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Biomedical subjects

J E Valenzuela

Publications and source records attributed to J E Valenzuela.

At least 37 records · Page 2Linked to original sources

Response of lower esophageal sphincter to alterations of intraabdominal pressure.

It is well documented that lower esophageal sphincter pressure increases significantly in response to increases in intraabdominal pressure in order to maintain the gastroesophageal barrier. The mechanism by which this response is elicited is controversial. It has been suggested that the response of the sphincter persists after the intraabdominal pressure stimulus is removed. The present study sought to define the response of the sphincter to increased intraabdominal pressure (achieved by straight leg raising) by continuously monitoring it with the Dent sleeve in a group of 10 normal volunteers. A reproducible pressure profile was observed in both the sphincter and the stomach, characterized by an initial peak, a sustained plateau, and a second peak. The pressure profiles of the stomach and the sphincter were closely approximated and peak and plateau pressures for both did not differ significantly. The onset and offset of the pressure increase were simultaneous in the stomach and the sphincter. No significant changes in sphincter pressure were noted when the rapid pull-through technique was used. This study defines the pressure profiles of the stomach and the lower esophageal sphincter zone during increased intraabdominal pressure in man. Our data suggest that the response of the sphincter is passively mediated.

Abdomen↗

Modulation of esophageal peristalsis by alterations of body position. Effect of bolus viscosity.

Previous studies have demonstrated that nonviscous liquids traverse the esophagus more rapidly with the subject in the upright rather than the supine position. Conversely, similar studies have shown that viscous liquids traverse the esophagus at similar rates for both upright and supine positions. Our purpose was to define the motor correlates of these differing responses. Six normal volunteers were studied with an infused catheter system incorporating a Dent sleeve for monitoring lower esophageal sphincter pressure. The subjects were given a series of swallows of a water and a viscous (52 centipoise) bolus in both the supine and upright positions. In the upright position, the water bolus caused an increased velocity of propagation in the proximal esophageal segment that was associated with a shortening of lower esophageal sphincter relaxation time and reductions in amplitude and duration of contraction. No significant changes in the peristaltic wave were noted with the viscous bolus during alterations of body position. We conclude that the more rapid transit of a nonviscous water bolus through the esophagus in the upright position is reflected in specific alterations of esophageal peristaltic parameters. The possible mechanisms for these differing responses are discussed.

Adult↗

Effect of alcohol and alcoholic beverages on nonstimulated pancreatic secretion in humans.

The effects of alcoholic beverages on pancreatic secretion, blood trypsin levels, the release of gastrin and cholecystokinin were studied and compared with those of an alcohol and a glucose solution. Studies were done on six healthy male volunteers. The trypsin level was measured in the duodenal aspirate, while blood trypsin and gastrin levels were measured by radioimmunoassay and the cholecystokinin level was measured by bioassay. Studies were done on 5 different days, and on each day, the effects of either a glucose solution; an alcohol solution; or wine, beer, and gin solutions infused into the stomach were compared. The glucose solution stimulated trypsin secretion (a threefold increase above the basal measure) and the release of cholecystokinin without changes in the blood trypsin level. Blood alcohol levels, after the alcohol solution and all alcoholic beverages, were similar, and subjects showed mild symptoms of intoxication. Pancreatic enzyme secretion and trypsin blood levels were not significantly affected by either alcohol or the alcoholic beverages. Wine and beer caused significant release of gastrin and cholecystokinin. Under the conditions of this study, which reproduce those of excessive alcohol drinking, alcohol and alcoholic beverages did not stimulate pancreatic enzyme secretion, although wine and beer increased the release of gastrin and cholecystokinin. We conclude that alcohol and alcoholic beverages do not affect nonstimulated pancreatic enzyme secretion.

Adult↗

Abnormalities in the duodenal transit and motility in duodenal ulcer patients: studies with a new isotopic technique.

Abnormalities of duodenal motility have been described in patients with duodenal ulcer and in experimental ulcers in rats and it has been postulated that they could be pathogenic in peptic ulcer disease. We have investigated with an isotopic technique whether duodenal bulb clearance or duodenal transit are abnormal in duodenal ulcer. Six patients with inactive and six with active duodenal ulcers, all men, and six healthy male controls were studied. Motility of the duodenum was simultaneously monitored. A bolus of 99mTcDTPA was injected into the duodenum while water or acid were perfused on different occasions. Duodenal bulb clearance and transit to the ligament of Treitz were calculated. Duodenal transit in duodenal ulcer patients 108.8 (23) sec was faster than in controls, 194.9 (5.1) sec (p less than 0.05) during the quiescent period of the motility cycle. The frequency of duodenal bulb contractions during acid perfusion was higher in duodenal ulcer patients 1.7 (0.4) cont/min, than in controls 0.8 (0.1) cont/min (p less than 0.05). No other significant differences were observed between ulcer patients and controls. These data suggest that patients with duodenal ulcers do not have major abnormalities of duodenal bulb clearance, nor of duodenal transit and that duodenal motility does not play a primary role in the pathogenesis of the ulcer.

Adolescent↗

Effect of bolus osmolality on human esophageal function.

The effect of bolus osmolality on human esophageal function is undefined. We sought to define the response of the human esophagus to boluses with a wide range of osmolalities in 10 healthy male volunteers. Intraluminal pressure events were measured with an infused catheter system, and lower esophageal sphincter pressure was monitored continuously with a Dent sleeve. Each subject was given a series of 10 swallows of each of seven boluses, which consisted of water, mannitol solutions with osmolalities of 142, 296, 449, 704, and 1481 mOsm/kg, and orange juice (585 mOsm/kg), in a randomized fashion. Tracings were coded and analyzed blindly. Alterations in bolus osmolality did not elicit any significant changes in amplitude and duration of contraction, velocity of wave propagation, or the duration of relaxation of the lower esophageal sphincter. We conclude that bolus osmolality does not play a significant role in the control of human esophageal motility, and that this lack of effect is explained by consideration of esophageal muscle mechanics.

Adult↗

Campylobacter pylori: associations with antral and fundic mucosal histology and diagnosis by serology in patients with upper gastrointestinal symptoms.

We obtained a sample of serum and mucosal biopsies from the antrum and usually from the corpus of the stomach from 35 symptomatic patients during routine endoscopy to analyze for the relationship between Campylobacter pylori infection, inflammation, and the diagnostic utility of a C. pylori IgG antibody assay. C. pylori was identified prospectively by culture and/or silver stain in gastric biopsies from 24 patients, and the antibody was detected in 19 (79%) of these patients. The antibody assay was positive in three other patients, two of whom had C. pylori, on reexamination of their biopsies. The accuracy of the antibody assay was 83%. Inflammation was detected in all C. pylori-positive antral biopsies (N = 19). However, five (71%) of seven antral biopsies from patients in whom all tests were C. pylori negative, also had inflammation, constituting 17% of all patients with antral gastritis (N = 30). Both antral and fundic mucosa were obtained from 26 patients and, in this group, C. pylori was detected in fundic mucosa from all patients in whom the organism also was present in the antrum (N = 15). In significant (p less than 0.001) contrast to C. pylori-positive antral histology, fundic mucosal histology was normal in 6 (40%) of 15 C. pylori-positive biopsies, all from patients with peptic ulcer disease. We conclude that C. pylori antibody assays will be useful for epidemiological studies and initial screening of the C. pylori status of individual patients. In addition, there is a high concordance rate between antral and fundic mucosa for the prevalence of C. pylori, but in contrast to the probable etiological role of C. pylori in antral gastritis, the organism appears to be only a commensal of fundic mucosa. Moreover, C. pylori infection is not evident in all patients with type B gastritis.

Adult↗

Prevalence of Campylobacter pylori and association with antral mucosal histology in subjects with and without upper gastrointestinal symptoms.

To determine the incidence and significance of Campylobacter pylori in patients undergoing routine endoscopic evaluation at this hospital, biopsies of the antrum were obtained from 132 patients and from 15 asymptomatic volunteers. Specimens were cultured and silver stained for the presence of C. pylori and were examined histologically. C. pylori was detected in 67 (51%) patients and two (13%) volunteers (P = 0.006). In patients, C. pylori was found significantly more often when the mucosa was inflamed (67%) than when the mucosa was normal (13%), and both volunteers with C. pylori had chronic gastritis on histological examination. When compared to the volunteers, patients with upper gastrointestinal symptoms had a significantly increased prevalence of antral inflammation, even if the endoscopic examination was normal. C. pylori is infrequently found in young asymptomatic adults but is found in both asymptomatic volunteers and patients in association with all forms of histological antral gastritis which is prevalent in patients with both normal endoscopic findings and peptic ulcer disease.

Adult↗

Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy.

Exocrine pancreatic insufficiency has been observed in some diabetics with peripheral neuropathy and diarrhea. Several mechanisms may be responsible for this insufficiency: (1) pancreatic atrophy, (2) disruption of the cholinergic enteropancreatic reflexes, or (3) elevated serum levels of peptides such as glucagon and pancreatic polypeptide which are known to inhibit pancreatic exocrine secretion. To clarify the mechanism(s) involved in this exocrine pancreatic impairment, we studied 10 diabetics with diarrhea and peripheral neuropathy. Their results were compared to those of eight normal volunteers. Each subject underwent a standardized pancreatic function study which assessed nonstimulated secretion, the response to intrajejunal infusion of a mixture of amino acids, and the output following intravenous administration of secretin and cholecystokinin (CCK). In separate studies, the effect of a background infusion of bethanechol and secretin on the pancreatic response to CCK was assessed in six patients and six normal controls. Compared to normals, all diabetics exhibited a significant reduction in both enzyme and bicarbonate secretion to all stimuli. This reduction was not corrected by administering bethanechol. Plasma glucagon and pancreatic polypeptide levels in diabetics were not significantly higher than those in controls. We conclude that diabetics with diarrhea and peripheral neuropathy exhibit impairment of their exocrine pancreatic secretion and possible mechanisms for this are discussed.

Adult↗

Effect of nifedipine on gastric emptying and gastrointestinal motility in man.

Nifedipine, a calcium-blocking agent, inhibits smooth muscle contractions in various organs including gastric muscle in vitro. Despite this, nifedipine has been found to have no effect on gastric emptying in man. We have investigated the effect of nifedipine on gastric emptying of liquids and solids and on gastrointestinal motility in six healthy subjects. For this, isotopic techniques and manometric methods were used. We confirm that nifedipine 30 mg per os does not modify gastric emptying of liquids or solids. By contrast, antral motility was significantly inhibited (P less than 0.05) and duodenal motility increased. These results could be interpreted as (1) gastroduodenal motility changes are not severe enough to alter emptying or (2) isotopic techniques are not sensitive enough to detect subtle changes in gastric emptying.

Adult↗

Studies of the role of opioids in control of human pancreatic secretion.

Opioids, both endogenous and exogenous, have been shown to exert a modulating influence on many gastrointestinal functions. Animal studies suggest an inhibitory role for opioids in the control of pancreatic secretion, which may be exerted through their inhibitory effect on acetylcholine release from intramural neurons. We studied pancreatic secretion in six healthy male volunteers (mean age 42 years) by means of duodenal aspiration using PEG-4000 as a recovery marker. Pancreatic secretion was stimulated with duodenal perfusion of mannitol (510 mosmol/kg) and an equimolar solution (0.3 M/liter) of L-phenylalanine and L-tryptophan and also with an intravenous bolus of secretin and cholecystokinin (each 1 CU/kg). Each subject underwent six studies on separate days with intravenous infusion of saline, naloxone 40 micrograms/kg/hr, morphine sulfate 40 micrograms/kg/hr, morphine and naloxone combined, naloxone and atropine 13 micrograms/kg/hr, and morphine and bethanechol 16 micrograms/kg/hr. Naloxone caused a significant increase in amylase outputs during the basal period and in response to all stimuli, without affecting bicarbonate outputs. This effect was blocked by atropine. Morphine caused significant reductions in both amylase and bicarbonate outputs with all stimuli. This was accompanied by a reduction in amylase concentrations but not in those of bicarbonate. Bethanechol counteracted these effects of morphine. The combination of morphine and naloxone had no significant effect on pancreatic secretion. Changes in pancreatic polypeptide levels did not explain the observations. In conclusion, these studies suggest that endogenous opioids exert a modulating influence on human pancreatic secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pectin delays gastric emptying and increases satiety in obese subjects.

As pectin delays gastric emptying in normal subjects and satiety may be linked to the rate of gastric emptying, we designed this study to evaluate, in a group of obese subjects, the effect of adding pectin to a meal on gastric emptying, sensation of satiety, and postprandial plasma cholecystokinin and pancreatic polypeptide levels. We studied gastric emptying of solids in 9 adult obese subjects on 2 separate days in a randomized fashion. On day 1, 15 g of pectin was added to the meal, and on day 2 15 g of methylcellulose was added and served as control. Satiety was evaluated by an analogue rating scale. Pectin significantly delayed gastric emptying time [t1/2 = 116 +/- 23 min vs. 71 +/- 17 min observed with methylcellulose (p less than 0.001)]. Pectin also significantly increased subjects' sensation of satiety [98 +/- 7 vs. 74 +/- 17 (p less than 0.001)]. Postprandial release of cholecystokinin and pancreatic polypeptide was not modified by pectin. As pectin induces satiety and delays gastric emptying in obese patients, it may be a useful adjuvant in the treatment of disorders of overeating.

Adult↗

Effects of alterations in bolus viscosity on esophageal peristalsis in humans.

The effect of increased bolus viscosity on esophageal peristaltic function was studied in six healthy volunteer subjects. Intraluminal pressure events were measured with an infused catheter system and lower esophageal sphincter pressure was monitored continuously with a Dent sleeve. Boluses with viscosities of 2.5, 8.7, 48, and 860 centipoise (cP) were compared with a water bolus. Increasing bolus viscosity to 48 and 860 cP elicited a slowing of wave velocity, an increase in wave duration, and a prolongation of lower esophageal sphincter relaxation. The initial change noted at lower viscosities was an increased duration of contraction wave. Maximal changes were noted at the 48 cP bolus. In conclusion, increased bolus viscosity significantly alters human esophageal peristalsis. These changes may be mediated by esophageal stretch reflexes or by the intrinsic properties of the esophageal musculature or both.

Adult↗

Antropyloroduodenal activity during gastric emptying of liquid meals in humans.

The present study examines the possible roles of the pylorus and the proximal duodenum in the gastric emptying of two liquid meals in six healthy volunteers. Gastric emptying of a saline meal (150 mM) and an acid meal (120 mM hydrochloric acid) were measured by the double-sampling dye dilution technique while antroduodenal motility was monitored with a continuously perfused catheter system. Pyloric region pressures were measured with a Dent sleeve. The acid meal (t1/2 = 13.5 +/- 1.8 min) emptied significantly (P less than 0.01) slower than the saline meal (t1/2 = 3.5 +/- 0.7 min). This slowing in the emptying of the acid meal was associated with significant (P less than 0.05) increments in tonic pyloric activity and phasic contractions of the proximal duodenum. Thus the gastric emptying of liquid meals is a complex process involving all components of the gastroduodenal region.

Adult↗

Abnormalities of the migrating motor complex in diabetics with autonomic neuropathy and diarrhea.

Diarrhea is a common symptom in long-standing diabetes. The pathogenesis of this diarrhea remains obscure, although it appears to be related to the development of autonomic neuropathy, which may cause several abnormalities including altered gut motility. We studied fasting gastrointestinal motility for a mean of 210 min in a group of 12 type-II diabetics with diarrhea. All patients had peripheral neuropathy and symptoms of autonomic neuropathy. Their motor activity was compared with that of a group of six normal volunteers. In addition, gastrointestinal transit time was assessed by the hydrogen breath test. The presence of bacterial overgrowth was assessed by the hydrogen breath test and culture of jejunal secretions. The diabetics showed grossly disordered motor activity. There was a complete absence of phase-III activity in two patients. Most phase III's commenced in the distal duodenum or jejunum. The phase-III component was often of short duration at each recording site. There was increased velocity of propagation between sites. Continuous phase-II activity was noted in some patients. Antral activity was absent or reduced during phase II. Gastrointestinal transit time was significantly prolonged in the diabetics. Bacterial overgrowth was demonstrated in three diabetic subjects. These motility abnormalities are nonspecific and are unlikely to play a major role in the pathogenesis of diabetic diarrhea.

Adult↗

Dopamine receptors in human gastrointestinal mucosa.

Dopamine is a putative enteric neurotransmitter that has been implicated in exocrine secretory and motility functions of the gastrointestinal tract of several mammalian species including man. This study was designed to determine the presence of dopamine binding sites in human gastric and duodenal mucosa and to describe certain biochemical characteristics of these enteric receptor sites. The binding assay was performed in triplicate with tissue homogenates obtained from healthy volunteers of both sexes using 3H-dopamine as a ligand. The extent of nonspecific binding was determined in the presence of a 100-fold excess of unlabeled dopamine. Scatchard analysis performed with increasing concentrations of 3H-dopamine (20-500 nM) revealed a single class of saturable dopamine binding sites in gastric and duodenal mucosa. Binding parameters obtained from the regression lines of the Scatchard plots of gastric mucosa of males were Bmax = 73.4 +/- 4.0 pmoles/mg protein; KD = 154 +/- 20 nM and Bmax = 95 +/- 13.6 pmoles/mg protein and KD = 826 +/- 200 nM in females. In duodenal mucosa of males these parameters were Bmax = 63.9 +/- 15.9 pmoles/protein; KD = 235 +/- 53 nM and Bmax = 83.2 +/- 19.4 pmoles/mg protein; KD = 568 +/- 104 nM in females. The results of this report demonstrate the presence of specific dopamine receptors in human gastric and duodenal mucosa. These biochemical data suggest that molecular abnormalities of these receptor sites may be operative in the pathogenesis of important gastrointestinal disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Dopamine↗

Effect of 15(R),15-methyl prostaglandin E2 and indomethacin on pancreatic secretion in man.

UNLABELLED: In addition to gastric mucosal cytoprotective and antisecretory effects, prostaglandin E2 has a beneficial effect on experimental pancreatitis in some animal models, while prostaglandin synthesis inhibitors such as indomethacin and salicylates may induce pancreatitis at maximal doses. However, their effect on human pancreas is unclear. For this reason we considered it necessary to delineate their actions on human pancreatic secretion. Six healthy volunteers were studied on six separate days. On day 1, against a background of 1 pmol/kg/hr secretin, increasing doses of CCK were infused intravenously. On day 2, increasing doses of an amino acid mixture were infused intraduodenally and both studies were repeated on two occasions, following 100 micrograms 15(R), 15-methyl prostaglandin E2 per os on one and following indomethacin 50 mg orally 12 and 1 hr prior to the study on the other. Both indomethacin and PGE2 had no significant effect on pancreatic secretion in response to graded doses of CCK. 15(R),15-Methyl prostaglandin E2 and indomethacin caused a reduction of amylase output in response to the higher doses of intraduodenal amino acids. The prostaglandin E2 derivative also elicited a significant increase in basal bicarbonate output. IN CONCLUSION: the acute effects of 15(R),15-methyl prostaglandin E2 and indomethacin on human pancreatic secretion do not seem to offer an explanation for the mechanisms of protection against experimental acute pancreatitis or an association with pancreatitis, respectively.

Adult↗

Effect of pectin on gastric emptying and gastroduodenal motility in normal subjects.

The effects of pectin ingestion on gastric emptying, gastroduodenal motility, and plasma levels of glucose, insulin, and glucagon were studied. Initial studies demonstrated that 15 g of pectin was the optimal dose. Subsequently 6 healthy male volunteers were studied on 4 separate days at random. On day 1, gastric emptying of a liquid and a solid meal was assessed by radioisotope technique using 99mTc-dithiopropylthiomine. On day 2, the gastric emptying study was repeated with the addition of pectin to each meal. Plasma levels of glucose, insulin, and glucagon also were determined during these 2 days. On day 3, the effects of liquid and solid meals on gastroduodenal motility were assessed by means of a perfused catheter system. On day 4, the motility study was repeated with the addition of pectin to each meal. Pectin supplementation caused a significant prolongation of gastric emptying half-time of both liquid and solid meals (p less than 0.05). The addition of pectin, however, did not have any significant effect on gastroduodenal motility other than increasing the duodenal motility index 10 min after the liquid meal. The addition of pectin to the liquid meal lowered plasma levels of insulin at 15, 30, and 45 min, and glucagon levels 15 min after the meal. No effect was noted on blood sugar levels. On the other hand, the addition of pectin to the solid meal had no effect on plasma levels of glucose, insulin, and glucagon. We conclude that pectin supplementation delays gastric emptying of both liquid and solid meals in normal human subjects without causing notable changes in gastroduodenal motility or significant variations in pancreatic hormone plasma levels. The pectin effect on gastric emptying may be caused solely by increasing the viscosity of the meals.

Adult↗

Cholinergic stimulation of human pancreatic secretion.

The effect of graded doses of bethanechol on pancreatic secretion and plasma levels of pancreatic polypeptide and somatostatin was investigated in six healthy volunteers. In other studies the effect of a bethanechol background on the secretin-CCK stimulation of pancreatic secretion was also studied. Bethanechol caused a moderate stimulation of amylase secretion with a weak stimulation of bicarbonate secretion. These effects were not associated with significant changes in the plasma level of pancreatic polypeptide and somatostatin. Bethanechol enhanced the response to secretin and CCK. These results confirm a cholinergic pathway in the stimulation of pancreatic secretion in man.

Adult↗