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Biomedical subjects

A K Burroughs

Publications and source records attributed to A K Burroughs.

At least 109 records · Page 6Linked to original sources
PubMed1999

Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation.

BACKGROUND: Thrombocytopenia in cirrhotic patients may be due to deficient production of thrombopoietin. AIMS: To determine the relation between thrombopoietin and thrombocytopenia in cirrhotic patients before and after orthotopic liver transplantation. METHODS: Thrombopoietin concentrations and platelet counts were measured in 43 cirrhotic patients and 21 normal controls and serially for 14 days after transplantation in 23/43 patients. RESULTS: 27 of the 43 patients had thrombocytopenia (platelet count less than 120 x 10(9)/l; group 1) whereas 16 patients had normal platelet count (group 2). Thrombopoietin concentrations were lower in group 1 than in group 2 (92.5 (20.3-286.3) v 226.6 (30.1-848.3) pg/ml, p=0.003) and normal controls (92.5 (20.3-286.3) v 158.3 (22.5-232.9) pg/ml, p=0.028). Post-transplantation thrombopoietin concentrations increased with a peak at day 5. The rise was significant in patients with low pretransplantation platelet count (89.1 (21.29-247.6) to 545.1 (66.2-2569) pg/ml; n=16, p=0.001) but not in those with normal platelet count (262.8 (30.1-848.3) to 315.1 (114-954.6) pg/ml; n=7, p=0.47). No correlation was found pretransplantation between spleen volume and platelet count (r=-0.11, p=0.6) or thrombopoietin concentrations (r=-0.04, p=0.8). However, pretransplantation thrombopoietin concentrations correlated with platelet count (r=0.47, p=0.0015), whereas an inverse correlation was found between peak thrombopoietin concentrations and nadir platelet count (r=-0.41 p=0. 049) post-transplantation. CONCLUSIONS: Inadequate thrombopoietin production may contribute to cirrhotic thrombocytopenia. Thrombopoietin production is restored after liver transplantation leading to the resolution of thrombocytopenia.

Adult↗
PubMed1999

Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens.

BACKGROUND: The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients. METHODS: In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months. RESULTS: At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis. CONCLUSIONS: HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis.

Acute Disease↗
PubMed1999

Role of vasoactive drugs in the treatment of bleeding oesophageal varices.

Recent advances in the knowledge of the pathophysiology of portal hypertension has opened new indications for the pharmacologic treatment of acute variceal bleeding. Treatment with vasoactive agents is immediately available, easy to use and can be considered as definitive or adjunctive to endoscopic therapy. The data from randomised trials of vasoactive drug treatment for acute variceal bleeding are reviewed, using meta-analysis where applicable. The use of vasopressin has been decreased as a consequence of its questionable efficacy and its high incidence of side effects. Terlipressin is the only drug that has been shown to improve survival, albeit in small trials and there are insufficient data of its use over 5 days. Somatostatin has been shown to have similar efficacy with terlipressin with significantly less side effects. The demonstrated efficacy of octreotide in acute variceal bleeding is less than terlipressin and somatostatin and it cannot be considered as drug of first choice. Somatostatin combined with sclerotherapy represents the optimal therapy today as this combination has been shown to be more effective than sclerotherapy alone and it is safe given over 5 days.

Combined Modality Therapy↗
PubMed1998

Carcinoid tumour.

Carcinoid tumours are often indolent asymptomatic tumours. However, a small but significant proportion are malignant and difficult to manage. Multiple endocrine neoplasia type 1 (MEN-1) may be associated with carcinoid tumours and should therefore be considered in the investigation of these patients. This review puts into context the use of newer imaging modalities, including octreotide scintigraphy. The therapeutic treatment options are discussed, including the use of octreotide, the role of receptor-targeted therapy, hepatic-artery embolisation, and the arguments against chemotherapy. We review the need for careful patient selection when considering curative and palliative surgery, including liver transplantation. We conclude that there are now better diagnostic tools and therapeutic options available for those patients with malignant carcinoid tumours, and that these patients are best managed by a multidisciplinary approach. Earlier detection and treatment of these tumours should lead to improved quality of life and survival, which, ideally, should be assessed in formal trials.

Carcinoid Tumor↗
PubMed1998

Reconstitution of EBV-specific T cell immunity in solid organ transplant recipients.

EBV-specific autologous CTL were grown in vitro from three adults (two liver transplant recipients and one patient on hemodialysis awaiting kidney retransplant). All CTL lines were TCR alphabeta, CD8 positive cells, EBV specific, and MHC class I restricted. The CTL lines were expanded in vitro and infused in three escalating doses (5 x 10(7), 1 x 10(8), and 2 x 10(8) at monthly intervals. Weekly blood samples were collected following each infusion. EBV-specific CTL precursor cells in peripheral blood were quantitated by limiting dilution analysis, and their effect on EBV load in vivo was assessed by semiquantitative PCR. In all three patients, the numbers of CTL precursor cells increased during the weeks following the infusions and were highest after the third infusion. This level gradually declined but remained above the preinfusion levels for up to 3 mo. EBV genome copy number, on the other hand, dropped following the first infusion and became undetectable thereafter. The EBV DNA level remained lower than the pretransplant level in all patients for up to 3 mo after the last infusion. Our study shows that it is feasible to generate and expand EBV-specific CTL from pretransplant blood samples of solid organ transplant recipients, that these CTL can be stored and infused posttransplant, and that they remain cytotoxic and EBV specific in vivo. The aim of this study is to use these CTL for prevention and treatment of lymphoproliferative disease in solid organ transplant recipients.

Adult↗
PubMed1998

Alpha-glutathione-S-transferase in acute rejection of liver transplant recipients.

BACKGROUND: Alpha-glutathione-S-transferase (alphaGST) has been suggested as a sensitive marker of acute cellular rejection in liver transplantation. This study evaluated the usefulness of alphaGST as a marker of acute rejection in comparison with standard liver function tests. METHODS: Daily measurements of liver function tests and alphaGST (enzyme immunometric assay, Biotrin) were prospectively recorded in 23 consecutive liver transplant recipients up to the time of discharge. Liver biopsies were performed as protocol biopsies or after clinical or biochemical deterioration in liver function, 38 of 56 showed acute rejection. RESULTS: AlphaGST peaked on the second day (median, 125 microg/L; interquartile [IQ] range, 75-321 microg/L) and preceded the alanine transaminase (ALT) peak by 1 day. AlphaGST levels then steadily declined, reaching baseline by day 6, plateauing until day 8. After the initial peak, alphaGST still correlated well with the ALT (median correlation coefficient, 0.6; IQ range, 0.45-0.77) and with bilirubin concentration (median correlation coefficient, 0.47; IQ range, 0.14-0.6). There was no significant difference in alphaGST levels between those with rejection compared with other causes of hepatic dysfunction. The sensitivity and specificity of alphaGST for diagnosing acute rejection was 63.1% and 38.8%, respectively, compared with 97.4% and 16.7% for ALT. In 14 of the 16 patients treated for moderate or severe rejection, the improvement in the histological score of rejection was not associated with a consistent change in the alphaGST. CONCLUSIONS: AlphaGST is not more useful than ALT in diagnosing rejection or determining response to treatment, but is a sensitive marker of liver injury.

Adult↗
PubMed1998

Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage.

Bacterial infection is frequently diagnosed in cirrhotic patients with variceal hemorrhage. The aim of this study was to assess the incidence of failure to control bleeding in cirrhotic patients during the first 5 days after the episode of variceal bleeding in relation to the diagnosis of bacterial infection and use of antibiotics. One hundred seventy-seven consecutive admissions for gastrointestinal bleeding in 151 patients were evaluated prospectively. From them, 163 admissions for variceal bleeding in 137 patients were included in the main analysis. Bleeding was managed in a standardized protocol using octreotide or terlipressin with sclerotherapy or band ligation for active bleeding at endoscopy. The end points were defined as in Baveno guidelines related to transfusion requirement or fresh hematemesis after 6 hours from time zero. The standardized screening protocol for bacterial infection consisted of chest radiograph and blood, urine, and ascitic fluid cultures. Active bleeding was reported at endoscopy in 86 admissions (53%). Failure to control bleeding occurred in 76 patient admissions (47%). Empirical antibiotic treatment was used in 113 admissions (69%), whereas in 81% of them (91 admissions, 56%) 102 bacterial infections were documented. Multivariate analysis showed that proven bacterial infection (P < .0001) or antibiotic use (P < .003) as well as active bleeding at endoscopy (P < .001) and Child-Pugh score (P < .02) were independent prognostic factors of failure to control bleeding. The results remained unchanged when all patient admissions with gastrointestinal bleeding of any source were included in the multivariate analysis. Bacterial infection is associated with failure to control variceal bleeding and needs to be evaluated in the planning and analysis of clinical trials.

Adult↗
PubMed1998

Eosinophils in acute cellular rejection in liver allografts.

Eosinophils have a role in various allergic and inflammatory disease processes and participate in the process of acute rejection in solid organ allografts. Initial studies described the diagnostic value of eosinophils in kidney allograft rejection. Graft eosinophilia is a sensitive and specific marker of acute rejection in liver allografts and has been incorporated as one of the diagnostic criteria of acute rejection by the Royal Free Hospital scoring system. Blood eosinophilia also has been investigated and is a useful diagnostic marker of acute rejection in liver and kidney allografts, although studies differ in defining the day of onset of eosinophilia in relation to rejection. Eosinophils probably act through the chemokines interleukin-5 and RANTES (regulated on activation, normal T cells expressed and secreted) in the pathogenesis of acute rejection. Basic cytotoxic proteins, such as eosinophil cationic protein and major basic protein, are released by the eosinophils, and their effector role in acute rejection has been studied through the use of specific monoclonal antibodies. Successful treatment of acute rejection with corticosteroids has been associated with a decrease in graft and blood eosinophil counts. Eosinophils also act as prognostic markers of acute rejection, as shown by studies reporting that patients with elevated eosinophil counts and steroid-resistant rejection showed a worse prognosis. Further research into the effector mechanisms of eosinophils in acute rejection needs to be performed. The ability of eosinophils to distinguish those diseases with different responses to standard immunosuppression and other diseases in the context of acute rejection also needs to be studied.

Acute Disease↗
PubMed1998

Infection rates with and without T-tube splintage of common bile duct anastomosis in liver transplantation.

Stenting the bile duct over a T-tube after orthotopic liver transplantation (OLT) is the preferred method of biliary reconstruction. However, because of complications associated with the use of the T-tube, we evaluated the effect of various biliary anastomoses following 100 consecutive OLT (83 records were available for long-term evaluation) and assessed the clinical outcome of abandoning routine T-tube splintage. Of 16 OLT recipients with T-tube splintage (one died immediately following OLT and was excluded from the study), 6 patients (40%) developed six episodes of septicaemia secondary to biliary and/or intra-abdominal sepsis. Four of these six patients had a biliary leak (27%). Of 57 patients with duct-to-duct anastomosis without T-tube splintage, 7 patients developed biliary leak (12.3%) and only 1 developed septicaemia (1.7%) secondary to biliary and intra-abdominal sepsis (P = 0.0002). Of 11 patients with either a gallbladder conduit or Roux loop, only 1 patient had a biliary leak (9%) and there were no septicaemic episodes. In conclusion, direct duct-to-duct anastomosis resulted in significantly less morbidity due to infection without T-tube splintage than the use of a T-tube following OLT, but there were no significant differences in leakage and stricture rates.

Anastomosis, Roux-en-Y↗
PubMed1998

Ultrasound screening for hepatocellular carcinoma (HCC) in cirrhosis: the evidence for an established clinical practice.

Improvement in our current knowledge of epidemiology, natural history and treatment modalities form the background to generalize the use of ultrasound screening in cirrhosis. The cumulative probability of developing cancer is extremely high in cirrhotics and allows to focus screening programs on a well defined risk group thus maximizing cost-effectiveness. This review article highlights scientific evidences in favour of a generalized practice of US screening.

Carcinoma, Hepatocellular↗
PubMed1998

"Salvage" transjugular intrahepatic portosystemic shunts: gastric fundal compared with esophageal variceal bleeding.

BACKGROUND & AIMS: The optimal emergency treatment for gastric fundal variceal bleeding is still unclear. In this study, the efficacy of transjugular intrahepatic portosystemic stent/shunt (TIPS) in patients with uncontrolled gastric fundal vs. esophageal variceal bleeding was compared. METHODS: One hundred twelve consecutive patients with uncontrolled variceal bleeding required emergency TIPS, 84 with esophageal varices (EV group) unresponsive to endoscopic and vasoconstrictor therapy and 28 with gastric fundal varices (GV group) unresponsive to vasoconstrictor therapy. Clinical and biochemical data were retrieved, and the two groups were compared. RESULTS: Variceal bleeding was controlled in all patients after TIPS except for 1 in each group. There were no significant differences between the two groups in terms of markers of disease severity, severity of bleeding, or portal hemodynamics. During a median follow-up period of 7 months, 20 in the EV group (24%) and 8 in the GV group (29%) developed clinical rebleeding. Most early rebleeding (within 7 days after TIPS) was related to esophageal ulceration secondary to previous sclerotherapy. Rates of mortality were similar in both groups. CONCLUSIONS: These results suggest that emergency TIPS is equally effective in the immediate short-term control of gastric fundal variceal bleeding compared with esophageal variceal bleeding.

Adult↗
PubMed1998

Analysis of intrapulmonary right to left shunt in the hepatopulmonary syndrome.

BACKGROUND/AIMS: Severe hypoxaemia in patients with chronic liver disease in the absence of intrinsic lung disease, the hepatopulmonary syndrome, is associated with pulmonary vascular dilatation and may be an indication for liver transplantation. Divergence between two methods of measuring right to left shunt (radiolabelled albumin macroaggregates and 100% oxygen breathing) has been described, but the mechanism and reason for the inter-patient variability for this shunt difference are not well understood. METHODS: Eight hepatopulmonary syndrome patients were studied, with characteristic pulmonary diffusion abnormalities (carbon monoxide transfer factor 41+/-5 (mean+/-SE)% predicted) and significant decreases in arterial oxygen saturation (%) on standing vs. supine (-10%+/-3) and on exercise vs. rest (-15%+/-2). All had hypoxaemia at rest (arterial oxygen tension 8.2+/-0.6 kPa), partially corrected by breathing 100% oxygen (48.2+/-8.8 kPa). Pulmonary angiography was performed and right to left shunt measured by two independent methods: (a) 100% oxygen breathing and (b) i.v. injection of radiolabelled microspheres. RESULTS: Measurement of right to left shunt with 99mTc-labelled albumin macroaggregates confirmed significant intrapulmonary microvascular dilatation, i.e. an "anatomical" shunt equalling 32+/-4% of cardiac output. Shunt measurements made simultaneously by the classical 100% oxygen technique were significantly smaller (19+/-3%, p=0.01). For individuals, the difference between the 99mTc-albumin macroaggregate shunt and the 100% oxygen shunt ranged from 2% to 30% absolute, convergence suggesting larger shunt channels (pure anatomical shunt) and divergence representing a combination of anatomical shunt and alveolar-capillary diffusion limitation (smaller microvascular channels). CONCLUSIONS: Hypoxaemia in the hepatopulmonary syndrome may be due functionally either to right to left shunting or to diffusion limitation, depending upon the degree of dilatation of the pulmonary microvessels.

Adult↗
PubMed1998

Clinical vs haemodynamic response to drugs in portal hypertension.

BACKGROUND/AIMS: The combination of non-selective beta-blockers and nitrates is an effective therapy for the prevention of rebleeding from oesophageal varices. However, a significant number of patients fail to respond and have further haemorrhage. It has been suggested that measurement of the hepatic venous pressure gradient response to long-term drug therapy may allow early selection of non-responders. We aimed to test this hypothesis in 63 patients with cirrhosis and variceal bleeding treated with propranolol+/-isosorbide mononitrate. METHODS: Hepatic venous pressure gradient was measured before and during treatment. Response was defined as a reduction of 20% or more in hepatic venous pressure gradient, or a fall in hepatic venous pressure gradient to 12 mmHg or less. RESULTS: Forty-four patients were evaluable: 28 responders and 16 non-responders. Hepatic venous pressure gradient fell significantly in the responder group (17.5+/-0.5 mmHg vs 12.2+/-0.5 mmHg; p<0.01) but not in the non-responders (18.0+/-1.0 vs 17.9+/-1.2 mmHg; p=n.s.). Overall, there was no difference in rebleeding rates between the two groups: responders 43%, non-responders 25%. However, rebleeding was uncommon in compliant patients with alcoholic cirrhosis, in whom the hepatic venous pressure gradient fell to less than 12 mmHg (9%). CONCLUSIONS: In this study a fall in hepatic venous pressure gradient of 20% was not a reliable predictor of clinical response. A threshold value of 12 mmHg was useful, but applied to relatively few patients.

Adrenergic beta-Antagonists↗
PubMed1998

Health-related quality of life following liver transplantation.

The objectives of this study were to report on the health-related quality of life (QoL) experienced by patients following liver transplantation and to investigate the factors associated with its variation. A questionnaire comprising the SF-36 and EuroQol EQ-5D instruments was sent by post to 147 patients who had received a liver transplant, indicated by a chronic liver disease, in the previous 8 years. The scores of the respondents were compared to population norm scores. The variation in both the SF-36 and EQ-5D scores was explored. Many liver transplant patients experienced most satisfactory QoL levels post-transplantation although, in general terms, the levels were poorer than those seen in the general population. The variation in the post-transplant health-related QoL scores was found to be associated with a number of pre-transplant factors: disease severity (proxied by Child Pugh class), disease duration at the time of transplantation and liver transplant history (whether the patient had received a single or multiple transplants). In making clinical decisions about the use of transplantation for chronic liver diseases, consideration should be given to the key factors likely to affect subsequent health-related QoL.

Adolescent↗