摘要:

SUMMARYRationalization within the pharmaceutical industry to combat escalating costs has included the close examination of research portfolios. Gastroenterology has been one of the casualties of this exercise and few companies currently retain a specific gastrointestinal research programme.Acid‐peptic disease has been the victim of its own success, since the availability of a range of extremely effective drugs largely satisfies current medical needs. A safe, convenient and effective monotherapy able to eradicateHelicobacter pyloriwould be a commercially viable alternative to antisecretory drugs, leading to further expansion of the anti‐ulcer market. The irritable bowel syndrome is probably too diverse a target for logical research; inflammatory bowel disease is probably too small a market to be attractive.Potentially effective drugs to treat these and other gastrointestinal diseases could emerge from broader research programmes, provided that companies retain the expertise and desire to develop such agents for gastrointestinal indications. Cancer of the gastrointestinal tract and associated organs undoubtedly represents a commercially attractive target, but new anti‐tumour drugs are more likely to arise from generic research rather than programmes specifically directed at tumours of the gastrointestinal tract.The changing view of the pharmaceutical industry towards the development of gastrointestinal drugs is likely to have a negative impact on both fundamental and clinical research in gastroenter

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00407.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYInflammatory bowel disease is associated with an increased risk of gastrointestinal malignancy. There has been concern that either diagnostic medical radiation and long‐term drug therapy—particularly immunosuppression—might contribute to this increased cancer risk.For the major drug groups (5‐aminosalicylates, steroids and immunosuppressants) data are scant but broadly reassuring. Only azathioprine (including 6‐mercaptopurine) has been investigated at all carefully. Short‐ to medium‐term therapy probably poses a very slightly increased risk of malignancy which is easily accepted given the current limitation of this agent to second‐line use. Continuous therapy for more than two years is much less well documented, and caution should be maintained.A hypothetical model based on data from occupational radiation exposure has been constructed; this permits reasonable confidence that the medical use of ionising radiation contributes a negligibly increased risk of malignancy overall, and is particularly unlikely to add significantly to the incidence of gastrointest

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00408.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYMalnutrition is common and undiagnosed in the majority of affected hospital patients; it is associated with impaired organ function, morbidity, and increased length of hospital stay. Artifical nutritional support in malnourished patients leads to improvement in nutritional status and clinical outcome.Nutritional support is required in malnourished patients, patients who are unable to take normal diet and patients with intestinal failure. Gastroenterologists are required to supervise patients with intestinal failure, to insert endoscopic feeding devices, and increasingly to participate in, or lead, nutritional support teams.Major developments in nutrient delivery have included percutaneous endoscopic feeding devices, the recognition that enteral feeding is possible in patients with gastric stasis, and that nutrient needs can be met by peripheral parenteral nutrition. There is much interest in the use of new substrates, or substrates delivered in pharmacological doses such as glutamine and arginine, to manipulate the response to disease.Many hospitals lack an organized approach to artificial nutritional support. Patients continue to suffer from a lack of treatment or the consequences of inappropriate or inadequate treatment. This article reviews the current status of artificial nutritional support and provides guidelines for patient managment.

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00409.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: Helicobacter pylorieradication for peptic ulcer has been widely taken up. Evidence for the efficacy of different regimens is often derived from small series in clinical trials but there is little reporting of everyday practice with unselected patients. Freedom from ulcer relapse has been demonstrated, but not whether this equates with clinical success.Methods: We report on a series of 706 patients withH. pyloriinfection who, between January 1991 and April 1995, received eradication therapy followed by assessment of H. pylori status. Two‐hundred and seven of these patients were followed‐up by postal questionnaire, validated by parallel questionnaires to their general practitioners, covering clinical outcome measures.Results: The overall eradication rate was 81.7%, and a 1‐week course of omeprazole plus two antibiotics was significantly better than a 2‐week course of standard triple therapy (85.0% vs. 78.0%,P<0.05). Amongst 21 first‐time failures, a 7‐day course of a clarithromycin‐containing triple therapy succeeded in 18. The questionnaire replies indicate that, following successfulH. pylorieradication, ulcer patients are less likely to consult with ulcer symptoms (P<0.0005), take medication (P<0.0005), require further prescription (P<0.0005), or lose work‐time because of their ulcer (P<0.005). They are more likely to have a subjective sense of ulcer cure (P<0.0005).Conclusions: In addition to clear cost savings, social benefits are now demonstrated whenH. pyloriis eradicated. A well‐tolerated 1 week regimen is genuinely effective in

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00410.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYAims and Methods: To determine the effect of aminosalicylic acid derivatives on the concentration of nitric oxide produced in a cell‐free system, by the use of a sensitive and specific polarographic meter.Results: The aminosalicylic acid derivatives 3‐ASA (IC50100 μm), 4‐ASA (IC50350 μm) and 5‐ASA (IC505 μm) all decreased the nitric oxide signal. These drugs had a similar inhibitory effect on the formationin vitroof nitrite from sodium nitroprusside (IC50200 μm, 500 μmand 100 μm, respectively). Sulphasalazine (31.1 ± 5% decrease in signal at 1 mm) was less effective than 5‐ASA, but sulphapyridine, N‐acetyl 5‐ASA, indomethacin and hydrocortisone produced no decrease in nitric oxide signal at all.Conclusions: Nitric oxide binding may be part of the mechanism by which ASA derivatives exert their therapeutic effect, and this work suggests that it may be an important factor in the pathogenesis o

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00411.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: Ranitidine bismuth citrate (GR122311X) is a new drug which offers potential benefits in healing duodenal ulcers and prevention of relapse.Methods: This randomized, multi‐centre double‐blind study of 1620 patients compared the effect of 4 weeks of treatment with GR122311X 200 mg b.d. (n= 401), 400 mg b.d. (n= 404) or 800 mg b.d. (n= 404) or ranitidine hydrochloride 150 mg b.d. (n= 411) on the rates of duodenal ulcer healing and of overall success (ulcers healed and remaining ulcer free in the 24‐week follow‐up phase).Results: All four treatments were equally effective at ulcer healing (79%, 85%, 84% and 81% of patients, respectively). GR122311X 400 mg b.d. (38%) and 800 mg b.d. (37%) were significantly more effective than ranitidine hydrochloride 150 mg b.d. (32%) with respect to overall success (P = 0.050 and P = 0.030, respectively) but there was no difference with GR122311X 200 mg b.d. (31%). GR122311X caused effective, dose‐related suppression ofH. pylori(47%, 61% and 74%);H. pylorieradication rates were 18%, 21% and 22%. GR122311X was safe and well tolerated, with an adverse event profile similar to that of ranitidine hydrochloride 150 mg b.d. Median week 4 trough plasma bismuth levels were 1.3 ng/mL, 2.3 ng/mL and 3.3 ng/mL with GR122311X 200 mg b.d., 400 mg b.d. and 800 mg b.d. respectively. No individual plasma bismuth concentrations were of clinical concern.Conclusions: GR122311X is a safe and effective ulcer healing drug, and provides a platform on which anti‐H. pyloritherapy c

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00412.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: The mechanism of hypergastrinaemia during omeprazole therapy is unclear, but is generally assumed to be entirely a consequence of acid suppression. However, direct stimulation of G cells by omeprazole could also be a factor. In order to further investigate the mechanism of omeprazole‐induced hypergastrinaemia, we have studied the effects of the drug on plasma gastrin in patients with achlorhydria, in whom altered acid secretion cannot play a role.Methods: We estimated fasting and peptone meal stimulated plasma gastrin in nine patients (seven female) with pernicious anaemia and achlorhydria, before and on the final day of 4 weeks’dosing with omeprazole 40 mg daily.Results: Despite the high fasting gastrin concentrations, the peptone meal produced a further elevation in plasma gastrin concentrations, median gastrin concentrations rising from 1500 ng/L (range 225–10875 ng/L) to 3750 ng/L (range 585–15600 ng/L) post‐prandially (P = 0.004). The median post‐prandial rise in plasma gastrin at this initial visit was 44% (3–260%), and the median time interval until plasma gastrin concentrations returned to fasting levels was 120 min (range 10‐>150 min). There was a significant negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation (Spearman correlation coefficient ‐0.79,P= 0.01). Fasting plasma gastrin concentrations were similar pre‐omeprazole (median 1950 ng/L, range 240–16500 ng/L) and postomeprazole (median 1500 ng/L, range 315–7650 ng/L). Likewise, peak plasma gastrin concentrations were also similar pre‐omeprazole (median 2700 ng/L, range 585–16500 ng/L) and post omeprazole (median 3420 ng/L, range 720–11250 ng/L).Conclusions: (i) The hyperplastic G cell mass in patients with pernicious anaemia can be further stimulated by a peptone meal, which causes a prolonged rise in plasma gastrin concentrations. (ii) There is a negative correlation between fasting plasma gastrin concentrations and the percentage increase in plasma gastrin levels in response to meal stimulation. (iii) Omeprazole has no effect on plasma gastrin in achlorhydric patients, which is consistent with its hypergastrinaemic effect being entirely

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00413.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYAims: To compare the efficacy, safety and tolerability of an omeprazole/amoxycillin (OA) dual therapyHelicobacter pylorieradication regimen with an omeprazole/amoxycillin/metronidazole (OAM) triple therapy regimen.Methods: In this double‐blind trial, conducted in 19 hospitals, 119 patients with symptomatic duodenal ulcer disease were randomized to receive either 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and placebo followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 59) or 14 days treatment with omeprazole 40 mg daily, amoxycillin 500 mg t.d.s., and metronidazole 400 mg t.d.s., followed by a further 14 days’treatment with omeprazole 20 mg daily (n= 60).H. pyloristatus was assessed by13C‐urea breath test at entry and at 4 weeks post‐treatment.Results: H. pyloriinfection was eradicated in 46% of the OA treated patients and in 92% of the OAM treated patients, a mean difference of 46% (P<0.0001, 95% CI for the difference: + 30 to + 62). In only one patient was the duodenal ulcer not endoscopically healed after 4 weeks of treatment (OA 100%; OAM 98% healed). There were no significant differences in speed of symptom relief or improvement in symptoms between the two groups. Both regimens were well tolerated, with 96% of patients completing the course, and only one patient withdrawing due to an adverse event. The only side‐effect with a significantly higher incidence in the OAM group was diarrhoea, which occurred in 36% of patients compared to 16% of patients in the OA group (P<0.05).Conclusions: A regimen consisting of omeprazole 40 mg daily, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. for 14 days gives an appreciably higherH. pylorieradication rate than omeprazole and amoxycillin alone, with acceptable t

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00414.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: Lansoprazole is a new proton pump inhibitor for the treatment of peptic ulcer disease. Methods: A double‐blind, multicentre study was undertaken in 2 9 6 patients with endoscopically proven duodenal ulcer to compare the efficacy and safety of lansoprazole 15, 30 or 60 mg with placebo. Ulcer healing was documented by endoscopy at 2 and 4 weeks; patients whose ulcers healed after 4 weeks were followed for up to 6 months post‐treatment.Results: Four‐week healing rates of 89.4% 91.7% and 89.9% were obtained with lansoprazole 15, 30 and 60 mg, respectively, compared with 46.1 % on placebo (P<0.001). All three doses of lansoprazole produced rapid symptom relief, although patients taking 60 mg lansoprazole required fewer antacids than did those taking 15 mg. At 6 months, the percentages of patients healed were 45.3%, 40.0% and 38.4% in the lansoprazole 15, 30 and 60 mg dosage groups, respectively, and 2 5.3 % for the placebo group. No significant adverse events were documented during the period of this trial.Conclusion: Lansoprazole is an effective and safe treatment for duodenal ulcer and the 15 mg dose is as effective as 30 or

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00415.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARYBackground: The effects of erythromycin on small bows motility are controversial. Orocaecal transit time (OCTT) is considered to be a valid measure of small bowel motility.Methods: We studied the effect of erythromycin on OCTT in diabetic male subjects in a double‐blind placebo‐controlled crossover fashion. After an overnight fast, subjects received erythromycin 500 mf 250 mg or placebo, on 3 different days. A standard solid meal containing 20 g lactulose was administered 30 min after the erythromycin ingestion. Exhaled breath was collected and hydrogen concentration was assessed over 5 h. Breath hydrogen concentrations for each session were analysed over time by a generalized logistic function generating a sigmoidal curve. Front transit time was recorded as the time point when a sustained rise in breath hydrogen concentration of at least 5 p.p.m. was first observed.Results: The mean ± S.E.M. time taken for the front of the meal to reach the caecum was 92.5 ± 9.5, 86.1±16.5 and 62.3 ± 12.1 min for placebo, erythromycin 250 mg and erythromycin 500 mg, respectively. The OCTT was significantly decreased with erythromycin 500 mg compard to placebo (P<0.05).Conclusion: Oral administration of 500 mg erythromycin has prokinetic effect on orocaecal transit in male patients with diabetes m

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1995.tb00416.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY