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Biomedical subjects

B A Dijkmans

Publications and source records attributed to B A Dijkmans.

At least 19 recordsLinked to original sources

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis.

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.

Adult

Sesame oil in injectable gold: two drugs in one?

To investigate the potential anti-inflammatory effects of sesame oil, which is present in the injectable gold preparation Auromyose, the synthesis of tumour necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) by in vitro stimulated blood cells was measured before, during and after 12 weeks of dietary supplementation with 18 g of sesame oil daily in 11 healthy male volunteers. Neither TNF-alpha, PGE2 nor LTB4 production levels showed statistically significant changes during the 12 weeks of dietary supplementation with sesame oil. These results do not suggest an anti-inflammatory effect of sesame oil as present in injectable gold preparations which are used in the treatment of rheumatoid arthritis.

Adolescent

Do patients with systemic sclerosis have abnormal gallbladder function?

OBJECTIVE: To determine gallbladder motility in patients with systemic sclerosis. DESIGN: Case control study. SETTING: University hospital, out-patient department of rheumatology. PATIENTS: Ten patients with systemic sclerosis according to the criteria of the American Rheumatism Association with documented involvement of the gastrointestinal tract and 10 healthy controls matched for age, sex and body mass index. INTERVENTION: Cephalic vagal cholinergic simulation by modified sham feeding and hormonal stimulation by infusion of cholecystokinin. MEASUREMENTS: Gallbladder volume obtained by ultrasonography and determination of plasma cholecystokinin concentrations. RESULTS: Fasting gallbladder volumes were not significantly different between patients with systemic sclerosis and controls (19.6 +/- 1.9 cm3 and 23.3 +/- 2.9 cm3, respectively, mean plus or minus standard error of the mean). Neither were there significant differences in reduction of gallbladder volume in response to modified sham feeding (35 +/- 4% and 33 +/- 4%, respectively) nor during cholecystokinin infusion (56 +/- 4% and 60 +/- 6%, respectively). The increase in plasma cholecystokinin levels during infusion was not different in the two groups. CONCLUSION: Gallbladder motility in patients with systemic sclerosis is preserved in response to both cholinergic and hormonal stimulation, even when other gastrointestinal motor disturbances are present. These results suggest that patients with systemic sclerosis are not at increased risk for cholelithiasis because of gallbladder dysmotility.

Case-Control Studies

Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation.

OBJECTIVE: To assess the effect of resumption of second line drugs in patients with rheumatoid arthritis (RA) that flared after treatment discontinuation. METHODS: RA patients were studied whose RA flared up after discontinuation of second line treatment while being in remission and who received a second course of the drug. Disease activity parameters were prospectively assessed at the time of treatment discontinuation, during the period when the disease flared up, and three months thereafter. Furthermore the medical charts were reviewed at 12 months after treatment resumption. RESULTS: There were 51 patients included in the study: 25 patients treated with antimalarial drugs, 10 with parenteral gold, four with d-penicillamine, eight with sulphasalazine, two with azathioprine, and two with methotrexate. Disease activity parameters showed significant improvement within three months of treatment resumption, but remained significantly worse when compared with that measured before treatment discontinuation. Within three months 47% of the patients fulfilled 20% response criteria. Disease activity 12 months after treatment resumption was considered to be absent in 35%, mild in 43%, and moderate or active in 22% of the patients. In four (8%) patients the resumed treatment was stopped because of lack of efficacy. Side effects were recorded in four patients, which did not result in treatment discontinuation. CONCLUSIONS: Resumption of second line drugs in RA patients whose disease flared up after discontinuation of treatment is effective and safe in most patients. Half of the patients responded within three months after resumption of the second line drug.

Acute Disease

Incidence and sources of native and prosthetic joint infection: a community based prospective survey.

OBJECTIVES: To determine the incidence and sources of bacterial arthritis in the Amsterdam health district and the maximum percentage of cases that theoretically would be preventable. METHODS: Patients with bacterial arthritis diagnosed between 1 October 1990 and 1 October 1993 were prospectively reported to the study centre by all 12 hospitals serving the district. Data were gathered on previous health status, source of infection, and microorganisms involved. RESULTS: 188 episodes of bacterial arthritis were found in 186 patients. Most of the 38 children were previously healthy. Fifty per cent of the adults were 65 years or older. Of the adults 84% had an underlying disease, in 59% a joint disorder. Joint surgery constituted the largest part of direct infections (33%) and skin defects were the most important source of haematogenous infections (67%). Infection of joints containing prosthetic or osteosynthetic material by a known haematogenous source occurred 15 times (8%). Staphylococcus aureus was the causative organism in 44% of all positive cultures. CONCLUSION: The incidence of bacterial arthritis was 5.7 per 100,000 inhabitants per year. Preventive measures directed to patients with prosthetic joints or osteosynthetic material, and a known haematogenous source would have prevented at most 8% of all cases.

Adult

Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells.

OBJECTIVE: The efficacy of both chloroquine and hydroxychloroquine in rheumatoid arthritis (RA) has been proved in controlled clinical trials. Despite similar chemical characteristics, it is believed the clinical efficacy of chloroquine is superior to that of hydroxychloroquine in patients with RA. Excessive production of proinflammatory cytokines was shown to contribute to the pathogenesis of RA. From different studies testing either chloroquine or hydroxychloroquine, it could be concluded that both drugs differentially inhibit cytokine production. METHODS: We compared the effects of both chloroquine and hydroxychloroquine on stimulated peripheral blood mononuclear cells (PBMC) with respect to cytokine production. Therefore, PBMC were tested for tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interferon-gamma (IFN-gamma) by specific ELISA, after stimulation with phytohemagglutinin (PHA) or lipopolysaccharide (LPS) in the presence or absence of different concentrations of chloroquine or hydroxychloroquine. RESULTS: We observed that chloroquine and hydroxychloroquine equally inhibit PHA induced TNF-alpha and IFN-gamma production, and LPS induced TNF-alpha and IL-6 production, while PHA induced IL-6 production was not affected. CONCLUSION: Chloroquine and hydroxychloroquine display similar effects on PHA and LPS induced cytokine production by PBMC under identical in vitro conditions. These findings may help in understanding the mechanism of action of these drugs on RA.

Adult

Long-term prognosis in patients treated for erythema chronicum migrans and acrodermatitis chronica atrophicans.

OBJECTIVE: To determine whether Lyme borreliosis persisted or had recurred in patients treated for erythema chronicum migrans and acrodermatitis chronica atrophicans. DESIGN: Retrospective follow-up study. Mean time between treatment and follow-up study was 8.8 years (SD, 66.6 years). SETTING: Department of dermatology. PATIENTS: Patients (N = 52) treated from July 1964 to October 1992 for erythema chronicum migrans (ECM; n = 44) or acrodermatitis chronica atrophicans (ACA; n = 8). Fifty-two of the 56 successfully contacted and registered patients agreed to participate, for a response rate of 93%. MAIN OUTCOME MEASURES: Signs and symptoms of Lyme borreliosis; serum antibodies to Borrelia burgdorferi. RESULTS: The interval from the time of diagnosis to study entry was 0.8 to 28.7 years (mean, 8.2 years). No symptoms or signs of active Lyme borreliosis were observed in the 52 patients. Antibodies to B burgdorferi were found in the ECM group in 1 of the 23 patients who received a recommended treatment and 2 of the 21 patients who received other treatments; antibodies were found in the ACA group in all 5 adequately treated patients who received a recommended treatment and in 1 of the 3 patients who received other treatments. CONCLUSIONS: There was no association between serologic results and type of treatment or between serologic results and complaints or symptoms at the time of the study in either of the patient groups. The prognosis in most patients with Lyme borreliosis is excellent.

Acrodermatitis

The limited value of the Health Assessment Questionnaire as an outcome measure in short term exercise trials.

OBJECTIVE: To examine the value of the Health Assessment Questionnaire (HAQ) as an outcome measure in short term exercise trials. We studied the association of the objectives of exercise, namely joint mobility, muscle strength, and physical condition, with the HAQ. METHODS: Data for 100 patients with rheumatoid arthritis (RA) included in a study to examine the effect of exercise therapy were used for secondary analysis. Disease activity was determined by the disease activity score (DAS3), pain was scored on a visual analog scale (VAS), and depression was measured by the Dutch Arthritis Impact Measurement Scale. Aerobic capacity (VO2max) estimated from a submaximal ergometer test, grip strength (kPa), isokinetic muscle strength of the knee (Nm/kg), and the Escola Paulista de Medicina range of motion (EPM-ROM) score, a measure of general flexibility, were used as indicators for physical impairments. All variables were entered in a forward multiple regression analysis with the HAQ as dependent variable. RESULTS: The HAQ was significantly correlated with the DAS3 score (r = 0.53), pain (r = 0.51), depression (r = 0.40), joint mobility (r = 0.27), quadriceps strength (r = -0.35), and grip strength (r = -0.50), but not with physical condition. The DAS3 score was first entered in the multiple regression analysis model, followed by pain, quadriceps strength, and grip strength (R2 = 0.45). After 12 weeks of exercise therapy changes in the HAQ were significantly correlated with changes in pain (r = 0.41), in depression (r = 0.33), and in quadriceps strength (r = -0.25), but not with changes in joint mobility or physical condition. CONCLUSION: Physical impairments are weakly associated with the HAQ. The HAQ is not an appropriate instrument to detect changes in physical impairments due to short term exercise therapy.

Adult

Randomised placebo-controlled study of stopping second-line drugs in rheumatoid arthritis.

BACKGROUND: A favourable benefit/risk ratio for treatment of rheumatoid arthritis (RA) with second-line drugs has been established only in short-term studies. The present investigation addresses the question of whether RA patients with a good response to long-term treatment with second-line drugs benefit from continuation of such treatment. METHODS: A 52-week randomised double-blind placebo-controlled multicentre study was conducted to assess the effect of stopping second-line therapy in 285 RA patients with a good long-term therapeutic response. The patients either continued the second-line drug (n = 142) or received a placebo (n = 143). The endpoint was a flare, defined as recurrence of synovitis. FINDINGS: At entry into the study median duration of second-line drug therapy was 5 years (range 2-33). At 52 weeks the cumulative incidence of a flare was 38% for the placebo group and 22% for the continued therapy group (p = 0.002). The risk of a flare was 2.0 times higher for patients receiving placebo than for those continuing the second-line drug (95% CI 1.27 to 3.17). The same trend was found for each second-line drug separately, with the exception of d-penicillamine. Side-effects that necessitated dose reduction or discontinuation occurred in 2 patients in each group. INTERPRETATION: Second-line drugs continue to be effective in RA patients who have responded well to initial treatment.

Anti-Inflammatory Agents, Non-Steroidal

Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three-year randomized, double-blind trial.

OBJECTIVES: Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone-sparing agent in RA. METHODS: The study design was a 3-year randomized, double-blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12-month intervals was the primary efficacy parameter. RESULTS: In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate-treated group (by 8.4 +/- 6.9% [mean =/- SEMI] [P < 0.00011 and 5.2 =/- 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo-treated patients (increase of 0.6 =/- 5.2% and decrease of 1.2 =/- 5.8%, respectively). Femoral neck BMD increased in the pamidronate-treated group (by 2.6 =/- 8.6%) and decreased significantly in the placebo-treated group (by 4.0=/- 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups. CONCLUSION: The present study provides the first evidence that long-term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.

Adult

Renal biopsy findings and followup of renal function in rheumatoid arthritis patients treated with cyclosporin A. An update from the International Kidney Biopsy Registry.

OBJECTIVE: To review data from the International Kidney Biopsy Registry, which describes the occurrence of cyclosporin A (CSA)-induced nephropathy, and to discuss the potential risk factors for its development. METHODS: The report examines data on a total of 60 first and 14 second renal biopsies performed in rheumatoid arthritis (RA) patients treated with CSA for up to 87 months. RESULTS: Five of the 60 patients with RA included in the Biopsy Registry had findings consistent with CSA-induced nephropathy at first biopsy. One further patient had such findings at second biopsy. Of the 22 patients who started CSA at dosages < 4 mg/kg/day and subsequently received dosages no higher than 5 mg/kg/ day, none developed CSA-induced nephropathy. Continuous assessment of renal function did not show any evidence of deterioration over time in patients maintained on low-dose CSA. CONCLUSION: The data indicate that in RA patients being treated according to current dosing recommendations, the risk of developing CSA-induced nephropathy is low.

Adolescent

The effect of ranitidine on NSAID related dyspeptic symptoms with and without peptic ulcer disease of patients with rheumatoid arthritis and osteoarthritis.

The efficacy of ranitidine in the treatment of NSAID-related dyspeptic symptoms with and without peptic ulcer disease (PUD) was investigated in 124 patients with rheumatoid arthritis (RA) and osteoarthritis (OA). The patients, who continued the use of NSAIDs were investigated by gastroduodenoscopy. Patients with PUD received open label ranitidine 150 mg b.i.d. and the patients without PUD were randomly allocated to receive ranitidine 150 mg b.i.d. or placebo for 4 weeks. PUD was found in 36 (26%) consecutive patients who presented with dyspeptic symptoms. Of these patients dyspeptic symptoms had disappeared in 8 (26%) of 31 evaluable patients and PUD was healed in 18 (56%) patients after 4 weeks of treatment. After 8 weeks of treatment PUD was healed in 27 (87%) patients. Of the remaining patients without PUD dyspeptic symptoms had disappeared in 24 (26%) of the ranitidine-treated patients which was significantly better (p < 0.02) than the 5 (6%) placebo-treated patients. The minor mucosal lesions found in this patient group improved to a similar extent in the ranitidine and placebo-treated patients although 1 placebo-treated patient deteriorated and 2 placebo-treated patients developed PUD during the 4 weeks of study. The results of this study show that oral ranitidine 150 mg b.i.d. is effective in the treatment of both dyspeptic symptoms and mucosal lesions in RA and OA patient who continue the use of NSAIDs.

Adult

The cervical spine in rheumatoid arthritis: relationship between neurologic signs and morphology of MR imaging and radiographs.

OBJECTIVE: Comparison of clinically observed neurologic long tract signs in a heterogeneous group of patients with rheumatoid arthritis (RA), with morphologic abnormalities of the cervical spine as depicted on radiographs and magnetic resonance (MR) images. DESIGN: The patients were prospectively assigned to one of three classes on the basis of their neurologic status. Lateral cervical spine radiographs and sagittal T1-weighted and gradient echo images were performed. The qualitative MR features evaluated were erosion of the dens and atlas, brain stem compression, subarachnoid space encroachment, pannus around the dens, appearance of the fat body caudal to the clivus, and the signal intensity of the pannus. The quantitative imaging parameters were the cervicomedullary angle and the distance of the dens to the line of McRae. PATIENTS: Sixty-three consecutive patients with RA and subjective symptoms, especially neck or occipital pain, and/or clinical objective signs consistent with a compromised cervical cord were included in this study. RESULTS AND CONCLUSIONS: Damage documented with radiographs and MR imaging in patients with RA is often severe, even in those without neurologic signs (class 1). None of the abnormalities confined to the atlantoaxial level correlated significantly with neurologic classification. Subarachnoid space encroachment anywhere in the entire cervical spine did correlate significantly with neurologic classification.

Arthritis, Rheumatoid

Inflammatory and immunological parameters of disease activity in rheumatoid arthritis patients treated with minocycline.

The objective of this study was to analyze the anti-inflammatory effect of minocycline in rheumatoid arthritis. Serum samples of 65 RA patients who completed a 26-week randomized double-blind trial of minocycline (100 mg twice a day) versus placebo were studied. In this trial some clinical parameters and in particular the acute phase response decreased significantly in the minocycline-treated group. Serum levels of albumin and interleukin-6 (IL-6) were compared with CRP levels in order to study the acute phase response. Furthermore, rheumatoid factor (RF) and total immunoglobulin isotypes as well as serum levels of soluble interleukin-2 receptor (sIL2-2R) were determined in order to study immunological parameters of the disease. Immunoglobulins and cytokines were measured by ELISA. Serum levels of albumin remained stable, whereas serum CRP levels decreased both in the minocycline- and in the placebo-treated group. Serum levels of IL-6 decreased in the minocycline-treated group only and this decrease was positively correlated with the decrease in CRP levels. Minocycline significantly decreased serum IgM-RF, IgA-RF, total IgM and total IgA levels. In addition the ratio of IgM-RF/total IgM decreased in the minocycline-treated group. No such changes were observed in the placebo-treated group. The anti-inflammatory effect of minocycline in RA patients may be due to the reduction in the synthesis of IL-6 and rheumatoid factor.

Adult

Persistent CD3-crosslinking down-regulates interleukin-2 responsiveness in interleukin-2-competent cloned T cells: the possible involvement of protein kinase C.

To investigate the regulation of interleukin-2 (IL-2) responsiveness of T cells, a human CD4+ T-cell clone with constitutive expression of IL-2 receptors was stimulated with recombinant IL-2 (rIL-2) in the presence or absence of immobilized anti-CD3 monoclonal antibodies (alpha CD3imm MoAb). Incubation of T cells with alpha CD3imm MoAb decreased IL-2-induced proliferation which could not be ascribed to the modulation of IL-2 receptor expression nor to cell death. Phorbol-myristate-acetate (PMA), an activator of protein kinase C (PKC), also induced down-regulation of IL-2 responsiveness. The alpha CD3sol MoAb, inducing Ca(2+)-mobilization without activating PKC, did not inhibit IL-2 responsiveness whereas cyclosporine A (CsA), a drug that inhibits the Ca(2+)-dependent activation pathway, did not prevent the induction of IL-2 hyporesponsiveness induced by alpha CD3imm MoAb. It is concluded that modulation of IL-2 responsiveness of T cells via the T-cell receptor/CD3 complex (TCR/CD3) may be mediated by a PKC-activating signal.

Antibodies, Monoclonal

Differential therapy in early and late stages of rheumatoid arthritis.

Early and late stages of rheumatoid arthritis differ with respect to the severity of inflammation and the progression rate of irreversible joint destruction. There are no solid data showing that disease mechanisms underlying destructive arthritis differ between the various stages of the disease. Long-term observational studies have shown that rheumatoid arthritis is a severe progressive disease in many patients, highlighting the need for new therapeutic strategies. At present many centers are exploring whether early and aggressive treatment can improve long-term morbidity and mortality.

Arthritis, Rheumatoid

High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs.

BACKGROUND: Continuous therapy with low-dose ranitidine (150 mg b.d.) is known to be effective for the prevention of recurrent nonsteroidal anti-inflammatory drug (NSAID)-associated duodenal ulcer but not for gastric ulcer. AIM: To investigate, in a double-blind placebo-controlled study, the preventive effect of a high dose of ranitidine (300 mg b.d.) on the recurrence of both duodenal ulcers and gastric ulcers in rheumatoid arthritis patients with a continuous need for NSAIDs. METHODS: Rheumatoid arthritis patients with a history of peptic ulcer disease were randomized to receive either ranitidine 300 mg b.d. or placebo for 12 months. Endoscopy was performed at study entry and after 6 and 12 months. End-point was the recurrence of gastric or duodenal ulcers. RESULTS: The study was stopped after a blinded interim analysis; at that time 10 of the 15 included patients in each treatment group were evaluable. Recurrent duodenal ulcers had occurred in four patients treated with placebo and none of the patients treated with ranitidine (Fisher's exact one-tailed P = 0.04; 95% CI, - 0.70 to -0.10). Recurrent gastric ulcers had occurred in six patients in the placebo group and three patients in the ranitidine group (Fisher's exact one-tailed P = 0.18; 95% CI, -0.72 to 0.12). Two patients in the placebo group had developed both duodenal ulcers and gastric ulcers. No adverse events were observed. CONCLUSIONS: High dose ranitidine is effective for the prevention of recurrent duodenal ulcer but not for recurrent gastric ulcer in rheumatoid arthritis patients taking NSAIDs.

Aged

The tetracycline derivative minocycline differentially affects cytokine production by monocytes and T lymphocytes.

Minocycline is a tetracycline derivative that has beneficial effects in noninfectious forms of arthritis and dermatitis. To investigate whether this effect may be attributed to interference with cytokine production, we studied the effect of minocycline on cytokine production by T cells and monocytes. Minocycline exerted an inhibitory effect on tumor necrosis factor alpha (TNF-alpha) and gamma interferon production by stimulated T cells, whereas the production of interleukin 6 (IL-6) remained unaffected. The effect of minocycline on TNF-alpha mRNA synthesis by T cells was shown to be stimulus specific. T cells stimulated by a Ca2+-independent mode exhibited a decrease in TNF-alpha mRNA in the presence of minocycline, whereas the TNF-alpha mRNA level remained unaffected by minocycline when cells were stimulated in a Ca2+-dependent manner. In contrast to the effect on T cells, addition of minocycline to lipopolysaccharide-stimulated monocytes led to a dose-dependent increase in TNF-alpha and IL-6 production which was paralleled by an enhancement of TNF-alpha mRNA synthesis. These results indicate that minocycline exerts differential effects on the regulation of cytokine production by T cells and monocytes that are partly reflected at the mRNA level. Given the pleiotropic effects of minocycline, it is suggested that the immunostimulatory effect on monocytes might counteract its beneficial properties in the treatment of several forms of chronic inflammation.

Anti-Bacterial Agents