Regulation of CYP3A9 gene expression by estrogen and catalytic studies using cytochrome P450 3A9 expressed in Escherichia coli

BACKGROUND: In patients with reflux oesophagitis, endoscopic healing and symptom relief are considered important treatment goals in long-term care. AIM: To compare the effect of lansoprazole 15 and 30 mg daily on maintaining endoscopic healing and symptom relief in patients with moderate reflux oesophagitis. PATIENTS AND METHODS: In a single-centre, double-blind randomized clinical trial, 103 patients with grade 1 or 2 reflux oesophagitis who were endoscopically healed and asymptomatic after lansoprazole 30 mg daily for 12 weeks, were randomized to maintenance therapy with either lansoprazole 15 mg or 30 mg o.m. Endoscopy was repeated after 3, 6 and 12 months, and symptom relief assessed after 3, 6, 9 and 12 months. Relapse of oesophagitis or symptoms were considered end-points. RESULTS: After 12 months, 14/50 patients (28%) receiving lansoprazole 15 mg daily had suffered an endoscopic relapse compared to 8/53 patients (15%) treated with lansoprazole 30 mg daily. A life table analysis showed no statistically significant difference between the two groups (P = 0.086). Significantly more patients were kept in complete symptomatic remission in the 30 mg group (P < 0.01). In the 15 mg group, 23/50 (46%) had suffered either an endoscopic or symptomatic relapse on completion of the study, compared to 12/53 (23%) in the 30 mg group. A life table analysis showed this difference to be statistically significant (P = 0.010). Lansoprazole 15 and 30 mg daily were equally well tolerated. CONCLUSION: No statistically significant differences were found in endoscopic relapse rate or occurrence of adverse events, while lansoprazole 30 mg proved superior to 15 mg in maintaining patients in symptomatic relief and combined endoscopic and symptomatic remission.     

Lansoprazole. An update of its pharmacological properties and clinical efficacy in the management of acid-related disorders

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion. It has proved effective in combination regimens for the eradication of Helicobacter pylori and as monotherapy to heal and relieve symptoms of gastric or duodenal ulcers and gastro-oesophageal reflux. After initial healing, it may be used to prevent recurrence of oesophageal erosions or peptic ulcers in patients in whom H. pylori is not the major cause of ulceration and to reduce basal acid output in patients with Zollinger-Ellison syndrome. Usual dosages are 15 to 60 mg/day, although dosages of < or = 180 mg/day have been used in patients with hypersecretory states. In patients with duodenal or gastric ulcer, short term lansoprazole monotherapy was similar to omeprazole and superior to histamine H2 receptor antagonists in achieving healing rates > 90%. Lansoprazole was as effective a component of H. pylori eradication regimens as omeprazole, tripotassium dicitrato bismuthate (colloidal bismuth subcitrate) or ranitidine. Lansoprazole was superior to ranitidine in symptom relief and healing of gastro-oesophageal reflux disease and tended to relieve symptoms more rapidly than omeprazole, although initial healing was similar. As maintenance treatment, lansoprazole was similar to omeprazole and superior to ranitidine in relieving symptoms and preventing relapse. Lansoprazole was also superior to ranitidine in healing and relieving symptoms of oesophageal erosions associated with Barrett's oesophagus; healing was maintained for a mean of 2.9 years in > or = 70% of patients. Lansoprazole was also superior to ranitidine in prophylaxis of redilatation of oesophageal strictures. After > or = 4 years of use in patients with Zollinger-Ellison syndrome, lansoprazole 60 to 180 mg/day effectively controlled basal acid output. Dosages may be reduced in some patients once healing and symptom relief has been achieved. Preliminary studies of lansoprazole in patients at risk of aspiration pneumonia or stress ulcers show promise. Although studies show lansoprazole is potentially effective in treating gastrointestinal bleeding, future studies should assess patients' H. pylori status. Lansoprazole has been well tolerated in clinical trials, with headache, diarrhoea, dizziness and nausea appearing to be the most common adverse effects. Tolerability of lansoprazole does not deteriorate with age and the drug is well tolerated in long term use (< or = 4 years) in patients with Zollinger-Ellison syndrome or reflux disease. Thus, lansoprazole is an important alternative to omeprazole and H2 receptor antagonists in acid-related disorders. In addition to its efficacy in healing or maintenance treatment, it may provide more effective symptom relief than other comparator agents.     

Prospective, randomized, investigator-blind trial of Helicobacter pylori infection treatment in patients with refractory duodenal ulcers. Healing and long-term relapse rates

In this study, 26 patients with duodenal ulcers refractory to treatment with H2-receptor antagonists for 8-12 weeks were randomly assigned to eight weeks of treatment with colloidal bismuth subcitrate (120 mg four times a day) alone (N = 12) or in combination with tetracycline hydrochloride (500 mg four times a day, days 0-14) and metronidazole (500 mg three times a day, days 15-28). Symptoms were scored and endoscopy, histology, and CLO tests were performed before, on completion of treatment, and 3, 6, 12, and 18 months after treatment. Treatment was considered successful when Helicobacter pylori was not detected by CLO tests and Warthin-Starry stains on gastric biopsies taken from antrum, body, and fundus. On triple therapy, ulcers healed in 12/14 patients (85.71%) and 10/14 (71.42%) patients became Helicobacter pylori-negative. On bismuth, only one patient became Helicobacter pylori-negative (8.33%, P < 0.0001), but ulcers healed in 8/12 patients (67%, P = NS). Six patients on bismuth, whose ulcers remained unhealed or relapsed early after healing, were offered triple therapy, which resulted in ulcer healing in three and Helicobacter pylori clearance in two patients. At 18 months, none of the Helicobacter pylori-negative patients had ulcer relapse. On the contrary, ulcers relapsed in all but one patient, who remained Helicobacter pylori-positive. Smoking and drinking did not influence the therapeutic outcome. The data confirm previous reports that many duodenal ulcers are infectious and therefore curable.     

CT in Fournier''s gangrene

BACKGROUND: Few outcome studies directly compare Helicobacter pylori eradication therapy with maintenance H2-antagonist therapy in duodenal ulcer disease. AIM: To examine prospectively the efficacy of H. pylori eradication therapy with ranitidine maintenance therapy over 1 year in patients with confirmed chronic duodenal ulcer. METHODS: One hundred and nineteen patients with active H. pylori infection were randomized to receive ranitidine, 150 mg/day initially (58 patients), or omeprazole, 40 mg/day, amoxycillin 2 g/day and metronidazole 1.2 g/day for 14 days, or omeprazole 40 mg/day and clarithromycin 1.5 g/day, for 14 days (if penicillin-allergic). Symptoms were assessed using the Gastrointestinal System Rating Scale (GSRS) and SF36 quality of life index. RESULTS: 13C urea breath testing confirmed overall treatment success in 100% of patients (58/58) per protocol and 95.1% (58/61) on an intention-to-treat basis. At 4 and 12 months there were no differences in any GSRS symptoms between treatment groups. SF36 analysis showed a perceived health improvement at 4 and 12 months in patients who received H. pylori eradication. However, despite successful H. pylori eradication, one-fifth of patients still required antisecretory therapy. CONCLUSION: Following successful H. pylori eradication, chronic duodenal ulcer patients were at least as well symptomatically as when taking maintenance ranitidine. They perceived that their health had improved, but a subgroup was still acid-suppression dependent.     

A clinical trial of lansoprazole in the treatment of duodenal ulcer

To evaluate the efficacy of a second generation acid pump inhibitor-lansoprazole (L) a controlled clinical trial in 72 patients of duodenal ulcer was carried out with omeprazole (O) as control. The results showed that the ulcer healing rate after 4-week treatment was 97.4% in lansoprazole group and 91.2% in omeprazole, while the effective rate was 100% and 97.1% respectively (P > 0.05). Ulcer related pain was relieved more quickly in lansoprazole group. The pain relief rate after treatment of 3 days was different significantly between the two group, being 74.3% (L) and 51.6% (O) respectively (P < 0.05). No marked side-effect was observed in lansoprazole group. It is shown that lansoprazole is effective and safe for treatment of duodenal ulcer.     

Two year maintenance treatment of duodenal ulcer disease with ranitidine 150 mg: a prospective multicentre randomised study. GEMUD (Groupe d'Etude de la Maladie Ulcéreuse Duodénale)

Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was compared with placebo in a two year prospective multicentre randomised study. Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197) groups. Efficacy was assessed by the length of time to the first ulcer pain attack (with or without endoscopic confirmation) or DU complication. One hundred and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival curves of patients without ulcer pain (26 and 53% at two years in placebo and ranitidine groups, respectively) were significantly different (p < 0.0001). Endoscopies were performed depending on physicians' decision (mainly where there was severe pain or complication). Patients without relapses from endoscopy were more frequent in the ranitidine group (83%) than in the placebo group (47%, p < 0.0001). A greater incidence of complications, mainly bleeding, was also seen in the placebo group (13 complications v two in the ranitidine group, p < 0.002). No factor predicting DU relapse was identified. No important side effect was encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing ulcer pain attacks and DU complications for up to two years.     

Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin

BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication. AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies. METHODS: Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14-17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site). RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.     

Misoprostol and omeprazole in the prevention of chemotherapy-induced acute gastroduodenal mucosal injury. A randomized, placebo-controlled pilot study

BACKGROUND: Chemotherapy (CT) may induce acute mucosal injury to the stomach and duodenum, but its prevention has been scarcely investigated. METHODS: One hundred and eighty-two cancer patients with normal stomach and duodenum or having fewer than 3 erosions, selected to be treated with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (77 breast carcinoma patients) or 5-fluorouracil (5-FU) (105 colon carcinoma patients), were randomly assigned to prophylactic treatment with misoprostol, 400 micrograms twice a day; omeprazole, 20 mg once a day; or placebo, 1 tablet twice a day. Seven days after the end of the second source of CT, all patients underwent control esophagogastroduodenoscopy. Endoscopic findings were quantified on the basis of an arbitrary score: 0 = normal; 1 = less than 3 erosions; 2 = 3-15 erosions; 3 = more than 15 erosions or ulcer; 4 = giant ulcer (greatest dimension of more than 2 cm) or multiple ulcers with cumulative greatest dimension exceeding 2 cm. RESULTS: Mean score increased significantly in the placebo and misoprostol groups, either after CMF (P < 0.001 and P < 0.05, respectively) or after 5-FU (P < 0.001 for both), whereas it did not in the omeprazole group. Gastric and duodenal ulcers were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.05 after both CMF and 5-FU). No significant difference was observed between placebo and misoprostol. Omeprazole was significantly more effective than placebo and misoprostol in reducing the frequency and degree of the endoscopic worsening, either after CMF or after 5-FU (P < 0.05 for both CT regimens). Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole than in those receiving placebo (P < 0.01) or misoprostol (P < 0.001). CONCLUSIONS: The strong and prolonged inhibition of gastric acid production induced by omeprazole seems to be effective in preventing chemotherapy-induced gastroduodenal mucosal injury. Further trials are necessary to verify whether such a prevention of endoscopically observed injury can translate into prevention of clinically significant injury.     

Inter-rater reliability for function and strength measurements in the acute care hospital after elective hip and knee arthroplasty

AIM: To investigate the efficacy and safety of daily low-dose colloidal bismuth subcitrate in reducing duodenal ulcer relapse. DESIGN: Double-blind, double-dummy group comparative clinical trial with random allocation. Healing Phase: colloidal bismuth subcitrate 240 mg twice daily vs ranitidine 150 mg twice daily for up to 12 weeks. Maintenance Phase: nightly, colloidal bismuth subcitrate 120 mg vs ranitidine 150 mg vs placebo for up to 12 months (high-risk patients received active treatment only). Assessment: clinical, endoscopy, random blood bismuth levels (and rapid urease test for Helicobacter pylori in a subgroup). PATIENTS: 194 with active duodenal ulcer. OUTCOME: Cumulative healing at 12 weeks was 93% on colloidal bismuth subcitrate (of 92 patients) and 97% on ranitidine (of 102 patients). Relapse at 1 year was significantly less on active treatment as follows: placebo (50 patients) 60%; ranitidine (71 patients) 21%; colloidal bismuth subcitrate (64 patients) 33%. This was independent of the results of the rapid urease test which was positive in 78%, 88% and 76% of the patients respectively. Treatment was well tolerated. The highest median blood bismuth level (mcg/L) was 25 in the healing phase and fluctuated between 6 and 10 in the maintenance phase. CONCLUSIONS: Colloidal bismuth subcitrate, 120 mg nightly, is effective in reducing duodenal ulcer relapse and is well tolerated.     

Improving management of duodenal ulcer disease

Audit of treatment of duodenal ulcer disease has allowed management to improve and keep abreast of rapid advances in care. Eradication of Helicobacter pylori was assessed by 14C urea breath test one to two months after anti-Helicobacter therapy. The old triple therapy regime of bismuth, tetracycline and metronidazole for two weeks was found to be toxic and of low effectiveness (82%). Regimes with lansoprazole for one month and antibiotics for one week gave 90-98% success rates. The best success has been with regimes containing both clarithromycin and a nitro-imidazole. There was complete success in 98% of 109 patients given quadruple therapy with lansoprazole 30 mg daily for one month plus tetracycline 500 mg twice daily, clarithromycin 250 mg twice daily and metronidazole 400 mg twice daily for one week.     

Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.     

Prognostic factors for relapse of reflux oesophagitis and symptoms during 12 months of therapy with lansoprazole

BACKGROUND: Symptom relief and endoscopic healing are both important treatment goals in patients with reflux oesophagitis. Knowledge of predictive factors for treatment success could facilitate choice of treatment in individual patients. AIM: To assess the value of clinical data and data from baseline ancillary investigations in predicting the outcome of maintenance therapy with a proton pump inhibitor. METHODS: After healing and symptom relief had been obtained on open therapy with lansoprazole 30 mg daily, 103 patients with reflux oesophagitis grade 1 or 2 were randomized to maintenance therapy with lansoprazole 15 or 30 mg daily, and time until recurrence of symptoms and/or endoscopic changes was recorded. The predictive value of the following variables was assessed by Cox regression analysis: dose of lansoprazole, symptom severity, grade of reflux oesophagitis. Helicobacter pylori infection status, lower oesophageal sphincter resting tone, percentage of 24 h with an oesophageal pH of <4.0, and median 24 h intragastric pH before start of treatment. RESULTS: Dose of lansoprazole (P = 0.01) and symptom severity (P < 0.05) both significantly predicted time to relapse. Grade of reflux oesophagitis had only a borderline predictive value (P = 0.09), while H. pylori infection status and data from manometry and intraoesophageal 24-hour pH-metry did not predict relapse. CONCLUSIONS: Symptom severity before starting therapy is a significant predictive factor for treatment success during potent antisecretory therapy with lansoprazole, more so than endoscopic grade of reflux oesophagitis. In a group of patients with uncomplicated reflux oesophagitis being considered for maintenance therapy with lansoprazole, ancillary investigations with endoscopy, manometry and 24-hour pH-metry gave very limited prognostic information. H. pylori infected patients relapsed as early as patients who were not infected.     

Omeprazole and ranitidine in long-term treatment of duodenal ulcer: a double-blind comparison of length of time in remission

In most patients duodenal ulcer is a chronic relapsing disease. If no active maintenance treatment or eradication therapy is given after healing, around 70-100% of patients have a relapse during the first year. We conducted a double-blind multicenter study in 472 patients with duodenal ulcer. They were treated with omeprazole 20 mg every morning for four or eight weeks and when healed were randomly allocated to maintenance treatment with either omeprazole 20 mg every morning or ranitidine 150 mg at bedtime for up to six months. The patients were assessed by endoscopy at monthly intervals until healing occurred. Thereafter scheduled endoscopy was carried out after 1, 3, and 6 months of maintenance treatment or immediately in the event of a suspected relapse. Healing status (intention to treat approach) was 87% at four weeks and 93% at eight weeks. At six months the estimated remission rate was 90% for omeprazole and 82% for ranitidine (P = 0.03, 95% CI 1-15%). The incidence of adverse events was similar during the two maintenance treatments. Treatment with omeprazole 20 mg every morning maintained significantly more patients in remission than treatment with ranitidine 150 mg at bedtime.     

Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite

BACKGROUND: Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common in children with focal seizures. These are considered to represent solitary cysticercus granulomas. Controversy exists regarding their treatment. OBJECTIVE: To evaluate the efficacy of albendazole in cases of focal seizures with SSECTLs. DESIGN: Randomized, placebo-controlled, double blind trial. SETTING: Pediatric service of Nehru Hospital, PGIMER, an urban tertiary care teaching hospital. SUBJECTS: 63 children between 2 and 12 years of age with focal seizures for <3 months and SSECTLs. INTERVENTION: All children were randomly assigned to receive either albendazole (15 mg/kg/ day) or placebo for 28 days. CT scan was done at 1 and 3 months after beginning treatment. Codes opened after 6 months of inclusion in the study showed that 31 had received albendazole and 32 had received placebo. All children were followed up for at least 15 months. RESULTS: Disappearance of lesions on CT scan was noted in 41% of albendazole vs. 16.2% of placebo patients after 1 month of follow-up (P < 0.05) and 64.5% of albendazole- vs. 37.5% of placebo-treated patients after 3 months of follow-up (P < 0.05). During the first 4 weeks of therapy seizure recurrence was seen in 9.7% of albendazole vs. 3.2% of placebo-treated children (odds ratio, 3.32; 95% confidence interval, 0.33 to 33.8). After 4 weeks seizure recurrence was seen in 31.3% of placebo-treated children vs. 12.9% of albendazole-treated children (odds ratio, 3.07; 95% confidence interval, 1.18 to 11.15). CONCLUSIONS: Albendazole therapy results in significantly faster and increased resolution of solitary cysticercus lesions (SSECTLs) and appears to reduce the risk of late seizure recurrences.     

Age-dependent eradication of Helicobacter pylori with dual therapy

BACKGROUND: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. METHODS: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. RESULTS: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 +/- 1.7; 51 +/- 25%) than for omeprazole (5.4 +/- 1.1: 77 +/- 25%; P < 0.05) or lansoprazole (4.4 +/- 1.6: 68 +/- 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 +/- 13 years) than patients still H. pylori-positive (47 +/- 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75-83%) in subgroups of patients (> 50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. CONCLUSION: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.     

Protein and RNA synthesis in larvae of the yellow mealworm beetle (Tenebrio molitor) during cooling and cold acclimatization

Adult patients with symptoms of gastric disease were randomly assigned to two treatment groups (roxatidine group, n = 115; famotidine group, n = 113) or untreated control group (placebo, n = 111). The treatment groups randomly received 75 mg of roxatidine or 20 mg of famotidine at 9 pm, and 12 - 13 h later gastric juice secretion was measured with gastric X-ray films in both groups. Mean gastric juice secretion was significantly lower in the treated groups (roxatidine, 16.1 ml/12 h; famotidine, 19.9 ml/12 h) than in the untreated controls (placebo, 49.5 ml/12 h). Gastric juice suppression by roxatidine and by famotidine, respectively, was 82% and 37% in patients with gastric ulcer; 71% and 39% in patients with duodenal ulcer; 70% and 64% in patients with gastritis; and 68% and 86% in patients with no evidence of disease. It is concluded that roxatidine was more effective than famotidine for gastric juice suppression in patients with peptic ulcer. In patients with no evidence of gastric disease, however, famotidine was more effective than roxatidine.     

Catecholamine concentrations in biopsied gastroduodenal tissue specimens of patients with duodenal ulcer

We measured dopamine and norepinephrine concentrations in the biopsied gastroduodenal mucosa obtained from 12 ulcer-free dyspeptic patients, nine patients with active duodenal ulcer, and eight patients with inactive (or healed) duodenal ulcer using a high-performance liquid chromatography with electrochemical detection method. Biopsy specimens were taken from endoscopically normal-appearing mucosa in the gastric body and antrum as well as in the duodenal bulb. Additional specimens were obtained from the outer edge of the ulcer margin in patients with active duodenal ulcer. The mean (+/- SD) mucosal dopamine concentrations in the gastric body and duodenum (7.6 +/- 2.8 and 6.8 +/- 2.6 pg/mg tissue) obtained from patients with inactive duodenal ulcer were significantly (P < 0.05) lower than those from dyspeptic patients (13.6 +/- 6.9 and 10.9 +/- 3.5 pg/mg tissue, respectively). In contrast, no significant differences were observed in the mean norepinephrine concentrations in these gastroduodenal tissues among the three study groups. However, the mean mucosal norepinephrine concentration in the outer edge of duodenal ulcer (86.2 +/- 125.6 pg/mg tissue) was significantly (P < 0.05 and 0.01) reduced as compared with that in the ulcer-free area of duodenum obtained from patients with inactive duodenal ulcer (257.1 +/- 188.2 pg/mg tissue) and from dyspeptic patients (276.8 +/- 138.3 pg/mg tissue). The results suggest that an alteration in the catecholaminergic system may be associated with one of the pathogenic factors of duodenal ulcer.     

Helicobacter pylori eradication as a surrogate marker for the reduction of duodenal ulcer recurrence

OBJECTIVES: An abundance of data exists documenting the association of H. pylori eradication with the reduction in duodenal ulcer recurrence. AIM: To evaluate the validity of using H. pylori eradication as a surrogate marker for the reduction in duodenal ulcer recurrence using rigorously controlled studies. METHODS: Three controlled clinical trials were conducted in patients with uncomplicated, active duodenal ulcers. Patients were treated with various combinations of omeprazole and amoxycillin. Ulcer healing and H. pylori eradication were assessed. For patients whose duodenal ulcer healed, duodenal ulcer recurrence was determined over a 6-month period in patients with H. pylori eradication and those remaining positive for H. pylori at least 4 weeks after treatment. To support the data obtained from these clinical trials, a search of the medical literature was conducted to identify additional human clinical trials in which duodenal ulcer recurrence rates were measured and categorized by H. pylori status at least 1 month post-treatment. RESULTS: In 11 controlled trials, the overall 6-18-month duodenal ulcer recurrence rate was 54% among patients remaining positive for H. pylori at least 4 weeks after treatment compared to 6% among patients with H. pylori eradication following treatment. This finding was corroborated by the uncontrolled trials, in which the duodenal ulcer recurrence rate was 64% among patients found to be H. pylori-positive and 6% for patients found to be H. pylori-negative at least 4 weeks after treatment. A time course of duodenal ulcer recurrence rates using pooled data from both controlled and uncontrolled studies demonstrated that duodenal ulcer recurrence rates for H. pylori-negative patients persisted for up to 4 years following treatment. Duodenal ulcer recurrence rates for H. pylori-positive patients increased for the first year, then levelled off. A comparison of the duodenal ulcer recurrence rates for different treatment regimens revealed that eradication regimens based on omeprazole plus antibiotics and bismuth plus antibiotics exhibited similar duodenal ulcer recurrence rates for H. pylori-positive and -negative patients. CONCLUSION: Regardless of treatment regimens, H. pylori eradication produced a consistent and significant reduction in duodenal ulcer recurrence. Therefore H. pylori eradication, 4 weeks post-therapy, can be used as a surrogate marker for reduced duodenal ulcer recurrence in investigational clinical trials.     

Seminal vesicles are novel sites of luteinizing hormone/human chorionic gonadotropin-receptor gene expression

The effect of pentoxifylline (PTX) was tested for its capacity to modulate cytokine responses during therapy of severe Plasmodium falciparum malaria in a placebo-controlled, randomized study in 45 adult patients in Bangkok, Thailand. The patients received standard antimalarial treatment with artesunate (120 mg intravenously given immediately, then 60 mg every 12 hr for a total dose of 600 mg). The patients received either low-dose PTX (20 mg/kg/day, n = 15), high-dose PTX (40 mg/kg/day, n = 15), or placebo (n = 15) as continuous infusion for the first three days of antimalarial treatment. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were markedly elevated in all patients prior to treatment. After 6 hr of high-dose PTX treatment, TNF and IL-6 levels significantly decreased while an increase in TNF and IL-6 levels was seen after 6 hr of low-dose PTX or placebo treatment (P < 0.01). After 12 and 24 hr of high-dose PTX infusion, TNF-receptor plasma concentrations were lower than in low-dose PTX- or placebo-treated patients (P < 0.01), whereas no differences between the groups with regard to IL-6 receptor levels were observed. We conclude that 40 mg/kg/day of PTX reduces plasma levels of TNF, IL-6, and TNF-receptor in patients with severe malaria. Whether this reduction improves clinical outcome remains to be determined.     

Long-term treatment with lansoprazole for patients with Zollinger-Ellison syndrome

BACKGROUND: Normalization of gastric secretion and cure of associated upper gastrointestinal lesions by resection of gastrinoma is possible in approximately 20% of patients with Zollinger-Ellison syndrome, leaving approximately 80% dependent on medical treatment with proton pump inhibitors for acid suppression. METHODS: Lansoprazole was given for 3-48 months (median 28 months) to 26 Zollinger-Ellison syndrome patients with peptic ulcer manifestations in all and oesophagitis in 13. Starting with 60 mg/day. the dose was individualized to lower basal acid output to less than 5 mmol/h for those with intact stomachs and less than 1 mmol/h in those who had prior gastrectomy or with oesophagitis. The patients were studied every 3 months for 1 year and then every 6 months with gastric analysis (basal and maximal acid and pepsin output) and endoscopy with biopsy for enterochromaffin-like (ECL) cells. RESULTS: Lansoprazole inhibited basal acid output by 95%, pepsin output by 65% and remained effective at the initial mean (66 +/- 4.3 mg/day) or smaller doses (56 +/- 12 mg/day) at 48 months. Mucosal lesions healed and symptoms (ulcer-type pain, diarrhoea, heartburn, weight loss) resolved rapidly, usually within a few weeks. Serum gastrin and ECL cell populations, which were elevated before treatment, remained statistically unchanged but one of the three multiple endocrine neoplasia I (MEN-I) patients developed a small carcinoid. Of the three patients with metastatic gastrinoma at diagnosis one has died and one has progressed, while the third has had stable liver metastases for 26 years. Ulcer-type relapses occurred in three of the five post-gastrectomy patients, one with fatal jejunal ulcer perforation despite adequate acid suppression. No biochemical or clinical adverse events due to lansoprazole were encountered. CONCLUSION: Lansoprazole effectively inhibits acid and pepsin secretion in Zollinger-Ellison syndrome patients without any demonstrated side-effects. Despite strict acid control, post-gastrectomy Zollinger-Ellison syndrome patients were more liable to ulcer relapse, while oesophagitis was not a marker for therapeutic difficulty.