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Biomedical subjects

D Fromm

Publications and source records attributed to D Fromm.

At least 55 records · Page 3Linked to original sources

Effects of cyclic adenosine monophosphate and prostaglandins on Na+- and HCO3--induced dissipation of a proton gradient in isolated gastric mucosal surface cells of rabbits.

One mechanism that surface cells can use to regulate intracellular pH is Na+/H+ exchange. The presence of another means to modify intracellular pH, HCO3-, was investigated, as were the effects of cyclic adenosine monophosphate and prostaglandins on an intracellular proton gradient. Isolated surface cells were preincubated in NH4+ to establish an intracellular proton gradient, which was measured using acridine orange. The addition of HCO3- causes gradient dissipation, an effect sensitive to 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid but not to extracellular chloride. The HCO3--evoked dissipation of the proton gradient is diminished by cyclic adenosine monophosphate, isobutyl-methylxanthine, and prostaglandin E2, but not by prostacyclin. The Na+-evoked dissipation of the gradient is diminished by cyclic adenosine monophosphate and isobutylmethylxanthine, but not by prostaglandin E2 or prostacyclin. Cyclic adenosine monophosphate, isobutylmethylxanthine, and the prostaglandins are without effect in the absence of Na+ or HCO3-. The data suggest that extracellular HCO3- influences an intracellular proton gradient, but the precise mechanism involved is not established in this study. The data may also explain why prostaglandins are in some instances not cytoprotective for surface cells.

1-Methyl-3-isobutylxanthine↗

Rapid recovery from aphasia: a detailed language analysis.

The paper presents a daily analysis of the language recovery of a patient who was globally aphasic at the time of her first observation and who had recovered language, as measured by the Western Aphasia Battery, at the time of her discharge 14 days later. The paper emphasizes the relatively regular growth of normal syntactic, lexical, and pragmatic features coupled with similar regular decreases in aphasic features. Observations of both phenomena are necessary to describe language recovery.

Adult↗

The effect of exogenous fibronectin on wound breaking strength.

Experimental wounds in rats were tested for breaking strength at 4, 7, 11, 14, and 21 days to determine whether incisions treated with homogenous fibronectin differed from control incisions. At 7, 11, 14, and 21 days after wounding, the fibronectin-treated incisions were significantly stronger than the control incisions.

Animals↗

Effects of a naturally occurring polyamine on acid secretion by isolated gastric mucosa.

Determination of the effects of spermine on acid secretion by isolated rabbit gastric mucosa shows paradoxical responses at neutral luminal pH. Initial inhibition of acid secretion was followed by a return to near basal rates. However, measurement of mucosal and serosal rates of CO2 release indicated that spermine causes prolonged inhibition of acid secretion. Similar prolonged inhibition is seen with mucosa exposed to an acidic luminal pH. The inhibitory effect of spermine is reversed by the addition of K+ to the mucosal side, suggesting spermine interferes with a K+ site at the secretory membrane. Serosal addition of spermine is without effect. The apparent acid secretory rebound phenomenon observed after the addition of spermine is most likely related to formation of H+ in the luminal bathing solution rather than proton secretion by the mucosa.

Animals↗

H+ disposal by rabbit gastric mucosal surface cells.

Exposure of isolated gastric mucosal surface cells to NH4+ results in acidification of cells as determined by a fluorescent dye technique using acridine orange. The resulting intracellular pH gradient is maintained when cells are suspended in either buffered HCO3- -free Ringer's or choline chloride solution. Cells suspended in a Na+-containing but K+-free solution exhibit dissipation of the proton gradient. When Na+ is added to cells suspended in Na+, K+-free solution, the gradient rapidly dissipates with a half-maximal response occurring at 56 mM Na+. The effect of Na+ is amiloride sensitive with half-maximal inhibition occurring at 38 microM at a Na+ concentration of 50 mM. The K+ does not cause dissipation of the gradient and neither ouabain nor valinomycin have an effect. Yet, K+ has a modulating influence on Na+/H+ exchange by the isolated surface cells. The addition of K+ to acid-loaded cells resuspended in Na+-free solution decreases the ability of subsequent Na+ addition to evoke gradient dissipation. The data suggest that Na+/H+ exchange appears to be at least one mechanism whereby gastric mucosal surface cells could protect themselves against diffusing acid. This ion exchange mechanism is amiloride sensitive and appears to be unrelated to Na+, K+ adenosine triphosphatase activity, but is affected by the external K+ concentration.

Acridine Orange↗

Neuropsychological test performance in depressed patients before and after drug therapy.

Sixty psychiatrically depressed patients (female = 39, male = 21), classified as psychotic or neurotic, were neuropsychologically assessed on an expanded Halstead-Reitan battery before antidepressant medication. Extant normative data from a large control group (N = 142) were employed for comparative purposes. Statistical analysis of the pretreatment data revealed a selective impairment in the processing of visuospatial material and retention of both nonverbal and verbal information by both the Neurotic and Psychotic groups, with greater impairment shown by the latter group. Separation of the Psychotic group from the Neurotic and Control groups was possible using these data. Posttreatment data analysis, although tentative due to the high attrition rate (female = 19, male = 14), indicated significant improvement in those abilities most impaired initially and did not allow separation of the Neurotic and Psychotic groups from the Normal group. These results are consistent with previous research which suggest greater perturbation of the nondominant hemisphere in depressive disorders, attenuation of cognitive deficits with amelioration of symptomatology, and the presence of residual deficits after treatment in older subjects.

Adolescent↗

Gallstone pancreatitis. Support for a flexible approach.

We reviewed records of 63 patients with diagnosed gallstone pancreatitis. Most of them (89%) responded to nonoperative treatment. Nearly one quarter of patients undergoing operation 2.4 months later had a recurrent, uncomplicated episode of pancreatitis before the operation. Almost half of the patients who had early elective operations (9.7 days after admission) had common bile duct stones, compared with only 8% of those who underwent late elective operations. Eleven percent of patients had emergency operations during initial hospitalization because of failure to respond early to nonoperative treatment. Each of them had evidence of pancreatitis but also a potentially life-threatening and surgically curable disease. Although categoric emergency and elective operative approaches to patients with gallstone pancreatitis have been proposed, our study suggests that an absolute approach is neither necessary nor desirable.

Aged↗

Oral administration of spermine inhibits gastric acid secretion in rats.

Administration of spermine by oral route inhibits the histamine-stimulated gastric acid secretion in pylorous ligated rats. The extent of both the acid and volume of secretion is dependent on the dose of spermine. The polyamine is completely ineffective when injected by the intravenous route. A single oral dose of spermine suppresses acid secretion for at least 6 hr. An inverse relationship between the efficacy of oral spermine and age of the animals was observed. These data suggest a therapeutic potential for the naturally occurring polyamine compounds.

Administration, Oral↗

Persistent active hepatic necrosis with the enigmatic absence of abnormalities in laboratory test results.

Certain common clinical laboratory tests are employed regularly to determine the presence of active necrotizing processes in the liver. These include in particular bilirubin, several enzymes, clotting factors, and serum proteins. We have studied a patient with perihepatic and intrahepatic infection and extensive necrosis, who showed minimal changes in the usual biochemical markers associated with hepatocellular damage. The significance of these findings is discussed.

Adult↗

Effects of bile acid and salicylate on isolated surface and glandular cells of rabbit stomach.

Little is known about the response of surface cells and glandular cells of the gastric mucosa to various injurious agents. This study examines the effects of bile acid and salicylate on oxygen consumption and membraneolysis of isolated gastric mucosal surface cells and compares these responses to those of cells constituting the gastric glands. The effects of salicylate and bile acid on oxygen consumption by surface cells are similar to previous observations for intact gastric glands and isolated mitochondria, indicating alterations of oxidative phosphorylation. Salicylate does not appreciably alter lipid release from either surface or glandular cells. However, bile acid causes a profound increase in lipid release from both surface and glandular cells. Salicylate does not alter the number of visibly intact surface or glandular cells, but 1 mM of taurocholic acid decreases the number of surface cells by 45% without altering the glandular cells. In contrast, 5 mM of taurocholic acid completely destroys the surface cells and reduces the number of gastric glandular cells by 51%. These data suggest that surface cells are more susceptible to membraneolytic effects of bile acid than are gastric glandular cells. This may account for the superficial nature of bile acid-induced injury to the gastric mucosa. Although both bile acid and salicylate interfere with oxidative metabolism, this effect alone does not appear to account for cellular destruction.

Animals↗

Effects of sodium salicylate and acetylsalicylic acid on intramural pH and ulceration of rabbit antral mucosa.

This study examines the relationship between the pH within the middle third of antral mucosa (intramural pH [IMpH]) and the development of ulceration caused by salicylates. Luminal soldium salicylate does not significantly alter the IMpH or cause ulceration of mucosa maintained at luminal pH 7. Salicylate at pH 3.5 initially decrease IMpH (7.28 to 6.75), during which time ulceration occurs. IMpH subsequently increase, resulting in profound alkalinization (pH 7.67) associated with increased HCO3 secretion. Salicylate at pH 1 causes a sustained decrease in IMpH (6.57), which is associated with more severe ulceration. Neither sodium salicylate nor acetylsalicylic acid given intravenously affects. IMpH or causes ulceration at luminal pH 7 or 3.5. However, at pH 1 both salicylate compounds cause ulceration and subtle changes in net ion fluxes without altering IMpH. The data suggest that acidification of the midportion of the mucosa in general is not a prerequisite for the occurrence of gross damage, and the damaging effects of intravenous salicylates cannot be explained by thier metabolic actions alone. However, it appears that the metabolic effects of salicylate make the mucosa more susceptible to the deleterious effects of diffusing acid. Since intravenous sodium salicylate and acetylsalicylic acid both cause ulceration but only acetylsalicylic acid alters prostaglandin synthesis, interference with prostaglandin metabolism does not appear to be a prerequisite for the occurrence of ulceration.

Animals↗

Accessory splenectomy for idiopathic thrombocytopenic purpura.

Not all patients who undergo splenectomy for idiopathic thrombocytopenic purpura (ITP) respond to operation. This may be due to the presence of an accessory spleen. This is a report of three patients who underwent successful accessory splenectomy after relapse of their disease. Each patient initially experienced a complete response to splenectomy, but recurrence occurred months to years later. All of the patients had persistent Howell-Jolly bodies on peripheral blood smear, yet two of the patients had complete and sustained remissions of their disease after accessory splenectomy. Intraoperative localization of an accessory spleen may be exceedingly difficult in the patient who has undergone a previous operation. However, localization of accessory splenic tissue is greatly facilitated by use of a sterile isotopic detector probe intraoperatively after the injection of technetium-99m-labeled red blood cells. Given the morbidity and mortality rates of refractory ITP, patients who have a relapse after, or who fail to respond to, splenectomy should be evaluated for the presence of an accessory spleen, even if Howell-Jolly bodies are present on peripheral blood smear.

Adult↗

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↗