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PubMed1998

Gallbladder motility and gallstone formation in obese patients following very low calorie diets. Use it (fat) to lose it (well).

OBJECTIVE: Dieting obese subjects are at risk of developing gallstones. A gallbladder motor dysfunction could have a pathogenetic role. The principal aim of this study was to evaluate the long term effects of two very low calorie diets differing in fat content on gallbladder emptying and gallstone formation in obese subjects. DESIGN AND SUBJECTS: Gallbladder emptying in response to meals (breakfast, lunch and dinner) in two different diet regimens (3.0 vs 12.2 g of fat/d) was evaluated by ultrasonography in 32 gallstone-free obese patients on different days, before and during (at 45 d intervals) one or two 6-month weight reduction diets (for the first three months: 2.24 MJ (535.2 kcal), 3.0 g fat/d vs 2.415 MJ (577.0 kcal), 12.2 g fat/d; for the second three months, the same low calorie diet of 4.194 MJ (1002 kcal)/d for both groups). In 10 subjects, bile analysis was also performed. RESULTS: Twenty-two (69%) subjects concluded the study, eleven in each group, and a significant weight loss was achieved by all subjects. Gallstones (asymptomatic) developed in 6/11 (54.5%) (P < 0.01) of subjects following the lower fat diet, but in none with the higher fat regimen. In the dieters during the first three months (very low calorie phase) the higher fat meals always induced a significantly greater gallbladder emptying than the lower fat meals. The cholesterol saturation index initially increased significantly and then decreased, without difference between the two groups. CONCLUSION: In the obese during rapid weight loss from a very low calorie diet, a relatively high fat intake could prevent gallstone formation, probably by maintaining an adequate gallbladder emptying, which could counterbalance lithogenic mechanisms acting during weight loss.

Adolescent↗
PubMed1994

Gastrobiliary motility after liquid fatty meal in progressive systemic sclerosis. A sonographic study.

Gastric emptying, antral motility, and gallbladder emptying after a liquid fatty meal were studied by ultrasound in 25 patients with progressive systemic sclerosis and in 25 sex- and age-matched controls. In patients with systemic sclerosis, the possible role of autonomic dysfunction was evaluated by four noninvasive cardiovascular reflex tests. Despite a significant delay of gastric emptying and a significant postprandial antral hypomotility in the patients with systemic sclerosis, the fat-induced gallbladder emptying was only slightly reduced, reaching no significant level when compared to the controls. The prolongation of gastric emptying correlated significantly with the duration of the disease. Although 36% of the patients in the systemic sclerosis group exhibited signs of autonomic cardiac dysfunction, there was no evidence of an association between these signs and gastric motor dysfunction. In conclusion motility disorders of the gallbladder seem to play a minor role in the upper gut involvement of systemic sclerosis, whereas motility disorders of the stomach are frequent and can be easily recognized noninvasively by real-time ultrasound.

Adult↗
PubMed1995

Effects of cholestyramine on gallbladder and gastric emptying in obese and lean subjects.

Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through disinhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by real-time ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4 g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 +/- 6.9 vs. 21.6 +/- 1.7 mL, P < 0.02), larger residual volume (12.3 +/- 1.8 vs. 4.0 +/- 0.5 ml, P < 0.0006) and slower emptying time (T/2: 33 +/- 2 vs. 21 +/- 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 +/- 578 vs. 7908 +/- 491 %120 min-1, P < 0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.

Adolescent↗
PubMed2003

Acalculous biliary pain: new concepts for an old entity.

Biliary pain is commonly reported in household surveys with the presumed cause being gallstones. When gallstones are absent or other abnormalities as a potential cause of similar pain do not exist, a different approach is necessary. Although trans-abdominal ultrasound can detect stones down to 3-5 mm, the advent of endoscopic ultrasound provides an even better definition for microlithiasis of < 3 mm. Duodenal aspiration of bile can further detect cholesterol microlithiasis or bilirubin granules, another potential source of biliary-type pain and perhaps even pancreatitis. Only in this way can acalculous gallbladder disease be clearly defined. The percentage of cholecystokinin-stimulated gallbladder emptying has been reputed to be the most sensitive diagnostic test for 'biliary dyskinesia', but abnormality of gallbladder emptying can be due to a smooth muscle defect of the gallbladder itself or heightened tone in the sphincter of Oddi. The value of surgical intervention has not been clearly established. The advent of laparoscopic cholecystectomy, however, has increased the number of patients with acalculous biliary disease who undergo surgery. Surgery is best done using impaired gallbladder emptying as the criterion for operation with improved outcome. Often, following cholecystectomy, biliary pain does not resolve the so-called 'post cholecystectomy syndrome'. Absence of the gallbladder as a pressure reservoir leaves the sphincter of Oddi as the prime determinant of bile duct pressure. Sphincter of Oddi dysfunction also exists in patients with an intact biliary tract and may become evident following cholecystectomy. Biliary manometry has clarified who might benefit from sphincterotomy. Choledochoscintigraphy is a non-invasive preliminary test. Advent of visceral hypersensitivity and better definition of this entity has shown, that in some of these patients with type III sphincter of Oddi, dysfunction appears to reside in duodenal hyperalgesia. It is clear that improved criteria are required to perform gallbladder emptying and better techniques to detect visceral hypersensitivity. Nonetheless, functional biliary pain in the absence of gallstone disease is a definite entity and a challenge for clinicians.

Acalculous Cholecystitis↗
PubMed1996

Gallbladder dyskinesia in acalculous biliary colic.

AIMS: To test the hypotheses that: 1) postprandial gallbladder emptying might be abnormal in patients with acalculous biliary colic; and 2) that hymecromone, a drug that increases bile flow and relaxes biliary muscle might improve symptoms. METHODS: Twenty-four women were studied. Twelve patients presented recurrent biliary type of pain in the absence of gallstones, and persistence of contrast in the gallbladder, 24 hours after an oral cholecystogram, suggesting cholesterolosis. Twelve healthy volunteers used as controls had no symptoms and the gallbladder was not visible the day after an oral cholecystogram. Gallbladder emptying induced by an oral meal was studied with ultrasound in both groups before and after the administration of hymecromone. RESULTS: Gallbladder volumes were similar in both groups (23 +/- 10 ml vs. 31 +/- 11 ml; NS). Gallbladder emptying in the control group was simple exponential (R2 = 0.948 +/- 0.059) with a rate of 32 +/- 16 minutes. Gallbladder emptying was bimodal in patients. Gallbladder volume increased to 120% in the first 10 minutes, to empty exponentially thereafter (R2 = 0.964 +/- 0.040. Rate: 29 +/- 22 minutes). This resulted in a marked reduction in gallbladder volume emptied at 40 minutes when compared to controls (30% +/- 27% vs. 54% +/- 14%; p = 0.012). Pretreatment of controls with hymecromone induced an emptying pattern similar to that of patients. In patients, emptying after hymecromone did not change but symptoms were improved. CONCLUSIONS: An abnormal emptying pattern of the gallbladder was identified in patients with acalculous biliary colic, and hymecromone was partly effective to reduce pain, despite a minor effect on gallbladder emptying pattern.

Biliary Tract Diseases↗
PubMed1989

Mean residence time for drugs subject to enterohepatic cycling.

A physiologically realistic model of enterohepatic cycling (EHC) which includes separate liver and gallbladder compartments, discontinuous gallbladder emptying and first-order absorption from both an oral formulation and secreted bile (kapo and kab, respectively) has been developed. The effect of EHC on area under the first-moment curve (AUMC) of drug concentration in plasma and on parameters derived from the AUMC was investigated. Unlike AUC, AUMC is dependent on the time and time-course of gallbladder emptying, increasing as the interval between gallbladder emptying increases. Consequently, mean residence time (MRT) is also a time-dependent parameter. Analytical solutions for MRTiv and MRTpo were derived. Mean absorption time (MAT = MRTpo - MRTiv) is also time-dependent, contrary to findings previously published for a model of EHC with a continuous time lag. MAT is also dependent on kapo, kba and the hepatic extraction ratio. The difference between MRTpos for two formulations with unequal kapo values may deviate from the difference in the inverse of their absorption rate constants. Implications for design and interpretation of pharmacokinetic studies include (i) MAT values may be dominated by the time-course of recycling rather than the time-course of the initial absorption, depending on the extent of EHC and (ii) the unpredictable nature of the time of gallbladder emptying will contribute to intrasubject variability in derived parameters during crossover studies. Knowledge of the extent of EHC is invaluable in deciding whether modification of the in vitro release characteristics of an oral formulation will have any effect on the overall time-course of absorption in vivo. Techniques to monitor or control gallbladder emptying may be helpful for reducing variability in pharmacokinetic studies for compounds which are extensively cycled in bile.

Absorption↗
PubMed1994

Pathogenic factors in early recurrence of cholesterol gallstones.

BACKGROUND/AIMS: Supersaturation of bile with cholesterol, rapid nucleation of cholesterol crystals, and/or incomplete emptying of the gallbladder are believed to be required for gallstone formation. The importance of these factors for the recurrence of gallbladder stones was studied. METHODS: Twenty patients, untreated after successful shock wave therapy, were studied in a matched case-control design for bile acid turnover, composition of duodenal bile, and gallbladder emptying. In 10 of them, gallstones had recurred within 12 +/- 2 months (X +/- SEM); the other 10 had been free of stones since 22 +/- 3 months. RESULTS: In each group, duodenal bile was supersaturated with cholesterol in 8 of 10 patients and showed abnormal nucleation time of cholesterol crystals in half of the patients. Patients with recurrent stones had smaller pool sizes of cholic acid (-43%) and enhanced conversion of cholic acid to deoxycholic acid. The odds for stone recurrence were ninefold increased in the presence of excessive deoxycholic acid (exceeding cholic acid) in the bile acid pool or incomplete emptying of the gallbladder (residual volume > 5 mL) in response to cholecystokinin. The odds ratio was over 20-fold increased when incomplete emptying of the gallbladder coincided with supersaturated bile or with excessive deoxycholic acid. CONCLUSIONS: Enhanced conversion of cholic acid to deoxycholic acid and incomplete emptying of the gallbladder could be important cofactors for the recurrence of gallstones.

Bile↗
PubMed1995

Preduodenal mechanisms compensate completely for absent pancreatic enzymes to stimulate gallbladder after meals.

We studied gallbladder emptying with gamma scintigraphy in nine dogs prepared with chronic pancreatic fistulas, so that pancreatic enzymes could be either completely excluded from the duodenum or supplied in normal amounts. During duodenal perfusion of the fasted dogs with fat emulsions, gallbladder emptying was significantly less rapid when the emulsion contained inactive vs active enzymes, confirming the potency of lipolytic products in the intestine as stimuli of gallbladder emptying. However, after feeding either a 115-g or a 460-g meal, each 18% fat, the gallbladders emptied identically whether or not pancreatic enzymes were excluded from the duodenum. We concluded that while products of pancreatic lipolysis in the small intestine are potent stimuli of gallbladder contraction, preduodenal mechanisms can compensate completely for the absence of pancreatic hydrolysis in stimulating gallbladder emptying after a meal.

Animals↗
PubMed1990

Mechanism of cholecystokinin-induced contraction of the opossum gallbladder.

The present study evaluated the mechanism of cholecystokinin-induced gallbladder contraction in awake opossums. Each of 19 chronic animal preparations had an indwelling gallbladder cannula for monitoring changes in gallbladder volume and a jugular catheter for administration of cholecystokinin octapeptide and drugs. An intraduodenal catheter allowed intraduodenal infusion of Isocal (Mead Johnson Laboratories, Evansville, Ind.). Bipolar electrodes in the stomach, duodenum, and jejunum enabled monitoring of the duodenal migratory myoelectric complex cycle. One-hour infusions of cholecystokinin octapeptide (10 ng/kg/min), intraduodenal Isocal (0.4 ml/min), or feeding were started 20 min after cessation of phase 3 duodenal migratory myoelectric complex activity. Bolus intravenous doses of potential pharmacological antagonists were given 10 min before and 20 min after the onset of cholecystokinin octapeptide infusion, Isocal infusion, or feeding. Each test challenge induced about 60% gallbladder emptying at 30 min and 70% at 60 min. Cholecystokinin octapeptide-induced gallbladder emptying was converted to filling by hexamethonium and nearly abolished by atropine. Similar results were obtained for gallbladder emptying induced by feeding or duodenal infusion of Isocal. Phentolamine caused a modest decrease of cholecystokinin octapeptide-induced gallbladder contraction at 30 min, whereas postprandial or Isocal-induced gallbladder contraction was unaffected. Cholecystokinin octapeptide-induced gallbladder contraction was not affected by pirenzepine, 4-diphenylacetoxy-N-methylpiperidine methiodide, prazosin, pyrilamine, cimetidine, methysergide, naloxone, or propranolol. In acute studies of anesthetized animals, gallbladder contraction induced by a D100 intravenous bolus of cholecystokinin octapeptide (800 ng/kg) was not antagonized by hexamethonium, atropine, or tetrodotoxin. It is concluded (a) that cholecystokinin-induced physiologic contraction of the opossum gallbladder occurs through neural mechanisms rather than by a direct action of cholecystokinin on gallbladder smooth muscle, and (b) that studies using pharmacologic bolus doses of cholecystokinin octapeptide and tetrodotoxin indicate that cholecystokinin receptors exist on the gallbladder smooth muscle which do not seem to have any physiological role in gallbladder emptying.

Animals↗
PubMed1996

Role of intraduodenal proteases in plasma cholecystokinin and pancreaticobiliary responses to protein and amino acids.

BACKGROUND & AIMS: The role of small intestinal proteolytic activity in the regulation of upper gastrointestinal function in humans is poorly understood. The aim of this study was to determine the importance of proteolytic activity for protein- or amino acid-induced cholecystokinin release and pancreaticobiliary secretion. METHODS: In 9 healthy subjects, saline was perfused intraduodenally for 3 hours either with or without the synthetic protease inhibitor camostate. During the last hour, albumin or amino acids in the same molecular composition as albumin were also perfused. RESULTS: Perfusion with camostate, in concentrations that abolished intraduodenal proteolytic activity, had no effect on unstimulated plasma cholecystokinin concentrations or gallbladder emptying, but markedly (P < 0.05) increased unstimulated pancreatic enzyme output. Perfusion with protein distinctly stimulated cholecystokinin release, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Perfusion with camostate resulted in significantly lower protein-stimulated plasma cholecystokinin, gallbladder, and pancreatic enzyme responses (P < 0.05). Perfusion with amino acids also stimulated plasma cholecystokinin, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Camostate did not inhibit these values. CONCLUSIONS: This study shows that appropriate digestion of protein is required to stimulate plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion in humans.

Adult↗
PubMed1994

Effect of erythromycin administration on upper gastrointestinal motility in scleroderma patients.

BACKGROUND: Gastrointestinal involvement is frequent in patients with scleroderma. Erythromycin, a macrolide antibiotic, has been shown to accelerate gastric emptying in normal subjects and diabetic patients. The present study investigated the effects of acute erythromycin administration on gastric and gallbladder motility in patients with scleroderma and gastrointestinal involvement. METHODS: Twelve scleroderma patients and 14 healthy subjects were investigated. Each subject was investigated on 4 different days. Gastric and gallbladder emptying and gastric motility were determined by sonography and manometry, and the effect of 2 mg/kg/h erythromycin in fasted patients or after semisolid meal evaluated. RESULTS: The half-time of gastric emptying in response to semisolid meal was 121.3 +/- 14.0 min (SE) in scleroderma patients and 45.7 +/- 10.4 min in healthy subjects (P < 0.01). The peak of gallbladder emptying occurred later in scleroderma patients (95.0 +/- 5.0 min) than in healthy subjects (45.0 +/- 8.0 min) (P < 0.01). Erythromycin stimulated gastric and gallbladder motility in fasted subjects, as shown by manometry and sonography, and accelerated gastric and gallbladder emptying when administered immediately before the meal (P < 0.01). CONCLUSIONS: Erythromycin accelerates gastric and gallbladder emptying in scleroderma patients and might be helpful in the treatment of gastrointestinal motor abnormalities in these patients.

Adult↗
PubMedDate not supplied

Mechanisms of impaired gallbladder contractile response in chronic acalculous cholecystitis.

The mechanisms involved in the impaired gallbladder contractile response in chronic acalculous cholecystitis are unknown. To determine the mechanisms that may lead to impaired gallbladder emptying in chronic acalculous cholecystitis, gallbladder specimens removed during hepatic resection (controls) and after cholecystectomy for chronic acalculous cholecystitis were attached to force transducers and placed in tissue baths with oxygenated Krebs solution. Electrical field stimulation (EFS) (1 to 10 Hz, 0.1 msec, 70 V) or the contractile agonists, CCK-8 (10(-9) to 10(-5)) or K(+) (80 mmol/L), were placed separately in the tissue baths and changes in tension were determined. Patients with chronic acalculous cholecystitis had a mean gallbladder ejection fraction of 12% +/- 4%. Pathologic examination of all gallbladders removed for chronic acalculous cholecystitis revealed chronic cholecystitis. Spontaneous contractile activity was present in gallbladder strips in 83% of control specimens but only 29% of gallbladder strips from patients with chronic acalculous cholecystitis (P < 0.05 vs. controls). CCK-8 contractions were decreased by 54% and EFS-stimulated contractions were decreased by 50% in the presence of chronic acalculous cholecystitis (P < 0.05 vs. controls). K(+)-induced contractions were similar between control and chronic acalculous cholecystitis gallbladder strips. The impaired gallbladder emptying in chronic acalculous cholecystitis appears to be due to diminished spontaneous contractile activity and decreased contractile responsiveness to both CCK and EFS.

Adult↗
PubMed2003

Arris & Gale lecture. Regulation and responses of gallbladder muscle activity in health and disease.

A complex relationship links biliary symptoms with the mechanisms of gallbladder emptying and the presence of gallstones. This relationship has been investigated by clinical studies of symptoms associated with gallstones, by investigation of gallbladder emptying and cholecystokinin (CCK) release in patients with gallstones, and after cholecystectomy, or truncal vagotomy, and in the irritable bowel syndrome (IBS). Laboratory studies examined receptor density on bovine gallbladder, and contractility of human gallbladder in response to a variety of stimuli was studied in vitro. A set of six symptoms associated with the presence of gallstones was identified; IBS appeared to be present in two-fifths of patients before cholecystectomy but only one-third of these patients had persistent IBS symptoms one year after operation. Gallbladder emptying studies confirmed the poor contraction of stone-bearing gallbladders; abnormal patterns of emptying were also found in patients with IBS. Gallbladder emptying and filling appear to be largely neurally regulated. CCK receptor density was very low in gallbladder tissue, suggesting that receptors on nerve cells might mediate the action of CCK. Relaxation of gallbladder muscle was mediated by adrenergic and nitrergic nerves. The inflammatory mediator bradykinin, however, had a strong direct action on muscle cells to cause gallbladder contraction. The work reported here gives an overview of the symptoms and mechanisms of disease associated with the presence of stones in the gallbladder.

Cholelithiasis↗
PubMed1989

Role of the gastric phase in fat-induced gallbladder contraction and cholecystokinin secretion in humans.

The present study was undertaken to investigate the role of the gastric phase of fat-induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra-intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P less than 0.05) later increase in plasma CCK levels (20 +/- 2 min) compared to intraintestinal fat (5 +/- 1 min). Similarly, the onset of gallbladder emptying was significantly (P less than 0.05) delayed after intragastric fat (20 +/- 2 min) compared to intestinal fat (10 +/- 1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P less than 0.005-P less than 0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 +/- 1 min) and the onset of gallbladder emptying (15 +/- 2 min) were in the same range after intra-intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors.

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu-motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6-155.7) min for saline, 28.7 (21.0-33.2) min for motilin, and 39.3 (30.7-100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one-third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.

Adult↗
PubMed1987

Gallbladder volume and emptying in insulin-requiring male diabetics.

Gallbladder function was evaluated in 27 healthy male volunteers and 47 male insulin-requiring diabetics from a diabetic clinic. Three groups of patients were studied: 18 patients without neuropathy or retinopathy (A); 17 patients with evidence of peripheral neuropathy (B); and 12 patients with evidence of peripheral and autonomic neuropathy (C). Eleven patients complained of gastrointestinal symptoms (three in group B, eight in group C). Thirty minutes after a standard breakfast, fasting gallbladder volumes and gallbladder emptying rates were measured using a real-time mechanical sector ultrasound scanner. Fasting gallbladder volume in diabetic patients was similar to controls (24.9 +/- 2.7 N; 28.9 +/- 3.9 A; 23.7 +/- 2.2 B; 16.7 +/- 3.4 C ml mean +/- SEM). Postprandial gallbladder emptying was not significantly different in any groups (47.4 +/- 5.1% N; 43.2 +/- 7.7% A; 50.7 +/- 7.7% B; 46.8 +/- 11.1% C). Seven diabetics and two controls had poor gallbladder emptying. One screened patient had cholecystectomy, three patients had stones, and two had sludge with a thickened gallbladder wall for a total of 12.5% gallbladder disease. These data suggest that gallbladder dysfunction in male insulin-requiring diabetics is rare.

Adult↗
PubMed2004

Determinants of gallbladder kinetics in obesity.

Obese subjects are at risk of developing gallstones both by being overweight and by reducing their body weight. The aim of the present study was to investigate factors related to disturbances in gallbladder emptying measured by ultrasound. Detailed information about weight loss attempts, age at onset of obesity, parity, presence of menopause, use of contraceptive or hormonal replacement drugs, and phase of menstrual cycle was obtained. Smoking habits, alcohol use, dietary intake, and physical activity were recorded. Body composition and fat distribution were assessed by anthropometry. Blood samples were taken for CCK, lipids, glucose, and insulin. Mean (SD) fasting gallbladder volume was 30.0 (12.6) ml. The residual volume was 12.5 (9.8) ml 90 min after a test meal. CCK levels increased from a basal 1.64 (0.8) pM to a peak value of 2.9 (1.0) pM. Fasting gallbladder volumes were closely related to residual and ejection volumes. Body weight and fasting insulin levels explained 35.2% of the variance in fasting volume, lean body mass and insulin explained 28.1% of the residual volume, and waist circumference 23.6% of the ejection volume. None of the other factors were related to gallbladder emptying. Subjects with the largest fasting gallbladders had the largest residual and least emptying gallbladders, scored the highest in every aspect of body size, composition, and fat distribution, and also had the highest insulin levels. Body weight, lean body mass, central fat distribution, and insulin levels were the main determinants of gallbladder kinetics. Fasting and residual gallbladder volumes were closely related and both determined by obesity and its metabolic complication of hyperinsulinemia.

Adipose Tissue↗
PubMed1990

Effect of loxiglumide on gallbladder contractile response to cerulein and food in humans.

The present study investigated the effect of loxiglumide, a new selective cholecystokinin-receptor antagonist, on the gallbladder contractile responses to caerulein and to food in humans. In 6 healthy men, the gallbladder emptying driven by intravenous infusion of stepwise increasing doses of cerulein (10-80 ng/kg . h) and that induced by a 550-cal standard meal were monitored by ultrasonography. In both sets of experiments, the effect of loxiglumide was tested at various infusional rates against a control infusion of saline. An infusional rate of 2.5 mg/kg . h of loxiglumide abolished the gallbladder response even to maximal doses of cerulein, whereas a rate of 1.0 mg/kg . h counteracted the cholecystokinetic activity of cerulein up to the dose of 20 ng/kg . h. In postprandial experiments, the cholecystokinin antagonist dose-dependently inhibited the physiologic gallbladder contraction. The maximal gallbladder emptying, which always occurred 85 min after the meal, was 71.1% +/- 3.3% of basal volume in control studies, 39.2% +/- 1.8% during infusion of 2.5 mg/kg . h of loxiglumide, and 17.3% +/- 5.9% when 5.0 mg/kg . h were infused. A dose of 7.5 mg/kg . h of loxiglumide was able to prevent any postprandial emptying of the gallbladder. The present study shows that a selective cholecystokinin receptorial blockade competitively antagonizes cerulein-induced gallbladder contraction and dose-dependently inhibits postprandial gallbladder emptying.

Adult↗