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.     

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.     

Effects of malaoxon on phosphatidylinositol signaling in convulsing and non-convulsing non-pregnant and pregnant female rats and their offspring.

Phosphatidylinositol (PI) signaling during organophosphate (OP) induced convulsions and tissue Ca2+ changes in 10 weeks old male, and 14 weeks old non-pregnant and pregnant female rats, and the offspring of the latter were explored. Brain inositol and inositol-1-phosphate (Ins1P) served as indices of alterations in brain PI signaling, and brain tissue Ca2+ as an index of early neuronal injury. A dose of malaoxon OP, which produced convulsions in about 60% of the exposed rats in different rat groups, was 39.2 for male, and 8.2 mg/kg for pregnant female rats, respectively. Malaoxon (8.2 mg/kg) did not produce convulsions in non-pregnant female rats. All the rats were followed for 1 or 4 hr subsequent to malaoxon. Malaoxon decreased cerebral inositol in both male and female rats, and the decrease was similar in spite of the dose difference. The decrease was larger in the convulsing than in the non-convulsing rats. A tendency towards a decrease of brain inositol also occurred in the offspring. Ins1P levels were markedly increased in male, and also in non-pregnant female rats, but not in the brains of pregnant female rats. Ins1P was not markedly changed in the brains of the offspring. Malaoxon elevated brain tissue Ca2+ in male but not in female rats or their offspring. Cholinergic systems and PI signaling in the brain seem to be associated with OP-induced convulsions both in male and female rats; females seem to be more sensitive than males. Malaoxon may also have slightly modified PI signaling in the offspring brain. Hormonal factors are likely to modify OP CNS toxicity and cholinergic stimulation of brain PI signaling.