Phases Of Migrating Motor Complex Research Articles

Exploring the impact of real-life dosing conditions on intraluminal and systemic concentrations of atazanavir in parallel with gastric motility recording in healthy subjects

This work strived to explore gastrointestinal (GI) dissolution, supersaturation and precipitation of the weakly basic drug atazanavir in humans under different ‘real-life’ intake conditions. The impact of GI pH and motility on these processes was thoroughly explored. In a cross-over study, atazanavir (Reyataz®) was orally administered to 5 healthy subjects with (i) a glass of water, (ii) a glass of Coca-Cola® and (iii) a glass of water under hypochlorhydric conditions (induced by concomitant intake of a proton-pump inhibitor (PPI)). After intake, GI fluids were aspirated from the stomach and the duodenum and, subsequently, analyzed for atazanavir. In parallel, blood samples were collected to assess systemic concentrations. In general, the results of this study revealed that the acidic gastric pH in combination with gastric residence time played a crucial role in the dissolution of atazanavir along the GI tract. After intake of atazanavir with a glass of water (i.e., reference condition), complete gastric dissolution was observed. After GI transfer, supersaturation was noticed for a limited amount of time (1.25 h). With respect to the Coca-Cola® condition, complete gastric dissolution was also observed. A delay in gastric emptying, highly likely caused by the caloric content (101 kcal), was responsible for delayed arrival of atazanavir into the upper small intestine, creating a longer time window of supersaturated concentrations in the duodenal segment (3.25 h) compared to the water condition. The longer period of supersaturated concentrations resulted in a slightly higher systemic exposure of atazanavir compared to the condition when atazanavir was taken with a glass of water. A remarkable observation was the creation (when the drug was given in the migrating motor complex (MMC) phase 2) or maintenance (when the drug was given in MMC phase 1) of a quiescent phase for up to 80 min. With respect to the PPI condition, negligible gastric and intestinal concentrations were observed, resulting in minimal systemic exposure for all subjects. It can be concluded that gastric pH and residence time play a pivotal role in the intestinal disposition of atazanavir in order to generate sufficiently high concentrations further down in the intestinal tract for a sufficient period of time, thus creating a beneficial driving force for intestinal absorption.

The influence of gastric motility on the intraluminal behavior of fosamprenavir

In fasting conditions, the gastrointestinal system contracts according to the interdigestive migrating motor complex (MMC), in which phases of quiescence (MMC phase I) alternate with phases of medium (MMC phase II) to very strong (MMC phase III) contractions. The time of drug intake relative to this cyclic motility pattern may cause variations in formulation behavior. To explore this hypothesis, a cross-over study was performed in healthy volunteers with an immediate release tablet of fosamprenavir (Telzir) which was administered in either MMC phase I or MMC phase II, as determined by high-resolution manometry. In the intestinal tract, fosamprenavir is rapidly hydrolyzed to the active compound amprenavir by alkaline phosphatases. Drug concentrations of both prodrug and drug were determined in the stomach and duodenum and linked to simultaneously assessed systemic concentrations. In 5 out of 6 healthy volunteers, the gastric release of fosamprenavir and the systemic uptake of amprenavir were affected by the MMC phase in which the tablet was administered. The intragastric disintegration of the tablet was faster and less variable after administration in MMC phase II, resulting in faster and less variable uptake of amprenavir in the systemic circulation. Mean plasma tmax values were 157 (±72.0) and 73.3 (±27.3) min after administration in MMC phase I and MMC phase II, respectively. The study clearly identified the time of oral drug intake relative to the interdigestive motility pattern as a possible source of variation in gastrointestinal drug behavior and absorption.

Patients with dyspepsia have impaired mucosal integrity both in the duodenum and jejunum: in vivo assessment of small bowel mucosal integrity using baseline impedance

BackgroundRecent studies reported that impaired proximal duodenal mucosa, assessed by duodenal biopsy, could play an important role in the development of dyspeptic symptoms. The aims of this study were (a) to develop a method to measure “in vivo” duodenal and jejunal baseline impedance (BI) and (b) to assess small bowel mucosal integrity in patients with functional dyspepsia (FD) and healthy controls (HC).MethodsWe recruited 16 patients with FD and 15 HC. All subjects underwent ambulatory duodeno-jejunal manometry combined with impedance (HRM/Z), BI were determined by measuring impedance immediately after the passage of nocturnal migrating motor complex (MMC) phase IIIs.ResultsThe number of MMC phase IIIs in FD was significantly lower than that in HC (2.6 ± 1.4 vs 4.8 ± 1.7, p < 0.001). The BI in patients was significantly lower than that in HC in D1(164.2 ± 59.8 Ω in FD and 243.1 ± 40.5 Ω in HC, p = 0.0061), D2 (191.2 ± 34.1 and 256.5 ± 91.4 Ω, p = 0.01), D3 (214.0 ± 76.9 and 278.1 ± 45.3 Ω, p = 0.009), D4 (270.8 ± 54.2 and 351.8 ± 50.2 Ω, p < 0.001), and J1 (312.2 ± 55.4 and 379.3 ± 38.3 Ω, p = 0.001).ConclusionsThis is the first study reporting the duodenal and jejunal BI in vivo. The results have shown significantly lowered BI in the proximal small intestine in patients with FD compared to HC. Furthermore it suggests that measurements of small bowel BI could be used as a biomarker for diagnosis and follow up of patients with FD.

Propagation Characteristics of Fasting Duodeno-Jejunal Contractions in Healthy Controls Measured by Clustered Closely-spaced Manometric Sensors.

Background/AimsHigh-resolution methods have advanced esophageal and anorectal manometry interpretation but are incompletely established for intestinal manometry. We characterized normal fasting duodeno-jejunal manometry parameters not measurable by standard techniques using clustered closely-spaced recordings.MethodsTen fasting recordings were performed in 8 healthy controls using catheters with 3–4 gastrointestinal manometry clusters with 1–2 cm channel spacing. Migrating motor complex phase III characteristics were quantified. Spatial-temporal contour plots measured propagation direction and velocity of individual contractions. Coupling was defined by pressure peak continuity within clusters.ResultsTwenty-three phase III complexes (11 antral, 12 intestinal origin) with 157 (95% CI, 104–211) minute periodicities, 6.99 (6.25–7.74) minute durations, 10.92 (10.68–11.16) cycle/minute frequencies, 73.6 (67.7–79.5) mmHg maximal amplitudes, and 4.20 (3.18–5.22) cm/minute propagation velocities were recorded. Coupling of individual contractions was 39.1% (32.1–46.1); 63.0% (54.4–71.6) of contractions were antegrade and 32.8% (24.1–41.5) were retrograde. Individual phase III contractions propagated > 35 fold faster (2.48 cm/sec; 95% CI, 2.25–2.71) than complexes themselves. Phase III complexes beyond the proximal jejunum were longer in duration (P = 0.025) and had poorer contractile coupling (P = 0.025) than proximal complexes. Coupling was greater with 1 cm channel spacing vs 2 cm (P < 0.001).ConclusionsIntestinal manometry using clustered closely-spaced pressure ports characterizes novel antegrade and retrograde propagation and coupling properties which degrade in more distal jejunal segments. Coupling is greater with more closely-spaced recordings. Applying similar methods to dysmotility syndromes will define the relevance of these methods.

Bowel Sounds Identification and Migrating Motor Complex Detection with Low-Cost Piezoelectric Acoustic Sensing Device.

Interpretation of bowel sounds (BS) provides a convenient and non-invasive technique to aid in the diagnosis of gastrointestinal (GI) conditions. However, the approach’s potential is limited by variation between BS and their irregular occurrence. A short, manual auscultation is sufficient to aid in diagnosis of only a few conditions. A longer recording has the potential to unlock additional understanding of GI physiology and clinical utility. In this paper, a low-cost and straightforward piezoelectric acoustic sensing device was designed and used for long BS recordings. The migrating motor complex (MMC) cycle was detected using this device and the sound index as the biomarker for MMC phases. This cycle of recurring motility is typically measured using expensive and invasive equipment. We also used our recordings to develop an improved categorization system for BS. Five different types of BS were extracted: the single burst, multiple bursts, continuous random sound, harmonic sound, and their combination. Their acoustic characteristics and distribution are described. The quantities of different BS during two-hour recordings varied considerably from person to person, while the proportions of different types were consistent. The sensing devices provide a useful tool for MMC detection and study of GI physiology and function.

Sa1561 - Standardizing Parameters of Fasting Duodenojejunal Manometry in Healthy Volunteers Using Clustered High-Resolution Pressure Ports: Focus on Migrating Motor Complex Phase 2 Contractions

Sa1561 - Standardizing Parameters of Fasting Duodenojejunal Manometry in Healthy Volunteers Using Clustered High-Resolution Pressure Ports: Focus on Migrating Motor Complex Phase 2 Contractions

Using Computational Fluid Dynamics to Compare Shear Rate and Turbulence in the TIM-Automated Gastric Compartment With USP Apparatus II

We use computational fluid dynamics to compare the shear rate and turbulence in an advanced in vitro gastric model (TIMagc) during its simulation of fasted state Migrating Motor Complex phases I and II, with the United States Pharmacopeia paddle dissolution apparatus II (USPII). A specific focus is placed on how shear rate in these apparatus affects erosion-based solid oral dosage forms. The study finds that tablet surface shear rates in TIMagc are strongly time dependant and fluctuate between 0.001 and 360 s−1. In USPII, tablet surface shear rates are approximately constant for a given paddle speed and increase linearly from 9 s−1 to 36 s−1 as the paddle speed is increased from 25 to 100 rpm. A strong linear relationship is observed between tablet surface shear rate and tablet erosion rate in USPII, whereas TIMagc shows highly variable behavior. The flow regimes present in each apparatus are compared to in vivo predictions using Reynolds number analysis. Reynolds numbers for flow in TIMagc lie predominantly within the predicted in vivo bounds (0.01-30), whereas Reynolds numbers for flow in USPII lie above the predicted upper bound when operating with paddle speeds as low as 25 rpm (33).

Discrimination of Fasting and Fed Manometric Gastric and Small Bowel Contraction Morphology in Healthy Humans Using Principal Components Analysis

Introduction: The fasting migrating motor complex (MMC) serves a housekeeper function to clear the stomach and small bowel of undigested debris; the fed motor pattern spreads nutrients along the mucosa to optimize digestion. The MMC phase 3 is a distally migrating complex comprised of regular contractions while phase 2 and fed state contractions have more variable amplitudes suggesting different electrophysiologic mechanisms for induction vs. phase 3. Such manometric interpretations are typically done visually and are too qualitative to be amenable for automated analysis. We employed principal component analysis (PCA) to decompose variations in MMC phase 3 contractions vs. phase 2 and the fed state to quantify how contractile morphology varies in the different phases. Methods: 6 healthy subjects underwent placement of a 3 meter manometry catheter with ports in the antrum, duodenum, and jejunum. Manometry was performed for 4-12 hours. Principal components (PCs) were generated from the 3 seconds before and after each contractile peak: PC1 controlled maximal amplitude; PC2 reflected contractile width; PC3 controlled whether a contractile peak occurred early or late in the waveform. Results: 10,543 contractions were analyzed (5576 MMC phase 3, 2543 phase 2, 2334 fed). PC1 variations were higher during phase 2 and the fed state vs. phase 3, reflecting greater amplitude stability in phase 3 (Table 1). PC2 and PC3 variations were less than for PC1 but were greater in phase 2 and the fed state vs. phase 3, indicating less variability in peak width and timing in phase 3. 69% of phase 3 contractions had early peaks and 31% had late peaks, but PC3 lag autocorrelations between consecutive peaks were weak (r=-0.09) indicating poor temporal contraction shape stability. PC1 scores of phase 3 contraction amplitudes showed temporal variability, being highest 2.5 minutes after the start of the phase 3 complex and then staying constant after 5 minutes (Figure 1). Gastric phase 3 was shorter in duration vs. duodenojejunal complexes.Figure 1Table 1: Principal Component Variability Between Different Manometric PhasesConclusion: Principal component analyses defined differences in contractile amplitude, width, and shape that distinguished MMC phase 3 contractions from those during phase 2 and the fed state. These findings (i) warrant physiologic studies into electrophysiologic mechanisms underlying waveform generation in the different fasting and fed phases and (ii) form a foundation for automated intestinal manometry interpretation soft ware development.

Intragastric pH and pressure profiles after intake of the high-caloric, high-fat meal as used for food effect studies

The intraluminal conditions of the fed stomach are critical for drug release from solid oral dosage forms and thus, often associated with the occurrence of food effects on oral bioavailability. In this study, intragastric pH and pressure profiles present after the ingestion of the high-caloric, high-fat (964kcal) FDA standard breakfast were investigated in 19 healthy human subjects by using the telemetric SmartPill® capsule system (26×13mm). Since the gastric emptying of such large non-digestible objects is typically accomplished by the migrating motor complex phase III activity, the time required for recurrence of fasted state motility determined the gastric emptying time (GET). Following the diet recommendations of the FDA guidance on food effect studies, the mean GET of the telemetric motility capsule was 15.3±4.7h. Thus, the high caloric value of the standard breakfast impeded gastric emptying before lunch in 18 out of 19 subjects. During its gastric transit, the capsule was exposed to highly dynamic conditions in terms of pH and pressure, which were mainly dependent on further meal and liquid intake, as well as the intragastric capsule deposition behavior. Maximum pH values in the stomach were measured immediately after capsule intake. The median pH value of the 5min period after capsule ingestion ranged between pH3.3 and 5.3. Subsequently, the pH decreased relatively constantly and reached minimum values of pH0–1 after approximately 4h. The maximum pressure within the stomach amounted to 293±109mbar and was clearly higher than the maximum pressure measured at the ileocaecal junction (60±35mbar). The physiological data on the intraluminal conditions within the fed stomach generated in this study will hopefully contribute to a better understanding of food effects on oral drug product performance.

Motilin-induced gastric contractions signal hunger in man

RationaleHunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated...

The Role of Octreotide in Gastroparesis

Introduction: Gastroparesis is characterized by disordered gastric emptying in the absence of mechanical obstruction. Available therapies for gastroparesis are limited in options and efficacy. The prokinetic agents used most often to improve gastric motility include dopamine-2 receptor antagonists, motilin agonists, and serotonin receptor agonists. Octreotide is a long-acting somatostatin analogue which can be used to modulate gastrointestinal function in children with dysmotility. Octreotide is underutilized as an option for the treatment of gastroparesis. Here we present 2 patients with gastroparesis who were successfully treated with octreotide subcutaneous or parenteral injections. Case Reports: An 18-year-old female with gastroparesis with multiple episodes of nausea and vomiting and weight loss was admitted for dehydration. She had normal upper GI series, endoscopy, and ultrasound. She had delayed gastric emptying while on metoclopramide and erythromycin. She was subsequently started on octreotide 100 mcg (2 mcg/kg/dose) 3 times a day with resolution of symptoms and improved gastric emptying. The second patient was a 13-year-old male with complicated medical history including GERD, status post gastrostomy and Nissen fundoplication as an infant, vomiting, failure to thrive, anxiety, and constipation. He presented with severe nausea and weight loss. His gastric emptying scan showed moderate delay. While on prokinetic agents his symptoms persisted and he required total parenteral nutrition (TPN) to maintain weight. Antroduodenal manometry revealed neurogenic dysmotility. He was started on octreotide injections 100 mcg (2 mcg/kg/dose) twice a day through his central line. Subsequently, he was weaned off TPN and started tolerating enteral nutrition and transitioned to oral feeds. Discussion: Despite the reported inhibitory effect of octreotide on postprandial gastric motility, we report successful treatment of 2 patients with octreotide. We hypothesize that fundic relaxation and modification of duodenal motility by induction of migrating motor complex phase III activity can explain the symptomatic improvement in our patients. Octreotide should be considered as an alternative agent in prokinetic resistant gastroparesis.

Changing interdigestive migrating motor complex in rats under acute liver injury.

Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

Sonographic demonstration of human small intestinal migrating motor complex phase III

Migrating motor complex phase III (MMC phase III) of intestine is an important physiological mechanism traditionally recognized by myoelectric recordings or pressure tracings. Direct imaging is difficult and sonographic visualization in human has not been reported. We have demonstrated this unique phenomenon in three patients who underwent abdominal sonographic examinations. Characteristic images were recorded by videotape and both spatial and temporal features were analyzed. Occurrences of multiple equally spaced, rhythmic intestinal contractions were observed. Parameters including wave frequency, propagation velocity, and duration of the events agreed with those of the well-known phase III. The presence of distinct cyclic patterns observed in two and abolition by meal in the other patient further support our conclusion. We conclude that the migrating waves observed in our study represent the human MMC phase III. This unique finding in human subjects merits further investigation.

Migrating Motor Complex in Colectomized Ileo Stoma Patients

In colectomized patients with ileo stoma, the reflex modulation of small intestinal functions is disturbed, resulting in high enteric stoma outputs and malabsorption. Serotonin has a pivotal role in initiating motor and secretory reflexes involving activation of neuronal 5-HT(3) and smooth muscle muscarinic receptors. We aimed to evaluate the effect of 5-hydroxytryptamine (5-HT), ondansetron and atropine on fasting and stimulated antro-duodeno-jejunal migrating motor complex (MMC) in colectomized patients with ileo stoma compared with healthy subjects. Manometric recordings were obtained in a blinded, age- and gender-matched design. The effects of either standard meal or intravenous 5-HT (10 nmol/kg/min.) treatment with pre-treatment of saline (placebo) or ondansetron (250 μg/kg) or atropine (10 μg/kg) were compared. Adverse effects, blood pressure, heart rate and electrocardiographic data were also evaluated. 5-HT increased the frequency (threefold) and migration velocity (twofold) of MMC phase III in both experimental groups. Ondansetron reduced 5-HT-induced frequency of MMC phase III in patients (p < 0.05) but not in healthy subjects. Atropine reduced 5-HT-induced frequency of MMC phase III in healthy subjects (p < 0.05). Ondansetron did not alter fasting or postprandial MMC in either experimental group (p > 0.05). Atropine did not change fasting MMC in healthy subjects (p > 0.05). We conclude that 5-HT is a stimulator of MMC phase III and that ondansetron reduces the 5-HT-induced MMC phase III without affecting fasting or postprandial properties in colectomized patients with ileo stoma. Similar effects were observed for 5-HT and atropine in healthy subjects.

Indirect evidence for increased mechanosensitivity of jejunal secretomotor neurones in patients with idiopathic bile acid malabsorption

The interdigestive motor rhythm, the migrating motor complex (MMC), is accompanied by active secretion of chloride during periods of distally propagating maximal motor activity (MMC phase III). We studied the behaviour of this system in bile acid malabsorption (BAM), a relative common cause of chronic diarrhoea. We measured motor activity and transmucosal potential difference (PD, reflecting active chloride secretion), in the proximal jejunum in healthy controls (n = 18) and in a group of patients with BAM (n = 11). The phase III-generated voltage was related to the degree of BAM quantified by the (75)SeHCAT test. We used a multi-channel intestinal infusion system to simultaneously measure jejunal pressure and PD. Saline passing calomel half-cells was infused into the jejunum and subcutaneously. Pressure and PD were recorded in the fasting state and after a test meal. In the absence of motor activity, jejunal PD was not significantly different from zero in either group. During MMC phase III, PD reached significantly higher mean and peak levels in BAM patients. The product of MMC phase III length multiplied by voltage, over 3 h, was also significantly higher in BAM patients (controls: median 307 mV x cm, range 70-398; BAM: median 511, range 274-2271, P < 0.01). This value was also significantly correlated with the degree of BAM as reflected by the (75)SeHCAT test (P < 0.05). Phase III induced jejunal secretion may be upregulated in BAM patients, resulting in overload of colonic reabsorption capacity.

Effect of serotonin on small intestinal contractility in healthy volunteers

The physiological significance of serotonin released into the intestinal lumen for the regulation of motility is unknown in humans. The aim of this study was to evaluate the effect of serotonin infused into the lumen of the gastric antrum, duodenum or the jejunum, on antro-duodeno-jejunal contractility in healthy human volunteers. Manometric recordings were obtained and the effects of either a standard meal, continuous intravenous infusion of serotonin (20 nmol/kg/min) or intraluminal bolus infusions of graded doses of serotonin (2.5, 25 or 250 nmol) were compared. In addition, platelet-depleted plasma levels of serotonin, blood pressure, heart rate and electrocardiogram were evaluated. All subjects showed similar results. Intravenous serotonin increased migrating motor complex phase III frequency 3-fold and migrating velocity 2-fold. Intraluminal infusion of serotonin did not change contractile activity. Platelet-depleted-plasma levels of serotonin increased 2-fold following both intravenous and high doses of intraluminal infusions of serotonin. All subjects reported minor short-lived adverse effects following intravenous serotonin stimulation, while only half of the subjects reported minor short-lived adverse effects following intraluminal serotonin stimulations. We conclude that exogenous serotonin in the lumen of the upper part of the small intestine does not seem to change antro-duodeno-jejunal contractility significantly in healthy adult volunteers.

Elevated motility‐related transmucosal potential difference in the upper small intestine in the irritable bowel syndrome

The pathophysiology of irritable bowel syndrome (IBS) is complex and incompletely known. Very little has been studied regarding the role of submucous neuronal activity. We therefore measured small intestinal transmural potential difference (PD, reflecting mainly electrogenic chloride secretion), and its linkage with fasting motor activity [migrating motor complex (MMC)] in controls (n = 16) and patients with IBS [n = 23, 14 diarrhoea predominant (d-IBS) and nine constipation predominant (c-IBS)]. Transmural-PD and its relation to MMC phase III was measured by modified multilumen manometry for 3 h in the fasting state using one jejunal and one duodenal infusion line as flowing electrodes. The amplitude and duration of motor phase III was similar in controls and IBS patients, but the propagation speed of phase III was higher in IBS patients. In IBS patients, maximal PD during MMC phase III was significantly elevated in both the duodenum and jejunum (P < 0.05) and the PD decline after phase III was significantly prolonged in the jejunum (P < 0.01). The PD elevation was seen in both duodenum and jejunum in d-IBS patients, but only in the jejunum in the c-IBS patients. On the basis of previous modelling studies, we propose that the enhanced secretion may reflect disturbed enteric network behaviour in some patients with IBS.

Regulative effect of leptin on gastric motility: experiment with conscious rats

To observe the role of leptin on the regulation of inter-digestive migrating motor complex (MMC) and gastric motility of postprandial period, as well as the serum leptin level and its relationship with motilin during different fast and postprandial periods. Strain gauges were implanted on the serosa of corpus, antrum and pylorus in 50 conscious Wistar rats to record the gastric motility activities. Canula was inserted in the external jugular vein for drug perfusion and blood sampling. The rats were randomly divided into 5 groups: (1) Group 1 to observe the relationship between the postprandial fasting MMC and MMC after feeding. MMC on the empty stomach was recorded, soon afterwards test meal was fed, then the gastric motility was recorded for 60 minutes. Blood samples were collected during the phases I, II, III, and IV, 3 minutes after feeding and then every 5 minutes to test the serum leptin and motilin. (2) Leptin group. After the recording of the first MMC, leptin was perfused during the second MMC to observe its effect on the stomach motility. (3) Anti-leptin serum group. During the second MMC, 5 minutes before feeding and 60 minutes after feeding, anti-leptin serum was perfused to observe its effect on the postprandial stomach motility. (4) Leptin + atropine group. During the first MMC perfusion of atropine was followed by perfusion of leptin. and (5) leptin + cholecystokinin (CCK)-A receptor blocker group. Perfusion of CCK-A receptor blocker was followed by perfusion of leptin. Serum leptin and motilin levels were measured by radioimmunoassay. Typical MMC with phase I, II, III, and IV was recorded in the fasting rats. The phase III of antral MMC could migrate to the pylorus. During the postprandial period, the gastric motility patterns were persistent rhythmic peristaltic contractions. When the stomach was empty, the mean concentration of serum leptin was (5.6 +/- 1.0) microg/L, (11.4 +/- 2.1) microg/L, and (2.1 +/- 0.7) microg/L during the phase I, II and III respectively, being the highest in the phase II, significantly higher than those in the phase I and III (both P < 0.01). During digestive period, the serum concentration of leptin began to increase 3 minutes after the meal and reached its peak of (28.1 +/- 4.4) microg/L 10 minutes after the meal. The serum concentration of leptin remained on a high level till 30 minutes later (compared with that in the inter-digestive period, P < 0.01). On the contrary, the serum concentration of motilin was the highest in the phase III of MMC and the lowest in the digestive period. Intravenous infusion of leptin (2.5 microg x kg(-1) x 10 min) turned the inter-digestive pattern of gastric motility to digestive period pattern with corpus distension and contraction of antrum and pylorus. The effects of leptin on gastric motility were blocked by anti-leptin serum, atropine, and CCK-A receptor blocker loxiglumide. Leptin is a hormone to promote the inter-digestive MMC phase II and postprandial digestive motility activities of stomach, the concentration fluctuation of which will cause satiety related delay of gastric emptying. The effect of leptin on gastric motility is mediated by cholinergic nerve and CCK-A receptors.

Outcome of small-bowel motor impairment in systemic sclerosis--a prospective manometric 5-yr follow-up

To assess the 5-yr course of small-bowel motor disorders, using manometry in patients with systemic sclerosis (SSc), and to investigate for an association between small-bowel motor dysfunction outcome and other clinical manifestations of SSc. Fasting and post-prandial motor activity of the small-bowel was systematically assessed in eight consecutive patients with SSc, using 24 h manometry: initially and at 5-yr follow-up. At 5-yr follow-up, the eight SSc patients (100%) exhibited deterioration of small-bowel motor activity on manometry as follows: (1) more severe abnormalities of migrating motor complex phase III during the fasting period; (2) decreased median duodenal and duodeno-jejunal index during the post-prandial period; and (3) more frequent alterations of small-bowel motor activity in response to octreotide infusion. Furthermore, an association could be found between the deterioration of small-bowel motor function and pitting scars' onset. Our study underscores the rapid deterioration of small-bowel motor impairment in SSc patients (100%). It also highlights the usefulness of small-bowel manometry in symptomatic SSc patients in objectively defining both the characteristics and degree of motor impairment, which may influence the choice of medical treatment in patients, particularly octreotide therapy.

Motility of the pouch correlates with quality of life after total gastrectomy

Jejunal pouch reconstruction is used to provide reservoir function after total gastrectomy, but controversy remains regarding pouch functions and quality of life (QOL). In this study, pouch motility was studied in conjunction with postoperative QOL. Pouch motility of 23 patients with jejunal pouch interposition after total gastrectomy was examined by manometry under fasting conditions and by an emptying test using dual-scintigraphy under postprandial conditions. Residual food was graded by endoscopic examinations. QOL was evaluated using the Gastrointestinal Quality of Life Index, and a stasis- or dumping-related symptom score. The pouch showed interdigestive contractile activity. Bursts of contractile activity occurred frequently and were long-lasting compared with the migrating motor complex phase III of the control jejunum. The percentage of time of contractile bursts correlated with postprandial pouch emptying (liquid: R(2) = 0.229, P < .03; solid: R(2) = 0.243, P < .02). Patients with little or no residual food had more percentage of time of contractile bursts than those with moderate residual food (P < .01). The percentage of time of contractile bursts was correlated with the Gastrointestinal Quality of Life Index score (R(2) = 0.262, P < .02), stasis-related symptoms (R(2) = 0.279, P < .01), and dumping-related symptoms (R(2) = 0.218, P < .03). An interposed jejunum pouch showed bursts of contractile activity that affected postoperative gastrointestinal function and patient QOL.