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ID PMID Title PublicationDate abstract
12942154 Health and medical research down under in 2002. 2003 May The first part of this report on the Australian Health and Medical Research Congress, held November 25-29, 2002, in Melbourne, Australia, considers some of the symposia and three plenary lectures: Neurosteroids: Nature's Valium, G-Protein-Coupled Receptors and the Mike Rand Memorial Lecture. In the new era in relaxin research symposium, we learned that relaxin is a general antifibrotic agent rather than just a hormone of pregnancy. The drugs discussed in the drug discovery symposium included drugs from natural products, allosteric modulators, antibodies to cytokines and AM-336, an N-type Ca(2+) channel blocker. In the matrix proteases symposium, we learned of the importance of these enzymes in bone, endometrial remodeling and cardiovascular disease. The emphasis of the cytokine antagonist symposium was the involvement of cytokines in rheumatoid arthritis and how these effects could be inhibited with cytokine antagonists. The second part of this report is on the cardiovascular components of the meeting. One of the major strengths of Australian research is the cardiovascular area. Thus, it was not surprising that there were three major symposia with a cardiovascular theme this congress. Although the clinical trials of the NHE1 inhibitors in ischemia and reperfusion have been disappointing to date, evidence was presented in the sodium-hydrogen exchanger symposium that these agents might be beneficial in hypertrophy and heart failure. The discussion in the vessel wall biology in diabetes symposium ranged from molecular aspects to clinical trials. In this, and the NAD(P)H oxidases symposium, many new potential drug targets were discussed. The plenary lecture of the High Blood Pressure Research Council concerned the pathophysiology and management of obesity hypertension, and included a discussion of the drugs for weight reduction.
12926653 Musculoskeletal conditions in France. 2003 Aug Musculoskeletal conditions (MSC) are among the most frequent in adults in France, with over 20% of the population experiencing bone, joint, and muscle disorders. MSC are an increasing health concern in France, growing in importance on the public health agenda. Some of the present governmental plans are connected with MSC (Pain, the Disabled, Nutrition, Geriatrics). An overview of the present situation in France is provided, regarding the burden, the present situation, and steps forward. Scientific societies and patient groups are actively involved in campaigning in several fields; 2 examples are described: osteoporosis and rheumatoid arthritis and spondyloarthropathies. The Bone and Joint Decade initiative, officially endorsed by the French Government on June 20, 2000, provides the opportunity to develop more coordinated actions through the national network and international partnership as well (including the European League Against Rheumatism) to finally improve the health-related quality of life for people with MSC.
12839599 Clinical course of psoriasis during pregnancy. 2003 Jul BACKGROUND: Since the landmark study on rheumatoid arthritis, many reports have suggested that physiological changes during pregnancy often induce remission of systemic and cutaneous inflammatory diseases. In this study we investigated the clinical course of psoriasis during pregnancy. OBJECTIVE: In this retrospective study information was collected from Psoriasis Life History Questionnaires. The data obtained from 736 questionnaires were entered into a computerized database. Information relevant to the clinical course of psoriasis during pregnancy was evaluated in respect to improvement/worsening, number of pregnancies, severity of the disease, and certain other clinical parameters. RESULTS: In a majority of the patients psoriasis improved during pregnancy. Data available from 91 pregnancies revealed: psoriasis improved in 51 (56%), worsened in 24 (26.4%), and remained unchanged in 16 (17.6%). Also, appearance of psoriasis new lesions was found to be frequent during the early postpartum period. Patients who improved in the first pregnancy were found to have a similar response in the following pregnancies. CONCLUSION: Research on immuno-endocrine interactions during pregnancy is a relatively new field. Proinflammatory Th-1 cytokines are up-regulated in psoriasis and play a key role in the inflammatory cascades of psoriasis. It is likely that during pregnancy the Th-2 cytokine-mediated down-regulation of the immune response by virtue of its anti-inflammatory and antagonizing effects on the Th-1 cytokines improves psoriasis.
12591006 Could n-3 polyunsaturated fatty acids reduce pathological pain by direct actions on the ne 2003 Mar The intake of n-3 polyunsaturated fatty acids (PUFAs) in many industrialized countries is relatively low and its increased consumption has protective and modifying effects on such diverse conditions as atherosclerosis, ventricular arrhythmias, multiple sclerosis, major depression and inflammatory and autoimmune diseases. In addition, n-3 PUFAs have been shown to alleviate pain in patients with rheumatoid arthritis, inflammatory bowel disease and in a number of other painful conditions. This has been attributed to the inhibition of pro-inflammatory eicosanoid and cytokine production by peripheral tissues. n-3 PUFAs have also been shown to inhibit eicosanoid production in glial cells, block voltage-gated sodium channels (VGSCs), inhibit neuronal protein kinases and modulate gene expression. They also appear to have mood-stabilizing and sympatholytic effects. The present article explores the possibility that, based on what is known about their neural and non-neural effects, n-3 PUFAs directly attenuate the neuronal and glial processes that underlie neuropathic and inflammatory pain.
20704862 Getting a grip on antigen-specific CD4 T cells: Tracking autoimmune T cells in vivo. 2003 Oct Extract: Autoreactive T cells are part of the normal immune system and are kept under control by mechanisms known as anergy. Autoimmune diseases are caused by the breakdown of this tolerance, and T cell activation leads to severe inflammation and tissue damage. For example, in rheumatoid arthritis, synovial joints will be destroyed whereas in insulin-dependent diabetes mellitus (IDDM, type 1 diabetes), insulin-producing beta cells in the pancreatic islets of Langerhans will be the focus of the attack. The genetic makeup of susceptible individuals and the environmental factors leading to autoimmunity are complex and largely unknown. In many instances, the main genetic locus that has been determined is the MHC (major histocompatibility complex) class II locus. In the case of IDDM this locus encodes alleles such as HLA-DR4, -DR3, and -DQ8 in humans and I-Ag7 in the non-obese diabetic (NOD) mouse. Since MHC class II molecules present peptides to CD4 positive T cells, it is tempting to link genes and function and to study closely CD4+ T cells in the context of autoimmunity. It is now well established that, indeed, these cells are essential for the initiation and development of autoimmunity, however, in-depth investigation of them has been impeded by two major roadblocks. First, potential antigens, and therefore relevant peptides, are scarce and difficult to isolate. Secondly, reagents able to detect T cells in an antigen-specific fashion have remained elusive.
11887039 Cat-scratch disease in an immunocompromised host. 2002 Mar BACKGROUND: The main causative agents of cat-scratch disease are Bartonella henselae, tiny, gram-negative bacilli. The disease usually has a benign course with the development of a papule at the inoculation site, followed by regional lymphadenopathy. In most cases, complete resolution occurs, but in immunocompromised hosts, the course of the disease can be aggravated. CASE REPORT: A patient received methotrexate and corticosteroids for 3 months due to rheumatoid arthritis. He developed fever, exanthema and leukopenia under methotrexate therapy. Dark red indurations with central ulcerations at his right thigh revealed a further problem apart from the methotrexate-induced leucopenia and immunosuppression. The ulcerations were the remainders of recurrent scratches from the patient's cat. The patient's antibody titers against Bartonella henselae remained low and inguinal lymph node swelling was only for a short time to be observed, this reaction obviously weakened as a result of the immunosuppression. However, the typical course, the exclusion of other reasons for the exanthema and the rapid improvement of the patient's condition after antibiotic treatment ascertained the diagnosis. CONCLUSIONS: In immunocompromised hosts, diseases with a typically benign course can become severe and life-threatening illnesses. Ownership of pets should be taken into consideration before onset of an immunosuppressive therapy.
11791925 Studies on new polymeric biomaterials with tunable hydrophilicity, and their possible util 2002 Feb A well-known complication in corneal repair surgery is (recurrent) rejection of donor corneal tissue. particularly in patients suffering from an auto-immune disease such as rheumatoid arthritis. Down-regulation of their immune system, by means of drugs, is necessary in order to perform an allograft implantation afterwards. The patient may need a temporary prosthetic cornea while the immune system is inactivated. Recently, NeuroPatch, a mesh-type polyurethane, was used for this purpose. The material exhibits excellent biocompatibility and allows ingrowth of stromal fibroblasts which deposit matrix material into the pores. A serious drawback of NeuroPatch is its non-transparency, which impairs vision. In this work we attempted to develop an improved biomaterial that combines the advantages of NeuroPatch with optical transparency. Based on previous findings that copolymers of hexaethyleneglycolmethacrylate (HEGMA) and butylmethacrylate (BMA), are transparent and well accepted by human corneal epithelial cells, we studied these materials further in detail. (Bruining et al., Bio-Macromolecules 1 (2000) 418) Copolymerizations were studied by means of 1H NMR. The influence of the HEGMA content on hydrophilicity, flexibility and resistance to protein adsorption was studied. The results indicate that materials with a HEGMA content of approximately 20 mol% are potentially useful in corneal repair surgery. These biomaterials meet most of the stringent physical and biological requirements.
11782558 Macrophage migration inhibitory factor. 2002 Jan Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF.
15628321 Erythema nodosum and granulomatous lesions preceding acute myelomonocytic leukemia. 2004 Sep A 65-year-old female with a one-month history of painful eruptions on her lower extremities was admitted to our hospital. Histological examination revealed erythema nodosum (EN), and the patient was treated with oral prednisolone (PSL; 20 mg daily). The eruptions subsided in two weeks. One month later, painful reddish eruptions recurred on her upper limbs and abdomen in addition to her lower extremities. A skin biopsy from an abdominal erythematous plaque revealed a non-caseating granuloma without microorganisms or foreign-body materials. These eruptions also disappeared with treatment with oral PSL (20 mg daily). No underlying disease, including sarcoidosis, diabetes mellitus, or rheumatoid arthritis, was found. However, five months later, the patient developed conspicuous leukocytosis. She was diagnosed with acute myelomonocytic leukemia (M4) and treated with chemotherapy. After complete remission had been achieved, the EN reappeared, in association with an increase in blastic cells in the bone marrow. Serum levels of tumor necrosis factor-alpha and interleukin-1 beta, which are thought to be essential for granuloma formation and induction of EN, were markedly elevated. Physicians must remember that recurrent EN and granulomatous lesions can be a prodromal sign of leukemia.
15571451 Th1/Th2 cells in inflammatory disease states: therapeutic implications. 2004 Dec Inflammation is initiated as a protective response by the host, but can often result in systemic pathology. Among cells of the immune system, T lymphocytes play a major role in the inflammatory response. T cell inflammation is characterised histologically by an infiltration of mononuclear cells. Key regulators of this response are a subset of T lymphocytes called T helper (Th) cells. These cells secrete soluble mediators called cytokines, which orchestrate the immune response. The appropriate regulation of Th cell immunity is critical in the control and prevention of diverse disease states. This review will focus on the role of Th cells in the inflammatory process involved in allergic disease, diabetes, infectious disease, rheumatoid arthritis, heart disease, multiple sclerosis and cancer. In the area of autoimmunity, in particular, a basic understanding of Th cells and cytokines has contributed to the development of clinically efficacious biological agents. This review also examines current and novel treatment strategies under investigation at present that regulate Th cell immunity, which may result in better treatments for immune-mediated diseases.
15538828 [Invasive fungal infection in immunocompromised patients]. 2004 Jun At present, the concept of immunocompromised patient cannot be applied exclusively to the classic groups of cancer, HIV-infected or transplanted patients. The cytotoxic treatment of patients with much more common conditions such as asthma, inflammatory bowel disease or rheumatoid arthritis has produced an exponential increase in the universe of patients with different degrees of immunological commitment. The generalization of transplantation procedures, even in advanced ages of life, the prolonged survival of patients with cancer and the decrease of the viral load in HIV-infected patients have resulted in long-term immunosupresions. The prevalence of invasive fungal infections (IFIs) is increasing in immunocompromised patients but each group of immunocompromised patients present peculiarities that must be recognized to be addressed appropriately. Despite the recent advances in the diagnosis and treatment of IFIs, they still present unacceptable morbility and mortality rates. Although IFIs are commonly caused by Candida spp. or Aspergillus spp., a variety of fungi are emerging as agents of IFIs. These emerging fungi require an individualized basic and clinical study. The aim of this work is to review the IFIs caused by common and emerging fungi in the three more numerous groups of immunocompromised patients: HIV-infected patients, solid organ transplant recipients and cancer patients, especially those with hematological malignancies or hematopoietic stem-cell transplantation.
15323214 High resolution ultrasonography for imaging metacarpophalangeal joints. 2003 The purpose of the study was to examine the possibilities of high resolution US to visualize and diagnose the changes within the fissures of hand metacarpophalangeal joints and to assess the dimensions of metacarpophalangeal joints in healthy people and selected diseases. The study involved 44 individuals subjected to ultrasound examinations of the hands. The group included 35 healthy right-handed persons (22 women and 13 men), aged 21-53 (average - 33), 7 right-handed patients with rheumatoid arthritis (RA) (5 women and 2 men), aged 41-73 (average - 54) and 2 right-handed men treated for acromegaly, aged 43 and 58. The Logic 500 ultrasonograph (GE) was used. The images of metacarpophalangeal joints of both hands in the dorsal transverse and longitudinal projections were performed using the broad-band linear head with the frequency of 8.5-11 MHz. The analysis included 880 measurements of the metacarpophalangeal joints. The results were presented using the metacarpophalangeal joints of the 1st and 3rd fingers. The results in men and women, healthy and ill individuals were compared. In the authors' opinion high resolution US is a valuable method of imaging the anatomical structures of metacarpophalangeal joints, which may be used to evaluate morphological changes and to estimate the degree of joint destruction in some diseases.
15043086 The young adult with hip pain: diagnosis and medical treatment, circa 2004. 2004 Jan Hip pain in young adults (18-35 years old) often is characterized by nonspecific symptoms, normal imaging studies, and vague findings from the history and physical examination. In younger patients, pain is more likely to be caused by congenital hip dysplasia, athletic injuries, trauma, spondyloarthropathy, and by conditions that first appear during this stage of life, such as rheumatoid arthritis, osteoarthritis, intravenous drug use, alcoholism, or corticosteroid use. The history and physical examination may narrow the diagnosis to intraarticular, extraarticular, or referred sources of pain. Plain radiography and magnetic resonance imaging are the preferred initial imaging procedures. Analyses of the blood, urine, and synovial fluid can be helpful in diagnosing inflammation, infection, and systematic rheumatic disease. Fractures, infection, and ischemic necrosis should be ruled out early because they require immediate treatment to prevent damage to the joint. Hip trauma at a young age increases the risk of osteoarthritis with advancing age, and, unlike most older adults, young adults receiving total hip replacement can expect revision surgery. Medical treatment often involves patient education, physical therapy, and pharmacotherapy. Acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids for pain and antibiotics for infection are the most often prescribed drugs for this population.
15005000 Which are the best instruments for measuring disabilities in gait and gait-related activit 2004 Jan OBJECTIVES: Our first objective was to make an inventory of available instruments for the assessment of disabilities in gait and related activities in patients with rheumatic disorders. Our second aim was to investigate which of these instruments have acceptable methodological quality with regard to reliability and validity. Our third aim was to investigate the assumption that the evaluation of convergent construct validity results in stronger correlations when validated against a more similar construct. MATERIALS: A computer-aided literature search (1982-2001) of several databases was performed to identify studies focusing on the clinimetric properties of instruments to assess impairments in function in patients with rheumatic disorders. Data on intra-rater reliability, inter-rater reliability and convergent construct validity were extracted in a standardized manner and compared to a priori defined criteria. RESULTS: In total 78 instruments were eligible. Intra-observer reliability was investigated for 28 instruments and only 7 demonstrated good reliability as well as good validity. Surprisingly, the convergent construct validation against a similar construct resulted often in lower correlations than validation against a less similar construct. CONCLUSION: Based on the available information, the Rheumatoid Arthritis Quality of Life Scale and the Health Assessment Questionnaire seem to be the best instruments for assessing disabilities in gait and related activities in patients with rheumatic disorders.
14965213 Moderate hyperhomocysteinemia and immune activation. 2004 Feb Moderate hyperhomocysteinemia is associated with an increased risk of atherosclerosis, thrombosis and neurodegenerative diseases. Homocysteine accumulation in the blood can be due to many underlying causes, which may interact with each other, e.g. genetic disposition and B-vitamin status. The role of the sulfur-containing amino acid homocysteine in the pathogenesis of diseases remains unclear, even if many studies suggest a causal relationship between homocysteine-mediated processes like oxidative stress, NO-inactivation and endothelial deficiency and atherogenesis. Proposed mechanisms of action of homocysteine are discussed, and the question is addressed, whether effects that are attributed to homocysteine, are not rather the consequence of folate and vitamin B12-deficiency. Deficiency of these B-vitamins in parallel with moderate hyperhomocysteinemia is often found in patients with enhanced activation of the cellular immune system, like Alzheimer's disease, rheumatoid arthritis and also vascular diseases. In patients with these diseases an association between homocysteine metabolism, oxidative stress and immune activation exists. On the one hand proliferation of immunocompetent cells having an enhanced demand for B-vitamins leads to the accumulation of homocysteine. On the other hand macrophages stimulated by TH1-type cytokine interferon-gamma form reactive oxygen species (ROS), which oxidize antioxidants, lipoproteins and oxidation-sensitive B-vitamins. Thereby Th1-type immune response could contribute importantly to the development of hyperhomocysteinemia, and may also be a major determinant of disease progression.
14656023 Hyperhomocysteinemia and immune activation. 2003 Nov Hyperhomocysteinemia is an established risk factor for atherosclerosis, thrombosis and other vascular diseases. Homocysteine auto-oxidation is considered to be crucially involved in the pathogenesis of these diseases. However, the question remains to be elucidated whether vitamin deficiency and homocysteine accumulation are causal for disease development or rather comprise a secondary phenomenon. Most diseases accompanied by hyperhomocysteinemia are also associated with ongoing activation of the immune system. In vitro experiments show homocysteine to accumulate in stimulated peripheral blood mononuclear cells. In patients with coronary heart disease, with rheumatoid arthritis and in patients with dementia, an association between cellular immune activation and homocysteine metabolism is found. Homocysteine concentrations not only correlate inversely with folate concentrations, they also show a positive relationship with concentrations of immune activation markers like neopterin. Moreover, in patients with various kinds of dementia, increased concentrations of serum peroxides, homocysteine and neopterin correlate with each other. Studies support a role of immune system activation in the development of hyperhomocysteinemia. Stimulation and proliferation of immune cells may lead to the production of reactive oxygen species that may oxidize antioxidants and oxidation-sensitive B-vitamins. An enhanced demand for antioxidants as well as folate and vitamin B12 may develop, together with hyperhomocysteinemia, despite sufficient dietary intake.
14654305 Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions 2003 Dec Inflammation is a fundamental response to tissue injury and invasion of pathogens, but it is detrimental in clinically important inflammatory disorders. Leukocytes are key players in the inflammatory response because of their antimicrobial, secretory and phagocytic activities. They are recruited to the inflamed tissue by sequential adhesive interactions between leukocytes and the endothelium that are mediated by cell-adhesion molecules (CAMs) on the surface of the interacting cells. The effects of many anti-inflammatory drugs can be ascribed, in part, to inhibition of the expression of CAMs. However, in the search for more selective and potent drugs for clinically important diseases such as multiple sclerosis, asthma, rheumatoid arthritis, inflammatory bowel disease, allergies and atherosclerosis, direct inhibition of the function of CAMs has attracted increasing interest. In recent years, the development of synthetic antagonists has provided better opportunities for drug targeting. Future advances in this field hold new prospects for therapeutic intervention in human inflammatory disorders.
14587287 Proteolysis of the collagen fibril in osteoarthritis. 2003 The development of cartilage pathology in osteoarthritis involves excessive damage to the collagen fibrillar network, which appears to be mediated primarily by the chondrocyte-generated cytokines interleukin-1 and tumour necrosis factor alpha and the collagenases matrix metalloproteinase-1 (MMP-1) and MMP-13. The damage to matrix caused by these and other MMPs can result in the production of sufficient degradation products that can themselves elicit further degradation, leading to chondrocyte differentiation and eventually matrix mineralization and cell death. Knowledge of these MMPs, cellular receptors and cytokine pathways, and the ability to selectively antagonize them by selective blockade of function, may provide valuable therapeutic opportunities in the treatment of osteoarthritis and other joint diseases involving cartilage resorption, such as rheumatoid arthritis. The ability to detect the products of these degradative events released into body fluids of patients may enable us to monitor disease activity, predict disease progression and determine more rapidly the efficacy of new therapeutic agents.
12959629 Benefit-risk analysis : a brief review and proposed quantitative approaches. 2003 Given the current status of benefit-risk analysis as a largely qualitative method, two techniques for a quantitative synthesis of a drug's benefit and risk are proposed to allow a more objective approach. The recommended methods, relative-value adjusted number-needed-to-treat (RV-NNT) and its extension, minimum clinical efficacy (MCE) analysis, rely upon efficacy or effectiveness data, adverse event data and utility data from patients, describing their preferences for an outcome given potential risks. These methods, using hypothetical data for rheumatoid arthritis drugs, demonstrate that quantitative distinctions can be made between drugs which would better inform clinicians, drug regulators and patients about a drug's benefit-risk profile. If the number of patients needed to treat is less than the relative-value adjusted number-needed-to-harm in an RV-NNT analysis, patients are willing to undergo treatment with the experimental drug to derive a certain benefit knowing that they may be at risk for any of a series of potential adverse events. Similarly, the results of an MCE analysis allow for determining the worth of a new treatment relative to an older one, given not only the potential risks of adverse events and benefits that may be gained, but also by taking into account the risk of disease without any treatment. Quantitative methods of benefit-risk analysis have a place in the evaluative armamentarium of pharmacovigilance, especially those that incorporate patients' perspectives.
12808281 Calprotectin (S100A8/S100A9), an inflammatory protein complex from neutrophils with a broa 2003 Jun Calprotectin, a complex of two calcium-binding proteins that belong to the S100 protein family, is abundant in the cytosolic fraction of neutrophils. A high level of calprotectin reportedly exists in extracellular fluid during various inflammatory conditions, such as rheumatoid arthritis, cystic fibrosis and abscesses. However, the exact biological role(s) of the factor is now under investigation. We recently observed that neutrophils contain a factor that shows growth-inhibitory and apoptosis-inducing activities against various cell types including tumor cells and normal fibroblasts, and we identified that factor as calprotectin. The findings suggest that calprotectin exerts a regulatory activity in inflammatory processes through its effect on the survival or growth states of cells participating in the inflammatory reaction. It is also possible that calprotectin, at a high concentration, might have a deleterious effect on fibroblasts and influence the recovery of inflammatory tissue. Therefore, the protein factor may be a new drug target to control inflammatory reactions. We found that a few of the Amaryllidaceae alkaloids effectively inhibited the growth-inhibitory and apoptosis-inducing activities of calprotectin. In this article, we focus on the biological functions of calprotectin in extracellular fluids, focusing on its apoptosis-inducing activity.