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.     

Quantification of refractive error: comparison of autorefractor and focometer.

PURPOSE: The advantages of a focometer (FOCOMETER) over other methods of refraction for use in developing countries are that it is lightweight, compact, relatively inexpensive, fairly quick, and easy to use with minimal training. This clinical trial compared the repeatability, validity, and ease of use of the focometer with an autorefractor. METHODS: The refractive status of the right eye of 80 participants was determined with an autorefractor (Canon RK3). Three measurements were also taken with the focometer. RESULTS: The spherical equivalent (M) of the focometer was 0.25 D more positive than the autorefractor (p < 0.001) and 84% of measurements were within 0.75 D of the autorefractor. The autorefractor detected astigmatism in 91% (73) of the eyes, whereas the focometer identified only 32% (26). The design of the clock target restricts cylinder axis accuracy to the nearest 15 degrees . There was evidence of a learning effect for the focometer: the second and third measurements were more repeatable in the untrained group. There were no differences between the mean (1.03 +/- 2.28) and third focometer (-1.05 +/- 2.32) measurements (p = 0.34). However, using the third focometer measurement, 94% of participants had visual acuities of at least 6/12(-2). CONCLUSIONS: This study highlighted the focometer's restricted power range, inaccuracy of astigmatism and axis determination, and dependence on subject understanding and compliance. Therefore, in most clinical settings, the focometer would not be adequate for quantifying refractive error, but the focometer spherical equivalent was within acceptable limits of the autorefractor, and the visual acuity with lenses determined by the focometer indicates its potential usefulness in public health settings, especially where only spherical ready-made spectacles are dispensed. There may be more cost-effective ways to determine refractive error in these circumstances. A potentially important enhancement in focometer methodology that improves its ease of use was identified: use only the third measurement for each eye.     

Application of an augmented reality tool for maxillary positioning in orthognathic surgery – A feasibility study

BACKGROUND: An augmented reality tool for computer assisted surgery named X-Scope allows visual tracking of real anatomical structures in superposition with volume rendered CT or MRI scans and thus can be used for navigated translocation of bony segments. METHODS: In a feasibility study X-Scope was used in orthognathic surgery to control the translocation of the maxilla after Le Fort I osteotomy within a bimaxillary procedure. The situation achieved was compared with the pre-operative situation by means of cephalometric analysis on lateral and frontal cephalograms. RESULTS: The technique was successfully utilized in 5 patients. Maxillary positioning using X-Scope was accomplished accurately within a range of 1mm. The tool was used in all cases in addition to the usual intra-operative splints. A stand-alone application without conventional control does not yet seem reasonable. CONCLUSION: Augmented reality tools like X-Scope may be helpful for controlling maxillary translocation in orthognathic surgery. The application to other interventions in cranio-maxillofacial surgery such as Le Fort III osteotomy, fronto-orbital advancement, and cranial vault reshaping or repair may also be considered.     

Etanercept decreases tumor necrosis factor-α activity in chronic wound fluid

High levels of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-alpha binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.     

Approaches to end-of-life decision-making in the NICU: insights from Dostoevsky's The Grand Inquisitor.

For many parents stopping life-sustaining medical treatment on their dying infant is psychologically impossible. Dostoevsky's insights into human behavior, particularly the fact that individuals do not want the anxiety and guilt associated with responsibility for making difficult decisions, might change the way physicians approach parents for permission to withdraw life-prolonging medical interventions on dying infants.     

Increasing the efficiency of Monte Carlo cohort simulations with variance reduction techniques.

The authors discuss techniques for Monte Carlo (MC) cohort simulations that reduce the number of simulation replications required to achieve a given degree of precision for various output measures. Known as variance reduction techniques, they are often used in industrial engineering and operations research models, but they are seldom used in medical models. However, most MC cohort simulations are well suited to the implementation of these techniques. The authors discuss the cost of implementation versus the benefit of reduced replications.