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ID PMID Title PublicationDate abstract
1580335 Expression of cytolytic mediators by synovial fluid lymphocytes in rheumatoid arthritis. 1992 May To understand the role of cytolytic lymphocytes in the pathogenesis of rheumatoid arthritis, we investigated the expression of lymphocyte cytotoxicity mediators, perforin, and serine esterases, in lymphocytes derived from the synovial fluid of 15 patients with rheumatoid arthritis. Previous work has shown that CD8+ lymphocytes that possess markers of activation appear to be present in rheumatoid arthritis (RA). By means of in situ hybridization techniques and immunohistochemical analysis, the authors show that perforin and two serine esterases (serine esterase 1/Hanukah factor/granzyme A, and serine esterase 2/granzyme B) are expressed by subpopulations of CD8+ and CD56+ lymphocytes obtained from synovial fluid. The presence of these cytotoxic mediators suggests a possible mechanism for tissue damage, and provides evidence implicating cytolytic lymphocytes in the pathogenesis of RA.
8894360 Comparative study of the efficacy and safety of aceclofenac and tenoxicam in rheumatoid ar 1996 Sep To compare the efficacy and safety of aceclofenac (AC) and tenoxicam (TX) in the treatment of rheumatoid arthritis (RA), a multicentric parallel, randomized, double-blind trial of three months duration was performed in 292 patients: 145 were randomized to the AC treatment group and 147 to the TX treatment group. The trial was completed by 237 (81.1%) patients. Both treatment groups showed amelioration of clinical parameters monitored at 15 days, and this improvement continued until the end of the trial, no statistically significant differences being observed between AC and TX. Twenty-four patients (8.2%, 12 AC and 12 TX) did not complete the trial because of inefficacy, and 15 because of side effects (5.1%, 6 AC and 9 TX), in 7 of them due to gastrointestinal intolerance (2,4%, 1 AC, 6 TX, p = 0.052). These data demonstrate that AC shows similar efficacy to TX in the treatment of rheumatoid arthritis and better safety profile than TX, mainly regarding gastrointestinal tolerability.
8853164 Aceclofenac in rheumatoid arthritis: a useful and novel anti-inflammatory. 1996 Jul The efficacy and safety of 100 mg aceclofenac twice daily was investigated in 73 patients with active rheumatoid arthritis in a multi-centre, double blind, randomised, parallel group, placebo controlled study over a period of 4 weeks. Treatment with aceclofenac was effective in improving the Ritchie articular index (predetermined primary end point), duration of morning stiffness, joint swelling, ARA functional class, patient's and physician's global assessments, and pain. All these improved to a significantly (P < 0.05) greater extent than in placebo-treated patients. Grip strength showed a significant improvement from baseline in the aceclofenac-treated group and this was greater than the improvement measured in placebo treated patients. No significant difference was detected between the treatment groups for the number of subjects reporting an adverse event. Aceclofenac administered orally at 100 mg twice daily for four weeks thus produced significant improvements in patients with active rheumatoid arthritis. This treatment was well tolerated with an adverse event profile similar to that of placebo.
8523340 How low can you go? Use of very low dosage of gold in patients with mucocutaneous reaction 1995 Sep OBJECTIVE: We identified a group of patients with rheumatoid arthritis (RA) who were sensitive to both the beneficial and the side effects of intramuscular (im) gold treatment and whose disease was well controlled with doses of gold between 2 mg every 6 weeks and 5 mg weekly. We describe the clinical course of these patients and their management aimed at maximizing the effectiveness of gold therapy. METHODS: Patients successfully treated with maintenance doses of im gold (< 20 mg/mo and not more than 10 mg/dose) were identified by chart review. Clinic records were reviewed to extract clinical and laboratory data. RESULTS: The population consisted of 11 female and 2 male patients with RA. Eleven were seropositive and 2 had Felty's syndrome. All developed mucocutaneous side effects within 20 weeks of beginning im gold therapy, at a time when RA had improved markedly compared to pretreatment status. Side effects recurred with sequential dosage adjustments so that doses > 10 mg were not tolerated. Side effects were managed by temporary discontinuation of gold until side effects resolved and resumption of treatment using usually 50% lower dosage. When side effects recurred the dosage was reduced further by 50%. Final maintenance dose was 2 mg every 4 weeks in 1 patient, 2 mg weekly in 1, 3 mg weekly in 3, 5 mg monthly in 1, 10 mg every 3 weeks in 2, 10 mg every 4 weeks in 2, 10 mg every 6 weeks in 1, and 5 mg weekly in 2 patients. All patients improved and 6 are in complete remission. Mean duration of therapy was 5.5 yrs. CONCLUSION: The minimum effective dose of im gold is not known. Dose and dose intervals should be individualized for optimal benefits and tolerability.
8732792 Update on the epidemiology of the rheumatic diseases. 1996 Mar Epidemiologic studies continue to enhance our understanding of the rheumatic diseases. Such studies now indicate that 26 million American women are at risk for osteoporotic fractures. Contrary to previous recommendations, the identification and treatment of patients at risk for osteoporosis may be valuable even among very elderly people. Other epidemiologic studies suggest that the incidence of rheumatoid arthritis is decreasing and that it is a more benign disease than previously recognized. Osteoarthritis remains a leading cause of physical and work disability in North America. The roles of occupational physical activity, obesity, and highly competitive (though not low-impact) exercise as risk factors for osteoarthritis continue to be explored. Pharmacoepidemiologic research has recently demonstrated that a policy of prior authorization for prescription of nonsteroidal anti-inflammatory drugs may be highly cost effective. Finally, controlled epidemiologic studies have not confirmed an association between silicone breast implants and connective tissue diseases, a conclusion recently endorsed by the American College of Rheumatology.
8973608 A therapeutic human IgG4 monoclonal antibody that depletes target cells in humans. 1996 Dec It is traditionally held that human IgG4 MoAbs should not deplete target cells in vivo, as this isotype is inactive in a number of in vitro assays that measure effector function. We have previously challenged this dogma, and the current study was designed to investigate the in vivo biological effects in humans of a MoAb of human IgG4 isotype. Nine patients with refractory rheumatoid arthritis (RA) fulfilling ARA criteria, and one with ankylosing spondylitis (AS) received a human IgG4 Campath-1 MoAb (with specificity against the pan-lymphocyte antigen CD52) as part of a two-stage therapeutic protocol. In stage 1, patients received a single dose of this MoAb. Stage 2, starting 48 h later, comprised a 5-day course of a human IgG1 Campath-1 MoAb with identical V-region (CAMPATH-1H), as previously used in the management of RA patients. The intervening 48 h provided a window of opportunity to monitor the biological effects of the IgG4 MoAb for comparison with the IgG1. The two MoAbs were also compared for in vitro biological activity. IgG4 depleted peripheral blood lymphocytes (PBL), albeit less efficiently than IgG1. It produced a first-dose reaction of similar intensity, although associated circulating tumour necrosis factor-alpha (TNF-alpha) levels were lower. TNF-alpha release from whole blood in vitro was also greater with the IgG1 MoAb. The study design did not permit conclusions to be drawn regarding therapeutic efficacy of the IgG4 MoAb. In summary, a human IgG4 Campath-1 MoAb depletes target cells in vivo. Importantly, this study demonstrates for the first time in humans that in vitro assays may not predict the in vivo effector function of therapeutic MoAbs.
8663889 Three-dimensional joint co-ordination strategies of the upper limb during functional activ 1996 A triaxial flexible electrogoniometer has been developed to measure the three-dimensional angular motion of the shoulder joint during simulated activities of daily living. The motion of the elbow, forearm and wrist were also recorded and angle-angle diagrams were mathematically analysed to provide quantitative parameters regarding the control and co-ordination of the joints of the normal and the arthritic upper limb. Two parameters (slope and movement area quotient) were derived and used in the interpretation of joint motion during different activities.
1429929 [Arthroscopy of the shoulder]. 1992 May Arthroscopy of the shoulder is currently gaining importance because of the diagnostic aid it can provide to understand the pathology of this complex joint, and also because of the technical possibilities it offers for treatment. From a diagnostic point of view, it has allowed, for example, a better understanding of the anatomical lesions observed in instability, or a better analysis of partial rotator cuff lesions. The therapeutic possibilities are the reason for the current enthusiasm for this endoscopic technique: removal of a foreign body, articular washing, synovectomy, ligament reinsertion of abrasion are now accessible with some training. The two indications of shoulder arthroscopy that are most resorted to are the endoscopic treatment of some cases of shoulder instability with reinsertion of disinserted elements at the anterior capsular-ligamentous level, and anterosuperior decompression of the rotator cuff when there is a conflict between this tendinous area and the acromiocoracoid osteoligamentous dome.
8291509 Chenodeoxycholate: the bile acid. The drug. a review. 1994 Jan Chenodeoxycholate (3 alpha, 7 alpha-dihydroxy-5 beta-cholanic acid) is a primary bile acid directly synthesized from cholesterol. It is an amphipathic molecule, possessing both a hydrophobic side and a polar hydrophilic side, giving it the ability to solubilize lipids in a water environment. Bile acids are necessary for the absorption of fats and fat soluble vitamins. Chenodeoxycholate inhibits the rate-limiting step of cholesterol synthesis, the formation of hydroxymethyl-glutaryl-coenzyme A. It was first reported to be useful in the dissolution of cholesterol gallstones in 1972. Today, chenodeoxycholate has other medicinal uses and is used for the management of cerebrotendinous xanthomatosis, hypertriglyceremia, congenital liver diseases, rheumatoid arthritis, and constipation. This article details some finer points of chenodeoxycholate biochemistry and physiology and discusses in some detail the current and past clinical uses of chenodeoxycholate. This is not an exhaustive discussion on gallstone dissolution therapies, but an overview of some of the lesser-known uses for this drug.
1569234 The propionic acids: a personal perspective. 1992 Apr In searching during the early 1950s for new drugs for the treatment of rheumatoid arthritis, little information was available to allow a rational approach. The mode of action of the few drugs available was unknown and even the analgesic action of aspirin could not be demonstrated in animals. A speculative concept was developed that aspirin possessed a specific unidentified action in rheumatoid arthritis and that this and its analgesic properties were related to its ability to delay the development of ultraviolet (UV) erythema in the guinea pig. A series of substituted phenoxypropionic acids proved to be active as antierythemic agents, but the most potent was inactive clinically in rheumatoid arthritis. Refinements to the testing systems led to a series of substituted phenylacetic acids, three of which although active in rheumatoid arthritis produced unacceptable adverse reactions (ADRs). Attempts to relate laboratory data to clinical ADRs suggested that the substituted phenylpropionic acids (originally rejected because of concerns about toxicity) might be better tolerated than we had anticipated. Ibuprofen was selected from this large group. It was proven to be effective and well tolerated and became "the first of the propionics" when it was launched in 1969. In the 1970s, ibuprofen proved to be effective as a prescription drug in a range of painful nonrheumatic conditions and on the basis of its good safety record was approved as an OTC analgesic in 1983 in the United Kingdom and in 1984 in the USA. It has proven to be popular and effective and much safer than aspirin or acetaminophen in overdosage.
7704464 Incidence of myopathy in patients treated with antimalarials. A report of three cases and 1995 Feb A retrospective review of 4405 patients' charts identified 214 patients who initiated antimalarial therapy between January 1987 and April 1993 for different rheumatic disorders (mean duration of therapy of 17 months). From these, three patients with myopathy were found for a total of 303 patient-years of therapy, for an incidence of 1 in 100 patient-years (95%, confidence interval 0.2-3). All three patients had rheumatoid arthritis and had received chloroquine for between 12 and 18 months with a maximum dose of 250 mg/daily. All had a muscle biopsy, but only one showed the classical rimmed vacuoles. All patients improved within 2 months after the drug was stopped. A review of the literature was carried out with special reference to the significance of clinical myopathy with a negative biopsy. We found that positive biopsies are usual only if the duration of symptoms have been allowed to persist for more than 6 months.
1541844 Anti-type II collagen ELISA. Increased disease specificity following removal of anionic co 1992 Feb 14 The purification of type II collagen, for the detection of anti-type II collagen antibodies by ELISA procedures, involves removal of proteoglycans by guanidine-HCl, followed by pepsin solubilisation and salt fractionation. However, type II collagen purified in this way may contain contaminants, despite the apparent purity on SDS-polyacrylamide gels. In this paper we demonstrate how additional purification by DEAE chromatography reduces the degree of background binding in the type II collagen ELISA, leading to an increase in disease specificity. The contaminants included proteoglycan and bound serum IgG from both rheumatoid arthritis (RA) patients and healthy controls in ELISA. Furthermore, positive correlations were observed in the sera (n = 24) between degree of reactivity to the contaminants and to (1) purified proteoglycan (r = 0.50, P = 0.01) and (2) pepsin (r = 0.65, P = 0.001). Thus, inadequate purification of type II collagen produces false positive reactions in the collagen ELISA and gives rise to a high background. A lack of specificity has been frequently associated with this assay.
8308765 HLA-DR antigens, Gm allotypes and antiallotypes in early rheumatoid arthritis--their relat 1993 Nov OBJECTIVE: Evaluation of the prognostic value of immunogenetic markers in early rheumatoid arthritis (RA). METHODS: Ninety-nine patients with definite RA and disease duration 24 months or less were followed with standardized assessment. Disability was assessed by the HAQ index and radiographic changes in hands and feet by the Larsen method. The frequencies of HLA-DR genes were determined by serological typing, Gm allotype distribution by classical hemagglutination inhibition test, and occurrence of anti-Gm allotypes by use of anti-Rh coats. The immunogenetic findings were related to disease severity after 2 years' followup. RESULTS: Functional capacity was well preserved, disease activity was less, but radiographic changes in hands and feet had increased considerably at study finish. A group of 13 patients had developed rapidly progressive changes of hip and/or shoulder joints, all requiring arthroplasty. There was a significantly increased frequency of HLA-DR4. Twenty-seven of the 68 HLA-DR4 positive patients were putatively homozygous. HLA-DR4 was not related to disability or to severe small joint destruction. However, progressive large joint damage was significantly more prevalent in homozygous patients (p < 0.01). Gm allotype distribution was normal and not related to clinical findings. Anti-Gm antibodies were common and frequently specific for nonhost Gm allotype. Fifty-six patients carried anti-G1m(a), and occurrence of this antibody was significantly associated with radiographic progression of small joints (p = 0.01), presence of nodules (p < 0.01) and number of active joints (p = 0.001). CONCLUSION: Immunogenetic markers aided in identifying patients with early RA with more severe disease.
8047768 [Sports and inflammatory rheumatism]. 1994 Jun The author analyses the impact of sport and it's relation with inflammatory rheumatisms. The mechanisms introducing a muscle atrophy of the patients with inflammatory arthritis permits a good understanding of these relations. The role of the effusion in the articulation, the biochemical disturbances of the synovial fluid, a raised temperature, and finally intrinsic muscle biochemical disturbances are analysed. These different measures are in relation with the beginning and maintenance of muscle atrophy. The practice of sport, especially based on endurance, of patients suffering from inflammatory rheumatisms maintains the muscle bulk and force.
8298519 Wa idiotype in seropositive rheumatoid arthritis. 1993 Aug Antibodies against cross-reactive idiotypes (CRIs) may prove useful as phenotypic tracers of immunoglobulin variable region genes (VH or VL). CRIs of human rheumatoid factors (RFs) seem to be useful in the elucidation of the incidence and structural characteristics of the latter. Anti-Wa CRI antibodies were produced and an enzyme immunoassay was developed to test polyclonal RFs isolated from sera of 20 rheumatoid arthritis (RA) patients, 7 males and 13 females, aged 17 to 74 years. Seventeen patients had clinically active disease and three were in remission. Disease duration ranged from 1 to 25 years and RF titers ranged from 1:160 to 1:640. The immunoassay could detect as little as 8 ng of a monoclonal purified WaRF and positive results were found in 30% of patient sera. Therefore, we may conclude that at least part of the RFs seen in RA patients derives from germ line genes.
8354973 Glucocorticoid-induced osteoporosis: pathogenesis, prevention and treatment, with special 1993 Sep OBJECTIVES: To review factors associated with development of osteoporosis in patients with rheumatic diseases, as well as the preventive and therapeutic measures. DESIGN: A MEDLINE literature search. RESULTS: 1 Pathogenesis. Rheumatoid arthritis in itself causes reduction of bone mass; this process can be aggravated by glucocorticoid treatment. With glucocorticoid treatment, bone mineral density decrease is most pronounced during the first months of treatment. There is no agreement on the effects of daily dose, cumulative dose, and duration of glucocorticoid treatment on the rate of bone loss. However, with treatment by low doses (< 10 mg of prednisone equivalent per day), bone loss appears to be minimal or even undetectable compared to controls. Alternate day treatment, or treatment with steroid 'pulses' have not been shown to protect from bone loss. 2 Prevention and treatment. Prophylactic and therapeutic measures for glucocorticoid-induced osteoporosis include calcium supplementation, vitamin D in physiological doses and oestrogen in perimenopausal female patients. Efficacy has not always been shown in this particular indication but is extrapolated from other forms of osteoporosis. Limited data exist on treatment with anabolic steroids, calcitonin (with an additional analgesic effect) and biphosphonates and reduction of fracture rates has not yet been investigated. At present, there is insufficient evidence to show that altered steroid molecules can dissociate adverse effects on bone from clinically desirable effects. CONCLUSION: In view of the paucity of study data, prophylaxis and therapy of glucocorticoid-induced osteoporosis should receive more attention in future clinical studies.
1335465 Detection of hypodense eosinophils by Percoll multilayer density gradient centrifugation i 1992 Dec 8 In patients with marked hypereosinophilia 'hypodense' and 'normodense' eosinophils have been found after density gradient centrifugation. Subsequently this terminology has also been used in studies of patients with milder eosinophilia. However, in these cases the differentiation between normo- and hypodense eosinophils was less clear. This might be due to the high imprecision of the test of density gradient centrifugation, as demonstrated in the first part of this study: the mean within-assay variance of the number of eosinophils in the different density layers was 35%. It was calculated that the test must be performed eight times to obtain an estimate of the true mean for the individual patient. In the second part of the study, the absolute number of 'hypodense eosinophils' in groups of patients with asthma (adults and children) and rheumatoid arthritis (adults) were compared to normal controls. Although a difference in the absolute number of hypodense eosinophils between groups of patients and controls could be demonstrated, the high imprecision of the test of density gradient centrifugation suggested that the technique used was not useful in an individual with normal or slightly elevated eosinophils in the peripheral blood.
7924047 Modular total shoulder replacement. Design rationale, indications, and results. 1994 Oct Modular total shoulder systems offer many advantages over nonmodular designs. Modularity facilitates precise placement of the humeral head with respect to the rotator cuff and tuberosities, allows for soft tissue tensioning and balance with variable neck lengths, and simplifies revision surgery by allowing removal of the humeral head while maintaining a well-fixed humeral stem. This review includes 47 total shoulder arthroplasties performed in 40 patients from 1986 to 1991. The average patient age was 62.3 years, with followup averaging 54 months. Seventeen patients had rheumatoid arthritis, and 22 had osteoarthritis. In the remaining 8 patients, 5 had posttraumatic arthritis, 2 had avascular necrosis, and 1 had cuff tear arthropathy. Glenoid revision was required in 3 patients, and symptomatic loosening occurred in only 1. Pain relief was achieved in 93.5% of patients. Range of motion improved 34.9 degrees in forward flexion, 18.1 degrees in external rotation, and 4 vertebral levels of internal rotation. Lucent lines were evaluated on the anteroposterior (AP) and axillary radiographs. On the AP radiograph, 16 shoulders demonstrated lucency about the glenoid component. Progression beyond 2 mm occurred in 5 shoulders, and symptoms requiring revision developed in one patient. Twenty-two patients demonstrated a lucency on the axillary radiograph, and 9 patients progressed beyond 2 mm. None required revision. The authors present the results and discuss surgical and design considerations of modular total shoulder arthroplasty.
8505727 Paraneoplastic syndromes in patients with ovarian neoplasia. 1993 Apr The prevalence of several paraneoplastic syndromes associated with ovarian cancer was determined from a clinicopathological study of 908 patients with primary ovarian malignancy in the North East Thames Region. The diversity and rarity of these manifestations are great and the explanation for them is difficult. Circumstantial evidence suggests that in some cases an autoimmune phenomenon is the most plausible cause.
8870691 Evidence for a selected humoral immune response encoded by VH4 family genes in the synovia 1996 Oct The analysis of rearranged antibody-encoding genes from B cell foci in rheumatoid synovial tissue has characterized these cells as highly mutated memory B cells with a high proportion of members of the VH4 family. In order to characterize further the VH4 response in one patient, B cell-rich areas from different sections of synovial membrane (SM) were identified by CD20 staining, isolated by microdissection and pooled, in order to analyse highly enriched B cells without selection by in vitro culture procedures. From DNA of about 5 x 10(3) B cells rearranged VH genes were amplified by polymerase chain reaction (PCR) and cloned. Sequencing of 11 clones containing rearranged VH4 gene products revealed that seven were potentially functional, and all were mutated with 84-96% homology to known germ-line (gl) genes and VH4 gl genes amplified from the patient's genomic DNA. Analysis of the complementarity determining region (CDR) 3 revealed that two products represented members of one B cell clone which differed by five nucleotide changes. Three of the five mutations encoded amino acid replacements in CDRs indicating antigen-driven expansion of one specific clone. Additional analyses of 25 members of three B cell clones from isolated aggregates showing intraclonal diversity in one of three clones provided further evidence that antigen selection takes place in the SM. Overall, the pattern of mutations and the replacement to silent (R:S) ratios were diverse, with six products indicating antigen selection by their high R:S ratios in CDRs. Although DNA analysis does not allow a characterization of antibody specificities, we can conclude from our analysis does not allow a characterization of antibody specificities, we can conclude from our analysis of antibody-encoding genes that selection by antigen and expansion of specific clones occur in the SM against the background of polyclonal activation.