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ID PMID Title PublicationDate abstract
20681077 Polyethylene glycol–coated (PEG5000) gold nanoparticles. 2004 Gold nanoparticles belong to a small class of nanomaterials, while have been intensively investigated for biomedical use because of their excellent biocompatibility with human tissues and high affinity for functional groups such as thiols, phosphines, and amines (1-5). Gold nanoparticles have been approved by the United States Food and Drug Administration to treat human rheumatoid arthritis. They also have been used to enhance tumor sensitivity to radiation therapy. Surface-enhanced Raman scattering of gold nanoparticles has been tested for optical imaging of tumors (1, 6). Gold and gold-speckled silica nanoparticles have recently been developed as contrast agents for photoacoustic imaging (PAI) and multimodality imaging (3, 5, 7). Gold nanoparticles for PAI are based on either surface plasmon resonance (SPR) or fluorescent dyes attached to or encapsulated within nanoparticles. Nanoshells and nanorods are two representatives of SPR-based contrast agents (1, 7, 8). Peak absorption can be tuned throughout the visible and near-infrared (NIR) regions by controlling the physical dimensions of the metallic layer of nanoshells and the cylindrical symmetry of nanorods. Both nanoshells and nanorods exhibit good resistance to chemical/thermal denaturation and photobleaching. Dye-doped NIR nanoparticles function on the basis of strong optical absorption in the NIR region (3). Furthermore, dye encapsulation in nanoparticles significantly increases the circulation time of dyes in blood, allowing for extended imaging periods. On the other hand, proper comparison among nanoparticles appears difficult because shapes, sizes, materials, and mechanisms of different nanoparticles vary. Cai et al. reported the feasibility of gold nanoparticles modified with a methoxy-polyethylene glycol (PEG) sulhydryl moiety (molecular weight: 2.0 kDa) as a contrast agent for X-ray and computed tomography (MICAD chapter on PEG-AuNPs) (9). Recently, Zhang et al. modified gold nanoparticles with a PEG5000-thiol moiety and tested the PEGylated nanoparticles as a PAI contrast agent in vivo (5). Zhang et al. demonstrated the ability of PEGylated gold nanoparticles to detect tumors in vivo with photoacoustic tomography (PAT) (5). Their findings also suggest an opportunity for image-guided cancer therapy, with non-targeted gold nanoparticles serving as tumor-imaging contrast agents and mediators of cancer therapy.
15806729 Oral tolerance: overview and historical perspectives. 2004 Dec Oral tolerance was first detailed almost 100 years ago, and since then, it has been shown repeatedly that feeding a wide variety of nonpathogenic antigens can inhibit subsequent systemic immune responses. All systemic immune responses are susceptible, but the degree and scope of the suppression depends on the nature and dose of the fed antigen. Oral tolerance has been described in most mammals, including humans, and it may be the homeostatic mechanism that prevents hypersensitivity to food antigens, as is found in celiac disease. A similar process may prevent the aberrant immune responses to commensal bacteria that occur in inflammatory bowel disease. The ability of oral tolerance to modulate experimental models of autoimmune and inflammatory disease has led to clinical trials in such diseases as rheumatoid arthritis, multiple sclerosis, and type I diabetes, with only variable success. Despite intense research, the exact mechanisms responsible for the systemic tolerance and the reasons why tolerance is the default response to many fed antigens remain controversial. Early studies suggested that CD8(+) "suppressor" T cells were important, but it is now accepted that it may involve either anergy/deletion of CD4(+) T cells, or the induction of regulatory CD4(+) T cells that produce IL-10 and/or TGFbeta. There may also be a role for CD4(+) CD25(+) T(reg), but how and when all these different mechanisms operate is still unclear. The ability of fed antigens to induce tolerance probably reflects their uptake by "quiescent" antigen-presenting cells in the intestine, with presentation to specific CD4(+) T cells in the absence of costimulation, or with the involvement of inhibitory costimulatory molecules. Dendritic cells in the Peyer's patches or mucosal lamina propria are the most likely APCs involved, but it remains to be determined exactly where these interactions occur and what the precise nature of the relevant dendritic cells is.
15732722 [Use of meloxicam (movalis) in patients with rheumatic diseases with concomitant coronary 2004 The purpose of the study was to examine the clinical features of the course of coronary heart disease (CHD) in patients with rheumatoid arthritis (RA) and to evaluate the effects of the selective cyclooxygenase-2 (COG-2) inhibitor movalis (meloxicam) in two dosage forms (as injections and tablets) on the course of CHD in this group of patients. The developed questionnaire was used to make a comparative screening survey of 304 patients with RA and 152 patients with osteoarthrosis (OA), who were aged above 40 years. A comprehensive examination of the cardiovascular system was performed in 52 patients with RA concurrent with CHD and 25 patients with OA concurrent with CHD. Angina pectoris on exertion was detected in 37% of the patients with PA and in 35% of the patients with OA. Most (52%) patients with RA and CHD reported rare anginal attacks (once a month) whereas 24-day ECG monitoring revealed myocardial ischemia in 71% of the patients with RA concurrent with CHD; only silent ischemic episodes were recorded in 70% of them. The incidence of silent myocardial ischemia was higher in patients with RA concurrent with CHD than that in those with OA concurrent with CHD (p < 0.03). Examination of the incidence of anginal attacks showed that there was a tendency of the incidence of pains to decrease in patients with RA concurrent with CHD who took selective COG-2 inhibitors. Patients with RA concurrent with CHD who received movalis had atendency of arrhythmia to occur more rarely and of the duration of myocardial ischemia to reduce as compared with those who took nonselective COG-2 inhibitors.
15666726 An analysis of the microsporidian genus Brachiola, with comparisons of human and insect is 2004 Nov The genus Brachiola is the newest microsporidian genus established for a human infection with the type species being B. vesicularum in skeletal muscle. Subsequently, the microsporidium, Nosema algerae, identified from mosquitoes, was added to this genus because of morphological and physiological similarities. The present report illustrates a confirmed case of Brachiola algerae infecting skeletal muscle in a 56-year-old woman who was being treated for rheumatoid arthritis with immunosuppressive drugs. In the following study, these two human-infecting microsporidian species are ultrastructurally compared from human biopsy tissue. Additionally, Brachiola algerae from mosquitoes as reference B. algerae, was grown in athymic mice and compared to the human isolate in vivo, and in culture. B. algerae is morphologically identical in the host situations presented and different from B. vesicularum in human skeletal muscle. B. algerae has a consistently, slightly longer spore that typically contains one row of polar filament coils, while B. vesicularum typically contains two rows of polar filament coils and occasionally, one or three rows. In proliferative development, B. vesicularum forms protoplasmic extensions which do not occur on B. algerae, nor have they been reported on any other microsporidium. This report demonstrates that B. vesicularum and B. algerae are two different species of Brachiola that infect human skeletal muscle.
15645018 Focus on small molecule inhibitors for treatment of inflammatory and autoimmune diseases. 2004 Nov The 228th American Chemical Society (ACS) National Meeting was held August 22-26, 2004, in Philadelphia, Pennsylvania. More than 400 medicinal chemistry papers were presented, most in symposia, general sessions and poster sessions sponsored by the ACS Division of Medicinal Chemistry. One major focus of the meeting was the development of novel drugs for the treatment of inflammatory and autoimmune diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease (Crohn's disease), psoriasis, reperfusion injury and endotoxic shock. This report will center on said areas of research.
15526134 Simultaneous open and endoluminal repair of ruptured abdominal and thoracic aortic aneurys 2004 A 66-year-old woman was transferred to our hospital for emergency treatment of a ruptured abdominal aortic aneurysm (AAA) and impending rupture of a descending thoracic aortic aneurysm (TAA) caused by a Stanford type-B dissection. She had severe coronary artery disease and a highly calcified aorta, and had been taking long-term steroids for rheumatoid arthritis. Endovascular repair of the TAA failed because the femoral artery was too small, so we performed simultaneous repair of the TAA and the AAA. A temporary axillofemoral bypass was constructed and the AAA was replaced with a bifurcated prosthetic graft. A thoracic stent graft was delivered successfully through a chimney graft of the abdominal graft. About 4 months later, the TAA extended proximally, causing hemoptysis, which was stopped by placing a new stent graft proximal to the previous one. This case report shows that a combination of open and endovascular repair is useful for treating a TAA with an AAA, especially in a small or frail patient.
15487881 Risk assessment of NSAID-induced gastrointestinal toxicity in ambulatory care patients. 2004 Sep 15 PURPOSE: The risk of gastrointestinal (GI) toxicity associated with the use of a traditional nonsteroidal antiinflammatory drug (NSAID) versus a cyclooxygenase-2 (COX-2) inhibitor was compared among patients in a managed care organization. METHODS: Patients over 18 years old who received a prescription for ibuprofen, naproxen, celecoxib, or rofecoxib between March 2001 and June 2001 were included in this study. All subjects were followed for 12 months for GI complications, medication use, and changes in physical conditions from baseline. A simplified risk-scoring scale was used to measure patients' risk of GI complications. RESULTS: A total of 172 patients were randomly selected: 86 receiving traditional NSAIDs and 86 receiving COX-2 inhibitors. Patients receiving COX-2 inhibitors were older and more likely to be receiving treatment for osteoarthritis (OA) or rheumatoid arthritis (RA), while patients taking traditional NSAIDs were more likely to be receiving treatment for acute pain. The average risk scores for patients receiving traditional NSAIDs and COX-2 inhibitors were 0.23% and 0.36%, respectively (p = 0.11). When stratified by indication, there was a significant difference in the risk score for acute pain (p = 0.02) but not for OA, RA, or chronic pain. No GI adverse effects occurred in either group. CONCLUSION: Among patients in a managed care organization who were taking NSAIDs, most were at low risk for an NSAID-related GI adverse effect. The risk of GI adverse effects did not differ significantly between patients treated with a traditional NSAID and those treated with a COX-2 inhibitor.
15456709 Translating angiogenesis research into the clinic: the challenges ahead. 2003 The field of angiogenesis research has evolved to become one of the most rapidly growing biomedical disciplines. The interest in basic angiogenesis research is sparked by the translational therapeutic potential aimed at developing anti-angiogenesis as a novel therapeutic modality for tumours and a number of non-oncological diseases, such as rheumatoid arthritis, psoriasis, diabetic retinopathy and age-dependent macula degeneration. The molecular determinants of the angiogenic cascade have been characterized in great detail over the last few years. Likewise, intense ongoing efforts are aimed at identifying and validating additional vascular specific determinants that may be exploited as therapeutic targets for pro-angiogenic and anti-angiogenic therapy. At the same time, a large number of angiomodulatory compounds are in various phases of clinical trials. These include the neutralizing vascular endothelial growth factor (VEGF) antibody Avastin, which has successfully passed phase III clinical trials for the combination with chemotherapy in colorectal cancers. In view of the dramatic progress in basic angiogenesis research, surprisingly little is known about the nature of the neovasculature in human tumours. The inclusion and exclusion criteria of clinical trials of anti-angiogenic compounds are devoid of angiogenesis-related parameters and reliable biomarkers to trace the efficacy of an anti-angiogenic intervention are largely missing. Based on a brief review of the biology of the angiogenic cascade, this review provides an overview of the current concepts of the angiogenic vasculature in human tumours and discusses some key unanswered questions in translating angiogenesis research into the clinic.
15361392 Antiphospholipid syndrome associated with infections: clinical and microbiological charact 2004 Oct OBJECTIVE: To describe and analyse the clinical characteristics of 100 patients with antiphospholipid syndrome (APS) associated with infections. METHODS: Patients were identified by a computer assisted search (Medline) of published reports to locate all cases of APS published in English, Spanish, and French from 1983 to 2003. The bilateral Fisher exact test was used for statistics. RESULTS: 59 female and 41 male patients were identified (mean (SD) age, 32 (18) years (range 1 to 78)): 68 had primary APS, 27 had systemic lupus erythematosus, two had "lupus-like" syndrome, two had inflammatory bowel disease, and one had rheumatoid arthritis. APS presented as a catastrophic syndrome in 40% of cases. The main clinical manifestations of APS included: pulmonary involvement (39%), skin involvement (36%), and renal involvement (35%; nine with renal thrombotic microangiopathy, RTMA). The main associated infections and agents included skin infection (18%), HIV (17%), pneumonia (14%), hepatitis C (13%), and urinary tract infection (10%). Anticoagulation was used in 74%, steroids in 53%, intravenous immunoglobulins in 20%, cyclophosphamide in 12%, plasma exchange in 12%, and dialysis in 9.6%. Twenty three patients died following infections and thrombotic episodes (16 with catastrophic APS). Patients given steroids had a better prognosis (p = 0.024). The presence of RTMA and requirement for dialysis carried a worse prognosis (p = 0.001 and p = 0.035, respectively). CONCLUSIONS: Various different infections can be associated with thrombotic events in patients with APS, including the potentially lethal subset termed catastrophic APS. Aggressive treatment with anticoagulation, steroids, and appropriate antibiotic cover is necessary to improve the prognosis.
15320743 Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases 2004 Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor. To date, three PPARs isoforms have been isolated and termed alpha, beta (or delta), and gamma. Although PPAR gamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrated that PPAR gamma is present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D(2) (PGD(2)) metabolite, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), are well-known as ligands for PPAR gamma. After it has been reported that activation of PPAR gamma suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPAR gamma have grown and a huge research effort has been concentrated. PPAR gamma, is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Moreover, PPAR gamma ligands have potent tumor modulatory effects against colorectal, prostate, and breast cancers. Recent studies suggest that TZDs not only ameliorate insulin sensitivity but also have pleiotropic effects on many tissues and cell types. Although activation of PPAR gamma seems to have beneficial effects on atherosclerosis and heart failure, the mechanisms by which PPAR gamma ligands prevent the development of cardiovascular diseases are not fully understood. This review will focus on the latest developments in the PPAR gamma field and the roles of PPAR gamma-dependent pathway in cardiovascular diseases.
15257485 Percutaneous transarticular atlantoaxial screw fixation using a cannulated screw system an 2004 Apr In 2000 a cannulated screw stabilization system for posterior cervical instrumentation was introduced in our department for use in complex cervical fixation procedures. A special feature of the system is the use of thin Kirschner wires for drilling the screw paths and then placing the self-drilling, cannulated screws securely over the wires. Percutaneous application of C1-C2 transarticular screws is possible through tubes. An optional "atlas-claw" provides additional stability in cases of C1-C2 stabilization. 17 patients (10 female, 7 male, mean age 60 years) with complex cervical disorders and instability of different origin were stabilized using the Neon System (Ulrich Co., Ulm, Germany). Pathology included atlantoaxial instability based on rheumatoid arthritis (n = 12), odontoid fracture (n = 4) and os odontoideum mobile (n = 1). Computed navigation (STN 4.0, Zeiss or vector vision spine, brain lab) was used in 14 cases. Transarticular C1-C2 screw fixation was performed in 14 cases (4 patients with direct C1 massa lateralis screw fixation), craniocervical fixation (C0-C2/C3) was done in 3 patients. Percutaneous application of the C1-C2 screws was used in 7 patients. Atlas claws were applied in 8 patients. There was one medial perforation of a C2 pedicle wall and one malposition of the screw in C2 without reaching the lateral mass of C1. After a mean follow-up of 9 months there were no hardware failures and stable fusion in those cases followed after 12 months or more. Clinical results were excellent or good in 14/16 patients. Cannulated screws are an effective alternative in complex stabilization procedures of the cervical spine. The presented system is technically comfortable and allows safe percutaneous screw application as well as inclusion of computed navigation with high accuracy.
15251132 Therapeutic strategies to reduce IL-1 activity in treating local and systemic inflammation 2004 Aug All biological agents currently used for reducing TNFalpha activity in disease are neutralization strategies; however, there are several strategies for reducing interleukin (IL)-1 activities: the IL-1 receptor antagonist (IL-1Ra), anti-IL-1beta monoclonal antibodies, the IL-1 Trap, IL-1 receptor type I antibodies, antibodies to the IL-1 receptor accessory chain and inhibitors of IL-1beta-converting enzyme, now termed caspase-1. In fact, caspase-1 inhibitors are the first orally active agents that target cytokines, as these inhibitors prevent the processing and release of active forms for IL-1beta and IL-18, which is a member of the IL-1 family. The IL-1 Trap is a new concept in using soluble forms of cytokine receptors to bind and neutralize a specific cytokine. The Trap takes advantage of the high affinity of the two signaling chains of the cell surface IL-1 receptor linked by the Fc portion of IgG1. The IL-1Ra is currently approved to treat rheumatoid arthritis; in over 75 000 patients, the IL-1Ra has provided insights into the role of IL-1 in local and systemic inflammation, as well as the safety of long-term reduction of IL-1 activity.
15191406 Administration of exogenous tissue plasminogen activator reduces oedema in mice lacking th 2004 May It has recently become apparent that tissue plasminogen activator (tPA) modulates inflammation in diseases such as rheumatoid arthritis (RA) and acute respiratory distress syndrome (ARDS). We have shown previously that tPA has anti-inflammatory activity in in vivo models of oedema or inflammation. The present study investigated the ability of exogenous recombinant tPA (rtPA) to reduce carrageenan-mediated oedema in mice lacking the tPA gene, testing the hypothesis that rtPA treatment may be beneficial in diseases such as RA and ARDS in which there is a paucity of endogenous tPA. Knockout mice deficient in the tPA gene and matching wild-type mice received an intraplantar injection (25 micro L) of carrageenan (1.5%, w/v) following either vehicle (sterile water for injection) or tPA (12 mg/kg). Footpad oedema was measured, an oedema index was calculated and tissue myeloperoxidase (MPO) activity was determined. Mean oedema indices were higher in untreated tPA (-/-) mice than untreated wild-type mice. Pretreatment with rtPA in either tPA (-/-) or wild-type mice reduced the mean measured peak footpad oedema index by 63 and 48%, respectively. Tissue MPO activity was not different between treatment groups. We conclude that exogenous rtPA has the ability to reduce acute oedema without altering neutrophil infiltration into the site of injury in both tPA (-/-) and wild-type mice and that endogenous tPA may participate in the inflammatory process, as evidenced by higher oedema indices in untreated tPA (-/-) mice. These data provide support for the potential clinical utility of exogenous rtPA in the treatment of inflammatory diseases, such as RA and ARDS, in which there is a paucity of tPA.
15186263 Natural killer T cells as targets for immunotherapy of autoimmune diseases. 2004 Jun CD1d-restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during an immune response. The identification of alpha-galactosylceramide (alpha-GalCer), a marine sponge-derived glycosphingolipid, as a potent stimulator of NKT cells led many laboratories to investigate the effects of NKT cell activation on the regulation of immune responses. These studies revealed that alpha-GalCer induces rapid and robust cytokine production by NKT cells, secondary activation of a variety of innate and adaptive immune cells, and modulation of Th cell responses. Further, alpha-GalCer influences disease progression in a variety of experimental models of autoimmunity and inflammation in mice, including models for type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and atherosclerosis. While these studies have raised significant enthusiasm for manipulation of NKT cells as a means of preventing autoimmunity in the clinical setting, there are significant concerns regarding the safety of repeated alpha-GalCer injections in human subjects.
15161923 ADAMTS4 (aggrecanase-1) interaction with the C-terminal domain of fibronectin inhibits pro 2004 Jul 30 ADAMTS4 (aggrecanase-1), a secreted enzyme belonging to the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family, is considered to play a key role in the degradation of cartilage proteoglycan (aggrecan) in osteoarthritis and rheumatoid arthritis. To clone molecules that bind to ADAMTS4, we screened a human chondrocyte cDNA library by the yeast two-hybrid system using the ADAMTS4 spacer domain as bait and obtained cDNA clones derived from fibronectin. Interaction between ADAMTS4 and fibronectin was demonstrated by chemical cross-linking. A yeast two-hybrid assay and solid-phase binding assay using wild-type fibronectin and ADAMTS4 and their mutants demonstrated that the C-terminal domain of fibronectin is capable of binding to the C-terminal spacer domain of ADAMTS4. Wild-type ADAMTS4 was co-localized with fibronectin as determined by confocal microscopy on the cell surface of stable 293T transfectants expressing ADAMTS4, although ADAMTS4 deletion mutants, including Delta Sp (Delta Arg(693)-Lys(837), lacking the spacer domain), showed negligible localization. The aggrecanase activity of wild-type ADAMTS4 was dose-dependently inhibited by fibronectin (IC(50) = 110 nm), whereas no inhibition was observed with Delta Sp. The C-terminal 40-kDa fibronectin fragment also inhibited the activity of wild-type ADAMTS4 (IC(50) = 170 nm). These data demonstrate for the first time that the aggrecanase activity of ADAMTS4 is inhibited by fibronectin through interaction with their C-terminal domains and suggest that this extracellular regulation mechanism of ADAMTS4 activity may be important for the degradation of aggrecan in arthritic cartilage.
15127974 Leflunomide for chronic sarcoidosis. 2004 Mar BACKGROUND AND AIM: Leflunomide (Arava) is a cytotoxic drug which has been used as a single agent or in combination with methotrexate for the treatment of rheumatoid arthritis. It appears to have less toxicity than methotrexate. The use of leflunomide for sarcoidosis patients has not been systematically evaluated. METHODS: The records were reviewed from all patients treated at a tertiary sarcoidosis center from July 2002-July 2003, and information from patients treated with either leflunomide or methotrexate was analyzed for efficacy and toxicity. RESULTS: Thirty-two patients were treated with leflunomide; fifteen patients received concurrent therapy with methotrexate. The most common indications for therapy were ocular and lung disease. Complete or partial response to leflunomide was seen in 12 of 17 treated with leflunomide alone, and 13 of 15 treated with leflunomide plus methotrexate. There was no difference in the response rate for eye [23/28 (82%)] versus pulmonary disease [12/16 (75%)]. Seventeen patients were treated with leflunomide alone because of methotrexate toxicity (nausea in 12 and pulmonary symptoms in five). All but two tolerated leflunomide. Three patients experienced nausea leading to drug discontinuation, but no other serious adverse reaction was encountered with leflunomide. CONCLUSION: Leflunomide was well tolerated in patients with chronic sarcoidosis. It appears to be as effective as methotrexate, with less toxicity. It should be considered as an alternative in chronic sarcoidosis patients who cannot tolerate methotrexate.
15114258 [Effect of methotrexate on the immune response in selected experimental models]. 2004 Apr 20 Methotrexate (MTX) is one of the immunosuppressory compounds applied in the prophylaxis and treatment of several diseases, including: rheumatoid arthritis, systemic lupus erythematosus, psoriasis, graft-versus-host disease and, in combination with other drugs, neoplastic diseases. Studies in humans and in animal model, of clinical disease, have demonstrated that MTX diminishes the clinical symptoms of various immunological disorders. MTX, an antagonist of folic acid synthesis, causes apoptosis in activated cells, primarily in the G1 and S phases of the cell cycle. One of its actions, is inhibition of the synthesis or activity of several proinflammatory cytokines. At high doses, MTX is cytotoxic to hemopoietic cells; low doses, however, promote hemopoiesis. MTX also induces the differentiation of monocytic tumor cells, which may explain, in part, its therapeutic effects in the treatment of some disorders. The compound suppresses both cellular and humoral immune response and mitogen-induced lymphocyte proliferation. These effects are dose- and time-dependent. The strongest suppressory activity is exerted when MTX is applied 24 or 48 hours after immunization or mitogen stimulation. Administration of MTX in unfavorable conditions such as stress or other diseases, diminishes its tolerance and increases its toxicity. Side-effects of MTX may be ameliorated by application of pharmacological synthetic agents and plant extracts. In summary, MTX has been an effective agent in suppressing immunological disorders (for 50 years) and is still finding many applications.
15080948 Posterior transarticular screw fixation for chronic atlanto-axial instability. 2004 May Treatment for chronic atlanto-axial instability remains problematic despite recent innovations in new surgical techniques and instrumentation. Our team reviewed a series of 23 cases of patients with chronic atlanto-axial instability who underwent posterior transarticular screw fixation operations between May 1998 and September 2002. Etiologies of these patients included failed prior surgery, rheumatoid arthritis, congenital anomalies and old odontoid fractures. The clinical presentations were nuchal pain and cervical myelopathy or radiculopathy, with sensory and/or motor deficits that persisted for more than 3 months. We routinely used external reduction to realign the C1-C2 axis prior to operating, and operated on patients using halo-vest fixation. After surgery, the halo-vest was replaced by a collar. In the post-operative follow-up, 22 of the 23 patients (96%) were found to have achieved solid, bony or fibrous union of the C1-C2 axis. Eleven of the 14 (79%) patients with pre-operative neck pain experienced immediate relief or significant improvement. Thirteen of the 20 patients (65%) with myelo-radiculopathy demonstrated improvement of previous motor deficits. Major morbidity included a vertebral artery (VA) injury and a malpositioned screw. No cases of mortality or neurological complications occurred in this series. Posterior transarticular C1-C2 screw fixation results in a high fusion rate without the additional need for rigid external immobilization. It allows good neurological recovery in cases of chronic atlanto-axial instability. Judicious pre-surgical planning and meticulous operative technique may avoid neurological complications and vertebral artery injury.
14994410 Prevalence of rheumatic diseases in Brazil: a study using the COPCORD approach. 2004 Mar OBJECTIVE: To estimate the prevalence of rheumatic diseases in residents of Montes Claros, Brazil, of both sexes, aged above 16 years, using the COPCORD questionnaire. METHODS: This was a cross-sectional study of 3038 people; the sample was probabilistic, by conglomerates, multiple stages, within homogeneous strata, the sampling unit being the domicile. The COPCORD questionnaire was used for all subjects, and a rheumatologist evaluated those patients who presented pain and/or functional disability. Laboratory tests and radiographs of small and large joints were done in some patients to confirm the diagnosis. Subjects were identified by socioeconomic level in quintiles A, B, C, D, and E, A being the highest. RESULTS: Two hundred nineteen patients were identified with rheumatic diseases, mean age 37 (SD 27) years, with female predominance. Seventy-seven (35.2%) were unemployed and socioeconomic level D was the most prevalent. Of all patients with rheumatic disease, osteoarthritis (OA) was observed in 126 (57.5%) patients, fibromyalgia (FM) in 76 (34.7%), rheumatoid arthritis (RA) in 14 (6.4%), and lupus in 3 (1.4%). Women were predominant in all diseases except OA. The mean (SD) age was 56 (12.7) years for OA, 43.2 (9.1) for FM, 53.4 (13.9) for RA, and 40 (14) for lupus. CONCLUSION: The prevalence of rheumatic diseases evaluated by the COPCORD questionnaire was 4.14% for OA, 2.5% for FM, 0.46% for RA, and 0.098% for lupus.
14719376 Role of C1q and C1q receptors in the pathogenesis of systemic lupus erythematosus. 2004 The association between C1q and autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE) is well established. Deficiency in C1q is considered to be a strong susceptibility factor and is corroborated by the fact that > or = 92% of the known cases of hereditary deficiency in C1q develop rheumatic disease. Furthermore, the observation of the presence of high-affinity autoantibodies against C1q antibodies in patients with SLE provides a strong correlation between these antibodies and the inflammatory processes that occur in this disease. Recent evidence using C1q-deficient mice has shown the presence of glomerulonephritis with immune deposits and a large number of apoptotic bodies in the diseased glomeruli suggesting a defect in the clearance of apoptotic cell by macrophages and dendritic cells (DCs). Although these data are consistent with the hypothesis that C1q deficiency may induce a generalized failure to clear immune complexes and apoptotic cells, this concept alone cannot wholly explain why individuals with C1q deficiency are prone to develop SLE. Therefore, C1q alone or in conjunction with other surface molecules must play a much more fundamental role in immunoregulation, especially those processes that regulate T cell function and tolerance. In support of this hypothesis is the finding that C1q causes inhibition of mitrogen-induced T cell-proliferative response by interaction with C1q receptors. Furthermore, macrophages and possibly DCs not only synthesize but also display C1q as a type II cell surface molecule, especially at sites of inflammation. Although it is not yet known what role the surface-expressed C1q plays, it is tempting to assume that it plays a role in the priming of naïve T cells by DCs. This work will review the current concepts of the role of C1q and C1q receptors in autoimmunity.