PubMed Health⌕ Search

Biomedical subjects

A K Burroughs

Publications and source records attributed to A K Burroughs.

At least 19 recordsLinked to original sources
PubMed2004

Extensive homology between the major immunodominant mitochondrial antigen in primary biliary cirrhosis and Helicobacter pylori does not lead to immunological cross-reactivity.

BACKGROUND: Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic disease characterized by the presence of antibodies directed predominantly against the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). What provokes tolerance breakdown in PBC remains to be established, though there is evidence to indicate that microbes may induce anti-mitochondrial antibodies (AMA) through a mechanism of molecular mimicry. METHODS: Having found that urease beta (UREB)(22-36) antigen of Helicobacter pylori (HELPY) shares extensive (87%) similarity with PDC-E2(212-226), the major mitochondrial autoepitope, it was hypothesized that this would also lead to cross-reactivity. The UREB/PDC-E2 mimics were thus constructed and tested by ELISA in 112 PBC patients and 114 controls. RESULTS: Reactivity to PDC-E2(212-226) was found in 104 patients but to UREB(22-36) in only 2. In these two patients, the double reactivity was not cross-reactive. The lack of surface antibody accessibility to UREB(22-36), as demonstrated through three-dimensional model prediction analysis, may explain this unexpected finding. There was some speculation on whether HELPY UREB(22-36) might act as a cross-reactive CD4 T-cell epitope. All seven PBC patients, tested in a standard proliferation assay against PDC-E2(212-226), gave a positive response. All seven were unresponsive to HELPY UREB(22-36). The pattern of reactivity to HELPY antigens by immunoblot was similar between anti-PDC-E2-positive and negative PBC cases, as well as between PBC patients and controls. CONCLUSION: Contrary to common belief, extensive sequence homology (molecular mimicry) between self and microbe does not necessarily result in cross-reactivity. It is therefore likely that, when present, cross-reactivity between self and microbes is of biological importance.

Adult↗
PubMed2004

Effect of sodium valproate on esophageal motility in healthy subjects and patients with gastroesophageal reflux.

BACKGROUND: There is experimental evidence to show that upper gastrointestinal tract motility is influenced by a GABAergic mechanism. Sodium valproate acts as a GABA agonist, and has been proven to affect the human internal anal sphincter. The aim of this study was to evaluate any possible effect of sodium valproate on esophageal motility in healthy subjects and patients with gastroesophageal reflux disease (GERD). METHODS: Ten healthy volunteers (4 M, 6 F; age range: 20-61 years) and 12 patients (4 M, 8 F; age range: 25-70 years) with GERD were included in the study. Standard esophageal manometry and ambulatory 24-h esophageal pH monitoring were performed before and 5 days after oral administration of sodium valproate (400 mg four times per day). Main measurements included a) lower esophageal sphincter (LES) resting pressure and amplitude and duration of peristalsis at 5, 10 and 15 cm proximal to LES, and b) percentage of time with esophageal pH <4 and number of reflux episodes. RESULTS: Sodium valproate (i) significantly increased LES resting pressure in both groups (P<0.05), without affecting either the LES postdeglutition relaxation or any of the parameters of the esophageal peristaltic activity, (ii) significantly reduced the number of reflux episodes at the postprandial period in both healthy subjects (P=0.02) and reflux patients without hiatal hernia (P=0.04) and (iii) the time percentage with esophageal pH <4 at the postprandial period in reflux patients (P=0.01). CONCLUSIONS: Sodium valproate increases normal and reduced tonic activity of the human LES and reduces the number of reflux episodes in health and GERD. This action could be attributed to a central GABAergic mechanism.

Adult↗
PubMed2004

Monitoring target reduction in hepatic venous pressure gradient during pharmacological therapy of portal hypertension: a close look at the evidence.

Recurrent variceal bleeding is very frequent after variceal haemorrhage and pharmacological therapy is the first choice treatment. Recently, baseline and repeat measurements of hepatic venous pressure gradient (HVPG) have been considered necessary to optimally manage patients receiving pharmacological therapy so as to reduce the frequency of rebleeding. However, the clinical validity and applicability of monitoring for target HVPG reductions is not sufficiently proven and needs to be specifically evaluated in a prospective trial.

Antihypertensive Agents↗
PubMed2004

Systematic review of radiological imaging for hepatocellular carcinoma in cirrhotic patients.

We systematically reviewed the evidence for determining the best radiological imaging for characterizing hepatocellular carcinoma (HCC) in cirrhotic patients in 997 articles between 1995 and 2001. We selected only prospective and retrospective cohorts of patients, excluding both case reports and studies without separate data on HCC. Only 29 studies, comprising 918 patients, fulfilled the inclusion criteria: 10 used the explanted liver as the reference standard of diagnosis. All except one, either found no statistically significant difference between imaging modalities or had no direct comparison of sensitivity between different modalities of imaging; 16 studies evaluated HCC among cirrhotic patients and had biopsy or imaging as the reference standard for diagnosis. However, no one imaging technique was shown to be superior. In two studies, data of a HCC subgroup was derived from the studies evaluating different kinds of focal hepatic lesions. No conclusion could be drawn because of the small sample size. One study addressed the issue of therapeutic impact. The evidence for choosing the best modality of imaging for characterizing HCC in cirrhotic patients is inadequate. Large multicentre studies with defined reference standards for diagnosis, and studies evaluating therapeutic impact are needed.

Carcinoma, Hepatocellular↗
PubMed2003

Review article: pruritus in cholestatic and other liver diseases.

Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver-based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first-line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.

Anion Exchange Resins↗
PubMed2003

Is the use of albumin of value in cirrhosis? The case not so in favour, or is there an alternative?

A decreased effective arterial blood volume is the principal haemodynamic disturbance in cirrhosis, leading to activation of the renin angiotensin aldosterone and the sympathetic nervous systems, sodium and water retention and renal impairment. Albumin is a plasma expander that could be used in clinical settings in cirrhosis in which plasma expansion would reverse some of the decreased effective arterial blood volume, or prevent its iatrogenic (i.e., paracenteses) or spontaneous worsening (spontaneous bacterial peritonitis). However, apart from the issue of transmission of prion agents, which may become an important issue in clinical risk management of the use of albumin in the future, the problem with albumin is its expense. Every effort must thus be made to definitely prove albumin is always the best colloid for all clinical settings in cirrhosis. Further randomized trials are justified.

Albumins↗
PubMed2003

Association between the primary biliary cirrhosis specific anti-sp100 antibodies and recurrent urinary tract infection.

BACKGROUND AND AIMS: Recurrent urinary tract infections (rUTI) have been suggested to be involved in the induction of anti-mitochondrial antibodies (AMA), the serological hallmark of primary biliary cirrhosis (PBC), in view of the presence of AMA in rUTI women without liver disease and conversely of a high prevalence of rUTI in women with PBC. This prompted us to investigate whether PBC-specific anti-nuclear antibodies (ANA) to sp100, gp210 and lamin B receptor (LBR) antigens may also be related to rUTI. METHODS AND SUBJECTS: PBC-specific ANA reactivities were investigated in 20 women with rUTI but without liver disease, some of whom were AMA-seropositive; 40 women with PBC, with or without rUTI; and 104 pathological and 23 healthy controls. RESULTS: Among the women with rUTI but without liver disease, 8 (80%) of 10 AMA-positive women reacted with sp100 compared with none of the 10 AMA-negative women. Among the PBC patients, 14 (74%) of 19 with rUTI and 1 (4.8%) of the 21 without rUTI reacted with sp100. None of the rUTI women without liver disease reacted with gp210 or LBR. None of 127 pathological and healthy controls had PBC-specific ANA reactivity. CONCLUSIONS: Anti-sp100 reactivity strongly correlates with AMA seropositivity in rUTI women, with or without evidence of primary biliary cirrhosis. These findings provide additional support to the notion that E. coli infection is involved in the induction of PBC-specific autoimmunity. Additional factors must be involved in the progression to overt autoimmune disease.

Adult↗
PubMed2003

Review article: hepatocellular carcinoma: indications for liver transplantation.

The role of liver transplantation for hepatocellular carcinoma has evolved over the years and currently is one of the curative therapies for small tumours. The survival rates are similar with those for nonmalignant liver disease after transplantation. The treatment of small tumours eligible for both resection and transplantation depends on the experience of the transplant centre and the waiting time for a liver graft. With waiting times for liver transplant becoming gradually longer, prioritization of the tumour patients has been suggested. Adjuvant therapies may delay the tumour progression while patients wait for a transplant. The living donor and the domino liver transplantation are useful alternatives given the shortage of organs but the experience is still limited in the Western world and the selection for the domino livers is fairly restricted.

Carcinoma, Hepatocellular↗
PubMed2003

Focal nodular hyperplasia-like areas in cirrhosis.

AIMS: Focal nodular hyperplasia-like lesions have rarely been described in cirrhotic livers. We describe five cases of such lesions. METHODS AND RESULTS: Between 1998 and 2001, 146 liver transplants were performed at the Royal Free Hospital for cirrhosis of the liver. Nodular lesions identified in the livers removed at transplantation were defined histologically according to the International Working Party classification (Hepatology 1995; 22; 983). They were present in 63 of these livers, as follows: 36 dysplastic nodules, 121 macroregenerative nodules, and 71 hepatocellular carcinomas. In five patients, an additional 12 nodules (size range 4-23 mm, median 10.5 mm) showed histological features suggestive of focal nodular hyperplasia including mildly inflamed vascular fibrous septa, and ductular proliferation. Pre-transplantation imaging showed features suspicious for hepatocellular carcinoma, in three of these lesions (12, 23 and 23 mm diameter) from two different patients. These lesions were histologically indistinguishable from focal nodular hyperplasia occurring in non-cirrhotic livers, with fibrous scars and septa which contained vascular and ductular structures. CONCLUSIONS: It is important to recognize that these lesions may occur in the context of cirrhosis and that they should be considered in the differential diagnosis with hepatocellular carcinoma, dysplastic nodules and macroregenerative nodules.

Adult↗
PubMed2002

A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis.

BACKGROUND & AIMS: Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). METHODS: One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. RESULTS: The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). CONCLUSIONS: In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.

Adrenergic beta-Antagonists↗
PubMed2002

Assessment of therapeutic benefit of antiviral therapy in chronic hepatitis C: is hepatic venous pressure gradient a better end point?

Chronic hepatitis C is a major healthcare problem. The response to antiviral therapy for patients with chronic hepatitis C has previously been defined biochemically and by PCR. However, changes in the hepatic venous pressure gradient (HVPG) may be considered as an adjunctive end point for the therapeutic evaluation of antiviral therapy in chronic hepatitis C. It is a validated technique which is safe, well tolerated, well established, and reproducible. Serial HVPG measurements may be the best way to evaluate response to therapy in chronic hepatitis C.

Antiviral Agents↗
PubMed2001

The role of different immunosuppression in the long-term histological outcome of HCV reinfection after liver transplantation for HCV cirrhosis.

BACKGROUND: The effect of the type of immunosuppression on the course of posttransplant hepatitis C virus (HCV) infection is unclear. The aim of this study was to evaluate the histological outcome of posttransplant HCV infection with respect to initial immunosuppressive therapy in a cohort of 59 of 65 HCV positive transplant patients who survived at least 12 months. METHODS: Initial immunosuppressive therapy was triple (cyclosporine or tacrolimus and azathioprine and prednisolone) in 41, double (cyclosporine and prednisolone) in 5, and single (cyclosporine or tacrolimus) in 13 patients. There was blinded histological evaluation, based on necroinflammatory activity (grading score:0-18) and fibrosis (staging score: 0-6). The median histological follow-up was 36 (12-72) months. RESULTS: In the last liver biopsy, high necroinflammatory activity indicating chronic hepatitis (grading score > or =4) was found in 42 (71%) and severe fibrosis or cirrhosis (staging score > or =4) in 18 (30.5%) patients. High necroinflammatory activity was associated significantly with absence of pretransplant alcohol abuse (P=0.01) and relatively with occurrence of posttransplant acute lobular hepatitis C (P=0.055). Development of severe fibrosis or cirrhosis was significantly associated only with the type of initial immunosuppressive therapy. In particular, severe fibrosis or cirrhosis developed significantly more frequently in patients treated with triple or double (17/46 or 37%) than with single initial immunosuppressive therapy (1/13 or 7.7%) (adjusted for biopsy time: P=0.045). CONCLUSIONS: Severe fibrosis or cirrhosis appears to develop in 30% of HCV transplant patients in a median of 3 years and to be associated with heavier initial immunosuppression.

Adult↗
PubMed2001

CD8+ cytotoxic lymphocyte responses against cytomegalovirus after liver transplantation: correlation with time from transplant to receipt of tacrolimus.

The effects of the immunocompromised state after liver transplantation on the frequency of cytomegalovirus-specific cytotoxic T lymphocytes (CTL) were investigated in 93 patients by using HLA class I tetrameric complexes corresponding to HLA-A*0201, HLA-B*0702, HLA-B*0801, and HLA-B*3501 refolded with peptides from the ppUL83 matrix protein. ppUL83 CTL frequencies were suppressed during the first 6 months after transplantation. Patients with >1 HLA-restricted response detected had high correlation among ppUL83 CD8(+) CTL frequencies restricted by different HLA haplotypes (Spearman's rho=.67; P<.0001). There was an inverse correlation among levels of the calcineurin inhibitor, tacrolimus, and ppUL83 CD8(+) CTL frequencies (r=-.31; P=.005), which is consistent with the presence of a large proportion (70%) of activated (CD38(+)) ppUL83 CD8(+) CTL within the population of HLA class I tetramer-positive cells.

Adolescent↗