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Biomedical subjects

K Rolles

Publications and source records attributed to K Rolles.

At least 73 records · Page 4Linked to original sources

Monoclonal antibodies against eosinophils in liver allograft rejection.

There has been recent interest in eosinophils as a histological diagnostic marker of liver allograft rejection. However, the reliability of counting eosinophils in sections stained with hematoxylin and eosin (H&E) has not been evaluated previously. We quantified eosinophils in 10 day-5 protocol liver biopsy specimens in 10 patients. The control groups were 5 patients with cytomegalovirus infection, 5 patients with obscure liver dysfunction, and 6 patients with HCV infection. Eosinophil count was assessed using H&E and by specific monoclonal antibody staining using (1) an anti-ECP antibody (EG2) and (2) a monoclonal antibody against human eosinophil major basic protein (MBP) (BMK-13). The average percentage of the total inflammatory infiltrate of eosinophils in portal tracts was 9% in the moderate to severe rejection group as compared with 0.25% in the mild rejection group (P < .001) and 0% in the control group (P < .001). The eosinophil count decreased markedly after successful treatment of rejection. The H&E staining correlated with MBP+ the (BMK-13 immunoreactive) cells but were more numerous with BMK-13. BMK-13 also stained significantly more cells when compared with EG2 (P < .01). This difference may be because EG2 staining only activated eosinophils, whereas BMK-13 is a pan-eosinophilic maker, regardless of activation. This study confirms that eosinophils are a specific feature of acute cellular rejection and are an aid to its diagnosis. BMK-13 is a useful pan-eosinophilic marker that is more efficient in obtaining eosinophil count when compared with H&E.

Antibodies, Monoclonal↗

Long-term immunosuppression without corticosteroids after orthotopic liver transplantation: a positive therapeutic aim.

Long-term treatment with corticosteroids after orthotopic liver transplantation (OLT) may cause adverse effects, particularly hypertension, diabetes, and bone disease. The results of steroid withdrawal from long-term immunosuppression in 114 patients after OLT was reviewed. Initial treatment was with corticosteroids, azathioprine, and cyclosporine A in 76.3% and with antithymocyte globulin in 17.5%. Corticosteroids were stopped in 96 patients (84.2%) during mean follow-up of 6.7 +/- 3.9 months, and acute rejection subsequently developed in 8. By comparison 7 of 18 patients, in whom corticosteroids were continued, developed acute rejection. Six of these had received blood group (ABO)-compatible nonidentical grafts. Rates for retransplantation in the steroid withdrawal and nonwithdrawal groups were 4.2% and 22.2%, respectively, and mortality in the two groups was 14.6% and 44.4%, respectively. Azathioprine was not given or withdrawn in 28 patients in the group from which corticosteroids were also withdrawn, with no adverse effect. Diabetes mellitus improved following corticosteroid withdrawal, but there was no improvement in hypertension. We conclude that corticosteroids can be safely withdrawn in the majority of patients after OLT.

Adrenal Cortex Hormones↗

Duct-to-duct biliary reconstruction following liver transplantation for primary sclerosing cholangitis.

The biliary complications in patients undergoing biliary reconstruction by duct-to-duct (D-D) anastomosis or with a Roux-en-Y loop (RL) at the time of liver transplantation for primary sclerosing cholangitis (PSC, 16 D-D, 10RL) or primary biliary cirrhosis (PBC, 31 D-D, 1 RL) were reviewed and compared. Patients were followed up for a mean period of 32 months. Extrahepatic biliary strictures occurred in 18.7%, 10% and 9.7% of DD-PSC, RL-PSC and DD-PBC patients, respectively, leaks in 6.2%, 20% and 6.4% DD-PSC, RL-PSC and DD-PBC patients, respectively (P = NS). Four intrahepatic biliary abnormalities developed in the PSC group. Duct-to-duct anastomosis did not significantly increase the risk of stricture formation or bile leaks in PSC patients compared to PBC patients. We conclude that duct-to-duct biliary reconstruction following liver transplantation for PSC is satisfactory unless the distal common bile duct is strictured.

Adolescent↗

Liver biopsy in liver transplantation: no additional risk of infections in patients with choledochojejunostomy.

BACKGROUND/AIMS: This study aimed to determine whether there is an increased infectious risk following liver biopsy in liver transplant patients with choledochojejunostomy. METHODS: We evaluated the incidence of liver-biopsy-related sepsis in a consecutive series of 27 patients who underwent choledochojejunostomy, either during the transplant procedure (17 patients) or later following biliary complications (10 patients). We evaluated another 138 patients as a control group who had orthotopic liver transplantation during the same period and underwent duct-to-duct anastomosis. All liver biopsies had routine, prior ultrasound evaluation to detect dilated biliary ducts. RESULTS: In the 27 patients who underwent choledochojejunostomy, 96 liver biopsies were performed: the sepsis rate was 3.12% per biopsy (n = 96) or 7.4% per patient (n = 27). However, despite a normal ultrasound, subsequent ERCP demonstrated biliary obstruction in one patient. Thus the rate of sepsis was 2.1% per biopsy or 3.7 per patient. In the control group 338 liver biopsies were performed: the sepsis rate was 1.5% per biopsy (n = 338) or 2.9% per patient (n = 138). The difference was not significant. All septic episodes had positive blood cultures for a single enteric microorganism, and all responded to antibiotics CONCLUSIONS: Our data do not suggest that liver-transplanted patients with choledochojejunostomy are more at risk of sepsis following liver biopsy, providing there is no "occult" biliary obstruction; therefore, they do not require prophylactic antibiotics as has been suggested by other authors.

Adolescent↗

Endoscopic retrograde cholangiography in the diagnosis and endoscopic management of biliary complications after liver transplantation.

OBJECTIVE: Biliary reconstruction in orthotopic liver transplantation is increasingly being performed without T tube drainage. This increases the difficulty of diagnosing subsequent biliary tract problems, with a greater reliance placed on endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of biliary tract complications. The usefulness of ERCP was evaluated in patients who underwent liver transplant where biliary reconstruction was not done with T tube drainage. DESIGN AND PARTICIPANTS: A retrospective study of the case notes of 90 patients who underwent liver transplantation, and in whom the biliary reconstruction was by end to end choledochocholedochostomy without T tube splintage. RESULTS: ERCP was performed as the primary procedure to investigate a suspected biliary complication in 30 patients (33%). The procedure was successful in 26 patients (87%), and showed a biliary stricture in 12 patients and a bile leak in six patients. ERCP was normal in seven patients and demonstrated dilated ducts alone in one patient. Six of the biliary strictures were successfully dilated endoscopically (50%), but none of the bile leaks resolved with endoscopic drainage. CONCLUSION: This study confirms the diagnostic role of ERCP post liver transplant. The therapeutic role requires clearer evaluation with a controlled trial.

Adolescent↗

Hepatic phosphorus-31 magnetic resonance spectroscopy in primary biliary cirrhosis and its relation to prognostic models.

BACKGROUND: In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) provides biochemical information about phosphorus metabolism. AIM: To assess 31P MRS as a prognostic marker in patients with primary biliary cirrhosis (PBC) in relation to the current clinical prognostic models. PATIENTS AND METHODS: Twenty three patients with PBC of varying functional severity and 16 matched healthy volunteers were studied using in vivo 31P MRS. Spectra were acquired using a 1.5 T spectroscopy system. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) and nucleotide triphosphate (NTP) were calculated. Pugh score, Christensen prognostic index, and R value according to the Mayo model were calculated from the clinical data. RESULTS: The PME/NTP, Pi/NTP, PME/PDE, and PME/Pi ratios and the PME signal height ratio (SHR) were significantly higher, while the PDE/NTP and PDE/SHR were significantly lower in PBC patients compared with healthy volunteers (p < 0.01). Significant correlations were seen between PME/Pi ratio and the prognostic index according to Christensen (r = 0.63, p < 0.001), R value according to the Mayo model (r = 0.45, p < 0.03), and with the Pugh score (r = 0.55, p < 0.007). CONCLUSIONS: This study shows that PME/Pi ratio obtained from 31P MRS correlates well with all three of the commonly used models of prognosis in patients with PBC. A longitudinal study with larger number of patients is required to confirm these findings and elucidate the biochemical changes underlying this phenomenon.

Adult↗

Acute Budd-Chiari syndrome treated by liver transplantation in a woman homozygous for factor V Leiden.

We describe the first case of Budd-Chiari syndrome due to homozygosity for factor V Leiden resulting in resistance to activated protein C. This is now recognized as the most common procoagulant disorder, and may account for many cases of Budd-Chiari syndrome previously though to be idiopathic or due to a latent myeloproliferative disorder. A further unique feature of this case is that the patient required orthotopic liver transplantation following failure of portacaval shunting and progressive hepatic necrosis. We demonstrated that liver transplantation resulted in correction of the serum coagulation abnormality; however, it is unlikely to have cured the disorder as platelet factor V would still be of the Leiden phenotype.

Acute Disease↗

Morphometric image analysis and eosinophil counts in human liver allografts.

Histology of liver allografts is the gold standard for diagnosis of acute cellular rejection. However, scoring the severity of rejection and distinguishing it from other infiltrations is not easy. Only one group has evaluated biopsies morphometrically and also suggested that eosinophils are a specific diagnostic feature. We quantitated eosinophil count in 92 biopsies in a group of 25 patients and, in another group of 30 patients, used morphometric image analysis to measure the cross-sectional area and cell density in each portal tract in day 5 protocol liver biopsies. Rejection was diagnosed by pathological evaluation confirmed with clinical and biochemical graft dysfunction graded histologically into mild or moderate-to-severe. The control groups were five patients with no rejection, nine patients with CMV infection, and eight biopsies in eight patients for whom the cause of the liver dysfunction was obscure. The cross-sectional area, the inflammatory cell count of each portal tract and the mean portal tract inflammatory cell density (cells/mm2) increased with the severity of rejection. In each case the regression coefficient was statistically significant. Correlating the mean of the total inflammatory cell count with the mean of the portal inflammatory cell density (cell/mm2) gave far better separation of the mild rejection and moderate-to-severe rejection groups. Eosinophils were specific for the presence of acute cellular rejection and increased with the severity of rejection. They were absent in the no rejection group, in the CMV group and in those with obscure liver dysfunction. The eosinophil count fell markedly following treatment of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Eosinophils↗

Orthotopic liver transplantation for chronic hepatitis in two patients with common variable immunodeficiency.

Two patients with common variable immunodeficiency underwent orthotopic liver transplantation for chronic hepatitis, unequivocally caused by hepatitis C virus in one case. Although one patient had pneumonia 8 days after surgery and the other developed hepatic venular stenosis in the transplanted liver, both had a reasonably good quality of life for at least 15 months. However, both subsequently died of recurrent hepatitis C virus hepatitis or hemorrhage after splenectomy for hypersplenism. This shows that severe infection is not a major problem in patients with common variable immunodeficiency after liver transplantation provided they undergo prophylactic antimicrobial and immunoglobulin therapy. The longer term prognosis must be regarded as poor until more data are available following transplantation in similar patients.

Adolescent↗

Psychiatric and social outcome of liver transplantation.

BACKGROUND: This study measures psychiatric morbidity, quality of life, and cognitive function after liver transplantation. METHOD: We undertook a cross-sectional study, with a longitudinal subgroup. The setting was a tertiary referral centre for liver transplantation. The subjects were 30 post-liver-transplantation patients, including 11 also interviewed before the operation. The main outcome measures were the Clinical Interview Schedule (CIS), the General Health Questionnaire (GHQ), the Nottingham Health Profile (NHP), and the Mini-Mental State Examination (MMSE). RESULTS: Of the patients, 8/30 were CIS cases, and 7/30 were GHQ cases. NHP scores were higher than a previous postal study indicated, with less impairment after than before transplant. MMSE scores were 24-30. Median GHQ was 7.0 before operation and 1.0 after operation (P = 0.03), with no significant change in CIS score. CONCLUSION: Liver transplantation improves quality of life, but not to the level of the general population; post-transplantation patients have a prevalence of psychiatric morbidity comparable with that of general medical patients.

Adolescent↗

Grading of cellular rejection after orthotopic liver transplantation.

All 684 post-orthotopic liver transplantation (OLT) liver biopsies performed at the Royal Free Hospital (RFH) between 1988 and 1993, from 120 patients, were reviewed in order to try to define the relative importance of the histological features of immunosuppression-responsive cellular rejection. Twenty histological features considered to be possible contributors to the diagnosis of cellular rejection were documented in a binary (present/absent) fashion. These features in 106 biopsy specimens obtained 1 to 8 days after OLT were analyzed using stepwise logistic discriminant analysis. All clinical and treatment records were reviewed, and each biopsy specimen was assigned to a diagnostic category depending on these records and follow-up information. Important determinants of the histological diagnosis of cellular rejection (which occurred in 84 of the 106 cases) were moderate/severe mixed portal inflammation, eosinophils, endotheliitis, and bile duct damage. When these all occurred together, the odds of rejection increased 3.6-fold. The original histological diagnosis was recorded, and each biopsy specimen showing cellular rejection was regarded according to the specific criteria of Snover et al., Demetris et al., and a novel RFH scoring system. The latter consists of evaluating portal inflammation, endotheliitis, eosinophils, and bile duct damage, each on a 0 to 3 scale (none, mild, moderate, or severe, respectively) and summation. The resulting cellular rejection score thus can range from 0 to 12. The agreement between the different scoring systems was analyzed using K statistics, and there was good concordance (K, 0.64 to 0.78), despite different histological criteria being used to derive each score. Each system showed a similar degree of sensitivity (87% to 96%). The specificity ranged from 59% to 77%. We conclude that the histological diagnosis of cellular rejection relies mainly on the previously described features of mixed portal inflammation, endotheliitis, eosinophils, and duct damage. There is scope for unification and simplification of the existing grading systems, which depend on differing criteria, and we suggest one such scheme.

Biopsy↗

Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances.

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Incidence, risk factors, management, and outcome of portal vein abnormalities at orthotopic liver transplantation.

Portal vein thrombosis is often considered a contraindication to orthotopic liver transplantation. We have analyzed the incidence, risk factors, management and outcome of patients with portal vein thrombosis undergoing orthotopic liver transplantation. During the period from October 1988 to October 1992 140 grafts were performed on 132 patients. Fourteen had portal vein thrombosis with either partial (n = 7) or complete (n = 7) occlusion of the portal vein at surgery. Portal vein thrombosis was more common in patients with autoimmune chronic active hepatitis (3/5 vs. 11/127, chi 2 = 13.3, P < 0.001), cryptogenic cirrhosis (4/12 vs. 10/120, chi 2 = 7.2, P < 0.01), or those with tumors (6/22 vs. 10/110, chi 2 = 5.7, P < 0.05). In 13 of the 14 portal inflow was reestablished by flushing, balloon thrombectomy, or passage of a graduated dilator. In one patient complete fibrous obliteration necessitated a portal vein to right gastroepiploic vein anastomosis. On follow-up there have been 6 deaths in this group (6/14 = 43%) from recurrent cancer (n = 1), sepsis (n = 4), and cardiac and renal failure (n = 1). Four of these 6 patients had confirmation of PV patency on imaging. The remaining 8 patients are alive and well (median follow-up 37 months, range 6-53 months). Post-transplant portal vein thrombosis occurred in 3 of the 14 patients (21%) with a portal vein abnormality at surgery and in two of the 118 patients with a normal portal vein (3/14 vs. 2/118, chi 2 = 8.5, P < 0.01). Four of the 5 cases were successfully treated by surgical thrombectomy.

Adolescent↗

Donor-specific bone marrow infusion after orthotopic liver transplantation.

Donor-specific bone marrow infusion after organ grafting can induce tolerance in animals. In this randomised controlled study we show it has no benefit in patients undergoing liver transplantation. Of 25 patients, 9 received bone marrow 5 days after a 10 day course of antithymocyte globulin. Immunosuppression was maintained with cyclosporin only. An average of 3.0 rejection episodes per patient was seen in the bone marrow group compared to 3.1 in the controls. Chimerism was not found in peripheral blood or bone marrow of recipients using erythrocyte antigen markers, PCR for donor class II DNA or Y-probe in-situ hybridisation in one female recipient of male liver and bone marrow.

Antigens, Differentiation↗

Biliary anastomosis after liver transplantation does not benefit from T tube splintage.

T tubes are commonly used to splint biliary anastomoses after liver transplantation. Although several advantages are claimed for this approach, there is undoubtedly some iatrogenic morbidity associated with the use of T tubes in this situation. We have evaluated 120 consecutive biliary reconstructions after liver transplant, the majority of which were unsplinted end to end bile duct anastomoses. We have shown that biliary leakage and stricture rates are not significantly affected by T tubes. We have also shown that endoscopic retrograde cholangiopancreatography and percutaneous cholangiography are reliable posttransplant methods for cholangiography and stricture dilatation. Routine T tube splintage of post-liver transplant biliary anastomoses is unjustified.

Anastomosis, Surgical↗

Conjunctival oxygen tension monitoring during liver transplantation.

Conjunctival oxygen tension has been noted in animal studies to correlate with oxygen delivery. In order to assess this relationship in man, we compared the proportional changes in conjunctival oxygen tension with those in oxygen delivery that occur on the placement and release of the inferior vena caval clamps in 10 patients during orthotopic liver transplantation without veno-venous bypass. We also examined the changes in mixed venous oxygen saturation at these times. We found a statistically significant correlation between both parameters and oxygen delivery (p < 0.001). However, analysing the data on a Bland and Altman plot of difference versus mean, it is our conclusion that the variation in the data is such that neither conjunctival oxygen tension nor mixed venous oxygen saturation can be used clinically to predict the changes in oxygen delivery that occur during liver transplantation.

Blood Pressure↗