In primary anorexia nervosa, gastric motility is often impaired and ensuing symptoms further discourage eating. Prokinetic agents have been shown to accelerate gastric emptying in affected patients. This study investigated whether emptying of a radiolabelled semisolid 1168 kJ meal and antral contractility were enhanced by intravenous erythromycin. Eight women and two men with anorexia nervosa (21-46 years, 50-75% of ideal body weight) received 200 mg erythromycin or placebo under crossover double blind conditions. Gastric emptying and antral contractility were recorded scintigraphically for 90 minutes. In addition, plasma motilin and pancreatic polypeptide concentrations were determined. With placebo, antral contractions were of regular 3 cycles/minute frequency. With erythromycin, less frequent and partly arrhythmic long duration contractions set in and emptying was accelerated: after 90 minutes, the activity remaining in the stomach was markedly less than with placebo in all patients (Sign test, p < 0.002). Basal motilin and pancreatic polypeptide concentrations were normal and showed a normal response to the meal in all patients. Motilin concentrations decreased slightly more and pancreatic polypeptide concentrations increased markedly more with erythromycin than with placebo, possibly because the meal reached the intestine earlier. In conclusion, erythromycin accelerated emptying markedly and in most patients induced an antral motor activity characterised by long duration contractions occurring at often irregular intervals.

Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p < 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p < 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p < 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p < 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin.

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.

In an interim analysis of the Benelux trial, no difference in alanine aminotransferase normalisation has been found between the high (6 million units) and standard (3 million units) doses of interferon alfa-2b during the first eight weeks of treatment. The probability of achieving normal alanine aminotransferase activity on at least two successive occasions during treatment is 65% for the standard dose and 73% for the higher dose. Measurement of plasma hepatitis C virus-RNA suggests that hepatitis C virus-RNA negativity after four weeks of treatment is a prerequisite for sustained response to interferon alfa-2b.

Impairment of non-cholinergic innervation of the lower oesophageal sphincter has been suggested in idiopathic achalasia. As opioid nerves are present in the lower oesophageal sphincter and opioid peptides affect lower oesophageal sphincter motility, the effect of an opioid agonist, morphine (100 micrograms/kg iv), and an opioid blocker, naloxone (80 micrograms/kg iv), on lower oesophageal sphincter motor function was assessed in 10 healthy subjects and in 10 patients with untreated idiopathic achalasia on separate days and in randomised order. In addition, in six of the patients, naloxone 0.8 mg iv was injected 60 minutes after morphine and recordings continued for a further five minutes. Lower oesophageal sphincter pressure was monitored by a sleeve device. In the healthy subjects morphine decreased (p < 0.01) resting lower oesophageal sphincter pressure by 4 (1) mm Hg (23 (8)%). In the achalasia patients the effect was more marked, lower oesophageal sphincter pressure being reduced (p < 0.01) by 11 (2) mm Hg (46 (8)%). Naloxone reversed lower oesophageal sphincter pressure to basal. Both absolute and percentage decreases after morphine were significantly greater (p < 0.05) in the achalasia patients than in the healthy subjects. Swallow induced lower oesophageal sphincter relaxation was significantly decreased (p < 0.05) by morphine in the healthy subjects but not in the achalasia patients. Naloxone had no effect on resting lower oesophageal sphincter pressure or swallow induced relaxation in either healthy subjects or achalasia patients. In conclusion achalasia patients are hypersensitive to the effect of morphine on resting lower oesophageal sphincter pressure. This finding is unlikely to be the result of a denervation process involving opioid nerves.

In a study of low dose interferon alfa-2b in 587 patients expected to show a good response to treatment, 76-87% patients in different countries had alanine amino-transferase activities returned to normal after four months' treatment, 49-72% were negative for hepatitis B virus (HBV)-DNA, 51-66% were negative for hepatitis B e antigen (HBeAg), and 44-62% were anti-HBe positive. These effects were maintained after nine to 12 months' follow up. Side effects were mild, but led to discontinuation of treatment in 12 patients.

Fifty eight patients with chronic viral hepatitis B (HBV) were randomised in a prospectively controlled trial. Thirty patients were treated with 3 million units (MU) of interferon alfa-2b subcutaneously thrice weekly for four months. Twenty eight controls received no treatment. The follow up period after treatment was six months. Twenty eight treated patients and 27 controls completed the protocol. One woman in the treatment group showed a complete response, and eight other treated patients (32%) showed a partial response. Three patients in the control group (11%) lost hepatitis B e antigen and HBV-DNA spontaneously. This finding is statistically significant (p < 0.05). The elimination of HBV markers from the serum was associated with a return to normal of serum aminotransferase activities. Reactivation of hepatitis was not observed after seroconversion.

This study was designed to evaluate the safety and effectiveness of high dose interferon, with or without prednisone pretreatment, in patients with chronic hepatitis B. Patients were randomised to two treatment groups: group I (n = 26) received six weeks of prednisone followed by a two week, drug free period, and then 10 million units (MU) of interferon alfa-2b three times weekly subcutaneously for 16 weeks; group II (n = 24) were used as controls for 24 weeks and then treated with interferon. Loss of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV)-DNA, with a return to normal alanine aminotransferase (ALT) activity, was seen in 16 of 26 group I patients (61.5%), in one group II patient (4.2%) during the control phase, and in 13 of 23 group II patients (56.5%) after interferon. Three of 26 (11.5%) in group I and one of 23 (4.3%) in group II eliminated the surface antigen (HBsAg). There were no statistically significant differences in response between groups I and II. Liver biopsies carried out in 20 patients showed that responders had a noticeable reduction in inflammation and disappearance of core antigen in liver tissue, changes not seen in non-responders. On long term follow up (four years), nine out of 28 responders (32.1%) eliminated HBsAg, and four initial non-responders had a late seroconversion.

Twenty nine children (mean age 8.3 years, 18 boys, 11 girls) who had biopsy proved chronic hepatitis B virus infection (HBV) with active viral replication were given a 16 week course of interferon alfa-2b treatment (9 million units (MU)/m2, thrice weekly). Fourteen children (48%) showed persistent loss of HBV-DNA 8 months after the end of treatment; 11 (38%) lost hepatitis B e antigen (HBeAg), and two (7%) hepatitis B surface antigen (HBsAg). Alanine aminotransferase activities returned to normal in 12 children. Those who responded had significantly higher initial transaminase activities than those who did not (p < 0.01) but similar serum HBV-DNA. Results were compared with the natural evolution of the disease in a group of 25 children (mean age 8.3 years) with identical initial mean serum HBV-DNA values, followed up during the same period. Two of these (8%) lost HBeAg and one (4%) HBsAg. The 23 remaining control subjects had no decrease in serum HBV-DNA or in transaminase activities compared with values 1 year earlier. It is concluded that treatment with interferon alfa-2b in children may lead to inhibition of HBV replication similar to that described in adults, and may thus shorten disease evolution. Further studies are necessary to establish the best protocols and to identify those patients who are the most likely to respond to treatment.

Acute hepatitis B is a self limiting disease that resolves spontaneously in 95% of patients who acquire the infection in adulthood. Patients with acute hepatitis B, however, usually take between four and 12 weeks to recover; the personal, social, and sanitary costs associated with this are high. Also, 5-10% of patients with acute hepatitis B go on to develop chronic liver disease. Hepatitis C, by comparison, is an asymptomatic disease associated with a high progression to the chronic stage. At least 50% of patients with post-transfusion hepatitis C develop chronic liver disease or cirrhosis. While the efficacy of alpha interferon in chronic hepatitis B and C is now well established, only preliminary evidence for use in the acute phase exists. This paper reviews the preliminary evidence and concludes that, given the high risk of progression to the chronic stage, the use of interferon in acute hepatitis C should be recommended.

To confirm the positive results of a preliminary trial, 26 patients with mixed cryoglobulinaemia were enrolled in a controlled, randomised, crossover trial with interferon alfa-2b. A significant improvement was seen in the purpura score and alanine aminotransferase activities during six months' treatment, and was associated with a significant decrease in cryocrit and a returning to normal of the lymphocyte CD4/CD8 ratio (in eight of nine patients). No significant variations were seen during the six month period without interferon. Only six patients withdrew from treatment, three because of side effects and three because of poor compliance.

To assess whether the risk of chronic disease in patients with acute non-A, non-B/type C (NANB/C) hepatitis after transfusion could be reduced by treatment with interferon, patients were randomised to receive 3 million units interferon (IFN) alfa-2b three times a week for three months or no therapy. At the end of treatment, IFN had significantly reduced the number of patients with abnormal alanine aminotransferase activities compared with untreated patients but this difference was not maintained during a 15 month follow up. Treatment with IFN alfa-2b was considered safe and was well tolerated.

This randomised, controlled trial was designed to assess the response to a nine month course of interferon (IFN) alfa-2b, starting with a higher than usual dose. Forty eight patients received IFN 5 million units (MU) three times a week for eight weeks followed by 3 MU three times weekly for seven months; 25 patients in the control group received no treatment. The overall response to treatment was 68.7%, an improvement over other studies, but the high rate of relapse (85% in patients who responded) suggested that a nine month treatment period was insufficient in most cases. Histological improvement was seen in more than 80% of responders to interferon, including a reduction in inflammatory activity, necrosis, and fibrosis.

Four different dosage regimens of interferon (IFN) alfa-2b (3 million units (MU) three times weekly for three months, 3 MU three times weekly for six months, 6 MU two times weekly for six months, and 6 MU three times weekly for six months) were compared in patients with chronic hepatitis C. There was no significant difference measured by percentage of responders to treatment between the four groups, but the degree of response was inversely correlated with the severity of liver damage. Viraemia was undetectable in most (75%) of responders treated with interferon and also in 20% of those who did not respond to treatment.

In a study of 87 patients with chronic hepatitis C, 12 months' treatment with interferon alfa-2b at a dose of 6 million units (MU) three times per week seemed to be more effective than treatment with 3 MU three times a week for two months plus 1.5 MU three times a week for 10 months in increasing the percentage of long term responders. The percentage of patients in whom alanine amino-transferase activities returned to normal was highest in the 6 MU group, as was the percentage of responders who sustained this normal activity after treatment. Side effects were moderate and self-limited in most patients.

Chronic hepatitis C virus (HCV) associated liver disease is an important cause of morbidity and mortality in haemophilia. Recombinant interferon alfa-2b was used in a randomised controlled liver biopsy trial to treat haemophiliacs with chronic HCV. All 18 patients entered had antibodies to HCV. During the first year of the study, 10 patients were randomised on the basis of histology to receive interferon alfa-2b, 3 million units subcutaneously, thrice weekly and eight to receive no treatment (control group). After 12 months, all patients had a second liver biopsy and the control group patients were offered interferon at the same dosage but for only six months. The alanine aminotransferase (ALT) activity had returned to normal in four of 10 patients treated for one year and five of six patients treated for six months, compared with none of the eight patients in the control group (p < 0.01). Although the histological scores of the two groups were similar at entry into the study, after one year the biopsy specimens in the treated group showed significant improvement compared with controls (p < 0.01). It is concluded that interferon alfa-2b is effective in returning ALT values to normal and improving liver histology in at least 50% of patients treated.

One hundred and twenty six patients were enrolled in a study to assess the effect of different interferon alfa-2b treatment regimens on the rate of increase in alanine aminotransferase (ALT) activities after treatment. Results indicated that a high daily dosage of interferon (10 million units (MU)) given six times a week for two weeks followed by 12 weeks of thrice weekly dosing was more effective at producing sustained normal ALT values than either eight weeks of 10 MU interferon six times a week or four weeks of 10 MU six times a week followed by eight weeks of thrice weekly dosing. Multiple regression analysis of clinical parameters before treatment showed that the outcome was dependent upon treatment group (p < 0.001) and the initial hepatitis C virus (HCV)-RNA value (p < 0.05). Anti-HCV titre and liver histology had a considerable but not significant effect on the response to treatment. The most frequently observed side effect was flu like syndrome, which occurred in over 90% of patients. In addition, 21% of patients experienced some degree of hair loss. Treatment was stopped because of side effects in 11 of 126 (9%) patients, evenly distributed between the three groups.

One hundred and eleven patients with non-A, non-B/type C (NANB/C) chronic active hepatitis were randomly assigned to two groups to receive recombinant interferon alfa-2b treatment as follows: 3 million units (MU) interferon three times weekly for six months or 3 MU interferon three times weekly for the first six months, 2 MU for the next three months, and 1 MU for the last three months. At the end of treatment, the number who had responded completely was similar in both groups (47.2% in the six months group v 41.4% in the 12 months group). Cirrhosis was found to be the only predictive factor for response; a complete response was observed in 50.6% of patients without cirrhosis v 33.3% of those with cirrhosis (p = 0.04). After one year of treatment, the rate of relapse was lower in patients who had received longer treatment (33%) than in those who had received six months of interferon (60%). The difference between the groups was not statistically significant and the trend favouring longer treatment for sustained response requires further confirmation.

This paper presents the preliminary results of a study designed to evaluate the effects of alpha interferon in chronic hepatitis B. After six months' treatment with interferon alfa-2b (5 million units (MU), three times weekly) 15 of 25 (60%) patients achieved seroconversion of hepatitis B e antigen, 17 (68%) normalised alanine aminotransferase (ALT) activity, and 15 (60%) showed a decrease in the inflammatory reaction on liver histology. No seroconversions occurred in the control group (n = 10), and none of the control patients achieved a normal ALT or showed a reduction in the inflammatory reaction. Adverse effects were experienced by most patients who received interferon but none warranted stopping the treatment.

This trial was undertaken to establish the long term biochemical and serological outcome of patients with acute post-transfusion hepatitis C virus infection after treatment with interferon alfa-2b. After 12 months, 12 patients (eight treated, four controls) had self limited disease and 16 patients (seven treated, nine controls) had chronic disease. After a total mean 31 months of follow up in 23 patients, nine (six treated, three controls) had self limited disease while 14 (five treated, nine controls) developed chronic liver disease; all patients with spontaneous or self limited hepatitis C (HCV) infection maintained normal serum alanine amino-transferase activity and absence of HCV-RNA, and tended to lose anti-HCV antibodies.