Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration.

A double blind trial was conducted in seven centres to evaluate the safety and efficacy of cimetidine 800 mg given at night compared with 400 mg given at breakfast and at bedtime. Altogether 197 patients with active duodenal ulcer confirmed by endoscopy entered the study, of whom 187 were eligible for analysis. After four weeks'' treatment the ulcer was healed in 76 of 91 patients (84%) receiving the once daily regimen and in 65 of the 96 patients (68%) receiving the twice daily regimen (p less than 0.05). Both dosage regimens were equally effective in reducing ulcer pain and consumption of antacids. Pain relief was considerable within the first two weeks, and most of the patients were free of symptoms by the end of treatment. No patients were withdrawn because of adverse events as these were few and mild, consistent with the proved safety profile of cimetidine. Cimetidine 800 mg given at night is as effective as 400 mg twice daily; the single dose regimen may improve patient compliance, thus facilitating treatment.     

Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study

Serum coenzyme Q10 (Q10) concentrations were evaluated in healthy male volunteers supplemented with 30 mg or 100 mg Q10 or placebo as a single daily dose for two months in a randomised, double-blind, placebo-controlled study. Median baseline serum Q10 concentration in 99 men was 1.26 mg/l (10%, 90% fractiles: 0.82, 1.83). Baseline serum Q10 concentration did not depend on age, while borderline significant positive associations were found for body weight and smoking 1-10 cigarettes/d. Supplementation with 30 mg or 100 mg Q10 resulted in median increases in serum Q10 concentration of 0.55 mg/l and 1.36 mg/l, respectively, compared with a median decrease of 0.23 mg/l with placebo. The changes in the Q10 groups were significantly different from that in the placebo group, and the increase in the 100 mg Q10 group was significantly greater than that in the 30 mg Q10 group. The change in serum Q10 concentration in the Q10 groups did not depend on baseline serum Q10 concentration, age, or body weight.     

Enprostil and ranitidine in prevention of duodenal ulcer relapse: one year double blind comparative trial.

One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non-recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence.     

Community clinics for leg ulcers and impact on healing.

OBJECTIVE--To evaluate the effectiveness of community clinics for leg ulcers. DESIGN--All patients with leg ulceration were invited to community clinics that offered treatment developed in a hospital research clinic. Patients without serious arterial disease (Doppler ankle/brachial index > 0.8) were treated with a high compression bandage of four layers. SETTING--Six community clinics held in health centres in Riverside District Health Authority supported by the Charing Cross vascular surgical service. PATIENTS--All patients referred to the community services with leg ulceration, irrespective of cause and duration of ulceration. MAIN OUTCOME MEASURES--Time to complete healing by the life table method. RESULTS--550 ulcerated legs were seen in 475 patients of mean (SD) age 73.8 (11.9) years. There were 477 venous ulcers of median size 4.2 cm2 (range 0.1-117 cm2), 128 being larger than 10 cm2. These ulcers had been present for a median of three months (range one week to 63 years) with 150 present for over one year. Four layer bandaging in the community clinics achieved complete healing in 318 (69%) venous ulcers by 12 weeks and 375 (83%) by 24 weeks. There were 56 patients with an ankle/brachial arterial pressure index < 0.8, indicating arterial disease. The 50 patients with pressure index < 0.8 > 0.5 were treated with reduced compression, and 24 (56%) healed by 12 weeks and 31 (75%) by 24 weeks. The figures for overall healing for all leg ulcers were 351/550 (67%) at 12 weeks and 417/550 (81%) at 24 weeks, compared with only 11/51 (22%) at 12 weeks before the community clinics were set up. CONCLUSIONS--Community clinics for venous ulcers offer an effective means of achieving healing in most patients with leg ulcers.     

Method of healing diabetic forefoot ulcers.

Six diabetic patients with neuropathic ulceration of the sole of the foot (seven feet, eight ulcers) were treated by the application of a below knee walking plaster with a rubber rocker. All the ulcers healed with this treatment, greatly reducing the usual period of hospital inpatient stay. After healing, study of the forces acting on the sole of the foot showed that these ulcers occur at the site of maximal horizontal shear force and confirmed that they occur at the site of maximal vertical force. This treatment is highly effective for neuropathic ulcers of the sole not affecting bone or complicated by deep sepsis. There may be a high rate of recurrence, however, reflecting inadequacy of methods of protecting damaged neuropathic feet.     

Two year Cottbus reinfarction study with 30 mg aspirin per day.

All 701 heart infarction patients admitted to 15 hospitals in the district of Cottbus between 1981 and 1983 were randomly administered 30, 60 or 1000 mg aspirin daily according to the territorial affiliation of their local hospitals. The physical and drug therapy during the 2 years follow-up was highly standardized; deviations--as far as they occurred--were documented. Lower all-cause mortality was statistically demonstrated in patients over 60 and a lower fatal reinfarction rate in patients over 50 as well as in men. Deaths and fatal reinfarctions were significantly lower among patients with a history of angina pectoris, marked ST-depression, with an infarction location except for the posterior wall and among hypercholesterolemic patients. The preventive effect of 60 mg aspirin daily was less than that of 30 mg in comparison to the 1000 mg group. Side effects were seen in 4 and 8% (first and second year), respectively, of the patients administered 30 mg aspirin as opposed to 22 and 17% in patients allocated 1000 mg. We conclude that the optimum dose of aspirin for preventing reinfarctions could be as low as 30 mg daily.     

Sustained compression and healing of chronic venous ulcers.

STUDY OBJECTIVE--Comparison of four layer bandage system with traditional adhesive plaster bandaging in terms of (a) compression achieved and (b) healing of venous ulcers. DESIGN--Part of larger randomised trial of five different dressings. SETTING--Outpatient venous ulcer clinic in university hospital. PATIENTS--(a) Pressure exerted by both bandage systems was measured in the same 20 patients. (b) Healing with the four layer bandage was assessed in 148 legs in 126 consecutive patients (mean age 71 (SE 2); range 30-96) with chronic venous ulcers that had resisted treatment with traditional bandaging for a mean of 27.2 (SE 8) months. INTERVENTIONS--(a) Four layer bandage system or traditional adhesive plaster bandaging for pressure studies; (b) four layer bandaging applied weekly for studies of healing. END POINTS--(a) Comparison of pressures achieved at the ankle for up to one week; (b) complete healing within 12 weeks. MEASUREMENTS AND MAIN RESULTS--(a) Four layer bandage produced higher initial pressures at the ankle of 42.5 (SE 1) mm Hg compared with 29.8 (1.8) for the adhesive plaster (p less than 0.001; 95% confidence interval 18.5 to 6.9). Pressure was maintained for one week with the four layer bandage but fell to 10.4 (3.5) mm Hg at 24 hours with adhesive plaster bandaging. (b) After weekly bandaging with the four layer bandage 110 of 48 venous ulcers had healed completely within 12 (mean 6.3 (0.4)) weeks. CONCLUSION--Sustained compression of over 40 mm Hg achieved with a multilayer bandage results in rapid healing of chronic venous ulcers that have failed to heal in many months of compression at lower pressures with more conventional bandages.     

Critical effect of Helicobacter pylori infection on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users

Background. The recently reported OMNIUM and ASTRONAUT NSAID ulcer prevention trials using omeprazole to prevent endoscopic ulcer recurrence among chronic NSAID users suggested superiority over misoprostol or ranitidine. Aim. To test the hypothesis the results from the OMNIUM and ASTRONAUT studies would not be generalizible as ulcer healing and ulcer recurrence would differ in relation to Helicobacter pylori status. Methods. The data regarding H. pylori status were made available by AstraZenca allowing separate analysis of the outcome of those with NASID ulcers (i.e. without H. pylori infection) and those NSAID use was complicated with the presence of an active H. pylori infection. Results. Reanalysis confirmed that omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, overall omeprazole was not significantly better than the subtherapeutic dose (400 µg/day) of misoprostol (14.5% vs. 19.6%, respectively, p = .93); 400 µg of misoprostol was actually superior to omeprazole for the prevention of gastric ulcers among those NSAID ulcers (8.2% vs. 16.6% for misoprostol and omeprazole, respectively; p < .05). Omeprazole was also not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Omeprazole was not significantly different from 300 mg of ranitidine for the prevention of NSAID gastric ulcers (14.6% vs. 11.6%, respectively, p = .56). Duodenal ulcers were over represented among H. pylori infected NSAID users and duodenal ulcer prevention was more sensitive to acid suppression than gastric ulcer. Conclusion. The OMNIUM and ASTRONAUT trials may have provided an unrealistic sense of security regarding the effectiveness of omeprazole for protection against ulcer recurrence in chronic NSAID users.     

Effects of melatonin and tryptophan on healing of gastric and duodenal ulcers with Helicobacter pylori infection in humans

Melatonin (MT) and its precursor L-tryptophan (TRP) are implicated in the protection of gastric mucosa against aspirin-induced lesions and in the acceleration of healing of idiopathic gastro-duodenal ulcers, but no information is available whether these agents are also effective in healing of gastroduodenal ulcers accompanied by Helicobacter pylori (H. pylori) infection. In this study three groups A, B and C, each including 7 H. pylori-positive patients with gastric ulcers and 7 H. pylori-positive patients with duodenal ulcers, aging 28-50 years, were randomly assigned for the treatment with omeprazole 20 mg twice daily combined with placebo (group A), MT administered in a dose of 5 mg twice daily (group B) or TRP applied in a dose of 250 mg twice daily (group C). All patients underwent routine endoscopy at day 0 during which the gastric mucosa was evaluated and gastric biopsies were taken for the presence of H. pylori and histopathological evaluation. The rate of ulcer healing was determined by gastroduodenoscopy at day 0, 7, 14 and 21 after the initiation of the therapy. Plasma MT, gastrin, ghrelin and leptin were measured by specific RIA. At day 21, all ulcers were healed in patients of groups B and C but only 3 out of 7 in group A of gastric ulcers and 3 out of 7 in duodenal ulcers. Initial plasma MT showed similar low levels in all three groups but it increased several folds above initial values in ulcer patients at day 7, 14 and 21. Plasma gastrin and leptin levels showed a significant rise over initial values in patients treated with omeprazole and placebo, MT or TRP while plasma ghrelin levels were not significantly affected by these treatments. We conclude that MT or TRP added to omeprazole treatment, significantly accelerates healing rate of H. pylori infected chronic gastroduodenal ulcers over that obtained with omeprazole alone and this likely depends upon the significant rise in plasma MT and possibly also in leptin levels, both hormones involved in the mechanism of gastroprotection and ulcer healing.     

Effect of daily oral omeprazole on 24 hour intragastric acidity.

Twenty four hour intragastric acidity was measured in nine patients with duodenal ulcer before and after one week of treatment with oral omeprazole 30 mg daily, a drug that inhibits gastric secretion by inhibition of parietal cell H+K+ adenosinetriphosphatase (ATPase). Omeprazole virtually eliminated intragastric acidity in all patients: the median 24 hour intragastric pH rose from 1.4 to 5.3 and the mean hourly hydrogen ion activity fell from 38.50 to 1.95 mmol(mEq)/1 (p less than 0.001). This inhibition of 24 hour intragastric acidity is more profound than that previously reported with either cimetidine 1 g daily or ranitidine 300 mg daily.     

A comparative study of nerve healing in adult, neonatal, and fetal rabbits.

This experiment quantitatively compared the human equivalent of a nerve repair following surgical division in the fetal, adult, and early childhood period of development using a rabbit as an experimental animal model. Twelve time-dated pregnant New Zealand White rabbits at 24 days' gestation (term = 31 days) underwent hysterotomy; one hind limb was delivered through the uterine opening. The sciatic nerve was divided and repaired by primary neurorrhaphy using two 11-0 epineural sutures. Sciatic nerve repair was also performed in 10 neonatal and 10 adult New Zealand White rabbits. Following repair, each group was assessed using electromyography examination, measuring distal motor latency and amplitude at 1, 2, 3, and 4 months postrepair. There was no difference in any of the groups in distal motor latency. The amplitude rose incrementally in all groups, and the fetal group had significantly higher amplitudes (p < 0.02) at 1, 2, 3, and 4 months in comparison with the adult group. There was no statistically significant difference between fetal and neonatal nerve repairs at any of the time periods. At the completion of the study, the nerve repair sites were harvested for histologic estimation of mean myelinated fiber density and fiber diameter distribution distal and proximal to the repair site. A greater percentage of myelinated axons crossed the repair site in the fetal group (83 percent) in comparison with the adult group (63 percent) (p < 0.03). Our study also demonstrated significant increases in the number of larger myelinated fibers crossing the repair site in comparison with the neonatal and adult groups (p < 0.04). This study found that fetal nerve healing following surgical repair is superior to that found in adult animals and results in a higher number of larger myelinated fibers crossing the repair site in comparison with adult and neonatal repairs.     

Omeprazole and cimetidine in the treatment of ulcers of the body of the stomach: a double blind comparative trial. Danish Omeprazole Study Group.

OBJECTIVE--To see whether omeprazole was superior to cimetidine in healing ulcers of the body of the stomach. DESIGN--Double blind randomised parallel group study of omeprazole versus cimetidine for six weeks with assessment of healing at end of every second week. SETTING--Outpatient referrals in 11 centres in Denmark. PATIENTS--One hundred sixty one patients who satisfied the following criteria: age 18-79; one or more ulcers of body of stomach (that is, at or above the angulus) seen endoscopically within four days before study treatment; no H2 receptor antagonists taken within previous two weeks; no history of gastric surgery and no complications needing surgery; no concurrent treatment or disease that might confound assessment; oral contraception or an intrauterine device being used by women of childbearing age. INTERVENTIONS--Omeprazole 30 mg daily (one capsule in the morning) or cimetidine 1 g daily (one 200 mg tablet thrice daily, two tablets at bedtime) for six weeks. Inactive capsules and tablets provided so that all patients took same number of capsules and tablets daily. Compliance monitored by pill counts. END POINT--Endoscopic evidence of accelerated healing of type I gastric ulcers after four weeks of omeprazole. MEASUREMENTS AND MAIN RESULTS--Pain recorded on diary cards and patients assessed after two, four, and six weeks of treatment for clinical state and by endoscopy and biopsy and repeat laboratory tests. Twenty eight patients withdrawn during trial for violations of protocol. At two weeks healing rates were identical in the two treatment groups (omeprazole 41% (30/73 patients); cimetidine 41% (30/73]. At four weeks cumulative healing rates were 77% (53/69 patients) in the omeprazole treatment group and 58% (41/71) in the cimetidine treatment group (95% confidence interval of difference between groups 4% to 34%). By six weeks the cumulative healing rates in the two treatment groups differed by only 6% (60/68 patients (88%) given omeprazole; 53/65 (82%) given cimetidine). Log rank analysis with ulcer size used as covariable showed a significant difference in healing times in favour of omeprazole. There was no difference in the occurrence of pain relief between the two treatment groups. No serious clinical or biochemical side effects of treatment were noted. CONCLUSIONS--Omeprazole 30 mg daily accelerates healing of ulcers in the body of the stomach as compared with cimetidine 1 g daily. This effect is more pronounced in ulcers greater than 12 mm diameter.