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Biomedical subjects

A E Gimson

Publications and source records attributed to A E Gimson.

At least 19 recordsLinked to original sources
PubMed2005

Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection.

Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression.

Adult↗
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

Treatment of graft-versus-host disease after liver transplantation with basiliximab followed by bowel resection.

Graft-versus-host disease (GVHD) after orthotopic liver transplantation (OLT) is a serious complication with mortality rates over 80%. Two patients with established GVHD after OLT were treated with Basiliximab, a chimeric murine human monoclonal antibody which binds to the alpha-chain of interleukin-2 receptor (IL-2R). Two males, aged 45 and 56 years, presented after OLT with a clinical picture consistent with GVHD. Quantitative measurements of recipient peripheral blood donor lymphocyte chimerism were carried out by flow cytometric analysis, and showed peak chimerism levels of 5% and 8%, respectively. Treatment comprised 3 doses of 1 g methyl prednisolone followed by 2 doses of 20 mg of Basiliximab. In both, treatment resulted in complete disappearance of macro-chimerism in blood. There was resolution of skin rash by day 7; however, diarrhea persisted. White cell scan showed increased uptake in the terminal ileum and small-bowel resection was performed in both patients. One patient is alive and well 36 months after OLT. The other patient had resolution of GVHD, but died of recurrent hepatitis C 1 year after OLT. The combination of immunological and surgical treatment for GVHD following solid organ transplantation has not previously been described.

Antibodies, Monoclonal↗
PubMed2001

Hyperuricemia, gout, and renal function after liver transplantation.

BACKGROUND: Hyperuricemia is a recognized complication of renal and cardiac transplantation, but the development of hyperuricemia and gout following liver transplantation have received less attention. We have retrospectively assessed the prevalence of hyperuricemia in 134 consecutive liver transplant recipients. RESULTS: Forty-seven percent of the liver transplant recipients studied had hyperuricemia. Serum creatinine was higher in hyperuricemic than in nonhyperuricemic patients. Peak uric acid correlated significantly with corresponding serum creatinine (rs=0.694). Only 6% developed gout. All the patients with gout and 10 hyperuricemic patients with renal impairment but without gout were treated with allopurinol. Over a median period of 3 months, mean serum creatinine fell from 177 micromol/l to 160 micromol/l (P=0.01), without change in type or dose of immuno-suppression. CONCLUSIONS: There is an important association between liver transplantation and hyperuricemia. Treatment with allopurinol results in a significant reduction in serum creatinine in patients with gout and in those with hyperuricemia and renal impairment.

Adult↗
PubMed2001

Beneficial effects of converting liver transplant recipients from cyclosporine to tacrolimus on blood pressure, serum lipids, and weight.

Hypertension and hyperlipidemia are more prevalent after liver transplantation with cyclosporine as the primary immunosuppressive agent compared with tacrolimus. To determine whether blood pressure, serum lipid level, or weight improves when patients switch immunosuppression therapy, we retrospectively studied 26 liver transplant recipients with stable graft function who had been converted from cyclosporine to tacrolimus therapy with a median follow-up of 8 months. One of the 26 patients developed pruritus necessitating withdrawal of tacrolimus. The results therefore concern the remaining 25 patients. With the exception of a small decrease in bilirubin level (P <.05), there was no difference in graft or renal function after conversion. Mean systolic blood pressure decreased from 158 +/- 25 to 148 +/- 22 mm Hg over a mean of 8 +/- 3 months after conversion to tacrolimus (P =.015), whereas mean serum cholesterol level decreased from 5.3 +/- 0.9 to 4.9 +/- 0.9 mmol/L (P =.01). Sixty-eight percent of the patients lost weight, from a mean of 79.4 +/- 22.6 to 76.1 +/- 20.1 kg, in the 11 months after switching to tacrolimus therapy (P =.024). Serum triglyceride and blood glucose levels did not change, and no patient developed diabetes mellitus after conversion. These results indicate that switching from cyclosporine to tacrolimus can reduce blood pressure, serum cholesterol level, and weight after liver transplantation.

Blood Pressure↗
PubMed1999

Sirolimus: a potent new immunosuppressant for liver transplantation.

BACKGROUND: Sirolimus (rapamycin) is a new immunosuppressant that appears to be synergistic with cyclosporine in kidney transplantation, but with a different side-effect profile. This pilot study evaluated sirolimus in liver transplantation. METHODS: Patients undergoing orthotopic liver transplantation for primary tumors (8), and later for nonmalignant disease (7), received one of three sirolimus-based immunosuppressive regimens. Protocol A comprised sirolimus, microemulsion cyclosporine (target whole blood concentration: 100 ng/ml), and prednisolone; protocol B omitted prednisolone; and protocol C was sirolimus alone. By 3 months after transplantation, all patients were receiving sirolimus as monotherapy. RESULTS: Fifteen patients were treated with a follow-up of 117-806 days. Rejection was more common on monotherapy than double therapy, and absent on triple therapy. The drug was generally well tolerated, with only three patients discontinuing sirolimus: one for hyperlipidemia, one for pneumocystis pneumonia, and one for inability to tolerate the taste of the drug. Two patients discontinued cyclosporine early, both as a result of neurological complications; they continued on sirolimus monotherapy. Five patients died; one suffered a cardiac arrest, and four died from sepsis in association with graft-versus-host disease, recurrent tumor, a paralyzed right hemidiaphragm, and primary nonfunction. CONCLUSIONS: Sirolimus combined with cyclosporine provided potent immunosuppression of liver allografts, and sirolimus monotherapy was adequate and well tolerated as maintenance therapy. Side effects of sirolimus over the short period of follow-up were uncommon and reversible with dose reduction or cessation of therapy.

Adult↗
PubMed1999

MR cholangiopancreatography: prospective comparison of a breath-hold 2D projection technique with diagnostic ERCP.

The aim of this study was to compare prospectively a breath-hold projection magnetic resonance cholangiopancreatography (MRCP) technique with diagnostic endoscopic retrograde cholangiopancreatography (ERCP). Seventy-six patients with suspected strictures or choledocholithiasis were referred for MRCP and subsequent ERCP examination, which were performed within 4 h of each other. The MRCP technique was performed using fat-suppressed rapid acquisition with relaxation enhancement (RARE) projection images obtained in standardised planes with additional targeted projections as required by the supervising radiologist. Two radiologists (in consensus) assessed the MRCP results prospectively and independently for the presence of bile duct calculi, strictures, non-specific biliary dilatation and pancreatic duct dilatation, and recorded a single primary diagnosis. The ERCP was assessed prospectively and independently by a single endoscopist and used as a gold standard for comparison with MRCP. Diagnostic agreement was assessed by the Kappa statistic. The MRCP technique failed in two patients and ERCP in five. In the remaining 69 referrals ERCP demonstrated normal findings in 23 cases, strictures in 19 cases, choledocholithiasis in 9 cases, non-specific biliary dilatation in 14 cases and chronic pancreatitis in 4 cases. The MRCP technique correctly demonstrated 22 of 23 normal cases, 19 strictures with one false positive (sensitivity 100 %, specificity 98 %), all 9 cases of choledocholithiasis with two false positives (sensitivity 100 %, specificity 97 %), 12 of 14 cases of non-specific biliary dilatation and only 1 of 4 cases of chronic pancreatitis. There was overall good agreement for diagnosis based on a kappa value of 0.88. Breath-hold projection MRCP can provide non-invasively comparable diagnostic information to diagnostic ERCP for suspected choledocholithiasis and biliary strictures and may allow more selective use of therapeutic ERCP.

Adult↗
PubMed1996

Randomised study of endoscopic biliary endoprosthesis versus duct clearance for bileduct stones in high-risk patients.

BACKGROUND: The value of an endoprosthesis for long-term management of bileduct stones has not been formally established. The main theoretical advantage of endoprosthesis insertion (BE) over conventional endoscopic duct clearance (DC) is the prevention of stone impaction, with obstruction and consequent cholangitis or pancreatitis. In a randomised study we compared the results of these two methods in patients with symptomatic bileduct stones who were at high risk because of old age (> 70 yr) or serious debilitating disease. METHODS: 43 high-risk patients were randomised to BE with a 7F double-pigtail endoprosthesis and < 0.75 cm sphincterotomy, and 43 to DC with standard 1.25-1.50 cm sphincterotomy and stone extraction by balloon or basket, with or without mechanical lithotripsy. The principal endpoint was the rate of biliary related complications. FINDINGS: In the BE group biliary drainage was achieved in the first session in all but one patient (who required 2 sessions). In the DC group, 24 patients had duct clearance at the first attempt and 35 (81%) after a median of 2 sessions (range 2-4); eight of this group had an endoprosthesis inserted to maintain long-term drainage. At 72 h the complication rates were 7% in the BE group and 16% in the DC group (p = 0.18). However, the long-term complication rate for BE was higher: by Kaplan-Meier analysis, at a median of 20 months the proportions free of biliary complications were 64% BE and 86% DC (p = 0.03, log-rank test). INTERPRETATION: For immediate bileduct drainage, endoprosthesis insertion proved a safe and effective alternative to duct clearance. Because of the risk of subsequent cholangitis, its use as a definitive treatment should be confined to highly selected cases.

Aged↗
PubMed1996

Prospective study comparing the efficacy of prophylactic parenteral antimicrobials, with or without enteral decontamination, in patients with acute liver failure.

The efficacy of prophylactic parenteral antibacterials, with or without selective decontamination of the digestive tract, was compared in patients with acute liver failure (ALF) or severe acetaminophen hepatotoxicity. One hundred eight patients were randomized on admission to receive intravenous ceftazidime and flucloxacillin, plus either oral and enteral decontamination with colistin, tobramycin, and amphotericin B (group 1), or enteral amphotericin B alone (group 2). The two groups were comparable with respect to age, gender, etiology, coma grade on admission, international normalization ratio, presence of renal failure, Acute Physiology and Chronic Health Evaluation II score, and indicators of poor prognosis. Patients were monitored for clinical and microbiological evidence of infection. There were 15 episodes of infection in 10 of 47 patients (21%) in group 1 and 17 episodes in 12 of 61 patients (20%) in group 2. No differences in incidence, site, and causative organisms of infection were observed between the two groups. Overall, the incidence of infection was significantly higher in patients who developed encephalopathy than in those who did not. In patients who on arrival were not encephalopathic, the development of infection was associated with progression to coma. Duration of Liver Intensive Care Unit (LICU) stay was an independent risk factor for the development of infection. Parenteral antibiotics are effective at reducing the risk of infection in patients with ALF; enteral decontamination provided no additional benefit.

Adolescent↗
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↗
PubMed1993

Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding oesophageal varices.

Injection sclerotherapy of bleeding oesophageal varices is undoubtedly beneficial but it is associated with a substantial complication rate, and variceal rebleeding is common during the treatment period before variceal obliteration is achieved. We aimed to find out whether endoscopic variceal banding ligation is safer and more effective. The two methods were compared in a randomised controlled trial of 103 patients (54 assigned to banding ligation, and 49 to injection sclerotherapy) of whom 21 (39%) and 23 (47%), respectively, had active bleeding at index endoscopy. Both treatments were highly effective in controlling active haemorrhage (91% and 92% respectively). Variceal obliteration was not achieved for 22 patients in each group, but among those whose varices were eradicated, banding ligation achieved obliteration more quickly than did sclerotherapy (mean 39 [SD 4] vs 72 [7] days, p = 0.004) and in fewer endoscopy sessions (3.4 [2.2] vs 4.9 [3.5], p = 0.006). Rebleeding was less common in the banding ligation group than in the sclerotherapy group (16 [30%] vs 26 [53%], p < 0.05). There was no difference in outcome between the groups, but 14 sclerotherapy patients were withdrawn from the trial (7 for orthotopic liver transplantation) compared with only 5 (1 for liver transplantation) in the banding ligation group (p < 0.05). Complication rates were similar in the two groups. Variceal banding ligation is a safe and effective technique, which obliterates varices more quickly and with a lower rebleeding rate than injection sclerotherapy.

Adult↗
PubMed1992

Effects of vasopressor agents and epoprostenol on systemic hemodynamics and oxygen transport in fulminant hepatic failure.

Hypotension is a serious complication in patients with fulminant hepatic failure, because it is associated with tissue hypoxia and a further compromise to end-organ function. In this study we investigated the effects of epinephrine and norepinephrine on hemodynamics and oxygen transport variables in 30 patients with fulminant hepatic failure. All had a mean arterial pressure of less than 60 mm Hg, despite adequate intravascular filling pressures. Both epinephrine (n = 15) and norepinephrine (n = 15) improved mean arterial pressure (p less than 0.001 epinephrine and norepinephrine), although this was not associated with a rise in oxygen delivery. Oxygen consumption fell (p less than 0.05 epinephrine, p less than 0.001 norepinephrine) because of a lower oxygen extraction ratio (p less than 0.01 epinephrine and norepinephrine). The addition of epoprostenol, a microcirculatory vasodilator, in 10 patients from each group led to an increase in oxygen consumption (p less than 0.001 epinephrine and norepinephrine) because of a rise in oxygen delivery (p less than 0.05 epinephrine, p less than 0.01 norepinephrine) and oxygen extraction ratio (p less than 0.01 epinephrine, p less than 0.001 norepinephrine), without a fall in mean arterial pressure. The fall in oxygen consumption after the institution of vasopressor therapy could exacerbate tissue hypoxia and thus contribute to further organ damage in an already susceptible patient. In patients with fulminant hepatic failure who are given vasopressor support, the addition of epoprostenol may prevent the development of tissue hypoxia.

Adolescent↗
PubMed1991

Liver transplantation after paracetamol overdose.

OBJECTIVE: To evaluate the role of liver transplantation after paracetamol overdose. DESIGN: Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. SETTING: Liver unit, King's College Hospital, London. MAIN OUTCOME MEASURES: Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. RESULTS: 30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. CONCLUSION: Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol.

Acetaminophen↗