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ID PMID Title PublicationDate abstract
15447959 Normative data for ultrasound measurement of the calcaneus within different female ethnic 2004 Sep The purpose of this study was to generate normative broadband ultrasound attenuation data for UK resident Indian-Asian, African-Caribbean and Chinese women, aged 20-80 years, using the McCue Cubaclinical II device. Additionally, comparisons were made against available Caucasian data previously collected by the authors. Exclusions were: use of hormone replacement therapy, corticosteroids or thyroxine for more than 6 months; menopause before the age of 45 years; oophrectomy; lactation within the preceding year; rheumatoid arthritis or a previous osteoporotic fracture. 977 women were recruited from various community centres, from a local GP surgery and from university colleges in the London area. Broadband ultrasound attenuation and velocity of sound were determined for the left and right os calces. Repeat measures on each side after re-positioning, to allow for anatomical variation, were averaged. Significance was set at a minimum level of 0.05. There were significant differences in non-dominant and dominant measures in all ethnic groups except African-Caribbean. For comparison purposes the means of the non-dominant measurements were plotted against age using a polynomial model to give the best data fit. No significant difference was found between non-dominant broadband ultrasound attenuation measurements for either Asian or Chinese when compared with the Caucasian sample populations. A significant difference in broadband ultrasound attenuation was found between African-Caribbean and Caucasian, with African-Caribbean between 10% (age group 20-30 years) and 29% (age group 70-80 years) higher. There was no significant difference in body mass index between Caucasian and Chinese groups, but significant differences were found between Caucasian and Asian, and between Caucasian and African-Caribbean groups.
15370396 A comprehensive review and evaluation of the side effects of the tumor necrosis factor alp 2004 Sep For more than 5 years, infliximab and etanercept have been utilized to treat rheumatoid arthritis and Crohn's disease. There is therefore much post-approval data on their side effects. A variety of Medline searches were done at the beginning of June 2004 using the terms 'etanercept', 'infliximab' and 'adalimumab' and the words 'lymphoma', 'infection', 'congestive heart failure', 'demyelinating disease', 'lupus', 'antibodies', 'injection site reaction', 'systemic', 'side effects' and 'skin'. Approximately 150 articles were so identified. In addition, FDA and manufacturers' data obtained by internet searches using Google were reviewed. The important side effects that have been most extensively related to TNFalpha blockers include: lymphoma, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects. The risk of these side effects is very low. Nevertheless, it is important for clinicians to be aware of these side effects when prescribing therapy.
15352899 Review article: the role of nutrition in the treatment of inflammatory bowel disease. 2004 Oct Nutrients may be involved in the modulation of the immune response through at least three different mechanisms. First, the intestinal ecosystem plays a pivotal role in the pathogenesis of inflammatory bowel disease, triggering the uncontrolled inflammatory response in genetically predisposed individuals. Nutrients, together with bacteria, are major components of, and can therefore influence, the intestinal environment. Second, as components of cell membranes, nutrients can mediate the expression of proteins involved in the immune response, such as cytokines, adhesion molecules and nitric oxide synthase. The composition of lipids in the cell membrane is modified by dietary changes and can influence cellular responses. Indeed, various epidemiological, experimental and clinical data suggest that the immune response may be sensitive to changes in dietary composition. Finally, suboptimal levels of micronutrients are often found in both children and adults with inflammatory bowel disease, although, with the exception of iron and folate, it is unusual to discover symptoms attributable to these deficits. However, subclinical deficits may have a pathophysiological significance, as they may favour the self-perpetuation of the disease (due to defects in the mechanisms of tissue repair), cause defective defence against damage produced by oxygen free radicals and facilitate lipid peroxidation. These events can occur even in clinically inactive or mildly active disease, as well as in the development of dysplasia in the intestinal mucosa. Some dietary manipulations have been attempted as primary treatment for rheumatoid arthritis, and specially formulated diets for enteral nutrition have proved to be an effective treatment for Crohn's disease. Most trials, although lacking sufficient patient numbers, have demonstrated a role for dietary manipulation as primary therapy for inflammatory disease. Dietary lipids are one of the most active nutritional substrates modulating the immune response. Recently, it has been demonstrated that lipids may be a key factor explaining the therapeutic effect of clinical nutrition in Crohn's disease.
15339030 Effect of 5-lipoxygenase inhibition on events associated with inflammatory bowel disease i 2004 Jul Leukotrienes play a part in inflammatory response. The unique role of the enzyme 5-lipoxygenase (5-LOX) in the production of leukotrienes makes it a likely therapeutic target for inflammatory conditions like asthma, rheumatoid arthritis, psoriasis, and inflammatory bowel disease (IBD). The aim of the present study was to evaluate the effect of zileuton, an orally active selective 5-LOX inhibitor against the events associated with dextran sodium sulphate-induced colitis in a rat model of IBD. The animals were administered simultaneously zileuton (100mg/kg) or sulphasalazine (100mg/kg) orally for 7 days. On day eight, rats were sacrificed, and distal colon isolated to determine myeloperoxidase activity, in vivo superoxide dismutase activity, prostaglandin E2 levels and histological examination. Both zileuton and sulphasalazine significantly prevented the development of inflammatory events associated with colitis. The effect of zileuton was more pronounced towards reducing myeloperoxidase activity and increasing PGE2 levels in distal colon. The results show that chemotactic leukotrienes are responsible for inflammatory surge in damaged colon and, zileuton, significantly improved healing by inhibition of neutrophil recruitment and indirectly through increase in prostaglandins at the site of inflammation. It is suggested that inhibitors of 5-LOX enzyme may have useful therapeutic role in the treatment of chronic intestinal inflammation.
15334652 The role of substance P in inflammatory disease. 2004 Nov The diffuse neuroendocrine system consists of specialised endocrine cells and peptidergic nerves and is present in all organs of the body. Substance P (SP) is secreted by nerves and inflammatory cells such as macrophages, eosinophils, lymphocytes, and dendritic cells and acts by binding to the neurokinin-1 receptor (NK-1R). SP has proinflammatory effects in immune and epithelial cells and participates in inflammatory diseases of the respiratory, gastrointestinal, and musculoskeletal systems. Many substances induce neuropeptide release from sensory nerves in the lung, including allergen, histamine, prostaglandins, and leukotrienes. Patients with asthma are hyperresponsive to SP and NK-1R expression is increased in their bronchi. Neurogenic inflammation also participates in virus-associated respiratory infection, non-productive cough, allergic rhinitis, and sarcoidosis. SP regulates smooth muscle contractility, epithelial ion transport, vascular permeability, and immune function in the gastrointestinal tract. Elevated levels of SP and upregulated NK-1R expression have been reported in the rectum and colon of patients with inflammatory bowel disease (IBD), and correlate with disease activity. Increased levels of SP are found in the synovial fluid and serum of patients with rheumatoid arthritis (RA) and NK-1R mRNA is upregulated in RA synoviocytes. Glucocorticoids may attenuate neurogenic inflammation by decreasing NK-1R expression in epithelial and inflammatory cells and increasing production of neutral endopeptidase (NEP), an enzyme that degrades SP. Preventing the proinflammatory effects of SP using tachykinin receptor antagonists may have therapeutic potential in inflammatory diseases such as asthma, sarcoidosis, chronic bronchitis, IBD, and RA. In this paper, we review the role that SP plays in inflammatory disease.
15212616 Targeting Syk as a treatment for allergic and autoimmune disorders. 2004 Jul Recent advances in our understanding of allergic and autoimmune disorders have begun to translate into novel, effective and safe medicines for these common maladies. Examples include an anti-IgE monoclonal antibody recently approved for severe asthmatics and the TNF-alpha antagonists that have demonstrated their ability to suppress rheumatoid arthritis, Crohn's disease and other chronic inflammatory processes. However, protein therapies are difficult and expensive to develop, manufacture and administer. Clearly, there is also a need for small-molecule inhibitors of novel targets that have safe and effective characteristics. Syk is an intracellular protein tyrosine kinase that was discovered 15 years ago as a key mediator of immunoreceptor signalling in a host of inflammatory cells including B cells, mast cells, macrophages and neutrophils. These immunoreceptors, including Fc receptors and the B-cell receptor, are important for both allergic diseases and antibody-mediated autoimmune diseases and thus pharmacologically interfering with Syk could conceivably treat these disorders. In addition, as Syk is positioned upstream in the cell signalling pathway, therapies targeting Syk may be more advantageous relative to drugs that inhibit a single downstream event. Syk inhibition during an allergic or asthmatic response will block three mast cell functions: the release of preformed mediators such as histamine, the production of lipid mediators such as leukotrienes and prostaglandins and the secretion of cytokines. In contrast, commonly used antihistamines or leukotriene receptor antagonists target only a single mediator of this complex cascade. Despite its expression in platelets and other non-haematopoietic cells, the role of Syk in regulating vascular homeostasis and other housekeeping functions is minimal or masked by redundant Syk-independent pathways. This suggests that targeting Syk would be an optimal approach to effectively treat a multitude of chronic inflammatory diseases without undue toxicity.
15208431 Prevalence of leg ulceration in a London population. 2004 Jul BACKGROUND: Current prevalence estimates of chronic leg ulceration are frequently based on studies from the 1980s. During the last decade, major changes have occurred in the application of evidence-based practice to this condition. AIM: To determine the prevalence and cause of leg ulceration in a defined geographical population after 8 years of providing standardized evidence based protocols of care. DESIGN: Prospective survey. METHODS: Patients with leg ulceration of >4 weeks duration) within an integrated acute and community leg ulcer service were ascertained, interviewed and clinically assessed, using a standardized questionnaire on medical history, ulcer details and non-invasive vascular investigation to describe causes. Ulcers were classified by aetiology. RESULTS: We identified 113 patients in a population of 252 000, giving a crude prevalence of 0.45/1000 (95%CI 0.37-0.54/1000): 0.34/1000 in men, 0.54/1000 in women. Rates were highly dependent on age, increasing to 8.29 (men) and 8.06/1000 (women) in those aged >85 years. Of the responders, 62/113 (55%) had their ulcer for >1 year. Uncomplicated venous ulceration was observed in only 59/138 (43%) ulcerated limbs; a further 21 had ulceration primarily due to arterial disease. Complex causes were present in 48 (35%) limbs, mostly venous disease in combination with diabetes (35%), lymphoedema (42%) and rheumatoid arthritis (26%). DISCUSSION: Our prevalence of chronic leg ulceration is approximately one-third of that predicted by previous studies using similar methodologies in the 1980s. Patients with ulceration have more complex aetiologies than previously recognized, which may be a consequence of both increasing ulcer chronicity and age.
15032646 Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by diffe 2004 Mar Estrogen appears to play a central role in the immune response and immune-mediated diseases. Estrogen receptors are expressed in a variety of immunocompetent cells, including CD4(+) and CD8(+) T cells and macrophages. Clinical observations indicate that some autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, frequently remit during pregnancy but exacerbate, or have their onset during the postpartum period. Pharmacological levels of estrogen also appear to ameliorate certain autoimmune diseases. In addition, estrogen is known to suppress certain infectious diseases, as well as T cell-mediated responses toward oxazolone, keyhol lympet hemocyanin, Listeria soluble protein and purified protein derivatives. The immune basis for these phenomena is poorly understood. Based on a distinctive profile of cytokine production, data accumulated thus far have revealed modulatory effects for estrogen on the TH1-type and TH2-type cells, which represent two polarized forms of the effector specific immune response. Recent evidence indicates that estrogens inhibit the production of TH1 proinflammatory cytokines, such as IL-12, TNF-alpha and IFN-gamma, whereas they stimulate the production of TH2 anti-inflammatory cytokines, such as IL-10, IL-4, and TGF-beta. This can explain why estrogen suppresses and potentiates TH1- and TH2-mediated diseases, respectively. We hypothesize that exacerbation or suppression of inflammatory diseases by estrogen is mediated by skewing TH1-type to TH2-type response. This view represents a novel mechanism for the modulatory effect of estrogen on certain inflammatory diseases that can lead to beneficial or detrimental impacts depending on the type of immune involved. Such a concept is valuable when considering the application of combination therapies that include estrogen.
15032645 The possibilities and pitfalls for anti-complement therapies in inflammatory diseases. 2004 Mar The complement system is a key component of innate immunity, acting to protect the host from micro-organisms such as bacteria and other "foreign" threats, including tumor cells. However, excessive activation of complement can injure the host and can even be life threatening. These toxic effects are caused primarily by the excessive production of the anaphylatoxins C3a and C5a during complement activation and excessive formation of membrane attack complex on the host cell membrane. Many inflammatory diseases, including rheumatoid arthritis and glomerulonephritis, are thought to involve excessive activation of complement, both for their development and perpetuation. Uncontrolled complement activation is also implicated in post-ischemic inflammation and tissue damage and in sepsis. Therefore, it is important to regulate the complement system to treat disease. There are still no broadly applicable agents for the therapeutic regulation of excessive complement activation. However, there are now some agents in the development that might provide useful anti-complement therapies in the near future. Current strategies include the use of neutralizing antibodies, small synthetic antagonists, soluble recombinant forms of the natural complement regulators, and gene therapies to control excessive complement activation. Here we describe these new agents, their strengths and weaknesses and progress in testing the agents in relevant animal models.
14763716 A systematic review of the methodological quality and extent to which evaluation studies m 2004 Feb OBJECTIVE: To determine the methodological quality of studies evaluating orthopaedic shoes and orthopaedic shoe provisions. To what extent do studies evaluating orthopaedic shoes prescribed for patients with degenerative disorders of the foot, rheumatoid arthritis, diabetes mellitus and neurological foot disorders, focus on the aspects of the International Organization for Standardization (ISO) definition of usability, i.e., effectiveness, efficiency, satisfaction, and context of use? DESIGN: Systematic review. METHODS: A systematic literature search was performed to identify randomized controlled trials (RCTs) concerning orthopaedic shoes and orthopaedic shoe inserts. The methodological quality of the studies was assessed independently by two raters, based on the 19 items of the 'Maastricht-Amsterdam criteria list'. The studies were assessed against the parameters of the ISO definition of usability. RESULTS: Eleven RCTs were included. The methodological scores ranged from 8 to 14 out of 19 possible points. Eleven studies focused on the effectiveness of the orthopaedic shoes and orthopaedic shoe inserts, two of which reported outcome measures and conclusions related to the efficiency of the studied orthopaedic shoes and orthopaedic shoe inserts. Four studies reported some form of patient satisfaction and only three studies paid attention to the context of use. CONCLUSIONS: The methodological quality of the RCTs as assessed according to the 19 different criteria varied considerably. The present review shows that current scientific literature concerning the usability of orthopaedic shoes focuses mainly on effectiveness at the expense of the other domains of usability, i.e., efficiency, satisfaction and context of use.
14632813 Infliximab for hidradenitis suppurativa. 2003 Nov BACKGROUND: Hidradenitis suppurativa (HS) is a chronic disease characterized by significant morbidity. Current medical therapies are only minimally effective at treating the disease. Infliximab is a chimeric monoclonal antibody with high affinity for tumour necrosis factor (TNF)-alpha. TNF-alpha is known to induce proinflammatory cytokines and may play an important role in the therapy of a number of disparate inflammatory disorders. Infliximab has shown promise for the therapy of rheumatoid arthritis and psoriasis. OBJECTIVES: Retrospectively to evaluate the effectiveness of infliximab for the treatment of HS. METHODS: A retrospective chart review was performed for patients who received infliximab at the University of Miami Department of Dermatology. Patients were contacted and asked retrospectively to rate their disease activity immediately prior to and after therapy. RESULTS: Patients' self-reported disease activity scores were significantly decreased (P = 0.0001, paired t-test) following infliximab infusion. This correlated with physician-observed clinical improvement. CONCLUSIONS: Infliximab is a promising agent for the treatment of HS. These initial results suggest that infliximab is associated with objective and subjective improvement in HS. Further controlled studies of the efficacy of infliximab and its effect on the course of the disease are warranted.
14616155 Drug interaction between infliximab and azathioprine in patients with Crohn's disease. 2003 Nov 1 BACKGROUND: A drug interaction has been observed between infliximab and methotrexate in rheumatoid arthritis. AIM: To look for an interaction between infliximab and azathioprine in Crohn's disease patients using the active metabolites of azathioprine: 6-tioguanine nucleotides. METHODS: Patients receiving azathioprine who required infliximab for ileo-colonic or ano-perineal Crohn's disease were recruited prospectively. 6-tioguanine nucleotide levels were evaluated before infusion, within 1-3 weeks after the first infusion and 3 months after the first infusion. The clinical outcome was evaluated by the Harvey-Bradshaw index or the closure of ano-perineal fistulas. RESULTS: Thirty-two patients were included (17 received one infusion and 15 received three infusions). The mean 6-tioguanine nucleotide level was comparable before and 3 months after the first infusion, but a significant increase was observed within 1-3 weeks after the first infusion (P < 0.001). In parallel, a significant decrease in leucocyte count and increase in mean corpuscular volume were observed; these modifications were normalized 3 months after infusion. An increase in 6-tioguanine nucleotide level of greater than 400 pmol/8 x 108 erythrocytes was strongly related to good tolerance and a favourable response to infliximab, with a predictive value of 100%. CONCLUSIONS: This prospective study provides evidence for a drug interaction between azathioprine and infliximab.
14529400 Gastroduodenal safety of cyclooxygenase-2 inhibitors. 2003 Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual COX inhibitors (traditional NSAIDs). Clinical studies of the COX-2-selective inhibitors have demonstrated efficacy equivalent to nonselective NSAIDs with significantly lower rates of GI toxicity. The incidence of endoscopic ulcers in some studies with coxibs has approximated placebo. However, as the detection of endoscopic lesions is not always correlated with symptomatic ulcers and ulcer complications, outcome studies of GI safety were performed. The results of large outcome studies have evaluated rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID. The GI safety of coxibs for patients using low dose aspirin concomitantly with a coxib appears to be reduced, particularly with regard to ulcer complications. Such data provide support for the COX-2 hypothesis and demonstrate that coxibs provide effective treatment of pain and inflammation with a reduced risk of gastropathy.
12960247 The relative activity of CXCR3 and CCR5 ligands in T lymphocyte migration: concordant and 2003 Nov In chronic inflammatory reactions such as rheumatoid arthritis and multiple sclerosis, T cells in the inflamed tissue express the chemokine receptors CXCR3 and CCR5, and the chemokine ligands (CCL) of these receptors are present in the inflammatory lesions. However, the contribution of these chemokines to T cell recruitment to sites of inflammation is unclear. In addition, the relative roles of the chemokines that bind CXCR3 (CXCL9, CXCL10, CXCL11) and CCR5 (CCL3, CCL4, CCL5) in this process are unknown. The in vitro chemotaxis and in vivo migration of antigen-activated T lymphoblasts and unactivated spleen T cells to chemokines were examined. T lymphoblasts migrated in vitro to CXCR3 ligands with a relative potency of CXCL10 > CXCL11 > CXCL9, but these cells demonstrated much less chemotaxis to the CCR5 ligands. In vivo, T lymphocytes were recruited in large numbers with rapid kinetics to skin sites injected with CXCL10 and CCL5 and less to CCL3, CCL4, CXCL9, and CXCL11. The combination of CCL5 with CXCL10 but not the other chemokines markedly increased recruitment. Coinjection of interferon-gamma, tumor necrosis factor alpha, and interleukin-1alpha to up-regulate endothelial cell adhesion molecule expression with CXCL10 or CCL5 induced an additive increase in lymphoblast migration. Thus, CXCR3 ligands are more chemotactic than CCR5 ligands in vitro; however, in vivo, CXCL10 and CCL5 have comparable T cell-recruiting activities to cutaneous sites and are more potent than the other CXCR3 and CCR5 chemokines. Therefore, in vitro chemotaxis induced by these chemokines is not necessarily predictive of their in vivo lymphocyte-recruiting activity.
12926652 Bone and joint diseases around the world. Sweden: a brief update on burden and priority. 2003 Aug Musculoskeletal conditions are increasingly common with advancing age. The life expectancy increased early and rapidly in Sweden, and today 17% of the population is over age 65. Musculoskeletal problems are therefore common but in general are receiving low attention, despite enormous costs for society. The indirect costs for musculoskeletal conditions vastly exceed direct costs (80% vs 20%). This is obviated by the fact that in 2001, of all persons receiving disability pension or taking longterm sick leave, 60% had a diagnosis related to the musculoskeletal system. Further, in a population of 9 million, 70,000 fragility fractures occur each year, 18,000 of the hip and 25,000 of the forearm, corresponding to a hip fracture incidence of 20.14/10,000, among the highest in the world. Government policy is implemented through several agencies, national and local. State of the art reports are currently available in 12 areas of musculoskeletal condition, including osteoarthritis, rheumatoid arthritis, osteoporosis, and hip fracture, while no national evidence-based guidelines have been developed for these conditions. The Swedish Council on Technology Assessment in Health Care provides the scientific foundation of present methods for treatment through evidence-based evaluations. National registers are continuously evaluating orthopedic implant procedures, of which the Swedish Hip Register has provided valuable information on total hip replacements since 1979. For the future, there is a need for setting of priorities with regard to musculoskeletal conditions, including development of guidelines of mechanism of implementation.
12904102 Safety of immunisation and adverse events following vaccination against hepatitis B. 2003 May Hepatitis B vaccines (HBVs) are composed of highly purified preparations of hepatitis B virus surface antigen (HBsAg). An adjuvant, either aluminium phosphate or aluminium hydroxide, is added to the vaccines, which are sometimes preserved with thiomersal. In placebo-controlled studies, common side effects other than local reactions were reported no more frequently among vaccine recipients than among individuals receiving a placebo. A number of controversial adverse events have, however, been purported to be associated with HBVs, including rheumatoid arthritis (RA), diabetes, demyelinating diseases (e.g., multiple sclerosis [MS]), chronic fatigue syndrome, and more recently, lymphoblastic leukaemia. In addition, the safety of the thiomersal and aluminium contained in the vaccine has also been under close scrutiny. These issues have been reviewed by a number of country-specific or international independent review committees such as that of the US Institute of Medicine (IOM) and the World Health Organization's (WHO) Global Advisory Committee on Vaccine Safety (GACVS). Upon review of the scientific evidence, none of the serious allegations have so far been confirmed. On the contrary, scientific evidence has accumulated to disprove many of the allegations. In particular, the IOM committee has concluded that the evidence favoured rejection of a causal relationship between HBV administered to adults and incident MS or MS relapse. Whilst it is important to continue monitoring some of the safety issues, there is no evidence to suggest that the WHO should consider altering its recommendation that all countries should have universal infant and/or adolescent immunisation programmes. The risks of hepatitis B vaccination are only theoretical in comparison with clear benefits in terms of cirrhosis and cancer prevention, and the HBV remains one with an excellent safety profile.
12869881 Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator t 2003 Aug BACKGROUND: Immunomodulator therapy with the purine analogs azathioprine and 6-mercaptopurine (6-MP), is efficacious in the treatment of moderate to severe Crohn's disease (CD), but is not tolerated by a significant minority of patients. The pyrimidine analog, leflunomide, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) patients. Because established RA immunomodulator agents may demonstrate success in the treatment of CD, we reviewed our clinical open-label experience with leflunomide in a refractory CD population. GOALS Assess the effect of leflunomide 20 mg daily, on disease activity, steroid requirement and serologic measures of inflammatory activity in our series of CD patients intolerant to azathioprine/6-MP. STUDY: CD patients intolerant of azathioprine/6-MP were offered leflunomide treatment. The Harvey-Bradshaw (H-B) disease activity index, global assessment, serologic parameters and ability to taper corticosteroids of those who accepted were retrospectively assessed. RESULTS: Leflunomide was well tolerated and resulted in a significant reduction in the H-B score, global assessment and serologic parameters in 8/12 patients. Average follow-up was 38 weeks and a majority of steroid-dependent patients were able to successfully taper following leflunomide initiation. CONCLUSIONS: Our case series demonstrates that the pyrimidine analog leflunomide may be effective for treating moderate to severe CD patients intolerant to standard immunomodulator therapy and warrants further investigation in a randomized controlled trial.
12861393 Cellulose acetate beads induce release of interleukin-1 receptor antagonist, but not tumou 2003 Jun OBJECTIVE: Dramatic improvements in clinical symptoms of rheumatoid arthritis and ulcerative colitis were observed after patients received granulocyte and monocyte adsorptive apheresis with a column containing cellulose acetate (CA) beads as adsorptive carriers. This study was to investigate the effect of CA beads on the generation of anti-inflammatory and pro-inflammatory cytokines in human blood. MATERIALS AND METHODS: We incubated human whole blood with CA beads at 37 degrees C for up to 2 h and measured tumour necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta) and IL-1 receptor antagonist (IL-1ra) produced by leucocytes. IL-1ra was also measured at the inflow and outflow of a column containing CA beads as leucocyte adsorptive carriers for the treatment of patients with ulcerative colitis. RESULTS: CA beads induced significant release of IL-1ra from leucocytes, but not TNF-alpha or IL-1beta. In contrast, all three cytokines were released when leucocytes were stimulated with lipopolysaccharide. IL-1ra was also markedly elevated in the outflow of the leucocyte apheresis column. CONCLUSIONS: These results indicate that CA beads selectively induce IL-1ra release from leucocytes which should contribute to the anti-inflammatory effect of granulocyte and monocyte adsorptive apheresis with CA beads as apheresis carriers.
12855011 Preliminary evidence of genetic anticipation in Graves' disease. 2003 May Despite strong epidemiologic evidence in favor of a genetic component in the etiology of Graves' disease, few hereditary risk factors have been consistently identified. The term genetic anticipation denotes a decrease in the age of onset as disease is passed through generations. In the past 5 years, genetic anticipation has been described in immune-mediated diseases such as rheumatoid arthritis and chronic inflammatory bowel disease, and recently this phenomenon has been linked to unstable expanded trinucleotide repeat sequences in several diseases. If present in Graves' disease, anticipation could provide clues to its genetic etiology. The aim of the present study was to investigate whether genetic anticipation may occur in Graves' disease. Age at diagnosis and age at ascertainment were registered and compared in 33 same-gender parent-offspring pairs with Graves' disease from multiply affected families primarily ascertained for a genetic linkage study. The mean age at diagnosis was 46.6 years (range, 16-77) in the parents and 34.1 years (range, 16-44) in the children. The difference in the mean age at diagnosis between parents and their children was 12.5 years (95% confidence interval 3.0-21.9), p = 0.010. Children were younger than their parents at diagnosis in 25 of 33 pairs (76%). In 7 pairs (21%), the parent was diagnosed after the child according to the calendar years. Essentially similar results were obtained after controlling for gender and smoking habits. In conclusion, our data suggest that patients in the second affected generation seem to acquire their disease at an earlier time in life in familial cases of Graves' disease, indicating that genetic anticipation might occur.
12828905 Measurement of the mechanical condition of articular cartilage with an ultrasonic probe: q 2003 Jul OBJECTIVE: To develop a new diagnostic technology to evaluate articular cartilage quantitatively by introducing an ultrasonic probe into the knee joint under arthroscopy and analyzing the A-mode echogram by means of wavelet transformation. DESIGN: Quantitative evaluation using comparison of two indices on the wavelet map and macroscopic evaluation using the Outerbridge classification. As the quantitative indices on the wavelet map, the maximum magnitude and the echo duration which was defined as the length of time that included 95% of echo signal were selected. BACKGROUND: Quantitative evaluation of articular cartilage in situ is required for new tissue-engineered cartilage but an evaluation system that fully meets this requirement has yet to be established for clinical use. METHODS: Human articular cartilage specimens were analyzed using an ultrasonic probe after macroscopic evaluation and the cartilage characteristics on the echo duration-maximum magnitude graph were examined. RESULTS: There were significant differences between grade 1 and 3, and grade 2 and 3 in the echo duration and maximum magnitude. The cartilage specimens had a L-shaped distribution in echo duration-maximum magnitude graph. CONCLUSIONS: The present study is the new quantitative evaluation system of the articular cartilage in situ and a clinical trial under arthroscopy is presently underway. The ultrasonic measurement is highly reproducible, so we can expect this system to be suitable for in situ reliable examination under arthroscopy. RELEVANCE: Precise evaluation of articular cartilage is of particular importance for longitudinal clinical trials for determination of best surgical option or effect of new chondroprotective drugs in arthritic disease and rheumatoid arthritis.