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Biomedical subjects

D Fromm

Publications and source records attributed to D Fromm.

At least 73 records · Page 4Linked to original sources

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↗

Effects of bone wax on bacterial clearance.

The hemostatic benefit of bone wax placed in cancellous bone occurs at the expense of the wax persisting at the bony site for years. As such, bone wax appears to act as a foreign body. This study examines the effect of bone wax on the ability of cancellous bone to clear bacteria. The iliac crest of rabbits was penetrated to a standard depth with an 18-gauge needle. Subsequently, nothing or Staphylococcus aureus, 10(5) colony-forming units, was innoculated in the needle site and followed by the subcortical placement of a cylinder of bone wax or similarly sized stainless steel rod. Ten days later, the site of bony penetration was excised and cultured. Eighty percent of animals whose bone was implanted with bacteria and bone wax together had positive cultures. Forty percent of animals whose bone was implanted with bacteria and a steel rod also had positive cultures. The difference between these groups (bacteria with bone wax or with steel rod) was not statistically significant. However, these combinations of bacteria with foreign body were significantly different from the bacteria only or bone wax only or steel rod only groups in which no positive cultures were observed. The data indicate that bone wax significantly impairs the ability of cancellous bone of rabbits to clear a standard inoculum of S. aureus. This effect appears to be the same as that observed with a different but similarly sized foreign body (steel rod).

Animals↗

Portal hemodynamics in dogs during mechanical ventilation with positive end-expiratory pressure.

The effects of 10 and 15 cm H2O positive end-expiratory pressure (PEEP) on portal vein flow (PVF), superior mesenteric artery flow (SMAF), and cardiac output (CO) were studied. Portal vein pressure (PVP) and the intraluminal pressure gradient between portal vein and intrathoracic inferior vena cava (PVP-CVP) were also measured. PEEP caused a fall in CO and SMAF, and the fall in each was proportionately the same. PVF also fell and a linear correlation between PVF and SMAF during PEEP was observed. Although PVP increased relative to atmosphere, no increase in transmural PVP and no change in PVP-CVP gradient was observed with PEEP. These data suggest that the major effect of PEEP on portal hemodynamics is a reduction in portal flow secondary to the reduction of arterial inflow into the gut. These hemodynamic changes do not appear to be the result of an increase in resistance to protal flow at the liver but rather the result of PEEP reducing cardiac output.

Animals↗

Recognition of adrenal insufficiency in the postoperative patient.

The signs and symptoms of adrenal insufficiency in the postoperative patient are generally nonspecific, and the diagnosis is usually made at postmortem examination. Two patients in whom adrenal insufficiency developed in the postoperative period are reported on (one had metastatic carcinoma to the adrenal glands and in the other bilateral adrenal hemorrhage developed during anticoagulant treatment). Both patients survived multiple, successive stressful episodes before the diagnosis of adrenal insufficiency was established by the alpha1-24 corticotropin stimulation test.

Adenocarcinoma↗

Effect of bile salts and related compounds on isolated esophageal mucosa.

The effect of several potentially harmful agents in gastric juice and duodenal contents on esophageal mucosa was investigated in the presence or absence of luminal H+ using an in vitro technique. Isolated rabbit esophageal mucosae were incubated in an Ussing chamber, and during exposure to the test agents mucosal integrity was assessed by measurement of mucosal potential difference (PD), tissue electrical resistance (R), and when luminal acid was present, the tissue permeability to H+. At pH 3.5 taurocholate caused a marked decrease in the PD and R and a substantial increase in the rate of luminal H+ loss. This effect was dependent on the presence of luminal H+, since no changes were observed with taurocholate at pH 7.4. In contrast, two of the three deconjugated bile salts tested at pH 7.4, deoxycholate and chenodeoxycholate, caused a profound reduction in the PD and R, similar to that observed with taurocholate in the presence of H+. Pepsin in the presence of H+, lysolecithin to a lesser degree, and trypsin in the absence of H+ also adversely affected isolated esophageal mucosa, but the effects were less pronounced than those caused by bile salts. Our data suggest that different mechanisms are operative in the pathogenesis of acidic and alkaline reflux esophagitis. In the presence of gastric H+, pepsin, and conjugated bile salts are the substances responsible for the greatest injury. In contrast, when acid is absent, trypsin and especially deconjugated bile salts are more crucial pathogenetic factors.

Animals↗

Anastomotic dehiscence after low anterior resection of the rectum.

Thirty-two patients who had anastomoses to the extraperitoneal rectum underwent radiographic contrast studies about two weeks after operation in order to determine the incidence of anastomotic dehiscence. No extravasation occurred in the sixteen anastomoses in which the middle hemorrhoidal arteries were intact, but partial disruption occurred in four of seventeen (24%) anastomoses in which the middle hemorrhoidal arteries were sacrificed. Since not all patients with anastomotic dehiscence after low anterior resection are symptomatic, the incidence of anastomotic breakdown will be under-estimated unless x-ray studies are performed. More data are required for a better understanding of the technical features of operation which will reduce the incidence of leakage from anastomoses to the extraperitoneal rectum.

Adult↗

Gastric mucosal defense mechanisms: effects of salicylate and histamine.

Some of the recent concepts about the gastric mucosal defense mechanisms against damage by luminal acid and the effects of histamine and salicylate on these mechanisms are reviewed. The mucosal barrier to acid appears to consist of at least two physiologic components: a permeability mechanism and a metabolic mechanism related to cellular bicarbonate production as a result of acid secretion. In the absence of salicylate, histamine appears to exert some protection by affecting both mechanisms, but in the presence of salicylate, histamine's protective effect is limited to altering mucosal permeability. The actions of salicylate on the gastric mucosa are complex, related in part to the concentration of salicylate and the pH of the luminal fluid. The damaging effects of salicylate appear to be related more to the concentration of acid in the lumen than to the lipid solubility of the drug. Salicylate increases permeability regardless of pH; the increase is initially selective for cations and subsequently becomes nonselective, involving both cations and anions. Although both low and high concentrations of salicylate increase mucosal permeability to hydrogen ions, only high concentrations of salicylate affect cellular bicarbonate production.

Animals↗

Effect of the acid secretory state on intramural pH of rabbit gastric mucosa.

Intramural pH of the gastric mucosa was measured using a microelectrode technique in rabbit gastric pouches under different secretory conditions and luminal acidity. Exposure of spontaneously secreting or metiamide-treated fundic pouches to a relatively high concentration of luminal acid. HCl 120 mM, for 60 min, led to a marked net loss of luminal H+ which was associated with a significant decrease in the intramural pH (7.28 +/- 0.09 to 6.88 +/- 0.10 and 7.23 +/- 0.07 to 6.99 +/- 0.09, respectively). A linear relationship was observed between the rates of net disappearance of luminal acid and the intramural pH. All 10 spontaneously secreting and five metiamide-treated pouches had superficial mucosal erosions. In contrast, when fundic pouches were exposed to luminal acid in histamine-treated animals, the net loss of luminal H+ was negligible and the intramural pH remained at its base-line level (7.25 +/- 0.07). Histamine stimulation without acid in the lumen caused a small but insignificant increase in the intramural pH (7.27 +/- 0.03 to 7.39 +/- 0.05). Only three of the eight histamine-treated fundic pouches had lesions. In the antral pouches the intramural pH changes in response to exposure to luminal acid were smaller and histamine treatment did not influence the intramural pH. None of the antral pouches had lesions. The results suggest that acidification of the tissue by the diffusion of luminal acid may be an important factor in the pathogenesis of acute gastric ulceration. The acid secretory state of the gastric mucosa can significantly influence the acid-base balance in the mucosa and thus modify its response to acid diffusing from the lumen. Histamine stimulation protected the gastric mucosa by improving its buffering capacity and/or otherwise decreasing the diffusion of H+ from the lumen into the mucosa.

Animals↗

Salicylate and gastric mucosal damage.

The mechanism(s) of salicylate-induced damage of the gastric mucosa is complex. The presence of acid in the lumen is essential for the occurrence of such injury. Although the absorption of salicylate is greater in the presence of acid, salicylate can selectively increase cation permeability both in the absence and presence of acid. Recent studies suggest that this permits increased diffusion of luminal acid into the tissue, which leads to major permeability changes of the mucosa. Salicylate also affects metabolic processes of the gastric mucosa, which appear to be independent of the increased diffusion of acid into the tissue also caused by salicylate. The release of histamine, which has been shown to occur in vivo as a result of mucosal damage, does not appear to intensify existing mucosal injury in an isolated system.

Animals↗

Effects of compounds chemically related to salicylate on isolated antral mucosa of rabbits.

This study examines some of the gastric mucosal effects of compounds structurally related to salicylate (which consists of a hydroxyl and a carboxyl group attached to a benzene ring) in order to determine the importance of the various ligands of the salicylate molecule. The presence of carboxyl group increases mucosal permeability to acid. This increase in cation flow initially is associated with a decrease in anion permeability. These ion selective effects subsequently give way to a nonspecific increase in permeability. The presence of a carboxyl group also is associated with a more than 80% decrease in short circuit current. A similar decrease in short circuit current occurs when the mucosa is exposed to a pyridine molecule with an attached carboxyl group (pyridine-3-carboxylic acid), but in a relatively low concentration, this agent also decreases the back diffusion of acid. The above noted changes in mucosal permeability and short circuit current do not appear to be attributable to the benzene or phenolic ligands of the salicylate molecule. It is concluded that the presence of a sufficient concentration of an exposed carboxyl group on the mucosal side of the tissue causes an increase in the permeability of the mucosa to acid. The presence of a carboxyl group also appears to alter active ion transport, but this effect cannot be attributed to enhanced diffusion of acid into the tissue. The data implicate the carboxyl group of salicylate as being key to its damaging effects on the stomach.

Animals↗

Effects of lysolecithin on isolated gastric mucosa.

The effects of lysolecithin, a normal constituent of duodenal juice, on gastric mucosa were measured under isolated conditions. In a relatively low concentration (0.5 mg/ml), lysolecithin, added to the luminal side, caused liberation of organic acids without altering the spontaneous rate of mineral (i.e., HCl) acid secretion by fundic mucosa. The low concentration of lysolecithin also did not appear to affect other active ion transport processes or permeability of either fundic or antral mucosa. However, at a higher concentration (1 mg/ml) lysolecithin inhibited spontaneous mineral acid secretion by fundus, altered active transport of other ions, and increased mucosal permeability of both fundic and antral mucosa. The results suggest that intraluminal lysolecithin in concentrations found in vivo may contribute to gastric mucosal damage.

Animals↗

Secretory state of gastric mucosa and resistance to injury by exogenous acid.

The capacity of the stomach to resist the effects of highly acid solutions was assessed by comparing the effects of such solutions on spontaneously secreting, stimulated, and inhibited gastric mucosae of rabbits in vivo and frogs in vitro. Exposure of unstimulated resting mucosa to HC1, 120 mM, for 60 minutes produced superficial erosions in all rabbits, whereas such lesions were observed in only one of ten animals stimulated with histamine. Metiamide obviated the protective effect of histamine against ulcerations even though it did not reduce H+ secretion to zero. Exposure of inhibited isolated frog fundic mucosa to HC1 resulted in significant deterioration of electrical parameters, suggesting impairment of active transport processes and increased tissue permeability. These data are consistent with the hypothesis that actively secreting gastric mucosae from two species resist injury to exogenous acid more effectively than do resting or inhibited tissues, perhaps in part as a result of a greater alkaline tide.

Animals↗