无症状胆石症患者胆囊运动功能及阿斯匹林的作用

为研究无症状胆囊结石患者胆囊动力变化及阿斯匹林的影响.采用腹部超声法观察43例无症状胆囊结石(AG)患者和20名健康对照服用阿斯匹林(0.3/日,6天)前后胆囊容量的变化.结果:(1)AG组空腹胆囊容积(FGV)和剩余胆囊容积(RGV)明显增大(P＜0.01),胆囊排空率(GER)明显减少(P＜0.01).无论在快速排空或缓慢排空期,AG组胆囊排空功能均有明显损害;(2)服用阿斯匹林后未观察到正常组(NS)和AG组织胆囊排空率的改善.提示,AG组存在胆囊动力障碍,胆囊排空功能障碍可能是胆囊结石成因之一.前列腺素抑制剂阿斯匹林对胆囊的动力障碍无改善.     

无症状胆石症患者胆囊运动功能及阿期匹林的作用

为研究无症状胆囊结石患者胆囊动力变化及阿斯匹林的影响． 采用腹部超声法观察４３例无症状胆囊 结石（ＡＧ）患者和 ２０名健康对照服用阿斯匹林（０．３／日．６天）前后胆囊容量的变化，结果：（１）ＡＧ组空腹胆囊容积 （ＦＧＶ）和剩余胆囊容积（ＲＧＶ）明显增大（Ｐ＜０．０１），胆羹排空率（ＧＥＲ）明显减少（Ｐ＜０．０１）．无论在快速排空或 缓慢排空期．ＡＧ组胆囊排空功能均有明显损害；（２）服用阿斯匹林后未观察到正常组（ＨＳ）和ＡＧ组织胆囊排空率 的改善。提示．ＡＧ组存在胆囊动力障碍，胆囊排空功能障碍可能是胆囊结石成因之一：前列腺素抑制剂阿斯匹林 对胆囊的动力障碍无改善。     

The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study

OBJECTIVE: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. METHODS: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. RESULTS: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. CONCLUSIONS: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.     

Effect of single dose of oral erythromycin on gastric and gallbladder emptying

To evaluate the effects of a single oral dose of erythromycin on gastric and gallbladder emptying, 10 volunteers, without a known history of gastrointestinal disease, were investigated. Erythromycin stearate (500 mg) or placebo was given on separate mornings 30 min before a standard solid meal in a randomized, double-blind, crossover study. Gastric and gallbladder emptying rates were simultaneously evaluated by means of real-time ultrasonography. Gastric antral area and gallbladder volume were determined before the meal and 30, 60, 120, 180, 240, and 300 min after commencing eating. Erythromycin, compared to placebo, significantly accelerates and increases the degree of both gastric and gallbladder emptying. As previously reported for intravenous and chronic oral assumption, also a single dose of oral erythromycin is able to accelerate gastric and gallbladder emptying in normal human subjects.MIS: Member of Institute of Statisticians.This work was partially supported by a grant from Ministero dell'Universita e della Ricerca Scientifica e Tecnologica (fondi 60%).     

Lysosomal enzyme activities in gallbladder mucosa of gallstone-free subjects and patients with gallstones

Background/Aims: Gallstone patients have a reduced cellular lysosome content in the gallbladder mucosa cells compared with gallstone-free subjects. The purpose of the study was to further evaluate the possible role of lysosomes in the pathogenesis of cholesterol gallstone formation in humans.Methods: Lysosomal enzyme activities were assayed in gallbladder mucosa and for comparison in liver specimens of 19 gallstone-free subjects and 24 gallstone patients undergoing cholecystectomy.Results: Gallstone patients had 25–50% lower activities of the lysosomal proteases cathepsin B, D and L in their gallbladder mucosa compared with gallstone-free subjects. The activity of acid phosphatase also tended to be decreased in gallstone patients. The liver lysosomal enzyme activities were not significantly different between the two groups.Conclusions: The results show that gallstone patients have diminished lysosomal enzyme activities in the gallbladder mucosa, a finding which may be related to decreased intracellular degradation of proteins and/or mucin in the mucosal cells. This may lead to a higher concentration of mucin in gallbladder bile and thus an increased risk of precipitation of cholesterol crystals and gallstone formation.     

Gallbladder motility and gut hormone plasma levels in subjects with and without gallstones

Hormonal control of gallbladder motility is still unclear in patients with cholelithiasis. In a case-control study, we determined the characteristics of gallbladder emptying evaluated sonographically and the hormone levels of somatostatin, gastrin, and pancreatic polypeptide, before and after a fatty meal in 10 gallstone patients compared with 20 healthy subjects. Patients with lithiasis had a larger residual volume (median 12,0 ml vs 6,5 ml; P = 0.01) and a lower gallbladder ejection fraction (43% vs 70%, P = 0.02) than healthy subjects. During fasting, plasma pancreatic polypeptide concentrations were significantly higher in lithiasis patients (P < 0.03). In contrast, no differences between the two groups of patients were observed during the post prandial period. Somatostatin and gastrin plasma levels were similar in the two groups. Lastly, the serum bile salt levels were in the normal range and were not different between groups both during fasting and postprandial states. We conclude that large basal plasma concentrations of pancreatic polypeptide, a gut peptide inducing gallbladder relaxation, may constitute a factor facilitating lithogenesis.     

Effect of oral protease inhibitor administration on gallbladder motility in patients with mild chronic pancreatitis

Oral administration of a protease inhibitor (camostat) induces pancreatic hypersecretion via hormonal and neural systems in humans. Camostat may also affect gallbladder motility via these systems. The aim of this study was to evaluate the effect of camostat on gallbladder function. Gallbladder emptying in response to caerulein administration and to egg yolk ingestion was examined ultrasonographically in 15 patients with mild chronic pancreatitis before and after 6 months of camostat treatment, and in 10 control subjects. The plasma cholecystokinin concentration after yolk ingestion was measured by radioimmunoassay. Fasting gallbladder volume and contractile function, whether stimulated by caerulein or yolk, did not differ between pancreatitis patients before camostat treatment and controls. Plasma cholecystokinin levels, basal and yolk-stimulated, did not differ between nontreated pancreatitis patients and control subjects. Fasting volume had decreased significantly by 1, 3, and 6 months of camostat treatment, while contractile function was not affected. Camostat did not influence plasma cholecystokinin levels. Oral administration of a protease inhibitor appears to decrease fasting gallbladder volume via a mechanism other than cholecystokinin release.     

Effect of pectin on gastric emptying and gastroduodenal motility in normal subjects

The effects of pectin ingestion on gastric emptying, gastroduodenal motility, and plasma levels of glucose, insulin, and glucagon were studied. Initial studies demonstrated that 15 g of pectin was the optimal dose. Subsequently 6 healthy male volunteers were studied on 4 separate days at random. On day 1, gastric emptying of a liquid and a solid meal was assessed by radioisotope technique using 99mTc-dithiopropylthiomine. On day 2, the gastric emptying study was repeated with the addition of pectin to each meal. Plasma levels of glucose, insulin, and glucagon also were determined during these 2 days. On day 3, the effects of liquid and solid meals on gastroduodenal motility were assessed by means of a perfused catheter system. On day 4, the motility study was repeated with the addition of pectin to each meal. Pectin supplementation caused a significant prolongation of gastric emptying half-time of both liquid and solid meals (p less than 0.05). The addition of pectin, however, did not have any significant effect on gastroduodenal motility other than increasing the duodenal motility index 10 min after the liquid meal. The addition of pectin to the liquid meal lowered plasma levels of insulin at 15, 30, and 45 min, and glucagon levels 15 min after the meal. No effect was noted on blood sugar levels. On the other hand, the addition of pectin to the solid meal had no effect on plasma levels of glucose, insulin, and glucagon. We conclude that pectin supplementation delays gastric emptying of both liquid and solid meals in normal human subjects without causing notable changes in gastroduodenal motility or significant variations in pancreatic hormone plasma levels. The pectin effect on gastric emptying may be caused solely by increasing the viscosity of the meals.     

Hyperglycaemia stimulates pyloric motility in normal subjects.

The motor correlates of the delay in gastric emptying produced by hyperglycaemia were investigated in 11 healthy volunteers. Fasting gastroduodenal motility was measured during euglycaemia (blood glucose concentration 3-5 mmol/l) and during hyperglycaemia induced by intravenous dextrose (blood glucose concentration 12-16 mmol/l). Antral, pyloric, and proximal duodenal pressures were recorded by a sleeve/sidehole manometric assembly positioned across the pylorus, with the aid of measurements of transmucosal potential difference. During hyperglycaemia there was stimulation of isolated pyloric pressure waves when compared with the euglycaemia period (p less than 0.05). This was associated with inhibition of antral pressure waves (p less than 0.05). In nine of the 11 subjects an episode of duodenal 'phase III like' activity occurred within 15 minutes of the onset of hyperglycaemia. It is proposed that the stimulation of localised pyloric contractions and inhibition of antral contractions contribute to the delayed gastric emptying induced by hyperglycaemia. Abnormal gastric motility in patients with diabetes mellitus may be the result of hyperglycaemia itself, rather than irreversible autonomic neuropathy.     

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis

Acute pancreatitis is a severe complication of gallstones with considerable mortality. We sought to explore the potential risk factors for biliary pancreatitis. We compared postprandial gallbladder motility (via ultrasonography) and, after subsequent cholecystectomy, numbers, sizes, and types of gallstones; gallbladder bile composition; and cholesterol crystallization in 21 gallstone patients with previous pancreatitis and 30 patients with uncomplicated symptomatic gallstones. Gallbladder motility was stronger in pancreatitis patients than in patients with uncomplicated symptomatic gallstones (minimum postprandial gallbladder volumes: 5.8 +/- 1.0 vs. 8.1 +/- 0.7 mL; P = .005). Pancreatitis patients had more often sludge (41% vs. 13%; P = .03) and smaller and more gallstones than patients with symptomatic gallstones (smallest stone diameters: 2 +/- 1 vs. 8 +/- 2 mm; P = .001). Also, crystallization occurred much faster in the bile of pancreatitis patients (1.0 +/- 0.0 vs. 2.5 +/- 0.4 days; P < .001), possibly because of higher mucin concentrations (3.3 +/- 1.9 vs. 0.8 +/- 0.2 mg/mL; P = .04). No significant differences were found in types of gallstones, relative biliary lipid contents, cholesterol saturation indexes, bile salt species composition, phospholipid classes, total protein or immunoglobulin (G, M, and A), haptoglobin, and alpha-1 acid glycoprotein concentrations. In conclusion, patients with small gallbladder stones and/or preserved gallbladder motility are at increased risk of pancreatitis. The potential benefit of prophylactic cholecystectomy in this patient category has yet to be explored.     

Gastric motility and emptying in normal and post-vagotomy subjects.

The effects of proximal gastric vagotomy (PGV) and vagotomy with pyloroplasty (V and P) on gastric motility were studied using a solid meal labelled with a radiopharmaceutical agent. In having on-line computer facilities it was possible not only to record the rate of emptying but also to analyse the relative roles of the fundus and the antrum within the overall framework of gastric emptying. In normal subjects the fundus filled and then emptied in an almost linear pattern. The antrum, however, did not completely fill until well after the meal was eaten and thereafter appeared to maintain a constant volume during the study. The redistribution of contents between fundus and antrum was reflected in the total stomach emptying curve as a delay, or lag phase before gastric emptying commenced. After both types of vagotomy fundic filling was delayed, representing a slower eating time, which was presumably due to early satiety. Antral filling and volume was disturbed only after V and P, which was also reflected by a loss of the lag phase seen on the total stomach curve. PGV retained antral function but there was significant delay in the redistribution of contents between fundus and antrum, though this did not have clinical significance. The rate of emptying was unaffected by either operation. It was concluded PGV did maintain antral function and a more normal pattern of emptying compared with V and P. After V and P the changes in antral function were considerable and these changes are probably associated with some of the complications resulting from this operation.     

Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis.

The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase-3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications.     

Black pigment gallstones with cholesterol gallstones in the same gallbladder

We studied 1312 consecutive patients who underwent surgery for gallstones in the biliary tract at one university hospital in Siena, Italy, with a systematic classification of gallstones found within the gallbladder. Of these patients, 1226 were found to have gallbladder stones; 94 of these had black pigment gallstones. Of these, 13 patients were found to have black pigment gallstones and cholesterol gallstones within their gallbladder. They all had multiple black pigment gallstones, usually very small (all <6 mm diameter), in association with larger cholesterol stones in the gallbladder lumen. The cholesterol gallstones were single in seven cases, double in two cases, and multiple in four cases. All 13 of these patients with black pigment stones in association with cholesterol stones had histologic evidence of either adenomyomatosis or Rokitansky-Aschoff sinuses in the gallbladder wall. In nine of the 13 patients, the black pigment stones were located both in the gallbladder lumen and in close association with the gallbladder wall (in areas of adenomyomatosis or in Rokitanski-Aschoff sinuses). In the other four patients, the stones were found in close association with the gallbladder wall alone and not freely mobile within the gallbladder lumen. It is concluded that cholesterol stones and black pigment stones may be found in the same gallbladder. This association is infrequent with an incidence of 13 of 1226 (1.06%) in our series. There appears to be some relationship between the formation of the black pigment stones and the presence of adenomyomatosis or Rokitanski-Aschoff sinuses. However, the pathogenesis of these two compositionally distinctly different types of stones within the same gallbladder is not understood and deserves further study.     

双气消滞散对G豚鼠致石后胆囊调宁蛋白的影响

[目的]探讨双气消滞散促进胆管动力的作用机制。[方法]将受试豚鼠随机分为4组,即正常组、模型组、双气消滞散(中药)组、熊去氧胆酸(西药)组。后3组采用高胆固醇致石食饵诱发法建立豚鼠胆结石动物模型,并使其发生继发性胆囊运动功能障碍,其中中药组、西药组分别给予相应药物进行实验性治疗,连续7周后,分别对引起实验性豚鼠胆囊运动功能障碍的胆囊组织调宁蛋白(Cap)表达进行观察。[结果]中药组能有效促进胆囊动力(与模型组比较P<0.01),并且其效果优于西药组(P<0.01)。模型组动物胆囊组织Cap表达水平较正常组显著升高(P<0.01),中药组和西药组胆囊组织Cap表达水平虽均高于正常组(分别P<0.01、<0.05),但与模型组比较,其水平均明显降低(均P<0.01),且中药、西药2组胆囊组织Cap表达水平比较差异无统计学意义(P>0.05)。[结论]双气消滞散能显著促进胆囊动力,其作用机制可能与下调胆囊平滑肌组织Cap水平,提高胆囊平滑肌收缩能力有关。     

Effect of cisapride on gallbladder emptying and plasma CCK in normal and vagotomized human subjects

Previous studies have provided conflicting results on the effects of cisapride on gallbladder emptying in response to a meal. We studied six volunteers and six patients after a truncal vagotomy in a double-blind, placebo-controlled, prospectively randomized study using 10 mg cisapride four times a day for three days. Gallbladder volume was quantitated using ultrasonography, and plasma CCK levels were measured with a sensitive and specific radioimmunoassay using the DINO antibody before and for 90 min after a fatty, mixed meal. Plasma CCK levels were unchanged after treatment with cisapride in both groups. No prokinetic effect was observed on the gallbladder either in normal subjects or vagotomized patients. Paradoxically, residual volume (RV) was increased in the vagotomized patients after treatment with cisapride: RV cisapride 7.1 (4.1–15.9) ml, RV placebo 5.1 (3.8–14) ml,P<0.05. Further work is required to clarify the mechanisms of action of cisapride on the gallbladder and the sphincter of Oddi. The use of cisapride during litholytic therapy may impair gallbladder emptying and delay stone clearance.     

Stress and oesophageal motility in normal subjects and patients with irritable bowel syndrome.

Patterns of oesophageal motility were recorded in 17 healthy volunteers and 12 patients with the irritable bowel syndrome. Recordings were taken at rest and under stress by hyperventilation, a dichotic hearing challenge and a cold pressor test. In healthy volunteers the dichotic hearing challenge was associated with a significant increase in the mean amplitude of oesophageal peristalsis from 69.9 mmHg to 82.4 mmHg (p less than 0.01) and in the percentage of simultaneous waves from 9.7% to 24.5% (p less than 0.01). The cold pressor test increased the peristaltic amplitude from 69.9 mmHg to 87.1 mmHg (p less than 0.001) and the percentage of simultaneous waves from 9.7% to 34.4% (p less than 0.01). Both manoeuvres were associated with increases in pulse and blood pressure. In patients with irritable bowel syndrome, the resting mean oesophageal peristaltic amplitude was higher than that seen in normal volunteers (95.9 mmHg v 69.9 mmHg p less than 0.05). Changes in oesophageal motility during stress were similar in these patients to those seen in normal subjects although the changes were not significant. This study refutes the hypothesis that symptoms of irritable bowel syndrome and their association with stress are attributable to increased sensitivity of oesophageal motility to disruption by stressful stimuli.     

内镜乳头括约肌切开对胆囊运动功能的影响

目的观察乳头括约肌切开术(EST)对胆囊排空运动功能的影响.方法以超声测定38例患者行EST前一日,术后2周、1月、3月的空腹胆囊体积;并于脂餐后20～120 min每隔20 min测残余胆囊体积,以不同时间的最小值计算出胆囊排空率及排空速率.结果EST术后空腹胆囊体积及餐后残余胆囊体积较术前明显缩小,1月后趋于稳定,在术后3月空腹胆囊体积由术前(31.4±10.6)ml下降为17.2±8.7ml,P＜0.01;脂餐后残余胆囊体积由18.2±5.6ml下降为7.1±2.5ml,P＜0.01.EST术后胆囊排空率及排空速率较术前明显增加,在术后3月胆囊排空率由41.9±13.4%上升为59.9±11.7%,p＜0.01;胆囊排空速率由0.0038±0.0011/min上升为0.0067±0.0019/min,P＜0.01.结论EST后胆囊运动功能增强.     

Effects of intraduodenal bile on interdigestive gastrointestinal and gallbladder motility in healthy subjects

BACKGROUND/AIMS: The enterohepatic circulation of bile acids is related to normal inter-digestive gastrointestinal motility, with the gut peptide motilin also being involved. This study aimed to investigate the effect of intraduodenal artificial bile infusion on antroduodenal and gallbladder motility so as to further elucidate the controlling factors. METHODS: Twelve fasting, healthy male volunteers received artificial bile (80 mol% bile acids; 15 mol% phospholipids; 5 mol% cholesterol) or placebo (saline) intraduodenally for 10 min starting 30 min after the end of phase III, according to a double-blind, randomised, cross-over design. Antroduodenal motility, gallbladder volumes, and plasma motilin levels were measured. All values are means +/- SEM. RESULTS: The interval between infusion and the subsequent phase III, as well as the origin of this phase III were not significantly different between bile and saline. Antral pressure waves were significantly more frequent during and immediately after bile infusion compared with saline infusion (p < 0.05). The duration of phase I following infusion was significantly longer after bile (24.8 +/- 3.7 min) than after saline infusion (13.1 +/- 1.7 min; p < 0.05). The mean gallbladder volume tended to increase in the hours following bile infusion, but to decrease after saline infusion (p = 0.06). Plasma motilin increased after bile and saline infusion in an almost identical way. CONCLUSION: This study provides no clear evidence for a role of intraduodenal artificial bile (i.e. its main constituents) in the regulation of migrating motor complex cycling or feedback inhibition of inter-digestive gallbladder emptying.     

Effect of aspirin on gallbladder motility in patients with gallstone disease

Patients with gallstone disease have impaired gallbladder motility. Prostaglandins are thought to be important mediators of gallbladder hypomotility. We assessed the effect of aspirin, a prostaglandin inhibitor on gallbladder resting volume and ejection fraction according to a double-blind study protocol in 20 healthy volunteers and 30 patients with gallstone disease. Healthy volunteers had a higher ejection fraction compared to patients with gallstone disease (73.9±0.9% vs 60.4±1.0%,P<0.05). Aspirin in a dose of 350 mg/day for two weeks did not alter gallbladder motility in the healthy volunteers. Thirty patients with gallstone disease were randomized into three treatment groups: group I (placebo), group II (aspirin 350 mg/day), and group III (aspirin 1400 mg/day). After two weeks of treatment, gallbladder ejection fraction was improved in group II (74.0±1.7% vs 62.0±1.7%,P<0.01) and group III (69.8±3.8% vs 61.2±1.3%,P<0.01) but not in group I (60.4±2.6% vs 59.0±1.9%,P=NS). The higher dose of aspirin did not induce a greater increase in gallbladder emptying. It is concluded that impaired gallbladder motility in patients with gallstone disease is corrected by short-term oral aspirin even in low dosage. This may be clinically useful in secondary prophylaxis after nonsurgical therapy for gallstone disease.