{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:30:15Z","timestamp":1778567415135,"version":"3.51.4"},"reference-count":43,"publisher":"BMJ","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Variceal bleeding is a severe complication of portal hypertension. Somatostatin reduces portal pressure by decreasing splanchnic blood flow, and nitrates by diminishing intrahepatic resistance. Experimental studies have shown that the combination of somatostatin and nitrates has an additive effect in decreasing portal pressure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>AIM<\/jats:title>\n                  <jats:p>To compare the therapeutic efficacy of either intravenous infusion of somatostatin plus oral isosorbide 5-mononitrate or somatostatin alone in gastro-oesophageal variceal bleeding associated with liver cirrhosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec sec-type=\"methods\">\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>A unicentre, double blind, placebo controlled, clinical trial was conducted. Sixty patients bleeding from oesophageal or gastric varices were randomised to receive intravenous infusion of somatostatin (250 \u03bcg\/hour) plus oral isosorbide 5-mononitrate (40 mg\/12 hours) (group I) or somatostatin infusion plus placebo (group II) for 72 hours.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The two groups of patients had similar clinical, endoscopic, and haematological characteristics. Control of bleeding was achieved in 18 out of 30 patients (60%) in group I and 26 out of 30 patients (87%) in group II (p&lt;0.05). There was no significant difference in mean transfusion requirements between the two groups: 2.6 (2.2)<jats:italic>v<\/jats:italic> 1.8 (1.6) respectively; means (SD). Mortality and side effects were similar in the two groups, but development of ascites was higher in group I (30%) than in group II (7%) (p&lt;0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSION<\/jats:title>\n                  <jats:p>In cirrhotic patients with acute gastro-oesophageal variceal bleeding, addition of isosorbide 5-mononitrate to somatostatin does not improve therapeutic efficacy, induces more adverse effects, and should not be used.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gut.46.1.127","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:32:32Z","timestamp":1027751552000},"page":"127-132","source":"Crossref","is-referenced-by-count":13,"title":["Somatostatin plus isosorbide 5-mononitrate versus somatostatin in the control of acute gastro-oesophageal variceal bleeding: a double blind, randomised, placebo controlled clinical trial"],"prefix":"10.1136","volume":"46","author":[{"given":"F","family":"Junquera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J C","family":"L\u00f3pez-Talavera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Mearin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Saperas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Videla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J-R","family":"Armengol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Esteban","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J-R","family":"Malagelada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2000,1,1]]},"reference":[{"key":"2025090800044133000_46.1.127.1","unstructured":"Burroughs AK Bosch J (1991) Clinical manifestations and management of bleeding episodes in cirrhotics. in Oxford textbook of clinical hepatology. eds McIntire N Benhamou JP Bircher J Rizzeto M (Oxford University Press, Oxford), pp 481\u2013502."},{"key":"2025090800044133000_46.1.127.2","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(95)90388-7"},{"key":"2025090800044133000_46.1.127.3","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/0016-5085(81)90014-7","article-title":"Effects of somatostatin on hepatic and systemic hemodynamics in patients with cirrhosis of liver: comparison with vasopressin.","volume":"80","author":"Bosch","year":"1981","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0300-5089(21)00643-X","article-title":"Effect of pharmacological agents on portal hypertension: a haemodynamic appraisal.","volume":"14","author":"Bosch","year":"1985","journal-title":"Clin Gastroenterol"},{"key":"2025090800044133000_46.1.127.5","doi-asserted-by":"publisher","DOI":"10.1159\/000180979"},{"key":"2025090800044133000_46.1.127.6","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/0016-5085(90)91166-4","article-title":"Randomised double-blind placebo controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding.","volume":"99","author":"Burroughs","year":"1990","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.7","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840040315"},{"key":"2025090800044133000_46.1.127.8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840100612"},{"key":"2025090800044133000_46.1.127.9","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90917-Z"},{"key":"2025090800044133000_46.1.127.10","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90867-B"},{"key":"2025090800044133000_46.1.127.11","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(05)80105-9"},{"key":"2025090800044133000_46.1.127.12","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/0016-5085(89)91630-2","article-title":"Reduction of portal pressure by isosorbide-5-mononitrate in patients with cirrhosis. Effects on splanchnic and systemic hemodynamics and liver function.","volume":"96","author":"Navasa","year":"1989","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.13","doi-asserted-by":"publisher","DOI":"10.1007\/BF02361244"},{"key":"2025090800044133000_46.1.127.14","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/0016-5085(92)91514-5","article-title":"Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage.","volume":"103","author":"Soriano","year":"1992","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.15","first-page":"122","article-title":"Peptic ulcer in cirrhotic patients: a short and long-term study with antisecretory drugs.","volume":"24","author":"Di Mario","year":"1992","journal-title":"Ital J Gastroenterol"},{"key":"2025090800044133000_46.1.127.16","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/0016-5085(88)90250-8","article-title":"Lactulose detoxifies in vitro short-chain fatty acid production in colonic contents induced by blood: implications for hepatic coma.","volume":"94","author":"Mortensen","year":"1988","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.17","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(96)80127-9"},{"key":"2025090800044133000_46.1.127.18","unstructured":"ICH Topic E9. Note for guidance on statistical principles for clinical trials step 4, consensus guideline,5 Feb 1998.."},{"key":"2025090800044133000_46.1.127.19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2165\/00003495-199200442-00006","article-title":"Somatostatin in acute bleeding oesophageal varices.","volume":"44","author":"Jenkins","year":"1992","journal-title":"Drugs"},{"key":"2025090800044133000_46.1.127.20","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/64.2.191"},{"key":"2025090800044133000_46.1.127.21","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1002\/sim.4780090915","article-title":"Statistical interim monitoring of the Cardiac Arrhythmia Suppression Trial.","volume":"9","author":"Pawitan","year":"1990","journal-title":"Stat Med"},{"key":"2025090800044133000_46.1.127.22","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(87)90027-4"},{"key":"2025090800044133000_46.1.127.23","doi-asserted-by":"publisher","DOI":"10.1016\/0950-3528(92)90031-9"},{"key":"2025090800044133000_46.1.127.24","first-page":"81A","article-title":"Endoscopic measurement of variceal pressure during hemorrhage from esophageal varices [abstract].","volume":"16","author":"Ruiz del Arbol","year":"1992","journal-title":"Hepatology"},{"key":"2025090800044133000_46.1.127.25","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1136\/gut.35.3_Suppl.S23","article-title":"Octreotide in variceal bleeding.","volume":"35","author":"Burroughs","year":"1994","journal-title":"Gut"},{"key":"2025090800044133000_46.1.127.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(98)80259-6"},{"key":"2025090800044133000_46.1.127.27","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(94)90188-0"},{"key":"2025090800044133000_46.1.127.28","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1056\/NEJM199206043262304","article-title":"Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices.","volume":"326","author":"Stiegmann","year":"1992","journal-title":"N Engl J Med"},{"key":"2025090800044133000_46.1.127.29","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/hep.1840220536","article-title":"The role of transjugular intrahepatic portosystemic shunt for treatment of portal hypertension and its complications: a conference sponsored by National Digestive Diseases Advisory Board.","volume":"22","author":"Schiffman","year":"1996","journal-title":"Hepatology"},{"key":"2025090800044133000_46.1.127.30","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0031-6997(25)06656-6","article-title":"Cyclic GMP synthesis and function.","volume":"39","author":"Waldman","year":"1987","journal-title":"Pharmacol Rev"},{"key":"2025090800044133000_46.1.127.31","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/0016-5085(93)90356-H","article-title":"Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis.","volume":"104","author":"Angelico","year":"1993","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.32","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3109\/00365529409094851","article-title":"Oral isosorbide-5-mononitrate reduces the rebleeding rate during the course on injection sclerotherapy for esophageal varices.","volume":"29","author":"Bertoni","year":"1994","journal-title":"Scand J Gastroenterol"},{"key":"2025090800044133000_46.1.127.33","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840060314"},{"key":"2025090800044133000_46.1.127.34","first-page":"34","article-title":"Hemodynamic evaluation of the addition of isosorbide 5 mononitrate to nadolol in cirrhotic patients with insufficient response to the beta-blocker alone.","volume":"26","author":"Merkel","year":"1997","journal-title":"Hepatology"},{"key":"2025090800044133000_46.1.127.35","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(93)90344-M"},{"key":"2025090800044133000_46.1.127.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)05406-2"},{"key":"2025090800044133000_46.1.127.37","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/hep.1840110212","article-title":"Enhancement of portal pressure reduction by the association of isosorbide 5 mononitrate to propranolol administration in patients with cirrhosis.","volume":"11","author":"Garc\u00eda-Pag\u00e1n","year":"1990","journal-title":"Hepatology"},{"key":"2025090800044133000_46.1.127.38","first-page":"G274","article-title":"Effect of somatostatin on mesenteric vascular resistance in normal and portal hypertensive rats.","volume":"262","author":"Sieber","year":"1992","journal-title":"Am J Physiol"},{"key":"2025090800044133000_46.1.127.39","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/0016-5085(91)90411-D","article-title":"Glucagon hinders the effects of somatostatin on portal hypertension. A study in rats with partial portal vein ligation.","volume":"101","author":"Pizcueta","year":"1991","journal-title":"Gastroenterology"},{"key":"2025090800044133000_46.1.127.40","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(93)90371-S"},{"key":"2025090800044133000_46.1.127.41","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230530"},{"key":"2025090800044133000_46.1.127.42","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080532"},{"key":"2025090800044133000_46.1.127.43","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(93)90155-G"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.46.1.127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T07:04:50Z","timestamp":1757315090000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.46.1.127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,1,1]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2000,1,1]]},"published-print":{"date-parts":[[2000,1,1]]}},"alternative-id":["10.1136\/gut.46.1.127"],"URL":"https:\/\/doi.org\/10.1136\/gut.46.1.127","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,1,1]]}}}