Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.
The hemorheological effects of severe exertion were evaluated in eight males and six females before and after a marathon. A highly significant fall in red cell filterability (RCF) was accompanied by a significant rise in plasma osmolality. This correlation was further studied by a series of in vitro experiments to establish a cause-effect relationship. As plasma osmolality increased, RCF progressively diminished. These observations demonstrate that plasma hyperosmolality is an important etiological factor in reducing RCF during strenuous exercise.
The Scottish National Blood Transfusion Service is the main provider of bone for grafting in Scotland. Bone is procured only from live donors, following very strict selection criteria, and we have investigated whether the amount being collected was adequate.Our current harvest of approximately 1700 femoral heads per year is shown not to be enough to meet the future demand for revision surgery of the hip. Many more of these operations are being undertaken, and impaction grafting is being used increasingly.We have calculated the predicted rates of collection and usage for the next four to five years so that we can expand our service in a controlled fashion.J Bone Joint Surg [Br] 1998;80-B:595-9. Received 8 April 1997; Accepted after revision 9 December 1997 Small bone allografts are collected, tested, 'fresh frozen' and distributed by the five regional transfusion centres of the Scottish National Blood Transfusion Service (SNBTS) based in Glasgow, Edinburgh, Dundee, Aberdeen and Inverness.All these regions collect femoral head allografts from patients undergoing elective primary total hip replacement (THR), most with a diagnosis of osteoarthritis (OA). Some regions also collect tibial plateaux, but these are a small proportion of the total. Bone is not collected from patients with fractured neck of the femur or rheumatoid arthritis, or from cadavers or multi-organ donors.Collected bone is tested for mandatory viral markers and bacteriological infection. If these tests are negative it is frozen and quarantined for six months. The donor is then retested for the viral markers and, if these tests are clear, the bone is released for use. When a bacteriological infection is found, bone does not have to be discarded but can be processed further. This occurs in 10% to 15% of all available bone.Small bone allografts are used in a number of orthopaedic operations such as spinal fusion and in trauma, but particularly in revision of THR. We investigated the available supply of fresh-frozen bone allografts from live donors in Scotland, and attempted to predict the total demand for their use in revision THRs. Materials and MethodsSupply of fresh-frozen bone allografts. The overall availability of such allografts from live donors can be calculated by estimating the rates of primary elective THR for OA. The annual Standard Morbidity Records (SMR 1), as coded by the Office of Population Censuses and Surveys (OPCS), for primary THR in Scottish hospitals from 1989 to 1994, were studied 1 and the number of primary elective replacements calculated as described by Williams et al. 2,3 This was compared with the SNBTS 4 information on the number of potential bone donors in order to check the accuracy of coding in each hospital and to indicate whether the SNBTS was collecting bone from all available patients. Although the numbers are relatively small they were considered to be adequate to provide relatively crude predicted rates. Once we had shown that the SMR 1 figures were relatively accurate, estimates of the number of operations e...
Synthetic nanoparticles are promising tools for imaging and drug delivery; however the molecular details of cellular internalization and trafficking await full characterization. Current knowledge suggests that following endocytosis most nanoparticles pass from endosomes to lysosomes. In order to design effective drug delivery strategies that can use the endocytic pathway, or by-pass lysosomal accumulation, a comprehensive understanding of nanoparticle uptake and trafficking mechanisms is therefore fundamental. Here we describe and apply an RNA interference-based high-content screening microscopy strategy to assess the intracellular trafficking of fluorescently-labeled polystyrene nanoparticles in HeLa cells. We screened a total of 408 genes involved in cytoskeleton and membrane function, revealing roles for myosin VI, Rab33b and OATL1 in this process. This work provides the first systematic large-scale quantitative assessment of the proteins responsible for nanoparticle trafficking in cells, paving the way for subsequent genome-wide studies.
Bone allografts have been used clinically for a number of years. Understanding the biology of bone healing and the impact that bone banking has on this helps to improve the methodologies used in increasing the quality and safety of banked bone. Banked bone in its various forms has been used in a variety of surgical procedures, and although there is no doubt that it is clinically effective, most of the studies have been retrospective and non-randomized. The review attempts to summarize some of the data in this area and highlights some of the difficulties encountered in such work. Although there is no doubt that bone banking is nowadays better controlled, there are ever-increasing pressures to produce bone that is as safe as possible with the least impact on its effectiveness. This can only be achieved if the requirements of the providers and users of bone are better understood.
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