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Biomedical subjects

D Westaby

Publications and source records attributed to D Westaby.

At least 55 records · Page 3Linked to original sources
PubMed1992

Liver and biliary problems in cystic fibrosis.

There have been striking advances in the management of complications of cirrhosis in the 50 years since biliary cirrhosis was recognised as a feature occurring in a minority of patients with cystic fibrosis. Many questions remain unanswered with regard to its pathogenesis, its effect on other systems, morbidity and mortality and to its optimum management. Factors which may initiate liver disease and/or cause progressive biliary fibrosis leading to biliary cirrhosis in some cystic fibrosis patients are being defined but much is still poorly understood and further research is required. Clinical and pathological studies confirm that cirrhosis is frequently asymptomatic and only slowly progressive, with the prevalence rising with age. In a recent large epidemiological study, however, it was found that the age related prevalence fell in patients over the age of 20 years although deaths from liver disease were rare. Does the presence of liver disease cause premature respiratory death in teenagers? Current treatments control variceal bleeding, the important sequel for most patients with biliary cirrhosis, with less morbidity and mortality than in the past but require reappraisal as newer techniques become available. Endoscopic radiologically controlled methods are emerging as an important adjunct to the surgical control of biliary complications which cause symptoms in up to 4%. Ursodeoxycholic acid improves liver function tests but its effect on hepatic fibrosis and portal hypertension will only be demonstrated by large scale prospective controlled trials. Should liver transplantation have a larger role in management? In this chapter we have attempted to summarise the current state of knowledge and to assess the efficacy of present management.

Biliary Tract Diseases↗
PubMed1992

Management of common bile duct stones with a biliary endoprosthesis. Report on 40 cases.

Endoscopic placement of a biliary endoprosthesis has been proposed for the management of choledocholithiasis when stone extraction is difficult or considered hazardous. Over a two year period this approach was used in 40 such patients. There were 24 women and 16 men with a median age of 76 years. In seven patients with severe cholangitis no attempt was made to extract the stones. Twenty three (57.5%) patients underwent a sphincterotomy and four (10%) needle knife papillotomy. The endoprosthesis insertion was considered a temporary measure in 13 (32.5%) patients and definitive treatment in 27 (67.5%). Bile duct drainage was established in all patients. Early complications occurred in six patients (15%), but were without sequelae. Late complications developed in eight (20%) of the patients and included biliary colic (four), cholangitis (three), and cholecystitis (one). Two patients (one cholangitis and one cholecystitis) died as a consequence of the complication. Only patients without a sphincterotomy developed cholangitis. A total of eight patients (20%) underwent surgery (one as an emergency) and nine a repeat endoscopic retrograde cholangio pancreatography (two as an emergency) to clear the duct. The remaining 23 patients are asymptomatic at a median of 13 months (range five to 24 months). Biliary endoprosthesis insertion for choledocholithiasis is an important alternative means of establishing drainage in selected cases, and is probably the optimum method of management for the elderly and or debilitated patients with previous cholecystectomy. Caution must be exercised, however, in patients with an in situ gall bladder.

Adult↗
PubMed1992

Assessment of the percutaneous endoscopic gastrostomy feeding tube as part of an integrated approach to enteral feeding.

The insertion of percutaneous endoscopic gastrostomy has been well documented. The possible benefits for patient nutrition and nursing practice have, however, not been assessed. We report a study of enteral feeding by percutaneous endoscopic gastrostomy in 30 patients, the majority with a persistent vegetative state. All patients had previously been fed through a nasogastric tube using manual administration and a dietitian assessed protein calorie intake. Based upon body mass index (weight/height2), midarm circumference and triceps skinfold thickness, 20 (67%) were malnourished, with 10 patients having a body mass index less than 17 (severe malnutrition); attributed to high rates of both tube displacement and feed regurgitation. Patients were observed over six to 12 months after percutaneous endoscopic gastrostomy insertion combined with overnight continuous pump feeding. All patients attained a body mass index greater than 17, and 17 (56%) of the total number achieved the normal range with no change in protein-calorie intake (pre: 2110 kcal, post: 1880 kcal). Complications of percutaneous endoscopic gastrostomy in the study group included peritonitis (one), tube site infection (two) and displacement (two); all without serious sequelae. As part of an integrated approach percutaneous endoscopic gastrostomy proved a safe and efficient method of enteral feeding and justifies wider consideration in the United Kingdom.

Adult↗
PubMed1992

Pathophysiology of portal hypertension.

Portal hypertension is characterised by alterations in the splanchnic and systemic circulation associated with the development of portosystemic collateral channels, the most important of which are found in lower oesophagus and stomach. Bleeding from these gastro-oesophageal varices represents the major clinical complication and over the last decade there has been considerable interest in the pharmacological management of this condition. The factors underlying the development and maintenance of portal hypertension and the pathogenesis of variceal rupture are as yet not fully understood. Whilst an increase in portal vascular resistance, as a consequence of liver disease, appears to be the primary event in the majority of cases, increasing attention has focused on the potential importance of enhanced circulating levels of vasoactive compounds coupled with a proposed reduction in vascular sensitivity to endogenous vasoconstrictors. Consequently, portal hypertension is now being more widely considered as a multi-organ disorder associated with changes in blood flow within both systemic and splanchnic vascular beds. This article reviews the factors currently implicated in the development and maintenance of portal hypertension and considers the pathogenesis of variceal bleeding.

Esophageal and Gastric Varices↗
PubMed1991

Natural history and prognostic variables in primary sclerosing cholangitis.

The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation.

Adenoma, Bile Duct↗
PubMed1991

Endoscopic sclerotherapy in the management of gastric variceal haemorrhage.

The value of injection sclerotherapy in the management of active gastric variceal bleeding is unclear. A retrospective study was therefore performed of 46 episodes of acute variceal haemorrhage in 41 patients who were treated by endoscopic sclerotherapy. The site of gastric variceal haemorrhage was the lesser curve (Group 1) in 13, within a hiatus hernia (Group 2) in six, and fundal with or without associated oesophageal varices (Type 3) in 22 cases. Haemostasis was achieved by sclerotherapy in 54%, 71.4% and 26%, respectively. After additional measures including balloon tamponade or surgery 85% of the Group 1 cases had stopped bleeding significantly more frequently than was observed in Group 3 (44.4%). More patients in Group 3 died due to uncontrolled bleeding (41%) than in Group I (7.7%). Hospital mortality depended on the severity of the liver disease with 15% of Child's grade A and 56% of grade C cases dying. It is concluded that endoscopic sclerotherapy of gastric varices should be reserved only for lesser curve or hiatal varices and that early surgery (or sclerotherapy using tissue adhesive) be considered for variceal haemorrhage originating from fundal varices.

Esophageal and Gastric Varices↗
PubMed1991

Improving biliary-enteric drainage in primary sclerosing cholangitis: experience with endoscopic methods.

Six jaundiced patients with primary sclerosing cholangitis and a dominant biliary stricture were managed by endoscopic placement of endoprostheses. Five showed considerable improvement within weeks of stenting: their serum bilirubin concentration fell from mean (range) 266 mumol/l (63-681) to 65 mumol/l (10-280) after one month. One patient required a liver transplant at five months because of continued deterioration in hepatic function. Follow up of 12-49 months in the remaining five patients shows sustained biochemical improvement, with repeat cholangiograms indicating doubling of the minimum calibre of the extrahepatic bile duct in four patients and considerable shortening of stricture length in three. Three patients developed sepsis at the time of the initial endoprosthesis insertion: surgical drainage was necessary in one. Endoscopic methods of improving biliary-enteric drainage in jaundiced patients with primary sclerosing cholangitis may be preferable to surgical and percutaneous methods, which may complicate subsequent liver transplantation.

Adult↗
PubMed1990

A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term management of variceal bleeding.

This trial was carried out to assess the value of propranolol for the prevention of recurrent variceal bleeding in patients with well-compensated cirrhosis. We also compared propranolol therapy to long-term injection sclerotherapy. One hundred and eight patients, in whom the original variceal hemorrhage stopped spontaneously (before diagnostic endoscopy) and without sclerotherapy or surgical intervention, were included. All were Pugh grade A or B; 55% had alcoholic cirrhosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long-term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long-term sclerotherapy. Follow-up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long-term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (p less than 0.20). On an intention-to-treat basis, the risk of bleeding expressed per patient-month of follow-up was similar for the two groups, at 0.05 and 0.037, respectively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p less than 0.40). Stepwise regression analysis of possible factors predicting further bleeding in patients taking propranolol selected only two variables--the pretreatment pulse rate and the extent of pulse-rate reduction in response to propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Single, total paracentesis for tense ascites: sequential hemodynamic changes and right atrial size.

Hemodynamic changes induced by a single, total paracentesis were evaluated in 21 patients with tense ascites from whom 4 to 16 L of ascites were drained over 2 to 8 hr with no serious complications. At 60 min, compared to baseline, there was an increase in cardiac output (7.7 +/- 0.5 to 8.5 +/- 0.6 L/min, p less than 0.02) and a tendency for right atrial pressure to decrease (9.3 +/- 0.8 to 7.50 +/- 0.8 mm Hg, NS), with no change in pulmonary capillary wedge pressure (10.9 +/- 0.9 to 10.7 +/- 0.9 mm Hg). Between 3 and 12 hr later, there was a drop in right atrial pressure, pulmonary capillary wedge pressure and cardiac output to 5.6 +/- 0.6 (p less than 0.02), 7.2 +/- 0.8 mm Hg (p less than 0.002) and 7.2 +/- 0.6 L/min (NS) respectively, indicative of the development of relative hypovolemia and suggesting that therapeutic plasma expansion is appropriate at this time. Two-dimensional echocardiography before paracentesis (n = 8) showed a reduction in the right to left atrium area ratio as compared with values in patients with minimal ascites (0.54 +/- 0.04 vs 0.82 +/- 0.02, p less than 0.0001). This technique may help in identifying patients with right atrial compression caused by tense ascites.

Adult↗
PubMed1990

Omeprazole in the management of intractable esophageal ulceration following injection sclerotherapy.

Transient esophageal ulceration is a common finding after sclerotherapy of varices. A small proportion of these ulcers become chronic and resistant to conventional therapy. Such chronic ulcers have been associated with pain, stricture formation, and recurrent hemorrhage. The use of omeprazole, a proton pump inhibitor, was examined in the current study in the treatment of 10 patients (6 women, 4 men; age range, 27-86 years) with cirrhosis (PBC, 4; sclerosing cholangitis, 2; chronic active liver disease, 2; alcohol, 1; and cryptogenic, 1) who developed an esophageal ulcer after a mean of 13 (range, 8-21) sessions of sclerotherapy. The ulcers had been present for 3-54 months despite prolonged treatment with high-dose H2-receptor antagonists and sucralfate. In each case one or more complications had occurred: severe pain in 3, stricture formation in 4, and recurrent hemorrhage in 7 cases. After an 8-week course of omeprazole, 40 mg daily, endoscopy confirmed complete healing of the ulceration in all 10 cases with symptom resolution. In 2 cases the ulcer recurred, with associated bleeding within 6 weeks of discontinuing the treatment in 1 patient. Both cases responded to repeat therapy. These results confirm the efficacy of omeprazole for postsclerotherapy ulceration and imply that acid-pepsin has a role in perpetuating such ulcers.

Adult↗
PubMed1990

Status of sclerotherapy for variceal bleeding in 1990.

The enthusiasm for injection sclerotherapy over the last decade has almost certainly surpassed what was justified on the basis of objective evidence. This was most clearly emphasized by the widespread adoption of prophylactic sclerotherapy after the report of the first two trials, even though enough was known of the natural history of variceal hemorrhage in patients with cirrhosis to warrant caution. The use of sclerotherapy for an episode of variceal hemorrhage represents the role most supported by the available data. Diagnostic endoscopy, as an integral part of management, provides the optimum time to intervene with sclerotherapy. Sclerotherapy can then provide hemostasis in patients who are actively bleeding and prevent early rebleeding in those in whom bleeding has stopped spontaneously. The progression to long-term injection sclerotherapy is of proven benefit; however, doubts exist concerning the need for the intensive regimens currently in use. The continued use of long-term injection sclerotherapy is dependent not only on additional investigations, but also on the accumulating evidence arising from comparative studies encompassing other available therapy.

Acute Disease↗
PubMed1990

Impaired natriuretic response to atrial natriuretic peptide in the isolated kidney of rats with experimental cirrhosis.

1. Sodium retention in cirrhosis may be partly attributable to resistance to a putative circulating natriuretic factor. In cirrhosis, plasma concentrations of atrial natriuretic peptide are often increased in the presence of sodium retention. 2. In order to determine whether the kidney of cirrhotic animals may be insensitive to atrial natriuretic peptide, isolated perfused kidneys from six cirrhotic and five control rats were exposed to increasing concentrations of atrial natriuretic peptide. Cirrhosis had been induced by carbon tetrachloride administration. 3. Excretion in vivo of a 2 mmol sodium load, administered by gavage, was impaired in cirrhotic animal for up to 4 h as compared with control animals (4.2 +/- 1.9 vs 34.9 +/- 13.4% P less than 0.05). 4. During perfusion at 110 mmHg in the absence of atrial natriuretic peptide, sodium excretion by isolated kidneys of cirrhotic animals tended to be lower than in control animals, but the difference was not significant (4.93 +/- 1.01 vs 8.41 +/- 1.48 mumol min-1 g-1 kidney weight, P = 0.09). There was a smaller increase in urinary sodium excretion by the kidneys of cirrhotic rats compared with control rats in the presence of atrial natriuretic peptide at 10, 50 and 200 pmol/l (respectively: 0.06 +/- 0.08 vs 1.29 +/- 0.35 mumol/min-1 g-1 kidney weight, P less than 0.02; 0.49 +/- 0.08 vs 1.82 +/- 0.42 mumol min-1 g-1 kidney weight, P less than 0.03; 1.42 +/- 0.16 vs 3.23 +/- 0.73 mumol min-1 g-1 kidney weight, P less than 0.05), but not at 1000 pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Haemodynamic and pharmacokinetic study of intravenous fenoldopam in patients with hepatic cirrhosis.

1. The effect of intravenous fenoldopam-an arterial vasodilator-was assessed in twelve patients with cirrhosis and portal hypertension. Six patients had compensated (Grade A or B Child-Pugh classification) and six decompensated (Grade C) liver disease. 2. A significant dose dependent reduction in systemic blood pressure with a concomitant fall in systemic vascular resistance and increase in cardiac index was observed. Estimated portal pressure (WHVP-FHVP) increased (15.4 +/- 3.2 to 19.3 +/- 3.7 mm Hg, P less than 0.05) due to a rise in wedged hepatic venous pressure (24.6 +/- 4.3 to 29.0 +/- 5.8 mm Hg, P less than 0.05). Hepatic blood flow did not change significantly. Similar haemodynamic effects were observed in both compensated and decompensated patients. 3. Fenoldopam plasma clearance and ICG clearance were found to decrease with increasing infusion concentration, indicating possible increase of the intrahepatic shunting. 4. With the observed rise in portal pressure there must be some concern with respect to the long-term use of this drug in patients with previous variceal bleeding.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Taking the tension out of the portal system. An approach to the management of portal hypertension in the 1990s.

The past decade saw the emergence of sclerotherapy and vasoactive pharmacologic agents as alternatives to surgery in the prevention and treatment of variceal haemorrhage. Despite encouraging results from clinical trials with regard to the prevention of rebleeding, these modalities of therapy have made no major impact on survival. This failure to alter radically the clinical outcome results from the fact that in many patients with cirrhosis death is primarily related to the degree of hepatic decompensation rather than the prevention or control of variceal bleeding. Advances in our knowledge of vasoactive mediators, receptor function, and altered vascular reactivity have provided increased insight into the circulatory disturbances that characterise cirrhosis and portal hypertension. Earlier and more aggressive pharmacologic intervention with single or combination drug therapy may inhibit fibrogenesis, reduce portal vascular resistance, and improve liver function and therefore provide effective prophylaxis against variceal haemorrhage. The emergence of reliable prognostic indices for variceal bleeding should help identify patients at risk who would benefit from prophylaxis with either drugs or sclerotherapy. Transplantation will be increasingly considered in the patient at high risk of recurrent bleeding before the stage of severe hepatic decompensation (the risks of the transplant then become very much greater), as the definitive means for reducing mortality in cirrhosis and portal hypertension.

Adrenergic beta-Antagonists↗
PubMed1989

Liver disease and bile duct abnormalities in adults with cystic fibrosis.

A quarter of adults with cystic fibrosis, 57 of 233, had abnormal liver function. Patients with hepatic dysfunction were further investigated by ultrasound, hepatobiliary scintigraphy, and endoscopic retrograde cholangiography (ERC). 17 of the 23 patients studied had abnormalities on imaging. All 15 patients who underwent ERC had abnormal intrahepatic ducts, but only 2 had stricture of the common bile duct. These findings suggest that, in patients with cystic fibrosis, intrahepatic impairment of biliary drainage may be important in the pathogenesis of liver disease.

Adolescent↗