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Abstract The role of Emergency Medicine Physicians (EMP) in the care of trauma patients in North America has evolved since the advent of the specialty in the late 1980's. The evolution of this role in the context of the overall demands of the specialty and accreditation requirements of North American trauma centers will be discussed. Limited available data published in the literature examining the role of EMP's in trauma care will be reviewed with respect to its implications for an expanded role for EMPs in trauma care. Two training models currently in the early stages of development have been proposed to address needs for increased manpower in trauma and the critical care of trauma patients. The available information regarding these models will be reviewed along with the implications for improving the care of trauma patients in both Europe and North America.

In his only known historical sketch addressing the origin of the chemical atomic theory, John Dalton stated that different atoms have different sizes, a conclusion which led him to an investigation of combining number of atoms and relative weights. Although he stated the idea occurred to him in 1805, his laboratory notes show he developed the first table of atomic weights in 1803. Historians over the years have provided conflicting narratives to explain the different dates. In this paper, I examine Dalton's activities as a creative individual and a practicing chemist, arguing that Dalton's concept of atomic size was not an "aha" moment occurring in 1805, but one that he used right from the start in 1803 to develop his chemical atomic theory. The concepts of atomic size and relative atomic weights emerged in 1803 from his investigations into caloric and the composition of nitric acid, respectively, not from his studies on gaseous solubility. In 1805, Dalton applied his 1803 concept of atomic size to explain a different problem, one of gaseous diffusion. Dalton's 1805 epiphany should join the stage with other great insights in the history of science, such as those of Archimedes, Kekulé, and Poincaré.

During the years 1814-1819, William Higgins, an Irish chemist who worked at the Dublin Society, claimed he had anticipated John Dalton in developing the atomic theory and insinuated that Dalton was a plagiarist. This essay focuses not on William Higgins, but on his uncle Bryan Higgins, a well-known chemist of his day, who had developed his own theories of caloric and chemical combination, similar in many respects to that of Dalton. New evidence is first introduced addressing Bryan's disappearance from the scientific community after 1803. In his later years, Bryan apparently suffered from a condition resulting in a decline in his mental health, which explains why he never lodged any priority claims of his own against Dalton, or defended those of his nephew. Dalton's mention of Bryan's name in Part II of A New System of Chemical Philosophy, his laboratory notebook entries, and a fresh look at his correspondence with chemist Thomas Charles Hope indicate that Dalton adopted a Higgins-like caloric model in 1803. Together these factors provide evidence to support the argument that Dalton learned of Bryan's theories via a meeting he had with William Allen on 10 July 1803. Existing evidence related to the origin of the atomic theory is worthy of re-examination in light of Dalton's possible prior knowledge of Bryan's work.

In unanesthetized cats, continuous intravenous infusion of aspirin for 36 hr did not produce gastric ulcers when given alone but did when combined with 160 microgram kg-1 hr-1 of histamine-2HCl intravenously. The ulcers were mainly antral in location. The incidence and severity of ulcers increased with duration of the infusion up to 36 hr and with dose of aspirin up to 4 mg kg-1 hr-1. With the highest doses and longest durations some of the antral ulcers perforated. Antral ulcers occurred in more than half of the cats getting 0.25 mg kg-1 hr-1 or more of aspirin for 36 hr or getting 4 mg kg-1 hr-1 of aspirin for 6 or more hr. Intravenous aspirin plus intragastric infusion of 40 ml hr-1 of 150 mM HCl for 16 hr also produced gastric ulcers. Plasma salicylate concentrations were less than 350 microgram ml-1 with all doses and durations of aspirin used (400 microgram ml-1 is regarded as the upper limit of the therapeutic range in man). These studies show that when the stomach is acidified by giving histamine intravenously or HCl intragastrically, intravenous aspirin produces large deep gastric ulcers. The mechanism of the ulcerogenic action of intravenous aspirin is not known.

Although hospitalizations and deaths attributable to peptic ulcer have decreased notably during the past decade, it is not certain whether this decrease is because of reduced incidence of new cases or changes in other factors, such as the severity of the disease. Several genetic traits associated with peptic ulcer have been recognized. Hyperpepsinogenemia I is the most prevalent. Peptic ulcer is a heterogeneous group of disorders with multiple genetic and environmental causes. One manifestation of the diversity of ulcer disease is the variety of physiologic abnormalities seen in patients. The use of endoscopy has enabled more reliable evaluation of new treatments. Histamine H2-receptor antagonists are the dominant mode of treatment, but increasing attention is being given to agents that enhance the resistance of the mucosa to injury, such as prostaglandins. Because of the lower frequency of side effects, proximal gastric vagotomy is gradually replacing truncal vagotomy with drainage. The possibility that endoscopic treatments, such as laser coagulation, may reduce mortality from bleeding ulcers is being investigated.

In unanesthetized rats, dimaprit and histamine given by intravenous infusion were about equipotent in stimulating gastric acid secretion. The maximal rate of acid secretion in response to dimaprit was significantly greater than to histamine but not significantly different from the response to pentagastrin.

The peptides usually called gastrointestinal hormones belong to a broader group of regulatory substances distributed in many parts of the body and delivered to their targets not only by the blood but also by neural and paracrine paths. The neural, endocrine, and paracrine cells as a group might be called "regulator cells" and the chemical messengers they produce might be called "regulins." Twenty peptides have been isolated from the alimentary tract and pancreas: 12 have been sequenced, 4 have been partially sequenced, and 4 more have been identified only by immunoreactivity. Gastrin, gastric inhibitory peptide, glucagon, insulin, and secretin can be regarded as established hormones that are released into the blood by identified stimuli and produce identified physiological responses. The evidence for the hormonal status of cholecystokinin, pancreatic polypeptide, and motilin is incomplete but suggestive. The possible physiological roles of the other 12 peptides remain to be determined. If specific antagonists of these peptides can be found, they will greatly assist in elucidating the peptides' physiological roles.

There are apparent similarities in the mechanisms of the intestinal phase of exocrine and pancreatic polypeptide (PP) secretion by the pancreas. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and PP to graded doses of intravenous secretin, caerulein, CCK8, CCK33, bethanechol, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in dogs with gastric and pancreatic fistulas and compared them with average postprandial values. Secretin did not release PP at any dose studied, whereas intraduodenal HCl increased PP levels slightly at a load maximal for pancreatic secretion. Caerulein produced dose-related increases in PP secretion (maximal, 106% of meal response) but CCK8 and CCK33 had much less effect at doses equivalent for protein secretion. Bethanechol was a weak stimulant for PP only at the largest tolerable dose. L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated PP. Our results suggest a greater quantitative importance of the intestinal phase for exocrine than endocrine (PP) pancreatic secretion.

Antral ulcers were produced in unanesthetized rats in 3 hr by simultaneous intravenous administration of acetylsalicylic acid (ASA) and gastric perfusion with 0.15 M HCl. Intravenous infusion of ASA alone or gastric perfusion with HCl alone produced no antral ulcers. Plasma salicylate levels ranged from 250 to 350 microgram ml-1. 16-16 Dimethyl prostaglandin E2 (DMPGE2) (0.04, 0.40, 4.0 microgram kg-1 hr-1) and cimetidine (10, 50 mg kg-1 hr-1) significantly decreased the severity of antral ulcers in a dose-dependent fashion. In a separate group of unanesthetized rats prepared with gastric fistula and pylorus ligation, pepsin output during administration of parenteral ASA and gastric perfusion of HCl was reduced by the highest doses of 16-16 DMPGE2 and cimetidine. However, addition of exogenous pepsin to the HCl perfusate had no effect on the inhibition of ulceration afforded by 16-16 DMPGE2 and cimetidine. We conclude that both 16-16 DMPGE2 and cimetidine protect antral mucosa against injury by parenteral ASA plus topical HCl by some means other than their effect on acid and pepsin output.

We studied 25 duodenal ulcer patients and 14 age- and sex-matched normal controls to determine whether gastric acid secretion in duodenal ulcer patients is abnormally sensitive to stimulation by gastrin endogenously released in response to meals. Acid response to saline and to 0.5, 1.0, 2.0, 4.0, and 8.0% peptone infused into the stomach was measured by 30 min intragastric titration. Total serum gastrin (G-total) and serum heptadecapeptide gastrin (G17), fasting and 30 min after each test meal, were measured by specific radioimmunoassays. In 19 ulcer patients and 11 normal subjects (controls), acid response to graded doses (11, 33, 100, and 300 pmol kg(-1) h(-1)) of G17-I were also measured. Mean acid output in response to each dose of peptone was significantly higher in duodenal ulcer patients than in the controls. Gastrin levels in ulcer patients and controls were not significantly different. Within individual patients and controls, both G-total and G17 were significantly correlated with meal-stimulated acid output regardless of whether the absolute, basal-corrected, or distention-corrected values for acid output were examined (median r ranged from 0.82 to 0.94, P < 0.001). From the individual regression lines, the gastrin concentrations corresponding to half of the highest observed meal-stimulated acid response (D(50m)) were calculated. Mean D(50m) for G-total and G17 were significantly lower in duodenal ulcer patients than in controls both in the overall group and in pairs of ulcer patients and controls matched on the basis of highest observed meal-stimulated acid responses, or on the basis of maximal acid output in response to synthetic human G17. The dose of exogenously administered G17 required for half maximal G17 acid response mean D(50g), was significantly less in patients than in control subjects. In both ulcer and control subjects, D(50g) correlated significantly with D(50m). This and the significant correlation between meal-stimulated G17 and acid response strongly suggest that the endogenously released gastrin was responsible for most, if not all, of the postpeptone acid output.We conclude that after peptone test meals, gastric acid secretion in duodenal ulcer patients was abnormally sensitive to stimulation by endogenously released gastrin.

In animals, gastric acid secretion stimulated by the methyl xanthine, theophylline, was not inhibited by histamine H2-receptor antagonists. In this study the effect in man of the H2-receptor antagonist, cimetidine, on gastric acid secretion stimulated by the methyl xanthine, caffeine, was examined. Caffeine was given intravenously for 2 hr in a dose of 9 mg per kg-hr to 5 patients with duodenal ulcer and 5 normal subjects. Three hundred milligrams of cimetidine administered orally 30 min before the start of the caffeine infusion completely abolished the acid secretory response in all subjects, decreasing acid secretion to less than basal rates. It is concluded that in man the H2-receptor antagonist, cimetidine, abolished the acid secretory response to the methyl xanthine, caffeine.

We compared five graded doses of decaffeinated coffee and a widely used protein test meal (Bacto-peptone) as stimulants of acid secretion (intragastric titration) and gastrin release (radioimmunoassay) in eight healthy men. In each subject, for both acid and gastrin, the sums of the responses to all five doses were greater to decaffeinated coffee than to peptone. The mean +/- SE peak acid output in millimoles per hour was 18.5 +/- 2.9 to decaffeinated coffee and 14.7 +/- 2.7 to peptone, representing 70% and 55%, respectively, of the peak acid output to pentagastrin. The mean +/- SEM peak increment over basal rate in serum gastrin in picograms per milliliter was 84.8 +/- 4.4 to decaffeinated coffee and 44.8 +/- 2.1 to peptone. At equal concentrations, decaffeinated coffee was a more potent stimulant of acid secretion and of gastrin release than peptone. The ingredient(s) of decaffeinated coffee that accounts for its high potency in stimulating acid secretion and gastrin release has not been identified.

In dogs with gastric and pancreatic fistulas, we studied the effect of atropine on the pancreatic secretory response to secretin and intestinal HCl. Atropine sulfate (20 micrograms.kg-1.h-1 iv) significantly depressed basal bicarbonate and protein output. Atropine depressed bicarbonate responses to low doses (62.5, 125, 250, and 500 ng.kg-1.h-1) of secretin but had no significant effect on responses to high doses (1,000 and 2,000 ng.kg-1.h-1). Secretin, with or without atropine, did not stimulate pancreatic protein output above basal. Atropine depressed bicarbonate responses to low loads (3, 6, and 12 mmol.h-1) of HCl but had no significant effect on responses to high loads (12, 24, and 48 mmol.h-1). Intraduodenal HCl produced a dose-dependent increase in protein output. Atropine abolished protein responses to low loads (3 and 6 mmol.h-1) but did not affect responses to high loads (24 and 48 mmol.h-1) of HCl. These findings are compatible with the hypotheses that a) endogenous cholinergic activity augments the pancreatic bicarbonate response to secretin, and b) the pancreatic protein response to intraduodenal HCl is, at least in part, mediated cholinergically.

In dogs with gastric fistulae and with transposition of the portal vein and the inferior vena cava, we studied secretion of acid in response to portal or systemic venous infusion of a series of progressively longer fragments of the carboxyl terminal portion of human gastrin. Pentagastrin, G6, G7, G8, G9, G10, G13, G17, and G34 were studied. Potency by portal venous infusion relative to systemic venous infusion was used as an index of hepatic inactivation. Fragments with eight or fewer amino acid residues were more than 90% inactivated by hepatic transit. Fragments with nine or more amino acid residues were more resistant to hepatic inactivation than shorter fragments. For fragments with 7 to 17 amino acid residues, increasing the chain length was accompanied by progressive increase both in hepatic resistance to inactivation and in potency for stimulation of acid secretion, suggesting that resistance to hepatic inactivation may be a major determinant of potency.

In six conscious dogs with gastric and pancreatic Thomas fistulas, we studied the pancreatic bicarbonate response to intravenous bolus injections of synthetic secretin dissolved either in 5 ml of 0.15 M NaCl alone or in the same amount of NaCl to which dog albumin had been added, to give a 0.1% solution. The pancreatic bicarbonate (micromol . 10 min-1) response to the four lowest doses of secretin (12.5, 25, 50, 100 ng . kg-1) used was significantly (p less than 0.05) higher when secretin was dissolved in NaCl plus albumin than in NaCl alone. The pancreatic response to higher doses of secretin (200, 400, 800, 1600 ng . kg-1) was not significantly altered by the addition of albumin. The D50 of secretin was about 2.6 times greater in the absence than in the presence of albumin. This study suggests that albumin should be added to dilute solutions of secretin to preserve biological activity.

Using intragastric titration in dogs with gastric fistulas, dose-response studies were carried out with liver extract and with a mixture of amino acids that matched the free amino acids found in liver extract. All solutions were adjusted to pH 7.0 and osmolality to 290 mosmol x kg-1. Doses are expressed as the sum of the concentrations of all free amino acids. At each dose studied (free amino acid concentration: 2.8, 5.6, 11, 23, and 45 mM), acid secretion in response to the free amino acid mixture was not significantly different from that of liver extract. The peak response to both liver extract and the free amino acid mixture occurred with the 23-mM dose and represented about 60% of the maximal response to histamine. The serum concentrations of gastrin after liver extract and the amino acid mixture were not significantly different. It is concluded that in dogs with gastric fistula, gastric acid secretion and release of gastrin were not significantly different in response to liver extract and to a mixture of amino acids that simulated the free amino acid content of liver extract.

Indomethacin produces mucosal lesions in both the gastric antrum and small intestine in rats refed for 1 h after a 24-h fast. This study was designed to determine the role of bacteria in the formation of the antral lesions. A mixture of antibiotics (bacitracin, neomycin, and polymyxin B) prevented the antral lesions as well as intestinal lesions. The antibiotics also decreased the gastric corpus lesions induced by indomethacin in the fasted rat. Under a germ-free condition, indomethacin did not produce severe lesions in the small intestine of the refed rat but provoked many lesions in the antrum of the refed rat and in the corpus of the fasted rat. Corpus lesions induced by indomethacin in the fasted rat were decreased markedly by neomycin and slightly by polymyxin B, but not by bacitracin. Corpus lesions produced by an absolute ethanol, however, were prevented by each of the antibiotics. The inhibitory effect of neomycin on the corpus lesions was not blocked by pretreatment with indomethacin. In pylorus-ligated rats, neomycin did not decrease gastric acid secretion. The concentration of nonprotein sulfhydryls in the gastric mucosa was not altered by the treatment with neomycin. The antibiotic solutions were hypotonic. It is concluded that (a) bacteria are not important in the formation of antral and corpus lesions induced by indomethacin, and (b) antibiotics prevent gastric ulceration not by its antibacterial action, but by a "cytoprotective" action. The mechanism is unknown, but it may be different from that of antisecretory drugs, prostaglandins, mild irritants, hypertonic solutions, and sulfhydryl compounds.

Aspirin was given by continuous intravenous infusion to 35 intact cats for 7 days in doses ranging from 25 to 200 mg kg-1 day-1. Gastric mucosal lesions occurred in 50 to 70% of the animals in the various dosage groups, including deep ulcers in 20%. All of the ulcers were in antral mucosa near its border with oxyntic mucosa. The incidence of lesions, including ulcers, showed no apparent relation to the dose of aspirin. With all but the highest dose, plasma salicylate levels were within or below what is regarded as the therapeutic range for man. Asprin, 100 mg kg-1 day-1, was given for 7 days to 4 cats with pouches containing all of the antral mucosa plus some oxyntic mucosa. One or more deep ulcers occurred in the antral mucosa of the pouches in each of these 4 cats. The electrical potential difference across the mucosa did not decrease, and net fluxes of hydrogen ions out of the pouch and of sodium ions into the pouch did not increase during the 7 days of aspirin administration despite the occurrence of ulcers in the pouches. It is concluded that intravenous aspirin, in doses giving plasma levels within or below the therapeutic range for man, causes gastric mucosal lesions including deep ulcers within 7 days in cats. These lesions occur without the changes in electrical potential difference and hydrogen and sodium fluxes that are regarded as characteristic of the "broken barrier."

Biological properties of pure natural human "big gastrin" (designated G-34 because it contains 34 amino acid residues) were compared with those of pure natural heptadecapeptide gastrins (G-17) from human and porcine sources. Radioimmunoassay inhibition curves indicated that G-17 was nearly 1.5 times more potent than G-34 with the antibody used in this study. This difference was confirmed by demonstration of increased immunoreactivity generated when G-34 was converted to G-17 by trypsinization. When infused intravenously into dogs with gastric fistulas and Heidenhain pouches in equimolar doses, G-34 produced slightly higher acid secretory responses than G-17. Responses to sulfated and nonsulfated forms were not significantly different, nor were responses to human and porcine G-17. During infusion of equimolar doses, steady-state serum gastrin concentrations were more than fivefold higher with G-34 than with G-17. The difference in steady-state blood concentrations could be accounted for by a corresponding difference in removal rates. The half times of the G-34 preparations averaged 15.8 min and the half times of the G-17 preparations averaged 3.2 min. The calculated spaces of distribution for G-17 and G-34 were similar, about 25% of body weight. When the increment in serum gastrin was plotted against acid secretory response it was found that nearly five times greater increments in molar concentrations of G-34 than of G-17 were required to produce the same rate of acid secretion. The potency of these two molecular forms of gastrin can be expressed in two different ways. Based on exogenous molar doses, the potencies of G-34 and G-17 were similar. However, based on molar increments in serum gastrin concentration, G-17 was approximately five times more potent than G-34. Hence, fractionation of these gastrin components may be important in estimation of the acid-stimulating action represented by total serum gastrin as measured by radio-immunoassay.

Extracts were prepared from plasma of 12 subjects with normal serum gastrin concentration (less than 125 pg/ml), 5 normal subjects and 7 patients with duodenal ulcer and basal gastric acid hypersecretion (greater than 15 mEg/hr). Bioassays of plasma extracts were performed in anesthetized rats with perfused stomachs and acid out-puts were compared with those produced by normal saline and by 50 ng pentagastrin given in random order. Compared with saline, plasma extracts from 5 of 7 hypersecretor patients produced significant stimulation of acid secretion while none of the extracts from normal subjects produced acid stimulation. The stimulant identified in plasma from hypersecretor patients appears to be distinct from gastrin.

Isosmotic liquid peptone meals adjusted to pH 7, 3, and 1.5 were instilled on separate days into the stomachs of 8 duodenal ulcer patients and 7 healthy controls. Using a marker-dilution method, duodenal acid load (DAL) was measured as the amount of unbuffered hydrogen ions delivered to the duodenum per unit time. Gastric emptying was measured as the total volume of gastric contents, including meal plus gastric secretion, passing through the pylorus per unit time (VPP). Mean pentagastrin-stimulated acid output was significantly different between the two groups. However, after all three tests meals, mean DAL was significantly greater in duodenal ulcer than in normal subjects in both hours of the test, and VPP was significantly greater in ulcer than in normal subjects in the first 40 min. In both groups, following peptone meals of pH 7 and 3, the volume of gastric contents delivered through the pylorus decreased as the amount of free hydrogen ions entering the duodenum increased, but a given load of acid was less effective in slowing emptying duodenal ulcer patients than in controls. These studies indicate that duodenal ulcer patients empty liquid meals more rapidly than do normal subjects, independent of the initial pH of the meals, and that, in addition, acid inhibition of gastric emptying is defective in duodenal ulcer.

Thirteen patients who had rheumatoid arthritis and gastroduodenal lesion (erosions, ulcers) received 200 micrograms/d of 15(R)-15-methyl prostaglandin E2 (MPGE2) for one month in a controlled, randomized, double-blind crossover study. The patients continued their usual arthritis medications. Serial assessments were made with endoscopy and multiple antral biopsies. Seven patients improved on MPGE2 and 3 improved on placebo. Two patients worsened on MPGE2 compared with 3 on placebo. No dramatic benefit was observed after one month of therapy with MPGE2, although a moderate benefit could have been missed in a small study of this type. Our experience with this study suggests that future studies in rheumatoid arthritis should first establish the natural history of lesions in a given group of patients, that a cross-over design may actually hamper interpretation and that therapy should be more prolonged.

Release of gastrin is the only recognized mechanism by which chemicals in the stomach stimulate acid secretion. We report here that dietary components coming in contact only with oxyntic gland mucosa stimulate near maximal acid secretion through a local, H-sensitive mechanism that does not involve gastrin. In 4 dogs with gastric fistula and Heidenhain pouch (HP), 10% liver extract, 10% peptone, 0.4 M glycine, or Tris buffer, as control, was instilled into the HP in volumes of 40, 80, or 160 ml every 30 min. Instilled solutions were adjusted to pH 8.0 and HP acid secretion was measured by titrating a sample of the fluid recovered from the HP back to pH 8.0 with 0.2 M NaOH. Instillation of liver extract into the HP stimulated acid secretion from the HP but caused no change in serum gastrin and no change in acid secretion from the gastric fistula. The maximal response to liver extract occurred with the largest volume instilled and was 80% of the maximal response to histamine and 188% of the maximal response to pentagastrin. Expressed as per cent of maximal response to histamine, the maximal response to Tris buffer was 8%, to peptone 44%, and to glycine 14%. Intact bovine serum albumin gave no response, but after digestion by pepsin it stimulated acid secretion moderately. At pH 2.0, liver extract caused no stimulation of acid secretion. The pH threshold was about 2.5, and at pH 4.5 acid secretion was 55% of the response at pH 8.0. The response to liver extract at pH 8.0 was only minimally decreased by topical lidocaine or by intravenous atropine or metiamide. Since atropine and metiamide almost totally abolish the acid response to food in the main stomach, but do not inhibit secretion of acid evoked by instilling liver extract into the HP, there is reason to doubt whether this new mechanism operates under physiological conditions.

In dogs with gastric and pancreatic fistulas, the rate of delivery of acid from the stomach to the duodenum and the rate of pancreatic bicarbonate secretion were measured in response to a meal of liver extract. The time course of changes in quantity of bicarbonate secreted per minute closely paralleled that of changes in quantity of hydrogen ions delivered to the duodenum per minute. For each mole of hydrogen ion entering the duodenum, about 5 moles of bicarbonate were secreted.

Minigastrin, a gastrin with 13 amino-acid residues, was recently isolated from tissues by Gregory and Tracy (1974). In this study, pure human natural nonsulphated minigastrin (HG-13-I) and pure human natural nonsulphated heptadecapeptide gastrin (HG-17-I) were compared with regard to acid-stimulating potency and rate of disappearance from blood. Three dogs with gastric fistulae and Heidenhain pouches were given these gastrins by continuous intravenous infusion in doses of 100, 200, 400, and 800 pmol/kg-hr. Equimolar infusion rates of HG-13-I and HG-17-I caused equimolar increases over basal of serum immunoreactive gastrin but HG-13-I- was less than half as potent as HG-17-I in stimulating acid secretion (potency ratio 0.4, 95% confidence limits 0.2 to 0.6). The half time for disappearance of HG-13-I from blood was 1.8 minutes and its volume of distribution was calculated to be 0.17 1/kg, values similar to those found for HG-17-I in an earlier study. The role of minigastrin in health and disease awaits further study.

Although trophic actions of gastrointestinal peptides on exocrine pancreas have been shown, little is known regarding their effects in endocrine pancreas. Therefore, we measured the contents of somatostatin-like immunoreactivity (SLI), insulin and glucagon, in pancreatic extracts from rats that had been treated three times a day for 10 days with saline; 1 microgram/kg caerulein; 5, 25, and 100 microgram/kg secretin; 1 microgram/kg caerulein plus 5, 25, and 100 microgram/kg secretin; 25 microgram/kg pancreatic polypeptide; 15 microgram/kg glicentin; or 15 microgram/kg gastric-inhibitory polypeptide. Pancreatic SLI content was significantly increased in rats treated with glicentin and caerulein plus secretin at the two higher doses. No difference was noted between the control and the caerulein plus 100 microgram/kg secretin groups in delta-cell number per islet when examined by the immunoperoxidase technique. These data suggest that because of their effect on SLI content gastrointestinal polypeptides may modulate pancreatic endocrine function.

We studied the effect of prostacyclin, PGI2, its chemical decomposition product, 6-oxo-PGF1 alpha, and a stable 5-6-dihydro analogue, 6-beta-PGI1, on gastric acid secretion, mucosal blood flow (14C-aminopyrine clearance), and mean arterial pressure in unanesthetized dogs. During submaximal acid secretion from a gastric fistula induced by intravenous histamine dihydrochloride (20 microgram kg-1 h-1), prostacyclin and its stable analogue, 6-beta-PGI1, reduced acid output with ID50s (dose causing 50% inhibition) of about 0.2 and 3.0 microgram kg-1 min-1 i.v., respectively, whereas 6-oxo-PGF1 alpha was inactive at 100 times the effective dose of prostacyclin. The ratio of mucosal blood flow to acid output remained unchanged during prostacyclin administration and was significantly elevated during 6-beta-PGI1 infusion, suggesting that with both compounds the changes in mucosal blood flow were not the cause of the antisecretory action. For doses causing equivalent antisecretory action, 6-beta-PGI1 lowered systemic arterial blood pressure much less than prostacyclin, indicating selectivity of action. Prostacyclin is unlikely to be a circulating antisecretory agent, but may play a role as a local humoral modulator of secretion and blood flow in the gastric mucosa.