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Biomedical subjects

F G Moody

Publications and source records attributed to F G Moody.

At least 91 records · Page 5Linked to original sources

An evaluation of naloxone as a gastric cytoprotective agent during hemorrhagic shock.

Administration of naloxone, an opiate antagonist, is known to improve survival from hemorrhagic shock and to reverse the effects of septicemia on gastric mucosal O2 tension and potential difference (PD). We tested these potentially cytoprotective actions in the ex-vivo canine gastric chamber model with acid, bile, and hemorrhagic hypotension. Naloxone (2 mg/kg IV bolus, then 2 mg/kg/hr IV) was given before or during shock. Naloxone did not affect oxygen consumption, the bile-induced drop in PD, or the transmucosal oxygen consumption, the bile-induced drop in PD, or the transmucosal movements of H+, Na+, K+, and fluid. The reduction in average mucosal lesion formation with naloxone pretreatment (5.4 +/- 1.2 vs. 2.8 +/- 0.5%) was not statistically significant (p = 0.07). Similarly, administration of naloxone after the onset of shock also failed to protect the mucosa from stress ulceration. We conclude: 1) naloxone does not inhibit the effects of topical bile on the gastric mucosal barrier; 2) naloxone has no apparent effect on local gastric vascular resistance during hemorrhagic shock; and 3) the therapeutic potential of naloxone as an anti-ulcer drug is questionable. 24GM 23095

Acute Disease↗

Preoperative percutaneous transhepatic drainage: use or abuse. A clinical review.

The benefit of preoperative percutaneous transhepatic biliary drainage in patients with obstructive jaundice was reviewed in the literature from 1974 to July 1984. The role of preoperative drainage cannot be definitively assessed. Significant reduction of morbidity and mortality has been reported in some non-controlled studies; however, no benefit of preoperative "external" drainage was found in the only two reported randomized studies. At the present time external preoperative drainage cannot be advised routinely and the hazards of this technique and effect of bile losses may outweigh the benefits. The benefits of preoperative internal drainage without bile loss and closing of the enterohepatic cycle needs to be evaluated both percutaneously and endoscopically. Criteria, developed after specific identification of high risk patients, should be used to select patients for biliary drainage and to evaluate results of drainage studies. The clinical well-accepted drainage period of 2-4 weeks is controversial and the optimum period of drainage also requires further evaluation. The percutaneous approach carries significant morbidity and mortality.

Biliary Tract Surgical Procedures↗

Weight loss and metabolic changes of morbidly obese patients after gastric partitioning operation.

UNLABELLED: Weight loss, alterations in basal metabolic rate, and utilization of body fat, carbohydrate, and protein substrates were studied in nine patients before operation and 3 and 12 months after gastric partitioning operation for morbid obesity. Respiratory oxygen consumption and carbon dioxide excretion measurements were taken three consecutive mornings by the open circuit-Scholander technique. Measurements of urine urea nitrogen were made from 24-hour urine collections. Basal metabolic rate and utilization of fat, carbohydrate, and protein were calculated in kilocalories per minute by indirect calorimetry. Initial body weight was 124.5 +/- 19.0 kg (mean +/- SD). The weight losses between measurements at months 0 and 3 and at months 3 and 12 were 20.8 +/- 4.6 kg and 2.7 +/- 8.4 kg, respectively. Total weight loss between months 0 and 12 was 23.5 +/- 8.3 kg (19.3% +/- 7.4%). At 3 months the fraction of basal metabolic rate contributed by carbohydrate (p less than 0.05) and protein (p less than 0.01) utilization decreased significantly, while that contributed by fat increased (p less than 0.05). Between months 0 and 12 there was no significant difference in protein or carbohydrate utilization, but fat utilization increased (p less than 0.10). CONCLUSIONS: Gastric partitioning operation resulted in an initial rapid body weight loss over 3 months with a sustained reduction over 1 year; there was a metabolic utilization shift to fat with carbohydrate and protein sparing; no metabolic parameter was predictive of weight loss; and temporally, the rapid weight loss was paralleled by a significant metabolic utilization shift, and the sustained loss was paralleled by a stabilization of this shift.

Adipose Tissue↗

Transduodenal sphincteroplasty and transampullary septectomy for postcholecystectomy pain.

Ninety-two patients underwent a transduodenal sphincteroplasty and transampullary septectomy (extended papilloplasty) for chronic, incapacitating upper abdominal pain over an 11-year period. Seventy-nine had a prior cholecystectomy; 42 of 56 patients with reported pathology had documented gallstone disease. Serious morbidity included two moderately severe cases of postoperative pancreatitis and a pulmonary embolus. There were no deaths. Operative findings revealed stenosing papillitis (n = 45), transampullary septitis (n = 40), and papillary dysfunction (n = 7). Histologic examination of septal biopsy specimens revealed inflammation in 34 cases and fibrosis in 19 cases. There were no microscopic abnormalities in 39 biopsy specimens. The results at 1 to 10 years in 83 patients is as follows: good in 36 patients (no pain--43%), fair in 27 patients (occasional pain--33%), and poor in 20 patients (unrelieved by the procedure--24%). Patients with prior sphincteroplasty (12 of 15 with a fair to good result) benefitted the most from the procedure. Those who underwent concomitant cholecystectomy responded poorly. Risk factors for failure include alcoholism, drug addiction, mental illness, and duodenal ulcer disease. The finding of papillary cholesterolosis at operation also was accompanied by a less than optimal result. Transduodenal sphincteroplasty with transampullary septectomy provides long-term benefit to carefully selected patients with chronic abdominal pain after cholecystectomy.

Abdomen↗

The effect of diet on ouabain binding to erythrocytes from obese subjects.

Ouabain binding to erythrocyte membranes is increased in obese subjects. Three study groups are compared: 14 reference subjects, 102 +/- 16% of ideal weight; 9 obese on unrestricted diets, 207 +/- 16% of ideal weight; 11 obese on restricted diets, 202 +/- 35% of ideal weight. A reproducible (CV = 11.3%) ouabain-binding assay is used to measure Na+-K+ ATPase sites in erythrocyte membranes. The number of binding sites per red blood cell for obese subjects on unrestricted diets, 431 +/- 30, is greater than for the reference group, 346 +/- 66 (p less than 0.01), or for obese subjects on restricted diets, 371 +/- 68 (p less than 0.05). These data suggest that caloric intake influences the number of Na+-K+ ATPase sites. Scatchard plots indicate only one type of binding site for ouabain with an affinity constant of about 3 X 10(8) M-1.

Adolescent↗

Stimulation of canine gastric mucus secretion with intraarterial acetylcholine chloride.

This study was undertaken to develop an easily reproducible gastric mucus secretory model that would elicit maximal mucus secretion without gross mucosal injury. Acetylcholine chloride (50 micrograms/min) was infused intraarterially into a chambered wedge of exteriorized corpus mucosa via a branch of the gastrosplenic artery for 1 h. An alkaline secretion, pH 8.28 +/- 0.48, was produced and consisted of water (40-60 ml/h), electrolytes (Na+, K+, Cl-), soluble mucus, and a mucus gel (4-10 mm thick). Mucus was quantitated by monitoring the secretion of newly synthesized glycoproteins, radiolabeled with [3H]glucosamine and sodium [35S]sulfate. A transient increase in deoxyribonucleic acid efflux, and mucosal permeability as measured by albumin movement, occurred, both of which were reversible upon cessation of acetylcholine chloride infusion. The gastric epithelium was normal histologically, except for occasional apical vacuoles present only in interfoveolar mucus cells. Transmission electron microscopy revealed diminished numbers of apical mucus granules and greatly enlarged intercellular spaces in some mucus cells. Histochemically, the mucus gel consisted of alternating layers of sulfate-rich and sulfate-poor glycoproteins. This model provides a copious amount of mucus that is ideal for biochemical analysis and determination of mucus structure. It allows one to distinguish soluble mucus, gel mucus, and unsecreted granule-bound mucus.

Acetylcholine↗

Piperacillin distribution into bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue in surgical patients.

The concentrations of piperacillin in serum, bile, gallbladder wall, abdominal skeletal muscle, and adipose tissue were measured simultaneously at various times after the intravenous administration of a single 5-g dose to each of 14 patients undergoing biliary tract surgery. Piperacillin concentrated in the bile with peak levels exceeding 4,000 micrograms/ml. In a single patient with cystic duct obstruction, trace gallbladder bile piperacillin levels were measured. Gallbladder wall concentrations of piperacillin tended to be higher than corresponding serum concentrations, with a correlation observed between tissue values and the degree of acute gallbladder inflammation and gallbladder bile piperacillin concentrations. Mean peak muscle and adipose tissue piperacillin concentrations of 31 and 27 micrograms/g, respectively, were reached at between 2 and 3 h after the start of infusion. These concentrations exceeded the minimum inhibitory concentration for a majority of susceptible organisms. A single 5-g dose of piperacillin achieved therapeutic levels in gallbladder wall, intraabdominal skeletal muscle, and adipose tissue and concentrated in the bile of patients with patent biliary tracts.

Abdominal Muscles↗

Effect of gastrointestinal hormones on the biliary sphincter of the opossum.

The smooth muscle sphincter enveloping the terminal portion of the common bile duct in the opossum exhibits spontaneous electrical activity and simultaneous rhythmic contractions. The aim of our study was to define the influence of four gastrointestinal hormones on biliary sphincter electrical and mechanical activity. An array of five monopolar extracellular electrodes was placed along the opossum choledochal sphincteric smooth muscle and contiguous duodenum. A catheter in continuity with a pressure transducer, drop counter, and saline reservoir was placed in the common duct for simultaneous measurement of ductal pressure and flow. The cystic and distal common hepatic ducts were then ligated to isolate the common bile duct from the gallbladder and liver. In each opossum, biliary sphincteric and duodenal myoelectric activity, common bile duct and gallbladder pressure, and common duct flow were recorded simultaneously before and after the intravenous administration of five different doses of an enteric hormone. Ten animals were given 0.1-10.0 international dog units per kilogram body wt of cholecystokinin, 10 received 0.01-1.00 microgram/kg body wt of cholecystokinin-octapeptide, 10 were given 0.1-10.0 micrograms/kg body wt of secretin, and 5 were given 0.1-10.0 micrograms/kg body wt of pentagastrin. Cholecystokinin, cholecystokinin-octapeptide, and pentagastrin all effected a significant increase in sphincter electrical spike activity and common duct pressure with a decrease in common duct flow. This contractile response was consistent at a wide range of hormonal levels. Secretin had little effect on biliary pressure, flow, and myoelectric activity. The data lend support to the concept that cholecystokinin and gastrin contract the biliary sphincter, metering bile flow at the time of gallbladder emptying in the opossum.

Action Potentials↗

Surgical therapy for chronic pancreatitis: selecting the appropriate approach.

Surgical therapy of 37 patients with chronic pancreatitis is reviewed. Procedures included longitudinal pancreaticojejunostomy (10), DuVal (5), distal resection (4), pancreaticoduodenectomy (2), sphincteroplasty (7), pseudocyst drainage (6) and other miscellaneous procedures. Complication rates were 30 percent for lateral pancreaticojejunostomy, 28.5 percent for sphincteroplasty and 72.7 percent for resection procedures. The overall complication rate was 54.5 percent, and there were two deaths (5.4 percent). Follow-up is presented on 20 patients, of whom 16 are improved, 2 are unchanged and 2 are worse. Eight patients are dead and nine are lost to follow-up. Ductal anatomy is the most important consideration in the selection of a procedure. Lateral pancreaticojejunostomy, when applicable, is the procedure of choice. Resection should be considered when pancreaticojejunostomy has failed or is not indicated with pancreaticoduodenectomy, the procedure of choice in the diffusely diseased gland. Sphincteroplasty should be reserved for use in stenosing papillitis or as an ancillary procedure. Splanchnicectomy can be used for temporary palliation.

Adolescent↗

The cytoprotective effects of (+/-)-15-deoxy-16-alpha, beta-hydroxy-16-methyl PGE1 methyl ester (sc-29333) versus aspirin-shock gastric ulcerogenesis in the dog.

SC-29333 (SC) has been reported to protect the gastric mucosa from the effects of topical aspirin. We compared SC and 16,16-dimethyl PGE2 (16-dm) in 20 chambered canine stomachs (6 controls and 7 of each PG). Prostaglandin was added to an acid solution (100 mM HCl; 54 mM NaCl) at 0, .001, .01, 0.1, and 1.0 microgram/ml (two periods each). Then aspirin (20 mM) and PG (1.0 microgram/ml) (two periods) were followed by hemorrhagic shock (near 60 mm Hg mean arterial pressure). 16-dm caused a significant efflux of fluid (-6.5 +/- 5.3 to 17.3 +/- 6.7 microliters/min), Na+ (2.1 +/- 0.5 to 6.8 +/- 1.6 muEq/min), and Cl- (-0.9 +/- 2.4 to 5.3 +/- 1.3 muEq/min), but did not affect K+ or H+. 16-dm also caused a slight drop in potential difference (PD) (67.6 +/- 1.7 to 60.3 +/- 2.0 mV). 16-dm did not significantly affect total blood flow. Percent lesion formation was more severe than controls (20.2 +/- 3.5 vs 11.6 +/- 1.7 percent) but not statistically significant. SC had no significant effect on fluid, H+, Na+, K+, or Cl-. It caused an increase in blood flow (6.85 +/- 1.46 to 26.20 +/- 2.74 ml/min, p less than .001). SC significantly reduced percent lesion formation (1.9 +/- 0.9% p less than .001). We conclude: 1) SC causes an increase in mucosal blood flow and protects from aspirin-shock ulcerogenesis. 2) 16-dm stimulates an efflux of non-parietal extracellular fluid and fails to protect against aspirin injury during mucosal ischemia. 3) SC cytoprotection may be mediated by increased mucosal blood flow. 4) The mechanism of cytoprotection with 16-dm may require sufficient mucosal blood flow for filtration of non-acid fluid from blood to gastric lumen.

Animals↗

Surgical applications of sphincteroplasty and choledochoduodenostomy.

The papilla of Vater is subject to a variety of abnormalities that include congenital anomalies, inflammation, neoplasms, fibrosis, and motor dysfunction. Some of these lesions are clinically obvious (such as cancer or an impacted gallstone) and require aggressive therapy in order to provide relief from pain or biliary-pancreatic ductal obstruction. Other lesions, such as stenosing papillitis, are more subtle and provide few clues to their existence except recurrent episodes of abdominal pain. I have focused my discussion on the relative indications for sphincteroplasty and choledochoduodenostomy in the management of benign lesions of the papilla, especially those related to gallstone disease. I prefer a choledochoduodenostomy for the management of recurrent common duct stones when the bile duct is enlarged (greater than 2 cm) and thick-walled. The opening should be at least 2 cm in length when the anastomosis is completed. I employ a long anterior sphincteroplasty (greater than 2 cm) with a transampullary septectomy when treating inflammatory or fibrosing lesions of the papilla of Vater which are associated with recurrent episodes of severe, chronic (more than 1 year) abdominal pain. There is currently no standardized way to diagnose these latter conditions, therefore, the approach is empirical, and should be used sparingly and with a high degree of caution.

Ampulla of Vater↗

Myoelectric control of gastrointestinal and biliary motility: a review.

The movement of ingested food and secretions through the gastrointestinal and its appendages depends on a highly integrated and coordinated response of the smooth muscle contained within the wall of the gut. This review will consider, in detail, the various myogenic factors that contribute to the usual aboral propulsion of the gastrointestinal contents. The role of myoelectrical complexes as represented by slow waves and spike potentials are emphasized, for they appear to play a central role in the initiation of sphincter function and gastrointestinal peristalsis. The myoelectric control of the sphincter of Oddi is discussed in relationship to gastroduodenal motility, since disturbances in this finely modulated sphincter may lead to biliary-pancreatic dysfunction and symptoms of upper gastrointestinal disease.

Animals↗

Controlled intragastric pH and cimetidine inhibition of histamine-stimulated gastric acid secretion in the dog.

This study tested a circulating intragastric titration system with an examination of the kinetics of cimetidine inhibition of histamine-stimulated gastric acid secretion of pH 7.0. Dogs were anesthetized, intubated with a biluminal nasogastric device, and connected to the titrating system. The dogs were stimulated with histamine at 0.0, 0.25, 0.50, 1.0, 2.0, and 4.0 microgram/kg/min IV. The dose variations were repeated on separate days with cimetidine infusion at 0.0, 20, and 40 microgram/kg/min IV. Calculated maximal response was 4.52 mEq/kg/hr. Histamine D50 was 0.60 microgram/kg/min. Cimetidine ID50 was 22.6 microgram/kg/min when histamine was given at 1.0 microgram/kg/min. Although acid secretion was higher than other published values, cimetidine inhibition kinetics were not significantly different from published values. A positive correlation was found between cimetidine ID50 and the logarithm of the histamine infusion rate. Our data suggest that (1) a simple circulating intragastric titration system can give accurate results in acid secretion studies, (2) increased gastric pH may enhance histamine-stimulated acid secretion, (3) neutralization of gastric contents does not interfere with cimetidine inhibition kinetics which is competitive, and (4) at artifically high rates of histamine infusion, cimetidine can actually increase acid secretion. We suggest that a circulating intragastric system may be tested in a surgical intensive care unit to evaluate potential clinical value in antiulcer therapy.

Animals↗

Focal microcirculatory changes during the production of aspirin-induced gastric mucosal erosions.

Ischemia of the gastric epithelium has emerged as one of the more likely mechanisms for gastric ulceration. Radiolabeled microspheres (15 mu) were used to measure blood flow to exteriorized, chambered stomach segments in eight dogs during the development of aspirin erosions. Flow determinations were made before aspirin (20 mM in 140 mM HCl) exposure and at 2, 10, and 20 minutes after the initiation of the chemical insult. Lesions formed at 30 minutes of acetylsalicylic acid exposure. The epithelium was separated into normal and injured, based on gross discoloration caused by intramucosal hemorrhage. The calculated blood flows to the abnormal and normal mucosa were identical at 2 minutes (0.22 +/- 0.04 versus 0.15 +/- 0.03, NS) and at 10 minutes (0.39 +/- 20 versus 0.17 +/- 0.04, NS) after initiation of aspirin injury (all values in ml/gram-wet weight/min, mean +/- SEM). By 20 minutes of aspirin exposure, mucosal blood flow to areas that eventually became injured was greater than the blood flow to areas that remained normal (0.45 +/- 0.12 versus 0.13 +/- 0.05 P less than 0.05). The data suggest that ischemia does not play a role in chemical erosive gastritis.

Animals↗