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ID PMID Title PublicationDate abstract
19321099 Single transverse, dorsal incision for lesser metatarsophalangeal exposure. 2009 Mar BACKGROUND: The exposure of the lesser metatarsophalangeal joints is often difficult and inadequate in the presence of rheumatoid arthritis and associated deformities. We describe our results following the use of a single curved transverse, dorsal incision for the Mann-Thompson type of forefoot arthroplasty,(5, 9) multiple Weil osteotomies,(1, 2, 7, 11) and other forefoot procedures. MATERIALS AND METHODS: One hundred thirty-nine consecutive patients (163 feet) were included in the study. Wound healing, and patient and surgeon satisfaction were assessed. RESULTS: Ease of exposure and visualization of the target area was good-to-excellent in all patients. There were eight minor wound complications. There were no neurovascular complications. CONCLUSION: A single transverse incision offers adequate exposure of lesser metatarsophalangeal joints and good cosmesis.
19195885 Investigations of SCIO-469-like compounds for the inhibition of p38 MAP kinase. 2009 Mar 1 The p38 MAP kinase is implicated in the release of the pro-inflammatory cytokines TNFalpha and IL-1b. Inhibition of cytokine release may be a useful treatment for inflammatory conditions such as rheumatoid arthritis and Crohn's disease. A new lead structure for p38 MAP kinase inhibition was identified. Herein, we report the SAR of this new class of p38 inhibitors.
18955216 Regulation of Cellular Metabolism and Cytokines by the Medicinal Herb Feverfew in the Huma 2009 Mar The herb feverfew is a folk remedy for various symptoms including inflammation. Inflammation has recently been implicated in the genesis of many diseases including cancers, atherosclerosis and rheumatoid arthritis. The mechanisms of action of feverfew in the human body are largely unknown. To determine the cellular targets of feverfew extracts, we have utilized oligo microarrays to study the gene expression profiles elicited by feverfew extracts in human monocytic THP-1 cells. We have identified 400 genes that are consistently regulated by feverfew extracts. Most of the genes are involved in cellular metabolism. However, the genes undergoing the highest degree of change by feverfew treatment are involved in other pathways including chemokine function, water homeostasis and heme-mediated signaling. Our results also suggest that feverfew extracts effectively reduce Lipopolysaccharides (LPS)-mediated TNF-alpha and CCL2 (MCP-1) releases by THP-1 cells. We hypothesize that feverfew components mediate metabolism, cell migration and cytokine production in human monocytes/macrophages.
21437020 The Role of MicroRNA in Inflammatory Bowel Disease. 2010 Nov Inflammatory bowel disease (IBD) is the consequence of an abnormal immune response to environmental factors in genetically susceptible hosts. microRNAs (miRNAs) are small, 22-nucleotide, noncoding, single-stranded RNA molecules involved in the post-tran-scriptional regulation of 30% of protein-coding genes. Differential expression of miRNAs is described in multiple autoimmune-related conditions such as psoriasis, rheumatoid arthritis, lupus, and asthma. Recently, unique miRNA expression profiles have been described in epithelial cells of patients with active ulcerative colitis, Crohn's ileitis, and Crohn's colitis, as well as in the peripheral blood of patients with active ulcerative colitis and Crohn's disease. miRNA expression profiles also change in the progression from normal colonic tissue to dysplastic tissue, with unaffected tissue from IBD patients and inflamed tissue from IBD patients showing intermediate profiles. Understanding the role of miRNAs in IBD may lead to future insights into disease pathogenesis, diagnosis, and treatment.
21143872 Vitamin D in health and disease: current perspectives. 2010 Dec 8 Despite the numerous reports of the association of vitamin D with a spectrum of development, disease treatment and health maintenance, vitamin D deficiency is common. Originating in part from the diet but with a key source resulting from transformation by exposure to sunshine, a great deal of the population suffers from vitamin D deficiency especially during winter months. It is linked to the treatment and pathogenesis and/or progression of several disorders including cancer, hypertension, multiple sclerosis, rheumatoid arthritis, osteoporosis, muscle weakness and diabetes. This widespread deficiency of Vitamin D merits consideration of widespread policies including increasing awareness among the public and healthcare professionals.
21038465 At last - rats lacking B cells. 2010 Oct The rat model is a widely used animal model in research, its popularity perhaps only surpassed by the mouse model. Rats are the preferred models for the study of transplantation and certain tumor and autoimmune diseases. In particular, the understanding of cardiovascular-related diseases and chronic inflammation has depended widely on the rat, from which models for both multiple sclerosis and rheumatoid arthritis have been derived. Until now, research in the rat has been hampered by a lack of precise gene-targeting technology in this model. This limitation, however, is rapidly changing; a recent example is the availability of B-cell-deficient rat strains obtained by the newly established zinc finger nucleases-targeting technology. As described in this issue of the European Journal of Immunology, genetic targeting of the rat, for example, using zinc finger nucleases-targeting technology, is likely to rapidly drive progress in the understanding of not only B-cell biology but also in the general understanding of rat disease models.
20974590 Co-morbidity of migraine with somatic disease in a large population-based study. 2011 Jan INTRODUCTION: The aim of this study was to determine sex specific co-morbidity of migraine and its subtypes migraine without aura (MO) and migraine with aura (MA) with a number of common somatic diseases. SUBJECTS AND METHODS: In 2002, a questionnaire containing previously validated questions to diagnose migraine and its subtypes as well as questions regarding some somatic diseases was sent to 46,418 twins residing in Denmark and born between 1931 and 1982. The twins are representative of the whole Danish population and were used as such in the present study. RESULTS: We found that 21, 23 and 12 conditions were co-morbid with migraine, MA and MO, respectively. Co-morbid diseases included previously documented diseases: asthma, epilepsy and stroke as well as new conditions: kidney stone, psoriasis, rheumatoid arthritis and fibromyalgia. MA had more co-morbidities than MO and females more than males. CONCLUSIONS: Migraine occurs in 20-30% of several medical conditions. It should be diagnosed and treated along with the primary disease.
20969550 Musculoskeletal ultrasound in the diagnosis of rheumatic disease. 2010 The use of musculoskeletal ultrasound (MSKUS) in rheumatology practice and research has increased steadily over the last decade. An ever-growing body of literature shows parity and even superiority of MSKUS when compared to physical examination, plain radiography, and more expensive and static imaging modalities such as MRI. While many use the modality for procedure guidance, investigators continue to demonstrate its ability to impact diagnoses in a variety of rheumatic diseases. Initial efforts focused on establishing MSKUS as a helpful tool for rheumatoid arthritis (RA), especially in the detection of synovitis and joint erosions, but numerous studies are validating the use of MSKUS as a helpful diagnostic tool for the spondyloarthropathies, crystal diseases, osteoarthritis, and other rheumatic diseases. Advances in ultrasound technology are translating into more sensitive and accurate studies. Within the research community, current efforts aim at maximizing the direct clinical impact of MSKUS by developing global or patient level assessments and simplified joint scoring systems, with improvements in intra- and inter-reader reproducibility.
20676807 Regulation of peripheral inflammation by the central nervous system. 2010 Oct In inflammatory disorders such as rheumatoid arthritis, cytokines and danger signals are sensed by the central nervous system, which adapts behavior and physiologic responses during systemic stress. The central nervous system can also signal the periphery to modulate inflammation through efferent hormonal and neuronal pathways. The brain and spinal cord are involved in this bidirectional interaction. A variety of neuronal pathways that modulate synovial inflammation have been implicated, including the sympathetic and the parasympathetic branches of the autonomic system. Another mechanism, the dorsal root reflex, involves antidromic signaling along somatic afferent fibers that influences joint inflammation by releasing neuropeptides and other neuromediators in the periphery. Some of the neurotransmitters and neuroreceptors involved have been identified in preclinical models and represent novel targets for the treatment of rheumatic diseases.
20586505 Adverse effects of biological agents in the treatment of psoriasis. 2010 Tumour necrosis factor (TNF) antagonists are generally well tolerated, but carry the risk of side effects. In patients with psoriasis, the potential risks with anti-TNF agents may be overestimated because the most commonly reported adverse events are based on studies in patients with rheumatoid arthritis or inflammatory bowel disease. Whereas patients with psoriasis typically receive monotherapy, these patients are treated with biological-based combination therapies. Furthermore, patients with psoriasis have distinctive and different comorbidities, which could play a role in the development of different adverse events. However, the potential risks of the use of biological agents should always be taken into consideration.
22958737 Methotrexate-induced pneumonitis in Crohn's disease. Case report and review of the literat 2010 Oct 31 Methotrexate (MTX) is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable frequency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA) is reported.In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exercise. Chest X-ray demonstrated bilateral interstitial infiltrates and at computed tomography (CT) ground-glass opacities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alterations was achieved through MTX withdrawal and the introduction of corticosteroid therapy.
20865034 Does the KIR2DS5 gene protect from some human diseases? 2010 Aug 26 BACKGROUND: KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation. METHODOLOGY/PRINCIPAL FINDINGS: In our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p=0.003, odds ratio [OR]=0.47, confidence interval [CI]=0.28-0.79), endometriosis (p=0.03, OR=0.25, CI = 0.07-0.82) and acute rejection of kidney graft (p=0.0056, OR=0.44, CI=0.24-0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p=0.0003, OR=0.35, CI=0.19-0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p=0.0017, OR=1.92, CI=1.28-2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p=0.005, OR=1.47, CI=1.13-1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p=0.017, OR=0.47, CI=0.25-0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p=0.0015, OR=2.13, CI=1.34-3.37). CONCLUSIONS/SIGNIFICANCE: Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.
20191513 Self-directed learning of basic musculoskeletal ultrasound among rheumatologists in the Un 2010 Feb OBJECTIVE: Because musculoskeletal ultrasound (MSUS) is highly user dependent, we aimed to establish whether non-mentored learning of MSUS is sufficient to achieve the same level of diagnostic accuracy and scanning reliability as has been achieved by rheumatologists recognized as international experts in MSUS. METHODS: A group of 8 rheumatologists with more experience in MSUS and 8 rheumatologists with less experience in MSUS participated in an MSUS exercise to assess patients with musculoskeletal abnormalities commonly seen in a rheumatology practice. Patients' established diagnoses were obtained from chart review (gout, osteoarthritis, rotator cuff syndrome, rheumatoid arthritis, and seronegative arthritis). Two examining groups were formed, each composed of 4 less experienced and 4 more experienced examiners. Each group scanned 1 predefined body region (hand, wrist, elbow, shoulder, knee, or ankle) in each of 8 patients, blinded to medical history and physical examination. Structural abnormalities were noted with dichotomous answers, and an open-ended answer was used for the final diagnosis. RESULTS: Less experienced and more experienced examiners achieved the same diagnostic accuracy (US-established diagnosis versus chart review diagnosis). The interrater reliability for tissue pathology was slightly higher for more experienced versus less experienced examiners (kappa = 0.43 versus kappa = 0.34; P = 0.001). CONCLUSION: Non-mentored training in MSUS can lead to the achievement of diagnostic accuracy in MSUS comparable to that achieved by highly experienced international experts. Reliability may increase slightly with additional experience. Further study is needed to determine the minimal training requirement to achieve proficiency in MSUS.
20020136 A retrospective review of rheumatology referral wait times within a health centre in Quebe 2010 Mar It is important that inflammatory arthropathies such as rheumatoid arthritis be diagnosed promptly so that treatment can be administered in a timely fashion. However, there is considerable evidence that this process of care is delayed in many people. The aim of the study is to assess wait times between primary care referral and rheumatology assessment for new-onset inflammatory arthropathies. We performed a retrospective review related to new rheumatology consultations (N = 202) between September and November 2008 within the McGill University Health Centre, Montreal, Canada. At this centre, no formal triaging of rheumatology referrals exists. Of the 202 charts reviewed, wait times could be calculated in 164 cases. Only consultations for new-onset conditions were analyzed (N = 161). The results showed that patients with inflammatory arthritis were seen approximately 34.6 days (median 26) post-referral. Wait times for individuals who were ultimately diagnosed with non-urgent conditions (osteoarthritis, fibromyalgia and soft-tissue rheumatism) averaged 41.0 days (median 29). In conclusions, compared to non-urgent cases, individuals with inflammatory arthritis were seen about 1 week sooner. Nevertheless, provisional diagnosis provided on referrals did not appear to expedite wait times for persons with suspected inflammatory arthritis. This suggested that other factors, such as the concern of the patient, may have an influence on referral wait times. Implementation of a rapid access program or triage system may be helpful to further decrease wait times for inflammatory arthropathies.
20941956 Cutaneous lupus erythematosus and anti-TNF-alpha therapy: a case report with review of the 2010 Oct Anti-tumor necrosis factor-alpha (TNF-alpha) immunotherapy is revolutionizing the treatment of immune disease, particularly Crohn's disease, rheumatoid arthritis, psoriatic arthritis and psoriasis. The role of anti-TNF-alpha agents in the management of cutaneous lupus erythematosus (LE), however, is not as clear. While experimental reports have suggested a potential benefit of anti-TNF-alpha therapy in severe cutaneous LE, newer reports have identified these medications as instigators or exacerbators of the disease. In this review, the authors present a case of a patient whose persistent discoid LE (DLE) was exacerbated by a trial of adalimumab, one of the currently available TNF-alpha-blocking agents. The authors review 128 cases in the literature in which anti-TNF-alpha therapy was implicated in cutaneous LE pathogenesis, with emphasis on DLE, and consider a number of mechanisms whereby this arguably paradoxical effect may occur. The authors then propose possible approaches to the management of anti-TNF-alpha therapy-induced cutaneous LE.
20363696 Formulation and evaluation of mouth dissolving tablets of the Etoricoxib. 2010 Apr The demand for mouth dissolving tablets has been growing during the last decade especially for elderly and children who have swallowing difficulties. Etoricoxib is a new non-steroidal anti-inflammatory drug (NSAID) with selective cox-2 inhibitory activity, selective inhibition of cox-2 provides anti-inflammatory and analgesic activity it is commonly used for osteo-arthritis, rheumatoid arthritis, primary dysmenorrhoea, post operative dental pain and acute gout. The main criteria for mouth dissolving tablets are to disintegrate or dissolve rapidly in oral cavity with saliva in 15 sec to 60 sec with need of water. The disintegrants used should fulfill the criteria by disintegrating the tablets in specified time limit.in the present investigation variety of super disintegrants like primogel, kollidone, Ac-Di-sol, L-HPMC, L-HPC, were selected and tablets were prepared by direct compression method in different concentration like 4% and 8%. The prepared tablets were evaluated for weight variation, hardness, friability, in vitro disintegration time, wetting time, in vitro dissolution study, etc. formulation f-9 shows the lowest disintegration time (44 sec) and wetting time (52 sec). In vitro dissolution studies revealed that formulation F-9 containing 8% L-HPC showed 97% drug release at the end of 20 min.
20162662 PI3K inhibition in inflammation: Toward tailored therapies for specific diseases. 2010 Mar In the past decade, the availability of genetically modified animals has enabled the discovery of interesting roles for phosphatidylinositol 3-kinase-gamma (PI3Kgamma) and -delta (PI3Kdelta) in different cell types orchestrating innate and adaptive immune responses. Therefore, these PI3K isoforms appear to be attractive drug targets for the treatment of diseases caused by unrestrained immune reactions. Currently, pharmacological targeting of PI3Kgamma and/or PI3Kdelta represents one of the most promising challenges for companies interested in the development of novel safe treatments for inflammatory diseases. In this review we provide a general outline of PI3Kgamma- and PI3Kdelta-specific functions in distinct subsets of inflammatory cells. We also discuss the therapeutic impact of novel compounds targeting PI3Kgamma, PI3Kdelta or both, in mouse models of autoimmune disorders (systemic lupus erythematosus (SLE) and rheumatoid arthritis), respiratory diseases (allergic asthma and chronic obstructive pulmonary disease) and cardiovascular dysfunctions (atherosclerosis and myocardial infarction).
20369317 Role of chemokines in the biology of natural killer cells. 2010 Natural killer (NK) cells represent a major subpopulation of lymphocytes. These cells have effector functions as they recognize and kill transformed cells as well as microbially infected cells. In addition, alloreactive NK cells have been successfully used to treat patients with acute myeloid leukemia and other hematological malignancies. NK cells are also endowed with immunoregulatory functions since they secrete cytokines such as IFN-γ, which favor the development of T helper 1 (Th1) cells, and chemokines such as CCL3/MIP-1α and CCL4/MIP-1β, which recruit various inflammatory cells into sites of inflammation. In human blood, NK cells are divided into CD56(bright) CD16(dim) and CD56(dim) CD16(bright) subsets. These subsets have different phenotypic expression and may have different functions; the former subset is more immunoregulatory and the latter is more cytolytic. The CD56(bright)CD16(dim) NK cells home into tissues such as the peripheral lymph nodes (LNs) under physiological conditions because they express the LN homing receptor CCR7 and they respond to CCL19/MIP-3β and CCL21/SLC chemokines. They also distribute into adenoid tissues or decidual uterus following the CXCR3/CXCL10 or CXCR4/CXCL12 axis. On the other hand, both NK cell subsets migrate into inflammatory sites, with more CD56(dim)CD16(bright) NK cells distributing into inflamed liver and lungs. CCR5/CCL5 axis plays an important role in the accumulation of NK cells in virally infected sites as well as during parasitic infections. CD56(bright)CD16(dim) cells also migrate into autoimmune sites such as inflamed synovial fluids in patients having rheumatoid arthritis facilitated by the CCR5/CCL3/CCL4/CCL5 axis, whereas they distribute into inflamed brains aided by the CX₃CR1/CX₃CL1 axis. On the other hand, CD56(dim)CD16(bright) NK cells accumulate in the liver of patients with primary biliary disease aided by the CXCR1/CXCL8 axis. However, the types of chemokines that contribute to their accumulation in target organs during graft vs. host (GvH) disease are not known. Further, chemokines activate NK cells to become highly cytolytic cells known as CC chemokine-activated killer (CHAK) cells that kill tumor cells. In summary, chemokines whether secreted in an autocrine or paracrine fashion regulate various biological functions of NK cells. Depending on the tissue and the chemokine secreted, NK cells may ameliorate the disease such as their roles in combating tumors or virally infected cells, and their therapeutic potentials in treating leukemias and other hematological malignancies, as well as reducing the incidence of GvH disease. In contrast, they may exacerbate the disease by damaging the affected tissues through direct cytotoxicity or by the release of multiple inflammatory cytokines and chemokines. Examples are their deleterious roles in autoimmune diseases such as rheumatoid arthritis and primary biliary cirrhosis.
19525845 Musculoskeletal impairments in the Norwegian working population: the prognostic role of di 2009 Jun 15 STUDY DESIGN: Population-based, 5-year prospective cohort study. OBJECTIVE: To assess the incidence of musculoskeletal disorders (MSDs) in sickness absence longer than 8 weeks in Norway, and to identify diagnostic and socioeconomic predictors of the transition to disability pension (DP). SUMMARY OF BACKGROUND DATA: MSDs are prevalent and of major concern for sickness absence. Previous epidemiological studies are largely cross-sectional and based on self-reports, often with low response rates, selection, and reporting bias. Prospective studies with physician-verified diagnoses might be a better approach. METHODS: Thirty-seven thousand nine hundred forty-two females and 26,307 males with an episode of sickness absence >8 weeks in 1997, certified with a MSD were followed up for 5 years. Diagnostic and sociodemographic data were obtained from a national database. Cases were divided into 9 diagnostic subgroups, based on the International Classification of Primary Health Care. Survival analysis was performed with granting of DP as the endpoint, in the full sample and for diagnostic subgroups. RESULTS: Over all 20% of cases obtained DP during follow-up. Among those aged 50 to 62 and among those with only basic education 46% obtained DP. DP rates were highest for osteoarthrosis (47%), rheumatoid arthritis (46%), and myalgia/fibromyalgia (38%). Fractures/injuries had the lowest rate. Controlled for age, education and income, relative risk of DP was 1.5 (95% CI: 1.4-1.6) for upper limb problems, 2.0 (95% CI: 1.8-2.1) for back problems, 2.8 (95% CI: 2.5-3.1) for osteoarthrosis, 3.3 (95% CI: 3.0-3.6) for myalgia/fibromyalgia, and 4.2 (95% CI: 3.9-4.7) for rheumatoid arthritis, compared to "fractures and injuries." CONCLUSION: Age, diagnoses, and socioeconomic variables were important predictors of an adverse outcome among workers with a sickness absence of 8 or more weeks. Further research is needed to determine whether differentiated follow-up strategies might prevent permanent disability.
20238219 Transient osteoporosis of the hip: successful treatment with teriparatide. 2012 May A 62-year-old man presented with a 2-month history of increasing pain in the left hip. Magnetic resonance imaging (MRI) showed bone marrow edema (BME) of the left femur, dual energy X-ray absorptiometry (DXA) showed osteopenia at the same level, whereas pelvis X-rays failed to show any objective findings. After ruling out other possible causes of BME such as aseptic osteonecrosis, infectious arthritis, primary or metastatic malignancy, tuberculosis, osteomyelitis, rheumatoid arthritis, and seronegative spondyloarthropathies, a diagnosis of transient osteoporosis of the hip (TOH) was made, and treatment with teriparatide at a daily dose of 20 μg was started and continued for 4 weeks. Disappearance of the symptoms and normalization of MRI were obtained.