PubMed Health⌕ Search

Biomedical subjects

H R van den Brink

Publications and source records attributed to H R van den Brink.

15 recordsLinked to original sources
PubMed2001

[Short-term steroid therapy, sometimes with long-term sequelae].

Two patients developed osteonecrosis, respectively one and two years after the short-term intravenous use of dexamethasone. A 35-year-old man received 150 mg over a period of 3 weeks associated with a craniotomy for a subarachnoidal haemorrhage. He developed bilateral osteonecrosis of the femoral and humeral heads, which necessitated bilateral hip replacement surgery. He still experiences pain in both shoulders. A 45-year-old woman received 42.5 mg over a period of 1 week as a treatment for reflex dystrophy with oedema. She developed bilateral osteonecrosis in the femoral condyles, the talus and the calcaneus and after treatment she continued to experience pain in her right knee and ankle whilst walking. The only other risk factor for osteonecrosis identified in these patients was hyperlipidaemia in the man. Corticosteroid-induced osteonecrosis is typically multifocal and usually occurs 0.5 to 3 years after the therapy was initiated. There is a relationship with the dose and length of therapy. Even the short-term use of corticosteroids for 3 weeks or less, may lead to this dehabilitating complication.

Adult↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1994

Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of corticosteroid pulse (CP) therapy on soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6) and IL-8 levels in patients with active rheumatoid arthritis (RA). METHODS: Twenty-five patients with active RA were studied before and after treatment with intravenous CP therapy. In 12 patients lymphocyte subsets were also assessed. RESULTS: All patients showed a significant decrease in clinical disease activity variables after 4 to 8 weeks of CP therapy. Baseline levels of sIL-2R were higher among patients with active RA than healthy controls; after CP therapy, sIL-2R levels decreased significantly, but not as much as the erythrocyte sedimentation rate or C-reactive protein. In most cases baseline levels of both IL-6 (n = 23) and IL-8 (n = 17) could be measured and both decreased significantly after CP therapy. Cortisol levels were suppressed shortly after CP therapy but had returned to pretreatment values at 4 weeks. After CP therapy there was a temporary increase in the number of HLA-DR positive cells and a decrease in the number of CD3 positive cells, while the CD4/CD8 ratio and IL-2 receptor (CD25) positive cells remained unchanged. CONCLUSION: High dose corticosteroids influence serum levels of sIL-2R, IL-6 and IL-8 in patients with active RA.

Adult↗
PubMed1993

Transient decrease in osteocalcin and markers of type 1 collagen turnover during high-dose corticosteroid pulse therapy in rheumatoid arthritis.

The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption.

Aged↗
PubMed1993

Adjuvant oestrogen therapy does not improve disease activity in postmenopausal patients with rheumatoid arthritis.

OBJECTIVE: To investigate whether oestrogens can be used as treatment to diminish disease activity in women with rheumatoid arthritis. METHODS: Forty postmenopausal female patients with active rheumatoid arthritis participated in a placebo-controlled, double-blind study on the possible beneficial effect of adjuvant treatment of oestradiol on disease activity. RESULTS: Thirty three patients completed 52 weeks of treatment with 2 mg oestradiol-valerate or placebo. No statistically significant difference was found in and between both treatment groups with regard to articular indices, pain score by visual analogue scale, erythrocyte sedimentation rate and health questionnaire on daily activities before, during and at the end of the study. CONCLUSION: This first randomised prospective placebo-controlled study shows no beneficial effect of oestrogens on disease activity in postmenopausal female patients with rheumatoid arthritis.

Aged↗
PubMed1993

Adjuvant oestrogen treatment increases bone mineral density in postmenopausal women with rheumatoid arthritis.

OBJECTIVES: The beneficial effect of oestrogens on bone mineral density in women with osteoporosis is well known. Patients with rheumatoid arthritis (RA) are at risk for osteoporosis. A study was therefore set up to investigate the effects of adjuvant oestrogen treatment on bone metabolism and bone mineral density in postmenopausal women with RA. METHODS: Forty postmenopausal women with active RA were admitted to a placebo controlled, double blind study investigating the beneficial effect of adjuvant oestradiols or placebo on bone metabolism and bone mineral density. Thirty three patients completed 52 weeks of treatment. RESULTS: At the start both treatment groups were comparable for all parameters. In the oestrogen group serum concentrations of osteocalcin decreased and concentrations of sex hormone binding globulin increased during the study. Bone mineral density measured by dual energy x ray absorptiometry increased significantly in the lumbar vertebral spine and femoral neck in the oestrogen group compared with the placebo group. CONCLUSIONS: This study shows that the use of adjuvant oestrogens in post-menopausal women with active RA increases bone mineral density.

Aged↗
PubMed1993

Evaluation of the Thompson articular index.

Three articular indices for measuring disease activity are compared. In a cross sectional study the Thompson articular index (a modified Lansbury index) correlated better with laboratory variables than the Ritchie articular index or a swollen joint score (Thompson 0.74-0.77; Ritchie 0.57-0.58; swollen joint count 0.51-0.59). In a longitudinal study it was shown that the Thompson articular index is sensitive to detect changes of disease activity. We suggest that this index is appropriate for clinical trials.

Adult↗
PubMed1992

Influence of steroid hormones on proliferation of peripheral blood mononuclear cells in patients with rheumatoid arthritis.

Sex steroids are believed to modulate the immune system in rheumatoid arthritis (RA). Since receptors for sex steroids are present on T-lymphocytes, which are thought to play a major role in the pathogenesis of RA, it is suggested that gonadal steroids can mediate their immunomodulating effect directly on T-lymphocytes. Recently a specific method for activating T-lymphocytes with immobilized anti-CD3 monoclonal antibodies was described. We investigated the influence of oestradiol, progesterone, testosterone and cortisol on lymphocytes stimulated by anti-CD3 mAb and PHA of postmenopausal women, comparing female patients with rheumatoid arthritis and age-matched control patients. The results show that oestradiol, progesterone and testosterone do not influence lymphocyte proliferation when stimulated with anti-CD3 mAb or phytohaemagglutinin (PHA). Cortisol, however, can suppress lymphocyte proliferation even at physiological concentrations in both patients with RA and controls. Inhibition of proliferation by cortisol is dose-related and has no significant correlation with RA disease activity. This inhibition differs individually and might explain the often variable response to corticosteroids in vivo.

Aged↗
PubMed1991

Eosinophilic fasciitis presenting with a reactive hepatitis.

We report a patient with eosinophilic fasciitis, reactive hepatitis and splenomegaly. Administration of prednisone resulted in normalization of liver enzymes and spleen-size and an improvement of his clinical condition. These uncommon manifestations are only part of the broadening clinical spectrum, which is discussed briefly.

Adult↗
PubMed1989

Can oestrogens be used as adjuvant therapy in female patients with rheumatoid arthritis?

In this review the arguments for a relation between female sex hormones and rheumatoid arthritis are discussed. Clinical evidence includes a relation between disease activity and menstrual cycle and a clear decrease in disease activity during pregnancy. A protective effect of oral contraceptives on the development of rheumatoid arthritis is claimed. There are conflicting data with regard to the plasma levels of sex hormones in women with rheumatoid arthritis. In vitro gonadal hormones suppress T-lymphocyte proliferation, while B-lymphocyte differentiation is enhanced by oestrogens and diminished by testosterone. Some pilot studies suggest that oestrogens may ameliorate disease activity in women with active rheumatoid arthritis. Presently we are conducting a randomized, double-blind trial comparing oestrogens with placebo as adjuvant therapy in women with rheumatoid arthritis.

Adjuvants, Immunologic↗
PubMed1979

Development of T and B cell areas in peripheral lymphoid organs of the rat.

In the present study the early development of peripheral lymphoid organs (spleen, popliteal lymph node, mesenteric lymph node and Peyer's patches) is described in terms of homing patterns of T and B cells, demonstrated with immunohistoperoxidatic detection of characteristic membrane antigen in normal rats and with routine histology in neonatally thymectomized rats. In the first days after birth the peripheral lymphoid organs are almost exclusively populated by T cells. After neonatal thymectomy lymphocytes appear in the dome areas of Peyer's patches from four to six days after birth, in mesenteric and popliteal lymph nodes lymphocytes are found in the outer cortex from day 6 and day 8 respectively and in the marginal zone of the spleen from eight days onwards. These lymphocytes showed no membrane staining when reacted for T antigen with immunohistoperoxidatic techniques. The morphological evidence for considering Peyer's patches of rats as central inductive sites for the generation of B cells is poor. The discrepancy in the order of appearance of T and B cell (sub)populations in spleen compartments in normal ontogenetic development and lethally irradiated, stem cell reconstituted animals is discussed.

Animals↗
PubMedDate not supplied

Influence of disease activity on steroid hormone levels in peripheral blood of patients with rheumatoid arthritis.

The steroid hormone status of 27 female patients (15 premenopausal and 12 postmenopausal) and 11 male patients with rheumatoid arthritis (RA) was investigated before and after a clinically significant deterioration in disease activity. In postmenopausal patients the serum level of cortisol decreased significantly with the progression of disease activity. No significant change in the serum levels of oestrone, oestradiol, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate or prolactin was found within the groups. In premenopausal patients serum cortisol levels also decreased, with progression of disease activity, but this difference did not reach statistical significance. In male patients with RA none of the measured steroid hormone levels changed significantly after exacerbation of disease activity. Our data indicate that the synthesis and/or utilization of cortisol might be abnormal in female patients with active rheumatoid arthritis.

Adult↗