Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK.

BACKGROUND: The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short- and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016. METHODS: First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics. RESULTS: Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non-HCC recipients (0-90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024). CONCLUSION: In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.

ANTECEDENTES: La creciente demanda de trasplante hepático ha determinado cambios considerables en las características de los donantes y receptores. En este estudio, se evaluó la mortalidad a corto y a largo plazo de los receptores de trasplante hepático por carcinoma hepatocelular (hepatocelular carcinoma, HCC) y no-HCC en el Reino Unido entre 1997 y 2016. MÉTODOS: Se identificaron los receptores adultos de un primer trasplante hepático electivo en el Reino Unido y se compararon cuatro eras sucesivas de trasplante. Se estimaron los cocientes de riesgos instantáneos ajustados (adjusted hazard ratio, aHR) que comparaban el impacto de la era en la mortalidad a corto plazo (primeros 90 días) y a largo plazo (de 90 días a 5 años) ajustando por las características del receptor y del donante. RESULTADOS: Se incluyeron 1.879 receptores HCC y 7.661 receptores no-HCC. Hubo un aumento en el uso de donantes después de parada cardíaca (donors following circulatory death, DCD) del 0% en la era 1 al 35,2% en la era 4 para los receptores HCC y del 0,2% al 24,1% para los receptores no-HCC. La mortalidad a los 3 años disminuyó de 28,3% en la era 1 a 16,9% en la era 4 (aHR 0,47, i.c. del 95% 0,35-0,63) para receptores HCC y de 20,4% a 9,3% (aHR 0,44, 0,36-0,53) para receptores no-HCC. Comparando la era 1 y la era 4, las mejoras en la mortalidad a corto plazo fueron más marcadas que en la mortalidad a largo plazo, tanto para receptores HCC (aHR 0-90 días 0,20, 0,10-0,39; 90 días-5 años 0,52, 0,35-0,75; P =舁0,04) como para receptores no-HCC (aHR 0-90 días 0,32, 0,24-0,42; 90 días-5 años 0,52, 0,40-0,67; P =舁0,02). CONCLUSIÓN: En los últimos 20 años, la mortalidad después del trasplante de hígado se ha reducido a más de la mitad, a pesar del uso cada vez mayor de donantes DCD. Las mejoras en la supervivencia global pueden explicarse por la disminución de la mortalidad a corto y largo plazo.

Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. METHODS: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. RESULTS: In total, 385 of 968 patients (39·8 per cent) received TACE. Five-year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). CONCLUSION: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation.

ANTECEDENTES: La quimioembolización transarterial (transarterial chemoembolization, TACE) en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) se utiliza como puente al trasplante hepático, aunque falta evidencia de que mejore los resultados y la morbilidad relacionada es motivo de preocupación. En este estudio se evaluó el impacto de la TACE en los resultados tras el trasplante para analizar las complicaciones. MÉTODOS: Se identificaron los receptores de trasplante hepático por HCC en el Reino Unido y se estratificaron según si habían recibido TACE entre 2006 y 2016. Se utilizó el método de regresión de Cox para estimar los cocientes de riesgos instantáneos (hazard ratio, HR) para la mortalidad post-trasplante y el fallo del injerto ajustados por las características del donante y del receptor. RESULTADOS: En total, 385 (39,8%) de 968 pacientes recibieron TACE, observándose similar supervivencia del paciente a los 5 años después del trasplante: 75,2% (i.c. del 95%: 68,8% a 80,5%) con TACE y 75,0% (70,5% a 78,8 %) sin TACE. Después de ajustar según las características del donante y del receptor, no hubo diferencias en la mortalidad (HR: 0,96, 0,67 a 1,38; P = 0,82) o en el fallo del injerto (HR: 1,01, 0,73 a 1,40; P = 0,96). El número de tratamientos con TACE (≥ 2 tratamientos TACE HR: 0,97, 0,61 a 1,55; P = 0,90) o el período de tiempo después del trasplante (mortalidad del paciente antes o después de 90 días; P = 0,29) no alteró el resultado. La incidencia de trombosis de la arteria hepática fue baja en aquellos que recibieron TACE o no (1,3% y 2,5%, respectivamente; P = 0,23). El fallo del injerto debido a eventos oclusivos fue similar en el grupo de pacientes que recibieron TACE (8,0% o 11/137) o que no la recibieron (6,7% o 5/75) TACE (P = 0,74). CONCLUSIÓN: La administración de TACE en pacientes con HCC antes del trasplante hepático no influyó en las complicaciones post-trasplante, la mortalidad del paciente o el fallo del injerto.

Comparison of liver transplantation outcomes from adult split liver and circulatory death donors.

BACKGROUND: Adult whole-organ donation after circulatory death (DCD) and 'split' extended right lobe donation after brain death (ERL-DBD) liver transplants are considered marginal, but direct comparison of outcomes has rarely been performed. Such a comparison may rationalize the use of DCD livers, which varies widely between UK centres. METHODS: Outcomes for adult ERL-DBD livers and 'controlled' DCD liver transplantations performed at the Cambridge Transplant Centre between January 2004 and December 2010 were compared retrospectively. RESULTS: None of the 32 patients in the DCD cohort suffered early graft failure, compared with five of 17 in the ERL-DBD cohort. Reasons for graft failure were hepatic artery thrombosis (3), progressive cholestasis (1) and small-for-size syndrome (1). Early allograft dysfunction occurred in a further five patients in each group. In the DCD group, ischaemic cholangiopathy developed in six patients, resulting in graft failure within the first year in two; the others remained stable. The incidence of biliary anastomotic complications was similar in both groups. Kaplan-Meier survival analysis confirmed superior graft survival in the DCD liver group (93 per cent at 3 years versus 71 per cent in the ERL-DBD cohort; P = 0·047), comparable to that of contemporaneous whole DBD liver transplants (93 per cent at 3 years). Patient survival was similar in all groups. CONCLUSION: Graft outcomes of DCD liver transplants were better than those of ERL-DBD liver transplants. Redefining DCD liver criteria and refining donor-recipient selection for ERL-DBD transplants should be further explored.

Unusual case of abdominal pain following liver transplant: causality or casualty?

This is an unusual case of chronic abdominal pain following two liver transplants with at least three potential causes: traumatic neuroma, intussusception of the small bowel of the Roux loop and biliary cast. Surgical removal of the latter two factors led to resolution of the pain. The management of the clinical case is discussed.

Selection of patients for liver transplantation and allocation of donated livers in the UK.

BACKGROUND: The increasing shortfall between the number of patients who would benefit from liver transplantation and the availability of donor livers means that rationing has to occur. The processes of selection of patients for transplantation and for allocation of donor livers should be done according to ethical and, where possible, evidence-based criteria so that there is clarity and that the competing requirements of equity, justice, utility and benefit can be balanced. METHODS: To achieve these goals for patients in the United Kingdom in need of transplantation, we have developed guidelines for the selection of patients to the national waiting list based on the risk of death without a transplant and the ability of the procedure to improve the recipient's quality of life. Guidelines have been developed for both those with acute liver failure and chronic liver disease. Allocation will depend on matching of the donor liver to the recipient. RESULTS: The proposed system, to be introduced into the UK compares with some other systems, where different models for selection and allocation have been introduced.

Cystic fibrosis liver disease: to transplant or not to transplant?

Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardio-respiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1- and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome.

Survival after liver transplantation in the United Kingdom and Ireland compared with the United States.

BACKGROUND AND OBJECTIVE: Surgical mortality in the US is widely perceived to be superior to that in the UK. However, previous comparisons of surgical outcome in the two countries have often failed to take sufficient account of case-mix or examine long-term outcome. The standardised nature of liver transplantation practice makes it uniquely placed for undertaking reliable international comparisons of surgical outcome. The objective of this study is to undertake a risk-adjusted disease-specific comparison of both short- and long-term survival of liver transplant recipients in the UK and Ireland with that in the US. METHODS: A multicentre cohort study using two high quality national databases including all adults who underwent a first single organ liver transplant in the UK and Ireland (n = 5925) and the US (n = 41,866) between March 1994 and March 2005. The main outcome measures were post-transplant mortality during the first 90 days, 90 days to 1 year and beyond the first year, adjusted for recipient and donor characteristics. RESULTS: Risk-adjusted mortality in the UK and Ireland was generally higher than in the US during the first 90 days (HR 1.17; 95% CI 1.07 to 1.29), both for patients transplanted for acute liver failure (HR 1.27; 95% CI 1.01 to 1.60) and those transplanted for chronic liver disease (HR 1.18; 95% CI 1.07 to 1.31). Between 90 days and 1 year post-transplantation, no statistically significant differences in overall risk-adjusted mortality were noted between the two cohorts. Survivors of the first post-transplant year in the UK and Ireland had lower overall risk-adjusted mortality than those transplanted in the US (HR 0.88; 95% CI 0.81 to 0.96). This difference was observed among patients transplanted for chronic liver disease (HR 0.88; 95% CI 0.81 to 0.96), but not those transplanted for acute liver failure (HR 1.02; 95% CI 0.70 to 1.50). CONCLUSIONS: Whilst risk-adjusted mortality is higher in the UK and Ireland during the first 90 days following liver transplantation, it is higher in the US among those liver transplant recipients who survived the first post-transplant year. Our results are consistent with the notion that the US has superior acute perioperative care whereas the UK appears to provide better quality chronic care following liver transplantation surgery.

Effects of converting enzyme inhibitor on hepatic blood flow in man.

The acute effects of the oral angiotension converting enzyme inhibitor captopril on hepatic blood flow and systemic hemodynamics were studied in six patients with essential hypertension. Mean arterial pressure decreased from 141.9 +/- 6.9 mm Hg to 130.2 +/- 6.7 mm Hg (p less than 0.05) one hour after the administration of captopril. There was no significant change in other hemodynamic values, but hepatic blood flow decreased uniformly from 1,127 +/- 115 ml per minute to 841 +/- 93 ml per minute (p less than 0.001).

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.

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.

Randomized trial to evaluate the clinical benefits of serum alpha-glutathione S-transferase concentration monitoring after liver transplantation.

BACKGROUND: An increase in serum alpha-glutathione S-transferase concentration (GST) has been shown to be a more sensitive and specific marker of hepatocellular damage than equivalent increases in transaminase activities. A randomized clinical trial of 60 liver transplants in 49 patients was carried out to assess the clinical benefits of GST monitoring as a supplementary test to routine liver function tests during the first 3 postoperative months after liver transplantation. METHODS: Mortality and morbidity were compared in graft recipients who had their GST reported daily to the ward (reporting group) and graft recipients who did not. RESULTS: The 3-month survival rate was significantly greater in the reporting group (P=0.033) and the risk of graft loss was halved (relative hazard ratio=0.50; P=0.29). The reporting group also had significantly more patients who spent less than 3 weeks in the hospital throughout the follow-up period (P=0.036). In addition, the reporting group experienced a lower frequency of biopsies per graft (P=0.038), less severe rejection (P=0.015), and a lower incidence of infection episodes per graft (P=0.03). GST increased by >50% above the upper limit of the reference range at a median of 1 day before the equivalent change in alanine transaminase in association with allograft rejection in the combined groups (95% confidence interval=1 to 2 days) but was lower on the day of diagnosis of rejection in the reporting group (P=0.02). This is compatible with the earlier diagnosis of rejection in the reporting group. CONCLUSIONS: We conclude that the monitoring of GST may improve patient care, reducing both mortality and morbidity.

Heparin response and clearance in acute and chronic liver disease.

Patients with liver disease are at risk of bleeding due to abnormalities of the clotting system although they must be anticoagulated if they require haemodialysis or haemoperfusion. The anticoagulant of choice is heparin. In this study we have investigated heparin kinetics in patients with fulminant hepatic failure (FHF) after a single intravenous dose of heparin (2,500 units) and found there was an increased clearance of heparin whether measured by its anti-Xa effect (t 1/2 = 27.8 +/- 2.9 min compared to t 1/2 = 50.2 +/- 2.7 min in normal controls p less than 0.001) or by the whole blood activated clotting time (t 1/2 = 23.7 +/- 2.2 min compared to t 1/2 = 37.0 +/- 2.0 min p less than 0.001). There was a decreased peak level of heparin measured by anti-Xa effect (peak level in FHF = 0.48 +/- 0.05 u/ml and in controls = 0.69 +/- 0.04 u/ml, p less than 0.02), but an increased sensitivity to heparin (sensitivity in FHF = 0.072 +/- 0.011 sec/unit, in controls 0.033 +/- 0.003 sec/unit, p less than 0.001). Patients with FHF had very low levels of antithrombin III (AT III), but there was no correlation between this and any parameters of heparin effect or clearance. In a group of patients with chronic liver disease heparin kinetics did not differ from controls despite low levels of AT III. The changes in heparin kinetics in FHF are likely to be complex with the balance between the proteins that act as cofactors, (e.g. AT III) and the proteins that have heparin neutralising activity, controlling the response of added heparin.

Expression of IGFBP-1 in normal and cirrhotic human livers.

Cirrhosis of the liver, a condition characterised by hepatocyte regeneration, is also associated with elevated insulin levels and insulin resistance. In animal models hepatic regeneration is associated with increased IGFBP-1 gene expression. Insulin is known to be an inhibitor of IGFBP-1 gene expression and circulating insulin levels in man demonstrate a negative correlation with IGFBP-1 levels. To further our understanding of the regulation of IGFBP-1 in cirrhosis we have studied steady state levels of IGFBP-1 mRNA in human liver from three groups of patients: Group 1, tissue obtained at the time of harvesting donor liver for orthotopic liver transplantation (n = 4); group 2, patients undergoing major liver resection with no histological evidence of chronic liver disease (n = 4); and group 3, patients undergoing orthotopic transplantation for chronic liver failure (n = 9). Simultaneous samples of serum were taken at the time of surgery in some patients and in these patients IGFBP-1 mRNA levels were related to circulating levels of IGFBP-1 and insulin. IGFBP-1 mRNA was detectable in all the human liver samples with the greatest levels seen from the normal livers of group 2 patients. Insulin levels were elevated in the cirrhotic group 3 patients compared to a normal range as were IGFBP-1 levels. There was no relationship between circulating levels of IGFBP-1 and IGFBP-1 gene expression. In conclusion, IGFBP-1 mRNA is present in human adult liver at the time of surgery and also in cirrhotic liver despite high levels of insulin suggesting that there are factors other than insulin regulating IGFBP-1 gene expression.

Expression of IGF-I and IGF-binding protein genes in cirrhotic liver.

The liver plays a central role in the IGF-I axis producing the majority of circulating hormone and some of its binding proteins (IGFBPs). Cirrhosis of the liver is characterised by changes in IGF-I and IGFBPs associated with liver fibrosis and regeneration. We have studied steady state levels of mRNA for the genes in the IGF-I axis in normal and cirrhotic human liver, localised the most highly expressed gene, IGFBP-1, and measured circulating IGFBP-3 by radioimmunoassay (RIA), IGFBP-2 and IGFBP-3 by Western ligand blot (WLB), and protease activity for IGFBP-3 in cirrhotic patients. Messenger RNA for IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 was detectable by Northern blotting in normal and cirrhotic liver although there was considerable variation in expression. IGFBP-2 and IGFBP-3 tended to be more highly expressed in cirrhotic liver and IGFBP-1 was more highly expressed in normal liver, although there were no significant differences. In normal liver, in situ hybridisation localised IGFBP-1 to hepatocytes. In cirrhotic liver the regenerating nodules showed expression of IGFBP-1 while there was none in fibrotic tissue. Circulating IGFBP-3 levels were low as measured by RIA and WLB but protease activity was only found in one patient. IGFBP-2 levels, assessed by WLB, were similar to the normal serum pool. Our data show that key mRNAs involved in the IGF-I axis continue to be expressed in cirrhotic liver despite end stage liver disease. The low levels of IGFBP-3 do not appear to be due to reduced gene transcription or increased protease activity.

Comparison of propranolol with injection sclerotherapy in prevention of rebleeding from oesophageal varices in cirrhotic patients.

Selected patients with variceal bleeding were randomly assigned to either weekly injection sclerotherapy (n = 56) or to oral propranolol (n = 52). During follow-up, 28 (54%) of the propranolol group and 25 (45%) of the sclerotherapy group had an episode of rebleeding. The long term risks of bleeding in the propranolol and sclerotherapy groups were 0.05 and 0.037 bleeds/patient-month, respectively, and the corresponding death rates during follow-up were 42 and 38%. There were no statistically significant differences between propranolol and the established therapy, but it was concluded that if propranolol is used in the prevention of rebleeding, it must be part of an overall approach that provides for the management of active variceal haemorrhage by other means if this condition continues.

Effect of liver and renal dysfunction on circulating methionine-enkephalin immunoreactivity.

Plasma methionine-enkephalin (Met-Enk) immunoreactivity has been determined in 24 patients with varying degrees of renal impairment and 14 patients with hepatic failure. Plasma Met-Enk immunoreactivity correlated inversely with creatinine clearance (r = -0.71, P less than 0.001) but was not affected by even severe hepatic failure in the absence of renal impairment. In two patients, with renal failure and elevated plasma prolactin, administration of naloxone (16 mg) had no effect on circulating prolactin concentrations. These studies indicate that the kidney has a major role in Met-Enk metabolism while the liver does not, and further suggest that elevated circulating endogenous opiates are not responsible for the increased production of prolactin found in renal failure.

Epidemiology, bacteriology and control of an outbreak of Nocardia asteroides infection on a liver unit.

An outbreak of Nocardia asteroides infection affecting seven patients is described. Over a 5-week period, five patients with liver disease admitted to a ward developed clinical and laboratory evidence of nocardiosis, and two further cases were diagnosed 3 and 5 months later. Three out of the five patients who received specific antimicrobial therapy responded to treatment; in three patients nocardia infection was considered to have contributed to death. In six out of the seven patients, nocardiosis followed immunosuppression. A common-source outbreak was considered to be responsible for infection in the first five patients. In two patients, presentation of infection 5 and 7 months after the first case may have been due to prolonged colonization or subclinical infection with Nocardia. Biotyping of the seven isolates using a fluorogenic biochemical method identified three distinct strains of N. asteroides. The most probable source of Nocardia was contaminated brick and plaster dust arising from building work in an area adjacent to the ward. However, samples of air, dust and water failed to yield N. asteroides. Infection control measures included ward closure followed by thorough cleaning, and formaldehyde fumigation.

Effects of serial resin hemoperfusion in fulminant hepatic failure.

Resin hemoperfusion using an albumin coated Amberlite XAD-7 column was performed in 19 patients in coma due to fulminant hepatic failure. The procedure was clinically well tolerated, with good blood compatibility, platelet and white cell levels being 97.3 +/- SE 3.2% and 105 +/- 3.8% of the respective initial values after four hours hemoperfusion. No significant changes were observed in beta-thromboglobulin, screen filtration pressure, plasma electrolytes, calcium, protein or albumin. The total plasma bilirubin fell by a mean of 24 mumol/l, with a reduction in 21 of the 25 perfusions studied of up to 104 mumol/l during perfusion. Mean plasma levels of total bile acids were 137 +/- 19 mumol/l and 115 +/- 16 mumol/l respectively before and after four hours hemoperfusion. The amount of bile acids recovered by elution of the resin column was over three times greater than that apparent from the change in plasma levels. Column chromatography on Sephadex G-25 of material eluted from the resin column showed various peaks to be removed, including substances in the middle molecular weight range (1000-5000 daltons). Of the patients treated, eight (42%) survived to leave hospital.

A comparison of direct and indirect measurements of oxygen delivery and consumption: the effects of prostacyclin in two human volunteers.

To examine the relation of oxygen delivery to uptake in normals, we have measured cardiac index, oxygen delivery and oxygen consumption directly and indirectly in two human volunteers before and during a prostacyclin (PGI2) infusion (5 ng/kg/min). We have also investigated the relation of direct and indirect measurements of delivery to consumption in two critically ill patients over a more prolonged study period of 24 hours. Overall, there were close correlations between both cardiac index measured by thermodilution with that calculated from the Fick equation (r = 0.97 p less than 0.001) and oxygen consumption measured directly by analysis of inspired gases (V O2) with that calculated by the reverse Fick method (OUI) (r = 0.95 p less than 0.001). Nevertheless, the limits of agreement between the two methods were wide (1.6 L/min.m2 for the cardiac index and 70.5 ml 02/min.m2 for oxygen consumption, 95% confidence limits). In the two human volunteers, PGI2 produced substantial increases in oxygen delivery but there was no change in oxygen consumption measured directly or indirectly; V O2 and OUI were unrelated and independent of oxygen delivery. However, in the two patients studied over 24 hours, there were close correlations between delivery and both V O2 (r = 0.93 p less than 0.001) and OUI (r = 0.94 p less than 0.001). These results suggest that the derivation of oxygen consumption by the reverse Fick method (OUI) is a reasonable substitute for direct measurements of V O2 but occasionally the absolute values so obtained may be somewhat different.(ABSTRACT TRUNCATED AT 250 WORDS)