Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17043481 Validation and crosscultural adaptation of an argentine spanish version of the health asse 2004 Jun BACKGROUND: The Health Assessment Questionnaire (HAQ) is one of the most frequently used instruments to assess functional capacity in activities of daily living. OBJECTIVE: The objective of our study was to determine the reproducibility and validity of an Argentinean version of the HAQ disability index (HAQ-DI) in patients with rheumatoid arthritis (RA). METHODS: Consecutive adult patients with RA from 3 different provinces in Argentina were included. The original English version of the HAQ-DI was translated and adapted into Spanish by 3 rheumatologists and the final version back translated into English by a bilingual person. The reproducibility of the questionnaire was assessed in 30 patients who came for a second visit 3 to 5 days later. The cross-sectional construct validity was assessed by comparing the HAQ with classic parameters of disease activity (number of swollen and tender joints, patient and physician visual analog scale for pain and activity as well as functional class, erythrocyte sedimentation rate, and C-reactive protein. RESULTS: Two hundred patients with RA were included. The reproducibility was r = 0.97 (P = 1 x 10-5); intraitem correlation analysis did not show any redundancy. Correlation between HAQ-A and parameters of disease activity were all significant. A stepwise multiple regression analysis showed that the main variables associated with HAQ-A scores were visual analog scale for pain and duration of morning stiffness. A weak although significant negative correlation was found between the HAQ-A and economic level (r = -0.21, P = 0.03). The median time to complete the questionnaire was 5 minutes and there were no problems with any questions. CONCLUSION: This version of the HAQ-DI would allow for more availability so that Spanish-speaking countries can select the version most suitable to their sociocultural environment.
15688804 [Retrospective study of 97 ANCA-positive patients: epidemiologic and clinical spectrum]. 2004 Apr We analysed the clinical profile of antineutrophil cytoplasmic antibodies (ANCA) positive patients in a retrospective study including all cases of ANCA positivity (determined by ELISA) from the Nephrology Clinic, Parhon University Hospital Iasi during the interval 1998-2003. There were 97 ANCA positive patients (mean age 43.7 ÅŸ18-75Å£ years, female/male ratio 1.55), of whom almost two thirds had c-ANCA, almost one third p-ANCA, while 9 patients had both types of antibodies. The incidence was 22.5/pmp for the North-Eastern province of Romania. Just 19.3% from the suspected cases with ANCA-associated disease were positive for these antibodies. 47.7% had systemic vasculitis (10 with microscopic polyangiitis--MA, 6 with Wegener's granulomatosis--WG, 1 with Churg-Strauss angiitis, 29 with non-specific vasculitis--NSV). Twenty-seven (27.8%) had connective tissue disease--CTD (systemic lupus erythematosus, rheumatoid arthritis, polymyositis, systemic sclerosis, mixed connective tissue disease, and sarcoidosis), while in 5 cases ANCA were associated with other diseases. Nine cases presented with rapid progressive glomerulonephritis (RPGN) without signs of systemic involvement, and other ten with advanced chronic renal failure (CRF). The most frequent clinical manifestations involved the kidney (71%), the skin, the muscles and joints, and the cardiovascular system. CONCLUSIONS: ANCA positivity is associated with a wide spectrum of diseases, mostly with CTD and NSV. c-ANCA was predominantly seen in WG and advanced CRF, while p-ANCA was associated with MA. In nonspecific vasculitis and connective tissue diseases, both patterns were present. We recommend ANCA determination as a screening method in all cases with renal dysfunction and nephritic syndrome and/or with signs of systemic vasculitis and/or collagenosis.
15681803 Inflammation and the degenerative diseases of aging. 2004 Dec Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson-dementia complex of Guam, all of the tauopathies, and age-related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two-edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte-directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue-based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti-inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti-inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti-inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti-inflammatory agents, are needed to achieve the suggested neurological benefits.
15544035 Complexity in the vascular permeability factor/vascular endothelial growth factor (VPF/VEG 2004 Sep The adult vasculature results from a network of vessels that is originally derived in the embryo by vasculogenesis, a process whereby vessels are formed de novo from endothelial cell (EC) precursors, known as angioblasts. During vasculogenesis, angioblasts proliferate and come together to form an initial network of vessels, also known as the primary capillary plexus. Sprouting and branching of new vessels from the preexisting vessels in the process of angiogenesis remodel the capillary plexus. Normal angiogenesis, a well-balanced process, is important in the embryo to promote primary vascular tree as well as an adequate vasculature from developing organs. On the other hand, pathological angiogenesis which frequently occurs in tumors, rheumatoid arthritis, diabetic retinopathy and other circumstances can induce their own blood supply from the preexisting vasculature in a route that is close to normal angiogenesis. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is perhaps the most important of pro-angiogenic cytokine because of its ability to regulate most of the steps in the angiogenic cascade. The main goal of this review article is to discuss the complex nature of the mode of action of VPF/VEGF on vascular endothelium. To this end, we conclude that more research needs to be done for completely understanding the VPF/VEGF biology with relation to angiogenesis.
15381284 Isolectin B4 binding neurons are not present in the rat knee joint. 2004 Small-diameter sensory neurons are key contributors in joint pain and have been implicated in the pathogenesis of rheumatoid arthritis (RA). Small-diameter sensory neurons can be separated into at least two distinct populations, which include isolectin B4 (IB4)-binding and tyrosine receptor kinase (trk) A-expressing. While trkA-expressing neurons have been identified in the rat knee joint there are no data, we are aware of, to suggest that IB4-binding neurons are also present. We aimed to determine whether or not there exists a population of IB4-binding neurons in the rat knee joint. Retrograde nerve tracing with fluoro-gold (FG) was used to identify the complete population of knee joint afferents in the lumbar dorsal root ganglia (DRG) L3 and L4 of female Wistar rats. IB4 conjugated to fluorescein isothiocyanate (FITC) was used to identify the cell bodies of IB4-binding neurons in the DRG. Of 1096 FG-labeled cell bodies in the DRG of knee joint injected animals (n=4), none were double labeled with FITC. Injection of FG into skin over the medial aspect of the rat knee (n=3) showed 48% of these cutaneous afferents in L3 and L4 DRG were double-labeled with FG and FITC. A complete absence of IB4-binding neurons in the rat knee joint makes it unlikely that this predominantly cutaneous, IB4-binding population of afferent neurons could have any significant influence in chronic inflammatory joint disease. This suggests that trkA-expressing neurons are the sole population of small-diameter sensory neurons in the knee joint and implies a significant role for these afferents in the progression of RA.
15166995 Silicone breast implants and connective tissue disease: an updated review of the epidemiol 2004 Jun Numerous meta-analyses, weight-of-the-evidence, and critical reviews have summarized data from case-control and cohort studies, published through 1999, which have been conducted to evaluate the potential association between cosmetic silicone breast implants and the occurrence of well-defined connective tissue diseases, as well as a hypothesized new atypical disease, which does not fulfill established diagnostic criteria for any known connective tissue disease. These reviews have unanimously concluded that there is no evidence of an association between breast implants and any of the traditional connective tissue diseases evaluated individually or combined or atypical connective tissue disease. We have performed an updated review of the results of epidemiologic studies published since 1999. Two long-term follow-up studies of women with breast implants in Denmark and a retrospective cohort study in Australia found no excess of definite connective tissue disease, including rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus and Sjogren's syndrome, among women with cosmetic breast implants compared with breast reduction or other plastic surgery controls or women in the general population. No consistent evidence was observed of increased risk of definite connective tissue disease in women with extracapsular ruptures in 2 studies which evaluated risk by rupture status among women with cosmetic breast implants. The results of several studies provide no evidence of a higher frequency of undefined connective tissue disease among women with cosmetic breast implants or of a rheumatic symptom profile unique to these women and/or indicative of a specific atypical connective tissue disease. In conclusion, the most recent epidemiologic investigations have been remarkably consistent with earlier epidemiologic studies in finding no evidence of an excess of any individual connective tissue disease or all connective tissue diseases combined, including both established and atypical or undefined connective tissue disease, among women with cosmetic silicone breast implants. Thus, the conclusions reached in earlier independent reviews have not changed based on data published during the subsequent years.
14702193 Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relev 2004 Jan Complement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles and altered self cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The initial activation of the alternative complement pathway occurs continuously and the early phase acts indiscriminatoryl and forms on any surface. However, the system discriminates between self and foreign, and therefore allows activation on foreign surfaces e.g. microbes, and restricts activation on host cells. Consequently, self cells and tissues are protected from the harmful activation products. This protection is mediated by specific regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound forms. Here we review a novel mechanism, i.e. the attachment of the soluble complement regulator factor H to the surface of self cells. This attachment, which is demonstrated experimentally by means of immunofluorescense microscopy and by flow cytometry, increases the inhibitory potential at the cell surface and mediates protection by reducing the local formation of toxic inflammatory products. This attachment is highly relevant and has pathophysiological consequences in several human diseases, including Factor H-associated hemolytic uremic syndrome (FH-HUS), membrano-proliferative glomerulonephritis type II, recurrent microbial infections and chronic inflammation, e.g. rheumatoid arthritis and immune evasion of tumor cells. Defects of this safeguard activity have been recently understood in patients with FH-HUS. Point mutations in the Factor H gene occurring in the C-terminus of the protein result in impaired cell binding capacity of Factor H and, consequently, during an inflammatory insult endothelial cells are not properly protected and are damaged.
12973717 Expression of estrogen receptor alpha (ER alpha) in the rat temporomandibular joint. 2003 Oct Numerous epidemiological studies have pointed out a higher frequency of temporomandibular disorder (TMD) in women than in men, which indicates the involvement of a sex hormone, such as estrogen, in the pathogenesis of TMD. Although estrogen is known to play pivotal roles in osteoarthrosis or rheumatoid arthritis in systemic joints, there have been few reports about the role of estrogen in the temporomandibular joint (TMJ). The effect of estrogen is generally mediated by the estrogen receptors (ERs) ER alpha (the predominant type) and ER beta. In this study we examined the expression of ER alpha protein and mRNA in the TMJ of adult male rats by immunocytochemistry and in situ hybridization histochemistry. Intense ER alpha immunoreactivity was localized in the synovial lining cells, stromal cells in the articular disc, and chondrocytes in the TMJ. These ER alpha-immunopositive synovial lining cells are characteristic of cytoplasmic processes identified with confocal and immunoelectron microscopy, which indicates that they are synovial type B cells. In situ hybridization histochemistry confirmed intense signals for ER alpha in the synovial lining cells and the sublining fibroblasts at mRNA levels. The nuclei of chondrocytes showed an intense immunoreaction for ER alpha in the maturative and hypertrophic layers of the articular cartilage. In addition to the nuclear localization of ER alpha, a weak immunoreaction appeared in the cytoplasm of some ER alpha-positive cells. These findings support the hypothesis that TMJ tissue-at least in the male rat-has the potential to be an estrogen target tissue.
12960479 The central role of dendritic cells and interferon-alpha in SLE. 2003 Sep PURPOSE OF REVIEW: Until recently, systemic lupus erythematosus has been viewed mainly as a B-cell disease resulting from altered T cell-B cell interactions. The recognition of the fundamental role of dendritic cells in the control of tolerance and immunity led to the hypothesis that systemic lupus erythematosus may be driven through unabated dendritic cell activation. This review summarizes the recently uncovered role of dendritic cell subsets and one of their products, interferon-alpha, in the pathophysiology of systemic lupus erythematosus. RECENT FINDINGS: CD14+ monocytes isolated from the blood of patients with systemic lupus erythematosus, but not those from healthy individuals, act as dendritic cells. Their activation is driven by circulating interferon-alpha that may come from one of the dendritic cell subsets (ie, plasmacytoid dendritic cells that infiltrate systemic lupus erythematosus skin lesions). Although only a fraction of patients with active systemic lupus erythematosus show circulating interferon-alpha, blood mononuclear cells from all of them display an interferon-alpha signature. SUMMARY: The disease model that the authors propose places interferon-alpha at the center of the immunologic abnormalities observed in systemic lupus erythematosus, and poses interferon-alpha and/or interferon-alpha-producing cells as novel targets for therapy in this disease. The authors surmise that type I interferon antagonists will bring systemic lupus erythematosus patients the relief that tumor necrosis factor antagonists brought to patients with rheumatoid arthritis.
12738993 Tetraarsenic oxide, a novel orally administrable angiogenesis inhibitor. 2003 Jun Arsenic compounds have been used to treat angiogenic diseases such as cancer, psoriasis, and rheumatoid arthritis in traditional oriental medicine. In recent years, arsenic trioxide (As2O3, diarsenic oxide) has been successfully used to treat acute promyelocytic leukemia. We investigated the antiangiogenic properties of tetraarsenic oxide (As4O6), another trivalent arsenic compound. In in vitro studies, tetraarsenic oxide inhibited the proliferation (IC50 = 99.7 nM), migration into the denuded area (IC50 = 27.4 nM), and invasion through a layer of Matrigel (IC50 = 73.5 nM) of basic fibroblast growth factor (bFGF)-stimulated bovine capillary endothelial (BCE) cells in a dose-dependent manner. Tetraarsenic oxide also inhibited the tube formation of human umbilical vein endothelial cells. Tetraarsenic oxide induced cell cycle arrest of bFGF-stimulated BCE cells in the G2/M phase and inhibited the secretion of matrix metalloproteinase-2 from BCE cells. Orally administered tetraarsenic oxide (50 mg/kg/day) inhibited bFGF-induced new-vessel formation in a rat corneal micropocket assay, and reduced by about 54% the number of experimental pulmonary metastatic nodules in mice implanted with B16F10 melanoma cells. Thus, we provide evidence that tetraarsenic oxide has effective antiangiogenic activities.
12735376 First metatarsal-phalangeal joint arthrodesis: a biomechanical assessment of stability. 2003 Apr BACKGROUND: First metatarsal phalangeal joint (MTP) arthrodesis is a commonly performed procedure for the treatment of hallux rigidus, severe and recurrent bunion deformities, rheumatoid arthritis and other less common disorders of the joint. There are different techniques of fixation of the joint to promote arthrodesis including oblique lag screw fixation, lag screw and dorsal plate fixation, crossed Kirschner wires, dorsal plate fixation alone and various types of external fixation. Ideally the fixation method should be reproducible, lead to a high rate of fusion, and have a low incidence of complications. METHODS: In the present study, we compared the strength of fixation of five commonly utilized techniques of first MTP joint arthrodesis. These were: 1. Surface excision with machined conical reaming and fixation with a 3.5 mm cortical interfragmentary lag screw. 2. Surface excision with machined conical reaming and fixation with crossed 0.062 Kirschner wires. 3. Surface excision with machined conical reaming and fixation with a 3.5 mm cortical lag screw and a four hole dorsal miniplate secured with 3.5 mm cortical screws. 4. Surface excision with machined conical reaming and fixation with a four hole dorsal miniplate secured with 3.5 mm cortical screws and no lag screw. 5. Planar surface excision and fixation with a single oblique 3.5 mm interfragmentary cortical lag screw. Testing was done on an Instron materials testing device loading the first MTP joint in dorsiflexion. Liquid metal strain gauges were placed over the joint and micromotion was detected with varying loads and cycles. RESULTS: The most stable technique was the combination of machined conical reaming and an oblique interfragmentary lag screw and dorsal plate. This was greater than two times stronger than an oblique lag screw alone. Dorsal plate alone and Kirschner wire fixation were the weakest techniques. CONCLUSIONS: First MTP fusion is a commonly performed procedure for the treatment of a variety of disorders of the first MTP joint. The most stable technique for obtaining fusion in this study was the combination of an oblique lag screw and a dorsal plate. This should lead to higher rates of arthrodesis.
12646580 A fusion protein of the gp130 and interleukin-6Ralpha ligand-binding domains acts as a pot 2003 May 9 Interleukin (IL)-6 is involved in the maintenance and progression of several diseases such as multiple myeloma, rheumatoid arthritis, or osteoporosis. The present work aims at the development of an IL-6 inhibitor for the use in anti-cytokine therapies. The IL-6 receptor is composed of two different subunits, an alpha-subunit (IL-6Ralpha) that binds IL-6 with low affinity and a beta-subunit (gp130) that binds the IL-6.IL-6Ralpha complex with high affinity and as a result triggers intracellular signaling. In its soluble form, gp130 is a natural antagonist that neutralizes IL-6.soluble IL-6Ralpha complexes. It was our strategy to appropriately fuse the two receptor subunit fragments involved in IL-6 receptor complex formation to bind IL-6 with high affinity and to antagonize its effects. The ligand-binding domains of gp130 (D1-D2-D3) and IL-6Ralpha (D2-D3) were connected using three different linkers. The resulting constructs were expressed in stably transfected insect cells and tested for their ability to inhibit IL-6 activity in several in vitro systems. All fusion proteins were strong inhibitors of IL-6 signaling and abrogated IL-6-induced phosphorylation of STAT3, proliferation of transfected Ba/F3 cells, and induction of acute-phase protein synthesis. As intended, the fused receptors were much more effective than the separately expressed soluble receptor proteins. The fusion protein strategy presented here can also be applied to other cytokines that signal via receptors composed of two different subunits to design new potent inhibitors for anti-cytokine therapies.
12641490 Inhibitors of p38 mitogen-activated protein kinase: potential as anti-inflammatory agents 2003 Asthma is an inflammatory disease of the airways, which in patients with mild to moderate symptoms is adequately controlled by either beta(2)-adrenoceptor agonists or corticosteroids, or a combination of both. Despite this, there are classes of patients that fail to respond to these treatments. In addition, there is a general trend towards increasing morbidity and mortality due to asthma, which suggests that there is a need for new and improved treatments. The p38 mitogen-activated protein kinases (MAPKs) represent a point of convergence for multiple signalling processes that are activated in inflammation and that impact on a diverse range of events that are important in inflammation. Small molecule pyridinyl imidazole inhibitors of p38 MAPK have proved to be highly effective in reducing various parameters of inflammation, in particular cytokine expression. Like corticosteroids, inhibitors of p38 MAPK appear to be able to repress gene expression at multiple levels, for example, by transcriptional, posttranscriptional and translational repression, and this raises the possibility of a similarly broad spectrum of anti-inflammatory activities. Indeed these molecules have proved to be effective in numerous in vitro and in vivo models of inflammation and septicaemia, which suggests that such compounds may be effective as therapeutic agents against inflammatory disorders. Despite these very promising indications of the possible therapeutic use of p38 MAPK inhibitors, a number of events that are p38-dependent are in fact also beneficial to the resolution or modulation of diseases such as asthma. We conclude that the overall effect of p38 MAPK inhibition would be beneficial in inflammatory diseases such as rheumatoid arthritis and asthma. However, these drugs may result in a complex phenotype that will require careful evaluation. Currently, a number of second or third generation inhibitors of p38 MAPK are being tested in phase I and phase II clinical trials.
12605039 Systemic linoleic and gamma-linolenic acid therapy in dry eye syndrome with an inflammator 2003 Mar PURPOSE: To evaluate the efficacy and anti-inflammatory activity of systemic linoleic (LA) and gamma-linolenic acid (GLA), which decrease chronic inflammation in rheumatoid arthritis, on the ocular surface of patients with keratoconjunctivitis sicca. METHODS: In a randomized clinical trial, 26 patients with aqueous-deficient keratoconjunctivitis sicca were consecutively selected from patients presenting to Department of Neurosciences, Ophthalmology and Genetics, University of Genoa. The diagnosis was based on dry eye symptom survey score, Schirmer-1 test values, positive vital staining with lissamine green, and fluorescein break-up time (FBUT). All patients had ocular surface inflammation based on HLA-DR expression, a major histocompatibility class II antigen, on epithelial bulbar conjunctiva samples. The subjects were randomly divided into two groups of 13 patients each. The study group received tablets containing LA (28.5 mg) and GLA (15 mg) twice daily for 45 days and used tears; the control group received a tear substitute and a placebo tablet for 45 days. RESULTS: Statistically significant changes in symptoms (p < 0.005), lissamine green staining (p < 0.005), and ocular surface inflammation (p < 0.05) occurred in the study group compared with controls. HLA-DR expression varied from 58.5 +/- 14.1% positive conjunctival cells to 41.3 +/- 18.9% in the treated group and from 61.4 +/- 21.9% to 58.0 +/- 13.3% in the controls. No statistically significant difference between groups was found for FBUT and the Schirmer-1 test. CONCLUSIONS: Therapy with LA and GLA and tear substitutes reduces ocular surface inflammation and improves dry eye symptoms. Long-term studies are needed to confirm the role of this new therapy for keratoconjunctivitis sicca.
12473262 Gold sodium thiomalate (GSTM) inhibits lipopolysaccharide stimulated tumor necrosis factor 2002 Sep TNF-alpha has emerged as the major pro-inflammatory cytokine involved in the pathogenesis of rheumatoid arthritis (RA). LPS is a potent stimulator of TNF-alpha production by human monocytes. Ceramide, a structural homolog of LPS and a second messenger in the sphingomyelin signal transduction pathway has been shown to stimulate TNF-alpha production from murine macrophages. We have previously shown that GSTM, an anti-rheumatic drug inhibits LPS stimulated TNF-alpha production by normal PBMCs. We studied the ability of ceramide to stimulate TNF-alpha production by human PBMCs and the mechanism of action of GSTM on ceramide and LPS induced TNF-alpha production. LPS induced significant TNF-alpha production in PBMCs and THP-1. However, C(2) ceramide stimulated TNF-alpha production in 5 of 10 PBMCs (ceramide responder); it did not do so in the other 5 PBMCs (ceramide non-responder) or the THP-1 cell line. GSTM inhibited LPS stimulated TNF-alpha productions in PBMCs of all 5 ceramide responders both at protein and mRNA expression level. We also found that GSTM inhibited LPS induced NF-kappaB level only in ceramide responder. Thus, we for the first time report that GSTM inhibits LPS stimulated TNF-alpha production through ceramide pathway and anti-inflammatory activity of GSTM in treatment of RA may depend on its ability to inhibit NF-kappaB activation and TNF-alpha production.
12447049 Wet wound healing. 2002 Dec Wound treatment in a flexible transparent chamber attached to the perimeter of the wound and containing a liquid has been extensively tested in preclinical experiments in pigs and found to offer several advantages. It protects the wound; the liquid medium or saline in the chamber provides in vivo tissue culture-like conditions; and antibiotics, analgesics, and various molecules can be delivered to the wound through the chamber. The wound chamber causes no injury to the wound itself or to the surrounding intact skin. Topical delivery of, for instance, antibiotics can provide very high concentrations at the wound site and with a favorable direction of the concentration gradient. A series of 28 wounds in 20 patients were treated with a wound chamber containing saline and antibiotics. Most patients had significant comorbidity and had not responded to conservative or surgical management with débridement and delayed primary closure or skin grafts. Six wounds had foreign bodies present; four of these were joint prostheses. Seven patients were on corticosteroids for rheumatoid arthritis, lupus, or chronic obstructive pulmonary disease, and four patients had diabetes. Most patients were treated with the wound chamber in preparation for a delayed skin graft or flap procedure, but one was treated with a wound chamber until the wound healed. Twenty-five of the wounds (89 percent) healed, and five wounds (18 percent) required additional conservative management after the initial chamber treatment and grafting procedure. Of the three wounds that did not heal, one healed after additional chamber treatment, one had a skin graft that did not take, and one required reamputation at a higher level. Antibiotic delivery was less than one intravenous dose daily, which avoided the potential for systemic absorption to toxic levels. Antibiotics such as vancomycin and gentamicin could be used in concentrations of up to 10,000 times the minimal inhibitory concentration. Forty-eight hours after application, 20 percent or more of the original antibiotic concentration was present in the wound chamber fluid. In conclusion, the wound chamber provides a safe, powerful tool in the treatment of difficult infected wounds.
12270922 SAF-2, a splice variant of SAF-1, acts as a negative regulator of transcription. 2002 Nov 29 Serum amyloid A-activating factor-1 (SAF-1), a Cys(2)His(2)-type zinc finger transcription factor, regulates inflammation-induced expression of serum amyloid A protein that is linked to the pathogenesis of reactive amyloidosis, rheumatoid arthritis, and atherosclerosis. Here we report the identification of a novel splice variant, SAF-2, of the SAF family bearing strong sequence similarity to SAF-1. The N-terminal 426 amino acids of both SAF-1 and SAF-2 are identical containing two polyalanine tracts, one proline-rich domain, and six zinc fingers. However, the C terminus of SAF-2 containing two additional zinc fingers is different from SAF-1, which indicates the capability of different biochemical function. We show that SAF-2 interacts more avidly with the SAF-binding element, but its transactivation potential is much lower than SAF-1. Furthermore, co-expression of SAF-2 markedly suppresses SAF-1-regulated promoter function. Finally, we show that the level of SAF-2 protein is reduced during many inflammatory conditions, whereas the SAF-1 protein level remains unchanged. Together, these data suggest that the relative abundance of SAF-2 plays a critical role in the fine tuned regulation of inflammation-responsive genes that are controlled by SAF-1.
12232494 [Short-term therapeutic fasting in the treatment of chronic pain and fatigue syndromes--we 2002 Aug BACKGROUND: Fasting followed by vegetarian diet has shown to be an effective treatment for rheumatoid arthritis, moreover fasting is frequently used as an adjunctive treatment in chronic pain and stress/exhaustion syndromes. Data on well-being and the frequency of side effects during fasting are mostly retrospective. Mineral supplements are frequently used in order to compensate for fasting-induced tissue acidosis and to reduce side effects. There are only limited data that support this practice. OBJECTIVE: To study the effects of oral mineral supplements on common side effects and well-being during short-term fasting. PATIENTS AND METHODS: 209 consecutive inpatients with chronic pain/exhaustion syndromes were recruited. In a controlled non-randomised study design all patients underwent fasting (250 kcal; 3 l fluid intake/day) over 7 days, in study phase 1 without (n = 103) and in study phase 2 with (n = 106) concomitant prescription of standardised oral mineral supplements (3 x 2 to 3 x 3 Bullrich's Vital). Weight, blood pressure and urinary pH were recorded daily. Well-being and mood as well as common side effects (i.e. fatigue, hunger, heart burn, headache) were assessed with standardised self-reports. RESULTS: Baseline characteristics of the 209 patients (mean age 54.7 +/- 10.5 years; 83.3% female) were balanced. Both groups showed a fasting-induced decrease of blood pressure, a slight decrease in mood and well-being on days 3 and 4 with consecutive increase and moderate hunger, i.e. in the evening. Side effects and general tolerability of fasting as well as well-being and mood were not different between the groups. There were no serious side effects in both groups. CONCLUSIONS: Short-term fasting in inpatients with pain and stress syndromes is safe and well tolerated, concomitant mineral supplements have no additive benefit.
11822347 Use of managed care claims data in the risk assessment of venous thromboembolism in outpat 2002 Jan BACKGROUND: Deep vein thrombosis (DVT) is a complication of immobilizing illness in both inpatient and outpatient settings and can lead to serious complications such as pulmonary embolism (PE). DVT and PE are collectively referred to as venous thromboembolism. OBJECTIVE: To develop DVT and PE risk assessment models that can be used in office-based practice and for population-based disease management efforts. METHODS: Data were culled from integrated medical and pharmacy claims paid by 37 health plans in the United States (the PharMetrics Integrated Outcomes Database, PharMetrics Inc., Watertown, MA), and included information on adult plan members enrolled during 1998 and 1999. Patients hospitalized for DVT or PE in 1999 were identified, and potential risk factors were assessed by reviewing claims for the entire study population in 1998 to document prior DVT or immobilizing illness. The contribution of each potential risk factor to the probability of the occurrence of DVT or PE was determined by means of multiple logistic regression analysis. A risk-scoring algorithm based on regression coefficients was then developed. RESULTS: Fifty-two percent of the study population of 2.8 million plan members were women. DVT or PE occurred in 1330 of those 2.8 million individuals (47 per 100,000). Logistic regression results confirmed the role of risk factors previously reported in the literature and revealed additional risk factors that have not been reported previously, including diabetes, renal failure, rheumatoid arthritis, cellulitis, use of warfarin, use of systemic corticosteroids, and use of potassium chloride. When risk scores were applied to the study population, the 1% identified as being at highest risk had a probability for the development of venous thromboembolism that was 10 times greater than that of the population average. CONCLUSIONS: This study confirms the feasibility of using managed care claims data to develop a risk assessment tool for venous thromboembolism that can be used in office-based practice and for population-based disease management.
23115803 (64)Cu-Labeled DOTA-conjugated rituximab, a chimeric murine/human anti-CD20 monoclonal ant 2004 Rituximab is a chimeric murine/human monoclonal antibody (mAb) that targets the CD20 antigen (also known as membrane-spanning 4-domains, subfamily A, member 1, or MS4A1) and has been approved by the United States Food and Drug Administration for the treatment of non-Hodgkins lymphomas (NHL; diffused large-B cell, low-grade, or follicular types), rheumatoid arthritis, granulomatosis with polyangiitis (Wegener's granulomatosis) and microscopic polyangiitis. The exact mechanism of action of rituximab has been discussed by Maloney (1). Although much is known about the pathogenesis of the different forms of NHL at the molecular level, the prognosis for an individual suffering from this disease is based on the morphological and histological information obtained with invasive methods used on the patients (2). Therefore, the use of noninvasive procedures, such as imaging with radiolabeled agents, is an attractive option to screen for patients who can benefit the most from an anti-cancer treatment, and the same imaging technique(s) can be used to monitor and assess the efficacy of a treatment (3). In the clinic, positron emission tomography (PET) is commonly used to detect, stage, and monitor the treatment outcome for various cancers because this imaging modality has superior penetration and sensitivity and it is more quantitative compared with other imaging techniques such as single-photon emission computed tomography, magnetic resonance imaging, ultrasound, and optical imaging (4). In this regard, there is much effort devoted to the development of radiolabeled mAbs that can be used with PET for the targeted imaging of neoplasms that express specific antigens, such as the epidermal growth factor receptor (5) and the carcinoembryonic antigen (6). (64)Cu-Labeled rituximab ([(64)Cu]-DOTA-rituximab) was developed in an effort to generate a PET imaging agent that can be used to monitor the treatment of NHL (2). The biodistribution of [(64)Cu]-DOTA-rituximab was studied with PET in huCD20 transgenic mice, which mimic the human B-cell lymphoma tumors (obtained from Genentech Corporation, CA) (2).