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ID PMID Title PublicationDate abstract
17946924 Development of a finger joint phantom for evaluation of frequency domain measurement syste 2006 For development and test of new optical imaging devices, phantoms are widely used to emulate the tissue to be imaged. Phantom design gets more difficult the more complex the tissue is structured. We report on developing and testing a solid, stable finger joint phantom to simulate transillumination of finger joints in frequency-domain imaging systems. The phantom consists of the bone, capsule, skin, the capsule volume, and the joint gap. Silicone was used to build the solid parts and a glycerol-water solution for the fluid in the capsule volume and joint gap. The system to test the phantom is an optical frequency-domain scanning set-up. Different stages of joint inflammation as they occur in rheumatoid arthritis (BA) were emulated by assembling the phantom with capsule and fluid having different optical properties. Reliability of the phantom measurement was investigated by repeated assembling. The results show clear discrimination between different stages of joints within the signal deviation due to reassembling of the phantom.
17874974 Emerging adenosine receptor agonists. 2007 Sep Adenosine receptors (ARs) are a four-member subfamily of G protein-coupled receptors and are major targets of caffeine and theophylline. There are four subtypes of ARs, designated as A1, A2A, A2B and A3. Selective agonists are now available for all four subtypes. Over a dozen of these selective agonists are now in clinical trials for various conditions, although none has received regulatory approval except for the endogenous AR agonist adenosine itself. A1AR agonists are in clinical trials for cardiac arrhythmias and neuropathic pain. A2AAR agonists are now in trials for myocardial perfusion imaging and as anti-inflammatory agents. A2BAR agonists are under preclinical scrutiny for potential treatment of cardiac ischemia. A3AR agonists are in clinical trials for the treatment of rheumatoid arthritis and colorectal cancer. The present review will mainly cover the agonists that are presently in clinical trials for various conditions and only a brief introduction will be given to major chemical classes of AR agonists presently under investigation.
17764616 Immunological effects of silica and asbestos. 2007 Aug Silicosis patients (SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis (known as Caplan syndrome), and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occur in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.
17661797 Carpal tunnel syndrome and metabolic syndrome. 2007 Aug Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy. Many factors such as diabetes mellitus, hypothyroidism, hormonal replacement therapy, corticosteroid use, rheumatoid arthritis and wrist fractures may cause CTS. Metabolic syndrome includes abdominal obesity, dyslipidemia, hyperglycemia, and hypertension that may cause CTS. In this study, we aimed to evaluate the relation between CTS and metabolic syndrome. We studied 107 (96 female and 11 male) right-handed patients who had a clinical and electrophysiologically confirmed diagnosis of CTS. We then divided the patients into two groups (patients with and without metabolic syndrome) according to the criteria of ATP III definition. Eighty (75%) of the patients with CTS had metabolic syndrome. Among the 80 patients with metabolic syndrome, CTS was found in 150 hands (43 mild, 58 moderate and 49 severe cases). Among the 27 patients without metabolic syndrome, CTS was found in 43 hands (27 mild, 14 moderate and 2 severe cases). The electrophysiological parameters (median nerve distal motor latency, median nerve motor amplitude, median nerve motor conduction velocity, median nerve sensory onset latency, median nerve sensory amplitude and median nerve sensory conduction velocity) were worse in patients with metabolic syndrome (P < 0.05). In conclusion, metabolic syndrome was found to be three times more common in patients with CTS and CTS was more severe in patients with metabolic syndrome when compared with those without metabolic syndrome.
17628183 Vitamin E and mast cells. 2007 Mast cells play an important role in the immune system by interacting with B and T cells and by releasing several mediators involved in activating other cells. Hyperreactivity of mast cells and their uncontrolled accumulation in tissues lead to increased release of inflammatory mediators contributing to the pathogenesis of several diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and allergic disorders such as asthma and allergic rhinitis. Interference with mast cell proliferation, survival, degranulation, and migration by synthetic or natural compounds may represent a preventive strategy for the management of these diseases. Natural vitamin E covers a group of eight analogues-the alpha-, beta-, gamma-, and delta-tocopherols and the alpha-, beta-, gamma-, and delta-tocotrienols, but only alpha-tocopherol is efficiently retained by the liver and distributed to peripheral tissues. Mast cells preferentially locate in the proximity of tissues that interface with the external environment (the epithelial surface of the skin, the gastrointestinal mucosa, and the respiratory system), what may render them accessible to treatments with inefficiently retained natural vitamin E analogues and synthetic derivatives. In addition to scavenging free radicals, the natural vitamin E analogues differently modulate signal transduction and gene expression in several cell lines; in mast cells, protein kinase C, protein phosphatase 2A, and protein kinase B are affected by vitamin E, leading to the modulation of proliferation, apoptosis, secretion, and migration. In this chapter, the possibility that vitamin E can prevent diseases with mast cells involvement by modulating signal transduction and gene expression is evaluated.
17584599 Association of Fc gamma receptor IIIB polymorphism with renal-allogrft in Chinese. 2007 Jul BACKGROUND: Several studies have identified FcgammaRIIIb (Fcgr3b) polymorphisms that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the study was to clarify whether FcgammaRIIIb allele polymorphism influence susceptibility to end stage renal disease (ESRD) patients with renal transplantation. METHODS: DNA fragments were amplified by PCR-SSP using genomic DNA from 172 unrelated, healthy blood donors and 171 renal recipients in our Kidney Disease Centre. We performed direct sequencing using 20 PCR products of renal recipients carrying different FcgammaRIIIb forms according to the allele-specific PCR. RESULTS: FcgammaRIIIb NA1/NA2 genotype frequency showed significant difference between renal recipients and healthy controls (chi(2)=19.3, P<0.005). In addition, the allele frequency also showed significant difference between the two groups. Lower frequency of genotype FcgammaRIIIb NA1/NA1 was observed in renal recipients than in healthy controls (chi(2)=5.06, P=0.024). In comparison with nonrejectors, rejectors displayed no significant defference of FcgammaRIIIb NA1/NA2 genotype frequency, as well as allele frequency. CONCLUSION: FcgammaRIIIb NA1/NA2 heterozygote genotype frequency was increased in ESRD patients in Chinese. The present findings showed that FcgammaRIIIb genotype related to the disease susceptibility, although FcgammaRIIIb polymorphisms did not affect the acute rejection.
17581111 A multidimensional health assessment questionnaire (MDHAQ) for all patients with rheumatic 2007 Rheumatic diseases differ from many chronic diseases in that no single measure provides a gold standard for diagnosis, prognosis, monitoring, and documentation of changes over long periods. Therefore, pooled indices of several measures have been developed, such as the American College of Rheumatology (ACR) Core Data Set and disease activity score (DAS) for rheumatoid arthritis (RA), systemic lupus erythematosus disease activity index (SLEDAI), Bath ankylosing spondylitis disease activity index (BASDAI), and others. Quantitative clinical rheumatology measures and indices are used primarily in clinical trials and other research studies, but generally not in standard clinical care, which usually is conducted without quantitative data, other than laboratory tests, often with noncontributory, false positive, or false negative results. Measures designed for research often are lengthy, not easily scored, and not designed to add to standard patient care. By contrast, measures designed for standard care are short, easily scored, and useful to monitor patient status at each visit. Some research measures have been adapted for standard care, such as the multidimensional health assessment questionnaire (MDHAQ) derived from the HAQ, which includes an index of the three RA core data set measures (physical function, pain, and global estimate), also known as routine assessment of patient index data 3 (RAPID 3). RAPID 3 can be scored in 10 sec, compared to 90 sec for a 28-joint count, and 40 sec for a standard HAQ. The MDHAQ is useful in all rheumatic diseases by saving time, documenting changes in status over long periods, and by improving rheumatology care and outcomes.
17572902 Bilateral femoral insuffiency fractures treated with inflatable intramedullary nails: a ca 2007 Sep Stress fractures could be classified as fatigue fractures and insufficiency fractures (IF). Fatigue fractures occur when abnormal mechanical stress is applied to a normal bone, on the other hand insufficiency fractures occur when normal to moderate pressure is applied to a bone that has decreased resistance (Daffner and Pavlov in Am J Radiol 159:242-245, 1992). IF have been observed mainly in patients with postmenopausal osteoporosis, and are becoming more common with the increase of elderly population (Daffner and Pavlov in Am J Radiol 159:242-245, 1992). Other systemic and metabolic conditions that can result in osteopenia and IF include osteomalacia, hyperparathyroidism, hyperthyroidism, rheumatoid arthritis, fluoride treatment, diabetes mellitus, fibrous dysplasia, Paget's disease, irradiation and mechanical factors (Daffner and Pavlov in Am J Radiol 159:242-245, 1992; Soubrier et al. in Joint Bone Spine 70:209-218, 2003; Epps et al. in Am J Orthop 33:457-460, 2004; Austin and Chrissos in Orthopedics 28:795-797, 2005). In this case report, the authors present an osteoporotic woman who developed bilateral insufficiency fracture of the femoral shaft after longstanding steroid, thyroxine replacement and alendronate therapy due to partial empty sella syndrome and osteoporosis, resulting in the treatment of the fracture by inflatable intramedullary nailing.
17497998 Efficacy of granulocyte and monocyte adsorption apheresis for three cases of refractory py 2007 Jun Pyoderma gangrenosum presents with chronic skin ulcers and is histologically characterized by neutrophil infiltration throughout the dermis. It is also occasionally associated with ulcerative colitis, a type of inflammatory bowel disease, against which granulocyte and monocyte adsorption apheresis (GCAP) has recently shown remarkable efficacy. We performed GCAP on three refractory cases of pyoderma gangrenosum with painful bilateral leg ulcers and hereby report the results obtained. Patient 1 was a 43-year-old woman with a four-year history of recurrent painful skin ulcers treated with prednisolone and cyclosporine. Patient 2 was a 29-year-old woman who had been suffering from pyoderma gangrenosum with severe pain for two weeks, associated with an 11-year history of ulcerative colitis treated with prednisolone and salazosulfapyridine. Patient 3 was a 63-year-old man with a three-year history of recurrent ulcers with pain, suffering from rheumatoid arthritis treated with prednisolone and cyclophosphamide. The sizes of the lesions were reduced in all three patients following a weekly GCAP treatment for 10 or 11 consecutive weeks, and the re-epithelialization of ulcers were additionally observed in two patients. The pain disappeared dramatically in all three patients following two sessions of GCAP therapy. No adverse effects were observed for up to at least eight months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, with regards to refractory cases of pyoderma gangrenosum.
17485377 Dendritic cells in autoimmune diseases and neuroinflammatory disorders. 2007 May 1 Dendritic cells are the most potent antigen presenting cells and have long been recognized as key regulators of the immune system, linking both stimulatory and inhibitory components of normal immunity. While DCs are fully characterized with respect to primary and secondary immune responses, their unique role in coordinating central and peripheral tolerance is just emerging. It is increasingly evident that the failure of DCs ability to maintain tolerance can lead to autoimmune and/or inflammatory diseases. However, existing literature highlighting participation of DCs in several autoimmune phenomena is scattered and remains underappreciated. This review is a comprehensive account of current knowledge characterizing the role of DCs in various autoimmune diseases including psoriasis, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, and diabetes. Additionally, it provides a rare description of DCs participation in various neuroinflammatory disorders including multiple sclerosis, HAM/TSP, Alzheimer disease and prion-associated diseases. Finally, a detailed description of the possible mechanisms of DC involvement in regulating immune response towards self versus non-self is discussed. Overall, the goal of this review is to establish DCs in the interface of tolerance and autoimmunity and generate a global interest in this field in order to exploit DC potential for the therapy of inflammatory diseases.
17420934 Colonization and impact of disease and other factors on intestinal microbiota. 2007 Sep The aim of this study was to review the process of microbial colonization and the environmental and host factors that influence colonization and microbial succession. The impact of some diseases on intestinal microbiota composition is also described. Microbial colonization of the gut by maternal vaginal and fecal bacteria begins during and after birth. During the first 2 years of life, specific microbes become established in a process designated microbial succession. Microbial succession in the gastrointestinal tract is influenced by numerous external and internal host-related factors, and by the second year of life, the intestinal microbiota composition is considered identical to that of adults. Nevertheless, intestinal microbiota in both infants and adults remain incompletely characterized and their diversity poorly defined. The main explanation is that many intestinal bacteria that live in an anaerobic environment are difficult or impossible to culture outside the intestine. However, recent advances in molecular biology techniques have initiated the description of new bacteria species. The composition of gut microbiota can be modulated by host, environmental, and bacterial factors, and strong evidence has emerged of substantial modifications during illness or exposure to threatening experiences. It has been postulated that improvements in hygienic measures have led to an increase in allergic diseases ("hygiene hypothesis"). Alterations in gut microbiota and their functions have been widely associated with many chronic and degenerative diseases, including inflammatory bowel disease, colon cancer, and rheumatoid arthritis.
17337643 Altered immunity as a risk factor for non-Hodgkin lymphoma. 2007 Mar This review examines the association between disorders of immunity, including immune deficiency, atopy, and autoimmune disease, and non-Hodgkin lymphoma (NHL). Immune deficiency is one of the strongest known risk factors for NHL. Risk is increased whether the immune deficiency is congenital, iatrogenic, or acquired. Risk of NHL increases with degree of immune deficiency, and there is no evidence of a threshold. In the profoundly immune deficient, NHL is frequently caused by infection with the ubiquitous EBV. Whether mild, subclinical immune deficiency is related to increased NHL risk is unknown. There is inconsistent evidence that atopic conditions, such as asthma, hayfever, and eczema, characterized by an immune response that is skewed toward Th2, are associated with a decreased risk of NHL. These data come mainly from case-control studies. Concern has been expressed that the association may be due to reverse causality if early symptoms of NHL include a lessening of atopic manifestations. Case-control and cohort studies of people with autoimmune conditions have generally shown that rheumatoid arthritis, systemic lupus erythematosis, and Sjogren's disease are associated with increased NHL risk. It seems to be the intensity of the inflammatory disease rather than its treatment which is related to increased risk of NHL. The study of altered immunity as a cause of NHL in case-control studies is limited by the fact that development of NHL in itself leads to altered immunity. Cohort studies of the role of altered immunity should be a top priority in epidemiologic studies of NHL etiology.
17191007 Osteoimmunology. 2007 Osteoimmunology is an interdisciplinary research field combining the exciting fields of osteology and immunology. An observation that contributed enormously to the emergence of osteoimmunology was the accelerated bone loss caused by inflammatory diseases such as rheumatoid arthritis. Receptor activator of nuclear factor kappaB ligand (RANKL), which is the main regulator of osteoclastogenesis, was found to be the primary culprit responsible for the enhanced activation of osteoclasts: activated T cells directly and indirectly increased the expression of RANKL, and thereby promoted osteoclastic activity. Excessive bone loss is not only present in inflammatory diseases but also in autoimmune diseases and cancer. Furthermore, there is accumulating evidence that the very prevalent skeletal disorder osteoporosis is associated with alterations in the immune system. Meanwhile, numerous connections have been discovered in osteoimmunology beyond merely the actions of RANKL. These include the importance of osteoblasts in the maintenance of the hematopoietic stem cell niche and in lymphocyte development as well as the functions of immune cells participating in osteoblast and osteoclast development. Furthermore, research is being done investigating cytokines, chemokines, transcription factors and co-stimulatory molecules which are shared by both systems. Research in osteoimmunology promises the discovery of new strategies and the development of innovative therapeutics to cure or alleviate bone loss in inflammatory and autoimmune diseases as well as in osteoporosis. This review gives an introduction to bone remodeling and the cells governing that process and summarizes the most recent discoveries in the interdisciplinary field of osteoimmunology. Furthermore, an alternative large animal model will be discussed and the pathophysiological alterations of the immune system in osteoporosis will be highlighted.
17186339 Is interstitial pneumonia in patients with collagen diseases a contraindication to lung ca 2007 PURPOSE: Lung cancer surgery can be dangerous in patients with interstitial pneumonia (IP) as acute exacerbation of the IP may prove fatal. It remains unclear if patients with collagen diseases (CD), who often suffer from IP, are also at increased risk during lung cancer surgery. METHODS: We retrospectively examined 17 (3.1%) patients with CD among 545 patients who underwent surgery for lung cancer at our institution. RESULTS: Nine patients with rheumatoid arthritis, five with systemic sclerosis, two with Sjögren's disease, and one with systemic lupus erythematosus were enrolled in this study. Eleven patients (65%) were taking corticosteroids at the time of surgery. Fourteen patients underwent lobectomy and lymph node dissection, and three patients with pStage IA lung cancer underwent pulmonary wedge resection. Pathologically, 11 (65%) patients had IP with various inflammatory cellular infiltrations, and three (18%) had honeycombing of the lung. Postoperatively, none of the patients suffered acute exacerbation of their IP. CONCLUSIONS: Despite the high incidence of IP in patients with lung cancer and CD, our results suggest that CD is not a contraindication to the surgical resection of lung cancer.
17121493 Osteoporosis: is there a rational approach to fracture prevention? 2006 The most effective way to manage osteoporosis is to prevent fractures before they occur. To do this, a clinician needs to be aware of both the clinical risk factors that predispose a patient to an osteoporotic fracture and the patient's bone mineral density (BMD). An assessment of risk factors that increase fracture risk, including age, weight less than 125 pounds as an adult, family history of hip fracture, low-impact fractures as an adult, inability to rise up from a chair without using one's arms, presence of rheumatoid arthritis (RA), and use of glucocorticoid medication, in addition to low BMD, is necessary to assess fracture risk. Therefore, a complete history and BMD will improve the identification and treatment of patients at high risk of an osteoporotic fracture. Also, patients with systemic inflammatory diseases like RA or systemic lupus erythematosus have an increased risk of fracture owing to systemic inflammation independent of glucocorticoid use. These patients should be screened for osteoporotic risk factors, and BMD tests should be obtained. Treatment to prevent fractures should be initiated at a BMD (T score) <-1 to improve skeletal health in these patients. This review provides an update on the epidemiology of fractures, reviews fracture risk-factor assessment, and makes recommendations on how to screen patients and decide which patients would benefit from an intervention. Lastly, this review analyzes the new initiative by the World Health Organization (WHO) to assess fracture risk and new information on assessment of bone health in rheumatic disease patients.
17110309 Possible pathogenic nature of the recently discovered TT virus: does it play a role in aut 2006 Nov Pathogenesis of viral origin has long been suggested in autoimmune rheumatic diseases. Beside the well-defined virus induced transient or chronic rheumatic diseases often resembling systemic autoimmune disorders such as rheumatoid arthritis, viruses can contribute to disease pathogenesis by several different pathomechanisms. TT virus is a recently discovered virus of extremely high genetic diversity which commonly infects humans. Despite accumulated evidence on the biological characteristics of TTV, its pathogenicity is still in question; many consider TTV as a harmless endosymbiont. The recent paper overviews the biology of TT virus and investigates the hypothesis that TTV might have a causative role in human diseases with special attention to the possibility that TTV might trigger autoimmunity in rheumatic disorders.
17101541 Interfering with leukocyte integrin activation--a novel concept in the development of anti 2006 Inflammation is a crucial response against invading pathogens, in which immune cells, including neutrophils and T cells, are recruited into tissue from the bloodstream to help clear infection. However, a prevailing inflammatory response where the immune cells attack healthy tissue is associated with many diseases, including asthma, rheumatoid arthritis, atherosclerosis and multiple sclerosis. Integrins are key players in the recruitment of immune cells from the bloodstream into tissues, and are thus therapeutic targets for intervention with inflammatory responses. Thus far, mainly extracellularly acting therapeutics (monoclonal antibodies) have been developed against integrins, targeting ligand binding sites in these heterodimeric adhesion receptors. However, since these therapeutics nonselectively block all integrin functions, some side effects are expected and have been observed. Therefore, novel concepts need to be developed in the therapeutic targeting of integrins. Recently, major advances have been made in the understanding of integrin biology. Integrin structures have been solved by X-ray crystallography, revealing unexpected data about the activation mechanism of integrins in cells. Additionally, several intracellular factors in the integrin activation process have been identified, providing potential specific targets for therapeutic intervention. Here, we present key events and players in leukocyte integrin activation, and discuss potential new drug targets in the prevention of inflammatory disease.
17080203 The role of galactosyltransferases in cell surface functions and in the immune system. 2006 Sep The immune system relies on cellular communication and often on the recognition of carbohydrates by mammalian lectins. Galactose (Gal)-containing structures are involved in both the innate and adaptive immune systems. Gal is a ligand for Gal/N-acetylgalactosmine (GalNAc) receptors and galectins, and is part of the scaffold structure that synthesizes oligosaccharide ligands for selectins, siglecs and other lectins of the immune system. Gal residues are added to glycoproteins and glycolipids by members of a large family of galactosyltransferases. The expression of many of these enzymes is regulated by the action of cytokines, and becomes altered in various disease states. Specific galactosyltransferases have been shown to control cell adhesion and leukocyte functions. Antibodies need to be galactosylated for normal function, and undergalactosylated immunoglobulin (Ig) is associated with rheumatoid arthritis, while Gal is lacking in the IgA of patients with IgA nephropathy. Interactions involving Gal play important roles in host defenses; they can also result in serious pathophysiology. Galactosyltransferases represent potential targets for the control of cell growth and apoptosis, inflammation and infections.
17039336 [Insoles for the rheumatic foot. A clinical and pedobarographic analysis]. 2006 Nov BACKGROUND: Insoles are regarded as an appropriate tool for the management of rheumatic foot disorders. However, a quality control for this purpose has not been established. In our study, the clinical effectiveness of insoles used in patients with rheumatic foot disorders was addressed. In addition, we sought to establish pedobarography as a means of quality control for orthotic management of the rheumatic foot. MATERIAL AND METHODS: Our study included 20 rheumatoid arthritis patients with painful rheumatic foot deformities who were provided with insoles. Clinical data were obtained by physical examination and a 100-mm pain scale. Pedobarography was performed using the novel pedar cable system with new and individually designed insoles and after a 6-month follow-up. A shoe-only trial served as control. The parameters maximum force, peak pressure, force-time integral, and average pressure were analyzed in anatomical regions and an individually defined overloaded forefoot region. RESULTS: Clinical improvement was significant after a 6-month follow-up in spite of a heterogeneous group of patients. However, our results could not confirm consistent changes in plantar pressure distribution. CONCLUSION: As a conclusion, further efforts are necessary to establish a quality control for orthotic management of the rheumatic foot.
17003846 Analgesic, antiinflammatory, and ulcerogenic studies of meloxicam solid dispersion prepare 2006 Sep Meloxicam is a nonsteroidal antiinflammatory drug, used in the treatment of rheumatoid arthritis and oestoarthritis. It is practically insoluble in water, leading to poor dissolution, variations in bioavailability, and gastric irritation on oral administration. In the attempt to reduce its gastric side effect and to increase aqueous solubility, physical mixture and solid dispersion of the drug were prepared with polyethylene glycol 6000. The analgesic, antiinflammatory, and ulcerogenic effects were assessed for physical mixture and solid dispersion in comparison with meloxicam alone. The results indicate that both physical mixture and solid dispersion possess better analgesic and antiinflammatory properties with less ulcerogenic potential when compared with pure meloxicam.