We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 29 patients with relapsing-remitting multiple sclerosis every 4 weeks over a period of 12 months. During this period 27 relapses occurred in 14 patients (48%). Progression of disease activity as assessed by the occurrence of new lesions on nonenhancing T2-weighted magnetic resonance images of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative polymerase chain reaction we demonstrated significant increases in tumor necrosis factor-alpha mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor-alpha mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor-beta and interleukin-10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor-alpha were also observed in 6 patients with stable disease who had active magnetic resonance scans on follow-up. No correlation of disease activity was observed with interleukin-1 beta, -4, or -6, inferferon gamma or endothelin-1 mRNA expression. From these data it can be concluded that variations in cytokine mRNA expression in blood mononuclear cells are correlated with disease activity in relapsing-remitting multiple sclerosis. It may be a valuable parameter to monitor the immunological status of patients in future clinical trials.
We determined the serum levels for circulating adhesion molecules (circulating intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with relapsing-remitting MS serially over a period of 12 months. During this period there were 27 relapses in 14 patients (48%). There was progression of disease activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on nonenhancing, T2-weighted MRIs of the head. Clinically active patients with relapse or disease progression on MRI (n = 18) had frequent fluctuations in their serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There were significant differences in the cumulative cICAM-1 production between the two groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p < 0.005). A significant increase in cICAM-1 levels was present at the time of a relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were significantly higher than in healthy donors, whereas there were no differences for cELAM-1. These results reflect distinct changes of inflammatory variables in serum of patients with MS and revealed that cICAM-1 is an indicator for disease activity and that high serum levels for cTNF-R p60 are associated with remission.
Summary:Between February 1998 and October 1999, 24 patients with advanced leukemia, lymphoma or solid tumors received G-CSF mobilized peripheral blood stem cells (PBSC) from HLA-matched sibling donors after dosereduced conditioning therapy. Only patients with reduced performance status or major infectious complications, not eligible for standard transplant procedures, were included. The 5-day conditioning therapy consisted of 3.3 mg/kg intravenous busulphan × 2 days and 30 mg/m 2 fludarabine × 5 days. GVHD prophylaxis was performed with either CsA alone (n = 5), CsA combined with short course methotrexate (n = 5) or mycophenolate mofetil (n = 14). The day 100 survival was 95.2% for the whole group. All patients engrafted after a median of 15 days (range, 11-19) and 12.5 days (range, 10-19) for neutrophils and platelets, respectively. The median time to a neutrophil count of Ͻ0.5 × 10 9 /l was 7 days (range, 2 to 12). Acute GVHD ϾI was observed in six patients, whereas eight patients have signs of chronic GVHD. The prospective 12 month overall survival with a median follow-up of 7 months is 63%. Relapse of disease and toxicity associated with chronic GVHD were the main causes of death. The treatment-related mortality was 12.5%. Dose-reduced conditioning using intravenous busulphan and fludarabine allows stable engraftment without ATG in related transplants and leads to a reduction of transplant-related mortality. Bone Marrow Transplantation (2000) 26, 119-125.
71 women, 64 post-menopausal, were examined by single-energy quantitative computed tomography (SEQCT) and by high-resolution computed tomography (HRCT) scans through the middle of lumbar vertebral bodies. Computer-assisted image analysis of the high-resolution images assessed trabecular morphometry of the vertebral spongiosa texture. Texture parameters differed in women with and without age-reduced bone density, and in the former group also in patients with and without vertebral fractures. Discriminating parameters were the total number, diameter and variance of trabecular and intertrabecular spaces as well as the trabecular surface (p < 0.05)). A texture index based on these statistically selected morphometric parameters identified a subgroup of patients suffering from fractures due to abnormal spongiosal architecture but with a bone mineral content not indicative for increased fracture risk. The combination of osteodensitometric and trabecular morphometry improves the diagnosis of osteoporosis and may contribute to the prediction of individual fracture risk.
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