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Biomedical subjects

E A Shaffer

Publications and source records attributed to E A Shaffer.

At least 91 records · Page 5Linked to original sources
PubMed1987

Gallbladder pressure, compliance, and hysteresis during cyclic volume change.

The gallbladder has both storage and contractile properties, but is pressure-volume characteristics have not been fully described. We studied gallbladder pressure, compliance, stress relaxation, and the work performed during infusion-withdrawal of fixed volumes of bile at increments of base-line volume under halothane anesthesia in 13 dogs. Two cannulae were inserted in the gallbladder fundus: one for cyclic infusion-withdrawal of bile, and one for pressure monitoring. Following ligation of the cystic duct, the gallbladder was fully aspirated and then filled to successive predetermined base-line volumes (15, 20, 25, 30, or 35 mL). At each base-line volume, 5 mL of bile was infused and withdrawn at 2.47 mL/min. Studies were performed under basal conditions and with cholecystokinin octapeptide (CCK) infusion (10 or 30 ng.kg-1.h-1iv). Pressure was measured at base-line, after infusion, and after withdrawal. Compliance during infusion (delta V/delta P) was calculated for each cycle. Stress relaxation was defined as the difference between base-line pressure and any reduction in pressure after withdrawal. Hysteresis, the difference between work of infusion and work of withdrawal, was calculated. The results were such that base-line, end-infusion, and end-withdrawal pressures; work of infusion, work of withdrawal, and hysteresis; and stress relaxation all increased significantly with increases in the predetermined base-line volumes (p less than 0.001). Compliance decreased significantly (p less than 0.001) with increasing base-line volume. CCK at 10 ng.kg-1.h-1iv had no effect, but infusion of CCK at 30 ng.kg-1.h-1 significantly (p less than 0.05) increased pressure and work, decreased compliance, and increased stress relaxation compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effect of epidermal growth factor on growth and postnatal development of the rabbit liver.

The effect of epidermal growth factor (EGF) on the postnatal development of the liver was examined. New Zealand White rabbits received 40 micrograms.kg-1.day-1 EGF from days 3 to 17 of age either intraperitoneally or orogastrically, whereas controls received saline. At days 18-20, animals underwent cannulation of the common duct using halothane anesthetic. Biliary output was measured directly for three 1-h periods: under basal conditions and in response to intravenous infusion of exogenous glycodeoxycholic acid at 0.75 and 1.5 mumol.min-1.kg-1, respectively. The bile salt pool size was measured by isotope dilution. Final mean body weight of intraperitoneal and orogastric groups did not differ from controls. Liver we weight, DNA, and protein content were significantly increased in intraperitoneally treated animals without morphological or biochemical evidence of fat deposition. Both intraperitoneal and orogastric EGF significantly increased bile salt secretion in the basal period and as a response to exogenous bile acid infusion. Bile flow was significantly increased in response to 1.5 mumol.min-1.kg-1 infusion of glycodeoxycholic acid. The bile salt pool was increased by both intraperitoneal and orogastric EGF. Administration of EGF resulted in a precocious development of glucokinase (EC 2.7.1.2) activity in the liver. EGF had no effect on serum cortisol, corticosterone, triiodothyronine, thyroxine, or free thyroxine levels. These findings suggest that in the neonatal period EGF can promote hepatic growth and maturation.

Animals↗
PubMed1987

Aspiration after percutaneous gastrostomy. Assessment by Tc-99m labeling of the enteral feed.

Aspiration pneumonia, a recognized complication of enteral feeding via a nasogastric tube, is considered uncommon with percutaneously placed gastrostomy tube feeding. We report aspiration pneumonia during enteral alimentation in a neurologically compromised but conscious patient. Aspiration continued despite changing the route of enteral feeding from nasogastric to percutaneous gastrostomy. Quantitative scintigraphic studies with Tc-99m-labeled enteral infusion demonstrated frequent episodes of gastroesophageal reflux and aspiration of gastric contents, which increased when the infusion rate was speeded up for nutritional replacement. Gastric retention also occurred at the higher infusion rate. Thus, percutaneous gastrostomy may not decrease the frequency of aspiration in patients at risk.

Adult↗
PubMed1987

Benign recurrent intrahepatic cholestasis. Evidence for an intrinsic abnormality in hepatocyte secretion.

The cholestasis of benign recurrent intrahepatic cholestasis (BRIC) may be secondary to factors present in the circulation or to an intrinsic abnormality in hepatocyte bile salt secretion. In the present study, we documented the effect of BRIC sera on hepatic bile flow in rats and in vitro [14C]taurocholate bile salt uptake and efflux from isolated rat hepatocytes. Sera from patients with cholestatic disease (2 patients with primary biliary cirrhosis) and healthy volunteers served as controls. Rat hepatic bile flow increased significantly (p less than 0.05) during intravenous infusions of BRIC sera but remained unaltered during infusions with disease and healthy control sera. [14C]Taurocholate uptake by isolated rat hepatocytes was decreased to a similar extent by BRIC and disease control sera. [14C]Taurocholate efflux from hepatocytes was unaltered by BRIC, disease, or healthy control sera. Quantitative technetium-diisopropyliminodiacetic acid cholescintigraphy in the BRIC patient revealed prompt uptake of the radiolabeled organic anion but no biliary excretion after 21 h. Disease control patients also demonstrated prompt hepatic uptake of radiotracer, but some biliary excretion was evident. These results suggest that BRIC cholestasis is not mediated by a circulating cholestatic agent but rather is secondary to an intrinsic abnormality in hepatocyte bile salt secretion.

Adult↗
PubMed1986

Collagenous colitis: a disease of pericryptal fibroblast sheath?

Mucosal biopsies from four women with collagenous colitis and ten controls were studied. By light microscopy the cells of the pericryptal fibroblast sheath appeared diminished in number but increased in size in collagenous colitis. Electron optically in the controls the pericryptal fibroblasts were in intimate contact with the epithelial basal lamina in the crypts. On the free surface the fibroblasts maintained contact with the epithelial cells by attenuated cell processes. In collagenous colitis, in the middle and upper thirds of the crypts the fibroblasts sheath was separated from the epithelium and the fibroblasts assumed the characteristics of myofibroblasts. The separation was accentuated towards the mouths of the crypts. Beneath the surface epithelium the attenuated fibroblast cell processes seen in normal colon were grossly deficient. The basal lamina was also deficient focally and the surface epithelial cells were resting directly on a thickened collagen table. In collagenous colitis the excess collagen appeared to be secreted by the activated myofibroblasts of the pericryptal sheath.

Adult↗
PubMed1986

Cholescintigraphic detection of functional obstruction of the sphincter of Oddi. Effect of papillotomy.

Unexplained abdominal pain after cholecystectomy has been attributed to sphincter of Oddi dysfunction, but no objective diagnostic criteria exist. Biliary excretion was quantitated by computer-assisted cholescintigraphy in 35 postcholecystectomy controls without symptoms, 9 patients with suspected sphincter of Oddi dysfunction (studied before and after sphincterotomy), and 18 patients with overt cholestasis from other causes (6 with extrahepatic obstruction and 12 with parenchymal liver disease). In patients with sphincter of Oddi dysfunction or with cholestasis, the time to attain maximal activity in the biliary system was significantly (p less than 0.05) longer, the percent of radiotracer excreted at 45, 60, and 90 min was less, and the emptying rate was slower compared with the controls. Cholecystokinin (0.02 U/kg X min) did not abolish biliary output, excluding a paradoxical response of the sphincter. After sphincterotomy, biliary activity peaked earlier and the percent excreted at 45 min increased but did not revert to normal. Relief of symptoms occurred in 8 of 9 patients. The one failure had normal emptying characteristics before sphincterotomy, and did not change after surgery. Another developed recurrent pain and a corresponding deterioration in biliary emptying on serial scans. Thus, functional obstruction at the sphincter of Oddi exists, is not due to any paradoxical response to cholecystokinin, and in the absence of overt cholestasis, can be detected by quantitative cholescintigraphy. Successful sphincterotomy may not completely restore biliary emptying to normal.

Adult↗
PubMed1986

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.

Animals↗
PubMed1986

Ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma in the Canadian Richardson ground squirrel (Spermophilus richardsonii).

Sera and livers from 40 Richardson ground squirrels were examined for evidence of ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma. Twenty-five sera were obtained from fully grown adult ground squirrels and 15 from young ground squirrels estimated to be between 6-8 weeks of age. All animals had been caught in the wild and had spent less than 1 month in captivity. Sixteen sera (40%) had at least one serologic marker of GSHV (2 with GSHV surface antigen, 3 GSHV core antigen, 5 GSHV antibody to core antigen and 11 GSHV antibody to surface antigen). Two cases of hepatocellular carcinoma were detected, both in adult ground squirrels. Tumour tissue and adjacent normal liver tissue were negative for GSHV surface and core antigen by direct immunofluorescence in both livers and negative for GSHV-DNA by molecular hybridization in the one tumour examined. These results indicate that: A) GSHV is geographically more widespread than previously considered; B) viral transmission occurs early in life, probably via the vertical route; and C) hepatocellular carcinoma is a relatively common finding in these animals while still in their wild state. Any causal relationship between hepatocellular carcinoma and GSHV infection in these animals, however, has yet to be demonstrated.

Animals↗
PubMed1986

Preoperative oral fluids: is a five-hour fast justified prior to elective surgery?

The effects of preoperative oral administration of 150 ml fluid were studied prospectively in 140 unpremedicated, ambulatory outpatients presenting for first trimester therapeutic abortion. Intraoperative gastric fluid volume, pH, and rate of gastric emptying were measured in the four groups to which patients were randomly assigned. At an average time of 2 1/2 hr preoperatively all patients received either oral ranitidine, 150 mg, or a placebo tablet, with the nonabsorbable marker dye bromosulphthalein (BSP, 50 mg in 10 ml water, followed by either 150 ml water or no further fluid. The effect of volume ingested was assessed by comparing the volume of gastric contents obtained by gastric tube suctioning at the completion of surgery in the two groups given placebos. The gastric volume was significantly less in patients given 150 ml water (17.6 +/- 14.5) than in those given only BSP (26.7 +/- 18.9) (P less than 0.02), and was further significantly decreased in the two groups given ranitidine (8.3 +/- 7.3, 9.5 +/- 7.7 ml) (P less than 0.001). Mean pH values were significantly higher in the two ranitidine groups (5.52 +/- 1.79, 5.03 +/- 1.79) than in the two placebo groups (1.75 +/- 0.94, 1.92 +/- 1.27). The combination of a residual volume of 25 ml and pH less than 2.5 was found in 46% of patients given only BSP with placebo, in 23% of those given 150 ml water with placebo, and in no patient given ranitidine. There was no correlation between the gastric volume or pH values with the ingestion-surgery interval in patients given 150 ml water.

Adult↗
PubMed1985

Postnatal development of hepatic bile formation in the rabbit.

To investigate postnatal maturation of hepatic bile formation, bile output was measured in four groups of rabbits: suckling infants at ages 10-14, 18-22, and 26-30 days, and adults. Bile output was collected directly from the common duct during three 1-hr periods: a basal period followed by intravenous infusion of 1 and then 2 mumol/min/kg of glycodeoxycholic acid. [14C]Erythritol and [3H]inulin clearances measured canalicular bile flow and biliary permeability. Under basal conditions and with the exogenous bile acid, bile flow and bile salt secretion were lowest in 10- to 14-day-old infants and showed a gradual increase with increasing age. Bile salt-dependent flow, the linear increase in flow relative to bile salt secretion, was higher in the 10- to 14- and 17- to 22-day-old compared to the adult and 25- to 30-day-old groups. The ratio of chloride to bile salt secreted was also higher in the two younger groups. Bile salt-independent flow at theoretical zero bile salt secretion was absent in the younger groups, but evident in the adult and 25- to 30-day-old rabbits. Canalicular flow estimated by erythritol clearance was linearly related to bile salt secretion. Inulin clearance relative to erythritol clearance was higher in the 10- to 14-day-old infants than the adults. Thus, bile flow and bile salt secretion are reduced in the young infant but rise to near adult levels at the time of weaning, 25-30 days in the rabbit. The increase in flow results from increased bile salt secretion and the appearance of bile salt-independent flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1985

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.

Cholecystokinin↗
PubMed1985

Reduced bile output with chronic enteral and parenteral infusion of amino acids, glucose, and fat emulsion in rabbits.

To assess the effect of chronic administration of amino acids, glucose, and fat on hepatic excretory function, bile flow and bile salt secretion were directly measured in adult rabbits alimented either intravenously or intragastrically. Five groups of animals were studied after 9-11 days on different nutritional regimes: the first, controls, received 154 mM NaCl intravenously and rabbit chow ad libitum; the second, 2.5% amino acid-10% glucose-10% fat emulsion intravenously; the third, the same nutrients intragastrically; the fourth, reduced intake of rabbit chow to match the weight change in the intragastrically fed animals; the fifth was allowed rabbit chow ad libitum and then received the nutrient solutions intragastrically only during bile collection. Bile was collected directly at laparotomy from the common bile duct during three 1-h periods: a basal period when no exogenous bile salt was infused, then with the addition of 1, and finally 2 mumol/min/kg of glycodeoxycholic acid, the main bile acid of rabbits. During the 3-h experiment either saline (control) or the nutrient solution was administered by the respective route. Chronic administration of the nutrient solutions, whether intravenously or intragastrically, significantly (p less than 0.05) reduced bile flow and bile salt secretion compared with controls and the rabbits on a reduced chow intake. The chronic intravenous route had a more pronounced cholestatic effect than the intragastric route. Acute intragastric nutrient infusion had no effect. The decreased bile output in the chronic groups resulted from a reduction in both bile salt secretion and bile salt-independent flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1985

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.

Animals↗
PubMed1985

Regulation of fasting canine duodenal bile acid delivery by sphincter of Oddi and gallbladder.

Bile delivery into the duodenum during fasting is rhythmic and coordinated with the migrating myoelectric complex (MMC). To determine the role of the sphincter of Oddi (SO) and gallbladder (GB) in regulating duodenal bile acid delivery, three dogs were surgically prepared with a duodenal cannula and eight bipolar electrodes implanted from the duodenum to the terminal ileum. Fasting intestinal myoelectric activity was recorded during continuous intravenous infusion of [14C]taurocholic acid (TCA). Duodenal delivery of TCA was quantitated under four conditions: indirectly with the SO intact monitoring output with duodenal marker perfusion and directly with the SO cannulated and draining at three levels to vary outflow resistance (5 cm above, level with, or 20 cm below the SO). GB filling or emptying represented the algebraic difference between hepatic secretion (equal to the intravenous infusion rate) and rate of TCA delivery into the duodenum. With the sphincter intact the rate of bile acid delivery averaged one-half the intravenous infusion rate at 0-40% of the MMC cycle period, rose to exceed the intravenous infusion rate at 60-70% of the cycle period, and then fell to lower levels before the next MMC began. The pattern of delivery was identical with the SO cannulated, but the rate and percent infused TCA delivered into the duodenum depended significantly (P less than 0.01) on outflow resistance. They were least with the reservoir elevated 5 cm, intermediate when level, and greatest when 20 cm lower. Thus, duodenal bile acid delivery and GB filling or emptying during fasting were cyclically coordinated with the MMC. Peak rates of duodenal bile acid delivery and active GB emptying occur at 70% of the duodenal cycle period. Elimination of the SO does not eliminate the pulsatile pattern of fasting duodenal bile acid delivery, but outflow resistance determines the quantities delivered into the duodenum or stored in the GB. Thus, during the interdigestive period the net effect of SO function does not differ from a constant output resistance favoring the partition of hepatic biliary secretion into the GB and away from the duodenum, while the pulsatile pattern of duodenal bile acid delivery associated with the MMC results from cyclic active contraction of the GB.

Ampulla of Vater↗
PubMed1985

Total parenteral nutrition-associated cholestasis: acute studies in infant and adult rabbits.

To assess the basis of cholestasis associated with total parenteral nutrition (TPN), we studied the short-term effect of the component solutions on bile flow and bile salt secretion in infant and adult rabbits. Groups of four to six adult and infant rabbits received intravenously 154 mM NaCl (control), 2.5% amino acid, 10% glucose, or 10% fat emulsion alone or in combination. Bile was collected directly from the common bile duct for 3 h. Solutions containing both amino acids and glucose significantly (p less than 0.05) reduced bile flow and bile salt secretion in both age groups. Glucose alone also decreased bile flow and bile salt secretion, whereas amino acids as the sole infusate significantly (p less than 0.05) decreased bile flow only. The suppressive effect of the amino acid-glucose solutions on bile flow was more pronounced in infants than in adults. Fat emulsion alone had no effect on bile formation. Our findings demonstrate that short-term intravenous administration of nutrient solutions containing amino acids and glucose reduces bile flow and bile salt secretion, suggesting that these components are responsible for TPN-associated cholestasis.

Age Factors↗