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- Dahlberg, L., et al.
(författare)
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Cartilage metabolism in the injured and uninjured knee of the same patient
- 1994
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967. ; 53:12, s. 823-827
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-l, and tissue inhibitor of metalloproteinases-l (TIMP-1) in the contralateral uninjured knee. Methods-Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-l, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. Results-Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-l and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-l increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations ofall markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. Conclusions-The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 'exchange' of molecular markers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury.
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| 2. |
- Sigurdsson, H, et al.
(författare)
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Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels
- 1990
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Ingår i: British Journal of Cancer. - 1532-1827. ; 62:5, s. 786-790
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Tidskriftsartikel (refereegranskat)abstract
- The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
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| 3. |
- Sigurdsson, H, et al.
(författare)
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Indicators of prognosis in node-negative breast cancer
- 1990
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
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Tidskriftsartikel (refereegranskat)abstract
- Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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