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ID PMID Title PublicationDate abstract
12903047 [Genome-wide scanning for susceptibility genes in researches on six HLA-associated disease 2003 Aug Six human leucocytic antigen(HLA)-associated diseases, including ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes mellitus and psoriasis, were selected as objects of this review. The characteristics of these diseases in whole-genome scans on susceptibility genes or loci undertaken to date were analyzed and compared. Meanwhile, the potential proposals for dealing with the existing problems were put forward.
12921121 Immusorba TR and PH. 2003 Feb Immusorba TR (IM-TR) and PH (IM-PH) were developed as adsorbents with non-biological materials as affinity ligands to remove pathogenic autoantibodies. The adsorbents of IM-TR and IM-PH are polyvinyl alcohol gel immobilized with tryptophan and phenylalanine as ligand, respectively. IM-TR is clinically applied for treatment of autoimmune neurological diseases such as myasthenia gravis and Guillain-Barre syndrome. IM-PH is used for not only neurological diseases such as GBS and multiple sclerosis but also collagen diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). As many autoantibodies with different specificities have been found to have similar affinities to the ligand of Immusorba, it is expected that Immusorba will be applied to more diseases and contribute to the clarification of the mechanisms of the development of diseases by the identification of adsorbed unknown pathogenic substances with Immusorba.
12673074 Two-year follow-up study after human parvovirus B19 infection. 2003 BACKGROUND: Acute human parvovirus B19 (B19) infection induces systemic lupus erythematosus (SLE)-like symptoms. It has been controversial whether B19 infection causes SLE and rheumatoid arthritis (RA). OBJECTIVES: This study prospectively investigated whether symptoms of B19 infection persisted for more than 2 years and whether persistent symptoms contributed to the development of SLE and RA. METHODS: In this prospective study, clinical findings were examined and laboratory examinations were performed in 42 adult patients 1, 2, 6, 12 and 24 months after the first consultation. RESULTS: Most acute symptoms disappeared within 2 weeks. However, arthralgia continued for 2 months in 2 women, 6 months in 1 woman and more than 2 years in 1 woman with positive antinuclear antibody and hypocomplementemia. The clinical findings of the patient with persistent arthralgia did not fulfill the criteria for SLE and RA. CONCLUSION: The symptoms caused by B19 infection were transient in most cases but persisted in 1 case in our series.
15222243 [Rheumatoid nodule and complete heart block: diagnosis by transesophageal echocardiography 2004 Mar We report a case of 48 years old women with a 8 years history of rheumatoid arthritis and severe articular deformation treated during the last 6 months by prednisone (5 mg daily) and chloroquine (200 mg daily), admitted in the emergency room because of syncope. The electrocardiogram showed a complete atrioventricular block. Transesophageal echocardiography was performed and revealed an hyperechogenic mass (6 x 2.5 mm) in the interventricular septum probably related to a fibrous rheumatoid nodule. This potentially explain the atrioventricular block by infiltration of the conduction pathways. A permanent double chamber pacemaker was inserted. The chloroquine, another factor of conduction disturbances was not incriminated in this case. The conduction disturbances should be systematically detected in case of severe rheumatoid arthritis. Therefore, every patient must be submitted to a transthoracic echocardiography. Transesophageal echocardiography may be helpful to detect rheumatoid nodule.
14644854 Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibo 2003 Dec OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p
15160244 [Biologicals: a new therapeutic approach for inflammatory diseases]. 2004 Jun The pathogenesis of inflammatory diseases is determined by a malfunction of the immune system. Up to now therapies have not been able to cure but to interfere in a more or less specific way with the immune function. The great increase of knowledge in immunology made it possible to develop new medications, which alter the immune system in a specific way. The advantage is the relative simple way of developing new medications by using monoclonal antibodies against specific antigens and testing the hypothesis in animal model and in small but clear phase II trials. Biologicals are similar or identical to human proteins and rarely have side effects, which exceed their interference with the immune system. Because of the clinical success of anti-TNF-therapies and the increased knowledge about immune mechanisms, biologicals are now used in various fields of medicine. This paper reviews data from biologicals that are either already approved or in an advanced stage of clinical testing.
12729116 Role of abrasion of the femoral component in revision knee arthroplasty. 2003 Apr We carried out 60 revision procedures for failed porous coated anatomic total knee replacements in 54 patients, which were divided into two groups. The 14 knees in group I had a well-fixed femoral component at surgery which was retained, and in the 46 knees in group II both tibial and femoral components were loose and were revised using a variety of implants. Our review comprised clinical and radiological assessment. A total of 13 knees required a second revision. Six (42%) in group I failed very early (mean 2.1 years) when compared with seven (15%) in group II (mean 6.8 years). Failure was due to wear of the polyethylene insert by the abraded, retained femoral component (crude odds ratio 4.07; 95% CI 1.07 to 15.5). We recommend a complete change of primary bearing surfaces at the time of revision of an uncemented total knee replacement in order to prevent early wear of polyethylene.
15479877 DREAMing about arthritic pain. 2004 Nov The experience of acute pain serves a crucial biological purpose: it alerts a living organism to environmental dangers, inducing behavioural responses which protect the organism from further damage. In contrast, chronic pain arising from disease states and/or pathological functioning of the nervous system offers no advantage and may be debilitating to those afflicted. Despite recent advances in our understanding of pain mechanisms, the satisfactory management of pathological pain eludes current treatment strategies. We have demonstrated in a previous study on dream deficient mice the pivotal role of downstream regulatory element antagonistic modulator (DREAM) in modulating pain sensitivity in a number of behavioural models, including acute and chronic neuropathic pain. DREAM is a novel calcium binding transcriptional repressor for the prodynorphin gene in spinal cord neurones. The marked attenuation in pain behaviour exhibited by dream-/- mice was shown, by pharmacological and biochemical analyses, to be due to increased activation of the endogenous kappa-opioid system. Importantly, loss of DREAM also attenuated inflammatory pain. Thus, DREAM and the DREAM pathway constitute a novel therapeutic paradigm for the treatment of chronic pain in arthritis.
12491065 [Rheumatoid arthritis - pathogenetic role of neuroendocrine axes and the peripheral nervou 2002 Dec 15 BACKGROUND: Local innate and adaptive immune processes are of importance during the acute phase of rheumatoid arthritis (RA). In the advanced inflammatory phase alterations of systemic anti-inflammatory feedback mechanisms might be important features which may support chronic inflammation. ALTERATIONS: Similarly, like in other chronic inflammatory diseases, inadequately low cortisol and androgen serum levels can be detected in RA patients. In addition, there is a marked reduction of anti-inflammatory sympathetic nerve fibers in the inflamed joints paralleled by an enhanced number of pro-inflammatory sensory nerve fibers. Thus, an uncoupling of synergistically acting endocrine and neuronal, anti-inflammatory mechanisms (cortisol, dehydroepiandrosterone, androgens, sympathetic neurotransmitters) and a preponderance of pro-inflammatory mechanisms (estrogens, sensory neurotransmitters) may lead to chronic inflammatory disease. CONCLUSION: From this pathogenetic point of view new therapeutic strategies could be developed for the treatment of patients with RA.
12205730 The effects of sulphasalazine on urinary excretion of the hydroxypyridinium crosslinks of 2002 Aug Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 +/- 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 +/- 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 +/- 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 +/- 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 +/- 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 +/- 3.16 nmol/mmol cr) than in the inactive (8.25 +/- 4.23 nmol/mmol cr) period in patients with premenopausal RA (p < 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 +/- 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 +/- 2.13 nmol/mmol cr) and inactive periods (5.08 +/- 0.87 nmol/mmol cr) (p > 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p < 0.01, r=0.5953 p < 0.01, r=0.6125 p < 0.01 and r=0.6232, p < 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.
15051620 Increased incidence of cardiovascular disease in patients with rheumatoid arthritis: resul 2004 Aug OBJECTIVE: To investigate the first-ever incidence of acute myocardial infarction and stroke in a community based RA cohort compared with the general population. METHODS: The RA cohort consisted of all patients in a local RA register in Malmö, Sweden (n = 1022). The patients were recruited from private and hospital based rheumatology practices, and made up the absolute majority of patients with RA in the city. The general population of Malmö, aged 16 and above, served as controls. From the Swedish National Hospital Discharge Register and the national Swedish Causes of Death Register, information about all first-ever myocardial infarctions and strokes in Malmö residents between July 1997 and December 1999 was retrieved. The age and sex adjusted standardised morbidity ratio (SMR) of the two cohorts was calculated. RESULTS: Fifty four patients with RA had first-ever myocardial infarctions or stroke during the study period, compared with 3862 subjects in the general population. The age and sex adjusted SMR was 161 (95% confidence interval (CI) 121 to 210). The first-ever incidence of cardiovascular disease was increased among female and male patients when studied separately. The increase of cardiovascular events in the RA cohort was mainly due to an excess of myocardial infarctions (n = 36; SMR = 176 (95% CI 123 to 244). CONCLUSION: Patients with RA in Malmö had an increased first-ever incidence of myocardial infarction or stroke compared with the general population. This confirms that cardiovascular comorbidity is of major importance in RA.
12355448 IL-4-deficient mice develop less acute but more chronic relapsing collagen-induced arthrit 2002 Oct Rheumatoid arthritis as well as collagen-induced arthritis (CIA) is thought to involve T cell autoimmunity of the Th1 type and the Th2 cytokine IL-4 has been proposed to play a suppressive role. To exclude a possible skewing role of the mycobacteria used in the complete Freund's adjuvant (CFA) we induced CIA with type II collagen (CII) in incomplete Freund's adjuvant (IFA). Our results show that IL-4 deficiency leads to a lesser susceptibility to arthritis and lower B and T cell responses if induced with CII/IFA but not if induced with CII/CFA. In addition, IL-4-deficient mice were less susceptible to arthritis induced with monoclonal anti-CII antibodies. However, mice immunized with CII/IFA later developed a chronic relapsing disease, which was promoted by IL-4 deficiency. We conclude that IL-4 plays different roles depending on the type of adjuvant used and the phase (acute or chronic) of the clinical disease.
11740700 Immunogenicity and safety of pneumococcal vaccination in patients with rheumatoid arthriti 2002 Jan 15 Prevention of bacterial infection, which is a leading cause of morbidity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), is a priority. However, the safety and immunogenicity of the pneumococcal vaccine in such patients remain controversial. We evaluated the currently available pneumococcal vaccine in patients with RA or SLE. Pneumococcal vaccination was not associated with an appreciable deterioration in any clinical or laboratory measure of disease activity in either group. One month after vaccination, patients in both groups had significant increases in geometric mean concentrations of pneumococcal polysaccharide-specific IgG to all 7 serotypes tested, as did control subjects. However, 14 (33.3%) of 42 patients with RA and 5 (20.8%) of 24 patients with SLE responded either to none or to only 1 of the 7 polysaccharides. Pneumococcal vaccination is generally safe and immunogenic in patients with RA or SLE, but a subset of patients may remain unprotected by the currently available vaccine.
12915944 IL1-beta and TNF-alpha induce changes in the nuclear polyphosphoinositide signalling syste 2003 Sep Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint diseases that can lead to destruction of cartilage and structural changes in the subchondral bone. In this study we show by western blot and quantitative immunocytochemistry that nuclear phospholipase C beta(1) (PLC beta(1)) and phosphatidylinositol 4,5-bisphosphate (PIP(2)), two key elements of the polyphosphoinositide signal transduction system that regulate different cellular processes, increase in primary osteoblast cultures of RA patients when compared with post-traumatic after fall (PT) patients, whilst those of OA are not significantly affected. Moreover, we demonstrate that these alterations could be induced in PT osteoblasts by proinflammatory cytokines IL-1 beta and TNF-alpha. This suggests that proinflammatory cytokines, highly produced by RA infiltrating mononuclear cells, can modulate the nuclear polyphosphoinositide signalling pathway of the osteoblasts involved in bone remodelling.
14704886 Self-rated emotional functioning of patients with neurological or asymptomatic form of Wil 2003 Aug Psychopathology was assessed in 50 patients with the neurological form of Wilson's disease (WD-N) and in 17 asymptomatic patients (WD-A) compared to matched healthy controls and to rheumatoid arthritis (RA) control patients using The Hopkins Symptom Checklist. As hypothesized, WD-N patients had significantly lower interpersonal sensitivity and aggression/hostility scores than had healthy controls, but did not differ from them either in depression or anxiety levels. Retarded depression and anxiety were higher among RA patients than in WD-N patients. This nondistressed response to the chronic disabling disease was even more salient in 19 WD patients with lesions in basal ganglia only. WD-A patients did not differ from their healthy peers, which suggests a tendency towards hypercompensation and denial in the former. WD-N patients' limited awareness of their deficits (including impaired control of affective behavior) seems to result from their brain damage implicating the basal ganglia.
12707707 [Dissection of four cerebral arteries after protracted birth]. 2003 Apr A 37-year-old woman suffered from middle cerebral artery infarction secondary to dissection of the left internal carotid artery. Nine days before, a cesarean section had been performed on her after 20 h of unsuccessful labor. Cerebral angiography at admission revealed no further vascular abnormalities. A few days later, however, the patient developed additional dissections of the right internal carotid artery and both vertebral arteries. Pregnancy, childbirth, and a history of rheumatoid arthritis in this patient may have contributed to the dissections; however, due to the unknown etiology of cervical dissections, the pathogenetic contribution of all of these factors is incompletely understood.
15597212 Mini-open approach combined with percutaneous transarticular screw fixation for C1-C2 fusi 2005 Jan This paper describes a limited exposure for posterior C1-C2 arthrodesis aided by percutaneous transarticular fixation. The purpose of this study was to report the fusion rate using the aforementioned method. Fifty-seven patients (54 females and three males) with C1-C2 instability due to rheumatoid disease constituted the material of this study. The exposure was restricted to C0-C3 levels. The drilling and insertion of the screws was done through two mini stab wounds. A special sleeve and screwdriver were developed to facilitate this step. An autogenous iliac bone graft was fixed between the decorticated posterior arch of the atlas and the lamina of the axis vertebra. The mean of the atlantodental interval decreased from 8.5 mm (SD 2.3 mm) to 2.6 mm (SD 0.6 mm) at the immediate postoperative periods and reached 2.7 mm (SD 0.7 mm) after a mean follow-up of 30.4 months (SD 5.6 months). Malposition of the screws was observed in two patients and warranted a second operation in one. Fusion was evident in 98% of the cases. Percutaneous insertion of the screws in posterior C1-C2 transarticular fixation reduces the size of the exposure and the surgical trauma to the cervical segments below the fixation.
14600925 Preparation of Holmium-166 Labelled Macroaggregates for radionuclide synovectomy. 2003 BACKGROUND: Radionuclide synovectomy (radiation synovectomy) is an alternative method that cures patients with rheumatoid arthritis diseases without surgery. During treatment, the suspension of the (166)Ho-macroaggregates radioactive particles ((166)Ho-MA) is administrated via intra-articular injection into the target joint to destroy the inflamed synovium. MATERIAL AND METHODS: The isotope of (166)Ho (E(beta) max = 1.84 MeV, T((1/2)) = 26.8 hr) was prepared by the (165)Ho(n, gamma)(166)Ho reaction in the LWR-15 nuclear reactor (8-10 MW) using approximate neutron flux 10(14) cm-2s-1. RESULTS: The particles of Ho-Macroaggregates with suitable dimension 1-20 microm and the mean diameter of 8.5 microm were prepared. High in-vitro stability was obtained after incubation of neutron-irradiated Ho-Macroaggregates in saline solution (0.9% NaCl). The in-vivo stability on rats was verified as well. CONCLUSIONS: High in-vivo and in-vitro stability as well as supporting gamma radiation of Ho-166 make the Macroaggregates a prospective agent for radionuclide synovectomy. The method of preparation is relatively easy and allows for the production of particles of a suitable dimension with a sufficient amount of radioactivity of Ho-166 for the treatment of the rheumatoid arthritis.
12780696 Measurement of soluble Fcgamma receptor type IIIa derived from macrophages in plasma: incr 2003 Jun FcgammaRIII (CD16) is found in two alternative forms, a transmembrane FcgammaRIIIa expressed on NK cells and macrophages, and a glycosylphosphatidylinositol-linked FcgammaRIIIb present on neutrophils. Previously, we measured soluble FcgammaRIIIa (sFcgammaRIIIa) in plasma of NA(1 +, 2-) phenotyped donors with the anti-FcgammaRIII monoclonal antibody (MoAb) GRM1, which recognizes NA2-FcgammaRIIIb and FcgammaRIIIa. The level of sFcgammaRIIIa, as well as the total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb) in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy controls. In this study, we measured sFcgammaRIIIa(M)(phi) in plasma with a newly developed anti-FcgammaRIII MoAb, MKGR14 (mIgM), which recognizes FcgammaRIIIa(M)(phi) specifically. From the recovery of purified sFcgammaRIIIa(M)(phi), the amount of sFcgammaRIIIa(M)(phi) present was about half that of sFcgammaRIIIa(NK), and that of sFcgammaRIIIa was about 50 times lower than that of sFcgammaRIIIb in pooled plasma from healthy NA(1 +, 2-) phenotyped donors. The level of sFcgammaRIIIa(M)(phi) in RA patients was about four times higher than that in healthy controls. In RA patients, both the sFcgammaRIIIa(M)(phi) and sFcgammaRIIIa levels were increased as proportionally as the Lansbury Index. The sFcgammaRIIIa, but not sFcgammaRIIIa(M)(phi) levels, were increased directly proportional to C-reactive protein. sFcgammaRIIIa(M)(phi) may be a novel marker of disease activity in RA.
14711021 A new era in rheumatoid arthritis treatment. 2003 Rheumatoid Arthritis (RA) is a systemic autoimmune disease that primarily manifests as a chronic symmetric polyarthritis. Treatment in the past was aimed at symptomatic pain relief. The initiation of disease modifying anti-rheumatic drugs (DMARDs) was historically started only after significant disease activity was present in order to reduce side effects from drug toxicities. Unfortunately, irreversible joint damage may occur early in the disease course. Evidence of bony destruction is common on radiographs within the first 2 years after disease onset. Therefore, more aggressive treatment became the standard with earlier introduction of DMARDs in hopes of preventing joint destruction. Within the past few years, greater understanding of the pathophysiology of RA has permitted development of therapies targeted at specific cytokines. Tumor Necrosis Factor-alpha (TNF-alpha) is a pro-inflammatory cytokine believed to play a key role in the inflammatory response in RA. Three drugs--etanercept, infliximab, and adalimumab--are anti-TNF-alpha agents approved in the United States for the treatment of RA. This article is a review of indications, clinical trials, and toxicities of these 3 agents.