Organ donation in Switzerland: a survey on marginal or extended criteria donors (ECD) from 1998 to 2009

The widening gap between the numbers of patients on the waiting list for organ transplantation and the insufficient numbers of organ donors results in the use of "critical" donors, so-called marginal donors or extended criteria donors. Data concerning the evaluation of extended criteria donors (ECD) in Switzerland are sparse.

Preparation of intact bovine tail intervertebral discs for organ culture

The intervertebral disc (IVD) is the joint of the spine connecting vertebra to vertebra. It functions to transmit loading of the spine and give flexibility to the spine. It composes of three compartments: the innermost nucleus pulposus (NP) encompassing by the annulus fibrosus (AF), and two cartilaginous endplates connecting the NP and AF to the vertebral body on both sides. Discogenic pain possibly caused by degenerative intervertebral disc disease (DDD) and disc herniations has been identified as a major problem in our modern society. To study possible mechanisms of IVD degeneration, in vitro organ culture systems with live disc cells are highly appealing. The in vitro culture of intact bovine coccygeal IVDs has advanced to a relevant model system, which allows the study of mechano-biological aspects in a well-controlled physiological and mechanical environment. Bovine tail IVDs can be obtained relatively easy in higher numbers and are very similar to the human lumbar IVDs with respect to cell density, cell population and dimensions. However, previous bovine caudal IVD harvesting techniques retaining cartilaginous endplates and bony endplates failed after 1-2 days of culture since the nutrition pathways were obviously blocked by clotted blood. IVDs are the biggest avascular organs, thus, the nutrients to the cells in the NP are solely dependent on diffusion via the capillary buds from the adjacent vertebral body. Presence of bone debris and clotted blood on the endplate surfaces can hinder nutrient diffusion into the center of the disc and compromise cell viability. Our group established a relatively quick protocol to "crack"-out the IVDs from the tail with a low risk for contamination. We are able to permeabilize the freshly-cut bony endplate surfaces by using a surgical jet lavage system, which removes the blood clots and cutting debris and very efficiently reopens the nutrition diffusion pathway to the center of the IVD. The presence of growth plates on both sides of the vertebral bone has to be avoided and to be removed prior to culture. In this video, we outline the crucial steps during preparation and demonstrate the key to a successful organ culture maintaining high cell viability for 14 days under free swelling culture. The culture time could be extended when appropriate mechanical environment can be maintained by using mechanical loading bioreactor. The technique demonstrated here can be extended to other animal species such as porcine, ovine and leporine caudal and lumbar IVD isolation.

Homing of mesenchymal stem cells in induced degenerative intervertebral discs in a whole organ culture system

Homing of human bone marrow-derived mesenchymal stem cells (BMSCs) was studied using ex vivo cultured bovine caudal intervertebral discs (IVDs).

Early detection of subclinical organ dysfunction by microdialysis of the rectus abdominis muscle in a porcine model of critical intra-abdominal hypertension

The aim of this study was to evaluate microdialysis of the rectus abdominis muscle (RAM) for early detection of subclinical organ dysfunction in a porcine model of critical intra-abdominal hypertension (IAH). Microdialysis catheters for analyses of lactate, pyruvate, and glycerol levels were placed in cervical muscles (control), gastric and jejunal wall, liver, kidney, and RAM of 30 anesthetized mechanically ventilated pigs. Catheters for venous lactate and interleukin 6 samples were placed in the jugular, portal, and femoral vein. Intra-abdominal pressure (IAP) was increased to 20 mmHg (IAH20 group, n = 10) and 30 mmHg (IAH30, n = 10) for 6 h by controlled CO2 insufflation, whereas sham animals (n = 10) exhibited a physiological IAP. In contrast to 20 mmHg, an IAH of 30 mmHg induced pathophysiological alterations consistent with an abdominal compartment syndrome. Microdialysis showed significant increase in the lactate/pyruvate ratio in the RAM of the IAH20 group after 6 h. In the IAH30 group, the strongest increase in lactate/pyruvate ratio was detected in the RAM and less pronounced in the liver and gastric wall. Glycerol increased in the RAM only. After 6 h, there was a significant increase in venous interleukin 6 of the IAH30 group compared with baseline. Venous lactate was increased compared with baseline and shams in the femoral vein of the IAH30 group only. Intra-abdominal pressure-induced ischemic metabolic changes are detected more rapidly and pronounced by microdialysis of the RAM when compared with intra-abdominal organs. Thus, the RAM represents an important and easily accessible site for the early detection of subclinical organ dysfunction during critical IAH.

Quantitative measurements in 3-dimensional datasets of mouse lymph nodes resolve organ-wide functional dependencies

Deep tissue imaging has become state of the art in biology, but now the problem is to quantify spatial information in a global, organ-wide context. Although access to the raw data is no longer a limitation, the computational tools to extract biologically useful information out of these large data sets is still catching up. In many cases, to understand the mechanism behind a biological process, where molecules or cells interact with each other, it is mandatory to know their mutual positions. We illustrate this principle here with the immune system. Although the general functions of lymph nodes as immune sentinels are well described, many cellular and molecular details governing the interactions of lymphocytes and dendritic cells remain unclear to date and prevent an in-depth mechanistic understanding of the immune system. We imaged ex vivo lymph nodes isolated from both wild-type and transgenic mice lacking key factors for dendritic cell positioning and used software written in MATLAB to determine the spatial distances between the dendritic cells and the internal high endothelial vascular network. This allowed us to quantify the spatial localization of the dendritic cells in the lymph node, which is a critical parameter determining the effectiveness of an adaptive immune response.

Sense and nonsense of an extended pelvic lymph node dissection in prostate cancer

Lymph node metastases associated with prostate cancer (PCa) has been shown to be a poor prognostic factor. The role of pelvic lymph node dissection (PLND) itself in relation to survival remains unclear, however. A Medline search was conducted to address this issue. The following conclusions were drawn. Only recently, improved survival due to completion of radical prostatectomy (RP) (compared to abandoning RP) in known or presumed lymph-node-positive patients has been shown. Lymph node sampling can only be considered representative if an adequate number of nodes is removed. While several authors have suggested that a therapeutic benefit in patients undergoing RP is not provided by PLND, the reliability of these studies is uncertain. Contrary to this, several studies have indicated the possibility of long-term survival even in the presence of limited lymph node metastases. The role and timing of initiation of adjuvant androgen deprivation therapy (ADT) in patients who have node-positive disease after RP is controversial. Recent studies suggest that delaying ADT may not adversely impact survival.

Immunosuppressive drugs in organ transplant recipients--rationale for critical selection

Transplantation is the treatment of choice for many different organ failures. Despite growing experience in surgery and immunosuppression protocols, the long-term mortality of the procedure remains much higher than in the general population. Second only to cardiovascular diseases as the cause of death in organ transplant recipients, cancer is now known to be at least partly related to the immunosuppression regimen. Nevertheless, if calcineurin inhibitors have a demonstrated pro-oncogenic effect, other classes, such as mTOR inhibitors, are antiproliferative, and even demonstrated as an efficient therapy in some advanced oncological situations. Therefore, the adaptation of the therapy protocol evolves now towards an individualized medicine based on the risk factors of each transplant recipient in terms of cardiovascular, infectious and oncological diseases. As the first organ involved by tumor is the skin, many different guidelines have been published to try and adapt the therapy to the occurrence of a new lesion. If, for example, limited actinic keratosis or the first episode of a non-melanoma skin cancer usually requires no change of the immunosuppressive therapy, but a local specialized care and frequent clinical controls, more advanced lesions imply the adaptation of the drug regimen. In any case, the collaboration between general practitioners, dermatologists and the transplantation team is mandatory.

Pre- and posttransplant management of solid organ transplant recipients: risk-adjusted follow-up

Solid organ transplant recipients (SOTR) have an increased risk of skin cancer due to their long-term immunosuppressive state. As the number of these patients is increasing, as well as their life expectancy, it is important to discuss the screening and management of skin cancer in this group of patients. The role of the dermatologist, in collaboration with the transplant team, is important both before transplantation, where patients are screened for skin lesions and the individual risk for skin cancer development is assessed, and after transplantation. Posttransplant management consists of regular dermatological consultations (the frequency depends on different factors discussed below), where early skin cancer screening and management, as well as patient education on sun protective behavior is taught and enforced. Indeed, SOTR are very sensitive to sun damage due to their immunosuppressive state, leading to cumulative sun damage which results in field cancerization with numerous lesions such as in situ squamous cell carcinoma, actinic keratosis and Bowen's disease. These lesions should be recognized and treated as early as possible. Therapeutic options discussed will involve topical therapy, surgical management, adjustment of the patient's immunosuppressive therapy (i.e. reduction of immunosuppression and/or switch to mammalian target of rapamycin inhibitors) and chemoprevention with the retinoid acitretin, which reduces the recurrence rate of squamous cell carcinoma. The dermatological follow-up of SOTR should be integrated into the comprehensive posttransplant care.

The sense of the body in individuals with spinal cord injury

Increasing evidence suggests that the basic foundations of the self lie in the brain systems that represent the body. Specific sensorimotor stimulation has been shown to alter the bodily self. However, little is known about how disconnection of the brain from the body affects the phenomenological sense of the body and the self. Spinal cord injury (SCI) patients who exhibit massively reduced somatomotor processes below the lesion in the absence of brain damage are suitable for testing the influence of body signals on two important components of the self-the sense of disembodiment and body ownership. We recruited 30 SCI patients and 16 healthy participants, and evaluated the following parameters: (i) depersonalization symptoms, using the Cambridge Depersonalization Scale (CDS), and (ii) measures of body ownership, as quantified by the rubber hand illusion (RHI) paradigm. We found higher CDS scores in SCI patients, which show increased detachment from their body and internal bodily sensations and decreasing global body ownership with higher lesion level. The RHI paradigm reveals no alterations in the illusory ownership of the hand between SCI patients and controls. Yet, there was no typical proprioceptive drift in SCI patients with intact tactile sensation on the hand, which might be related to cortical reorganization in these patients. These results suggest that disconnection of somatomotor inputs to the brain due to spinal cord lesions resulted in a disturbed sense of an embodied self. Furthermore, plasticity-related cortical changes might influence the dynamics of the bodily self.

Waiting for evidence seems to make sense - exept for the one providing the evidence

A 58-year-old male presented with a history of two prior transient ischaemic attacks and was found to have a patent foramen ovale (PFO) in the absence of atrial fibrillation or relevant carotid atheromatosis. PFO closure was deferred at this stage due to the lack of clinical evidence. Three years later the patient was re-admitted after a major stroke with residual symptoms and finally underwent PFO closure in a minimally invasive procedure using an Amplatzer PFO Occluder.

Psychological Sense of Community: A New Construct for the Field of Management

This article introduces a new construct to the field of management called Psychological Sense of Community (PSOC). This is important because management scholars are calling for the creation of communities in organizations in an environment that lacks appropriate construct development. The aims of this article are threefold: (a) develop a working definition of PSOC via a review of the extant literature on PSOC from other disciplines with the goal of translating it into the domain of management, (b) synthesize findings from parallel literatures on the outcomes of PSOC with an eye toward exploring the relevance of such outcomes in management contexts, and (c) assess the value of PSOC as it relates to its uniqueness in relation to other prominent management constructs and its scope of applicability in a variety of management inquiry areas.