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ID PMID Title PublicationDate abstract
22033794 Carotid artery intima-media thickness in patients with autoimmune connective tissue diseas 2013 Dec Patients with autoimmune rheumatic disorders have an increased incidence of cardiovascular (CV) events and mortality. Despite this being related to a high prevalence of the traditional CV risk factors, systemic inflammation has been postulated to be an independent CV risk factor, particularly in patients with rheumatoid arthritis (RA). However, data are still controversial. We designed a case-control study, in which patients with autoimmune rheumatic disorders were matched with age-, sex-matched controls. Prevalence of early atherosclerosis was assessed by carotid artery intima-media thickness (IMT) measurement. IMT values were considered normal (IMT ≤ 0.9 mm) or abnormal (IMT > 0.9). Multivariate analysis was performed to identify predictors of pathological IMT. Overall, 152 patients and 140 matched controls were enrolled. Prevalence of >0.9 mm IMT values did not significantly differ between patients with autoimmune rheumatic disorders and controls (61 vs. 69%, p = 0.1). In detail, a similar IMT distribution between the 69 RA patients and controls was observed. Cases with a CV risk factor showed a higher prevalence of pathological IMT as compared to those without any risk factor, both in patients (77.1 vs. 38.6%; p < 0.0001) and controls (84.6 vs. 25%; p < 0.0001). At multivariate analysis, age and presence of CV risk factors were found to be independent predictors of >0.9 mm IMT, while RA as well as any other considered rheumatic disease were not. Our data found a similar prevalence of preclinical arterial wall atherosclerotic damage in patients with autoimmune rheumatic diseases and matched controls. Presence of traditional CV risk factors and patient age remain the main factors involved in preclinical atherosclerosis in patients with autoimmune rheumatic disorders, including RA.
22017805 Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-e 2011 Oct 21 Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.
21947186 Down-regulation of HLA-A mRNA in peripheral blood mononuclear cell of colorectal cancer. 2012 Jan PURPOSE: It has been demonstrated that the alteration of human leukocyte antigen (HLA) class I expression frequently occurs in colorectal tumor. Previous studies mainly focused on the expression of HLA-A in tumor cells. The expression of HLA-A in peripheral blood mononuclear cells (PBMC) was unknown. To develop a non-invasive diagnostic method for colorectal cancer (CRC), this work investigated the expression of HLA-A mRNA in PBMC in patients with CRC. METHODS: Real-time quantitative RT-PCR was used to study the expression of HLA-A mRNA in PBMC from 48 patients with colorectal cancer, 38 patients with benign colorectal lesions, 20 patients with rheumatoid arthritis, 20 patients with esophageal cancer and 40 healthy individuals. Protein chip was utilized to detect the levels of serum CEA, CA 19-9, and CA 242 in all the cases. Overall results from the two methods were compared. RESULTS: The relative expression of HLA-A mRNA in PBMC was 1.11 ± 0.45 in healthy group, 0.81 ± 0.42 in benign colorectal lesion group, and 0.39 ± 0.34 in cancer group, respectively. The diagnostic sensitivity of HLA-A mRNA, CEA, CA19-9, and CA242 was 81%, 59%, 61%, and 63%, and their diagnostic specificity was 75%, 64%, 52%, and 67%, respectively. CONCLUSIONS: The expression of HLA-A mRNA in PBMC from colorectal cancer group was significantly lower than those in both benign group and healthy group (P < 0.001). It could be potentially developed as a tumor assistant marker in future.
21932048 Non-steroidal anti-inflammatory drugs and cognitive function: are prostaglandins at the he 2012 Mar Studies of non-steroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis imply that inflammation is important in the development of Alzheimer's disease (AD). However, these drugs have not alleviated the symptoms of AD in those who have already developed dementia. This suggests that the primary mediator targeted by these drugs, PGE2, is not actively suppressing memory function in AD. Amyloid-β oligomers appear to be important for the mild cognitive changes seen in AD transgenic mice, yet amyloid immunotherapy has also proven unsuccessful in clinical trials. Collectively, these findings indicate that NSAIDs may target a prodromal process in mice that has already passed in those diagnosed with AD, and that synaptic and neuronal loss are key determinants of cognitive dysfunction in AD. While the role of inflammation has not yet become clear, inflammatory processes definitely have a negative impact on cognitive function during episodes of delirium during dementia. Delirium is an acute and profound impairment of cognitive function frequently occurring in aged and demented patients exposed to systemic inflammatory insults, which is now recognised to contribute to long-term cognitive decline. Recent work in animal models is beginning to shed light on the interactions between systemic inflammation and CNS pathology in these acute exacerbations of dementia. This review will assess the role of prostaglandin synthesis in the memory impairments observed in dementia and delirium and will examine the relative contribution of amyloid, synaptic and neuronal loss. We will also discuss how understanding the role of inflammatory mediators in delirious episodes will have major implications for ameliorating the rate of decline in the demented population.
21826033 Endoscopic image-guided transcervical odontoidectomy: outcomes of 15 patients with basilar 2012 Feb BACKGROUND: Ventral decompression with posterior stabilization is the preferred treatment for symptomatic irreducible basilar invagination. Endoscopic image-guided transcervical odontoidectomy (ETO) may allow for decompression with limited morbidity. OBJECTIVE: To describe the perioperative outcomes of patients undergoing anterior decompression of basilar invagination with the use of ETO. METHODS: Fifteen patients who had a follow-up of at least 16 months were retrospectively reviewed. Intraoperatively, the vertebral body of C2 was removed and the odontoid was resected in a "top-down" manner using endoscopic visualization and frameless stereotactic navigation. Posterior instrumented stabilization was subsequently performed. RESULTS: The average (± standard deviation) age of the patients was 42.6 ± 24.5 (range, 11-72) years. Postoperative complications occurred in 6 patients, including a urinary tract infection (n = 2), upper airway swelling (n = 2), dysphagia (n = 2), gastrostomy tube placement (n = 1), and an asymptomatic pseudomeningocele (n = 1). No patients required a tracheostomy, had bacterial meningitis, or developed a venous thromboembolic event; only 1 patient was intubated for more than 48 hours postoperatively. With a mean follow-up of 41.9 ± 14.4 (range, 16-59) months, myelopathy improved in all patients and no patient experienced late neurological deterioration. The mean modified Japanese Orthopedic Association (JOA) score increased from 11.2 ± 4.2 to 15.9 ± 1.4 (P = .002). Patients with a diagnosis other than rheumatoid arthritis or who had a higher preoperative JOA score had a significantly better postoperative neurological recovery (P = .005). CONCLUSION: ETO may be a valid treatment for patients with symptomatic irreducible basilar invagination that avoids some of the morbidity of transoral surgery and leads to long-term improvement in myelopathy.
21816146 Fatty acids and inflammation: the cutting edge between food and pharma. 2011 Sep Inflammation underlies many common conditions and diseases. Fatty acids can influence inflammation through a variety of mechanisms, including acting via cell surface and intracellular receptors/sensors that control inflammatory cell signalling and gene expression patterns. Some effects of fatty acids on inflammatory cells appear to be mediated by, or at least are associated with, changes in fatty acid composition of cell membranes. Changes in these compositions can modify membrane fluidity, lipid raft formation, cell signalling leading to altered gene expression, and the pattern of lipid and peptide mediator production. Cells involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these may have differing properties from those of arachidonic acid-derived eicosanoids. EPA and DHA give rise to resolvins which are anti-inflammatory and inflammation resolving. Thus, fatty acid exposure and the fatty acid composition of human inflammatory cells influences their function. As a result of their anti-inflammatory actions marine n-3 fatty acids have therapeutic efficacy in rheumatoid arthritis, although benefits in other inflammatory diseases and conditions have not been unequivocally demonstrated. The anti-inflammatory effects of marine n-3 fatty acids may contribute to their protective actions towards atherosclerosis, plaque rupture and cardiovascular mortality. The therapeutic dose of n-3 fatty acids is not clear.
21755372 Clinical characteristics of patients with lymphoproliferative neoplasms in the setting of 2012 Sep Clinical features of 40 lymphoproliferative neoplasm patients in the setting of systemic autoimmune diseases managed in the Clinic of Hematology during 1994-2006 were analyzed retrospectively. The classification of systemic autoimmune disease patients was as follows: 15 systemic lupus erythematosus--SLE, 11 rheumatoid arthritis--RA, 12 Sjögren's syndrome--SS, 1 scleroderma, and 1 dermatomyositis. Patients comprised 31 women and 9 men of mean age 55 years (range 33-76). Systemic autoimmune diseases preceeded the development of lymphoproliferative neoplasms in 37/40 (92.5%) patients. Mean latency period between the onset of systemic autoimmune diseases and lymphoproliferative neoplasms occurrence was significantly longer in RA (113 months) than in SLE (75 months) and SS patients (65 months)--P < 0.05. The most frequent lymphoproliferative neoplasms were non-Hodgkin's lymphoma--NHL (35/40; 88%), diffuse large B-cell lymphoma (DBCL)--12 (34%), follicular lymphoma (FC)--7 (20%), small lymphocytic (SL), and marginal zone lymphoma (MZL)--5 (14%) each. The primary site of NHL was extranodal in 18/35 (51.5%) cases. Advanced disease on diagnosis (III + IV clinical stages), constitutional symptoms, and bulky disease were diagnosed in 27/35 (77%), 26/35 (74%), and 3/35 (8.5%) patients, respectively. The overall survival (OS) was as follows (months): DBCL-12, FC-63, SLL-60, and MZL-48. There was no association between the lymphoproliferative neoplasm histological subtype and the systemic autoimmune diseases type or antirheumatic treatment P > 0.05. Our findings are in line with earlier reports showing a high proportion of patients with advanced disease, constitutional symptoms, extranodal manifestations, high grade histology, and low OS in the systemic autoimmune diseases setting.
21749307 T-cell and natural killer-cell large granular lymphocyte leukemia neoplasias. 2011 Dec Large granular lymphocyte (LGL) leukemia is a rare disorder of cytotoxic lymphocytes. LGL cells play an integral role in the immune system and are divided into two major lineages of CD3(-)natural killer (NK) cells and CD3(+) T cells that circulate throughout the blood in search of infected cells, in which they will make contact through a receptor ligand and induce cell death. LGL cells are also programmed to undergo apoptosis after contact with an infected target cell; however, they continue to survive in individuals with LGL leukemia. This unchecked proliferation and cytotoxicity of LGLs in patients results in autoimmunity or malignancy. Rheumatoid arthritis is the most common autoimmune condition seen in individuals with LGL leukemia; however, LGL leukemia is associated with a wide spectrum of other autoimmune diseases. Patients may also suffer from other hematological conditions including hemolytic anemia, pure red cell aplasia, and neutropenia, which lead to recurrent bacterial infections. Currently, the only established treatment involves a low dose of an immunosuppressive regimen with methotrexate, in which 40-50% of patients are either resistant or do not respond. In order to establish new therapeutics it is important to understand the current state of LGL leukemia both in the clinic and in basic research.
21513711 Contrasting effects of TNF and anti-TNF on the activation of effector T cells and regulato 2011 Dec 1 Anti-TNF treatment is effective in a majority of rheumatoid arthritis (RA), however, this treatment can unexpectedly trigger the onset or exacerbate multiple sclerosis (MS). Recent progress in cellular immunology research provides a new framework to analyze the possible mechanism underlying these puzzling contradictory effects. The delicate balance of protective CD4(+)FoxP3(+) regulatory T cells (Tregs) and pathogenic CD4(+)FoxP3(-) effector T cells (Teffs) is crucial for the outcome of anti-TNF treatment of autoimmune disease. There is convincing evidence that TNF, in addition to stimulating Teffs, is able to activate and expand Tregs through TNFR2, which is preferentially expressed by Tregs. Therefore, the contrasting effects of TNF on Tregs and Teffs are likely to determine the therapeutic effect of anti-TNF treatment. In this review, we discuss the current understanding of the general effect of TNF on the activation of T cells, and the impact of TNF on the function of Teffs and Tregs. Understanding the differential effects of TNF on Teffs and Tregs is fundamentally required for the design of more effective and safer anti-TNF or anti-TNF receptor(s) therapeutic strategy for autoimmune diseases.
21511075 Psychiatric morbidity in HIV-positive subjects: a study from India. 2011 May OBJECTIVE: To study the psychiatric morbidity in HIV-positive subjects. DESIGN: Cross-sectional. METHODS: The purposive sample included HIV-positive subjects not receiving antiretroviral therapy (HIV) (n=100). Rheumatoid arthritis (severe) subjects not receiving steroids or disease-modifying antirheumatic drugs (RA) (n=40) were included as a comparison group. The 12-item General Health Questionnaire in Hindi (GHQ) was used to screen the psychiatric morbidity in both groups. In GHQ-positive cases, psychiatric diagnoses were made using the Structured Clinical Interview for DSM-IV (SCID). RESULTS: The HIV group reported sexual contact as the commonest source of infection (58%) and had a lower age at onset (32.53 vs. 36.60 years, P=.011), shorter duration of illness (12.95 vs. 83.37 months, P<.001), lower GHQ score (28.3 vs. 30.15, P=.043), similar Mini Mental State Examination (MMSE) score (28.01 vs. 27.37, P=.093) and lower psychiatric morbidity by both GHQ (score >2) (52% vs. 85%) and current SCID diagnoses (45% vs. 60%, P=.021), as compared to the RA group. The HIV group also had a lower prevalence of psychiatric disorders (45% vs. 60%), mood disorders [24% vs. 52% including major depressive disorder (19% vs. 45%)] and anxiety disorders (1% vs. 2.5%), but a higher prevalence of substance use disorders (17% vs. 2.5%), adjustment disorders (7% vs. 5%) and psychotic disorders (1% vs. 0), as compared to the RA group. CONCLUSION: The high prevalence of psychiatric disorders, especially the mood disorders, in our HIV-positive subjects was generally similar to that reported from the rest of the world.
21504255 Fracture risk tool validation in an integrated healthcare delivery system. 2011 Mar OBJECTIVE: To evaluate the utility of the Fracture Risk Calculator (FRC, Foundation for Osteoporosis Research and Education) for predicting 10-year hip fracture risk within a "real world" population. STUDY DESIGN: Retrospective cohort study. METHODS: We identified female members of Kaiser Permanente Northern California aged ≥50 years with bone mineral density (BMD) measured during 1997-2003. Hospitalization for hip fracture was ascertained up to 10 years following the BMD date, and 10-year observed hip fracture probabilities were calculated. Baseline data for fracture risk calculation were extracted from health plan databases, including age, race/ethnicity, smoking, body mass index, prior fracture, rheumatoid arthritis, glucocorticoid use, disorders associated with bone loss, and femoral neck BMD. Predicted 10-year FRC hip fracture probabilities were compared with observed 10-year hip fracture probabilities. RESULTS: Among 94,489 women (mean age 62.8 +/- 8.6 years, average femoral neck Z-score +0.1),the median duration of follow-up was 6.6 years, during which 1579 (1.7%) hip fractures occurred. Using the FRC, 23% met or exceeded the National Osteoporosis Foundation's 3% hip fracture threshold. The FRC somewhat underestimated observed hip fracture probabilities; across 10-year risk categories <1%, 1% to 2.9%, and 3% to 4.9%, ratios of observed to median predicted probabilities ranged from 1.3 to 1.4. CONCLUSIONS: The FRC tool can be applied to assess fracture risk in large populations using data from administrative databases. Despite some underestimation, this relatively simple tool may assist targeting of at-risk populations for more complete fracture risk assessment.
21320518 Characterization of protoberberine analogs employed as novel human P2X7 receptor antagonis 2011 Apr 15 The P2X(7) receptor (P2X(7)R), a member of the ATP-gated ion channel family, is regarded as a promising target for therapy of immune-related diseases including rheumatoid arthritis and chronic pain. A group of novel protoberberine analogs (compounds 3-5), discovered by screening of chemical libraries, was here investigated with respect to their function as P2X(7)R antagonists. Compounds 3-5 non-competitively inhibited BzATP-induced ethidium ion influx into hP2X(7)-expressing HEK293 cells, with IC(50) values of 100-300nM. This antagonistic action on the channel further confirmed that both BzATP-induced inward currents and Ca(2+) influx were strongly inhibited by compounds 3-5 in patch-clamp and Ca(2+) influx assays. The antagonists also effectively suppressed downstream signaling of P2X(7) receptors including IL-1β release and phosphorylation of ERK1/2 and p38 proteins in hP2X(7)-expressing HEK293 cells or in differentiated human monocytes (THP-1 cells). Moreover, IL-2 secretion from CD3/CD28-stimulated Jurkat T cell was also dramatically inhibited by the antagonist. These results imply that novel protoberberine analogs may modulate P2X(7) receptor-mediated immune responses by allosteric inhibition of the receptor.
21247220 Incidence of infusion-associated reactions with rituximab for treating multiple sclerosis: 2011 Feb 1 BACKGROUND: Rituximab is a monoclonal antibody approved for treating CD20-positive B-cell non-Hodgkin's lymphoma and rheumatoid arthritis but is used off-label for treating many autoimmune disorders, including multiple sclerosis (MS). Similarly to other monoclonal antibodies, the incidence of infusion-related reactions to rituximab is high. Reactions to monoclonal antibodies, including rituximab, vary widely in type and severity, but may include mild pruritis and rash to more severe complications such as Stevens-Johnson syndrome and anaphylactic reactions. OBJECTIVE: To assess the incidence of infusion-associated reactions in our MS patients receiving rituximab infusions and compare it to previous trials investigating rituximab for treating MS. METHODS: From 1 to 30 November 2009, we retrospectively reviewed medical charts from Partners Multiple Sclerosis Centre, Brookline, MA, USA, of patients being treated with rituximab for MS between 20 November 2007 and 24 November 2009 for evidence of infusion-associated reactions and further classified reactions on a grading scale. RESULTS: During the period studied, 70 patients were infused with rituximab. Infusion-associated events occurred in 25.7% of our patients. Reactions were mild to moderate and most commonly occurred during the first infusion. Most patients were able to complete the infusion after appropriate treatment of the reaction was administered, and most patients went on to receive subsequent doses without any further reactions. CONCLUSIONS: The occurrence of infusion-associated reactions to rituximab in patients with MS is fairly common. However, premedication that includes corticosteroids may reduce the incidence of reactions dramatically. Should they occur, proper treatment of reactions with histamine H(1) or H(2) receptor antagonists and infusion rate reduction is an effective management strategy in this situation.
21221595 The prevalence of fibromyalgia syndrome in a group of patients with diabetes mellitus. 2012 Apr We have studied the prevalence of fibromyalgia syndrome (FMS) in patients with type 1 and type 2 diabetes mellitus (DM). Relationship with disease control of DM and the presence of FMS was also evaluated. We have studied 93 consecutive patients with DM (85 with type 2 DM and 8 patients with type 1 DM) followed in Diabetes Center. Single researcher took the history and did physical examination including manual tender point examination according to Manual Tender Point Survey instructions. For the diagnosis of FMS, 1990 American College of Rheumatology Classification Criteria for FMS was used. We measured patients' fasting blood sugar levels and HbA1c levels around the same time period. Patients were excluded from the study if they had any other serious disease, and if there was any history of drug use that interferes with the symptoms of FMS. Patients with rheumatoid arthritis (RA) were accepted as controls. FMS was found in 18% of patients with DM type 2 (no patients with FMS in type 1 DM group), in 34% of patients with RA. Female patients with DM type 2 had significantly higher FMS rates. Mean fasting blood sugar levels and mean HbA1c levels were not significantly different between type 2 DM patients with FMS and DM patients without FMS. In RA group, in RA patients without FMS, the use of steroids was significantly higher. We have found an increased prevalence rate of FMS in patients with DM type 2 and RA. There was no correlation between the prevalence rate of FMS and good DM disease control.
21095183 Stable formyl peptide receptor agonists that activate the neutrophil NADPH-oxidase identif 2011 Feb 1 The neutrophil formyl peptide receptors (FPR1 and FPR2) are G-protein coupled receptors that can induce pro-inflammatory as well as anti-inflammatory activities when activated. Accordingly, these receptors may become therapeutic targets for the development of novel drugs to be used for reducing the inflammation induced injuries in asthma, rheumatoid arthritis, Alzheimer's disease, cardiovascular diseases and traumatic shock. We screened a library of more then 50K small compounds for an ability of the compounds to induce a transient rise in intracellular Ca(2+) in cells transfected to express FPR2 (earlier called FPRL1 or the lipoxin A(4) receptor). Ten agonist hits were selected for further analysis representing different chemical series and five new together with five earlier described molecules were further profiled. Compounds 1-10 gave rise to a calcium response in the FPR2 transfectants with EC(50) values ranging from 4×10(-9)M to 2×10(-7)M. All 10 compounds activated human neutrophils to release superoxide, and based on the potency of their activity, the three most potent activators of the neutrophil NADPH-oxidase were further characterized. These three agonists were largely resistant to inactivation by neutrophil produced reactive oxygen species and shown to trigger the same functional repertoire in neutrophils as earlier described peptide agonists. Accordingly they induced chemotaxis, granule mobilization and secretion of superoxide. Interestingly, the oxidase activity was largely inhibited by cyclosporine H, an FPR1 selective antagonist, but not by PBP10, an FPR2 selective inhibitor, suggesting that FPR1 is the preferred receptor in neutrophils for all three agonists.
22390927 Mechanical loading prevents the stimulating effect of IL-1β on osteocyte-modulated osteoc 2012 Mar 30 Inflammatory diseases such as rheumatoid arthritis are often accompanied by higher plasma and synovial fluid levels of interleukin-1β (IL-1β), and by increased bone resorption. Since osteocytes are known to regulate bone resorption in response to changes in mechanical stimuli, we investigated whether IL-1β affects osteocyte-modulated osteoclastogenesis in the presence or absence of mechanical loading of osteocytes. MLO-Y4 osteocytes were pre-incubated with IL-1β (0.1-1 ng/ml) for 24h. Cells were either or not subjected to mechanical loading by 1h pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) in the presence of IL-1β (0.1-1 ng/ml). Conditioned medium was collected after 1h PFF or static cultures. Subsequently mouse bone marrow cells were seeded on top of the IL-1β-treated osteocytes to determine osteoclastogenesis. Conditioned medium from mechanically loaded or static IL-1β-treated osteocytes was added to co-cultures of untreated osteocytes and mouse bone marrow cells. Gene expression of cysteine-rich protein 61 (CYR61/CCN1), receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) by osteocytes was determined immediately after PFF. Incubation of osteocytes with IL-1β, as well as conditioned medium from static IL-1β-treated osteocytes increased the formation of osteoclasts. However, conditioned medium from mechanically loaded IL-1β-treated osteocytes prevented osteoclast formation. Incubation with IL-1β upregulated RANKL and downregulated OPG gene expression by static osteocytes. PFF upregulated CYR61, RANKL, and OPG gene expression by osteocytes. Our results suggest that IL-1β increases osteocyte-modulated osteoclastogenesis, and that mechanical loading of osteocytes may abolish IL-1β-induced osteoclastogenesis.
20224922 MEFV gene mutations and its impact on the clinical course in ulcerative colitis patients. 2011 Jul Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa. The presence of gene responsible for FMF, MEFV, which frequently causes inflammation, may aggravate the clinical course of UC. We aimed to determine the prevalence of MEFV mutations in UC patients and its impact on the clinical course. Four groups were formed as group 1 UC with distal disease, group 2 UC with pancolonic disease, group 3 UC with total colectomy, and group 4 Rheumatoid Arthritis (RA) patients. Eleven mutations of FMF gene were investigated. The mean age of group 1, 2, 3, and 4 were 46.7 ± 13.9, 43.8 ± 12.9, 44.8 ± 14.2, and 45.8 ± 10.9 years, respectively. The mutations were identified in 19 of the 54 UC patients (35.2%). Homozygous E148Q in 2 patients (3.7%) and heterozygous in 17 patients (31.5%) (E148Q 11.1%, M694V 5.6%, V726A 5.6%, K695R 1.8%, M680I 1.8%, and compound heterozygous 5.6%) were determined. Frequencies of MEFV mutations in group 1, 2, and 3 were 30, 27.3, and 58.3%, respectively. The mutations were identified in 3 of the 20 RA patients (15%). All of them were heterozygous. The rate of MEFV mutations were higher in group 3 than in group 4 (P = 0.018), and the number of attacks that were treated with steroid in all UC patients with mutation positive was higher than in mutation negative (P = 0.016). FMF gene mutations may be identified in UC patients up to 58.3%. It may be suggested that the UC patients with severe form should be identified for MEFV mutations before the judgment of colectomy.
23286253 Implication of antithrombotic agents on potential bleeding from endoscopically determined 2013 Jan BACKGROUND AND AIM: Little is known about the clinical significance of treatment for endoscopically determined peptic ulcers (EPU), incidentally detected as surrogate endpoints for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulcers complication, such as overt bleeding and perforation. Even uncomplicated-EPU without overt bleeding signs when antithrombotic agents (AT) were cotherapied may be of potential bleeding sites. The aim of the present study was to evaluate whether microcytic anemia, implying potential bleeding, is associated with NSAIDs-associated EPU or cotherapies with AT. METHODS: Two hundred and thirty-eight outpatients with rheumatoid arthritis under long-term NSAIDs therapies underwent upper endoscopy and were divided into the following four groups according to the pattern (presence: + or absence: -) of AT cotherapy/EPU, respectively: A, -/- (n = 165); B, -/+ (n = 44); C, +/- (n = 25); and D, +/+ (n = 4). RESULTS: EPU were found in 48 of the 238 studied patients (20.2%). After significant interactions among four groups hadstatistically been identified, hemoglobin (Hb) and mean corpuscular volume (MCV) as biomarkers for potential bleeding were compared between the groups.Hb and MCV were significantly lower in the D group than in the A,B, or C groups (Hb: P < 0.01, respectively; P < 0.05, MCV; P < 0.01 or P < 0.05, respectively). CONCLUSIONS: Patients with NSAIDs-associated EPU and AT cotherapy indicated significantly more severe microcytic anemia pattern than those without EPU or AT cotherapy, despite no evidence of overt bleeding. Even uncomplicated-EPU without overt bleeding when ATs were cotherapied may be of potential bleeding sites.
23253613 Exercise therapy for bone and muscle health: an overview of systematic reviews. 2012 Dec 19 BACKGROUND: Musculoskeletal conditions (MSCs) are widely prevalent in present-day society, with resultant high healthcare costs and substantial negative effects on patient health and quality of life. The main aim of this overview was to synthesize evidence from systematic reviews on the effects of exercise therapy (ET) on pain and physical function for patients with MSCs. In addition, the evidence for the effect of ET on disease pathogenesis, and whether particular components of exercise programs are associated with the size of the treatment effects, was also explored. METHODS: We included four common conditions: fibromyalgia (FM), low back pain (LBP), neck pain (NP), and shoulder pain (SP), and four specific musculoskeletal diseases: osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and osteoporosis (OP). We first included Cochrane reviews with the most recent update being January 2007 or later, and then searched for non-Cochrane reviews published after this date. Pain and physical functioning were selected as primary outcomes. RESULTS: We identified 9 reviews, comprising a total of 224 trials and 24,059 patients. In addition, one review addressing the effect of exercise on pathogenesis was included. Overall, we found solid evidence supporting ET in the management of MSCs, but there were substantial differences in the level of research evidence between the included diagnostic groups. The standardized mean differences for knee OA, LBP, FM, and SP varied between 0.30 and 0.65 and were significantly in favor of exercise for both pain and function. For NP, hip OA, RA, and AS, the effect estimates were generally smaller and not always significant. There was little or no evidence that ET can influence disease pathogenesis. The only exception was for osteoporosis, where there was evidence that ET increases bone mineral density in postmenopausal women, but no significant effects were found for clinically relevant outcomes (fractures). For LBP and knee OA, there was evidence suggesting that the treatment effect increases with the number of exercise sessions. CONCLUSIONS: There is empirical evidence that ET has beneficial clinical effects for most MSCs. Except for osteoporosis, there seems to be a gap in the understanding of the ways in which ET influences disease mechanisms.
23115808 (99m)Tc-Labeled rituximab, a chimeric murine/human anti-CD20 monoclonal antibody. 2004 Rituximab is a chimeric murine/human monoclonal antibody (mAb) that targets the CD20 antigen (also known as membrane-spanning 4-domains, subfamily A, member 1; or MS4A1), which is expressed on 95% of the transformed B-cells that participate in the pathogenesis of non-Hodgkin lymphomas (NHL; diffused large-B cell, low-grade, or the follicular types), a hematological malignancy, and autoimmune diseases such as rheumatoid arthritis (RA), granulomatosis with polyangiitis (Wegener's granulomatosis), and microscopic polyangiitis. The CD20 antigen is not expressed on any other hematopoietic cells and is not shed for circulation into the plasma or internalized by the cells (1). Therefore, the CD20 antigen is considered to be an excellent target for the treatment of the various B-lymphocyte, cell-based diseases such as those mentioned above. The United States Food and Drug Administration has approved the use of rituximab for the treatment of NHL and the other diseases mentioned above. The exact mechanism of action of rituximab has been discussed by Maloney (2). Although much is known about the pathogenesis of the different forms of NHL at the molecular level, the prognosis for an individual suffering from this disease is based on the morphological and histological information obtained with invasive methods used on the patients (3). As an alternative to the invasive methods, noninvasive procedures, such as imaging with radiolabeled agents using single-photon emission computed tomography (SPECT) or positron emission tomography, are attractive options to screen for patients who can benefit the most from an anti-cancer treatment, and the same imaging technique(s) can be used to monitor and assess the efficacy of a treatment (4). Rituximab was labeled with (99m)Tc ([(99m)Tc]rituximab) and used with SPECT for the imaging of NHL (1) and several inflammatory autoimmune diseases such as RA, Behcet’s disease, sarcoidosis, and others, in humans (5).