Gastric endoscopic features in portal hypertension: final report of a consensus conference, Milan, Italy, September 19, 1992.
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Canada↗
Biomedical subjects
A K Burroughs
Publications and source records attributed to A K Burroughs.
Altered prostacyclin synthesis by aortae from hepatic portal vein-constricted rats: evidence for effects on protein kinase C and calcium.
To investigate the mechanisms causing reduced systemic vascular reactivity to vasoconstrictor agents in portal hypertension, we studied receptor- and signal-transduction-linked PGI2 (a vasodilator) synthesis (measured as 6-oxo-PGF1 alpha by radioimmunoassay) in the aorta (ex vivo) of portal vein-constricted rats. PGI2 synthesis was stimulated by adrenaline (via heterogeneous alpha-adrenoceptors), phorbol ester dibutyrate (a protein kinase C activator), arachidonic acid (the substrate for PGI2 synthesis) and the Ca2+ ionophore A23187 (A23187) and thapsigargin (both of which elevate intracellular Ca2+, which in turn elicits the release of arachidonic acid). The release of PGI2 by the aortae of rats with portal hypertension in comparison to sham-operated controls was: 1) enhanced in response to adrenaline, 2) reduced in response to phorbol ester dibutyrate, A23187 and thapsigargin and 3) unchanged in response to arichidonic acid. These data indicate that in aortae from rats with experimental portal hypertension: i) there are no changes in the enzymes involved in PGI2 synthesis (cyclooxygenase, PGI2 synthase), ii) there is a specific increase in adrenoceptor-linked PGI2 synthesis in aortae which may contribute to arterial vasodilation in this experimental model and 3) the diminished response of PGI2 synthesis to A23187, phorbol ester dibutyrate and thapsigargin indicates that there is a generalised attenuation of protein kinase C activator activity and of Ca2+. Since Ca2+ is a key component of excitation-contraction coupling and protein kinase C activator has been implicated in mediating this event, attenuation of these systems may also explain, at least in part, the known reduced vasoactivity of aortae from rats with portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Thalidomide as therapy for primary biliary cirrhosis: a double-blind placebo controlled pilot study.
Thalidomide has been reported to be effective in treating graft-versus-host disease, a condition with many clinical and pathological similarities to primary biliary cirrhosis. We performed a double-blind, placebo-controlled pilot study to assess the efficacy of thalidomide in 18 patients with biopsy-proven primary biliary cirrhosis (10 thalidomide, 8 placebo). Each patient was treated for 6 months and had a liver biopsy before and after treatment. Side effects, particularly sedation and fatigue, were more common on thalidomide and two patients were withdrawn from this group. There were no improvements in liver function tests or in liver histology, assessed morphometrically. A number of patients treated with thalidomide reported an improvement in pruritus. This study suggests that thalidomide is unlikely to be effective in altering the natural history of primary biliary cirrhosis.
Biopsy↗
Review article: the transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of portal hypertension.
The transjugular intrahepatic portosystemic shunt (TIPS) is a non-surgical intrahepatic shunt connecting the hepatic and portal veins. The shunt can be inserted successfully in more than 90% of patients and it effectively decompresses the portal venous circulation. Serious complications, such as intraperitoneal bleeding, occur but they are uncommon. The role of TIPS in the treatment of portal hypertension is currently being evaluated. There are few controlled data available to compare TIPS with established treatment such as drugs, injection sclerotherapy, endoscopic banding or shunt surgery. TIPS has also been used to treat ascites, the Budd-Chiari syndrome and cirrhotic hydrothorax. Concerns over the long-term patency and the true incidence of encephalopathy following TIPS raise doubts about its long-term efficacy. Controlled trials are required to demonstrate the cost-effectiveness of TIPS for individual indications before it is widely adopted. TIPS may find its most immediate application in the emergency treatment of active variceal haemorrhage refractory to standard medical and endoscopic therapy, as there is no satisfactory treatment currently available for this high-risk group. TIPS may also have a role in patients awaiting liver transplantation who bleed from varices. Long-term patency should not be an issue in this patient group and portal decompression may reduce blood transfusion requirements during transplant surgery.
Clinical Trials as Topic↗
Octreotide in variceal bleeding.
Bleeding from oesophageal varices has a high death rate. Injection sclerotherapy is the most appropriate treatment but facilities for this are not always available. Balloon tamponade and vasoactive therapy may be used as stop gap measures. Somatostatin and octreotide are therapeutic candidates for the treatment of variceal bleeding and there are several trials that have compared somatostatin and octreotide with other treatments for this condition. The results of these trials are summarised and discussed. A meta analysis of the group of trials of placebo or H2 antagonists v somatostatin or octreotide showed a significant advantage of somatostatin or octreotide in terms of efficacy, but no difference in mortality. The trials discussed seem to show that somatostatin and octreotide are at least as effective as other treatments, with the benefit of fewer adverse effects, and thus represent the best vasoactive agents. Additionally, they may have a role as adjuvant treatment to emergency sclerotherapy for active bleeders and this must be further investigated.
Clinical Trials as Topic↗
Cyclosporin associated headache.
Despite successful orthoptic liver transplantation some patients develop a recurrent headache that interferes with their quality of life. To estimate the frequency of this symptom 34 patients who had undergone orthoptic liver transplantation were questioned about the history and character of any headache. Six patients described a recurrent headache typical of migraine only since transplantation. In two patients the pain improved after reduction of cyclosporin dosage and thereby plasma cyclosporin concentration.
Cyclosporine↗
Hepatic venular stenosis after orthotopic liver transplantation.
Fibrous stenosis of hepatic venules and other features of venous outflow obstruction, including zone 3 congestion and hemorrhage, are sometimes seen after orthotopic liver transplantation. similar changes associated with endothelial damage have recently been ascribed to azathioprine toxicity and may be forerunners of chronic rejection. Other potential causative agents such as viral hepatitis have yet to be considered. We reviewed 49 liver biopsy specimens from 21 consecutive patients after orthotopic liver transplantation, in whom full data including further follow-up biopsy samples were available. Hepatic venous stenosis was identified in seven patients who had received azathioprine and two additional patients in whom this change could not be ascribed to azathioprine. Stenosis was always associated with zone 3 hemorrhage and congestion and was first noted between 5 and 30 days after transplantation in all but two cases; in these two patients they were first noted after 72 and 133 days. Cellular rejection, including endotheliitis involving terminal hepatic venules, was found in five of the seven patients who had received azathioprine. Chronic (ductopenic) rejection was not seen during a follow-up period of between 97 and 540 days. In three of the nine patients with hepatic venular stenosis, zone 3 changes persisted, and in two of these azathioprine could not be held responsible. Of the 12 patients without hepatic venular stenosis, 10 had received azathioprine. Two of these 12 patients had peliosis-like foci but no other vascular abnormalities. Both also had moderate cellular rejection. Hepatic venular stenosis was found in 43% of patients after liver transplantation; this was usually associated with azathioprine administration and concomitant cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Spontaneous rupture of a normal portal vein causing severe retroperitoneal and intraperitoneal bleeding.
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Female↗
Autoimmune disease and molecular mimicry: an hypothesis.
Helper T lymphocytes are normally only stimulated to initiate an immune reaction through the recognition of peptides bound to class II major histocompatibility complex (MHC) molecules. Class II MHC molecules are constitutively expressed on antigen-presenting cells which play a critical role in the initiation of immune responses. In disease states, however, other cells often express class II MHC molecules inappropriately. This article suggests an hypothesis for the pathogenesis of autoimmune diseases based on molecular mimicry. The mimicry described is between microbial or viral peptides presented by antigen-presenting cells and self peptides presented inappropriately on a target tissue. This leads to helper T cells, stimulated by peptides derived from infectious organisms, initiating an autoimmune attack on the target tissue.
Amino Acid Sequence↗
Transjugular intrahepatic portosystemic stent shunt: which metal stent?
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Aged↗
Diurnal pattern of variceal bleeding in cirrhotic patients.
The aim of this paper was to assess diurnal periodicity in the time pattern of the time of onset of acute gastrointestinal bleeding related to portal hypertension manifested by hematemesis or melena in cirrhotic patients over a period of 24 h. The study was a prospective evaluation of separate and consecutive episodes of bleeding requiring admission to hospital following hematemesis or melena in cirrhotic patients with the use of cosinor statistical analysis to determine rhythmicity. A total 744 episodes of bleeding were studied during separate and consecutive hospital admissions over a 68-month period. The time of onset of manifestation of variceal bleeding (n = 608) in both alcoholic (n = 279) and non-alcoholic (n = 329) cirrhosis and bleeding from non-variceal sources excluding peptic ulcer (n = 136) showed a significant diurnal rhythm (P = 0.005 and P < 0.05, respectively), with two peaks at 08:00 h and 20:00 h. This pattern was not modified by sex, age, severity of liver disease, seasonal variations or initial presentation with hematemesis or melena on its own. This is the first study showing significant diurnal periodicity in the time of onset of bleeding in cirrhotic patients. It is also the first study to show periodicity of upper gastrointestinal bleeding from any source. The cause for the observed rhythmicity is not apparent but parallel changes in portal pressure and/or changes in hemostatic factors could explain this observation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of hypothermic storage in liver allograft preservation solutions on vasoactivity and prostacyclin synthesis by the rabbit aorta, in vitro.
Primary graft dysfunction following orthoptic liver transplantation has been ascribed to thrombotic and ischemic complications in a high proportion of cases. It has been suggested that hypothermic storage of livers in preservation solutions elicits damage to the vascular endothelium. Since the endothelium controls vasoactivity and hemostasis via release of endothelium derived relaxing factor (EDRF) and prostacyclin (PGI2), storage injury to the endothelium may predispose the allograft to thrombosis, ischemia and impaired perfusion. In order to test this, the effect of long-term hypothermic storage in modified University of Wisconsin solution (UW), kidney perfusion solution (KPS) and minimum essential medium (MEM) on phenylephrine (PE)-stimulated contraction and acetylcholine (ACh)-stimulated relaxation, as well as PGI2 release by rabbit aortic rings was investigated. Following cold storage for 24, 48 and 72 h, PE and ACh dose response curves were unaffected by storage in MEM, UW or KPS. Following hypothermic storage for 24 h and 48 h, PGI2 release (stimulated with PE, ACh, arachidonate, fluoride, calcium ionophore and phorbol ester) was not significantly altered from zero time responses. These results demonstrate that hypothermic storage of rabbit aortic rings in both UW and KPS do not influence two key endothelial functions (the release of EDRF or PGI2) which in turn indicates that endothelial damage associated with reperfusion following hypothermic storage is not causally related to alterations in EDRF and PGI2 release.
Animals↗
Gastric secretion and peptic ulceration in cirrhosis.
Stomach function and secretions are altered significantly in patients with cirrhosis, both with or without portal hypertension. This review covers the abnormalities of gastric acid and pepsin secretion, and gastrin release. Histological and endoscopic changes, and the impaired cytoprotection associated with cirrhosis, are discussed in the context of abnormal gastric secretion. In addition, the symptomatology and association of H. pylori, and treatment of duodenal ulceration in cirrhosis are discussed. It is clear from this review that additional studies are needed to further understand gastric function in cirrhotic patients.
Female↗
M2 mitochondrial antibodies and urinary rough mutant bacteria in patients with primary biliary cirrhosis and in patients with recurrent bacteriuria.
Primary biliary cirrhosis (PBC) patients have a higher incidence of recurrent urinary tract infection and an increased prevalence of rough forms (mutants) of E. coli in their stool samples than other chronic liver disease patients. PBC patients exhibit autoantibody reactivity against mitochondria, the most common antigen (M2) being a family of antigens with the major components having approximate molecular weights of 74, 56, 52 and 48 kD. Cross-reactivity between M2 antigen components and corresponding antigenic bands of bacteria has been demonstrated with PBC sera. Patients with recurrent urinary tract infections, all of whom had normal liver function and were taking prophylactic antibiotic treatment, had weak anti-mitochondrial antibody (AMA) reactivity (69%), with reactivity against the 74-kD antigen alone being the most common. When antibody to the 74-kD band was eluted, it was found to cross-react with bacterial membrane fractions. In the controls, 12/77 chronic liver disease patients and 2/24 normals possessed AMA. Rough forms of bacteria were found in the urine of patients with significant bacteriuria: 39% PBC, 5.3% chronic liver disease and 41% of the recurrent urinary tract infection group. M2 antibodies may be induced by urinary organisms in 'normal' women with recurrent bacteriuria and in females with PBC.
Autoantibodies↗
The natural history of varices.
Variceal bleeding and its ensuing complications correlate positively with the severity of liver disease. The average risk of bleeding in patients with cirrhosis who have not previously bled is 30%, with a 50% mortality rate within 6 weeks. This mortality rate is the rationale for prophylaxis. However, although fatal bleeding causes 35% of all deaths, patients who die after the first episode of bleeding represent only 15% of patients with cirrhosis and varices. Portal and intravariceal pressure, the appearance of oesophageal varices on endoscopic examination, severity of liver disease and alcohol abuse are independent risk factors for the occurrence of the first bleeding episode. In sinusoidal portal hypertension, the presence of varices indicates a hepatic venous pressure gradient > or = 12 mmHg. Although hepatic venous pressure gradient tends to be higher in patients who bleed or have large varices, bleeding risk is not related linearly to pressure above this threshold. Tension on the variceal wall relative to varix radius may be critical and increasing variceal size, in conjunction with wall thinness, may favour rupture at lower intraluminal pressures. The North Italian Endoscopic Club's simplified index for the risk of a first bleeding episode is based on Child class, variceal size and presence of red wale markings, although there may be other independent risk factors. Abstention from alcohol can decrease variceal size and the number of cherry-red spots. Because large varices are unlikely to develop de novo within 2 years, biennial endoscopic screening is sufficient for patients without varices; annual endoscopy is recommended for those with small varices.(ABSTRACT TRUNCATED AT 250 WORDS)
Esophageal and Gastric Varices↗
Superior mesenteric artery blood flow in man measured with intra-arterial Doppler catheters: effect of octreotide.
Changes in splanchnic blood flow are important in the pathogenesis of portal hypertension, but research in this area is hampered by the difficulty in measuring splanchnic arterial blood flow in man. We therefore investigated the use of intra-arterial Doppler catheters in measuring superior mesenteric artery blood flow in man and assessed the effect of intravenous octreotide on superior mesenteric artery blood flow in a placebo-controlled double-blind study. Nine experiments were performed in a flow model using vessels with internal diameters of 6.5, 4.5 and 3.0 mm, with flow rates ranging from 50 to 700 ml/min. In this model the catheters gave instantaneous, reproducible measurements of blood flow in vessels of 6.5 mm internal diameter with a mean error ranging from +5.3% to +36.4%, compared to electromagnetic flowmetry, but were less accurate in smaller vessels. When used in patients, the catheters provided stable, reproducible measurements of superior mesenteric blood flow, in 16 out of 20 patients studied. In a double-blind placebo-controlled study, including 12 subjects, superior mesenteric artery blood flow was significantly reduced in patients receiving octreotide. We suggest that measurement of splanchnic arterial blood flow using intra-arterial Doppler catheters may be a useful additional investigation in the assessment of splanchnic vascular pathophysiology and pharmacology in man.
Adenoma↗
A comparison of transjugular and plugged-percutaneous liver biopsy in patients with impaired coagulation.
Patients with liver disease frequently have impaired blood coagulation. The optimal method for liver biopsy in this situation is not established. To investigate this issue we randomised 117 patients with impaired blood coagulation, in whom liver biopsy was required, to receive either transjugular or plugged-percutaneous biopsy. Seventeen patients were excluded prior to biopsy and a protocol biopsy was performed in 100 patients (44 transjugular, 56 plugged-percutaneous). Liver tissue was obtained in 97 (42 transjugular, 55 plugged-percutaneous). Plugged-percutaneous liver biopsy was quicker and easier than transjugular liver biopsy and the biopsies obtained were significantly larger (12 +/- 5 mm vs. 6 +/- 4 mm; p < 0.001). However, 2 of 56 (3.5%) patients who received plugged-percutaneous biopsy had haemorrhage which required transfusion, while none of the 44 patients who received transjugular biopsy had haemorrhage (not significant). Both methods of liver biopsy were associated with a high success rate and a low incidence of complications. Plugged-percutaneous liver biopsy provides larger biopsies but may be associated with an increased risk of haemorrhage.
Biopsy↗
Review article: S-adenosyl-L-methionine--a new therapeutic agent in liver disease?
The established biochemical effects of exogenous S-Adenosyl-L-Methionine (SAMe) are diverse and are still being explored in liver disease. Putative therapeutic effects could be exerted via different mechanisms. The established deficiency of SAMe synthetase in cirrhosis could by bypassed by exogenous SAMe, leading to increased levels of sulphur-containing amino acids and glutathione which would protect against oxidant stress and drug-induced hepatotoxicity (for example, paracetamol). Furthermore SAMe could act by improving membrane fluidity, and thus potentially improve or restore the function of receptors, enzymes and transporters in the cell surface. Membrane fluidity is known to be affected by alterations in cell membrane lipid composition in chronic liver disease. Very few therapeutic agents are effective for the symptomatic or specific treatment of chronic liver disease. SAMe has established biochemical and biophysical effects which in pilot studies ameliorate symptoms and biochemical parameters of cholestasis. Moreover, abnormalities in liver function tests (including transaminase values) also improve. Before SAMe can be considered as an established therapy for patients with hepatic disease, long-term controlled clinical trials of SAMe are needed to assess the benefit for patients' symptoms, well being, histological changes and progression of liver disease.
Animals↗