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ID PMID Title PublicationDate abstract
8535351 Antineutrophil cytoplasmic autoantibodies (ANCA)--markers in diagnosis and monitoring syst 1995 Jan We present a new class of autoantibodies--ANCA (antineutrophil cytoplasmic autoantibodies) which recognize as target antigen different enzyme constituents of primary granules of neutrophil granulocytes. These autoantibodies are present in a large number of diseases, such as: systemic vasculitides, idiopathic crescentic glomerulonephritis, inflammatory bowel diseases and in some other conditions, including rheumatoid arthritis, SLE, Felty syndrome, acute and chronic infections. ANCA not only facilitate the diagnosis but also have a pathophysiological role for some of the idiopathic vasculitides. In our study, including 110 patients referred to the laboratory for ANCA testing by indirect immunofluorescence technique, only 25 patients were positive with a diffuse cytoplasmic (c ANCA) or perinuclear (p-ANCA) pattern on alcohol fixed slides. Some relevant cases are presented in order to emphasize that ANCA antibodies are a useful marker in the early diagnosis of systemic vasculitides, allowing effective therapeutic handling.
7810463 The numb arm and hand. 1995 Jan Trauma and compression along the course of the median, ulnar or radial nerve from the brachial plexus to the fingers may cause pain, weakness, numbness or tingling of the upper extremity. Diabetes, smoking, alcohol consumption, rheumatoid arthritis and hypothyroidism are risk factors for nerve entrapment, although these disorders typically produce bilateral symptoms. Carpal tunnel syndrome, the most common nerve entrapment condition, results from median nerve compression at the wrist. The diagnosis is suggested by decreased pain sensation and numbness in the thumb and index and middle fingers; symptoms are reproduced by wrist hyperflexion and median nerve percussion. Volar splinting and steroid injection often ameliorate symptoms. Decreased sensation of the little finger and the ulnar aspect of the ring finger, along with intrinsic muscle weakness, may be caused by cervical radiculopathy, thoracic outlet syndrome or compression of the ulnar nerve above the elbow (cubital tunnel syndrome) or at the wrist (ulnar tunnel syndrome). Electromyography and radiography may help differentiate these conditions. Radial tunnel syndrome occasionally accompanies inflammation of the common wrist extensors and lateral epicondylitis ("tennis elbow"). A radial nerve block can help exclude concomitant radial tunnel syndrome in patients with symptoms of lateral epicondylitis.
8072454 [Effect of heredity and environment in immune diseases. Presentation of twin data]. 1994 Jun 15 BACKGROUND: The study of twins is an important and informative tool in the investigation of the influence of genetic and environmental factors on the pathogenesis of familial traits. MATERIAL: Seven diseases were analysed by carrying out an intensive study of the literature to search for concordance of monozygotic and dizygotic twins. Apart from single case studies, large unselected series have been reported, some of which show considerable differences in concordance rates. Data from twins were collected for myasthenia gravis, systemic lupus erythematosus, rheumatoid arthritis and type 1 diabetes mellitus, Crohn's disease and, for comparative purposes, also type 2 diabetes mellitus. RESULTS: On the basis of the above-mentioned calculated concordance rates, differences in the influence of genetic factors were established, which may be of importance for the genetic counselling of affected families. These findings based on twins also confirm the multifactorial inheritance model.
7932438 Chronic modulation of the autoimmune response following parvovirus B19 infection. 1994 Jun We describe 2 patients with prolonged autoimmune alterations following parvovirus B19 infection. B19 induced aplastic crises were the revealing manifestations of asymptomatic hemolytic conditions in the 2 patients: a Coombs' positive hemolytic anemia induced by D-penicillamine in the first and congenital spherocytosis in the second. Both patients had transient clinical and serological manifestations highly suggestive of systemic lupus erythematosus. In addition, prolonged clinical and serological remission of rheumatoid arthritis was observed in the first patient, while arthralgias, FANA, and anti-Ro antibodies persisted in the second, previously healthy patient. Our data suggest that parvovirus B19 infection may lead to chronic modulation of the autoimmune response in predisposed individuals.
7523242 Immunosuppressive agents in chronic severe asthma. 1994 May Previous immunosuppressive agents utilized as therapies for immune system mediated diseases such as chronic allergic asthma, and rheumatoid arthritis include purine antagonists, methotrexate, and gold salts. These treatment modalities have been shown to elicit either limited treatment efficacy or to produce undesirable side effects in many individuals. Cyclosporin A is a potent immunosuppressive agent which appears to arrest division of T lymphocytes and inhibit mediator release from mast cells. However, like other immunosuppressive agents, cyclosporin A may also produce many potentially serious side effects; among these is the possibility of irreversible renal damage. Nephrotoxicity can be attenuated, because renal pathological changes seem to be high cumulative dose-related. If whole blood levels of cyclosporin A are maintained between 200 and 500 ng/mL, serious renal toxicity is unusual. Investigation of cyclosporin A in individuals who have severe long-term corticosteroid-dependent chronic asthma has demonstrated the efficacy of this agent, resulting in clinically significant improvement in pulmonary function. Therefore, it can be hypothesized that T lymphocytes may act as effector cells in cell-mediated hypersensitivity reactions in atopic allergic inflammation.
7991642 Comparative toxicity of non-steroidal anti-inflammatory agents. 1994 Apr Comparative toxicity of non-steroidal anti-inflammatory drugs was assessed using the Stanford Toxicity Index consisting of weighted symptoms, laboratory abnormalities and hospitalizations in 2976 consecutively enrolled rheumatoid arthritis patients from eight data bank centers with 27,936 patient-years of observation. Scores ranged from 1.77 (SE 0.20) for aspirin to 5.94 (SE 0.92) for meclofenamate, with many differences between drugs being 2- to 3-fold and highly statistically significant. Results are consistent with our prior data, persist when assessed by several different scoring algorithms, are consistent across data bank centers and are consistent with data of others. There are major and reproducible differences in the overall toxicity of different non-steroidal anti-inflammatory drugs.
7515220 Endothelial-leukocyte adhesion molecules in human disease. 1994 An effective host response to infection or tissue damage requires focal accumulation of leukocytes. Leukocyte adhesion to the vessel wall, a key step in this process, depends on the ordered expression of specific endothelial cell surface molecules. The endothelial molecules that support adhesion include selectins that recognize leukocyte cell surface glycoconjugates as well as members of the immunoglobulin superfamily that interact with leukocyte integrins. Although inflammation can occur with minimal damage to the vessel wall and surrounding tissues, control mechanisms sometimes appear to fail, and the inflammatory response itself becomes a significant clinical problem. In this review, we discuss endothelial-leukocyte adhesion molecules with particular emphasis on their expression and function in human disease. Pathophysiological processes presented include atherosclerosis, ischemia-reperfusion injury, acute lung injury, rheumatoid arthritis, and graft rejection. A more detailed description of the discovery and characterization of the key molecules appears in the antecedent article entitled "Endothelial-Leukocyte Adhesion Molecules".
8183167 Early results of total knee replacements: "a clinical and radiological evaluation". 1993 Dec From March 1986 to June 1992, 100 primary total knee arthroplasties were done in 69 patients. The demographic data and complications were analysed in these 69 patients. The first 50 knees with a minimal follow-up of one year (range 1-6 years) were analysed in more detail according to the International Knee Society Rating System. Detailed radiological evaluation was also carried out to assess positioning of the components. There were 79 knees with osteoarthritis, 20 knees with rheumatoid arthritis and one with Systemic Lupus Erythromatosus (SLE). The knee score was poor in all knees pre-operatively. Post-operatively 78% had good to excellent score and the other 22% had fair knee score. However the functional score remained poor in 50% of the knees. Ideal tibio-femoral alignment was obtained in 68% of the knees. Twenty four percent of the knees had 0.4 degrees of varus and eight percent had 10-12 degrees valgus. Complication rate was low with 1% of infection (one knee). Overall early results were satisfactory.
1409562 Modeling of substrate and inhibitor binding to phospholipase A2. 1992 Sep Molecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate-enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermediate complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma.
1509295 Therapeutic use of immunotoxins. 1992 Jul Much progress has been made in the therapeutic use of immunotoxins since the first clinical trials, especially in the prevention and treatment of AGVHD. This is also further discussed in this symposium by Champlin. Research in immunotoxin use has gone beyond cancer and into the treatment of immunologic disorders, such as rheumatoid arthritis and HIV infection. Before further advances can take place several problems must be overcome, including the rapid clearance of immunotoxin by the liver, the generation of anti-immunotoxin antibodies, and poor penetration by the immunotoxin in solid tumors. Other obstacles to the wide use of immunotoxins are the heterogeneity of tumor cells, the shedding of tumor antigens into the circulation, and the inability to identify neoplastic renewal cell specific antigens that are not cross-reactive with normal tissues. Despite these obstacles, the early success of immunotoxins, especially in hematologic malignancies, reinforces the feasibility of designing rational targeting reagents in cancer therapy.
1593600 The emerging role of biologics in rheumatic disease. 1992 Apr Biologically based therapeutics may be classified as agents which (1) restore altered immunoregulatory, hematopoietic or other disease resistant functions, (2) modulate immunologic effector mechanisms (immunomodulators), or (3) upregulate or downregulate a specific cell function. There are several characteristics which differentiate biologic agents from more traditional pharmaceutical drugs. Administered parenterally, they often generate systemic effects, and may be associated with a higher placebo response. Many are administered not at pharmacologic, but "industrial strength" doses. The specific desired effect may be obscured by cytokine and other immunoregulatory networks. A host immune response typically occurs with repetitive administration; this may alter the pharmacokinetics of the agent but not necessarily the biologic or clinical effects. The use of biologic markers, both disease specific and agent specific, may allow more efficient clinical development of these agents. A variety of biologic agents are in clinical trials for the treatment of autoimmune diseases. These include interferon gamma, the IL-1 receptor antagonist and monoclonal antibodies to the T cell surface antigens CD4 and CD7. Two immunotoxins, CD5-ricin A chain, and diphtheria AB toxin-IL-2 are undergoing evaluation in rheumatoid arthritis. Data regarding these agents will be reviewed. Issues specific to their use in pediatric clinical applications will be discussed.
1345954 Abnormal sulphur oxidation in systemic lupus erythematosus. 1992 Jan 4 S-carboxy-L-methylcysteine was used to assess the activity of the S-oxidation pathway of sulphur metabolism in 35 patients with systemic lupus erythematosus (SLE); 25 (71%) showed impaired sulphoxidation and 21 (60%) produced virtually no sulphoxides, compared with 17 (36%) and 2 (4%), respectively, of 47 healthy controls. The substrate/product ratio of cysteine oxygenase (plasma cysteine/sulphate) was significantly higher in SLE patients than in controls (median [interquartile range] 362 [224-588] vs 65 [44-111]; p less than 0.00001). The alternative pathway of sulphur metabolism, S-methylation, catalysed by thiolmethyltransferase, was not impaired in the SLE patients. There is a biochemical difference in sulphur metabolism between SLE and rheumatoid arthritis, since both pathways are impaired in the latter disorder.
1571478 Myasthenia gravis with thymoma is not associated with an increased incidence of non-muscle 1992 Three groups of thymectomized patients with myasthenia gravis (MG) were selected for study, 16 with thymoma, 16 with thymic atrophy and 32 with follicular hyperplasia of the thymus. All 16 patients with thymoma, 15/16 with thymus atrophy and 30/32 with follicular hyperplasia had AChR antibodies. Non-receptor muscle (CA) antibodies were found in sera of 15/16 patients with thymoma, 3/16 with thymus atrophy and in none of the sera from patients with follicular hyperplasia. There were 2 patients with thymoma and polymyositis, but none of the thymoma patients had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or other autoimmune disorders. Among the 32 patients with follicular hyperplasia of the thymus were 2 with SLE, 2 with RA and 1 with juvenile diabetes mellitus. In this study, there was an increased incidence of non-muscle autoimmune disorders among MG patients with follicular hyperplasia of the thymus but not among MG patients with thymoma.
19078084 Successful Treatment of Perianal Ulcers in a Patient with Felty's Syndrome Using Granulocy 1996 Oct We report a case of Felty's syndrome in a 65-year-old woman with chronic nonhealing perianal ulcers caused by persistent granulocytopenia. She was successfully treated with low dose recombinant human granulocyte-colony stimulating factor (G-CSF) 300 mug twice weekly. G-CSF contributed to an increase in neutrophil counts and gradual healing of the ulcers. There was no evidence of exacerbation of the rheumatoid arthritis during the 3-month treatment period. Discontinuation of the G-CSF resulted in a return to the baseline neutropenic state without recurrence of ulceration. Intermittent use of G-CSF may be useful therapy for patients who have Felty's Syndrome and develop complications from their neutropenia. A literature review of treatment modalities for these complications suggests that G-CSF appears to be reliable and efficacious, with few reported adverse events in this group of patients.
9201331 [Biological activity of fish oil]. 1996 Jul Omega-3 fatty acids (n-3) found specially on fish oil are represented by the acid alfa-linolenic, eicosapeniaenoic and docosahexaenoic. After 72 hours of n-3 fatty acids intake there are changes on membrane composition and decrease of synthesis of prostaglandin (PG), leucotriens (LT) and thromboxanes (TX) of the 2 and 4 series production and substitution for prostaglandin, thromboxanes and leucotriens of 3 and 5 series respectively. These alterations can modulate the inflammatory response in some diseases. N-3 fatty acid have been used in cardiology on hypercholesterolemy and hypertension control and on immunologic diseases as psoriasis, rheumatoid arthritis and Crohn disease. Experimentally the n-3 fatty acid inhibit tumor growth and metastasis. The authors consider the biophysiological actions of n-3 fatty acids and discuss the results of its use on clinical results.
20470557 [Complications of hinged endoprostheses of the knee joint, endomodell link.]. 1996 The authors implanted in 1985-1992 25 hinged endoprostheses of the knee joint, type Endomodell Link. It is a type of endoprosthesis which belongs into the group of so-called modified hinged prostheses. In addition to flexion and extension the design of the implant permits also 15 degree axial rotation. Indication for operation were deformities of the knee joint in 21 cases, re-operation in two knee joints and bony ankylosis associated with rheumatoid arthritis in two knee joints. The mean age of the patients was 64 years. In two patients infectious complications developed and the implant had to be removed. The authors did not record in any of the patients aseptic loosening with migration of the components or formation of radiolucencies. In one female patient the movable portion of the endoprosthesis broke of and after reimplantation of the damaged part 1.5 years later mechanical failure occurred due to wear of the thin-walled polyethylene capsule which caused laxity of the joint in the varus - valgus sense. During clinical check-up of the patients the authors found a similar condition - laxity of the knee joint in another 10 patients. It may be assumed that in these patients mechanical failure and the necessity of re-operation is only a question of time. Based on this experience the authors ceased to use this type of endoprosthesis. Key words: hinged prosthesis of the knee joint, mechanical failure.
9085350 Direct measurement of nitric oxide in the cardiovascular system. 1996 Nitric oxide generated from L-arginine is a messenger for cell-to-cell communication. Abnormalities in nitric oxide release have been implicated in diseases ranging from hypertension and atherosclerosis to septic shock and rheumatoid arthritis. We report here the in vivo and in vitro measurements of nitric oxide in the cardiovascular system using a porphyrinic sensor specific for NO. The sensor has a detection limit 10(-9) M, response time of 0.1-10 ms and diameter of 1-20 microns. Protected by an intravenous catheter or Swan-Ganz catheter, the sensor can be implanted into tissues as well as into the blood stream. Nitric oxide concentrations were measured directly in the heart and also in veins and arteries, ranging in diameter from 100 microns to 5 mm. Nitric oxide production was induced by the action of different physical agents (shear stress, stretching) as well as various chemical substances agonists (bradykinin, acetylcholine, ATP).
7704000 Autoimmunity and heavy metals. 1994 Dec This brief review is focused on those heavy metals (cadmium, gold and mercury) that have strong associations with autoimmunity. Cadmium treatment of rats and mice results in autoimmune responses that vary with species and inbred strain of animals. However, there is no solid evidence demonstrating that the renal pathology observed in humans exposed to cadmium has an autoimmune pathogenesis. More clear-cut are the autoimmune effects of preparations containing gold salts, that have been widely used in the treatment of rheumatoid arthritis. Gold may cause autoimmune thrombocytopenia, immune complex-mediated glomerulonephritis and other autoimmune disorders. Similarly, there is solid evidence that mercury can induce autoimmune disease both in humans and experimental animals. The lessons to be derived from metal-induced autoimmunity relate to structure-activity relationship, pathogenesis, etiology and genetics. They probably apply to xenobiotic-induced autoimmune disease in general.
1643291 The evidence for interleukin-6 as an autocrine growth factor in malignancy. 1992 Feb Interleukin-6, IL-6, is a pleiotropic cytokine which plays a central role in defense mechanisms, including the immune response, acute phase reaction and hematopoiesis. Abnormal expression of the IL-6 gene has been suggested to be involved in the pathogenesis of a variety of diseases, especially rheumatoid arthritis, Castleman's disease, mesangial proliferative glomerulonephritis, multiple myeloma and Kaposi's sarcoma. In the case of multiple myeloma and Kaposi's sarcoma, the existence of an IL-6-IL-6 receptor autocrine loop has been implicated in the oncogenesis process. On the other hand, IL-6 has a potent anti-tumor activity against certain types of tumors. This anti-tumor effect is mediated by in vivo induction of tumor specific cytotoxic T cells and in part by a growth inhibitory activity of IL-6.
8864834 Anti-lactoferrin autoantibodies: relation between epitopes and iron-binding domain. 1996 Aug Anti-neutrophil cytoplasm antibodies (ANCA) have been found in the sera of patients presenting systemic necrotizing microscopic vasculitis, i.e. Wegener's granulomatosis and microscopic polyangiitis. Lactoferrin (LF) is one of the antigens rarely recognized by ANCA, and anti-LF autoantibodies are found in several autoimmune conditions, including rheumatoid vasculitis, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, primary sclerosing cholangitis and Crohn's disease. We analysed the epitopes recognized by human anti-LF antibodies to test whether the heterogeneity of clinical presentation might be due to a different epitope recognition profile. Several monoclonal antibodies were raised and used in competition studies with six human sera. Four distinct epitopes were identified on LF, and LF binding of only one of six sera was inhibited by one of the monoclonals. Thus, anti-LF autoreactivity appears to be polyclonal and not restricted to an immunodominant epitope. Specific epitope profiles cannot be determined in these autoimmune conditions. We hypothesized that the interaction of anti-LF antibodies with the LF iron binding domain might contribute to pathogenesis by inhibiting iron chelation after neutrophil activation, thereby providing increased iron availability for endothelial cell damage. The relation of anti-LF mouse monoclonals or polyclonal human or rabbit antibodies to the LF iron-binding domain was studied in competition assays between 59Fe and these antibodies. Preincubation of LF with monoclonals or anti-LF human sera did not affect the binding of 59Fe on LF. 59Fe-binding kinetic studies showed that rabbit anti-LF polyclonal, but not mouse monoclonals or human anti-LF positive sera, was capable of inhibiting iron binding on LF. Therefore, anti-LF autoantibodies did not appear to modulate LF iron-binding activity. We conclude that LF is a rare antigen specificity for ANCA and that the clinical and pathophysiological relevance of anti-LF autoreactivity remains uncertain.