The Italian journal of gastroenterology最新文献

As the majority of patients with chronic arthritis are treated, for many years, with non-steroidal anti-inflammatory drugs (NSAID), it is only natural to expect the long-term use of these agents to be associated with a range of oesophago-gastro-duodenal histopathological changes. We have demonstrated that oesophagitis (defined as basis of papillary length, basal cell hyperplasia and inflammatory cell infiltration) is less prevalent in patients taking NSAID. This phenomenon can be utilised in the treatment of certain conditions such as post-irradiation oesophagitis and Barrett's oesophagitis. It also implies that NSAID-related oesophageal ulceration is due to lodging of tablets in the oesophagus and is, in turn, preventable by swallowing of some fluids or solids after taking NSAID. In the stomach, long-term use of NSAID is associated with a specific entity known as chemical or reactive gastritis in about 25% of cases. This is frequently associated with ulceration. Chronic active superficial gastritis, in the presence of Helicobacter pylori, can be found in about 70% of cases. Not unlike oesophagitis, the prevalence of active duodenitis is low in chronic NSAID users. Local ulceration still takes place. This implies that duodenitis is not required in at least some cases of NSAID-related duodenal ulcers, and demonstrates the multi-factorial nature of the pathogenesis of mucosal damage in long-term users of a NSAID.

As far as concerns ultrastructural lesions in the gastric epithelium following NSAIDs, a review has been made of existing data and ideas for future research concerning the ultrastructural field are advanced. Specific ultrastructural damage of the gastric epithelial cells has been recognized in patients taking NSAIDs: this pattern of damage appears characterized by a proliferative phenomen of "desquamation" of contiguous epithelial cells. Studies in animal models indicate that the first-level of epithelial damage involves a mitochondrial derangement and an alteration of tight junctions and cytoskeletal. The length of time of local drug action on the gastric mucosa could be the reason for the characteristic morphological presentation seen in vivo. If ulcers are the result of an imbalance between cell necrosis and cell regeneration, the high progression speed of cell necrosis to contiguous cells should play a basic role in the genesis of ulcers.

Inhibition of constitutively expressed cyclo-oxygenase (COX-1) by NSAIDs is thought to play an important role is the gastrointestinal toxicity of NSAIDs. To minimise the intestinal toxicity of NSAIDS, highly selective COX-2 (induced at inflammatory sites) inhibitors have been developed. One such is flosulide. We assessed the gastroduodenal tolerability of flosulide (20 mg twice a day) in man and compared it with that of naproxen (500 mg twice a day) in a randomised, double blind crossover fashion in 19 patients with osteoarthrosis. Treatment period was 2 weeks with a 2-week washout period with endoscopy before and after each treatment. Gastroduodenal damage was assessed as by Lanza (Grades 0-4) and by the Gastroscopic Rating Scale (Grades 0-9). Flosulide was significantly better tolerated (p < 0.005, analyses of deviance) than naproxen. No stomach damage was seen in 13 (68%) patients following flosulide and 5 (37%) following naproxen (p < 0.001). Lanza scores following flosulide (0.58) were significantly better than that of naproxen (1.47) (p < 0.001). The duodenal damage was mild with both treatments. The selective COX-2 inhibitor, flosulide, is significantly better tolerated and causes less gastric mucosal damage than naproxen when given for two weeks.

Relatives of Helicobacter pylori positive patients show a higher incidence of Helicobacter pylori infection than the general population, probably due to relapses and/or reinfections between members of the family. Aim of this study was to evaluate the prevalence of the infection in 121 relatives of 41 children with Helicobacter pylori positive gastritis. Specific IgG antibodies (ELISA) were evaluated, and bacteria on gastric biopsy specimens were investigated by urease-rapid test, culture test and GIEMSA or acridine orange staining. Of the eighty-two relatives, 68% were antibody positive. Thirty-five agreed to undergo endoscopy. With the exception of one brother, all subjects (97%) were found to be infected by Helicobacter pylori. Two symptomatic relatives, with normal antibody titres, were submitted to endoscopy and found to be colonized by Helicobacter pylori. The present data confirm the high prevalence of infection within families and appear to demonstrate the usefulness of endoscopy for all subjects showing positive antibody titres as well as for symptomatic relatives, even if serologically negative, to confirm the presence of any pathological conditions and reduce the risk of relapses within families.

A number of studies show that the idea that inhibition of cyclooxygenase is the sole mechanism of NSAID-induced gastrointestinal damage is no longer tenable. We re-examined various aspects of the mechanism of small intestinal damage due to NSAIDs in rat. Subcellular organelle marker enzyme studies show selective alterations in mitochondrial and brush border marker enzymes. Electron microscopy shows changes compatible with uncoupling of mitochondrial oxidative phosphorylation. In vitro, all common acidic-NSAIDs (n = 15) were found to uncouple oxidative phosphorylation at concentrations (microM) easily achievable within intestinal epithelium. Experiments in bile duct ligated animals show that intact indomethacin within the gastrointestinal lumen is required for uncoupling. Relative importance and pathophysiological consequences of uncoupling and inhibition of cyclooxygenase were assessed following administration of R and S flurbiprofen: the former selectively uncouples whilst the latter is also an effective cyclooxygenase inhibitor. R flurbiprofen uncoupled in vitro and in vivo, increased intestinal permeability and caused mild intestinal inflammation, but had not significant effect on prostanoid levels and produced no ulcers. S flurbiprofen uncoupled and increased intestinal permeability equally but was associated with significant decreases in intestinal prostanoid levels, more inflammation and numerous ulcers. Collectively these studies suggest that uncoupling may underlie the "topical" phase of NSAID damage which leads to increased intestinal permeability and inflammation, but concomitant inhibition of cyclooxygenase is essential to drive the inflammation to ulcers.

Bowel wall thickening in Crohn's disease can be demonstrated by Computed Tomography. The aim of this investigation was to correlate different patterns of bowel wall thickening, detected with Computed Tomography, with serological parameters of activity of Crohn's disease. Thirty-eight patients (24 males, 14 females, aged 21 to 62 years) were studied. Patients were divided into 3 groups according to Computed Tomography appearance of bowel wall: 1) homogeneous symmetrical thickening of wall; 2) bowel showing a layer of submucosal low attenuation; 3) scarred narrowing of wall producing stenosis. A patient was considered to have biochemically active disease if at least 2 of the following parameters were abnormal: ESR, C-reactive protein, seromucoids, serum albumin, serum alpha-2 globulin. The first group comprised 20 patients (16 active disease, 4 inactive) and the second group 13 (all inactive); the 2 groups showed a significant difference (Fisher exact test: p < 0.0005) in biological activity. Since only 5 patients belonged to the third group (3 active, 2 inactive disease), no definite conclusion can be drawn on the possible correlation between this Computed Tomography pattern and activity of disease. Results shows a correlation between Computed Tomography patterns of bowel wall disease and biochemical activity of Crohn's disease.

The effect of the histamine H3 receptor agonist (R) alpha-methylhistamine on duodenal bicarbonate secretion was investigated in the anaesthetized rat. (R) alpha-methylhistamine (3-30 mumol/kg i.v.) caused a dose-dependent increase in alkaline secretion which was completely blocked by the H3 receptor antagonist clobenpropit (3 mumol/kg i.v.). This antagonist caused a slight reduction (19%) of the secretory response to PGE2 50 micrograms/kg i.v. These data indicate that the alkaline response to (R) alpha-methylhistamine is related to the activation of histamine H3 receptors and suggest that this could be an additional mechanism involved in the previously observed gastroprotective effect of this compound.

The role is reviewed of gastric antisecretory and mucosal protective drugs in the prevention of NSAID-induced gastric and duodenal mucosal lesions. The results of the randomized, double-blind, controlled trials show that misoprostol is the only antiulcer drug proven to be effective in the prevention of NSAID-induced gastric and duodenal ulcers as well as for reducing serious upper gastrointestinal complications (perforation and/or haemorrhage). However, recent data suggest that even omeprazole and high dose of H2-receptor antagonists may have a role in the prevention of NSAID-induced gastric and duodenal ulcerations.

Chronic active hepatitis due to HCV represents a severe progressive disorder of the liver, At present, Interferon seems to be the most efficacious treatment available, however, only 20-25% of the patients treated achieve complete remission. The efficacy has, therefore, been evaluated of Ribavirin, a nucleoside analogue active both on DNA and RNA viruses, in the treatment of non responders to a previous course of interferon. Twenty patients were randomly assigned to two groups: A) received the association R (800 mg/day for 2 months)+interferon (9 Mu/week for 6 months); B) received IFN (9 Mu/week for 6 months). All patients completed the study without important side effects. Four patients in group A presented reduced ALT and loss of viraemia during treatment with Ribavirin. Only one patient in group B had reduced indices of cell lysis and was negative for HCV-RNA during the course of the study. However, viremia and an increase of ALT values were observed in all of these subjects once treatment was interrupted. The results emerging from this study indicate that Ribavirin therapy, at the dose and duration of treatment employed, is not sufficient to change the natural course of events of chronic active hepatitis from HCV.