Transcapillary fluid balance consequences of missing initial lymphatics studied in a mouse model of primary lymphoedema

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 (COP_if) 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.     

Time trends and occupational risk factors for pleural mesothelioma in Sweden.

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.     

An epitope shared by central nervous system myelin and peripheral blood macrophages

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.     

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.     

Alignment of 3-dimensional cardiac structures in O-15-labeled water PET emission images with mutual information.

BACKGROUND: The aim of this study was to develop a method to correct the heart position between two oxygen 15-labeled water cardiac positron emission tomography (PET) image sets to be able to use the equivalent regions of interest for the quantification of the perfusion values in the same myocardial segments. METHODS AND RESULTS: Independent component analysis was applied to the dynamic image sets (simulated phantom and 6 rest-pharmacologic stress and 10 rest-rest image sets of healthy female volunteers) acquired at different time points to separate the cardiac structures (ventricles and myocardium). The separated component images from independent component analysis from the 2 studies of the same individual were aligned with a normalized mutual information-based registration method. The alignment parameters were applied to position the regions of interest in the floating image sets for calculation of the myocardial blood flow values. In the rest case the mean myocardial blood flow value was 0.76 +/- 0.12 mL x g(-1) x min(-1) for the manual method and 0.79 +/- 0.10 mL x g(-1) x min(-1) for the proposed method (by use of the right ventricle component in the alignment), and in the stress case these values were 3.39 +/- 0.70 mL x g(-1) x min(-1) and 4.01 +/- 0.71 mL x g(-1) x min(-1), respectively. No statistically significant difference was found between the methods. CONCLUSION: In the tests with the phantom and patient images the alignment of cardiac structures was shown to be successful. The alignment could be done without the use of information from the myocardial compartment.     

Fracture repair during external fixation: Torsion tests of rabbit osteotomies

Bone repair was studied in the rabbit tibiofibular bone after a midshaft transverse osteotomy stabilized by external fixation and heavy compression. Both subendosteal and subperiosteal callus formation with concomitant contact healing were observed within 3 weeks, and were further succeeded by subendosteal resorption and increased porosis resulting in atrophy of the cortical bone. Subjected to the torsion test, the bones exhibited restoration of strength within 3 weeks, with maximal energy absorption and elasticity at 6 weeks. The failure of the osteotomy in the torsion test, with radiographic visibility of the osteotomy, characterized the soft-tissue type of behavior of the bones. Hard-tissue like behaviour of the bones with resistance to torsion at the osteotomy site and radiographic obliteration of the osteotomy line occurred by 12 weeks, indicating complete union of the osteotomy. Our experiments demonstrate that elastic external fixation is preferable to the rigid compression plate.