Ultrasound-guided intervention: expanding horizons.

Ultrasound-guided intervention has enjoyed a period of unprecedented growth because its many advantages over other guidance modalities have been recognized. The decreased procedure time, increased accuracy, and safety of procedures performed under ultrasound guidance are of obvious benefit to radiologist and patient alike for all interventional applications. Lesions once considered unsafe to sample are now reasonably approached with ultrasound guidance. As equipment technology continues to improve and radiologists increasingly recognize the benefits of guiding procedures with ultrasound, the shift of procedures away from CT and fluoroscopic guidance will continue and ultrasound guidance will become the guidance method of choice for most interventional procedures.

Coffee stimulation of cholecystokinin release and gallbladder contraction in humans.

We studied the effect of the ingestion of 400 mL regular coffee on plasma cholecystokinin (CCK) concentrations and of 165 mL regular and decaffeinated coffee on plasma CCK and gallbladder contraction in six healthy regular coffee drinkers. Plasma CCK concentrations rose 3.3 +/- 0.4 pmol/L after 400 mL and 2.8 +/- 0.9 pmol/L after 165 mL regular coffee compared with 1.8 +/- 0.6 pmol/L after 165 mL decaffeinated coffee. These plasma CCK increments were greater than those after 400 and 165 mL of an isosmotic and isothermic sodium chloride solution (0.6 +/- 0.2 and 0.4 +/- 0.1 pmol/L, respectively). An average gallbladder contraction of 33 +/- 7% was observed after 165 mL regular coffee and 29 +/- 10% after 165 mL decaffeinated coffee, whereas after 165 mL sodium chloride the contraction was only 10 +/- 12%. We conclude that both regular coffee and decaffeinated coffee give rise to increments in plasma CCK and contractions of the gallbladder.

Effect of various triglycerides on plasma cholecystokinin levels in rats.

In the rat model, polyunsaturated vegetable oil has been shown to stimulate pancreatic secretion and promote pancreatic carcinogenesis, whereas dietary fish oil has been found to protect against carcinogenesis. Because cholecystokinin (CCK), a hormonal polypeptide secreted from the upper small intestine after food stimulation, is the most important known humoral stimulus of pancreatic secretion and also because this gut hormone has been shown to promote pancreatic carcinogenesis in the rat, we decided to study the effects of various triglycerides on CCK secretion in this species. Small amounts (2.5 mL) of corn oil, beef tallow, fish oil, medium-chain triglyceride (MCT) oil or saline (control) were administered to groups of five fasted rats. Plasma CCK levels were measured using a specific and sensitive radioimmunoassay. The maximal CCK increments for corn oil, beef tallow, fish oil and MCT oil were 3.0 +/- 0.5, 2.1 +/- 0.6 and 7.2 +/- 0.4 pmol/L, respectively. All the increments were significantly greater (p less than 0.05) than the change found after saline administration (-0.8 +/- 0.3 pmol/L). In another experiment, plasma CCK levels after intragastric administration of MCT oil reached a peak increment of 6.4 +/- 0.4 pmol/L after 240 min and continued to be significantly increased for the entire 480-min study period. It was concluded that all four triglycerides caused a significant CCK release in the rat and that the MCT oil was the most powerful stimulator of CCK secretion among the triglycerides studied.

Comparison of the effect of lorglumide on pancreatic growth stimulated by camostate in rat and hamster.

We conducted a 14 day experiment in which we administered camostate (a trypsin inhibitor) and cholecystokinin alone or in combination with lorglumide, a cholecystokinin receptor antagonist, to both rats and hamsters. Plasma cholecystokinin levels were 21.7 +/- 3.2 pM and 19.6 +/- 2.5 pM with camostate, 16.3 +/- 2.4 pM and 14.8 +/- 2.2 pM with exogenous cholecystokinin, and 3.7 +/- 0.4 pM and 4.2 +/- 1.0 pM in control experiments in rats and hamsters, respectively. Both cholecystokinin and camostate were found to promote pancreatic growth in rats (18 +/- 4 and 111 +/- 7%, respectively) and hamsters (76 +/- 18 and 61 +/- 12%, respectively). Although lorglumide caused a decrease of this effect of camostate in both rats (78 +/- 5%) and hamsters (25 +/- 10%), it only became significant in rats. We therefore conclude that there are important interspecies differences in the role cholecystokinin plays in mediating the trophic effects of trypsin inhibitors on the pancreas.

Effect of loxiglumide (CR-1505) on bombesin- and meal-stimulated plasma cholecystokinin in man.

Cholecystokinin (CCK)-receptor antagonists have been reported to inhibit the effects of the hormone on the gastrointestinal tract. Their effect on plasma CCK levels in man has not been described. The present study in 5 normal subjects demonstrated that i.v. infusion of the potent, specific CCK-receptor antagonist loxiglumide (CR 1505) significantly augmented plasma CCK levels during infusion of bombesin (402 pM per 30 min) and after administration of a meal (1390 pM per 300 min) when compared to the bombesin- (192 pM per 30 min) and meal- (886 pM per 300 min) stimulated CCK responses during infusion of saline. The basal plasma CCK during saline infusion (0.1 pM per 40 min) was not significantly influenced by CR 1505 (-1.8 pM per 40 min). Thus, both enteral (meal) and parenteral (bombesin) stimulation of CCK secretion are augmented by CCK-receptor blockade.

The effect of loxiglumide (CR-1505) on basal and bombesin-stimulated gallbladder volume in man.

This study was undertaken in 5 normal subjects to determine the role of cholecystokinin (CCK) in the regulation of basal gallbladder volume and gallbladder contraction stimulated by infusion of bombesin. Administration of the CCK-receptor antagonist, loxiglumide (CR-1505), led to doubling of the gallbladder volume (increase 104 +/- 26%; P less than 0.05) and reduced the bombesin-stimulated gallbladder contraction from 69 +/- 17 to 19 +/- 17% (P less than 0.05). The findings provide evidence suggesting that CCK plays an important role in the regulation of basal gallbladder tone and in mediating the gallbladder contraction induced by the administration of bombesin.

Modulation by CR-1409 (lorglumide), a cholecystokinin receptor antagonist, of trypsin inhibitor-enhanced growth of azaserine-induced putative preneoplastic lesions in rat pancreas.

Feeding of raw soya flour or other trypsin inhibitors such as camostate is a well-established method for promoting growth of (pre)neoplastic foci induced in the exocrine pancreas of rats by azaserine. The effect of trypsin inhibitors is thought to be mediated through an increased release of cholecystokinin. Using the specific cholecystokinin receptor antagonist lorglumide (CR-1409), we performed a 16-wk study to investigate the potential of this drug in inhibiting growth of putative preneoplastic foci and to determine whether and to what extent cholecystokinin is responsible for the effect of trypsin inhibitors on pancreatic growth. After initiation with 30 mg/kg of azaserine at 19 days of age, six groups of 15 rats each received one of the following treatments: camostate, cholecystokinin-8, or gelatin control, either or not in combination with CR-1409, once daily, 3 days wk for 16 wk. Plasma cholecystokinin levels, measured 30 min after the stimulus, were similar after camostate and cholecystokinin octapeptide administration. After 16 wk the pancreata were removed, weighted, and quantitatively analyzed for the number and size of putative preneoplastic foci by light microscopy. Both camostate and cholecystokinin octapeptide stimulated pancreatic growth and development of acidophilic putative preneoplastic foci, whereas growth of basophilic putative preneoplastic foci was inhibited by camostate but stimulated by cholecystokinin. CR-1409 almost completely abolished the effect of cholecystokinin and was found to cause a significant decrease in the effects of camostate. It is concluded that (a) cholecystokinin plays a significant role in camostate-stimulated growth of acidophilic putative preneoplastic foci in rat pancreas and (b) CR-1409 inhibits growth of putative preneoplastic foci induced in rat pancreas by azaserine and hence may be of potential value for the treatment of pancreatic cancer in humans.

Study into the role of cholecystokinin in bombesin-stimulated pancreatic growth in rats and hamsters.

The effects of cholecystokinin and bombesin on growth of the exocrine pancreas have been studied extensively in rats but not in hamsters. Since hamsters are frequently used for studying pancreatic carcinogenesis it seems highly relevant to determine the effects of these peptides on growth of the hamster pancreas as well. In order to determine whether or not bombesin stimulates pancreatic growth in hamsters and to investigate the role of cholecystokinin in mediating this effect, we conducted a 2-week experiment in which cholecystokinin and bombesin were administered to both rats and hamsters, either with or without lorglumide (CR-1409; a specific cholecystokinin receptor antagonist). Rats were included in the study for comparison. Cholecystokinin and bombesin were found to stimulate pancreatic growth and DNA synthesis in both species. Lorglumide did not significantly influence the effect of bombesin on pancreatic weight but did significantly inhibit DNA synthesis in both species. The effect of cholecystokinin on pancreatic weight was greater in hamsters than in rats. This effect was significantly inhibited by lorglumide in hamsters but not in rats, whereas a significant decrease in DNA content was attained in both species. Thus, this study shows marked differences between rats and hamsters in the pancreatic growth response to cholecystokinin and bombesin.

Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas.

Both cholecystokinin and bombesin have been shown to promote pancreatic carcinogenesis in the azaserine-rat model. The present study was undertaken to discriminate between the effects of cholecystokinin and bombesin and to establish the modulating properties of the specific cholecystokinin receptor antagonist CR-1409 on pancreatic carcinogenesis. After initiation with 30 mg/kg of azaserine, six groups of 15 Wistar rats were treated for 16 wk with cholecystokinin, bombesin, or gelatin (control), some in combination with CR-1409. Doses of cholecystokinin (2.5 micrograms/kg) and bombesin (10 micrograms/kg) were chosen that rendered approximately equal plasma cholecystokinin levels. Both cholecystokinin and bombesin were found to stimulate pancreatic growth, whereas CR-1409 only inhibited the growth-promoting effect of cholecystokinin significantly. Furthermore, both peptides stimulated the development of putative preneoplastic lesions, whereas CR-1409 only inhibited the effect of cholecystokinin significantly. It is concluded that (a) CR-1409 inhibits the promoting effect of cholecystokinin on pancreatic growth and azaserine-induced early pancreatic lesions and (b) the effects of bombesin cannot be fully ascribed to stimulation of the secretion of endogenous cholecystokinin.

The influence of different nutrients on plasma cholecystokinin levels in the rat.

Isocaloric and isovolemic amounts of protein (casein), fat (intralipid) and carbohydrate (saccharose) and an isovolemic control solution of water were administered intragastrically to conscious rats. The plasma CCK levels, determined by a sensitive and specific radioimmunoassay, showed an increment of 6.3 +/- 0.6, 2.7 +/- 0.5, 1.7 +/- 0.4 and -0.9 +/- 0.4 pM, respectively (basal value 2.5 +/- 0.3 pM). The threshold increment of plasma CCK to stimulate pancreatic enzyme secretion by exogenous CCK was found to be 1.5 pM. It is therefore concluded that casein is a potent stimulus for CCK secretion and pancreatic secretion, but that fat and even carbohydrate, although less potent, also produce a CCK increment above the threshold for pancreatic secretion.