sincalide and Chronic-Disease

Since the early 1980s interventions have been used in conjunction with (99m)Tc-iminodiacetic acid (IDA) radiopharmaceuticals in many different clinical situations, eg, to prepare the patient for the study, to reduce the time of a study, to improve its diagnostic accuracy, and to make diagnoses not otherwise possible. Interventions all have underlying physiological rationales. Some of these interventions are as simple as having the patient fast before the study or eat a meal with high fat content. However, most are pharmacologic interventions, eg, morphine sulfate, cholecystokinin, and phenobarbital. Although these are probably the most common interventions used today, numerous other interventions have been used during the years and likely will be in the future. Interventions have aided in the diagnosis of acute cholecystitis, chronic cholecystitis, biliary obstruction, and sphincter of Oddi dysfunction. This review will discuss in detail the interventions commonly is use today and in somewhat less detail many that have been successfully used on an investigational basis and may have some larger role in the future.

Topics: Biliary Tract Diseases; Cholecystitis; Cholecystitis, Acute; Cholecystokinin; Chronic Disease; Gallbladder Emptying; Humans; Morphine; Radionuclide Imaging; Radiopharmaceuticals; Sincalide; Technetium Tc 99m Diethyl-iminodiacetic Acid

Chronic acalculous gallbladder and chronic acalculous biliary disease are considered functional hepatobiliary diseases. Cholescintigraphy provides physiologic imaging of biliary drainage, making it ideally suited for their noninvasive diagnosis. For chronic acalculous gallbladder disease, calculation of a gallbladder ejection fraction during sincalide cholescintigraphy can confirm the clinical diagnosis and has become a common routine procedure in many nuclear medicine clinics. Published data generally confirm a high overall accuracy for predicting relief of symptoms with cholecystectomy. However, data also exist suggesting it is not useful. The discrepant results probably are caused by the various different methodologies that have been used for sincalide infusion. Proper methodology of sincalide infusion is critical for providing accurate reproducible results, minimizing false positive studies, and preventing adverse side effects. The most common causes for the postcholecystectomy pain syndrome are partial biliary obstruction secondary to stones or tumor and sphincter of Oddi dysfunction. The latter is a partial biliary obstruction at the level of the sphincter. This has long been considered a functional hepatobiliary disease because of the lack of anatomical abnormalities. Sphincterotomy is the present treatment; however, diagnosis requires invasive procedures, such as endoscopic retrograde cholangiopancreatography and sphincter of Oddi manometry, which has a high complication rate and is not widely available. The unique ability of cholescintigraphy to image biliary drainage allows noninvasive diagnosis. Different methodologies have been reported, many with good overall accuracy. Various pharmacologic interventions and quantitative methodologies have been used in conjunction with cholescintigraphy to enhance its diagnostic capability. Further investigations are needed determine the optimal methodology; however, cholescintigraphic methods have already a clinical role in the diagnosis of sphincter of Oddi dysfunction and will be used increasingly in the future.

Topics: Biliary Tract; Biliary Tract Diseases; Chronic Disease; Gallbladder; Gallbladder Diseases; Humans; Radionuclide Imaging; Sincalide; Sphincter of Oddi Dysfunction

Topics: Acute Disease; Biomarkers; Chronic Disease; Diagnostic Techniques, Endocrine; Humans; Jaundice, Obstructive; Liver Cirrhosis; Pancreatitis; Radioimmunoassay; Sincalide; Specimen Handling

The mechanisms responsible for the abnormalities of gallbladder emptying in patients with chronic acalculous gallbladder disease (AGD) have not been elucidated. This study was designed to determine whether a muscle defect could explain this gallbladder dysfunction.. Gallbladder contraction induced by a continuous intravenous cholecystokinin octapeptide (CCK-8) infusion was determined by ultrasonography in control subjects, patients with AGD, pigment stones, and cholesterol stones. Muscle cells were obtained by enzymatic digestion. (125)I-CCK-8 binding and [(35)S]guanosine triphosphate gamma S (GTP gamma S) binding studies were performed.. In vivo gallbladder contraction induced by CCK-8 was significantly lower in AGD (29.4%) and cholesterol stones (28.8%) than in pigment stones (59.8%) and normal controls (57.8%; P < 0.01). In vitro muscle cell contraction induced by CCK-8 was also lower in AGD than in pigment stones. It remained impaired in AGD after stimulation with the G-protein activators GTP gamma S and AlF(4) and with the second messenger 1,2-dioctanoyl-sn-glycerol. However, GTP gamma S binding induced by CCK-8 and vasoactive intestinal polypeptide and the binding capacity of CCK receptors were not different between AGD and pigment stones.. These findings suggest that there is a good correlation between in vivo and in vitro gallbladder response to CCK-8 in patients with AGD. Unlike those found in cholesterol stones, the muscle defects in AGD appear to reside in the contractile apparatus.

Topics: Cell Membrane; Cholelithiasis; Cholesterol; Chronic Disease; Colic; Diglycerides; Gallbladder; Gallbladder Diseases; Gallbladder Emptying; Guanosine 5'-O-(3-Thiotriphosphate); Humans; In Vitro Techniques; Iodine Radioisotopes; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Smooth; Receptors, Cholecystokinin; Sincalide; Sulfur Radioisotopes; Ultrasonography; Vasoactive Intestinal Peptide

Antipsychotic properties of cholecystokinin have been suggested both in laboratory studies and in some open clinical trials, mainly in patients suffering from chronic schizophrenia. Eighteen patients (14 males, 4 females) meeting Research Diagnostic Criteria for schizophrenia had been receiving neuroleptics at a dosage that had not changed for 3 months, and to which the patients were at best only partially responsive. The patients were randomized into groups that received weekly intravenous injections of 10 micrograms of CCK-8 or normal saline over 8 weeks. Neuroleptic medication was unchanged for the study. Baseline and weekly assessments were carried out using the Brief Psychiatric Rating Scale (BPRS) and the Schizophrenia Subscale of the Present State Examination (SS-PSE). Analysis of covariance revealed significant differences between CCK-8 and placebo over the study period on the Thought Disturbance Factor and Total Score of the BPRS, and on the Nuclear Syndrome, Total Delusion Factor, and Total Score of the SS-PSE. No important side effects were noted. It is concluded that CCK-8 has definite antipsychotic properties in patients with chronic schizophrenia. Clinical trials in neuroleptic-free patients are warranted.

Topics: Animals; Brief Psychiatric Rating Scale; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Schizophrenia; Sincalide

Eight neuroleptic-resistant schizophrenic patients were treated with ceruletide diethylamine, a cholecystokininlike peptide, in a placebo-controlled, double-blind, cross-over study. Ceruletide or placebo was administered intramuscularly twice a day for four consecutive days while patients received a constant dose of fluphenazine hydrochloride. Cholecystokinin octapeptide was also administered to four different schizophrenic patients in a double-blind, cross-over study. Cholecystokinin or placebo was administered as a slow intravenous infusion daily for four days. There were no changes in either the positive or negative symptoms of schizophrenia between the periods of placebo, ceruletide, or cholecystokinin administration. Furthermore, there was no tendency for the patients' conditions to either improve or worsen during the course of ceruletide or cholecystokinin treatment. In contrast to previous reports from uncontrolled studies, cholecystokininlike peptides appear to be devoid of antipsychotic properties when administered parenterally.

Topics: Adult; Ceruletide; Chronic Disease; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Placebos; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sincalide

Chronic cholangitis caused by hepatolithiasis is a common disease in Southeast Asia. Few studies have addressed the effects of chronic cholangitis on cyclic activity of the sphincter of Oddi (SO). In this study, we investigated the changes of myoelectric activity in rabbits with chronic cholangitis in vivo and in vitro.. Chronic cholangitis was induced in rabbits by initially introducing three pieces of 2-0 silk suture and sequentially injecting E. coli into the choledochus through the tube in ductus cysticus. In in vivo experiments, myoelectric activity of SO was recorded by a circular electrode through the jejunum stump in conscious animals. In in vitro experiments, the SO was completely isolated and the myoelectric activity was recorded by a circular electrode in a 10-mL organ bath filled with Krebs solution, with or without addition of cholecystokinin-8 (CCK-8), KCl, ionomycin or induction of capacitative calcium entry (CCE).. In comparison with control and non-infected rabbits, the rabbits with chronic cholangitis showed higher levels of alkaline phosphatase and gamma-glutamyltransferase and significant pathological changes including increased inflammatory infiltration and collagen deposition in mucosae or muscular layer. Cyclic myoelectric activity of SO at phases 2 and 3 of migrating motor complex and the excitatory response to CCK-8 were dramatically decreased in animals with chronic cholangitis. Myoelectric activity of SO was also significantly decreased in vitro with or without agonists or with induction of CCE.. Myoelectric activity of SO and its response to agonists are decreased in rabbits with chronic cholangitis both in vivo and in vitro.

Topics: Animals; Calcium; Cholangitis; Cholecystectomy; Cholecystokinin; Chronic Disease; Electromyography; Muscle Contraction; Muscle, Smooth; Peptide Fragments; Rabbits; Random Allocation; Sphincter of Oddi

Major aspects of temporal lobe epilepsy (TLE) can be reproduced in mice following a unilateral injection of kainic acid into the dorsal hippocampus. This treatment induces a non-convulsive status epilepticus and acute lesion of CA1, CA3c and hilar neurons, followed by a latent phase with ongoing ipsilateral neuronal degeneration. Spontaneous focal seizures mark the onset of the chronic phase. In striking contrast, the ventral hippocampus and the contralateral side remain structurally unaffected and seizure-free. In this study, functional and neurochemical alterations of the contralateral side were studied to find candidate mechanisms underlying the lack of a mirror focus in this model of TLE. A quantitative analysis of simultaneous, bilateral EEG recordings revealed a significant decrease of theta oscillations ipsilaterally during the latent phase and bilaterally during the chronic phase. Furthermore, the synchronization of bilateral activity, which is very high in control, was strongly reduced already during the latent phase and the decrease was independent of recurrent seizures. Immunohistochemical analysis performed in the contralateral hippocampus of kainate-treated mice revealed reduced calbindin-labeling of CA1 pyramidal cells; down-regulation of CCK-8 and up-regulation of NPY-labeling in mossy fibers; and a redistribution of galanin immunoreactivity. These changes collectively might limit neuronal excitability in CA1 and dentate gyrus, as well as glutamate release from mossy fiber terminals. Although these functional and neurochemical alterations might not be causally related, they likely reflect long-ranging network alterations underlying the independent evolution of the two hippocampal formations during the development of an epileptic focus in this model of TLE.

Topics: Action Potentials; Animals; Brain Chemistry; Calbindins; Chronic Disease; Disease Models, Animal; Down-Regulation; Electroencephalography; Epilepsy; Epilepsy, Temporal Lobe; Functional Laterality; Galanin; Hippocampus; Kainic Acid; Mice; Mossy Fibers, Hippocampal; Nerve Degeneration; Neural Pathways; Neuropeptide Y; Neurotoxins; Pyramidal Cells; S100 Calcium Binding Protein G; Sincalide; Status Epilepticus; Theta Rhythm; Up-Regulation

Current pancreatic function tests are cumbersome and unavailable to the clinical gastroenterologist. We have developed a function test that can be modified to a purely endoscopic collection method (ePFT). The aim of this study was to compare the endoscopic and traditional Dreiling tube collection methods.. Two separate groups of healthy subjects and patients with chronic pancreatitis underwent pancreatic function testing. One group underwent the endoscopic collection method (ePFT). Intravenous cholecystokinin (CCK 40 ng x kg(-1) x h(-1)) was started in preprocedure area. Duodenal fluid was collected with upper endoscope during endoscopy at 30, 40, 50, and 60 minutes during infusion. Another group underwent the traditional Dreiling collection method. Intravenous CCK was started in postprocedure area after endoscopic tube placement. Duodenal fluid was collected at 0, 20, 40, 60, and 80 minutes during infusion. Lipase concentration was determined (IU/L) on laboratory autoanalyzer.. Seventy-three patients were studied. Thirty-four underwent endoscopic collection and 39 underwent Dreiling collection. The mean peak lipase concentrations (+/- standard deviation) for healthy subjects and patients with chronic pancreatitis in the endoscopic collection method group were 1612500 +/- 556152 IU/L and 369594 +/- 281624 IU/L, respectively (P < 0.001). The mean peak lipase concentrations (+/- standard deviation) for healthy subjects and patients with chronic pancreatitis in the Dreiling tube collection method group were 1670324 +/- 786731 IU/L and 478956 +/- 406061 IU/L, respectively (P < 0.001). There was no statistical difference between collection methods at distinguishing healthy subjects and patients with chronic pancreatitis. Receiver operating characteristic curves (ROC) for the endoscopic and Dreiling collection methods were 0.993 (standard error of mean, 0.009) and 0.921 (standard error of mean, 0.041). A lipase concentration cut point of 810600 IU/L distinguishes healthy subjects from patients with chronic pancreatitis with a sensitivity and specificity of 92% and 95%, respectively. The ePFT was safe, short in duration, minimized costs (US dollars 1890 vs. US dollars 2659), required small amounts of fluid for analysis (1-3 mL), and eliminated radiation exposure.. Analysis of timed endoscopic aspirations of pancreatic juice after hormonal stimulation can distinguish healthy subjects from patients with chronic pancreatitis. This new endoscopic collection method (ePFT) is less cumbersome and more time efficient, when compared to traditional collection methods. The ePFT broadens the availability of function testing to the practicing clinical gastroenterologist.

Topics: Adult; Aged; Chronic Disease; Duodenum; Endoscopy, Digestive System; Female; Humans; Intubation, Gastrointestinal; Lipase; Male; Middle Aged; Pancreatic Function Tests; Pancreatic Juice; Pancreatitis; ROC Curve; Sensitivity and Specificity; Sincalide

Numerous publications have reported that a low gallbladder ejection fraction (GBEF) determined by cholecystokinin (CCK) cholescintigraphy has a high positive predictive value for the diagnosis of chronic acalculous cholecystitis (CAC). Clinicians and surgeons have found this test to be clinically useful as an objective method to confirm their clinical diagnosis. However, an abnormally low GBEF is not specific for CAC. For example, numerous other diseases have been associated with a low GBEF, and various therapeutic drugs can cause poor gallbladder contraction. Importantly, improper CCK infusion methodology can result in an erroneously low GBEF. More than one third of healthy subjects and patients who receive sincalide, 0.02 microg/kg infused over 1-3 min, will have an erroneously low GBEF but will have a normal GBEF with a slower infusion (30-60 min) of the same total dose. Because of enthusiastic acceptance of CCK cholescintigraphy by clinicians, the types of patients referred for this test have changed over time. Patients investigated in publications confirming the usefulness of CCK cholescintigraphy had a high pretest likelihood of disease. They underwent extensive workup to rule out other diseases and were followed up for months or years before CCK cholescintigraphy was performed, allowing other diseases to become manifest or symptoms to resolve. However, CCK cholescintigraphy is now being used by clinicians to shorten the workup and follow-up time based on the rationale that CCK cholescintigraphy can quickly confirm or exclude the diagnosis. This new group of referral patients has a lower likelihood of the disease. Many will ultimately be diagnosed with diseases other than CAC. The positive predictive value of this test will likely be lower and the false-positive rate will likely be higher. Nuclear medicine physicians must work to minimize false-positive studies to maintain the confidence of referring clinicians. First, we can educate referring physicians as to the proper use of this study. Next, we must perform CCK cholescintigraphy using optimal methodology that will result in the lowest possible false-positive rate. And finally, we must interpret CCK cholescintigraphy in light of the patient's history, prior workup and clinical setting.

Topics: Cholecystitis; Cholecystokinin; Chronic Disease; False Positive Reactions; Female; Gallbladder; Gallbladder Emptying; Humans; Male; Radionuclide Imaging; Sincalide

We compared pancreatic exocrine secretion in 5-month-old WBN/Kob rats, a model of chronic pancreatitis, with that in Wistar rats of the same age in a conscious state. Basal pancreatic secretion and pancreatic wet weight in WBN/Kob rats were lower than the values for Wistar rats. There was no difference in plasma cholecystokinin (CCK) concentration between the two types of rats. When CCK-8 was intravenously administered, the stimulation of pancreatic protein secretion in WBN/Kob rats was weaker than that in Wistar rats. When bile and pancreatic juice were diverted from the duodenum, the resulting increase in the plasma CCK concentration was similar in both types of rats, but stimulation of the volume and protein output of pancreatic juice in WBN/Kob rats was weaker than that in Wistar rats. In addition, WBN/Kob rats exhibited little increase in pancreatic wet weight because of this diversion. When secretin was intravenously administered, the stimulation of fluid secretion in WBN/ Kob rats was also weaker than that in Wistar rats. The binding of CCK-8 to pancreatic membrane fractions in WBN/Kob rats was much weaker than that in Wistar rats. Histological findings in WBN/Kob rat pancreas showed proliferation of fibrous tissue and atrophy of acinar cells. In conclusion, pancreatic exocrine secretion in response to the gastrointestinal hormones, CCK and secretin, was lower in WBN/Kob rats than in Wistar rats. These findings suggest that the hyposecretion of pancreas in WBN/Kob rats is hyporeaction of pancreatic membrane to gastrointestinal hormones.

Topics: Animals; Bile; Cholecystokinin; Chronic Disease; Disease Models, Animal; Male; Pancreas; Pancreatic Juice; Pancreatitis; Proteins; Rats; Rats, Wistar; Secretin; Sincalide

Cholecystokinin (CCK) levels were measured in cerebrospinal fluid (CSF) of patients with adult chronic hydrocephalus syndrome (ACHS) (n = 16) and compared with levels from a control group (n = 11). The CSF concentration of CCK in the ACHS group (0.79 +/- 0.53 fmol/mL) was significantly reduced (p = .002) with respect to the controls (1.55 +/- 0.54 fmol/mL). As CCK-8, the most prevalent from of CCK in the central nervous system, has been demonstrated to play a significant role in several physiological and behavioral actions, the reduced octapeptide values found in ACHS could be involved in the disturbances associated with this disorder. Continuous monitoring of intracranial pressure (ICP) demonstrated different ICP profiles in ACHS. We found that all patients with abnormal ICP records except one showed CCK values under the detection limit. Three of the 4 patients with normal ICP had CCK levels within the normal range. These preliminary studies could evidence that ICP alterations are responsible for part of the loss of brain neuropeptide levels in ACHS.

Topics: Adult; Aged; Cholecystokinin; Chronic Disease; Female; Humans; Hydrocephalus, Normal Pressure; Intracranial Pressure; Male; Middle Aged; Monitoring, Physiologic; Neurologic Examination; Reference Values; Sincalide

We retrospectively reviewed the medical records of 107 patients in two community hospitals who had undergone cholecystokinin-stimulated cholescintigraphy with ejection fraction to determine whether this test is reliable in identifying patients whose symptoms will improve following cholecystectomy. Patients with cholelithiasis or incomplete medical records and patients who could not be interviewed were excluded from the study. Forty-two of 58 study patients (72%) had an abnormal ejection fraction (defined as 35% or less); 27 of 42 patients (64%) underwent cholecystectomy. Twenty-six of 27 (96%) reported lessening of or resolution of symptoms following cholecystectomy. Sixty-seven per cent of the surgical specimens from the 27 patients demonstrated chronic cholecystitis. Fifteen of 42 patients (36%) with abnormal ejection fractions did not undergo cholecystectomy; 12 of 15 (80%) also reported lessening or resolution of symptoms. Of the 16 of 58 patients with a normal ejection fraction, 2 underwent cholecystectomy and reported resolution of symptoms. Five of 14 (36%) with normal ejection fractions who did not undergo cholecystectomy reported improvement. In this series, most patients with an abnormal ejection fraction had lessening of symptoms regardless of whether they underwent cholecystectomy.

Topics: Adult; Aniline Compounds; Case-Control Studies; Cholecystectomy; Cholecystitis; Chronic Disease; Female; Gallbladder; Gallbladder Emptying; Glycine; Humans; Imino Acids; Logistic Models; Male; Middle Aged; Organotechnetium Compounds; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Retrospective Studies; Sincalide

Pancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis.. Little is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis.. WBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1-6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by i.v. administration of cerulein at a rate of 10 micrograms/kg/h for 4 h 4 d after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration.. In WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant at 3-6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopically showed prominent interstitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and cholecystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.

Topics: Acute Disease; Amylases; Animals; Ceruletide; Chronic Disease; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Pancreas; Pancreatic Function Tests; Pancreatic Juice; Pancreatitis; Rats; Rats, Inbred Strains; Sincalide

Clinical and animal studies were performed to evaluate the effect of repeated transcutaneous electric nerve stimulation (TENS) applied on acupoints of pain patients and the effect of repeated electroacupuncture (EA) at acupoints of the rat on experimental arthritic pain models. Attempts were also made to evaluate whether substance P (SP), cholecystokinin octopeptide (CCK-8), and met5-enkephalin (MEK) are involved in the mechanism of the cumulative effect of repeated EA on experimental arthritis using neuropharmacological (receptor antagonists) and neurochemical (radioimmunoassay, RIA) approach. The main results show that repeated TENS of 100 Hz relieves spinal spasticity in a cumulative manner, while TENS of 2/15 Hz is effective in relieving chronic pain. In animal chronic pain models, repeated EA suppressed the hyperalgesia in arthritic rats in a cumulative manner. Further studies revealed that in pain patients there was a plastic change in the release and metabolic rate of spinal opioid peptides. In arthritic rats there was also a change in the releasing rate of spinal SP, CCK-8, and MEK as compared to control rats, an effect modulated by repeated EA. These plastic changes occured under chronic pain condition and their modulation by repeated acupoint stimulation may explain the mechanisms of the cumulative effect of acupuncture on chronic pain.

Topics: Acupuncture Analgesia; Animals; Arthritis, Experimental; Chronic Disease; Electroacupuncture; Humans; Pain Management; Rats; Sincalide; Substance P

To determine whether dopamine receptors in the brain stem can mediate inhibition of feeding behaviour male rats in which the forebrain was disconnected from the brain stem were studied. Such decerebrate rats do not approach food but display ingestive responses if infused intraorally with a 1 M solution of sucrose at 0.6 ml min-1. Intraperitoneal injection of 5 micrograms cholecystokinin octapeptide, a physiological satiety peptide, or 400 micrograms apomorphine, a dopamine D1-D2 receptor agonist, suppressed intake of the sucrose solution. The results support a role of brain stem dopamine receptors in the control of ingestive behaviour.

Topics: Animals; Apomorphine; Brain Stem; Chronic Disease; Decerebrate State; Depression, Chemical; Feeding Behavior; Male; Rats; Rats, Wistar; Sincalide

Cholecystokinin (CCK) has been shown to stimulate the growth of both normal pancreas and azaserine-induced putative preneoplastic pancreatic lesions in the rat. The present study was performed to determine whether these effects are mediated by way of CCK-A receptors, CCK-B receptors, or both. Sixteen-day-old male Lewis rats were given i.p. injections of azaserine at 30 mg/kg body weight. Starting on day 21, rats were given s.c. injections, 5 days/week for 16 consecutive weeks, of either (a) CCK octapeptide (nonselective CCK agonist) (2.50 micrograms/kg body weight, n = 17), (b) tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2-methylphenylaminocarbonyl++ +)-Asp- (N-methyl)-Phe-NH2 (highly selective CCK-A agonist) (1.84 micrograms/kg body weight, n = 18), (c) [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 (highly selective CCK-B agonist) (2.40 micrograms/kg body weight, n = 18), or (d) normal saline solution (control, n = 17). Rats were subsequently sacrificed, pancreatic weights were determined, and quantitative morphometric analysis of atypical acinar cell foci and nodules was performed. Both CCK octapeptide and the selective CCK-A agonist tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 stimulated pancreatic growth and the development of acidophilic atypical acinar cell foci and nodules. Furthermore, the effect produced by the selective CCK-A agonist tert-butyloxycarbonyl-Trp-Lys(epsilon-N-2- methylphenylaminocarbonyl)-Asp-(N-methyl)-Phe-NH2 was greater than that produced by CCK octapeptide. In contrast, the selective CCK-B agonist [(2R,3S)-beta-MePhe28,N-MeNle31]CCK26-33 had no effect. These findings suggest that the growth of putative preneoplastic lesions (acidophilic atypical acinar cell foci and nodules) in the rat pancreas during the early stages of azaserine-induced pancreatic carcinogenesis is mediated specifically by way of CCK-A receptors.

Topics: Animals; Azaserine; Cholecystokinin; Chronic Disease; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Pancreatitis; Peptide Fragments; Precancerous Conditions; Rats; Rats, Inbred Lew; Receptors, Cholecystokinin; Sincalide; Tetragastrin

Thirty patients with chronic upper abdominal pain and no evidence of cholelithiasis were entered into this study. All had negative ultrasonography of the gallbladder, and most had a host of other negative investigations. These patients were referred to a surgeon to evaluate the possibility of atypical biliary colic associated with chronic acalculous cholecystitis. All patients underwent cholecystokinin-stimulated cholescintigraphy and were offered cholecystectomy if the ejection fraction was less than 35 per cent. Of the 30 patients, 27 (90%) had pathologically abnormal gallbladders. Follow-up averaged over 1 year (13.2 mo), and relief of symptoms occurred in 28 (94%). The authors conclude that in appropriately selected patients with symptoms of biliary colic (typical or atypical) and no evidence of cholelithiasis, a cholecystokinin-stimulated cholescintigram is a significant help in predicting not only which patients have gallbladder disease, but also how likely cholecystectomy is to result in an improvement in their symptoms.

Topics: Adolescent; Adult; Cholecystectomy; Cholecystitis; Cholecystography; Cholelithiasis; Chronic Disease; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Pain; Radionuclide Imaging; Sincalide

Topics: Adult; Chronic Disease; Drug Therapy, Combination; Female; Flour; Glycine max; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Sincalide

The gut hormone motilin can initiate the interdigestive migrating motor complex. There are synchronous cyclic changes in plasma motilin-like immunoreactivity (MLI) levels and pancreatico-biliary secretion during the interdigestive period which may be causally related. The purpose of this study was to investigate the role of pancreatico-biliary secretion into the gut as a modulator of plasma MLI concentrations. In six healthy subjects, the mean basal plasma MLI level was 130 +/- 16 pg/ml. Infusion of cholecystokinin octapeptide (CCK-8) stimulated MLI secretion, with an integrated (30 min) response of 2028 +/- 340 pg/min X ml. Intraduodenal perfusion of pancreatico-biliary juice produced a similar increase in plasma MLI, with a 30 min integrated response of 2190 +/- 270 pg/min X ml. Neither enzyme activity, osmolarity, or pH accounted for the response. In six patients with exocrine pancreatic insufficiency, although their mean basal plasma MLI concentration of 205 +/- 44 pg/ml was significantly higher than that observed in healthy subjects, there was no significant plasma MLI increase after CCK-8 infusion. Pancreatic exocrine secretion was severely compromised in these patients, as evidenced by the markedly reduced peak lipase (3.8 +/- 0.6 kU/h) and trypsin (2.4 +/- 0.5 kU/h) outputs. In contrast, infusion of pancreatico-biliary juice obtained from healthy subjects caused a rise in plasma MLI, with a 60 min integrated response of 3912 +/- 1031 pg/min X ml, which was similar to that of 3947 +/- 472 pg/min X ml in healthy subjects. We conclude that there is an undefined factor in pancreatico-biliary juice that stimulates MLI release. A deficiency of pancreatic exocrine secretion may be responsible for the impaired MLI response to CCK-8 stimulation in chronic pancreatitis. Since MLI is known to initiate the formation of the interdigestive migrating motor complexes, diminished motilin release secondary to pancreatic exocrine deficiency may result in disordered gastrointestinal motor activity in patients with chronic pancreatitis.

Topics: Adolescent; Adult; Bile; Chronic Disease; Gastrointestinal Hormones; Humans; Kinetics; Lipase; Middle Aged; Motilin; Pancreatic Juice; Pancreatitis; Sincalide; Trypsin

Topics: Adolescent; Adult; Celiac Disease; Cholecystokinin; Chronic Disease; Female; Humans; Lipase; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; Pentagastrin; Peptide Fragments; Secretin; Sincalide; Trypsin

The effect of 3-week CCK-OP treatment on test meal stimulated pancreatic secretion was investigated in chronic pancreatitis patients. One drop of a 1 mg/ml CCK-OP solution applied intranasally, three times daily during 3 weeks resulted in a significant increase in volume, trypsin, lipase and amylase secretion in response to the Lundh test meal. Augmentation of trypsin secretion was the most pronounced. Functional capacity of pancreatic enzyme secretion remained elevated for 3 months after treatment. Nearly all patients became symptom free during and for some time after treatment. The results were attributed to a trophic effect of CCK-OP on human pancreas.

Topics: Administration, Intranasal; Adult; Cholecystokinin; Chronic Disease; Diet; Female; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Sincalide