Proximal Gastric Motor and Sensory Function in Slow Transit Constipation

Background: Slow transit constipation may be part of a more generalized gastrointestinal motility disorder. Methods: Gastric motor and sensory function were evaluated using a barostat in 17 patients with slow transit constipation and in 16 healthy controls. A step-wise isobaric distension procedure was performed, followed by a barostat procedure including a liquid meal. Symptoms were scored using visual analog scales. Plasma levels of gastrointestinal hormones were determined postprandially. Results: Proximal gastric compliance was significantly reduced in the patients. Basal gastric volume did not differ between patients and controls. Postprandial fundus relaxation was significantly reduced in the patients and correlated significantly with daily upper gastrointestinal symptoms. Postprandial secretion of cholecystokinin and gastrin was reduced in the patients. Conclusions: In patients with slow transit constipation, proximal gastric compliance is reduced and postprandial fundus relaxation is impaired. These findings support the hypothesis that slow transit constipation may be part of a pan-enteric disorder.     

Impaired Accommodation of Proximal Stomach in Patients with Alcoholic Liver Cirrhosis

Background: Impaired gastric emptying has previously been detected by ultrasonography in cirrhotic patients, and the role of the type of meal has also been discussed. While these earlier studies dealt with the distal part of the stomach, the aim of our study was to examine the effects of three different types of meal on the proximal stomach in cirrhotic patients. Methods: The proximal stomach was examined by ultrasonography in 15 healthy volunteers and in 21 alcoholic cirrhotic patients. The subjects received a liquid meal with a low calorie content and two different semisolid test meals with a low calorie content or high calorie and fat contents. The proximal gastric size was assessed by ultrasonography in a sagittal area and a frontal diameter. On the basis of assessment of the autonomic nervous function, the cirrhotic patients were divided into two groups: autonomic neuropathy positive and autonomic neuropathy negative. Results: The postcibal gastric size immediately after ingestion of the liquid test meal was significantly lower in the cirrhotic patients than in the healthy controls. In the healthy volunteers, the measures of the proximal gastric size were significantly higher than in either group of cirrhotic patients at t 0 , and at 10, 20 or 30 min after ingestion of a semisolid test meal with low calorie and fat contents. The proximal gastric sizes in the three groups of investigated subjects did not differ when the meal with high fat and calorie contents was tested. When the liquid meal was administered, the proximal gastric size was significantly lower in the cirrhotic patients with autonomic neuropathy. A significant intragroup difference was not observed when the semisolid meals were tested. Conclusions: This study reveals an impairment of the proximal stomach in alcoholic cirrhotic patients. The low calorie liquid meal distinguishes between the two groups of cirrhotic patients and healthy controls.     

Eradication of Helicobacter pylori Restores the Inhibitory Effect of Cholecystokinin on Gastric Motility in Duodenal Ulcer Patients

Background: Increased gastric emptying and defective action of endogenous cholecystokinin (CCK), that is known to inhibit this emptying, have been implicated in the pathogenesis of duodenal ulcer (DU). The aim of this double blind study was to assess whether CCK and somatostatin participate in the impairment of gastric motility in active DU patients before and after Helicobacter pylori eradication. Methods: Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide, a selective CCK-A receptor antagonist, before and 4 weeks after eradication of H. pylori with 1 week triple therapy that resulted in healing of all DUs tested. The gastric emptying rate after feeding was determined using the ¹³C-acetate breath test. Before each test, samples of gastric juice were obtained by aspiration using a nasogastric tube for determination of somatostatin using specific radioimmunoassay. Results: Prior to H. pylori     

Cholecystokinin hyperresponsiveness in functional dyspepsia

Functional dyspepsia (FD) is a common disorder of yet uncertain etiology. Dyspeptic symptoms are usually meal related and suggest an association to gastrointestinal (GI) sensorimotor dysfunction. Cholecystokinin (CCK) is an established brain-gut peptide that plays an important regulatory role in gastrointestinal function. It inhibits gastric motility and emptying via a capsaicin sensitive vagal pathway. The effects on emptying are via its action on the proximal stomach and pylorus. CCK is also involved in the regulation of food intake. It is released in the gut in response to a meal and acts via vagal afferents to induce satiety. Furthermore CCK has also been shown to be involved in the pathogenesis of panic disorder, anxiety and pain. Other neurotransmitters such as serotonin and noradrenaline may be implicated with CCK in the coordination of GI activity. In addition, intravenous administration of CCK has been observed to reproduce the symptoms in FD and this effect can be blocked both by atropine and loxiglumide (CCK-A antagonist). It is possible that an altered response to CCK may be responsible for the commonly observed gastric sensorimotor dysfunction, which may then be associated with the genesis of dyspeptic symptoms.     

Radiographic Evidence of Cholecystokinin Octapeptide Receptors in the Hamster Gallbladder

The distribution of Cholecystokinin receptors in the hamster gallbladder was investigated by ¹²⁵I-labeled Bolton-Hunter-cholecystokinin octapeptide autoradiography. Light microscopic examination showed a marked accumulation of radiolabeled Cholecystokinin within the domain of the muscle layer of the gallbladder. The electron microscopic study further disclosed the presence of radiolabeling mostly in those areas corresponding to cell-to-cell junctions of smooth-muscle cells. Our results suggest that contraction of the gallbladder may primarily be induced by cholecystokinin interacting with its specific receptor in smooth-muscle cells. That Cholecystokinin receptors were more abundant in the junctional complexes of smooth-muscle cells suggests that Cholecystokinin may have a major role in muscle contraction of the gallbladder, which eventually produces an effective bile emptying.     

肠易激综合征患者近端胃舒张和排空功能的研究

背景：实时B超检查测量近端胃舒张和排空功能在胃肠动力障碍性疾病中的应用已越来越受到临床工作者的关注。目的：探讨腹泻型肠易激综合征（D-IBS）和便秘型肠易激综合征（C-IBS）患者近端胃舒张和排空功能的改变。方法：D-IBS患者、C-IBS患者和健康志愿者各20例，以实时B超检查测定饮用标准营养液（500ml）后不同时间点近端胃容积的变化。结果：D-IBS组、C-IBS组和对照组之间胃底气体评分无显著差异。D-IBS组除试餐后5、60min以及C-IBS组除试餐后60min外。其余时间点两组近端胃容积均显著低于对照组。D-IBS组与C-IBS组0min时近端胃容积和最大近端胃容积均显著低于对照组。D-IBS组所有时间点的近端胃容积与C-IBS组无显著差异。D-IBS组、C-IBS组的胃延迟排空相与对照组无显著差异。D-IBS组近端胃液体半排空时间（T1/2）较对照组显著提前，C-IBS组T1/2与对照组无显著差异。结论：IBS患者近端胃舒张功能受损，但D-IBS与C-IBS间无差异，IBS患者的近端胃排空加快。     

Purification and Partial Amino Acid Sequence of a High-Activity Human Stomach Alcohol Dehydrogenase

To understand the relative importance of alcohol dehydrogenase (ADH) isoenzymes in gastric ethanol metabolism, a stomach-specific ADH (σ-ADH) was purified to homogeneity from human transplant donor and surgical tissues, and its activity for ethanol oxidation was examined. The enzyme from these tissues had a specific activity at pH 10 of ˜70 units/mg, about 10 times that reported by Moreno and Parés ( J. Biol. Chem. 266:1128–1133, 1991). The enzyme exhibited a high K _m for ethanol at pH 7.5 and 10 (29 and 5.2 mM, respectively). This high-activity α-ADH isoenzyme migrated on starch and isoelectric focusing gels to a position slightly anodic to the liver σ isoenzyme. It was subjected to digestion by endoproteinases, and ˜40% of the protein was sequenced. The σ-ADH exhibited 75%, 68%, and 62% sequence identity to the human class I ( β ₁), II (π), and III (χ) isoenzymes, respectively, and 61% identity to the deduced ADH6 amino acid sequence. Phylogenetic analysis indicated that precursors to this high-activity σ-ADH and the class I isoenzymes diverged more recently than precursors to the class II and III isoenzymes, after reptilian and avian divergence. The high-activity σ-ADH isoenzyme therefore represents a distinct class of ADH (class IV), more closely related in evolution to the class I isoenzymes than to the other known human isoenzymes.     

糖尿病消化不良患者的自主神经功能及其对近端胃功能的影响

背景:神经病变是糖尿病患者的常见并发症。研究表明糖尿病消化不良患者存在近端胃功能障碍,但糖尿病自主神经病变对近端胃功能的影响尚不清楚。目的:了解糖尿病消化不良患者的自主神经功能及其对近端胃功能的影响。方法:23例糖尿病消化不良患者和10名健康志愿者分别行自主神经功能测定(标准心血管反射试验)和近端胃功能测定(水负荷试验),以B超测量近端胃(胃底)和远端胃(胃窦)的横截面周长和面积。结果:糖尿病消化不良组自主神经功能异常者占95.7%,其交感、副交感和自主神经功能计分均显著高于健康对照组,副交感神经功能受损更为明显。糖尿病消化不良组的阈值饮水量和饱足饮水量均较健康对照组显著减少(518.04ml±205.52ml对640.00ml±154.20ml,887.39ml±277.17ml对1185.00ml±266.72ml,P<0.05),饱足饮水量与饱足饮水后近端胃面积的变化呈正相关(r=0.441,P=0.035),交感神经功能计分与饱足饮水后近端胃周长的变化呈负相关(r=-0.566,P=0.005)。结论:糖尿病消化不良患者有明显的自主神经功能异常,其中副交感神功能受损更为明显,且近端胃感觉阈值减低,适应性舒张功能减退。糖尿病患者近端胃功能障碍可能与自主神经功能受损有一定关系。     

The Effect of Vagal Stimulation on the Release of Cholecystokinin in Anaesthetized Pigs

The effect of electrical vagal stimulation on the release of cholecystokinin (CCK) was studied in nine anaesthetized pigs. Plasma CCK concentrations were measured radioimmunologically by means of an antiserum specific for the sulphated tyrosine region of CCK. Stimulation of both vagal nerves for 10 min induced an increase in CCK concentrations from 1.9 ± 0.4pmol/l to a peak value of 3.6 ± 0.4pmol/l in portal vein plasma and from 1.5 ± 0.3 to 2.7 ± 0.4pmol/l in arterial plasma. Mean integrated increments during stimulation were 12.0 ± 2.5 pmol/1/10 min (p < 0.01) and 8.3 ± 1.0 pmol/1/10 min (p < 0.001), respectively. The results suggest a vagal innervation of the CCK cell in the upper small intestine.     

Cholecystokinin in acute alcoholic and biliary pancreatitis

Summary Background. Recent studies have shown that cholecystokinin (CCK) agonist, cerulein can induce acute pancreatitis in animals. The role of CCK in the induction of acute pancreatitis in humans is unclear. We investigated plasma CCK levels in alcoholic and biliary pancreatitis on admission and during the episode of acute pancreatitis. Methods. Plasma CCK concentrations were determined by a specific and sensitive radioimmunoassay using CCK antiserum (Euro-Diagnostica, Malm?, Sweden) in 35 patients with acute alcoholic pancreatitis, in 27 patients with acute biliary pancreatitis, in 34 patients with nonpancreatic acute abdominal pain, and in 43 healthy subjects. The mean time from the first symptoms to the plasma sample was 31 (±3.7) h in alcoholic pancreatitis patients and 25 (±5.1) h in biliary pancreatitis patients. We also determined CCK levels in 20 patients during the episode of acute pancreatitis. Normal fasting level of CCK is ≤1.12 pmol/L according to manufacturer. Results. Basal plasma CCK concentrations were significantly lower both in alcoholic pancreatitis (mean ± SEM, 0.04±0.03 pmol/L, p<0.0001) and biliary pancreatitis patients (0.17±0.13 pmol/L, p<0.0001) than in nonpancreatic acute abdominal pain patients (1.23±0.32 pmol/L) or healthy subjects (1.18±0.20 pmol/L). Plasma CCK levels also remained low until the patient was well-recovering and had started oral diet. Conclusion. Basal plasma CCK concentrations are significantly decreased in acute alcoholic and biliary pancreatitis after the first day from the beginning of the symptoms until the patient was well-recovering.     

Effect of Phasic Contractions and Tone of the Proximal Stomach on Triggering of Transient Lower Esophageal Sphincter Relaxation

We hypothesized that transient lower esophageal sphincter relaxation (TLESR) is triggered by a discrete motor event, i.e., a phasic contraction or a tonic change of the proximal stomach. The combined esophageal manometry-gastric barostat tracings obtained from 11 healthy subjects during 2-hr continuous isobaric gastric distension were reviewed. Volume waves, i.e., phasic contractions, were analyzed in the 1 and 5 min before onset of each TLESR and in corresponding control periods. Intrabag volume, i.e., proximal gastric tone, was also measured in the 5-min periods. The number of volume waves was similar in the 1- and 5-min pre-TLESR and control periods (0 [0-1], median [IQ range], vs 0 [0-1] and 4 [0.8-5] vs 3 [2-4], respectively], and so were their amplitude, duration, and frequency distribution. Five-minute intrabag volume was also similar (529 +/- 77 [mean +/- SE] vs 532 +/- 74 ml). Our observations suggest that TLESR is not triggered by a preceding phasic contraction or by a different tone of the proximal stomach.     

Effect of Cholecystokinin on Histamine- and Pentagastrin-Stimulated Acid Secretion in Conscious Cats

The effect of a rapid intravenous injection of cholecystokinin (CCK) on acid secretion stimulated by a continuous intravenous infusion of histamine dihydrochloride (40 or 320 μg per kg b.w./h.) or pentagastrin (4 μg per kg b.w./h.) was studied in conscious cats with gastric fistulas. Against background stimulation with the low dose of histamine, producing about half the maximal acid response, 1 and 20 Ivy dog units (U) of CCK per kg body weight significantly increased acid secretion by 30 and 60%, respectively; with the large dose of histamine, producing close to maximal response, 20 U of CCK per kg significantly inhibited acid secretion by 25%. Against background stimulation with pentagastrin in a dose producing submaximal response, 5 or 20 U of CCK per kg did not alter acid secretion.     

Proximal Stomach Function in Systemic Sclerosis

Gastrointestinal involvement is frequent in patients with systemic sclerosis (SSc); however, studies on the proximal stomach and its regulation are lacking. It has been hypothesized that the primary event in the pathogenesis of gastrointestinal involvement in SSc is an early neural lesion. This study investigates proximal stomach function and its relation to autonomic nerve function in SSc. Twenty SSc patients classified in to clinical subsets, underwent measurement of proximal stomach function with and without glucagon by electronic barostat and an assessment of autonomic nerve function. SSc patients were not significantly different from 11 controls for gastric compliance (59.5+/-5.0 vs 47.7+/-4.2 ml/mm Hg, P = 0.1). The pressure-volume curves in each participant with and without glucagon were significantly different (P < 0.001). A significant positive association was found between gastric compliance and autonomic nerve function (P < 0.05). The change in gastric compliance during glucagon administration was significant-associated with autonomic function (P < 0.05). The perception cumulative scores did not differ between SSc patients and control subjects (P = 0.2). In conclusion, proximal stomach function is associated with autonomic nerve function in SSc patients. This confirms the frequent association of motility disorders with autonomic dysfunction in SSc.     

Cholecystokinin activation of central satiety centers changes seasonally in a mammalian hibernator

Hibernators that rely on lipids during winter exhibit profound changes in food intake over the annual cycle. The mechanisms that regulate appetite changes in seasonal hibernators remain unclear, but likely consist of complex interactions between gut hormones, adipokines, and central processing centers. We hypothesized that seasonal changes in the sensitivity of neurons in the nucleus tractus solitarius (NTS) to the gut hormone cholecystokinin (CCK) may contribute to appetite regulation in ground squirrels. Spring (SPR), late summer (SUM), and winter euthermic hibernating (HIB) 13-lined ground squirrels (Ictidomys tridecemlineatus) were treated with intraperitoneal CCK (100 μg/kg) or vehicle (CON) for 3 h and Fos expression in the NTS was quantified. In CON squirrels, numbers of Fos-positive neurons in HIB were low compared to SPR and SUM. CCK treatment increased Fos-positive neurons in the NTS at the levels of the area postrema (AP) and pre AP during all seasons and at the level of the rostral AP in HIB squirrels. The highest absolute levels of Fos-positive neurons were found in SPR CCK squirrels, but the highest relative increase from CON was found in HIB CCK squirrels. Fold-changes in Fos-positive neurons in SUM were intermediate between SPR and HIB. Thus, CCK sensitivity falls from SPR to SUM suggesting that seasonal changes in sensitivity of NTS neurons to vagally-derived CCK may influence appetite in the active phase of the annual cycle in hibernating squirrels. Enhanced sensitivity to CCK signaling in NTS neurons of hibernators indicates that changes in gut-brain signaling may contribute to seasonal changes in food intake during the annual cycle.     

Gastric Relaxation in Response to a Soup Meal in Healthy Subjects A Study Using a Barostat in the Proximal Stomach

Background: Meal-induced relaxation of the proximal stomach can be investigated by means of a barostat. Using a standard liquid meat soup that elicits symptoms and a wide antrum in patients with functional dyspepsia, we aimed at finding the best meal size and fat load for studying gastric relaxation. Method: In the first trial 200ml and 500 ml meat soup (1 g fat/200 ml) was given to six healthy individuals. In the second trial a constant volume of soup (200ml) containing graded amounts of fat (1, 10, and 20g/200ml) was given to seven healthy individuals. Gastric relaxation was investigated for 1 h after consumption of the soup. A sagittal cross-sectional antral area was assessed ultrasonographically every 10min, and abdominal discomfort was scored. Results: Overall, a positive response (volume increase of 30 ml or more within 5 min after consumption of the meal) was found in 26 of 30 (87%) investigations. Individual maximal responses ranged from 38 to 482 ml (mean, 180 ml ± 128). Area under the time-volume curve (AUC) was similar after 200 and 500 ml soup (mean, 100 ml/30 min and 107 ml/ 30 min, respectively). AUC increased with increasing fat content, with a significant difference between the low-fat and high-fat meal (p < 0.05). The barostat bag induced fed-state antral contractions in most individuals (p < 0.001). There was a negative correlation between AUC and postprandial abdominal discomfort (p = 0.04). Conclusions: The barostat is a sensitive technique for detecting gastric relaxation, also in response to our standard meat soup meal. The postprandial relaxation response in healthy individuals is dependent on the fat content of the meal. The barostat bag may alter gastric motor activity. Abdominal discomfort after soup ingestion may be related to poor gastric relaxation.     

Human Stomach Class IV Alcohol Dehydrogenase: Molecular Genetic Analysis

A partial human stomach alcohol dehydrogenase (ADH) encoding cDNA has been isolated, cloned, and sequenced, which contains 222 nucleotides encoding amino acid residues 227–299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat stomach class IV ADH sequence recently reported (81.1% sequence identity). Homology with other human ADH classes was also observed: class I, 58.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These results support a proposal that the isolated cDNA encodes a partial sequence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at this position reported for rat class IV ADH. This ala residue may contribute to the very high K_m values with ethanol for the latter enzyme. In addition, three substitutions are reported for key residues in the coenzyme binding site: 251, gln/ser; 260, gly/asn; and 261, gly/asn, which may contribute to the weak coenzyme binding properties reported for human class IV ADH.     

Clinical and Endoscopic Features of Metastatic Tumors in the Stomach

Background/AimsMetastasis to the stomach is rare. The aim of this study was to describe and analyze the clinical outcomes of cancers that metastasized to the stomach.MethodsWe reviewed the clinicopathological aspects of patients with gastric metastases from solid organ tumors. Thirty-seven cases were identified, and we evaluated the histology, initial presentation, imaging findings, lesion locations, treatment courses, and overall patient survival.ResultsEndoscopic findings indicated that solitary lesions presented more frequently than multiple lesions and submucosal tumor-like tumors were the most common appearance. Malignant melanoma was the tumor that most frequently metastasized to the stomach. Twelve patients received treatments after the diagnosis of gastric metastasis. The median survival period from the diagnosis of gastric metastasis was 3.0 months (interquartile range, 1.0 to 11.0 months). Patients with solitary lesions and patients who received any treatments survived longer after the diagnosis of metastatic cancer than patients with multiple lesions and patients who did not any receive any treatments.ConclusionsProper treatment with careful consideration of the primary tumor characteristics can increase the survival period in patients with tumors that metastasize to the stomach, especially in cases with solitary metastatic lesions in endoscopic findings.