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Biomedical subjects

E A Shaffer

Publications and source records attributed to E A Shaffer.

At least 109 records · Page 6Linked to original sources
PubMed1984

The effect of a progestin on gallbladder function in young women.

Female sex hormones have been considered to be a risk factor for the development of cholesterol gallstone disease, because of increased cholesterol saturation of bile. Impaired gallbladder function is an additional factor which is suspect but unproved. We investigated gallbladder function in 10 young women on two occasions: first during the follicular phase of the menstrual cycle, when endogenous progesterone is low, and again after the ingestion of medroxyprogesterone acetate, 10 mg/day for 10 days, just prior to the next menstrual period. Another group, 15 young women, was studied during their luteal phase, when endogenous progesterone is high. Gallbladder filling and emptying in response to cholecystokinin (0.02 U/kg-min) was quantitated by 99mTc-HIDA cholescintigraphy. Gallbladder filling and emptying were no different in women in the follicular phase than in women in the luteal phase of the menstrual cycle. In both menstrual phases, the administration of the exogenous progestin significantly (p less than 0.05) reduced the fraction of hepatic bile entering the gallbladder. Gallbladder emptying was also depressed: the total amount ejected was less, the time to empty half the contents was prolonged, and the rate was slower (p less than 0.05). Thus, different phases of the normal menstrual cycle do not appear to have any effect on gallbladder function. Administration of an exogenous progestin, however, significantly impairs both gallbladder filling and emptying, factors which could predispose to the formation of cholesterol gallstones.

Adolescent↗
PubMed1983

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.

Acetylcholine↗
PubMed1983

A simple and safe method of anesthetizing infant rabbits for abdominal surgery.

There is a great lack of information about general anesthesia in small infant animals. We developed a safe method using Halothane to maintain anesthesia in 20 infant rabbits weighing 100-150 g. Halothane was administered through a modified T piece using a small finger cot in order to minimize the dead space of the system. Halothane concentrations of 0.5 to 1.5% were safe and efficient to perform a laparotomy and to keep the rabbits alive after surgery.

Abdomen↗
PubMed1983

Cholestasis and total parenteral nutrition: in vivo studies on dogs.

The effect of total parenteral nutrition (TPN) on bile formation was evaluated in 10 studies performed on three adult dogs. The bile duct was directly cannulated via a Thomas cannula while bile salt secretion was maintained by intravenous [14C]taurocholic acid infusion. After a 1.5-h basal period, either an amino acid solution (2.5% Travasol) with 10% glucose, or a lipid emulsion (10% Intralipid) was added intravenously for 2 h, followed by a second control period. The amino acid-glucose solution resulted in a significant (p less than 0.05) increase in bile flow which rose (+33%) while bile salt secretion increased transiently (+11%) and then returned to basal levels. The specific activity of taurocholate secreted did not decrease during the amino acid-glucose infusion, indicating that the unexpected increase in bile salt secretion was mainly due to a washout of the biliary tree rather than to enhanced synthesis. Cholesterol, phospholipid, and bilirubin outputs did not change significantly. Intralipid had no effect on bile flow or solute secretion. Thus, short-term TPN therapy with amino acids and glucose had no cholestatic effect in dogs, but rather produces a transient choleresis which is largely independent of bile salts.

Amino Acids↗
PubMed1983

Defective gallbladder contractility in the ground squirrel and prairie dog during the early stages of cholesterol gallstone formation.

To examine the effect of changes in bile lithogenicity on gallbladder muscle function, in vitro gallbladder contractility was studied in an animal model of cholesterol gallstones: Richardson ground squirrels fed either a trace (control) or a 1% wt/wt cholesterol (test) diet. Lithogenic index of gallbladder bile increased on the test diet from 0.52 +/- 0.03 to 0.81 +/- 0.04 (p less than 0.001). Isometric tensions generated in response to cholecystokinin-octapeptide, acetylcholine, or potassium depolarization, were all reduced greater than 50% in the test gallbladder muscles (p less than 0.05), without any significant shift of the normalized dose-response curves. Tension in response to cholecystokinin-octapeptide differed significantly (p less than 0.05) between each stage of stone formation compared with controls: 42% decrease in test animals before development of stones; 65% decrease in those with gallstones. Ileal muscle from these animals, when tested with the same three stimuli, showed no adverse effects of the high-cholesterol diet. Another animal model, the prairie dog, also demonstrated a similar in vitro defect in gallbladder contractility associated with increases in bile lithogenicity. Thus, in the ground squirrel, a progressive defect in smooth muscle contractility to three different stimuli coincides with early changes in bile lithogenicity. The defect is not associated with any loss of sensitivity to these stimuli, and appears to be localized specifically to the gallbladder muscle. Its presence in two animal models of cholelithiasis suggests that biliary stasis is an important factor in the early stages of cholesterol stone formation.

Acetylcholine↗
PubMed1982

The effect of vagotomy on gallbladder function and bile composition in man.

Vagotomy and gastric surgery have been implicated in gallstone formation, although the association remained unproven. Gallbladder function was investigated in 11 patients with a pyloroplasty and truncal vagotomy, 5 with a subtotal gastrectomy, and 16 healthy controls. Gallbladder filing and emptying in response to cholecystokinin (CCK 0.01 U/kg min), when quantitated by 99m-Tc-HIDA cholescintigraphy, did not show any differences between the control and the surgical groups. In each group, over 70% of hepatic activity partitioned into the gallbladder rather than the duodenum, filing the gallbladder at 2.1%/min. Gallbladder emptying began five minutes after initiating the CCK infusion and ejected half of its contents during the next 12 minutes. Biliary lipid compositions was determined in 20 patients who underwent elective pyloroplasty and vagotomy for duodenal ulcer disease. Gallbladder bile collected at surgery was compared to bile-rich duodenal fluid aspirated eight months after recovery from surgery. Cholesterol saturation decreased significantly (p less than 0.05) both in terms of the relative cholesterol content (6.9% leads to 5.2%) and the lithogenic index (1.24 leads to 0.84). To determine if a selective increase in one of the conjugated bile salts could explain this improvement, bile salt composition was analyzed by high pressure liquid chromatography in eight patients and showed no change after surgery. Thus, vagotomy does not adversely affect gallbladder function, but instead improves cholesterol solubility.

Adolescent↗
PubMed1981

The importance of triglyceride hydrolysis for the release of gastric inhibitory polypeptide.

Gastric inhibitory polypeptide is released from the small intestine after the ingestion of fat, but it is not known if triglyceride itself or one of its hydrolytic products is the stimulus to gastric inhibitory polypeptide secretion. Children with cystic fibrosis and defective fat lipolysis were studied to help define the exact stimulus to gastric inhibitory polypeptide secretion. Pancreatic enzyme therapy was withheld from the children with cystic fibrosis during these tests. Ten normal children and 10 children with cystic fibrosis each ingested corn oil and serum immunoreactive gastric inhibitory polypeptide measured. The normal children had a 10-fold increase in serum gastric inhibitory polypeptide levels after the triglyceride, but no increase in immunoreactive gastric inhibitory polypeptide occurred in the children with cystic fibrosis. When three of the children with cystic fibrosis received their pancreatic enzymes and then ingested the triglyceride, gastric inhibitory polypeptide values increased 10-fold. To assess the relative importance of the products of triglyceride hydrolysis and the chain length of the component fatty acids, 6 normal adults consumed, on separate days, 40 mmol of corn oil, medium-chain triglycerides, long-chain fatty acids, or glycerol. Long-chain fatty acids caused a fourfold increase and triglyceride a 12-fold increase in gastric inhibitory polypeptide levels. There was no increase after medium-chain triglyceride or glycerol. This indicates that long-chain fatty acids-the end product of triglyceride hydrolysis-are a stimulus to gastric inhibitory polypeptide secretion; that this release is apparently proportional to the quanitity of long-chain fatty acid present; and that hydrolysis of triglyceride is required before gastric inhibitory polypeptide release can normally occur after fat ingestion.

Adolescent↗
PubMed1980

Gallstones: current concepts of pathogenesis and medical dissolution.

Gallstone disease constitutes a major health problem in the western world, despite a successful form of surgical therapy, cholecystectomy. The past decade has witnessed considerable advances in our understanding of the physiochemical changes in bile that lead to cholesterol gallstone formation. This knowledge has resulted in a rational basis for identifying agents that could dissolve gallstones and for defining conditions that predispose to gallstone formation which might be eliminated or treated prophylactically. This review examines the concepts of gallstone formation and indicates the current status of medical therapy.

Adult↗
PubMed1980

Quantitative cholescintigraphy: assessment of gallbladder filling and emptying and duodenogastric reflux.

To accurately quantitate dynamic events associated with gallbladder filling and emptying, we developed a cholescintigraphic technique in which the radionuclide 99mTc-HIDA excreted in bile was externally measured by a gamma camera interfaced to a computer programmed for data processing. Changes in activity with time were measured over the liver, bile ducts, gallbladder, small intestine, and stomach. The first 60 min were used to detect activity filling the gallbladder. Cholecystokinin was then infused at 0.020 U/kg/min for 30 min to initiate gallbladder contraction, while monitoring the evacuation of radionuclide into the small intestine and/or stomach. The stomach region was defined by a 99mTc-sulphur colloid swallow. With computer assistance, we were able to measure the rate at which the gallbladder filled, the fraction of liver activity that partitioned into the gallbladder instead of the duodenum, the rate of gallbladder empyting, and any gastric reflux. In 12 fasting, healthy subjects, three-fourths of the hepatic activity entered the gallbladder. After a 5-min time lag, gallbladder empyting commenced in response to the cholecystokinin, ejecting half its contents in 12 min, but still having a residual 25% after 30 min. Gallbladder evacuation was definitely slower in 6 patients with cholelithiasis, although filling appeared normal. One patient with gallstones underwent a repeat study after 4 mo on chenodeoxycholic acid therapy: Gallbladder filling, and especially emptying, deteriorated. Gastric reflux occurred only in 2 patients with gastroenterostomies who refluxed 2% of their gallbladder contents into the gastric remnant. Quantitative cholescintigraphy offers a new objective means to define gallbladder function and document bile reflux.

Adult↗
PubMed1979

Gallbladder emptying in response to cholecystokinin. A cholescintigraphic study.

The threshold and dynamics of gallbladder emptying in human subjects in response to cholecystokinin (Pancreozymin, Boots Co. Ltd) were defined by radionuclide imaging with a gamma camera. The radiopharmaceutical employed, 99mTc-HIDA, was taken up rapidly by the liver and efficiently excreted into the biliary system so that gallbladder filling was easily distinguishable from negligible background activity. Counts were recorded continuously on magnetic tape during i.v. infusion of sequentially increasing doses of cholecystokinin: Each dose level was maintained for 15 min. At later playback, the area of interest was adjusted to include only the gallbladder and to exclude radioactivity present in the gut during gallbladder emptying. In 19 normal subjects (10 male and 9 female), a threshold dose of cholecystokin was identified for gallbladder contraction: 0.010 Crick-Harper-Raper units/kg-min in 16 subjects, and 0.020 Crick-Harper-Raper units/kg-min in the remaining 3. The rate of emptying appeared smooth and linear at each dose level: Doubling the dose of cholecystokinin in every case significantly increased the emptying rate. There appeared to be no effect of increasing age on emptying more rapidly than females, but the difference was not significant. This cholescintigraphic technique would appear to offer a simple, accurate, yet noninvasive method for continuously monitoring the events during gallbladder contraction in humans.

Adult↗
PubMed1978

Nonvisualization of the gallbladder by 99mTc-HIDA cholescintigraphy as evidence of cholecystitis.

Cholescintigraphy with N-substituted iminodiacetic acid (HIDA) labelled with technetium-99m is a new noninvasive technique for evaluation of the hepatobiliary system. The significance of nonvisualization of the gallbladder by this method in comparison with standard radiologic examinations was studied. In 43 healthy subjects the gallbladder was visualized by the two methods. By contrast, all 27 patients in whom the gallbladder was not visualized by cholescintigraphy had cholecystitis. When visualization failed to occur, a repeat cholescintigraphic study after an injection of cholecystokinin demonstrated the status of the cystic duct. Visualization excludes cystic duct obstruction and acute cholecystitis, whereas persistent nonvisualization indicates cystic duct obstruction.

Acetanilides↗
PubMed1978

Definition of a conjugation of dysfunction in Gilbert's syndrome: studies of the handling of bilirubin loads and of the pattern of bilirubin conjugates secreted in bile.

1. Intravenous doses of bilirubin (3.4 mumol/kg) were given to normal subjects and patients with Gilbert's syndrome. Both groups displayed an identical initial disappearance of a substantial proportion of the bilirubin but, late in time, the Gilbert's patients exhibited reduced clearance with a sustained elevation of the plasma bilirubin and no reflux into the plasma space of conjugated bilirubin. Increasing the dose in normal subjects (by factors of 3 and 6) failed to reproduce the response found in the Gilbert's patients. 2. In the the bile-containing duodenal aspirates of Gilbert's patients the average proportion of bilirubin found as bilirubin diglucuronide was 68% (normal 88%) and of bilirubin monoglucuronide, 23% (normal 7%). Both differences were significant at the P less than 0.001 level. In the Gilbert's patients restriction of caloric intake to 1569 kJ/day for 2 days characteristically raised the serum bilirbuin with no modification of the biliary pigment pattern; phenobarbital (180 mg/day for 2 weeks) decreased the plasma bilirubin to the normal range with, concomitantly, a reversion of the biliary pigment pattern towards normal. 3. We conclude that there is no hepatic uptake defect in Gilbert's syndrome but that there is decreased activity in the conjugation process underlying the addition of the second glucuronic acid moiety to bilirubin, to form bilirubin diglucuronide.

Adolescent↗