Early acid perception in NERD.

Heartburn is the hallmark of gastroesophageal reflux disease. The hypothesis tested in this study is that the time of onset of this symptom may play a role in the development of mucosal lesions. During endoscopy of 61 patients complaining of heartburn and nine control subjects, gastric fluid was aspirated using a catheter introduced through the operative channel, and blindly instilled onto the esophageal mucosa before withdrawing the endoscope. Saline was used as control. Evocated symptoms and endoscopic lesions were recorded. Thirty-seven patients did not present esophageal lesions (nonerosive reflux disease [NERD]); 24 presented esophagitis (ERD). Instillation of gastric fluid on the esophageal mucosa elicited heartburn in 46% of patients with NERD, 8.3% with ERD, and 11.1% of controls. Symptoms lasted throughout the procedure but were no longer present when the gastroscope was withdrawn. The NERD value was significantly higher than that of ERD (P= 0.02) and controls (P= 0.02), while no difference was found between ERD and controls. Saline did not induce symptoms either in controls or patients. NERD patients show an early response to gastric fluid instillation much more frequently than ERD and controls. It is hypothesized that the early onset of symptoms in NERD patients may be a possibility to avoid the progress of mucosal lesions by claiming an earlier medical care.

N-Butyrate rectal transport in cirrhotic patients.

Data about colonic mucosa transport of short-chain fatty acids in cirrhotic patients are still lacking. The aim of the present study was to compare the rectal mucosa transport of n-butyrate and its effect on transport of other electrolytes and endoluminal pH in normal subjects and in cirrhotic patients by using a rectal dialysis technique. Thirteen subjects with normal hepatic function tests and 17 cirrhotic patients were enrolled. Dialysis bags containing 80 mmol/liter of butyrate in a neutral pH (6.8) electrolyte solution were placed in the rectum of enrolled subjects for 60 min. Net transport rate was calculated for butyrate, sodium, chloride, potassium, and bicarbonate. The differences in pH between initial and final dialysis solutions was also evaluated in the two groups in the study. Net butyrate absorption was significantly lower in cirrhotic patients than in controls (65.2 +/- 38.6 vs 101.2 +/- 45.3 nmol/min/cm2, respectively; P = 0.02). Furthermore, cirrhotic patients showed a lower HCO3 secretion than controls (-26.9 +/- 19.9 vs -45.1 +/- 20.0, respectively; P = 0.01). No differences were found in transport of the other electrolytes. The pH in the final dialysis solution in cirrhotic patients was not significantly lower than in the controls (7.15 vs 7.35; P = 0.1). In conclusion, the impairment of butyrate absorption and the concurrent reduction of bicarbonate secretion observed in cirrhotic patients may suggest a selective hypoactivity of apical HCO3-/SCFA- antiport located at the colonocyte apical membrane.

Effects of cisapride on abnormally prolonged endogastric alkalinity time and delayed gastric emptying in cirrhotic patients.

BACKGROUND/AIMS: An abnormally prolonged alkalinity time in endogastric long-term pH monitoring has been previously demonstrated in cirrhotic patients. Recently a growing body of evidence suggest the existence of severe abnormalities of gastric emptying in the same patients and more generally of gastrointestinal motility changes in many portal hypertensive animal models. Assuming that there was a good correlation between endogastric alkalinity and a delayed emptying of gastric bile reflux, the aim of this study was to evaluated the effect of a gastrokinetic drug, Cisapride, both on circadian gastric pH and on gastric emptying in cirrhotic patients compared with controls. MATERIALS AND METHODS: Ten in patients with chronic liver disease and portal hypertension (six males, four females, median age 49.5, range 28-59) were enrolled. The control group included twelve inpatients without cirrhosis (seven females and five males, average age 45 years, range 31-54) free from endoscopic esophagogastro-duodenal lesions. The subjects were submitted to a 24h endogastric pH monitoring and gastric emptying study before and after administration of Cisapride (10 mg tid for three days). To gastric emptying study we used an ultrasonographic method evaluating the ratio between the antropyloric region volume before and at a fixed time after a solid/liquid standard meal. RESULTS: Basal 24 h gastric pH monitoring in cirrhotic patients showed a significant prolonged time of alkalinity (pH conventionally over 4) during the entire registration and mainly in postprandial period vs controls. The same patients group showed also a delayed gastric emptying when compared to controls. Cisapride administration significantly reduced both the abnormally prolonged alkalinity time and delayed gastric emptying in cirrhotic group without affecting the same parameters in the control group. CONCLUSIONS: Cisapride significantly reduces both the delayed gastric emptying time and the abnormally prolonged alkalinity time in cirrhotic group. Taken together, the results offered an indirect evidence that abnormally prolonged alkalinity in cirrhotic patients may be due, at least in part, to changes in gastroduodenal motility leading to a reduced gastric clearance of potentially noxious duodeno-gastric alkaline reflux.

Is early gastric cancer, diffuse type, a forerunner of advanced gastric cancer.

AIMS AND BACKGROUND: Gastric cancer (GC) represents one of the most important causes of death by malignancy world wide. Our retrospective study was carried out on surgical stomach specimens obtained from a series of 552 consecutive cases of GC observed in the Departments of Surgical Pathology of the Public Hospitals of L'Aquila and Atri which cover the 17% of the entire population of the Italian Region Abruzzo. The aim of the study was to compare the anatomo-clinical characteristics of early GC (EGC) and advanced GC (AGC). METHODS: The diagnosis was achieved by the criteria of the Lauren's histopathological classification (intestinal and diffuse types). Our study also stratified the cases by sex, age, lymph node metastases and associated lesions such as chronic atrophic gastritis, intestinal metaplasia and dysplasia. RESULTS: On an average, patients affected by EGC were 8.1 years younger than those with AGC. This age gap could support the hypothesis that early lesions represent the first stage of AGC. However, when patients were subdivided according to Lauren's classification, the mean age of patients with EGC, diffuse type, was 12.2 years less than that of AGC patients of the corresponding histological type. Furthermore, the subset of patients with EGC, diffuse type, and lymph node metastases was 17.8 years younger than patients affected by AGC diffuse type, with lymph node metastases. CONCLUSIONS: The present study offers an original survey on GC in a defined Italian population. As far as the intestinal histotype is concerned, the slight age difference between EGC and AGC suggests that these tumors are different steps of the same process. On the contrary, the age distribution suggests that EGC, diffuse type, has a different biological behaviour.

Do colon and rectum exhibit an opposite cancer risk trend versus cholecystectomy? A case--double control study.

A case-double control study on 318 personally interviewed patients with large bowel neoplasia has been carried out to establish the possible role of cholecystectomy in the development of colorectal cancer. The dietary habits both of the cancer patients and control subjects were investigated. All controls were considered free of neoplastic lesions on the basis of a negative fecal occult blood test. Data from the study showed that the prevalence of cholecystectomy in the overall patients was similar to that of the two control groups. However, analysing the data for colon and rectum, the relative risk of colonic cancer after cholecystectomy was significantly increased in males (RR = 2.75; p less than 0.05), whereas that of rectal cancer appeared to be decreased in females (RR = 0.18; p less than 0.02). Subsite analysis demonstrated that right-sided neoplasia after long-standing cholecystectomy (greater than or equal to 10 years) was responsible for the increased colonic risk. In conclusion, the present data support the hypothesis that cholecystectomy may be considered a risk factor for right-sided colon cancer, but indicate that this operation seems to play a protective role for rectal cancer.

A re-appraisal of the mode of action of 5-HT in inhibiting GABA-induced cholinergic contractions in the guinea-pig ileum.

In the guinea-pig ileum, pretreatment with 5-hydroxytryptamine (5-HT) (5 microM) for 4-5 min inhibited both 5-HT- and gamma-aminobutyric acid (GABA)-induced cholinergic contractions without consistently altering those induced by electrical field stimulation. Cisapride (1 micron) antagonized 5-HT-induced cholinergic contractions but left those induced by GABA or twitch responses unchanged. These results indicate that the 5-HT action in inhibiting GABA-induced cholinergic responses may arise at the interneuronal level, thus suggesting that GABA may also indirectly activate cholinergic terminal neurons. These findings rule out the possibility of 5-HT acting as an intermediate transmitter in this type of response.

5-hydroxytryptamine desensitization fails to modify GABA-induced inhibitory responses in the guinea-pig colon.

In segments of guinea-pig colon, treated with 1 microM hyoscine, a 5-HT desensitization procedure that decreased the potency of 5-HT 41-fold in relaxing the longitudinal musculature, failed to modify the non-adrenergic GABA-induced inhibitory responses, suggesting that the action of GABA in this preparation is not 5-HT-mediated. These results are at variance with those obtained in the guinea-pig ileum where 5-HT seems to play a role in GABA-induced cholinergic contractions.

5-HT mediated GABA excitatory responses in the guinea-pig proximal ileum.

GABA (3--100 microM) and 5-HT (0.03--30 microM) caused concentration-dependent transient contractions of the longitudinal muscle of the guinea-pig ileum. The contractile response to GABA was antagonized by hyoscine (2.2 microM). TTX (0.7 microM), bicuculline (3 microM), furosemide (25 microM) and desensitization to GABA itself, while hexamethonium (20 microM) and methysergide (20 microM) were without effect. The contractile response to 5-HT was antagonized by hyoscine (2.2 microM), TTX (0.7 microM) and desensitization to 5-HT itself and was unaffected by bicuculline (10 microM), hexamethonium (20 microM), furosemide (25 microM) and methysergide (20 microM). A desensitization procedure that caused a 84.7-fold increase in the 5-HT EC50 also resulted in a 74.1-fold increase of the GABA EC50. Desensitization to GABA caused a reduction of 5-HT induced response but only in preparations desensitized by high (50 microM) concentrations of GABA. The results indicate that GABA-induced contractions in the guinea-pig ileum are mediated by activation of cholinergic motor neurones. This effect appears to be mediated by interneuronal release of 5-HT rather than by a direct stimulatory action of GABA on the effector neurones.

Dilazep: an inhibitor of adenosine uptake with intrinsic calcium antagonistic properties.

Concentrations of dilazep which were ineffective in altering the muscular tone of the guinea-pig taenia caeci (0.03, 0.3 microM) or the phasic mechanical activity of the rabbit proximal ileum (0.03 microM) markedly potentiated the inhibitory action of adenosine on both these parameters. Dilazep, 0.3 microM or greater, dose-dependently inhibited the mechanical activity of the proximal ileum. This inhibitory action was probably mediated by more than one mechanism, as shown by the fact that theophylline (50, 100 microM) antagonized the effect at lower dilazep concentrations (up to 3 microM) leaving essentially unchanged the response to higher concentrations (6, 10 microM). Similarly, the responses to low doses of dilazep were reduced after desensitization of the organ to adenosine, whilst the responses to higher doses were unaffected by this procedure. In a Ca2+-free, high-K+ medium, dilazep (1-10 microM) caused a parallel shift to the right of the Ca2+-induced contractions of the guinea-pig taenia caeci. Adenosine showed only slight Ca2+-antagonistic properties within the mM range of concentrations. These findings suggest that, at the higher concentration tested, dilazep exhibits Ca2+-antagonistic properties unrelated to its adenosine-mediated mode of action.