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ID PMID Title PublicationDate abstract
8474063 Dicyanogold (I) is a common human metabolite of different gold drugs. 1993 Feb Gold based drugs and their metabolites have been characterized using reversed phase, ion pairing chromatography with an inductively coupled plasma mass spectrometer as an element specific detector. For a patient receiving gold sodium thiomalate the principal gold species in the urine is [Au(CN)2]-, which is also seen in a low molecular weight infiltrate of the blood. The same compound is also identified in the urine and blood of a patient taking auranofin and in patients taking solganol. This represents the first identification of a specific gold metabolite in biological fluids taken from patients undergoing gold therapy and the first evidence that different gold drugs have common metabolites.
9122453 [The ankle and hindfoot of rheumatoid arthritis patients: study with computerized tomograp 1996 Dec To study ankle and hindfoot involvement, we used Computed Tomography (CT) in 38 rheumatoid arthritis (RA) patients (32 women, 6 men, mean age: 56.3 +/- 10.1 years, mean disease duration: 9.9 +/- 6 years) all presenting a definite clinical disease of these joints. The scans were performed on 3rd generation CT equipment (GE ProSpeed SX), with coronally oriented scans 3 mm thick. Bone erosions and joint space narrowing (present/absent) of both talocrural and posterior talocalcaneal joints were assessed and heel valgus angle was measured. Ankle changes (erosion plus joint narrowing) were observed in 15 patients (39.5%, 17 of 76 lower limbs), talocalcaneal changes in 18 (47.4%, 31 lower limbs) and valgus deformity of the hindfoot in 22 (57.9%, 40 lower limbs). Involvement of talocrural and talocalcaneal joints as well as alignment abnormalities were symmetrical in 13.3%, 77.8% and 81.8% of the cases, respectively. All the CT findings were significantly related to disease duration (p = 0.02) and hindfoot injuries to Ritchie index too (p < 0.05). No relationship with seropositivity was observed. Our study confirms that radiographic changes do not entirely mirror clinical evidence and shows that CT does not represent a routine examination for RA patients, but could be reserved to those with prolonged disease or severe heel deformity to plan surgery.
8639181 Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid 1996 May OBJECTIVE: To examine the capacity of bone marrow progenitor cells to generate CD14+ cells, in order to assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA). METHODS: CD14- cells purified from bone marrow specimens of 11 patients with active RA and 8 control patients (osteoarthritis or trauma) were cultured in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 pg/ml). After incubation for various lengths of time, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. RESULTS: The spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells was accelerated in RA patients compared with control patients. Moreover, the expression of HLA-DR on the bone marrow-derived CD14+ cells was also accelerated in RA patients compared with controls. GM-CSF significantly enhanced the generation of CD14+ cells, as well as the expression of HLA-DR, on CD14+ cells of control patients, but not those of RA patients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RA patients and control patients (undetectable in most cases). CONCLUSION: These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into HLA-DR+ cells play an important role in the pathogenesis of RA. Moreover, the data suggest a functional alteration of RA bone marrow CD14- cells in their responsiveness to GM-CSF.
9201758 Effective electroconvulsive therapy for stupor in the high risk patient: a report of two c 1996 Jun We report two cases of stupor in which the patients were safely treated by electroconvulsive therapy (ECT) despite high risk conditions. Case 1 was a 72 year old schizophrenic woman who had developed catatonic stupor and had joint contractures as a complication of rheumatoid arthritis. Case 2 was a 52 year old woman who developed a stuporous state which was complicated by severe dehydration with hypernatremia. In both cases, psychotic symptoms were improved by ECT without event. Careful application of ECT seemed to be effective and safe even for stupor in high risk patients.
8594657 [A long-term clinical analysis of the rheumatoid patients treated by a combination of GST 1995 Oct It has been well known that DMARDs are very effective for rheumatoid arthritis but lose their effect after long term administration. The authors would expect that Lobenzarit disodium (CCA) could slow the reduction of effectiveness of the DMARDs. The aim of this paper is to clarify the effects of Lobenzarit disodium (CCA) for the rheumatoid patients maintained by sodium aurothiomalate and D-penicillamine. The classical and definite rheumatoid patients were divided into two groups. One (group-A) was the rheumatoid patients who were treated in combination with CCA (79 patients). Another (group-B) was rheumatoid patients who were treated by sodium aurothiomalate or D-penicillamine (78 patients). All of them were followed for four years. In group-A, Lansbury index didn't improve in comparison with group-B. However, in the parameters of Lansbury index, improvement of the swelling joints was clearly higher in group-A than in group-B. Furthermore, this effect started in three months after administration of CCA and continued until the end of this study. On the other hand, according to roentogenographic examination utilizing MD's method, density of the metacarpal bones decreased more in group-B than in group-A. The sid-effects were few. They were five cases of gastrointestinal disorders and three cases of renal dysfunction. However, the renal dysfunction seems unlikely to be causally related to CCA. The authors could confirm the certain and expected results of combination therapy with CCA and sodium aurothiomalate and D-penicillamine for the rheumatoid patients.
8345273 Wrist arthrodesis in rheumatoid arthritis. A comparison of two methods of fusion. 1993 Jun 17 wrists were arthrodesed in 13 patients with severe wrist disease due to rheumatoid arthritis. Eight fusions in seven patients were carried out using a radial sliding bone graft technique whilst nine fusions in nine patients were undertaken using a third tubular AO plate. Subjective, objective and radiological assessments confirmed the efficacy of both methods but indicated a shorter period of post-operative immobilization for patients treated using the AO plate fixation technique. The importance of this is discussed.
8371892 Comparison of 99Tcm-labelled specific murine anti-CD4 monoclonal antibodies and nonspecifi 1993 Aug Inflamed joints in human rheumatoid arthritis (RA) can be imaged employing 99Tcm-labelled anti-CD4 monoclonal antibodies (MAbs). These MAbs recognize the CD4 molecule expressed on T-helper cells and, with a lower density, on macrophages, which are both abundantly present in RA inflammatory infiltrates. However, it is at present unclear whether specific binding to target molecules in the inflamed joint determines the joint uptake of anti-CD4 MAbs, i.e. whether the uptake of anti-CD4 MAbs differs from that of control immunoglobulins with irrelevant specificity. Eight patients with severe, active RA were examined after intravenous injection of a 99Tcm-labelled murine anti-human CD4 MAb (MAX.16H5; 200-300 micrograms, 370-550 MBq) or polyclonal human immunoglobulin (HIG; Technescan, MDH-67, Mallinckrodt Diagnostica; 1 mg, 370 MBq); five patients received both the anti-CD4 MAb and HIG. Whole body and joint scans in anterior and posterior views were obtained 1, 4 and 24 h after injection. As early as 4 h after injection, the anti-human CD4 MAb showed a higher target-to-background ratio in arthritic knee and elbow joints in comparison to polyclonal HIG used for conventional imaging, indicating that that anti-CD4 MAb allows more specific detection of inflammatory infiltrates rich in CD4-positive cells.
1363986 [Sulfasalazine in the treatment of rheumatoid arthritis. A multicenter open study of 150 p 1992 Nov 30 One hundred and fifty patients with rheumatoid arthritis were given sulfasalazine in a daily dosage of 2 g during an open-label, multicenter, six-month trial. Improvements were apparent as early as four weeks after initiation of the drug. Improvements in clinical parameters and erythrocyte sedimentation rate were statistically significant. In the patients who remained on the study protocol, clinical and biological improvements continued over time and were more marked after six months. Overall clinical safety was satisfactory: 30 patients were withdrawn from the trial for adverse events, all of which resolved after discontinuation of the study drug. Most of these adverse events (93%) developed within two months of initiation of the drug, demonstrating the need for hematologic and hepatic tests at regular intervals during the first three months of sulfasalazine therapy. Thirty-four patients had not previously received maintenance therapy; in this subgroup, only one patient was withdrawn for ineffectiveness. In view of its favorable risk/benefit ratio and fast action, sulfasalazine may be a useful first-line drug in patients with rheumatoid arthritis.
7674232 Cardiovascular mortality in women with rheumatoid arthritis. 1995 Jun OBJECTIVE: To investigate the relationship of deaths from cardiovascular causes in mortality of women with rheumatoid arthritis (RA). There is increasing evidence that subjects with RA have increased mortality from cardiovascular causes, but little is known of its determinants. METHODS: Our study included all women subjects in Finland who died during 1989 and who were entitled to reimbursement for medication for RA under the national health insurance plan. Demographic data on the Finnish population and health insurance statistics were used for computations. RESULTS: Half of the 1186 deaths of women were due to cardiovascular causes. The distribution of specific diagnoses within this disease group did not differ appreciably from that in the female population as a whole. However, there was a 34% excess of deaths due to cardiovascular causes. The median age at death in women with RA was 2.5 years lower than that in the whole population with deaths due to cardiovascular causes. CONCLUSION: Deaths due to cardiovascular causes constitute and important determinant in the surplus of mortality associated with RA in women.
1588739 [NSAIDs (non steroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis] 1992 Mar Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed to patients with rheumatoid arthritis (RA), as the first line drugs, and are administered over a long term. NSAIDs are classified principally into acidic and basic preparations, and the former is more widely used for the treatment, since the latter possesses no anti-rheumatic effect. Moreover, the acidic NSAIDs are classified into salicylates, arylacetic acid, pyrazolone, fenamates and oxicams. Arylacetic acid has a strong analgesic effect. Pyrazolone is well balanced between analgesic, anti-inflammatory and antifebrile effects. The fenamates and oxicams are long acting. On the other hand, NSAIDs sometimes inhibit adverse reactions, such as gastroduodenal diseases and renal insufficiency, which are probably induced by the inhibition of cyclo-oxygenase to reduce prostaglandin content. Therefore, appropriate NSAIDs must be selected after consideration on the character, property and adverse reaction of each drug.
8763544 Noncemented femoral components in total hip arthroplasty for patients with rheumatoid arth 1996 Jul Twenty-seven patients with rheumatoid arthritis underwent cementless total hip arthroplasty from 1982 through 1989. We performed all operations through a posterior approach. Postoperatively, patient convalescence consisted of ambulation with crutches, followed by weight bearing as tolerated until pain and discomfort subsided. We contacted 25 (92.5%) patients for follow-up. Combined, these patients received 34 total hip arthroplasties. The patients ranged in age from 14 to 69 years old with a mean age of 42.9 years. The follow-up period ranged from two to eight years with a mean of five and one-half years. The mean preoperative total Harris hip score was 48 (range 31-68). The mean total Harris hip score at latest follow-up was 80 (range 44-95). Hip pain status and functional ability were important indicators of treatment efficacy. The lower incidence of pain, as well as the increase in functional abilities experienced by the patients, suggests that cementless total hip arthroplasty is a preferable alternative to fixed arthroplasty in patients with rheumatoid arthritis.
8792797 Impact of patient with patient interaction on perceived rheumatoid arthritis overall disea 1996 To determine whether patient interaction impacts on perceived disease severity and ability to cope with rheumatoid arthritis (RA) forty RA patients were assessed using joint counts, clinician global assessment, patient global assessment (PGA), VAS pain scale and Health Assessment Questionnaire (HAQ). All participants had six one-on-one conversations about their disease activity and the effect of RA on their lives. Follow-up questionnaires asked about recall of pre-conversation PGA; post-conversation PGA; change in PGA; and change in ability to cope as a result of the conversations. 87.5% of the questionnaires were returned. Pre- and post-conversation PGA were statistically reliable; PGA score improved (P = 0.004); 60.0% of participants felt their ability to cope with their disease improved as a result of this interaction. RA patients benefit from sharing information with like patients. Support groups may be an integral part of treatment strategy in patients with RA.
8216416 DAB486IL-2 fusion toxin in refractory rheumatoid arthritis. 1993 Sep OBJECTIVE: To evaluate the safety and antiarthritic effects of DAB486IL-2. This agent is a fusion toxin and the product of a synthetic gene, engineered by replacing the codons for the receptor-binding domain of diphtheria toxin (DT) with the codons for human interleukin-2 (IL-2). DAB486IL-2 targets cells expressing the 2-chain, high-affinity form of the IL-2 receptor (IL-2R), and achieves selective diphtheria toxin-mediated cytotoxicity of activated T cells by inhibition of protein synthesis. METHODS: Nineteen patients with rheumatoid arthritis (RA) that had been refractory to methotrexate participated in an open-label, phase I/II trial evaluating 3 dose levels of intravenous DAB486IL-2 given for 5 or 7 consecutive days. Thirteen patients received additional courses, at higher doses if the original response had been inadequate or at an equivalent dose if the original course produced a response, for a total of 38 courses. Arthritis response was assessed at 28 days, with biweekly followup of patients with substantial response (> or = 50% improved) or meaningful response (> or = 25% improved). Laboratory monitoring included measurement of CD4+ cells and circulating shed IL-2R. RESULTS: Nine of 19 patients treated with high- or medium-dose DAB486IL-2 had a substantial or meaningful response after 1 or 2 treatment courses. No significant responses occurred with the low-dose regimen. Clinical benefit was rapid, with full effect noted by 14 days following completion of infusions. Antibodies to DT developed in all patients, or levels of preexisting antibodies were boosted. Adverse effects included transient elevation of transaminase levels (55% of the patients), fever (40%), nausea or anorexia (30%), hypersensitivity (6%), and thrombocytopenia (5%). Repeat courses were associated with less transaminase elevation and were clinically effective despite induction of anti-DT antibodies. CONCLUSION: The results of this open trial provide preliminary evidence for a potential therapeutic effect of DAB486IL-2 in RA, with an acceptable safety profile. Reversible transaminase elevations limit escalation of the dosage beyond 0.1 mg/kg/day. A controlled study of DAB486IL-2 is required to determine the efficacy of this high-affinity IL-2R-targeted fusion toxin in the treatment of RA.
7777825 IgM, IgA, and IgG rheumatoid factors in early rheumatoid arthritis predictive of radiologi 1995 The significance of IgM, IgA and IgG rheumatoid factors (RF) for the prediction of radiological progression, and as process variables during follow-up, was evaluated in a three-year prospective study of 149 patients with early rheumatoid arthritis (symptoms < 1 year at study entry). The occurrence of IgA-RF and IgG-RF at study entry without simultaneous occurrence of IgM-RF, and the seroconversion from RF-negative at entry to RF-positive during follow-up appeared to be unusual. A significant correlation was found between each of the RF-isotype levels at entry and radiological progression after three years. However, no significant prognostic value of IgA-RF and IgG-RF could be demonstrated if analysed in combination with IgM-RF, initial disease activity (as measured by C-reactive protein level), initial radiologic score, HLA-DR4 and HLA-DR2. Although IgM-RF levels generally reflected the course of disease activity and did so better than IgA-RF and IgG-RF levels, their clinical significance as process variables appeared to be limited compared to C-reactive protein.
8323398 Thyroid dysfunction in rheumatoid arthritis: a controlled prospective survey. 1993 Jun OBJECTIVES: To determine whether thyroid dysfunction is found with increased frequency in patients with rheumatoid arthritis (RA). METHODS: A controlled prospective survey was conducted on a cohort of patients with RA derived from a hospital clinic and a private surburban rheumatology practice. A control group with similar demographic features was generated from the same sources and included subjects with either osteoarthritis or fibromyalgia. Consecutive patients were evaluated over a six month period. The evaluation included a complete history and physical examination, and determination of serum thyroxine, free thyroxine, triiodothyronine, thyroid stimulating hormone (IRMA), antinuclear antibodies, and rheumatoid factor. RESULTS: Of the 91 women with RA evaluated, 29 (30%) had evidence of thyroid dysfunction compared with 10 (11%) of 93 controls. The excess thyroid dysfunction is due to either hypothyroidism or Hashimoto's thyroiditis and was independent of age, increasing duration of disease, rheumatoid factor, and antinuclear antibodies. CONCLUSIONS: Thyroid dysfunction is seen at least three times more often in women with RA than in women with similar demographic features with non-inflammatory rheumatic diseases such as osteoarthritis and fibromyalgia.
7939729 Efficacy of standard slow-acting antirheumatic drugs. 1994 Jun There are few published reports of the efficacy of slow-acting antirheumatic drugs (SAARDs) specific to the treatment of persons with early rheumatoid arthritis. Two published meta-analyses of the literature on SAARD therapy are reviewed, together with some empirical data on patients with less than 2 years' disease duration treated over an 8-year period. Although the literature suggests short-term benefit of SAARDs compared with placebo therapy, there is little to warrant considering presently available drugs to be disease-remittive agents. Based on known toxicities and purported benefits of available SAARDs, a treatment schema is proposed that responds incrementally to the course of the illness when treatment is started before irreversible joint injury occurs. The advent of new classes of therapeutic agents (eg, biologicals) for the treatment of rheumatoid arthritis warrants examination of present methods for the evaluation of antirheumatic drugs.
7543348 A comparative study of tenidap, a cytokine-modulating anti-rheumatic drug, and diclofenac 1995 Jun Tenidap is a novel anti-rheumatic drug that combines cytokine modulation with cyclo-oxygenase inhibition. This 24-week, multicentre, double-blind, randomized study compared the clinical efficacy, biochemical effects and safety of tenidap 120 mg/day (once daily) with diclofenac 150 mg/day (50 mg t.i.d) in the treatment of 384 patients with active rheumatoid arthritis. After 24 weeks, improvement with tenidap was significantly greater than with diclofenac for all five primary efficacy parameters, two of the four secondary efficacy parameters and 11 of the 13 Arthritis Impact Measurement Scales assessments. The superior efficacy of tenidap was apparent after 4 weeks of treatment with further improvements observed by 24 weeks. The probability of discontinuation due to lack of efficacy was significantly greater in the diclofenac group. Tenidap but not diclofenac was associated with significant, rapid and sustained reductions in C-reactive protein and serum amyloid A levels and with a significant reduction in plasma interleukin-6. The nature and frequency of side-effects were similar in the two groups as was the discontinuation rate for treatment-related safety reasons. Tenidap was associated with an equal incidence of elevated transaminases, but a higher incidence of mild (> or = 500 mg/24 h < 1500 mg/24 h) non-progressive, proteinuria of proximal tubular origin compared with diclofenac.
7928636 Problems and paradigms in joint pathology. 1994 Jun This short review outlines aspects of joints relevant to current problems in articular, connective tissue disease and describes the pathology of rheumatoid arthritis and osteoarthrosis. The synovial joints display greatly varying degrees of anatomical specialisation. There is also heterogeneity of microscopic structure, to illustrate which the synovial components of the sacroiliac joints are considered. The chondron is regarded as a functional unit of hyaline articular cartilage but the responses of this tissue in disease are strongly influenced by its avascularity and by the need for chondrocytes to communicate with each other and with their local and systemic environments. Hyaline cartilage is capable of molecular replacement or substitution but not of repair by regeneration; it can, however, be replaced by fibrocartilage. The bearing surfaces of hyaline articular cartilage are never planar or smooth. Rheumatoid arthritis is a paradigm of connective tissue disease. It is not only a systemic disorder which may abbreviate life but, characteristically, is an aseptic form of symmetric polyarthritis. The inheritance of HLA-DR beta 1 and of female sex predispose to rheumatoid arthritis but the cause is unknown; it may be viral. Central to the disease is destruction of articular cartilage by sustained inflammation in which activated macrophages and TH cells, possibly of restricted clonality, combine to release cytokines, proteinases and the mediators of inflammation. Osteoarthrosis is a synovial joint syndrome, not a single disease. It is characterised by a loss of and change in the composition of cartilage proteoglycans leading to failure of normal responses to stress. The results include cartilage fibrillation and loss, bone exposure and a clinical syndrome of pain and disability. Rare forms of heritable chondrodysplasia lead to premature osteoarthrosis but, in most instances, the cause of osteoarthrosis appears to be either excess, inappropriate or insufficient mechanical demand, or traumatic, infective, inflammatory, endocrine or metabolic disease. There remain idiopathic ('primary') cases in which no cause is demonstrable.
8473487 Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health a 1993 Apr Plasma and whole-body turnover studies of human C-reactive protein (CRP), isolated from a single normal healthy donor and labeled with 125I, were undertaken in 8 healthy control subjects and 35 hospitalized patients including cases of rheumatoid arthritis, systemic lupus erythematosus, infections, and neoplasia. Plasma clearance of 125I-CRP closely approximated to a monoexponential function and was similar in the control and all patient groups. There was no evidence for accelerated clearance or catabolism of CRP in any of the diseases studied. The 19-h half-life was more rapid than that of most human plasma proteins studied previously, and the fractional catabolic rate was independent of the plasma CRP concentration. The synthesis rate of CRP is thus the only significant determinant of its plasma level, confirming the validity of serum CRP measurement as an objective index of disease activity in disorders associated with an acute-phase response. Approximately 90% of injected radioactivity was recovered in the urine after 7 d, and scintigraphic imaging studies with 123I-labeled CRP in 10 patients with different focal pathology showed no significant localization of tracer. The functions of CRP are thus likely to be effected predominantly in the fluid phase rather than by major deposition at sites of tissue damage or inflammation.
8184239 [Fatal outcome of pneumocystis-carinii pneumonia under low-dose methotrexate and prednison 1994 Apr 12 New therapeutic schemes have been proposed recently for treatment of rheumatoid arthritis. Among these, methotrexate at low doses is recommended as basic therapy, already shortly after the diagnosis is established. We report on a 68-year-old female with rheumatoid arthritis who developed bilateral pneumocystis-carinii pneumonia with a lethal course and bilateral sinusitis maxillaris with candida lusitaniae. Various opportunistic infections have been described in the literature after low-dose methotrexate. It is our view that the use of methotrexate in rheumatoid arthritis should still be considered cautiously until further data on the risk-benefit ratio of long-term use become available.