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ID PMID Title PublicationDate abstract
10419850 New targets for anti-inflammatory drugs. 1999 Aug Inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, psoriasis and asthma, provide drug discoverers with a tremendous challenge. The precise causes of these diseases are not known, but our understanding of the molecular and cellular mechanisms associated with inflammatory diseases has increased dramatically. As a consequence, a wide array of gene targets have emerged that control cell influx and activation, inflammatory mediator release and activity, and tissue proliferation and degradation. Since multiple gene products have been identified at the sites of inflammation, there has been a surge of interest in identifying intracellular signaling targets, including transcription factors that control inflammatory gene expression and which are amenable to drug discovery.
10102534 Negative conversion of antimitochondrial antibody in primary biliary cirrhosis: a case of 1999 Feb Autoimmune cholangitis is a clinical constellation of chronic cholestasis, histological changes of chronic nonsuppurative cholangitis and the presence of autoantibodies other than antimitochondrial antibody (AMA). It is uncertain whether this entity is definitely different from AMA positive primary biliary cirrhosis (PBC), though it shows some differences. We report a case of autoimmune cholangitis in a 59-year-old woman, who had been previously diagnosed as AMA-positive PBC associated with rheumatoid arthritis, has been converted to an AMA-negative and anticentromere antibody-positive PBC during follow-up. The response to ursodeoxycholic acid treatment is poor except within the first few months, but prednisolone was dropping the biochemical laboratory data.
10102221 Pathogenesis and medical therapy of primary sclerosing cholangitis. Any news? 1999 Feb Primary sclerosing cholangitis is characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. Medical therapy has focused on anticholestatic, antiinflammatory and immunosuppressive drugs. Although inflammation, fibrosis and cholestasis may all occur at the same time, inflammation dominates the early phase and fibrosis and cholestasis the later stages. With inflammatory bowel disease and rheumatoid arthritis as stimulants, research on anti-inflammatory drugs is in a very active stage, with an emphasis on cytokines and cytokine antagonists. For patients with primary sclerosing cholestasis to fully benefit from these developments, it is necessary to define the early disease stage that constitutes a potential therapeutic window for these agents.
9739601 [Cross-sectional therapeutic programs--an example of a cooperative health care system. A r 1998 Aug 24 There is no tradition for sharing the responsibility for episodes of care between the primary and secondary sectors in the Danish health care system. Concurrently with increased international experience with shared care programmes, there is also a growing interest in Denmark in cooperation between the sectors. Based on literature research, shared care programmes are presented as a method of ensuring continuity and quality in treatment of chronic diseases. Experiences in the areas of diabetes, asthma, rheumatoid arthritis, and cancer are described. It is concluded that the Danish health care system is well prepared for the implementation of shared care programmes; there are only few sources of payment in the system, and an extensive continuing medical education system ensures that general practitioners can participate in relevant education. The implementation of shared care programmes in Denmark should be followed by scientific evaluation and documentation of the quality of the treatment programmes.
9531831 [Diphosphonates--pharmacology and clinical use]. 1998 Mar 10 Based upon recent research, bisphosphonates have now attained a ranking as the first alternative to oestrogen replacement therapy in women with postmenopausal osteoporosis. The efficacy of these drugs has been clearly documented in recent years, particularly as a result of extensive clinical trials with alendronate. The studies have also confirmed the favourable risk/benefit ratio. The specific affinity of bisphosphonates for bone tissue has been recognized for many years, and explains the diagnostic use of radio-labelled species in skeleton scintigraphy. Bisphosphonates deposited in bone tissue reverse the osteoporotic process by inhibiting osteoclastic bone resorption. This mechanism also explains their role as the treatment of choice in patients with Paget's disease and cancer induced hypercalcaemia. In addition, the same drugs are useful adjuvants in the treatment of patients with multiple myeloma or bone metastases to lessen the pain and risk of fracture. A possible role of bisphosphonates in the management of cancer patients without detectable bone metastases or patients with rheumatoid arthritis has been discussed, but further research is needed in these areas.
9379070 Role of nitric oxide in the physiopathology of pain. 1997 Oct Many painful disorders, including joint dysfunctions such as rheumatoid arthritis (RA) or temporomandibular joint disorders (TMD), are associated with hyperthermia of the overlying skin. The same is true of certain intractable chronic pain conditions, such as chronic orofacial pain, which may be associated with TMD. We suggest that this skin hyperthermia, caused by regional vasodilation, is induced by extravascular nitric oxide (NO). Extravascular NO can be produced in the affected joint by osteoblasts, chondrocytes, and macrophages, by mechanical stimulation of endothelial cells, or by stimulated neurons. In view of a strong correlation between pain and skin hyperthermia in these disorders, and the evidence that NO enhances the sensitivity of peripheral nociceptors, we also suggest that at least this kind of pain is associated with excessive local level of NO. This hypothesis can be verified by dynamic area telethermometry, assessing the effect of NO on the sympathetic nervous function. This mechanism, which is in line with the general role of NO as a mediator between different organ systems, also may be relevant to any pain associated with enhanced immune response. Clinical implications of the proposed mechanism are discussed.
9200947 [Application of chimeric and humanized antibodies to autoimmune diseases therapy]. 1997 Jun Monoclonal antibodies (MAbs) have been extensively developed for treating autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and intestinal bowl diseases. Recombinant DNA technology made it possible to manufacture chimeric and humanized MAbs, resulting in lower antigenicity, longer half-life in serum and higher biological activities compared to the original murine MAbs. Here, chimeric and humanized MAbs under clinical investigations in the field of autoimmune diseases are reviewed. At this time, non-deleting type of anti-CD4 MAb and anti-TNF alpha MAb have an attractive attention because of their excellent efficacy in the clinical trials. Although deleting type of anti-CD4 MAb failed to show the efficacy in double-blind phase III trials reproducibly, it should be re-evaluated on the administration dosage and duration. In the near future, MAbs to adhesion molecules and co-stimulatory molecules will be studied in clinics.
9200925 [TCR repertoire of autoreactive T cells in autoimmune disorders]. 1997 Jun In human autoimmune diseases such as rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis, it has been clarified that autoreactive T cells play a crucial role in the generation of autoimmune disorders. Immunohistochemical studies have shown that most infiltrating lymphocytes are CD4 positive alpha beta T cells. Recent studies with polymerase chain reaction (PCR) provides evidence about the T cell receptor (TCR) V beta and V alpha genes on their T cells. Sequence analysis of the complementarity determining region 3 (CDR3), which is a central portion for recognition of antigens by T cells, indicates some conserved amino acid motifs, supporting the notion that infiltrating T cells recognize relatively few epitopes on autoantigen.
18031094 [Not Available]. 1997 Mar The association of HIV infection with rheumatic syndromes is reviewed, with emphasis on the specific differences between the rheumatic diseases in their idiopathic form compared with their occurrence with HIV infection. Alterations in presentation, pathogenesis and treatment are stressed. The first section of the article concentrates on joint and articular involvement, and the second on autoimmune phenomenon in relation to lymphatic organs, muscle and vasculature. Wherever possible, the direct effect of the HIV organism or its effect on the immune system modifying or contributing to the aetiology of each disease is discussed. HIV infection has many manifestations, and involvement of the musculoskeletal system is not uncommon. Various infections of bone, joint and muscle have been described, which is not surprising considering the immunodeficiency associated with HIV. Reiter's syndrome and the seronegative arthropathies and reactive arthritides also may be expected, particularly with the possible occurrence with sexually transmitted organisms. New onset of psoriasis in an adult should prompt the physician to consider HIV infection in the differential diagnosis. Perhaps more surprising is the occurrence of autoimmune diseases in association with HIV. However, as will be described, some of the associations such as rheumatoid arthritis and HIV are controversial and we attempt to describe current theories on pathogenesis, recognising that much more investigation is needed before we have a complete understanding of this disease.
9088530 Health economics in rheumatology. 1997 Feb Economic evaluations of health-care technologies are playing an increasingly central role in determining which therapies are available to clinicians in the treatment of a whole range of conditions. In rheumatology, a large body of work has already been done on the cost effectiveness of alternative non-steroidal anti-inflammatory drugs (NSAIDs), and much of the current work on disease modifying therapies incorporates economic evaluations. This chapter describes the main techniques of economic evaluation and reviews the strengths and weaknesses of each. Two published economic evaluations are discussed in order to highlight what economic evaluations can offer to the care of people with rheumatoid arthritis, as well as the current limitations of economic evaluation. The objective of this chapter is to equip readers with a critical understanding of economic evaluation that can be used in considering the increasing volume of health economic data that they encounter in their clinical work.
9444794 Vascular endothelial growth factor: a key mediator of neoangiogenesis. A review. 1997 Jan Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that exerts in vivo a key role in physiological and pathological neoangiogenesis by stimulating endothelial cell proliferation and vessel hyperpermeability. VEGF exists as one of four different isoforms, respectively, VEGF 121, VEGF 165, VEGF 189, VEGF 206, and seems to be a crucial mediator of physiological neoangiogenesis during the embryonic development and the female cycle. VEGF also has a major role in the pathogenesis of many diseases including hypervascularized tumors, rheumatoid arthritis, cutaneous diseases and proliferative retinopathies. Anti-VEGF anti-bodies or VEGF agonists may represent a novel approach in the treatment of these diseases.
9466462 Peptide plasticity in primary sensory neurons and spinal cord during adjuvant-induced arth 1998 Jan Chronic polyarthritis due to complete Freund's adjuvant injection is characterized by severe inflammation and pain. In the present immunocytochemical and in situ hybridization study on the rat, we quantitatively investigated peptide and peptide messenger RNA expression in the sensory circuit at the spinal level, i.e. sensory neurons in the dorsal root ganglia and in nerve endings and local neurons in the dorsal horn of the spinal cord. The immunocytochemical experiments were carried out five, 13 and 21 days after complete Freund's adjuvant injection, whereas in situ hybridization study was performed after 21 days from complete Freund's adjuvant injection. The main results in the present study are the following: (i) a decrease in substance P-, calcitonin gene-related peptide- and galanin-like immunoreactivities in dorsal root ganglia is observed five days after complete Freund's adjuvant injection, with recovery (calcitonin gene-related peptide and galanin) or even an increase (substance P) after 21 days; (ii) calcitonin gene-related peptide, substance P and galanin peptide levels are increased in dorsal root ganglia after 21 days; (iii) opioid peptide (enkephalin and dynorphin), substance P and galanin messenger RNAs are strongly up-regulated in dorsal horn neurons after 21 days; (iv) neuropeptide Y content increases in dorsal root fibres and neuropeptide Y messenger RNA levels decrease in spinal neurons after 21 days; and (v) a dramatic decrease in calcitonin gene-related peptide and cholecystokinin messenger RNA levels is found in motoneurons in the ventral horn after 21 days. These data indicate that peptide expression in dorsal root ganglia and the spinal cord is markedly influenced by severe inflammation with distinct and individual temporal patterns, which are also related to the severe rearrangement of joint structure during polyarthritis. The increase in galanin levels in dorsal root ganglia 21 days after complete Freund's adjuvant injection can be related to the structural damage of nerve fibres. Thus, there may be a transition from inflammatory to neuropathic pain, which could have consequences for treatment of patients with rheumatoid arthritis.
10630653 The clinical associations of mitotic spindle autoantibodies in a South Australian cohort. 1999 Oct BACKGROUND: The mitotic spindle apparatus (MSA) is a unique structure of microtubules and associated proteins involved in the segregation and reorganisation of chromosomes during cell division. Autoantibodies to the MSA (anti-MSA) are reported to occur rarely, but are easily identified during the immunofluorescent detection of anti-nuclear antibodies (ANA), and are generally reported as part of that investigation. AIMS: As the clinical significance of these antibodies is unknown, our aim was to identify the clinical features of subjects identified with anti-MSA, and in a subset investigate the co-association with organ specific anti-thyroid antibodies. METHODS: All ANA results from the three major immunology laboratories serving South Australia between January 1993 and June 1998 were retrospectively reviewed to identify anti-MSA subjects. Clinical details were extracted from hospital or general practice records using a standard proforma. Thyroid autoantibodies were measured using standard technique. A control group of consecutive ANA positive, anti-MSA negative individuals had anti-thyroid antibodies measured. Statistical comparison used chi2 test. RESULTS: Fifty-five subjects (43F) were identified with mean age 59.8 (range 17-91); 39 had specific diagnoses, with 16 identified as part of non-specific investigations. 'Arthritis' broadly accounted for the largest group, transient inflammatory arthritis n=7, degenerative joint disease n=6, rheumatoid arthritis n=5. Adenocarcinoma and mesothelioma accounted for one case each. Thirty-two subjects had anti-thyroid antibodies tested, with ten of 21 and two of 11 positive among the groups with anti-MSA titre >1:80 and <1:40 respectively, chi2=2.7, p=0.1. Anti-thyroid antibodies were detected more frequently among the high titre anti-MSA group (ten of 21) compared with high titre positive ANA, negative anti-MSA group (two of 11), RRisk 4.4, chi2=5.34, p=0.02. CONCLUSION: This study confirmed the relative rarity of anti-MSA and that its association is primarily with rheumatic diseases. The coincidence of mesothelioma is novel with only two previous reports of malignancy and anti-MSA. The co-association of high titre anti-MSA and thyroid autoantibodies suggest that the latter should be a follow up investigation if the former is identified as part of an investigative screen.
11673052 The structure of calcium-free human m-calpain: implications for calcium activation and fun 2001 Aug The calpains form a growing family of structurally related intracellular multidomain cysteine proteinases containing a papain-related catalytic domain, whose activity depends on calcium. The calpains are believed to play important roles in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction, but are also implicated in muscular dystrophy, cardiac and cerebral ischemia, platelet aggregation, restenosis, neurodegenerative diseases, rheumatoid arthritis and cataract formation. The best characterized calpains, the ubiquitously expressed mu- and m-calpains, are heterodimers consisting of a common 30-kDa small and a variable 80-kDa subunit. The recently determined crystal structures of human and rat m-calpain crystallized in the absence of calcium essentially explain the inactivity of the apoform by catalytic domain disruption, indicate several sites where calcium could bind causing reformation of a papain-like catalytic domain, and additionally reveal modes by which phospholipid membranes could reduce the calcium requirement. Current evidence points to a cooperative interaction of several sites, which, upon calcium binding, trigger the reformation of a papain-similar catalytic domain.
11642636 Immunomodulators. 2001 Oct Cytokine immunomodulators have received considerable attention. Interferon-alpha has broad clinical application for treatment of a number of viruses. The neutrophil-stimulatory effects of interferon-gamma are useful in neutrophil disorders. TNF antagonists are useful in rheumatoid arthritis but carry the risk of activating intracellular organisms. Hemopoietic growth factors have considerable clinical effect in patients receiving immunosuppressive chemotherapy. A number of cytokines and cytokine antagonists are undergoing research development.
11082224 Amyloid goiter: the first evidence in secondary amyloidosis. Report of five cases and revi 2000 Apr Amyloid deposition in secondary amyloidosis frequently involves thyroid gland, but rarely is responsible of a goiter. Amyloid goiter in secondary amyloidosis is characterized by deposition of amyloid A protein (AA) in the gland, associated to atrophic follicles. We identified cases of amyloid goiter in the files of our department in the period from 1985 to 1998. Five cases of amyloid goiter with ingravescent symptomatology, characterized by dyspnea, dysphagia and hoarseness were selected. In four cases of five we observed predisposing conditions as, for example, tuberculosis, Crohn's disease, or rheumatoid arthritis. In all cases the symptoms relative to thyroid enlargement preceded or, anyway, predominated over other clinical evidence of systemic amyloidosis. In one case a symptomatology of systemic amyloidosis was not evident. We would like to underline that in all cases the immunoreactivity for amyloid A in the amorphous material present in the gland permitted the diagnosis of secondary amyloidosis even in the absence of systemic symptoms.
11051022 [Correlation between degenerative changes of the thoracic spine and the finger joints--a r 1999 Jul PURPOSE: Different studies in patients with rheumatoid arthritis demonstrated a correlation between degenerative changes of the cervical spine and peripheral joints. The aim of study therefore was to assess the relations of degenerative changes of the cervical spine and peripheral joints. METHODS: 106 patients suffering on Generalized Osteoarthritis were examined by standard radiography of the hands and cervical spine. All images were evaluated according to Kellgren grades. The mean values of the cervical spine and finger joints were compared in three calculations, for this purpose the finger joints were "segmental", "functional" and randomized arranged. RESULTS AND CONCLUSIONS: Concerning quality and quantity the highest correlation was observed in the group of the so-called "segmental-arrangement". Therefore a association between the cervical spine and the finger joints seems possible relating to manifestation, pattern and graduation of degenerative processes. At this stage there is no statement possible about the direction of the correlation.
10829362 Afelimomab. 2000 Apr Tumour necrosis factor-alpha (TNF-alpha) is well established as a key mediator in the inflammatory response seen in various disease processes including sepsis. TNF-alpha is involved in virtually all features of septic shock and multiple organ failure. Anti-TNF-alpha strategies are thus appealing and have been effective at reducing inflammation and morbidity in certain conditions including rheumatoid arthritis and Crohn's disease. Afelimomab is the F(ab')2 fragment of a murine anti-TNF-alpha antibody, and has been evaluated in clinical trials in septic patients. The results suggest that the drug is well tolerated, and may be of benefit in certain groups of patients with sepsis. A large, randomised, clinical trial of afelimomab in patients with severe sepsis has recently been completed and the results are eagerly awaited. More work is necessary to identify a means of selecting which patients are most likely to benefit from this type of therapy in sepsis.
10767709 Sweet's syndrome in a patient with idiopathic progressive bilateral sensorineural hearing 2000 May Acute febrile neutrophilic dermatosis, or Sweet's syndrome, was first described in 1964 and consists of a triad of erythematous cutaneous plaques infiltrated by neutrophils in association with fever and leukocytosis. Sweet's syndrome has been reported to be associated with conditions ranging from upper respiratory tract infections to inflammatory bowel disease to rheumatoid arthritis. We report a patient with a 2-year history of Sweet's syndrome in whom idiopathic progressive bilateral sensory neural hearing loss (IPBSNHL) developed. IPBSNHL is a suspected immunologically mediated hearing loss first described by McCabe in 1979. On the basis of this association, hearing evaluation should be considered in the initial and subsequent examinations of the patient with Sweet's syndrome.
10602452 Generalized periodontal involvement in a young patient with systemic lupus erythematosus. 1999 Inflammation is considered to be a leading cause of morbidity in systemic lupus erythematosus (SLE), yet inflammatory periodontal involvement is rarely encountered. A young lady suffering from active SLE accompanied by severe periodontal loss, manifested by gingival recession of all her teeth, was referred to our clinic for treatment. The association between periodontal involvement and connective tissue diseases is unclear, and the literature dealing with periodontal involvement in patients suffering from Sjogren's syndrome and rheumatoid arthritis is comprised of studies showing both normal and pathological periodontal status. We discuss the possible underlying mechanisms.