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The present double-blind controlled study compared with a crossover design, the efficacy of cisapride with that of placebo in the treatment of constipation in 10 paraplegic patients. The trial consisted of a 5-week run-in period and two 12-week test periods, separated by a 4-week washout period. Total and segmental large-bowel transit times were assessed by means of radiopaque markers during the last week of the run-in and of the two test periods. Bowel frequency during run-in, placebo, and cisapride periods was, respectively, 2.9 · 2, 4.1 · 3, and 3.6 · 2.7 evacuations per week (NS). Neither the use of laxatives nor the modality of evacuation changed among the study periods. Oro-anal transit time during run-in, placebo, and cisapride periods was, respectively, 146 · 45, 93 · 49 (p < 0.01 vs. run-in), and 103 · 53 h (p < 0.02 vs. run-in; NS vs. placebo). The measurement of the large-bowel segmental transit times showed that transit through the right colon, left colon, and rectum did not differ during the three study periods. In conclusion, cisapride at the dosage of 10 mg four times a day was no more effective than placebo in improving bowel frequency and oro-anal or segmental large-bowel transit times in paraplegic patients.

The efficacy and safety of omeprazole, in 241 patients with active recurrent duodenal ulcer from 21 Italian centres, was studied in a multicentre double-blind randomized trial comparing 20 mg omeprazole o.m. or 40 mg famotidine nocte with endoscopic examination, symptom recording, laboratory screening and gastrin assay. In a per protocol analysis, the duodenal ulcer healing rates for omeprazole and famotidine, documented by endoscopy, were 62% (68/109) and 33% (39/117) after 2 weeks of treatment (P less than 0.001), 92% (96/104) and 80% (86/108) cumulative after 4 weeks (P less than 0.05), and 99% (102/103) and 92% (96/104) after 6 weeks (P less than 0.05), respectively. The results of this trial demonstrate that 20 mg omeprazole o.m. is superior to 40 mg famotidine nocte in duodenal ulcer healing.

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.

Antral G cell hyperfunction (AGCH) is a rare condition, often associated with severe duodenal ulcer disease poorly responsive to medical therapy. Up to now, no studies have been designed to investigate a possible role of medical treatment in the management of this syndrome. In this study we treated 9 AGCH patients with duodenal ulcer, unhealed with the prolonging standard doses of H2 antagonists (300 mg/day ranitidine or 800 mg/day cimetidine), with a nonantacid therapy, tripotassium dicitrato bismuthate (TDB). 6 out of 9 patients showed a complete healing after 8 weeks of treatment. The healing was irrespective to eradication of Campylobacter pylori. After 9 weeks' suspension of H2 blockers basal gastrin levels decreased significantly by 31.5%, whereas peak meal-stimulated levels, although decreased in 6 out 9 patients, were not significantly affected by the withdrawal of the H2 antagonists. Nonantisecretory therapy seems to be an efficacious alternative in the management of AGCH patients.

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.

Objective: The aim of this study was to assess whether a single noninvasive technique, ultrasonography, is able in vivo: 1) to evaluate the time-related patterns of gallbladder bile storage and emptying, and 2) to quantitate the amount of bile flux through the gallbladder (GB). Methods: Healthy volunteers were submitted to the simultaneous assessment of gallbladder volume variations by frequent serial ultrasonographic (US) measurements and of hepatic bile flow through the GB by quantitative cholescintigraphy (QC) during continuous i.v. infusion of 99 mTc-HIDA. An ad hoc mathematical analysis of US GB volume measurements was used to estimate the amount of bile flux through the GB. The QC-derived measurements of the flux of hepatic bile through the GB was used to substantiate the US-derived estimates. Results: The curves expressing the time-related GB handling of hepatic bile obtained independently from US and QC measurements were statistically equivalent, and both techniques showed that the patterns and the amount of hepatic bile handled by the gallbladder after meal ingestion is remarkably different during three successive phases. After meals, hepatic bile was mainly 1) stored in the GB in the first phase; 2) emptied from the GB in a second phase; and 3) stored in the GB in the third phase. The ultrasonographic analysis estimated that 1) 23.8 ± 12.5 ml (0.44 ± 0.11 ml/min), 5.1 ± 3.9 ml (0.15 ± 0.10 ml/min), and 33.2 ± 10.5 ml (0.53 ± 0.16 ml/min) of hepatic bile entered into the GB during the three successive postprandial phases, and 2) the entire amount of bile flowing bidirectionally through the cystic duct, during the observation period (132.6 ± 23.3 ml) was about five-fold greater than that estimated by the usually employed variables. Conclusion: The proposed mathematical analysis of frequent ultrasonographic measurements of the GB volumes enables one to estimate noninvasively the flux of bile through the gallbladder in humans.

Duplex-Doppler was used to visualize intestinal peristalsis in 30 patients with intestinal distension. The series included 12 patients with acute mechanical obstruction, 13 with long-standing mechanical obstruction, and five with paralytic ileus. The Duplex-Doppler recordings showed several patterns characterized by different degrees of intensity and frequency of the signals according to the type of obstruction, its duration, and the site of Doppler sampling relative to the obstructed segment. Duplex-Doppler evaluation provided both qualitative and quantitative data about intestinal peristalsis, allowing differentiation between mechanical and paralytic ileus. The visualization of intestinal segments having different degrees of peristaltic activity proved useful in localizing the site of mechanical obstruction.

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; P0.001) 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.

This study assessed the effect of prolonged intraluminal acidification on the motor activity of the entire oesophageal body (under controlled conditions). Intraoesophageal pressures were recorded in 13 endoscopy negative subjects with gastro-oesophageal reflux disease in whom saline, HC1 0.1 N, and saline solutions were infused (1.5 ml/min) blindly in the oesophageal body, 6 cm distal to the upper oesophageal sphincter for three consecutive periods of 45 minutes each. These findings were compared with those of a control group. Intraoesophageal acidification caused an increase in the deglutition frequency (p < 0.02), the occurrence of multipeaked waves (p < 0.04) as well as a decrease of the propagating velocity (p < 0.04) of the primary peristaltic contractions. Furthermore, intraoesophageal acidification determined an increase, at all levels of the oesophagus, of the duration (p < 0.04) and, more noticeable in the proximal oesophageal body, of the amplitude (p < 0.02) of primary peristaltic contraction waves. In conclusion prolonged intraoesophageal acidification can considerably affect frequency of deglutition, morphology, and propagating patterns of primary peristaltic contractions. This study shows that these effects are independent from volume distension of the oesophagus and supports the presence of acid sensitive receptors in the oesophageal mucosa.

The location and mobility of pelvic floor in different body positions and their relation to age and gender was assessed in 117 patients (19 men, 98 women, age range 10-77 years) with chronic nonorganic constipation (defined as less than three bowel movements per week for at least three years) by means of defocography. Eleven females (age range 16-69 years), without gastrointestinal symptoms, affected by noninvasive carcinoma of the cervix represented a control group. Pelvic floor location was measured as the distance in centimeters of the anorectal junction from the pubococcygeal line; pelvic floor mobility was measured during squeezing, straining, and defecation assuming the pelvic location at rest as zero reference. Pelvic floor location and mobility did not differ between controls and constipated patients. In both groups pelvic floor location at rest was significantly higher (P = 0.001) with patients lying down than sitting up, whereas pelvic floor mobility during squeezing was greater with the patients sitting up than lying down (P = 0.003). In both positions, pelvic floor location at rest was significantly lower (P = 0.01) in females than in males. Pelvic floor mobility during squeezing was significantly different between gender. Parity and hysterectomy did not appear to affect pelvic floor location. Data emerging from this study indicate that body position is one of the major determinants of the pelvic floor location.

The aim of this study was to evaluate in Crohn's disease the possible usefulness of alpha 1-antitrypsin clearance and fecal concentration in the early detection of postoperative asymptomatic recurrence. Eleven adult patients with small bowel Crohn's disease undergoing elective resection were enrolled in the study and prospectively followed for one year. Three, six, and 12 months after surgery the alpha 1-antitrypsin clearance and fecal concentration were measured, and the disease activity was assessed. All patients were free of active symptoms throughout the study. One year after surgery small bowel radiology was performed in all patients. Radiographic evidence of recurrent macroscopic disease was found in five of the 11 patients. Three months after surgery both alpha 1-antitrypsin clearance and fecal concentration were significantly lower (P less than 0.01) than before surgery. There was no difference at this time between patients with recurrence and those with no recurrence. In patients with recurrence both alpha 1-antitrypsin clearance and fecal concentration significantly increased at six months in comparison with the values at three months (P less than 0.02). Both measurements were significantly higher at six and 12 months in this group of patients than in those with no recurrence and in normal controls (P less than 0.01). At six and 12 months alpha 1-antitrypsin clearance was above the upper normal limit in all patients with recurrence. We conclude that fecal alpha 1-antitrypsin clearance is a noninvasive, inexpensive, sensitive marker of asymptomatic recurrence in CD patients who are under regular supervision after surgery.

SUMMARY Background: Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis. Methods: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. Results: Fourteen patients on SCFA improved (overall score 11.3 ± 2.0 vs. 7.4 ± 3.5) as compared to five in the placebo group (overall score 10.0 ± 1.9 vs. 8.9 ± 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pre-trial differences between the two groups. Conclusion: the present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.

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.

Picarelli A, Di Tola M, Sabbatella L,Mastracchio A, Trecca A, Gabrielli F, Di Cello T,Anania MC, Torsoli A (University of Rome ‘‘LaSapienza’’, Rome, Italy). Identification of a newcoeliac disease subgroup: antiendomysial and anti-transglutaminase antibodies of IgG class in theabsence of selective IgA deficiency. J Intern Med2001; 249: 181–188.Objective. The aim of the present study was toincrease the sensitivity of the antiendomysial anti-body (EMA) test by evaluating also EMAs of IgG1isotype.Design and subjects. Over the last 2 years, serumEMAs IgA and IgG1 were determined in 1399patients, referred to our gastrointestinal unit due toclinical suspicion of malabsorption. Serum anti-tissue transglutaminase (tTG) antibodies IgA andIgG, as well as total IgA levels, were also investigated.Furthermore, EMAs IgA and IgG1 were evaluated inbiopsy culture supernatants. Biopsy specimens werealso admitted to histological and immunohistochem-ical evaluation. Twenty-six patients with gastroente-rological disease other than coeliac disease (CD) wereused as a disease control group. Ninety-nine blooddonors were used as a healthy control group.Results. Diagnosis of CD was based on histologicalfindings in the 110/1399 patients showing EMAIgA positivity, and in a further 56/1399 patientspresenting both EMA IgA and IgG1 positivity in seraas well as in culture supernatants. Of the remaining1233 EMA IgA-negative patients, 60 showed onlyEMA IgG1 positivity both in sera and in culturesupernatants. It is noteworthy that anti-tissuetransglutaminase antibodies IgG (anti-tTG) werepositive in all 60 EMA IgG1-positive patients aswell. By contrast, a selective IgA deficiency wasfound in only 11 out of the 60 EMA IgG1-positivepatients. Villous height/crypt depth ratio was < 3:1in 38 of the 60 EMA IgG1-positive patients (63.3%),whilst overexpression of ICAM-1 and CD25 wasobserved in all these patients.Conclusions. In this study, we observed a group ofCD patients who were EMA IgG1-positive even inthe absence of EMA IgA positivity and IgA defici-ency. The diagnosis was based on the finding of thegluten-dependent clinical and histological featurestypical of CD. Data emerging from the presentinvestigation thus suggest that the prevalence ofCD should be reassessed and that the determinationof EMA IgG1 could offer a new tool in the diagnosticarmamentarium of CD.Keywords: coeliac disease, antiendomysial antibod-ies, IgG isotype, tissue transglutaminase.

The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB “contractor” patients with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P

Measurement in faeces of the principal nutrients, fat (F), water (W) and nitrogen (N) is useful to assess digestive and absorptive functions and thus to monitor patients' progress and response to therapy in malabsorption/maldigestion syndromes. Presently available techniques are not ideal in clinical practice for serial analysis as they are time-consuming and require unpleasant and prolonged handling of the stools. The present study aimed to evaluate the accuracy and precision of near infrared reflectance analysis (NIRA) in routine measurement of fat, nitrogen and water faecal contents compared with Van de Kamer (VDK), Kjeldahl (KJ) and gravimetric-by-lyophilization (LY) methods, respectively. Fat, nitrogen and water (n = 34), were measured in the 1-day faecal collections of 15 healthy subjects and 19 patients (10, coeliac disease; 6, chronic pancreatitis; 3, small-bowel Crohn's disease). A highly significant linear correlation was found between VDK, KJ, LY methods and NIRA analysis. Very low values of intra-assay coefficient of variation indicated a remarkable analytical precision of NIRA. A recovery test at different concentrations in the useful range was performed for all three nutrients, to assess the accuracy of NIRA. Quantitative recoveries were between 95 and 105%. Data from the present study show that NIRA analysis is reproducible, accurate and rapid (less than 1 min). These characteristics make NIRA serial analysis useful in clinical practice to monitor progress and response to therapy in patients with malabsorption/maldigestion syndromes.

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.

The technique of perendoscopic manometry was used to study the motor patterns of the ileocecal junction and distal ileum. An expert endoscopist cannulated the distal ileum of 20 unsedated subjects in 260 ± 252 (mean ± SD) seconds, causing no discomfort beyond that of an ordinary colonoscopic examination. No sphincter-like motor activity was detected at the ileocecal junction, and four distinct motility patterns were identified in the distal ileum: (1) tone variations, (2) slow phasic contractions, (3) regular rapid phasic contractions, and (4) prolonged rapid phasic contractions. Previous appendectomy and insertion of the colonoscope into the distal ileum to position the manometric catheter did not affect the manometric recordings. Perendoscopic manometry of the distal ileum was compared with transileostomy manometry in 9 subjects. Perendoscopic and transileostomy manometric recordings showed the same motor patterns except for a longer occurrence of tone variations with perendoscopic manometry. In conclusion, this study shows that perendoscopic manometry of the distal ileum and ileocecal junction is feasible; recorded motor patterns are not affected. (Gastrointest Endosc 1994;40:685-91.)

This study aimed to evaluate whether serial ultrasound measurements of antral volumes are reproducible and, if so, whether they are representative of the entire gastric contents and reliably measure gastric emptying. The antral volume was measured in man after oral and intragastric administration of known amounts of 5% glucose solutions, and on two separate occasions in the same subjects, after the ingestion of a standardised solid-liquid meal (1050 kcal). Antral volume measurements were performed in both supine and upright positions; inter- and intraobserver measurement errors were also assessed. After ingestion or intragastric administration of equal amounts of liquid, antral volumes determined by ultrasound showed a wide intersubject variability. In each individual subject, however, a linear trend was found between the antral volume and amount of ingested or administered liquid. Intrasubject variability of antral volume measurements was at its minimum in fasting conditions and 300 minutes after ingestion of the solid-liquid meal. Intra- and interobserver variations and whether the patient was erect or supine did not affect measurements of antral volumes. These results support the use of real time ultrasound in determining the gastric emptying time. Results at fasting and 300 minutes after a solid-liquid meal are stable end points of measurement.

In the present study we have investigated whether in patients with Crohn's 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 less than 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 less than 0.005). These data indicate that the clinical course of Crohn's 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.

Previous manometric studies of the ileocolonic junction were performed without assessing the precise spatial relationship between recording sensors and ileocolonic junction. In the present study, the motor activity of the ileocolonic junction was recorded using manometric sensors localized under direct colonoscopic control in 11 patients (4 men, 7 women; mean age, 55 years) referred for hematochezia with normal stool frequency. No medications were administered before and during endoscopy. A perfused catheter (OD 1.7 mm, with three side holes 4 mm apart and marked by evenly spaced black rings in the distal 6 cm) was passed through the biopsy channel of the endoscope and advanced through the ileocolonic junction and 6 cm into the ileum. The catheter was then withdrawn into the cecum by 1-cm steps, and motor activity was recorded for 4–6 minutes at each station. A single catheter taped to the endoscope continuously recorded cecal pressure. An ileocecal pressure gradient could not be identified in the majority of subjects; individual values ranged from −8 to +4 mm Hg, and gradients were maintained over the entire length of the ileum. In the distal ileum, tonic and phasic pressure waves were detected. Tonic variations were present for 70.1% of the recording time, either alone (44%) or together with phasic waves (56%). Phasic waves were present for 10.3% of the recording time and, according to their duration, were subdivided into those compatible with the rate of ileal slow waves and prolonged waves not compatible with the rate of ileal slow waves. Regular phasic waves could be either isolated or in clusters; prolonged waves were always isolated. A similar proportion of regular (27.9%) and prolonged (31.2%) phasic waves propagated aborally along the ileum or from ileum to cecum. Clusters presented an average of 8.7 ± 0.6 peaks/min, and 44% of them propagated aborally. The manometric characteristics did not vary between the segments 5-3 cm and 2-0 cm proximal to the ileocecal junction. In conclusion, a powerful ileocecal sphincter was not detected at the human ileocecal junction, and motor activity of the distal ileum was characterized by tonic changes and rapid phasic contractions.

Imaging is the science of seeing the unseeable. Its application in medicine is to both diagnostic procedures and the evaluation of the effects of treatment, as well as to education and communication. Imaging makes use of radiation not visible to the human eye; when directed towards the patient’s body by means of the appropriate device, this produces a result that is directly perceptible. In gastroenterology, imaging techniques are employed at various levels. At one level this is represented by methods such as abdominal echography and abdominal X-ray, which are often requested immediately after hospital admission for diseases of the biliary tract, pancreas, or intestine. Endoscopy, conventional radiology with contrast media, microscopy, and radioisotope imaging belong to a second level. Computed axial tomography and nuclear magnetic resonance represent a third level of investigation. The great interest among gastroenterologists in imaging techniques is also shown by the inclusion of a special heading, “Imaging in Gastroenterology,” in the new journal Gastroenterology International.

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 less than 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.

Bile is secreted continuously, although at various rates, from the liver into the biliary tree; whether bile is then diverted into the gallbladder or the duodenum depends on the relative resistance to flow mainly determined by the contractile state of the gallbladder and the choledochoduodenal junction. The resistance of the sphincter of Oddi is considered the principal factor in the regulation of the intracholedochal pressure and, therefore, of the common bile duct-gallbladder pressure gradient; however, filling of the gallbladder may also take place after total sphincterotomy. During late phase II of the interdigestive period intragallbladder pressure increments favour flow of a small amount of bile into the bile duct and, through the sphincter of Oddi, into the duodenum. During phase III of the interdigestive period maximal frequency of sphincter of Oddi phasic contractions blocks bile flow into the duodenum. After a meal tonic active contraction of the gallbladder causes an increase of the intraluminal pressure followed shortly by volume reduction of the viscus and outflow of bile accompanied by an intracholedochal pressure increment. Gallbladder hypotonia is a relevant factor in the pathogenesis of gallbladder stones. The gallbladder acts as a reservoir, since intracholedochal pressure is higher after than before cholecystectomy, and this may explain post-cholecystectomy choledochal dilatation and biliary pain by obstructed bile flow due to either stenosis or dyskinesia of the sphincter of Oddi.

• ABNORMAL GASTROINTESTINAL TRANSIT IN RATS WITH CHRONIC ILEITIS. V M Pifieiro-Carrero, C Sullivan, NAli , J Goldhill, T Shea-Donohue. Departments of Pediatrics and Medicine, USUHS, Bethesda, MD. Patients with Crohn's disease often complain of postprandial abdominal pain and early satiety, These symptoms may contribute to the anorexia and poor oral intake seen in these patients. We have previously demonstrated that acute ileitis eausas marked alterations in intestinal myoelectric activity. Our objective was to further investigate intestinal motility in an animal model of chronic ileitis. METHODS: Inbred female Lewis rats (180 220g) were sensitized with a s.c. injection of trinitrnbenzene sulfonic acid (TNBS, 2.5 rag) mixed with incomplete Freund's adjuvant or adjuvant alone. Seven days later, TNBS (100 mg/kg) in 50% ethanol or saline (1 ml) was given intraluminally 30 cm proximal to the ileocecal junction. The rats were studied 3 or 7 days later. Small intestinal transit (SIT, geometric center) and gastric emptying (GE, % emptied from stomach) were determined by measuring the progress of an 5= IG bolus (0.2 mL) of Cr (5 p_Ci/rat). After 25 min, the rats were sacrificed and the intestine was divided into 10 equal segments and counted..RESULTS: In TNBS-treated rats, microscopic findings on day 3 included mucosal atrophy, edema of lamina propria and PMN infiltration. By day 7, rats had developed thickened bowel wall, adhesions, intestinal perforation (33%) and histologic findings of lymphocytic infiltration and circular muscle hypertrophy. GE was reduced by 44% at 3 days but returned to normal by day seven. SIT was delayed on both days.

The introduction of the microprocessor technology into the field of biomedical instrumentation puts a problem of considerable interest, since great advantages are expected from the new technique both as regards project completion time and final performance capabilities of the instrumentation. Another point to be stressed from the point of view of industrial application of microprocessors, is that no definite leadership exists at the moment in this field; which means that a unique opportunity is now offered to the European and particularly to the Italian industry.

During the last 25 years relevant data which contribute to the clarification of pancreatico-biliary sphincter function, have been derived from physiological and pharmacological studies, and from cinefluorographic and manometric observations in man. The human sphincter of Oddi appears to be a complex device, relatively independent of the duodenum and endowed with a primarily occluding action. Perendoscopic, pre- and post-operative sphincter of Oddi manometry has opened up new prospectives for a better definition of old concepts, such as biliary dyskinesia and post-cholecystectomy syndrome. In addition, manometric measurement may provide a more rational basis for sphincterotomy, and could allow endoscopists and surgeons to objectively evaluate the extent of sphincter splitting.

The aim of the present investigation was to study the efficacy and safety of famotidine (MK-208), a new, potent, histamine H2 receptor antagonist, in promoting the healing of active gastric

A six month, double blind, controlled study was performed in 107 asymptomatic duodenal ulcer patients who, after short term cimetidine treatment, showed complete or incomplete endoscopic healing. Patients were stratified according to the type of healing and randomly allocated to cimetidine (200 mg at lunch, 400 mg at bedtime) or placebo. Endoscopic examinations were carried out after six months or when symptoms recurred. Eighty seven patients completed the maintenance trial. Of the 56 patients admitted to the study with complete healing, 30 were placed on cimetidine and 26 on placebo. Of the 31 patients admitted with incomplete healing, 15 were placed on cimetidine, and 16 on placebo. Results showed that, regardless of maintenance treatment, patients with incompletely healed ulcers had a higher ulcer crater recurrence rate, than patients with complete healing (71% vs 34%; p less than 0.005). A significantly higher ulcer crater recurrence was observed in incompletely healed ulcer patients, even when cimetidine or placebo treatment groups were considered separately. Irrespective of the type of healing, ulcer crater recurrence was more frequent in placebo treated patients than in those treated with cimetidine (67% vs 29%; p less than 0.001). We conclude that, in order to prevent a high ulcer recurrence rate, maintenance treatment should start only after the assessment of a complete endoscopic healing of duodenal ulcers.

Lower oesophageal sphincter response to infusion of graded doses (0.003--0.050 microgram kg-1min-1) of pentagastrin was evaluated in four antrectomised patients as well as in six healthy subjects and seven achalasic patients in whom inhibition of antral gastrin release was maintained by continuous acidification (HC1 0.1 N) and aspiration of gastric antrum. In normal subjects and in antrectomised patients doses of pentagastrin required for half-maximal gastric acid secretion (0.012 microgram kg-1min-1) produced statistically significant increases of LES pressure. In achalasic patients, the infusion of pentagastrin did not affect LES pressure. These data seem to indicate that gastrin plays, at least in some degree, a physiological role in the regulation of LES tone. Insensitivity of LES to pentagastrin in achalasia suggests that the raised sphincter pressure in this disorder can not be attributed to gastrin.

The relationship between intraoesophageal pH value and motor activity of the lower oesophageal body and sphincter was investigated by simultaneous evaluation of intraluminal pressure and pH in 13 patients complaining of heartburn and regurgitation. One hundred and thirty one episodes of gastro-oesophageal reflux were recorded. One hundred and eighteen (90.1%) were preceded by a swallow (one to 12 seconds), 13 reflux episodes (9.9%) were not preceded by a swallow. Gastro-oesophageal refluxes preceded by swallow were accompanied by an equal number of normal and abnormal primary peristaltic sequences and, while recording at level of the lower oesophageal sphincter, occurred during inhibition of the sphincter. Frequency of abnormal primary peristalsis increased (p less than 0.01) during periods of low intraluminal pH (less than 5.0). An increase of at least 0.5 U in intraluminal pH occurred with 45.2% of normal primary peristalsis, 29.3% of abnormal primary peristalsis, 4.3% of secondary peristalsis, 3.5% of non-peristaltic contractions. The results of this study indicate that in patients with symptoms of reflux oesophagitis, gastro-oesophageal reflux appears to be related to swallow-induced lower oesophageal sphincter inhibition and not related to abnormal motor activity of the distal oesophageal body where an increased frequency of abnormal primary peristalsis appears to occur during low intraluminal pH and primary peristalsis appears to be the most important mechanism of oesophageal clearing.

Studies were performed on the mechanical activity of iso- and antiperistaltic colon segments used to replace the esophagus. Transplants were challenged with a semiliquid bolus and/or a 0.1 N HCl solution, considered as common stimuli for an in situ esophagus, and the mechanical activity was investigated by means of synchronized manometric and cinefluorographic recordings. Basal activity of the interposed colon was limited to occasional monophasic waves of the segmenting type; the acid solution and the semiliquid bolus constantly elicited a peristaltic motor response transporting the contents to the gastric fundus or, in antiperistaltic colon, from the distal to the proximal part.

Basal frequency of sphincter of Oddi phasic contractility has been repeatedly measured during endoscopic manometry and reported to range, in control subjects, from (M +/- SE) 3.0 +/- 0.6 to 7.5 +/- 0.7 c/min. Recently, high frequency (greater than 8 c/min) phasic contractions or absence of phasic activity were recorded in patients with postcholecystectomy or pancreatic complaints, possibly suggesting a sphincter of Oddi dysfunction. In the present study, sphincter of Oddi (biliary tract) phasic contractility was measured by perendoscopic manometry in 13 subjects without specific clinical symptoms of biliopancreatic disease and with a normal common bile and pancreatic duct at ERCP. Four T-tube patients with no evidence of common bile duct stones or papillary stenosis were studied for comparison (transductal sphincter of Oddi manometry). Basal frequency was found to range from 0 to 7 c/min (M +/- SE: 2.99 +/- 0.46) in perendoscopic manometry (85 min of recording time) and from 0 to 12 c/min (2.0 +/- 0.3) in transductal manometry (2546 min of recording time). Long lasting transductal recordings also showed that frequency of activity derived from the sphincter area varied cyclically in close relation with the duodenal migrating motor complex. It is concluded that the sphincter of Oddi in man is likely to participate in the interdigestive gastrointestinal motor activity and that short perendoscopic recordings may not be representative of the overall sphincter of Oddi activity.

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.

The effect of intraluminal pH on motor activity of the lower oesophageal body was studied in patients with pathological gastro-oesophageal reflux. Liquid boluses with a pH range of 6.98-1.1, infused in the distal oesophagus of 21 patients during manometric recording of motor activity, elicited either secondary peristalsis or simultaneous contractions. Acid pH did not affect the threshold of distension required to elicit secondary peristalsis. Oesophageal responses to volumes of instillate did not differ in patients with normal and abnormal acid clearing test, nor in patients with a negative and positive acid perfusion test.

A multicenter study that involved 15 Italian institutions was carried out to compare the efficacy and safety of famotidine 40 mg at bedtime, famotidine 20 mg b.i.d., famotidine 40 mg b.i.d., and ranitidine 150 mg b.i.d. in promoting the healing of acute duodenal ulcer. Two hundred and twenty-four patients with endoscopically proven duodenal ulcer were randomly allocated into four treatment groups. Efficacy results for the four groups were similar at weeks 2, 4, and 8 of therapy. At week 8, the percentage of patients healed in each group was as follows: 92% in the famotidine 40-mg bedtime group, 97% with 20 mg b.i.d., 93% with 40 mg b.i.d., and 90% with ranitidine 150 mg b.i.d. Day pain and night pain were markedly reduced in all four groups, antacid consumption fell considerably, and therapy was generally well tolerated. The adverse experiences evaluated by the investigator as possibly, probably, or definitely related to test medication were rare and moderate.