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ID PMID Title PublicationDate abstract
18570757 Infections and treatment of patients with rheumatic diseases. 2008 Jan Glucocorticoids (GCs) have many complex quantitative and qualitative immunosuppressive effects which induce cellular immunodeficiency and increase host susceptibility to various viral, bacterial, fungal and parasitic infections. As cortisol secretion is inadequate in chronic immune/inflammatory conditions, and current therapies have the aim of providing adequate (low) compensatory doses, the timing of GC administration, such as during the nocturnal turning-on phase of tumour necrosis factor (TNF) secretion, can be extremely important. The use of the lowest possible GC dose, at night, and for the shortest possible time should therefore greatly reduce the risk of infections. Infection is a major co-morbidity in rheumatoid arthritis (RA), and conventional disease-modifying anti-rheumatic drugs (DMARDs) can increase the risk of their occurrence, including tuberculosis. TNF-alpha plays a key role in the pathogenesis of RA, and the data concerning infections in RA patients treated with anti-TNF agents are controversial. Patients and physicians should vigilantly monitor for signs of infection when using anti-TNF agents. Recombinant gene technologies now make it possible to produce protein drugs that are almost identical to naturally occurring human polypeptides, including antibody (Ab) constructs; unfortunately, all human biological agents are potentially immunogenic. An increasing number of recent studies have demonstrated the safety of influenza and pneumococcal vaccines administered to patients with systemic lupus erythematosus (SLE) or RA. These vaccinations are generally immunogenic (i.e., capable of inducing a protective level of specific antibodies) but may not induce an adequate response in a substantial proportion of patients.
18490409 Atherosclerosis and systemic lupus erythematosus: the role of altered lipids and of autoan 2008 May The accelerated atherosclerosis that occurs in some patients with systemic lupus erythematosus (SLE) has a complex pathogenesis, including alterations in lipids, inflammation and the immune system. In this article, we review the evidence that peroxidase-related alteration of normal, protective high-density lipoprotein (HDL) converts them to pro-inflammatory HDL (piHDL), characterized by lower content of the cholesterol transport lipoprotein ApoA1 and impaired function of the antioxidant enzyme paroxonase, which prevents oxidation of low-density lipoprotein (LDL). Forty-five per cent of women with SLE have piHDL compared with 20% of patients with rheumatoid arthritis and 4% of healthy controls. The presence of piHDL increases risk for coronary artery events and carotid artery plaque. Another result of lipid oxidation in patients with SLE is generation of highly oxidized LDL and phospholipids (PL), probably stimulating antibodies to OxPL phospholipids. These antibodies along with promoting thrombosis also interfere with deposits of Annexin V onto endothelial cells, which probably promote increased instability of atherosclerotic plaque. Thus, piHDL and anti-OxPL promote plaque formation, plaque instability and thrombosis, accounting for some of the large increase in atherosclerosis and coronary artery events in SLE.
18374278 Prevalence in two-phase surveys: accuracy of screening procedure and corrected estimates. 2008 Apr BACKGROUND: Two-phase surveys often are used to estimate prevalence, in particular when the disease is rare or the case ascertainment procedure difficult and/or costly. However, few authors of such surveys take into account the sensitivity error associated with the use of a screening procedure in the first phase and its imprecision in correcting the prevalence estimate and confidence interval. METHODS: Two examples of two-phase surveys of rheumatic diseases (hip and knee osteoarthritis, rheumatoid arthritis and spondyloarthropathies) are used to present methodological approaches to obtain corrected prevalence estimates. Two methods for assessing the accuracy of the screening procedure are described--two-phase pilot and case-control designs--that are best suited for frequent and rare diseases, respectively, and naive and corrected estimates of prevalence compared. RESULTS: When the sensitivity error is not taken into account, prevalence is underestimated, as is, especially, the width of its confidence interval. In our examples, the corrected confidence interval width increased up to 50% as compared with naïve one. CONCLUSIONS: The screening procedure accuracy should be thoroughly assessed in two-phase prevalence surveys and prevalence estimates and their confidence intervals corrected accordingly.
18347116 Wound complications from surgeries pertaining to the Achilles tendon: an analysis of 219 s 2008 Mar BACKGROUND: A retrospective review of one surgeon's practice was conducted to assess the prevalence of wound complications associated with acute and chronic rupture repair, peritenolysis, tenodesis, debridement, retrocalcaneal exostectomy/bursectomy, and management of calcific tendinopathy of the Achilles tendon. METHODS: We evaluated the incidence of infection and other wound complications, such as suture reactions, scar revision, hematoma, incisional neuromas, and granuloma formation. RESULTS: A total of 219 surgical cases were available for review (140 males and 70 females; mean +/- SD age at the time of surgery, 46.5 +/- 12.6 years; age range, 16-75 years). Seven patients experienced a wound infection, three had keloid formation, six had suture granulomas, and six had suture abscesses, for a total complication rate of 10.0%. Six patients had more than one complication; therefore, the percentage of patients with complications was 7.3%. There were no hematomas. Seven patients had additional surgery after their wound complications; some had simple granuloma excision, and one necessitated a flap. Patients with risk factors such as diabetes mellitus, smoking, and rheumatoid arthritis necessitating corticosteroid therapy were more likely to have a wound complication (Fisher exact test, P = .03). CONCLUSIONS: Complications with Achilles tendon surgery may be unavoidable. Suture granulomas may appear in a delayed manner. Absorbable and nonabsorbable sutures can be implicated.
18256087 A new technique for reconstruction of the proximal humerus after three- and four-part frac 2008 Feb The results of proximal humeral replacement following trauma are substantially worse than for osteoarthritis or rheumatoid arthritis. The stable reattachment of the lesser and greater tuberosity fragments to the rotator cuff and the restoration of shoulder biomechanics are difficult. In 1992 we developed a prosthesis designed to improve fixation of the tuberosity fragments in comminuted fractures of the proximal humerus. The implant enables fixation of the fragments to the shaft of the prosthesis and the diaphyseal fragment using screws, washers and a special toothed plate. Between 1992 and 2003 we used this technique in 50 of 76 patients referred to our institution for shoulder reconstruction after trauma. In the remaining 26, reconstruction with a prosthesis and nonabsorbable sutures was performed, as the tuberosity fragments were too small and too severely damaged to allow the use of screws and the toothed plate. The Constant score two years post-operatively was a mean of 12 points better in the acute trauma group and 11 points better in the late post-traumatic group than in the classical suture group. We recommend this technique in patients where the tuberosity fragments are large enough to allow fixation with screws, washers and a toothed plate.
18250135 A/C polymorphism in the interleukin-18 coding region among Taiwanese systemic lupus erythe 2008 Feb Interleukin-18 (IL-18) is associated with chronic inflammation, autoimmune diseases and various cancers and infectious diseases. An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma and rheumatoid arthritis. We tested a hypothesis that the IL-18 genetic polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Taiwanese SLE patients and a healthy control group. Our results indicate (1) a significantly higher A allele frequency in SLE patients (P = 0.003; OR = 1.97; 95% CI = 1.26-3.08) and (2) a significantly higher A allele frequency in SLE patients with a central nervous system disorder (P = 0.027; OR = 7.18; 95% CI = 0.95-54.28). Our results suggest that the A/C polymorphism contributes to SLE pathogenesis.
18220954 Gastrin-releasing peptide receptor as a molecular target for inflammatory diseases. 2007 Dec Bombesin-like peptides (BLP) and its receptors are widely distributed in mammalian peripheral tissues and in the central nervous system. Recently, effects of these peptides on the production and release of cytokines were described both in animal models and humans with inflammatory diseases. Some pathological conditions such as exposure to tobacco smoke, chronic obstructive pulmonary diseases and eosinophilic granuloma have recently been found to be associated with an increase of pulmonary BLP-producing cells. Proinflammatory neuropeptides have a key role in the pathogenesis and maintenance of rheumatoid arthritis and sepsis. Together, these findings support the view that the GRPR should be considered a therapeutic target for a subset of inflammatory diseases.
18212811 Drug insight: selective agonists and antagonists of the glucocorticoid receptor. 2008 Feb Glucocorticoid hormones exert a wide spectrum of metabolic and immunological effects. They function through the glucocorticoid receptor, a member of the nuclear receptor superfamily. Glucocorticoids are particularly effective as anti-inflammatory agents but often cause severe side effects. The structure of the ligand-binding domain of the glucocorticoid receptor has now been elucidated, and a series of studies have shown that even subtle changes to the ligand structure alter the final conformation of the ligand-receptor complex, with consequences for both protein recruitment and the function of the receptor. This has led to concerted efforts to find selective ligands for the glucocorticoid receptor that preserve the beneficial anti-inflammatory activity but reduce the side-effect profile. The direct health-care benefits of such a simple, safe, orally active agent targeting the underlying inflammatory process in, for example, rheumatoid arthritis would be considerable in terms of reduced patient suffering; furthermore, the indirect benefits in terms of reducing the costs of therapeutic delivery and preventing loss of productivity would be even greater.
17934105 Regulatory T cells and toll-like receptors: regulating the regulators. 2007 Nov Regulatory T cells (Treg) play a crucial role in maintaining control of leucocytes. Several studies have shown that in vivo Treg depletion results in autoimmune syndromes like thyroiditis, gastritis, diabetes mellitus and colitis, but at the same time, may also result in improved anti-tumour vaccination. Although Treg are recognised to maintain peripheral tolerance in healthy individuals, recent research has shown that Treg also suppress immune responses during infections to prevent tissue damage. How the Treg themselves are regulated is still under investigation. Their suppressive activity must be regulated in order to allow for the effective elimination of pathogens. Until recently, this control of Treg function was found to be through modulation via cytokines or by stimulation via co-stimulatory molecules on antigen-presenting cells. It is now demonstrated, however, that the presence of pathogens can be communicated to Treg directly through toll-like receptors (TLRs). Up until now, Treg have been reported to respond to ligands for TLR2, 4, 5 and 8, and different TLRs can have alternative effects on Treg resulting in more suppression or, in contrast, abrogation of suppression. As TLRs can also recognise endogenous proteins, such as heat shock proteins, it is tempting to speculate on the role of these proteins in modulating Treg function during chronic inflammation. In this review, we will discuss the implications of TLR engagement on Treg and any consequences this may have for chronic autoinflammatory diseases like rheumatoid arthritis (RA).
17968485 Involvement of alpha(v)beta3 integrins in osteoclast function. 2007 Integrins are heterodimeric adhesion receptors that mediate cell-matrix interaction. Osteoclast exhibits high expression of the alpha(v)beta(3) integrin, which binds to a variety of extracellular matrix proteins including vitronectin, osteopontin, and bone sialoprotein. Arg-Gly-Asp (RGD)-containing peptides, RGD-mimetics, and blocking antibodies to alpha(v)beta(3) integrin were shown to inhibit bone resorption in vitro and in vivo, suggesting that this integrin may play an important role in regulating osteoclast function. Several lines of evidence have demonstrated that a number of signaling molecules are involved in the alpha(v)beta(3) integrin-dependent signaling pathway, including c-Src, Pyk2, c-Cbl, and p130(Cas). In this article, we review the history of "alpha(v)beta(3) integrin and osteoclasts" and discuss the involvement of alpha(v)beta(3) integrins in osteoclast function at tissue, cellular, and molecular levels. A better understanding of the role of alpha(v)beta(3) integrin in osteoclastic bone resorption would provide opportunities for developing new therapeutics to treat human bone diseases, including rheumatoid arthritis, osteoporosis, and periodontal disease.
17935516 T-cell receptor repertoire in pyoderma gangrenosum: evidence for clonal expansions and tra 2007 Nov BACKGROUND: The cause of pyoderma gangrenosum (PG) is unknown, but it is likely to be an immune-mediated disease because it is often associated with conditions such as inflammatory bowel disease and rheumatoid arthritis. T cells play an important role in these conditions and have been implicated in the pathogenesis of other skin diseases such as psoriasis. OBJECTIVES: We examined the T-cell receptor repertoire in PG in order to test the hypothesis that if the T cells were responding to antigen, there would be expanded T-cell clones in the skin and the circulation of these patients. PATIENTS AND METHODS: We studied five patients with PG and examined the T-cell receptor repertoire in cells taken from the peripheral blood and from biopsies of the ulcers, using complementarity determining region 3 spectratyping. RESULTS: We were able to demonstrate expanded clones in the peripheral blood lymphocyte population of each patient. Clonal expansions within the skin were found in four of the five patients. Most significantly, expanded clones that were shared between the blood and the skin were revealed in four of the five patients. CONCLUSIONS: These findings imply that T cells play an integral role in the development of PG and suggest that T cells are trafficking to the skin under the influence of an antigenic stimulus.
17906466 Potential of mesenchymal stem cell therapy. 2007 Nov PURPOSE OF REVIEW: Mesenchymal stem cells have the capacity to differentiate into several mesenchymal tissues, including the components of the hematopoietic stem cell niche. Mesenchymal stem cells also exhibit a powerful immunosuppressive activity. Here we review the most recent data to identify the properties of therapeutic significance. RECENT FINDINGS: Mesenchymal stem cells are attractive not only in regenerative medicine but also for the treatment of autoimmune diseases and graft-versus-host disease. Initial experience in animal models and the clinical setting have produced very encouraging results whereby mesenchymal stem cells have been shown to accelerate recovery after myocardial infarction, improve growth velocity in children with osteogenesis imperfecta, and ameliorate severe graft-versus-host disease as well as, in mouse models, rheumatoid arthritis and multiple sclerosis. Their use in the clinical setting, however, must be considered with caution because there is evidence that mesenchymal stem cells may also contribute to the maintenance of cancer stem cells. SUMMARY: The interest generated by mesenchymal stem cells has rapidly favored several initiatives to test their therapeutic potentials. There is still much to investigate to characterize their phenotype, understand their mechanisms of action, and optimize their in-vitro expansion for clinical use.
17714033 Phosphodiesterase 4 inhibitors and inflammatory bowel disease: emerging therapies in infla 2007 Sep Crohn's disease and ulcerative colitis (UC) are common, chronic inflammatory bowel diseases (IBDs) characterized by episodes of life-altering symptoms such as diarrhea, bleeding, fecal urgency and incontinence, abdominal pain and cramps, and fever lasting weeks to months at a time. Existing treatments are 5-aminosalicyclates or immunosuppressants, but long-term control of IBD is a major problem for a large number of patients. Phosphodiesterase 4 (PDE4) is a key enzyme in cell homeostasis and inflammation and its inhibition has been useful in diseases such as asthma and chronic obstructive pulmonary disease, rheumatoid arthritis and multiple sclerosis. This review focuses on the role of oxidative stress in IBD and the PDE4 inhibitor OPC-6535 (tetomilast), an investigational agent for the treatment of UC. The authors detail the clinical development of the compound and report and provide insight into some of the unpublished data from the recently completed multicenter Phase III trials in UC.
17558693 Haemopoietic stem cell transplantation--an evolving treatment for severe autoimmune and in 2007 Jun The concept of haemopoietic stem cell transplantation (HSCT) to treat severe autoimmune diseases has been around for several decades. Advances in the safety of HSCT have made it a clinical reality since 1995. Databases have registered around a thousand patients treated specifically for a wide range of diseases, predominantly multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Phase I/II prospective and retrospective studies have supported the potential of autologous HSCT as a treatment option in severely affected patients, with profound and prolonged clinical responses in some diseases, although procedures are generally not curative. Allogeneic HSCT appears to offer curative potential, but the potential of high toxicity has limited its use in this context. The exact role of HSCT remains to be defined, particularly in the context of other advances in the treatment of autoimmune disease. Along with other groups, the European Group for Blood and Marrow Transplantation (EBMT) are overseeing several phase III trials in autologous transplantation. Given the risks of the HSCT, eligibility is restricted to patients who have severe, treatment resistant disease, in whom the prognosis is otherwise poor. This review aims to summarise the current published data in this evolving treatment for relatively rare patients with resistant or rapidly progressive disease where treatment options are otherwise limited. This cross-fertilization of knowledge between many specialties may provide increasing therapeutic opportunities in otherwise untreatable diseases. Moreover, destroying and rebuilding immune systems may provide insights into autoimmune diseases.
17502863 Effects of etanercept are distinct from infliximab in modulating proinflammatory genes in 2007 May Proinflammatory diseases like rheumatoid arthritis, Crohn's disease, and psoriasis have been treated by the tumor necrosis factor (TNF) antagonists infliximab and etanercept with different degrees of success. Although these agents are widely used in humans, little is known about their mechanisms of action or why etanercept and infliximab have differences in clinical activity. In this study, we define leukocyte genes that are suppressed by etanercept within 24 hours of exposure. Compared to previous work with infliximab, fewer immune-related genes are suppressed by etanercept. Importantly, the range of genes suppressed by these alternative TNF inhibitors is only partially overlapping, suggesting each has unique immune modulating effects. In sharp contrast to etanercept, infliximab strongly suppresses genes associated with "Type 1" immune responses (IFN-gamma and the IL-12-receptor beta 2 subunit), providing a clear mechanism for clinically relevant immune suppression.
17493365 [Progress of study on suppressor of cytokine signaling-1 - review]. 2007 Apr Suppressor of cytokine signaling (SOCS) is a new family of proteins produced in cells. It may play an important role in classic negative feedback loop to regulate cytokine signal transduction. SOCS-1 was observed and confirmed firstly. Expression of SOCS-1 can inhibit cytokine signal transduction of some cytokines, such as IL-6, LIF, OSM, INF-gamma, GH, and so on, many immune responses are regulated by them in vivo. Abnormal expression of SOCS-1 is closely related to some human diseases. It plays an important role in the development of leukemia, rheumatoid arthritis, liver cirrhosis and liver cancer. In this review, the advances of research on the relationship between SOCS-1 and cytokine, and its correlation with some diseases were summarized.
17427525 Risk factors of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) at Phramong 2007 Mar BACKGROUND: There have been sporadic reports on the Asian risk factor of DVT after total knee arthroplasty. OBJECTIVE: To determine the risk factors of DVT MATERIAL AND METHOD: Retrospective review of one hundred patients who had undergone TKA and postoperative Contrast Venography in bilateral legs between 2002 and 2005 were performed to identify risk factor of DVT The patients were divided into two groups, positive and negative venography which the patients who had positive venography were indicating the development to DVT RESULTS: One hundred patients were evaluated associated to DVT Eighteen of these patients were men, and eighty-two were women. The median age at the time of the procedure was seventy-five years old (range: 62 - 79 years old). Sixty-one patients showed positive venography for D VT Five critical risk factors were identified to develop DVT: 1. Underlying cardiovascular disease 2. Underlying hematological disease 3. Underlying rheumatoid arthritis 4. Patients who took oral herbal medicine about one year before the operation 5. Patients who received revision TKA. CONCLUSION: The risk factors of DVT in the presented patients at Phramongkotklo Hospital were similar to other countries. The research study could identify statistically significant risk factors and stimulate surgeons undertaking TKA to be aware of the probability of the patient to develop DVT.
17409534 Genetic polymorphism of C452T (T127I) in human gamma-glutamyl hydrolase in a Japanese popu 2007 Apr We investigated the genotype distribution and allele frequency of C452T polymorphism of gamma-glutamyl hydrolase (GGH) gene, which causes the decreased enzymatic activity affecting the efficacy of methotrexate (MTX), in a Japanese population. The polymerase chain reaction-restriction fragment length polymorphism assay was applied to determine the genotype of C452T polymorphism in 269 Japanese healthy individuals. The genotype distribution was as follows: C/C, 89.2% (n=240); C/T, 10.4% (n=28); T/T, 0.4% (n=1). The frequency of C and T allele was 0.944 and 0.056, respectively. The obtained genotype distribution was well agreed with those expected by Hardy-Weinberg equilibrium. The genotype distribution and allele frequency in a Japanese population were found to be similar to those of African-Americans but significantly different from Caucasians. Although the frequency of variant T allele in a Japanese population is not so high as compared to Caucasians, determination of C452T polymorphism of GGH may be useful for monitoring of efficacy and side-effects of MTX for treatment of diseases such as rheumatoid arthritis or childhood acute leukemia. To our knowledge, this is the first report about the examination of C452T polymorphism of GGH in a Japanese population.
17351778 The role of MR imaging in scaphoid disorders. 2007 Nov The scaphoid bone of the wrist is one of the most commonly fractured bones in the body. Due to its importance in the biomechanics and functionality of the wrist, it is important to depict and characterize the type of injury. Plain radiographs and scintigraphy may fail to disclose the type and severity of the injury. In patients with normal initial plain radiographs, MR imaging can discriminate occult fractures from bone bruises and may also demonstrate ligamentous disruption. MR imaging can also discriminate the proximal pole viability versus avascular necrosis secondary to previous fracture, which is important for treatment planning. Treatment of non-united fractures with vascularized grafts can be evaluated with contrast-enhanced MR imaging. Idiopathic osteonecrosis or Preiser's disease was originally described after trauma. The non-traumatic disorders of the scaphoid include post-traumatic osteoarthritis, inflammatory bone marrow edema in patients with rheumatoid arthritis, and osteomyelitis. MR imaging is helpful in all the above disorders to demonstrate early bone marrow edema, cartilage degeneration and associated subchondral marrow changes. The most commonly found tumors in the scaphoid are usually benign and include enchondroma, osteoblastoma and osteoid osteoma. MR imaging is not mandatory for the initial diagnosis, which should be based on plain X-ray findings.
17285813 The use of therapeutic interchange for biologic therapies. 2007 Jan Therapeutic interchange is the practice of switching or dispensing drugs that are chemically distinct but therapeutically similar in terms of their efficacy, safety, and tolerability profiles. The stated goal of therapeutic interchange is to achieve an improved or neutral outcome with the new agent while reducing overall treatment costs. Until recently, most interchange programs have been limited to switches within drug classes, such as angiotensin-converting enzyme (ACE) inhibitors, proton pump inhibitors (PPIs), HMG-CoA reductase inhibitors (statins), and selective serotonin reuptake inhibitors (SSRIs), and generally to drugs that use the same routes of administration. Therapeutic interchange now is being applied to some biologic agents, such as those used to treat psoriasis and rheumatoid arthritis (RA). In some cases, these agents differ in structure and mode of administration. Patients who require a biologic agent are often difficult to manage, and the comorbidities that are prevalent in these patients further complicate management and agent selection. Population-based outcomes among various agents may not appear notably different, but because there is no a priori means to determine the effects of a given biologic agent on any individual patient, therapeutic interchange is inadvisable once a patient receiving RA or psoriasis therapy has been stabilized. However, if a biologic agent has been designated as preferred on a formulary, it is reasonable to initiate treatment with that agent in a patient who is naive to biologic therapy if that agent is not contraindicated. Respectful, two-way communication between health care professionals and managed care organizations (MCOs) will help ensure that a patient receives the appropriate therapy at the right time.