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ID PMID Title PublicationDate abstract
11706458 Nonsteroidal anti-inflammatory drugs in the elderly. 2000 Jun Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the elderly for the treatment of fever, pain, pain associated with inflammation in rheumatoid arthritis and osteoarthritis, neuromuscular disorders, headache, and musculoskeletal conditions. Each year in the United States, people spend 5 to 10 billion dollars to purchase prescription and over-the-counter NSAIDs. Gastrointestinal side effects such as ulcers and bleeding are the most prevalent and life-threatening problems associated with NSAIDs. Specifically in the elderly, NSAIDs have become a leading cause of hospitalization and may increase the risk of death from ulceration more than 4-fold. NSAIDs and the new class of cyclo-oxygenase-2 selective NSAIDs continue as drugs of choice for analgesia and anti-inflammatory effects. Physiological changes of aging worsen the side-effect profile of NSAIDs in the elderly. These side effects, when added to the increased potential for drug interactions, lead to a much greater risk for adverse outcomes when NSAIDs are used in the elderly patient. The similarities and differences in the NSAID agents warrant review in light of the newer drugs--celecoxib and rofecoxib--with their expected improvement in gastrointestinal side effects. This article reviews current information about using NSAIDs in elderly persons.
11517928 Structural basis for possible calcium-induced activation mechanisms of calpains. 2001 May The calpains form a growing family of structurally related intracellular multidomainal cysteine proteinases, which exhibit a catalytic domain distantly related to papain. In contrast to papain, however, their activity in most cases depends on calcium. The calpains are believed to play important roles in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction, but have also been implicated in muscular dystrophy, ischemia, traumatic brain injury, neurodegenerative diseases, rheumatoid arthritis and cataract formation. The best characterized calpains are the ubiquitously expressed mu- and m-calpains, consisting of a common 30 kDa small S-subunit (domains V and VI) and slightly differing 80 kDa large L-subunits (domains I to IV). We have recently determined the 2.3 A structure of recombinant full-length human m-calpain in the absence of calcium, which reveals that the catalytic domain and the two calmodulin-like domains, previously believed to represent the unique calcium switch, are not positioned adjacent to each other, but are separated by the beta-sandwich domain III, which distantly resembles C2 domains. Although the catalytic domain of apocalpain is strongly disrupted compared to papain (which explains its inactivity in the absence of calcium), the crystal structure reveals several sites where calcium could bind, thereby causing a subdomain fusion to form a papain-like catalytic center. All current evidence points to the cooperative interaction of several calcium binding sites. Sites identified include the three EF-hand binding sites in each calmodulin-like domain, the negatively charged segments arranged around the active-site cleft (provided by both catalytic subdomains), as well as an exposed acidic loop of domain III, whose charge compensation could allow the adjacent barrel-like subdomain IIb to move toward the helical subdomain IIa. The Gly-rich S-chain N-terminus and the calcium-loaded acidic loop could target the conventional calpains to cellular/nuclear membranes, thereby explaining their strongly reduced calcium requirement in vivo and in vitro in the presence of acidic phospholipids.
11458980 Immunomodulatory effects of etanercept (TNFR:Fc) and its use in a patient with Crohn's dis 2001 Jul Designer drug etanercept (TNFR:Fc) is an inhibitor of TNF-alpha that binds with greater affinity than membrane receptors. Its full immunomodulatory effects are unknown. Approved for rheumatoid arthritis, its therapeutic potential in Crohn's disease has yet to be explored. We describe the course of a steroid-dependent patient with Crohn's disease given etanercept, and its effects on cytokine protein and mRNA expression and transcription factor activity in human leukocytes. Etanercept 25 mg s.c., was given twice weekly for 1 month. Weekly ESR, disease activity index, prednisone requirement, and serum cytokines were determined. In vitro, effects of physiologic concentrations of etanercept on cytokine protein and mRNA, and NFKB and GR transcription factor activity, were determined using MOT and U937 cell lines and peripheral blood mononuclear cells. Rapid clinical, biochemical, and immunologic improvement occurred, but obstruction due to stricture developed after 4 weeks. In vitro, constitutive and stimulated production of TNF-beta, IL-1beta, MIP-1beta, and IL-8 by normal mononuclear cells declined with etanercept, detectable TNF-alpha increased. MOT TNF-alpha expression tripled, mRNA for IL-12 p40 doubled, GR activity declined in U937 cells, NFKB was unaffected. Etanercept has complex immunomodulatory effects, and may be useful in Crohn's disease, but acutely decreased inflammation could worsen stricture.
11385505 Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory 2001 Jun The beta2 integrin leukocyte function antigen-1 (LFA-1) has an important role in the pathophysiology of inflammatory and autoimmune diseases. Here we report that statin compounds commonly used for the treatment of hypercholesterolemia selectively blocked LFA-1-mediated adhesion and costimulation of lymphocytes. This effect was unrelated to the statins' inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A reductase; instead it occurred via binding to a novel allosteric site within LFA-1. Subsequent optimization of the statins for LFA-1 binding resulted in potent, selective and orally active LFA-1 inhibitors that suppress the inflammatory response in a murine model of peritonitis. Targeting of the statin-binding site of LFA-1 could be used to treat diseases such as psoriasis, rheumatoid arthritis, ischemia/reperfusion injury and transplant rejection.
11354543 Cytokine and chemokine blockade as immunointervention strategy for the treatment of diffus 2001 Mar Cytokines and chemokines are essential components for the pathophysiology of sarcoidosis. In the last decade, evidence has accumulated indicating that most of the events that lead to the alveolitis, granuloma formation and tissue injury are regulated by these mediators and their receptors. Recently, information on the possible pathogenetic role of cytokines has been translated into the development of potent cytokine antagonists which have proved to be powerful means of controlling disease activity in some inflammatory diseases. Molecules capable of neutralizing tumor necrosis factor-alpha (TNF-alpha) are currently used in the clinical setting of rheumatoid arthritis and active Crohn's disease. TNF-alpha is one of most important cytokines in the pathogenesis of sarcoidosis: not unexpectedly, data suggest the real possibility of using anti-TNF strategies to treat refractory sarcoidosis. These data are preliminary and should promote further clinical trials to confirm both the efficacy and tolerability of anti-TNF agents when used in patients with sarcoidosis and other interstitial lung diseases which are characterized by an up-regulation of TNF-alpha expression in the pulmonary milieu. Blockades of other inflammatory cytokines are also expected to be therapeutic in sarcoidosis and other T-cell mediated diffuse lung diseases. In particular, therapies directed at neutralizing chemokines and other molecules which control trafficking and accumulation of immunocompetent cells are potentially more selective and attractive but require a priori knowledge of precise pathways regulating the inflammation state involving the alveolar and interstitial structures.
11347507 [Clinical features and response to systemic treatment of primary and secondary episcleriti 2000 Nov BACKGROUND: Scleritis and episcleritis may extend to adjacent ocular tissues with blinding consequences and may be associated with potentially lethal systemic disorders. AIM: To evaluate the ocular complications and systemic disease associations of the different types of scleritis and episcleritis. PATIENTS AND METHODS: Forty six patients with refractory scleritis and episcleritis were studied and treated during the period 1991 to 1998. RESULTS: Necrotizing type was the most common and severe category in the scleritis group of patients. A decrease in vision occurred in 58.3% of patients with scleritis v/s a 23.5% of patients with epiescleritis (p < 0.05). Uveitis was present in 35.4% of patients with scleritis and scleromalacia was present in 33.3% (p < 0.05). A specific disease association was uncovered in 51% of scleritis and in 38% of episcleritis patients. Rheumatoid arthritis, primary systemic vasculitic disease and Sjögren syndrome with vasculitis were the most common associated systemic diseases. Three patients with scleritis had tuberculosis. CONCLUSIONS: Scleritis is more severe than episcleritis, and necrotizing scleritis is the most severe type of scleritis. Classification of scleritis and episcleritis provides valuable prognostic information. A meticulous approach for the detection of a specific associated disease must be undertaken. Scleritis associated with vasculitis has a worse ocular prognosis than other non infectious diseases. Cyclophosphamide is the most effective immunosuppressive treatment to control severe ocular involvement.
11239864 Multilayered amniotic membrane transplantation for severe ulceration of the cornea and scl 2001 Mar PURPOSE: To examine the efficacy of amniotic membrane transplantation in the treatment of deep corneal and scleral ulcers. PATIENTS: A total of 11 patients were recruited for this study: four patients (four eyes) with corneal perforation, five patients (five eyes) with a deep corneal ulcer and descemetocele, and two patients (two eyes) with a scleral ulcer. METHODS: Ulcers were treated by amniotic membrane transplantation. Separate amniotic membranes were transplanted as material to fill the stromal layer (amniotic membrane filling), as a basement membrane (amniotic membrane graft), and as a wound cover (amniotic membrane patch). After surgery, all cases were treated with artificial tears, autologous serum drops, antibiotic eyedrops, topical corticosteroids, and sodium hyaluronate eyedrops. RESULTS: Eight eyes (72.7%) healed with epithelialization in 16.5 +/- 8.0 days (range, 7 to 29 days), with five and three eyes showing corneal epithelialization and conjunctival epithelialization, respectively. A persistent epithelial defect was noted in one eye with corneal ulcer after limbal allograft transplantation for a chemical burn and in two eyes with corneal ulcers as a complication of rheumatoid arthritis. CONCLUSION: Multilayered amniotic membrane transplantation may be effective for the treatment of deep ulceration of the cornea and sclera. In some eyes with total corneal limbal dysfunction or autoimmune disorders, amniotic membrane transplantation alone is not effective.
11091366 The re-emergence of thalidomide: results of a scientific conference. 2000 Dec BACKGROUND: The use of thalidomide during the 1950s resulted in teratogenic effects in thousands of infants. Although thalidomide is currently approved for the treatment of a complication of leprosy, it is commercially available to treat other diseases through a controlled distribution system. This article presents a summary of a scientific conference organized to assess clinical research on thalidomide, its new clinical applications, and the social and ethical implications for its use. METHODS: Summaries of 10 presentations and two panel discussions were developed from the authors's, oral presentations, conference slides, responses to questions, and supporting literature. RESULTS: Thalidomide shows promise in treating several diseases, including HIV/AIDS, rheumatoid arthritis, Crohn's disease, and multiple myeloma. The STEPStrade mark (System for Thalidomide Education and Prescribing Safety) Program has been developed by Celgene, the commercial manufacturer of thalidomide, to ensure compliance with prescription and usage protocols. A surveillance system is also in place to monitor and report compliance patterns. CONCLUSIONS: Despite the tragic past associated with thalidomide, the drug shows promise as a treatment for many clinical disorders. The challenge is to answer lingering questions of risks and benefits through clinical trials and discovery, to monitor participation and compliance with protocols developed to avoid use of the drug during pregnancy, and to continue to search for safer and more effective treatment options.
11020289 Synthesis and opioid receptor affinity of a series of 2, 4-diaryl-substituted 3,7-diazabic 2000 Oct 5 3,7-Diazabicyclo[3.3.1]nonan-9-ones having aryl rings in positions 2 and 4 with systematically varied substituents were synthesized using a double Mannich procedure. Radioligand binding assays were performed to measure the affinity of the compounds to the mu-, delta-, and kappa-opioid receptors. The affinity of all 2, 4-diphenyl-substituted 3,7-diazabicyclo[3.3.1]nonan-9-ones to the mu- and delta-receptors was found to be low. In contrast, with exception of the nitro- and cyanophenyl-substituted compounds, most of the diazabicycles showed considerable affinity for the kappa-receptor. In particular, the m-fluoro-, p-methoxy-, and m-hydroxy-substituted compounds have an affinity in the submicromolar range. Due to solubility problems in aqueous media, salts of HZ2 were synthesized. The methiodide shows high kappa-affinity and may, thus, be a promising candidate for development of a peripheral kappa-agonist, e.g. for use in the case of rheumatoid arthritis.
10936147 Proinflammatory cytokines. 2000 Aug STUDY OBJECTIVES: To review the concept of proinflammatory cytokines. DESIGN: Review of published literature. SETTING: Academic (university hospital). RESULTS: Cytokines are regulators of host responses to infection, immune responses, inflammation, and trauma. Some cytokines act to make disease worse (proinflammatory), whereas others serve to reduce inflammation and promote healing (anti-inflammatory). Attention also has focused on blocking cytokines, which are harmful to the host, particularly during overwhelming infection. Interleukin (IL)-1 and tumor necrosis factor (TNF) are proinflammatory cytokines, and when they are administered to humans, they produce fever, inflammation, tissue destruction, and, in some cases, shock and death. Reducing the biological activities of IL-1 and TNF is accomplished by several different, but highly specific, strategies, which involve neutralizing antibodies, soluble receptors, receptor antagonist, and inhibitors of proteases that convert inactive precursors to active, mature molecules. Blocking IL-1 or TNF has been highly successful in patients with rheumatoid arthritis, inflammatory bowel disease, or graft-vs-host disease but distinctly has not been successful in humans with sepsis. Agents such as TNF-neutralizing antibodies, soluble TNF receptors, and IL-1 receptor antagonist have been infused into > 10,000 patients in double-blind, placebo-controlled trials. Although there has been a highly consistent small increase (2 to 3%) in 28-day survival rates with anticytokine therapy, the effect has not been statistically significant. CONCLUSIONS: Anticytokine therapy should be able to "rescue" the patient whose condition continues to deteriorate in the face of considerable support efforts. Unfortunately, it remains difficult to identify those patients who would benefit from anticytokine therapy for septic shock.
10818676 New paradigms for the treatment of cancer: the role of anti-angiogenesis agents. 2000 Angiogenesis, the sprouting of new blood vessels, plays a role in diverse disease states including cancer, diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, psoriasis, atherosclerosis, and restenosis. With regard to cancer, the clinical association of tumor vascularity with tumor aggressiveness has been clearly demonstrated in numerous tumor types. The observation of increased microvessel density in tumors not only serves as an independent prognostic indicator, but also suggests that anti-angiogenic therapy may be an important component of treatment regimens for cancer patients. The complexity of the angiogenic process, which involves both positive and negative regulators, provides a number of targets for therapy. Many positive regulators, including growth factor receptors, matrix metalloproteinases, and integrins, have been correlated with increased vascularity of tumors and poor prognosis for patient survival. Thus, these serve as ideal targets for anti-angiogenesis therapy. Many inhibitors of these targets are currently undergoing clinical evaluation as potential anti-cancer agents. In this article, we discuss the role of positive regulators in angiogenesis and tumor growth and describe the anti-angiogenic agents under development.
10796491 Local opinion leaders: effects on professional practice and health care outcomes. 2000 BACKGROUND: Both the theory of diffusion of innovations and the social influences model of behaviour change suggest that using local opinion leaders to transmit norms and model appropriate behaviour may improve health professional practice. OBJECTIVES: To assess the effects using local opinion leaders on the practice of health professionals or patient outcomes. SEARCH STRATEGY: We searched MEDLINE to May 1998, the Research and Development Resource Base in Continuing Medical Education, and reference lists of related systematic reviews and articles. SELECTION CRITERIA: Randomised trials of the use of local opinion leaders (defined as health professionals nominated by their colleagues as being educationally influential). The participants were health care professionals responsible for patient care. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Eight studies were included involving more than 296 health professionals. A variety of patient problems were targeted, including acute myocardial infarction, cancer pain, osteoarthritis, rheumatoid arthritis, chronic lung disease, vaginal birth after caesarean section, labour and delivery, and urinary catheter care. Six of seven trials that measured health professional practice demonstrated some improvement for at least one outcome variable, and in two trials, the results were statistically significant and clinically important. In three trials that measured patient outcomes, only one achieved an impact upon practice that was of practical importance: local opinion leaders were effective in improving the rate of vaginal birth after previous caesarean section. REVIEWER'S CONCLUSIONS: Using local opinion leaders results in mixed effects on professional practice. However, it is not always clear what local opinion leaders do and replicable descriptions are needed. Further research is required to determine if opinion leaders can be identified and in which circumstances they are likely to influence the practice of their peers.
10762555 Evidence for a new Graves disease susceptibility locus at chromosome 18q21. 2000 May Graves disease (GD) is a common autoimmune thyroid disorder that is inherited as a complex multigenic trait. By using a single microsatellite marker at each locus, we screened the type 1 diabetes loci IDDM4, IDDM5, IDDM6, IDDM8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs with GD. This showed a two-point nonparametric linkage (NPL) score of 1.57 (P=.06) at the IDDM6 marker D18S41, but NPL scores were <1.0 at the other five loci. Thus, the investigation of the IDDM6 locus was extended by genotyping 11 microsatellite markers spanning 48 cM across chromosome 18q12-q22 in 81 sib pairs affected with autoimmune thyroid disease (AITD). Multipoint analysis, designating all AITD sib pairs as affected, showed a peak NPL score of 3.46 (P=.0003), at the marker D18S487. Designation of only GD cases as affected (74 sib pairs) showed a peak NPL score of 3.09 (P=.001). Linkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheumatoid arthritis, and systemic lupus erythematosus, which suggests that this locus may have a role in several forms of autoimmunity.
10742156 Angiopoietin-1 protects the adult vasculature against plasma leakage. 2000 Apr Pathological increases in vascular leakage lead to edema and swelling, causing serious problems in brain tumors, in diabetic retinopathy, after strokes, during sepsis and also in inflammatory conditions such as rheumatoid arthritis and asthma. Although many agents and disease processes increase vascular leakage, no known agent specifically makes vessels resistant to leaking. Vascular endothelial growth factor (VEGF) and the angiopoietins function together during vascular development, with VEGF acting early during vessel formation, and angiopoietin-1 acting later during vessel remodeling, maturation and stabilization. Although VEGF was initially called vascular permeability factor, there has been less focus on its permeability actions and more effort devoted to its involvement in vessel growth and applications in ischemia and cancer. Recent transgenic approaches have confirmed the profound permeability effects of VEGF (refs. 12-14), and have shown that transgenic angiopoietin-1 acts reciprocally as an anti-permeability factor when provided chronically during vessel formation, although it also profoundly affects vascular morphology when thus delivered. To be useful clinically, angiopoietin-1 would have to inhibit leakage when acutely administered to adult vessels, and this action would have to be uncoupled from its profound angiogenic capabilities. Here we show that acute administration of angiopoietin-1 does indeed protect adult vasculature from leaking, countering the potentially lethal actions of VEGF and inflammatory agents.
10633533 The potential role of hypocortisolism in the pathophysiology of stress-related bodily diso 2000 Jan Representing a challenge for current concepts of stress research, a number of studies have now provided convincing evidence that the adrenal gland is hypoactive in some stress-related states. The phenomenon of hypocortisolism has mainly been described for patients, who experienced a traumatic event and subsequently developed post-traumatic stress disorder (PTSD). However, as presented in this review, hypocortisolism does not merely represent a specific correlate of PTSD, since similar findings have been reported for healthy individuals living under conditions of chronic stress as well as for patients with several bodily disorders. These include chronic fatigue syndrome, fibromyalgia, other somatoform disorders, rheumatoid arthritis, and asthma, and many of these disorders have been related to stress. Although hypocortisolism appears to be a frequent and widespread phenomenon, the nature of the underlying mechanisms and the homology of these mechanisms within and across clinical groups remain speculative. Potential mechanisms include dysregulations on several levels of the hypothalamic-pituitary adrenal axis. In addition, factors such as genetic vulnerability, previous stress experience, coping and personality styles may determine the manifestation of this neuroendocrine abnormality. Several authors proposed theoretical concepts on the development or physiological meaning of hypocortisolism. Based on the reviewed findings, we propose that a persistent lack of cortisol availability in traumatized or chronically stressed individuals may promote an increased vulnerability for the development of stress-related bodily disorders. This pathophysiological model may have important implications for the prevention, diagnosis and treatment of the classical psychosomatic disorders.
10402496 DNA polymorphism-diet-cofactor-development hypothesis and the gene-teratogen model for sch 1999 Aug 20 Three problems in identifying genes causing schizophrenia and other developmental disorders may be locus heterogeneity, high disease allele frequency, and unknown mode of inheritance. The DNA polymorphism-diet-cofactor-development (DDCD) hypothesis addresses the first two. The gene-teratogen model addresses the third. The DDCD hypothesis is that schizophrenia results in part from brain abnormality in utero from the aggregate effect of multiple mutations of small effect of genes related to important cofactors (e.g., folate, cobalamin, or pyridoxine) potentiated by maternal dietary deficiency of these cofactors and by pregnancy. The effect results from insufficiency of the cofactors and from resulting effects such as impaired DNA synthesis, immune deficiency, effects on niacin and serotonin metabolism, and teratogens, e.g., hyperhomocysteinemia. The hypothesis addresses all of the unusual features of schizophrenia: e.g., decreased brain gray matter, birth-month effect, geographical differences, socioeconomic predilection, association with obstetrical abnormalities, decreased incidence of rheumatoid arthritis, and association with famine and viral epidemics. In the gene-teratogen model, a teratogenic effect in utero produces a developmental disorder through a teratogenic locus and a modifying or specificity locus, as well as through environmental factors. An example is the major intrauterine effect seen in offspring of phenylketonuric mothers. Thus, the mode of inheritance of genes acting prenatally may in some cases be fundamentally different from that of genes acting postnatally. The model is interesting because it is simple and because teratogenic loci will be difficult to locate by conventional linkage mapping techniques due to misspecification of the affection status of both mother and affected children. A new study design is suggested for identifying teratogenic loci.
10364902 Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prosp 1999 Apr OBJECTIVE: To determine the clinical characteristics of patients with "pure" remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome, and to investigate its relation with polymyalgia rheumatica (PMR). Magnetic resonance imaging (MRI) was used to describe the anatomical structures affected by inflammation in pure RS3PE syndrome. METHODS: A prospective follow up study of 23 consecutive patients with pure RS3PE syndrome and 177 consecutive patients with PMR diagnosed over a five year period in two Italian secondary referral centres of rheumatology. Hands or feet MRI, or both, was performed at diagnosis in 7 of 23 patients. RESULTS: At inspection evidence of hand and/or foot tenosynovitis was present in all the 23 patients with pure RS3PE syndrome. Twenty one (12%) patients with PMR associated distal extremity swelling with pitting oedema. No significant differences in the sex, age at onset of disease, acute phase reactant values at diagnosis, frequency of peripheral synovitis and carpal tunnel syndrome and frequency of HLA-B7 antigen were present between patients with pure RS3PE and PMR. In both conditions no patient under 50 was observed, the disease frequency increased significantly with age and the highest frequency was present in the age group 70-79 years. Clinical symptoms for both conditions responded promptly to corticosteroids and no patient developed rheumatoid arthritis during the follow up. However, the patients with pure RS3PE syndrome were characterised by shorter duration of treatment, lower cumulative corticosteroid dose and lower frequency of systemic signs/symptoms and relapse/recurrence. Hands and feet MRI showed evidence of tenosynovitis in five patients and joint synovitis in three patients. CONCLUSION: The similarities of demographic, clinical, and MRI findings between RS3PE syndrome and PMR and the concurrence of the two syndromes suggest that these conditions may be part of the same disease and that the diagnostic labels of PMR and RS3PE syndrome may not indicate a real difference. The presence of distal oedema seems to indicate a better prognosis.
10229410 Testing an instrument to screen for fibromyalgia syndrome in general population studies: t 1999 Apr OBJECTIVE: To develop and test an instrument to screen for fibromyalgia syndrome (FM) in general population surveys. METHODS: We designed a questionnaire with 4 pain and 2 fatigue items. A positive screen was defined 2 ways: (1) positive responses to all 4 items on pain, and (2) positive responses to all pain and fatigue items. Sensitivity was tested in the clinic on 31 outpatients with FM, specificity on 30 outpatients with rheumatoid arthritis (RA) and 30 healthy controls. Test-retest reliability (TRR) was estimated in a community survey of 672 noninstitutionalized adults. Positive predictive value (PPV) was estimated as part of a community survey of 3395 noninstitutionalized adults, in which 100 cases of FM were confirmed by examination. RESULTS: For pain criteria alone sensitivity was 100% (95% confidence intervals 90.3%, 100%); in patients with RA specificity was 53.3% (35.4%, 71.2%). For the pain plus fatigue criteria, sensitivity was 93.5% (83.8%, 100%), and specificity in patients with RA 80% (65.7%, 94.3%). In nonpatient controls, specificity was 100% (89.3%, 100%) using either definition of a positive screen. For those initially screening negative, TRR was 100% (93.2%, 100%) using either definition. For positive screens, TRR was 95.0% (88.8%, 100%) for the pain criteria alone, and 81.0% (69.1%, 92.8%) for the combined criteria. PPV was 56.8% (53.0%, 60.6%) using the pain criteria alone, and 70.6% (CI 55.3%, 85.9%) using the combined criteria. CONCLUSION: The instrument appears to be useful in screening for FM in general population surveys of noninstitutionalized adults. Confirmation of FM among those who screen positive requires a personal interview to reestablish pain duration and distribution, and an examination for tender points.
10227813 The geoepidemiology of primary biliary cirrhosis: contrasts and comparisons with the spect 1999 May Recent data have suggested that the prevalence of many autoimmune diseases is higher than originally suspected. Indeed, the incidence of some autoimmune diseases may be increasing. Part of the problem in these latter two issues is that there is a dearth of well-designed and controlled epidemiologic studies, and often confounding variables in diverse populations and geographic areas that are not well controlled. Primary biliary cirrhosis (PBC) is a highly directed, organ-specific autoimmune disease that results in the destruction of intrahepatic bile ducts. It is primarily a disease of middle-aged women. Although there is no obvious association with MHC class I or class II alleles, the relative risk of a family member of a first-degree relative within a family having a member with PBC is a hundred-fold that of the general population. Unfortunately, most epidemiologic studies have been descriptive, providing incidence and prevalence rates with many methodologic problems, including lack of an appropriate case definition, varying criteria for inclusion of cases, and inaccurate estimate of the time period to which the rate applies. Because PBC is a very definable disease with significant clinical and serologic overlaps among patients throughout the world, we believe that a review of the geoepidemiology of PBC is not only specifically of value to workers interested in autoimmune liver disease, but also of generic interest in the study of autoimmune disease. In this review, we discuss the nature of the existing epidemiologic data and the possible roles of genetic and environmental factors in the etiology of the disease and compare such data to similar observations for multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.
10218672 The cutaneous pathology associated with seropositivity for antibodies to SSA (Ro): a clini 1999 Apr Antibodies to Ro/SSA are found in patients with subacute cutaneous lupus erythematosus (SCLE), complement deficiency lupus erythematosus, systemic lupus erythematosus (SLE), neonatal lupus erythematosus, and Sjögren syndrome (SS). Most studies describing the cutaneous pathology associated with anti-Ro antibodies have been of patients with SCLE. Over a 42-month period, we encountered skin biopsy specimens from 23 anti-Ro-positive patients who did not have SCLE: 15 had SLE variably manifesting as SCLE-like rashes; malar erythema; a dermatomyositis-like rash; vascular disease involving cutaneous, cardiac, peripheral, and central nervous systems; restrictive pulmonary disease; periorbital edema; and myositis. Two patients had primary Sjögren syndrome, one had primary antiphospholipid antibody syndrome, and two had rheumatoid arthritis; all five had clinical evidence of cutaneous vasculopathy encompassing livedo, perniosis, and palpable purpura. Three additional patients presented with folliculocentric purpura without other stigmata to permit classification as a specific connective tissue disease. In the SLE patients, biopsy specimens of photodistributed eruptions showed an interface dermatitis accompanied by superficial vascular plexus density reduction. Vasculopathic reactions in patients with and without SLE comprised neutrophilic, lymphocytic, or pauciinflammatory thrombogenic subtypes. Although at times a marker of SCLE, the identification of anti-Ro antibodies may isolate a subset of patients at higher risk of multiorgan vasculopathy, myositis, and progressive pulmonary disease. We postulate that many of the features seen in these patients reflect the sequelae of antibody mediated endothelial cell injury.