A position paper in support of hand transplantation in the blind

Blind upper extremity amputees have historically been excluded from consideration for hand allotransplantation. Although no formal position statement regarding their exclusion has been published to date, functional, rehabilitative, and ethical concerns related to blind amputee candidacy for hand transplantation may be inferred. The authors provide a summary of these reservations and a counterargument to their assumptions, drawing on outcomes measures reported for hand transplantations completed to date. The authors therefore provide a rationale for the inclusion of blind amputees in hand transplantation protocols in the future.     

Psychosocial implications of disfigurement and the future of human face transplantation

Although the first face transplants have been attempted, the social and psychological debates concerning the ethics and desirability of the procedure continue. Critics contend that these issues have not yet been sufficiently addressed. With this in mind, the present article seeks to elaborate on key psychological and social factors that will be central for addressing the ethical and psychosocial challenges necessary to move face transplantation into mainstream medicine. The goals of this article are to (1) discuss the psychosocial sequelae of facial disfiguration and how face transplantation may relieve those problems, and (2) delineate inclusion and exclusion criteria for the selection of research subjects for face transplantation. The article uses concepts from symbolic interaction theory in sociology to articulate a theoretically coherent scheme for comprehending the psychosocial difficulties of facial disfiguration and the advantages offered by facial transplantation. The authors conclude that the psychosocial implications of disfigurement warrant surgical intervention and that research in the area of face transplantation should continue.     

Perspectives on establishing a public cord blood inventory in South Africa

The South African population is highly diverse, both ethnically and genetically. This diversity is particularly true for the African ancestry and various mixed ancestry population groups. These groups are under-represented in national and international bone marrow and peripheral blood donor registries, making it challenging to identify HLA-matched and mismatched unrelated donors when patients from these groups require allogeneic hematopoietic stem and progenitor cell transplantation. In most high-income countries, banked cord blood (CB) units provide an attractive source of hematopoietic progenitor cells for genetically diverse populations. SA does not have a public CB inventory, leaving many patients without access to this important treatment modality. Haploidentical transplantation provides an alternative. In recent years, the use of post-transplant cyclophosphamide has significantly reduced the incidence of graft-versus-host disease after haploidentical transplantation and has improved transplantation outcomes. However, it is difficult to identify suitable haploidentical donors in SA because of family disruption and a high prevalence of HIV. Here the authors provide a brief historical overview of the ethnic and genetic diversity of the country and region. The authors provide a southern African perspective on HLA diversity, consider the allogeneic hematopoietic stem and progenitor cell transplantation landscape and explore the need to establish a public CB bank (CBB) in SA. The health policy and regulatory frameworks that will impact on a CBB in the country SA are also explored. Finally, the authors discuss several matters we believe require attention when considering the establishment of a sustainable public CBB in the South African context.     

Localization of feeding of Anomalococcus indicus (Hemiptera: Lecanodiaspididae) and supplementary biological notes: towards the biological management of the invasive tree Vachellia nilotica indica (Fabales: Mimosoideae) in North-Eastern Australia

Summary. Management of the invasive Vachellia nilotica indica infesting tropical grasslands of Northern Australia has remained unsuccessful to date. Presently Anomalococcus indicus is considered a potential agent in the biological management of V. n. indica. Whereas generic biological details of A. indicus have been known, their feeding activity and details of their mouthparts and the sensory structures that are associated with their feeding action are not known. This paper provides details of those gaps. Nymphal instars I and II feed on cortical-parenchyma cells of young stems of V. n. indica, whereas nymphal instars III and adult females feed on phloem elements of older shoots. Nymphal instars and adults (females) trigger stress symptoms in the feeding tissue with cells bearing enlarged and disfigured nuclei, cytoplasmic shrinkage, cytoplasmic trabeculae, abnormal protuberances and uneven cell wall thickening, unusual cell membrane proliferation, and exhausted and necrosed cells. Continuous nutrient extraction by A. indicus can cause stem death. We provide evidence that A. indicus, by virtue of its continuous feeding activity and intense population build up, can be an effective biological-management agent to regulate populations of V. n. indica in infested areas.     

Kidney transplantation in Canada, 1981-84.

The Canadian Renal Failure Register was established in 1980. Data have been collected annually for all Canadian patients in whom irreversible kidney failure developed and who required dialysis or transplantation. The authors present actuarial patient and graft survival rates for 1981-84. In 1984, patients with a functioning renal graft accounted for 43.9% of the patients with end-stage renal disease. The number of transplants performed increased from 482 in 1981 to 662 in 1984; however, 1,022 patients undergoing dialysis (25.2%) were on an active waiting list for a transplant at the end of 1984. Greater effort is needed to increase the transplantation rate.     

Therapeutic challenges to retinitis pigmentosa: from neuroprotection to gene therapy

Syndromic retinitis pigmentosa (RP) is the result of several mutations expressed in rod photoreceptors, over 40 of which have so far been identified. Enormous efforts are being made to relate the advances in unraveling the patho-physiological mechanisms to therapeutic approaches in animal models, and eventually in clinical trials on humans. This review summarizes briefly the current clinical management of RP and focuses on the new exciting treatment possibilities. To date, there is no approved therapy able to stop the evolution of RP or restore vision. The current management includes an attempt at slowing down the degenerative process by vitamin supplementation, trying to treat ocular complications and to provide psychological support to blind patients. Novel therapeutic may be tailored dependant on the stage of the disease and can be divided in three groups. In the early stages, when there are surviving photoreceptors, the first approach would be to try to halt the degeneration by correction of the underlying biochemical abnormality in the visual cycle using gene therapy or pharmacological treatment. A second approach aims to cope with photoreceptor cell death using neurotrophic growth factors or anti-apoptotic factors, reducing the production of retino-toxic molecules, and limiting oxidative damage. In advanced stages, when there are few or no functional photoreceptors, strategies that may benefit include retinal transplantation, electronic retinal implants or a newly described optogenetic technique using a light-activated channel to genetically resensitize remnant cone-photoreceptor cells.     

Development of tolerogenic strategies in the clinic

The study of tolerance in the clinic can be divided into three areas: (i) focused evaluation of existing tolerant transplant recipients as to their mechanism of tolerance; (ii) prospective tolerance trials, such as combined bone marrow and kidney transplantation as well as T cell depletion followed by subsequent weaning of immunosuppression; and (iii) immunologic assays to assess the likelihood of rejection or tolerance. Frankly, a very small number of patients have been transplanted with the intention of removing all immunosuppressive therapy, but several clinical trials with this aim are currently in progress, largely sponsored by the Immune Tolerance Network, a joint venture between the National Institutes of Health and the Juvenile Diabetes Research Foundation. Similarly, a reliable assay to assess tolerance has not yet been developed but a variety of approaches towards assessing rejection, and in some cases tolerance, are being developed. It would be accurate to state that many of the experimental and preclinical approaches to the induction of tolerance have resulted in better immunosuppression for human transplantation, but reliable tolerance strategies in humans have not yet been achieved. Combined bone marrow and kidney transplantation may be considered as one exception to this, but such a strategy is not generally applicable to the vast majority of solid organ transplant recipients. This review will summarize efforts to date, particularly focusing on kidney transplantation.     

Advancing cartilage tissue engineering: the application of stem cell technology

The treatment of cartilage pathology and trauma face the challenges of poor regenerative potential and inferior repair. Nevertheless, recent advances in tissue engineering indicate that adult stem cells could provide a source of chondrocytes for tissue engineering that the isolation of mature chondrocytes has failed to achieve. Various adjuncts to their propagation and differentiation have been explored, such as biomaterials, bioreactors and growth hormones. To date, all tissue engineered cartilage has been significantly mechanically inferior to its natural counterparts and further problems in vivo relate to poor integration and deterioration of tissue quality over time. However, adult stem cells--with their high rate of proliferation and ease of isolation--are expected to greatly further the development and usefulness of tissue engineered cartilage.     

人工视觉辅助系统：现状与展望

通过视觉获取图像信息是人类学习和生活的重要功能,失明则会显著降低其生活质量. 因视网膜色素变性、青光眼和黄斑变性等疾病而造成后天失明者,以及由意外事故、战争等造成眼部创伤者,有可能通过人工视觉辅助系统的帮助恢复部分视觉,或者完成复杂的生活任务. 一些盲症患者视觉通路的神经传导剩余部分依然有功能,因此可以借助电极阵列刺激视神经向大脑传递视觉信息,也可在大脑视觉皮层贴敷电极阵列的方法输入视觉信息. 此外,还能借助体外装置,如通过人工智能将视觉转换成语音指令、触觉阵列编码等,帮助盲症患者获得环境信息. 本文综述各类人工视觉辅助系统的现状,展望其发展趋势,并提出了新的植入器件与随身体外装置的新设想.     

Panniculectomy in preparation for renal transplantation: a new indication for an old procedure to reduce renal transplantation-associated wound complications

End-stage renal disease patients who have lost a significant amount of weight are increasingly being evaluated for kidney transplantation. An abdominal panniculus, almost uniformly observed, creates an area predisposed to wound complications. Consequently, a panniculus may limit a patient's candidacy for transplantation. The authors describe their preliminary experience utilizing panniculectomy as a prophylactic procedure to reduce wound complications following kidney transplantation in patients whose panniculus would exclude them from renal transplantion. A single-institution chart review was conducted of nine patients with end-stage renal disease who underwent a panniculectomy in preparation for transplantation. Clinical outcomes and complications were reviewed. The nine patients included three men and six women with a mean age of 54.5 years and a mean body mass index of 28.3 kg/m. Four patients had diabetes. All patients underwent an uncomplicated panniculectomy, with a mean resected weight of 3.0 kg, and a mean length of hospital stay of 1.75 days. No one required blood transfusions. All patients were followed postoperatively for 3 months. Complications included an abscess and a skin dehiscence treated with local wound care. After recovery, patients were referred to the transplant center for re-evaluation for kidney transplantation. Thus far, four of these nine patients have undergone transplantation. This case series suggests that panniculectomy can be performed safely in patients with end-stage renal disease. Furthermore, panniculectomy gives these otherwise unsuitable kidney transplant candidates access to a life-saving operation.     

Brain death and marginal grafts in liver transplantation

It is well known that most organs for transplantation are currently procured from brain-dead donors; however, the presence of brain death is an important risk factor in liver transplantation. In addition, one of the mechanisms to avoid the shortage of liver grafts for transplant is the use of marginal livers, which may show higher risk of primary non-function or initial poor function. To our knowledge, very few reviews have focused in the field of liver transplantation using brain-dead donors; moreover, reviews that focused on both brain death and marginal grafts in liver transplantation, both being key risk factors in clinical practice, have not been published elsewhere. The present review aims to describe the recent findings and the state-of-the-art knowledge regarding the pathophysiological changes occurring during brain death, their effects on marginal liver grafts and summarize the more controversial topics of this pathology. We also review the therapeutic strategies designed to date to reduce the detrimental effects of brain death in both marginal and optimal livers, attempting to explain why such strategies have not solved the clinical problem of liver transplantation.     

Dendritic cells: the driving force behind autoimmunity in rheumatoid arthritis?

Dendritic cells (DC) are likely to play a significant role in immune-mediated diseases such as autoimmunity and allergy. To date there are few treatments capable of inducing permanent remission in rheumatoid arthritis (RA) and elucidation of the role of DC may provide specific strategies for disease intervention. Dendritic cells have proven to be powerful tools for immunotherapy and investigations are under way to determine their clinical efficacy in transplantation and viral and tumour immunotherapy. The present review will focus on the current view of DC and their role in autoimmunity, in particular RA. Two possible roles for DC in the pathogenesis of RA will be proposed, based on recent advances in the field.     

Histologic change of arteriovenous malformations of the face and scalp after free flap transfer

In three patients with long-standing vascular malformations of the face and scalp, radial forearm free flaps were transferred after a near-total excision of the lesion. All patients had typical high-flow malformations with thrill and bruit. The onset and progression of the malformations were analyzed through clinical and histologic studies. After free flap transfer, the vascular malformations were followed up grossly and histologically for between 4 and 9 years. There was no recurrence of arteriovenous malformation after free flap transfer. The portion of the residual lesion adjacent to the transferred free flap disappeared, and the remaining discoloration also vanished grossly. Histologic comparison of immediate postoperative and 4-month postoperative specimens from the margin and residual lesion using Victoria blue staining showed that the typical preoperative findings for arteriovenous malformation-an intermingling of thick-walled vessels with abundant elastic fibers and thin-walled vessels without elastic fibers-had undergone change, resulting in the disappearance of the thick-walled vessels and leaving only homogeneous, thin-walled vasculature. The highly vascularized free flap, which does not contain abnormal fistulas, impacted the histologic change of the arteriovenous malformation by blocking the vicious cycle of ischemia and anatomic replacement of disfigured skin and subcutaneous tissues.     

Clinical use of rHuEPO in bone marrow transplantation

Recipients of bone marrow (BMT) or peripheral blood progenitor stem cells (PBSCT) transplant have in the period following transplantation a frequent need for red blood cell transfusions and therefore an increased risk of blood-transmitted infections. The anaemia is caused mainly by myelosuppression after high-dose chemotherapy, but an impaired erythropoietin (EPO) production and an inappropriate EPO response may also contribute. Since recombinant human erythropoietin (rHuEPO) has been established as a treatment for renal anaemia it has been of interest whether treatment may be of benefit in the transplant setting. This paper gives an overview of the studies conducted to date with rHuEPO treatment in patients receiving bone marrow transplants. Current data donot support any transfusional benefits when rHuEPO is used in patients receiving autologous transplants. However, in patients receiving allogeneic transplants several studies clearly indicate a therapeutic role for rHuEPO with patients showing accelerated erythroid engraftment, increased haemoglobin levels, a reduced requirement for red blood cell transfusions, and a shortened time to transfusion independence. Especially patients with immune haemolysis after transplantation seems to benefit from the treatment. In addition, rHuEPO treatment has been used for lateonset anaemia after BMT and to prevent the need for homologous red blood cell transfusions to the BMT donor. To reduce costs, it is important in future studies to identify not only the optimal dose and route of administration of rHuEPO but also the most effective combination with other haematopoietic growth factors and cytokines that are used before and after transplantation.     

Circadian genes in a blind subterranean mammal III: molecular cloning and circadian regulation of cryptochrome genes in the blind subterranean mole rat, Spalax ehrenbergi superspecies

The blind subterranean mole rat superspecies Spalax ehrenbergi is an extreme example of mammalian adaptation to life underground. Though this rodent is totally visually blind, harboring a drastically degenerated subcutaneous rudimentary eye, its daily activity rhythm is entrainable to LD cycles. This indicates that it confers light information to the clock, as has been previously shown by the authors in behavioral studies as well as by molecular analyses of its Clock/MOP3 and its three Per genes. The Cryptochrome (Cry) genes found in animals and plants act both as photoreceptors and as essential components of the negative feedback mechanism of the biological clock. To further understand the circadian system of this unique mammal, the authors cloned and characterized the open reading frame of Spalax Cry1 and Cry2. The Spalax CRY1 protein is significantly closer to the human homolog than to the mice one, in contrast to the evolutionary expectations. They have found two isoforms of Cry2 in Spalax, which differ in their 5' end of the open reading frame and defined their expression in Spalax populations. They found a large and significant excess of heterozygotes of sCry2 (sCry2L/S genotype). Both sCry1 and sCry2 mRNAs were found in the SCN, the eye, the harderian gland, as well as in a wide range of peripheral tissues. Their expression pattern under different LD conditions has also been analyzed. As was already shown for other circadian genes, despite being blind and living in darkness, the Cry genes of Spalax behave in a similar, though not identical, pattern as in sighted animals. Once again, the results indicate that the uniquely hypertrophied harderian gland of Spalax plays a key role in its circadian system.     

Verifying surgical results and risk factors of the lateral thoracodorsal flap

In 1986, the combined use of the lateral thoracodorsal flap and an implant was introduced as an alternative method of delayed reconstruction of small to medium-size breasts for postmastectomy patients who are reluctant or unable to consider reconstruction by tissue expansion or by more extensive autologous tissue transplantation. So far, the technique has only been proven reproducible in Sweden. Postmastectomy radiotherapy has been proven to increase the risk of wound-healing complications after lateral thoracodorsal transplantation, and additional risk factors such as advanced age, obesity, smoking, and some general health characteristics have been indicated. The authors initiated a prospective study to assess the reproducibility of this technique outside Sweden and to confirm the proven risk factor, prove or refute the alleged ones, and possibly identify additional factors. Additionally, they applied the technique for immediate breast reconstruction and tried to expand the indications and applications of the lateral thoracodorsal flap even further. The authors report on their initial experience with 60 lateral thoracodorsal flaps and conclude that the use of this flap is a well-reproducible technique for breast reconstruction, with few complications leading to failure. Using the lateral thoracodorsal flap in combination with tissue expanders allows for reconstruction of breasts of larger than medium size. Moreover, the authors successfully applied fully deepithelialized lateral thoracodorsal flaps for additional indications. The statistical significance of postmastectomy radiotherapy as a risk factor could not be confirmed, but some general health characteristics were found to be significant patient-related risk factors. Out of five procedure-related characteristics, only increased flap length was proven to negatively influence the outcome of the procedure.     

Application of liver stem cells for cell therapy

The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver disease. Embryonic stem cells can be readily differentiated into hepatocytes, and their transplantation into animals has improved liver function in the absence of teratoma formation: their use in bioartificial liver support is an obvious application. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted foetal or adult hepatocytes have proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells is clearly vital for survival in many cases of acute liver failure, but surprisingly little progress has been made with these cells in terms of transplantation. Finally there is the controversial subject of autologous bone marrow, and while the contribution of these indigenous cells to liver turnover seems at best, trivial, results from a small number of phase 1 studies of transplantation of bone marrow to cirrhotic patients have been moderately encouraging.