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Biomedical subjects

T Reedy

Publications and source records attributed to T Reedy.

15 recordsLinked to original sources
PubMed1994

A controlled study of ranitidine for the prevention of recurrent hemorrhage from duodenal ulcer.

BACKGROUND: Hemorrhage is the most common complication of duodenal ulcer disease, but there is little information about the effectiveness and safety of long-term maintenance therapy with histamine H2-receptor blockers. METHODS: We conducted a double-blind study in patients with endoscopically documented hemorrhage from duodenal ulcers. Patients were randomly assigned to maintenance therapy with ranitidine (150 mg at night) or placebo and were followed for up to three years. Endoscopy was performed at base line (to document that the ulcers had healed), at exit from the study, and when a patient had persistent ulcer symptoms unrelieved by antacids or had gastrointestinal bleeding. Symptomatic relapses without bleeding were treated with ranitidine; if the ulcer healed within eight weeks, the patient resumed taking the assigned study medication. RESULTS: The two groups were similar at entry, which usually occurred about three months after the index hemorrhage. After a mean follow-up of 61 weeks, 3 of the 32 patients treated with ranitidine had recurrent hemorrhage, as compared with 12 of the 33 given placebo (P < 0.05). Half the episodes of recurrent bleeding were asymptomatic. One patient in the ranitidine group withdrew from the study because of asymptomatic thrombocytopenia during the first month. CONCLUSIONS: For patients whose duodenal ulcers heal after severe hemorrhage, long-term maintenance therapy with ranitidine is safe and reduces the risk of recurrent bleeding.

Double-Blind Method↗
PubMed1994

Myth of substituted judgment. Surrogate decision making regarding life support is unreliable.

OBJECTIVE: To identify factors predicting the accuracy of surrogate decision making in life support decisions. DESIGN: Questionnaire. SETTING: Urban Veterans Affairs hospital. PATIENTS AND DESIGN: Fifty hospitalized patients and their chosen surrogates were given questionnaires describing life support modalities and four common medical scenarios in which life support would be contemplated. An additional 50 patients also completed the questionnaire. Patients gave their choices of life support in the different scenarios. Surrogates guessed the patients' answers (substituted judgment). Details of the patient-surrogate relationship were asked. Patients completed a depression inventory. MAIN RESULTS: Surrogates correctly guessed patients' wishes about life support overall on 59.3% of the questions, not better than random chance (kappa = .09). The only predictor of accurate surrogate decision making was specific discussion between patient and surrogate about life support. SECONDARY RESULTS: Patients had an overall low desire for life support (35%), and a majority favored euthanasia under some circumstances (62%). There was no relationship between depression score and desire for life support. CONCLUSIONS: Substituted judgment by surrogates is not more accurate than random chance. Discussion between patient and surrogate about life support correlated with more accurate substituted judgment.

Adult↗
PubMed1993

Effects of cyclooxygenase and lipoxygenase inhibition on eicosanoids and healing of acetic acid colitis in rats.

Both cyclooxygenase products, such as prostaglandin (PG) E2, and lipoxygenase products, such as leukotriene (LT) B4, are increased in colitis and have potent proinflammatory actions. We studied effects of specific inhibitors of cyclooxygenase and 5-lipoxygenase on the healing of acetic acid colitis in rats. Acetic acid colitis was induced 24 hr before enzyme inhibition began. Four days after induction of colitis, the area of gross colonic mucosal damage was determined by image analysis. Eicosanoid content in the intestinal lumen was quantitated by radioimmunoassay following chromatographic purification. Under these conditions, indomethacin significantly retarded the healing of colonic lesions and inhibited PGE2 by > 90% compared to placebo-treated colitis rats. AA861 had no effect on the healing of lesions, although > 75% inhibition of leukotriene synthesis was demonstrated. These results suggest that inhibition of endogenous colonic prostaglandins can impair healing mechanisms in acute colitis even after inflammation has developed. In contrast, inhibition of leukotriene synthesis did not affect healing.

Acetates↗
PubMed1992

Regulation of gastric acid secretion by gastrin in duodenal ulcer patients and healthy subjects.

To examine the role of gastrin as a major mediator of meal-stimulated acid secretion at low and high intragastric pH, gastric acid secretory responses after exogenous and endogenous stimulation were studied in relation to circulating plasma gastrin levels in 19 healthy control subjects and in 18 patients with inactive duodenal ulcer disease. Gastrin was given intravenously in stepwise fourfold-increasing doses from 3.1 to 800 pmol.kg-1.h-1 over consecutive 30-minute periods. Circulating plasma gastrin and acid secretion rates, measured by intragastric titration, were compared with the values obtained during endogenous stimulation by intragastric meals of 0.5, 1, 2, 4, and 8 g% peptone at either pH 5.5 or pH 2.5. The studies showed that circulating gastrin is a major regulator of acid secretion in the presence of peptone in both healthy controls and subjects with duodenal ulcers. Patients with duodenal ulcers had higher acid secretion rates in response to endogenous and exogenous stimulation. In duodenal ulcer subjects and healthy controls, acid secretion in response to higher doses (2-8 g%) of peptone was inhibited at low intragastric pH. This pH inhibition could be fully explained by diminished gastrin release. Patients in the DU group differed from the controls by diminished inhibition of acid secretion at intragastric pH 2.5 when low doses (1 g%) of peptone meals were used. In summary, gastrin is a major regulator of endogenously stimulated acid secretion at high and low intragastric pH in healthy subjects. DU patients differ from healthy controls by higher total acid secretion rates and diminished inhibition of acid secretion when low concentrations of peptone are present in the stomach.

Adult↗
PubMed1990

Calcium compartmentation and exchange rates in primary hepatocyte culture.

We utilized a technique, previously used to study myocardial cells (G. A. Langer, J. S. Frank, and L. M. Nudd, 1979, Amer. J. Physiol. 237, H239-H246), to study 45Ca2+ isotope exchange kinetics in hepatocyte monolayers, cultured on scintillation disks, and perfused in a flow-through chamber. Isolated rat hepatocytes were plated directly on Primaria-coated disks impregnated with scintillation fluors which made up the walls of the perfusion chamber. Following the labeling of the cells with radioactive calcium (45Ca2+), to apparent asymptote, the washout of 45Ca2+ from the cells was measured. A large very fast turnover compartment, as well as small fast and slow turnover compartments, were identified in each experiment. Surface calcium (Ca2+) was determined by its displacement with 1 mM La3+ after asymptote had been reached during 45Ca2+ labeling (1.59 mmol Ca2+/kg dry wt). The rate constant for this compartment was faster than the washout of the chamber (greater than 3.4 min-1 with a t1/2 less than 12 s). The rate constants for the fast and slow exchangeable compartments were 0.11 min-1 (t1/2 = 6.5 min) and 0.013 min-1 (t1/2 = 56 min), respectively. The fast compartment contained 0.40 mmol Ca2+/kg dry wt and the slow compartment contained 0.27 mmol Ca2+/kg dry wt. Neither the fast nor the slow compartment was lanthanum displaceable. Release of 45Ca2+ in response to 100 microM phenylephrine, 10 nM angiotensin II, and 100-microM 2,5-ditert-butyl hydroquinone was measured during the washout phase. Ca2+ released by these compounds was determined to be 0.50 mmol 0.44, and 0.43 mmol Ca2+/kg dry cell wt, respectively. These agents had an effect only during the washout of the fast compartment. In conclusion, this novel technique of on-line measurement of 45Ca2+ exchange in hepatocyte monolayers identified three exchangeable compartments: (1) a very rapidly exchangeable surface compartment, (2) a fast "microsomal" hormone-releasable compartment, and (3) a slow, non-hormone-releasable compartment.

Angiotensin II↗
PubMed1989

Pancreatobiliary responses to an intragastric amino acid meal: comparison to albumin, dextrose, and a maximal cholecystokinin stimulus.

Little is known about how gastric and pancreatobiliary responses differ after intake of elemental diets from responses to polymeric food. We therefore compared pancreatic and biliary secretions after gastric instillation of albumin (7 g%, with dextrose 21 g%) with an elemental diet in 6 healthy volunteers. The elemental diet contained amino acids (7 g%, with dextrose 21 g%) in the same molar composition as the albumin. Furthermore, we studied the effect of a pure intragastric dextrose solution (21 g%) on pancreatobiliary secretions, as glucose constitutes a major component of elemental diet formulas. The various pancreatobiliary responses were tested against a maximal i.v. cholecystokinin stimulus. The dextrose, amino acid, and albumin meals emptied at similar rates, and gastric emptying was completed within 3 h. Similar pancreatobiliary responses were observed after the albumin and amino acid meals, but response to both the amino acid and albumin meals was smaller than to the intravenous cholecystokinin stimulus. The glucose meal caused a marked and sustained stimulation of pancreatobiliary outputs, which did not differ significantly from the other test meals. However, lower cholecystokinin levels were observed after the glucose meal compared with distinct cholecystokinin release after the albumin and amino acid meals. We conclude first that there are no major differences in secretory responses between elemental (amino acid) and polymeric (protein) meals and second, that intragastric pure glucose meals strongly stimulate pancreatobiliary secretions. The marked pancreatic and biliary responses to intragastric dextrose cannot be fully explained on the basis of cholecystokinin release, suggesting that this response is probably mediated by neural mechanisms.

Adult↗
PubMed1989

Computerized curve fitting in the analysis of hydrogen gas clearance curves.

Hydrogen gas clearance curves obtained from the rat gastric corpus were digitized into a computer and then analyzed by three methods: 1) linear regression of log-transformed data, 2) direct curve fitting with a modified Gauss-Newton nonlinear regression algorithm, and 3) Zierler's height-over-area algorithm. For linear regression of log-transformed data, if the initial base-line estimate was inaccurate or normal amounts of experimental noise were present, the log-transformed data was skewed, leading to deviation of the regression line and incorrect estimation of blood flow. By utilization of the direct-fit routine, the initial estimate of the parameters or experimental noise had little influence on the blood flow determination because of iterative improvement of the parameters. In a study of isoproterenol-stimulated gastric blood flow, Zierler's algorithm underestimated the blood flow estimate. We conclude that analysis of hydrogen gas clearance curves by linear regression of log-transformed data or by Zierler's algorithm may potentially introduce errors in blood flow estimates that may be avoided by analysis with a direct-fitting, nonlinear regression algorithm.

Algorithms↗
PubMed1987

Reflectance spectrophotometry for the assessment of gastroduodenal mucosal perfusion.

Reflectance spectrophotometry in assessing gastroduodenal mucosal perfusion was evaluated. Ischemia without congestion, e.g., during hemorrhagic hypotension or celiac artery occlusion, was associated with a reduction in the indexes of mucosal hemoglobin concentration and of oxygen saturation. Ischemia with congestion, e.g., during portal vein occlusion, or in absolute ethanol or suction-induced mucosal lesions, was associated with an increase in the index of mucosal hemoglobin concentration but a reduction in the index of oxygen saturation. An increase in the index of mucosal hemoglobin concentration associated with a normal index of oxygen saturation was found in the postischemic hyperemia after release of celiac artery occlusion and during the sustained increase in corpus mucosal blood flow induced by vagus nerve stimulation. Thus reflectance spectrophotometric measurements reflected ischemia, without or with congestion, and hyperemia. Additionally, although regional differences in reflectance spectrophotometric measurements were demonstrated in the duodenal, antral, and corpus mucosa, such differences bore no consistent relationship to regional differences in blood flow demonstrated in previous studies.

Animals↗
PubMed1986

Effects of viscosity and fluid outflow on postcibal gastric emptying of solids.

It is known that the food-filled stomach retains large spheres or pieces of food, allowing the passage of food particles or of plastic spheres with diameters mainly below 2 mm. We have recently shown that spheres having densities greater or less than water emptied from the food-filled canine stomach more slowly than spheres of the same diameter with a density of 1. Thus, hydrodynamics seem to govern gastric emptying of spheres. The present studies were undertaken to determine how altering other hydrodynamic factors, viscosity and velocity of fluid outflow, might affect gastric sieving. Ten mongrel dogs were prepared with chronic duodenal fistulas, which allowed collecting and measuring of emptied spheres and food. The dogs were fed a standard meal of 75 g of steak plus 25 g of 99mTc-labeled chicken liver. Immediately afterward, 50 3.2-mm Teflon spheres were instilled into the stomachs along with 200- or 800-ml volumes of saline or saline plus guar (a viscous polysaccharide). Whether 200- or 800-ml volumes were instilled, the guar significantly sped the emptying of the spheres. Fluid outflow was twice as fast after the 800-ml instillates, but the faster outflow with the 800 ml of saline did not speed emptying of spheres. With the guar instillates, the faster outflow slightly sped the emptying of the spheres and significantly increased the diameter of emptied particles of 99mTc-labeled chicken liver. We conclude that meal viscosity significantly affects gastric sieving.

Animals↗
PubMed1985

The histology of the stomach in symptomatic patients after gastric surgery: a model to assess selective patterns of gastric mucosal injury.

We assessed selective patterns of histological injury in the gastric mucosa of 25 patients (12 Billroth II, 8 Billroth I, 5 vagotomy and pyloroplasty) with symptoms of alkaline reflux gastritis. Each patient had 12 biopsies taken from standardised sites. Histology was scored separately for surface epithelial changes and for inflammatory cells. The traditional grading of gastritis was also done using the categories of superficial and atrophic gastritis. The main histological changes were epithelial, especially in the pits (foveolae) of Billroth II patients. Although mild to moderate atrophic gastritis was present, the inflammatory cell density was only mild. Differences between surgery types for any given histological parameter became apparent only upon the analysis of regional changes within the stomach. Conventional grading of gastritis is based mainly on degrees of gland loss and thus is mainly of value to study chronic changes. However, the type of histological evaluation used here, with standardised biopsy sites, and separate scoring of epithelial and inflammatory changes is potentially more suitable to study shorter term changes as might occur with cytoprotective or damaging agents.

Biopsy↗
PubMed1984

Glucose perfusion intragastric titration.

A comparison was made between use of isotonic 0.15 M sodium chloride and 5.8 g/100 ml glucose solutions for measurement of gastric acid secretion by intragastric titration in normal and ulcer subjects. Glucose distention did not cause significantly different acid secretion than saline distention in either group. The total amounts of glucose entering the duodenum over the 3.5-hr study period were 99 g in normal subjects and 122 g in ulcer subjects. In normal subjects, circulating gastrin-related acid secretion curves were not significantly different during endogenous peptone and exogenous G-17 stimulation using either the glucose or the saline meals. This finding provides evidence that glucose meals of this size do not alter sensitivity to gastrin. With glucose meals, inhibition of gastric emptying caused retention of a sufficient volume in the stomach to permit accurate continuous intragastric titration. Saline meals caused pronounced diarrhea which was not seen after glucose meals. Glucose distention intragastric titration allows reliable comparisons of endogenously and exogenously stimulated gastric acid secretion without serious side effects and is especially suitable for studying acid secretion in duodenal ulcer subjects.

Adult↗
PubMed1984

Similar acid stimulatory potencies of synthetic human big and little gastrins in man.

A newly synthesized human big gastrin (G34) that was prepared according to the revised structure and that contained less than 3% oxidized methionine residues was compared with synthetic human little gastrin (G17) for acid-stimulating activity and clearance in human subjects. Prolonged infusions of each type of gastrin revealed that the time required to approach stable plasma concentrations was much longer for G34 than for G17. The time course of plasma gastrin concentration could be described by one-compartment models with half-lives of 44 min for G34 and 8 min for G17. After rapid intravenous infusion, G34 produced a much larger total acid response than did an equimolar dose of G17, and the responses were directly proportional to the integrated plasma gastrin increments. During the third hour of prolonged intravenous infusions of G34 and G17, the exogenous dosage of G34 required to produce the same blood concentration of gastrin was only one-fourth that of G17. Equivalent blood concentrations of G34 and G17 were associated with similar rates of acid secretion. These results suggest that G34 is more potent than has been thought, that it has an activity similar to that of G17 and that it must not be ignored in estimating total acid-stimulating activity of circulating gastrins. The measurement of total carboxyl-terminal immunoreactive gastrin can produce a good estimate of total acid-stimulating activity.

Adult↗
PubMed1984

Gastric emptying and sieving of solid food and pancreatic and biliary secretions after solid meals in patients with nonresective ulcer surgery.

This study was undertaken to compare with previously published findings in normal subjects and subjects after truncal vagotomy and antrectomy the effects of nonresective ulcer surgery on (a) gastric emptying, grinding, and sieving of solid food and on (b) pancreatic and biliary secretions. Six subjects with proximal gastric vagotomy and 7 subjects with truncal vagotomy with pyloroplasty were studied using a previously validated indicator perfusion system with its aspiration port placed in the proximal jejunum. All subjects were given a meal of 30 g of 99mTc-liver, 60 g of beefsteak, and 100 ml of H2O. In conjunction with a gamma-camera to measure total gastric emptying of 99mTc-liver, this method allowed us to estimate the fraction of 99mTc-liver emptied from the stomach as particles of less than 1-mm diameter; in addition, we were able to measure jejunal concentrations and outputs of bile salts and pancreatic enzymes. In subjects with proximal gastric vagotomy, all parameters studied were indistinguishable from normal. Subjects with truncal vagotomy and pyloroplasty behaved similarly to subjects with vagotomy and antrectomy, showing (a) early precipitous emptying of food, (b) heterogeneous distribution of half-emptying times, (c) near normal concentration of biliary and pancreatic secretions, (d) markedly reduced jejunal flow rates, and (e) a reduction in postcibal trypsin secretion. In contrast to subjects after truncal vagotomy and antrectomy, however, the majority of subjects with vagotomy and pyloroplasty did not show a persistent defect in grinding and sieving of solid food.

Bile↗
PubMed1981

Simultaneous gastric emptying of two solid foods.

A variety of radionuclide-labeled, solid foods have been used to measure gastric emptying. Implicit is the idea that the nuclide label identifies the rate of emptying of meal contents. The present studies tested whether different foods empty from the human stomach at different rates. Eight volunteers were fed meals of 200 ml of water + 213 g of beef stew + 52 g of chicken liver, with half the liver as 0.25-mm particles and half as 10-mm chunks, labeled with 99mTc and 113mIn, respectively, or the reverse. Another 8 subjects ingested 200 ml of water + 75 g of noodles, labeled with 123I, + 30 g of liver, labeled with 113mIn. Gastric emptying of each radionuclide was determined for 3 h by measuring the decline of counts in the gastric region of interest, using an Ohio Nuclear S410 gamma camera interfaced to a DEC computer. In each case, appropriate corrections were made for nuclear decay, down-scatter from 113mIn, and septal penetration. Seven of 8 subjects emptied 0.25-mm liver particles more quickly than 10-mm chunks of liver, while 1 subject emptied the two sizes of liver at the same rate. The t 1/2 for the 0.25-mm liver was 70 +/- 10 min; and for the 10-mm liver, 117 +/- 19 min (p less than 0.05). Six of 8 subjects emptied noodles much faster than liver, while 2 emptied the two foods at similar rates. The t 1/2 for the noodles was 52 +/- 8 min; and for the liver, 82 +/- 5 min (p less than 0.02). Since different foods in the same meal were found to empty at different rates, we conclude the gastric emptying of every food in a meal is not accurately represented by the emptying of a single, nuclide-labeled food. The different t 1/2s for the emptying of 10-mm liver in the two meals (p less than 0.05) probably reflected the influence of other meal components on gastric motility.

Food↗