Defining the functions of cholecystokinin.
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Adult↗
Biomedical subjects
S L Werlin
Publications and source records attributed to S L Werlin.
Pancreatitis associated with bone marrow transplantation in children.
Vomiting, abdominal pain and distension, common findings in children who receive bone marrow transplants (BMT), are usually attributed to chemo-irradiation and mucositis, universally found in these patients. We report seven children, 3.5% of BMT patients at our institutions, with these symptoms who were found to have mild to severe pancreatitis during conditioning for or after receiving BMT. All patients were receiving drugs known to cause pancreatitis, such as adrenocorticosteroids and sulfonamides as well as numerous putative pancreatotoxins such as cyclosporin A and cytosine arabinoside. Five of the seven patients had suffered from graft-versus-host disease. In patients who have received BMT, upper gastrointestinal symptoms should not be attributed to mucositis or chemo-irradiation without first testing for pancreatitis.
Adolescent↗
Modulation of lingual lipase development by glucocorticoid in the rat.
Lingual lipase in the rat is present in the neonatal period and undergoes developmental increase during postnatal life. To evaluate the role of glucocorticoid in the control of lingual lipase during development, suckling rats were adrenalectomized at d 10 and various hormone replacements were performed. Adrenalectomy abolished the developmental increase of lingual lipase. Low doses of dexamethasone (0.2 and 0.5 microgram/100 g body wt) restored the lingual lipase to near normal level in adrenalectomized animals. High doses of dexamethasone (20 micrograms/100 g body wt), when given to similarly adrenalectomized animals, however, led to a reduction of lingual lipase levels. Inhibition by dexamethasone is through the action of the hormone inasmuch as the coadministration of RU38486, a glucocorticoid type II receptor antagonist, completely abolished the inhibitory action. Inhibition is also steroid specific, with dexamethasone and triamcinolone acetonide being more effective. The results suggest a unique bimodal regulation of lingual lipase by dexamethasone in the rat serous glands. Because of the possible importance of lingual lipase as an alternative enzyme for fat digestion in neonates, the inhibitory action of high doses of glucocorticoid on lingual lipase development may have important implications. The use of steroidal compounds in the hastening of lung maturation and treatment of inflammatory disease might conceivably compromise their lingual lipase development, hence their capacities of fat digestion and malabsorption in the same period.
Adrenal Glands↗
Gastrointestinal myoelectric activity in an infant with congenital idiopathic motility disorder.
We investigated myoelectric activity in an 8-month-old male who presented with a perinatal bowel obstruction, duodenal band, congenital short small intestine, and persistent feeding intolerance. Serosal electrodes were surgically implanted on stomach, duodenum, and jejunum during Nissen fundoplication and ileostomy. A 5-cm ileal specimen was taken for in vitro studies. Spontaneous migrating myoelectric complexes (MMC) were present in stomach and small intestine. Bethanechol increased electrical response activity (ERA) in stomach and duodenum. Morphine induced intense ERA and distinct phase III activity. Pentagastrin infusion did not disrupt MMC cycling. Feeding disrupted MMC complex cycling 30-40 min after the meal. Metoclopramide before feeding delayed disruption of the MMC cycling after the feeding. Intermittent gastric arrhythmias were present after the fifth postoperative day. In vitro muscle strips showed spontaneous contractions and electrical control activity (ECA). Bethanechol, McNeil A-343, motilin, and cholecystokinin induced contractions, but pentagastrin had no effect. We conclude that in spite of a major clinical motility dysfunction, several of our findings were normal. The abnormalities include short MMC period, absence of disruption of MMC by pentagastrin, and gastric arrhythmias.
Bethanechol↗
Cholecystectomy and cholelithiasis in sickle cell anemia.
Elective cholecystectomy was performed on 12 children (eight male and four female; age range, 4 to 19 years; and mean age, 11.2 years) with abdominal pain that was related to gallstones. Seven patients had jaundice, six had nausea, five had fat intolerance, and three had biliary colic. Two simple transfusions (10 mL/kg of packed red blood cells), designed to decrease the hemoglobin S content to less than 30% and to increase the total hemoglobin level to greater than 100 g/L, were given preoperatively two to three weeks apart. A third transfusion was given on the day before surgery if the total hemoglobin level was less than 100 g/L. The preoperative mean hemoglobin S content was decreased from 88% to 31%, and the mean total hemoglobin level was raised to 122 g/L. There were no preoperative or intraoperative complications. Post-operatively, no patients developed complications that were related to sickle cell anemia. Hospitalization averaged 6.3 days. Recurrent abdominal pain resolved shortly after surgery in all patients. With proper preoperative transfusions, elective cholecystectomy is safe in children with sickle cell anemia. Elective cholecystectomy should be recommended at the time of diagnosis of cholelithiasis.
Adolescent↗
Ischemic hepatitis in children: diagnosis and clinical course.
Hepatic hypoperfusion can result in ischemic hepatitis, a clinical syndrome characterized by a sudden rise in serum transaminases followed by resolution to near normal levels within 7 to 10 days. Although described in adults, this syndrome has not been well defined in pediatric patients. We report 22 children who developed ischemic hepatitis during an acute illness. Fifteen of 22 patients had a documented hypotensive episode or no cardiac output before the onset of the ischemic hepatitis episode. Four of the seven patients without documented hypotension required pressor therapy to maintain their BP. SGOT showed a marked rise (mean 2294 IU/L, range 438 to 6652) from admission to 96 h (mean 34) with a rapid decline to near normal levels within 9 days (mean 5.1). Serum bilirubin levels also rose transiently, but generally not to the extent of transaminase levels. A clinically significant coagulopathy occurred in six patients. Although nine patients expired, none died as a direct result of the hepatic damage. Ischemic hepatitis can occur during illnesses associated with diminished hepatic blood flow and follows a characteristic course that usually can be differentiated from viral or drug-induced hepatitis on clinical and biochemical criteria.
Adolescent↗
Effects of cholecystokinin and hydrocortisone on DNA and protein synthesis in immature rat pancreas.
To define the developmental pattern of the trophic effects of cholecystokinin octapeptide (CCK-8) and hydrocortisone on immature rat pancreas, we injected newborn rats, rats aged 4, 7, 11, 18, and 25 days and 3 months, and adult rats with CCK (5 and 10 micrograms/kg) in gelatin and hydrocortisone (10 mg/kg) for 3 days. Animals were killed, the pancreata were removed, and the concentrations of DNA and protein were measured and DNA and protein synthesis rates determined by incorporation of [3H]thymidine and [14C]leucine, respectively. These values were compared with those of saline-injected controls. DNA concentration was significantly increased over control at ages 2 days to adult by hydrocortisone and by CCK (10 micrograms/kg) in the adult. Protein concentration was increased on days 3-14 by hydrocortisone. DNA synthesis was increased by CCK and decreased by hydrocortisone at 3 months and adult. Protein synthesis was decreased by hydrocortisone at ages 3-14 days. Thus, each agent has its own developmental pattern with age on the rat pancreas.
Age Factors↗
Ontogeny of secretory function and cholecystokinin binding capacity in immature rat pancreas.
Isolated acini were prepared from the pancreas of immature rats (age less than 1 hr. - 48 hrs) in order to study the development of the secretory process. The ultrastructural integrity of the acinar cells was maintained after digestion and stimulation with secretagogues. Acini prepared from rats aged 24 - 48 hours responded to both CCK-8 and carbachol with significant increases in amylase release. Although typical biphasic dose response curves were obtained, the curves were shifted to the right by 1 - 2 log units, compared to the responses of adult acini. At ages younger than 24 hours, acini were insensitive to secretagogues but were sensitive to the calcium ionophore A23187. CCK receptors were virtually absent from membranes prepared from newborn pancreases, but binding of CCK, although small, was measurable at 12 hours and slowly increased up to 48 hours. A greater amount of binding was seen at 72 hours, which appeared constant up to 14 days. At 21 days, adult levels of binding were found. These results confirm previous studies that the rat pancreas is insensitive to secretagogues in the first 24 hours of life. After age 24 hours the secretory process is intact but less sensitive to secretory agents than the more mature pancreas. In the case of CCK, this may be due to lesser numbers of CCK receptors and/or affinity of CCK for its receptor.
Age Factors↗
Endoscopic retrograde cholangiopancreatography in children.
Endoscopic retrograde cholangiopancreatography (ERCP) is a universally used diagnostic and therapeutic modality in adults with pancreaticobiliary tract disease; its use in children with similar problems has been limited. We have performed ERCP procedures in 39 children and adolescents (aged 6 months to 18 years; mean 12.5 years), using the standard adult and pediatric side-viewing endoscopes. In selected cases, ERCP manometric study of the sphincter of Oddi, endoscopic sphincterotomy, or balloon extraction of common bile duct stones was performed. Nineteen patients had significant or abnormal structural findings, including pancreas divisum (four patients); sclerosing cholangitis (three); and choledochal cyst, chronic pancreatitis, choledochocele, pancreatic pseudocyst, common bile duct stone, and sphincter of Oddi motor dysfunction (two each). In all instances in which patients required operation, ERCP examination provided specific anatomic detail that was useful for planning appropriate intervention. The only significant complication after ERCP was mild pancreatitis, which occurred in four patients and responded to supportive, short-term measures.
Adolescent↗
DNA and protein synthesis in developing rat pancreas.
To define developmental patterns, we determined the rate of protein and DNA synthesis in rat pancreas at birth, 1, 2, 3, 7, 10, 14, 21, 28 days, 2 months, 3 months, and in adults. Fragments of freshly minced pancreas were incubated with [3H]-thymidine and [14C]-leucine and the DNA and protein synthesis rates were measured. We found that DNA content was lowest at birth, rose through day 3, plateaued at about 8 mg/g wet weight through day 14, then slowly decreased to the adult value of about 5 mg/g at 2 months; protein content, although high at birth, decreased rapidly to a value of 80 mg/g at day 3 and slowly rose to the adult value of 160 mg/g; protein synthesis, low at birth, rapidly increased to about five times the adult value by day 3, and remained elevated for the 1st month; DNA synthesis was 15 times the adult rate at birth, increased to 30 times at 3 days of age, then declined slowly in an exponential fashion to the adult value. We conclude that the pancreas at birth is poised biosynthetically to undergo a rapid hyperplastic and hypertrophic response, and this process reaches a maximal rate at about 3 days of age.
Aging↗
Intrahepatic biliary tract abnormalities in children with corrected extrahepatic biliary atresia.
Three children with surgically corrected extrahepatic biliary atresia developed recurrent cholangitis associated with bile lakes that failed to drain via the hepatoportoenterostomy. Surgical or percutaneous drainage of these cysts was followed by both resolution of the infection and spontaneous internal drainage. We postulate that the ongoing inflammatory process resulted in intrahepatic biliary obstruction, which caused cholangitis and bile cysts. Successful treatment required not only antibiotics but drainage of the bile lakes. Development of bile cysts is a new cause of recurrent cholangitis seen in extrahepatic biliary atresia.
Bile↗
Aeromonas hydrophila colitis in a child.
A 5-year-old girl presented with chronic bloody diarrhea. Evaluation including sigmoidoscopy, rectal biopsy, and barium enema was consistent with the diagnosis of ulcerative colitis. Culture of the stool grew Aeromonas hydrophila. A. hydrophila colitis may be more common than presently realized.
Aeromonas↗
Neuromuscular dysfunction and ultrastructural pathology in children with chronic cholestasis and vitamin E deficiency.
The ultrastructural pathology of nerve and muscle and the neurological dysfunction in children with cholestatic liver disease and vitamin E deficiency have not been previously correlated. We studied two children with this syndrome. One child, 11 years of age, had severe hyporeflexia and decreased vibratory sense. Nerve conduction was delayed. The second child, 2 years of age, was neurologically normal. Both children showed ultrastructural evidence of damage to the sural nerve and accumulation of electron-dense deposits in the muscle fibers. Abnormalities of the nerves included disruption of the myelin sheath and separation and degeneration of the inner and outer components of the Schmidt-Lanterman incisure.
Biopsy↗
Pancreatic structure and function in the immature reserpinized rat.
Immature rats were reserpinized to determine whether the model used for adults may be suitable for the study of pancreatic exocrine insufficiency seen in infants with cystic fibrosis. Rats were reserpinized by injections either into pregnant dams or into newborn rats. The dose of reserpine used by others was lethal to immature rats, so lower doses were used. Pancreas from 1-day-old fetal-treated pups was hypoplastic, but concentration of chymotrypsinogen was elevated. At age 7 days hyperplasia was seen. When rats were reserpinized as neonates, hypoplasia and decrease in all parameters measured was observed at age 7 days. Progressive recovery occurred during the following 2 weeks in both groups. Electron microscopic study of the fetal-treated 24-hr-old pancreas revealed evidence of acinar cell degeneration with the presence of abnormal zymogen granules. At age 7 days the pancreas from neonatal-treated rat pups appeared to have a reduced number of granules. At ages 14 and 21 days the pancreas was similar to that seen at age 7 days except that the granules were larger and some acinar lumina were filled with a finely granular, homogeneously dense material. It is concluded that prenatal and neonatal reserpinization of rats induces changes in pancreas similar to those found in cystic fibrosis.
Amylases↗
Hepatic ultrastructure in leukemic children treated with methotrexate and 6-mercaptopurine.
Methotrexate (MTX) and 6-mercaptopurine (6MP), the two drugs most commonly used for maintenance treatment of childhood leukemia, are both potent hepatotoxins. In order to assess MTX-6MP-induced damage, we obtained biopsies from 11 children with acute lymphocytic leukemia (ALL) for light microscopic and transmission electron microscopic study. Prednisone, vincristine, and L-asparaginase were used for induction of remission in all patients. Although light microscopic findings were minimal, we found significant ultrastructural abnormalities in all patients. Changes included nuclear abnormalities, disruption of rough and smooth endoplasmic reticulum, a variety of mitochondrial changes, steatosis, fibrosis, and changes in peroxisomes and lysosomes. These abnormalities could not have been predicted from liver function tests or histopathology. Three of the eleven patients studied had also received cyclophosphamide and cytosine arabinoside during maintenance therapy. The ultrastructural abnormalities in this group were not distinguishable from those observed in the group that did not receive these additional chemotherapeutic agents. The long-term clinical significance of these findings is not known.
Adolescent↗
Effects of cholecystokinin octapeptide and hydrocortisone on the development of fetal rat pancreas.
Mechanisms and development of pancreas and pancreatic secretory function were studied in the rat. Injections of cholecystokinin octapeptide and hydrocortisone into pregnant rats altered pancreatic size, zymogen enzyme, and DNA content in the fetal newborn pancreas. These studies suggest that the developmental signals for pancreatic function may be related to endogenous release of cholecystokinin or hydrocortisone in the perinatal period.
Amylases↗
Effects of cholecystokinin octapeptide and hydrocortisone on the exocrine pancreas of fed and fasted 24-hour-old rats: an electron microscopic study.
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Animals↗
Effects of hydrocortisone and cholecystokinin-octapeptide on neonatal rat pancreas.
Hydrocortisone and cholecystokinin-octapeptide (CCK-8) were injected into newborn rats on days 1-5 of life. Both agents induced significant increases in pancreatic weight, protein, DNA, and specific activities of amylase, chymotrypsinogen, and lipase. The ability of the pancreas to secrete amylase in response to carbachol was decreased by the administration of hydrocorticosterone at age 7 days. CCK-8 increased basal secretion at 7 days. We conclude that growth and secretory capacity of the newborn rat pancreas are under the control of both glucocorticoids and cholecystokinin.
Amylases↗