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K Rolles

Publications and source records attributed to K Rolles.

At least 37 records · Page 2Linked to original sources
PubMed2000

Non-invasive measurement of hepatic oxygenation by an oxygen electrode in human orthotopic liver transplantation.

Precise evaluation of graft reperfusion is difficult in clinical liver transplantation. The oxygen electrode (OE) is a novel technique to detect blood flow indirectly by measuring the quantity of oxygen which can diffuse from the hepatic tissue to the surface electrode. Application of the surface OE does not influence the liver blood flow or parenchymal perfusion. Adequate graft oxygenation is essential to the outcome of organ transplantation and has not previously been analysed intra-operatively in liver transplant recipients. The OE was applied to the surface of the graft intra-operatively in 22 human liver grafts after restoring portal vein and hepatic artery inflow. OE readings were compared with liver blood flow using an electromagnetic flowmeter (EMF). Intra-operative haemodynamics and donor organ parameters known to influence graft function were correlated with the OE readings. There was a significant correlation (r=0.89; p<0.001, n=14) between tissue oxygenation using the OE and total liver blood flow measured by EMF. The tissue oxygenation measurements were reproducible with a coefficient of variation of 5%. The hepatic tissue oxygenation increased significantly from baseline following venous reperfusion of the graft (282+/-23 vs 3107+/-288 (+/-SE) nA, p<0.001). Hepatic arterial revascularisation resulted in a significant (p<0.001) increase of 41+/-7% in liver oxygen perfusion. There was significant negative correlation (r=0.80, p<0.001, n=22) between cold ischaemic time and graft tissue oxygenation. The OE provides a reliable, cheap and non-invasive method of monitoring liver graft oxygenation and perfusion during transplantation.

Adult↗
PubMed2000

Idiopathic fibrosing pancreatitis and Crohn's disease: an interesting association.

Idiopathic fibrosing pancreatitis is an uncommon condition in children and adolescents of unknown aetiology. This syndrome has been reported in 36 cases so far. To our knowledge none of these cases was definitively associated with Crohn's disease. In this report we describe a young female patient who developed Crohn's disease of the colon 5 years after having been diagnosed with idiopathic fibrosing pancreatitis. The differential diagnosis between this syndrome associated with Crohn's disease and pancreatic Crohn's disease or fibrosing colonopathy, an entity related to pancreatic enzyme therapy, is discussed.

Adolescent↗
PubMed1999

A pilot study of immunosuppressive monotherapy in liver transplantation: tacrolimus versus microemulsified cyclosporin.

BACKGROUND: Many reports of successful early withdrawal of regular maintenance steroids in transplant recipients have appeared in recent years. The question now arises whether, in the current age of powerful nonsteroidal immunosuppressants such as Neoral and Tacrolimus, routine administration of steroids posttransplant is necessary at all. This single center pilot study reports on the feasibility, safety, and efficacy of single agent immunosuppression "ab initio" with either Neoral or Tacrolimus, and no routine or maintenance steroids. METHODS: A total of 64 adult patients receiving first liver grafts for a variety of indications were randomized to receive either Neoral 5 mg/kg BDS or Tacrolimus 0.05 mg/kg BDS orally. Liver biopsies were performed on postoperative days 5 and 10, and whenever else clinically indicated. Rejection episodes were treated with 1.0 g of Methylprednisolone daily for 3 consecutive days. A further episode of rejection after two courses of Methylprednisolone was considered to be monotherapy failure, and consequently other immunosuppressive agents, usually Prednisolone 1 mg/kg/day, was started on a regular basis, tapering slowly. RESULTS: Actuarial 1 year survival was 85% for Tacrolimus patients, and 78% for Neoral patients (P = NS), with 80% for Tacrolimus and 73.5% for Neoral at 30 months. Graft survival at 1 and 2.5 years was 73 and 62% for Tacrolimus and Neoral, respectively (P = NS). Two-thirds of patients in both groups showed biopsy evidence of acute cellular rejection. Rejection severity measured by a histological scoring system was similar for both patient groups. Additional longterm immunosuppressive therapy was necessary in 36% of patients receiving Neoral, compared with 13% of Tacrolimus patients (P = NS). No graft was lost on account of acute or chronic rejection. Short-term pulse steroid therapy to treat acute rejection was necessary for 60% of Tacrolimus patients and 40% of Neoral patients. CONCLUSION: Tacrolimus or Neoral monotherapy after liver transplantation provides adequate immunosuppression for 87% of Tacrolimus patients and 64% of Neoral patients. In this study, 33% of patients in both groups showed no evidence of acute rejection, either clinically, biochemically or histologically, and were not exposed to steroids at any time. Evaluation of the long-term morbidity related to the side effects of the immunosuppressants given as monotherapy, for example, renal impairment and posttransplant lymphoproliferative disorder, and the effect on recurrent viral hepatitis in the graft, would be suitable areas for further study.

Adult↗
PubMed1999

Mycophenolate mofetil monotherapy in stable liver transplant patients with cyclosporine-induced renal impairment: a preliminary report.

BACKGROUND: Cyclosporine is the most common maintenance immunosuppressant in liver transplants patients, but it is often associated with nephrotoxicity. METHODS: We evaluated the safety and efficacy of monotherapy with mycophenolate mofetil (1 g twice daily) in five stable liver transplant patients with cyclosporine-induced renal impairment despite reduction of cyclosporine to subtherapeutic levels. Follow-up was 8.4+/-2.4 (range: 6-12) months. RESULTS: No major side effects have been observed to date. Serum creatinine levels were significantly reduced from a median of 201 micromol/L before to 142 micromol/L at 3 months after mycophenolate (P=0.04) and remained low at 6 months. New onset cellular rejection occurred in only one patient after 3 months on mycophenolate monotherapy, and it responded completely to an intravenous course of methylprednisolone. CONCLUSIONS: Monotherapy with mycophenolate mofetil in a dose of 1 g twice daily seems to significantly improve cyclosporine-induced renal impairment in stable liver transplant patients without major side effects or significant risk of rejection.

Creatinine↗
PubMed1999

Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus.

Because cytomegalovirus (CMV) is an important opportunistic infection after liver transplant, we conducted a prospective study to see if the same applied to human herpesviruses (HHV)-6 and -7. We used polymerase chain reaction (PCR) methods optimised to detect active, not latent, infection and studied patients not receiving antiviral prophylaxis for CMV. Post-transplant, 536 blood samples were tested by PCR (median 7; range 4-50). Active infection with CMV was detected in 28/60 (47%), HHV-6 in 19/60 (32%), and HHV-7 in 29/60 (48%) of patients. The PCR-positive samples were tested by quantitative-competitive PCR to measure the virus load of each betaherpesvirus. The median peak virus load for CMV was significantly greater than that for HHV-6 or HHV-7. Detailed clinicopathological analyses for the whole population showed that CMV and HHV-6 were each significantly associated with biopsy-proven graft rejection. Individual case histories suggested that HHV-6 and HHV-7 may be the cause of some episodes of hepatitis and pyrexia. It is concluded that HHV-6 is a previously unrecognized contributor to the morbidity of liver transplantation, that HHV-7 may also be important and that both viruses should be included in the differential diagnosis of graft dysfunction.

Adult↗
PubMed1999

Posttransplantation lymphoproliferative disorder in liver recipients: characteristics, management, and outcome.

Posttransplantation lymphoproliferative disorder (PTLD) is a well-recognized complication of organ transplantation. The aim of this study, performed over 9 years, was to examine the histopathological findings, clinical course, and outcome of patients who, having undergone orthotopic liver transplantation (OLT), developed PTLD. The sample included 7 adult liver allograft recipients (1.7%), 4 men and 3 women, with a mean age of 53 years (range, 40 to 61 years) who developed PTLD 1 to 36 months post-OLT (mean, 6 months). Four patients received either antithymocyte globulin as primary immunosuppression or OKT3 for steroid-resistant cellular rejection. Four patients had localized hepatic tumor with or without regional lymph node involvement, 2 patients had extralymphoreticular disease (head of pancreas and chest wall), and 1 patient had spleen and lymph node involvement. All tumors were B-cell lymphomas; three polymorphic and four monomorphic. Clonality was assessed by immunostaining for kappa and lambda and gene rearrangement. Monoclonality was found in 4 patients and polyclonality in 2 (1 of whom progressed to monoclonality); in 2 patients, clonality could not be determined. Immunohistochemistry findings for the presence of the Epstein-Barr virus (EBV)-determined nuclear antigen and the latent membrane protein 1 were noted in lymphoma tissue in 6 patients. Immunosuppressive therapy was decreased in all patients. Polyclonal tumors were treated with acyclovir (1 patient is in complete remission and 1 patient died), and monoclonal tumors with systemic chemotherapy (2 patients are in complete remission and 2 patients died). One patient was treated with monoclonal antibodies (CD20) but failed to respond, and 1 patient was treated with excision and is in complete remission. The mortality rate was 43%; for the remainder, median survival is 21 months (range, 10 to 42 months). We conclude that PTLD may re-present early after OLT. EBV has a special role in the pathogenesis, combined with immunosuppressive therapy. The outcome is poor, and new therapeutic approaches are needed.

Adult↗
PubMed1999

Psychiatric and social outcome following liver transplantation for alcoholic liver disease: a controlled study.

Psychiatric outcome, quality of life, and alcohol consumption were compared between patients transplanted for alcoholic liver disease and those transplanted for other chronic liver diseases. Instruments used included the Clinical Interview Schedule, the 28-item General Health Questionnaire, the Hospital Anxiety and Depression Scale, and the Nottingham Health Profile. There was no difference between the two groups with regard to median scores or "caseness" on these instruments, except for physical mobility on the Nottingham Health Profile, where the alcoholic group was more likely to experience difficulties (p = 0.03). The majority of those transplanted for alcoholic liver disease remained abstinent, although 7 of the 31 in the alcoholic group (23%) were drinking above recommended safe limits. Psychosocial outcome is similar for individuals transplanted for alcoholic liver disease and those transplanted for other chronic liver diseases. Patients should not be excluded from transplantation on grounds of their drinking history.

Adult↗
PubMed1999

Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation.

BACKGROUND: Biliary reconstruction is the Achilles heel of liver transplantation. Side-to-side anastomosis of donor and recipient bile duct has been claimed to be superior to end-to-end anastomosis in uncontrolled studies. METHODS: A total of 100 consecutive patients undergoing orthotopic liver transplantation were randomized after commencement of the transplant procedure to end-to-end or side-to-side anastomosis. No T tube drainage was employed. Endoscopic retrograde cholangiography was performed 2 weeks after transplantation and findings were reported by an experienced endoscopist as normal, leak or stricture. Median follow-up was 53 (range 35-63) months. RESULTS: Patient age, sex, the graft preservation time and indication for transplantation were similar in both groups. Sixty patients received end-to-end and 40 side-to-side anastomosis. Ten patients randomized to side-to-side anastomosis had an end-to-end procedure. The total number of biliary complications was similar in both groups (end-to-end 32 per cent versus side-to-side 30 per cent) as were the number of leaks (17 versus 18 per cent) and biliary strictures (15 versus 12 per cent). There was no difference in the number of biliary complications that required interventional treatment (22 per cent in both groups). CONCLUSION: Side-to-side and end-to-end biliary anastomosis at liver transplantation are equally effective.

Adolescent↗
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↗
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

In vivo demonstration of impaired microcirculation in steatotic human liver grafts.

The perfusion of human donor livers was studied during organ retrieval using laser Doppler flowmetry to assess the microcirculatory alteration caused by fatty infiltration (steatosis). Using a multichannel laser Doppler flowmeter, we measured the hepatic perfusion as flux units in 21 liver donors, eight of which were macroscopically fatty. Perfusion was recorded continuously for 2 minutes from two sites on each lobe at the beginning of organ retrieval, after the vascular dissection, and during sequential occlusion of the hepatic artery and portal vein. Mean flux value and SEM were calculated, and paired Student's t test was used for comparison between stages of perfusion. Multiple ANOVA was used to determine whether factors other than the normal or fatty parenchyma influenced the perfusion measurements. Mobilization of the graft did not affect parenchymal perfusion. Perfusion was significantly (P < 0.001) and rapidly reduced with hepatic artery or portal vein occlusion in both groups. Macroscopically steatotic livers (n = 8) had diminished microcirculation compared with normal livers (n = 13) (125 +/- 18 v 252 +/- 24 flux units; P = 0.002). Donors receiving inotropes (n = 10) had a lower mean perfusion rate (150 +/- 20 v 252 +/- 29 flux units; P = 0.026), but this effect was found in both the normal and steatotic groups with no interaction (ANOVA; P = 0.658). Steatosis diminishes the tissue perfusion in human liver grafts. Laser Doppler flowmetry may help identify grafts with a compromised microcirculation.

Adolescent↗
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

Combined liver-kidney transplantation in methylmalonic acidemia.

A 13-year-old boy with non-B12-responsive methylmalonic acidemia (MMA) had chronic renal failure. Hemodialysis led to symptomatic and biochemical improvement. He subsequently received a combined liver-kidney transplant. After 16 months of follow-up he has a normal lifestyle and a marked reduction in plasma and urine methylmalonate.

Adolescent↗