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PubMed1997

Mycotic aneurysm of a coronary artery in SLE--a rare complication of salmonella infection.

We describe a 27y old female systemic lupus erythematosus (SLE) patient with salmonella bacteraemia who presented with fever, back pain and an enlarging heart size. A two dimensional echocardiogram (2D Echo) showed a mass in the right atrium. Subsequent computer tomographic (CT) and magnetic resonance imaging (MRI) studies showed that this had become a ring shaped lesion at the posterior end of the interventricular septum with an area communicating with the right atrial cavity. At operation a ruptured mycotic aneurysm of the right coronary artery was found. This is the first report of an SLE patient with a coronary artery mycotic aneurysm due to salmonella and the first reported case of survival following rupture of such aneurysm.

Adult↗
PubMed1997

Accelerated atherosclerosis and coronary disease in SLE.

Atherosclerosis may represent a significant cause of death and morbidity in patients with systemic lupus erythematosus. Coronary involvement is more premature in lupus patients. We present the case of a young woman diagnosed with SLE at the age of 20 years who had a myocardial infarction at age 29 years. We review the mechanisms of atherosclerosis, the interrelations between atherosclerosis and autoimmunity, and between atherosclerosis and SLE. We also review the risk factors, influence of disease and treatment and the guidelines for management of accelerated atherosclerosis in lupus patients.

Adult↗
PubMed1999

The association between the antiphospholipid antibody syndrome and neuropsychological impairment in SLE.

OBJECTIVE: To examine the relationship between neuropsychological impairment and antiphospholipid antibody syndrome (aPL syndrome) in patients with systemic lupus erythermatosus (SLE). PATIENTS: Sixty-nine patients satisfying ACR criteria were studied. Sixteen patients with the aPL syndrome and 53 patients without the syndrome were subjected to eight neuropsychological tests, a physical examination and serological investigations. No patients with other pathology, known to cause acute or chronic impairment of neuropsychological function, were included. Sixty-five underwent MRI scans. RESULTS: There were no significant differences in age, level of education, incidence of hypertension or disease activity in the two groups. Pearson's correlation coefficients revealed a significant negative correlation with duration of disease in six out of eight tests in the aPL positive group and one out of eight in the aPL negative group. This suggests that aPL syndrome may be involved in the psychological impairment in SLE patients. A larger cohort needs to be studied to confirm this observation.

Adolescent↗
PubMed2005

Beta2 glycoprotein 1 in Indian patients with SLE.

Forty-five patients with systemic lupus erythematosus (SLE) were investigated to evaluate the role of antiphospholipid antibodies in causation of thrombosis in Indians. The antiphospholipid antibodies studied included lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-beta(2)-glycoprotein 1 (a beta(2)-GP1). Twenty-seven patients (60%) had clinical manifestations of antiphospholipid antibody syndrome. Nineteen patients (42.2%) had a history of thrombosis, and eight (17.7%) had a history of recurrent fetal loss. aBeta(2)-GP1 was (IgG) was positive in 23 (51.1%), aCL in 13 (28.8%), and LAC in four (8.8%). Of 19 patients with thrombosis, 14 (73.6%) were positive for abeta(2)-GP1, eight (42.1%) for aCL, and none of them was positive for LAC. Of the eight patients with recurrent fetal loss, two (25%) patients were positive for beta(2)-GP1, five (62.5%) for aCL, and one (12.5%) for LAC. Of 18 patients without any manifestations of antiphospholipid syndrome (APS), seven patients (38.8%) were positive for abeta(2)-GP1, and three (16.6%) for aCL and LAC each. It is concluded that presence of abeta(2)-GP1 increases the risk of thrombosis and therefore should be looked for in all cases of SLE to consider prophylactic antithrombotic therapy in these patients.

Adolescent↗
PubMed2001

Suppression of renal disease and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE) by chenodeoxycholic acid.

The objective of this study was to examine the effects of ursodeoxycholic (UDCA) and chenodeoxycholic acid (CDCA) on autoimmune disease in the NZB x NZW F1 (B/W) mouse model of systemic lupus erythematosus (SLE). The development of murine lupus was assessed in female B/W mice given UDCA or CDCA. At 6 week intervals mice were examined for weight change, albuminuria, anti-DNA antibody and total IgG levels. Morbidity and mortality were assessed daily. UDCA- and CDCA-treated mice were examined at 24 weeks of age for serum cytokines, lymphocyte phenotype, and in vitro cytokine production after immunization with DNP-KLH. Liver and kidneys were examined histopathologically. The administration of UDCA and CDCA was tolerated without side effects. Weight gain in UDCA- or CDCA-treated and control mice was identical through 24 weeks of age. CDCA, but not UDCA, suppressed the development of renal disease. CDCA-treated B/W mice also had improved survival compared to UDCA-treated or control B/W mice. There were no significant effects of CDCA on anti-DNA antibodies, serum total IgG, or other immunologic parameters. CDCA-treated mice had lower serum IFN-gamma concentrations compared to control and UDCA-treated mice. The bile acid, CDCA, significantly inhibited the development of renal disease and modestly prolonged lifespan in the female B/W mouse model of SLE. Suppression of glomerulonephritis was associated with lower serum IFNgamma concentrations. Further investigation is needed to verify potential mechanisms of action, but these findings suggest that bile acids may alter the development or progression of autoimmunity.

Albuminuria↗
PubMed2002

Management of pregnancy in women with pulmonary hypertension secondary to SLE and anti-phospholipid syndrome.

Pulmonary hypertension is found in about 10% of patients with systemic lupus erythematosis (SLE). Pulmonary hypertension may be present at the time of diagnosis or may develop after the diagnosis of SLE or anti-phospholipid syndrome (APS). It often presents in the reproductive years and has a significant impact on pregnancy outcome, being a significant cause of indirect maternal deaths. In our observational case series of three patients there were two deaths (66%). In cases 1 and 2 the pulmonary hypertension developed during pregnancy and deteriorated rapidly with markedly abnormal mean pulmonary artery pressures of 80 and 70 mmHg respectively prior to death. Both patients died within 48 hours of delivery. In case 3 the pulmonary hypertension was milder and was diagnosed very early in pregnancy. The patient received multidisciplinary care from the first trimester and the management of the pregnancy, delivery and the early puerperium was planned. Careful epidural anaesthesia was used and the patient had invasive monitoring on the intensive therapy unit (ITU) for 72 hours. Women with pulmonary hypertension need to be aware of the high risk of maternal mortality associated with pregnancy but we believe that an improvement in outcome can be achieved by careful assessment and the use of a multidisciplinary approach from early in pregnancy.

Adult↗
PubMed1998

Enhancement of hydroxyl radical DNA cleavage by serum anti-dsDNA antibodies in SLE.

Autoantibodies reactive with double-stranded (ds) DNA are a hallmark of systemic lupus erythematosus (SLE), but it is not fully elucidated how these antibodies contribute to the various pathological changes observed in lupus patients. In a previous study, we have found a significant enhancement effect of two murine monoclonal anti-dsDNA antibodies on DNA cleavage by the hydroxyl radical. We have extended this study and have found that purified polyclonal anti-dsDNA antibodies from sera of lupus patients and an MRL/lpr mouse, but not anti-ssDNA antibodies, also enhanced radical cleavage of DNA. The cleavage was inhibited by EDTA, DMSO and thiourea. The antibody preparations per se did not cleave DNA. These results suggest that such an enhancement effect on DNA cleavage is a feature of a significant part of anti-dsDNA antibody population and a possible clue in understanding the roles of anti-dsDNA antibodies in the pathophysiology of SLE under certain circumstances.

Administration, Topical↗
PubMed1998

The hypothalamic-pituitary response in SLE. Regulation of prolactin, growth hormone and cortisol release.

It has been suggested that neuroendocrine regulation plays an important role in the pathogenesis and activation of autoimmune diseases. The aim of this investigation was to clarify the hypothalamic-pituitary response to a well-defined stimulus under standardised conditions in patients with SLE. Plasma concentrations of prolactin (PRL), growth hormone (GH) and cortisol were determined in venous blood drawn through an indwelling cannula during insulin-induced hypoglycaemia (0.1 U/kg b.w., i.v.) in ten patients and in 12 age-, gender- and weight-matched healthy subjects. Basal PRL concentrations were higher in patients vs healthy controls (12 vs 6 ng/ml, P < 0.01), though still within the physiological range. Insulin-induced plasma PRL and GH were significantly increased both in patients and healthy subjects; however, the increments or areas under the curves were not different in the two groups. Plasma cortisol response showed moderate attenuation in patients. Sensitivity of pituitary lactotrothrops to thyrotropin-releasing hormone (TRH) administration (200 microg, i.v.) was the same in patients and control subjects. In SLE patients with low activity of the disease the sensitivity of pituitary PRL release to TRH administration remained unchanged. The hypothalamic response to stress stimulus (hypoglycaemia) was comparable in patients and healthy subjects.

Adult↗
PubMed1998

Successful treatment with immunosuppression, anticoagulation and vasodilator therapy of pulmonary hypertension in SLE associated with secondary antiphospholipid syndrome.

Severe pulmonary hypertension (PHT) occurring in patients with systemic lupus erythematosus (SLE) is uncommon. Different modalities have been tried in the treatment for this condition but have not been effective because of progressive increase of pulmonary resistance over time. Our patient with SLE and PHT with antiphospholipid syndrome (APS), a condition which has previously never been described, responded rapidly to combination treatment with immunosuppression, anticoagulation and vasodilator therapy.

Adult↗
PubMed1999

Validation of the medical outcomes study family and marital functioning measures in SLE patients in Singapore.

OBJECTIVE: To validate the Medical Outcomes Study Family and Marital Functioning Measures (FMM and MFM) in a multi-ethnic, urban Asian population in Singapore. METHODS: English speaking Chinese, Malay or Indian SLE patients (n=120) completed a self-administered questionnaire containing the FFM and MFM at baseline, after 2 weeks and after 6 months. Lupus activity, disease-related damage and quality of life were assessed using the British Isles Lupus Assessment Group (BILAG), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (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. RESULTS: Factor analysis of scores obtained at baseline and after 6 months identified 3 factors corresponding to the FFM (1 factor) and the MFM (2 factors). Both scales showed acceptable internal consistency, with Cronbach's alpha of 0.95 for the FFM and 0.70 for the MFM. Mean (s.d.) test-retest differences were -0.31 (3.82) points for the FFM and -0.70 (4.26) points for the MFM. Eleven out of 13 a priori hypotheses relating both the FFM and MFM to demographic, disease and quality of life variables were confirmed, supporting the construct validity of these scales. CONCLUSION: The FFM and MFM are valid and reliable measures of family and marital functioning in a multi-ethnic cohort of Asian SLE patients in Singapore.

Adolescent↗
PubMed1999

Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE.

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.

Adult↗
PubMed1999

Primary subcutaneous nocardial infection in a SLE patient.

A patient with systemic lupus erythematosus (SLE) developed primary subcutaneous nocardiosis during steroid and cyclophosphamide therapy for diffuse proliferative glomerulonephritis. In spite of local process the patient manifested signs of general deterioration mimicking SLE exacerbation. The diagnosis was made by bacteriologic examination of the material obtained by CT guided aspiration. Surgical drainage and systemic treatment with trimethoprim/sulphamethoxazole (TMT/SMZ) 960 mg twice/d led to a clinical recovery and enabled the continuation of the steroid and cytotoxic regimen.

Adult↗
PubMed1999

Sample size considerations for superiority trials in systemic lupus erythematosus (SLE).

For reasons of efficiency and ethics, sample size calculations are an important part of the design of all clinical trials. This paper highlights the statistical issues inherent to the estimation of sample size requirements in superiority trials particular to SLE. Calculations based on statistical power for testing hypotheses have historically been the method of choice for sample size determination in clinical trials. The advantages of using confidence intervals (CI's) rather than P-values in reporting results of clinical trials is now well established. Since the design of a trial should match the analysis that will eventually be performed, sample size methods based on ensuring accurate estimation of important parameters via sufficiently narrow CI widths should be preferred to methods based on hypothesis testing. Methods and examples are given for sample size calculations for continuous and dichotomous outcomes from both a power and confidence interval width viewpoint. An understanding of sample size calculations in association with expert statistical consultation will result in better designed clinical trials that accurately estimate clinically relevant differences between treatment outcomes, thereby furthering the treatment of patients with SLE.

Confidence Intervals↗
PubMed1999

Quality of life and economic evaluation in SLE clinical trials.

Outcome in SLE patients should include assessment of disease activity and chronic damage and also measurement of health-related quality of life and the economic impact of the disease. This paper reviews the methods available for doing this and the results of existing studies in SLE patients.

Anxiety↗
PubMed1999

Development of an FDA guidance document for clinical trials in SLE.

To make the process of developing new therapeutic agents more efficient, it is critical that investigators and industry sponsors understand in advance what information they will need to provide to the US Food and Drug Administration (FDA) in order to license and market their product. To facilitate that process, the FDA publishes guidance documents describing current thinking about various issues that arise at all stages of product development. The FDA is currently in the process of formulating a guidance document about clinical development programs for systemic lupus erythematosus (SLE). The goal of this document is to describe some of the types of clinical trials that could be used to demonstrate safety and efficacy of therapeutic agents in SLE.

Clinical Trials as Topic↗
PubMed2000

Biochemical characterization of 60S acidic ribosomal P proteins from porcine liver and the inhibition of their immunocomplex formation with sera from systemic lupus erythematosus (SLE) patients by glycyrrhizin in vitro.

The three casein kinase II (CK-II) phosphate acceptors (p35, p17 and p15) in the Superdex CK-II fraction prepared from a 1.5 M NaCl extract of porcine liver were selectively purified by glycyrrhizin (GL)-affinity column chromatography (HPLC) as a heterocomplex associated with CK-II. Determination of the N-terminal amino acid sequences and immunological tests confirmed that these three CK-II phosphate acceptors belong to the family of 60S acidic ribosomal proteins (P0, P1 and P2). Three polyphenol-containing anti-oxidant compounds [catechin, epigallocatechin gallate (EGCG) and quercetin] inhibited CK-II activity (phosphorylation of these ribosomal P proteins) in a dose-dependent manner in vitro. Quercetin (ID50 = approx. 50 nM) was found to be an effective CK-II inhibitor. In contrast, CK-II activity was significantly stimulated by lower doses (0.3-3 microl) of GL, but was inhibited at high doses above 30 microM. As expected, GL at high doses above 200 microM inhibited the immunocomplex formation of 60S acidic ribosomal P proteins with their specific antibodies in the sera from patients with systemic lupus erythematosus (SLE). These results suggest that (i) a GL-affinity column is useful for effective purification of 60S acidic ribosomal P proteins from various mammalian cells as a heterocomplex associated with CK-II; and (ii) a relative high dose of GL may prevent the immunocomplex formation of 60S acidic ribosomal P proteins with their specific antibodies in the sera of SLE patients.

Amino Acid Sequence↗
PubMed2003

Osteonecrosis in patients with SLE.

Osteonecrosis is a clinical entity characterized by death of bone marrow and trabecular bone as a result of disruption of blood supply to the bone (1,2). Other aspects of this condition include avascular necrosis, aseptic necrosis, and osseous ischemic necrosis of bones. Osteonecrosis is classified into two main forms; post-traumatic and nontraumatic. The post-traumatic form of osteonecrosis usually develops as a result of traumatic displacement of bone fragments, which leads to impaired blood supply and ischemia to the affected bone. Osteonecrosis of the femoral head is common following fracture of the femoral neck. A variety of systemic diseases and clinical conditions are associated with nontraumatic osteonecrosis. These include autoimmune rheumatic diseases, alcoholism, pregnancy, Gaucher's disease, thrombophilia, corticosteroid therapy, Sickle-cell anemia, pancreatitis, inflammatory bowel diseases, and use of cytotoxic drugs and others. Idiopathic forms of osteonecrosis have also been reported (2-4). Among the rheumatic diseases, osteonecrosis is strongly associated with systemic lupus erythematosus (SLE) (5). However, osteonecrosis has been diagnosed in patients with primary antiphospholipid syndrome (APS) (6), rheumatoid arthritis (7), and systemic vasculitis (8). This article reviews the causes, clinical and epidemiological features, diagnosis, and treatment options for osteonecrosis among patients with SLE.

Humans↗