Cyanoacrylate in the treatment of gastric varices complicated by multiple pulmonary emboli.

Bleeding gastric varices are increasingly being obliterated with the aid of endoscopic injection of n-butyl-cyanoacrylate (histoacryl) diluted with lipiodol. This glue acts as a tissue adhesive that polymerizes on contact with blood in a gastric varix. Severe glue pulmonary embolism is a rare complication of injection therapy. This case involves a 52-year-old man with fundal gastric varices, who developed multiple pulmonary emboli following glue injection with profound hypoxia requiring hospital admission for 13 days, but with eventual recovery of normal lung function.

Fasting serum bile acid levels in the primary hyperlipoproteinemias.

A newly developed radioimmunoassay specific for conjugates of cholic acid (CCA) was used to measure the fasting serum levels of these bile acids in 233 patients with primary hyperlipoproteinemia classified as type IIa, IIb, III, IV, or V hyperlipoproteinemia as well as in 80 healthy control subjects. Subjects with type IIa hyperlipoproteinemia had significantly lower levels of CCA (0.9 plus or minus 0.06 muM, mean plus or minus SE) than did healthy controls (0.50 plus or minus 0.08 muM). Patients with type IIb, III, IV, and V hyperlipoproteinemia had values similar to those of the control group. The abnormally low fasting value of CCA in type IIa patients is considered to reflect decreased secretion of bile acid into the intestine in such patients, who are known to have defective bile acid synthesis rates and decreased bile acid pool sizes.

Biliary bile acid composition in Wilson's disease.

Biliary bile acid composition and pattern of bile acid conjugation with glycine or taurine were found to be within normal limits in six patients with documented Wilson's disease. Four patients had previous biopsy evidence of cirrhosis (three with active hepatitis), but most conventional liver function tests gave normal results at the time of the study. Serum levels of conjugates of cholic acid, measured by radioimmunoassay, were not increased. However, plasma disappearance if intravenously injected glycine conjugate of cholic acid was significantly delayed in all subjects, suggesting that this is a more sensitive test of hepatic excretory function and may be of value for assessing hepatic function in patients with this rare genetic disorder. No evidence of a primary disturbance in bile acid metabolism was found in these patients.

In-vivo anti-reflux and raft properties of alginates.

The comparative efficacy of two alginate-containing anti-reflux preparations (Gaviscon, Algicon) was assessed in a single blind crossover study of 20 patients with gastro-oesophageal reflux disease. The clinical efficacy study was preceded by two studies in healthy volunteers to assess the intragastric effects of Algicon and Gaviscon by pH measurement, endoscopic visualization and gamma scintigraphy. Algicon and Gaviscon were shown to form a raft in the fasting and fed human stomach, with Algicon alone having a potent antacid effect below and within the raft. Both Algicon and Gaviscon liquids significantly reduced the frequency and severity of reflux symptoms from baseline when given at their recommended doses (10 ml and 20 ml four times daily, respectively). There were no significant differences between Algicon and Gaviscon, although 12 patients preferred Algicon (vs 5 for Gaviscon) for control of reflux symptoms. It was concluded that both Algicon and Gaviscon were effective for the symptomatic control of gastro-oesophageal reflux disease.

The effect of atropine and vagal stimulation on the release of neurotensin-like immunoreactivity in man.

This study investigated the food stimulated release of neurotensin-like immunoreactivity (NTLI) in man with and without the administration of atropine, and the influence of vagal stimulation by modified sham feeding and insulin hypoglycaemia. NTLI was measured, after ethanol extraction, by specific C- and N-terminally directed antisera. With both a liquid fat meal and a mixed meal an early peak of NTLI occurred. The mixed meal also produced a second sustained rise in plasma NTLI. An intramuscular injection of 0.6 mg atropine sulphate abolished the early peak, but had no effect on the late peak. Modified sham feeding and insulin hypoglycaemia did not release NTLI. We conclude that it is possible that a cholinergic non-vagal mechanism is responsible for the early phase of food stimulated release of NTLI in man, and that the second sustained rise may be cholinergically independent.

Management of upper gastrointestinal haemorrhage.

Upper gastrointestinal haemorrhage is a life threatening situation. Peptic ulcer disease, oesophageal varices and Mallory-Weiss tear are the major causes. Initial management usually includes hospital admission and, ideally, care by a specialized team involving Physician, Surgeon and Nursing Staff. Prompt and adequate blood replacement is the most important measure followed by diagnosis, usually based on flexible endoscopy. Specific treatment protocols for peptic ulcer and oesophageal varices aid definitive management. Prognosis is influenced by age, presence of complicating disease, aetiology and the severity of the bleed.

Duodenal ulcer.

Duodenal ulcer is a common disease which places heavy demands on health care costs. The aetiology is unknown, but its pathogenesis is related to acid secretion. The characteristic symptom is chronic epigastric pain which precedes meals, occurs one to three hours after food, and one to two hours after retiring. The pain is relieved by food or antacids. Barium meal remains the prime investigation, but flexible endoscopy allows accurate visualization of the ulcer particularly in a scarred deformed duodenum. Complications include haemorrhage, perforation and obstruction. Time-honoured therapy including diet, antacids and anticholinergics simply relieves pain, whilst newer drugs (Tagamet, De-Nol, and Duogastrone) are effective in healing the ulcer. Surgery is indicated for complications or inadequately relieved pain.

Influence of initial therapy on outcome of peptic ulcer.

Histamine 2 (H2) receptor antagonists, proton pump inhibitors, prostaglandin analogues, colloidal bismuth and sucralfate have all proved safe and effective in the initial treatment of peptic ulcer. Yet, most ulcers will recur when treatment is stopped. Continuous maintenance with H2 antagonists results in low symptomatic relapse, complications occur rarely, and such treatment is safe. An alternative is Symptomatic Self Care (on-demand therapy), which provides an economic option for patients with no concomitant disease or previous complications. Meta-analyses suggest a higher relapse rate after H2 antagonist therapy than that following sucralfate or bismuth. Whilst improved morphology and/or functional status of the gastro-duodenal mucosa ('quality of healing') has been claimed, the difference has not been explained. Successful prolonged eradication of Helicobacter pylori leads to a very low relapse rate, but more effective, predictable and safer eradication regimens are needed.

Helicobacter pylori eradication: therapy other than with bismuth or proton-pump inhibitors.

Antibiotics alone do not achieve Helicobacter (H. pylori) eradication perhaps because of reduced activity in an acid environment. Some reports suggest that ranitidine combined with amoxicillin and metronidazole is highly successful in eradicating H. pylori, but other have found less success with H2-antagonists. Studies have shown that sucralfate is equally as effective as omeprazole when combined with clarithromycin and metronidazole in achieving H. pylori eradication. Similarly, sucralfate triple therapy (substituted for bismuth) may provide cost efficient treatment. Whilst immunization to protect against Helicobacter infection seems attractive, a large amount of animal work needs to be done before the necessary tedious human trials. Future trends in H. pylori eradication may involve 1-week therapy combining proton-pump inhibitors, bismuth or sucralfate and two antibiotics. It is hoped that such regimens will be simple, effective, relatively inexpensive and free of side effects.

Helicobacter pylori: fact or fiction?

The recent isolation and classification of the spiral gastric bacteria Helicobacter pylori has led to an explosion of worldwide research. The data strongly suggest that H. pylori is the causative agent for type-B active chronic gastritis. The role of H. pylori in duodenal ulcer awaits clarification, and, more importantly, potential treatment regimens need clear documentation and further detailed research. The past decade has revealed many intriguing facts about H. pylori infection. If, during the 1990s, eradication of H. pylori by means of appropriate and safe medication can lead to the control and prevention of gastroduodenal disease, then major clinical and economic benefits can be anticipated.

Quality of Life in duodenal ulcer.

A Quality of Life questionnaire was administered to 200 duodenal ulcer patients taking daily H2 antagonists and compared with the responses given by 50 newly diagnosed duodenal ulcer patients. Assessment involved 17 questions which attempted to measure ulcer symptoms, emotional and social function. Age, sex and percentage of smokers were identical in the two groups. Patients on long-term daily H2 antagonists showed high Quality of Life scores and this is hardly surprising, given the safety, efficacy and economy of H2 antagonists. By contrast, the low scores demonstrated in newly diagnosed ulcer patients reflect the troublesome nature of ulcer pain and the disruption it causes to social and emotional performance.

Long-term strategies for peptic ulcer.

Commonly when treatment is stopped most peptic ulcers recur. The prevention of ulcer recurrence by continuous long-term therapy, usually with H2-receptor antagonists, provides effective and convenient management in patients at risk in order to reduce the chance of relapse, complications, and associated mortality. High relapse rates of peptic ulcer suggest the need for continuous H2-antagonists in elderly patients, those receiving NSAID, aspirin or anticoagulants, those with coexistent medical conditions and those with previous haemorrhage or perforation. Patients suitable for intermittent therapy include those who are < 60 years, with no previous ulcer complications, no coexistent medical conditions and few recurrences. Long-term H2-antagonists have an enviable safety profile and are cost effective. Despite this, the possibility of permanent cure of peptic ulcer by Helicobacter pylori eradication suggests that long-term therapy may not be needed. We face the exciting prospect of placing peptic ulcer into the annals of history.

Helicobacter pylori and peptic ulcer.

Helicobacter pylori is an important pathogen causing both gastric and duodenal ulcer. The causal relationship is based on the strong association of peptic ulcer with H. pylori-induced gastritis, the improved rate of healing with H. pylori suppression, and markedly low recurrence rates for ulcer after H. pylori eradication. The ideal regimen for H. pylori eradication should be simple, inexpensive, free of side effects, and effective in at least 90% of patients. Triple therapy involving bismuth, metronidazole and tetracycline or amoxicillin results in the best and most consistent eradication data, but there is a significant incidence of side effects and problems with compliance. Acid suppression with ranitidine or omeprazole combined with antibiotics is effective but expensive with variable results in clinical trials. Sucralfate may also reduce H. pylori density and enhance the action of antibiotics used in eradication regimens. Studies reported in this Journal suggest that sucralfate can be successfully substituted for bismuth in triple therapy regimens with documented efficacy and few side effects. Considerable progress in developing newer regimens to eradicate H. pylori has been made. However, the development of an ideal drug or regimen remains a challenge.

Campylobacter pylori--a role in non-ulcer dyspepsia?

Non-ulcer dyspepsia (NUD) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified. The pathophysiology of NUD is probably heterogeneous. Eighty-two subjects with NUD were studied in a prospective randomized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate (CBS) chewable tablets at a dose of four tablets daily for 1 month. The role of Campylobacter pylori and associated histological gastritis was evaluated. Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25% of age-matched controls. C. pylori was associated with acute and chronic inflammation (P less than 0.001) in the antrum. C. pylori was cleared in 59% of CBS-treated subjects compared with only 4% placebo (P less than 0.05). Both acute and chronic inflammation improved in subjects cleared of bacteria. Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms. In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups. This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia.

Quality of healing in peptic ulcer disease--are H2 receptor antagonists all we need?

The rapid relief of symptoms and ulcer healing can now be achieved in most patients with peptic ulcer. Histamine2 (H2) receptor antagonists, proton pump inhibitors, prostaglandin analogues, colloidal bismuth and sucralfate have all proved safe and effective for the initial treatment of peptic ulcer. However, most ulcers will recur when treatment is stopped. Meta-analyses suggest a higher relapse rate after H2 antagonist therapy than that following sucralfate or bismuth. This difference has not been explained although improved morphology and/or functional status of the gastroduodenal mucosa ("quality of healing") has been claimed. Eradication of Helicobacter pylori leads to marked reduction in relapse rate but more effective and safer eradication regimens are needed. Since most ulcers do recur, maintenance therapy with H2 antagonists remains a commonly used option. Continuous maintenance results in low symptomatic relapse, complications occur rarely, and such treatment is safe. An alternative is Symptomatic Self Care (on-demand therapy) which provides an economic option for patients with no concomitant disease or previous complications. Future research should decide the exact role of Helicobacter eradication; but for now, we can still rely on maintenance therapy with the widely-used and proven H2 receptor antagonists.

Twice-a-day dosage of cimetidine in the short-term treatment of peptic ulcer.

The effect of cimetidine (400 mg twice a day) on the short-term healing of chronic peptic ulcer is reported. In benign gastric ulcer, 17 of 25 patients (68%) healed in six weeks and 23 of 25 patients (92%) by 12 weeks. In duodenal ulcer, 33 of 42 patients (80%) healed in six weeks and 40 of 42 patients (95%) by 12 weeks. In stomal ulcer after a previous Polya gastrectomy, eight of 10 patients (80%) healed in six weeks and 10 of 10 patients (100%) by 12 weeks. In this study, the cimetidine regimen of 400 mg twice a day has produced healing rates in gastric, duodenal or stomal ulcer which compare favourably with those reported for the currently recommended regimen of 200 mg three times a day and 400 mg at night. Twice a day dosage is likely to improve patient compliance, costs less, and may reduce dose-related side effects. Perhaps 400 mg of cimetidine twice a day should become the recommended dosage for the initial treatment of peptic ulcer.

Cholestyramine induced hyperchloremic metabolic acidosis.

The first reported case, in an adult, of cholestyramine induced hyperchloremic metabolic acidosis is a 70 year old female with a two year history of primary biliary cirrhosis confirmed by histologic and immunologic criteria. After taking cholestyramine II sachets twice daily for two months she presented with lethargy, confusion and drowsiness. Examination revealed confusion, jaundice, signs of chronic liver disease, portal hypertension and hepatic encephalopathy. Laboratory investigations confirmed a metabolic acidosis (pH 7.15) and hyperchloremia. Multiple cultures failed to reveal sepsis and a urinary pH of 4.85 together with tests of renal acidification, excluded renal tubular acidosis. She received 600 mEq of sodium bicarbonate intravenously over 36 hours by which time her mentation, electrolytes and pH were normal. It is presumed that her hyperchloremic metabolic acidosis was secondary to cholestyramine because of the similarity to pediatric reports; the rapid and lasting response to intravenous sodium bicarbonate; the absence of another etiology; normal serum potassium, chloride and bicarbonate despite continued spironolactone therapy after recovery.

Long-term cimetidine in duodenal ulcer disease.

Forty patients with chronic duodenal ulcer who had healed endoscopically with a 6-week course of cimetidine were randomized double blind to 1 year of either placebo or cimetidine tablets 400 mg bid (20 patients in each group). Patients were seen at monthly intervals, and endoscopy was performed at clinical relapse or on completion of 1 year. One of 20 patients on active cimetidine relapsed clinically and endoscopically at 3 months; 16 of 20 patients on placebo relapsed clinically and endoscopically within 9 months, the majority within 3 months, and 2 were shown to have asymptomatic chronic ulcers at routine 12-month endoscopy. None of the 19 patients on active cimetidine routinely endoscoped at 12 months showed evidence of ulceration. This study confirms a high relapse rate when short-term cimetidine is ceased and indicates that maintenance treatment with cimetidine prevents relapse.

Serum gastrin in duodenal ulcer. I. Basal levels and effect of food and atropine.

Fasting serum gastrin has been measured by radioimmunoassay in 72 patients with duodenal ulcer and compared with that in normals, patients with gastric ulcer, and with the Zollinger-Ellison syndrome. The mean (+/- SEM) gastrin levels were 15.7 +/- 1.5 pg/ml in the duodenal ulcer group, 32.1 +/- 4.3 pg/ml in normals, 118 +/- 18.1 pg/ml in gastric ulcer, and between 450 and 2,000 pg/ml in the Zollinger-Ellison syndrome. There were no difficulties in distinguishing simple ulcer from the Zollinger-Ellison syndrome as the presence of hyperchlorhydria in combination with hypergastrinaemia led to a confident diagnosis of the latter disease.The effect of protein, glucose, and cream feeding with and without atropine was also assessed in a group of these patients with duodenal ulcer. As in normals, there was no stimulation of gastrin release by either atropine alone, distilled water, glucose, or cream. However, protein alone produced a greater rise in serum gastrin levels compared with that in normals and prior atropinization augmented this response greatly in duodenal ulcer. This indicates an increased amount of releasable gastrin in the latter disease, the release of which, under basal conditions, is suppressed by the high acidity in the antrum.

Serum gastrin in chronic gastritis.

Fasting gastrin levels in serum were measured in 49 patients with different types of chronic gastritis and in matched controls. In 15 patients with established pernicious anaemia the mean (+/- S.E. of mean) level of gastrin was greatly raised (699 +/- 99 pg/ml). In 17 patients with chronic atrophic gastritis, seropositive for parietal cell antibody but with adequate vitamin-B(12) absorption, the level was also raised (476 +/- 74 pg/ml). By contrast, in "simple" atrophic gastritis seronegative for parietal cell antibody the gastrin levels were significantly lower for both diffuse atrophic gastritis (129 +/- 31 pg/ml) and multifocal gastritis (14 +/- 4 pg/ml). These levels were similar to those in the controls (46 +/- 7 pg/ml).The mechanism of the raised gastrin levels remains uncertain, but neither achlorhydria nor in vivo action of the parietal cell antibody wholly accounted for the hypergastrinaemia.We conclude that hypergastrinaemia is characteristic of gastritis associated with autoimmune reactions to gastric antigens and pernicious anaemia and that a raised serum gastrin is a useful marker of the type of gastritis that tends to progress to the gastric lesion of pernicious anaemia. The findings suggest that this type of gastritis is an essentially different disease from "simple" atrophic gastritis, and the differences in gastrin levels may be due to sparing of the antral mucosa in the autoimmune type but not in "simple" gastritis.