bluuebunny/crossref_metadata_2025_split huggingface dataset:
Six years of continuous cimetidine treatment in peptic ulcer disease: efficacy and safety
Authors: BARDHAN K. D. ,   FOR THE ANGLO‐IRISH CIMETIDINE LONG‐TERM STUDY GROUP
Published: July 2010

SUMMARYThe management of peptic ulcer disease with up to 6 years of continuous cimetidine treatment has been studied at four centres in the UK and Ireland. Cimetidine, 1 g daily for up to 12 weeks, was used to heal duodenal or gastric ulceration, alternating with 400 mg each night to maintain remission.After an initial healing phase, 402 patients started maintenance therapy. Classical life‐table analyses showed that after 5 years one‐quarter of the patients had suffered a symptomatic relapse, about half during the first year of maintenance treatment. Prevalence analyses (reflecting the cyclical nature of H2‐antagonist use in peptic ulcer disease) over 6 years show that, on average, over 97% remain free of symptomatic ulceration at any one time. Patients ‘lost’ to the study due to withdrawal or default may, however, bias the results. A model designed to account for these estimates that during the long‐term management of peptic ulcer with cimetidine, on average around 95% of patients remain free of symptomatic ulceration at any one time.Safety studies, including haematological and biochemical testing over the whole period, revealed no previously unknown adverse reaction. Seven patients were withdrawn for events considered to be related to the drug. Eleven patients died; none of the deaths appears to be connected with the treatment.It is concluded that long‐term use of cimetidine is effective in the management of peptic ulcer disease, and continuous treatment for up to 6 years has not revealed any previously unknown hazard.
The anti‐secretory effect and pharmacokinetics of omeprazole in chronic liver disease
Authors: McKEE R. F. , MacGILCHRIST A. J. , GARDEN O. J. , FORREST J. A. H. , CARTER D. C. 
Published: July 2010

SUMMARYThe anti‐secretory effects and pharmacokinetics of omeprazole were investigated in ten patients with chronic liver disease. Plasma omeprazole concentrations were measured after a 10‐mg intravenous dose of omeprazole and on the first and seventh days of a 7‐day course of 10 mg oral omeprazole daily. Pentagastrin tests were performed on the day before oral omeprazole was commenced and 24 h after the last oral dose.The pre‐treatment basal and peak gastric acid outputs were low (mean rates of 1.44 mmol/h and 9.26 mmol/h, respectively) and following 7 days of oral 10 mg omeprazole daily, were lowered by 95% and 90% respectively. Following 10 mg intravenous omeprazole, plasma clearance was reduced, and plasma half‐life and area under the concentration curve were increased, in comparison with previous studies in healthy subjects. The plasma concentration curves for oral and intravenous doses were very similar. After both the first and seventh oral doses, maximum plasma concentration and area under the curve were higher than in healthy subjects. No accumulation of omeprazole was demonstrated.The pharmacokinetics of omeprazole in chronic liver disease could be influenced by low gastric acidity, poor liver function and/or portasystemic shunting. A dose of 10 mg omeprazole daily has been shown to be an effective anti‐secretory agent in chronic liver disease.
The effects of omepmzole and cimetidine on duodenal ulcer healing and ihe relief of symptoms
Authors: DAHLGREN S. , DOMELLÖF L , HRADSKY M. , NORRYD C. , BRUNKWALL J. , SVENSSON G. , SVENSSON J.‐O. , KARLSSON J. , KNUTSON U. , GASSLANDER T. , LINDHAGEN J. , ARBMAN G. , JANSSON R. , SANDSTRÖM R. , HULDT B. , PETTERSSON B.‐G. , JANUNGER K.‐G. , SJÖLUND B. , HERNQVIST H. 
Published: July 2010

SUMMARYIn a Swedish double‐blind multicentre study, omeprazole (30 mg o.m.) was compared with the H2‐receptor antagonist cimetidine (400 mg b.d.) in 152 patients. Clinical assessments and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks in unhealed patients. Endoscopy was performed at 2 weeks, and again at 4 and 6 weeks in unhealed patients. The patients in the two groups were well‐matched prior to treatment.Omeprazole was superior to cimetidine in ulcer‐healing rate after 2, 4 and 6 weeks. After 2 weeks of treatment, 66% of the omeprazole‐ and 45 % of the cimetidine‐treated patients were healed (P= 0.02), after 4 weeks 97 and 84% (P= 0.01), and after 6 weeks 100 and 92% (P= 0.02), respectively.There was a more pronounced improvement in the patients' symptoms in the omeprazole group after 2 weeks (P= 0.05).Both drugs were well‐tolerated, but there was a high prevalence of patients with adverse events in the cimetidine group (51%, compared to 30% of the omeprazole group; P= 0.02).A total of 125 patients were followed for 6 months after healing. The patients were investigated by endoscopy after 6 months, or whenever symptoms occurred. There was no significant difference in the rate of relapse within 6 months between the two treatment groups: 54% relapsed in the omeprazole group and 52 % in the cimetidine group.In conclusion, 30 mg of omeprazole, given once daily, is superior to 400 mg of cimetidine twice daily in duodenal ulcer healing; but ulcer relapse in the two groups appears to be equivalent.
The benefit of pancreatic enzyme substitution after total gastrectomy
Authors: ARMBRECHT U. , LUNDELL L. , STOCKBRÜGGER R. W. 
Published: July 2010

SUMMARYThe aim of the present study was to evaluate the effect of the pancreatic enzyme preparation Kreon on abdominal symptoms, bowel habits, faecal fat excretion and oro‐caecal transit time in patients after total gastrectomy for carcinoma of the stomach with Roux‐en‐Y anastomosis. A hydrogen breath test was carried out in each patient to detect bacterial overgrowth.In a double‐blind crossover trial, 15 patients were treated with either Kreon or placebo (3.6 g/day) in two test‐periods each of seven days.During treatment with the active substance, the stool consistency became more solid (P < 0.05). The number of bowel movements and the abdominal symptoms, however, remained statistically unchanged.Treatment with Kreon did not influence the oro‐caecal transit time. Faecal fat excretion did not significantly decrease in the whole group of patients. However, in those patients with massive steatorrhoea (free and esterified fatty acids > 350 mmol/72 h; upper reference limit 60 mmol/72 h) a significant (P < 0.05) reduction from a median excretion of 643 mmol/72 h to 501 mmol/72 h was seen. Such a decrease in faecal fat excretion did not occur in patients with steatorrhoea below this limit. Bacterial overgrowth or rapid upper intestinal transit were not over‐represented in patients with a high‐degree of steatorrhoea.We conclude that after total gastrectomy pancreatic enzyme substitution reduces massive steatorrhoea and improves stool consistency.
Should we use non‐steroidal anti‐inflammatory drugs?
Authors: HASLOCK I. 
Published: July 2010

SUMMARYBoth the relative efficacy and inefficacy of non‐steroidal anti‐inflammatory drugs (NSAIDs) contribute to their use in chronic rheumatic diseases. There are also sociological trends in patients, and in the population as a whole, increasing demand for treatment. In view of the risks of such treatment, the most rational approach to prescribing would be the use of a scientific risk‐benefit analysis. Unfortunately, the data, especially those related to symptom relief, are inadequate for such an analysis. Until more meaningful figures are produced, good clinical practise concentrates on the responsibilities of physicians who both start and stop drugs, and makes it essential that strategies to minimize risk are produced.
The role of H2‐receptor antagonists in the prevention of NSAID‐induced gastrointestinal damage
Authors: RACHMILEWITZ D. 
Published: July 2010

SUMMARYNon‐steroidal anti‐inflammatory drugs (NSAIDs) induce gastric and duodenal damage in animals and humans. The possible protection afforded by cimetidine against acute and short‐term NSAID‐induced mucosal damage was evaluated in five studies. Cimetidine 200 mg once daily and 400 mg once daily was found to protect the gastric mucosa against damage induced by a single dose of aspirin 1300 mg; this protection was found to be independent of gastric acid secretion. Cimetidine 200 mg q.d.s. was found to protect the stomach and duodenum against damage induced by 14 days’treatment with aspirin 650 mg q.d.s. Duodenal and gastric damage induced during a 7‐day treatment period with naproxen 500 mg b.d. was prevented by cimetidine 400 mg b.d.; this dose of cimetidine also provided significant duodenal protection against damage induced by I week of therapy with indomethacin 50 mg t.d.s. There is no correlation between upper gastrointestinal symptoms, or between mucosal prostanoids, and the presence or absence of mucosal damage. Cimetidine is therefore effective in the prevention of mucosal damage induced by short‐term treatment with NSAIDs.
Treatment of NSAID‐induced gastrointestinal lesions with cimetidine: an international multicentre collaborative study
Authors: BIJLSMA J.W.J. 
Published: July 2010

SUMMARYThe efficacy of cimetidine 800 mg nocte in the treatment of erosions or ulcers induced by non‐steroidal anti‐inflammatory drugs (NSAIDs) was evaluated in an uncontrolled multicentre study of 187 patients requiring continuation of their NSAID therapy. After 4 weeks of treatment, endoscopic healing was achieved in 62 % of patients. After 8 weeks of therapy, 88% of patients were lesion‐free. Patients with ulcer had a healing rate of 49% at week 4, which increased to 81 % at the completion of 8 weeks. The majority of patients (82 %) with erosions healed in 4 weeks. By week 8, erosions were healed in 97 % of patients. Following endoscopically verified lesion healing, 113 patients entered a maintenance phase of the study, which assessed the efficacy of cimetidine 400 mg nocte in preventing recurrence of erosions or ulcers while continuing NSAID therapy. During a 6‐month observation period, the cumulative probability of endoscopically observed recurrence of lesions was 12 % (with a mean time to recurrence of 116 days), which is similar to the incidence of relapse achieved with cimetidine 400 mg nocte in patients with uncomplicated peptic ulcer. The results of this study suggest that cimetidine 800 mg nocte is effective in healing NSAlD‐induced lesions despite continued NSAID use, and that maintenance treatment with cimetidine 400 mg nocte can prevent lesions and reduce lesion recurrence during chronic NSAID administration.
Bismuth accumulates in the body during treatment with tripotassium dicitrato bismuthate
Authors: GAVEY C. J. , SZETO M.‐L. , NWOKOLO C. U. , SERCOMBE J. , POUNDER R. E. 
Published: July 2010

SUMMARYBismuth concentration was measured in plasma, dried leucocytes and urie in nine patients before, during and after treatment with tripotassium dicitrato bismuthate (De‐Noltab 2 b.d.) for 6 weeks. During treatment there was an 8.5‐fold rise in median plasma bismuth concentration (P < 0.01), a non‐significant doubling of leucocyte bismuth content, and a 349‐fold rise in 24‐h urinary bismuth excretion (P < 0.01). The significantly increased urinary bismuth excretion continued for at least 3 months after cessation of treatment with tripotassium dicitrato bismuthate, indicating accumulation of bismuth during treatment with this drug.
Effect of omeprazole on intragastric and duodenal bulb acidity in duodenal ulcer patients
Authors: BENDTSEN F. , OVESEN L. , ROSENKILDE‐GRAM B. , RUNE S. J. 
Published: July 2010

SUMMARYIntraluminal pH was measured simultaneously in the stomach and duodenal bulb with six small, glass electrodes tied together at 1.5‐cm intervals. Ten patients with duodenal ulcer disease were studied under fasting conditions and for 3 h after a standard liquid meal on three occasions: day 1, before treatment; day 8, when the proton pump blocker omeprazole had been taken in a daily dose of 30 mg for 7 days consecutively, including the day of the pH study; day 9, 24 h after the last dose of omeprazole. Mean hydrogen ion activity and the percentage of time with pH below 3 was calculated from the digital pH data sampled at a frequency of 1 per second from each electrode.On day 8, five of the patients were permanently anacidic (pH > 4) in the stomach and duodenum, while the food‐stimulation broke off anacidity for shorter periods in the other five patients. The pH pattern in the duodenal bulb was markedly altered in all patients with disappearance of the typical pH fluctuations, and a decrease in the time that the pH was below 3 from a median value of 30% before treatment to 0% in seven patients and close to 0% in three patients. On day 9, a large patient‐to‐patient variation was observed in gastric pH: three patients were still anacidic, four were markedly suppressed, but three patients reached near pre‐treatment acidity. Duodenal bulb acidity was still decreased significantly on day 9 in all patients, with post‐prandial pH below 3 for less than 5% of the time, compared with 30% before treatment.
Review article: dissolution of gallstones in the biliary tree
Authors: SUMMERFIELD J. A. 
Published: July 2010

SUMMARYThere are a variety of methods for dissolving gallstones in the biliary tree, which include oral therapy and direct contact dissolution. Cholesterol gallstones are most amenable to dissolution. Developments in non‐operative physical methods to remove gallstones (particularly endoscopic papillotomy and extracorporeal shock‐wave lithotripsy have diminished the use of chemical dissolution. However, in selected patients, there remains a place for chemical dissolution, but often in conjunction with the physical techniques.
Review article: mechanisms of drug release from tablets and capsules. I: Disintegration
Authors: MELIA C. D. , DAVIS S. S. 
Published: July 2010

SUMMARYVariable drug release from solid oral dosage forms has been an important cause of bioavailability problems in the past, and is a factor now carefully controlled in pharmaceutical products. In two reviews, we describe briefly the composition and manufacture of tablets and capsules, and the two main processes by which they release drugs; disintegration and dissolution. We will explain what is presently understood of the actual mechanisms of drug release and the physico‐chemical factors that affect the release process. The strategies adopted by pharmaceutical scientists in designing modern oral solid dose forms to release drugs at reproducible and therapeutically optimal rates will be discussed. Finally, the role of gamma scintigraphy in assessing dosage form performance in vivo will be described.
Effect of BMY‐25368, a potent and long‐acting histamine H2‐receptor antagonist, on gastric secretion and aspirin‐induced gastric lesions in the dog
Authors: CAVANAGH R. L. , BUYNISKI J. P. 
Published: July 2010

SUMMARYBMY‐25368, 1‐amino‐2‐[3‐(3‐piperidinomethylphenoxy) propylamino]‐1‐cyclobutene‐3,4‐dione, a new histamine H2‐receptor antagonist, has been compared to ranitidine as an inhibitor of gastric acid secretion in the Heidenhain pouch dog. Intravenous infusion of BMY‐25368 antagonized histamine‐stimulated gastric secretion in a competitive manner. BMY‐25368 also antagonized gastric secretion stimulated by pentagastrin, bethanechol and food. When compared to ranitidine in histamine‐stimulated dogs, BMY‐25368 was nine times more potent after bolus intravenous administration. Oral potency relative to ranitidine and ranged from 2.8 to 4.4, depending on the secretagogue used. BMY‐25368 also exhibited a significantly longer duration of action than ranitidine. Thus, its potency relative to ranitidine after oral administration, in histamine‐stimulated dogs, increased from 3.2 to 28 when determined 1–3 and 10–12 h post dose, respectively. BMY‐25368 administered orally also antagonized aspirin‐induced gastric lesions in the dog and was nine times more potent than ranitidine in this respect.
Octreotide (a somatostatin analogue) improves the quality of life in some patients with a short intestine
Authors: NIGHTINGALE J. M. D. , WALKER E. R. , BURNHAM W. R. , FARTHING M. J. G. , LENNARD‐JONES J. E. 
Published: July 2010

SUMMARYSix patients with short intestine (jejunal length 25–70 cm) on long‐term parenteral nutrition, needing 4–5 L of intravenous fluid daily, were given octreotide (a somatostatin analogue, SMS 201–995) to investigate whether it would reduce beneficially their secretory diarrhoea (3.6–6.9 kg/day). They consumed the same diet for 2 control days, followed by 2 test days. Octreotide was given intravenously, initially in a dose of 50 μg b.d. through the central feeding line. There was a significant reduction of daily stomal output (0.5–5.0 kg) and daily sodium and potassium output; however there was no significant change in energy absorption. The response to octreotide was greatest in those patients who absorbed least nutrients. A dose increase to 100 μg t.d.s. gave no further measurable benefit though the patients found it smoothed‐out the post‐prandial rise in stomal output. Two patients were continued on long‐term octreotide therapy, which allowed for a daily reduction in intravenous fluid of 1 and 1.5 L. Octreotide's anti‐secretory effect was found to have been maintained when it was retested in one patient after a year of continuous therapy.
The effect of tripotassium dicitrato bismuthate on pepsin activity
Authors: DE BEAUX A. C. , DEFIZE J. , HUNT R. H. 
Published: July 2010

SUMMARYWe have studied the effect of tripotassium dicitrato bismuthate on the peptic activity of gastric juice, both basal and pentagastrin‐stimulated, from five healthy volunteers using porcine pepsin solution as a control. Tripotassium dicitrato bismuthate showed no inhibition of the proteolytic activity of either the pure porcine or the human pepsin in the gastric juice. The ulcer healing efficacy of tripotassium dicitrato bismuthate is unlikely to be related to a gastric anti‐protease effect.
A comparison of metoclopramide and trimebutine on small bowel motility in humans
Authors: GRANDJOUAN S. , CHAUSSADE S. , COUTURIER D. , THIERMAN‐DUFFAUD D. , HENRY J. F. 
Published: July 2010

SUMMARYTrimebutine maleate and metoclopramide increase small bowel motility. The present manometric study of the human normal interdigestive duodeno‐jejunal motility demonstrated two different pharmacological effects in 15 healthy volunteers. Trimebutine constantly induced a premature phase 3 activity (0.81 ± 0.4 min after a 100‐mg intravenous injection) with patterns similar to spontaneous phase 3. Metoclopramide increased the motility index (contractile activity) during phase 2 without inducing a premature phase 3. No significant variations in plasma motilin concentration were noticed after either trimebutine or metoclopramide. The pancreatic polypeptide concentration rose significantly after metoclopramide injection.
A pilot study of thymus extract in chronic non‐A, non‐B hepatitis
Authors: CIVEIRA M. P. , CASTILLA A. , MORTE S. , SERRANO M. , PRIETO J. 
Published: July 2010

SUMMARYIn previous studies it has been suggested that activation of cellular immunity may have a role in controlling the activity of chronic non‐A, non‐B liver disease. We conducted a pilot study of therapy with a bovine thymus extract for 6 weeks in 15 consecutive patients with chronic non‐A, non‐B hepatitis, most of them sporadic cases. Treatment induced immunomodulation, and in five patients a significant but transient diminution in aminotransferase levels was observed associated with increments in several parameters of cellular immunity. This suggests that a longer administration of this or other related compounds, or treatment with a more potent immunomodulating agent, might be effective in these patients.
The effects of fasting on 24‐h gastric secretion of patients with duodenal ulcers resistant to ranitidine
Authors: JOHNSTON D. A. , WORMSLEY K. G. 
Published: July 2010

SUMMARYWe compared the effects of fasting and feeding on the antisecretory actions of ranitidine in 19 patients whose duodenal ulcers remained unhealed or relapsed despite treatment with the drug. Nine of the patients received, and continued with, 150 mg ranitidine b.d. and 10 took 300 mg ranitidine b.d. In all patients, gastric secretion was inhibited during the night, with near‐neutral pH and acid output less than an average of 2 mmol in 8 h. Gastric secretion was not inhibited during the day by either of the therapeutic regimens. However, on the day when the patients fasted, gastric acidity was, on average, 20–50 mmol/L less than on the day when food was consumed. Food‐induced interference with the therapeutic inhibition of gastric secretion produced by H2‐receptor antagonists may be responsible for the unsatisfactory clinical response of some patients with duodenal ulcers. Prolonged fasting can improve the control of gastric secretion and may allow resistant ulcers to heal.
Nature and time‐course of piroxicam‐induced injury to human gastric mucosa
Authors: FELLOWS I. W. , BHASKAR N. K. , HAWKEY C. J. 
Published: July 2010

SUMMARYThe nature and time‐course of acute piroxicam‐induced gastric mucosal injury was determined in ten healthy volunteers treated with 10 mg piroxicam twice daily by mouth for 21 days. Mucosal injury was measured endoscopically by visual analogue scales and by the method of Lanza, and luminal blood loss by haemoglobin measurements in gastric washings, 10 h after the first drug dose and then after 5, 10 and 21 days.Acute mucosal injury, consisting mainly of haemorrhagic lesions in the gastric body, developed to a maximum extent within 10 h of the first dose of piroxicam, and did not increase thereafter. By contrast intraluminal bleeding increased little for 10 days and then rose significantly at 21 days, when plasma piroxicam levels reached values likely to affect platelet function.We conclude that gastric mucosal injury and bleeding may be dissociated and may constitute different targets for prophylaxis. Gastric mucosal injury is probably exerted topically as it is maximal at low plasma drug concentrations, whereas bleeding may arise because of interference with platelet‐dependent mechanisms.
A comparison of low‐dose maintenance treatment with enprostil against ranitidine in the prevention of duodenal ulcer recurrence
Authors: BARDHAN K. D. , MORRIS P. , HINCHLIFFE R. F. C. , SAUNDERS J. H. B. , MACDOUGALL B. R. D. , BOLD J. M. , FREEMAN P. R. 
Published: July 2010

SUMMARYEnprostil, a prostaglandin E2 analogue, is effective in healing acute duodenal ulcer but its value in preventing recurrence, when given daily for maintenance therapy, is uncertain. In this three‐centre study we compared enprostil and ranitidine maintenance therapy; the latter is known to reduce duodenal ulcer relapse rates. Patients whose duodenal ulcers had been healed by treatment with an H2‐receptor antagonist were randomized to receive single‐blind treatment with either 35 μg enprostil (n = 64) or 150 mg ranitidine (n = 64) at bedtime for periods of up to 1 year. Endoscopy was routinely performed at 3 months at one centre, and at 6 and 12 months at all three centres, or whenever ulcer symptoms recurred. Clinical assessment and laboratory investigations were performed every 3 months. Relapse, defined as recurrent ulcer with or without pain, or erosions with pain, was significantly greater in patients on enprostil, the comparative rates at 3, 6 and 12 months were: enprostil 23, 31 and 36% ranitidine 6, 12 and 17% (P= 0.013; P= 0.03 and P= 0.03, respectively).