Search

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 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.

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.

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.

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.

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.

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.

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.

Rats were given subcutaneous injections of secretin (12.5 microgram kg-1) plus caerulein (0.5 microgram kg-1) in a depot carrier or depot carrier alone every 8 hr for 10 days. Basal pancreatic secretion and responses to secretin and cholecystokinin were then studied while the rats were under urethane anesthesia. In the treated animals, basal secretion of fluid was more than six times greater, basal bicarbonate output more than three times greater, and and basal protein output more than two times greater than in the control rats (P less than 0.01 for each). After subtracting basal values and normalizing for body weight, the treated group means were statistically significantly greater than those of the control for: maximal bicarbonate output (1.81 times control) to secretin; and maximal outputs to cholecystokinin of volume (2.46 times control), bicarbonate (2.69 times control), and protein (2.28 times control). The mean pancreatic weight per kilogram of body weight in the treated group was 1.65 times (P less than 0.01) that of the control group. When normalized for pancreatic weight (basal values subtracted), the increse in maximal protein output (1.37 times control) to cholecystokinin was still statistically significant (P less than 0.05). We conclude that chronic treatment with secretin plus caerulein exerts a trophic effect on the pancreas associated with increased maximal protein output to cholecystokinin and increased maximal bicarbonate output to secretin.

The secretory potency and disappearance rates of pure synthetic human non-sulphated minigastrin (HG-14-I) and pure natural human non-sulphated heptadecapeptide (HG-17-I) were compared in five dogs with gastric fistulas and Heidenhain pouches. Intravenous infusion of equimolar doses of the two gastrins produced equimolar increases over basal of serum immunoreactive gastrin and no statistically significant differences in acid output. Also HG-14-I and HG-17-I did not differ significantly in half-times for disappearance, clearance rates, calculated volumes of distribution, or mean plateau serum levels.

In dogs with gastric and pancreatic fistulas, porcine pancreatic polypeptide (PP) was infused intravenously in doses of 50, 100, 200, 400, and 800 pmol kg-1 hr-1 in the basal state and in doses of 100, 200, and 400 pmol kg-1 hr-1 during stimulation with submaximal doses of secretin (125 ng kg-1 hr-1) plus caerulein (50 ng kg-1 hr-1). Plasma concentrations of PP were measured by radioimmunoassay, and pancreatic bicarbonate and protein outputs were monitored. The half-time for disappearance of PP was 5.5 +/- 1.0 min, the metabolic clearance rate was 25.6 +/- 1.0 ml kg-1, and the volume of distribution was 209 +/- 42 ml kg-1. Basal pancreatic flow and protein output were significantly inhibited by the lowest dose of PP tested, 50 pmol kg-1 hr-1. The lowest dose of PP significantly inhibiting stimulated pancreatic secretion was 100 pmol kg-1 hr-1 for bicarbonate output and 200 pmol kg-1 hr-1 for protein output. The mean +/- SE peak increment in PP concentration in response to a meal of meat, 210 +/- 39 pM, was greater than the mean peak increment with the 400 pmol kg-1 hr-1 dose of exogenous PP, 175 +/- 19 PM. We conclude that exogenous doses of PP that produce smaller increments in PP concentration than those seen after feeding inhibit pancreatic bicarbonate and protein secretion stimulated by secretin and caerulein. This suggests that the amount of PP released by a meal is sufficient to inhibit pancreatic secretion.

This study was designed to determine whether cholecystokinin (CCK) plays a physiological role in the inhibition of gastric emptying. Physiological conditions were simulated by giving CCK by continuous intravenous infusion rather than by bolus injection, by using doses known to be distinctly submaximal for pancreatic protein secretion, and for gallbladder contraction, and by releasing endogenous CCK. The rate of gastric emptying was determined in 4 dogs with gastric fistulas by measuring the volume of fluid remaining in the stomach 10 min after instillation of 300 ml of 0.15 M NaCl. Rate of emptying was studied during intravenous infusion of saline (control) and of different doses of 98% pure CCK, commerically available 20% pure CCK, synthetic COOH-terminal octapeptide of CCK (OP-CCK), pentagastrin, and heptadecapeptide gastrin. The effect of endogenously released CCK was studied by measuring the rate of emptying of solutions in which different concentrations of tryptophan replaced equiosmolar amounts of NaCl. The d50's of 20% pure CCK (3 U kg minus-1 hr minus-1) and of OP-CCK (125 ng kg minus-1 hr minus-1) for inhibition of gastric emptying were about the same as their D50's for cholecystokinetic and pancreozyminic actions. By contrast, although both pentagastrin and heptadecapeptide gastrin inhibited gastric emptying, the doses required for this action were much higher than the D50's required for stimulation of gastric acid secretion. The effectiveness of OP-CCK indicates that inhibition of gastric emptying is attributable to CCK itself and not to an impurity in the CCK preparation. We have confirmed this directly by showing that pure CCK is a potent inhibitor of gastric emptying. Tryptophan also inhibited gastric emptying. In other dogs pancreatic protein secretion and gallbladder contraction were shown to be stimulated during the time tryptophan was inhibiting gastric emptying. This evidence supports the view that inhibition of gastric emptying is one of the physiological actions of CCK, but in the case of gastrin it must be regarded as a pharmacological action.

During the period 1970-1978, admissions to short-term nonfederal hospitals in the U.S. for duodenal ulcer decreased by 43%, whereas admissions for gastric ulcer did not change significantly. The decline in admissions for duodenal ulcer was greatest for uncomplicated cases, less for those with hemorrhage, and least (and not significant) in those with perforation. During the period 1970-1977, U.S. Vital Statistics reports of deaths from peptic ulcer decreased 31%, with about equal declines in total deaths, those associated with hemorrhage, and those associated with hemorrhage, and those associated with perforation. The fall in death rate involved both gastric and duodenal ulcer in both men and women. The male/female ratio has been falling steadily, and now stands at about 1.2 for hospitalizations and about 1.5 for deaths. From 1970 to 1978 the percentage of persons over 60 yr of age rose from 14 to 15% in the U.S. population as a whole, from 23 to 29% in persons hospitalized for all causes, from 27 to 36% in those hospitalized for duodenal ulcer, and from 40 to 48% in those hospitalized for gastric ulcer.

The effect of graded doses of pentagastrin (2.7-6,000 ng/kg times h) on gastric acid secretion was measured in 20 duodenal ulcer (DU) and 20 non-DU subjects. Confirming many previous studies, the mean observed highest response and the mean calculated maximal response were significantly greater in DU than in non-DU subjects. The mean dose (plus or minus SE) in ng/kg times h for half maximal response, calculated from responses corrected for basal secretion and normalized for maximal secretion, was 92.1 plus or minus 1.7 in DU and 246.8 plus or minus 24.6 in non-DU subjects, a significant difference. By parallel line bioassay non-DU subjects required 2.8 times more pentagastrin (95% confidence limits 2.1-3.7) than DU highest response. Thus, this study shows that, compared with non-DU subjects, DU patients not only secrete more acid in response to stimulation by pentagastrin but also are more sensitive to stimulation by pentagastrin, that is, need smaller doses to achieve the same fraction of maximal response.

In 5 human subjects, 95% pure cholecystokinin (CCK) given as a background infusion in doses of 42, 84, or 168 pmol kg-1 h-1 did not significantly alter acid secretion in response to graded doses (11-300 pmol kg-1 h-1) of synthetic human gastrin-17-I. The 168 pmol kg-1 h-1 dose of CCK produced maximal pancreatic amylase output. In 3 subjects, 337 pmol kg-1 h-1 of CCK slightly stimulated acid secretion when given alone and tended to reduce acid secretion in response to gastrin, but each of the subjects experienced cramping abdominal pain. The increment in acid secretion produced by CCK alone was similar to that produced by maximally effective doses of carboxyl-terminal octapeptide of CCK. In dogs with gastric and pancreatic fistulas, 168 pmol kg-1 h-1 of CCK produced maximal pancreatic protein output and slightly stimulated gastric acid secretion. In dogs with gastric fistulas and Heidenhain pouches, the lowest dose of CCK that inhibited gastrin-stimulated acid secretion was 674 pmol kg-1 h-1. We conclude that in man and dog 95% pure CCK weakly stimulates gastric acid secretion and inhibits gastrin-stimulated acid secretion but these actions occur only with doses of CCK that are maximal or supramaximal for pancreatic enzyme secretion. Because of the high dose requirement, these effects are unlikely to be physiologically significant.

In 6 anesthetized dogs receiving 400 pmoles kg-1 hr-1 of natural human little gastrin intravenously, blood samples for radioimmunoassay of gastrin were taken repeatedly from a carotid artery, jugular vein, femoral vein, renal vein, and mesenteric vein. The calculated removal of gastrin in a single passage through these four vascular beds ranged from 21 to 30% and did not differ significantly among them. In 6 additional dogs, the carotid arterial to hepatic venous removal was 40%. We conclude that the percentage removal of gastrin is about the same in all of the major vascular beds of the body.

This study was undertaken to determine the role of food in indomethacin-induced gastrointestinal lesions. Following a 24- or 48- fast, rats were given various amounts of rat Chow pellets or various types of diets (high-bulk non-nutritive diet, equicaloric liquid diet, or liquid diet containing cellulose) for 1 h. One half hour after the feeding, 30 mg/kg of indomethacin was administered subcutaneously, and 6 h later the animals were killed and gastrointestinal lesions measured. In the fasted rat, indomethacin produced lesions predominantly in the gastric corpus. In the rat that was fed Chow pellets, indomethacin produced lesions in both the gastric antrum and small intestine. By increasing food intake, the corpus lesions decreased while antral and intestinal lesions increased. In the rat that was fed cellulose or sawdust pellets, indomethacin produced lesions in all three areas. In contrast, indomethacin did not produce any lesions in the liquid diet group. However, when cellulose was added to the liquid diet, indomethacin produced lesions in both the antrum and small intestine, the lesions increasing in proportion to increasing concentrations of cellulose. It is concluded that in indomethacin-induced gastrointestinal lesions: (a) the nutritional component of food prevents the formation of corpus lesions, and (b) the solid component of food, whether nutritive or not, plays an essential role in the formation of antral and intestinal lesions.

These studies were designed to determine whether the intestinal phase of gastric acid secretion is accompanied by an increase in serum gastrin concentration. Seven dogs with a gastric fistula and a duodenal fistula prepared so as to allow perfusion into the duodenum without reflux into the stomach were used. Gastric secretion and blood samples for serum gastrin determination were collected during intestinal perfusion with either 0.15 M NaCl or 5% liver extract at 200 ml hr(-1) for 2 hr. The mean +/- SE gastric acid secretory response during the second hour of perfusion with 0.15 M NaCl was 3.1 +/- 1.0% of the maximal acid output (MAO) to histamine, significantly (P less than 0.05) greater than the control value with no intestinal perfusion (0.18 +/- 0.07%). The mean +/- SE response during the second hour of perfusion with 5% liver extract was 7.4 +/- 2.2% of MAO, significantly (P less than 0.05) greater than both control and NaCl perfusion values. There was no significant change in peripheral serum gastrin concentration during the response to perfusion with either NaCl or liver extract. We conclude that, under the conditions of the present study, the intestinal phase of gastric acid secretion was not accompanied by an increase in serum gastrin concentration.