Peptic ulcer. Surgical alternatives.
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Biomedical subjects
Publications and source records attributed to J Rudick.
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Effects of a synthetic prostaglandin analog--16,16-dimethyl prostaglandin E2 methyl ester (16-diMe-PGE2)--on parotid secretion were evaluated in eight dogs under anesthesia. Graded doses of 16-diMe-PGE2 (0.3, 0.5, 1.0 and 2.5 microgram./kg.) were administered intravenously with the parotid in the resting state or in response to urecholine (intravenous infusion or subcutaneous injections). Profound and prolonged inhibition of volume occurred. Amylase concentration was increased but output was unchanged. Bicarbonate concentration was increased but output was decreased. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects. Although these studies do not establish a physiologic role for prostaglandins in the regulation of salivary secretion, they do demonstrate a wide-ranging effect of prostaglandins on the gastrointestinal tract.
Parallel studies in parotid and pancreatic function and histology were carried out in Thomas fistula dogs with irradiation-induced chronic pancreatitis. After completion of base line studies of parotid and pancreatic secretion, four dogs were subjected to 2,400 rads tumor dose over two weeks (with a nominal single dose of 1,175 rets); two additional dogs served as control. Sequential studies were performed on pancreatic secretion in response to secretin and on parotid secretion in response to urecholine. After a short-lived period of hypersecretion. There was a progressive reduction in pancreatic secretory rate, bicarbonate and enzyme outputs (greater than 90% after three months). Parotid secretion increased over this period but subsequently decreased, so that at eight months there was a marked reduction both in pancreatic and parotid function. Whereas pancreatic histology showed diffuse interstitial fibrosis and reduction of acinar tissue, no histologic changes were noted in the parotid glands. Although the mechanisms are unclear, alterations in parotid secretion may be of value in the diagnosis of chronic pancreatitis, in the evaluation of its severity, and may yield information on the duration of the disease.
Alterations in composition of isosmotic acid solutions were studied in exteriorized segments of the proximal (Brunner's gland area) and distal canine duodenum, mounted in lucite chambers. Varying concentrations of HCl (40, 80, 120, 160 mEq/l) made isotonic by the addition of NaCl were instilled into the chamber, removed in 15 minutes and analyzed for volume, electrolytes, protein content and osmolality. Both proximal and distal duodenal mucosa modified the instilled solution with a loss of H+ and a gain in Na+ and K+, which occurred at similar rates independent of the acid concentration of the instilled solution. The rate of ionic movement was twice that for the antrum, and 30-100 times that of the fundus. Calculated H+ loss across the entire duodenal mucosa at these rates could account for 17.5% of the peak acid output from the canine stomach. The loss of H+ could not be accounted for on the basis of neutralization and probably represented transmucosal insorption. In addition to the neutralization of gastric acid by pancreatic juice and bile, duodenal mucosa thus plays an important role in the maintenance of intraluminal pH. Duodenal mucosal permeability to H+ may be related to the vulnerability of the duodenal mucosa to acid-peptic ulceration.
Effect of isosmotic biocarbonate-rich solutions on the Brunner's gland area were studied by means of proximal duodenal explants in eight anesthetized dogs. Volume gain occurred with all instillates and varied indirectly with the concentration of the bicarbonate in the instilled solutions. Net bicarbonate gain occurred with instillate of 40 mEq./1.; net insorption occurred with instillates of higher bicarbonate concentration, the rate of which was dependent on the instillate concentration. Insorption of chloride occurred with the lower bicarbonate solutions and enterosorption occurred at higher concentrations. The modification of intraluminal bicarbonate by the proximal duodenal mucosa is important in the regulation of intraduodenal pH and abnormal function of this mechanism may play a role in the pathogenesis of duodenal ulceration because of incomplete hydrochloric acid neutralization.
Effects of duodenal alkalinization on pancreatic secretion were evaluated in seven dogs including two antrectomized dogs with chronic duodenal fistulas. Continuous intravenous injection of secretin or secretin plus CCK PZ was administered as a stimulus for the pancreatic secretion. Intraduodenal infusion of alkaline solutions such as pancreatic juice (pH 8.6), bile (pH 8.1), bicarbonate solution (160 mEq./I., pH 8.6) and TRIS buffer solution (0.3 M, pH 9.5) caused a moderate increase in protein output and a modest or no increase in flow but no change in bicarbonate output. During infusion of pancreatic juice, varied doses of secretin (0, 0.015, 0.03, 0.06 u./kg./min.), or secretin (0.03 u./kg./min.) plus CCK-PZ (0.05 u./kg./min.) were administered intravenously. For example, under the stimulation of secretin (0.03), flow increased modestly (17.7%), an increase which was of statistical significance. Protein output also showed a significant increase of 35.7%. There was, however, no response of the pancreas to the infusion of pancreatic juice when the gland was stimulated by secretin plus CCK-PZ. Antrectomy did not alter the effect of alkaline intraduodenal infusions on pancreatic secretion.
A continent reservoir ("gastric bladder") has been developed as an alternative to ileal conduits after urinary diversion procedures. The reservoir is fashioned from vagally denervated gastric fundus and has antireflux ureterogastric anastomoses and a continent "neourethra," the latter which is easily catheterized to empty the contents; the main stomach retains vagal innervation. Continent reservoirs were prepared in six dogs, and Heidenhain pouches (without urinary diversion) were prepared in six control dogs. Effects of short-term and long-term exposure of gastric mucosa to urine and 1M, 2M and 4M urea solutions were studied. Basal and food-stimulated acid outputs were unaffected by prolonged exposure. Mucosal permeability to H+, Na+, K+ and Cl- after exposure to urine remained unaltered, but 4M urea solutions produced a temporary increase in permeability. Mucosal blood flow was unchanged. Reservoir capacity rapidly increased up to 2,000 ml without any change in serum electrolytes. No precipitation of uric acid occurred. No histologic differences were noted between the main stomach and the reservoir. Because gastric mucosa (especially when acidified) is relatively impermeable to ions, secretes rather than absorbs Cl-, and is unaffected by prolonged exposure to urine, a gastric pouch may be useful as a continent urinary reservoir while allowing the maintenance of normal serum electrolytes.
The role of the antrum on vagally mediated pancreatic secretion was studied in 8 conscious dogs prepared with chronic pancreatic and gastric fistulae. After completion of control studies 6 were subjected to antrectomy and 2 to antroneurolysis (to interrupt submucosal nerve connections); secretory studies were repeated. With the animals secreting in response to secretin(0.03 u per kg-min) or secretin with cholecystokinin (0.05 u per kg-min), the following were administered: 1) insulin 0.2 u/kg; 2) atropine 0.2 and 0.4 mg/kg; 3) insulin after atropine. Insulin hypoglycemia elicited a marked enzyme response. Both antrectomy and antroneurolysis markedly reduced (80%) the enzyme response to insulin hypoglycemia. Atropine 0.2 mg/kg abolished the insulin response and at 0.4 mg/kg inhibited (50%) the enzyme response to cholecystokinin; these effects were unaltered by antrectomy or antroneurolysis. These experiments suggest that the pancreatic enzyme response to insulin hypoglycemia is predominantly mediated through the vagal release of antral gastrin. Furthermore, antrectomy and antroneurolysis do not affect the enzyme response to cholecystokinin nor do they alter the inhibitory effects of atropine. The inhibitio- by atropine suggests that a cholinergic background exerts a permissive effect on CCK-mediated enzyme secretion.
Effects of irradiation on the pancreas was studied in 6 dogs receiving a dose equivalent to the biologic effect of 4000 R/6 weeks (with a nominal stnadard dose of 1175 rets) given to patients with Hodgkins disease. After control secretory, histologic and pancreatographic studies, 6 Thomas fistula dogs were subjected to 2400 R tumor dose over two weeks. There was a biphasic response to secretin alone or secretin with cholecystokininpancreozymin. An initial hypersecretion occurred at 2 weeks --volume was increased, but bicarbonate and enzyme output remained unchanged. Thereafter there was a progressive reduction in volume, bicarbonate and enzyme outputs ( greater than 90% after 3 months). Histology showed early ductal reduplication but with progressive fibrosis, features compatible with chronic pancreatitis. Pancreatic insufficiency may contribute to post-irradiation gastrointestinal symptomatology. Close field irradiation of the pancreas results in actual destruction of the parenchyma.
Effects of a synthetic prostaglandin analog-16--16-dimethyl prostaglandin E2, methyl ester (16-diMe-PGE2)--on pancreatic secretion were evaluated in seven dogs with chronic duodenal fistulas. Graded doses of 16-diMe-PGE2 were administered intravenously (0.1, 0.3, 0.5, and 1.0 mug per kilogram, intraduodenally, or intragastrically (15, 30, 50, 100 mug per kilogram) with the pancreas in the resting state or in response to (1) secretin and (2) secretin with cholecystokinin-pancreozymin. Profound and prolonged inhibition of volume and bicarbonate concentration of secretion occurred in the resting and stimulated gland. ED50 was 0.31 mug per kilogram intravenously (1/75 the ED50 for PGE1) and 25 mug per kilogram intraduodenally. As with PGE1, stimulation of enzymes occurred, even with doses that were subthreshold for inhibition of volume and HCO3. Like PGE1, 16-diMe-PGE2 has a dual action on the intact canine pancreas (stimulation of enzymes and inhibition of volume and electrolytes), but is much more potent, has a prolonged action, and is active intraduodenally and intragastrically. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects.
Pancreatitis occurring in late pregnancy and in the puerperium has been documented as an entity unrelated to cholelithiasis or hyperlipidemia. Canine pancreatic exocrine function has been studied during pregnancy and the puerperium. Pancreatic secretion was evaluated in eight pregnant female mongrel dogs prepared with Thomas duodenal and gastric fistulae, during pregnancy (corresponding to the third trimester in humans), during the puerperium, and several months after whelping. Basal secretion (volume and HCO3) was increased during pregnancy and the puerperium. The response to exogenous secretin (submaximal and maximal) was unchanged during pregnancy but decreased in the puerperium. Resting enzyme output was increased during pregnancy and the puerperium; the responses to cholecystokinin-pancreozymin during pregnancy were even more profoundly increased. Although the mechanism is speculative, these alterations in pancreatic function might contribute to the development of pancreatitis in pregnancy and the puerperium.
The growth and metabolic activity of cultured cells derived from human adipose tissue (CAT cells) were studied and compared to cultured skin fibroblasts. The morphological appearance of the CAT cells was distinctly different from that of fibroblasts. The growth rate of CAT cells as measured by 3H-thymidine incorporation was much slower than the fibroblast growth rate. Cultured CAT cells synthesized significantly 14C-glucose, while fibroblast cultures had a higher metabolic rate as measured by CO2 production. Insulin stimulated 3H-thymidine incorporation in both CAT and fibroblast cultures. The CAT cells did not show a consistent insulin response of lipid or CO2 production, but this may be a reflection of donor age or nutritional status. Even though the CAT cell may be a type of stromal cell peculiar to adipose tissue rather than a preadipocyte or adipocyte, it may prove useful in studies of human obesity.
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