Two point analysis 15-minute 14C-urea breath test for diagnosing Helicobacter pylori infection.

The value of a two point analysis (double sample) 14C-urea breath test in diagnosing Helicobacter pylori (HP) infection in patients with suspected acid peptic disease has been studied and compared to histology and to a rapid agar plate urease test in 76 patients. Using the histological finding of HP as the gold standard, the 14C-breath test was positive in 59 of the 61 histologically confirmed infected patients and in 3 of the 15 noninfected ones, giving a sensitivity of 97% and specificity of 80%. In 12 patients, a smaller dose of 3 mu Ci 14C-urea was used. The results correlated well with those in whom the higher dose of 10 mu Ci was used. We conclude that a two point 14C-urea breath test with analysis at 5 and 15 min is effective in diagnosing HP infection thus obviating the need for endoscopy and biopsy.

Effect of chlorpromazine (CPZ) on cholecystokinin-induced gallbladder contraction: the role of calcium.

Smooth muscle contraction is initiated by a rise in intracellular calcium, which binds to calmodulin resulting in myosin phosphorylation. CPZ impairs smooth muscle contraction by either interfering with calcium influx at low concentrations (less than 1.25 x 10(-5) M) or inactivating calcium-calmodulin at higher levels. This chlorpromazine effect was used to determine if gallbladder agonists act through different intracellular mechanisms. Guinea pig gallbladders were mounted in an organ bath and auxotonic contractions induced by bethanechol, KCl and the octapeptide of cholecystokinin (CCK). Bethanechol and KCl-induced contractions were profoundly inhibited by 1.25 x 10(-5) M CPZ throughout the dose-response curve. In contrast, CPZ did not affect CCK-mediated contractions at CCK concentrations less than 5.7 x 10(-8) M. At maximal CCK doses (3 x 10(-7) M), CPZ had only a modest inhibitory effect of 20%, compared with tension losses of 62 and 80% for bethanechol and KCl, respectively. This inhibition with high-dose CCK was offset by increasing extracellular calcium in the organ bath. The resistance of CCK to CPZ inhibition at low doses within the physiologic range implies that CCK acts independently of extracellular Ca2+ unlike the other agonists. Higher CPZ concentrations, greater than or equal to 1.25 x 10(-4) M, markedly suppressed CCK throughout the dose-response curve. Cholecystokinin may act via myosin phosphorylation, but unlike other agonists any rise in cytoplasmic calcium likely originates from an intracellular site.

The effects of prosthetic gallstones on gallbladder function and bile composition.

Diminished gallbladder emptying has been implicated in the pathogenesis of gallstone formation. This study assessed the effect of the physical presence of inert, prosthetic gallstones on gallbladder contractility, histopathology, and bile composition. Three glass beads, each 3 mm in diameter, were implanted in the guinea pig gallbladder. Six weeks later the in vitro contractility was assessed in response to cholecystokinin. Sham-operated animals underwent cholecystotomy without bead implantation. The gross and microscopic appearance of gallbladders from sham-operated and implanted animals was the same. The presence of stones moderately inhibited gallbladder contraction reaching 20.5% (P less than 0.05) at the maximally effective dose of cholecystokinin compared to sham-operated animals. Sham-operated and control (unoperated) animals had similar gallbladder contractility. Thus surgery itself did not alter gallbladder motility. The presence of stones had no effect on biliary lipid composition. It thus appears that gallstones, in the unobstructed gallbladder, cause only a moderate inhibition of gallbladder contractility and have little effect on biliary physiology.

Direct determination of the contractility of the guinea pig gallbladder: a new in vivo model.

In vivo methods to study gallbladder contractility either equate gallbladder emptying with contraction or have relied on changes in gallbladder intravesicular pressure to reflect active transmural tension. We therefore devised an animal model in which the contractile force of the intact gallbladder is measured directly while the blood and neural supply remains uncompromised. Under general anesthesia one pole of the guinea pig gallbladder is anchored to the sternum and the other connected to a force displacement transducer. Any contraction--relaxation between these two points is recorded. This model was validated by measuring gallbladder response to both neuronal and humoral stimulation. Nerve stimulation was accomplished by means of two silver collar electrodes placed in contact with the cystic duct. With nerve stimulation, a frequency (0.5-10 Hz) or amplitude (1-10 V) dependent contraction occurred. Intravenous bethanechol (10 X 10(4) ng . kg-1 . h-1) and cholecystokinin (3 X 10(4) ng . kg-1 . h-1) both induced dose-dependent gallbladder contraction. This model should prove useful in assessing the physiologic control of gallbladder contraction.

Abnormal gallbladder emptying in a subgroup of patients with gallstones.

Gallbladder stasis has been implicated in gallstone formation. Gallbladder filling and emptying were quantitated by computer-assisted cholescintigraphy in 41 normal subjects versus 26 patients with gallstones. Gallbladder contraction was induced by low-dose (1.2 U/kg . h) cholecystokinin infusion. Gallstone patients exhibited normal gallbladder filling, but emptying was significantly (p less than 0.01) reduced compared with controls. On closer inspection, the patients fell into two subgroups, separated by t1/2, the time to empty 50% of gallbladder contents, 19.1 min (mean + 2 SD of control). Fifteen patients (57.7%) with a normal t1/2 (less than 19.1 min) exhibited both normal filling and normal emptying. The remaining 11 patients (43.3%) with t1/2 greater than 19.1 min had grossly abnormal gallbladder emptying, significantly (p less than 0.001) different from both the previous patient subgroup and the controls. There was no significant difference in age, sex, prevalence of obesity, presence or absence of biliary colic, and gallstone size, number, or calcification between these two subgroups. Thus, defective gallbladder emptying is evident in a subgroup of gallstone patients, and is independent of clinical features, stone size, and number. Impaired emptying should be considered when assessing pathogenesis or medical therapy.

In vitro effects of pancreatic polypeptide and motilin on contractility of human gallbladder.

In vivo studies have indicated that pancreatic polypeptide induces gallbladder relaxation, whereas motilin initiates contraction of the gallbladder. To determine if these two polypeptides act directly on the gallbladder muscle, their effect on strips of human gallbladder was studied in vitro. Preparations were suspended in an organ bath and the isometric tension recorded. Dose-response curves to cholecystokinin and acetylcholine were first established. The ability of pancreatic polypeptide to cause relaxation under basal conditions and during 50% maximal stimulation by cholecystokinin-octapeptide (2 X 10(-8) M) was assessed on four strips at approximate physiological concentration (300 pmol/liter) and on four additional strips at 10(3) higher concentration. Pancreatic polypeptide did not have any effect on the basal or the cholecystokinin-generated tension at either concentration. The response to motilin was evaluated on four gallbladder strips at concentrations ranging from 10(-11) to 6.7 X 10(-7) M. Although the highest concentration was more than 10(5) greater than levels reported in fasting serum, motilin did not initiate any gallbladder strip contraction. Whereas the preparation was unresponsive to pancreatic polypeptide and motilin, it was capable of contracting in a dose-related fashion to the known agonists cholecystokinin and acetylcholine, and the response was blocked by the respective antagonists dibutyryl cyclic GMP and atropine. It thus seems that pancreatic polypeptide and motilin exert their respective actions as sites remote from the gallbladder without directly affecting gallbladder muscle.