摘要:

SUMMARYThe role that the sympathetic nervous system plays in modulating physiological processes in the gastrointestinal tract is becoming clearer. It is now known that motor, secretomotor and vasomotor activity are all modulated independently by the system. Adrenoreceptor stimulation appears to reduce intestinal contraction (except at sphincters), both via alpha‐receptors which inhibit neurotransmitter release and also by a direct beta‐receptor mediated action on smooth muscle. There is also evidence for tonic activity in the beta‐adrenergic pathway, since betaantagonists tend to increase contraction pressures. In animals alphareceptor‐mediated pathways modulate fluid and electrolyte absorption, and alpha‐adrenergic agonists enhance net absorption and reduce net secretion. In man there is also evidence for a beta‐adrenergic pathway which controls secretomotor function. Carbohydrate absorption appears to be dependent on activity in a beta‐adrenergic pathway, although this may be an indirect effect of changes in motor function. The time course of changes of both secretomotor and motor activity, induced by modulating sympathetic or adrenergic input, differ from the vascular changes indicating that the effects occur independently of each other. The gastrointestinal response to stressors is mediated, in part at least, by the sympathetic nervous system. Differences between individuals are likely to prove important.Since the sympathetic nervous system regulates gastrointestinal function both in the basal state and under stressful conditions, it will have effects on pathophysiological responses. Modification of such responses is likely to ameliorate symptoms, as has already been found for alpha‐2‐adrenergic agonists which have an anti

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00257.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe gastrointestinal side effects of non‐steroidal, anti‐inflammatory drugs extend beyond the duodenal bulb, and comprise a variety of lesions in all parts of the gut. Gastroduodenal ulceration is quantitatively dominant, although a major part of these lesions probably go unnoticed and heal spontaneously. Adaptation has been demonstrated for acetylsalicylic acid, and may be of importance for other substances as well. Non‐steroidal anti‐inflammatory drugs (NSAIDs) may induce relapse of inflammatory bowel disease. Permeability changes and mucosal inflammation are found in the small and large bowel in the majority of subjects taking NSAIDs, although the clinical significance is still not clear. Ulceration and perforation do, however, occur in this part of the gut as well. Treatment of NSAID‐associated ulceration is similar to traditional ulcer treatment, possibly with extended treatment duration if the NSAID is continued. Prophylaxis is of some value, but is not required for every patient receiving

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00258.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYIncreased mucosal eicosanoid synthesis occurs in active ulcerative colitis; suppression of the synthesis of pro‐inflammatory leucotrienes could be therapeutically useful. Neutrophil 5‐lipoxygenase is calcium‐dependent. In this study, the effect of the calcium channel antagonist, verapamil, on the release of eicosanoids by colitic rectal mucosal biopsies has been examined. Verapamil in therapeutic concentration (5μg/ml, 10‐5M) reduced leucotriene B4 release from actively inflamed rectal mucosa by 30% (from 60 (5.0 S.E.M.) ng/g wet weight/20 min without, to 42 (5.7 S.E.M.) with verapamil,P<0.05), but had no effect on leucotriene B4 release by rectal biopsies taken from patients with quiescent ulcerative colitis (39 (2.8 S.E.M.) ng/g wet weight/20 min without, and 43 (5.0 S.E.M.) with verapamil). Verapamil did not affect mucosal prostaglandin E2release. The results suggest that, in active ulcerative colitis, verapamil inhibits mucosal 5‐lipoxygenase activity and warrants therapeutic

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00259.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe effect ofHelicobacter pylorilipopolysaccharide on guinea pig gastric mucosal pepsinogen secretion has been examined using an Ussing chamber technique. Luminal addition ofH. pylorilipopolysaccharide resulted in a fifty‐fold stimulation of pepsinogen secretion compared to a twelve‐fold increase withE. coillipopolysaccharide. Electron microscopy showed marked degranulation of zymogen granules but no evidence of chief cell disrupt

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00260.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYNine hundred and sixty‐six patients’compliance with drug therapy of peptic ulcerations and reflux oesophagitis in four clinical trials were studied. The mean compliance rates varied from 90.5% (95% C.I. 89.0–92.1%) to 99.2% (95% C.I. 98.2–100.1%). Compliance declined significantly with increasing complexity of the dosage schedule in all trials, and toward the end of the treatment period in two of them. Patients with adverse events had a significant drop in compliance during the Iast part of the treatment period in one of the trials. There was a significant inter‐centre variation in compliance. Overall, the variation was of little clinical significance. Patient compliance was independent of age, sex, use of alcohol and tobacco, effect of treatment, concomitant drug therapy and whether the pill was active drug or placebo. The study shows that a simplified dosage schedule, shortening of the treatment period, use of drugs with minimal side‐effects, and meticulous selection of centres could improve patient compliance with drug therapy in clin

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00261.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe effects of identical morning (08.05 hours) and evening (20.05 hours) meals on intragastric pH were compared in 12 healthy volunteers receiving gastric antisecretory medication. Dosing included continuous intravenous infusion ranitidine (50 mg bolus followed by 12.5 mg/h) or a matching placebo which were randomly administered prior to and following 7 days of treatment with oral omeprazole (40 mg mane). Intragastric pH was monitored continuously using a tethered indwelling pH probe. Subjects were divided into groups, one of which began the pH monitoring session in the morning, the other in the evening. The median 24‐h intragastric pH was significantly increased by all active dosing regimens (P<0.05). Combined omeprazole and ranitidine produced the highest median pH, 5.92. However, a breakthrough drop in intragastric pH occurred during the evening after all active dosing. Intragastric pH fell prior to and after consumption of the evening meal with median pH values less than 4 during all sessions. The evening meal led to significantly lower intragastric pH compared to the morning meal for omeprazole and the combined omeprazole and ranitidine dosing periods (P<0.05). There was no difference between morning and evening pH during the placebo or ranitidine periods. Ranitidine and omeprazole, either alone or in combination, were unable to prevent the mealstimulated decline in intragastric pH during the evening time perio

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00262.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe mechanisms by which administration of the H+, K+‐ATPase inhibitor B 831–78 or intragastric perfusion with NaHCO3induces plasma gastrin release were studied in the rat. Experiments were performed after a washout of residual intragastric contents in fasted animals provided with chronic gastric fistulae. Acute and chronic administration of B 831–78 elevated plasma gastrin dose‐dependently up to 5–6 times above control levels, while the increase was only twofold with intragastric NaHCO3infusion despite similar neutralization of gastric acidity.The profound hypergastrinaemia induced by the H+, K+‐ATPase inhibitor, after both acute and chronic treatment, was completely prevented or reversed by intragastric perfusion with physiological amounts of acid (0.15 N HCl, 2.5 ml/h). The hypergastrinaemia was, however, largely resistant to high doses of atropine (4.3μmol/kg) and of the M1selective muscarinic antagonist telenzepine (10μmol/kg). In contrast, the modest increase in plasma gastrin induced by gastric perfusion with NaHCO3was completely suppressed by the high atropine dose and was attenuated by small doses of atropine or telenzepine (0.01μmol/kg and 1μmol/kg).These results demonstrate that, in the rat, blockade of the H+, K+‐ATPase can potently induce gastrin release in the absence of a meal. Moreover, they suggest that interruption of the negative feedback between acid and gastrin release is the main mechanism through which this class of drugs releases gastrin in the rat. Since a similar degree of gastrin release cannot be achieved by alkalinization of gastric contents, additional hormonal or neural regulatory factors may contribute to the drug‐induce

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00263.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe use of the drug cyclosporin is limited by toxicity. It would be advantageous to develop therapeutic monitoring of cyclosporin which would predict the development of clinical toxicity. In the present study, alternative methods of measuring cyclosporin levels were evaluated in a heterogenous population of transplant patients, comparing a fluorescent polarization immunoassay using a non‐specific polyclonal antibody, which measures both cyclosporin and its main metabolites, and a specific high‐performance liquid chromatography assay for unchanged cyclosporin in blood.Neither measured variable alone correlated with laboratory evidence of renal toxicity (serum creatinine) or liver toxicity (serum glutamate transaminase, lactic dehydrogenase, alkaline phosphatase, or serum bilirubin). The relationship between metabolites and parent cyclosporin was quantitated using the ratio of cyclosporin levels determined by fluorescent polarization immunoassay over levels determined by high‐performance liquid chromatography. A cohort of patients with markedly elevated ratios of cyclosporin were identified. When patients’data were reviewed collectively and individually there was a correlation between an elevated ratio and the serum bilirubin (r= 0.41,P<0.001). This association could be either due to cyclosporin as a cause of cholestasis or to cholestasis from any cause resulting in netaboite accumulation. Further studies are needed to clarify the role of cyclosportin in hepatic dysfunction and develop erly, specific markers for this cyclosporin‐associated

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00264.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe effects on gastric emptying and gastrointestinal symptoms of treatment with cisapride alone and in combination with domperidone were investigated in 25 patients with chronic idiopathic dyspepsia. In a double‐blind study, 9 patients were randomly assigned to receive cisapride 2.5 mg three times daily, and 8 patients to receive placebo. After 7 days of treatment, gastric emptying was significantly accelerated and the score of gastrointestinal symptoms was significantly reduced in patients treated with cisapride. Placebo treatment had no significant effect. A randomized, double‐blind crossover study of 8 patients compared the effects of combined treatment with cisapride 2.5 mg plus domperidone 10 mg three times daily for 7 days against the effects of cisapride plus placebo. Administration of cisapride plus domperidone gave significantly higher gastric emptying and lower gastrointestinal symptoms than cisapride plus plac

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00265.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SUMMARYThe usefulness of micronutrient antioxidant therapy for recurrent (non‐gallstone) pancreatitis has recently been endorsed by a 20‐week double‐blind double‐dummy cross‐over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600μg organic selenium, 9000 i.u.β‐carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross‐over stage and upon completion of trial. Baseline serum concentrations of selenium,β‐carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker—the 9‐cis, II‐trans isomer of linoleic acid—was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post‐placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S‐adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S‐adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans‐sulfuration

ISSN:0269-2813    

DOI:10.1111/j.1365-2036.1992.tb00266.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY