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ID PMID Title PublicationDate abstract
12371610 A synthetic corticosteroid, dexamethasone regulates generation of soluble form of interleu 2002 In contrast to most of the soluble cytokine receptor antagonists properties, the soluble IL-6 receptor (sIL-6R) occurring in various body fluids of healthy persons and patients with various diseases is an agonist. The enhancing effect is due to its ability to form complex with IL-6 and to bind to gp130 making constitutively IL-6 receptor negative cells responsive for IL-6. The generation as well as the functional role of soluble IL-6 receptor is poorly understood. Earlier, we found that the sIL-6R levels in sera of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were higher than those of the control group measured by ELISA sandwich technology. In the present study we detected different levels of sIL-6R in the supernatants of lymphocyte cultures of healthy persons and patients with RA as well as SLE. Moreover, we found, that in vitro dexamethasone treatment stimulated generation of sIL-6R in both healthy persons and in active SLE, while it strongly suppressed production of sIL-6R in both RA groups. At mRNA level, we found that in SLE both the IL-6R mRNA encoding the membrane spanning and alternatively spliced (soluble) variants increased. Surprisingly, the strong decrease of sIL6R protein in RA was not found at mRNA level.
12139676 Decreased MMP-9 activity in the serum of patients with diffuse cutaneous systemic sclerosi 2002 Jun Matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitors of metalloproteinases-1 (TIMP-1) are involved in tissue inflammation and fibrotic processes. We previously reported an elevated serum TIMP-1 level in patients with systemic sclerosis (SSc). We measured serum TIMP-1 and active MMP-9 levels in 62 patients with SSc, 10 patients with rheumatoid arthritis (RA) and 15 normal controls using a modified enzyme-linked immunosorbent assay. The active MMP-9 level in the serum of the patients with RA or SSc was not significantly different from that of controls. Serum MMP-9 activity in patients with diffuse cutaneous SSc was significantly decreased compared with that of limited cutaneous SSc or normal controls. The MMP-9 activity and modified-Rodnan total skin thickness score in patients with SSc were negatively correlated. Serum MMP-9 activity and TIMP-1 level in patients with SSc were not correlated. Serum MMP-9 activity might be a useful indicator of disease activity, especially skin severity, in SSc patients.
12086160 Exposure to solvents in female patients with scleroderma. 2002 May The role of exposure to solvents was investigated in female patients with connective tissue disease and Raynaud's phenomenon using a questionnaire. Sixteen out of the 63 patients with systemic sclerosis had been exposed to solvents. A borderline significance was demonstrated compared to matched female controls (P < 0.05). Fourteen out of the 66 patients with undifferentiated connective tissue disease, 18/86 of patients with Raynaud's phenomenon, 6/45 with systemic lupus erythematosus, 1/16 with dermatopolymyositis, 1/15 with rheumatoid arthritis and 0/13 with primary Sjögren's syndrome had been exposed to solvents. None of these groups of patients showed a statistical significance compared to matched controls. Our present findings indicate that, at least in certain areas of the world, exposure to solvents may be a provoking factor in female scleroderma, but it must be emphasised that only a borderline significance was found between the scleroderma patients and controls. A large multicenter study seems to be required to clarify the importance of solvents as provoking factors of scleroderma. Furthermore, exposure to solvents does not seem to be a provoking factor among females for the other connective tissue diseases.
12068287 Immunoglobulin-free light chains elicit immediate hypersensitivity-like responses. 2002 Jul Immunoglobulin (Ig)-free light chains IgLC are present in serum and their production is augmented under pathological conditions such as multiple sclerosis, rheumatoid arthritis and neurological disorders. Until now, no (patho)physiological function has been ascribed to circulating Ig light chains. Here we show that IgLCs can confer mast cell dependent hypersensitivity in mice. Antigenic stimulation results in plasma extravasation, cutaneous swelling and mast-cell degranulation. We show that IgLCs have a crucial role in development of contact sensitivity, which could be completely prevented by a novel IgLC antagonist. Although IgE and IgG(1) are central to the induction of immediate hypersensitivity reactions, our results show that IgLCs have similar activity. IgLCs may therefore be a novel factor in the humoral immune response to antigen exposure. Our findings open new avenues in investigating the pathogenesis of autoimmune diseases and their treatments.
12041736 Novel molecular targets for systemic lupus erythematosus. 2002 Jun For a long time the complement cascade has been believed to be the predominant pathway to inflammation and tissue destruction in autoimmune diseases such as systemic lupus erythematosus. Recently, new evidences show that FcRs may share the primacy with complement cascade, playing an equal or greater role in the disease process. The generation of specific mouse strains deficient in individual components has clarified the different role played by complement and Fc receptors in their interaction with ICs, illustrating that complement is essential for innate immunity against microbial pathogens, requiring natural antibodies to mediate its protective effects, whereas FcyRs have evolved as the principal system for coupling antigen-antibody complexes to effector cells and initiate the inflammatory cascade. Validation of FcRs as new therapeutic targets for autoimmune diseases, in particular for Systemic Lupus Erythematosus (SLE), has been provided by a large number of studies where the biological action of soluble forms of FcyRs or of monoclonal antibodies targeting Fc receptors has been assessed. Additional support to the role of FcRs in SLE has been provided by data obtained with compounds derived from combinatorial chemistry, such as TG19320, a tetrameric tripeptide which interferes with IgG/FcgammaR interaction in vitro and prevents glomerulonephritis in vivo in a SLE susceptible mouse strain. These findings might open the way to new therapeutic approaches for disorders where the role of FcRs has been established, including not only autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis, multiple myeloma, but also acquired immunodeficiency syndrome (AIDS).
12028629 Spontaneous ureteral rupture: is immediate surgical intervention always necessary? Present 2002 Apr PURPOSE: We report our experience with spontaneous ureteral rupture (SUR) managed conservatively. CASE REPORTS: Data on three men and one woman 53 to 89 years old (mean age 73) with SUR were retrospectively evaluated. The common complaint was sudden-onset abdominal and concomitant flank pain. On physical examination, all patients had abdominal tenderness and pain with costovertebral angle tenderness on the associated side. One patient had rheumatoid arthritis treated with corticosteroids, and one had carcinoma of the prostate. All patients had urinary extravasation on CT scans. Two patients had ureteral obstruction by stones, and another had bladder outlet obstruction secondary to prostate cancer. Interestingly, irrespective of the obstruction level, the rupture was near the ureteropelvic junction in all patients. The symptoms regressed within hours after basket catheterization and ureteral stent placement in one patient and close follow-up and supportive treatment in three patients. In two patients, disappearance of extravasation and reabsorption of perirenal fluid were confirmed by second- and third-day CT scans. The patients were followed for a mean of 17 (range 14-21) months without any problems. CONCLUSIONS: We believe that SUR cases are more frequent than reported. It is the authors' opinion that if the clinical scenario is suspected in the acute phase and investigated by appropriate radiologic techniques, many more SUR cases will be diagnosed. Careful monitoring with supportive measures may be curative in the majority of the patients, obviating a surgical intervention.
11980582 Internet hand x-rays: A comparison of joint space narrowing and erosion scores (Sharp/Gena 2002 Apr 30 BACKGROUND: The objective of the study is to examine the reliability of erosion and joint space narrowing scores derived from hand x-rays posted on the Internet compared to scores derived from original plain x-rays. METHODS: Left and right x-rays of the hands of 36 patients were first digitized and then posted in standard fashion to a secure Internet website. Both the plain and Internet x-rays were scored for erosions and joint space narrowing using the Sharp/Genant method. All scoring was completed in a blind and randomized manner. Agreement between plain and Internet x-ray scores was calculated using Lin's concordance correlations and Bland-Altman graphical representation. RESULTS: Erosion scores for plain x-rays showed almost perfect concordance with x-rays read on the Internet (concordance 0.887). However, joint space narrowing scores were only "fair" (concordance 0.365). Global scores demonstrated substantial concordance between plain and Internet readings (concordance 0.769). Hand x-rays with less disease involvement showed a tendency to be scored higher on the Internet versions than those with greater disease involvement. This was primarily evident in the joint space narrowing scores. CONCLUSIONS: The Internet represents a valid medium for displaying and scoring hand x-rays of patients with RA. Higher scores from the Internet version may be related to better viewing conditions on the computer screen relative to the plain x-ray viewing, which did not include magnifying lens or bright light. The capability to view high quality x-rays on the Internet has the potential to facilitate information sharing, education, and encourage collaborative studies.
11979139 Delayed hypersensitivity reaction and acute respiratory distress syndrome following inflix 2002 May Infliximab, a chimeric human/murine monoclonal antibody directed against the proinflammatory cytokine tumor necrosis factor alpha, is an effective therapy for Crohn's disease (CD) and rheumatoid arthritis refractory to standard medical treatment. We report a case of adult respiratory distress syndrome associated with infliximab therapy. A 33-year-old white male presented with an exacerbation of CD and was treated with his second infliximab infusion (15 months following the first infusion). Within 7 days he developed arthralgias, myalgias, and fever, followed by respiratory failure. He required intubation and mechanical ventilation. Open lung biopsy demonstrated eosinophilic pneumonia. Human antichimeric antibodies were present at high concentrations. An extensive investigation for infectious etiologies was negative. The patient was treated with intravenous corticosteroids, and fully recovered after a prolonged hospitalization. We review the infectious and immunologic complications of infliximab.
11940117 Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the co 2002 Apr Differentiated dendritic cells (DC) have been identified by the presence of nuclear RelB (nRelB) and HLA-DR, and the absence of CD20 or high levels of CD68, in lymph nodes and active rheumatoid arthritis synovial tissue. The current studies aimed to identify conditions in which nRelB is expressed in human tissues, by single and double immunohistochemistry of formalin-fixed peripheral and lymphoid tissue. Normal peripheral tissue did not contain nRelB+ cells. nRelB+ DC were located only in T- or B-cell areas of lymphoid tissue associated with normal organs or peripheral tissues, including tonsil, colon, spleen and thymus, or in association with T cells in inflamed peripheral tissue. Inflamed sites included skin delayed-type hypersensitivity reaction, and a wide range of tissues affected by autoimmune disease. Nuclear RelB+-HLA-DR- follicular DC were located in B-cell follicles in lymphoid organs and in lymphoid-like follicles of some tissues affected by autoimmune disease. Lymphoid tissue T-cell areas also contained nRelB(-)-HLA-DR+ cells,some of which expressed CD123 and/or CD68. Nuclear RelB+ cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.
11923364 Immunoglobulin M (IgM)-glycoinositolphospholipid enzyme-linked immunosorbent assay: an imm 2002 Apr In the present study we developed an enzyme-linked immunosorbent assay (ELISA) to measure immunoglobulin M (IgM) specific for glycoinositolphospholipids (GIPL) derived from tachyzoite membrane (IgM-GIPL ELISA). The sensitivity and specificity of the assay were compared with those of commercially available Toxoplasma-specific IgM serological tests, namely, immunofluorescence assay (IFA) with fixed tachyzoites and capture ELISA employing tachyzoite extracts. Our results show that all patients with acute toxoplasmosis, as determined by clinical data and conventional serological tests, were also positive by the IgM-GIPL ELISA. Interestingly, many patients that were classified as indeterminate, who had IgG with high avidity but positive results in the IgM-specific IFA and capture ELISA, were negative by the IgM-GIPL ELISA. Finally, we tested the sera from patients with rheumatoid arthritis and various parasitic infections and found no evidence of false positives in the IgM-GIPL ELISA.
11846437 Psychoneuroimmunology of depression: clinical implications. 2002 Feb Psychoneuroimmunology is a field that investigates the interactions between the brain and the immune system. One important goal of this field of research is to translate basic research in order to understand how behavior affects health and resistance to disease in humans. This review evaluates the impact of depression on morbidity and mortality risk and asks whether neuroimmune mechanisms contribute to this association. Examples are drawn from three diseases: cardiovascular disease, infectious disease, and rheumatoid arthritis. Finally, the potential for biobehavioral interventions to impact psychological adaptation and the course of immune related disease is discussed.
15856862 Implantable direct current stimulation in para-axial cervical arthrodesis. 2004 Nov This retrospective, case-controlled pilot study was designed to examine the efficacy and safety of an implantable direct current bone growth stimulator (IDCBGS) as an adjunct to cervical arthrodesis in patients at high risk for nonunion after undergoing cervical fusion in region from the occiput to C3. Twenty patients underwent para-axial cervical arthrodesis (involving posterior spine fusion and instrumentation using standard surgical techniques) for the correction of instability. All were at high risk for nonunion due to advanced age, rheumatoid arthritis, prior failed fusion attempts, infection, or immunosuppressive drug use. An IDCBGS was used to augment the surgical procedure. The mean follow-up period was 19 months, and 16 patients were available for follow-up. Radiographic evidence of fusion was demonstrated in 15 of 16 patients (94%). After surgery, all patients demonstrated clinical stabilization, a resolution of symptoms in combination with an improvement in neurologic status, or both. The mean elapsed time before fusion occurred was 4.6 months. No neurologic complications related to cathode or generator placement were observed. The use of the stimulator as an adjunct to instrument- or non-instrument-assisted surgical fusion of the para-axial region in these high-risk patients appeared both safe and efficacious. Further investigation is warranted to define the possible role and clinical utility of the IDCBGS in selected patients requiring cervical fusion, particularly those at high risk for nonunion.
15615235 [Disease associations in 250 patients with temporal (giant cell) arteritis]. 2004 Nov 6 INTRODUCTION: Miscellaneous disorders have been described in association with temporal (giant cell) arteritis (TA), most often anecdotally, except with arteriosclerosis. METHOD: In a retrospective study, we reported our personal experience of disease associations in a series of 250 patients diagnosed with TA and followed-up in the department between 1976 and 2003. RESULTS: Disease associations were found in 43 patients, i.e. 17% of cases: concurrent malignancy (23 patients: 17 cancers and 6 blood diseases), primary Gougerot-Sjögren's syndrome (6 cases), endocrine disease other than Hashimoto's thyroiditis (7 cases: 3 hyperparathyroidism [HPP], 3 hyperthyroidism, 1 association HPP + hyperthyroidism), polyneuropathy (3 cases), essential thrombocythaemia (2 cases), anti-neutrophilic cytoplasmic (anti-myeloperoxidase) antibodies (2 cases), and miscellaneous associations (1 case of RS3PE syndrome, nephrotic syndrome, myasthenia, sarcoidosis, and macro-creatine kinase type 2). More than one disease associated was present 5 patients. In 77% of the patients, there was a strong temporal association between TA and the alternate illness. No systemic necrotizing vasculitis or rheumatoid arthritis was observed in any patient. CONCLUSION: In our experience, there was a frequent, non-fortuitous, association between TA and malignancy. Auto-immune conditions were rare, but the prevalence of Gougerot-Sjögren's syndrome might have been underestimated. Hyperthyroidism and HPP are not exceptional and must be recognised in order to avoid severe bone loss induced by corticosteroids.
15579071 Coumarin and isocoumarin as serine protease inhibitors. 2004 Serine proteases are attractive targets for the design of enzyme inhibitors since they are involved in the etiology of several diseases. Within the class of serine proteases, HLE is one of the most destructive enzymes in the body. It is implicated in the promotion or exacerbation of a number of diseases including pancreatitis, acute respiratory syndrome, rheumatoid arthritis, atherosclerosis, pulmonary emphysema, and cystic fibrosis. Thrombin, a trypsin-like serine protease, plays a dual role in thrombogenesis, including fibrin formation and platelet activation. As a result, thrombin constitutes one of the most widely studied targets for antithrombotic strategy. Numerous inhibitors of serine proteases have been reported during the past three decades. Among them, coumarin-type molecules displayed a high inhibitory potency towards various serine proteases. At that time, halomethyl dihydrocoumarins have been shown to behave as the first general suicide inhibitors of serine protease. These molecules inhibit several proteases such as human leucocyte elastase, porcine pancreatic elastase, thrombin, urokinase and human plasmin. Isocoumarins are very effective as mechanism-based inhibitors of serine proteases. Pharmacomodulation on the 3-alkoxy-4-chloroisocoumarins and the 3-alkoxy-7-amino-4-chloroisocoumarins led to strong inhibitors of numerous serine proteases such as HLE, human factor XIa and XIIa, thrombin, urokinase and kallikrein. Recently, a series of coumarins characterised by an alkyl, aryl ester, amide, thioester or ketone in the position 3 and an electrophilic chloromethyl moiety in the position 6 have been developed. These compounds were found to be high inhibitors of alpha-chymotrypin, HLE and human thrombin.
15315082 Education and multidisciplinary team approach in childhood diabetes. 2004 Apr Type 1 diabetes is one of the most frequent chronic diseases in childhood. As in other chronic diseases (asthma, cystic fibrosis, rheumatoid arthritis, epilepsy) children and their families become the focus of self-treatment and the directors of their own care; thus, the health care team should be the guides who set the stage, provided advice and oversight and helped to re-focus efforts when goals were not being met all centered around the patient and family. Rather than the diabetes health care team being the only ones to initiate treatment, patient and parents have to be empowered to analyze their own data, identify patterns, problem solve with food and activity and do so based upon actual blood glucose results. Home record keeping and memory meters facilitate such analysis just as the algorithms currently in use attempt to mimic the basalbolus pattern of endogenous insulin secretion previously provided by a working pancreas. In the past, often disaster control was the modus operandi for the person with diabetes. Parents and health care providers were involved with criticism and accusations about "cheating" rather than learning how better to supervise and provide oversight. Nowadays, better knowledge of physiopathology of diabetes, availability of new insulins and devices, as well as different education of health providers pave the way for ameliorating self-care in children and adolescents with diabetes, with the aim of improving metabolic control and quality of life of children and their family, with the ultimate aim of preventing macrovascular and microvascular complications.
15245533 Multicentric reticulohistiocytosis with generalized systemic involvement. 2004 Jul We describe a 33-year-old woman with a 2-year history of rheumatoid arthritis-like joint changes and a 1-year history of papulonodules on the fingers, ears, oral mucosa, forearm, elbows and thighs, and erythematous plaques on the buttocks. Six months after the onset of the cutaneous lesions she had dyspnoea, 3 months later she developed a husky sound. Biopsies from the nodules on the ear and left forearm revealed multinucleated giant cells with eosinophilic 'ground-glass' cytoplasm. Bronchoscopy revealed that there were nodules in the bronchus. A biopsy taken from a nodule from the bronchus was consistent with multicentric reticulohistiocytosis. Fibrostic laryngoscopy showed a mass 1.5 x 2.0 cm(2) in size on the left aryepiglottic fold and posterior commissure. Magnetic resonance imaging revealed a large pleural effusion and pericardiac effusion. Ultrasound revealed splenomegaly and peritoneal fluid. Combination therapy with prednisone, cyclophosphamide and methotrexate significantly improved cutaneous and joint symptoms. The huge cutaneous erythematous plaques and the generalized systemic involvement make this case interesting.
15228371 Injectable biologic case studies. 2004 May OBJECTIVE: To identify strategies used by a commercial managed care organization (MCO) to affect appropriate cost-effective use and prioritize payment for biologic agents. SUMMARY: With the rapid increase in the number of biologic agents and the lack of head-to-head comparative trials, determining clinical superiority of one agent may be challenging. Four case studies are presented that highlight strategies used by a commercial MCO to manage the costs and utilization of these agents and identify a preferred biologic therapy to recommend for its internally developed prior-authorization (PA) criteria for rheumatoid arthritis, asthma, psoriasis, and multiple sclerosis. The first case illustrates how the route of drug administration, differences in distribution channels, and the need for cotherapy can impact the overall cost of therapy. The second case demonstrates the need for tight control of drug utilization when a biologic agent offers only marginal incremental clinical benefit over existing options but at a substantial increase in cost. The third case provides an example of the relationship between increased efficacy and the cost of therapy, and the fourth case demonstrates that PA criteria can be flexible with respect to drug coverage when clear therapeutic differences have not been demonstrated among drugs. CONCLUSION: As more biologic agents become available, it is critical that pharmacy decision makers critically evaluate these innovative new therapies by using the best available evidence to determine the products that provide the greatest clinical and economic value.
15218409 Complementary and alternative approaches to the treatment of persistent musculoskeletal pa 2004 Jul OBJECTIVE: To review common complementary and alternative treatment modalities for the treatment of persistent musculoskeletal pain in older adults. METHODS: A critical review of the literature on acupuncture and related modalities, herbal therapies, homeopathy, and spinal manipulation was carried out. Review included 678 cases within 21 randomized trials and 2 systematic reviews of herbal therapies: 798 cases within 2 systematic reviews of homeopathy; 1,059 cases within 1 systematic review of spinal manipulation for low back pain, and 419 cases within 4 randomized controlled trials for neck pain. The review of acupuncture and related modalities was based upon a paucity of well-controlled studies combined with our clinical experience. RESULTS: Insufficient experimental evidence exists to recommend the use of traditional Chinese acupuncture over other modalities for older adults with persistent musculoskeletal pain. Promising preliminary evidence exists to support the use of percutaneous electrical nerve stimulation for persistent low back pain. While some herbals appear to have modest analgesic benefits, insufficient evidence exists to definitively recommend their use. Drug-herb interactions must also be considered. Some evidence exists to support the superiority of homeopathic remedies over placebo for treating osteoarthritis and rheumatoid arthritis. The benefits of spinal manipulation for persistent low back and neck pain have not been convincingly shown to outweigh its risks. DISCUSSION: While the use of complementary and alternative modalities for the treatment of persistent musculoskeletal pain continues to increase, rigorous clinical trials examining their efficacy are needed before definitive recommendations regarding the application of these modalities can be made.
15151766 [Development and preliminary application of a double mAb sandwich ELISA for detecting solu 2003 Mar AIM: To develop a double mAb sandwich ELISA for detecting sCD226 and apply it to clinical specimens. METHODS: The optimal concentrations of coating mAb and HRP-mAb, and the optimal diluents were determined. A double mAb sandwich ELISA then was established. The specificity, sentivity and stability of the method were identified. And clinical specimens were detected by this method. RESULTS: The optimal concentrations of coating mAb LeoA1 and HRP-mAb FMU3 were 2.5 mg/L and 1:400, respectively, and the optimal diluents for standard antigen and HRP-mAb were 1 g/L BSA 1 mL/L Tween20-PBS and 30 g/L PEG-PBS.The ELISA achieved satisfactory results in respect to specificity (no cross-reaction to human IgG, in block test blocking effect was does-dependent), sensitivity (the detected threshold was 110 ng/L) and stability (CV<10.2%). Statistical analysis showed that the serum sCD226 level in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy adults. CONCLUSION: A double mAb sandwich ELISA with high specifity, and relative sensitivity for detection of sCD226 has been developed. It is shown to be an applicable method of detecting sCD226 in clinical specimens.
15134003 Noninvasive treatment of inflammation using electromagnetic fields: current and emerging t 2004 Magnets, electric current and time varying magnetic fields always have played a role in human medicine. Natural magnetic stones were used in ancient cultures to induce a therapeutic effect and modern clinical practice would be far less effective without nuclear magnetic resonance imaging, cardiac pacemakers, and bone growth stimulators. This paper presents a summary of natural and artificial electromagnetic field (EMF) characteristics that are currently in use or under investigation for other therapeutic applications. This background understanding provides a basis for discussion on the success and possible risks of emerging and novel EMF therapies. Although interest in energy medicine has existed for centuries in some parts of the world, in recent years this is an area of heightened interest for western healthcare practitioners. This awareness has been triggered by the growing body of knowledge on how EMFs interact with cellular systems. EMF therapy for the treatment of pain, cancer, epilepsy, and inflammatory diseases like psoriasis, tendinitis and rheumatoid arthritis is currently being explored. The long-term success of this new area of medicine is still unknown. On the one hand, it remains to be seen whether positive human outcomes with EMF therapy could be explained by enhancement of the placebo effect. Optimistically, EMF therapy has the potential to revolutionize medicine, which is currently dominated by pharmaceutical and surgical interventions. In this case, new therapeutic tools may be developed for future clinicians to provide noninvasive treatments with low risk of side effects and no problem with drug interactions.