Continuous positive airway pressure-associated cutaneous amoebiasis in an immunosuppressed patient.

Organisms of the genus Acanthamoeba are environmentally ubiquitous and colonizers of the oral mucosa in humans. While largely asymptomatic in healthy persons, Acanthamoeba infection can cause disseminated disease with poor prognosis in immunosuppressed populations. Here we report a unique case of cutaneous amoebiasis associated with continuous positive airway pressure use in an immunosuppressed patient.

Method for home monitoring of urinary amylase after pancreas transplantation.

Urinary amylase activity (UAA) is used for diagnosis of rejection in bladder-drained pancreas grafts. Unfortunately, most rejection episodes occur after the patient has been discharged. In those cases, an early diagnosis is often difficult, and a method for home UAA monitoring is needed. We have developed a method that can be used for this purpose. The method, based on Kodak dry-film technology, is shown to have good response to the wide range of UAA seen in these patients compared with responses to standard laboratory kinetic methods. The analysis (performed by the patient) involves 1) collecting urine for 24 h in a 4-L container, 2) diluting the urine with tap water to a total urine of 4 L, and 3) placing a drop of this dilution onto a slide. The slide is read by a handheld spectrophotometer that displays the UAA in secreted units per hour. The reliability of this system has been tested for wide changes of urine pH, volume of the drop applied to the slide, and tap water from different sources. Temperature coefficients have been determined to correct changes in ambient temperatures. The final handheld prototype is being developed based on these preliminary studies. This device could be of benefit for the early diagnosis of rejection episodes in recipients of bladder-drained pancreas grafts after hospital discharge.

The chyloesophageal fistula. A new approach to thoracic duct drainage.

The main reason for the virtual abandonment of external thoracic duct drainage as an immunosuppressive measure is not its lack of efficacy, but the time-consuming technical problems of maintaining cannula patency and replacing the large obligatory losses of fluid and protein. In an effort to overcome these problems we have devised a method of diverting thoracic duct lymph internally into the esophagus of the sheep, our hypothesis being that fluid and protein should be resorbed, but lymphocytes and antibodies destroyed. By isolating that part of the venous system into which the thoracic duct drains and anastomosing this conduit to the cervical esophagus a chyloesophageal fistula was created. A mean patency of 19 days was demonstrated radiologically and there was a reproducible peripheral blood lymphopenia of over 50% of preoperative values at 4 weeks. Although plasma albumin levels fell from 37 g/L to 29 g/L at 1 week, they remained stable thereafter. No parenteral fluid or protein was administered, yet the animals remained well with no significant weight loss or overt signs of dehydration or hypoproteinemia. Skin allograft mean survival time was prolonged from 9 to 11.8 days (P less than 0.01).

Adenosine triphosphate regeneration and function in the rat kidney following warm ischaemia.

Tissue levels of adonosine triphosphate (ATP) have been measured in rat kidneys following periods of warm ischaemia: (1) immediately after the ischaemic period and (2) after the kidney had been reperfused with blood for 10 min. ATP levels at the end of the period of ischaemia are similar for ischaemic periods of 10 to 60 min and give no indication of the kidneys subsequent functional ability. The amount of ATP regenerated in 10 min of reperfusion correlates both with the duration of the period of ischaemia and with the subsequent functional ability of the kidney.

Evaluation of sequential plasma and urinary tumor necrosis factor alpha levels in renal allograft recipients.

The macrophage cytokine tumor necrosis factor-alpha is released early in immune activation and may be detected in the peripheral circulation. This study has investigated the occurrence of plasma and urinary TNF in 30 renal allograft recipients. Although circulating TNF may be detected in 20% of pretransplant or normal control samples, levels were significantly elevated during 65% of allograft rejection episodes. Plasma TNF levels did not rise in graft failure due to acute tubular necrosis, but were always highly raised in systemic infection. In contrast, urinary TNF was only detected in association with acute rejection (49%) or tubular necrosis (14%), and no controls had detectable urinary TNF. These findings indicate that evaluation of circulating and excreted TNF may give further insight into the immunobiology of graft rejection.

The new chimaera: the industrialization of organ transplantation. International Forum for Transplant Ethics.

Clinical organ transplantation has evolved through advances in patient care in parallel with investigations in associated biologies. It has developed from a cottage industry to an important medical specialty driven increasingly by the availability of newer and more effective immunosuppressive drugs, and dependent on consistently close collaborations between university-based clinical scientists and the pharmaceutical industry. Particularly during the past decade, however, this industry has undergone striking changes, consolidating into huge multi-national corporations, each competing for patients, their doctors, and for support of the allied hospitals. Because of the growth of "Big Pharma," the relationship between academia and industry has changed. There have been many advantages to such mutually dependent interactions. A combination of university-based expertise and the specialized knowledge and resources of industry have produced important scientific gains in drug development. Commercial sponsorship of applied research has been crucial. The orchestration of multicenter controlled clinical drug trials has provided invaluable information about the effectiveness of newer agents. But there are also disadvantages of increasing concern. Indeed, the power of "Big Pharma" in many medical fields including transplantation is such that presentation of data can be delayed, adverse results withheld, and individual investigations hampered. Clinical trials may be protracted to stifle competition. Monetary considerations may transcend common sense. Several measures to enhance the clinical relationship between the pharmaceutical industry and those involved with organ transplantation are suggested, particularly the use of third party advisors in the production of clinical trials, support for more basic research and in the dissemination of results. In this way, the increasingly problematic phenomenon of commercialization of the field of transplantation can be tempered and controlled.

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation.

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.

Localization of C-X-C and C-C chemokines to renal tubular epithelial cells in human kidney transplants is not confined to acute cellular rejection.

Chemokines are important mediators of leucocyte chemoattraction to inflammatory sites. Previous work has shown that the expression of some chemokines is upregulated during renal transplant rejection. The objectives of the present study were to determine whether chemokine expression is increased during renal transplant rejection. Immunohistochemistry was used to localize the C-X-C (alpha) chemokine interleukin-8 (IL-8) and the C-C (beta) chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) in 30 needle biopsies of human kidney transplants taken for diagnosis of renal dysfunction. Urine samples from transplant patients taken immediately prior to biopsy were assayed for chemokine content using enzyme-linked immunosorbent assays (ELISAs). Results from groups of patients having different clinicopathological diagnoses were then compared. All three chemokines were detected in most renal transplant biopsies showing acute cellular rejection but, although infiltrating leucocytes were often positive, staining was predominantly localized to renal tubular epithelium. Staining for MCP-1 was generally weaker than for the other chemokines, and collecting tubules were usually stained more strongly than proximal convoluted tubules. Tubular epithelial staining was also found in biopsies from patients without signs of acute cellular rejection. There were significantly higher amounts of IL-8 in the urine of patients with acute cellular rejection, even when patients with urinary tract infections were excluded, but mean titres of urinary MIP-1beta did not differ between patient groups. This was also found when titres were normalized for urine volume and creatinine levels. Production of IL-8, MCP-1 and MIP-1beta is not confined to kidney transplants showing acute cellular rejection, and may be a relatively nonspecific response of tubular epithelial cells to renal damage.

Contaminated renal allografts.

Bacterial contamination of a renal allograft may cause infection of the transplant with eventual loss of the graft and possibly death of the patient. We report two cases that illustrate these complications and that support the suggestion that culture of the transport medium is a valuable investigation prior to transplantation.

Pregnancy does not adversely affect renal transplant function.

Women with functioning transplanted kidneys often become fertile again. Indeed, renal function, endocrine status and libido rapidly improve after renal transplantation, and 1:50 women of childbearing age become pregnant. However, there is concern regarding the haemodynamic changes of pregnancy, which could lead to a decline in graft function (temporary or permanent). We examined obstetric data and renal parameters in 29 patients and 33 pregnancies. Mean serum creatinine and creatinine clearance remained stable throughout pregnancy and 1 year postpartum. However, there was a significant increase in proteinuria from a mean of 0.45 g/24 h around the time of conception to 1.11 g/24 h at delivery (p<0.05). The proteinuria resolved to baseline levels at 3 months postpartum. We highlight certain parameters to be considered before conception to allow a good obstetric outcome and prolong stable renal function: serum creatinine <150 micromol/l, proteinuria <1 g/day, absence of histological evidence of chronic allograft rejection, controlled blood pressure (140/90) and stability of maintenance immunosuppression.

Ocular complications of systemic steroid after renal transplantation and their association with HLA.

The eyes of 62 patients who had received allogenic renal transplants were examined for eye disease. Thirty-six patients were found to have steroid induced cataract. Six patients had ocular hypertension. Twelve patients showed arteriosclerotic changes in their fundi relating to their previous hypertensin. There was no significant difference in HLA type in patients who developed cataract and those who did not. 83.3% of the 6 patients with ocular hypertension had HLA B12 in common. None of the patients had cytomegalic retinitis.

Stabilisation of diabetic retinopathy following simultaneous pancreas and kidney transplant.

BACKGROUND/AIMS: Simultaneous pancreas and kidney transplantation (SPK) has become an important option in selected IDDM patients with end stage renal disease (ESRD). Successful SPK transplants are associated with long term normoglycaemic control and improved quality of life. However, debate still continues on the benefit to patients in terms of stabilisation or amelioration of diabetic retinopathy. The progression of diabetic retinopathy (DR) in a cohort of 20 SPK transplant patients is reported. METHODS: All patients were reviewed postoperatively with corrected visual acuity, slit lamp examination, and fundal biomicroscopy. Preoperative data were collected retrospectively and DR was considered unstable if there had been a drop in Snellen acuity greater than three lines or a need for laser photocoagulation or vitrectomy in the 2 years preoperatively. RESULTS: 20 patients who received SPK transplants between March 1983 and April 1994 were reviewed (mean age 35.1 years; mean duration of IDDM = 24.6 years). 17 patients still had functioning grafts at a mean follow up of 5.1 years. Nine of these patients had unstable DR before transplantation. Of these, 89% (8/9) had stabilised DR following transplantation with only a single case requiring laser photocoagulation. Of the eight patients that had stable DR before transplantation all had stable DR following transplantation. 41% of cases (7/17) required cataract surgery during the follow up period. CONCLUSIONS: Advanced diabetic retinopathy is present in a high proportion of cases managed with SPK transplant as a consequence of the duration of IDDM and the presence of ESRD. More than 90% of cases have stable DR following transplant.

Some ethical issues in organ retrieval, 1982 to 1992.

The debate on incentive payments and related issues will continue so long as dialysis and cadaver donation remain out of the reach of physicians in developing countries. This article (from a Western doctor) steps outside the usual debate on these issues by making a practical suggestion which aims at easing the ethical tension of incentive donation rather than insisting on its abolition. "Donors' trusts" may help the situation in India, but should not be applied in any country where effective dialysis is generally available. Nor would I be happy for such a model to be developed in any country where the aim to introduce cadaveric organ donation was not being energetically pursued.

Core needle biopsy in renal transplantation.

Core biopsies have been done by ultrasound assisted 18-G disposable needles with a spring loaded gun (Biopty) system in 140 renal transplant cases either for investigation of an early non-functioning graft or evaluation of deteriorating graft functions. The biopsy procedure was successfully completed in 99.5% and sufficient amount of renal tissue was obtained in 88% of cases. The pathological diagnoses were confirmed 100% by the other clinical parameters of cases with acute cellular rejection, pyelonephritis, acute tubular necrosis and there was disease recurrence. In another 8 patients (6%) where the pathological picture was showing either no or nonspecific changes there was no major change in clinical outcome. In addition, clinical diagnoses of chronic vascular rejection and Cyclosporin A toxicity were confirmed in 93.7% and 91.7%, respectively, in biopsies of these cases. Complications were seen in 3 patients as a bowel perforation, intra-abdominal bleeding and formation of an intrarenal arterio-venous fistula. In former two complicated cases there was no need for any extra treatment but the arterio-venous fistula was successfully embolized through an angiography catheter without losing the graft. We conclude that the Biopty system is more efficient than the fine needle aspiration biopsy especially when the pathological diagnosis can be made upon tissue components rather than cells alone.

Elective ventilation of potential organ donors.

Elective ventilation describes the procedure of transferring selected patients dying from rapidly progressive intracranial haemorrhage from general medical wards to intensive care units for a brief period of ventilation before confirmation of brain stem death and harvesting of organs. This approach in Exeter has led to a rate of kidney retrieval and transplant higher than has been achieved elsewhere in the United Kingdom, with a stabilisation of numbers on patients on dialysis. Recently doubt has been cast on the legality of our practice of elective ventilation on the grounds that relatives are not permitted to consent to treatment of an incompetent person when that treatment is not in the patient's best interests. We are thus faced with the dilemma of a protocol that is ethical, practical, and operates for the greater good but which may be illegal. This article explores various objections to the protocol and calls for public, medical, and legal debate on the issues.