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ID PMID Title PublicationDate abstract
19049702 Glomerular crescent formation in renal amyloidosis. A clinicopathological study and demons 2008 Dec BACKGROUND: Several studies examined glomerular crescents associated with renal amyloidosis. However, the incidence of crescents, the association between the 2 lesions, treatment and outcome are still controversial. PATIENTS AND METHODS: We studied 107 consecutive biopsies of renal amyloidosis, and found cellular or fibrocellular crescents in 13 cases (12.1%). We investigated the clinical characteristics, pathological findings, treatment and outcome. We also performed immunohistochemical staining using T cell, macrophage and osteopontin (OPN) markers. RESULTS: Amyloid was of the AA type in 12 cases, and all patients had rheumatoid arthritis. Six cases with AA amyloidosis had crescentic glomerulonephritis (CrGN), and 5 presented with rapidly progressive glomerulonephritis (RPGN). The percentage of crescents correlated negatively with serum albumin (r = -0.83, p < 0.001), and positively with serum creatinine (r = 0.72, p < 0.01) and urinary protein excretion (r = 0.85, p < 0.001). All RPGN patients developed end-stage renal disease, and 2 patients died shortly after treatment. Microscopic examination showed inflammatory cells within the glomeruli, and immunohistochemical study revealed abundant intrarenal T cells and macrophages in CrGN cases. Strong expression of OPN was observed in tubular epithelial cells and intraglomerular macrophages. CONCLUSION: Cellular immune responses play a crucial role in glomerular crescents in renal amyloidosis. Immunosuppressive treatment is often ineffective and raises the risk of complications in CrGN with abundant glomerular sclerosis and tubulointerstitial injury.
19027584 Gastrointestinal symptoms in children with an autism spectrum disorder and language regres 2008 Dec Few studies have compared gastrointestinal problems in children with an autism spectrum disorder with and without a history of language regression. A cross-sectional study was conducted with structured interviews in 100 children with autism spectrum disorder, using a gastrointestinal questionnaire and a familial autoimmune questionnaire. By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%, P = 0.006) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%, P = 0.001) and of rheumatoid arthritis (30% vs 11%, P = 0.03). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%, P = 0.001) than in those without. An association was observed between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Additional studies are needed to examine a possible shared autoimmune process.
19026190 [Arthroscopic treatment for calcaneal spur syndrome]. 2008 Oct PURPOSE OF THE STUDY Arthroscopic treatment of calcaneal spur syndrome is a tissue-sparing and effective approach when conservative therapy has failed. This method, its results and our experience with the treatment of this syndrome are presented here. MATERIAL Between January 2003 and November 2007, 26 patients underwent an arthroscopic procedure for calcaneal spur syndrome; of these, 20 were women with an average age of 49 years, and six were men with an average age of 45 years. Four, three women and one man, were lost to follow-up, therefore 22 patients with 24 heels were eventually evaluated. All had conservative therapy for 3 to 6 monts. METHODS The arthroscopic method used was developed by the arthroscopic group of the Orthopaedic Service of Hospital Hermanos Ameijeiras in Havana, Cuba. The surgical technique insolves treatment of the spur and plantar fasciitis commonly found in calcaneal spur syndrome, but it also addresses adjacent calcaneal periostitis. RESULTS The results were evaluated on the scale that is part of the foot function index developed by Budiman-Mak for measuring rheumatoid arthritis pain. The patients were asked mine questions on pain intensity during various activities before and after surgery. Pain was evaluated on a scale with grades from 0 to 9. The average value was 5.9 before surgery and 1.4 after surgery. A 0-1 pain range was reported by 25 %, 1-2 by 26 % and 2-4 by 22 % of the patients. All patients reported improvement. DISCUSSION The orthopaedic group in Havana led by Carlos achieved 85 % excellent outcomes (pain range, 0-2) at one-year followup; this was 79 % in our study, in which no problems with foot arches or wound infection were recorded. CONCLUSIONS The heel spur syndrome is a result of an inflamed ligament (plantar fascia) due to repeated microtrauma. It is not a traction osteophyte,but a reaction of the tissue where it attaches to the calcaneus. Adjacent calcaneal periostitis is usually present as well. Therefore, this method treting all three causes of the syndrome appears to be more effective than mere fasciotomy.
19021375 Multiparameter classifications of optical tomographic images. 2008 Sep This research study explores the combined use of more than one parameter derived from optical tomographic images to increase diagnostic accuracy which is measured in terms of sensitivity and specificity. Parameters considered include, for example, smallest or largest absorption or scattering coefficients or the ratios thereof in an image region of interest. These parameters have been used individually in a previous study to determine if a finger joint is affected or not affected by rheumatoid arthritis. To combine these parameters in the analysis we employ here a vector quantization based classification method called Self-Organizing Mapping (SOM). This method allows producing multivariate ROC-curves from which sensitivity and specificities can be determined. We found that some parameter combinations can lead to higher sensitivities whereas others to higher specificities when compared to singleparameter classifications employed in previous studies. The best diagnostic accuracy, in terms of highest Youden index, was achieved by combining three absorption parameters [maximum(micro a), minimum(micro a), and the ratio of minimum(micro a) and maximum(micro a)], which result in a sensitivity of 0.78, a specificity of 0.76, a Youden index of 0.54, and an area under the curve (AUC) of 0.72. These values are higher than for previously reported single parameter classifications with a best sensitivity and specificity of 0.71, a Youden index of 0.41, and an AUC of 0.66.
18986345 Goeckerman's therapy for psoriasis with special reference to serum pentraxin 3 level. 2008 Oct BACKGROUND: Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Pentraxin 3 (PTX3) is a newly identified acute phase reactant with non redundant functions in innate immunity. PTX3 has been shown to be a reliable prognostic marker in patients with various inflammatory disorders including rheumatoid arthritis, vasculitis, and psoriasis. METHODS: The aim of this study was to evaluate the influence of Goeckerman's therapy of psoriasis on levels of two pentraxins: long pentraxin PTX3 and C reactive protein in 49 patients with chronic plaque psoriasis. CRP was assessed by immunonephelometry on IMMAGE 800 (Beckman, USA). PTX3 was detected using sandwich ELISA detection set (Alexis Biochemicals, Switzerland). RESULTS: The serum levels of both parameters (expressed as average +/- 1 SD) were significantly diminished after GT. The level of PTX3 dropped from 1.92 +/- 0.72 ng/ml before GT to 1.66 +/- 0.58 ng/ml after GT (P= 0.0396) and the level of CRP fell from 4.64 +/- 3.93 mg/l to 1.66 +/- 0.58 mg/l (P < 0.0001).Comparing to healthy controls, the serum levels of both parameters before GT were significantly higher than those found in healthy blood donors and remained significantly increased after GT. CONCLUSION: Increased serum concentrations of pentraxin 3 and CRP are alleviated by GT in patients with psoriasis.
18971914 Severity of Lyme disease with persistent symptoms. Insights from a double-blind placebo-co 2008 Oct Lyme disease is a global health concern and is the world's leading tick borne infection caused by the spirochete, Borrelia burgdorferi, that has been associated with numerous neurologic, rheumatologic and psychiatric manifestations. The symptoms of Lyme disease have been characterized as either severe or ''related to the aches and pains of daily living.'' A randomized double-blind, placebo-controlled clinical trial (RCT) was conducted in a primary internal medicine practice in Westchester County, New York, USA. A total of 84 adults with Lyme disease with persistent symptoms (LDPS) were studied; 52 received amoxicillin and 34 received placebo. The subjects received either placebo or amoxicillin 3 g per day orally for 3 months. The SF-36 was used as the outcome measure of the patient's perceived Quality of Life (QOL). For subjects enrolling in this RCT, the average SF-36 physical component summary (PCS) of QOL (40+/-9, range 29-44) and mental component summary (MCS) of QOL (39+/-14, range 23-46) were worse than the general USA population and worse than individuals with diabetes, heart disease, depression, osteoarthritis or rheumatoid arthritis. The improvements in the SF-36 measure of QOL for subjects randomized to amoxicillin vs. placebo was significant (46% vs 18%, P=0.007). It is important for clinicians to be aware that LDPS can be severe. A significant gain in the QOL for subjects randomized to amoxicillin in this RCT without serious adverse events is consistent with the goal of improving patient's QOL and consequently worthy of further study.
16712837 Targeting cytosolic phospholipase A2 by arachidonyl trifluoromethyl ketone prevents chroni 2006 Jun 13 Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in inflammation by catalyzing the release of arachidonic acid, a substrate for lipoxygenase and cyclooxygenase enzymes, from membrane phospholipids. In the present study we examined the role of cPLA(2) in inflammatory responses through the use of a specific inhibitor of the enzyme, cPLA(2), arachidonyl trifluoromethyl ketone (AACOCF3). Interestingly, we observed that AACOCF3 is an inhibitor of chronic but not acute inflammatory responses. Specifically, AACOCF3 inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice. Additionally, oral treatment of ovalbumin-sensitized/ovalbumin-challenged BALB/c mice with 20 mg/kg AACOCF3 prevented the development of airway hyper-responsiveness in a model of asthma. Furthermore, AACOCF3 decreased cellular recruitment in the airway lumen and airway inflammation after the ovalbumin challenge. Taken together, these results suggest that a potent and specific chemical inhibitor of cPLA(2) may be useful for the treatment of chronic inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and asthma.
16709321 Co-occurrence and comorbidities in patients with immune-mediated inflammatory disorders: a 2006 May OBJECTIVE: Research in immune-mediated inflammatory disorders (IMIDs) suggests that several diseases share disruptions in key cytokines. A common pathogenesis may present as similar patterns of disease co-occurrence and comorbidity, which could be observed through the analysis of healthcare claims datasets. METHODS: Adult patients continuously enrolled from 2001-2002 were identified in two US healthcare datasets containing medical and drug claims from health plans and self-insured employers. Patients with treatment records indicating an IMID were selected (e.g., rheumatoid arthritis, psoriasis, Crohn's disease); controls for each disorder were matched 3:1 based on age, gender, region, and previous insurance coverage. IMID cohorts and comorbidities were identified using International Classification of Diseases, 9th revision codes. Prevalence relative risk was used to assess co-occurrence and comorbidity rates in IMID cohorts and controls. Medical and drug utilization patterns were also explored. RESULTS: Findings were similar across the two datasets. IMID patients represented about 4% of the population; specific IMID prevalence matched the epidemiology literature. Patients with at least one IMID had a higher risk for another IMID when compared to controls. The risk for infectious, renal, liver, and ulcerative comorbidities was also elevated. Selected drug utilization patterns confirmed comorbidity findings. IMID patients used more healthcare resources compared to controls; findings were robust under sensitivity analyses. CONCLUSIONS: IMID patients were generally more likely than controls to have another IMID, supporting the concept that the diseases are related. These patients also had higher comorbidity rates. Findings may be limited by the nature of claims datasets and the confounding effect of current treatments. Prospective studies are needed to determine whether IMIDs have a common pathogenesis.
16567522 Atorvastatin fails to prevent the development of autoimmune diabetes despite inhibition of 2006 Apr Statins, the widely used inhibitors of cholesterol biosynthesis, also have immunomodulatory properties. Statins have recently been shown to have beneficial prophylactic and therapeutic effects in actively induced, short-term animal models of the autoimmune diseases multiple sclerosis and rheumatoid arthritis, leading to clinical trials. We therefore investigated whether statins' protective effects could be reproduced in the nonobese diabetic (NOD) mouse, a spontaneous, chronic model of autoimmune diabetes. Mice were treated with 0, 1, 10, or 50 mg x kg(-1) x day(-1) oral atorvastatin from 6 or 12 weeks of age, without effect on the rate or prevalence of diabetes development, islet infiltration, or islet major histocompatibility complex class II expression. However, there was clear evidence of a disease-relevant immunological effect of statins in vivo, since short-term (12-day) treatment significantly reduced the number of proinflammatory (gamma-interferon-producing) CD8 cells recognizing a dominant pathogenic epitope. This effect was absent in mice treated for longer periods, suggesting that atorvastatin loses efficiency in inhibiting autoantigen-specific T-cells over time. This observation may explain the discrepancy between the reported success of statins in acutely induced models and the lack of it in a chronic, spontaneous model of autoimmune disease and has implications for the adoption of such therapy in humans.
16510263 Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin 2006 Sep Thioredoxin reductase (TrxR) reduces thioredoxin (Trx), thereby contributing to cellular redox balance, facilitating the synthesis of deoxy-ribose sugars for DNA synthesis, and regulating redox-sensitive gene expression. Auranofin is a gold compound that potently inhibits TrxR. This inhibition is one suspected mechanism of auranofin's therapeutic benefit in the treatment of rheumatoid arthritis. The use of other gold compounds to treat cancer or inflammatory disease may rely on their ability to inhibit TrxR. In the current study, we tested the hypothesis that a variety of gold compounds may inhibit TrxR. METHODS: We exposed rat-TrxR1 to auranofin, gold sodium thiomalate, sodium aurothiosulfate, triphenyl phosphine gold chloride, or gold acetate, and measured TrxR activity ex vivo. We then compared TrxR1 inhibitory levels of gold compounds to those that inhibited mitochondrial activity of THP1 monocytes and OSC2 epithelial cells, estimated by succinate dehydrogenase activity. RESULTS: All gold compounds inhibited TrxR1 at concentrations ranging from 5 to 4000 nM (50% inhibitory concentration). The oxidation state of gold did not correlate with inhibitory potency, but ligand configuration was important. Au(I)-phosphine compounds (triphenyl phosphine gold chloride and auranofin) were the most potent inhibitors of TrxR. All TrxR1 inhibitory concentrations were sublethal to mitochondrial activity in both THP1 and OSC2 cells. CONCLUSIONS: Diverse types of gold compounds may be effective inhibitors of TrxR1 at concentrations that do not suppress cellular mitochondrial function. Inhibition may be optimized to some degree by altering the ligand configuration of the compounds. These results support future study of a variety of Au compounds for therapeutic development as inhibitors of TrxR1.
16397146 Acute antiinflammatory properties of statins involve peroxisome proliferator-activated rec 2006 Feb 17 Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase used in the prevention of cardiovascular disease (CVD). In addition to their cholesterol-lowering activities, statins exert pleiotropic antiinflammatory effects, which might contribute to their beneficial effects not only on CVD but also on lipid-unrelated immune and inflammatory diseases, such as rheumatoid arthritis, asthma, stroke, and transplant rejection. However, the molecular mechanisms involved in these antiinflammatory properties of statins are unresolved. Here we show that the peroxisome proliferator-activated receptor (PPAR) alpha mediates antiinflammatory effects of simvastatin in vivo in models of acute inflammation. The inhibitory effects of statins on lipopolysaccharide-induced inflammatory response genes were abolished in PPARalpha-deficient macrophages and neutrophils. Moreover, simvastatin inhibited PPARalpha phosphorylation by lipopolysaccharide-activated protein kinase C (PKC) alpha. A constitutive active form of PKCalpha inhibited nuclear factor kappaB transrepression by PPARalpha whereas simvastatin enhanced transrepression activity of wild-type PPARalpha, but not of PPARalpha mutated in its PKC phosphorylation sites. These data indicate that the acute antiinflammatory effect of simvastatin occurs via PPARalpha by a mechanism involving inhibition of PKCalpha inactivation of PPARalpha transrepression activity.
18710009 [Anesthetic management of awake off-pump coronary artery bypass grafting (ACAB) with remif 2008 Aug Two patients with total occlusion of the right internal carotid artery, were anesthetized for ACAB with remifentanil and thoracic epidural anesthesia. Case 1: A 71-year-old man with hypertension and diabetes mellitus underwent single-vessel ACAB under IV remifentanil analgesia, the dose of which was adjusted to 0.04-0.05 microg x kg(-1) x min(-1), along with an epidural infusion of 10 ml x hr(-1) of a mixture of 2% lidocaine and 2.5 microg x ml(-1) of fentanyl, the PaCO2 being maintained at 52-55 mmHg. When the patient felt pain, the remifentanil dose was elevated to 0.08 microg x kg(-1) x min(-1) and PaCO2 increased to 60 mmHg. Case 2: A 66-year-old man with rheumatoid arthritis underwent ACAB for two grafts. An intraaortic balloon pump (IABP) was inserted preoperatively. The anesthetic method used was the same as in case 1, except for an additional right femoral block to provide anesthesia for extraction of the saphenous vein. Remifentanil was infused at 0.05 microg x kg(-1) x min(-1) and PaCO2 maintained at 49-53 mmHg. In response to the patient's pain and movement, the remifentanil dose was increased to 0.07-0.10 microg x kg(-1) x min(-1) and PaCO2 to 60 mmHg.
18644698 Polyautoimmunity and familial autoimmunity in systemic sclerosis. 2008 Sep Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity.
18569386 Immune-Mediated Diseases II Congress: summary. 2008 Apr The remarkable progress in basic immunological research during the past 50 years can account for the emerging of medical or clinical immunology as a novel discipline, which may be defined as the application of basic immunology rules to the diagnosis, treatment, and prophylactics of patients with diseases in which immunological pathways may play an important etiological and/or pathogenetic role. The immune system has a central role not only in fighting infections, but also in many other diseases and disorders including cancer, AIDS, and organ transplantation. In addition, the immune system imbalance is responsible for primary and secondary immunodeficiencies, hypersensitive illnesses, such as asthma, dermatitis, and other allergies, as well as systemic and organ-specific autoimmune disorders, such as multiple sclerosis, lupus, rheumatoid arthritis and diabetes. Immune-mediated diseases such as autoimmune diseases and allergic diseases are important health problems in many countries. For instance, autoimmune diseases afflict up to 8% of the United States population; allergic diseases represent the sixth leading cause of chronic illness and disability in the United States, and the leading cause among children. Thus, immune-mediated diseases represent an enormous medical, social, and economical problem and require serious and instant attention from clinicians, scientists, pharmacists, and biotech professionals. The goal of the Second International Immune-Mediated Diseases (IMD) Congress was to advance medical and biomedical immunological sciences and clinical practice via the organization of multiple sessions and training courses as well as providing an environment for stimulating scientific discussions, the exchange of ideas, and consideration of novel clinical diagnostic and therapeutic approaches. Selected contributions from the participants of this Congress who are eager to share some of the academic and clinical enthusiasm are presented in this issue (and the subsequent issue) of the Journal of Immunotoxicology.
18466524 Density-based clustering in haplotype analysis for association mapping. 2007 Clustering of related haplotypes in haplotype-based association mapping has the potential to improve power by reducing the degrees of freedom without sacrificing important information about the underlying genetic structure. We have modified a generalized linear model approach for association analysis by incorporating a density-based clustering algorithm to reduce the number of coefficients in the model. Using the GAW 15 Problem 3 simulated data, we show that our novel method can substantially enhance power to detect association with the binary rheumatoid arthritis (RA) phenotype at the HLA-DRB1 locus on chromosome 6. In contrast, clustering did not appreciably improve performance at locus D, perhaps a consequence of a rare susceptibility allele and of the overwhelming effect of HLA-DRB1/locus C, 5 cM distal. Optimization of parameters governing the clustering algorithm identified a set of parameters that delivered nearly ideal performance in a variety of situations. The cluster-based score test was valid over a wide range of haplotype diversity, and was robust to severe departures from Hardy-Weinberg equilibrium encountered near HLA-DRB1 in RA case-control samples.
18465156 Using multifocal ERG ring ratios to detect and follow Plaquenil retinal toxicity: a review 2009 Feb Multifocal ERG ring ratios provide a sensitive and objective method to detect ocular toxicity in patients taking hydroxychloroquine (Plaquenil). In order to measure ring ratios, the average mfERG amplitude was calculated for each of five concentric rings of a 61-hexagon mfERG. The age-corrected amplitude of the central hexagon (R(1)) and the ratios of R(1) to each of the successive rings (R(1)/R(2), R(1)/R(3), etc.) were then computed. Normative values for ring ratios were established from a population of 67 normal controls. In the study population, a ring was considered abnormal if it was above the 99% confidence limits for the normal population. The technique was evaluated on 131 eyes of 62 patients taking Plaquenil for a variety of conditions including rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Patients who had taken Plaquenil for an extended period showed a higher incidence of retinal toxicity, regardless of the condition for which they were taking the drug. Among patients who had taken a cumulative dose of less than 1,250 g, 7 of 67 eyes (10%) showed a characteristic mfERG defect, while in patients with a cumulative dosage of 1,250 g or more, 26 of 64 eyes (41%) showed one of these defects. In at least one patient, the technique was able to detect the early onset of Plaquenil toxicity followed by reversal of the toxic effects after the medication was discontinued. It appears appropriate to recommend that mfERG testing be done on all patients on Plaquenil therapy.
18461290 Spontaneous remission of "methotrexate-associated lymphoproliferative disorders" after dis 2009 There are a number of intriguing reports of lymphoproliferative disorders (LPDs) diagnosed during immunosuppressive treatment for underlying autoimmune disease, and spontaneously abated shortly after treatment discontinuation. Such LPDs, completely or partially regressing, occur in the clinical setting of "Methotrexate (MTX)-associated LPDs", recognized by the World Health Organization (WHO) among the "Immunodeficiency-associated LPDs". We identified 26 literature patients achieving spontaneous complete remission (CR) of their LPD, and eight others showing partial remission (PR). Most of them were affected by rheumatoid arthritis, received low-dose and long-term pulsed MTX alone or combined with other immunosuppressants, and developed a lymphoma. By reviewing the patients achieving CR, the following can be drawn: the absence of a unique type of LPD, the occurrence of an increased incidence of diffuse large B cell lymphoma as well as of frequent extranodal involvement, and EBV-infection. Further, CR mostly occurred within 4 weeks after discontinuation of immunosuppressant, and appeared to be persistent overtime. Conversely in the patients experiencing PR, the interval between discontinuation of immunosuppressive treatment and clinical response was mostly reported as longer than 4 weeks; moreover, in many cases the persistence of LPD or its progression induced to start cytotoxic therapy. Increased awareness is needed on the possible occurrence of LPD spontaneous remission following immunosuppressant discontinuation, after that it is therefore advisable to have a careful monitoring of the patient for some weeks, before starting cytotoxic therapy.
18455947 The "sclerodermic hand": a radiological and clinical study. 2008 Jul OBJECTIVE: To assess the clinical and radiographic features of hand involvement in patients with systemic sclerosis (SSc). METHODS: Forty-one unselected Sardinian SSc patients (32 women, 9 men; mean age 58.9, range 31-81 years; mean disease duration 11.8 years, range 1-36 years) were evaluated in this observational cross-sectional study. Twenty-six patients had diffuse scleroderma (dSSc) and 15 limited scleroderma (lSSc). Radiological examination of the hands was performed and the films were read by two independent rheumatologists blinded to the diagnosis using a classification system of four predefined radiological patterns (normal/minimal changes, articular degenerative, articular inflammatory and periarticular pattern). Correlations between radiological pattern, clinical and serological features were assessed. RESULTS: The skeletal and articular involvement of the hand was frequent in SSc, being clinically evident in 30/41 (73%) and radiologically in 33/41 (80%) of patients. The periarticular pattern (defined as the occurrence of bone resorption of ungueal tufts, soft tissue calcifications and/or flexion deformities) was the most frequent pattern detected (14/41, 34.1%) and finger flexion contractures and bone resorptions were significantly associated with interstitial lung disease, reduced FVC, oesophagus involvement and prostacycline therapy. Calcinosis (29.2%) was found to be associated with erosions, suggesting a pathogenic link. An inflammatory pattern was also radiologically frequent (8/41, 19.5%), but erosions, with the exception of those localized at distal interphalangeal joints, were demonstrated mainly in patients with clinical picture of rheumatoid arthritis overlapped with SSc. We found no significant differences in terms of radiographic findings between lSSc and dSSc with the exception of calcinosis, which was more frequent in patients with lSSc. CONCLUSION: This cross-sectional study confirms that the skeletal and articular involvement of the hand is frequent in SSc.
18088406 Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I and II and 2007 Dec 18 BACKGROUND: A disturbance in the immune system has been described in Turner syndrome (45,X), with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X), thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common. Otitis media and a progressive sensorineural hearing disorder are commonly seen. In the normal population there are known inner ear disorders related to autoimmune diseases. The aim of this study was to investigate patients with Turner syndrome regarding autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine syndrome type I and II and Addison's disease, to screen for overlapping profile of autoantibodies. Blood samples from 110 Turner patients (7-65 years) were investigated using in vitro transcription, translation and immunoprecipitation techniques regarding autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease (21-hydroxylase, 17alpha-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, tyrosine hydroxylase and tryptophan hydroxylase). RESULTS: The autoantibodies investigated were not overrepresented among the Turner patients. CONCLUSION: The autoimmune disorders associated with Turner syndrome do not seem to be of the same origin as Addison's disease, the type I or II autoimmune polyendocrine syndrome.
18046763 Issues in association mapping with high-density SNP data and diverse family structures. 2007 Genetic association studies have the potential to identify causative genetic variants with small effects in complex diseases, but it is not at all clear which study designs best balance power with sample size, especially when taking into account the difficulty of obtaining a sample of the necessary structure. The 14 contributions from the Genetic Analysis Workshop 15 group 3 used data sets with rheumatoid arthritis as primary phenotype from problem 2 (real data) and Problem 3 (simulated data) to investigate design and analysis problems that arise in candidate-gene, candidate-region, and genome-wide association studies. We identified three major themes that were addressed by multiple groups: (1) comparing family-based and case-control study designs with each other and with hybrid designs incorporating both related and unrelated individuals; (2) exploring and comparing techniques of combining information from multiple, correlated single-nucleotide polymorphisms; and (3) comparing analyses that select the model(s) of best fit with the ultimate aim of detecting the joint effects of several unlinked single-nucleotide polymorphisms. These contributions achieved some success in improving upon existing methods. For example, tests using related cases and unrelated controls can achieve higher power than the tests using unrelated cases and unrelated controls. Aside from these successes, the group 3 contributions highlight some interesting areas for future research.