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Biomedical subjects

L B van de Putte

Publications and source records attributed to L B van de Putte.

At least 19 recordsLinked to original sources
PubMed1995

Purine enzyme activities in peripheral blood mononuclear cells: comparison of a new non-radiochemical high-performance liquid chromatography procedure and a radiochemical thin-layer chromatography procedure.

Purine enzyme activities are usually assayed by radiochemical procedures and often TLC is part of the separation method. In screening patients with rheumatic diseases, these procedures have shown disadvantages like a relatively large coefficient of variation (C.V.) and time-instability. We describe a non-radiochemical reversed-phase HPLC micro-method with UV detection for measurement of activities of purine 5'-nucleotidase (5'NT; EC 3.1.3.5), purine nucleoside phosphorylase (PNP; EC 2.4.2.1) and hypoxanthine guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) in human peripheral blood mononuclear cells (PBMC). The HPLC procedure is compared with the radiochemical TLC procedure by testing both with a 5'NT and a PNP assay. Reproducibility is tested with 14 healthy controls in each procedure. Short-term and long-term time-stability is tested by comparing enzyme activities measured immediately after preparation of the PBMC (week 0) with those found after freezing and storage at -20 degrees C for a maximum of 10 weeks. The HPLC procedure is preferable to the radiochemical TLC procedure because it shows significantly better reproducibility and better time-stability and in addition is non-radiochemical and less time-consuming.

Adult↗
PubMed1995

Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis.

OBJECTIVE: The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts. METHODS: These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated. RESULTS: No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists). CONCLUSION: The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.

Adult↗
PubMed1995

Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis.

OBJECTIVE: Azathioprine (AZA) metabolism largely parallels the endogenous purine pathways. To date, thiopurine methyltransferase (TPMT) deficiency has been reported as a cause of AZA-related bone marrow toxicity in 1 patient with rheumatoid arthritis (RA). We therefore studied purine enzyme activities in 3 patients with RA who experienced AZA-related bone marrow toxicity. METHODS: Lymphocyte activity of purine nucleoside phosphorylase and 5'-nucleotidase (5NT) and erythrocyte activity of TPMT, key enzymes in thiopurine catabolism, were measured in 3 RA patients who had experienced AZA-related bone marrow toxicity and in 16 RA patients without signs of toxicity despite at least 6 months of treatment with AZA. RESULTS: Two patients with AZA-related bone marrow toxicity were found to have a TPMT deficiency, 1 partial and 1 total. In the third patient, 5NT activity was found to be well below the lowest level observed in the control subjects. CONCLUSION: All 3 patients with severe AZA-related bone marrow toxicity had abnormal purine enzyme activities. Deficiency of purine enzymes, including TPMT and 5NT, may be a cause of AZA-related bone marrow toxicity in patients with RA.

5'-Nucleotidase↗
PubMed1995

Infections during low-dose methotrexate treatment in rheumatoid arthritis.

We studied the infection rate in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) in a 6-year open prospective study and in a 12-month randomized double blind trial comparing MTX with azathioprine (AZA) that was followed by a 3-year open prospective study. The literature on infections during low dose MTX in RA was reviewed. We also did a search for therapy-related opportunistic infections in RA and in MTX-treated psoriasis and psoriatic arthropathy patients. In our studies the infection rate during MTX treatment was higher in severe RA than in moderate RA. In severe RA there were often 2 infections simultaneously. The majority of the infections occurred in the first 1.5 years of treatment. There was no difference in the infection rate of MTX and AZA in the comparative trial. In the literature the infection rate was highest in short-term double-blind studies. Opportunistic infections are increasingly reported in RA treated with MTX and rarely with AZA, cyclosporine A, and cyclophosphamide or in MTX treated psoriasis and psoriatic arthropathy. In RA it appears that the initial period of treatment with MTX is the most vulnerable phase for infections, with the exception of opportunistic infections, which are not limited to a certain treatment period. Probably there are more MTX-associated infections in severe RA than in moderate RA.

Adult↗
PubMed1995

Oral steroids as bridge therapy in rheumatoid arthritis patients starting with parenteral gold. A randomized double-blind placebo-controlled trial.

The efficacy of oral prednisone as bridge therapy in rheumatoid arthritis (RA) was studied. Forty patients starting aurothioglucose were randomized to receive either prednisone or placebo for 18 weeks. The dose was 10 mg/day in the first 12 weeks, 7.5 mg/day in weeks 13 and 14, 5 mg/day in weeks 15 and 16, and 2.5 mg/day in weeks 17 and 18. Patients were followed for 44 weeks. We found that disease activity was significantly lower in the prednisone group as early as week 1 and continued up to week 12. Response to prednisone was noticed in 60% of the patients. After tapering prednisone, a rebound deterioration was noticed at weeks 20 and 24 in 58% of the responders. No significant differences in X-ray progression were found between the two groups. We concluded that oral prednisone (10 mg/day) significantly reduces short-term disease activity in 60% of patients with active RA. The rebound deterioration after tapering the dose means that bridge therapy with prednisone using this dose-reduction scheme is not recommended.

Administration, Oral↗
PubMed1995

A tumour necrosis factor alpha polymorphism is not associated with rheumatoid arthritis.

OBJECTIVE: To determine whether a polymorphism within the tumour necrosis factor alpha (TNF alpha) gene is associated with susceptibility to, or severity of, rheumatoid arthritis (RA). METHODS: Consecutive patients with recent onset RA were enrolled in a prospective trial. DNA was collected, disease activity was measured at presentation, and radiographic progression at three years was assessed. Typing of TNF alpha was by polymerase chain reaction and single stranded conformation polymorphism analysis. RESULTS: No association of TNF alpha alleles and susceptibility to, or severity of, RA was demonstrated. CONCLUSIONS: These results indicate that this TNF alpha polymorphism does not play a part in the genetic background of RA.

Arthritis, Rheumatoid↗
PubMed1995

Methotrexate in severe ankylosing spondylitis: an open study.

OBJECTIVE: To study the efficacy and toxicity of methotrexate (MTX) for patients with ankylosing spondylitis (AS) in a 36 week, open, single observer study. METHODS: Patients were selected for study if they had evidence of active disease and had failed to respond to treatment with nonsteroidal antiinflammatory drugs (NSAID) and sulfasalazine. Eleven patients entered the study, and 9 were evaluated at the end. Oral MTX (7.5-15 mg weekly) was given for at least 24 weeks; NSAID were kept at a stable dose. Efficacy was evaluated by calculating the relative difference of assessed variable between Week 0 and 24 and by patient evaluation. RESULTS: Assessed variables showed good relative improvement. Four patients decided to continue MTX; 3 used a lower dose of NSAID; one stopped NSAID: Five patient patients discontinued MTX: 3 of these had disease flares and restarted MTX. Side effects were mild and reversible. CONCLUSION: Results of our study showed that the majority of our patients with AS taking MTX had beneficial effects.

Adolescent↗
PubMed1994

Second-line treatment in seronegative spondylarthropathies.

The literature concerning second-line treatment of seronegative spondylarethropathies from 1940 to August 1993 was reviewed. Sulfasalazine appeared to be effective in the treatment of ankylosing spondylitis (AS) and promising in reactive arthritis (ReA) and Reiters' syndrome (RS). Methotrexate and azathioprine were associated with a remarkable improvement in some cases of AS and RS. Methylprednisolone and levamisole were both efficacious in AS, but levamisole was associated with occasional severe side effects. Radiation therapy led to short-term improvement in AS, but was abandoned because of severe long-term side effects. Only sulfasalazine has been studied in sufficient detail to allow definitive conclusions, but methotrexate and azathioprine may be promising drugs.

Antirheumatic Agents↗
PubMed1994

Interrelationship of outcome measures and process variables in early rheumatoid arthritis. A comparison of radiologic damage, physical disability, joint counts, and acute phase reactants.

OBJECTIVE: To investigate the relationship between different outcome and process measures in early rheumatoid arthritis (RA). METHODS: A 3-year prospective study of 149 patients with early RA (symptoms < 1 year at entry). Results of serial measurements of process variables were transformed into time integrated values for comparison with the outcome measures. RESULTS: A highly significant correlation was found between the acute phase response, swollen joints, and radiological progression whereas none of these measures correlated with joint tenderness. Physical disability as estimated by the Health Assessment Questionnaire (HAQ) however, appeared to be determined by joint tenderness rather than by joint swelling. CONCLUSION: In early RA, joint swelling and acute phase reactants appear to be the most appropriate process variables for the prediction of radiological outcome, whereas joint tenderness is a strong determinant of physical disability (HAQ).

Activities of Daily Living↗
PubMed1994

Anergy of antigen-specific T lymphocytes is a potent mechanism of intravenously induced tolerance.

Intravenous (i.v.) injection of an antigen before immunization has been shown to be a potent way to induce suppression at the T-cell level. In this study we demonstrate an almost complete suppression of arthritis (using antigen-induced arthritis as a model) by i.v. injection of 100 micrograms hen egg lysozyme (HEL) 7 days before immunization. Underlying mechanisms, including suppression by CD8+ T lymphocytes, suppression by T-helper 2 (Th2) or anergy of antigen-specific T lymphocytes, were studied. In vivo treatment with either anti-CD8 or anti-interleukin-4 (IL-4) could not abrogate i.v.-induced tolerance. Lymphocyte stimulation assays showed reduced antigen-specific proliferative responses and IL-2 production in tolerized mice. The possible role of soluble suppressive cytokines was examined in vitro by adding anti-IL-4, anti-IL-10 or anti-transforming growth factor-beta (TGF-beta). Neutralization of these factors could not diminish suppression. Finally, anergy of antigen-specific T lymphocytes was tested as a possible mechanism for i.v.-induced tolerance. Results demonstrated that reduced proliferative T-cell responses were reversible: incubation of tolerized lymph node cells for 5 days in added recombinant (r)IL-2 fully restored proliferative capacity back to normal. We therefore conclude that the main mechanism of i.v.-induced tolerance in our model is anergy of antigen-specific T lymphocytes.

Animals↗
PubMed1994

Antiperinuclear factor and disease activity in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy.

OBJECTIVE: To study the correlation between antiperinuclear factor (APF) titer and disease activity variables in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) or azathioprine (AZA) and to investigate whether changes are dependent on the drug used. METHODS: Serial measurements of APF titers (2-fold dilutions) and disease activity variables in a 48-week double blind trial comparing MTX and AZA in 64 patients with RA. APF titers at baseline and during followup, and correlations between APF titers and disease activity variables and their changes from baseline were studied in the patient group as a whole and in the 2 treatment groups. RESULTS: The prevalence of the APF at baseline in the MTX group and in the AZA group with undiluted serum was 15/31 (48%) and 19/33 (58%), respectively. With serum diluted 1:10 this was about 25% higher. The APF titer ranged from 1/10 to 1/640. No sustained changes in APF titers were observed during followup. Statistically significant correlations were found between APF titers and 2 of the 4 disease activity variables, as well as for their changes from baseline at some time points and were most pronounced in the AZA group. However, no consistent correlation between APF titers and disease activity variables could be established. APF changed from negative to positive during followup in 4 patients (6.3%) and from positive to negative in 4 (6.3%). Changes in APF titer between 2 consecutive measuring points did not exceed 2 dilution steps. CONCLUSION: The APF titer showed no sustained change during the followup period. There was no consistent correlation between APF titer and disease activity variables. We conclude that serial measurements of the APF in longitudinal studies do not give additional information.

Adult↗
PubMed1994

DC-ART: preventing or significantly decreasing the rate of progression of structural joint damage.

Progressive joint damage, increasing deformity, and declining function characterize rheumatoid arthritis (RA). The evidence suggests structural joint damage is the predominant cause of functional impairment. Structural changes of joints are evaluated by imaging methods. Plain joint radiographs remain the best method for determining the extent and nature of structural changes at present. Newer technologies such as magnetic resonance imaging may eventually replace them. Clinical studies of antirheumatic drugs involving the assessment of prevention or significant decrease in the rate of progression of structural joint damage in RA should meet several standards. All patients who enter a study, whether they continue medication or not, must be assessed on its completion. Studies require sufficient power to determine realistic differences due to therapy. They should last long enough for a reliable analysis of the effects of joint damage; 1 year would be the minimal period for such a study, and 2 years would be preferable. Evaluation should concentrate on erosions and related structural changes in juxtaarticular bone; mapping osteoporotic areas in early disease may be a sensitive and objective measure. Assessments ought to use changes within the hands and wrists to indicate overall progression, with the feet included in evaluating early disease. There should be different therapeutic aims at various stages of RA, focussing on preventing new erosions developing in early disease (< 2 years from diagnosis), preventing new erosions occurring in established disease (2-5 years from diagnosis), reducing the rate erosions develop in established disease (< 5 years from diagnosis), and reducing the rate of joint destruction in late disease (> 5 years from diagnosis).

Antirheumatic Agents↗
PubMed1994

DC-ART: what proportion of response constitutes a positive response?

In most clinical trials, patients' mean improvement scores are compared either for active against active treatment or active against placebo treatment. Testing drugs or strategies to qualify as disease controlling antirheumatic therapy will require treated patients to satisfy set criteria. But what proportion must fulfill the requirement if the therapy is to be classified as DC-ART? While the answer must address the problems of semantics, disease characteristics, and absolute levels of improvement, it may be easiest to begin by defining a significant degree of change in terms of a single disease activity index.

Antirheumatic Agents↗
PubMed1994

Role of IL-2 and IL-4 in exacerbations of murine antigen-induced arthritis.

In this study the roles of different T-cell subsets, and produced cytokines, were investigated in an animal model for acute exacerbations. Flare-up reactions are inducible in the chronic phase of a smouldering antigen-induced inflammation by injection of a small amount of an antigen into a hyper-reactive knee joint. In vivo treatment with anti-CD4 monoclonal antibodies (mAb) almost totally blocked the flare reaction, whereas anti-CD8 treatment did not exert any effect. The role of T-helper 1 (Th1) cells in delayed-type hypersensitivity-resembling diseases is generally entitled proinflammatory, whereas Th2 cells act in an anti-inflammatory manner. To investigate the role of these T-cell subsets in flare-up reactions, anti-interleukin-2 (IL-2) and anti-IL-4 mAb treatments were performed. Anti-IL-2 treatment partly blocked the flare reaction, and anti-IL-4 treatment, although the result was unexpected, blocked the flare more efficiently. Furthermore, when human recombinant IL-2 (hrIL-2) and murine recombinant IL-4 (mrIL-4) were co-injected with the antigen to test their ability respectively to potentiate or down-regulate the flare reaction, both cytokines demonstrated additional pro-inflammatory effects, although hrIL-2 was more potent than mrIL-4. The mere effect of hrIL-2 and mrIL-4 was studied by direct injection into a hyperreactive joint. No flare-up reaction or cell-influx could be induced, suggesting that other mediators are needed to exert pro-inflammatory effects of IL-2 or IL-4. We conclude that not only Th1 cells, but also Th2 lymphocytes (at least regarding IL-4 production) may play a pro-inflammatory role in flare-up reactions of chronic arthritis. Considering therapeutic application of Th2 cell-derived cytokines, one should be aware of the possible pro-inflammatory potential of IL-4.

Acute Disease↗
PubMed1992

Biannual radiographic assessments of hands and feet in a three-year prospective followup of patients with early rheumatoid arthritis.

In a prospective followup study of 147 patients with rheumatoid arthritis of recent onset, we assessed the progression of radiographic evidence of joint damage on films of the patients' hands and feet obtained biannually. Patients were receiving first-line and second-line treatment. Ninety patients were followed up for 3 years, and 57 were followed up for only 2 years. Radiographic damage was determined by a modification of the method described by Sharp, and to ensure comparability of findings, we determined the percentage of damage per joint group (actual score divided by the maximum possible score). After 3 years, radiographic damage was present in 70% of the patients, all of whom could be identified after 1 year of study. Overall, 18-20% of the joints of the hands and feet were affected after 3 years, with relatively little abnormality per joint (approximately 8% of maximum possible score). During the entire followup, more foot joints than hand joints were affected. The rate of progression in the first year was significantly higher than in the second and third years of study, indicating a flattening of the curve of radiographic progression of joint damage.

Adult↗
PubMed1992

Quantitative immunohistologic criteria are superior to the lymphocytic focus score criterion for the diagnosis of Sjögren's syndrome.

OBJECTIVE: The aim of the present study was to evaluate the diagnostic value of quantitative immunohistologic criteria for Sjögren's syndrome (SS) in labial salivary gland biopsies. METHODS: Quantitative immunohistologic examination was performed on labial salivary gland biopsy samples from 80 healthy controls, 32 patients with primary SS, 14 patients with secondary SS, 5 with "probable" SS, 36 with keratoconjunctivitis sicca (KCS) with a lymphocytic focus score less than 1 on the lip biopsy, and 18 with rheumatoid arthritis (RA) without clinical evidence of SS. RESULTS: This is the first study to show that immunohistologic criteria for SS, based on the percentages of IgA-containing and IgG-containing plasma cells, are able to 1) confirm the diagnosis of SS in labial salivary glands of KCS patients in the absence of grade IV lymphocytic adenitis; and 2) distinguish between a grade IV focal lymphocytic adenitis in the labial salivary glands of SS patients and of RA patients without SS. CONCLUSION: Quantitative immunohistologic criteria were shown to be much more sensitive and disease specific than the widely accepted grade IV lymphocytic adenitis criterion, which corresponds to a lymphocytic focus score greater than 1, and these criteria should be included in the international diagnostic criteria for Sjögren's syndrome.

Adolescent↗