Microactuator device for integrated measurement of epithelium mechanics

Mechanical forces are among important factors that drive cellular function and organization. We present a microfabricated device with on-chip actuation for mechanical testing of single cells. An integrated immersible electrostatic actuator system is demonstrated that applies calibrated forces to cells. We conduct stretching experiments by directly applying forces to epithelial cells adhered to device surfaces functionalized with collagen. We measure mechanical properties including stiffness, hysteresis and visco-elasticity of adherent cells.     

Apert syndrome variant with overlapping features of Crouzon syndrome

A rare variant of Apert syndrome having overlapping features of Crouzon syndrome is described. The salient features of the two syndromes are briefly discussed and overlapping features are highlighted. A possible genetic explanation for the same is mentioned.     

Allogene Gesichtstransplantation: Fiktion oder Realität?

BACKGROUND: The aim of this study was to describe two methods of face-harvesting techniques -- a skin and soft tissue flap and a combined osteocutaneous flap -- and to demonstrate the compatibility between donor and recipient in a human fresh cadaver model. METHODS: In fresh human cadavers the skin and soft tissue of the face (type 1) and a combined osteocutaneous flap (including a le Fort III segment, type 2) were harvested. The faces were subsequently exchanged among the donor crania, simulating full-face transplantation. RESULTS: Both flaps are based on the external blood supply of the faciotemporal vessels and the external jugular vein. The end branches of the trigeminal nerve could potentially be used for restoration of sensation (type 1 flap). With type 2 flaps the facial expression may be restored with the inclusion of the facial nerve. Four morphological parameters determine the donor/recipient compatibility: skin color and texture, anthropometric head dimensions, specific soft tissue components (nose, lip, cheek, and eyebrow), and gender. CONCLUSION: Apart from ethical considerations, long-term immunosuppression will remain the limiting factor of full facial transplantation in the near future.     

Intravenous immunoglobulin in autoimmune disorders: an insight into the immunoregulatory mechanisms

Intravenous immunoglobulin (IGIV) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases in addition to supportive therapy of immunodeficient patients. IGIV is beneficial in several diseases, including acute and chronic/relapsing diseases, autoimmune diseases and inflammatory disorders. Therapeutic efficacy of IGIV has also been established in a number of dermatologic diseases. Although a considerable progress has been made in understanding the mechanisms by which IGIV exerts immunomodulatory functions in autoimmune diseases, they remain not fully elucidated. The mode of action of IGIV is complex, involving modulation of expression and function of Fc receptors, interference with activation of complement and the cytokine network, modulation of idiotype network, regulation of cell growth, alteration of cellular adhesion process, and effects on the activation differentiation and effector functions of T and B cells and of antigen-presenting cells. The therapeutic effects of IGIV most likely reflect the functions of natural antibodies in maintaining immune homeostasis in healthy people. The ability of IGIV to interact through V regions with complementary V regions of antibodies and antigen receptors as well as with relevant soluble and surface molecules provides the basis for inducing the selection of immune repertoires. Since IGIV is frequently used to treat autoimmune and inflammatory diseases for which evidence of its efficacy is insufficiently documented, controlled trials, particularly of some neurologic and dermatologic diseases, are imperative.     

17-beta estradiol independently regulates erythropoietin synthesis and NOS activity during hypoxia

We reported previously that 17-beta estradiol (E2-beta) attenuates hypoxic induction of erythropoietin (EPO) synthesis in rats. We hypothesized this attenuation is mediated by increased nitric oxide (NO) bio-availability. To investigate this hypothesis, ovariectomized estrogen-depleted rats were instrumented with arterial and venous catheters and treated with either E2-beta (20 microg/24 hrs) or vehicle (polypropylene glycol) for 7 days. Rats were placed in Plexiglas boxes and administered a bolus of either the NO synthase inhibitor, Nomega-nitro-L-arginine (l-NNA, 15 mg/kg) or saline. Following this bolus, saline or l-NNA was continuously infused (15 mg/kg/h) throughout the 8 hours of hypoxic exposure (12% O2). Hypoxia increased plasma NO metabolites (NOx) in both saline groups but more in E2-beta-treated rats. l-NNA prevented this increase in both groups. Renal endothelial NO synthase (NOS) expression was unaltered by hypoxia, l-NNA, or E2-beta. Despite preventing increases in plasma NOx during hypoxia, l-NNA did not affect E2-beta attenuation of EPO synthesis. We conclude that E2-beta independently attenuates hypoxic induction of EPO and augments hypoxic increases in NO synthesis.     

Assessing patient utilities for varying degrees of low back pain

RATIONALE AND OBJECTIVES: We sought to quantify patient preferences for mild, moderate, and severe low back pain via time-tradeoff analysis and utility measurement. MATERIALS AND METHODS: Forty-one patients being treated for low back pain in a tertiary care teaching hospital participated in the study. Patients were asked to decide which of three health states they were currently experiencing as well as which of the three health states was the worst experienced during their lifetime. A time-tradeoff analysis was performed, during which patients were asked the amount of time in each of the health states they would exchange for complete resolution of symptoms. We correlated (1) subjects' current health state with reported utility and (2) degree of previous low back pain with results of time-tradeoff measurements. RESULTS: All patients were willing to trade a greater number of life-years for resolution of symptoms given a more severe perceived health state. Utility decreased as severity of back pain scenarios increased, with an average utility of 0.93 +/- 0.11 for mild, 0.65 +/- 0.21 for moderate, and 0.18 +/- 0.17 for severe pain. No significant difference in time-tradeoff among subjects was identified based upon current health state on the day of interview. A statistically significant difference was seen in patients' willingness to trade time among those who had actually experienced severe pain versus those who had not. Kendall's correlation revealed that subjects who had experienced severe back pain exhibited significantly lower utilities (P < 0.01) compared with subjects who had never experienced severe pain. CONCLUSIONS: As expected, patients with severe low back pain were willing to sacrifice more potential years of life for resolution of symptoms, suggesting time-tradeoff can accurately reflect patient utility. 2. However, we found no correlation between a subject's current health state and reported utility.     

Perianal fistulae caused by Mycobacterium fortuitum

Mycobacterium fortuitum is a rapidly growing Mycobacterium , which usually colonizes the soil, dust and water. It commonly causes skin and soft tissue infections especially in patients who have preceding trauma. We report a case of perianal fistulae caused by M. fortuitum.     

Red blood cell transfusions are associated with alterations in self-reactive antibody repertoires of plasma IgM and IgG,independent of the presence of a specific immune response toward RBC antigens

Immunization to allogeneic RBC antigens occurs in transfused patients, and may be associated with the development of RBC-destructive antibodies directed against autologous RBC. The present study investigates the effect of transfusion of allogeneic RBC on self-reactive antibody repertoires, independent of the presence of a specific immune response directed toward RBC antigens. Antibody repertoires of IgM and IgG in plasma of hematological patients prior to starting a transfusion regime and of hematological patients receiving regular transfusions of leukocyte-depleted RBC were analyzed using quantitative immunoblotting on a panel of antigens derived from tissue and cell extracts, followed by multiparametric statistical treatment of the data. Multiparametric statistical analysis discriminated between self-reactive antibody repertoires of patients prior to starting a transfusion regime and those receiving regular RBC transfusions (IgM, 0.0001 < P < 0.0244/IgG, 0.0002 < P < 0.0088, depending on the tissue extract), whereas antibody repertoires of plasma IgM and IgG toward bacterial antigens were similar between groups of patients (P > 0.05). We conclude that the challenge of the immune system with allogeneic RBC antigens influences self-reactive antibody repertoires of plasma IgM and IgG, independent of the presence of a specific immune response toward RBC antigens.