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Biomedical subjects

D Kuntz

Publications and source records attributed to D Kuntz.

At least 19 recordsLinked to original sources

Dialysis arthropathy: outcome after renal transplantation.

PURPOSE: Patients treated by long-term maintenance hemodialysis frequently develop a form of chronic arthropathy that is strongly associated with beta 2-microglobulin amyloid deposition and related, at least in part, to beta 2-microglobulin retention. Successful renal transplantation is followed by a rapid fall in serum beta 2-microglobulin levels and might allow dissolution of amyloid deposits. The purpose of this work was to investigate the effects of renal transplantation on dialysis arthropathy. PATIENTS AND METHODS: Fourteen renal transplant recipients were selected on the basis of previous hemodialysis treatment for at least 10 years (mean 16) and a history of chronic joint pain prior to transplantation. They all received 10 to 17.5 mg/d of prednisone. Posttransplant rheumatologic manifestations were studied prospectively and compared to pretransplant rheumatologic manifestations recorded in medical charts and reported during patient interviews. Pretransplant and posttransplant articular roentgenograms were separately analyzed by three observers who were blinded to timing of the films. Beta 2-microglobulin amyloid was identified by Congo red staining and immunohistology. RESULTS: After a mean posttransplant interval of 54 months (range 12 to 121), the articular condition was improved in 10 patients, unchanged in 1, and worsened in 3, according to patients' assessments. The number of painful joints decreased significantly (P < 0.05) as compared to the pretransplant period. However, the number and size of subchondral bone erosions remained unchanged, destructive arthropathies generally worsened, and articular beta 2-microglobulin amyloid deposits were identified in 2 patients, 2 and 10 years after renal transplantation, respectively. CONCLUSION: Renal transplantation appeared to arrest progression of beta 2-microglobulin amyloid in dialysis patients, but it neither led to dissolution of deposits nor prevented progression of destructive arthropathies. Most articular symptoms were improved, probably as a result of corticosteroid therapy.

Adult

Methotrexate related B lymphoproliferative disease in a patient with rheumatoid arthritis. Role of Epstein-Barr virus infection.

A 57-year-old woman receiving low dose methotrexate (MTX) for rheumatoid arthritis (RA) developed a B lymphoproliferative disease (LPD) that was initially considered as large cell non-Hodgkin's lymphoma of B cell phenotype. Epstein-Barr virus (EBV) cytotoxic latent membrane protein-1 (LMP-1) expression was found in some large cells. The lymphoproliferative disease reversed with MTX discontinuation and without chemotherapy. These EBV-associated LPD in patients with RA receiving MTX or other immunosuppressive agents seem to be similar to those triggered by EBV in transplant patients receiving cyclosporine A. MTX withdrawal and short followup should be considered before chemotherapy since spontaneous regression is possible.

Arthritis, Rheumatoid

Bioavailability of fluoride in postmenopausal women: comparative study between sodium fluoride and disodium monofluorophosphate-calcium carbonate.

Fluoride (F) increases trabecular bone mass and can be used in the treatment of osteoporosis with crush fractures. As the bioavailability of sodium fluoride (NaF) can be impaired by concomitant absorption of calcium, both drugs have to be ingested separately. However, disodium monofluorophosphate-calcium carbonate (MFP-Ca), another F compound, allows a single administration. In a cross-over randomized study, we compared the bioavailability of both drugs under regular conditions of prescription. Ten postmenopausal women (aged 48-77 years) with glomerular filtration rate (GFR) greater than 70 ml/minute and without bone disease entered the study. Each received 25 mg of NaF [i.e., 11.3 mg F ion (F-)] fasting and 100 mg of Na2FPO3-1250 mg CaCO3 (i.e., 13.2 mg F-) with breakfast in a single dose separated by an 8-day washout. After dosing, plasma F levels and fractionated and total urinary F collection were determined during a 24-hour period using a specific electrode. Results show a significant shorter lag time absorption (Tmax = 1.4 +/- 0.2 hour) and a higher maximal concentration (Cmax = 260 +/- 60 ng/ml) for MFP-Ca than for NaF (Tmax = 2.5 +/- 0.4 hour; Cmax = 200 +/- 85 ng/ml). However, areas under curve (AUC) for MFP-Ca (1711 +/- 195 micrograms/liter/hour) and for NaF (1202 +/- 147 micrograms/liter/hour) were not significantly different. The relative bioavailability of both F compounds related to their fluoride content (i.e., 1.22 for AUC ratio) was equivalent, according to the Westlake method. These data provide the first evidence of comparable bioavailability of two F compounds in a population of postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Long-term survival and prognostic factors in stage II-III multiple myeloma treated with conventional chemotherapy].

In this retrospective study, survival and prognostic factors were analysed in 65 patients with stage II-III multiple myeloma with osteolytic lesions. Multiple myeloma was diagnosed from 1976 to 1984, and patients were treated with conventional chemotherapy. The response rate to initial chemotherapy was 46%. The median survival time was 31 months. The 10-year survival rate was 10%. Four variables were individually prognostic: response to initial chemotherapy, bone marrow plasma cell percentage, the Durie and Salmon staging system, a biological staging system derived from Durie and Salmon's biological criteria regardless of bone lesions. In the multivariate analysis, only two prognostic variables were retained, namely the response to chemotherapy and the biological staging system. No prognostic value was observed for the extent of osteolytic lesions. This study suggests that, in conventionally treated multiple myeloma, long-term survival has improved compared with the previous decade. It also indicates that the extent of osteolytic lesions has little value for the definition of high-risk myeloma.

Adult

[Therapeutic maintenance and tolerance of sulfasalazine in rheumatoid polyarthritis. Retrospective study of 95 patients].

This retrospective study evaluated treatment with sulfasalazine (SAS) in a mean dosage of 2.1 g/day in 95 patients with rheumatoid arthritis (RA) who were followed-up for 3 months to 4 years. Mean disease duration was 7 years; 79 patients had previously received at least one disease-modifying drug. Four per cent of patients were lost to follow-up. Mean duration of treatment was 15 months (3 weeks-50 months). Treatment continuation rates were 57% at one year, 40% at two years, and 26% at three years. Reasons for discontinuation of SAS included adverse effects (n = 24), inefficacy (n = 33), and death unrelated to SAS therapy (n = 2). In four patients, SAS was discontinued within three months of the first dose because of a severe adverse effect (diffuse erythematous rash, diffuse bullous rash, hepatitis with jaundice, agranulocytosis). SAS-induced biologic markers for lupus were seen in one patient. Furthermore, 12% of evaluable patients developed antinuclear antibodies during SAS therapy. The SAS treatment continuation rate was higher (p = 0.05) among patients under 40 years of age (n = 18) than among older patients. This difference was due to a correlation between age and tolerance with less SAS-induced side effects in patients under 40 years of age (p = 0.03). The SAS treatment continuation rate was unrelated to the duration of rheumatoid arthritis or number of previous maintenance treatments. This study suggests that rheumatoid arthritis patients under 40 years of age exhibit better tolerance to SAS therapy.

Adolescent

[Bone demineralization and cytokines].

Cytokines are secreted by several cell types in the bone microenvironment. These peptides act on bone cells by a paracrine or autocrine mechanism and play an important role, although not completely clarified, in the regulation of bone remodeling. Postmenopausal osteoporosis could be due to a local overproduction of some osteoclast-stimulating cytokines in response to estrogen deficiency. During chronic inflammatory joint diseases, such as rheumatoid arthritis, synovial cells produce large amounts of cytokines leading to increased local bone resorption and juxta-articular bone destructions. The local action of cytokines is also involved for interactions between tumoral cells and bone cells. These are secreted by the tumoral (metastatic or hemopoietic) cells, bone marrow cells, bone cells, or even could be released from the bone matrix during bone resorption. Recent progress in our knowledge in the field of cytokines have improved the understanding of the pathogenesis of these diseases and let hope future promising developments for more specific treatments.

Arthritis, Rheumatoid

Inhibition of human endothelial cell growth by human monocytes in coculture.

Previous studies conducted in different experimental models have shown that human monocytes (Mo) possess both stimulating and inhibiting factors for endothelial cell growth. Since Mo are frequently found in the vicinity of endothelial cells, we examined the direct effect of human peripheral blood Mo on the proliferation of human umbilical vein endothelial cells (HEC) in in vitro culture systems. Mo obtained either by counter centrifugation elutriation or by selective adhesion on gelatin-autologous plasma or purified fibronectin coated plastic surfaces inhibited HEC growth as determined by HEC count or 3H-methyl thymidine incorporation. This growth inhibitory effect was dependent on the number of monocytes: 50% inhibition of 3H-thymidine uptake by HEC was achieved for a Mo-EC ratio of 1:4. Mo isolation by selective adhesion on gelatin-plasma resulted in a significantly higher inhibitory effect (p less than 0.02) than that observed with Mo isolated on fibronectin coated surfaces or by elutriation techniques, suggesting a possible stimulation of Mo by contact with gelatin-plasma. Endothelial cell growth factor plus heparin did not reverse this inhibition of HEC growth. Results obtained in diffusion chamber and coculture systems showed that soluble products of Mo origin can inhibit HEC proliferation but the inhibition was greater when Mo and HEC were in contact. The effect was not due to cytotoxicity as evaluated by cell counting and 51Chromium release from HEC. These in vitro results suggest that normal monocytes could exert a regulatory role on the proliferation of endothelial cells.

Animals

[Age at the onset and incidence of chronic pain in knee osteoarthrosis].

The incidence and age of onset of daily knee pain for more than 3 months each year were determined in the various topographical varieties of knee osteoarthrosis (404 knees, 258 patients: 195 women and 63 men). Statistical calculation revealed no significant difference between the incidence of forms without chronic pain in the various topographical types of knee osteoarthrosis. In women, the mean age of onset of chronic pain in lateral femoro-patellar osteoarthrosis was 56.6 +/- 12, in medial femora-tibial osteoarthrosis was 62.7 +/- 12, in the combination of the two 65.2 +/- 10 and in lateral femoro-tibial osteoarthrosis was 69.2 +/- 10. In men, this age in lateral femoro-patellar osteoarthrosis was 60.5 +/- 10 and in medial femoro-tibial osteoarthrosis was 64 +/- 10. Thus lateral femoro-patellar osteoarthrosis caused chronic pain an average of 5 years before medial femoro-tibial osteoarthrosis, and the latter an average of 7 years before lateral femoro-tibial osteoarthrosis.

Age Factors

[Treatment of common osteoporosis with fluoride: current trends].

The pharmacology of fluoride is reviewed. Efficacy criteria of sodium fluoride in osteoporosis are analysed. An increase in bone mass of the order of 8 per cent per year is seen in 60-70 per cent of osteoporotics whether evaluated by histomorphometry or by bone densitometry in double-blind controlled trials. Fluoride has no effect on bone mass in 30 to 40 per cent of osteoporotics. The reason(s) for such resistance is/are not fully understood. It is not possible at present to state that there is a decrease in the incidence of vertebral fractures on the basis of data from double-blind trials. The incidence of bone fissures affecting the bones of the lower limbs is significantly increased in osteoporotics treated with fluoride, above all if doses of elemental fluoride are greater than 25 mg or in the presence of unrecognised renal insufficiency. The incidence of these fissures is of the order of 20 to 30 per cent.

Fluorides

Bone mastocytosis. A report of nine cases with a bone histomorphometric study.

Bone mastocytosis is characterized radiographically in some patients by diffuse osteosclerosis and in others by demineralization. The reason for these apparently conflicting bone features is unknown. Bone remodeling and marrow mastocytosis infiltration were studied in nine cases of mastocytosis with bone marrow involvement. Six men, ranging from 42 to 78 years of age, and three women, 43, 55, and 73 years old, comprised the series. Two patients had severe and diffuse osteosclerosis. Seven had diffuse demineralization, with crushed vertebrae in four, suggesting common osteoporosis. In three of the seven, cutaneous mastocytosis was absent. Bone biopsies were undecalcified and stained with toluidine blue. In the seven patients with demineralization, the number of marrow mastocytes was increased (154 +/- 24 versus 2 +/- 0.5/mm2 in normal postmenopausal osteoporosis). Mastocyte nodules covering 1-9% of the marrow area were present in all seven patients. These patients showed a significant increase in remodeling; bone formation rate was increased, coupled with a decrease in mean wall thickness. Concomitantly, osteoclast surfaces were increased, with an increased amount of bone resorbed. The two patients with diffuse osteosclerosis had a markedly different histology; mast cell infiltration was dramatically increased (mastocyte count greater than 1000/mm2) with diffuse marrow fibrosis. Bone volume was increased as well, and most of the bone was woven with an intratrabecular mineralization defect. High bone remodeling and decreased osteoblast activity can explain bone loss in mastocytosis with demineralization. Mastocytosis with osteosclerosis is characterized by a more extensive marrow mast-cell infiltration and fibrosis.

Adult