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ID PMID Title PublicationDate abstract
15903393 A cetylated fatty acid topical cream with menthol reduces pain and improves functional per 2005 May This investigation was an extension of a previous study conducted in our laboratory in which we showed that 1 month of treatment with a topical cream (Celadrin) consisting of cetylated fatty acids was effective for reducing pain and improving functional performance in individuals with osteoarthritis (OA) of the knee (Kraemer et al., Journal of Rheumatology, 2004). We wanted to verify that the addition of menthol to the compound would produce a similar percentage of improvement in therapeutic effects. We used a single treatment group with a pre-post experimental design to examine % treatment changes. Individuals diagnosed with OA of the knee (N = 10; age, 66.4 +/- 11.5 years) and severe pain (e.g., OA, rheumatoid arthritis) of the elbow (N = 8; age, 59.1 +/- 18.2 years) and wrist (N = 10; age, 60.3 +/- 16.8 years) were tested for pain and functional performance before and after 1 week of treatment with a topical cream consisting of cetylated fatty acids and menthol applied twice per day. In individuals with knee OA, significant improvements in stair-climbing ability (about 12%), "up-and-go" performance (about 12%), balance and strength (about 16.5%), and range of motion (about 3.5%) were observed, as were reductions in pain. In individuals with severe pain of the elbow and wrist, significant improvements in dynamic (about 22 and 24.5%, respectively) and isometric (about 33 and 42%, respectively) local muscular endurance were observed, as was a reduction in pain. Neither group demonstrated significant changes in maximal grip strength or maximal force production. One week of treatment with a topical cream consisting of cetylated fatty acids and menthol was similarly effective for reducing pain and improving functional performance in individuals with arthritis of the knee, elbow, and wrist. The % changes were consistent with our prior work on the compound without menthol. Further work is needed to determine the impact of menthol in such a cream. Nevertheless, our data support the use of a topical cream consisting of cetylated fatty acids (with or without menthol) for enhancing the potential for exercise training in this population.
16255020 Effects of antirheumatic treatments on the prostaglandin E2 biosynthetic pathway. 2005 Nov OBJECTIVE: Microsomal prostaglandin E synthase 1 (mPGES-1) is up-regulated in experimental arthritis and markedly expressed in synovial tissue biopsy samples from patients with rheumatoid arthritis (RA). This study was carried out to determine the effects of tumor necrosis factor (TNF) blockers and glucocorticoids on mPGES-1 and cyclooxygenase (COX) expression, as well as biosynthesis of PGE(2) in rheumatoid joints. METHODS: In vitro effects of TNF blockers and dexamethasone on the PGE(2) biosynthetic pathway were examined in RA synovial fluid mononuclear cells (SFMCs) by flow cytometry. PGE(2) levels in culture supernatants were measured by enzyme immunoassay. Expression of enzymes responsible for PGE(2) synthesis ex vivo was evaluated by immunohistochemistry in synovial biopsy samples obtained from 18 patients before and after treatment with TNF blockers and from 16 patients before and after intraarticular treatment with glucocorticoids. Double immunofluorescence was performed using antibodies against mPGES-1, COX-1, COX-2, and CD163. RESULTS: Double immunofluorescence revealed that mPGES-1 and COX-2 were colocalized in SFMCs as well as in RA synovial tissue cells. The addition of either TNF blockers or dexamethasone suppressed lipopolysaccharide-induced mPGES-1 and COX-2 expression in synovial fluid monocyte/macrophages in vitro and decreased the production of PGE(2). Intraarticular treatment with glucocorticoids significantly reduced both mPGES-1 and COX-2 expression in arthritic synovial tissue ex vivo. The number of COX-1-expressing cells in synovial tissue was also significantly decreased by glucocorticoid treatment. In contrast, neither mPGES-1 nor COX-2 expression in synovial tissue was significantly suppressed by anti-TNF therapy. CONCLUSION: These data are the first to demonstrate the effects of antirheumatic treatments on mPGES-1 expression in RA and suggest that the inhibition of PGE(2) biosynthesis, preferably by targeting mPGES-1, might complement anti-TNF treatment for optimal antiinflammatory results in RA.
16482643 Preliminary validation of clinical remission criteria using the OMERACT filter for select 2006 Apr OBJECTIVE: To begin the validation process of the preliminary criteria for inactive disease (ID), clinical remission on medication (CRM), and clinical remission off medication (CR) in children with select forms of juvenile idiopathic arthritis (JIA). METHODS: We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter's 3 components: truth, discrimination, and feasibility, in 5 categories of JIA: systemic arthritis, persistent and extended oligoarthritis, and rheumatoid factor-positive and negative polyarthritis. Data sources for determining validity estimates included a Delphi questionnaire survey sent to 246 pediatric rheumatologists in 34 countries, a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries, a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years, and the literature. RESULTS: Truth component: face and content validity. These aspects of validity were largely established via the Delphi questionnaire exercise and the consensus conference. Using an 80% consensus level, participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID, CRM, and CR. Criterion validity could not be irrefutably established because no gold standard for inactive disease exists for JIA. As an alternative, published investigations of remission in JIA were used to estimate concurrent and convergent validity, as surrogates for criterion validity and as indicators of overall construct validity. Correlational analyses revealed the new criteria to have good construct validity. Discrimination component: the criteria demonstrated moderate to high levels of classification, prognosis, and responsiveness (sensitivity to change) using data from the chart review. Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM. Responsiveness was evidenced by the ability of the criteria to allow movement of most patients between the disease states, consistent with what is known of the course of the disease. Feasibility component: Results of the Delphi and consensus conference produced a set of criteria that are easily, quickly, and inexpensively completed in the physician's office, and present minimal or no risk to the patient. CONCLUSION: The preliminary criteria demonstrated moderate to excellent validity characteristics in some, but not all components of the OMERACT filter. Prospective validation studies are under way.
16255044 Patterns of clinical remission in select categories of juvenile idiopathic arthritis. 2005 Nov OBJECTIVE: To characterize disease activity patterns in a large cohort of children with juvenile idiopathic arthritis (JIA), by applying newly developed preliminary definitions of inactive disease, clinical remission on medication, and clinical remission off medication. METHODS: Children with persistent or extended oligoarthritis, polyarthritis (either rheumatoid factor [RF] positive or RF negative), or systemic JIA who had been followed up for a period of at least 4 years were evaluated for episodes of inactive disease, clinical remission on medication, and clinical remission off medication. Descriptive statistics, correlation analyses, and survival analyses were performed. RESULTS: Four hundred thirty-seven children met the criteria for review. Three hundred ninety-one patients (89%) experienced a total of 878 episodes of inactive disease, with a median episode length of 12.7 months. Two hundred twenty-eight episodes of inactive disease (26%) resulted in clinical remission off medication; it was equally as likely that episodes of inactive disease would or would not follow a period of clinical remission on medication. Thirty-six percent of episodes of clinical remission off medication persisted for at least 2 years, and only 6% of such episodes persisted for 5 years. RF-positive patients were the least likely to achieve clinical remission off medication (5%), and patients with persistent oligoarticular JIA were the most likely (68%). Among patients with persistent oligoarticular JIA, most of the disease course was characterized by inactive disease; in most other patients the majority of the disease course involved active disease. CONCLUSION: Using newly developed preliminary criteria for inactive disease, clinical remission on medication, and clinical remission off medication, we observed that only one-fourth of 878 episodes of inactive disease resulted in clinical remission off medication during followup of at least 4 years. Only a small proportion of episodes of clinical remission off medication were sustained for >5 years. These results highlight the critical need for therapies that have the ability to induce sustained remission of JIA.
17589405 Postoperative evaluation of plasma interleukin-6 concentration in patients after total hip 2006 Oct 31 Background. The aim of this study was to examine the circulating IL-6 in patients after orthopedic surgery, and the correlation between IL-6, body temperature and the level of postoperative pain. Material and methods. We studied 27 patients undergoing orthopedic hip arthroplasty, including 14 with osteoarthritis and 13 with rheumatoid arthritis. The local medical ethics committee approved the study, and all patients signed informed consent upon being enrolled. All patients received spinal anesthesia. Samples were collected just before and at 24, 48, and 72 hours after surgery; at the same time, body temperature and reported pain were monitored. Results. Plasma IL-6 levels showed a decrease after surgery. This suggests some influence of plasma cytokines on the possible beneficial effects of regional anesthesia on the clinical course after surgery. The level of IL-6 was associated with body temperature and pain in patients after operation. Conclusions. The plasma concentration of IL-6 is a significant factor affecting body temperature and pain after surgery in patients who have undergone hip arthroplasty.
17110139 Glutamate receptors and pain. 2006 Oct Pain is an important survival and protection mechanism for animals. However, chronic/persistent pain may be differentiated from normal physiological pain in that it confers no obvious advantage. An accumulating body of pharmacological, electrophysiological, and behavioral evidence is emerging in support of the notion that glutamate receptors play a crucial role in pain pathways and that modulation of glutamate receptors may have potential for therapeutic utility in several categories of persistent pain, including neuropathic pain resulting from injury and/or disease of central (e.g., spinal cord injury) or peripheral nerves (e.g., diabetic neuropathy, radiculopathy) and inflammatory or joint-related pain (e.g., rheumatoid arthritis, osteoarthritis). This review focuses on the role of glutamate receptors, including both ionotropic (AMPA, NMDA and kainate) and metabotropic (mGlu1-8) receptors in persistent pain states with particular emphasis on their expression patterns in nociceptive pathways and their potential as targets for pharmacological intervention strategies.
16918413 Leukocyte adhesion: a suitable target for anti-inflammatory drugs. 2006 Inflammatory responses in all tissue compartments require the emigration of leukocytes from the microvasculature through endothelial cells into the respective microenvironment. Adhesion to endothelial cells is the most crucial step in order to facilitate selective and effective capture of leukocytes. The sequence of adhesions events, e.g. rolling, tethering, and firm adhesion are tightly regulated by a variety of molecules expressed by endothelial cells and leukocytes either constitutively or after induction by mainly inflammatory mediators. In diseases with a prominent inflammatory response such as psoriasis, rheumatoid arthritis, or Crohn's disease, interference with leukocyte adhesion and/or emigration may be of substantial clinical effect. A number of therapeutic approaches by using monoclonal antibodies, designed molecules, and other modulators of adhesion molecule expression have been investigated in clinical trials. This review aims to give an overview about the current knowledge of targeting adhesion molecules as a therapeutic strategy to treat inflammatory diseases.
16710576 Autoimmune diseases and vitamin D receptor Apa-I polymorphism are associated with vitiligo 2006 Vitiligo has been associated with the host's genetic profile, metabolic abnormality and immunostatus. The purpose of this study was to investigate the association of vitiligo with autoimmune diseases for 31 out of 39 subjects with vitiligo and their first-degree relatives living in a small Caucasian inbred rural community. They were compared with healthy individuals. A 2.28% prevalence of vitiligo was calculated and the presence of consanguine marriages (72.3%) was noted for this community. Our results indicate an increased prevalence of thyroidopathies, diabetes mellitus and rheumatoid arthritis in families with vitiligo. We also show that the Apa-I polymorphism of the vitamin D receptor gene is associated with vitiligo. This is the first study of its kind performed in Romania suggesting that the vitamin D receptor gene might play a role in the aetiopathogenesis of skin depigmentation.
16294789 [Secondary bladder amylodosis with severe recurrent hematuria: transurethral Mikuliz proce 2005 Sep OBJECTIVES: Primary localized amyloidosis of the urinary bladder generally has a benign course. On the contrary, secondary amyloidosis, a consequence of systemic amyloidosis, may have massive bleeding and produce complications such as bladder rupture or lifethreatening hemodynamic problems requiring desperate hemostatic procedures such as hypogastric artery embolization or ligature, or cystectomy. We report one case in which hemostasis was achieved by a Mickulicz transurethral bladder tamponage. METHODS: 58 year old female with very aggressive rheumatoid arthritis and secondary renal amyloidosis under chronic hemodialysis presenting with severe hematuria after hip replacement. An inflamed bladder was found, the biopsy of which showed edema in all layers with blood vessel walls enlarged by amiloyd deposits. After several unsuccessful transurethral hemostatic procedures, intravesical formalin irrigation was carried out together with a Mikulicz type gauze packaging after urethral dilation. The gauze was withdrawn three days later without bleeding recurrence; however she presented subsequent neurological impairment and finally died 14 days after the last urological procedure. CONCLUSIONS: Transurethral packaging of the urinary bladder in a woman with massive hematuria is a hemostatic option that we recommend to be used before other more dramatic or invasive options are chosen.
16259218 JNK: bridging the insulin signaling and inflammatory pathway. 2005 Oct Obesity and insulin resistance are strongly associated with systemic markers of inflammation and endoplasmic reticulum stress. c-Jun N-terminal kinases (JNK) are activated by inflammatory cytokines and have a key role in beta-cell apoptosis and in negative regulation of insulin signaling. JNK1-deficient mice are protected from diet-induced obesity and insulin resistance, while genetically obese mice with targeted mutations in JNK1 are leaner and have reduced insulin and blood glucose levels. These studies validate JNK as a link between inflammation and metabolic diseases and as a promising drug target. This review highlights recent advances in small-molecule inhibitors of JNK that have also been targeted for other diseases with an inflammatory component such as stroke, rheumatoid arthritis, and Alzheimer's and Parkinson's diseases.
16209908 A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol a 2006 This study examines the current knowledge of physiological and clinical effects of tetrahydrocannabinol (THC) and cannabidiol (CBD) and presents a rationale for their combination in pharmaceutical preparations. Cannabinoid and vanilloid receptor effects as well as non-receptor mechanisms are explored, such as the capability of THC and CBD to act as anti-inflammatory substances independent of cyclo-oxygenase (COX) inhibition. CBD is demonstrated to antagonise some undesirable effects of THC including intoxication, sedation and tachycardia, while contributing analgesic, anti-emetic, and anti-carcinogenic properties in its own right. In modern clinical trials, this has permitted the administration of higher doses of THC, providing evidence for clinical efficacy and safety for cannabis based extracts in treatment of spasticity, central pain and lower urinary tract symptoms in multiple sclerosis, as well as sleep disturbances, peripheral neuropathic pain, brachial plexus avulsion symptoms, rheumatoid arthritis and intractable cancer pain. Prospects for future application of whole cannabis extracts in neuroprotection, drug dependency, and neoplastic disorders are further examined. The hypothesis that the combination of THC and CBD increases clinical efficacy while reducing adverse events is supported.
16033689 The restless legs syndrome. 2005 Aug The restless legs syndrome is a common disorder that encompasses an idiopathic form of genetic or unknown origin and symptomatic forms associated with many causes. Symptomatic forms occur during pregnancy and are coincident with uraemia, iron depletion, polyneuropathy, spinal disorders, and rheumatoid arthritis. For the hereditary forms, at least three gene loci, located on chromosomes 12, 14, and 9, have been traced so far. Prevalence in the general population is between 3% and 9%, increases with age, and is higher in women than in men. Treatment is needed only in the moderate to severe forms of the disorder and mostly in elderly people. Pathophysiology and treatment may be closely linked to the dopaminergic system and iron metabolism. Dopaminergic treatment with levodopa and dopamine agonists is the first choice in idiopathic restless legs syndrome, but augmentation and rebound should be monitored in long-term treatment. Various other drugs, such as opioids, gabapentin, and benzodiazepines, provide alternative treatment possibilities.
16023115 Methylation of the guanidino group of arginine residues prevents citrullination by peptidy 2005 Aug 1 Peptidylarginine deiminase IV (PAD IV) catalyzes the citrullination of Arg residues of proteins, such as histones. Suzuki et al. recently reported that haplotypes of the PAD IV gene are associated with susceptibility to rheumatoid arthritis. To investigate the mechanism of substrate specificity and inhibitors of PAD IV, a series of the Arg derivatives were synthesized and their reactivity to PAD IV examined. The results suggest that both imino and carboxyl groups are important in the molecular recognition of PAD IV and that methylation of the guanidino group prevents citrullination. In addition, the findings herein show that Bz-N(G)-monomethyl-Arg and Bz-N(G),N(G)-dimethyl-Arg specifically inhibit citrullination.
15992355 Progress in the development of aminopeptidase N (APN/CD13) inhibitors. 2005 May Aminopeptidase N (APN; CD13) is a member of zinc-containing ectoenzymes family involved in the degradation of neutral or basic amino acids (Ala>Phe>Leu>Gly) from N-terminal of bioactive peptides and amide or arylamide derivatives of amino acids. The expression of APN being up regulated has been implicated in the pathogenesis of a variety of diseases such as cancer, leukemia, diabetic nephropathy, and rheumatoid arthritis. Thus, APN inhibitors (APNIs) are expected to be useful for the treatment of these disorders. This article reviews briefly the structure characteristic and possible function of APN. The proposed biomolecular structures and mechanism of action used in the design of APNIs are thoroughly covered. Major emphasis is on recently published potent, small molecular weight APNIs and their essential structure activity relationship (SAR). Finally, available clinical results of compounds in development are summarized in this review.
15759082 Clinical holistic medicine: chronic pain in the locomotor system. 2005 Feb 24 Most pains from the locomotor system arise due to involuntary, chronic tensions in the muscles or other tissues. When the patient is motivated, the pain is easily cured in most of the cases by using the tools of consciousness-based medicine, primarily therapeutic touch, conversation, and coaching the patient in a positive philosophy of life. The pains are often caused by "blockages" that may cause problems other than just pain. Often it turns out that the blocked areas develop actual physical damage over time: a slipped disk in the back, articular degeneration, or osteoarthritis when the cartilage is affected, can often be explained in this way. Apparently, the exact areas where the blockage is situated cause cellular problems, disrupting cellular order. The holistic process theory of healing and the related quality of life theories state that return to the natural state of being is possible, whenever the person gets the resources needed for existential healing. The resources needed are "holding" in the dimensions of awareness, respect, care, acknowledgment, and acceptance with support and processing in the dimensions of feeling, understanding, and letting go of negative attitudes and beliefs. The preconditions for holistic healing are trust and the intention for the healing to take place. Case stories of holistic treatment of patients with chronic back pain, low back pain, muscle problems, knee pain, and symptoms of rheumatoid arthritis are discussed with exercises relevant for patients with these conditions in the holistic clinic.
15937555 Complementary and Alternative Medicine Approaches for Pediatric Pain: A Review of the Stat 2005 Jun In recent years, the use of complementary and alternative medicine (CAM) in pediatric populations has increased considerably, especially for chronic conditions such as cancer, rheumatoid arthritis and cystic fibrosis in which pain may be a significant problem. Despite the growing popularity of CAM approaches for pediatric pain, questions regarding the efficacy of these interventions remain. This review critically evaluates the existing empirical evidence for the efficacy of CAM interventions for pain symptoms in children. CAM modalities that possess a published literature, including controlled trials and/or multiple baseline studies, that focused on either chronic or acute, procedural pain were included in this review. The efficacy of the CAM interventions was evaluated according to the framework developed by the American Psychological Association (APA) Division 12 Task Force on Promotion and Dissemination of Psychological Procedures. According to these criteria, only one CAM approach reviewed herein (self-hypnosis/guided imagery/relaxation for recurrent pediatric headache) qualified as an empirically supported therapy (EST), although many may be considered possibly efficacious or promising treatments for pediatric pain. Several methodological limitations of the existing literature on CAM interventions for pain problems in children are highlighted and future avenues for research are outlined.
15916451 Infliximab: in ankylosing spondylitis. 2005 Infliximab is a monoclonal antibody that binds to tumour necrosis factor-alpha and blocks its biological activity. It is approved for use in patients with rheumatoid arthritis, Crohn's disease and ankylosing spondylitis.black triangle In well designed, placebo-controlled trials of 12 or 24 weeks' duration in patients with active ankylosing spondylitis, more infliximab 5 mg/kg recipients achieved a response than placebo recipients according to Ankylosing Spondylitis Assessment Study 20% (61.2% vs 19.2%) or Bath Ankylosing Spondylitis Disease Activity Index 50% (53% vs 9%) criteria (primary endpoints). black triangle Infliximab was also superior to placebo in terms of various secondary clinical endpoints and in reducing spinal inflammation (as assessed by magnetic resonance imaging).black triangle Prolonged efficacy has been demonstrated in patients with ankylosing spondylitis who received infliximab for up to 3 years.black triangle Infliximab is generally well tolerated in patients with ankylosing spondylitis, with most adverse events being of mild-to-moderate severity.
15826920 Non-thyroid autoantibodies in autoimmune thyroid disease. 2005 Mar Autoimmune thyroid disease is frequently accompanied by other organ-specific and non-organ-specific diseases, most likely because there is sharing of genetic and possibly environmental susceptibility factors. These associations are well recognized in the autoimmune polyglandular syndromes; autoimmune thyroid disease is one of the three major endocrinopathies in the type 2 syndrome and occurs in around 4% of type 1 patients. This review considers the frequency of disease-specific autoantibodies in patients with thyroid autoimmunity and briefly examines the role of such antibodies in performing screening for the associated conditions. Recommendations are made for using such autoantibody tests in the setting of patients with autoimmune thyroid disorders, and also for the utility of screening for thyroid autoimmunity in patients with pernicious anaemia, Addison's disease, coeliac disease, primary biliary cirrhosis, myasthenia gravis, lymphocytic hypophysitis, systemic lupus erythematosus and rheumatoid arthritis. At present, however, there are no large-scale trials that have shown the cost-benefit ratio of autoantibody screening for autoimmunity screening, and clinicians must use individual judgement combined with heightened awareness to identify who to test.
15894123 Antioxidant approach to disease management and the role of 'Rasayana' herbs of Ayurveda. 2005 Jun 3 The disease preventive and health promotive approach of 'Ayurveda', which takes into consideration the whole body, mind and spirit while dealing with the maintenance of health, promotion of health and treating ailments is holistic and finds increasing acceptability in many regions of the world. Ancient Ayurvedic physicians had developed certain dietary and therapeutic measures to arrest/delay ageing and rejuvenating whole functional dynamics of the body system. This revitalization and rejuvenation is known as the 'Rasayan chikitsa' (rejuvenation therapy). Traditionally, Rasayana drugs are used against a plethora of seemingly diverse disorders with no pathophysiological connections according to modern medicine. Though, this group of plants generally possesses strong antioxidant activity, only a few have been investigated in detail. Over about 100 disorders like rheumatoid arthritis, hemorrhagic shock, CVS disorders, cystic fibrosis, metabolic disorders, neurodegenerative diseases, gastrointestinal ulcerogenesis and AIDS have been reported as reactive oxygen species mediated. In this review, the role of free radicals in these diseases has been briefly reviewed. 'Rasayana' plants with potent antioxidant activity have been reviewed for their traditional uses, and mechanism of antioxidant action. Fifteen such plants have been dealt with in detail and some more plants with less work have also been reviewed briefly.
15886935 MRSA-infected external iliac artery pseudoaneurysm treated with endovascular stenting. 2005 May A 48-year-old woman with severe juvenile-onset rheumatoid arthritis presented with a bleeding cutaneous sinus distal to her right total hip replacement scar. Methicillin resistant Staphylococcus aureus (MRSA) was isolated on culture. She had previously undergone bilateral total hip and knee replacements at aged 23 and six years later had the right knee prosthesis removed for infection, with subsequent osteomyelitis of the femoral shaft and right total hip prosthesis disruption. Peripheral arteriography was performed in view of persistent bleeding from the sinus, which revealed a 6 cm false aneurysm filling from and compressing the right external iliac artery (EIA). A PTFE-covered, balloon expandable JOSTENT was deployed in the right EIA, successfully excluding the false aneurysm and preventing further bleeding from the sinus. No graft infection was reported at 12 months. This case illustrates the potential use of endovascular stent-grafting in the treatment of an infected pseudoaneurysm.