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We thank Geluk and Zijlstra for their kind words as well astheir considerations and proposals. The latter hits right intothe heart of the issue: should one stick to the ‘anatomic’paradigm urging us to detect and treat coronary stenoses andcalcifications rather than follow  相似文献   
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To investigate the phenotypic consequences of a deranged lymphangiogenesis in relation to tissue fluid accumulation and the possible role of inflammation in the pathogenesis of lymphoedema, we measured determinants of transcapillary fluid filtration and inflammatory mediators in the interstitial fluid in genetically engineered Chy mice, a model for primary congenital lymphoedema (Milroy's disease). Although initial lymphatics were not present in dermis in any of the areas studied (fore paw, hind paw, thigh and back skin) interstitial fluid pressure ( P if), measured with micropipettes, and tissue fluid volumes were significantly increased only in the areas with visible swelling – the fore and hind paw, whereas interstitial colloid osmotic pressure (COPif) was increased in all the skin areas examined. A volume load of 15% of body weight resulted in a more pronounced increase in P if as well as a four-fold increase in interstitial fluid volume in Chy relative to wild-type (wt) mice, showing the quantitative importance of lymphatics for fluid homeostasis during acute perturbations. A similar level of proinflammatory markers in interstitial fluid in early established lymphoedema (3–4 months) in Chy and wt suggests that inflammation does not have a major pathogenetic role for the development of lymphoedema, whereas a reduced level of the immunomodulatory cytokine interleukin (IL)-4 may result in a reduced immunological defence ability and thus lead to the increase in inflammatory cytokines IL-2 and IL-6 observed at a later stage (11–13 months). Our data suggest that primary lymphoedema results in a high interstitial fluid protein concentration that does not induce an interstitial inflammatory reaction per se , and furthermore shows the paramount importance of the initial lymphatics in tissue fluid homeostasis, especially during perturbations of transcapillary fluid balance.  相似文献   
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Epidemiologic data on pleural mesothelioma are scarce on regional and occupational time trends, which would monitor the effects of changes in exposure to asbestos. We aim to characterize time trends, regional, socioeconomic, and occupational risk factors for pleural mesothelioma in Sweden in the years from 1961 to 1998. The Swedish Family-Cancer Database was used to identify patients with pleural mesothelioma. Age-standardized incidence rates and standardized incidence ratio (SIR) were calculated for the population in the Database. A total of 1298 male and 233 female pleural mesotheliomas were retrieved. Age-standardized incidence of the disease was highest, and the trend increased in residents of large industrial and shipbuilding cities. In the last follow-up period, the male rate exceeded the female rate about 10-fold. Among male socioeconomic groups, manual workers showed the highest and ever-increasing SIR. No female socioeconomic group was at risk. For men, plumbers and seamen had the highest risk of 4.56 and 2.83, respectively, but the risks appeared to be decreasing for plumbers, whereas no clear trend was noted for seamen, probably because of indirect expose in ships. Farmers showed an SIR of 0.28, indicating that the population at large was at four times higher risk than farmers. The SIRs of many academic/college-educated groups were two to six times higher than those of farmers, suggesting indirect exposure to asbestos in these groups.  相似文献   
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Lewis rats were immunized with a homogenate of human spinal cord. Splenocytes from the immunized rats were fused with cells from the SP2/0-Ag14 cell line to form hybrids that were subsequently screened immunohistochemically for secretion of antibodies against myelin. Thirty hybrids secreting anti-myelin antibodies were cloned. One secreted antibody (774) that immunohistochemically stained central nervous system (CNS) myelin but not peripheral nervous system (PNS) myelin also bound to the surface of peripheral blood macrophages. Hence we have identified an epitope that is shared by peripheral blood macrophages and CNS myelin.  相似文献   
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Bone turnover before and after withdrawal of estrogen/gestagen treatment was studied in a randomized trial with 110 healthy female volunteers, who had passed a natural menopause 6 months to 3 years before the start of the study. Urinary excretion of intravenously injected 99m-technetium diphosphonate was measured as an index of bone turnover; plasma bone Gla protein and serum alkaline phosphatase were measured as indices of bone formation; and fasting urinary excretion of hydroxyproline and calcium were measured as estimates of bone resorption. During 2 years of hormone treatment, all variables decreased highly significantly (p less than 0.001) to a constant low level. Three months after withdrawal all variables increased highly significantly (p less than 0.001) towards, but not above, pretreatment and placebo levels. We conclude that withdrawal of estrogen/gestagen replacement therapy in postmenopausal women increases bone turnover, but not in excess of pretreatment values. This indicates that bone loss (after withdrawal) is similar to that seen in the placebo group and that a rebound phenomenon is unlikely.  相似文献   
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Background Chromium allergy has traditionally been caused by occupational skin contact with cement. In 1983, Danish legislation made the addition of ferrous sulphate compulsory in cement to reduce the water‐soluble chromium content to not more than 2 ppm. An effect from this intervention has previously been demonstrated among Danish construction workers. Objectives To investigate the development of chromium allergy among patients with dermatitis tested between 1985 and 2007 in Denmark. Furthermore, to determine causative exposures in patients with chromium allergy. Patients and methods A retrospective analysis of patch test data was performed (n = 16 228) and charts from patients with chromium allergy were reviewed. Comparisons were made using a χ2 test. Logistic regression analyses were used to test for associations. Results The prevalence of chromium allergy decreased significantly from 3·6% in 1985 to 1% in 1995 (Ptrend < 0·001) but increased to 3·3% in 2007 (Ptrend < 0·001). The frequency of clinically relevant cement exposure decreased significantly among patients with chromium allergy from 12·7% in 1989–1994 to 3·0% (P < 0·01) in 1995–2007, whereas the frequency of relevant leather exposure increased significantly from 24·1% during 1989–1994 to 45·5% during 1995–2007 (P < 0·02). Conclusions Chromium allergy is currently increasing in Denmark due to leather exposure.  相似文献   
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