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ID PMID Title PublicationDate abstract
26282628 Arthralgia and blood culture-negative endocarditis in middle Age Men suggest tropheryma wh 2015 Aug 18 BACKGROUND: Whipple's disease is a rare, often multisystemic chronic infectious disease caused by the rod-shaped bacterium Tropheryma whipplei. Very rarely the heart is involved in the process of the disease, leading to culture-negative infective endocarditis. Up to 20 % of all infective endocarditis are blood culture-negative and therefore a diagnostic challenge. We present two unusual cases of culture-negative infective endocarditis encountered in two different patients with prior history of arthralgia. A history of rheumatic arthritis or even a transient arthralgia should put Tropheryma whipplei on the top of differentials in patients of this age group presenting with culture-negative infective endocarditis, especially in cases of therapy resistance to antirheumatic agents. CASE PRESENTATION: The first patient was a 55 year-old Caucasian male with culture-negative Whipple-related adhesive pericarditis and endocarditis of the aortic valve. Importantly, the patient reported a 15-year history of therapy resistant sero-negative migratory polyarthritis. Aortic valve endocarditis developed during treatment with tocilizumab. The second patient was a 65-year-old male patient with no prior history of the classic Whipple's disease who presented with a culture-negative aortic valve endocarditis. His past medical history revealed episodes of transient arthralgia, which he was not treated for however, due to the self-limiting nature of the symptoms. Both patients underwent aortic valve replacement surgery. During surgery, pericardectomy was necessary in the first patient due to adhesive pericarditis. Post surgery both patients were started on long-term treatment with trimetoprim-sulfamethoxazol. At 1-year follow-up of both patients, echocardiographic and clinical assessment revealed no signs of persistent infection. Both men reported negative history of arthralgia during the one year period post surgery. CONCLUSION: Tropheryma whipplei culture negative-infective endocarditis is an emerging clinical entity, predominantly found in middle-aged and older men with a history of arthralgia. These data highlight the need for ruling out Whipple's disease in patients with a history of arthralgia prior to initiation of biological agents in treatment of rheumatoid arthritis. There is also a need to assess for Tropheryma whipplei in all patients with culture- negative infective endocarditis.
28144381 Clinical Outcomes of Patients with Valgus Deformity Undergoing Minimally Invasive Total Kn 2016 OBJECTIVE: The purpose of this study was to compare the clinical outcomes between patients with a valgus or varus deformity undergoing minimally invasive total knee arthroplasty through the medial approach. METHODS: The patients were classified into 2 groups according to the preoperative femorotibial angle measured on an anteroposterior long leg roentgenogram. The valgus group comprised of 26 knees in 21 patients with a femorotibial angle <170° (163.5 ± 5.7), and the varus group comprised of 24 knees in 21 patients with a femorotibial angle >190° (195.9 ± 5.5). The following background variables were compared between the groups: age at the time of the operation, sex, causative disease, preoperative femoral mechanical-anatomical angle, and postoperative knee range of motion, Knee Society score, femorotibial angle, and implant position. RESULTS: There were significant differences between the valgus and varus groups in the age (68.0 ± 6.9 vs 75.8 ± 6.2 years), percentage of males (23.8% vs 0%), percentage with rheumatoid arthritis (61.9% vs 4.8%), and preoperative femoral mechanical-anatomical angle (6.2 ± 1.0° vs 7.4 ± 2.1°). Clinical outcome variables of postoperative femorotibial angle (173.1 ± 3.9° vs 175.2 ± 1.6°) and α angle (96.6 ± 3.1° vs 95.0 ± 1.9°) also differed. CONCLUSION: It was assumed that over-valgus resection of the femur is a contributory factor to residual valgus alignment. However, knee range of motion and Knee Society score did not differ between the groups. We suggest that minimally invasive total knee arthroplasty through the medial approach is one of the treatment options for patients with valgus deformity.
27816176 A grayanotox-9(11)-ene derivative from Rhododendron brachycarpum and its structural assign 2017 Jan A growing body of evidence points to the useful roles of computational approaches in the structural characterization of natural products. Rhododendron brachycarpum has been traditionally used for the control of diabetes, hepatitis, hypertension, and rheumatoid arthritis and classified as an endangered species in Korea. A grayanotox-9(11)-ene derivative along with five known diterpenoids, were isolated from the MeOH extract of R. brachycarpum. Extensive 1D and 2D NMR experiments were conducted to establish the 2D structure and relative configuration of the grayanotox-9(11)-ene derivative. Comparison of simulated and experimental ECD spectra resulted in an inconclusive outcome to assign its absolute configuration. Alternatively, gauge-including atomic orbitals (GIAO) NMR chemical shift calculations, with support by the advanced statistical method DP4 plus, and acid hydrolysis were employed to establish its absolute configuration. This work exemplifies how NMR analysis, combined with quantum mechanics calculations, is a viable approach to accomplish structural assignment of minor abundance molecules in lieu of X-ray crystallography or chiroptical approaches.
27789680 Mutation-Induced Functional Alterations of CCR6. 2017 Jan The Cys-Cys chemokine receptor 6 (CCR6) is a well-established modulator of inflammation. Although several genetic associations have been identified between CCR6 polymorphisms and immune system disorders (e.g., rheumatoid arthritis and Crohn's disease), the pharmacological effects of naturally occurring missense mutations in this receptor have yet to be characterized. In this study, we initially assessed G protein-mediated signaling and observed that wild-type (WT) CCR6 exhibited ligand-independent activity. In addition, we found that the five most frequent CCR6 missense variants (A89T, A150V, R155W, G345S, and A369V) exhibited decreased basal and/or ligand induced Gαi protein signaling. To complement the study of these loss-of-function variants, we engineered a set of constitutively active CCR6 receptors. Selected mutations enhanced basal G protein-mediated signaling up to 3-fold relative to the WT value. Using a bioluminescence resonance energy transfer assay we investigated the ability of each naturally occurring and engineered CCR6 receptor mutant to recruit β-arrestin. In contrast to G protein-mediated signaling, β-arrestin mobilization was largely unperturbed by the naturally occurring loss-of-function CCR6 variants. Elevated recruitment of β-arrestin was observed in one of the engineered constitutively active mutants (T98P). Our results demonstrate that point mutations in CCR6 can result in either a gain or loss of receptor function. These observations underscore the need to explore how CCR6 natural variants may influence immune cell physiology and human disease.
27714662 Personality and uveitis. 2016 Dec BACKGROUND: Psycho-immunology is an emerging branch of science which studies the interaction between the brain and the immune system. The purpose of this study is to identify the types of personality factors in patients with non-infectious uveitis and to find its association with a particular uveitic entity if any. This is a prospective, observational, case-control study of 186 patients with non-infectious uveitis (group A) and controls from general ophthalmology outpatient department (group B). "Global 5/SLOAN" personality questionnaire was used which is based on the five-factor theory of personality which describes personality factors based on the presence or absence of five primary dimensions, viz extroversion, orderliness, emotional stability, accommodation, and intellectual curiosity. Personality factors of patients from groups A and B were compared. History of present illness, clinical diagnosis, details of systemic ailment, and demographic information were collected. RESULTS: Group A comprised HLA-B27-related uveitis (n = 30), uveitis due to sarcoidosis (n = 10), Vogt-Koyanagi-Harada syndrome (n = 5), sclero-kerato-uveitis due to rheumatoid arthritis (n = 5), and idiopathic uveitis in rest. Forty-five patients with uveitis had associated systemic ailment. Uveitis patients (n = 56) showed positive personality trait: S (social), C (calm), O (organized), A (accommodative), and I (inquisitive). In contrast, the control group (group B) which mainly comprised patients with non-pathological refractive error and visually insignificant cataract showed more number of negative personality traits (n = 62): R (reserved), L (limbic), U (unstructured), E (egocentric), and N (non-curious). This difference between the uveitis and control group was found to be statistically significant (p ≤ 0.001). The difference was also statistically significant for O (p = 0.008), U (p = 0.004), and C (p = 0.022) with chi-square test. Calm personality was found to be significantly associated with HLA-B27-related uveitis (p = 0.002). N, S, and A traits were seen almost equal in numbers in both the groups. U trait was absent in group A, whereas I trait had negligible presence in group B. CONCLUSIONS: Our finding of an association between organized personality type and uveitis and calm personality and HLA-B27-related uveitis warrants further studies to understand the complex mechanism of psycho-immunology in uveitis.
27567495 Resistin as potential biomarker for chronic periodontitis: A systematic review and meta-an 2017 Jan OBJECTIVES: To determine the serum and gingival crevicular fluid (GCF) levels of resistin between individuals with chronic periodontitis (CP) and those without CP, and to evaluate the role of resistin in CP. MATERIALS AND METHODS: The addressed focused question was "Is there a difference in the resistin levels between individuals with CP and those without CP?" four electronic databases: Medline, PubMed (National Institutes of Health, Bethesda), EMBASE, and Science direct databases from 1977 up to March 2016 for appropriate articles addressing the focused question. EMBASE and Medline were accessed using OVID interface which facilitated simultaneous search of text words, MeSH or Emtree. Unpublished studies (gray literature) were identified by searching the Open-GRAY database and references of the included studies (cross referencing) were performed to obtain new studies. In-vitro studies, animal studies, studies that reported levels of other cytokines but not resistin, letters to the editor and review papers were excluded. RESULTS: Ten studies were included. Nine studies compared resistin levels between CP and periodontally healthy (H) individuals and reported higher mean serum and GCF levels of resistin in CP patients than the H controls. Two studies showed comparable resistin levels from GCF and serum between diabetes mellitus with CP (DMCP) and CP groups. Three studies included obese subjects and showed comparable serum and GCF resistin levels between obese subjects with CP (OBCP) and CP subjects. CONCLUSIONS: CP patients were presented with elevated levels of GCF or serum resistin as compared with H individuals. Resistin modulates inflammation in chronic periodontal disease and may be used as surrogate measure to identify subjects at risk for periodontitis. Resistin levels in patients with CP and systemic inflammatory disorders such as diabetes, obesity, or rheumatoid arthritis was not significantly higher than the levels in patients with only CP.
27328803 Prevalence of systemic autoimmune rheumatic diseases and clinical significance of ANA prof 2016 Sep It is necessary and useful to explore prevalence of various systemic autoimmune rheumatic diseases (SARDs) in patients with suspicion of having SARDs and to characterize antinuclear antibodies (ANA) profile for identifying different populations (SARDs and non-SARDs). A total of 5024 consecutive patients with available medical records were investigated, whose sera had been tested for ANA profile, including ANA, anti-dsDNA and anti-extractable nuclear antigen (ENA) antibodies, between 31 January 2012 and 26 March 2014. Only 594 (11.8%) patients were diagnosed with SARDs of those suspected with SARDs. The prevalence of systemic lupus erythematosus (SLE) was highest (3.2%), followed by rheumatoid arthritis (RA) (2.5%), primary Sjögren's syndrome (pSS) (1.7%), ankylosing spondylitis (AS) (1.5%), etc. Of females, SLE also showed the highest prevalence (6%), while of males, AS showed the highest prevalence (1.9%). The prevalence of most SARDs was closely associated with age, except mixed connective tissue disease (MCTD), and the variation characteristics among different age groups were different among various SARDs. The prevalence of ANA was significantly increased in most SARD patients [especially in SLE, systemic sclerosis (SSc) and MCTD]. For anti-ENA antibodies, in contrast to some autoantibodies associated with multiple SARDs (e.g. anti-SSA, SSB, nRNP), others were relatively specific for certain diseases, such as anti-dsDNA, Sm, histone, nucleosome and Rib-P for SLE, anti-SCL-70 for SSc and anti-Jo-1 for polymyositis/dermatomyositis (PM/DM). Of note, ANA profile appeared to be of little significance for AS, ANCA-associated vasculitis (AAV), polymyalgia rheumatic (PMR), adult-onset Still's disease (ASD) and Behcet's disease (BD). The younger were more likely to have the presence of anti-dsDNA, Sm, histone or Rib-P for SLE, and anti-SSA for RA or MCTD. No significant differences for frequencies of ANA and anti-ENA autoantibodies were found between sexes in most SARDs, with the exception of RA and AS. The present study suggests that, of patients with SARDs-like clinical manifestations, the proportion of those with true SARDS is small, for most of whom tests for autoantibodies are necessary and useful to help make a prompt and precise diagnosis.
27073018 Modulation of endothelial function by Toll like receptors. 2016 Jun Endothelial cells (EC) are able to actively control vascular permeability, coagulation, blood pressure and angiogenesis. Most recently, a role for endothelial cells in the immune response has been described. Therefore, the endothelium has a dual role controlling homeostasis but also being the first line for host defence and tissue damage repair thanks to its ability to mount an inflammatory response. Endothelial cells have been shown to express pattern-recognition receptors (PRR) including Toll-like receptors (TLR) that are activated in response to stimuli within the bloodstream including pathogens and damage signals. TLRs are strategic mediators of the immune response in endothelial cells but they also regulate the angiogenic process critical for tissue repair. Nevertheless, endothelial activation and angiogenesis can contribute to some pathologies. Thus, inappropriate endothelial activation, also known as endothelial dysfunction, through TLRs contributes to tissue damage during autoimmune and inflammatory diseases such as atherosclerosis, hypertension, ischemia and diabetes associated cardiovascular diseases. Also TLR induced angiogenesis is required for the growth of some tumors, atherosclerosis and rheumatoid arthritis, among others. In this review we discuss the importance of various TLRs in modulating the activation of endothelial cells and their importance in immunity to infection and vascular disease as well as their potential as therapeutic targets.
27043356 Protective role of R381Q (rs11209026) polymorphism in IL-23R gene in immune-mediated disea 2016 May Interleukin-23 (IL-23) is a regulator of cellular immune responses involved in controlling infection and autoimmune diseases. Strong evidence has shown that IL-23 plays a role in the maintenance of immune responses by influencing the proliferation and survival of IL-17-producing T-helper (TH)-17 cells. The critical role of the IL-23/TH17 axis in immune-mediated diseases has emerged from different studies. It has also been seen that polymorphisms in the IL-23 receptor (IL-23R) gene might influence IL-23 responses. Interestingly, a functional single nucleotide polymorphism (SNP) in the IL-23 receptor gene (IL-23R; rs11209026, 1142 G wild-type A reduced function, Arg381Gln, R381Q) seems to confer a measure of protection against development of inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis), ankylosing spondylitis, rheumatoid arthritis, psoriasis, thyroiditis, recurrent spontaneous abortion and asthma, suggesting that a perturbation in the IL-23 signaling pathway is likely to be relevant to the pathophysiology of these diseases. The aim of this review was to provide an evaluation of what is currently known about the protective role of R381Q variant in IL-23R gene in immune-based diseases.
26773923 Depression-related treatment and costs in Germany: Do they change with comorbidity? A clai 2016 Mar 15 BACKGROUND: Existing diverse bottom-up estimations of direct costs associated with depression in Germany motivated a detailed patient-level analysis of depression-related treatment (DRT), -costs (DRC) and Comorbidity. METHODS: A large sickness fund's claims data was used to retrospectively identify patients aged 18-65 years with new-onset depression treatment between January 1st and February 15th 2010, and follow them until December 31st 2010, describe DRT, estimate associated DRC, and predict DRC with a generalised linear model. RESULTS: A total of 18,139 patients were analysed. Mean direct DRC were €783. Predictors of DRC regarding psychiatric comorbidities were: "Delusion, psychotic disorders and personality disorders" (DRC-ratio 1.72), "Alcohol/drug addiction" (1.82), "abuse of alcohol/drugs" (1.57). Predictors of DRC regarding medical comorbidities were: "Rheumatoid arthritis" (0.77), "atherosclerosis" (0.65), "pregnancy" (0.66), and "Osteoarthritis" (1.87). Of all patients, 60.8% received their most intense/specialised DRT from a general practitioner, a medical specialist (23.7%), a psychotherapist (8.0%), a medical specialist and psychotherapist (2.9%), or in hospital (4.6%). Serious psychiatric comorbidity nearly tripled depression-related hospitalisation rates. LIMITATIONS: Seasonal affective disorder and missing psychiatric outpatient clinic data must be considered. CONCLUSIONS: Estimated DRC are significantly below the assessment of the German national guideline. Differing definitions of observation period and cost attribution might explain differing German DRC results. Signs of hospital psychiatric comorbidity bias indicate overestimation of hospital DRC. Identified associations of DRC with certain medical diseases in older adults warrant further research. Up to one quarter of patients with severe depression diagnosis might lack specialist treatment.
26770183 The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro- 2015 Dec GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation.
26460575 [Clinical Findings in Patients with Non-Arteritic Anterior Ischemic Optic Neuropathy (NA-A 2016 Jan BACKGROUND: The aim of our study was to determine the prevalence of NA-AION patients younger than 50 years among all our NA-AION patients and to compare clinical findings between young and elderly NA-AION patients. METHODS: This was a retrospective review of complete ophthalmic examinations, including fluorescein angiography and visual field testing, performed on all patients with the first attack of acute NA-AION admitted to our department during the period of ten years (2004 to 2013). Of 120 NA-AION patients, 10 (8.3 %) were under 50 years of age. RESULTS: The majority of these were men: 8 of 10 (80 %). The average best corrected visual acuity on admission was 0.34 (fingers counted up to 1.0) and on discharge 0.53 (fingers counted up to 1.0). Of 10 eyes, 6 were emmetropic and 4 hyperopic, from + 0.50 D to + 2.0 D. Aside from the clinical picture of AION, other ophthalmological findings were normal. In fluorescein angiography, typical changes for ischaemic optic neuropathy were observed in all patients. In a majority of patients, an inferior altitudinal visual field defect was found. As regards systemic risk factors, hyperlipidaemia was observed in 7, arterial hypertension in 3, diabetes mellitus without diabetic retinopathy in 3, and ischaemic heart disease in 1 of 10 patients. One patient was treated for rheumatoid arthritis without signs of vasculitis. In 3 patients, more than one systemic risk factor was observed. Two of our patients had no systemic risk factors except moderate hyperopia. Bilateral manifestation was observed only in one patient 8 months after the first attack. None of the patients experienced recurrent attacks. CONCLUSION: The prevalence of younger patients in our study was lower than in previous studies. The reason could be the better medical prevention in our region. Our study confirmed that even in young NA-AION patients, moderate hyperopia could be a predisposing factor. Our study did not confirm the differences between young and elderly NA-AION patients as observed in previous studies. During a period of 10 years, we did not observe recurrences, high risk of other eye involvement or severe vision loss in our young patients compared to the elderly.
25981892 Family history of autoimmune diseases is associated with an increased risk of autism in ch 2015 Aug BACKGROUND: We conducted a systematic review and meta-analysis to summarize the current evidence on the relationship between family history of autoimmune diseases (ADs) and risk of autism in children, as current evidence suggests inconsistent results. METHODS: We identified relevant studies by searching PubMed, EmBase, and Web of Science databases up to Dec 2014. Risk estimates from individual studies were pooled using random-effects models. Sub-groups analyses were conducted by some study-level factors. Publication bias was assessed by funnel plots, Egger's regression test and Begg-Mazumdar test. RESULTS: A total of 11 articles were included in the meta-analysis, including 3 cohort studies, 6 case-control studies, and 2 cross-sectional studies. The meta-analysis showed that family history of all ADs combined was associated with a 28% (95% CI: 12-48%) higher risk of autism in children. For some specific ADs, evidence synthesis for risk of autism in children showed a statistically significant association with family history of hypothyroidism (OR=1.64, 95% CI: 1.07-2.50), type 1 diabetes (OR=1.49, 95% CI: 1.23-1.81), rheumatoid arthritis (OR=1.51, 95% CI: 1.19-1.91), and psoriasis (OR=1.59, 95% CI: 1.28-1.97). The results varied in some subgroups. CONCLUSION: An overall increased risk of autism in children with family history of ADs was identified. More mechanistic studies are needed to further explain the association between family history of ADs and increased risk of autism in children.
25849372 Apolipoprotein-A1 as a damage-associated molecular patterns protein in osteoarthritis: ex 2015 Osteoarthritis (OA) is associated with a local inflammatory process. Dyslipidemia is known to be an underlying cause for the development of OA. Therefore, lipid and inflammatory levels were quantified ex vivo in blood and synovial fluid of OA patients (n=29) and compared to those of rheumatoid arthritis (RA) patients (n=27) or healthy volunteers (HV) (n=35). The role of apolipoprotein A-I (ApoA1) was investigated in vitro on inflammatory parameters using human joint cells isolated from cartilage and synovial membrane obtained from OA patients after joint replacement. Cells were stimulated with ApoA1 in the presence or not of serum amyloid A (SAA) protein and/or lipoproteins (LDL and HDL) at physiological concentration observed in OA synovial fluid. In our ex vivo study, ApoA1, LDL-C and total cholesterol levels were strongly correlated to each other inside the OA joint cavity whereas same levels were not or weakly correlated to their corresponding serum levels. In OA synovial fluid, ApoA1 was not as strongly correlated to HDL as observed in OA serum or in RA synovial fluid, suggesting a dissociative level between ApoA1 and HDL in OA synovial fluid. In vitro, ApoA1 induced IL-6, MMP-1 and MMP-3 expression by primary chondrocytes and fibroblast-like synoviocytes through TLR4 receptor. HDL and LDL attenuated joint inflammatory response induced by ApoA1 and SAA in a ratio dependent manner. In conclusion, a dysregulated lipidic profile in the synovial fluid of OA patients was observed and was correlated with inflammatory parameters in the OA joint cavity. Pro-inflammatory properties of ApoA1 were confirmed in vitro.
25485728 Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance wit 2015 Mar CONTEXT: Hyperthyroidism in women of reproductive age is predominantly caused by Graves' disease. Pregnancy associated changes in the immune system may influence the onset of disease, but population-based incidence rates in and around pregnancy have not been reported. OBJECTIVE: The objective of the study was to estimate the incidence of maternal hyperthyroidism (defined by redeemed prescription of antithyroid drugs) in and around pregnancy and to compare this with the incidence of other autoimmune diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). DESIGN: This was a population-based cohort study. SETTING: The study used the Danish nationwide registers. PARTICIPANTS: The participants were women who gave birth to singleton liveborn children in Denmark from 1999 to 2008 (n = 403,958). MAIN OUTCOME MEASURE(S): Incidence rates (IR) of maternal hyperthyroidism during a 4-year period beginning 2 years before and ending 2 years after the date when the mother was giving birth for the first time in the study period were measured. RESULTS: Altogether 3673 women (0.9%) were identified with an onset of hyperthyroidism from 1997 to 2010, and the overall IR of maternal hyperthyroidism was 65.0/100,000/year. The IR of hyperthyroidism in and around pregnancy varied widely and was high in the first 3 months of pregnancy [incidence rate ratio (IRR) vs the remaining study period: 1.50 (95% CI 1.09-2.06)), very low in the last 3 months of pregnancy (0.26 (0.15-0.44)], and reached the highest level 7-9 months postpartum [3.80 (2.88-5.02)]. The incidence variation in and around pregnancy was different for RA and IBD. CONCLUSION: These are the first population-based data on the incidence of hyperthyroidism in and around pregnancy. The incidence of hyperthyroidism was high in early pregnancy and postpartum, whereas such particular pattern was not observed for other diseases of autoimmune origin.
25308530 Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases? 2015 May 1,25-Dihydroxyvitamin D is a steroid hormone derived from vitamin D, playing an important role in maintaining an adequate serum level of calcium and phosphorus. It is now clear that vitamin D exerts an endocrine action on the cells of the immune system, generating anti-inflammatory and immunoregulatory effects. The mechanisms underlying the role of vitamin D in autoimmunity are not completely understood. Lower vitamin D levels have been found in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases, autoimmune thyroid diseases (i.e. Hashimoto's thyroiditis and Graves' disease) and autoimmune gastritis. Several genetic studies have demonstrated an association between thyroid autoimmunity susceptibility and gene polymorphisms of vitamin D receptor, vitamin D binding protein, 1-alpha-hydroxylase and 25-hydroxylase. Of note, some papers do not confirm this connection. With regard to the role of vitamin D in autoimmune thyroid diseases, available data remain controversial. Only few reports have analyzed the supposed association between autoimmune thyroid diseases and vitamin D concentration with inconclusive results. In our experience, low serum levels of vitamin D do not correlate either with Hashimoto's thyroiditis or with Graves' disease. The inability to achieve an unambiguous conclusion is in part due to the limitations in study design. In fact, most of the studies are cross-sectional surveys with a small number of subjects. In addition, the heterogeneity of the study population, seasonal variation of blood sampling, inter-method analytical variability of vitamin D assays and different definitions of vitamin D deficiency/insufficiency contribute to contradicting results. Therefore, further randomized, controlled, prospective trials are needed in order to demonstrate the causality of vitD in AITD and consequently the role of vitamin D supplementation in prevention or improvement of AITD, providing also information on the best formulation, dose and timing of supplementation.
25240809 The effect of osteoporosis management on proximal humeral fracture. 2015 Feb HYPOTHESIS AND BACKGROUND: Proximal humeral fractures comprise 10% of fractures in the Medicare population. The effect, if any, of treating osteoporosis to prevent these fractures has not been determined. The primary objective is to determine the effectiveness of a systematic osteoporosis screening and treatment program on the hazard of developing a fracture over the treatment period. The secondary aim is to determine demographic risk factors. METHODS: This is a retrospective cohort study in a health care organization serving 3.3 million members. Individuals selected for dual-energy x-ray absorptiometry screening were (1) women aged 65 years or older; (2) men aged 70 years or older; and (3) individuals aged 50 years or older who have a history of fragility fracture, use glucocorticoids, have a parental history of hip fracture, have rheumatoid arthritis, use alcohol at a high rate, or are cigarette smokers. Treatment consisted primarily of pharmacologic intervention with bisphosphonates. RESULTS: Individuals diagnosed with osteoporosis had a hazard ratio of 7.43 for sustaining a fracture over the study period. Patients screened with dual-energy x-ray absorptiometry had a hazard ratio of 0.17 whereas those treated medically had a hazard ratio of 0.55 versus untreated controls. Risk factors that significantly increased the risk of a fracture developing included age, female gender, white race, diabetes mellitus, and history of a distal radius fracture. DISCUSSION AND CONCLUSION: Over the study period, screening and treatment for osteoporosis significantly decreased the hazard ratio for proximal humeral fracture. This information broadens the impact of such programs because current best practices are primarily based on prevention of spine and hip fractures.
24809534 Extrahepatic autoimmune conditions associated with primary biliary cirrhosis. 2015 Jun There is a paucity of information on extrahepatic autoimmune (EHA) conditions associated with primary biliary cirrhosis (PBC) and on the impact of EHA conditions on PBC patients' survival. Our goal was to assess the association between PBC and other autoimmune diseases and the impact of EHA conditions on the natural history of PBC. We took advantage of 361 consecutive PBC patients enrolled between 1975 and 2012 (22 males, 339 females; mean follow-up 8 ± 6.9 years). Any associated EHA conditions, PBC histological stage at diagnosis, biochemical data, physiological history, and extrahepatic malignancies developing during the follow-up were recorded. Survival was analyzed by means of Kaplan-Meier curves. Importantly, 221 patients (61.2 %) had at least one EHA conditions: 45 patients (20.4 %) had Hashimoto thyroiditis; 7 (3.2 %) had Graves' thyroiditis; 65 (29.4 %) had Raynaud's phenomenon; 124 (56.1 %) had Sjogren's syndrome; 8 (3.6 %) had systemic lupus erythematosus; 22 (9.9 %) had scleroderma; 22 (9.9 %) had rheumatoid arthritis; 18 (8.1 %) had cutaneous autoimmune diseases; 8 (3.6 %) had vasculitis; 5 (1.4 %) had celiac disease; and 25 (13.1 %) had other EHA conditions. The proportion of patients with associated EHA conditions enrolled during representative periods (1975-1980, 1981-1990, 1991-2000, 2001-2010, 2011-2012) remained stable. No differences emerged between patients with versus without EHA conditions in terms of mean age at PBC diagnosis, antimitochondrial antibody (AMA), or antinuclear antibody (ANA) positivity, histological stage at diagnosis, smoking habits, alcohol consumption, or BMI >25. Multiple logistic regression analysis showed that only female gender was significantly associated with positivity for EHA conditions (OR 4.8; 95 % CI 1.6-13.7, p = 0.004). The mean survival after the diagnosis of PBC was much the same in patients with and without EHA conditions. In conclusion, EHA conditions are often associated with PBC, especially in female patients, but they do not reduce patient survival.
28065372 Dynamic high-resolution ultrasound of intrinsic and extrinsic ligaments of the wrist: How 2017 Feb Wrist ligaments are crucial structures for the maintenance of carpal stability. They are classified into extrinsic ligaments, connecting the carpus with the forearm bones or distal radioulnar ligaments, and intrinsic ligaments, entirely situated within the carpus. Lesions of intrinsic and extrinsic ligaments of the wrist have been demonstrated to occur largely, mostly in patients with history of trauma and carpal instability, or rheumatoid arthritis. Ultrasound allows for rapid, cost-effective, non-invasive and dynamic evaluation of the wrist, and may represent a valuable diagnostic tool. Although promising results have been published, ultrasound of wrist ligaments is not performed in routine clinical practice, maybe due to its technical feasibility regarded as quite complex. This review article aims to enlighten readers about the normal sonographic appearance of intrinsic and extrinsic carpal ligaments, and describe a systematic approach for their sonographic assessment with detailed anatomic landmarks, dynamic manoeuvres and scanning technique.
27933673 A biophysical and computational study unraveling the molecular interaction mechanism of a 2017 Jun The interaction of a recently certified kinase inhibitor Tofacitinib (TFB) with bovine serum albumin (BSA) has been studied, by spectroscopic and molecular docking studies. Spectrofluorimetric measurements at 3 different temperatures (288, 298, and 310 K) showed that TFB quench the intrinsic fluorescence of BSA upon forming a nonfluorescent complex. The intrinsic fluorescence data showed that TFB binds to BSA with binding constant (K(b) ) of approximately 10(4) M(-1) , affirming a significant affinity of TFB with BSA. The decrease in Stern-Volmer quenching constant with increasing temperature exhibited the static mechanism of quenching. Negative value of ΔG (-6.94 ± 0.32 kcal·mol(-1) ), ΔH (-7.87 ± 0.52 kcal·mol(-1) ), and ΔS (-3.14 ± 0.42 cal·mol(-1) ·K(-1) ) at all 3 temperatures declared the reaction between BSA and TFB to be spontaneous and exothermic. Far-UV circular dichroism spectroscopy results demonstrated an increase in helical content of BSA in the presence of TFB. Moreover, dynamic light scattering measurements showed that TFB resulted into a decrease in the hydrodynamic radii (from 3.6 ± 0.053 to 2.9 ± 0.02 nm) of BSA. Molecular docking studies confirmed that TFB binds near site II on BSA, hydrogen bonding, and hydrophobic interaction were involved in the BSA-TFB complex formation. The present study characterizing the BSA-TFB interaction could be significant towards gaining an insight into the drug pharmacokinetics and pharmacodynamics and also in the direction of rational drug designing with better competence, against emerging immune-mediated diseases, ie, alopecia and rheumatoid arthritis.