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ID PMID Title PublicationDate abstract
14665529 Pulmonary cryptococcosis after initiation of anti-tumor necrosis factor-alpha therapy. 2003 Dec Many patients with rheumatoid arthritis are being treated with immunosuppressive regimens that include an agent directed at blocking tumor necrosis factor (TNF)-alpha. Although reportedly safe, tuberculous and fungal infections have emerged as significant complications of therapy. We report a case of pulmonary cryptococcosis soon after the initiation of therapy with the anti-TNF-alpha antibody, infliximab. A diagnosis was made early in the disease course, and the patient responded quickly to antifungal therapy. This case should alert clinicians to the increased incidence of pulmonary mycoses in patients receiving anti-TNF-alpha therapy.
12187348 Gigantomastia induced by bucillamine. 2002 Aug Drug-induced mammary hyperplasias have been reported as rare complications of D-penicillamine and Neothetazone. The authors report the first case of bucillamine-induced giant mammary hyperplasia. Bucillamine is used as an antirheumatic drug that is structurally analogous to D-penicillamine. A 25-year-old woman with rheumatoid arthritis for the past 5 years started to develop gradual enlargement of her breasts 15 months before presentation. She had been on a combined treatment of steroid and lobenzarit disodium for the first 3 years, and then continued with a combined treatment of steroid and bucillamine for the following years until she was found to have pulmonary tuberculosis, at which time the steroid was suspended 10 months before she visited the authors' clinic. An almost total breast reduction was performed; 5 kg of right breast tissue and 7 kg of left breast tissue were excised. Retrospectively, bucillamine was believed to be the cause of the giant hypertrophy because of its structural similarity to D-penicillamine, which was the subject of an abundance of reports of mammary hyperplasia.
12806141 Low-avidity antibodies to carbonic anhydrase-I and -II in autoimmune chronic pancreatitis. 2002 Jun 11 Antibodies (Abs) to carbonic anhydrase (isoforms CA-I and CA-II) have been considered pathogenic factors in the development of autoimmune pancreatitis. Besides, such autoAbs might accelerate the pancreatic damage in alcoholic chronic pancreatitis (CP). The aim of the present study was to evaluate the presence of serum Abs to CA-I and CA-II in CP and the relative affinity of these Abs. Serum anti-CA-I and -CA-II Abs were measured in 89 patients with CP (48 alcoholic and 41 nonalcoholic) by an ELISA technique. The prevalence of those autoAbs in CP was compared with other autoimmune diseases where they have also been found. The presence of other serological manifestations of autoimmunity, such as hypergammaglobulinemia or antinuclear Abs, was determined in CP patients as well. Elevated serum levels of both anti-CA-I (24%) and -CA-II (18%) Abs were observed in CP, although their prevalence was lower than in autoimmune diseases like rheumatoid arthritis (44 and 25%, respectively) or systemic lupus erythematosus (39% for anti-CA-I Abs). Furthermore, these Abs were of low average avidity. On the other hand, a significantly higher proportion of nonalcoholic CP had anti-CA-II Abs with respect to alcoholic CP (15.2 vs. 2.4%, p < 0.05). Anti-CA-I and -CA-II Abs might be helpful in the diagnosis of autoimmune CP, and the detection of the latter Abs seems to discard alcoholic etiology. Although it does not discard any pathogenic role in autoimmune CP, the low-avidity of anti-CA Abs argues against such idea.
13680152 CD13/aminopeptidase N in collagen vascular diseases. 2003 Nov To determine the significance of CD13/aminopeptidase N in collagen vascular diseases (CVD), we examined its activity and expression in sera and disease sites of patients with CVD. Significantly higher aminopeptidase activity was detected in bronchoalveolar lavage fluid from patients with interstitial lung diseases due to rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), and Sjögren's syndrome than from control subjects. Increased aminopeptidase activity and increased expression of CD13/aminopeptidase N protein were found in alveolar macrophages from CVD patients with interstitial lung diseases. Significantly higher aminopeptidase activity was detected in pleural effusions from patients with systemic lupus erythematosus (SLE) than in transudate effusions. The mean aminopeptidase activity in synovial fluids from RA patients was significantly higher than from patients with osteoarthritis. The mean value of serum aminopeptidase activity was significantly higher in patients with SLE, RA, SSc, and PM/DM than in normal subjects. This study suggests that the activity of CD13/aminopeptidase N, locally produced in the disease site, is a useful marker for CVD and that CD13/aminopeptidase N may have an important role in the pathogenesis of CVD.
12581487 Ingested type I interferon: a potential treatment for autoimmunity. 2002 Dec We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN) immunodeficiency syndrome. We have examined toxicity and potential efficacy in three phase I (type 1 diabetes, rheumatoid arthritis, multiple sclerosis) and one phase II clinical trials in multiple sclerosis (MS). In a phase I open-label trial in type 1 diabetes, ingested IFN-alpha preserved residual beta cell function in recent onset patients. In a second phase I trial, treatment of rheumatoid arthritis (RA) with ingested IFN-alpha reduced the secretion of interleukin-1 (IL-1), a proinflammatory cytokine. In a third phase I trial in MS, there was a significant decrease in peripheral blood mononuclear cell (PBMC) IL-2 and IFN-gamma production after ingesting IFN-alpha. In a phase II randomized, placebo-controlled, double-blind trial in MS, 10,000 IU ingested IFN-alpha significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-alpha on decreasing gadolinium enhancements. Ingested IFN-alpha was not toxic in any of these clinical trials. These studies suggest that ingested IFN-alpha may have a potential role in the treatment of autoimmunity.
15291251 [Collagen diseases with gastrointestinal manifestations]. 2004 Jun Collagen vascular diseases are known to present with a diverse array of gastrointestinal manifestations. These can be classified as: 1) gastrointestinal damage due to the collagen vascular disease itself; 2) adverse events caused by pharmacotherapies; or 3) gastrointestinal infections following immunosuppression due to corticosteroid (CS) administration. The first group includes lupus enteritis and protein-losing gastroenteropathy in systemic lupus erythematosus (SLE), reflux esophagitis, chronic intestinal pseudo-obstruction, and pneumatosis cystoids intestinalis in systemic sclerosis, amyloidosis in rheumatoid arthritis, bowel ulcer and bleeding in rheumatoid vasculitis and microscopic polyangiitis, and ileocecal ulcer in Behcet disease. In particular, colonic ulcers associated with SLE represent refractory lesions resistant to CS. Analysis of reported cases showing colonic lesions with SLE (22 cases in Japan) revealed that mean duration of SLE was 9.9 years and 77% of colonic lesions were observed in the rectum and sigmoid colon. Half of the patients developed intestinal perforation or penetration, and 6 of the 11 patients with perforation died. The second group includes lesions in the small and large intestine due to nonsteroidal anti-inflammatory drugs (NSAIDs) and CSs, in addition to peptic ulcers. As perforation in CS-treated patients displays relatively high incidence with poor prognosis, careful attention to such complications is needed. The third group includes candidal esophagitis and cytomegalovirus (CMV) enteritis. Prompt diagnosis is required to prevent colonic bleeding and perforation due to CMV.
12387527 Single infusion of neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonate) in patient 2002 Jun AIMS: The aim of this study was to assess the effects of a single infusion of the bisphosphonate neridronate (N) on parameters of inflammation and bone resorption in rheumatoid arthritis (RA). METHODS: Forty-five patients with active RA were randomly allocated on a double blind basis to receive a single intravenous infusion of either N 25 mg (15 patients), N 50 mg (15 patients), or placebo (15 patients). At baseline and after 7 and 21 days, we assessed the following: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Ritchie's articular index as indices of disease activity; and urinary free deoxypyridinoline (DPyr), N-telopeptide of type I collagen (NTx) and hydroxyproline (OHP) as indices of bone resorption. RESULTS: At day 7, N 25 mg significantly decreased ESR compared to N 50 mg (p=0.002), and CRP compared to placebo (p=0.036). With regard to bone resorption markers, at day 7, both N 25 mg and 50 mg compared to placebo significantly decreased NTx (p<0.0005 and p=0.003, respectively) and OHP (p=0.001 and p=0.004, respectively). At day 21, N 50 mg significantly decreased OHP compared to placebo (p=0.017). DPyr levels remained unchanged in the three groups. CONCLUSIONS: N 25 mg and 50 mg exerted different effects on RA activity parameters, since only the lower dose significantly decreased ESR and CRP. Both doses of N inhibited bone resorption, with a transient, significant reduction in urinary NTx and OHP, but without any effect on DPyr.
14599803 A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of g 2003 Nov Rheumatoid arthritis (RA) is characterized by progressive destruction of the affected joints. The pathophysiology results from genetic susceptibility and autoimmune phenomena, leading to tissue inflammation and synovial hyperplasia termed pannus, which irreversibly destroys cartilage and bone. The current treatment options, which suppress immune responses or ameliorate inflammation, do not halt the destructive process. We found that the histone deacetylase (HDAC) inhibitors (phenylbutyrate and trichostatin A) causing histone hyperacetylation to modulate multiple gene expression not only induced the expression of p21(Cip1) and p16(INK4) in synovial cells but also inhibited the expression of tumor necrosis factor-alpha in affected tissues in adjuvant arthritis, an animal model of RA. Based on the observations that joint swelling is reduced, subintimal mononuclear cell infiltration is decreased, synovial hyperplasia is inhibited, pannus formation is suppressed, and no cartilage or bone destruction is seen, the HDAC inhibitors may represent a new class of compounds for the treatment of RA by simultaneously, coordinately, synergistically, or epigenetically modulating multiple molecular targets in the pathogenesis of RA.
15614176 [Mycobacterium chelonae myositis]. 2004 Dec 4 INTRODUCTION: Mycobacteria are only exceptionally responsible for infection of the skin and soft tissues. A Mycobacterium chelonae myositis occurred in an immunodepressed patient. OBSERVATION: A 49 year-old man, treated for many years with corticosteroids for vasculitis of the lower limbs associated with rheumatoid polyarthritis, was hospitalized for invasive pulmonary aspergillosis. Ten days later he developed myositis of the right arm with multiple subcutaneous abscesses. Culture of the purulent substance isolated Mycobacterium chelonae. Treatment with ciprofloxacine and clarithromycine led to the regression of the lesions. He was followed-up for 12 months. DISCUSSION: M. chelonae is found in large quantities in the environment. Infection with this mycobacteria is enhanced by immunodepression, notably that secondary to corticosteroid therapy. Resistance to antibiotics are frequent. Clarithromycine is highly effective against this mycobacteria. Bi-therapy is recommended to avoid the emergence of resistance.
12652413 [Chloroquine-induced myopathy and neuropathy: progressive tetraparesis with areflexia that 2003 Mar 16 INTRODUCTION: Chloroquine is a drug that is widely used in rheumatology and occasionally prescribed in dermatology. From a neurotoxicological point of view, chloroquine can have effects on the peripheral nerves, muscles, neuromuscular junctions and the central nervous system. In this study we analyse the clinical, neurophysiological and anatomopathological findings in two patients with chloroquine induced neuromyopathy, which took the form of a polyradiculoneuropathy. CASE REPORTS: Case 1: a 75 year old female with rheumatoid arthritis treated with daily doses of 250 mg of chloroquine for four years. The patient visited because of several months history of predominantly proximal progressive tetraparesis with areflexia. Analytical tests and lumbar puncture were normal. Electromyogram (EMG): proximal myopathic and distal neuropathic patterns. Muscular biopsy: vacuolar myopathy with accumulations of phagolysosomes, lipids, lipofuscin, myelinic curvilinear bodies. Case 2: a 74 year old female with arthropathy treated with daily doses of 250 mg of chloroquine for nine months. The patient presented a progressive proximal paraparesis with generalised areflexia. Analytical tests and lumbar puncture were normal. EMG: mixed sensory motor polyneuropathy, myogenic pattern with high frequency discharges in the iliac psoas and a neurogenic pattern in the distal muscles. Muscular biopsy: vacuolar myopathy suggesting a myopathy due to chloroquine. After stopping treatment with this drug the patients progressed favourably. CONCLUSION: Chloroquine can induce a clinical pattern that suggests a polyradiculoneuropathy. It is important to establish a history of having taken this drug. If this is indeed the case, then an electromyographic study of the most proximal muscles should be performed in order to detect a myogenic pattern and the same exploration should be applied to the distal muscles to reveal a neurogenic pattern. The final diagnosis will be established by muscular biopsy.
15492850 Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associ 2004 Nov Molecular defects of TNFRSF1A was investigated in members of a family presenting with typical phenotypes of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members of a family with typical TRAPS, as well as from 100 patients with SLE, 100 patients with RA and 100 healthy individuals, was studied for mutations in exons 2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel missense mutations were identified in the TNFRSF1A. The C70G mutation was identified in family members with typical TRAPS, which was the second case in eastern Asian population. In addition, the T61I and R104Q mutations were each identified in 2 of the 100 SLE patients. The T61I mutation was identified in one of the 100 healthy individuals. No mutations were identified in the 100 RA patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from PBMCs was impaired in a patient carrying T61I. A larger scale of study will clarify whether these two mutations, T61I and R104Q, are associated with chronic inflammatory disorders, such as SLE, or not.
12375336 Frequency of abnormal hand and wrist radiographs at time of diagnosis of polyarticular juv 2002 Oct OBJECTIVE: To determine the frequency of radiographic abnormalities in hand/wrist radiographs of children with newly diagnosed polyarticular juvenile rheumatoid arthritis (polyJRA) because radiographs of small joints are an important tool in assessing outcomes in RA and there are clinical similarities between RA and polyJRA. METHODS: A medical record review was performed to identify cases of polyJRA seen at Mayo Clinic from January 1, 1994, to December 31, 2001. Hand/wrist radiographs, obtained at the time of diagnosis, were reviewed by 3 radiologists with attention to periarticular osteopenia, joint space narrowing (JSN), or erosion. At least 2 radiologists had to independently identify abnormal findings on the same radiograph. The relative carpal length (RCL), judged by Poznanski's method, was also determined. RESULTS: From the review of 159 medical records, 60 cases of newly diagnosed polyJRA were identified. Twenty-five of these had hand/wrist radiographs at diagnosis; 18 sets were available for this study. Of those, 2/3 were female, 6% (1/18) had subcutaneous nodules, 7% (1/14) had elevated levels of serum rheumatoid factor, and 44% (7/16) had elevated serum levels of antinuclear antibodies. Median age at diagnosis was 10.2 years, median duration of hand/wrist symptoms at diagnosis was 10 months, and median number of joints with either swelling, pain on range of motion (ROM), or limited ROM was 14.5. Sixty-one percent of radiographs taken at the time of diagnosis of polyJRA were abnormal. While 44% had periarticular osteopenia, 28% had either erosions or JSN. Six (33%) had RCL > 2 SD below the mean for age. Five (83%) of those with RCL, > 2 SD below the mean for age, had periarticular osteopenia, JSN, or erosion. CONCLUSION: We conclude the frequency of abnormal hand/wrist radiographs is very high very early in the course of polyJRA. More studies are needed to determine to what extent these radiographic abnormalities correlate with clinical outcomes.
12115222 Identification of citrullinated rheumatoid arthritis-specific epitopes in natural filaggri 2002 May OBJECTIVE: To identify immunodominant epitopes in natural filaggrin that are reactive with antifilaggrin autoantibodies (AFA) in the sera of patients with rheumatoid arthritis (RA) and to explore their use in a diagnostic assay format. METHODS: Based on the results of epitope mapping of human natural filaggrin as well as molecular modeling and computational chemistry, synthetic peptides together with recombinant citrullinated filaggrin were evaluated by a line immunoassay (LIA) for AFA detection. Diagnostic performance was assessed using 336 RA and 253 disease control sera and was compared with that of reference methods. RESULTS: Several immunoreactive epitopes were identified in natural filaggrin, all of which contained at least 1 citrulline residue. Three antigenic substrates, including 2 synthetic peptides and recombinant citrullinated filaggrin showing maximal reactivity on LIA, were finally selected. Using the 3-antigen LIA3, overall sensitivity, specificity, and positive predictive value for RA were 65.2%, 98.0%, and 89.1%, respectively, compared with 61.9%, 98.8%, and 92.8% using the 2-antigen LIA2 (without recombinant protein). Thirty-seven percent of the rheumatoid factor (RF)-negative RA samples (30 of 81) were AFA-positive by LIA2, and 52 of 54 RF-positive control samples had no AFA detected on LIA2. Higher specificity and sensitivity were obtained by LIA2 versus anti-RA33 immunoblot, whereas good agreement was observed with antikeratin antibody testing. LIA performed significantly better than AFA immunoblotting using natural filaggrin, at a specificity level of 99% (P = 0.0047). CONCLUSION: Citrullinated residues are present in immunoreactive epitopes of natural human filaggrin. AFA can be readily detected by citrullinated peptides in an LIA-based test, resulting in high specificity and positive predictive value for RA. The LIA could serve as a user-friendly alternative to existing immunofluorescence tests and AFA immunoblot techniques. Given its complementarity to RF, this test can be a valuable tool in the differential diagnosis of arthritis.
15380043 Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a ba 2004 The pathogenesis of chronic inflammatory joint diseases such as adult and juvenile rheumatoid arthritis and Lyme arthritis is still poorly understood. Central to the various hypotheses in this respect is the notable involvement of T and B cells. Here we develop the premise that the nominal antigen-independent, polyclonal activation of preactivated T cells via Toll-like receptor (TLR)-2 has a pivotal role in the initiation and perpetuation of pathogen-induced chronic inflammatory joint disease. We support this with the following evidence. Both naive and effector T cells express TLR-2. A prototypic lipoprotein, Lip-OspA, from the etiological agent of Lyme disease, namely Borrelia burgdorferi, but not its delipidated form or lipopolysaccharide, was able to provide direct antigen-nonspecific co-stimulatory signals to both antigen-sensitized naive T cells and cytotoxic T lymphocyte (CTL) lines via TLR-2. Lip-OspA induced the proliferation and interferon (IFN)-gamma secretion of purified, anti-CD3-sensitized, naive T cells from C57BL/6 mice but not from TLR-2-deficient mice. Induction of proliferation and IFN-gamma secretion of CTL lines by Lip-OspA was independent of T cell receptor (TCR) engagement but was considerably enhanced after suboptimal TCR activation and was inhibitable by monoclonal antibodies against TLR-2.
15056499 Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogene 2004 Apr Angiogenesis, the development of new blood vessels is a crucial process both for tumor growth and metastatic dissemination. Additionally, dysregulation in angiogenesis has been implicated in the pathogenesis of cardiovascular disease, proliferative retinopathy, diabetic nephropathy, and rheumatoid arthritis (RA). The neuropeptide somatostatin has been shown to be a powerful inhibitor of neovascularization in several experimental models. Furthermore, somatostatin receptors (sst) are expressed on endothelial cells; particularly, sst2 has been found to be uniquely up-regulated during the angiogenic switch, from quiescent to proliferative endothelium. The present manuscript reviews the anti-angiogenic activity of somatostatin and its analogues in neoplastic and nonneoplastic disease. The role of sst subtypes particularly sst2 in mediating its angioinhibitory activity is described. Somatostatin agonists may also exert their anti-angiogenic activity indirectly by inhibition of growth factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis or through its immunomodulatory effects. However, the therapeutic utility of somatostatin agonists as anti-angiogenic drugs in these diseases remains confusing because of conflicting results from different studies. More basic research, as well as patient-oriented studies, is required to firmly establish the clinical potential of somatostatin agonists in therapeutic angiogenesis. The currently available somatostatin agonists have high affinity of sst2 with lower affinities for sst3 and sst5. The emergence of novel somatostatin agonists especially bispecific analogues (agonists targeting multiple cellular receptors) and conjugates (synthesized by chemically linking somatostatin analogues with other antineoplastic agents) with improved receptor specificity signify a new generation of anti-angiogenics, which may represent novel strategies in the treatment of neovascularization-related diseases.
12571838 Eligibility of patients in routine care for major clinical trials of anti-tumor necrosis f 2003 Feb OBJECTIVE: To identify the proportion of patients with rheumatoid arthritis (RA) in 2 cohorts from Nashville, Tennessee, who met basic criteria for inclusion in 2 important recent clinical trials of anti-tumor necrosis factor alpha (anti-TNFalpha) agents, the early RA (ERA) trial of etanercept versus methotrexate, and the anti-TNFalpha trial in RA with concomitant therapy (ATTRACT) study of infliximab plus methotrexate versus methotrexate. METHODS: Two cohorts of patients, all of whom had met the American College of Rheumatology criteria for RA at some time, were studied. Cohort E (early) comprised 232 patients who were under the care of 5 private practice rheumatologists, whose duration of RA was fewer than 3 years, and who were reviewed for basic inclusion criteria for the ERA clinical trial. Cohort L (long-term) comprised 152 consecutive patients who had been under care at a weekly academic rheumatology clinic for a mean of 4.5 years, and were reviewed for basic inclusion criteria for the ATTRACT study. RESULTS: In cohort E, basic inclusion criteria for the ERA trial were met by 11 of 36 patients (31%) who had not taken methotrexate, 8 of 19 patients (42%) who were at their first visit and had not taken methotrexate, and 37 of all 232 patients (16%). In cohort L, 5% of patients met the basic inclusion criteria for the ATTRACT study. CONCLUSION: Most patients who were seen in routine care in these 2 cohorts did not meet the criteria for inclusion in these 2 important recent clinical trials. The conclusion that anti-TNFalpha therapy has greater efficacy than methotrexate may be valid only in a limited number of patients with the most severe RA. Anti-TNFalpha therapy may be desirable in most patients with RA, but this possibility has not been studied formally. Criteria for inclusion in RA clinical trials might be modified for greater generalizability of results.
15762338 Prevalence of systemic diseases in Brisbane general and periodontal practice patients. 2004 Dec BACKGROUND: Periodontitis has been associated with a number of systemic diseases such as atherosclerosis, coronary heart diseases, and respiratory diseases. This study aimed to determine whether there is a significant difference in the prevalence of systemic diseases (a) in patients referred for periodontal care compared to the general practice population, (b) in patients attending a public hospital and private practices, (c) in patients attending public and private periodontal practices, and (d) among patients with periodontitis of varying severity. METHODS: Charts of 1000 adult patients were selected from four clinics (University of Queensland (UQ) School of Dentistry Admissions Clinic, UQ School of Dentistry Periodontics Clinic, Private Periodontal Practice, and Private General Dental Practice). The prevalence of medical conditions was evaluated using validated self-reported health questionnaires. The periodontal condition was assessed from the most recent relevant radiographs in the files. RESULTS: Periodontal patients had a higher prevalence of systemic diseases compared to the general practice population. Public patients had a greater prevalence of systemic diseases compared to patients in private practice for both general practice and periodontal patients. In patients with advanced periodontitis, bronchitis, hepatitis and rheumatoid arthritis were most prevalent. Patients with periodontitis also took more medications and were more likely to suffer from multiple conditions compared to the general dental population. CONCLUSIONS: Patients attending public dental facilities have an increased prevalence of systemic disease compared to those attending private practices. Furthermore periodontal patients have a greater prevalence of diseases compared to general practice patients. Patients with moderate or advanced periodontitis show an increase in the prevalence of some systemic diseases previously reported to be risk factors for periodontal disease.
15566416 Clinical implications of migraine in systemic lupus erythematosus: relation to cumulative 2004 Dec The aim of this study was to determine the clinical implications of migraine in systemic lupus erythematosus (SLE) using the cumulative organ damage scores (SLICC-DI). Eighty SLE, 40 rheumatoid arthritis (RA) patients and 40 controls (non SLE, nor RA out-patients), all women, were included. Migraine was defined according to the International Headache Society (IHS) criteria for neuropsychiatric SLE. Disease activity was measured by MEX-SLEDAI and cumulative organ damage by SLICC-DI. Statistics were obtained by Chi-square and Fischer's exact tests. anova was used for comparing means. Migraine was identified in 42.5% of SLE patients, compared to 12.5% of RA patients (P < 0.05) and 10.0% (P < 0.05) in the control group. In the SLE group, a significant association between migraine and Raynaud's phenomenon (P = 0.003, OR = 10.1; 95%CI 2.9-35) and antiphospholipid antibodies (P = 0.0012; OR = 7.5; 95%CI 2.5-22.9) was noted. SLE patients with active migraine had higher MEX-SLEDAI scores than SLE patients without migraine. SLE patients with past history of migraine had significantly higher SLICC scores than SLE patients without migraine. History of migraine was associated with greater organ damage. Active migraine was associated with higher disease activity, antiphospholipid antibodies and worsening of Raynaud's phenomenon. The increased cumulative organ damage in SLE patients with past history of migraine justifies the routine evaluation of migraine in clinical practice.
14512349 Identification and quantification of disease-related gene clusters. 2003 Sep 22 MOTIVATION: DNA microarray technology and the completion of human and mouse genome sequencing programs are now offering new avenues for the investigation of complex genetic diseases. In particular, this makes possible the study of the spatial distribution of disease-related genes within the genome. We report on the first systematic search for clustering of genes associated with a polygenic autoimmune disease. RESULTS: Using a set of cDNA microarray chip experiments in two mouse models of rheumatoid arthritis, we have identified approximately 200 genes based on their expression in inflamed joints and mapped them into the genome. We compute the spatial autocorrelation function of the selected genes and find that they tend to cluster over scales of a few megabase pairs. We then identify significant gene clusters using a friends-of-friends algorithm. This approach should aid in discovering functionally related gene clusters in the mammalian genome.
12701994 A review of sleep in selected immune and autoimmune disorders. 2003 Mar Evidence for the reciprocal role of the immune system in sleep is growing. Sleep disturbances are believed to be both a cause and a consequence of various immune and autoimmune conditions.