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ID PMID Title PublicationDate abstract
15123942 Higher cumulative revision rate of knee arthroplasties in younger patients with osteoarthr 2004 Apr This study was designed to test the hypothesis that younger patients treated for osteoarthritis and similar conditions using total knee arthroplasty and unicompartmental knee arthroplasty have a lower implant survival rate when compared with older patients. Previous studies have been done on a small number of patients and only included the younger patients. In many cases patients treated for rheumatoid arthritis have been included in the studies and exceptional survival rates have been reported. The current study compared the cumulative revision rate of the components in 33,251 patients older than 60 years and 2606 patients younger than 60 years treated with total knee arthroplasty or unicompartmental knee arthroplasty for osteoarthritis or similar conditions. Cox regression was used to compare the risk for revision between the two age groups and between gender and the effect of year of operation. The results showed a higher cumulative revision rate for the group of younger patients in all statistical analyses and the risk ratio for revision was significantly lower for the group of older patients. The risk for revision decreased for both groups when considering the year of surgery. This is probably attributable to better implant components and surgical techniques.
15068837 Celecoxib: a potent cyclooxygenase-2 inhibitor in cancer prevention. 2004 Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used therapeutic agents in the treatment of pain, inflammation and fever. They may also have a role in the management of cancer prevention, Alzheimer's disease and prophylaxis against cardiovascular disease. These drugs act primarily by inhibiting cyclooxygenase enzyme, which has two isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Selective COX-2 inhibitors provide potent anti-inflammatory and analgesic effects without the side effects of gastric and renal toxicity and inhibition of platelet function. Celecoxib is a potent COX-2 inhibitor being developed for the treatment of rheumatoid arthritis and osteoarthritis. Chemoprevention is the use of pharmacological or natural agents to prevent, suppress, interrupt or reverse the process of carcinogenesis. For this purpose, celecoxib is being used for different cancer types. The effects of NSAIDs on tumor growth remain unclear, but are most likely to be multifocal. In this article, we reviewed COX-2 selectivity, the pharmacological properties of celecoxib, the use of celecoxib for cancer prevention and the mechanisms of chemoprevention.
15025613 Development and validation of a brief, descriptive Danish pain questionnaire (BDDPQ). 2004 Apr BACKGROUND: A new pain questionnaire should be simple, be documented to have discriminative function, and be related to previously used questionnaires. METHODS: Word meaning was validated by using bilingual Danish medical students and asking them to translate words taken from the Danish version of the McGill pain questionnaire into English. Evaluative word value was estimated using a visual analog scale (VAS). Discriminative function was assessed by having patients with one of six painful conditions (postherpetic neuralgia, phantom limb pain, rheumatoid arthritis, ankle fracture, appendicitis, or labor pain) complete the questionnaire. RESULTS: We were not able to find Danish words that were reliably back-translated to the English words 'splitting' or 'gnawing'. A simple three-word set of evaluative terms had good separation when rated on a VAS scale ('let' 17.5+/-6.5 mm; 'moderat' 42.7+/-8.6 mm; and 'staerk' 74.9+/-9.7 mm). The questionnaire was able to discriminate among the six painful conditions with 77% accuracy by just using the descriptive words. The accuracy of the questionnaire increased to 96% with the addition of evaluative terms (for pain at rest and with activity), chronicity (acute vs. chronic), and location of the pain. CONCLUSIONS: A Danish pain questionnaire that subjects and patients can self-administer has been developed and validated relative to the words used in the English McGill Pain questionnaire. The discriminative ability of the questionnaire among some common painful conditions has been tested and documented. The questionnaire may be of use in patient care and research.
15015828 Expression of Y7 cross-reactive idiotope on human IgM molecules. 2004 Feb In this paper we report data regarding the IgM Y7 cross-reactive idiotope (CRIo) obtained by analysis of: 1) its V-gene subgroup dependance, 2) the frequency of its expression on human monoclonal IgMs and IgM molecules from normal and pathological sera. Furthermore, comparison of epitopic repertoire and nature of binding of human monoclonal IgMs expressing Y7 CRIo was performed to confirm the natural antibody properties of these molecules. IgM isolated from sera of patient DJ (IgM DJ) which expresses the Y7 idiotope has been classified to VH3/VL2 subgroup. From ten IgMs tested only IgM from patient RD (IgM RD) has been shown to express Y7 idiotope. Y7+ human IgMs bound to ssDNA, lactic acid bacteria, mouse laminin, porcine thyroglobulin and mouse IgG. Higher percentage of the expression of Y7 CRIo was detected in the sera of patients suffering from autoimmune diseases such as lupus, rheumatoid arthritis and psoriasis vulgaris as well as in patients suffering from chronic infections of the lower urinary tract. Antigen binding repertoire and properties of Y7+ monoclonal IgM, frequency of Y7 expression on monoclonal IgMs and its concentration in normal and pathological sera indicate the important biological role of this CRIo within the immune system.
15000337 Ankylosing spondylitis. Not just another pain in the back. 2004 Feb OBJECTIVE: To review recent developments in diagnosis and treatment of ankylosing spondylitis (AS). QUALITY OF EVIDENCE: Level I evidence from three randomized placebo-controlled trials shows that AS is highly responsive to anti-tumour necrosis factor-alpha (anti-TNFalpha) therapies when the standard approach of nonsteroidal anti-inflammatory drugs (NSAIDs) and physical modalities fails. MAIN MESSAGE: Ankylosing spondylitis is associated with disability comparable to that of rheumatoid arthritis. Diagnosis should first focus on eliciting a history of nocturnal back pain, diurnal variation in symptoms with prolonged morning stiffness, and a good response to NSAID therapy. Physical examination is often unrevealing. Pelvic x-ray results are often normal in early disease. Magnetic resonance imaging is the most sensitive imaging technique for detecting early inflammatory lesions and should be considered when history supports the diagnosis but results of plain radiography are normal. When patients have failed at least two courses of NSAID therapy, anti-TNF(alpha)therapies are of proven benefit. CONCLUSION: New magnetic resonance imaging techniques and highly effective therapies make AS more readily detectable and managable.
14680788 [Non contraceptive benefits of oral contraception]. 2003 Dec Both women and the medical profession underrate the non-contraceptive benefits of oral contraception, imbued as they are with its sole deleterious effects, such as thromboembolic ones, in particular. However, the pill is quite an efficient means of preventing against troubles of the menstrual cycle, with a betterment of cycle regularity, a diminishing of menstrual flux and a lowering of the frequency and the severity of primary dismenorrhoea. A review of the literature also demonstrates that oral contraception reduce by 40-50% the incidence of endometrial and ovarian cancer, inclusive of women with a previous history, or genetic predispositions. This effect is correlated with time of use and continues until 10 years or more after stopping taking the pill. Also, the positive part of the pill may well be considered as far as colorectal cancer is concerned, with a 40% or so reduction in risk, by means of decreasing bile acids in the colon. Other benefits of oral contraception have been documented, such as prevention of postmenopausal osteopenia when used during perimenopause, decrease in the incidence of adenofibromas, uterine fibromyomas, fibrocystic mastosis and uterine adnexial infections, and, finally, a favourable effect on acne. Preventive action of the pill on rheumatoid arthritis is debatable, the current feeling being that it diminishes severity as well as symptomatology more than risk of occurrence.
14662599 Interpolated conjunctival pedicle flaps for the treatment of exposed glaucoma drainage dev 2003 Dec OBJECTIVE: To describe an alternative method to repair exposed glaucoma drainage devices (GDDs) when conventional attempts have failed. METHODS: Four eyes, from 3 patients, with severe ocular surface disease were included in the study. All eyes had previously received a Baerveldt GDD for uncontrollable intraocular pressure and postoperatively had exposed GDDs. The conjunctival defects were unrepairable with a scleral patch or pericardium, conjunctival advancement, or a conjunctival patch graft. Two eyes had chemical burns, one eye had extensive scarring from multiple surgical procedures, and one patient had rheumatoid arthritis. Each patient provided informed consent, and was given the option of removing the GDD and undergoing diode cyclophotocoagulation or attempting to save the GDD by a conjunctival pedicle flap. An interpolated conjunctival pedicle flap was taken from the cul-de-sac (fornix). The conjunctiva and Tenon capsule were incised radially to the tube, rotated from the fornix at a 90 degrees angle, and sutured to the remaining healthy conjunctiva to cover the exposed tube. RESULTS: Postoperatively, all eyes had vascularized flaps that showed viable tissue. All eyes retained the GDDs, and the intraocular pressure has been under control during follow-up (7, 13, 25, and 27 months). CONCLUSION: Interpolated conjunctival pedicle flaps seem to be a viable alternative to repairing exposed GDDs when other methods are impractical or impossible.
14644847 Cytokines in the seronegative spondyloarthropathies and their modification by TNF blockade 2003 Dec Rheumatoid arthritis (RA) is a disease well characterised by proinflammatory cytokine secretion (particularly tumour necrosis factor, interferon gamma, interleukin (IL) 1, and IL6). Less has been reported about the cytokine profiling in the spondyloarthropathies (SpA). Several trials suggest that, similar to RA, proinflammatory cytokines are globally expressed in the SpA. However, other studies report a down regulation of these cytokines in the SpA, with a relative anti-inflammatory polarisation (featuring increases in IL4, IL5, and IL10). This review summarises current published reports and the variation in cytokine data in the SpA. Additionally, results of cytokine profiles in patients with ankylosing spondylitis before and after treatment with etanercept are reported.
14629819 Therapy with 188Re-labeled radiopharmaceuticals: an overview of promising results from ini 2003 Oct The development of an in-house 188W/188Re-generator has greatly increased the use of 188Re for treating various diseases. 188Re is of widespread interest due to its attractive physical and chemical properties. Many new radiopharmaceuticals labeled with 188Re have been developed and are currently in clinical trials, such as: 188Re-labeled renal excreting agents like 188Re-mercaptoacetylglycylglycylglycine (MAG3) and 188Re-diethylenetriamine pentaacetic acid (DTPA) for prevention of coronary arterial restenosis; 188Re-labeled phosphonates such as 188Re-hydroxyethylidene diphosphonate (HEDP), 188Re-alendronate (ABP), and 188Re-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphoric) acid (EDTMP) for palliation of metastatic bone pain; 188Re-labeled lipiodol such as 188Re-n-hexyldiaminedithiol (HDD)-lipiodol for treatment of liver cancer; and 188Re-labeled colloids and microspheres for treatment of diseases such as rheumatoid arthritis, peritoneal effusion, and other solid tumors. However, there is still a need to develop new 188Re-labeled radiopharmaceuticals that are more specific for target lesions such as cancer-specific monoclonal antibodies and peptides. The availability of 188Re from a generator at a reasonable cost may help increase not only the research activities but also the clinical applications of 188Re-labeled radiopharmaceuticals.
12941340 Indole-based heterocyclic inhibitors of p38alpha MAP kinase: designing a conformationally 2003 Sep 15 p38alpha Mitogen Activated Protein Kinase (MAP kinase) is an intracellular soluble serine threonine kinase. p38alpha kinase is activated in response to cellular stresses, growth factors and cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). The central role of p38alpha activation in settings of both chronic and acute inflammation has led efforts to find inhibitors of this enzyme as possible therapies for diseases such as rheumatoid arthritis, where p38alpha activation is thought to play a causal role. Herein, we report structure-activity relationship studies on a series of indole-based heterocyclic inhibitors that led to the design and identification of a new class of p38alpha inhibitors.
12895187 Assessment of non-steroidal anti-inflammatory drug (NSAID) damage in the human gastrointes 2003 Aug Aspirin is widely prescribed and confers considerable benefit to patients by reducing cardiovascular and cerebrovascular morbidity and mortality. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics, antipyretics and reduce the inflammatory component in conditions such as rheumatoid arthritis. However, both agents are associated with an increased risk of gastrointestinal symptoms and the potentially serious consequences of gastroduodenal ulceration, bleeding and perforation. The introduction of highly selective cyclo-oxygenase (COX)-2 inhibitors or the coprescription gastroprotective agents with nonselective NSAIDs have offered strategies to reduce the incidence of such events. This review article analyzes the quantitative techniques that can be employed by clinical pharmacologists and the clinical studies performed to assess NSAID damage in the gastrointestinal tract.
12876488 Degos' disease: a distinctive pattern of disease, chiefly of lupus erythematosus, and not 2003 Aug Degos' disease, known confusingly as malignant strophic papularis, is an uncommon condition of unknown cause characterized by distinctive infarctive lesions in the skin, gastrointestinal tract, and central nervous system; the lesions at the two latter sites often result in death. We deem Degos' disease to be analogous to lupus erythematosus in the sense that each is fundamentally a systemic pathologic process involving several organs, among them the skin, but, moreover, we regard Degos' disease, in most instances, to be an actual manifestation of lupus erythematosus. Histopathologically, the findings in sections of tissue of skin lesions of Degos' disease are indistinguishable from those of one expression of cutaneous lupus erythematosus; immunopathologically, some patients with morphologic findings stereotypical of Degos' disease display signs characteristic of lupus erythematosus. For these reasons, we consider Degos' disease to be a distinctive pattern of disease, rather than a specific disease per se, just as are erythema multiforme, erythema nodosum, leukocytoclastic vasculitis, Sweet's syndrome, and pyoderma gangrenosum, to name but five of scores of them. The singular pattern that is designated Degos' disease usually is an expression of lupus erythematosus, but, episodically, of conditions like dermatomyositis and rheumatoid arthritis.
12831719 Athletes, nonsteroidal anti-inflammatory drugs, coxibs, and the gastrointestinal tract. 2002 Apr Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common self-administered and prescribed drugs taken in the United States. From 30% to 50% of those using these medications experience some degree of gastrointestinal (GI) side effect. Independent of NSAID use, a majority of athletes suffer GI symptoms, most of which has been documented in endurance athletes. Studies of NSAID use in patients with chronic osteo- and rheumatoid arthritis have defined a set of factors that can identify those who are at higher risk of serious GI events. Using such a model, clinicians can choose either to discontinue NSAID use, or prescribe a lower-risk NSAID or coxib (rofecoxib, celecoxib), prophylaxis with misoprostol, or proton pump inhibitor. Coxibs have been designed to decrease GI ulceration and bleeding by selective inhibition of cyclooxygenase-2, and offer an option for patients at high risk of GI hemorrhage. There are data suggesting that rofecoxib may be associated with an increased risk of myocardial infarction, and until further data are available, caution should be used when considering its prescription to patients at high risk of cardiovascular events.
12794257 Osteonecrosis in patients with SLE. 2003 Aug Osteonecrosis is a clinical entity characterized by death of bone marrow and trabecular bone as a result of disruption of blood supply to the bone (1,2). Other aspects of this condition include avascular necrosis, aseptic necrosis, and osseous ischemic necrosis of bones. Osteonecrosis is classified into two main forms; post-traumatic and nontraumatic. The post-traumatic form of osteonecrosis usually develops as a result of traumatic displacement of bone fragments, which leads to impaired blood supply and ischemia to the affected bone. Osteonecrosis of the femoral head is common following fracture of the femoral neck. A variety of systemic diseases and clinical conditions are associated with nontraumatic osteonecrosis. These include autoimmune rheumatic diseases, alcoholism, pregnancy, Gaucher's disease, thrombophilia, corticosteroid therapy, Sickle-cell anemia, pancreatitis, inflammatory bowel diseases, and use of cytotoxic drugs and others. Idiopathic forms of osteonecrosis have also been reported (2-4). Among the rheumatic diseases, osteonecrosis is strongly associated with systemic lupus erythematosus (SLE) (5). However, osteonecrosis has been diagnosed in patients with primary antiphospholipid syndrome (APS) (6), rheumatoid arthritis (7), and systemic vasculitis (8). This article reviews the causes, clinical and epidemiological features, diagnosis, and treatment options for osteonecrosis among patients with SLE.
12769747 CCR1 chemokine receptor antagonist. 2003 The selective accumulation and activation of leukocytes in inflamed tissues contributes to the pathogenesis of inflammatory and autoimmune diseases such as infection, rheumatoid arthritis, allergic asthma, atopic dermatitis, and multiple sclerosis. A substantial body of reports suggests that chemokines and their receptors, which belong to a family of seven transmembrane G-protein coupled receptors (GPCR), may be involved in the selective accumulation and activation of leukocytes in inflamed tissues, and in the pathogenesis of inflammatory and autoimmune diseases. One such receptor is CCR1 which is a receptor for CC chemokines, such as CCL5 (RANTES) and CCL3 (MIP-1alpha). The involvement of CCR1 in immunological diseases now is documented in several preclinical studies with CCR1 deficient mice, anti-CCR1 antibodies and CCR1 antagonists, suggesting that CCR1 may be an attractive therapeutic target for a variety of diseases. Publications and patents describing CCR1 antagonists and their pharmacological effects have recently been disclosed. This review highlights the biology and pathophysiology of CCR1, and some of its currently reported antagonists. Additionally, our approach to CCR1 drug discovery is summarized.
12517977 Chemoattraction of human T cells by IL-18. 2003 Jan 15 Cell locomotion is crucial to the induction of an effective immune response. We report here the chemoattraction of CD4(+) T cells by IL-18, a member of the IL-1 cytokine family. Recombinant IL-18 increased the proportion of T cells in polarized morphology in vitro and stimulated their subsequent invasion into collagen gels in an IL-18 concentration gradient-dependent manner. Immunofluorescent microscopy studies determined that the major cell type responding to IL-18 was IL-18R(+)CD4(+). Importantly, synovial CD4(+) T cells from patients with rheumatoid arthritis responded to IL-18, adopting polarized morphology and gel invasion without further activation ex vivo, indicating the physiologic relevance of our observations. Finally, injection of rIL-18 into the footpad of DBA/1 mice led to local accumulation of inflammatory cells. These data therefore demonstrate for the first time lymphocyte chemoattractant properties of a member of the IL-1 cytokine family and its relevance in inflammatory diseases.
12473150 Mannan-binding lectin and its role in innate immunity. 2002 Dec Mannan-binding lectin (MBL) is a plasma collectin (C-type lectin with a collagen-like domain) and is considered an important component of innate immunity. Circulating MBL is genetically determined for the major part, but plasma concentration is also markedly influenced by nongenetic factors. The carbohydrate-binding ability of MBL can be inhibited by simple sugars like mannose, fucose and N-acetylglucosamine, but its greatest avidity appears to be for repeating mannose-based structural patterns typical of microbial surfaces. By this means, MBL can bind to a wide variety of bacteria and other microbes, neutralizing them and/or opsonizing them by activating complement using the recently discovered lectin pathway of complement activation. Individual humans differ 1000-fold in MBL concentration, and individuals with low circulating MBL appear to be more vulnerable to infections in a number of clinical settings, especially when combined with secondary immune deficiency. The best evidence that MBL deficiency or insufficiency is physiologically relevant comes from a rapidly expanding literature of clinical studies. MBL insufficiency appears to be a significant risk factor for infections in infants, and for individuals of any age undergoing chemotherapy or post-transplant immunosuppression. Moreover, MBL appears to have a significant influence on the course of certain chronic diseases like rheumatoid arthritis and cystic fibrosis. Replacement therapy with a plasma-derived product is safe and seems promising, while recombinant MBL provides hope for large-scale therapeutic applications. Randomized clinical trials of MBL therapy, which are now on the horizon, should provide unambiguous evidence for the physiological significance of MBL in innate immunity.
12463448 No alterations of serum levels of adrenal and gonadal hormones in patients with ankylosing 2002 Nov Ankylosing spondylitis (AS) is a chronic inflammatory disease with a marked preponderance of affected males compared to females of approximately 6 to 1. During the last two decades, this circumstance stimulated several research groups to investigate serum levels of gonadal and adrenal sex hormones. From available results of cross-sectional studies, there seems to be no particular defect in secretion or production of adrenal, gonadal, and pituitary hormones. This is in striking contrast to diseases such as rheumatoid arthritis and other chronic inflammatory diseases. In the latter diseases, low serum levels of dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), and testosterone have been described in an advanced chronic disease stage, whereas estrogen serum levels remain normal. Although AS is an inflammatory disease with signs of systemic inflammation such as elevated erythrocyte sedimentation rate or increased circulating proinflammatory cytokines, serum levels of adrenal and gonadal androgens are normal. It is unclear whether this can be considered as unexpected. It may be that inflammation does not reach the pituitary, adrenal, and gonadal glands or does not alter the aromatase complex in peripheral tissue. Furthermore, the inflammation-induced changes may be subtle so that only specific endocrine examination of these axes may reveal signs of alterations. In conclusion, current data on sex steroid hormones provide no straightforward explanation for the male predominance in AS. At the moment, there is no rationale to treat AS patients with sex steroid hormones.
12214844 Angiogenesis in health and disease: insights into basic mechanisms and therapeutic opportu 2002 Aug Angiogenesis, the process that leads to the formation of new blood vessels or neovascularization, continues to be a topic of major scientific and public interest. As knowledge of the molecular mechanisms that regulate neovascularization continues to emerge, there is increasing hope that new discoveries will lead to newer therapies that target angiogenesis as a reliable option for disease therapy. For example, it may be possible to develop strategies that, on the one hand, are designed to limit angiogenesis for the treatment of chronic diseases such as cancer or rheumatoid arthritis and, on the other, to promote angiogenesis in the ischemic heart or diabetic limb. With the emergence of tissue engineering as a discipline, it has become increasingly clear that long-term success in organ and tissue reconstruction will depend on the ability to develop a stable, renewable supply of blood vessels. In this review, I will provide a brief overview of this remarkably versatile biological response and discuss how recent discoveries in the field of angiogenesis have influenced the development of novel therapies, forced a reconsideration of conventional therapies, and revolutionized approaches to organ and tissue reconstruction.
12213436 Simultaneous quantification of prostaglandins in human synovial cell-cultured medium using 2002 Jul A liquid chromatographic-tandem mass spectrometric (LC/MS-MS) method was developed for the simultaneous quantification of prostaglandin (PG) E(2), PGF(2alpha), 6-keto-PGF(lalpha) and thromboxane (TX) B(2). These eicosanoids and their deuterium derivatives, using as internal standards, were extracted by solid-phase extraction and analyzed using LC/MS-MS in the selected reaction-monitoring (SRM) mode. A good linear response over the range of 10 pg to 10 ng for each eicosanoid was demonstrated. The accuracy of added eicosanoids ranged from 94.1 to 106.6% and coefficients of variation ranged from 0.62 to 7.8%. Furthermore, we applied this method for the determination of eicosanoids in the human synovial cell-cultured medium, stimulated by lipopolysaccharide (LPS). LPS produced each eicosanoid and they increased in a time-dependent manner. The production levels after 24 h stimulation were 6-keto-PGF(1alpha) > PGE(2) > TXB(2) >> PGF(2alpha). This simultaneous quantification method is so useful to clarify the function of synovial cells in rheumatoid arthritis (RA).