A. Torsoli

Effect of wheat bran in treatment of chronic nonorganic constipation : a double-blind controlled trial

After a two-week basal period, 24 patients were randomly allocated to receive, with a crossover double-blind design, for two consecutive four-week periods, bran (20 g/24 hr) or placebo. The daily intake of water and dietary fibers was standardized. Symptomatology, oroanal transit time, bowel frequency, and stool weight were assessed in basal conditions and at week 4 and 8 of the treatment. Oroanal transit time decreased and bowel frequency and stool weight increased significantly during both bran and placebo administration in comparison with basal period. Bran treatment was more effective than placebo in improving bowel frequency and oroanal transit. During bran treatment oroanal transit time became normal only in patients with slow colonic transit and not in those with slow rectal transit. Neither the occurrence nor the severity of the most frequent accompanying symptoms of chronic constipation differed significantly between placebo and bran treatments.

Gastrointestinal transit time, frequency of defecation, and anorectal manometry in healthy and constipated children.

Total gastrointestinal transit time (TGITT), frequency of defecation, and anorectal manometry were evaluated in 63 pediatric patients referred for chronic nonorganic constipation; in 39, segmental transit times of the right and left colon and rectum were also measured. TGITT was significantly longer in chronically constipated children than in matched normal controls. Although bowel frequency was highly significantly correlated with TGITT in patients with prolonged transit time, not all children with prolonged TGITT had reduced bowel frequency. Moreover, not all children with constipation had prolonged TGITT. In children with idiopathic chronic constipation, slowing of intestinal transit occurred most frequently at the level of the distal colon and rectum. Anorectal motility variables were not significantly different in children with functional chronic constipation and in normal children. Maximal resting and pressure and mean intrarectal distending volume causing threshold inhibition in constipated patients did not significantly differ from the control values. Therefore, anorectal manometry did not detect relevant motor abnormalities in constipated children.

Combined oral sodium butyrate and mesalazine treatment compared to oral mesalazine alone in ulcerative colitis.

Butyrate represents the main source of energy for colonic epithelial cells; however, its availabilty/utilization is impaired in ulcerative colitis (UC). In the present randomized, double-blind, placebo-controlled pilot study, the safety and efficacy of colonic targeted oral sodium butyrate tablets, coated with a pH-dependent soluble polymer, have been evaluated in ulcerative colitis. Thirty patients with mild to moderate colitis underwent a six-week course of oral sodium butyrate (4 g/day) plus oral mesalazine (2.4 g/day), (Group A) or of oral mesalazine plus placebo (Group B). Clinical, endoscopic, and histologic data were collected at the beginning and the end of the study. Twenty-five patients completed the study (12 in group A, 13 in group B). No untoward side effects were reported. In group A, seven patients underwent remission and four improved; in Group B the numbers were 5 and 5, respectively. After treatment, all clinical parameters had significantly improved in both treatment arms compared to pretreatment findings. The UC disease activity index (UCDAI) score decreased from 7.27 ± 2.02 to 2.58 ± 2.19 (P < 0.05) in the combined treatment group and from 6.07 ± 1.60 to 3.46 ± 1.98 (P < 0.05) in group B. The endoscopic and histologic scores also significantly improved after treatment in both groups (P < 0.05). The difference between the two treatment arms was not significant, but a significantly better improvement vs baseline values (P < 0.05) was observed in the combined treatment group vs the mesalazine group, when considering both the clinical index (Δ9.58 ± 4.19 vs 5.92 ± 3.48) and the UCDAI score (Δ4.67 ± 2.19 vs 2.54 ± 2.18). A more favorable trend, although not significant, was observed for all individual parameters in group A. In conclusion, results of the present pilot study indicate that oral butyrate is safe and well tolerated. These data also suggest that oral butyrate may improve the efficacy of oral mesalazine in active ulcerative colitis and prompt the need of a large scale investigation to confirm the present findings.

Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate

Nine patients with distal ulcerative colitis refractory to standard therapy were treated with intrarectal instillation of a sodium butyrate solution and 5-ASA. A marked clinical, endoscopical and, to a smaller extent, histological improvement was observed in seven of nine patients. The clinical improvement usually occurred within the second week of therapy, and thus earlier than in previous cases treated with butyrate alone. This preliminary experience suggests that the combined butyrate-5-ASA treatment may prove a useful therapeutic tool in refractory distal ulcerative colitis and possibly increase the effectiveness of the individual therapeutic regimens.

Outcome of endoscopic sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction as predicted by manometry and quantitative choledochoscintigraphy

Background: Sphincter of Oddi dysfunction is diagnosed at manometry and, after cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients may benefit from endoscopic sphincterotomy. Aims: The aim of this study was to assess the usefulness of choledochoscintigraphy compared with manometry in predicting outcome of sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction. Patients and methods: Thirty patients with biliary-type pain complying with the Rome diagnostic criteria of sphincter of Oddi dysfunction and belonging to biliary group I and II were subjected to clinical evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic manometry. Twenty two biliary group I and II patients with prolonged hepatic hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen patients underwent sphincterotomy; eight refused. Clinical and scintigraphic assessments were performed at follow up. Results: Hepatic hilum-duodenum transit time was delayed in all patients with manometric evidence of sphincter of Oddi dysfunction, in all biliary group I patients and in 64% of biliary group II patients. At follow up, all patients who underwent sphincterotomy were symptom free and hepatic hilum-duodenum transit time had either normalised or significantly improved. A favourable post sphincterotomy outcome was predicted in 93% of cases at choledochoscintigraphy and in 57% at manometry. Conclusions: Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy outcome in post cholecystectomy biliary group I and II patients, irrespective of clinical classification and manometric findings.

HEPATODUODENAL BILE TRANSIT IN CHOLECYSTECTOMIZED SUBJECTS : RELATIONSHIP WITH SPHINCTER OF ODDI FUNCTION AND DIAGNOSTIC VALUE

The hepatic hilum-duodenum transit time (HHDT) was evaluated in cholecystectomized subjects to assess its relationship with the motor function of the sphincter of Oddi (SO) and its diagnostic accuracy in the detection of SO dysfunction. The study was performed in asymptomatic controls and symptomatic patients with SO dysfunction before and after sphincterotomy. HHDT showed a direct correlation with manometric SO maximal basal pressure (r=0.77;P<0.001) but not with SO phasic activity. In sphincterotomized subjects HHDT did not differ from that of the asymptomatic subjects, and HHDT, which was prolonged before sphincterotomy, normalized after sphincterotomy. HHDT had a 100% specificity and an 83% sensitivity in diagnosing SO dysfunction when compared to SO manometry. In conclusion, the cholescintigraphic HHDT is mainly related to the SO maximal basal pressure, presenting an elevated specificity and a satisfactory sensitivity in the diagnosis of SO dysfunction in cholecystectomized subjects.

Analysis of clinical course of postoperative recurrence in Crohn's disease of distal ileum.

In the present study we have investigated whether in patients with Crohns Disease the clinical course remains the same from the initial disease to postoperative recurrent disease. Fifty-eight resected patients who developed a postoperative recurrence were followed for 4.2±3 years (median 3 years). The yearly frequency of flare-up was 1.9±1.0 (median 1.5) in the initial disease and 1.7±1.0 (median 1.7) in recurrent disease. In patients who experienced complications during the initial disease, the frequency of complications during the course of recurrent disease was significantly higher than in the others (27/42 vs 3/16,P=0.002). The frequency of obstruction and extraintestinal manifestations in the recurrent disease was higher in patients who suffered these complications in the initial disease than in those who did not (19/29 vs 6/29,P=0.0006, and 4/5 vs 4/53,P=0.0008). The cumulative probability of complication during the course of recurrent disease was higher in patients with complications during the initial disease (P<0.001). The survival analysis showed that the cumulative probability of obstruction and extraintestinal complication in recurrent disease was higher in patients who suffered these complications in the initial disease (P<0.005). These data indicate that the clinical course of Crohns disease of the distal ileum remains the same from the initial disease to postoperative recurrent disease. This study also suggests that the short-term course of recurrent disease can reasonably be predicted.

Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying.

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7±1.6 ml after placebo and 8.2±3.5 ml after loxiglumide; P<0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5±16.5 ml after placebo and 59.4±24 ml after loxiglumide; at 300 min after the meal 20.8±13.3 ml after placebo and 18.9±9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.

Bombesin effects on human GI functions.

In this article some of the actions of amphibian skin peptide Bombesin (BBS) on human gastrointestinal and pancreatic functions are reviewed. BBS causes increases of lower esophageal sphincter pressure, delay of gastric emptying, inhibition of mechanical activity of duodenum and jejunum and gallbladder emptying. BBS also releases in man gastrin and stimulates gastric acid secretion. BBS administration induces release of insulin, glucagon and pancreatic polypeptide from human Islet of Langerhans and causes secretion of pancreatic bicarbonates and enzymes in duodenal juice and release of pancreatic enzymes in blood stream.

Effects of bombesin on gastrin and gastric acid secretion in patients with duodenal ulcer

The effect of bombesin, a possible neurotransmitter of gastrin release, upon gastrin and gastric acid secretion was investigated in 25 patients with duodenal ulcer and in 16 normal subjects. In patients with duodenal ulcer bombesin (10 ng/kg/min) produced an increase in plasma gastrin output (median 22·4 (range 7·5-75·8) pmol/l/min) similar to that obtained in normal subjects (median 24·4 (range 5·8-56·5) pmol/l/min), whereas gastrin stimulated by a meal was significantly higher in the group of patients with duodenal ulcer (median 20·7 (range 9·2-42·9) vs 16·2 (range 3·4-22·2) p<0·05). Peak acid output induced by bombesin was significantly higher in patients with duodenal ulcer than in normal subjects (median 24·4 (range 9·0-63·8) vs 14·0 (range 3·0-24·8) mmol/h, p<0·05) despite identical gastrin outputs. The ratio (%) obtained by dividing the acid secretory response to bombesin by the response to pentagastrin, however, was similar in both normal subjects and patients with duodenal ulcer (median 55 (range 20-116) vs 58 (range 31-95) respectively). The difference between the gastrin response to food and bombesin could be explained by the fact that bombesin releases gastrin directly, whereas a protein meal involves several mechanisms (neural, peptidergic, paracrine, endocrine), either stimulatory or inhibitory. The above results indicate that a higher concentration in antral and/or duodenal gastrin is unlikely to be present in patients with duodenal ulcer. An increased parietal cell mass could explain the higher gastric acid response after bombesin infusion in our group of patients with duodenal ulcer.