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Biomedical subjects

P J Friend

Publications and source records attributed to P J Friend.

At least 55 records · Page 3Linked to original sources
PubMed1996

Heart-lung-liver transplantation.

We report three patients with cystic fibrosis and one patient with primary biliary cirrhosis and plexogenic pulmonary hypertension who have undergone heart-lung-liver transplantation as a combined procedure. Liver transplantation was necessary in the three patients with cystic fibrosis because of portal hypertension secondary to either hepatic fibrosis or established cirrhosis in addition to their advanced lung disease. Three of the four patients were alive at 20, 50, and 100 months after transplantation (one patient with cystic fibrosis died on day 16 of pneumonia) with well-preserved pulmonary function (forced expiratory volume in 1 second 110%, 49%, and 100% predicted, respectively), normal hepatic function and New York Heart Association class 1 performance status. Heart-lung and concurrent liver transplantation is a feasible and successful procedure with a satisfactory long-term outcome in selected patients with advanced pulmonary and hepatic disease.

Adult↗
PubMed1995

Anti-CD45 monoclonal antibody perfusion of human renal allografts prior to transplantation. A safety and immunohistological study. CD45 Study Group.

The perfusion of kidneys with anti-CD45 monoclonal antibodies prior to transplantation offers a means of targeting passenger antigen-presenting cells with the aim of reducing the subsequent incidence of rejection episodes. A safety study was performed in humans of such pretreatment in 40 unsensitized recipients of first cadaveric renal grafts, who were followed for 3 months after transplantation. A 50-ml solution containing 2 mg of each of the rat anti-CD45 mAbs YTH 24.5 and YTH 54.12 was injected into the allograft renal artery ex vivo and just before transplantation while the renal vein was kept clamped. No patients died, but 4 grafts were lost. Two were lost due to primary nonfunction, 1 was lost because of late renal artery thrombosis, and 1 was lost to rejection. There were no cases of renal vein thrombosis and 1 trivial renal artery stenosis, and only 2 patients produced human anti-rat antibodies. Between 63.5% and 100% (median 96.4%) of CD45+ cells in the postperfusion biopsies were coated with anti-CD45 as determined by double-immunolabeling. The number of patients experiencing rejection episodes was inversely associated with this "antibody uptake": 75% of the low uptake group (< 95%) had at least 1 rejection episode, compared with 22% of the high uptake group (> or = 95%) (P = 0.001). The complement components C3 and C5b-9 colocalized with perfused anti-CD45 in 32/33 (97.0%) and 11/33 (33.3%) of the biopsy specimens, respectively. We conclude that: (1) this technique appears free of adverse effects, (2) high antibody uptake within the kidney is associated with a lower incidence of rejection, and (3) the antibodies used fix and activate complement in vivo.

Adult↗
PubMed1995

CsA levels in the early posttransplant period--predictive of chronic rejection in liver transplantation?

The increasing success of clinical liver transplantation has brought rejection to the forefront as a cause of morbidity and graft loss. The relationship of immunosuppressive drug doses and levels to acute and chronic rejection remains a matter of debate. The effect of blood CsA levels and drug doses on the incidence of acute and chronic rejection and the impact of acute rejection episodes on the occurrence of chronic rejection were studied in 146 grafts in 132 patients. These patients were transplanted in the 4-year period from June 1989 using CsA-based immunosuppression (CsA, azathioprine, prednisolone). Liver grafts in patients maintained on median CsA levels (whole blood, trough level) of > or = 175 micrograms/L in the first 28 days posttransplant had a significantly lower incidence of chronic rejection (2 out of 49 vs. 22 out of 97; P = 0.002). There was no significant difference in incidence of graft loss due to fatal sepsis (6% vs. 5%) or nephrotoxicity between the high and low CsA level groups. The overall graft loss rate was lower in the higher CsA level group (22% vs. 37%). The total doses of the individual drugs did not correlate with the incidence of acute or chronic rejection. Although the occurrence of acute rejection itself did not determine later chronic rejection, late occurrence (P < 0.00001) and multiple episodes (two or more; P = 0.0002) of acute rejection were significant risk factors for the occurrence of chronic rejection. We conclude that to minimize graft loss to rejection, CsA levels should be maintained at greater than 175 micrograms/L in the early posttransplant period, and late and recurrent episodes of acute rejection should be prevented.

Adult↗
PubMed1995

Liver transplantation in patients with situs inversus.

Seven patients with situs inversus abdominis and one with situs inversus totalis underwent liver transplantation; all are alive at follow-up of between 7 months and 5 years. Two patients required retransplantation within the first 3 weeks (for primary non-function and thrombotic infarction). Seven had additional abnormalities associated with the polysplenia-biliary atresia syndrome. Liver transplantation in these patients involved selection of relatively small donor organs or use of reduced-size grafts. Delayed abdominal wall closure was necessary in two patients and all required a modification of the 'piggy-back' technique of suprahepatic vena caval anastomosis to overcome recipient venous anomalies. Biliary drainage by Roux-en-Y choledochojejunostomy was the preferred technique. Although technically challenging, situs inversus is not a contraindication to liver transplantation and patients should expect full recovery.

Anastomosis, Roux-en-Y↗
PubMed1995

Liver transplantation for hepatic arteriovenous malformation in hereditary haemorrhagic telangiectasia.

Symptomatic hepatic involvement is a rare complication of hereditary hemorrhagic telangiectasia and most commonly consists of fibrosis or cirrhosis. We describe a 33-year-old woman in whom multiple hepatic arteriovenous malformations led to high output cardiac failure and liver failure due to biliary necrosis with refractory biliary sepsis, requiring orthotopic liver transplantation. Hepatic arteriovenous malformations were the first manifestation of the disease and a similar asymptomatic hepatic tumour was subsequently detected in her 60-year-old father who also had the classical cutaneous stigmata of the syndrome. Unrecognised genetic factors may determine the clinical spectrum of hereditary haemorrhagic telangiectasia including the hepatic manifestations.

Adult↗
PubMed1995

Twenty-seven years of liver transplantation at Addenbrooke's Hospital, Cambridge.

Twenty-seven years ago, liver transplantation at Addenbrooke's Hospital was a very experimental procedure. It is now recognized as an accepted mode of treatment for end-stage liver failure. In the coming year, over 600 liver transplants will take place in the United Kingdom. All western European countries now have an active liver transplantation program and more than 17,000 liver transplants have already been performed. As results improve and the procedure becomes more readily and widely accepted, the donor shortage is likely to get worse, and will be only partially met by the introduction of split livers and living-related donors.

Adolescent↗
PubMed1994

Serum alpha-glutathione S-transferase--a sensitive marker of hepatocellular damage associated with acute liver allograft rejection.

The wide hepatic distribution, high cytosolic concentration, and short in vivo plasma half-life of serum alpha-glutathione s-transferase are properties which may make monitoring this enzyme more clinically useful than conventional biochemical liver function tests as a marker of hepatocellular damage associated with acute liver allograft rejection. In a prospective longitudinal study of 58 liver transplants in 45 patients, serum alpha-glutathione S-transferase concentrations rose significantly more consistently and more rapidly than conventional liver function tests in association with acute rejection. However, a rise in alpha-glutathione S-transferase was less specific for rejection than conventional liver function tests although none of the tests had a positive predictive value for rejection of greater than 32%. Compatible with the particularly short in vivo plasma half-life of this enzyme, alpha-glutathione S-transferase concentrations fell to or toward normal more rapidly than conventional liver function test measurements following uncomplicated transplantation as well as during high-dose steroid treatment of rejection. This may be valuable, both in improving the resolution of biochemical changes associated with early rejection episodes and in determining when treatment of rejection has been successful. Further studies are warranted, however, to assess whether the fall in GST during rejection treatment does genuinely reflect the histological resolution of rejection.

Adolescent↗
PubMed1994

Biliary tract reconstruction: comparison of different techniques after 187 paediatric liver transplantations.

Biliary complications after liver transplantation are common and cause significant morbidity and mortality. In order to evaluate the complications related to different sorts of biliary reconstruction, from January 1984 to July 1992 we retrospectively analysed 187 consecutive liver transplants in 136 paediatric patients at Addenbrooke's Hospital, Cambridge. There were 51 (27.2%) retransplantations. Biliary reconstruction consisted of: type 1-common bile duct-Roux loop (CBD-RL); n = 90 (48.1%); type 2-gallbladder conduit-Roux loop (GC-RL), n = 51 (27.2%); type 3-gallbladder conduit-common bile duct (GC-CBD), n = 20 (10.6%); type 4-common bile duct-common bile duct (CBD-CBD), n = 18 (9.6%); and type 5-common bile duct-common bile duct+gallbladder drainage (CBD-CBD+GB), n = 8 (4.2%). There were, in all 26 biliary complications (14%). Of these 26 complications, biliary stricture was the most common (17/26; 65.3%) and 6 out of these 17 (35.2%) were associated with chronic rejection. Hepatic artery thrombosis was directly related to biliary leakage in 6 out of 26 (23.1%) biliary tract complications. This series demonstrated that type 1 and type 4 reconstructions were related to fewer biliary complications (9/90, 10% and 2/18; 11%, respectively) than the other techniques: 8/51 (16%) for GC-RL 5/20 (25%) for GC-CBD and 2/8 (25%) for CBD-CBD+GB (P = 0.09).

Adolescent↗
PubMed1994

Antibiotic irrigation and conservative surgery for major aortic graft infection.

PURPOSE: Traditional surgical treatment for panprosthetic aortic graft infection entails radical excision of the graft, aortic stump closure, and extraanatomic revascularization of the lower limbs. This carries an early mortality rate of 24% to 45%. Amputation rates range from 11% to 37%. Multiple operations and prolonged hospital stay are usual. We have developed a more conservative management technique with the aim of improving outcome. METHODS: We describe an innovative method of treating the condition with prolonged, high-dose, local antibiotic irrigation therapy, systemic antibiotic treatment, surgical debridement, and graft conservation in a prospectively studied series of 10 patients. RESULTS: The actual 30-day patient survival rate is 90%, the 1-year survival rate is 80%, and the 4-year survival rate is 67%. Two patients died because of graft infection, and the third died, uninfected, of an unrelated cause. No limbs have been amputated. Only two patients required a second operation. Mean postoperative hospital stay was 32 days. The seven survivors have been closely followed up with regular computed tomography or indium scanning and clinical examination and appear to be free from infection at a mean of 61 months after cessation of irrigation therapy. CONCLUSION: The technique appears to represent a significant improvement in the management of this major complication of vascular surgery.

Adult↗