Ugo Germani

Upper gastrointestinal motor activity in patients with slow-transit constipation. Further evidence for an enteric neuropathy.

Recent evidence indicates that patients complaining of severe chronic idiopathic constipation may have motor abnormalities not limited to the colon. We studied by manometric means gastric and small bowel motility in a homogeneous group of patients with chronic idiopathic constipation ie, the slow transit type. Twenty-one patients were recruited for the study and compared to 33 healthy subjects. Manometric examination was carried out for about 5 hr fasting and 1 hr after a standard meal. Analysis of the manometric tracings revealed during fasting no abnormalities in number and configuration of migrating motor complex with respect to controls. However, in 70% of patients motor abnormalities were detected, represented by bursts of nonpropagated contractions and discrete clustered contractions. After feeding, the patient group displayed a significantly shorter antral motor response to the meal with respect to controls; moreover, intestinal bursts of nonpropagated contractions were found in 19% of patients, and 14% of them had an early return of the activity fronts. We conclude that patients with slow transit constipation frequently display motor abnormalities of the upper gut. These findings further strengthen the concept that this condition may represent a panenteric disorder.

Endoluminal Instillation of Bisacodyl inPatients with Severe (Slow Transit Type)Constipation Is Useful to Test Residual ColonicPropulsive Activity

Background: Chronic constipation is a frequent symptom among the general population, and a minority of cases do not respond to any therapeutic measures, except surgery. The purpose of this study was to test the residual colonic motor propulsive activity with a pharmacologic stimulus in a series of patients referred for severe constipation. Patients: Twenty-five chronically constipated patients, slow transit type, age range 16–71 years, unresponsive to conventional medical treatment and referred for functional evaluation, entered the study. Methods: Colonic manometry by means of an endoscopically positioned probe was carried out in all patients. Following a basal recording period, a placebo solution followed by 10 mg bisacodyl solution was infused into the colon through the more proximal recording port. Results: After bisacodyl infusion, about 90% of patients showed a motor response characterized by the appearance (within on average 13 ± 3 min) of one or more high-amplitude propagated contractions, the manometric equivalent of mass movements, and about 75% of these were followed (mean 18.5 ± 4 min) by defecation. Conclusions: Physiological and pharmacological testing of colonic motor activity may be important in severely constipated patients, especially in those labeled as ‘intractable’, in whom more in depth investigation planning may encourage further therapeutic efforts.

Gluten-Free Diet Normalizes Mouth-to-Cecum Transit of a Caloric Meal in Adult Patients with Celiac Disease

The mechanisms responsible for boweldisturbances in celiac disease are still relativelyunknown. Recent reports suggested that small bowel motorabnormalities may be involved in this pathologicalcondition; however, there are no studies addressing smallbowel transit in celiac disease before and after agluten-free diet. We studied the mouth-to-cecum transittime of a caloric liquid meal in a homogeneous group of celiac patients presenting with clinical andbiochemical evidence of malabsorption and complaining ofdiarrhea. Sixteen patients were recruited andinvestigated by means of hydrogen breath test through ingestion of 20 g lactulose together with anenteral gluten-free diet formula. A urinary D-xylosetest was also done in each patient. Both breath testsand D-xylose tests were carried out basally and after a period of gluten-free diet. Twenty healthyvolunteers were recruited as a control group andunderwent the same breath testing. At the time of thediagnosis, mouth-to-cecum transit time was significantly prolonged in celiacs with respect to controls(243 ± 10 vs 117 ± 6 min, P = 0.0001). TheD-xylose test was also abnormal (average urinaryconcentration 2.8 ± 0.25 g, normal values>4.5). No correlation was found in patients between mouth-to-cecum transit timeand urinary D-xylose output (r = 0.22). After thegluten-free diet period, mouth-tocecum transit time inceliacs was significantly reduced compared to prediet transit (134 ± 8 vs 243 ± 10 min,P = 0.0001) and did not show statistical difference whencompared to that found in controls (P = 0.1). TheD-xylose test reverted to normal in all but twosubjects, who were found to be noncompliant with the diet.Mouth-to-cecum transit time is significantly prolongedin patients affected by untreated celiac disease whencompared to healthy controls. This alteration might notbe correlated to intestinal malabsorption, and theprolonged orocecal transit could be due to impairedsmall bowel function (deranged motility?). Sinceintestinal transit returned to normal values after an adequate gluten-free period, a link with severeactive mucosal lesions is suggestive.

Esophageal Manometric Abnormalities in Parkinson's Disease

Abstract. The gastrointestinal tract, and especially the esophagus, is frequently involved in neurological diseases; however, objective studies of gut motor function are few. We carried out an esophageal manometric study in 18 patients with various stages of Parkinsons disease (4 stage I, 4 stage II, 7 stage III, and 3 stage IV) to evaluate the function of the viscus in this disease. Clinical assessment showed that 61% complained of esophageal symptoms such as dysphagia, acid regurgitation, pyrosis, and noncardiac chest pain. Manometric abnormalities were documented also in 61% patients, and were represented by repetitive contractions, simultaneous contractions, reduced LES pressure, and high-amplitude contractions. However, only 33.3% of patients had both symptoms and manometric abnormalities. We conclude that esophageal motor abnormalities are frequent in Parkinsons disease, and may appear at an early stage of the disease.

Cisapride and erythromycin prokinetic effects in gastroparesis due to type 1 (insulin-dependent) diabetes mellitus

Erythromycin, a macrolide antibiotic, has been shown to have gastric prokinetic effects and has been proposed as an alternative therapeutic option for diabetic gastroparesis. However, its efficacy has not yet been compared with that of other prokinetic drugs.

Gastric emptying of solids in patients with nonobstructive Crohn's disease is sometimes delayed.

To date, only a few studies of gastric emptying in Crohns disease have been published in the literature. This might be clinically important because slow-release drug formulations are increasingly available for treatment. Studies in children with gastric involvement suggest that gastric emptying may be delayed in this condition. We studied the scintigraphic gastric emptying of 21 adult patients with nonobstructive Crohns disease and without gastric or duodenal involvement by the disease, compared with that of 20 healthy volunteers. Overall, no significant differences were found, but subgroup analysis showed that symptomatic patients [half-time (t1/2) 133 +/- 75.9] and those with colonic involvement (t1/2 127.2 +/- 64) had a significantly (p < 0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p < 0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohns disease and in those with colonic involvement. This may have therapeutic implications.

Flatus-related colorectal and anal motor events

Although complaints of excessive “gas” symptoms are frequently encountered in clinical practice, the physiologic and pathophysiologic grounds of flatus events are poorly understood, partly because of the social taboos associated with the topic and partly because of technical difficulties in measuring flatus. For these reasons, we studied the colorectal and anal motor events occurring during artificially evoked flatus events and compared them to those that occurred spontaneously. Five healthy male volunteers were studied by multilumen probes placed in the left colon and rectum and across the anal canal, to observe the flatus-related motor events that occurred after instillation of air into the colon. Flatus-related spontaneously occurring motor events were also checked in 24-hr motility tracings obtained in three patients with functional bowel disorders. Analysis of the tracings showed that both artificially induced and spontaneously occurring flatus-related motor phenomena were characterized by colonic propagated contractions associated with a rise in rectal pressure and early relaxation of the anal sphincter, in a sequence resembling that observed following swallowing. Spontaneous flatus events were associated with colonic waves of lesser amplitude than those following insufflation of air into the colon.

Idiopathic megarectum in adults : an assessment of manometric and radiologic variables

Outlet obstruction is thought to be one of the major factors responsible for idiopathic constipation. However, outlet obstruction itself may be due to several mechanisms. Among these, the presence of a megarectum is a leading one. Pathophysiological studies in adult patients with idiopathic megarectum are scarce. We studied by manometric and defecographic means 15 adult subjects with idiopathic megarectum and severe chronic constipation. Twenty-five healthy volunteers of both sexes acted as controls. Manometric variables showed significant differences between patients and controls with respect to internal anal sphincter pressure (P=0.02), minimum relaxation volume (P<0.001), defecatory sensory threshold (P<0.001), mean rectal tolerable volume (P<0.001), and rectal compliance (P<0.001). An altered response to straining was observed in 46.6% of patients and in 12% of controls (P=0.04); the ability to expel a 50-ml balloon per anum was 13.3% in patients and 100% in controls (P<0.001). Although all patients opened the anorectal angle and had descent of the pelvic floor, thereby confirming an adequate expulsion effort, evacuation of contrast material appeared extremely difficult. In fact, no subject was able to expel more than 30% of the rectal contents during fluoroscopic screening. These results confirm previous hypotheses that idiopathic megarectum displays features of a neuropathic process as an underlying mechanism. Further studies are needed that also take into consideration the muscle tone component of the rectum in these patients.

Intact colonic motor response to sudden awakening from sleep in patients with chronic idiopathic (slow-transit) constipation.

PURPOSE: There are few data about the relationships between colonic motor behavior and higher brain functions, such as sleep. Previous studies were done in healthy subjects, and it is unknown whether patients with functional motor disorders of the colon behave differently. This study was designed to characterize colonic motor activity in patients with constipation, both during sleep and after sudden awakening, and to compare it with that of healthy subjects. Our working hypothesis was that patients with constipation would have an impaired response to sudden awakening. PATIENTS AND METHODS: Twelve chronically constipated women, 22 to 49 years old, were recruited for the study, and their data were compared with those obtained from 12 healthy female volunteers, 21 to 38 years old. Manometric studies were performed in the descending and sigmoid colon for 30 minutes during sleep (immediately before awakening) and 30 minutes after being awakened suddenly. A motility index was calculated before and after the stimulus. RESULTS: In both groups motility in the descending and the sigmoid colon was almost absent during sleep and significantly increased after sudden awakening. No difference in postawakening values was found between patients with constipation and controls. CONCLUSIONS: In patients with chronic constipation, the brain-gut control of some fundamental mechanisms governing colonic motility is preserved. These data suggest that the alterations of colonic motility described in chronic constipation may be caused by an intrinsic dysfunction of the viscus.

Effects of octreotide on manometric variables in patients with neuropathic abnormalities of the small bowel.

At present, there are few therapeutic options inpatients with chronic intestinal dysmotilities.Octreotide, a long-acting somatostatin analog, hasrecently been shown to be a potentially useful drug in this setting, being able to start activityfronts (AF) in the small bowel in both healthy subjectsand patients with intestinal motor disorders. We studiedthe effects of octreotide on manometric variables in 10 patients with chronic uppergastrointestinal symptoms and an intrinsic neuropathicdisorder of the small intestine. Gastrointestinalmanometry was carried out for 6 hr during fasting and 2hr after a standard 605-kcal mixed meal. Thereafteroctreotide, 50 μg subcutaneously was administered andthe recording session continued for a further hour.Analysis of the tracings during fasting showed that 44% of the AF were abnormal; octreotidesignificantly increased the hourly number of AF (2± 0.26 vs 0.67 ± 0.14, P < 0.0001) andtheir duration (8.33 ± 1.3 vs 6.12 ± 0.34min, P < 0.05) with respect to the baseline (fasting) period, and the propagation velocityalso significantly slowed (3.4 ± 0.4 vs 11± 0.6 cm/min, P < 0.05). After the drug, 80%of patients displayed two AF and 10% more than two AF;the first AF after octreotide was always abnormally propagated. Analmost complete inhibition of small bowel postprandialcontractile activity was observed in 80% of patients,and the remaining 20% showed decreases. In three subjects, octreotide injection evoked theappearance of pylorospasm. From these results weconclude that octreotide could be of some benefit inpatients with neuropathic disorders of the small bowel,although it remains to be established whether it is mostuseful in patients with more severe conditions,characterized by the complete absence of AF. Theappearance of pylorospasm may contribute to the delayedgastric emptying observed after the drug isadministered.