Advances in the clinical management of pediatric kidney transplantation

Renal transplantation is the best form of renal replacement therapy for children reaching end-stage renal failure. The first human transplantation was performed by Dr. Voronoy from a cadaver donor in 1933; however, because of the lack of immunological laboratory assessments, this transplantation resulted in rejection. Progress in immunological evaluation and new immunosuppressive drugs have improved survival in renal transplantation. The first renal transplantation in Turkey was performed by Dr. Haberal et al. on November 3, 1975. This child was one of five siblings with juvenile nephronophytisis, and the mother was the donor. Dr. Haberal has thus pioneered renal transplantation in Turkey. In the following years Dr. Haberal initiated cadavral transplantation in our country in collaboration with Eurotransplant. He has also contributed to the law concerning transplantation in Turkey. Subsequently many transplantation centers have been developed in the country. In spite of marked progress in transplantation technology, pediatric transplantation has not improved as fast as adult transplantation. This is due to several factors, such as the difference in the etiological factors leading to chronic renal failure, technical factors, growth and sexual development, factors relevant to infections and vaccinations, and psychological problems.     

Disease recurrence after orthotopic liver transplantation

With the advent of cyclosporine immunosuppression in the late 1970s, liver transplantation became a widespread modality for the treatment of end-stage liver disease. Several metabolic disorders that produce liver injury, such as Wilson's disease and alpha-1-antitrypsin deficiency, are cured by liver transplantation. However, many other diseases for which transplantation is undertaken may recur in the allograft. As follow-up increases and newer diagnostic modalities become available, those diseases that recur, and their natural histories, are becoming better understood. This new information may lead to a reevaluation of the suitability of some conditions for transplantation. This article briefly reviews disease recurrence in orthotopic liver transplants.     

In vivo measurement of implant loads in a patient with a fractured vertebral body

For several medical interventions, increasing experience results in improved outcome. This finding may result from better patient selection or increased skill levels. This report examines whether there is a relationship between center experience and patient outcome for liver transplantation, and if so, whether the relationship is explained by patient or donor selection or level of experience required to obtain optimal results. The United Network for Organ Sharing Scientific Liver Transplant Registry includes all procedures performed in the United States since October 1987. The date of the first transplantation and the number of operations performed were used to define 42 new and 27 experienced centers. Within new centers, experience was quantified by the sequence number of each transplantation. Characteristics of 6,180 recipients and donors were compared between new and experienced centers using the chi 2 test for association. A linear trend test identified whether these characteristics varied with experience within new centers. The independent association between experience in new centers and perioperative mortality was examined using logistic regression. Patient and donor selection criteria differ between experienced and new centers and change within new centers as experience is gained. Adjusting for calendar year and various patient and donor characteristics, perioperative mortality rates decrease in new centers as experience is gained. After 20 transplantations are performed, perioperative mortality in new centers is not significantly different than that in experienced centers. Criteria for recipient and donor selection change as centers gain experience. Despite these differences and improvements that have occurred over time, increasing experience in centers performing liver transplantations is associated with reduced perioperative mortality.     

End-stage cystic fibrosis: improved diabetes control 2 years after successful isolated pancreatic cell and double-lung transplantation

Over a period of years, insulin-dependent diabetes and respiratory insufficiency developed in a 35-year-old patient with end-stage cystic fibrosis. After waiting more than 4 years while receiving maintenance treatment with continuous liquid O2 and nasal ventilation, the patient underwent double-lung and pancreatic islet cell transplantation. Subsequently, the patient has enjoyed a normal life with full employment and much better control of his diabetes. Pancreatic islet cell transplantation is a simple and innocuous technique easily added to the end of lung transplantation. These new pancreatic cells, although locally injected, are still secreting more than 2 years later as assessed by repeated C-peptide measurements.     

Stem cells from bone marrow, umbilical cord blood and peripheral blood for clinical application: current status and future application

Bone marrow transplantation (BMT) has progressed rapidly during the past two decades to that of a treatment of choice as a therapeutically effective modality for the treatment of selected patients with malignant disease and non-malignant hematological disorders. However, its use is limited by availability of human leukocyte antigens (HLA)-matched donor cells, engraftment and graft-versus-host disease (GVHD). Prevention of GVHD, improvement in the speed and quality of marrow reconstitution, and screening of new immunomodulating agents which improve engraftment and augment hemopoiesis are intense areas of investigation. To this end there has clearly been progress in purification and characterization of human stem cells from different tissue sources. Discussed in this review are: (a) stem cell purification, characterization and ex vivo expansion; (b) bone marrow stem cell transplantation; (c) cord blood stem cell transplantation; (d) peripheral blood stem cell transplantation; (e) fetal liver stem cell transplantation; (f) in utero stem cell transplantation; and (g) evaluation of the capacity of stem cells to serve as targets for gene therapy.     

Role of cyclosporin in renal transplantation

The cyclosporine era started 10 years ago in organ transplantation, especially in renal transplantation. Following the pioneering works showing the efficacy and its synergism with other immunosuppressors, a second step consisted in a better use by decreasing the induction dose and a closer definition of its side effects. A major improvement in the results (increase of 5 to 10% in patient survival and of 10 to 20% in graft survival), a decrease in the number of acute rejection episodes, in the cumulative doses of steroids, in the duration of hospitalization and in the total cost of transplantation made this drug as the worldwide used agent, now considered as the milestone in immunosuppression. Over all, organ transplantation is needing a more specific immunological agent, deprived if possible of major side effects. In these regards, each new agent should be considered only if compared to the "gold standard", namely cyclosporine.     

Knee dislocation without anterior cruciate ligament disruption. A report of three cases

The development of liver transplantation has led to technical refinements such as liver graft reduction or splitting for transplantation in two recipients, the use of living related donors, and the temporary orthotopic transplantation of auxiliary liver grafts. Regarding immuno-suppression, new drugs are currently under evaluation, such as tacrolimus (FK 506) which could be effective on some severe rejections. On the other hand, the indications of liver transplantation have been revisited according to clinical results. In France, the increasing development of organ and tissue transplantation has led to the creation of the Etablissement Fran?ais des Greffes, which has the following missions: managing the waiting lists, supporting organ donation, ensuring sanitary safety, and evaluating transplantation activities. Future alternatives to allogenic liver transplantation are mainly represented by xenografting with monkey or pig livers, hepatic assistance and bioartificial liver, and gene therapy.     

Intestinal transplantation: a clinical reality in 1998

Each year, thousands of peoples die, suffering from an anatomical or functional loss of their intestine; these patients would benefit from bowel transplantation; the difficulties of bowel transplantation are as follows: 1. the physiological characteristics of the small bowel, and the fact that denervation, lymphatics interruption and ischemia, independently from rejection, may disturb its function; 2. secondly, the organ is septic; thus, its transplantation causes major infectious problems; 3. at last, the immunological characteristics of the intestinal allograft. Bowel transplantation causes a two-way immunological conflict, not only a standard rejection response, but also a graft-versus-host disease, similar to that observed after bone marrow transplantation; this reaction is caused by the lymphoid tissue conveyed within the bowel graft. The introduction of a new immunosuppressive molecule, FK 506, in combination with profound antibiotic prophylactic regimens, decontamination protocols and vigorous anti-viral protection (against cytomegalovirus and Epstein-Barr), have significantly improved the results. Bowel transplantation has recently reached clinical application. The one-year survival rate of intestinal grafts reaches now 70%. Still, there is no doubt that, due to its microbiological and immunological characteristics, the small bowel will remain the most challenging abdominal organ to transplant.     

A rapid organ recovery program for non-heart-beating donors

We report a successful method for rapid organ recovery from the non-heart-beating donor, which can open a new resource of organs for transplantation. The RORP is not controversial, is simple in design and execution, and results in kidneys that are viable for transplantation. Special personnel and equipment are needed but are easily incorporated in the overall budget of an OPO or donor hospital. Clearly more research is needed to rebuild ischemically damaged cells ex vivo and to develop new agents/methods to minimize the reperfusion response. When these processes are better understood and managed, the full potential of the NHBD as a donor resource will be fully achieved. We agree with others that the donor shortage could be entirely relieved by routine organ recovery from NHBD trauma victims.     

Current status of cardiac transplantation

Cardiac transplantation, first introduced 30 years ago, has become a widely used and increasingly important procedure for treatment of truly end-stage heart disease. Current use is limited strictly by donor supply, making selection of appropriate recipients an important ethical and societal issue. Survival rates after transplantation rose in the 1980s with the use of cyclosporine and have remained relatively consistent since then, although recipients older than 65 years or younger than 1 year have lower survival rates than recipients of other ages. Although immunosuppressive drugs have helped establish cardiac transplantation as a successful procedure, risks of opportunistic infection and rejection, as well as coronary arteriopathy, have led to development of new immunosuppressive agents currently under study. Future alternatives to the current technology of cardiac allotransplantation may include xenotransplantation and/or nonbiological replacement of the heart with mechanical devices.     

Injury prevention programmes in primary care: a high risk group or a whole population approach?

Assessments of the acceptability of new transplantation practices require a pinpointing of not only the meaning of death, but also the timing of death. They typically perceive elective ventilation as occurring just prior to death and non-heart-beating donor protocols as operative just after death. However, such practices in fact highlight the general vagueness and ambiguity surrounding these issues in both law and ethics. Supply-side dilemmas in transplantation lend real urgency to this "life or death" debate.     

The first decade of continuous progress in retinal transplantation

In recent months, neural fetal retina has been transplanted into blind human patients affected by Retinitis Pigmentosa. Initial success, as documented by improved visual activity, has been reported (del Cerro et al., Neuroscience Abstract, 1996). With the rapid progress in human patients, additional questions are arising concerning transplantation issues. Additional answers and further success in treating clinical disease will necessarily come from new laboratory research in animal models as well as in vitro systems. This increases the need for evaluation of the data already gathered over the first decade of retinal transplantation. The extensive experimental background work that preceded the current wave of human retinal transplants is reviewed in this paper, with particular emphasis given to the work dealing with the transplantation of neural retina.     

Role of B.A. Petrov in foundation and development of free flap skin transplantation problem

The article reviews the history of development of free-flap skin transplantation and basic role of acad. B.A. Petrov who was the first to show the role of dermatom skin transplantation in vast granulating wounds as the only method saving the life of patients with severe burns. He also suggested to solve an actual problem--deficiency of resources of donor skin--by repeated excision of skin flaps from previously used donor sites and use of cadaver skin. Very important is ales the role of B.A. Petrov in development of such particular questions as the role of patient's condition, wound bed am microbial flora of the wound in survival of skin transplants. In aspect of historical relationships the perspective of new approach to treatment of deep burns by transplantation of ceratinocytes, cultivated outside the patient's organism is shown.     

The association of gonorrhoea and syphilis with premature birth and low birthweight

The indications and results of single and double lung transplantation are described on the basis of 66 operations performed by the authors and on the background of the world literature. Lung transplantation is considered a new and promising therapeutic mode for treating patients with end-stage pulmonary failure related to fibrosis, emphysema, infective conditions, and pulmonary hypertension yielding satisfactory early results. The long-term prognosis of patients undergoing lung transplantation, like that of any other organ transfer, remains guarded.     

Primary cardiac sarcoma treated by orthoptic cardiac transplantation. Apropos of a case

The authors report a new case of cardiac sarcoma treated by cardiac transplantation. This treatment has been proposed for these malignant tumours of poor prognosis when simple excision is impossible, with variable results. This patient is in good general condition 20 months after transplantation. Transplantation is a therapeutic procedure which should be considered in malignant tumours limited to the heart.     

Risks and costs of end-stage renal disease after heart transplantation

OBJECTIVES: To estimate the risks and costs of end-stage renal disease (ESRD) after heart transplantation. BACKGROUND: Previous studies have shown high rates of ESRD among solid-organ transplant patients, but the relevance of these studies for current transplant practices and policies is unclear. Limitations of prior studies include relatively small, single-center samples and estimates made before implementing suggested practice changes to reduce ESRD risk. METHODS: Medicare beneficiaries who underwent heart transplantation between 1989 and 1994 were eligible for study inclusion (n=2088). Thirty-four patients undergoing dialysis or who had the diagnosis of ESRD before or at transplantation were excluded from the study. ESRD was defined as any patient undergoing renal transplantation or requiring dialysis for more than 3 months. Mortality and ESRD events were recorded up to 1995. ESRD risk was estimated using the Kaplan-Meier product-limit estimator and logistic regression analyses. Linear regression was performed to determine expenditures for treating ESRD, and we developed long-term models of the risk and direct medical costs of ESRD care. RESULTS: The annual risk of ESRD was 0.37% in the first year after transplant and increased to 4.49% by the sixth posttransplant year. There was no significant trend in the risk of ESRD based on the year of transplantation, even after adjusting for patient characteristics. The average cumulative 10-year direct cost of ESRD per patient undergoing heart transplantation exceeded $13,000. CONCLUSIONS: In a large, national sample of patients undergoing heart transplantation, ESRD is not rare, even for patients undergoing transplant after the development of new practices intended to reduce its occurrence. ESRD remains an important component of the costs of heart transplantation.     

Photochemical and photobiological studies with acridine and phenanthridine hydroperoxides in cell-free DNA

The main problem in organ transplantation is the continuing shortage of organ donors. Despite all efforts no major significant increases in organ availability are observed during the year 1996 in the participating Eurotransplant counties, while the demand i.e. the waiting lists are still increasing. Shortage of organs will also have its effects and constraints on the distribution i.e. the allocation of scarce organs. To meet the demand of the renal transplantation programs a special kidney allocation system was designed based upon many simulation studies. Already a few months after implementation of the new system very promising results were observed i.e. the discrepancies between the different countries in terms of kidney procurement and transplantation frequencies disappeared. Furthermore, twice as much long waiting kidney patients have been transplanted as previously and the percentage of well matched HLA donor-recipient combinations remained surprisingly high, nearly 24%.     

The prevention and treatment of complications related to the removal of the mandibular third molar when it is retained

Whole pancreas transplantation is becoming a real and safe option for treatment of type 1 diabetic patients. Several controversial issues are still waiting for answers. Portal drainage has been reported to be a possible alternative to systemic drainage, but no prospective data comparing the two techniques is available yet. Further data comparing enteric and bladder drainage is also overdue. With new immunosuppressive agents, isolated pancreas transplantation may also gain better survival and wider application.     

Successful transplantation of porcine livers after warm ischemic insult in situ and cold preservation including postconditioning with gaseous oxygen

BACKGROUND: In order to reduce the shortage of viable donor livers for organ transplantation, a method has been developed that allows even predamaged livers from nonheartbeating donors to be used as transplantable organs. METHODS: Porcine livers were harvested 45 min after cardiac arrest of the nonheparinized donor, preflushed with heparinized saline solution, and subsequently rinsed with University of Wisconsin solution, to which superoxide dismutase was added as an oxygen free radical scavenger. Thereafter, the livers were persufflated with gaseous oxygen via the venous vascular system while immersed in University of Wisconsin solution at 4 degrees C for 4 to 5 hr. RESULTS: After orthotopic transplantation, all of the livers conditioned with gaseous oxygen were able to support life-sustaining function during the whole observation period of 7 days post transplantation, while no survival of the recipients could be obtained without the described treatment. CONCLUSIONS: The present study establishes a new perspective for the use of ischemically altered livers from nonheartbeating donors for organ transplantation under clinical circumstances.