Our results suggest that tumor cell spillage and less frequently hematogenous dissemination may be associated with operative manipulation of the prostate during radical retropubic prostatectomy and may potentially represent mechanisms of failure after radical retropubic prostatectomy.
Objectives To investigate the relation between anatomic changes of the synovium, the bone, the bone marrow and the cartilage to biochemical properties of the cartilage in patients with rheumatoid arthritis (RA). Methods 33 patients with RA received 3-T MRI scans of the metacarpophalangeal joints. Two independent methods, (A) the delayed gadolinium enhanced MRI of the cartilage (dGEMRIC, T2-mapping), which was used to assess the biochemical properties of the cartilage; (B) synovitis, osteitis and bone erosions were quantified according to the RA MRI scoring (RAMRIS) method and cartilage thickness (CT), interbone joint space (IBJS, distance between proximal and distal bone surface) and intercartilage joint space (ICJS, distance between proximal and distal cartilage surface) were measured. Results Biochemical changes of the cartilage, corresponding to low dGEMRIC and high T2 values, were more likely to be seen in joints with decreased IBJS and ICJS as well as decreased CT. For instance, dGEMRIC was directly correlated to the IBJS ( p=0.001) and ICJS ( p=0.001), whereas T2 mapping was inversely correlated to IBJS and ICJS (both p=0.017). Moreover, the degree of osteitis, and to some extent synovitis, was correlated to biochemical cartilage changes as measured by dGEMRIC ( p=0.003) or the T2 mapping ( p=0.013). By contrast, bone erosions did not correlate to the degree of biochemical cartilage changes. Discussion These data support the concept that synovitis and osteitis may be two main triggers for cartilage damage. Thus, the actual inflammatory state of a joint, but not so much the degree of bone erosion, appears to influence cartilage properties in RA.
Arylsulfatase A (ASA) is found to be deficient in healthy individuals (pseudo arylsulfatase A deficiency) who usually show in vitro ASA levels in the range of metachromatic leukodystrophy patients. The in vitro properties of ASA in pseudodeficiency were studied in cultured fibroblasts. The residual ASA activity showed apparent Km with the synthetic substrate (2.6 mM), pH optimum of activity (pH 5.0), and sensitivity to heat denaturation at 65 degrees C (T1/2, 10 min) similar to those found in controls. To test whether the low in vitro activity is a result of extreme sensitivity to the homogenization procedure, cells were disrupted by five different techniques, including rapid freezing and thawing, hand homogenization, ultrasonication, mild osmotic shock, and nitrogen cavitation; all yielded similar ASA ratio of the pseudodeficient to control. The use of antiproteases phenylmethylsulfonyl fluoride and leupeptin did not affect the residual ASA activity in the pseudodeficient line. These results imply that the ASA that is formed in this condition has properties similar to those of the normal hydrolase, so that even if it is synthesized in lower amounts, it is still sufficient to promote normal catabolism of sulfatide. Screening for ASA activity in lymphocyte extracts of a random sample of 250 individuals revealed 7 individuals with enzyme level in the MLD heterozygote range or lower. These individuals apparently represent homozygosity for pseudodeficiency (pd/pd). This implies that the frequency of the pseudodeficient allele is about 15% in the general population, leading to polymorphism of the ASA.
Our results suggest that tumor cell spillage and less frequently hematogenous dissemination may be associated with operative manipulation of the prostate during radical retropubic prostatectomy and may potentially represent mechanisms of failure after radical retropubic prostatectomy.
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