Browse

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

ID PMID Title PublicationDate abstract
15175485 Patients' problems with new medication for chronic conditions. 2004 Jun OBJECTIVES: To assess patients' adherence to new medication for a chronic condition (and whether non-adherence was intentional), patients' problems with their medication, and their further information needs. METHODS: A longitudinal survey with data collection at 10 days and 4 weeks was performed on 258 patients recruited from 23 community pharmacies in south east England. Patients were eligible to participate if they were starting a new chronic medication and were either 75 years or older or had one of the following chronic conditions: stroke, coronary heart disease, asthma, diabetes, and rheumatoid arthritis. At each time point a semi-structured telephone interview was conducted and a postal questionnaire was sent. MAIN OUTCOME MEASURES: Self-reported adherence, causes of non-adherence, problems with medication, information needs. RESULTS: Sixty seven (30%) of 226 patients still taking their medication at 10 days and 43 of 171 (25%) still taking their medication at 4 weeks were non-adherent. At 10 days 55% of the non-adherence was unintentional and the remainder was intentional; these proportions were similar at 4 weeks. 138 of 208 (66%) participants still taking their new medication at 10 days reported at least one problem with it. 137 of 226 patients (61%) expressed a substantial and sustained need for further information at 10 days and 88 of 171 (51%) at 4 weeks. Several patients who were adherent or reported no problems at 10 days were non-adherent or had problems at 4 weeks. CONCLUSIONS: A significant proportion of patients newly started on a chronic medication quickly become non-adherent, often intentionally so. Many have problems with their medication and information needs. Patients need more support when starting on new medication for a chronic condition and new services may be required to provide this.
15158661 The third chains of living organisms--a trail of glycobiology that started from the third 2004 Jun 15 Application of a finger-printing method to the analysis of human milk oligosaccharides led to the finding that several oligosaccharides were missing in the milk of non-secretor or Lewis-negative individuals. This finding helped us in opening the door of elucidating the enzymatic basis of blood types in human. Based on these successful studies, a strategy to establish reliable techniques to elucidate the structures and functions of the N-linked sugar chains of glycoproteins was devised. It was to contrive enzymatic and chemical means to release quantitatively the N-linked sugar chains as oligosaccharides, and finger-print them by using appropriate methods to demonstrate the sugar pattern of a glycoprotein. These methods enabled us to determine that the N-linked sugar chains of glycoproteins can be classified into three subgroups: high mannose-type, complex-type, and hybrid-type. By comparative studies of the sugar patterns of a glycoprotein produced by different organs and different animals, occurrences of organ- and species-specific glycosylation were found in many glycoproteins. By comparative studies of the glycosylation patterns of the subunits constructing human chorionic gonadotropin and other glycoproteins, occurrence of site-directed N-glycosylation was also found, indicating that the processing and maturation of the N-linked sugar chains of a glycoprotein might be controlled by the structure of polypeptide moiety. Furthermore, these methods enabled us to elucidate the structural alteration of the sugar chains of a glycoprotein induced by diseased state of the producing cells, such as rheumatoid arthritis and malignancy. Recent studies of glycoproteins in the brain-nervous system through aging revealed that N-glycosylation of P(0) in the rat spinal cord is induced by aging. Therefore, glycobiology is expanding tremendously into fields such as pathological and gerontological research.
15123937 Souter arthroplasty for elbows with severe destruction. 2004 Apr One hundred fifty-eight primary Souter elbow arthroplasties were done on 134 patients (121 women) with severe joint destruction (Larsen Grade 5) or large bone defects or both. Joint replacement operations were done at our institution from 1985-1997. The study group comprised 156 joints in 132 patients with rheumatoid arthritis or other variants of chronic inflammatory joint disease, one in a patient with osteoarthritis, and one patient with posttraumatic arthrosis. The mean age of the patients at the time of surgery was 57 years (range, 26-81 years) and the mean disease duration was 27 years (tinge, 2-70 years). Radiographically, severe bone defects were detected in 100 humeri and 134 ulnas. Retentive (snap-fit) ulnar components were implanted in 110 joints, and bone grafts were used on 26 humeri and 14 ulnas. Major complications led to five early and 16 late reoperations in 19 patients. Four reoperations were done because of dislocation and eight because of aseptic loosening. One reoperation was done because of early infection and five were done because of late infection. One patient had reoperation because of superficial infection in the bursa olecrani and one triceps tendon rupture also was repaired. One patient had wound repair because of marginal necrosis. In the survival analysis, the cumulative success rate without revision for aseptic loosening at 5 years followup was 97%. Despite the demanding nature of these arthroplasties, the primary results are encouraging. Technically, it is possible to do elbow replacement, even on elbows where the humeral condyles or olecranon or both are missing, if there is sufficient bone left on the diaphyseal areas for primary stem fixation. However, in these extreme cases, the poor general condition of the patient or the difficult soft tissue problems in the elbow region may prove to be a contraindication for joint replacement.
15123036 The process of identifying and understanding cytokines: from basic studies to treating rhe 2004 Feb This is a historical overview seen from a personal angle. It covers the insights made during the past 20 years into the destructive processes of rheumatoid arthritis (RA) related to cytokines. The biochemical knowledge of the matrix components (i.e. collagen) and enzymology (i.e. collagenase) available in the 1950s led to the identification of cells from synovial tissue producing collagenase (fibroblast-like cells) and their interaction with other immune cells, i.e. monocyte-macrophages (Mphi) and lymphocytes (1976-1979). This insight led to the isolation of soluble factors produced by Mphi, such as interleukin-1 (IL-1) and TNF, the principal cytokines inducing collagenase and PGE(2) in many target cells (i.e. synovial fibroblasts, chondrocytes, bone-derived cells) (1981-1985). Further advances resulted from observations that, in clinical conditions (i.e. leukaemia, juvenile RA), a remission of fever and inflammation may occur spontaneously and that tissue catabolism may persist despite the absence of systemic inflammation; this gave rise to the concept and identification of endogenous cytokine inhibitors (i.e. IL-1 receptor antagonist and TNF soluble receptor) (1984-1989). The fourth milestone was the observation that the production of IL-1 and TNF by Mphi was induced mainly by direct contact with lymphocytes, prompting studies of the ligands and counter-ligands on Mphi and lymphocytes as well as inhibitors involved in this cell-cell contact, some of these inhibitors being involved in lipid metabolism and acute-phase proteins (HDL-apo A-1).
15078135 Anti-cytokine therapy for the treatment of graft-versus-host disease. 2004 Acute graft-versus-host disease (GVHD) and chronic GVHD remain the major barriers to successful hematopoietic cell transplantation. The induction of GVHD may be divided into three phases--(I) recipient conditioning, (II) donor T cell activation, and (III) effector cells mediating GVHD. Cytokines have been shown to be extremely important in the initiation and propagation of GVHD. Of note, IL-2 and TNF-alpha lead to cellular activation as well as local tissue damage. There has been a major development in the last few years of monoclonal antibodies that target cytokines. Drugs that target the IL-2 receptor (daclizumab and basiliximab) are now commonly used to prevent renal transplant rejection. Furthermore, drugs that target TNF-alpha (infliximab and etanercept) are used in rheumatoid arthritis and Crohn's disease but are also being tested for a number of other autoimmune diseases. These agents are very selective immunosuppressants that have different mechanisms of action than the calcineurin inhibitors and therefore are potentially promising for treatment or prevention of GVHD. The authors present up-to-date data regarding the use and development of anti-cytokine therapy for GVHD. The most effective approach to GVHD prevention will likely be a combination regimen where the three phases of the GVHD cascade are disrupted. Once GVHD has occurred, all three phases of the cascade are activated. Developments of combination therapy for treatment of both acute and chronic GVHD will likely yield better results than monotherapy. The numerous new treatment modalities presented should improve the outlook for acute and chronic GVHD.
15041044 Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients. 2004 May We prospectively analyzed the diagnostic sensitivity and specificity as well as the clinical relevance of antinucleosome antibodies in SLE. One hundred and one consecutive SLE patients were followed for 3 years. Three serial serum samples from each patient were tested for antinucleosome antibodies by ELISA (optimum cut-off value 10 U/ml), and for anti-dsDNA antibody (by ELISA and IIF on Crithidia luciliae), and anti-dsDNA avidity (by Scatchard plot analysis). Sera from 100 healthy individuals (HI), 35 patients with systemic sclerosis (SSc), 30 with primary Sjögren's syndrome (SS), 20 with rheumatoid arthritis (RA) and 48 with infectious diseases (ID), were assayed as controls. SLE activity and damage were evaluated using the ECLAM score and the SLICC/ACR index. At baseline, antinucleosome antibodies were found in 87 patients with SLE (86.1%), in 8 patients with SSc (22.8%), in 2 HI (2%), and in 1 ID (2.1%). The sensitivity and specificity of antinucleosome testing for SLE were 86.1% and 95.3%, respectively. The prevalence of antinucleosome antibodies in SLE was significantly higher than that of anti-dsDNA antibodies, with a correlation between them. No relevant relationship was found between antinucleosome antibodies and disease features, including renal involvement, disease activity, and disease damage. During follow-up, no significant variation was observed in antinucleosome level, nor in anti-dsDNA antibody level or avidity. We conclude that antinucleosome antibodies are commonly found in SLE. Low antibody levels can be detected in SSc, whereas medium/high levels are highly specific for SLE. Their clinical relevance during the disease course and utility for monitoring the individual patient seem to be poor.
14996097 Medical conditions associated with venous leg ulcers. 2004 Feb BACKGROUND: In patients who have a venous leg ulcer, very little is known about the frequency of their concomitant medical conditions. OBJECTIVES: To evaluate the frequency that other medical conditions are associated with a new venous leg ulcer. METHODS: We studied a 10% random sample of elderly patients registered in the General Practice Research Database between 1988 and 1996. We describe the frequency of medical conditions using simple percentages. In order to assess the associations between medical conditions and the onset of a venous leg ulcer, we used logistic regression models. RESULTS: Several medical conditions occur commonly in patients who develop venous leg ulcers, including anaemia, angina, asthma, cellulitis of the lower extremity, depression, diabetes, limb oedema, hypertension, osteoarthritis, pneumonia and urinary tract infection. After statistical adjustment many medical conditions were significantly associated with those who had recent onset of a venous leg ulcer, including asthma, cellulitis of the lower extremity, congestive heart failure, diabetes, deep venous thrombosis, lower limb oedema, osteoarthritis, peripheral vascular arterial disease of the lower extremity, rheumatoid arthritis, history of hip surgery, and history of venous surgery/ligation. Unexpectedly, some illnesses were inversely associated with those that had recent onset of a venous leg ulcer, including angina, cerebral vascular accident, depression, malignancy, myocardial infarction, pneumonia and urinary tract infection. CONCLUSIONS: Physicians caring for individuals with venous leg ulcers need to be aware that it is likely that these individuals may have one of the comorbid illnesses listed above.
14722211 Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by h 2004 Feb BACKGROUND: Although osteoarthritis (OA) is thought to derive from defective chondrocyte metabolism and thus inherently lack the large scale systemic response of rheumatoid arthritis, there is increasing interest in the acute phase proteins in OA. OBJECTIVE: To assess the association between high sensitivity C reactive protein (hsCRP) and severity and extent of OA in patients with advanced hip and knee OA. METHODS: Preoperative hsCRP was measured in frozen serum samples from 770 consecutive patients with hip or knee joint replacement due to advanced OA recruited between 1995 and 1996. Pain was measured by a visual analogue scale and the Western Ontario and McMaster Universities OA index (WOMAC). The extent of OA in different joints was assessed clinically and radiographically. RESULTS: The (geometric) mean hsCRP was 2.5 mg/l among all patients. Severity of pain was associated with mean hsCRP (adjusted elevation highest v lowest quintile = 35%, p = 0.01) after controlling for known or suspected predictors of hsCRP, including age, smoking, and body mass index. Neither the bilateral nor the generalised extent of OA, nor any of the dimensions of the WOMAC were associated with mean hsCRP levels. CONCLUSIONS: Severity of pain, but not extent of OA, was associated with hsCRP levels in this group of patients with advanced OA. Longitudinal studies with repeated assessments of hsCRP and pain are needed to assess the possible value of hsCRP for monitoring or predicting the clinical course of OA.
14662005 Adenosine receptor agonists: from basic medicinal chemistry to clinical development. 2003 Nov Adenosine is a physiological nucleoside which acts as an autocoid and activates G protein-coupled membrane receptors, designated A(1), A(2A), A(2B) and A(3). Adenosine plays an important role in many (patho)physiological conditions in the CNS as well as in peripheral organs and tissues. Adenosine receptors are present on virtually every cell. However, receptor subtype distribution and densities vary greatly. Adenosine itself is used as a therapeutic agent for the treatment of supraventricular paroxysmal tachycardia and arrhythmias and as a vasodilatatory agent in cardiac imaging. During the past 20 years, a number of selective agonists for A(1), A(2A) and A(3) adenosine receptors have been developed, all of them structurally derived from adenosine. Several such compounds are currently undergoing clinical trials for the treatment of cardiovascular diseases (A(1)and A(2A)), pain (A(1)), wound healing (A(2A)), diabetic foot ulcers (A(2A)), colorectal cancer (A(3)) and rheumatoid arthritis (A(3)). Clinical evaluation of some A(1) and A(2A) adenosine receptor agonists has been discontinued. Major problems include side effects due to the wide distribution of adenosine receptors; low brain penetration, which is important for the targeting of CNS diseases; short half-lifes of compounds; or a lack of effects, in some cases perhaps due to receptor desensitisation or to low receptor density in the targeted tissue. Partial agonists, inhibitors of adenosine metabolism (adenosine kinase and deaminase inhibitors) or allosteric activators of adenosine receptors may be advantageous for certain indications, as they may exhibit fewer side effects.
14571268 The deleted in colorectal carcinoma (DCC) gene 201 R --> G polymorphism: no evidence for g 2003 Nov The product of the deleted in colorectal carcinoma (DCC) gene has a role in apoptosis and is a positional candidate for IDDM6, the putative chromosome 18q12-q23 autoimmune disease locus. We hypothesised that a nonconservative substitution (DCC 201 R --> G; nucleotide (nt) 601 C --> G), located in an extracellular immunoglobulin-like domain of DCC, is an aetiological determinant of autoimmunity. We tested this hypothesis by genetically testing the nt 601 C --> G polymorphism for association with three autoimmune phenotypes in a large population-based case-control study. There was no evidence for association of DCC nt 601 C --> G with autoimmune disease in cohorts comprising 2253 subjects with rheumatoid arthritis, type I diabetes and Graves' disease, and 2225 control subjects, from New Zealand and the United Kingdom. Furthermore, using the transmission disequilibrium test, there was no significant evidence for biased transmission of the nt 601 C --> G polymorphism to probands within a 382 family type I diabetes affected sibpair cohort from the United Kingdom. Thus, the DCC 201 R --> G polymorphism does not appreciably influence risk of developing the autoimmune diseases tested.
12963137 Antiinflammatory and antiulcer activities of Bambusa arundinacea. 2003 Oct The extracts of Bambusa arundinacea have been used in Indian folk medicine to treat various inflammatory conditions. The plant has got antiulcer activity also. It is thought that these two properties in the same extract are very much useful in the treatment of inflammatory conditions. It is well known fact that the most of the available antiinflammatory drugs are ulcerogenic. The antiinflammatory effect of the methanol extract of the leaves of Bambusa arundinacea against carrageenin-induced as well as immunologically induced paw oedema and also its antiulcer activity in albino rats have been studied and found to be significant when compared to the standard drugs. The combination of methanol extract and phenylbutazone (Non-Steroidal Antiinflammatory Agent, NSAIA) has been studied and found to be the most potent antiinflammatory activity experimentally with least toxic (no ulcerogenic) activity. Thus, the combination of herbal product (methanol extract of Bambusa arundinacea) with modern medicine (NSAIAs) will produce the best antiinflammatory drug and will be useful for long-term treatment of chronic inflammatory conditions like rheumatoid arthritis with peptic ulcer, which are common.
12924609 Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro mo 2003 Jun Granulocyte and monocyte adsorptive apheresis (GMA) using a column filled with cellulose acetate (CA) beads (carriers) has been associated with a significant clinical efficacy in patients with rheumatoid arthritis and ulcerative colitis. To obtain further understanding on the mechanisms of disease modification by cellulose acetate-carrier-based GMA, in the present study, we investigated the mechanisms of granulocyte and monocyte adhesion to CA beads following exposure of human peripheral blood to the carriers at 37 degrees C for up to 60 min under controlled conditions. Cellulose acetate beads selectively adsorbed granulocytes, monocytes. CD19+ (B cells) and CD56+ (NK cells) lymphocyte subpopulations. The granulocyte and monocyte adsorption was inhibited by heat-inactivated plasma and EDTA, indicating that the adsorption was plasma protein (immunoglobulin, complement) and calcium dependent. Accordingly, granulocyte and monocyte adsorption was markedly enhanced by coating the carriers with IgG. Similarly, C3b was adsorbed onto the CA beads as a marker of complement activation. The results indicated that IgG and active complement fragments mediated leukocyte adhesion to CA beads via the FcgammaR and/or leukocyte complement receptor like CR3. Additionally, CA beads induced loss of expression of TNF receptors on CD16- granulocytes and CD14+ monocytes, but not on CD3+ lymphocytes In conclusion, CA beads might be an appropriate biomaterial for inducing extracorporeal immunomodulation as a treatment for auto-immune diseases which are associated with pathological leukocyte activity.
12773095 Principles of interleukin (IL)-6-type cytokine signalling and its regulation. 2003 Aug 15 The IL (interleukin)-6-type cytokines IL-6, IL-11, LIF (leukaemia inhibitory factor), OSM (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of IL-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). IL-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, LIF receptor and OSM receptor leading to the activation of the JAK/STAT (Janus kinase/signal transducer and activator of transcription) and MAPK (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of IL-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the JAK/STAT signalling pathway mediated by tyrosine phosphatases, the SOCS (suppressor of cytokine signalling) feedback inhibitors and PIAS (protein inhibitor of activated STAT) proteins. Also the cross-talk between the JAK/STAT pathway with other signalling cascades is discussed.
12762503 Consequences of immunogenicity to the therapeutic monoclonal antibodies ReoPro and Remicad 2003 The clinical consequences of immune antibodies generated to abciximab (ReoPro) and infliximab (Remicade) are described. Abciximab, a chimaeric Fab fragment that binds to the beta3 integrin of the GPIIb/IIIa and alphavbeta3 receptors on human platelets, is approved in the US and Europe for use in percutaneous coronary intervention (PCI) to prevent cardiac ischaemic complications. The effects of induced antibodies upon the safety and efficacy of repeat administration of abciximab have been evaluated in the ReoPro Re-administration Registry Study, in which 5.7% of patients were HACA positive before re-treatment. An interim evaluation of 1000 patients has indicated that re-administration of abciximab can be accomplished in the setting of PCI with an acceptable safety and efficacy profile. Infliximab is a chimaeric IgG1 antibody specific for human TNFalpha, and is approved in the US and Europe for the acute treatment of the signs and symptoms of Crohn's disease and for the chronic treatment of rheumatoid arthritis (RA). The incidence of antibodies to infliximab is reported to be approximately 10%; however, an inverse dose-immunogenicity relationship was observed, indicating that higher doses of infliximab (> or = 3 to 10 mg/kg) could reduce the incidence of immune antibodies. The induction of immune antibodies could also be reduced by concomitant administration of low-dose methotrexate and other immunosuppressant agents. Although antibodies to infliximab appeared to be associated with lower serum infliximab concentrations and a slightly higher incidence of infusion reactions, these immune antibodies were generally not associated with a reduction in clinical efficacy. In addition, the antibodies induced to infliximab are specific for infliximab, and do not cross-react with other currently available therapeutic antibodies.
12720610 Medical conditions as risk factors for pressure ulcers in an outpatient setting. 2003 May OBJECTIVES: the purpose of this study was to evaluate the likelihood that the presence of certain medical conditions in older ambulatory patients are associated with the risk of developing a new pressure ulcer. DESIGN: a cohort study. SETTING AND SUBJECTS: a large outpatient record database from the United Kingdom called the General Practice Research Database. METHODS: the frequency of disease was reported as simple percentages and the associations between the medical conditions and the development of a pressure ulcer as instantaneous rate ratios. RESULTS: we studied 75,168 older individuals. Pressure ulcers occurred in 1,211 individuals. The medical conditions that were significantly associated with the development of a pressure ulcer after adjustment were: Alzheimer's disease, congestive heart failure, chronic obstructive pulmonary disease, cerebral vascular accident, diabetes mellitus, deep venous thrombosis, hip fracture, hip surgery, limb paralysis, lower limb oedema, malignancy, malnutrition, osteoporosis, Parkinson's disease, rheumatoid arthritis, and urinary tract infections. Angina, hypertension, and pneumonia were inversely associated with the development of a pressure ulcer. CONCLUSIONS: it is important that physicians recognise that patients with many medical conditions may be at higher risk for pressure ulcers so that even in the ambulatory care environment appropriate prevention and detection strategies can be directed towards the patients who are most likely to benefit.
12707575 Upcoming biologic agents for the treatment of rheumatic diseases. 2003 May The development of biologic agents has provided rheumatologists with a variety of new and effective treatment options. The success of early biologics, especially etanercept and infliximab for the treatment of rheumatoid arthritis, has spurred research into novel targets for the management of systemic inflammatory and autoimmune diseases. In addition, existing biologics approved for use in other diseases, such as rituximab, are now under study for the treatment of new indications. This article reviews ongoing research on the treatment of rheumatic diseases with new and existing biologic agents.
12702139 Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin canc 2003 Apr Many normal biological processes, such as reproduction, fetal development and wound healing, are critically dependent on controlled degradation of extracellular matrix (ECM) macromolecules. However, excessive degradation of matrix components occurs in pathologic tissue destruction, e.g. in atherosclerosis, rheumatoid arthritis, and cancer. Matrix metalloproteinases (MMPs) are degradative enzymes that play an important role in all aspects of tumor progression by enhancing tumor-induced angiogenesis and destroying local tissue architecture and basement membranes to allow tumor invasion and metastasis. Efficient breakdown of the ECM surrounding invasive cancer islands involves interplay between tumor cells, stromal cells, and inflammatory cells, all of which express a distinct set of MMPs. Besides the classical role of MMPs in degradation of ECM, MMPs may also indirectly influence the tumor microenvironment through the release of growth factors, cryptic sites or angiogenic factors, or through the generation of matrix fragments that inhibit tumor cell proliferation, migration and angiogenesis. This makes the contribution of MMPs to tumorigenesis much more complex than initially thought. Currently, a number of clinical studies have focused on testing MMP inhibitors as potential antineoplastic agents. In this review we discuss the present role of MMPs in the development and progression of cancer, focusing on non-melanoma skin cancers basal (BCC) and squamous (SCC) cell carcinoma, and the possible influence of MMPs in their differences.
12685200 Chromium-induced lymph node histiocytic proliferation after hip replacement. A case report 2003 Mar BACKGROUND: Prosthetic joint replacement is frequently used for the treatment of degenerative joint disease, rheumatoid arthritis, bone tumors and traumatic lesions. The prostheses contain such materials as titanium, cobalt and chromium. We describe a patient who, after total hip arthroplasty, developed an inguinal-pelvic mass. Fine needle aspiration revealed metallic particles, also seen on light microscopy in reactive pelvic lymph nodes. Ultrastructure was consistent with the presence of foreign particles, while energy dispersive x-ray microanalysis established the presence of chromium. To our knowledge, this is the first report of chromium-related lymph node metallosis diagnosed by fine needle aspiration. CASE: Eight years after total hip arthroplasty, a 78-year-old woman developed a right pelvic cystic mass. Aspiration drainage was performed. Smears from fine needle aspiration showed numerous macrophages with abundant, foamy cytoplasm and round nuclei without atypia. Small, birefringent particles were seen in the cytoplasm. Histopathology showed fibroconnective tissue with chronic inflammation and marked lymph node sinus histiocytosis. Within histiocytes, numerous particles were present, identical to those seen in the smears. Their nature as "foreign bodies" was confirmed by electron microscopy, and the presence of chromium was shown by energy dispersive x-ray analysis. CONCLUSION: Fine needle aspiration and polarized microscopy are excellent techniques to evaluate foreign materials in lymph nodes draining the sites of joint prostheses, thus precluding confusion with other conditions, such as metastatic carcinoma.
12540989 [Stem cell transplantation in primary systemic vasculitis]. 2003 Jan 15 BACKGROUND: Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage, and development of secondary malignancies. THERAPY: Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation might be an alternative for otherwise refractory patients. This concept has been used mainly in patients with scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. PATIENTS: Patients with primary systemic vasculitis (PSV) seem to be suitable candidates for high-dose chemotherapy (HDCT). Although complete, long-term remissions are possible with standard immunosuppressive therapy, there is a subgroup of patients who cannot be cured by standard therapy. They need long-term immunosuppression and eventually die due to progression of the disease or cumulative therapy-related toxicity. In large series, the 5-year mortality rate was > 20%. The severity of vasculitis rather than the distinction between subgroups should determine whether HDCT might be a life-saving treatment. RESULTS AND CONCLUSION: Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports as well as our own single-center experience in HDCT with a limited number of patients with severe PSV have shown that long-term remissions are possible even in patients refractory to conventional immunosuppression.
12535706 Vasoactive intestinal peptide binding autoantibodies in autoimmune humans and mice. 2002 Dec Autoantibodies capable of binding the immunoregulatory neuropeptide vasoactive intestinal peptide (VIP) were detected in the sera of a mouse strain prone to autoimmune disease due to the lpr mutation (MRL/lpr). The autoantibodies were not present in control wildtype MRL/lpr mice, but they were readily detected in humans without autoimmune disease. The binding was due to low affinity VIP recognition. Increased VIP binding activity was evident in patients with systemic lupus erythematosus but not systemic sclerosis, Sjögren's syndrome (SS), rheumatoid arthritis or autoimmune thyroiditis. Recombinant VIP binding Fv clones (fragment variable; the variable domains of the light and heavy chains antibody subunits joined with a peptide linker) were isolated from a phage display library prepared from lupus patients. One Fv clone displaying VIP-selective binding and several clones displaying cross-reactivity with unrelated peptides were identified. Replacement mutations in the VIP-selective clone were preferentially localized in the regions known to make contacts with the antigen, i.e. the complementarity determining regions, suggesting that the selective binding activity is due to immunological maturation of the antibodies. Frequent occurrences of autoantibody responses to VIP indicate that immunological tolerance to this neuropeptide can be readily broken. The depletion of VIP by specific antibodies in autoimmune disease may interfere with VIP regulation of T cells and inflammatory cells and result in further amplification of autoreactive immunological responses.