bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of a long‐acting somatostatin analogue on portal and systemic haemodynamics in cirrhosis
Authors: PRINGLE S. D. , McKEE R. F. , GARDEN O. J. , LORIMER A. R. , CARTER D. C. 
Published: July 2010

SUMMARYCurrent interest in the pharmacological manipulation of portal pressure centres on the long‐acting somatostatin analogue SMS 201‐995. Nine haemodynamically stable cirrhotic patients who had previously bled from oesophageal varices had wedged and free hepatic venous pressures and cardiac index measured, using a Swan—Ganz catheter, before and at 60, 120 and 180 min after beginning a 60‐min infusion of 25 μg/h of SMS 201‐995. Seven clinically similar patients had the same measurements performed without SMS 201‐995. In all patients cardiac index was found to decrease and systemic vascular resistance increase at 60 min, although heart rates and arterial blood pressures were unchanged. The group given SMS 201‐995 was significantly different from the control group in sustaining a fall in wedged hepatic venous pressure and trans‐hepatic venous gradient at 60 min. SMS 201‐995 causes a fall in portal pressure without a significant systemic haemodynamic effect.
A double‐blind placebo‐controlled trial of BRL 24924 on lower oesophageal sphincter pressure and gastro‐oesophageal reflux in healthy volunteers
Authors: ROBERTSON C. S. , EVANS D. F. , HICKS F. , ATKINSON M. 
Published: July 2010

SUMMARYBRL 24924 is a new gastrointestinal prokinetic agent with properties similar to metoclopramide but with increased potency and devoid of side‐effects associated with blockade of dopamine receptors in the central nervous system. A double‐blind placebo‐controlled trial of the effect of a single oral dose of 2.2 mg BRL 24924 on lower oesophageal sphincter pressure and gastro‐oesophageal reflux has been performed in 20 healthy volunteers. BRL 24924 significantly increased mean lower oesophageal sphincter pressure (21.9 cmH2O BRL; 15.9 cmH2O placebo: P < 0.017) but failed to alter either the frequency or the duration of gastrooesophageal reflux after provocation following a test meal. BRL 24924 has significant effects on lower oesophageal sphincter pressure but no effect on provoked post‐prandial reflux in healthy volunteers. Further studies in patients with gastro‐oesophageal reflux and oesophagitis are needed to evaluate the clinical efficacy of this compound.
A comparative study of the effects on colon function caused by feeding ispaghula husk and polydextrose
Authors: TOMLIN J. , READ N. W. 
Published: July 2010

SUMMARYPolydextrose is a new soluble food ingredient which cannot be digested by intestinal enzymes and so may affect colonic function. Studies in healthy volunteers compared the effects of diet supplementation with 30 g/day polydextrose, a standard dose of 7 g/day ispaghula and two mixtures containing 2 g/day ispaghula with either 30 g/day polydextrose or 10 g/day polydextrose with a control period. During the 10‐day periods, the mass, frequency and consistency of faeces were assessed as well as the whole‐gut transit time, ease of defaecation, flatulence and palatability of the preparations.All preparations significantly increased the weekly faecal mass above control values (P < 0.05) but there were no significant differences between the preparations. Transit time and stool frequency were not affected significantly by any of the preparations (P > 0.05). Both preparations supplying 30 g/day polydextrose softened stool consistency equally but the other preparations had no effect. All preparations caused flatulence and other gas‐related problems but polydextrose caused more than ispaghula, even at the lowest dose of 10 g/day. More volunteers preferred taking the polydextrose drinks than the sachets of ispaghula which formed a viscous drink with water.Despite superior palatability and equally effective stool bulking, polydextrose is unlikely to be an alternative laxative to ispaghula because of the unacceptable levels of flatulence.
The effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of metoprolol
Authors: CHELLINGSWORTH M. C. , LAUGHER S. , AKHLAGHI S. , JACK D. B. , KENDALL M. J. 
Published: July 2010

SUMMARYThe impact of cimetidine, ranitidine and placebo on the pharmacokinetics of metoprolol, given either as a single dose (100 mg) or for 7 days (100 mg b.d.), has been evaluated in two separate studies. The doses used were 800 mg cimetidine daily and 300 mg ranitidine daily. The subjects were all young, healthy volunteers. In the single dose study, cimetidine produced a marked increase in the peak plasma concentration of metoprolol and in the area under the plasma concentration‐time curve; ranitidine had less effect, though the area under the curve was significantly greater than placebo. In the chronic dosing study, the area under the curve for metoprolol was also significantly higher on cimetidine (1796 ng h/ml;P< 0.001) whereas the area under the curve on ranitidine (1258 ng h/ml) was comparable to that on placebo (1183 ng h/ml). Despite these drug‐induced changes in plasma metoprolol concentration, neither cimetidine nor ranitidine altered the change in exercise‐induced heart rate during dosing with metoprolol.
Epidemiology of NSAID‐induced gastrointestinal problems and the role of cimetidine in their prevention
Authors: GIERCKSKY K‐E. , HUSBY G. , RUGSTAD H. E. , REVHAUG A. 
Published: July 2010

SUMMARYIt is difficult to ascertain the incidence of gastrointestinal side‐effects associated with intake of non‐steroidal anti‐inflammatory drugs (NSAIDs). In retrospective studies, some NSAIDs have been reported to be associated with a higher incidence of gastrointestinal side‐effects than others. However, this has not been verified either in a prospective casereview study or in a large double‐blind study. Serious side‐effects, such as bleeding, perforation and heart failure, occur in approximately 1 % of patients using NSAIDs. One‐third of all patients receiving NSAIDs will have gastrointestinal complaints. Since at least 10% of patients terminate treatment with NSAIDs as a result of side‐effects, even reduction of those that are not life‐threatening would be of great benefit. H2‐receptor antagonists have proved effective in ulcer treatment, and their use as prophylaxis against the side‐effects of NSAIDs is being widely studied. In a recent study, 63 patients who had experienced serious upper gastrointestinal side‐effects were given cimetidine while continuing their NSAID therapy. All but 4 of the 47 who had gastric or duodenal ulcer on first admission were healed at 8 weeks, and none of the remaining 16 with diffuse bleeding gastritis experienced further clinical episodes of bleeding or ulcer‐related dyspepsia.
Mechanisms of NSAID‐induced gastrointestinal mucosal injury: a basis for preventing ulceration and symptoms from these agents
Authors: RAINSFORD K. D. 
Published: July 2010

SUMMARYConcepts are reviewed of the effects of anti‐ulcer agents in counteracting the biochemical and cellular pathology of gastrointestinal injury by non‐steroidal anti‐inflammatory drugs (NSAIDs). While some measure of control of NSAID‐induced mucosal damage is achieved in the upper gastrointestinal tract by the currently available anti‐ulcer drugs, none can effectively counteract the major biochemical changes induced by NSAIDs. Some experimental approaches, which have been developed from recent studies in laboratory animals, are considered as a possible basis towards developing improvements in preventive procedures against NSAID‐induced gastrointestinal injury in man.
Non‐steroidal anti‐inflammatory drugs and the gastric mucosa: mechanisms of damage and protection
Authors: HAWKEY C.J. 
Published: July 2010

SUMMARYProstaglandins have numerous mucosal protective properties, impairment of which contribute to NSAID injury. It is not clear which is the most important injurious factor affecting patients taking NSAIDs. Is it the NSAID itself, either by topical toxidty and/or production of toxic mediators or does the patient become more sensitive to NSAIDs as a result of some other luminal component, such as acid or bile acids, food (by physical or chemical mechanisms) or accompanying alcohol? Intrinsic irritancy/toxicity probably accounts for the greater mucosal toxicity of aspirin, although it is not clear whether this is due to a direct (non‐prostaglandin‐dependent) effect on mucus or bicarbonate secretion, membrane integrity, interference with intermediary metabolism or the production of toxic products. Similarly, the relationship of irritancy to the symptom of dyspepsia, to which patients on aspirin are prone, is as yet not well understood. While strategies for short‐term protection of experimental animals and humans are well established, protection against important, but relatively rare clinical events, is more difficult to study and much less well understood. In particular, the importance of the ability of NSAIDs to exacerbate bleeding, independent of injury, has been largely neglected in the context of presentation with haematemesis and melaena.
NSAIDs: a clinical approach to the problems of gastrointestinal side‐effects
Authors: BUTT J. H. , BARTHEL J. S. , HOSOKAWA M. C. , MOORE R. A. 
Published: July 2010

SUMMARYDespite the fact that non‐steroidal anti‐inflammatory drugs (NSAIDs) are among the most widely used drugs in medicine today, 2–10% of patients must discontinue their use primarily due to gastrointestinal (GI) side‐effects. While the development of non‐aspirin NSAIDs (NA‐NSAIDs) has significantly reduced GI side‐effects, major problems persist. A practical clinical approach to these problems includes informing the patient about the risks and benefits of NSAIDs, risk management during treatment with NSAIDs and investigation of symptomatic side‐effects during treatment. Prophylaxis of GI side‐effects is feasible in selected populations, but it has not been studied widely and may not be cost‐effective. At present, costs of prophylaxis in all but selected populations with multiple risks probably outweigh the benefits.
Review article: the management of hepatitis A, B, D and non‐A non‐B
Authors: DUSHEIKO G. M. 
Published: July 2010

SUMMARYThis paper reviews the modern management of viral hepatitis: hepatitis A, hepatitis B, hepatitis D and non‐A non‐B hepatitis. It describes the treatment of uncomplicated acute viral hepatitis, complicated acute viral hepatitis, and chronic viral hepatitis. The roles for corticosteroids, synthetic nucleotides, and interferons are reviewed. Finally, passive and active immunization against viral hepatitis are discussed.
Determining the optimal dosage regimen for H2‐receptor antagonist therapy—a dose validation approach
Authors: YOUNG M. D. , FRANK W. O. , DICKSON B. D. , PEACE K. P. , BRAVERMAN A. , MOUNCE W. 
Published: July 2010

SUMMARYA large number of clinical studies have been performed to establish the safety and efficacy of H2‐receptor antagonist therapy. Few if any of these studies have attempted to address the rationale for the dosage and/or dosage regimens being studied. This study is the first large‐scale clinical trial, the purpose of which is to validate the chosen regimen and to address the issue of an optimal therapy for a specific patient population. A regimen of a single nightly dosage is generally acknowledged to offer the potential for improved patient compliance. Furthermore, recent research had suggested that suppression of nocturnal acid secretion is all that is required to heal duodenal ulcers. Hence such a regimen offered the potential for an effective lowered dosage of cimetidine with minimal interference with gastric physiology, increased safety and substantial efficacy. This multicentre, double‐blind, placebo‐controlled trial therefore evaluated a 4‐week course of single night‐time dosage of cimetidine. After 4 weeks of treatment the cumulative, endoscopically proven, ulcer healing rate with an 800 mg regimen was 73%, which was statistically higher and significantly superior to the 41% healing seen with placebo (P < 0.001). The 400 mg nocte dosage regimen of cimetidine normally used as maintenance therapy was significantly inferior to the 800 mg nocte regimen (P = 0.01), and increasing the dosage to 1600 mg nocte for 4 weeks failed to provide a significant improvement in healing over the 800 mg nocte regimen. This 800 mg nocte regimen provided rapid pain relief, with 75 YO of the patients being free of night‐time pain and 65% free of day‐time pain, by the end of the first week. The 400 mg ‘maintenance dosage’ was unable to provide this degree of rapid, complete and early relief to patients with a duodenal ulcer. Furthermore, increasing the dosage to 1600 mg nocte failed to increase the level of early pain relief significantly, perhaps because the extensive response of duodenal ulcer patients to the 800 mg nocte regimen leaves little room for improvement. Based both on the early symptom relief and the ulcer healing rate during 4 weeks of treatment, it is concluded that an 800 mg night‐time dosage of cimetidine may be an optimal regimen for many duodenal ulcer patients, particularly those who in the physician's opinion will benefit from a once‐daily regimen.
Cyclosporin for the treatment of severe inflammatory bowel disease
Authors: BAKER K. , JEWELL D. P. 
Published: July 2010

SUMMARYA pilot study was performed to assess the role of cyclosporin in the management of severe inflammatory bowel disease. Twelve patients with Crohn's disease and 12 with ulcerative colitis were admitted to hospital with a severe attack. They were treated with an intravenous regimen of corticosteroids for 5 days followed by oral therapy. In addition, they received a 6‐week course of oral cyclosporin, initially 15 mg kg−1 day−1 reduced to 7.5 mg kg−1 day−1. In comparison with historical controls, the addition of cyclosporin to standard corticosteroid therapy appeared to have no benefit. Adverse effects were common but minor. The expression of Class II molecules on the inflamed epithelium was rapidly reversed by cyclosporin therapy which may indicate a potential therapeutic benefit over longer periods of time.
Comparative efficacy of coated, oral 5‐aminosalicylic acid (Claversal*) and sulphasalazine for maintaining remission of ulcerative colitis
Authors: RUTGEERTS P. 
Published: July 2010

SUMMARYThe safety and efficacy of Claversal (coated, oral 5‐aminosalicylic acid (5‐ASA) 0.75 g/day) and sulphasalazine 1.5–2.0 g/day were compared for the maintenance treatment of ulcerative colitis in a 1‐year double‐blind trial. Three hundred and thirty‐four patients, whose disease was controlled on a stable dose of sulphasalazine (1.5–2.0 g/day) for a 1‐month pre‐trial, entered the study. On entry, patients were assigned in a random manner to continue sulphasalazine or to switch to coated 5‐ASA. One hundred and thirty‐one patients in the coated 5‐ASA group and 142 on sulphasalazine were analysed for efficacy.No significant difference was observed between treatments with respect to the cumulative rate of relapse. Over the 12 months, 30 (28%) of the coated 5‐ASA patients versus 29 (23%) of those treated with sulphasalazine had an exacerbation of their disease (log rank testP= 0.7011).The incidence of drug‐related adverse events and subsequent withdrawals was similar. The high incidence of side‐effects usually associated with sulphasalazine was not observed, probably due to the fact that this population was tolerant of sulphasalazine pre‐trial. Of the 37 patients who reported adverse events with previous sulphasalazine therapy, however, only two (8%)of the 24 experienced those events when randomized to coated 5‐ASA while five (38%) of the 13 who continued on sulphasalazine reported those same events. Coated 5‐ASA is a safe, effective therapy for maintaining ulcerative colitis in remission.
The trophic effects of gastrin on fundic neuroendocrine cells of the rat stomach
Authors: EASON C. T. , SPENCER A. J. , PATTISON A. , BONNER F. W. 
Published: July 2010

SUMMARYThe histomorphological effect of multidose administration of 6 mg/kg pentagastrin b.d. for 5 weeks, and 1000 mg/kg sodium bicarbonate b.d. for 13 weeks, on the rat fundic mucosa has been examined. Sodium bicarbonate induced a significant hypergastrinaemia (plasma gastrin concentrations were 370.5 pg/ml in the control versus 642.6 pg/ml in sodium bicarbonate‐treated rats after 13 weeks, P < 0.01). Both treatment regimens induced fundic neuroendocrine cell hyperplasia. The cellular proliferation that occurred following hypergastrinaemia of endogenous or exogenous origin suggests that systemic gastrin concentrations play a major role in the control of fundic neuroendocrine cell populations.
Twenty‐four‐hour intragastric acidity in duodenal ulcer patients during dosing with placebo, and 150 mg ranitidine twice or four times daily
Authors: HOWDEN C. W. , TSAI H. H. , REID J. L. 
Published: July 2010

SUMMARYTwenty‐four‐hour intragastric acidity was measured in 10 patients with past history of duodenal ulcer on the fourth day of dosing with placebo, and either 150 mg ranitidine given twice or four times daily. The order the treatments was randomized and a double‐blind design was employed. Ranitidine (150 mg) b.d. decreased median integrated 24‐h intragastric acidity by 65.1%, nocturnal acidity by 89.1%, and daytime acidity by 54.6% (all P < 0.01 compared to placebo). The corresponding decreases with 150 mg ranitidine q.d.s. were 62.3, 89.9 and 48.8%, respectively (all P < 0.01 compared to placebo). There were no significant differences between the two dosage regimens of ranitidine (P > 0.05).This study shows that giving extra doses of 150 mg ranitidine during the day does not increase the degree of suppression of intragastric acidity.
Acute treatment of reflux oesophagitis: a multicentre trial to compare 150 mg ranitidine b.d. with 300 mg ranitidine q.d.s.
Authors: JOHNSON N. J. , BOYD E. J. S. , MILLS J. G. , WOOD J. R. 
Published: July 2010

SUMMARYH2‐receptor antagonists administered in conventional dosage regimens fail to heal a significant proportion of patients with moderate or severe reflux oesophagitis. We have compared the effects of a higher dose of ranitidine (300 mg q.d.s.) with the currently recommended dosage regimen (150 mg b.d.) in 138 patients suffering from reflux oesophagitis. After 4 weeks of treatment 29% of patients who received 150 mg ranitidine b.d., and 63% of patients who received 300 mg ranitidine q.d.s. had complete endoscopic healing of their lesions (P < 0.0001). After 8 weeks these proportions had increased to 54% and 75%, respectively (P < 0.01). After 4 weeks of treatment, compete symptomatic relief had been achieved in 46% of patients who received 150 mg ranitidine b.d and in 67% of patients who received 300 mg ranitidine q.d.s. (P < 0.05). After 8 weeks these proportions were 64% and 84%, respectively (P < 0.05). Both dosage schedules were well‐tolerated. We conclude that more rapid symptom relief and healing in reflux oesophagitis can be achieved with 300 mg ranitidine q.d.s. than with 150 mg ranitidine b.d.
Pharmacokinetics of a 5‐aminosalicylic acid enteric‐coated tablet and suppository dosage form
Authors: NORLANDER B. , GOTTHARD R. , STRÖM M. 
Published: July 2010

SUMMARYAn Eudragit‐L coated oral 5‐aminosalicylic acid (5‐ASA; mesalazine) product (Mesasal), has been formulated to deliver 5‐ASA to the distal small intestine and colon for the treatment of inflammatory bowel disease. The purpose of this study was to compare the pharmacokinetic profile of this product to sulphasalazine (SASP; Salazopyrin) and to assess the pharmacokinetics of a suppository 5‐ASA dosage form.Twelve healthy volunteers randomly received four single doses of 5‐ASA delivering formulations not less than 1 week apart. (a) Mesasal tablets, 2 × 250 mg, fasting; (b) Mesasal tablets, 2 × 250 mg, fed; (c) Salazopyrin tablets, 3 × 500 mg (corresponding to 576 mg 5‐ASA), fasting; and (d) Mesasal suppository, 1 × 500 mg, fasting. Plasma 5‐ASA and acetyl‐5‐ASA (Ac‐5‐ASA) concentrations were followed for 48 h and urine and faecal concentrations for 72 h.Mesasal tablets (fasting) produced a greater area under the concentration–time curve (AUC), peak and time to peak for both plasma 5‐ASA and Ac‐5‐ASA than Salazopyrin. Median urinary recovery values were 21.7% for Salazopyrin and 35.5% for Mesasal (fasting) (P < 0.01). This means that the systemic absorption was higher after Mesasal than after Salazopyrin. The total faecal recovery values were 38.3 and 26.5%, respectively (NS). Except for a delay of 1.5–3 h in the time to peak of 5‐ASA and Ac‐5‐ASA plasma levels, the pharmacokinetics of Mesasal tablets were essentially the same in fasting or fed subjects. Suppository administration of 5‐ASA resulted in a low median urinary recovery of 10.8%.
Geographical differences of gastric ulcer healing rate in patients treated with ranitidine or placebo
Authors: DIXON J. S. , WORTHINGTON P. R. , MILLS J. G. , WOOD J. R. 
Published: July 2010

SUMMARYThe literature was searched for clinical trials evaluating the use of 300 mg ranitidine daily in the acute treatment of gastric ulcer. All available trials were examined, and the results compared between countries to determine the extent of any geographical variation in ulcer healing rates. Published placebo studies in gastric ulcer were also reviewed for comparison. Sixty‐six publications were inspected to determine the trial design, country of origin, gastric ulcer healing rates, determined endoscopically, and details of patient demography.Overall worldwide healing rates for ranitidine treatment were 63% at week 4 and 86% at week 8 (n= 2349 and 2256 respectively), compared with 34% at week 4 and 52% at week 8 for placebo (n= 790 and 231 respectively). Statistically significant differences were found between the healing rates for individual countries at week 4 (P < 0.001) and week 8 (P < 0.001). However, after exclusion of the results from Japan (35%, n= 278) and Yugoslavia (97%, n= 32) at week 4, and from Japan (80%, n= 467) and France (65%, n= 52) at week 8, the healing rates from the remaining countries were not statistically different from one another. The limited data available in relation to age, sex and smoking habits, or placebo healing rates contributed little to explaining these aberrant results.It is concluded that there is variation in gastric ulcer healing rates between countries, but only results from Japan seem to be out of line with the rest of the world.
Does misoprostol given as a single large dose improve its antisecretory effect?
Authors: CHIVERTON S. G. , BURGET D. W. , SALENA B. J. , HUNT R. H. 
Published: July 2010

SUMMARYH2‐receptor antagonists have been shown to be effective in the suppression of nocturnal acidity. This double‐blind, randomized, crossover Latin‐square study of 24‐h intragastric pH in 12 normal volunteers investigated the effect of large single‐dose administration of misoprostol on intragastric acidity. Efficacy of 800 μg misoprostol h.s., 600 μg h.s., 400 μg h.s. and 800 μg after supper was compared to placebo and 200 μg misoprostol q.d.s. Twenty‐four hour mean pH ± s.d. was placebo 2.1 ± 0.3, misoprostol 200 μg q.d.s. Twenty‐four hour mean pH ± s.d. was placebo 2.1 ± 0.3, misoprostol 200 μg q.d.s. 2.2 ± 0.3, 800 μg p.m. 2.6 ± 1.1, 400 μg h.s. 2.6 ± 0.7, 600 μg h.s. 2.6 ± 0.4, 800 μg h.s. 2.6 ± 0.5. The effect of misoprostol on gastric acidity was short and limited to the nocturnal period. Only misoprostol 800 μg and 600 μg reduced 24‐h acidity compared to placebo (P < 0.04).