[Aggressive non-Hodgkin lymphoma in 3 patients with rheumatoid arthritis: discontinue the use of methotrexate]. / Agressief non-hodgkinlymfoom bij 3 patiënten met reumatoïde artritis: eerst methotrexaat staken.

3 female patients who were being treated with methotrexate developed a non-Hodgkin lymphoma. The first patient, 67 years old, presented with an enlarged thyroid gland. The cytological punction was inconclusive and an open biopsy revealed a B cell non-Hodgkin lymphoma, which was localised. A week before the biopsy the methotrexate was discontinued. The patient herself reported that the swelling of her thyroid gland was diminished after cessation of methotrexate. The lymphoma showed a complete remission without chemotherapy being given. The second patient, a 78-year-old woman, developed a non-Hodgkin lymphoma in one of her tonsils that showed a partial remission after withdrawal of the methotrexate therapy. The third patient, a 66-year-old woman, presented herself with a pulmonary non-Hodgkin lymphoma. In this patient withdrawal of the methotrexate resulted in a complete remission of the non-Hodgkin lymphoma as well. Although no epidemiological study has shown an increased risk of lymphoproliferative disorders during the use of methotrexate, these spontaneous remissions suggest an aetiological link. If a non-Hodgkin lymphoma develops in a patient being treated with methotrexate then the therapy should be discontinued and chemotherapy should not be given straightaway.

Immunologic, virologic, and genetic aspects of mammary tumor virus-induced cell-surface antigens: presence of these antigens and the Thy 1.2 antigen on murine mammary gland and tumor cells.

The distribution of the normal differentiation antigen Thy 1 and the mammary tumor virus (MTV)-induced antigens or antigen complexes MLm and MLr were studied in mouse mammary gland cells, mammary tumor cells, and other cell types, by use of ascites leukemia cells of the GR mouse strain as target cells in the cytotoxicity test. The Thy 1.2 antigen was detected by an AKR antiserum to C3Hf thymocytes. MLm was shown by a homologous C57BL antiserum to GRSL2 leukemia (absorbed in vivo in GR mice); MLr was detected by a rabbit heterologous antiserum (absorbed in vivo in C57BL or GR mice and in vitro with BALB/c milk) prepared against Tween 80- and ether-treated purified B particles. Sera from Sprague-Dawley rats bearing murine leukemia virus (MuLV)-producing syngeneic tumors were not cytotoxic or only slightly cytotoxic for GR leukemias transplanted in vivo, which indicated that MuLV-induced antigens were absent or present in very low quantity in such leukemias. The MLr and MLn antigens or antigen complexes were possibly identical to the mammary leukemia (ML) antigen, since they could be detected not only on GR but also on DBA/2 leukemia cells and since their distribution was exactly the same as that of MTV. Both the MLr and MLm antigens were present in purified B particles, and antigenic activity were present in purified B particles, and antigenic activity was enhanced by destruction of the purified virus particles. The antigens were about eightfold enriched in a preparation of B-particle envelopes, as shown by quantitative cytotoxicity absorption (CYTA) tests. Purified nucleoid fractions of B particles were only lightly positive for the antigen, probably due to envelope contamination. One dominant gene was responsible for the expression of MLr, as shown by CYTA tests with mammary glands of individual animals of segregating crosses between the GR strain with high mammary cancer incidence and strains with low incidence. This gene was closely linked with or was possibly identical to 1) the gene for cytoplasmic MTV gs antigen expression as seen by fixed cell immunofluorescence, and 2) the gene causing mammary tumors in the GR mouse strain.

Distribution and antibody-induced redistribution of a mammary tumor virus-induced and a normal antigen on the surface of mouse leukemia cells.

By means of the indirect membrane immunofluorescence test, the distribution and antibody-induced redistribution (patching and capping) of a mammary tumor virus-induced (MLr) and a normal (Thy 1.2) cell-surface antigen were compared on mouse thymocytes and leukemia cells (GRSL2). At 0 degrees C Thy 1.2 fluorescence was ringlike and more intense on GRSL2 cells than on thymocytes, whereas MLr fluorescence on GRLS2 cells at this temperature was patchlike and brighter than Thy 1.2 fluorescence. At 20 or 37 degrees C, capping of Thy 1.2 on both cell types was readily achieved but MLr capping occurred only in a few GRSL2 cells and was less pronounced. However, after addition of the secondary antibodies, MLr capping was markedly increased by gradual cooling of cells to about 17 degrees C. Conversely, after addition of antibodies at 0 degrees C, gradual warming of cells under the fluorescence microscope resulted in extensive capping both of MLr and Thy 1.2 at approximately 13-14 degrees C. Rapid cooling or rapid warming led to almost instantaneous capping. These results may be explained by the occurrence of phase transitions or phase separations in the particular temperature range. Another difference between capping of Thy 1.2 and MLr was that the former caps were small and eventually were endocytosed, whereas the MLr caps were large and were exfoliated from the cells.

Antineutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in a patient with anti-glomerular basement membrane disease.

An unusual case is described of a patient with both anti-glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity (MPO-ANCA) presenting with acute renal failure. Four years before a seronegative arthritis of the left wrist was diagnosed. Tests for ANCA by indirect immunofluorescence were repeatedly negative. The diagnosis was made by renal biopsy and by testing the serum with specific enzyme-linked immunosorbent assays (ELISA) for MPO-ANCA and anti-GBM antibodies. To our knowledge, this is the first patient presenting with such findings in the Dutch literature.

Cognitive-behavioural therapies and exercise programmes for patients with fibromyalgia: state of the art and future directions.

This review provides an overview of the effects of non-pharmacological treatments for patients with fibromyalgia (FM), including cognitive-behavioural therapy, exercise training programmes, or a combination of the two. After summarising and discussing preliminary evidence of the rationale of non-pharmacological treatment in patients with FM, we reviewed randomised, controlled trials for possible predictors of the success of treatment such as patient and treatment characteristics. In spite of support for their suitability in FM, the effects of non-pharmacological interventions are limited and positive outcomes largely disappear in the long term. However, within the various populations with FM, treatment outcomes showed considerable individual variations. In particular, specific subgroups of patients characterised by relatively high levels of psychological distress seem to benefit most from non-pharmacological interventions. Preliminary evidence of retrospective treatment analyses suggests that the efficacy may be enhanced by offering tailored treatment approaches at an early stage to patients who are at risk of developing chronic physical and psychological impairments.

Atrioventricular conduction disturbance as an early feature of Reiter's syndrome.

Atrioventricular (A-V) conduction disturbances in Reiter's syndrome are usually described in longstanding disease. This report deals with two male patients with Reiter's syndrome who developed an A-V block early in the course of the disease. One of these patients developed a second degree A-V block, Wenckebach type, which has not been described before at an early stage of this syndrome.

Lack of activation of C1, despite circulating immune complexes detected by two C1q methods, in patients with rheumatoid arthritis.

The activation of C1 by circulating immune complexes in patients with rheumatoid arthritis was investigated. C1rC1s(C1-In)2 complexes in EDTA-plasma, reflecting C1 activation in vivo, were slightly raised in 35 of 57 patients with rheumatoid arthritis, though most patients had elevated levels of circulating immune complexes as measured with either the 125I-C1q binding test or the C1q solid phase assay. The activation of C1 by circulating immune complexes in vitro was investigated by measuring the generation of C1rC1s(C1-In)2 complexes during 60 minutes at 37 degrees C in diluted recalcified EDTA-plasma. In 16 of the 57 patients, a slightly increased C1 activation in vitro was observed. These patients tended to have high levels of circulating immune complexes. However, the majority of the patients with high levels of circulating immune complexes showed a normal C1 activation in vitro. Therefore, it was concluded that measurement of circulating immune complexes by either of the two C1q methods in patients with rheumatoid arthritis does not imply that these circulating immune complexes are able to activate C1.

Familial hypokalemia/hypomagnesemia and chondrocalcinosis.

OBJECTIVE: Familial occurrence of Bartter's syndrome is well known, but the simultaneous occurrence of hypokalemia/hypomagnesemia and chondrocalcinosis in one family has not been described. We present the clinical, laboratory and radiological findings of a family, in which 7 members were affected by disease. METHODS: A total of 43 members of the family could be interviewed concerning their general health, past diseases and joint complaints. Serum potassium and magnesium were determined in all and radiographic studies were performed in those who had hypokalemia and hypomagnesemia or those with merely articular complaints. Urinary excretion of potassium, magnesium and calcium were determined in the affected persons. RESULTS: Seven patients were found with hypokalemia and hypomagnesemia. Urinary potassium and magnesium excretion was inappropriately high when compared to the serum levels of these electrolytes. All patients had hypocalciuria and extensive chondrocalcinosis, mainly in the knees, elbows and shoulders. In one patient, most probably as a result of magnesium supplementation, a striking reduction of chondrocalcinosis was observed during a followup of 10 years. CONCLUSION: A family with familial hypokalemia/hypomagnesemia and chondrocalcinosis is described. The reduction of chondrocalcinosis, after years of magnesium supplementation in one patient, suggests that hypomagnesemia is an important factor in the pathogenesis of chondrocalcinosis in these patients.

Methotrexate versus azathioprine in the treatment of rheumatoid arthritis. A forty-eight-week randomized, double-blind trial.

We conducted a double-blind, randomized trial comparing azathioprine (AZA) and methotrexate (MTX) in the treatment of patients with rheumatoid arthritis in whom parenteral gold and/or D-penicillamine treatment had been unsuccessful. Patients were randomly assigned to receive either AZA (100 mg daily) or oral MTX (7.5 mg weekly). After 8 weeks, the dosage was increased depending on the clinical improvement. Sixty-four patients were followed up for 48 weeks (33 AZA, 31 MTX). Comparison of values at week 24 with baseline values revealed significant improvement in 12 of 13 disease variables in the MTX group and in 6 of 13 in the AZA group. Comparison between the 2 treatment groups at 24 weeks, by area-under-the-curve analysis, showed significantly more improvement in the MTX group in terms of the swollen joint count, pain score, erythrocyte sedimentation rate, C-reactive protein level, hemoglobin level, thrombocyte level, and disease activity score. A significant overall clinical improvement (disease activity score) was found in 7 of 20 patients treated with AZA and 18 of 30 patients treated with MTX after 24 weeks of therapy, and in 6 of 12 AZA-treated patients and 19 of 25 MTX-treated patients after 48 weeks. The number of withdrawals due to side effects was significantly higher in the AZA group. After 48 weeks, only 12 patients from the AZA group (36%), but 25 from the MTX group (81%), were still using the initial drug. These results demonstrate MTX to be superior to AZA in the treatment of rheumatoid arthritis, with a more rapid clinical improvement which is sustained after 1 year, accompanied by a lower rate of serious adverse reactions.