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Biomedical subjects

E A Shaffer

Publications and source records attributed to E A Shaffer.

At least 19 recordsLinked to original sources
PubMed1992

The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.

The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced gallbladder smooth muscle contraction are considered both extracellular and intracellular, but the relative need for intracellular calcium especially at low, physiological concentrations is not clear. To better define the calcium sources responsible for guinea-pig gallbladder contractions in vitro, we inhibited calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium-free Krebs' solution. Availability and release of intracellular calcium stores were depleted by strontium substitution and ryanodine. CCK-OP was compared to bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl. Methoxyverapamil, however, had little effect on the time-dependent generation of tension to CCK-OP, but significantly reduced the response to bethanechol and KCl, each at ED50. The duration of the contractile response in the calcium-free Krebs' solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM) significantly attenuated the response to CCK-OP and bethanechol, but not to KCl. Ryanodine significantly reduced contractions induced by CCK-OP but not for bethanechol, both at low dose ED25. These results indicate that contraction of the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires extracellular calcium influx. Further, the initiation and maintenance of contraction by CCK-OP and bethanechol necessitates calcium mobilisation from intracellular stores. CCK-OP may have a greater penchant for these calcium stores, particularly at physiological doses.

Animals↗
PubMed1992

Defense system in the biliary tract against bacterial infection.

Bacteria can invade the biliary tract by ascending from the duodenum and via the hematogenous route from the hepatic portal venous blood. The sphincter of Oddi, situated at the junction of the biliary tract and the upper gastrointestinal tract, forms an effective mechanical barrier to duodenal reflex and ascending bacterial infection. Conversely, Kupffer cells and the tight junctions between hepatocytes help prevent bacteria and toxic metabolites from entering the hepatobiliary system from the portal circulation. The continuous flushing action of bile and the bacteriostatic effects of bile salts keeps the biliary tract sterile under normal conditions. Secretory immunoglobulin A (sIgA), the predominant immunoglobulin in the bile, and mucus excreted by the biliary epithelium probably function as antiadherence factors, preventing microbial colonization. When barrier mechanisms break down, as in surgical or endoscopic sphincterotomy and with insertion of biliary stents, pathogenic bacteria enter the biliary system at high concentrations and take up residence on any foreign bodies. Intrabiliary pressure is a key factor in the development of cholangitis. Chronic biliary obstruction raises the intrabiliary pressure. This adversely influences the defensive mechanisms such as the tight junctions, Kupffer cell functions, bile flow, and sIgA production in the system, resulting in a higher incidence of septicemia and endotoxemia in these patients. Knowledge of biliary defense against infection is still quite primitive. Unclear are the roles of sIgA in the bile, mechanism of bacterial adhesion to the biliary epithelium, Kupffer cell function in biliary obstruction, and the antimicrobial activity of bile salts.

Animals↗
PubMed1992

Efficacy, duration, and absorption of a paediatric oral liquid preparation of ranitidine hydrochloride.

The objectives of this study were to assess the clinical efficacy of a new oral ranitidine liquid preparation in reducing gastric acidity and volume, to determine the degree of absorption of the drug, and to determine the duration of drug effect. Eighty preoperative children between the ages of one and six years were enrolled in each of three centres. Each subject was allocated to one of the following groups: Group A - apple juice, 5 ml.kg-1 plus placebo liquid; Group B - apple juice, 5 ml.kg-1 plus ranitidine hydrochloride 2 mg.kg-1; Group C - water, 5 ml and placebo liquid; or Group D - water, 5 ml and ranitidine liquid 2 mg.kg-1. All study agents were administered at least two hours before surgery along with a dye marker, sulfobromophthalein 1 ml (50 mg.ml-1). Following induction of anaesthesia, gastric fluid was aspirated, and analyzed for pH, volume, and sulfobromophthalein content (as an index of the ingested fluids). A serum sample was also drawn and analyzed for ranitidine content by high performance liquid chromatography. Groups B and D had fewer subjects with pH below 2.5 and gastric volume > 0.4 ml.kg-1. The duration of reduced volume and acidity was shown to be greatest from two to four hours after drug administration. Thirty-three percent of subjects receiving oral ranitidine, 2 mg.kg-1 hydrochloride as a single dose demonstrated no measurable effect on gastric pH and volume; 28 of those subjects had adequate ranitidine serum levels.

Absorption↗
PubMed1992

The influence of bile salts on small intestinal motility in the guinea pig in vitro.

The effect of bile salts on intestinal motility is unclear. In the current study, isometric contractions of the guinea pig terminal ileum were examined in vitro. Dose-response curves to known agonists cholecystokinin (CCK), bethanechol, and KCl were constructed alone and in the presence of atropine (10(-6) mol/L), tetrodotoxin (10(-6) mol/L), and different bile salts, namely, taurodeoxycholate, tauroursodeoxycholate, taurocholate, glycodeoxycholate, and glycoursodeoxycholate. These bile salts, at levels as low as 5 and 50 mumol/L, significantly depressed (P less than 0.05) CCK-induced contractions throughout the dose-response curves and were concentration dependent. This depressant effect was not dependent on the bile salt species or any apparent physicochemical differences between them. The inhibitory effect was also specific for certain agonists such as CCK (the action of which was partially mediated by cholinergic nerves, being depressed by atropine and abolished by tetrodotoxin), field stimulation, and nicotine. Bile salts had no effect on either bethanechol- or KCl-induced contractions. Such bile salt inhibition of excitatory, cholinergic, enteric neurons may slow transit through the ileum, enhancing the time for absorption and conserving the bile salt pool.

Animals↗
PubMed1992

Differential sensitivities of the sphincter of Oddi and gallbladder to cholecystokinin in the guinea pig: their role in transsphincteric bile flow.

Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax the sphincter of Oddi with meals. In this study, we examined this hypothesis by investigating the action of CCK on the sphincter of Oddi and gallbladder of the guinea pig. The experimental design used an in vitro preparation of the sphincter of Oddi to measure contraction of the circular muscle. CCK increased tone in both the gallbladder and the sphincter of Oddi in a concentration-dependent manner. The normalized concentration-response curves for CCK, however, revealed that the gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated maximally with CCK in the presence of atropine (10(-6) M) or tetrodotoxin (10(-6) M), the contractile response was significantly reduced (p < 0.05) although not abolished. Conversely, atropine completely abolished the responses to bethanechol (10(-3) M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s). Transmural field stimulation of the sphincter that had been precontracted with CCK (26 nM) caused a transient, initial relaxation followed by contraction. Pretreatment with atropine augmented the duration of this relaxation, which could be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic) mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via noncholinergic inhibitory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Chronic biliary-type pain in the absence of gallstones: the value of cholecystokinin cholescintigraphy.

Radiologic criteria for the diagnosis of gallbladder disease largely rest on the detection of calculi. Surgeons are reluctant to do a cholecystectomy in patients with symptoms of gallbladder disease if the results of sonography or cholecystography are normal. Consequently these patients are often left with no satisfactory treatment. Such patients may have chronic acalculous cholecystitis, partial obstruction of the cystic duct, or gallbladder dyskinesia. Increasing evidence indicates that at least some of these patients have decreased gallbladder emptying in response to a stimulus such as a test meal or cholecystokinin. Impaired emptying shown by cholecystokinin cholescintigraphy may be useful for predicting which patients with typical biliary-type pain but no evidence of calculi will be cured by cholecystectomy.

Cholelithiasis↗
PubMed1991

Bacterial invasion of the biliary system by way of the portal-venous system.

It has been suggested that bacteria in the intestine gain access into the biliary tract by entering the portal-venous blood. We have tested the hypothesis of hematogenous infection of the biliary system in cats. The animals were treated in three different groups: group A (no biliary obstruction), group B (acute biliary obstruction) and group C (chronic biliary obstruction). A mutant strain of Escherichia coli was infused into the splenic vein of cats at three different dosages (10(7), 10(5) and 10(3) with sham controls. In the unobstructed biliary system, the mutant E. coli was isolated from the bile 30 min and 90 min after the infusion of 10(7) and 10(5) E. coli, respectively. No bacteria were found in the bile with the infusion of 10(3) E. coli and in the control animals. Bile flow was significantly reduced with the infusion of bacteria. The biliary excretion of E. coli in group B was similar to that in group A. In group C, the bile output in the first hour was very high but declined rapidly. E. coli was excreted into the bile at all three dosages of infusion after 30 min. Histological sections of the liver showed that the infused bacteria entered the sinusoidal blood and that some were phagocytosed by Kupffer cells. The portal-venous blood was considered an important route of bacterial invasion into the biliary system, and the penetration of bacteria was facilitated in biliary obstruction.

Acute Disease↗
PubMed1990

Gastric fluid volume and pH in elective surgical patients: triple prophylaxis is not superior to ranitidine alone.

The effect of oral ranitidine alone was compared with sequentially administered ranitidine, metoclopramide, and sodium citrate on gastric fluid volume and pH in 196 healthy, elective surgical inpatients, each of whom was randomly assigned to one of four groups. Patients in all groups received oral ranitidine 150 mg 2-3 hr before the scheduled time of surgery. Those in Group 1 also received oral metoclopramide 10 mg one hour before surgery, and sodium citrate 0.3 M 30 ml on call to the operating room; Group 2 received sodium citrate but no metoclopramide; Group 3 received metoclopramide but no sodium citrate; Group 4 received ranitidine alone. Following induction of anaesthesia a #18 Salem sump tube was passed into the stomach and all available gastric fluid was aspirated. Volumes were recorded and pH measured. In all groups mean pH was greater than 5.8, although at least one patient in each group had pH less than 2.5. Mean volumes were significantly greater in patients who received citrate (Groups 1 and 2: 22 and 19 ml) than in those in those who did not (Groups 3 and 4: 10 and 8 ml). One patient in Group 2 and one in Group 3 had pH less than 2.5 with volume greater than 25 ml. Our results do not demonstrate any advantage of double or triple prophylaxis over ranitidine alone. The practical difficulty of correctly administering two or even three medications, each at different but exact preoperative intervals, is emphasized.

Administration, Oral↗
PubMed1990

The effect of cyclosporine A on bile secretion in dogs.

Cyclosporine A is reported to cause cholestasis, but the evidence is confounded by anesthesia and surgery used in acute experiments. To better investigate the effect of cyclosporine on the liver, bile output was directly measured in three cholecystectomized dogs by cannulating the common duct through a chronic duodenal fistula. Control studies were done 1 month after surgery. Cyclosporine in oral doses of 5, 15, and 50 mg.kg-1.d-1 was then given for consecutive 1-week periods. Twice during each study period, bile output was measured for 5 h in fasted, awake animals: 3 h to establish basal conditions, followed by 2 h of taurocholate infusions at 1 and then 2 mumols.kg-1.min-1. Under basal conditions, bile flow rose with each dose of cyclosporine, increasing 63, 127, and 179% above control with cyclosporine 5, 15, and 50 mg.kg-1,d-1, respectively. Bile flow increased similarly during taurocholic acid stimulation. Cyclosporine had no effect on bile salt or bilirubin secretion. In this chronic dog model isolated from other causes of cholestasis, cyclosporine did not induce cholestasis but rather caused a dose-related choleresis without any change in bile salt secretion.

Animals↗
PubMed1990

Absorption of triglycerides in the absence of lipase.

Medium chain triglycerides are considered to be readily absorbed intact in the absence of pancreatic lipase, unlike long chain triglycerides. Commercial medium chain triglyceride oils comprise various medium chain fatty acids from 6 to 12 carbons in length resulting in triglyceride molecules of different sizes and molecular weights. The effect of molecular weight and hence fatty acid chain length on the efficiency of intact medium chain triglyceride absorption is unknown. Therefore, this study measured, using a single-pass marker perfusion technique, intestinal jejunum absorption of five medium chain and one long chain triglycerides in anesthetized Sprague-Dawley rats. The molecular weights of the five medium chain triglycerides were 470.7, 498.8, 526.8, 554.9, 639.0, and the long chain triglyceride, 885.4. Residual luminal pancreatic lipase was removed prior to lipid perfusion. This study demonstrated that medium chain triglycerides were absorbed in the absence of lipase whereas long chain triglyceride was not. There was no significant variation in the absorption of the five different medium chain triglycerides perfused. The molecular weight of the medium chain triglyceride did not affect its intact absorption by the small intestine.

Animals↗
PubMed1990

Protein-losing enteropathy in systemic lupus erythematosus associated with intestinal lymphangiectasia.

This case report concerns a young woman with systemic lupus erythematosus who presented with a protein-losing enteropathy. Intestinal biopsy revealed lymphangiectasia. Mesenteric lymph nodes showed paracortical lymphoid depletion and multiple small sinusoids. Elevated cholesterol levels and normal lymphocyte counts characterized the peripheral blood samples. Lymph nodes, though enlarged, showed no evidence of obstructive pathology. No secondary cause of lymphangiectasia could be identified. The patient exhibited antinuclear antibodies and antibodies to dsDNA at the onset, and then, 5 yr later, the classic features of systemic lupus erythematosus (SLE). The lymphocytopenia and hypolipidemia that characterizes lymphangiectasia is not a feature of the SLE cases reported to date. Furthermore, the mechanism for the dilated lymphatics and villous edema is more likely immunological than mechanical disruption of lymphatics.

Adolescent↗
PubMed1990

Chronic right upper quadrant pain without gallstones: does HIDA scan predict outcome after cholecystectomy?

Patients with chronic right upper quadrant pain who do not have gallstones on ultrasound or cholecystography are often referred for surgery for presumed acalculous chronic cholecystitis. We followed 26 patients who had cholecystokinin (CCK) cholescintigraphy for evaluation of chronic right upper quadrant pain without demonstrable gallstones on ultrasound who underwent cholecystectomy so that it could be determined whether there was any relation between a low ejection fraction (EF), morphological features of chronic cholecystitis, and clinical outcome. Eighteen patients (69%) were considered therapeutic successes, whereas eight (31%) were failures after an average 2-yr follow-up. Both patient groups had significantly reduced EF: the successful group at 0.39 and the failures at 0.25. Thus, a low EF did not predict clinical outcome, since the failure group had an even lower EF than the success group. Seven gallbladders demonstrated chronic acalculous cholecystitis; the average EF of this group was 0.35. The remaining 19 gallbladders were normal, yet also had an EF of 0.35. Thus, decreased EF does not predict the histologic features of chronic cholecystitis without gallstones. The diagnostic value of cholescintigraphy in patients with acalculous right upper quadrant pain is low, probably because this entity represents a variety of processes, including inflammation, gallbladder dysmotility, and the irritable bowel syndrome.

Abdominal Pain↗