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ID PMID Title PublicationDate abstract
19092842 Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrom 2009 Jan Primary Sjögren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) >1.4 and P-values <0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P=2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.
20591075 Analysis of VH gene rearrangement and somatic hypermutation in Sjogren's syndrome and IgG4 2010 Jul IgG4-related sclerosing sialadenitis is currently considered as an autoimmune disease distinct from Sjogren's syndrome (SS) and responds extremely well to steroid therapy. To further elucidate the characteristics of IgG4-related sclerosing sialadenitis, we analysed VH fragments of IgH genes and their somatic hypermutation in SS (n = 3) and IgG4-related sclerosing sialadenitis (n = 3), using sialolithiasis (n = 3) as a non-autoimmune control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of rearranged IgH genes, at least 50 clones per case (more than 500 clones in total) were sequenced for VH fragments. Monoclonal IgH rearrangement was not detected in any cases examined. When compared with sialolithiasis, there was no VH family or VH fragment specific to SS or IgG4-related sclerosing sialadenitis. However, rates of unmutated VH fragments in SS (30%) and IgG4-related sclerosing sialadenitis (39%) were higher than that in sialolithiasis (14%) with statistical significance (P = 0.0005 and P < 0.0001, respectively). This finding suggests that some autoantibodies encoded by germline or less mutated VH genes may fail to be eliminated and could play a role in the development of SS and IgG4-related sclerosing sialadenitis.
20235486 [Neuromyelitis optica in a patient with Sjögren syndrome with distal renal tubular acidos 2010 Mar We report the case of a 31-year-old woman who presented with neuromyelitis optica (NMO) associated with Sjögren syndrome and distal renal tubular acidosis. She was hospitalized because of cervical transverse myelopathy and right optic neuritis. She had been clinically diagnosed with Sj6gren syndrome, with a high titer of anti-SS-A antibody (1:500) and anti-SS-B antibody (1:498). She also showed hypokalemia, metabolic acidosis, and nephrocalcinosis caused by distal renal tubular acidosis associated with Sjögren syndrome. T2-weighted magnetic resonance imaging (MRI) revealed long lesions extending from the medulla oblongata to the lower thoracic cord. In addition, gadolinium-enhanced MRI revealed a right optic nerve lesion in the optic canal. High titer of anti-aquaporin-4 (AQP4) antibody was detected in the patient's serum (1:131,072). A combination therapy comprising steroid pulse therapy and plasmapheresis improved her clinical symptoms, and the administration of oral prednisolone (20 mg/ day) was effective in preventing the recurrence of NMO. In patients with myelitis/transverse myelopathy associated with autoimmune disorders such as Sjögren syndrome, examining the titer values of anti-AQP4 antibody is indispensable in determining the appropriate therapy.
19813014 [Pattern recognition in the differential diagnosis of salivary lymphoepithelial lesions]. 2009 Nov The prototype of a salivary lymphoepithelial lesion is the autoimmune disease Sjögren's syndrome with the characteristic lymphoepithelial duct lesions (LEL). The distinction of Sjögren's syndrome from cases with initial transformation into associated marginal zone B-cell lymphoma (MALT type) can be very challenging, whereby the presence of small "halos" can lead to over-diagnosis. The HIV-associated cystic lymphoepithelial lesion can be histologically almost identical to Sjögren's syndrome and often needs clinical correlation. The sporadic lymphoepithelial cyst of the parotid gland is a frequent finding and has no clinical consequence; however, this entity needs to be identified and distinguished from the above-mentioned entities. The most frequent diagnosis in resected submandibular glands is chronic-fibrosing sialadenitis, so-called Küttner's tumour. Altogether, there is a wide spectrum of lymphoepithelial interaction in the area of salivary glands, including biphasic lymphoepithelial tumours with an obligate lymphoid component, epithelial tumours with facultative tumour-associated lymphoid proliferation, and different processes of intraparotid lymph nodes. The immunohistological reaction for pan-keratin can be very helpful for a thorough pattern analysis of the different lymphoepithelial lesions. The relative frequency of the lesions in different salivary glands can also be diagnostically helpful.
20811902 Expression of pro-inflammatory TACE-TNF-α-amphiregulin axis in Sjögren's syndrome saliva 2010 Oct The tumor-necrosis-factor-converting-enzyme (TACE)-TNF-α-Amphiregulin (AREG) axis plays an important pathogenic role in inflammatory and autoimmune disorders. However, the pathological roles of these proteins in the chronic autoimmune disease Sjögren's syndrome (SS) remain to be elucidated. It is known that the TACE-AREG axis is clearly part of a larger cascade of signals that starts with the activation of Furin, responsible for maturation of TACE that, in turn, determines the production of active TNF-α, directly involved in the up-regulation of AREG expression. This study showed that Furin, TACE, TNF-α, and AREG proteins, detected in acinar and ductal cells of human salivary glands from SS patients, increased remarkably in comparison with biopsies of labial salivary glands from healthy controls. The changes in Furin, TACE, TNF- α, and AREG proteins' level detected in salivary glands biopsies of SS patients could be responsible for pro-inflammatory cytokines overexpression characterizing Sjögren's syndrome.
20237294 An autoimmune response to odorant binding protein 1a is associated with dry eye in the Air 2010 Apr 15 Sjögren's Syndrome (SS) is a human autoimmune disease characterized by immune-mediated destruction of the lacrimal and salivary glands. In this study, we show that the Aire-deficient mouse represents a new tool to investigate autoimmune dacryoadenitis and keratoconjunctivitis sicca, features of SS. Previous work in the Aire-deficient mouse suggested a role for alpha-fodrin, a ubiquitous Ag, in the disease process. Using an unbiased biochemical approach, however, we have identified a novel lacrimal gland autoantigen, odorant binding protein 1a, targeted by the autoimmune response. This novel autoantigen is expressed in the thymus in an Aire-dependent manner. The results from our study suggest that defects in central tolerance may contribute to SS and provide a new and clinically relevant model to investigate the pathogenic mechanisms in lacrimal gland autoimmunity and associated ocular surface sequelae.
20856230 IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene t 2011 Jan Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears that eventually result in dry mouth and dry eye diseases. T(H)17 cell populations secreting IL17A have been shown to have an important function in an increasing number of autoimmune diseases, including SS. In this study, we investigated the function of IL17A on SS development and onset. Adenovirus-5 vectors expressing either IL17R:fragment of crystallization (Fc) fusion protein or LacZ were injected through retrograde cannulation into the salivary glands of SS-susceptible (SS(S)) C57BL/6.NOD-Aec1Aec2 mice between 6 and 8 weeks of age (a pre-disease stage) or 15 and 17 weeks of age (a diseased stage). The mice were subsequently characterized for their SS phenotypes. Mice cannulated with the Ad5-IL17R:Fc viral vector at either 7 or 16 weeks of age exhibited a rapid temporal, yet persistent, decrease in the levels of serum IL17 as well as the overall numbers of CD4+IL17+T cells present in their spleens. Disease profiling indicated that these mice showed decreased lymphocytic infiltrations of their salivary glands, normalization of their antinuclear antibodies repertoire, and increased saliva secretion. In contrast, mice cannulated with the control Ad5-LacZ viral vector did not exhibit similar changes and progressed to the overt disease stage. The capacity of the Ad5-IL17R:Fc-blocking factor to reduce SS pathology in SS(S) mice strongly suggests that IL17 is an important inflammatory cytokine in salivary gland dysfunction. Thus, therapeutic approach targeting IL17 may be effective in preventing glandular dysfunction.
20854935 Clinical and laboratory aspects of Ro/SSA-52 autoantibodies. 2011 Jan Anti-Ro/SSA antibodies, which were described for the first time in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), are the most prevalent extractable nuclear antigen (ENA) specificity identified in laboratories. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature. The sites involved and the symptoms associated with these autoantibodies depend on the antigen's structural variability. Isolated congenital complete atrioventricular block (CAVB) shows a close association with maternal anti-Ro/SSA and anti-La/SSB antibodies; the highest relative risks of CAVB are seen in offspring of mothers with antibodies against 52-kDa Ro and 48-kDa La proteins. Anti-Ro/SSA52 antibodies have little impact on adult rheumatic autoimmune diseases or adult cardiac arrhythmias, but the course of autoimmune liver diseases is greatly worsened by their presence, and solid tumours tend to relapse. Their diagnostic role in rheumatic diseases is controversial, although a significant association between isolated anti-Ro/SSA52-kDa positivity and myositis and to a lesser extent with systemic sclerosis (SSc) has been described. However, the majority of the specific diagnosis is mostly based on the simultaneous presence of other autoantibodies that seems diagnostically more relevant.
20039395 Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype 2010 Jan OBJECTIVE: In the sanroque mouse model of lupus, pathologic germinal centers (GCs) arise due to increased numbers of follicular helper T (Tfh) cells, resulting in high-affinity anti-double-stranded DNA antibodies that cause end-organ inflammation, such as glomerulonephritis. The purpose of this study was to examine the hypothesis that this pathway could account for a subset of patients with systemic lupus erythematosus (SLE). METHODS: An expansion of Tfh cells is a causal, and therefore consistent, component of the sanroque mouse phenotype. We validated the enumeration of circulating T cells resembling Tfh cells as a biomarker of this expansion in sanroque mice, and we performed a comprehensive comparison of the surface phenotype of circulating and tonsillar Tfh cells in humans. This circulating biomarker was enumerated in SLE patients (n = 46), Sjögren's syndrome patients (n = 17), and healthy controls (n = 48) and was correlated with disease activity and end-organ involvement. RESULTS: In sanroque mice, circulating Tfh cells increased in proportion to their GC counterparts, making circulating Tfh cells a feasible human biomarker of this novel mechanism of breakdown in GC tolerance. In a subset of SLE patients (14 of 46), but in none of the controls, the levels of circulating Tfh cells (defined as circulating CXCR5+CD4+ cells with high expression of Tfh-associated molecules, such as inducible T cell costimulator or programmed death 1) were increased. This cellular phenotype did not vary with time, disease activity, or treatment, but it did correlate with the diversity and titers of autoantibodies and with the severity of end-organ involvement. CONCLUSION: These findings in SLE patients are consistent with the autoimmune mechanism in sanroque mice and identify Tfh effector molecules as possible therapeutic targets in a recognizable subset of patients with SLE.
21125152 Immediate complications of 3,555 injections of anti-TNFα. 2010 Mar OBJECTIVE: To evaluate the immediate complications of anti-TNFα drugs at the "Center for Dispensation of High Cost Medications" of HC-FMUSP. PATIENTS AND METHODS: All patients who received anti-TNFα agents between August 2007 and March 2009 were included in this study. Immediate complications (up to 1 hour after the injection) were classified as mild (headache, rash, dizziness, itching, nausea), moderate (fever, urticaria, palpitation, chest pain, dyspnea, blood pressure variations between 20 and 40 mmHg), or severe (fever with chills, dyspnea with wheezing, variations in blood pressure > 40 mmHg). RESULTS: Two hundred and forty-two patients were evaluated: 94 (39%) with rheumatoid arthritis, 64 (26%) with ankylosing spondylitis, 32 (13%) with psoriatic arthritis, 26 (11%) with juvenile idiopathic arthritis; and 27 (11%) with other diagnoses. A total of 3,555 injections were administered: 992 (28%) adalimumab, 1,546 (43%) etanercept, and 1,017 (29%) infliximab. Immediate adverse events were observed in 39/242 (16%) patients. Injection related complications were observed in 46/3,555 (1.2%) injections. They were more common with infliximab than adalimumab (3.7% vs. 0.5%, P < 0.0001) and etanercept (3.7% vs. 0.25%, P < 0.0001). Complications were classified as mild 14/45 (31%), moderate 21/45 (47%), and severe 10/45 (22%), and occurred mainly in the first six months of treatment (56%) and after intravenous injections, especially (76%) in the first hour. CONCLUSION: Although rare, acute reactions can be severe, being observed more commonly after the initial injections, both intravenous and subcutaneous. More studies are necessary to define whether those immunobiological agents should be administered only in facilities capable of managing medical emergencies.
20149316 Prevalence of chondrocalcinosis in Italian subjects from northeastern Italy. The Pro.V.A. 2009 Nov OBJECTIVES: To undertake an epidemiological survey of the prevalence of radiological chondrocalcinosis (CC) of the lower limbs in the elderly Italian population of the Pro.V.A. study. METHODS: Knee and pelvic basin radiographs were performed on 3099 subjects aged 65 and older, residing in the Veneto Region of Italy (Rovigo and Camposampiero areas). Two readers independently analysed the knee, coxofemoral and pubic symphysis x-rays of a consecutive sample of 1629 subjects according to Altman. Some laboratory indexes, such as serum parathyroid hormone (PTH), vitamin D (vit D), bone alkaline phosphatase (bALP), deyidroepiandrosterone (DHEA), urinary CrossLaps (XL), and inflammatory biomarkers were evaluated. Quantitative variables were summarised as mean + or - standard deviation and qualitative ones as distributions. Unpaired t-test was used to compare mean values among groups for normally distributed variables, and non-parametric Mann-Whitney test for non normal variables. RESULTS: CC was found in 169 (mean age 78.2 + or - 8.0 yrs) out of the 1629 subjects studied (10.4%). After adjusting for the sex and age structure of the target population, the prevalence was 10.0%. CC was more often observed in women than in men (M: 7.0%; F: 12.8%, p=0.0002), and increased in occurrence with age, rising from 7.8% in subjects aged 65-74 yrs, to 9.4% in those aged 75-84 yrs, and to 21.1% in subjects older than 85 yrs. The knee was the most prevalent location since it was affected in 94.1% of all the subjects with CC, in particular the right limb. Knee CC was bilateral in 71.7% of the affected patients. The occurrence of rheumatic disorders did not differ significantly between the subjects with CC and those without (rheumatoid arthritis 0.59% vs. 0.48%, p=ns). CONCLUSIONS: Although the detection of CC was limited to few joints with the knee being the most affected location, our study confirms the frequent presence of CC at different sites, in keeping with the possible role of systemic factors. Articular CC is an age-related disorder, which could partly explain the prevalence discrepancies reported by various studies. The prevalence of CC found in our survey based on standardised x-ray reading was high, suggesting that CC could be an underdiagnosed disease in the absence of radiographic investigation.
19306076 T-cell large granular lymphocytic (T-LGL) leukemia: a single institution experience. 2010 Jun BACKGROUND: T-cell large granular lymphocytic (T-LGL) leukemia is a rare lymphoproliferative disease which usually affects elderly people. The clinical course of T-LGL leukemia is generally indolent, with lymphocytosis and splenomegaly in 20-50% patients, hepatomegaly in 5-20% of patients, and less commonly, lymphadenopathy. T-LGL leukemia is associated with immunological abnormalities: rheumatoid factor with or without rheumatoid arthritis (RA), Coombs positive hemolytic anemia, idiopathic thrombocytopenic purpura (ITP), pure red cell aplasia (PRCA), positive anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), hypogammaglobulinemia, and polyclonal hypergammaglobulinemia. Aim To compare clinical and laboratory features of T-LGL leukemia patients and their responses to different chemotherapy regimens. METHODS: Six patients (3 males and 3 females) with T-LGL leukemia were analyzed. The diagnosis was based on accepted morphologic criteria, immunophenotype, and polymerase chain reaction (PCR) detection of T-cell receptor (TCR) gene rearrangements. RESULTS: All patients exhibited lymphocytosis, mainly with unusual morphologies, splenomegaly, and elevated serum lactate dehydrogenase (LDH). Three patients were treated with a Fludarabine-Cyclophosphamide (FC) combination as initial therapy while three patients received CHOP. Two patients received more than one treatment regimen. One patient died due to T-LGL leukemia in first year after diagnosis, one patient died 4 years after diagnosis, two patients interrupted their treatment, and two patients are still alive. CONCLUSIONS: Further prospective studies are needed for establishing a gold standard therapy for T-LGL leukemia.
19915732 A Selective Role for alpha3 Subunit Glycine Receptors in Inflammatory Pain. 2009 GlyR alpha3 has previously been found to play a critical role in pain hypersensitivity following spinal PGE(2) injection, complete Freund's adjuvant (CFA) and zymosan induced peripheral inflammation. In this study, although all models displayed typical phenotypic behaviours, no significant differences were observed when comparing the pain behaviours of Glra3(-/-) and wild-type littermates following the injection of capsaicin, carrageenan, kaolin/carrageenan or monosodium iodoacetate, models of rheumatoid and osteoarthritis, respectively. However, clear differences were observed following CFA injection (p < 0.01). No significant differences were observed in the pain behaviours of Glra3(-/-) and wild-type littermates following experimentally induced neuropathic pain (partial sciatic nerve ligation). Similarly, Glra3(-/-) and wild-type littermates displayed indistinguishable visceromotor responses to colorectal distension (a model of visceral pain) and in vivo spinal cord dorsal horn electrophysiology revealed no differences in responses to multimodal suprathreshold stimuli, intensities which equate to higher pain scores such as those reported in the clinic. These data suggest that apart from its clear role in CFA- and zymosan-induced pain sensitisation, hypersensitivity associated with other models of inflammation, neuropathy and visceral disturbances involves mechanisms other than the EP2 receptor - GlyR alpha3 pathway.
21158728 CXCL12-CXCR4 axis in angiogenesis, metastasis and stem cell mobilization. 2010 Chemokines are key players in the attraction and activation of leukocytes and are thus implicated in the recruitment of immune cells at sites of infection and/or inflammation. They exert their action by binding to seven-transmembrane G protein-coupled receptors. The chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 represents the single natural ligand for the chemokine receptor CXCR4. CXCL12 possesses angiogenic properties and is involved in the outgrowth and metastasis of CXCR4-expressing tumors and in certain inflammatory autoimmune disorders, such as rheumatoid arthritis. CXCR4 expression on tumor cells is upregulated by hypoxia and angiogenic factors, such as vascular endothelial growth factor (VEGF). CXCR4 also acts as a co-receptor for entry of human immunodeficiency virus (HIV) in CD4(+) T cells. Finally, CXCL12/CXCR4 interactions were shown to play an important role in the migration of hematopoietic stem cells and their progenitors from, and their retention within, the bone marrow, a site characterized by high CXCL12 expression. As such, CXCR4 inhibitors may be utilized to inhibit HIV-1 infection, tumor growth and metastasis and to mobilize hematopoietic stem cells from the bone marrow in the circulation, where they can be collected for autologous stem cell transplantation. Here, we discuss the different aspects of CXCL12/CXCR4 biology as well as the development and anti-cancer/stem cell mobilizing activity of CXCR4 antagonists.
21094154 A comparison of restriction fragment length polymorphism, tetra primer amplification refra 2011 Feb 20 BACKGROUND: From the wide range of methods currently available for genotyping, we wished to identify a quick, reliable and affordable approach for routine use in our laboratory for LTA+252 C>T SNP screening. METHODS: We set up and compared three genotyping methods for SNP detection: restriction fragment length polymorphism (RFLP), tetra primer amplification refractory mutation system PCR (TPAP) and unlabeled probe melting analysis (UPMA). The SNP model used was LTA+252 C>T, a cytokine gene polymorphism that has been associated with response to treatment in rheumatoid arthritis. The study was performed using 46 samples from healthy Caucasian volunteers. RESULTS: Allele and genotype distribution was similar to that previously described in the same population. All three genotyping methods showed good reproducibility and are suitable for a medium scale throughput molecular platform. UPMA was the most cost effective, reliable and safe method since it required the shortest technician time, could be performed in a single closed tube and involved automatic data analysis. CONCLUSION: This work is the first to compare these three genotyping techniques and provides evidence for UPMA being the method of choice for LTA+252 C>T SNP genotyping.
21039740 PADI4 gene polymorphism is not associated with ankylosing spondylitis in Chinese Han popul 2010 Nov The cause of ankylosing spondylitis (AS) remains unelucidated. Both genetic and environmental factors are suspected playing an important role in AS development. Peptidyl arginine deiminase type IV (PADI4) is a member of gene family that encodes enzymes responsible for the conversion of arginine to citrulline residues. A strong linkage between PADI4 polymorphism and rheumatoid arthritis has been found in Japanese and Korean patients, but there is no association study about PADI4 in AS. We speculated that PADI4 may be a pivotal gene for AS development. So we investigated the PADI4 polymorphisms in AS in Chinese Han population. A total of 316 Chinese AS patients of Han nationality and 439 healthy controls were recruited. Five single-nucleotide polymorphisms (SNP), PADI4-89 (rs11203366), PADI4-90 (rs11203367), PADI4-92 (rs874881) PADI4-94 (rs2240340) and PADI4-104 (rs1748033), of PADI4 gene were selected, and the major allele frequencies between cases and controls were assessed as 0.571 versus 0.597, 0.565 versus 0.585, 0.565 versus 0.574, 0.446 versus 0.421 and 0.614 versus 620, respectively. No significant differences in the frequency of PADI4 alleles and genotypes between the cases and controls were observed. Two haplotypes ACGGC and GTCGC were significant with AS even after Bonferroni's correction but were with a tiny frequency in AS cases as 1.0% and 1.2%, respectively. These results indicate that PADI4 polymorphisms may not play an important role in the development of AS in Chinese Han population.
21029209 Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients. 2011 Jul BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ-specific autoimmune disease was described in case reports. OBJECTIVES: To evaluate the presence of a broad spectrum of organ-specific and non-organ-specific autoantibodies other than anti-desmoglein antibodies in pemphigus patients. PATIENTS AND METHODS: Serum samples were obtained from 105 pemphigus foliaceus (PF) patients, 51 pemphigus vulgaris (PV) patients and 50 controls. Both indirect immunofluorescence assay and ELISA were used to assess the presence of autoantibodies related to connective tissue diseases, autoimmune hepatitis, vasculitis, rheumatoid arthritis, coeliac disease, diabetes and thyroiditis. RESULTS: Significant difference was observed between the three groups for anti-thyroglobulin antibodies in the pemphigus foliaceus group (18% vs. 4%, P=0.03). A significantly higher occurrence of IgM anti-cardiolipin (P=0.03), IgG anti-reticulin (P=0.01) and IgG anti-gliadin antibodies (P=0.008) were observed in the PV group. Cases with more than four autoantibodies were frequently positives for both anti-desmoglein 1 and anti-desmoglein 3. CONCLUSION: Autoantibodies other than anti-desmoglein antibodies are not rare in pemphigus patients. Clinical and serological follow-up of pemphigus patients with positive autoantibodies are needed to clarify their impact in disease evolution.
20725943 Long-term complications, extraintestinal manifestations, and mortality in adult Crohn's di 2011 Jan BACKGROUND: Crohn's disease (CD) is a chronic, progressive, destructive disease. Numerous intestinal and extraintestinal complications and manifestations can occur during its clinical course. This literature review summarizes our current knowledge of the long-term complications, extraintestinal complications, and mortality in CD in adults as reported in population-based studies that include long-term follow-up results. METHODS: A literature search of English and non-English language publications listed in the electronic databases of Medline (source PubMed, 1935 to July, 2009). RESULTS: The relative risk of incident fractures is increased in CD patients by ≈30%-40%. These patients have also have a 3-fold increased risk of deep venous thrombosis and pulmonary embolism. A variety of extraintestinal manifestations (primary sclerosing cholangitis, ankylosing spondylitis, iritis/uveitis, pyoderma gangrenosum, erythema nodosum) and diseases (asthma, bronchitis, pericarditis, psoriasis, rheumatoid arthritis, and multiple sclerosis) are associated with CD. The risks of colorectal and small bowel cancers relative to the general population are 1.4-1.9 and 21.1-27.1, respectively. A slightly increased risk of lymphoma, irrespective of medication use, has been reported in a recent meta-analysis of population-based studies. Overall mortality is slightly increased in CD, with a standardized mortality ratio of 1.4. CONCLUSIONS: CD is frequently associated with disease complications and extraintestinal conditions. Whether the impact of changing treatment paradigms with increased use of immunosuppressives and biologic agents can reduce disease complications and associated conditions is unknown.
20708428 Is latero-medial patellar mobility related to the range of motion of the knee joint after 2010 Dec Diminished range of motion (ROM) of the knee joint after total knee arthroplasty (TKA) is thought to be related to reduced patellar mobility. This has not been confirmed clinically due to a lack of quantitative methods adequate for measuring patellar mobility. We investigated the relationship between patellar mobility by a reported quantitative method and knee joint ROM after TKA. Forty-nine patients [osteoarthritis--OA: 29 knees; rheumatoid arthritis--RA: 20 knees] were examined after TKA. Respective medial and lateral patellar mobility was measured 1 and 6 months postoperatively using a patellofemoral arthrometer (PFA). Knee joint ROM was also measured in each of those 2 sessions. Although the flexion and extension of the knee joints improved significantly from 1 to 6 months after TKA, the medial and lateral patellar displacements (LPDs) failed to improve during that same period. Moreover, only the changes in knee flexion and medial patellar displacement (MPD) between the two sessions were positively correlated (r = 0.31, p < 0.05). However, our findings demonstrated that medial and lateral patellar mobility had no sufficient longitudinal relationship with knee ROM after TKA.
20666718 A review of natural and synthetic antioxidants important for health and longevity. 2010 Reactive oxygen species (ROS) generated in the presence of O(2) by mitochondria, phagocytic cells, peroxisomes, and cytochrome P450 enzymes under physiological conditions, may play a dual function in the human organism. On the one hand, they participate in cell signal transduction cascades, leading to the activation of some transcription factors responsible for regulating of the expression of genes relevant for cell growth and differentiation. On the other hand, they cause oxidative damage of cellular DNA, protein and lipids, resulting in the initiation or development of numerous diseases such as cancer, cardiovascular diseases, type 2 diabetes mellitus, cataract, rheumatoid arthritis, or different neurodegenerative diseases. Both endogenous compounds (glutathione, ubiquinol, urate, bilirubin) and enzymes (superoxide dismutase, catalase, glutathione peroxidase) are engaged in the detoxification of ROS. In addition, numerous dietary components such as vitamin C, vitamin E, carotenoids, and polyphenols are thought to be involved in the antioxidant defense system. The present review article is focused on the summary and the assessment of research on the impact of dietary antioxidants in the prevention of chronic diseases, particularly cancer and cardiovascular diseases.