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Biomedical subjects

D Westaby

Publications and source records attributed to D Westaby.

At least 73 records · Page 4Linked to original sources
PubMed1989

Controlled clinical trial of injection sclerotherapy for active variceal bleeding.

In a prospective, randomized clinical trial, immediate injection sclerotherapy was compared with treatment by a combined infusion of vasopressin (0.4 unit per min) and nitroglycerin (40 to 400 micrograms per min) in 50 consecutive patients with 64 episodes of endoscopy-proven variceal hemorrhage. Control of bleeding was assessed over a 12-hr period following entry into the trial. Patients in the vasopressin + nitroglycerin group were then treated by sclerotherapy, as were those in the sclerotherapy group who continued to bleed. At 12 hr, bleeding was controlled in 29 (88%) of the 33 episodes treated by sclerotherapy compared with 20 (65%) of 31 episodes treated by vasopressin + nitroglycerin (p less than 0.05). Recurrence of variceal bleeding occurred at the same frequency (31%). Although admission mortality was less in those initially treated by sclerotherapy compared to those managed by vasopressin + nitroglycerin, this did not reach statistical significance (27 and 39%, respectively, p greater than 0.20). Sclerotherapy carried out as the first treatment of the active variceal hemorrhage proved both safe and effective, even in the presence of major hemorrhage, and as compared to combined vasopressin and nitroglycerin it proved superior.

Clinical Trials as Topic↗
PubMed1989

Sucralfate for the prevention of early rebleeding following injection sclerotherapy for esophageal varices.

One hundred eighty patients with variceal bleeding and treated by long-term sclerotherapy were randomized into a prospective randomized controlled clinical trial to assess the efficacy of sucralfate in reducing the frequency of rebleeding from esophageal ulceration prior to variceal obliteration. Overall, 29 (32%) of the 92 patients treated with the addition of sucralfate rebled, compared to 37 (42%) of 88 patients managed by sclerotherapy alone (p less than 0.10), but when patients with well-compensated liver disease were considered, the respective figures were 14 (24%) and 25 (42%)--a statistically significant difference (p less than 0.05). The frequency (approximately 70%), number (per patient) and extent of sclerotherapy-induced esophageal mucosal ulceration were not different for the two groups, although proven rebleeding from the ulceration occurred less frequently in those receiving sucralfate (10 and 20 occasions, respectively, p less than 0.05). Mortality was not different for the two groups. Thus, use of sucralfate will reduce the frequency of rebleeding during long-term treatment by sclerotherapy, although benefit appears to be restricted to well-compensated patients and without an endoscopic overt effect upon esophageal mucosal ulceration.

Combined Modality Therapy↗
PubMed1989

Comparison of propranolol with injection sclerotherapy in prevention of rebleeding from oesophageal varices in cirrhotic patients.

Selected patients with variceal bleeding were randomly assigned to either weekly injection sclerotherapy (n = 56) or to oral propranolol (n = 52). During follow-up, 28 (54%) of the propranolol group and 25 (45%) of the sclerotherapy group had an episode of rebleeding. The long term risks of bleeding in the propranolol and sclerotherapy groups were 0.05 and 0.037 bleeds/patient-month, respectively, and the corresponding death rates during follow-up were 42 and 38%. There were no statistically significant differences between propranolol and the established therapy, but it was concluded that if propranolol is used in the prevention of rebleeding, it must be part of an overall approach that provides for the management of active variceal haemorrhage by other means if this condition continues.

Esophageal and Gastric Varices↗
PubMed1988

Haemodynamic response to intravenous vasopressin and nitroglycerin in portal hypertension.

We have evaluated the haemodynamic effects of intravenous (iv) nitroglycerin (NG) and vasopressin (VP) alone and in combination, in 12 patients with cirrhosis and recent variceal haemorrhage (two to seven days). Nitroglycerin infusion alone (200 micrograms/min) produced a significant fall in portal pressure (WHVP-FHVP) (from 16.4 (0.6) to 13.3 (1.2) mmHg; p less than .001) associated with hypotension (mean arterial pressure from 95 (7) to 78 (9) mmHg; p less than 0.005). Vasopressin alone (0.4 IU/min) reduced portal pressure (20.7 (1.3) to 14.0 (1.3) mmHg; p less than 0.001), but there was considerable variation in the systemic haemodynamic changes with increased cardiac output in four of six patients. The combination of vasopressin and nitroglycerin corrected all systemic haemodynamic disturbances produced by either agent alone. This combination led, however, to a further reduction in portal pressure (from 13.7 (0.9) to 11.7 (0.7) mmHg p less than 0.01). These results show that: (1) intravenous nitroglycerin reduces portal pressure, and (2) the combination of nitroglycerin and vasopressin reverses systemic haemodynamic disturbances produced by either agent alone and leads to a further decrease in portal pressure.

Drug Therapy, Combination↗
PubMed1988

Effect and mechanism of action of isosorbide-5-mononitrate.

Nitrates have been shown to decrease portal pressure in cirrhotic patients with portal hypertension and this has been attributed to decreased portal venous resistance. We studied the effect and mechanism of action of oral administration of isosorbide-5-mononitrate (Is-5-Mn) (20 mg), which, unlike the dinitrate, does not require hepatic biotransformation to a vasoactive metabolite on portal and systemic haemodynamics in 11 patients with portal hypertension complicating cirrhosis. A significant reduction in portal pressure gradient (WHVP-FHVP) (from 23.9 (3.4) to 21.8 (3.4) mmHg: p less than 0.005) occurred 60 minutes after Is-5-Mn due entirely to a fall in WHVP, associated with decreased estimated liver blood flow (from 1940 (159) to 1639 (179) ml/min: p less than 0.05). Right atrial and pulmonary artery pressures and cardiac index fell significantly whilst mean arterial pressure remained unaffected. Heart rate and the calculated systemic vascular resistance index increased significantly. Significant correlations existed between the reduction in portal pressure gradient and fall in cardiac index (r = 0.65, p less than 0.05) and increase in systemic vascular resistance index (r = 0.72, p less than 0.02). The observed decrease in estimated liver blood flow, in association with an increase in systemic vascular resistance index, suggests that baroreceptor mediated splanchnic vasoconstriction may be one of the factors responsible for the fall in portal pressure, rather than portal venous dilatation.

Female↗
PubMed1988

Long-term injection sclerotherapy for the primary and secondary management of variceal haemorrhage.

The beneficial effects of long-term sclerotherapy upon rebleeding from esophageal varices have been well established by several controlled trials, although the high frequency of early recurrent hemorrhage remains an important limitation. The beneficial effect of sclerotherapy on survival in such patients is less clear, but may also be concluded when the comparison is with control groups managed by conservative methods alone. The future probably lies with concepts of less intensive regimes of sclerotherapy. The evidence available with respect to prophylactic sclerotherapy is clearly conflicting. However, there is little to support the further use of this therapy in unselected groups of patients. Subsequent studies should be aimed specifically towards the selection of patients at high risk of first variceal hemorrhage, which might then be candidates more likely to benefit from prophylactic treatment.

Clinical Trials as Topic↗
PubMed1987

Normal venous circulation of the gastroesophageal junction. A route to understanding varices.

A study into the normal anatomy of the venous circulation of the gastroesophageal junction was undertaken using three complementary techniques (radiology, corrosion casting, and morphometry). Four distinct zones of venous drainage were defined as follows: (a) gastric zone, characterized by a longitudinal venous distribution; (b) palisade zone, composed of parallel vessels arranged in groups, lying mainly within the lamina propria; (c) perforating zone, characterized by "treble clef" shaped veins, which collect and channel blood into extrinsic veins; and (d) truncal zone, composed of four or five deep lying descending veins. This venous system appeared to be mainly distributed within the esophageal mucosal folds. The anatomic pattern suggests that venous flow is bidirectional at the palisade zone, which acts as a high-resistance watershed region between the portal and azygos systems. In patients with portal hypertension this normal vascular system has to accommodate greatly increased venous flow, and the anatomy as demonstrated here offers insight into variceal development.

Aged↗
PubMed1987

Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy.

Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.

Colon↗
PubMed1986

Endoscopic sclerotherapy for esophageal varices.

Sclerotherapy for esophageal varices is now well established as a method of treatment for varices which have bled initially and then have been controlled by medical means. The long term outcome of such treatment is now under study. The value of sclerotherapy for acutely bleeding varices or as a prophylactic measure in patients with varices that have not bled is more controversial and its role awaits the outcome of additional controlled trials.

Clinical Trials as Topic↗
PubMed1986

Elective sclerotherapy--technique and results.

Elective sclerotherapy, to obliterate oesophageal varices, is discussed with particular reference to the results of three controlled trials. There is strong support from each of these studies for the prevention of rebleeding. However, the results for overall survival are conflicting. This discrepancy is discussed in relationship to major differences in trial design. Different techniques of injection sclerotherapy are reviewed, although there is a paucity of comparative data. A prospective study is reported in which 147 patients were followed after initial obliteration of varices, in order to document the rate of recurrence of varices, the associated rate of rebleeding and hence the need for, and timing of, follow-up endoscopy.

Clinical Trials as Topic↗
PubMed1985

B1 selective adrenoreceptor blockade for the long term management of variceal bleeding. A prospective randomised trial to compare oral metoprolol with injection sclerotherapy in cirrhosis.

Oral metoprolol, in a dose sufficient to reduce resting pulse rate by 25%, was compared with repeated injection sclerotherapy for the long term management of variceal bleeding. The prospective, randomised study was undertaken in 32 patients with biopsy proven cirrhosis and variceal bleeding who were Grade A or B on a modified Child's classification. In the 15 patients receiving metoprolol, portal pressure showed a mean fall of 3.7 mmHg (17.3 +/- 1.2 to 13.6 +/- 1.2 mmHg, p less than 0.01) after four weeks of continuous therapy, as compared with pretreatment levels. Nine of the 15 patients taking metoprolol had further bleeding (total of 21 episodes) compared with six of 17 in the sclerotherapy group (nine episodes). The risk of bleeding per patient/month of follow up was three times higher in the metoprolol group compared with those treated by sclerotherapy (0.14 and 0.04 respectively, p less than 0.025). Rebleeding in the metoprolol group occurred in six of the patients who had a fall in portal pressure of 10% or more.

Clinical Trials as Topic↗
PubMed1984

Effects of converting enzyme inhibitor on hepatic blood flow in man.

The acute effects of the oral angiotension converting enzyme inhibitor captopril on hepatic blood flow and systemic hemodynamics were studied in six patients with essential hypertension. Mean arterial pressure decreased from 141.9 +/- 6.9 mm Hg to 130.2 +/- 6.7 mm Hg (p less than 0.05) one hour after the administration of captopril. There was no significant change in other hemodynamic values, but hepatic blood flow decreased uniformly from 1,127 +/- 115 ml per minute to 841 +/- 93 ml per minute (p less than 0.001).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

Reductions in portal pressure by selective beta 2-adrenoceptor blockade in patients with cirrhosis and portal hypertension.

In order to elucidate the mechanisms by which beta-adrenoceptor blockade leads to a reduction in portal pressure, we have measured portal pressure, heart rate and cardiac index in 17 patients with cirrhosis and portal hypertension following the oral administration of the selective beta 2-adrenoceptor blocking agent, ICI 118551, in the two dosage ranges 10-20 mg and 50-100 mg. There was a fall in portal pressure in 14 of the 17 patients from a median of 17 mm Hg to a median of 15 mm Hg, P less than 0.01, that occurred only at 60 min following administration of the drug. Although there were early systemic haemodynamic changes, with a significant fall in heart rate and cardiac index from before to 30 min after the ingestion of ICI 118551 (median heart rates 86 and 80 beats/min respectively, P less than 0.01, median cardiac indices 3.5 and 3.31 min-1 m-2, P less than 0.05), these occurred before the fall in portal pressure and were unrelated to changes in portal pressure. This reduction in portal pressure independent of systemic haemodynamic changes is consistent with beta 2-adrenoceptor blockade within the splanchnic and hepatic arterial circulations; subsequent increases in splanchnic and hepatic arterial resistances with a concomitant fall in portal blood flow and hepatic portal resistance may lead to the reduction in portal pressure.

Adrenergic beta-Antagonists↗