Reestablishment of a percutaneous jejunostomy.
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Adenocarcinoma↗
Biomedical subjects
W Silen
Publications and source records attributed to W Silen.
Restitution of the surface epithelium of the in vitro frog gastric mucosa after damage with hyperosmolar sodium chloride. Morphologic and physiologic characteristics.
Frog fundic mucosas mounted in Ussing chambers between HCO-3-buffered nutrient and unbuffered secretory solutions were exposed to 1 M NaCl on the mucosal surface for 10 min. After washing and return to control solutions, transmucosal potential difference, short-circuit current, and tissue electrical resistance decreased markedly, but within 6 h these measurements had gradually returned to almost control values. A net luminal alkalinization occurred during the first 4 hours, changing into a net acid secretion of approximately 1.1 mumol . cm-2 . h-1 at 6 h. Histamine increased H+ secretion in all tissues at 8 h. In seven metiamide-treated tissues, an average alkaline flux of approximately 0.75 mumol . cm-2 . h-1 was obtained during the first 4 h after damage, decreasing to approximately 0. 40 mumol . cm-2 . h-1 during the ensuing 4 h. With HCO-3-free nutrient solution (n = 7) luminal alkalinization was decreased by about 80% 2-4 h after injury. After 1 M NaCl, the surface epithelium and gastric pit cells were destroyed and partially lifted from the gastric glands. The lamina propria between the remaining intact glands was open to the lumen or contiguous with the damaged mass of cells and mucus. During the 6 h after damage, there was a gradual process of restitution of epithelial integrity, beginning with squamous-shaped cells that appeared to be migrating from the glands and ultimately concluding with complete epithelialization by cuboidal and columnar cells. Typical junctional complexes were present between adjacent epithelial cells. The uniformity of the restoration process was such that it was possible to predict blindly in toluidine blue-stained semithin sections whether the recovery stage was short (30 min or less), intermediate (1-2 h), or advanced (4-6 h). These observations indicate that there is a very intimate correlation between the restoration of epithelial continuity and the reestablishment of secretory and electrical activity of frog gastric mucosa damaged by hypertonic NaCl in Ussing chambers.
Animals↗
Cryoprotection: a word of caution.
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Animals↗
The pathophysiology of stress ulcer disease.
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Duodenal Ulcer↗
Alkaline secretion by amphibian duodenum. I. General characteristics.
Stripped, proximal bullfrog duodenum was mounted in an Ussing chamber between HCO3--buffered nutrient (serosal) and unbuffered secretory (luminal) solutions. This preparation showed stable electrical parameters and caused alkalinization of the secretory solution at a rate of 0.95 +/- 0.03 mueq.cm-2.h-1 (mean +/- SE; n = 100). Anoxia and 2,4-dinitrophenol each reduced alkalinization by 50-60%, but acetazolamide (5 X 10(-4)M) had no effect. Removal of nutrient HCO3- and CO2 reduced alkalinization by over 90%, whereas increasing nutrient [HCO3-] at constant partial pressure of CO2 (PCO2) or increasing nutrient PCO2 at constant [HCO3-] each caused saturable increases in alkalinization, despite opposite effects on nutrient pH. Dibutyryl adenosine 3',5'-cyclic monophosphoric acid, but not dibutyryl guanosine 3',5'-cyclic monophosphoric acid, increased luminal alkalinization to 167 +/- 21% of control. Removal of nutrient, but not secretory, Na+ reduced alkalinization by 74%. Changes in the rate of alkalinization were accompanied by corresponding changes in potential difference and short-circuit current. Removal of Cl- or nutrient K+ or addition of histamine, thiocyanate, or catecholamines had no effect on electrical or secretory characteristics. We conclude that a) the amphibian duodenum transports alkali from nutrient to secretory solutions by both active and passive processes, b) there is a small secretion of endogenous HCO3-, c) alkaline secretion is electrogenic, d) Cl- does not contribute to the short-circuit current, e) alkaline secretion is partially dependent on nutrient Na+ that acts in a facilitatory, not cotransport, role, f) there is no Cl--HCO3- exchange, and g) alkaline secretion is independent of nutrient pH.
Acid-Base Equilibrium↗
Alkaline secretion by amphibian duodenum. II. Short-circuit current and Na+ and Cl- fluxes.
The relations among alkaline secretion, short-circuit current (Isc), and fluxes of Na+ and Cl- are examined. The Isc (1.15 +/- 0.03 microeq.cm-2.h-1) was significantly greater than the rate of alkaline secretion (1.02 +/- 0.02 microeq.cm-2.h-1). Regression analysis (n = 300) showed a highly significant correlation between alkaline secretion and Isc and indicated a residual Isc of 0.26 microeq.cm-2.h-1. In the absence of HCO3-, there was a residual Isc of 0.25 +/- 0.04 microeq.cm-2.h-1. This residual Isc is accounted for by an observed net Na+ absorption of 0.28 +/- 0.04 microeq.cm-2.h-1. Fluxes of Na+ fail to fit the flux-ratio equation and were not significantly affected by 2 X 10(-6) M ouabain, 5 X 10(-5) M amiloride, or anoxia but were significantly reduced by 2,4,6-triaminopyrimidine. The net Cl- flux was not significantly different from zero. Cl- fluxes conform to the flux-ratio equation and were reduced by anoxia or 2,4,6-triaminopyrimidine but were not affected by 4-acetamido-4'-isothiocynostilbene-2,2'-disulfonic acid (SITS). Anoxia or ouabain significantly inhibited alkaline secretion and Isc without affecting net fluxes of Na+ or Cl-, whereas amiloride or SITS had no effect on any of these parameters. There is no NaCl-coupled transport nor anion exchange, but solute-coupled Na+ absorption is demonstrated. We conclude that alkaline secretion by the duodenum involves a transcellular, energy-requiring, Na+-dependent, ouabain-sensitive, electrogenic mechanism that accounts for at least 80% of the Isc. Net Na+ absorption accounts for the residual Isc. Movements of Cl- are passive, do not contribute to Isc, and are not involved in the mechanism of alkaline secretion. Two hypothetical models of transcellular alkaline secretion are proposed.
Amiloride↗
Alkaline secretion by amphibian duodenum. III. Effect of DBcAMP, theophylline, and prostaglandins.
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Animals↗
Surgical pathology of hyperparathyroidism. Usefulness of fat stain and problems in interpretation.
Thirty-six adult patients with classical hyperparathyroidism had parathyroidectomy in which tissue evaluation included oil red O stains. Neutral lipid staining has been reported to distinguish hyperfunctioning parathyroid from suppressed or normal tissue. In normal glands, parathyroid chief cells show abundant coarse and fine intracytoplasmic neutral lipid droplets. In contrast, the cytoplasm of chief cells is essentially free of neutral lipid droplets in adenomatous, hyperplastic, or carcinomatous glands. This study shows that to limit or alter surgical exploration solely on the basis of the findings of the oil red O technique will lead to significant judgmental error (6/36 patients). Such errors are especially likely in the patient who has enlarged parathyroid glands containing a normal distribution of parenchymal to adipose tissue. There was excellent agreement between clinical outcome, surgical-pathological findings, and the oil red O stain in 30 cases of parathyroid adenoma, nodular hyperplasia, and a control group (12 patients) who had biopsies of normal parathyroid tissue during the course of thyroidectomy.
Adenoma↗
Experimental ulceration of rabbit antral mucosa.
The mechanism of acute ulceration and the nature of mucosal protective mechanisms were investigated in rabbit antrum, which is more resistant to injury than fundus of the same species, with particular reference to the relationship between H+ back diffusion, tissue acidification, and occurrence of ulceration. Exposure of antral pouches to increasing luminal [H+] during short-term hemorrhagic shock caused progressive acidification of the mucosa as measured by a microelectrode in the lamina propria, but ulceration of the mucosa did not occur unless an unphysiologically high [H+] (225 mM) was used. Addition of exogenous pepsin to a luminal [H+] of 80 mM increased the rate of H+ back diffusion and the degree of mucosal acidification, but ulcerations did not develop, suggesting that endogenous pepsin does not account for the ulceration of fundic mucosa under the same experimental situation. In contrast, addition of sodium taurocholate (5 mM) to the same luminal [H+] (80 mM) produced ulcerations and increased the rate of H+ back diffusion. Systemic administration of acetazolamide, an inhibitor of carbonic anhydrase, enhanced the development of ulceration without increasing the rate of back diffusion or the degree of tissue acidification. The results suggest that rabbit antral mucosa is protected from excessive acidification and ulceration by its relative impermeability to H+. When the rate of H+ back diffusion is artificially augmented to a level encountered in the fundus in an ulcerogenic situation, profound acidification with ulcerogenic situation, profound acidification with ulceration also occurs in the antral mucosa. The data also suggest that carbonic anhydrase, an enzyme abundantly present in gastric mucosa, may have a protective function in the mucosa, possibly by contributing to the regulation of intracellular pH and/or to the maintenance of mucosal HCO3- secretion.
Acetazolamide↗
The role of mucosal carbonic anhydrase in the protection of gastric mucosa against luminal H+.
Carbonic anhydrase is exceptionally abundantly present in the gastric mucosa, including the epithelia surface cells. Inhibition of carbonic anhydrase activity with acetazolamide enhances the susceptibility to ulceration in rabbit antrum. It also abolishes the protection against ulceration afforded by intravenous HCO3- in rats. Acetazolamide likewise abolishes the protection against ulceration afforded by the presence of HCO3- in the incubation medium for isolated frog gastric sacs. These findings suggest a protective function for carbonic anhydrase in gastric mucosa.
Acetazolamide↗
Effect of bile salts and related compounds on esophageal mucosa.
Several potentially harmful agents present in the gastric juice or duodenal contents were assessed in terms of their ability to cause damage to the esophageal mucosa using an in vitro technique. In the presence of luminal acid (pH 3.5), taurocholate and pepsin and, to a lesser degree, lysolecithin adversely affected the mucosa causing increased diffusion of luminal H+ into the mucosa, a mechanism which may play a significant role in the pathogenesis of acidic reflux esophagitis. In the absence of luminal acid (pH 7.4) trypsin and the deconjugated bile salts cholate, chenodeoxycholate and deoxycholate affected the mucosa and possibly play a more important role in the pathogenesis of alkaline reflux esophagitis.
Animals↗
H+ back diffusion stimulating gastric mucosal blood flow in the rabbit fundus.
The effect of barrier breakers on gastric mucosal blood flow (MBF) has been disputed, but the influence of acid back diffusion alone has never been studied. In anesthetized New Zealand white rabbits, intramural pH (pHi) and gastric MBF were measured with an antimony microelectrode and with radioactive microspheres (51Cr, 85Cr, 141Ce), respectively. Innervated fundic pouches were perfused with solutions of varying [H+] at 37 degrees C. In the rabbit, back flux of H+ is linearly dependent on luminal [H+] and in the present studies a direct positive linear correlation was found between luminal [H+] and MBF (r = 0.97 P < 0.001) while pHi remained unchanged up to luminal [H+] of 80 mM. The usual 80% increase in MBF induced by 80 mM HCl was prevented by pretreatment with vasopressin, which decreased pHi and caused gross ulceration. Without vasopressin, [H+] of 120 mM HCl produced gross mucosal ulceration and a decrease in MBF and pHi. Our data suggest that back diffusion of H+ influences MBF in the rabbit. There is an increasing MBF caused by increasing luminal [H+] up to 80 mM, beyond which MBF decreases. When the balance between back diffusion and MBF is disturbed by a vasoconstrictor or a high luminal [H+], pHi decreases and gross ulceration occurs.
Animals↗
Antacid versus cimetidine in preventing acute gastrointestinal bleeding. A randomized trial in 75 critically ill patients.
Over a 15-month period, 75 critically ill patients at risk of acute gastrointestinal bleeding were randomized into two groups: one group (38 patients) received the H2-blocker cimetidine intravenously at an initial dosage of 300 mg every six hours, and the other group (37 patients) received antacid (Mylanta II) through a nasogastric tube at an intial dosage of 30 ml every hour. Gastric pH was measured hourly and titrated above 3.5. Upper-gastrointestinal-tract bleeding occurred in seven of 38 cimetidine-treated patients but in none of 37 antacid-treated patients (P less than 0.01). When antacid titration was added to the cimetidine regimen in four of seven patients with bleeding, all four stopped bleeding. Renal failure, sepsis, peritonitis, hypotension, respiratory failure, jaundice, multiple trauma, and major operative procedures were associated with an increased incidence of bleeding. Cimetidine does not adequately protect seriously ill patients from acute upper-gastrointestinal-tract bleeding. Antacid is better for this purpose.
Acute Disease↗
PGE2 stimulates gastric chloride transport: possible key to cytoprotection.
Prostaglandins protect the stomach against a variety of noxious agents independently of effects on acid secretion, but the mechanism of this 'cytoprotection' is unknown. We recently proposed that gastric surface cells extrude or eliminate luminal acid by a process analogous to that described in squid axon, snail neurone, and barnacle muscle. Influxing luminal H+ combines with HCO3- which has entered the cell in exchange for intracellular chloride, probably at the nutrient membrane. Dehydration of the resulting H2CO3 into CO2 and H2O is catalysed by carbonic anhydrase, which is present in surface cells in large amounts. Interference with this chain of reactions at any point frequently causes ulceration. We have examined the effect of 16,16-dimethylprostaglandin E2 (PGE) on different segments of this protective mechanism and show here that the protective effects are intimately associated with stimulation of chloride transport. All experiments were done in vitro thus eliminating any effects of prostaglandin on mucosal circulation.
Animals↗
Chemical antroneurolysis with and without highly selective vagotomy.
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Animals↗
The gastric mucosal barrier and ulceration.
The gastric mucosal barrier is that property which defends against acid and which impedes diffusion of acid from the lumen into the mucosa. The disappearance of luminal H+ is linearly related to luminal (H+) both in the normal stomach and in stomachs exposed to barrier breakers. The latter invaribaly produce anatomic evidence of surface cellular injury. Strong direct evidence for back diffusion of luminal H+ derives from the recent demonstration of a highly significant correlation between the disappearance of luminal H+ and the pH of the lamina propria measured by an implanted microelectrode. The permeabilities of the antrum and fundus to H+ differ from each other in the same species and in different species. Gastric ulceration does not occur in the absence of luminal acid and is not dependent upon the absolute loss of H+ from the luminal solution. Mucosal ischemia induced by hemorrhage reduces tolerance against ulceration as does inhibition of acid secretion, acidification of the tissue caused by absence of nutrient bicarbonate, inhibition of carbonic anhydrase, and blockade of anion exchange by SITS. A tentative schema is proposed by which defense against luminal acid is accomplished in gastric mucosa.
Acid-Base Equilibrium↗
The prevention and management of stress ulcers.
Multiple, shallow erosions of the gastric mucosa occur with near universality after severe physiologic stress - e.g., burns, trauma, septic shock - and heal spontaneously after restoration of normal defense mechanisms. But in the interim, they may lead to exsanguinating hemorrhage. The key to prevention and management is maintenance of normal gastric pH, particularly in the presence of known risk factors.
Acute Disease↗
Role of nutrient HCO3(-) in protection of amphibian gastric mucosa.
In in vitro bullfrog fundic mucosa inhibited with 10(-3) M metiamide and exposed to a luminal pH of 2 a progressive slow decline in potential difference (PD) and short-circuit current (Isc) and a rise in resistance (R) were observed when the nutrient solution (N) contained 18 mM HCO3(-), but these changes were restored by an N containing 50 mM HCO3(-). Substitution of PO4(3-) or N-tris(hydroxymethyl)-methyl-2-aminoethanesulfonic acid for NHO3(-) in N caused a rapid drop in PD and Isc in inhibited tissues, changes that could be prevented by 10(-4) M histamine. Ulceration occurred more frequently in metiamide-inhibited gastric sacs exposed to artificial gastric juice with an N of 18 mMHCO3(-) than with 50 mM HCO3(-), but histamine prevented ulceration in the 18 mM HCO3(-) solution. JnetCl approximated Isc under most experimental conditions in inhibited mucosa and was reduced dramatically as were both Jn leads to sCl and Js leads to nCl when HCO3(-) was removed from N. In histamine-stimulated tissues, removal of nutrient HCO3(-) did not influence Cl- transport. Our results are consistent with the proposal that HCO3(-) in N supports normal Cl- flux and that the alkaline tide of actively secreting oxyntic cells can do the same in the absence of ambient HCO3(-).
Animals↗