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Biomedical subjects

A K Burroughs

Publications and source records attributed to A K Burroughs.

At least 73 records · Page 4Linked to original sources
PubMed2001

Terbinafine-induced hepatic dysfunction.

A 41-year-old man developed severe hepatic dysfunction following a 3.5-week course of terbinafine (250 mg/day). He suffered marked pruritus, jaundice, malaise, anorexia and loin pain. Serum bilirubin rose to a peak value of 718 micromol/l with alkaline phosphatase at 569 U/l, alanine aminotransferase at 90 U/l, aspartate aminotransferase at 63 U/l and a prolonged prothrombin time of 21 s, unresponsive to vitamin K. Transjugular liver biopsy showed canalicular cholestasis consistent with a drug reaction. Symptoms resolved 11 months after drug cessation, with liver function tests returning to normal values after 15 months. This case represents the most severe cholestatic reaction reported to date, resulting in patient recovery without liver transplantation. A comprehensive literature review is provided.

Adult↗
PubMed2000

The influence of cytomegalovirus viraemia on the outcome of recurrent hepatitis C after liver transplantation.

BACKGROUND: Several interrelated host and hepatitis C virus (HCV) associated factors have been proposed to explain the variable outcomes in HCV recurrence. Recent evidence suggests that cytomegalovirus (CMV) infection not only is co-factor in progression of HCV recurrence but may precipitate allograft rejection. We investigated whether short-term CMV viremia influences HCV recurrence, the number and grade of acute rejection episodes, and the histological course of HCV recurrence during the first year after orthotopic liver transplantation (OLT) for HCV-related cirrhosis. METHODS: A cohort of 39 patients transplanted for cirrhosis HCV-related was analyzed. Patients were evaluated twice weekly for CMV infection by a blood polymerase chain reaction (PCR) assay. Triple therapy with cyclosporine or tacrolimus, azathioprine and prednisolone was the initial immunosuppressive regimen. Preemptive treatment with ganciclovir was started when two consecutive PCRs for CMV were positive. Liver biopsies were performed on day 7 after OLT or when indicated. A 3-day IV 1 g methilprednisolone was given to patients with moderate or severe rejection. Ishak's score was used to grade inflammation and to stage fibrosis. RESULTS: Neither CMV viremia nor CMV disease after OLT for HCV-related cirrhosis adversely influenced the incidence and grade of acute rejection episodes nor the histological outcome of post transplant HCV recurrence, during the first year after liver transplantation. CONCLUSION: CMV viremia as detected by PCR does not affect the progression of HCV recurrence in liver grafts.

Adult↗
PubMed2000

Relationship between IgM antibody to human cytomegalovirus, virus load, donor and recipient serostatus, and administration of methylprednisolone as risk factors for cytomegalovirus disease after liver transplantation.

A retrospective study was performed on a selected cohort of 40 liver transplant recipients derived from the previous prospective follow-up of 162 liver transplant patients. The criterion for selection of this cohort was the presence of human cytomegalovirus (HCMV) DNAemia after transplantation, as determined by qualitative polymerase chain reaction (PCR). These 40 patients were followed longitudinally by quantitative PCR and by the new recombinant antigen-based AxSYM immunoassay for IgM to HCMV. The detection of IgM to CMV after transplantation was significantly associated with the development of HCMV disease in patients who had evidence of active HCMV replication in the blood by PCR (P=.01). On the basis of multivariate logistic regression analyses, the maximum titer of IgM detected after transplantation was a risk factor that was independent of augmented methylprednisolone and donor seropositivity. However, in multivariate analyses, elevated virus load continued to be the predominant risk factor for progression to HCMV disease.

Anti-Inflammatory Agents↗
PubMed2000

Recurrent hepatitis C after liver transplantation.

Cirrhosis due to hepatitis C is now the commonest indication for liver transplantation in Western Europe and in the United States. Graft reinfection is almost universal. The natural history of recurrent hepatitis C ranges from minimal damage to cirrhosis in a few months or years. Different virus and host immune factors are involved in the pathogenesis of hepatitis and are determinants of the outcome. The association between immunosuppression and severity of HCV recurrence is conflicting and remains to be evaluated fully. The treatment of recurrent HCV disease with IFN or ribavirin, as monotherapy, is ineffective. Preliminary results from combination therapy, however, are encouraging. Currently, a reasonable approach would be to treat patients with histological and clinical disease progression. New approaches for the prophylaxis of recurrent hepatitis C are under evaluation but whether this treatment will influence the severity of liver disease or the outcome of recurrence is still unknown.

Antiviral Agents↗
PubMed2000

Diurnal changes of fibrinolysis in patients with liver cirrhosis and esophageal varices.

Variceal bleeding, whose triggering mechanisms are largely unknown, occurs with a circadian rhythmicity, with 2 peaks, one greater, in the evening, and one smaller, in the early morning. We assessed some clotting and hemodynamic parameters, possibly involved in variceal hemorrhage, over a 24-hour period, at 4-hour intervals, in 16 patients with cirrhosis and esophageal varices and in 9 controls. At each time interval, tissue plasminogen activator (tPA) and tPA inhibitor-1 (PAI-1) antigens and activities and total euglobulin fibrinolytic activity were determined and portal-vein flow velocity, volume, and congestion index were measured by duplex-Doppler. Significant circadian rhythms were searched for by least-squares and cosinor methods. tPA activity showed a circadian rhythm in cirrhosis, with a peak of 2.85 times the trough value, calculated at 18:42, and remained over 2.5-fold until shortly after 22:00. Total fibrinolytic activity showed a similar pattern, which was statistically significant also in controls. tPA and PAI antigens also showed significant circadian rhythm both in controls and cirrhotics, with higher values in the morning. Among the portal hemodynamic parameters only the congestion index showed significant rhythmic changes and only in cirrhosis, with the highest values in the late evening, but with limited diurnal excursion (+/- 5.5%). In conclusion, we showed the existence of a circadian rhythm of fibrinolysis in cirrhosis, whose temporal distribution might suggest a role of fibrinolysis in variceal hemorrhage on the basis of the comparison to the known chronorisk of variceal bleeding.

Blood Flow Velocity↗
PubMed2000

Development of ductopaenic liver allograft rejection includes a "hepatitic" phase prior to duct loss.

BACKGROUND/AIM: Recent reports suggest the possible role of a parenchymal inflammatory reaction in the developing phase of chronic rejection. The aim of this study was to identify both clinical and histological abnormalities related to the development of chronic rejection, especially the topography of the inflammatory reaction occurring in the post-transplant period. METHODS: We studied retrospectively, 103 liver allograft biopsies from 10 patients. These 10 patients represented all the patients who developed chronic rejection (confirmed by duct loss and foamy arteriopathy in these grafts removed at retransplantation) and who had non-viral-related disease originally; in the study period 1990-1998 at the Royal Free Hospital (during which 451 liver transplants were performed). As a control population, we reviewed 28 patients who had been transplanted for non-viral end-stage liver disease at our institution in the same study period and who were retransplanted for complications other than chronic rejection. RESULTS: In nine patients documented histologically lobular hepatitis preceded chronic rejection. In one patient, although non-specific lobular changes were present in the early post-transplant period, lobular hepatitis was identified repeatedly after chronic rejection had been diagnosed. Cytomegalovirus was identified immunohistochemically in one patient. In the remaining nine patients extensive clinical and histological investigations failed to demonstrate the presence of any known viral agent. Features of hepatitis were found in only 3 of the 28 patients of the control group. CONCLUSIONS: A "hepatitic" phase anticipates chronic ductopaenic rejection. Further studies are necessary in order to clarify the pathogenesis of this reaction.

Adolescent↗
PubMed2000

Review article: primary prophylaxis for portal hypertensive bleeding in cirrhosis.

Variceal bleeding is a consequence of portal hypertension, which in turn is the major complication of hepatic cirrhosis. Given the high rate of mortality of the first bleeding episode, primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identification of patients with varices who will bleed, before they do so, can justify a strategy of treating all patients with varices prophylactically. We evaluated the various therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta-analysis where applicable. The current first choice treatment is non-selective beta-blockers; it is cheap, easy to administer, and is effective in preventing the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug therapy of beta-blockers and nitrates looks promising, but needs further evaluation in randomized controlled trials. The conflicting results of the randomized studies of endoscopic banding ligation and the small number of patients and clinical events, as well as the cost, do not warrant any change in current practice. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to beta-blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials.

Adrenergic beta-Antagonists↗
PubMed2000

Posttransplantation prevention and treatment of recurrent hepatitis C.

Hepatitic C virus (HCV) viremia is universal after orthotopic liver transplantation (OLT) for HCV cirrhosis. 2. At 5 years post-OLT, approximately 20% of patients have cirrhosis caused by recurrent hepatitis C. 3. Progression of disease is related to immunosuppression, immune response (CD4(+) lymphocytes), HCV genotype, and HCV quasispecies homogeneity. 4. Whether a therapeutic strategy of pre-OLT or early (preemptive) antiviral therapy is better than treating a clinically important hepatitis and the duration of treatment are not known. 5. Monotherapy with recombinant interferon-alpha or ribavirin is not useful in the long term. 6. Combination therapy (interferon and ribavirin) has given better results, but long-term data are not available. 7. HCV recurrence will benefit from randomized studies.

Anti-Inflammatory Agents↗
PubMed2000

Toxicity of high-activity 111In-Octreotide therapy in patients with disseminated neuroendocrine tumours.

Disseminated neuroendocrine tumours are difficult to treat and are generally not responsive to radiotherapy or chemotherapy. Nuclear medicine techniques using a radiolabelled somatostatin analogue, 111In-Octreotide, have been used for the diagnosis of neuroendocrine tumours. It has been suggested that high activities of such an agent may have a therapeutic effect. The aims of this study were to assess toxicity and to determine if there had been evidence of efficacy. Eight patients with known disseminated neuroendocrine tumours were enrolled in the study; six had carcinoid tumours, one had a medullary cell carcinoma of the thyroid and one patient had a malignant gastrinoma. Between 1.3 and 4.6 GBq of 111In-Octreotide were administered to each patient for up to five administrations over 12 months. A total of 23 administrations were given. Tests of vital signs, renal, liver and endocrine function as well as haematological markers were taken before and after treatment. The treatment was well tolerated with only one patient suffering from a sensation of flushing during the infusion but no changes in vital sings. There was a transient (up to 48 h) drop in circulating lymphocytes in four patients and platelets in two patients; no supportive therapy was needed. One patient with severe renal impairment had a slight reduction in glomerular filtration rate. We conclude that high-activity 111In-Octreotide is well tolerated with low toxicity and can be considered for use in patients with disseminated neuroendocrine tumours. Further work is now being performed to assess efficacy.

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↗
PubMed2000

Alcoholic hepatitis-the case for intensive management.

Alcoholic hepatitis is a common condition with a high mortality. Although treatment options for established alcoholic hepatitis are limited, many of the complications of this condition are preventable. This case report and discussion illustrate the important role of early diagnosis and intervention in this patient group. Important management points are stressed to aid physicians who may encounter this condition rarely.

Adult↗
PubMed2000

Prevention of first upper gastrointestinal bleeding in cirrhosis.

Variceal bleeding due to portal hypertension, is a major complication of hepatic cirrhosis. There is a high mortality rate after first bleeding so that primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identifying individual patients with varices who will bleed before they do so, can justify a strategy of prophylactic treatment for all patients with varices. We have evaluated the different therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta-analysis where applicable. The current treatment of first choice is non-selective beta-blockers; it is cheap, easy to administer, and is effective in preventing the first variceal hemorrhage and bleeding from gastric mucosa. Combination drug therapy of beta-blockers and nitrates probably gives little added advantage. Injection sclerotherapy is contraindicated. The conflicting results of the randomized studies of endoscopic banding ligation, as well as its cost, do not warrant its use at present. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to beta-blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials.

Journal Article↗
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↗