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T J Layden

Publications and source records attributed to T J Layden.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effects of taurine-conjugated bile salts on ionic transport of the rabbit esophageal mucosa.

Bile salts have been implicated as a cause of esophageal injury. We examined in vitro the changes in ionic transport of the rabbit esophagus resulting from taurine-conjugated bile salts at neutral pH to define and characterize their actions independent of hydrogen ion. In an Ussing chamber changes in potential difference (PD, mV), short-circuit current (SCC, microA X cm-2) and resistance (R, omega X cm2) resulting from taurocholate (TC), taurodeoxycholate (TDC) and taurochenodeoxycholate (TCDC) were studied. Transport properties were unaffected by TC at 5 and 10 mM. With TDC (5 mM) there was an initial rise in SCC and PD. After 60 min PD and R declined in association with an increase in paracellular permeability as measured by [14C]sucrose flux. TCDC (5.0 and 7.5 mM) caused a sustained rise in PD and SCC with a greater rise seen at 7.5 mM. The rise in SCC after TCDC was secondary to an increase in net sodium absorption as basal net sodium absorption increased threefold from 0.15 +/- 0.03 to 0.44 +/- 0.10 mu eq X cm-2 X h-1. Increased net sodium absorption accounted for 73% of the TCDC-induced rise in SCC. Amiloride (10(-4) M) added to the mucosal solution significantly inhibited this bile salt-induced rise in SCC. We conclude that bile salts alter ionic transport in the esophageal mucosa independent of hydrogen ion. These changes are characterized by an early selective increase in apical membrane cation conductance and with longer exposure, particularly in the presence of more hydrophobic bile salts, there is a marked increase in paracellular conductance.

Amiloride↗
PubMed1985

Limitations of 24-hour intraesophageal pH monitoring in the hospital setting.

Prolonged intraesophageal pH monitoring is considered by some to be the most sensitive and specific test of gastroesophageal reflux. We prospectively examined the ability of the test to discriminate 64 hospitalized patients with typical reflux symptoms from 20 age-matched hospitalized control subjects. Patients were subdivided based on endoscopic findings into two groups: group 1, normal endoscopy (n = 30); group 2, erosive esophagitis (n = 34). Six different individual reflux variables and a scoring system were evaluated. Total esophageal acid exposure time and the number of reflux episodes requiring longer than 5 min to clear were each found to have greater discriminatory power than other variables and the scoring system. Although the 64 patients had significantly more acid reflux than controls, only 48% had abnormal results (defined as 2 SD from the control mean). Group 1 patients had significantly more reflux than controls, though only 21% had abnormal results. Group 2 patients were significantly different than both controls and group 1, but 29% had normal studies. Ninety-three percent of the group 1 patients with normal studies responded to antireflux therapy, and only 1 patient had another explanation for the symptoms. The finding that 24-h pH monitoring was normal in half of the individuals presenting with reflux symptoms and in 29% of the patients with erosive esophagitis indicates that negative test results must be interpreted with caution. The insensitivity of the test may relate to the manner in which the study has traditionally been performed in the hospital, and outpatient ambulatory monitoring may improve its reliability.

Aged↗
PubMed1984

Endoscopic control of upper gastrointestinal hemorrhage with a bipolar coagulation device.

It has been difficult to determine the real efficacy of endoscopic treatment for upper gastrointestinal tract bleeding sites for several reasons. First, since 80 per cent of an unselected group are expected to stop bleeding spontaneously, it is important to focus upon those individuals who continue to bleed instead of a group in whom bleeding would have stopped spontaneously in the majority. Second, it is difficult, if not impossible, to have comparable groups of patients with similar lesions and similar rates of bleeding who can be randomized into different treatment groups. This report describes the use of a bipolar endoscopic coagulation device in 28 patients with active massive upper gastrointestinal tract hemorrhage who represent 10 per cent of the patients with hemorrhage during a one year interval. Endoscopic treatment controlled bleeding initially in 23 of these patients. Another eight patients with recent hemorrhage who were at high risk for recurrent bleeding (visible vessels) had endoscopic coagulation without subsequent hemorrhage. Immediate operations were required in five of the 28 and delayed operations in another four. Mortality in the patients treated by endoscopic or surgical therapy was comparable (20 per cent), but no patient died of hemorrhage. The high mortality in this group of patients is explained by associated illnesses. B-C is as effective as other endoscopic treatments for nonvariceal sources of upper gastrointestinal tract hemorrhage. This modality is relatively cheap compared with other devices, is theoretically less complicated and has minimal risk to the individual patient. Because of these considerations, it is a technique which deserves wider application and may become the endoscopic treatment of choice for control of upper gastrointestinal tract hemorrhage. Patients with endoscopic control of upper gastrointestinal tract bleeding avoid perioperative morbidity, have a lower transfusion requirement and may have a shorter hospital stay than comparable individuals who require operative control of bleeding sites.

Clinical Trials as Topic↗
PubMed1982

Emergency transumbilical embolization of bleeding esophageal varices.

Eight patients had major hemorrhage from esophageal varices; in seven, one or two embolizations of the coronary and short gastric veins resulted in cessation of hemorrhage. This procedure can be used in patients with massive ascites, severe coagulopathy, or profound liver failure, as the access route through the dilated umbilical vein can be reached via a supraumbilical incision done with the patient under local anesthesia. All patients died; two deaths were attributable to complications of the procedure, the other six to the severity of the cirrhosis. Sclerotherapy may be combined with coronary vein embolization, but the risk of esophageal perforation may be greater than with sclerotherapy alone.

Adult↗
PubMed1980

An evaluation of total parenteral nutrition in the management of inflammatory bowel disease.

Total parenteral nutrition (TPN) is commonly used in the management of inflammatory bowel disease (IBD). Claims of its effectiveness are conflicting, and most reports have been limited to short-term assessments. We undertook a nonrandomized prospective study of the effects of TPN on the course of IBD in 30 patients whose disease was refractory to medical therapy, 20 with Crohn's disease and 10 with ulcerative colitis. Parameters of nutritional improvement, subjective and objective clinical response during TPN, and long-term outcome were assessed. All but one of the patients gained weight. Seven of the 20 Crohn's patients, including 3 of 4 with fistulas, had no response to TPN. The other 13 had reduction of diarrhea, relief of abdominal pain, and an improved sense of well-being during TPN. On long-term follow-up, five of these patients relapsed and required surgery; five remain improved with active disease controlled by medication 2--24 months later, and three are symptom-free and off all medication 20--48 months later. Clinical improvement during TPN was observed in only four of the 10 ulcerative colitis patients; six required colectomy after 9--24 days of TPN. Of the four responders, one relapsed and had colectomy one month later, two continue to have active disease controlled by medication five and 43 months later, and one has been symptom-free and off all medication for over three years. We conclude that TPN is useful adjunctive therapy for IBD patients requiring bowel rest and nutritional repletion. Dramatic clinical improvement occurs in some patients but is unpredictable.

Adolescent↗
PubMed1978

Bile formation in the rat: the role of the paracellular shunt pathway.

Transepithelial movement of water and solute occurs both through the cell membrane as well as across the intercellular junctional complex (paracellular shunt pathways). Permeability of paracellular shunt pathways is increase by transmucosal osmotic gradients, and in certain epithelia these changes are associated with bullous-like deformations (blisters) of the zonula occludens and localization of lanthanum within junctional complexes. Although bile acids increase biliary secretion by osmotic forces, the source of this water movement into bile is not known. In the present studies we examined whether a choleretic infusion of sodium dehydrocholic acid (DHC) or its taurine conjugate, taurodehydrocholate, altered the solute permeability characteristics and morphologic appearance of the junctional complexes of rat hepatocytes. Animals were continuously infused for 1 hr with 1% albumin--0.9% NaCl alone or 120 mumol of DHC and bile flow and biliary clearance of [14C]sucrose, an indirect marker of biliary permeability were measured. The number of intercellular blisters adjacent to the bile canaliculus were counted in an unbiased manner from photographs obtained with scanning electron microscopy. Bile flow and the biliary sucrose clearance remained unchanged in control animals whereas DHC infusions resulted in a progressive increase in the biliary clearance of [14C]sucrose during the 60 min of infusion even though the choleretic response to DHC was stable during the final 30 min of infusion. DHC infusions produced surface invaginations, or blisters, (0.1--0.7 micrometer in diameter) which were located immediately adjacent to the hemi-bile canaliculus and occurred with a frequency of 1.62 +/- 0.08 per hepatocyte surface, which was fivefold greater than observed in controls. In separate groups of animals 5 mM ionic lanthanum chloride was perfused intraportally after taurodehydrocholate infusions, and the number of junctional complexes that contained the electron dense marker were quantitated by transmission electron microscopy. Localization of lanthanum in the junctional complexes of fasted control animals was not observed, whereas approximately equal to 50% of the zonula occludens in DHC-infused animals contained lanthanum which was also occasionally identified within the lumen of the bile canaliculus. These results indicate that infusions of DHC cause blisters adjacent to the junctional complex of rat hepatocytes in association with changes in solute conductivity of the zonula occludens to cations such as ionic lanthanum chloride, and presumably to larger solutes such as sucrose. Qualitatively similar morphologic findings were also observed during the infusion of sodium taurocholate at physiologic rate (40 mumol/h). These studies suggest that the paracellular shunt pathway in the liver is an important site for bile acid-induced water and solute movement into bile.

Animals↗
PubMed1977

Effects of chronic choleretic infusions of bile acids on the membrane of the bile canaliculus. A biochemical and morphologic study.

To determine whether choleretic infusions of bile acids modified the function or structure of the membrane of the bile canaliculus, sodium taurocholate (NaTc) or dehydrocholate (DHC) was infused into male rats at a rate of 80 mumoles per hour over an 18-hour period. Bile was collected by fistula and phospholipid and cholesterol content was measured in bile, liver homogenates, and isolated liver plasma membranes (LPM) enriched in bile canaliculi. Na+, K+-ATPase, Mg2+-ATPase, 5'-nucleotidase, and alkaline phosphatase activities were also measured in LPM. NaTc infusions enhanced cholesterol and phospholipid output in the bile in association with a significant increase in phospholipid in both LPM and liver homogenate. Although DHC infusions resulted in a comparable excretion of bile acid, phospholipid and cholesterol output in bile did not increase from control values and the concentration of these lipids in LPM and liver homogenate also did not change. However, LPM Na+, K+-ATPase significantly increased after DHC infusions compared to NaTc-infused animals or controls. Neither bile acid altered the activities of Mg2+-ATPase, 5'-nucleotidase, or alkaline phosphatase. Both bile acids increased the diameter of the lumen of the bile canaliculus as assessed by scanning electron microscopy and produced irregularities and outpouchings in the canalicular membrane. Diverticuli and loss of microvilli were most prominent with DHC infusions whereas canalicular side branching and the density of microvilli, either remained unchanged or increased following NaTc infusions. Although the morphologic findings are qualitative, the results of these studies indicate that chronic choleretic infusions of NaTc and DHC have divergent effects, not only on enzyme activities in liver plasma membrane, but on phospholipid composition and 3-dimensional structure. These findings suggest that bile acids may after biliary secretion not only through their osmotic effects, but by modifying lipids and enzymes in the membrane of the bile canaliculus.

Adenosine Triphosphatases↗
PubMed1976

The effect of thyroid hormone on bile salt-independent bile flow and Na+, K+ -ATPase activity in liver plasma membranes enriched in bile canaliculi.

The relationship between bile salt-independent canalicular flow and ATPase activity in liver plasma membranes (LPM) enriched in bile canaliculi, was studied in control, hyperthyroid, and hypothyroid rats. Canalicular bile production was significantly increased in hyperthyroid rats (3.19 +/- 0.23 mul/min per g liver) compared to controls (2.27 +/- 0.24 mul/min per g liver), while it diminished in hypothyroid animals (1.58 +/- 0.17 mul/min per g liver). Although bile salt excretion was also increased in hyperthyroid animals (62.4 +/- 13.3 vs. 41.2 +/- 8.4 nmol/min per g liver), the stimulation in canalicular secretion was primarily related to enhancement of the bile salt-independent fraction of flow (2.47 mul/min per g liver in hyperthyroid rats vs. 1.67 mul/min per g liver in controls). LPM Na+, K+-ATPase activity doubled in hyperthyroid animals (21.5 +/- 5.8 vs. 10.7 +/- 3.1 mumol Pi/mg protein per h) while Mg++-ATPase activity remained unchanged and 5'-nucleotidase activity increased to a small but significant extent. In hypothyroid rats, bile salt excretion remained unchanged from control values so that the reduced secretion was entirely secondary to an inhibition of bile salt-independent secretion (1.19 mul/min per g liver). Na+, K+-ATPase activity in the LPMs from hypothyroid animals decreased by nearly 50% (5.4 +/- 1.6 mumol Pi/mg protein per h), although comparable reductions in the specific activity of Mg++-ATPase and 5'-nucleotidase were also observed. Administration of L-thyroxine to hypothyroid animals restored both bile salt-independent canalicular secretion and membrane enzymes to control values within 2 and 4 days, respectively. Sodium dodecyl sulfate gel electrophoresis demonstrated no significant changes in LPM protein fractions from any of the treatment groups. These studies indicate that thyroid hormone has a parallel effect on bile salt-independent canalicular secretion and LPM Na+, K+-ATPase activity, supporting the hypothesis that Na+ transport and Na+, K+-ATPase may be determinants of bile salt-independent canalicular flow.

Adenosine Triphosphatases↗