Bicarbonate Output Research Articles

Effect of the cholecystokinin-receptor antagonist lorglumide on pancreatic enzyme secretion stimulated by bombesin, food, and caerulein, giving similar plasma cholecystokinin concentrations in the dog.

This study was undertaken to determine the role of cholecystokinin in pancreatic enzyme secretion stimulated by bombesin and a meal by (a) comparing the pancreatic enzyme output during bombesin infusion and after a meal to output during caerulein infusion and (b) comparing the inhibitory effect of the cholecystokinin-receptor antagonist lorglumide (CR-1409) on enzyme output in response to bombesin and food with the response to caerulein. Bombesin (90 pmol/kg per h) and caerulein (30 pmol/kg per h) were infused into seven dogs in doses giving similar plasma cholecystokinin peak increments as a meal (mean (SEM) 6.8 (0.8), 6.3 (1.2), and 5.7 (0.8) pM, respectively), together with either saline or 2 mg/kg per h of lorglumide. A background infusion of synthetic secretin 20.5 pmol/kg per h was given in each experiment. In addition, gastric acid secretion was determined in the experiments with bombesin and caerulein infusion. Pancreatic protein responses to bombesin (1231 (247) mg/h) and food (1430 (220) mg/h) were similar to the responses to caerulein (1249 (201) mg/h). Lorglumide inhibited pancreatic protein output during stimulation with bombesin by 60%, after the meal by 45%, and during caerulein infusion by 68%. Pancreatic bicarbonate output by bombesin, caerulein, and food was inhibited by lorglumide by 28%, 40%, and 38%, respectively. In contrast, lorglumide significantly increased gastric acid secretion from 1.12 to 7.98 mmol/h during bombesin infusion and from 0.52 to 7.62 mmol/h during caerulein infusion. In conclusion, cholecystokinin plays an important part in the stimulation of pancreatic enzyme secretion by bombesin and a meal in conscious dogs and it is involved in the regulation of gastric acid during stimulation by infusions of caerulein and bombesin.

加齢によるすい外分泌機能の変化 新しく提案されたセクレチン静注法を用いて

The authors studied the relationship between aging and exocrine pancreatic function by the secretin test which was recently standardized by the Japanese Society of Gastroenterology. Pancreatic juice was collected at 10 min intervals for 60 minutes after a bolus intravenous injection of secretin (Secrepan, Eisai Co., Ltd., 100 U/body) through a quadruple-lumen doudenal tube equipped with double balloons. Exocrine pancreatic function was evaluated by three parameters: secretory volume, maximal bicarbonate concentration or bicarbonate output, and enzyme (amylase and lipase) output. Control subjects consisted of 65 outpatients presenting with mild vague abdominal symptoms who fulfilled the following three criteria: 1) good general condition with no known diseases; 2) no abnormality in the liver, bile duct, pancreas, kidney and metabolism judged from blood chemistry, urine and stool analysis, upper GI series, abdominal ultrasonography (US), and endoscopic retrograde cholangiopancreatography (ERCP); 3) alcohol consumption less than 25 g/day. Control subjects were divided into three groups: 15 subjects below 40 years of age (group A), 32 subjects from 40 to 65 years (group B), and 18 subjects of 65 years and above (group C). Nineteen patient with chronic pancreatitis were also studied. The group C showed significantly lower values in secretory volume, bicarbonate output, and enzyme output than group A and B. Enzyme output showed a gradual decrease with aging. However, secretory volume and bicarbonate output showed a gentle convex curve with a peak around age 40 and a rather steep down-slope after late 50s. The degree of the decrease was significantly more marked in volume and bicarbonate output than in enzyme output in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of Cholecystokinin-Stimulated Pancreaticobiliary Output in Man by the Cholecystokinin Receptor Antagonist MK-329

MK-329 (formerly L-364,718) is a new nonpeptide antagonist for the peripheral (type-A) cholecystokinin (CCK) receptor, which has proved effective in blocking the actions of both exogenous and endogenous CCK in several species. To evaluate the effect of MK-329 on CCK-stimulated pancreaticobiliary output in man, six normal subjects received 10 mg MK-329 or placebo orally in a randomized, crossover fashion, before a background intravenous infusion of secretin (5 pmol/kg/h) and two doses of CCK-8 (approximately 15 and 40 pmol/kg/h, each for 1 h). Gastric and duodenal juice were aspirated separately via two double-lumen tubes, with 51Cr-ethylene-diaminetetraacetic acid as a duodenal marker. After placebo treatment the background infusion of secretin produced maximum plasma concentrations of secretin similar to postprandial values, averaging about 5 pM. After placebo treatment the low dose CCK-8 infusion (15 pmol/kg/h) increased circulating CCK concentrations from basal levels of 1.8 +/- 0.2 pM to levels similar to those observed postprandially, averaging 9.2 +/- 1.3 pM, and the high dose of CCK-8 (40 pmol/kg/h) induced supraphysiologic levels of CCK, averaging 23.4 +/- 3.2 pM. Plasma concentrations of secretin and CCK were not significantly different during MK-329 treatment. As expected, infusion of CCK-8 at both doses stimulated pancreatic exocrine secretion and gallbladder contraction in placebo controls, as indicated by increases in the output of trypsin, amylase, bicarbonate, and bilirubin. Whereas MK-329 did not significantly reduce basal pancreatic secretion, the integrated incremental output of trypsin, amylase, and bicarbonate in response to stimulation with the low (physiologic) CCK dose was inhibited by 74% (p less than 0.01), 89% (NS), and 75% (p less than 0.05), respectively. Basal bilirubin output was virtually abolished after treatment with MK-329, and the response to the low dose of CCK was reduced by 98% (p less than 0.01), indicating almost complete inhibition of gallbladder contraction at physiologic circulating concentrations of CCK. It is concluded that MK-329 is an orally active antagonist of CCK-stimulated pancreaticobiliary output in man and could thus be utilized to explore the physiologic regulation of the exocrine pancreas and gallbladder by CCK.

Changes in Pancreatic Exocrine Secretion with Age: Pancreatic Exocrine Secretion Does Decrease in the Elderly

Pancreatic exocrine secretion was estimated in 180 normal control patients, free of abdominal and pancreatic disease, aged from 16 to 83 years. Duodenal juice was collected in two 15-min fractions after a single intravenous injection of 1 U/kg secretin + 3 U/kg CCK. Volume, maximal concentration and output of bicarbonate, lipase, phospholipase and chymotrypsin were estimated as well as minimal concentration and output of chloride and calcium. Each parameter was plotted against age, either individually or after separation into two age groups. Volume linearly increased up to the 3rd decade, and thereafter linearly decreased. Bicarbonate secretion paralleled fluid secretion and also decreased after the 3rd decade. The changes in chloride and calcium concentrations were different: concentrations linearly increased after the 3rd decade. Calcium concentration linearly increased with age (p less than 0.02) while chloride output was unchanged. The three enzymes that were studied linearly decreased in concentration as well as in output with age from the 3rd decade (p less than 0.02). Protein secretion decreased before water and bicarbonate secretion. One can conclude that pancreatic secretion changes in humans with age. Aging alters pancreatic secretion, through a decrease in flow rate, bicarbonate and enzyme secretion while calcium concentration is enhanced. Although not requiring substitutive therapy in the whole population, individual cases of pancreatic exocrine insufficiency might be explained by aging, without malnutrition.

Influence of the M<sub>1</sub>-Receptor Antagonists Telenzepine and Pirenzepine on Pancreatic Secretory Response to Intraduodenal Tryptophan in Dogs

In conscious dogs with gastric and pancreatic fistulas, we compared the action of different doses of telenzepine (ranging from 9 to 243 nmol kg-1 h-1 i.v.) and pirenzepine (ranging from 43 to 1,170 nmol kg-1 h-1 i.v.) on the pancreatic secretory response to graded loads of intraduodenal infusions of tryptophan, given with a secretin background. Both, telenzepine and pirenzepine caused an overall significant inhibition of the cumulative incremental pancreatic protein output by 65.8 and 66.8%, respectively. The pancreatic bicarbonate output was also reduced by 38.3 and 40.5%, respectively, but the effect did not reach statistical significance. The inhibitory potency of the effective doses of telenzepine or pirenzepine did not differ significantly. Only the highest doses of telenzepine (243 nmol kg-1 h-1 i.v.) and of pirenzepine (1,170 nmol kg-1 h-1 i.v.) significantly increased heart rate from 59.9 +/- 3.4 to 63.1 +/- 4.5 bpm, respectively. These findings indicate that (1) in the intact animal, the M1-receptor antagonists telenzepine and pirenzepine are capable of inhibiting pancreatic bicarbonate and protein output in response to intraduodenal tryptophan with secretin background, and (2) telenzepine is 4.7 times more potent than pirenzepine.

Effects of MCI-727, a New Anti-Ulcer Agent, on Plasma Secretin Concentration in Rats and Dogs and Pancreatic Exocrine Secretion in Rats.

In the present study, we investigated the effects of MCI-727, a new anti-ulcer agent, on plasma immunoreactive secretin concentration in rats and dogs using secretin specific RIA with the ethanol extraction method. Plasma secretin levels were increased dose-dependently 10 min after oral administration of MCI-727 in rats (control: 5.5 +/- 0.6; MCI-727, 10 mg/kg: 10.4 +/- 2.6; 30 mg/kg: 15.3 +/- 1.5; 100 mg/kg: 20.7 +/- 2.6 pg/ml, n = 6). Teprenone also caused a significant increase of plasma secretin at 10 min after oral administration at the doses of 30, 100 and 300 mg/kg. Under the same conditions, MCI-727 and teprenone did not alter the plasma immunoreactive gastrin concentration in rats. From the results of the time course study, the increasing effect of MCI-727 (30 mg/kg, p.o.) on plasma secretin remained for at least 240 min after administration. On the other hand, the increasing effect of teprenone (200 mg/kg, p.o.) was only observed at 30 and 60 min after administration. Furthermore, MCI-727 had increasing effects on plasma secretin concentration in dogs, but teprenone had no effects in this species. The volume of pancreatic secretion and the pancreatic bicarbonate output increased after intra-duodenal administration of MCI-727 at 30 and 100 mg/kg in rats. Similar effects were also observed with teprenone (30-300 mg/kg, i.d.) or secretin (Secrepan, 0.1-1.0 unit/kg, i.v.).

Initial pathophysiological changes in chronic pancreatitis induced by pancreatic ductular obstruction model.

An experimental chronic pancreatitis model was made in five dogs with chronic pancreatic fistula by injection of microspheres into the peripheral pancreatic duct. Sequential changes of pancreatic exocrine and endocrine functions with morphology were studied. Significant decreases in volume bicarbonate output and amylase output were detected in each sample collected separately on secretin and secretin cerulean stimulation. While the viscosity of pancreatic juice was significantly increased with a concomitant increase in hexosamine concentration, chronic pancreatitis was demonstrated morphologically. These results suggest that concentrated pancreatic juice caused by a decrease in volume and an increase in viscosity of pancreatic juice with a concomitant increase in hexosamine concentration brings about the progression of chronic pancreatitis in this experimental model.

Vasoactive Intestinal Peptide and Secretin: Effects of Combined and Separate Intravenous Infusions on Bile Secretion in Man

The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion bile volume increased by 60%, and during the combined VIP and secretin infusion bile volume increased by another 70%. VIP increased bile bicarbonate concentration by some 30%. Although secretin did not increase the concentration, bicarbonate output increased threefold during secretin infusion but only twofold during VIP infusion. The outputs of bile acids were not significantly affected by the two peptides, whereas the concentrations decreased by 40% and 70% after VIP and secretin, respectively. The canalicular bile flow, measured by [14C]erythritol, was unaffected by VIP infusion, whereas secretin alone and the combination of the two peptides increased the canalicular clearance by 80%. The choleretic effect of VIP thus seems to occur only at the ductular level. Secretin exerts its effect at the ductular level and possibly also at the canalicular level. It is concluded that the two peptides have additive effects on the ductular bile flow.

Hormonal mechanism of sodium oleate-stimulated pancreatic secretion in rats

We have investigated the role of two intestinal hormones, secretin and cholecystokinin (CCK), on the pancreatic exocrine secretion stimulated by sodium oleate in anesthetized rats. Each rat was prepared with a polyethylene tube in the proximal duodenum and ligation of the pylorus. To collect pancreatic juice, the common bile-pancreatic duct was cannulated near the duodenal wall while bile was diverted to the exterior. Intraduodenal infusion of sodium oleate at doses of 0.03, 0.06, 0.12, and 0.24 mmol/h resulted in significant increases in pancreatic secretion including fluid, bicarbonate, and protein output. The increases of the three parameters were dose dependent and were correlated well with the increases in plasma secretin and CCK concentrations. To further clarify their hormonal roles, we have repeated identical experiments under intravenous administration of a rabbit anti-secretin serum (0.1 ml) or CR 1409 (4 mg.kg-1.h-1), a CCK-receptor antagonist, or a combination of both the antiserum and CR 1409. The antiserum significantly suppressed volume flow and bicarbonate secretion with a minor inhibitory effect on protein secretion, whereas a normal rabbit serum did not. CR 1409 significantly suppressed all three parameters. The combined treatment with both the antiserum and CR 1409 almost completely abolished the pancreatic secretion. Atropine given intravenously significantly inhibited the protein output but did not influence volume flow or bicarbonate output in response to sodium oleate. We thus conclude that, in rats, fat-stimulated pancreatic secretion of volume flow and bicarbonate depends entirely on the circulating endogenous secretin and CCK but that the protein output appears to be under control of both hormonal and cholinergic controls.

Time-dependent effects of maximal doses of cerulein on the secretory response of the rat pancreas

The present study was performed to determine the time-dependent effects of chronic administration of maximal doses of cerulein on the secretory function of the rat pancreas. Four groups of rats, one treated with 0.9% NaCl (control) and the others with cerulein (2, 5, and 10 μg/kg twice a day ip, respectively) were used. After a treatment period of 15, 30, or 60 d, eight rats were taken from each group, the pancreatic bile duct was surgically cannulated, and the pancreatic juice was collected after CCK or secretin stimulation. Then the rats were killed and the pancreas was removed and weighed. Administration of 2 μg/kg of cerulein for 15 d induced a significant increase (p<0.05) in the volume of pancreatic juice in response to hormonal stimulation. The enzyme and bicarbonate outputs increased only in response to CCK, not to secretin. The above-mentioned increases are significant only when related to body weight, not to pancreatic weight. There was good correlation between pancreatic weight and the increase in the secretory parameters. The secretion pattern was not significantly modified by higher doses of cerulein nor by longer duration of treatment. We conclude that 1) increase in pancreatic secretory function induced by 2 μg/kg of cerulein is not enhanced by higher doses of peptide and 2) the functional capacity of the acinar cells is not affected by the length of treatment. These data are of interest as experimental backing to therapeutic use of CCK-like peptides in pancreatic exocrine insufficiency.

Mechanism of acid-induced release of secretin in rats. Presence of a secretin-releasing peptide.

In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin. To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas. Donor rats were infused intraduodenally with 0.01 N HCl, 0.15 M NaCl, or a combination of 0.01 N HCl and 0.05 N NaHCO3 at 0.3 ml/min for 1.5 h, and the perfusates were collected via jejunal cannulas. The perfusates with pH adjusted to 6.0 were concentrated threefold and infused into the duodena of recipient rats. The concentrate of acid perfusate (CAP) significantly increased both pancreatic volume flow and bicarbonate output and plasma concentration of secretin, whereas concentrates of the saline perfusate (CSP) or the perfusate of a combination of 0.01 N HCl and 0.05 N NaHCO3 (CABP) did not influence pancreatic secretion or plasma concentration of secretin. The increased pancreatic secretion by CAP was attributed to increased circulating secretin because when secretin was immunoneutralized by a rabbit antisecretin serum, CAP-stimulated pancreatic secretion was abolished. The bioactivity of CAP was trypsin-sensitive and heat stable. The active substance in CAP had a molecular weight of less than 5,000 and greater than 1,000, as determined by ultrafiltration and bioassay. In conclusion, dilute HCl releases an S-RF into the upper small intestinal lumen to stimulate release of secretin. This substance, with molecular weight of less than 5,000, is heat stable and trypsin sensitive. Thus, the acid-stimulated release of secretin is mediated by a secretin-releasing peptide in the upper small intestinal lumen.

The effects of synthetic human secretin on calcium carbonate solubility in human bile

This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 μg · kg−1 · h−1 for 45 minutes followed by 0.5 μg · kg−1 · h−1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and Pco2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ionspecific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 ± 3 mmol/L to 41 ± 3 mmol/L (P < 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 ± 2 mmol/L to 4.7 ± 1 mmol/L (P < 0.05). Ionized calcium concentrations decreased from 0.7 ± 0.005 mmol/L to 0.5 ± 0.02 mmol/L (P < 0.05) while pH increased significantly from 7.44 ± 0.06 to 7.6 ± 0.04 (P < 0.05). Carbonate concentrations increased significantly from 0.15 ± 0.02 mmol/L to 0.26 ± 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 ± 0.002 (mmol/L)2 to 0.135 ± 0.015 (mmol/L)2 (P < 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for calcium carbonate precipitation.

Pancreatic function and gene deletion F508 in cystic fibrosis.

In view of the possible relation between pancreatic function and cystic fibrosis (CF) gene mutations, a detailed study on Italian patients was performed. Seventy pancreatic insufficient and 48 pancreatic sufficient patients were included after very accurate characterisation of their pancreatic and digestive function, all performed in the same CF centre. The CF gene deletion F508 was tested to define the patients' genotypes. The results confirm that the mutation correlates with pancreatic insufficiency, and is recessive to other, as yet unreported, mutant alleles that determine pancreatic sufficiency. An indication that duodenal bicarbonate output is more severely reduced in the presence of deletion F508 is also presented. The data are discussed in relation to a hypothesis on the primary effects of CF gene deletion F508.

Vagal and sympathetic control of gastric and duodenal bicarbonate secretion

This report summarizes data concerning the extrinsic neural control of bicarbonate secretion by the gastric and duodenal mucosa. Parasympathetic vagal effects have been studied in experimental animals and in man by means of direct electrical vagal stimulation, sham-feeding procedures and intracerebroventricular peptide injections. The results show that the vagal nerves have a stimulatory effect on gastroduodenal bicarbonate secretion. Furthermore, both conventional nicotinic and muscarinic cholinoceptor, as well as non-cholinergic transmission, mediate the vagal effect. Sympathetic splanchnic nerve effects have been investigated by means of nerve sections, direct electrical stimulation, reflex activation and stereotaxic electrical hypothalamic stimulation. The data show that the splanchnic nerves have a predominantly inhibitory action on gastroduodenal bicarbonate secretion by use of peripheral adrenergic neurones and receptors of the alpha-2 subtype. The role of the adrenal glands is not fully understood. It is concluded that gastroduodenal bicarbonate secretion is under autonomic neural control, mainly in the classical antagonistic fashion; the parasympathetic vagal nerves stimulate bicarbonate output, whereas the sympathetic splanchnic nerves are mainly inhibitory.

Proximal duodenal prostaglandin E2 release and mucosal bicarbonate secretion are altered in patients with duodenal ulcer

Proximal duodenal mucosal bicarbonate production is impaired in patients with duodenal ulcer disease. Because prostaglandins of the E class increase human proximal duodenal bicarbonate secretion, this study tested the hypothesis that endogenous prostaglandin E2 production is defective in patients with duodenal ulcer. Ten patients, five with active and five with inactive duodenal ulcer disease, were studied along with 10 normal volunteers. The proximal 4 cm of duodenum, the bulb, was isolated and continuously perfused with 154 mmol/L NaCl. Basal bicarbonate secretion was measured for 30 minutes. The test segment was then acidified with a physiological amount of HCl (2 mmol over 5 minutes), and acid-stimulated bicarbonate secretion was measured by pH/PCO2 and back-titration for 55 more minutes. Prostaglandin E2 was measured in the effluents by a radioimmunologic assay validated by gas chromatography-mass spectrometry. Compared with the normal subjects after luminal acidification, the duodenal ulcer patients had significantly greater PGE2 release and decreased total 1-hour bicarbonate output. The peak 5-minute acid-stimulated bicarbonate responses were not significantly different between the duodenal ulcer patients and normal subjects. After luminal acidification, PGE2 output remained elevated in the duodenal ulcer patients but returned promptly to basal in the normal subjects. Furthermore, the ratio of bicarbonate secreted to the amount of PGE2 released was significantly less in the ulcer patients. These findings suggest that patients with duodenal ulcer disease have an impaired mucosal bicarbonate response to endogenous PGE2. The increased acid-stimulated PGE2 response in duodenal ulcer patients suggests a compensatory phenomenon in response to the diminished mucosal bicarbonate production.

Influence of backward perfusion on ursodeoxycholate-induced choleresis in isolated in situ rat liver

Ursodeoxycholate-induced bicarbonate-rich hypercholeresis was studied in isolated in situ forward- or backward-perfused rat livers. Both spontaneous bile flow and bile acid secretion were similar regardless of the direction of the perfusion. The choleretic effect of tauroursodeoxycholate infusion (400 nmol.min-1.100 g-1 body weight) was not significantly different in forward- or backward-perfused livers either. Ursodeoxycholate infusions at low rate (800 nmol.min-1.100 g-1 body weight) induced similar bile flow, bile acid output and bicarbonate output in both forward- and backward-perfused livers. Net ursodeoxycholate uptake, measured as [14C]ursodeoxycholate uptake over the bile acid infusion period (30 min), was not significantly different during forward- or backward-perfusion (4.8 and 5.1 mumol/g liver, respectively); i.e., approx. 67% of infused dose (approximately 7.5 mumol/g liver per 30 min). A 2-fold increase in the dose of ursodeoxycholate infusion (1600 nmol.min-1.100 g-1 b.wt.) induced additional enhancement in both bile flow and bicarbonate biliary secretion, but not in bile acid uptake or output, in forward-perfused livers. Moreover, infusion of the same dose of ursodeoxycholate to backward-perfused livers had a significantly lower choleretic effect (-29%, p less than 0.001) even though ursodeoxycholate uptake and biliary output were similar regardless of perfusion direction. Net ursodeoxycholate uptake, was only 2.4 mumol/g liver; i.e., approx. 16% of infused dose (approximately 15 mumol/g liver per 30 min). These findings indicate that a process related with the hepatic microanatomy may be involved in the hypercholeretic response to ursodeoxycholate.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure measurement in adults: large cuffs for all?

The aim of the study was to determine whether a single size of cuff for adult blood pressure measurements is appropriate for general clinical practice. The study was a prospective survey of a sample of adult blood pressure measurements using two cuffs with different bladder sizes (12 X 23 cm and 15 X 33 cm) in a randomised design using a random zero sphygmomanometer. Blood pressures were measured in a general practice and in a hospital outpatient clinic. The participants were 35-60 year old men and women invited to attend a blood pressure screening programme in the general practice (n = 170), and 35-74 year old patients attending a general medical outpatients (n = 72). The small cuff gave higher readings of systolic blood pressure than the large cuff (mean difference 4.4 mm Hg). The difference increased as systolic pressure increased but did not show a clear association with arm circumference. The small cuff also gave higher diastolic pressure readings (mean difference 3.0 mm Hg), but only when arm circumference exceeded 30 cm. The variability of the differences between readings from the two cuffs was wide, little affected by arm circumference, and was similar to the variability between measurements using the same cuff size. In terms of precision there is no basis for using two different cuff sizes unless it is physically difficult to obtain a reading with one or the other. Since readings with large cuffs are closer to intraarterial pressures in large arms, and the large cuff used here did not underestimate diastolic pressure in small arms, the large cuff alone could be recommended for general use.

Human duodenal mucosal bicarbonate secretion: Evidence suggesting active transport under basal and stimulated conditions

When the proximal duodenum of animals or humans is perfused with isoosmolar NaCl, bicarbonate enters the luminal effluent. In addition, duodenal bicarbonate output is stimulated by luminal acidification and prostaglandins of the E class. The hypothesis that in vivo human duodenal bicarbonate transport persists in the absence of a plasma-to-lumen bicarbonate gradient and therefore is probably an active transport process was tested. In healthy subjects, a 4-cm segment of the proximal duodenum was isolated from gastric and pancreaticobillary secretions. Net duodenal bicarbonate secretion remained similar to basal levels during luminal perfusion with either 24 or 32 mM bicarbonate (each isoosmolar with plasma by the addition of NaCl). In addition, peak increases in acid-induced bicarbonate outputs with luminal perfusion of 154 mM NaCl and 32 mM NaHCO 3 (+122 mM NaCl) were similar. Moreover, prostaglandin E 2-stimulated bicarbonate secretion with perfusion of 154 mM NaCl and 32 mM NaHCO 3 (+122 mM NaCl) was similar. It was concluded that in humans, proximal duodenal mucosal bicarbonate transport remains unaltered in the absence of a plasma-to-lumen bicarbonate gradient at rest and after stimulation with HCl or prostaglandin E 2. These observations suggest that human proximal duodenal bicarbonate secretion involves active transport.

Rat pancreastatin inhibits both pancreatic exocrine and endocrine secretions in rats

Effects of synthetic rat pancreastatin C-terminal fragment on both exocrine and endocrine pancreatic functions were examined in rats, in vivo and in vitro. Pancreastatin (20, 100 pmol, 1 nmol/kg/h) significantly inhibited CCK-8-stimulated pancreatic juice flow and protein output in a dose-related manner, in vivo. The inhibitory effect on bicarbonate output was not statistically significant. Pancreastatin did not significantly inhibit basal pancreatic secretions in vivo, and did not inhibit amylase release from the dispersed acini, in vitro. Insulin release stimulated by intragastric administration of glucose (5 g/kg) was significantly inhibited by pancreastatin (1 nmol/kg/h), in vivo. Plasma glucose concentrations were increased by pancreastatin infusion, but the increase was not statistically significant. Furthermore, pancreastatin inhibited insulin release from isolated islets, in vitro. Synthetic rat C-terminal pancreastatin fragment has bioactivities on both exocrine and endocrine pancreatic functions in rats.

Cronkhite Canada syndrome: case report with some features not previously described

A 69-year-old woman was admitted to our unit with a history of diarrhea and weight loss lasting 1 year. Diarrhea consisted of 10 to 15 bowel movements per day without either blood or mucus. No abdominal pain was present. Her weight had fallen from 100 kg to 70 kg the year prior to examination. She also noted gradual loss of hair and increasing thinness and brittleness of fingernails and toenails. On examination, the patient appeared to be overweight and dehydrated. She presented irregular alopecia and hair fell out upon being touched. There was brown pigmentation on the back of her hands and in the periorbital region, while the fingernails and toenails were atrophied with onychodystrophy. The remainder of the physical examination was unremarkable. Serum laboratory values were: white blood count 3100, hemoglobin 11 g, hematocrit 29%, and iron 49 /lgjdl. Electrolytes were: sodium 136 mmol/liter, and potassium 2.4 mmol/liter. Total proteins were 6 gjdl and albumin was 2.7 gjdl. Gastrin was 1000 pgjml (NV, 20 to 80) and there was no gastric acid production (MAO, 0); anti-gastric parietal cell antibody test was positive. Fecal microscopy and culture were negative for pathogens. Liver and kidney function tests were normal. Evaluation of endocrine function was normal. Secretion test of pancreatic function showed normal volume and bicarbonate output. Double-contrast barium enema and x-rays of the upper gastrointestinal tract revealed multiple filling defects of the colon and stomach. A small bowel enema did not show any polypoid lesions. The upper gastrointestinal endoscopy showed about 10 (0.5 to 3 cm) sessile polyps in the stomach (Fig. 1); the esophagus and the duodenum were free ofpolyps. The gastric mucosa between polyps was thin and pale, without erosions or ulcers. Colonoscopy revealed multiple (about 20) sessile and pedunculated polyps distributed throughout the colon. Histologic analysis of the gastric polyps showed the surface epithelium to be mostly flattened without ulceration