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Biomedical subjects

P J Friend

Publications and source records attributed to P J Friend.

At least 19 recordsLinked to original sources
PubMed2006

Retrieval of abdominal organs for transplantation.

BACKGROUND: Organ retrieval and donor management are not yet standardized. Different transplant centres apply various techniques, such as single or dual organ perfusion, dissection in the cold or warm, and single or en bloc organ removal. These different approaches may cause inconvenience, especially when more than one organ retrieval team is involved. METHODS: Cochrane Library, Medline and PubMed were searched for publications on multiorgan donor/donation, retrieval technique and procurement. Levels of evidence and grades of recommendation were evaluated based on current advice from the Oxford Centre for Evidence-Based Medicine. RESULTS: Multiorgan donation itself does not compromise the outcome of individual organ transplants. Dissection of abdominal organs for transplantation is best performed after cold perfusion. Abdominal organs should be removed rapidly, en bloc, and separated during back-table dissection in the cold, particularly if pancreas or intestine is included. Perfusion itself should be carried out after single cannulation of the aorta with an increased pressure. CONCLUSION: Although the literature on organ retrieval is extensive, the level of evidence provided is mainly low. Nevertheless, optimized donor treatment and organ retrieval should increase the number and quality of cadaveric donor organs and improve graft function and survival.

Abdomen↗
PubMed2006

Tamoxifen therapy in encapsulating sclerosing peritonitis in patients after kidney transplantation.

Sclerosing encapsulating peritonitis (SEP) is a serious complication of long-term continuous ambulatory peritoneal dialysis (CAPD) associated with obstructive symptoms and sclerosis of the peritoneal membrane. We present two cases that were successfully treated with tamoxifen and corticosteroids. Case 1: A 40-year-old patient developed end-stage renal failure (ESRF) and was managed with CAPD. He was hospitalized with symptoms of small bowel obstruction. He underwent laparotomy confirming the diagnosis of SEP. The patient was given tamoxifen 20 mg twice a day. Case 2: A 55-year-old patient with ESRF secondary to membranous glomerulonephritis. After having a cadaveric renal transplant in 1978 that failed 20 years later, the patient returned to CAPD. Six years later he had an uneventful kidney transplant and the peritoneal dialysis catheter was removed. However, 8 months later he presented with symptoms of small bowel obstruction and gross blood stained ascites. He also underwent a laparotomy that confirmed the diagnosis of SEP after biopsy. The patient was started on 20 mg of tamoxifen twice a day. Both patients' symptoms were improved gradually with an increase of serum albumin and body weight. Tamoxifen may be useful in the treatment of patients diagnosed with SEP.

Adult↗
PubMed2006

PBS140: new competition in the organ preservation market?

PBS140 offers good cold preservation in renal transplantation and now, crucially, has been shown to promote immediate function following warm ischemia. For a new cold preservation solution to compete with UW solution, improved efficacy and lower price may not be enough. Reducing rates of delayed graft function in organs from non-heart-beating and marginal donors might be the key.

Adenosine↗
PubMed2005

The safety and feasibility of extracorporeal high-intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population.

High-intensity focused ultrasound (HIFU) provides a potential noninvasive alternative to conventional therapies. We report our preliminary experience from clinical trials designed to evaluate the safety and feasibility of a novel, extracorporeal HIFU device for the treatment of liver and kidney tumours in a Western population. The extracorporeal, ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) has been used to treat 30 patients according to four trial protocols. Patients with hepatic or renal tumours underwent a single therapeutic HIFU session under general anaesthesia. Magnetic resonance imaging 12 days after treatment provided assessment of response. The patients were subdivided into those followed up with further imaging alone or those undergoing surgical resection of their tumours, which enabled both radiological and histological assessment. HIFU exposure resulted in discrete zones of ablation in 25 of 27 evaluable patients (93%). Ablation of liver tumours was achieved more consistently than for kidney tumours (100 vs 67%, assessed radiologically). The adverse event profile was favourable when compared to more invasive techniques. HIFU treatment of liver and kidney tumours in a Western population is both safe and feasible. These findings have significant implications for future noninvasive image-guided tumour ablation.

Adult↗
PubMed2005

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Acute Disease↗
PubMed2003

Adult small intestinal transplantation in England and Wales.

BACKGROUND: In 1996 two transplantation centres in the UK were commissioned by the National Specialist Commissioning Advisory Group for England and Wales to assess small intestinal transplantation in adults. The joint experience of the two centres is presented. METHODS: Patients with irreversible small intestinal failure and complications of parenteral nutrition, and those with abdominal disease requiring extensive visceral resection, were assessed as candidates and where appropriate listed for surgery. RESULTS: Thirty-six patients were assessed for small intestinal transplantation and, of these, 14 underwent surgery. Twelve patients survived the transplantation procedure. Of these, seven patients were alive at 1 year, five at 3 years and three at 5 years. Three patients remain alive. Patient and graft survival improved with experience; the 1-year survival rate improved in the last 4 years of this experience from 43 to 57 per cent, and the 3-year survival rate from 29 to 43 per cent. CONCLUSION: Small intestinal transplantation is associated with a high mortality rate but may benefit carefully selected patients in whom conservative management is likely to carry a greater mortality rate.

Adult↗
PubMed2003

Relapsing encephalopathy following small bowel transplantation.

We report a case of a 40-year-old man presenting with relapsing encephalopathy 4 years post-intestinal transplantation. Each episode was preceded by symptoms suggestive of subacute intestinal obstruction, marked dehydration, and, on one occasion, grade 4 encephalopathy. Physical examination revealed hypertonia, clonus, and hyperreflexia. Biochemistry was consistent with renal impairment, metabolic alkalosis, hyperammonaemia, and normal liver function. Plain radiographs and abdominal computed tomography revealed dilated proximal small bowel loops, and barium radiography demonstrated a strictured distal anastomosis. Hydrogen breath testing indicated bacterial overgrowth. Following rehydration and antibiotic therapy, the patient recovered fully between episodes. Further episodes of encephalopathy did not recur following resection of the distal anastomotic stricture and resolution of bacterial overgrowth. Unfortunately, one year later the patient died of pneumonia. To the best of our knowledge, encephalopathy secondary to intestinal transplant related porto-caval shunt and bacterial overgrowth in strictured bowel has not been previously reported but might have implications for the management of future patients.

Adult↗
PubMed2003

Hepatic control of perfusate homeostasis during normothermic extrocorporeal preservation.

BACKGROUND: We investigated the ability of the isolated porcine liver to maintain acid-base homeostasis in the perfusate and the impact of ischemia-reperfusion injury without or with extracorporeal perfusion. METHODS: Harvested livers were either stored for 24 hours in cold University of Wisconsin solution or preserved by continuous, normothermic, oxygenated sanguineous perfusion with supplemental nutrition, prostacyclin, and bile salts. After a further 24-hour period of reperfusion of both groups on an extracorporeal circuit, the perfusate was assessed for both biochemical indices of synthetic and metabolic liver function as well as hepatocellular injury and blood gas analysis. RESULTS: Livers injured by cold ischemia during preservation displayed inferior synthetic and metabolic functions. Perfused livers, which displayed minimal ischemic injury, produced more bicarbonate than the cold-stored organs, suggesting autoregulation of pH homeostasis in perfused livers in contrast to progressively worsening acidosis in cold-stored organs. CONCLUSIONS: Given proper physiologic substrate the porcine liver has the ability to maintain acid-base homeostasis, provided there is not a significant ischemia-reperfusion injury.

Adenosine↗
PubMed2002

Extended preservation of non-heart-beating donor livers with normothermic machine perfusion.

BACKGROUND: Non-heart-beating donor (NHBD) livers represent an important organ pool, but are seldom utilized clinically and require rapid retrieval and implantation. Experimental work with oxygenated perfusion during preservation has shown promising results by recovering function in these livers. This study compared sanguinous perfusion with cold storage for extended preservation of the NHBD liver in a porcine model. METHODS: Porcine livers were subjected to 60 min of in vivo total warm ischaemia before flushing, after which they were preserved by one of two methods: group 1 (n = 4), University of Wisconsin (UW) solution by standard cold storage for 24 h; group 2 (n = 4), oxygenated autologous blood perfusion on an extracorporeal circuit for 24 h. All livers were subsequently tested on the circuit during a 24-h reperfusion phase. RESULTS: Livers in group 1 showed no evidence of viability during the reperfusion phase with no bile production or glucose utilization; they also displayed massive necrosis. Livers in group 2 demonstrated recovery of function by synthetic function, substrate utilization and perfusion haemodynamics; these livers displayed less cellular injury by hepatocellular enzymes. All differences in parameters between the two groups were statistically significant (P < 0.05). These findings were supported by histological examination. CONCLUSION: Warm ischaemia for 1 h and simple cold storage (UW solution) for 24 h renders the liver non-viable. Oxygenated, sanguinous perfusion as a method of preservation recovers liver function to a viable level after 24 h of preservation.

Animals↗
PubMed2001

Combined transplantation of the heart, lung, and liver.

Combined transplantation of the heart, lung, and liver may be indicated in patients with either end-stage respiratory failure complicated by advanced liver disease or end-stage liver failure complicated by advanced lung disease. A retrospective review of nine patients who underwent combined heart-lung-liver transplantation in Cambridge (1986-99) was carried out. The 1-year and 5-year actuarial survival was 56% and 42%, respectively. Combined heart-lung-liver transplantation is a feasible option for a few patients and has a 5-year survival similar to heart-lung transplantation but with a lower incidence of acute and chronic rejection.

Adolescent↗
PubMed2001

Physiological aspects of pig-to-primate renal xenotransplantation.

BACKGROUND: Few data exist on the physiological aspects of pig-to-primate renal xenotransplantation. METHODS: Use of organs transgenic for human decay accelerating factor has allowed assessment of the metabolic and hormonal functions of these xenografts. RESULTS: Porcine renal xenografts largely maintain plasma electrolyte homeostasis. An increase in proteinuria was detected that may result from graft injury. In contrast to allotransplantation a severe anaemia developed requiring recipient treatment with exogenous human erythropoietin. CONCLUSIONS: Our experience provides qualified encouragement for the likely physiological compatibility of pig and primate species, but identifies areas where a xenograft may not match the performance of an allograft.

Anemia↗
PubMed2000

Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.

BACKGROUND: Recently, there has been a resumed interest in clinical xenotransplantation using pig organs. However, no data are available yet regarding the capacity of porcine organs to sustain the life of a primate beyond the first month. We have attempted to obtain long-term survival of nonhuman primates using human decay-accelerating factor (hDAF) transgenic pig organs and an immunosuppressive strategy particularly aimed at neutralizing the humoral component of the immune response. METHODS: hDAF transgenic or control kidneys were transplanted into 14 bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) that underwent splenectomy and were immunosuppressed with cyclosporine A, cyclophosphamide, and steroids. All animals also received recombinant erythropoietin. Postoperatively, the primates were monitored daily. Laboratory evaluations included serum biochemistry, hematology, and measurements of hemolytic antipig antibodies. To assess the role of splenectomy in the control of humoral response, historical data were also used from a group of monkeys (n=7) that received the same immunosuppressive regimen and an hDAF transgenic porcine kidney but did not have splenectomy or receive recombinant erythropoietin. RESULTS: This immunosuppressive approach obtained the longest survival time (78 days) described to date of a primate receiving a life-supporting porcine renal xenograft. Furthermore, four of nine animals in this series survived for 50 days or more. Most biochemical measurements in this study (including plasma urea, creatinine, sodium, and potassium concentrations) remained within normal ranges for several weeks in all of the longest-surviving animals. CONCLUSIONS: Normalization of renal function (urea and creatinine) in primate recipients of porcine renal xenografts suggests that pig kidneys may be suitable for future clinical xenotransplantation. Additional immunosuppressive approaches, specifically designed to prevent humorally mediated immunological damage, should be explored to further prolong survival of primates that have received porcine xenografts.

Animals↗
PubMed2000

Growth of porcine kidneys in their native and xenograft environment.

The increased survival of hDAF pig-to-primate renal xenografts for up to two months has afforded the opportunity to study physiological aspects such as organ growth. Experimental evidence exists of species restriction of the activity of growth hormone, although growth itself is also controlled by a number of other endocrine, paracrine and autocrine substances. This study consisted of four parts: (1) measurement of pig kidney size according to pig body weight; (2) measurement of pig kidney size according to pig age; (3) serial length measurement of pig-to-primate renal xenografts; (4) correlation of terminal weight of renal xenograft with age and histology. The xenografted pig kidneys in a primate recipient grow as they would in the pig for the first two weeks after transplantation. After this time there is a reduction in the rate of increase in the length of the xenograft. Over the same period, changes in weight are greatly increased by the presence of rejection. This observational study supports the notion that regulation of growth of a xenotransplanted porcine kidney occurs.

Animals↗
PubMed2000

Xenotransplantation.

BACKGROUND: The success of clinical transplantation has led to a large discrepancy between donor organ availability and demand; considerable pressure exists to develop an alternative source of organs. The use of animal organs for donation is a possible solution that is not yet clinically applicable. METHODS AND RESULTS: A literature review was performed based on a Medline search to find articles on xenotransplantation. Keywords included hyperacute, acute vascular, xenograft rejection combined with concordant and discordant. Additional references cited in these articles from journals not included in Medline were obtained from the British Library. Limited information on unpublished, preliminary work has been included from sources known to the authors, based on their research work in the field. One hundred and forty-six references and four personal communications have been included in this review article. CONCLUSION: A greater understanding of the pathogenesis of xenograft rejection is developing rapidly. Strategies to abrogate hyperacute rejection have proved successful, but control of antibody-driven acute vascular rejection has not yet been achieved. The safety and viability of xenotransplantation as a therapeutic modality are still unproven.

Animals↗
PubMed2000

Prope tolerance with induction using Campath 1H and low-dose cyclosporin monotherapy in 31 cadaveric renal allograft recipients.

The last 40 years has been a period of remarkable evolution of organ transplantation from nothing to a well-established form of treatment with good short-term and tolerable long-term results. Nevertheless by ten years approximately 50% of grafts will have been lost due, mainly, to chronic rejection or the side-effects of immunosuppressive therapy. We now have a number of extremely powerful immunosuppressive drugs and antibodies with different mechanisms of action and the stage is set for a move from current continuous high dose immunosuppressive maintenance therapy to low dose or no maintenance immunosuppression. True tolerance can occur in man, examples being successful bone marrow transplantation and patients with liver grafts who have stopped immunosuppression after years of good function. The antibody Campath 1H with a unique target CH52 on T & B lymphocytes and monocytes has been used to eliminate lymphocytes from the blood for a month in patients with renal allografts who have then been maintained on half dose Cyclosporin without any other maintenance drug. The results with a mean two year follow-up have been encouraging, 29 patients having good function without receiving maintenance steroids. It is likely that this protocol could be improved since dosage timing and various minimal maintenance immunosuppressive protocols have not been fully investigated. This almost or "Prope" tolerance could be a major step forward providing a better quality of life for patients and inexpensive maintenance immunosuppression.

Adult↗
PubMed1999

Phase I study of an engineered aglycosylated humanized CD3 antibody in renal transplant rejection.

BACKGROUND: The potential therapeutic benefits of CD3 monoclonal antibodies, such as OKT3, have been limited by their immunogenicity and their propensity to activate a severe cytokine release syndrome. This has constrained the clinical use of OKT3 to the treatment of acute rejection episodes of organ allografts. METHODS: We have humanized a rat CD3 antibody and created a single amino acid substitution in position 297 of the IgG1 heavy chain to prevent glycosylation and, consequently, binding of the therapeutic antibody to Fc receptors and to complement. This antibody has been given as first line antirejection therapy in nine kidney transplant recipients with biopsy-proven acute rejection episodes. RESULTS: None of the patients demonstrated any antiglobulin response nor any significant cytokine release syndrome. Seven of the nine showed evidence of resolution of their rejection, although some patients experienced re-rejection. CONCLUSIONS: These findings suggest that CD3 antibodies can be engineered to lose their toxicity while retaining their potency as immunosuppressants. Nonactivating humanized CD3 monoclonal antibodies now merit further investigation in the management of transplant patients and in therapy of autoimmune diseases.

Amino Acid Substitution↗