Comparison between small bowel manometric patterns and full-thickness biopsy histopathology in severe intestinal dysmotility.

BACKGROUND: Intestinal manometry is the current standard for direct evaluation of small bowel dysmotility. Patients with abnormal motility can either be diagnosed of pseudo-obstruction when there are radiological findings mimicking mechanical intestinal obstruction or of enteric dysmotility when these findings are absent. The aim of the present study was to prospectively compare small bowel manometric abnormalities with histopathological findings in intestinal full-thickness biopsies in patients with severe dysmotility disorders. METHODS: We investigated 38 patients with intestinal manometry and a subsequent full-thickness intestinal biopsy. Manometric recordings were read by 4 investigators and a diagnostic consensus was obtained in 35 patients. Histopathological analysis, including specific immunohistochemical techniques of small bowel biopsies was performed and compared to manometric readings. KEY RESULTS: Patients with abnormal intestinal manometry had abnormal histopathological findings in 73% of cases. However, manometric patterns did not match with the specific neuromuscular abnormalities. Among patients with a neuropathic manometry pattern and abnormal histopathology, only 23% had an enteric neuropathy, whereas 62% had neuromuscular inflammation, and 15% an enteric myopathy. On the other hand, patients with a myopathic manometry pattern all had abnormal histopathology, however, none of them with signs of enteric myopathy. CONCLUSION & INFERENCES: Small bowel dysmotility detected by intestinal manometry is often associated with abnormal neuromuscular findings in full-thickness biopsies. However, there is no correlation between the specific manometric patterns and the histopathological findings.

Colonic content: effect of diet, meals, and defecation.

BACKGROUND: The metabolic activity of colonic microbiota is influenced by diet; however, the relationship between metabolism and colonic content is not known. Our aim was to determine the effect of meals, defecation, and diet on colonic content. METHODS: In 10 healthy subjects, two abdominal MRI scans were acquired during fasting, 1 week apart, and after 3 days on low- and high-residue diets, respectively. With each diet, daily fecal output and the number of daytime anal gas evacuations were measured. On the first study day, a second scan was acquired 4 hours after a test meal (n=6) or after 4 hours with nil ingestion (n=4). On the second study day, a scan was also acquired after a spontaneous bowel movement. RESULTS: On the low-residue diet, daily fecal volume averaged 145 ± 15 mL; subjects passed 10.6 ± 1.6 daytime anal gas evacuations and, by the third day, non-gaseous colonic content was 479 ± 36 mL. The high-residue diet increased the three parameters to 16.5 ± 2.9 anal gas evacuations, 223 ± 19 mL fecal output, and 616 ± 55 mL non-gaseous colonic content (P<.05 vs low-residue diet for all). On the low-residue diet, non-gaseous content in the right colon had increased by 41 ± 11 mL, 4 hours after the test meal, whereas no significant change was observed after 4-hour fast (-15 ± 8 mL; P=.006 vs fed). Defecation significantly reduced the non-gaseous content in distal colonic segments. CONCLUSION & INFERENCES: Colonic content exhibits physiologic variations with an approximate 1/3 daily turnover produced by meals and defecation, superimposed over diet-related day-to-day variations.

Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites.

BACKGROUND: We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depends on the characteristics of the meal and the appropriateness of the digestive response. The aim of the present study is to identify metabolomic biomarkers of the cognitive response to meal ingestion. METHODS: In 18 healthy subjects, the response to a test meal (Edanec, 1 kcal/mL) ingested until maximum satiation (50 mL/min) was assessed. Perception measurements and blood samples were taken before, at the end of the meal, and 20 min after ingestion. The cognitive response and the hedonic dimension were measured on 10 cm scales. Metabolomic analysis was performed using nuclear magnetic resonance (NMR) spectroscopy and values of triglycerides, insulin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were determined using conventional laboratory techniques. KEY RESULTS: Ingestion up to maximum satiation induced sensation of fullness and decreased digestive well-being. The total amount ingested by each subject correlated with the basal sensation of hunger, but not with other sensations or blood metabolite levels. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043). Twenty-minutes after finalizing ingestion, triglyceride levels had significantly increased which correlated with the recovery in well-being (R = 0.48; p = 0.046) and the decrease in desire to eat a food of choice (R = -0.56; p = 0.016). The increase in lipids inversely correlated with abdominal discomfort (R = -0.51; p = 0.032). CONCLUSIONS & INFERENCES: Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites, which may serve as objective biomarkers of perception.

Colonic content in health and its relation to functional gut symptoms.

BACKGROUND: Gut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non-gaseous component may play a decisive role. METHODS: Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program. KEY RESULTS: In healthy subjects both gaseous (87 ± 24 mL) and non-gaseous colonic content (714 ± 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 ± 23 mL), but non-gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non-gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension. CONCLUSIONS & INFERENCES: In patients with functional gut disorders, abdominal distension is not related to changes in non-gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved.

Accumulative effect of food residues on intestinal gas production.

BACKGROUND: As mean transit time in the colon is longer than the interval between meals, several consecutive meal loads accumulate, and contribute to colonic biomass. Our aim was to determine the summation effect of fermentable food residues on intestinal gas production. METHODS: In eight healthy subjects, the volume of endogenous intestinal gas produced in the intestine over a 4-h period was measured by means of a wash-out technique, using an exogenous gas infusion into the jejunum (24 mL/min) and collection of the effluent via a rectal Foley catheter. The exogenous gas infused was labeled (5% SF6 ) to calculate the proportion of endogenous intestinal gas evacuated. In each subject, four experiments were performed ≥1 week apart combining a 1-day high- or low-flatulogenic diet with a test meal or fast. KEY RESULTS: Basal conditions: on the low-flatulogenic diet, intestinal gas production during fasting over the 4-h study period was 609 ± 63 mL. Effect of diet: during fasting, intestinal gas production on the high-flatulogenic diet was 370 ± 146 mL greater than on the low-flatulogenic diet (p = 0.040). Effect of test meal: on the low-flatulogenic diet, intestinal gas production after the test meal was 681 ± 114 mL greater than during fasting (p = 0.001); a similar effect was observed on the high-flatulogenic diet (599 ± 174 mL more intestinal gas production after the test meal than during fasting; p = 0.021). CONCLUSIONS & INFERENCES: Our data demonstrate temporal summation effects of food residues on intestinal gas production. Hence, intestinal gas production depends on pre-existing and on recent colonic loads of fermentable foodstuffs.

Intestinal gas content and distribution in health and in patients with functional gut symptoms.

BACKGROUND: The precise relation of intestinal gas to symptoms, particularly abdominal bloating and distension remains incompletely elucidated. Our aim was to define the normal values of intestinal gas volume and distribution and to identify abnormalities in relation to functional-type symptoms. METHODS: Abdominal computed tomography scans were evaluated in healthy subjects (n = 37) and in patients in three conditions: basal (when they were feeling well; n = 88), during an episode of abdominal distension (n = 82) and after a challenge diet (n = 24). Intestinal gas content and distribution were measured by an original analysis program. Identification of patients outside the normal range was performed by machine learning techniques (one-class classifier). Results are expressed as median (IQR) or mean ± SE, as appropriate. KEY RESULTS: In healthy subjects the gut contained 95 (71, 141) mL gas distributed along the entire lumen. No differences were detected between patients studied under asymptomatic basal conditions and healthy subjects. However, either during a spontaneous bloating episode or once challenged with a flatulogenic diet, luminal gas was found to be increased and/or abnormally distributed in about one-fourth of the patients. These patients detected outside the normal range by the classifier exhibited a significantly greater number of abnormal features than those within the normal range (3.7 ± 0.4 vs 0.4 ± 0.1; p < 0.001). CONCLUSIONS & INFERENCES: The analysis of a large cohort of subjects using original techniques provides unique and heretofore unavailable information on the volume and distribution of intestinal gas in normal conditions and in relation to functional gastrointestinal symptoms.

Intestinal gas homeostasis: disposal pathways.

BACKGROUND: Patients with functional gut disorders frequently complain of gas-related symptoms, but the role of intestinal gas in this context is not clear, because intestinal gas homeostasis is incompletely understood. Our aim was to compare the proportion of the gas produced by colonic fermentation that is evacuated per anus and that eliminated via alternative pathways. METHODS: In 20 healthy subjects, gas evacuated per anus was collected for 4 h after a standard flatulogenic test meal. Paired studies were performed without and with high-rate infusion of exogenous gas (24 mL/min) into the jejunum to wash-out of the gut the endogenous gas produced by bacterial fermentation. The exogenous gas infused was labeled (5% SF6) to calculate the proportion of endogenous gas evacuated. KEY RESULTS: In the experiments with gaseous wash-out, 1817 ± 139 mL of endogenous gas was produced over the 4-h study period. However, in the experiments without wash-out (basal conditions), 376 ± 43 mL were evacuated, indicating that only 23 ± 3% of the gas produced was finally eliminated per anus, while the rest (77 ± 3%) had been previously eliminated via alternative pathways. CONCLUSIONS & INFERENCES: Intestinal gas homeostasis is a highly dynamic process by which a large proportion of the gas produced by bacterial fermentation of meal residues is rapidly absorbed into the blood and/or metabolized by gas-consuming microorganisms, and only a relatively modest proportion is eliminated per anus. These data contribute to clarify the complex dynamics of intestinal gas and may help interpret the pathophysiology of gas-related symptoms.

Digestive, cognitive and hedonic responses to a meal.

BACKGROUND: Gut dysfunctions may be associated to digestive symptoms. We hypothesized that the gut can also originate pleasant sensations, and wished to demonstrate the hedonic component of the digestive response to a meal. METHODS: Healthy subjects (n = 42) were evaluated during basal fasting conditions and during experimentally induced fullness sensation (either by gastric distension or duodenal nutrient infusion). In each set of studies, a 240 mL test meal (12 kcal broth) and water, as inert control meal, were administered on separate days in a randomized, cross-over design. Gastric accommodation, the cognitive response and the hedonic dimension (both by 10 score scales) were measured 9 min before and 60 min after the meal. KEY RESULTS: In basal conditions, the test meal induced a significantly greater gastric relaxation than the control meal (166 ± 28 mL isotonic volume increase 67 ± 14 mL; p = 0.002). Both meals induced epigastric fullness (3.8 ± 0.7 score and 3.2 ± 0.8 score, respectively; p = 0.740), but contrary to the inert meal, with the active meal this conscious sensation had a pleasant dimension (digestive comfort increase by 1.3 ± 0.6 score with active meal vs -1.1 ± 0.6 decrease with inert meal; p = 0.015). Experimentally induced fullness was associated to a decrease in digestive well-being or abdominal discomfort, which improved only after the active meal but not the inert meal. CONCLUSIONS & INFERENCES: When appropriate conditions are met, the response to a meal includes a hedonic dimension involving pleasant sensation of digestive well-being.

Effect of a low-flatulogenic diet in patients with flatulence and functional digestive symptoms.

BACKGROUND: Diets rich in fermentable residues increase intestinal gas production. Our aim was to demonstrate the potential effects of diet on gas-related symptoms. METHODS: The effect of a low-flatulogenic test diet (restricted to foodstuffs low in fermentable residues; n = 15) was compared to that of a balanced control diet (Mediterranean type; n = 15) in 30 patients complaining of flatulence and other abdominal symptoms using a randomized parallel design. The following outcomes were measured daily: number of anal gas evacuations by an event marker, severity of gas-related symptoms by 0-10 scales, and sensation of digestive comfort by a -5 (unpleasant) to +5 (pleasant) scale. Measurements were taken pretreatment for 3 days on their habitual diet and for 7 days during the treatment phase. KEY RESULTS: No pretreatment differences were detected between patients allocated to the control or test diets. The test diet significantly reduced the number of gas evacuations (by 54 ± 10%; p = 0.002 vs basal diet) whereas the control diet had a lesser effect (reduction by 28 ± 9%; p = 0.059 vs basal diet; p = 0.089 vs test diet). Compared to the control diet, the test diet significantly reduced flatulence (by 48 ± 7% vs 27 ± 8%, respectively; p = 0.018), abdominal distension (by 48 ± 4% vs 22 ± 12%, respectively; p = 0.038), and enhanced digestive well-being (by 149 ± 18% vs 58 ± 22%, respectively; p = 0.006). CONCLUSIONS & INFERENCES: In patients with gas-related symptoms, a low-flatulogenic diet produces immediate beneficial effects with digestive, cognitive, and emotive dimensions. The number of gas evacuations is an objective biological marker of response to dietary treatment.

Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine.

BACKGROUND: Inhibitory neuromuscular transmission in the human colon is due to nitrergic and purinergic (P2Y1 -mediated) inputs. The aim of this study was to determine the mechanisms of neuromuscular transmission in different regions of the human small intestine. METHODS: Ileal (n = 6) and jejunal (n = 6) samples underwent histological examination and were studied using sharp microelectrodes in smooth muscle cells and conventional muscle bath techniques. Electrical field stimulation (EFS) was used to stimulate inhibitory neurons. KEY RESULTS: No histological abnormalities were found. Resting membrane potential was -39.7 ± 1.5 and -45.5 ± 2.1 mV in the jejunum and ileum, respectively. Slow waves and spontaneous contractions were recorded at a frequency of about 8-9 and 6-7 cpm in the jejunum and ileum, respectively. In non-adrenergic, non-cholinergic conditions, EFS caused an inhibitory junction potential and mechanical relaxation. Both responses were blocked by tissue incubation with the nitric oxide synthase inhibitor (Nω-nitro-l-arginine 1 mM) and the P2Y1 receptor blocker 2'-deoxy-N(6) -methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS2179; 10 µM). Both exogenous addition of sodium nitroprusside (1 µM) and the preferential P2Y1 receptor agonist ADPßS (1 µM) hyperpolarized and relaxed smooth muscle cells. MRS2179 (10 µM) blocked ADPßS-induced responses. CONCLUSIONS & INFERENCES: Similar to colon, inhibitory neurotransmission in the human small intestine is mainly mediated by purinergic (via P2Y1 receptors) and nitrergic inhibitory neurotransmission. Similar mechanisms of inhibitory neurotransmission are present in different regions of the human intestine.

Mechanisms of abdominal distension in severe intestinal dysmotility: abdomino-thoracic response to gut retention.

BACKGROUND: We previously showed that abdominal distension in patients with functional gut disorders is due to a paradoxical diaphragmatic contraction without major increment in intraabdominal volume. Our aim was to characterize the pattern of gas retention and the abdomino-thoracic mechanics associated with abdominal distension in patients with intestinal dysmotility. METHODS: In 15 patients with manometrically proven intestinal dysmotility, two abdominal CT scans were performed: one during basal conditions and other during an episode of severe abdominal distension. In 15 gender- and age-matched healthy controls, a basal scan was performed. KEY RESULTS: In basal conditions, patients exhibited more abdominal gas than healthy subjects, particularly in the small bowel, and the volume significantly increased during an episode of distension. During episodes of abdominal distension, the increase in abdominal content was associated with increased girth and antero-posterior abdominal diameter, as well as a cephalic displacement of the diaphragm, which reduced the height of the lung. The consequent reduction in the air volume of the lung was attenuated by an increase in the antero-posterior diameter of the chest. CONCLUSIONS & INFERENCES: Abdominal distension in patients with severe intestinal dysfunction is related to marked pooling of gut contents, particularly in the small bowel. This increase in content is accommodated within the abdominal cavity by a global and coordinated abdomino-phreno-thoracic response, involving an accommodative ascent of the diaphragm and a compensatory expansion of the chest wall.

Abdominal accommodation induced by meal ingestion: differential responses to gastric and colonic volume loads.

BACKGROUND: Using an experimental model of colonic gas infusion, we previously showed that the abdominal walls adapt to its content by an active phenomenon of abdominal accommodation. We now hypothesized that abdominal accommodation is a physiological phenomenon, and aimed to confirm that it can be induced by ingestion of a meal; a secondary aim was to determine whether the response to gut filling is region-specific. METHODS: In healthy subjects (n = 24) a nutrient test meal was administered until tolerated at a rate of 50 mL min(-1). Electromyographic (EMG) activity of the anterior wall (upper and lower rectus, external and internal oblique) was measured via four pairs of surface electrodes, and EMG activity of the diaphragm via intraluminal electrodes on an esophageal tube. To address the secondary aim, the response to gastric filling was compared with that induced by colonic filling (1440 mL 30 min(-1) anal gas infusion; n = 8). KEY RESULTS: Participants tolerated 927 ± 66 mL of meal (450-1500 mL). Meal ingestion induced progressive diaphragmatic relaxation (EMG reduction by 16 ± 2%; P < 0.01) and selective contraction of the upper abdominal wall (24 ± 2% increase in activity of the upper rectus and external oblique; P < 0.01 for both), with no significant changes in the lower rectus (4 ± 2%) or internal oblique (5 ± 3%). Colonic gas infusion induced a similar response, but with an overall contraction of the anterior wall. CONCLUSIONS & INFERENCES: Meal ingestion induces a metered and region-specific response of the abdominal walls to accommodate the volume load. Abnormal abdominal accommodation could be involved in postprandial bloating.

Double-balloon jejunal perfusion to compare absorption of vitamin E and vitamin E acetate in healthy volunteers under maldigestion conditions.

BACKGROUND/OBJECTIVES: The vitamin E derivative, α-tocopheryl acetate, is often included in formulations used in enteral nutrition. In this respect, we compared α-tocopherol and α-tocopheryl acetate absorption under 'maldigestion' conditions, such as occurring during enteral tube feeding, using differentially labeled RRR-[5,7-methyl-((2)H(6))]-α-tocopherol and RRR-[5-methyl-(2)H(3)]-α-tocopheryl acetate allowing direct comparison between free and esterified forms. SUBJECTS/METHODS: The two derivatives were given together in a single dose to six volunteers directly into the jejunum using a double-balloon perfusion system. Perfusion lasted for 1 h, and the collected blood and effluent samples were analyzed by liquid chromatography-mass spectrometry. RESULTS: In the isolated 20-cm length of exposed jejunum, on average ~ 6% of the two vitamin E forms were absorbed >1 h based on subtraction of effluent from influent. There was substantial difference in the absolute absorbed quantity between individuals, but no significant differences were observed in the absorption between the two labeled forms as assessed in the plasma. (2)H(3)-α-tocopherol was not present in the influent, but appeared in the effluent, indicating that the acetylated form of vitamin E is cleaved by brush border enzymes in the small intestine. CONCLUSIONS: This study shows that even in the absence of digestive enzymes and bile salts, the appropriately solubilized acetylated form of α-tocopherol exhibits the same bioavailability as free α-tocopherol. This suggests that both forms can be absorbed equally under maldigestion conditions such as present clinically during enteral tube feeding.

Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability.

BACKGROUND: Intestinal epithelial dysfunction is a common pathophysiologic feature in irritable bowel syndrome (IBS) patients and might be the link to its clinical manifestations. We previously showed that chronic psychosocial stress induces jejunal epithelial barrier dysfunction; however, whether this epithelial response is gender-specific and might thus explain the enhanced female susceptibility to IBS remains unknown. METHODS: Intestinal responses to acute stress were compared in age-matched groups of healthy women and men (n = 10 each) experiencing low background stress. A 20-cm jejunal segment, was perfused with an isosmotic solution, and intestinal effluents were collected under basal conditions, for 15 min during cold pain stress and for a 45-min recovery period. Epithelial function (net water flux and albumin output), changes in stress hormones, and cardiovascular and psychologic responses to cold stress were measured. KEY RESULTS: Heart rate and blood pressure significantly increased during cold pain stress with no differences between men and women. Adrenocorticotropic hormone and cortisol levels during cold pain stress were significantly higher in men. Basal net water flux and epithelial permeability were similar in men and women. Cold pain stress increased water flux in both groups (72 ± 23 and 107 ± 18 µL min(-1) cm(-1) , respectively; F(5, 90) = 5.5; P = 0.003 for Time) and, interestingly, this was associated with a marked increase of albumin permeability in women but not in men (0.8 ± 0.2 vs.-0.7 ± 0.2 mg/15 min; P < 0.0001). CONCLUSIONS & INFERENCES: Intestinal macromolecular permeability in response to acute experimental stress is increased in healthy women, a mechanism that may contribute to female oversusceptibility to IBS.

Accommodation of the abdomen to its content: integrated abdomino-thoracic response.

BACKGROUND: We previously showed that changes in intra-abdominal content induce a volume-dependent muscular response of the anterior abdominal wall and the diaphragm. We aimed to determine the contribution of the thorax to abdominal accommodation and the influence of the intra-abdominal expansion rate. METHODS: Gas (1440 mL total load) was infused into the colon of nine healthy subjects, while abdomino-thoracic perimeters (by tape measure), electromyography (EMG) activity of the diaphragm (via six ring electrodes over an esophageal tube in the hiatus), intercostals and anterior abdominal wall (via five pairs of surface electrodes) and the position of the diaphragm by ultrasonography were measured. Infusion rates of 24, 48, and 96 mL min(-1) were tested on separate days. KEY RESULTS: Gas infusion induced anterior abdominal wall contraction (18 ± 1% EMG increment; P < 0.001) with relatively modest girth increment (4.9 ± 0.9 mm; P = 0.001), diaphragmatic relaxation (by 15 ± 1%; P < 0.001) with cephalad displacement (by 23 ± 6 mm; P = 0.005), and intercostal contraction (by 19 ± 2%; P < 0.001) with increased thoracic perimeter (by 2.0 ± 0.5 mm; P = 0.009). Responses were similar with the three infusion rates. CONCLUSIONS & INFERENCES: Accommodation of intra-abdominal loads involves a volume-related integrated abdomino-thoracic response regardless of the expansion rate.

Functional gut disorders or disordered gut function? Small bowel dysmotility evidenced by an original technique.

BACKGROUND: This study aimed to determine the proportion of cases with abnormal intestinal motility among patients with functional bowel disorders. To this end, we applied an original method, previously developed in our laboratory, for analysis of endoluminal images obtained by capsule endoscopy. This novel technology is based on computer vision and machine learning techniques. METHODS: The endoscopic capsule (Pillcam SB1; Given Imaging, Yokneam, Israel) was administered to 80 patients with functional bowel disorders and 70 healthy subjects. Endoluminal image analysis was performed with a computer vision program developed for the evaluation of contractile events (luminal occlusions and radial wrinkles), non-contractile patterns (open tunnel and smooth wall patterns), type of content (secretions, chyme) and motion of wall and contents. Normality range and discrimination of abnormal cases were established by a machine learning technique. Specifically, an iterative classifier (one-class support vector machine) was applied in a random population of 50 healthy subjects as a training set and the remaining subjects (20 healthy subjects and 80 patients) as a test set. KEY RESULTS: The classifier identified as abnormal 29% of patients with functional diseases of the bowel (23 of 80), and as normal 97% of healthy subjects (68 of 70) (P < 0.05 by chi-squared test). Patients identified as abnormal clustered in two groups, which exhibited either a hyper- or a hypodynamic motility pattern. The motor behavior was unrelated to clinical features. CONCLUSIONS & INFERENCES: With appropriate methodology, abnormal intestinal motility can be demonstrated in a significant proportion of patients with functional bowel disorders, implying a pathologic disturbance of gut physiology.

Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial).

BACKGROUND: Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation. OBJECTIVE: To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine. METHODS: Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg(-1), to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric emptying [corrected] by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression. RESULTS: Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m(-2) (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P = 0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P = 0.004). From the best-fitted regression model (R (2) = 81%, P < 0.0001), a 10% increase in GE at 15 min induced on an average a 135 ± 43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P = 0.03) and insulin (P = 0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P = 0.01). Postprandial increase in CCK (P = 0.002) and PP (P = 0.02) was associated with postprandial symptoms. CONCLUSION: Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management.

Impaired intestinal gas propulsion in manometrically proven dysmotility and in irritable bowel syndrome.

BACKGROUND: Intestinal manometry is the current gold standard for diagnosing small bowel dysmotility; however, the functional significance of abnormal manometry is unknown. Our aim was to determine whether, and to what extent, intestinal gas propulsion is impaired in patients with manometrically proven dysmotility compared with healthy controls and patients with IBS. METHODS: Clearance and tolerance of a jejunal gas load (12 mL min(-1) for 2 h) were measured in 15 patients with severe abdominal symptoms and intestinal dysmotility evidenced by manometry, 15 patients with IBS and 15 healthy subjects. Thereafter, the effect of neostigmine (0.5 mg i.v. bolus) vs placebo (i.v. saline) was tested in six dysmotility patients. KEY RESULTS: After 2-h gas infusion, patients with dysmotility developed significantly more gas retention (717 +/- 91 mL) than IBS patients (372 +/- 82 mL; P = 0.0037) and healthy subjects (17 +/- 67 mL; P < 0.0001 vs dysmotility; P = 0.0060 vs IBS). Despite the greater retention in dysmotility patients, abdominal perception (2.5 +/- 0.6 score) and distension (7 +/- 2 mm girth increment) were similar to IBS (3.9 +/- 0.6 score and 7 +/- 2 mm, respectively). In dysmotility patients, neostigmine produced immediate clearance of gas, and by 30 min had reduced gas retention (by -552 +/- 182 vs 72 +/- 58 mL after saline; P = 0.008), abdominal symptoms (by -0.8 +/- 0.3 score vs 0.3 +/- 0.2 after saline; P = 0.019) and distension (girth change -5 +/- 1 mm; P = 0.003 vs-2 +/- 2 mm after saline). CONCLUSION & INFERENCES: Patients with manometric dysmotility have markedly impaired intestinal gas propulsion. In IBS patients, impaired gas propulsion is less pronounced but associated with concomitant sensory dysfunction and poor tolerance of gas retention.

Constipation: a potential cause of pelvic floor damage?

BACKGROUND: Pelvic floor damage is a major clinical problem usually attributed to obstetric injury. We speculated that constipation may also be an aetiological and preventable factor resulting from repeated stress on the perineum over many years, and this study aimed to test this hypothesis. METHODS: A total of 600 women attending a gynaecological clinic were assessed using a structured questionnaire gathering data on pelvic floor damage, constipation and obstetric trauma. Complete data were available on 596 subjects. KEY RESULTS: The prevalence of pelvic floor damage was 10% (61/596). In this group, constipation was identified in 31% (19/61) of women and obstetric trauma in 31% (19/61). In the group without pelvic floor damage, constipation was present in 16% (86/535) and obstetric trauma in 16% (83/535). In univariate analysis, pelvic floor damage was associated with age (OR: 1.05; 95% CI: 1.03-1.08; P < 0.0001), constipation (OR: 2.36; 95% CI: 1.31-4.26; P < 0.0001) and obstetric trauma (OR: 2.46; 95% CI: 1.37-4.45; P < 0.0028). In multivariate analysis, the OR for age was 1.05 (95% CI: 1.03-1.08; P < 0.0001), for constipation 2.35 (95% CI: 1.27-4.34; P < 0.0001) and for obstetric trauma 1.37 (95% CI: 0.72-2.62; P = 0.3398). CONCLUSIONS & INFERENCES: Constipation appears to be as important as obstetric trauma in the development of pelvic floor damage. Thus, a more proactive approach to recognizing and treating constipation might significantly reduce the prevalence of this distressing problem.

Intestinal motor activity, endoluminal motion and transit.

A programme for evaluation of intestinal motility has been recently developed based on endoluminal image analysis using computer vision methodology and machine learning techniques. Our aim was to determine the effect of intestinal muscle inhibition on wall motion, dynamics of luminal content and transit in the small bowel. Fourteen healthy subjects ingested the endoscopic capsule (Pillcam, Given Imaging) in fasting conditions. Seven of them received glucagon (4.8 microg kg(-1) bolus followed by a 9.6 microg kg(-1) h(-1) infusion during 1 h) and in the other seven, fasting activity was recorded, as controls. This dose of glucagon has previously shown to inhibit both tonic and phasic intestinal motor activity. Endoluminal image and displacement was analyzed by means of a computer vision programme specifically developed for the evaluation of muscular activity (contractile and non-contractile patterns), intestinal contents, endoluminal motion and transit. Thirty-minute periods before, during and after glucagon infusion were analyzed and compared with equivalent periods in controls. No differences were found in the parameters measured during the baseline (pretest) periods when comparing glucagon and control experiments. During glucagon infusion, there was a significant reduction in contractile activity (0.2 +/- 0.1 vs 4.2 +/- 0.9 luminal closures per min, P < 0.05; 0.4 +/- 0.1 vs 3.4 +/- 1.2% of images with radial wrinkles, P < 0.05) and a significant reduction of endoluminal motion (82 +/- 9 vs 21 +/- 10% of static images, P < 0.05). Endoluminal image analysis, by means of computer vision and machine learning techniques, can reliably detect reduced intestinal muscle activity and motion.