis-like condition
Authors: Pozo J Del , Peña C , Almagro M , Yebra M T , Martínez W
Published: November 2003

We report the case of a woman with clinical and histopathological features of reticular erythematous mucinosis syndrome (REM) who six years later developed diagnostic criteria for systemic lupus erythematosus (SLE). Two biopsies performed at the same area initially showed mucin dermal deposits and further development of characteristic dermo-epidermal changes of lupus erythematosus.

Our findings suggest that SLE may present with a REM-like condition.
Extensive lymphadenopathy as the first clinical manifestation in systemic lupus erythematosus
Authors: Kitsanou Margarita , Andreopoulou Eleni , Bai Maria K , Elisaf Moses , Drosos Alexandros A
Published: November 2003

Lymphadenopathy (LAP) is a frequent sign of systemic lupus erythematosus (SLE). The lymph nodes are usually soft, nontender, varying in size from 0.5 cm to several centimeters. However, generalized LAP in SLE is extremely rare, while to our knowledge, the presentation of extensive LAP with blocks of retrosternal, mesenteric, and retroperitoneal nodes has not been previously reported as the first clinical manifestation of the disease. In this report we describe a patient with extensive LAP and active SLE and we point out that generalized LAP should be included among the clinical findings indicating disease activity in SLE patients.
Thymoma associated with systemic lupus erythematosus and immunologic abnormalities
Authors: Bozzolo E , Bellone M , Quaroni N , Voci C , Sabbadini M G
Published: November 2003

The association between Systemic Lupus Erythematosus (SLE) and thymoma occurs with a greater frequency than dictated by coincidence alone. The immunologic effects of thymectomy on the appearance and/or the course of SLE are still to be elucidated. We report one case of SLE diagnosed at the same time as thymoma, and two cases of thymoma associated with immunologic disorders in the absence of clinical signs and symptoms diagnostic of SLE.
ANA negative systemic lupus erythematosus sera revisited serologically
Authors: Reichlin Morris
Published: November 2003

Objective: To better define the serology of a panel of sera from patients with a clinical diagnosis of systemic lupus erythematosus (SLE) or subacute cutaneous lupus erythematosus (SCLE) with a negative antinuclear antibody (ANA) test on mouse liver.

Methods: Sensitive ELISA methods for anti-Ro/SSA, anti-La/SSB, and anti-U1RNP were applied to a panel of 76 sera with either SLE or SCLE and a negative ANA test on mouse liver.

Results: These sera had previously been shown to have a high prevalence of anti-Ro/SSA (68%) and anti-La/SSB (27%) precipitins respectively. None had precipitins to U1RNP or Sm. ELISA methodology revealed that all of the sera 76=76 (100%) had elevated levels (Mean±2SDofa panel of 21 normal sera) of anti-Ro/SSA, 36=76 (46%) had elevated levels of anti-La/SSB, and 27 of 76 (35%) had elevated levels of anti-U1RNP.

Conclusion: The subset of patients with SLE and SCLE with a negative ANA test on mouse liver almost uniformly have antibodies to the Ro/SSA antigen by a sensitive ELISA. This adds evidence to the idea that this is a more homogeneous disease subset within the spectrum of SLE.
Serum levels of soluble Fas correlate with indices of organ damage in systemic lupus erythematosus
Authors: Al-Maini Mustafa H , Mountz John D , Al-Mohri Huda A , El-Ageb Elnour M , Al-Riyami Bazdawi M , Svenson Karin L G , Zhou Tong , Richens Elizabeth R
Published: November 2003

Objective: To evaluate whether the levels of soluble form of the Fas apoptosis antigen (sCD95=sFas) varied from those of healthy control subjects in a group of patients with systemic lupus erythematosus (SLE). This was done to determine whether sFas has a role in either the disease activity or the organ damage in SLE.

Methods: Serum levels of sFas were measured over a period of 4 y (277 determinations) in 39 Arab patients with SLE and 22 age-, gender-, and race-matched healthy controls using double antibody ELISA. SLEDAI scores for disease activity and SLICC/ACR scores for cumulative organ damage were determined. Serum levels of acute phase reactants, complement, inflammatory cell counts, levels of autoantibodies, and kidney and liver function test results were obtained retrospectively from clinical records.

Results: sFas levels were significantly higher in patients with SLE (n = 39, 277 determinations) (0.60 ng/ml± 0.38) than in healthy controls (n = 22) (0.26 ng/ml± 0.11) (P < 0.00001). The levels of sFas correlated with SLICC/ACR (r = 0.36; P < 0.02), but not with SLEDAI. sFas correlated with renal and liver function tests measured by s-creatinine (r = 0.38; P:30, P < 0.001), s-albumin (r =-0:28, P < 0.0001), and ALT (r = 0.35; P < 0.00001), but did not correlate with the levels of acute phase reactants.

Conclusion: sFas is elevated in sera of SLE patient. Since sFas correlates with indices of organ damage but not with disease activity, it may be a marker of organ damage in SLE and may act to protect certain organs from further damage by inhibiting Fas-mediated apoptosis.
Expression of complement regulatory proteins in diffuse proliferative glomerulonephritis
Authors: Arora M , Arora R , Tiwari S C , Das N , Srivastava L M
Published: November 2003

This study assessed the expression of complement receptor 1 (CR1), decay accelerating factor (DAF) and membrane inhibitor of reactive lysis (CD59) on the erythrocytes and glomerulus of diffuse proliferative glomerulonephritis (DPGN) of systemic lupus erythematosus (SLE) patients using flow cytometry and immunofluorescence techniques to elucidate their role in the pathogenesis of DPGN. Expression of CR1 on the erythrocytes and glomerulus of DPGN patients was reduced compared with expression in normal subjects. However, expression of DAF and CD59 was increased on both erythrocytes and glomerulus of DPGN patients, suggesting the generation of a protective response against complement-mediated injury.
How accelerated atherosclerosis in SLE has changed our management of the disorder
Authors: Hallegua D S , Wallace D J
Published: November 2003

Basic science insights along with the assessment of risk factors so clearly documented by the Canadian and Hopkins cohorts in earlier papers of this special issue have clearly led to a change in the way rheumatologists manage SLE. This review will highlight specific ways it should alter our day to day treatment of lupus patients.
Autoimmunity in atherosclerosis: lessons from experimental models
Authors: George J , Afek A , Gilburd B , Harats D , Shoenfeld Y
Published: November 2003

The modern view of atherosclerosis is of a chronic inflammatory disorder. In accord with this paradigm, the process of uninhibited influx of fat to the vessel wall results from an ‘adequate’ response to various forms of injury (i.e. turbulence, infections, modified lipoproteins). This idea has been further extended by several groups, to assume that the atherosclerotic lesion can be the target of an autoimmune mediated attack. According to this hypothesis, the site of initiation of the plaque should bear/express the target autoantigen, whereas concomitantly a respective immune response is generated in the periphery. The examples illuminating this notion are β2GPI as a target autoantigen, HSP60/65 an oxidized-LDL.

Herein we present evidence to support the involvement of autoimmune mechanisms in atherogenesis based on the experience from experimental models and human studies.
Vascular imaging: changing the face of cardiovascular research
Authors: Manzi S , Kuller L H , Edmundowicz D , Sutton-Tyrrell K
Published: November 2003

Patients with systemic lupus erythematosus (SLE) are at significant risk for premature cardiovascular disease, now a leading cause of death in this population. Most previous studies have used an overt clinical event to identify cardiovascular disease, likely underestimating the actual prevalence in these patients. Although the rates of myocardial infarction in SLE are high, the actual number of coronary events is low, precluding large clinical trials using a coronary event as the sole outcome. The ability to measure atherosclerosis, a known determinant of coronary heart disease, provides investigators with a desirable surrogate for the clinical cardiac event. With the advent of sensitive imaging techniques to identify subclinical atherosclerosis, we are now better equipped to determine the true prevalence and mechanisms of vascular disease in SLE. In this review, we will discuss several vascular imaging techniques and the current trend away from measuring flow-limiting vessel stenosis toward measuring earlier structural and functional aspects of the vascular system.
Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort
Authors: Petri M
Published: November 2003

Coronary artery disease (CAD) is a major cause of morbidity and mortality in SLE, including the Hopkins Lupus Cohort. Currently, 9% of the cohort have had clinical evidence (angina or myocardial infarction) of CAD. In our initial prospective study we found that duration of prednisone, hypertension, hyperlipidemia and obesity were risk factors for later CAD. We can now extend that list to include age, male sex, elevated homocysteine, renal insufficiency and antiphospholipid antibodies. Many of the risk factors are amenable to intervention, but the timing of intervention, and the effectiveness of intervention, must be determined.
The endothelium in atherogenesis
Authors: Hunt B J
Published: November 2003

The focus of this article is an overview of the endothelial changes that initiate and perpetuate the process of atherogenesis. The endothelium can undergo a series of changes which allow it to participate in the inflammatory response; this is known as endothelial cell activation (ECA). The five core changes of ECA are loss of vascular integrity; expression of leucocyte adhesion molecules; change in phenotype from antithrombotic to prothrombotic; cytokine production, and upregulation of HLA molecules. The diverse effects of ECA share a common intracellular control mechanism through the activation of the transcription factors including Nuclear Factor kB. ECA is an initiating step in atherogenesis. Modified low density lipoproteins are probably the major cause of endothelial cell activation in atherogenesis, and become especially so after oxidation, glycation (in diabetes) or incorporation in immune complexes. In antiphospholipid syndrome (APS), antiendothelial cell antibodies have been detected in up to 67% of patients. In vitro studies suggest that aPL causes ECA and thus lead to speculation that aPL by causing ECA may initiate atherogenesis. Further clinical and in vitro studies are required to address these issues.
Lipoprotein(a) oxidation and autoantibodies: a new path in atherothrombosis
Authors: Romero F I , Khamashta M A , Hughes G RV
Published: November 2003

Lipoprotein(a) (Lp(a)) is considered a vascular pathogen of outstanding importance. High plasma levels of this lipoprotein are associated with premature arterial disease; however, the mechanisms involved have not been clarified. The atherosclerotic process is increasingly regarded as a chronic inflammatory reaction in the arterial wall where oxidation-mediated endothelial injury involving modified forms of low-density lipoprotein (LDL) seems to be a key event. Autoimmune pathways are involved in the progression of atherosclerosis and humoral response to oxidatively modified LDL can be considered among these pathways.

A number of factors can be encountered in the pathogenesis of the accelerated arterial disease seen in patients with antiphospholipid (Hughes) syndrome (APS) and systemic lupus erythematosus (SLE). Among these, high levels of Lp(a) have been described in both and increasing evidence indicates that patients with antiphospholipid antibodies (aPL) are under oxidative stress. Recent studies suggest that the so-called ‘oxidation theory of atherosclerosis’ may also be applied to Lp(a). This fact makes this lipoprotein potentially suitable as a target of the immune system and antibodies reacting against oxidatively-modified Lp(a) by malondialdehyde have been recently described in APS and SLE. It is therefore likely that an immune response to the oxidized moiety of Lp(a) might be influential in the pathogenicity of this lipoprotein and, subsequently, of atherosclerosis.
Accelerated atheroma in lupus—background
Authors: Urowitz M B , Gladman D D
Published: November 2003

Observational cohort studies in SLE have led to the description of accelerated atherosclerosis as an important cause of mortality and morbidity in this disease. The clinical observation of coronary artery disease occurring in premenopausal females with SLE gave rise to the concept of the bimodal mortality pattern. This pattern was confirmed in autopsy and epidemiological studies. These studies identified hypercholesterolemia and particularly its persistence in the first three years of disease, hypertension, and lupus itself as important risk factors for the development of accelerated atherosclerosis in these patients. It also became evident that corticosteroid therapy plays an important role in the elevation of plasma lipids while antimalarials resulted in a reduction of plasma cholesterol, LDL, and VLDL, especially in steroid-induced hyperlipidemia. Studies of clinical outcomes for atherosclerotic disease (angina, myocardial infarction) have shown a prevalence of 6-12% in a number of SLE cohorts. However, more sensitive investigations including myocardial perfusion imaging and carotid ultrasound have demonstrated a prevalence of atherosclerotic disease in 40% of patients studied. Further studies of SLE disease process, including immunological factors, may more clearly define the pathogenesis of accelerated atherosclerosis in patients with SLE, and may help elucidate mechanisms of atherosclerosis in the general population.
Antibodies to oxidised LDL
Authors: Vaarala O
Published: November 2003

In prospective studies antibodies to oxidised LDL (low density lipoprotein) have been shown to predict myocardial infarction and progression of carotid athesclerosis in non-autoimmune subjects. The antibodies to oxidised LDL are crossreactive with antiphospholipid antibodies most likely due to their binding to oxidised phospholipids. The frequent occurrence of these antibodies and their association with arterial thrombosis in patients with SLE and antiphospholipid syndrome suggest their involvement in the development of accelerated atherosclerosis in these patients. Some in vitro studies suggest that antibodies to oxidised LDL may have an atherogenic effect by enhancing the lipid accumulation into macrophages in the atherosclerotic vessels. These antibodies can be considered as markers of the pathogenic determinants of atherosclerosis, such as enhanced lipid oxidation, proinflammatory stage and impaired vasodilatation.
Lost-to-follow-up study in systemic lupus erythematosus (SLE)
Authors: Gladman D D , Koh D-R , Urowitz M B , Farewell V T
Published: November 2003

Objective: To determine the extent of and reasons for lost-to-follow-up, as well as its impact on outcome studies in a cohort of lupus patients.

Methods: As of September 1991, 247 patients, in a cohort of 621 patients with SLE, being followed in a long-term prognosis study, had not been seen since 1 March, 1990 and were considered lost-to-follow-up. Patients were contacted and encouraged to return for an evaluation or to answer a questionnaire by telephone. Descriptive statistics were used to compare the lost-to-follow-up and non-lost-to-follow-up patients and the survival experience during the lost-to-follow-up period was compared with that when patients were not considered lost-to-follow-up. Estimated survival curves with and without the information gained through contacts with lost-to-follow-up patients were compared.

Results: Of the 247 patients, 29 have died, 66 returned for a full assessment, 84 completed a questionnaire and 68 (11%) were true lost-to-follow-up. The lost-to-follow-up patient group had 10% more Caucasians and 6% more males than the patients under regular follow-up. The estimated survival curves of the entire cohort with and without the new lost-to-follow-up data, calculated as of July 1992, were very similar. There was no evidence of a differential mortality rate during the period in which patients were lost-to-follow-up. Some suggestive evidence that the relative mortality rate comparing the rate during a period of lost-to-follow-up and during a period of active follow-up may depend on disease duration at the time of lost-to-follow-up was found.

Conclusions: While it would be prudent to limit lost-to-follow-up as much as possible, especially for outcomes such as mortality which do not necessarily require a clinic visit, it does not appear that significant bias will be present in prospective studies based on our single clinic database. Since the retrieved 179 lost-to-follow-up patients did not affect survival studies it is likely that the 68 true lost-to-follow-up patients will also not have an impact on prognostic studies.
A case of progressive systemic sclerosis complicated by massive pleural effusion with elevated CA125
Authors: Funauchi M , Ikoma S , Yu H , Sugiyama M , Ohno M , Kinoshita K , Hamada K , Kanamaru A
Published: November 2003

A tumor marker, CA125, is known to increase in the serum or other body fluids in various malignancies such as ovarian cancer. Here we present a case of progressive systemic sclerosis (PSS) with massive pleural effusion, in which CA125 in the serum and pleural fluid were elevated. The serum level of CA125 decreased in accordance with the change of the pleural effusion. CA125 level may be an indicator for the activity of serositis in some cases with collagen vascular diseases.
Evaluation of cerebrospinal anticardiolipin antibodies in lupus patients with neuropsychiatric manifestations
Authors: Lai N-S , Lan J-L
Published: November 2003

To evaluate the role of cerebrospinal fluid (CSF) anticardiolipin antibody (aCL) in lupus patients with neuropsychiatric manifestations, paired measurements of aCL, in the serum and CSF, were performed using the ELISA method in lupus patients (n = 31) and controls with other medical diseases (n = 8). High titers of CSF IgG-aCL were detected in cerebral lupus patients with lupus headache, acute psychosis, cognitive impairment, high cortical dysfunction, and altered consciousness. Intrathecal synthesis, rather than the diffusion of IgG-aCL from serum to compartment of the central nervous system, occurred in these NPLE patients. The binding of aCL to brain components might play a role in the development of neuropsychiatric manifestations in cerebral lupus patients.
Accuracy of medical record scoring of the SLICC/ACR Damage Index for systemic lupus erythematosus
Authors: Thumboo J , Lee H-Y , Fong K-Y , Chan S-P , Chapman CAT , Leong K-H , Feng P-H , Thio S-T , Boey M-L
Published: November 2003

Objective: To study the accuracy of medical record scoring of the SLICC/ACR Damage Index (DI) for SLE.

Methods: Medical record DI (MDI) scoring of 60 SLE patients by one physician was compared with prospective direct DI (DDI) scoring a median of 2 y earlier. Agreement between DDI and MDI total and organ system scores was compared using Cohen's kappa, the degree of misclassification by MDI and the significance of differences between DDI and MDI scores.

Results: The mean duration of SLE at DDI scoring was 5.2 y. The median/mean (SD) DDI and MDI total scores were 0=0.78 (1.38) and 0=0.85 (1.44). Damage was present on DDI and MDI scoring in 36.7% (22=60) and 38.3% (23=60) of patients. Qualitative MDI and DDI total scores (damage present/absent) showed good agreement (kappa ‘ 0.61, 95% CI ‘ 0.40–0.82, 18.3% misclassification). Quantitative MDI and DDI total scores (degree of damage) showed moderate agreement (kappa ‘ 0.47, 95% CI ‘ 0.28–0.66, 36.7% misclassification). 9 of 12 MDI organ system scores misclassified < 10% of subjects. There was no statistically significant difference between DDI and MDI total or organ system scores.

Conclusion: MDI total scoring is a good qualitative and moderate quantitative reflection of SLE related damage. MDI organ system scores are more accurate than MDI total scores.
A case of adult-onset Still's disease complicated by non-Hodgkin's lymphoma
Authors: Sono H , Matsuo K , Miyazato H , Sakaguchi M , Matsuda M , Hamada K , Tatsumi Y , Maeda Y , Funauchi M , Kanamaru A
Published: November 2003

Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adultonset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.
Complement component 9 deficiency is not a susceptibility factor for SLE
Authors: Kanemitsu S , Ihara K , Kira R , Kaku Y , Sakai K , Tsuzaka K , Takeuchi T , Hara T
Published: November 2003

Almost all complement component 9 (C9) deficiency in Japan shows Arg95Stop mutation of C9 gene. Therefore, we studied the prevalence of Arg95Stop mutation of C9 gene among 78 patients with SLE to elucidate the association of SLE and C9 deficiency. The Arg95Stop carrier frequency showed no significant difference between SLE patients and controls. Thus, C9 deficiency is not implicated in SLE susceptibility.
Evaluation of cardiac abnormalities and embolic sources in primary antiphospholipid syndrome by transesophageal echocardiography
Authors: Turiel M , Muzzupappa S , Gottardi B , Crema C , Sarzi-Puttini P , Rossi E
Published: November 2003

Objective: Valvular lesions are frequently present in Primary Antiphospholipid Syndrome (PAPS) patients using transthoracic and/or transesophageal echocardiography. The aim of this study was to describe the prevalence of cardiac abnormalities (valvular thickening and/or regurgitation) or potential embolic sources (spontaneous echocontrast and/or vegetations) in PAPS patients.

Methods: Multiplane transesophageal echocardiography was performed consecutively on 40 PAPS patients: 17 of them with thrombocytopenia, 27 with at least one thromboembolic event (stroke, transient ischaemic attack, arterial and/or venous thrombosis, pulmonary embolism) and 14 with recurrent fetal loss.

Design: Cardiac involvement (cardiac abnormalities and/or embolic sources) was present in 33/40 (82%) of PAPS patients. According to aCL titer these lesions were revealed in 17/24 (71%) of patients with aCL < 40 GPL-U, while these lesions were present in 100% of patients with aCL > 40 GPL-U. Three patients presented mitral stenosis and 3 non-infective valve masses or vegetations. Embolic sources were found in 4/24 (17%) patients with aCL <40 GPL-U, while they were observed in 6/16 (37%) of patients with titer of aCL >40 GPL-U (X2- 10.03, P <0.01). Regression analysis showed a positive correlation between mitral valve thickening and aCL antibodies titer (r= 0.5; P<0.001).

Conclusions: Valvular lesions are commonly found in PAPS patients. Our data showed a significant correlation among aCL titer, mitral leaflets thickening and thromboembolic events.
Central pontine myelinolysis a rare manifestation of CNS Sjogren's syndrome
Authors: Yoon K H , Fong K Y , Koh D R , Suri R
Published: November 2003

Central nervous involvement in Sjogren's syndrome (CNS-SS) is not uncommon and has a variety of manifestations. We describe a 47-year-old woman with Sjogren's syndrome who presented with distal renal tubular acidosis with severe hypokalemia and hypokalemic myopathy. She developed progressive obtundation after years of stable disease. ANA, anti-Ro antibodies were positive. Brain MRI showed a cleft in the mid pons which was hypointense on T1 and hyperintense on T2 which was considered to be classical of central pontine myelinolysis. Serial MRI showed initial enlargement of the lesion which persisted despite successful immunosuppressive therapy with pulse methyprednisolone, pulse cyclophosphamide, plasmapharesis and IVIG.
Parkinsonism as unusual neurological complication in childhood systemic lupus erythematosus
Authors: Kwong K L , Chu R , Wong S N
Published: November 2003

Parkinsonism complicating systemic lupus erythematosus (SLE) is extremely rare. We report two girls with SLE who developed extrapyramidal parkinsonian features after an initial stormy course. One patient presented with generalized tonic clonic seizure and was then noted to have akinetic mutism and masked face. MRI brain revealed abnormal signals in bilateral basal ganglia and single photon emission computed tomography (SPECT) showed hypoperfusion in the same area. EEG background was slow and disorganized. Symptoms persisted despite high dose intravenous methylprednisolone and cyclophosphamide. Intravenous immunoglobulin (IVIG) was prescribed empirically and was followed by complete recovery. Both EEG and MRI brain were normal on follow-up. The second patient was found unconscious and then developed bradykinesia, mutism and shuffling gait. MRI and SPECT both detected abnormalities in basal ganglia. EEG was slow. Intravenous immunoglobulin was given after methylprednisolone and cyclophosphamide. This was followed by clinical improvement. The pathogenesis of basal ganglia injury in SLE, along with the management of cerebral lupus and the mechanisms of action of IVIG, are discussed.
Cluster analysis of antinuclear autoantibodies in the prognosis of SLE nephropathy: are anti-extractable nuclear antibodies protective?
Authors: Tapanes F J , Vdsquez M , Ramirez R , Matheus C , Rodriguez M A , Bianco N
Published: November 2003

To investigate the possible role of anti-ENA autoantibodies in the pathogenesis of SLE nephropathy, we performed a cross sectional clustering study of 91 SLE patients using 75 clinical and laboratory variables examining the presence of anti-dsDNA and ENA autontibodies by ELISA and Western blot. We applied principal component, hierarchical cluster, multiple correspondence and logistical regression analysis. Two polar forms of SLE nephropathy and five clinical groups were identified: group 1 without overt nephropathy (n = 37), group 2 with nephropathy and only proteinuria (n = 19), group 3 nephropathy and only hematuria (n = 11), group 4 with hematuria and proteinuria (n = 14) and group 5 on renal failure (n = 10). When analyzed individually, levels of anti-dsDNA and single anti-ENA antibodies did not allow us to differentiate between renal and non-renal groups. However, when the anti-ENA autoantibodies were analyzed as a cluster, a high predictive value for clinical nephropathy was obtained. Thus, the absence of ENA antibodies (ENA ve or Venezuelan cluster) increased eleven-fold the odds ratio to develop SLE nephropathy. We suggested that the ENA ve cluster may predict development of the most severe forms of renal lupus while the ENA Sm/RNP and the ENA Ro/La/Sm/RNP clusters could be associated with the absence and the most benign form of SLE nephropathy. It must be interesting to apply similar cluster methodology in an SLE population with different ethnic background.
A novel treatment for lupus nephritis: lignan precursor derived from flax
Authors: Clark W F , Muir A D , Westcott N D , Parbtani A
Published: November 2003

Background: Flaxseed has renoprotective effects in animal and human lupus nephritis. We have recently extracted the lignan precursor (secoisolariresinol diglucoside) (SDG) to determine if this more palatable derivative of flaxseed would exert renoprotection similar to the whole flaxseed in the aggressive MRL/lpr lupus mouse model.

Methods: 131 MRL/lpr mice were randomly assigned to saline gavage, 600, 1200 and 4800 μg lignan gavage groups. At 7 weeks, 6 animals underwent platelet aggregating factor (PAF) lethal challenge and 40 were studied with urine collection to determine the levels of secoisolariresinol, enterodiol and enterolactone in the gavaged animals. A baseline study of 10 saline gavaged animals took place at 6 weeks. 25 animals in the saline gavage, 600 and 1200 μg lignan groups were studied at 14 and 22 weeks for GFR, spleen lymphocyte S-phase and organ weight studies.

Results: Metabolic studies indicated that secoisolariresinol is the major metabolite absorbed and the lowest lignan dose provides a lengthening in survival for the PAF lethal challenge. Body weight, fluid and water intake studies demonstrated that the lignan was well tolerated. Changes in proteinuria, GFR and renal size showed a time-and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in the S-phase demonstrated modest dose-dependent reductions in the lignan gavaged groups.

Conclusion: SDG was converted in the gut to secoisolariresinol, which was absorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidenced, in a dose-dependent fashion, by a significant delay in the onset of proteinuria with preservation in GFR and renal size. This study suggests that SDG may have a therapeutic role in lupus nephritis.
The validity of the ECLAM index for the retrospective evaluation of disease activity in systemic lupus erythematosus
Authors: Mosca M , Bencivelli W , Vitali C , Carrai P , Neri R , Bombardieri S
Published: November 2003

Aim: To determine whether the European Consensus Lupus Activity Measurement Index (ECLAM) can be used to evaluate disease activity in patients retrospectively from the data provided in their clinical charts.

Methods: The ECLAM score was calculated twice in a series of 64 consecutive SLE patients: first for each patient during the course of a standard clinical evaluation (direct-ECLAM), and then one to two weeks later solely on the basis of the data provided in the patient's clinical chart (chart-ECLAM). The scorings for each patient were performed by two different assessors.

Results: The direct-ECLAM and chart-ECLAM scores were highly correlated (Spearman's rank correlation coefficient = 0.86). The regression line was not significantly different from the identity line (t-test). The Pearson's coefficient was 0.88. The interobserver variability of the chart-ECLAM showed a low inter-rater variability.

Conclusion: ECLAM could represent a valid and reliable instrument for the retrospective analysis of disease activity in SLE patients.
Antiphospholipid antibodies in alcoholic liver disease are influenced by histological damage but not by alcohol consumption
Authors: Perney P , Biron-Andreani C , Joomaye Z , Fabbro-Peray P , Quenet F , Schved J F , Blanc F
Published: November 2003

Antiphospholipid antibodies (aPL) have been detected in various liver diseases, particularly cirrhosis. The role of alcoholic consumption per se has been suggested. The aim of our study was to assess the prevalence of aPL in patients with alcoholic liver disease at various states and to correlate the presence of aPL with both liver injury and alcoholic consumption.

Three groups were prospectively included. Group A: 74 controls (age-and sex-matched); group B: 46 patients with alcoholic steatosis; group C: 28 patients with alcoholic cirrhosis. For each patient, lupus anticoagulant, anticardiolipin antibodies and anti-j32-glycoprotein I antibodies were tested.

The prevalence of aPL (presence of at least one positive test) was 5% in group A, 20% in group B and 50% in group C (P < 0.04). No correlation appeared between aPL and Child Pugh score in group C. No correlation was found between the presence of aPL and alcohol intake in patients with either steatosis or cirrhosis. Our study confirms that aPL positivity is more frequently encountered in patients with alcoholic liver disease than in controls. Their prevalence increases with the degree of histological damage but not with the level of alcoholic intake.
Systemic lupus erythematosus associated with moyamoya syndrome
Authors: El Ramahi K M , Al Rayes H M
Published: November 2003

Moyamoya disease is an uncommon clinical entity, characterized by bilateral occlusion of the internal carotid artery and the development of collateral arteries. An 18-year-old Saudi male with systemic lupus erythematosus (SLE) presented with mild right hemiparesis, followed by recurrent ischemic stroke. Cerebral angiography showed bilateral internal carotid artery stenosis associated with the development of collateral circulation (moyamoya vessels). There was no evidence of active SLE or other risk factors for cerebral occlusion, such as antiphospholipid antibody syndrome. Medical and surgical interventions did not influence the poor outcome of the recurrent ischemic insults.
Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus
Authors: Wong C K , Ho CY Y , Li EK , Lam CWK
Published: November 2003

Previous studies have indicated that the autoimmune phenomenon might be caused by an imbalance of T helper cell (Th) cytokines. We measured the plasma concentrations of three novel proinflammatory cytokines interleukin (IL)-17, IL-18, IL-12 and a key Th2 cytokine IL-4 in patients with systemic lupus erythematosus (SLE) and correlated the ratio of proin/Th2 cytokines with SLE disease activity index (SLEDAI). Plasma IL-12, IL-17, IL-18 and IL-4 concentrations of 36 SLE patients and 18 sex-and age-matched control subjects were measured by enzyme linked immunosorbent assay. All were significantly higher in SLE patients than control subjects (IL-12, mean± s.d. of 166.7± 84.5 vs 93.5± 39.2 pg/ml, P < 0.001; IL-17, 76.5± 45.7 vs 37.6± 35.3 pg/ml, P = 0.002; IL-18, 368.7± 199.5 vs 141.1± 47.1 pg/ml, P < 0.001; and IL-4, 27.1± 15.3 vs 17.3± 7.2 pg/ml, P < 0.05), and IL-18/IL-4 ratio correlated positively and significantly with SLEDAI score (r = 0.435, P = 0.006). We propose that SLE is characterized by an elevation of both Th1 and Th2 cytokines: the elevation of proinflammatory cytokine IL-12, IL-17 and IL-18 may trigger the inflammatory process in SLE and the elevation of IL-18/IL-4 ratio suggests an imbalance of cytokine profile to mediate the inflammatory response.
High prevalence of antiphospholipid antibodies in leprosy: evaluation of antigen reactivity
Authors: de Larrañaga G F , Forastiero R R , Martinuzzo M E , Carreras L O , Tsariktsian G , Sturno M M , Alonso B S
Published: November 2003

Antiphospholipid antibodies (aPL) have been reported not only in autoimmune disorders but also in various infectious diseases. Accumulating evidence indicates that b2 glycoprotein I (b2GPI) and prothrombin are the main proteins to which autoimmune aPL bind. The aim of this study was to evaluate the prevalence of different aPL in patients with leprosy. We included 51 outpatients (42 lepromatous and 9 borderline leprosy) without any clinical feature of the antiphospholipid syndrome (APS). 35 had lupus anticoagulant and 31 had anticardiolipin antibodies (aCL). Anti-β2GPI antibodies were highly positive in 29=51 and anti-prothrombin antibodies (anti-II) were detected in 23=51. Almost all aCL and anti-b2GPI were of IgM isotype, while IgG isotype was more frequent among anti-II. No statistical difference was found when aPL were evaluated in patients grouped according to their bacteriological status. Furthermore, patients under treatment (n ‘ 33) had a similar frequency of positive aPL compared to patients in vigilance (n ‘ 14). Assessing the specificity of antibody binding to CL and b2GPI in ELISA by means of inhibition studies with cardiolipin-b2GPI liposomes, leprosy and APS sera showed a similar behaviour. Comparable results were also found in both groups of patients when inhibition experiments with lysate of Mycobacterium leprae were carried out. In summary, leprosy-related aPL resemble those found in patients with APS but the immunoglobulin isotype is different, with IgM much more prevalent in leprosy patients.