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Biomedical subjects

L DenBesten

Publications and source records attributed to L DenBesten.

At least 55 records · Page 3Linked to original sources

Animal models of human cholesterol gallstone disease: a review.

Human cholesterol gallstone disease has been a frequent and serious problem. A number of animal models have been reviewed for comparative study of cholesterol lithogenesis. These models in general have involved (1) decreasing bile salt excretion, (2) increasing dietary cholesterol, or (3) inducing gallbladder infection or stasis.

Animals↗

Subtotal colectomy for refractory pseudomembranous enterocolitis.

Pseudomembranous enterocolitis resulting from therapy with antibiotics such as clindamycin and lincomycin hydrochloride monohydrate does not always respond to drug and vigorous medical support. We describe two seriously ill patients who recovered after subtotal colectomy with ileostomy.

Adult↗

Duodenojejunostomy in gastric operations for postbulbar duodenal ulcer.

In two cases, two different techniques of duodenojejunostomy were employed as an alternative to an insecure closure of the "difficult duodenal stump." The arrangements are either duodenojejunostomy Roux-en-Y or isoperistaltic jejunal interposition. A single-layered suture line is employed. The ampulla of Vater is visualized during the construction of these anastomoses. In addition to obviating a tenuous stump closure, this technique has the theoretical advantage of providing internal drainage.

Aged↗

The mechanism of increased gallstone formation in obese human subjects.

Cholesterol gallstones occur three times more frequently in morbidly obese subjects than in normal controls. The present study tests the hypothesis that obese subjects develop gallstones because of relative and absolute excess cholesterol excretion in bile. The steady-state kinetics of biliary lipid excretion and bile acid pool sizes were determined in eight healthy obese subjects without gallstones by a noninvasive technique. Aliquots of resting gallbladder bile were obtained on consecutive days. Hepatic bile excretion was constantly sampled during the infusion of a liquid isocaloric cholesterol-free formula containing a dilution indicator over two 12 hour periods on consecutive days. Gallbladder bile of seven of eight subjects was saturated consistently with cholesterol. Mean hourly hepatic cholesterol excretion in bile was 0.232 mM. per hour, three times greater than that of normal subjects and twice that of subjects with gallstones. Phospholipid and bile acid excretion were 0.73 and 1.88 mM. per hour, respectively. The excretion rates of these cholesterol-solubilizing components of bile are higher than in normal subjects but are insufficient to compensate for the increased cholesterol excretion. The bile acid pool sizes were normal (X = 2.72 Gm.) but the daily synthesis of bile acids was increased (X = 0.86 Gm. of cholic acid). We conclude that the clinically observed high correlation of cholelithiasis with obesity is due to increased hepatic secretion of cholesterol which precipitates as cholesterol gallstones.

Absorption↗

Metabolic effects of amino acid vs dextrose infusion in surgical patients.

We tested the hypothesis that during infusion of amino acids without dextrose, there is less insulin stimulation, which, in turn, permits lipolysis. The results suggest that dextrose infusion stimulates insulin and inhibits lipolysis. During administration of crystalline amino acids without dextrose, nitrogen balance improved substantially from control values obtained during dextrose infusion, while the level of serum-free fatty acids and ketone bodies rose and that of serum immunoreactive insulin fell. Infusion of amino acids at 1.7 gm/kg appeared slightly more efficient than infusion at 1.0 gm/kg and did not stimulate insulin or inhibit lipolysis. Protein sparing may be useful in certain specific clinical situations. However, the results must be interpreted cautiously, primarily because it is difficult to establish the relationship between improvement in nitrogen balance and the derived clinical benefit. Absolute proof of the efficacy of this technique awaits further studies using indexes that more accurately measure protein synthesis.

Adult↗

Analysis of gallbladder bile in morbid obesity.

Thirty-seven per cent of our grossly obese patients selected for gastric bypass had cholesterol gallstones. To document the composition of the biliary lipids prior to weight loss, the bile taken from eleven obese patients at the time of gastric bypass was analyzed and the results compared with those in eleven nonobese patients undergoing elective surgery. There was extreme supersaturation of both gallbladder and hepatic bile in all obese patients. The gallbladder bile of all obese patients fell well outside the micellar zone whereas the bile from all but one of the controls fell within the micellar zone. These data provide biochemical support for the clinical association of obesity and cholesterol gallstone formation and are evidence against the possibility that gastric bypass is a lithogenic operation.

Adolescent↗

Hydrogen ion transport in the rabbit esophagus.

The lumen of the rabbit esophagus was perfused in vivo with solutions (one solution per esophagus) containing 0-160 mM HCl by a constant circulation technique for 5 h. During the 1st h, net H+ flux out of the lumen (efflux) was minimal at H+ concentrations of 80 mM or less, but increased linearly with increase in luminal H+ concentrations above 80 mM. After 3 h, the net H+ efflux increased proprtionately to increasing H+ concentrations above a threshold of 20 mM. At the 5th h a linear relationship between net H+ efflux and luminal concentration was seen at all concentrations. Histological damage accompanied increase in H+ efflux and correlated with luminal acid concentrations and duration of exposure. We conclude that the rabbit esophageal mucosa is essentially impermeable to H+ below a threshold concentration of 80 mM for up to 1 h of exposure. When exposure is prolonged, this threshold steadily decreases with time. The occurrence of passive H+ diffusion above threshold concentrations most probably results from an increase in mucosal permeability, possibly an initiating event in the genesis of esophagitis.

Animals↗

The development of essential fatty acid deficiency in healthy men fed fat-free diets intravenously and orally.

The hypothesis that clinical and biochemical essential fatty acid deficiency (EFA) might occur from the feeding of eucaloric, fat-free diets was tested in two experiments in healthy men. In Study I, eight men were given fat-free, eucaloric diets containing 80% of calories as glucose and 20% as amino acid hydrolysates by a constant drip over a 24-h period. The diets were fed in succession for periods of 2 wk each, either through a superior vena cava catheter or via a nasogastric tube. EFA deficiency was detected by decreases in linoleic acid and by the appearance of 5, 8, 11-eicosatrienoic acid in lipid fractions of plasma. Linoleic acid decreased significantly during 2 wk of the fat-free diet given intravenously from 48.8 to 9.8% (percent of total fatty acids) in cholesterol esters, from 21.2 to 3.2% in phospholipids, from 9.6 to 2.0% in free fatty acids, and from 14.1 to 2.6% in triglycerides. Eicosatrienoic acid, normally undetectable, appeared 0.6% in cholesterol esters, 2.5% in phospholipids, 0.2% in free fatty acids, and 2.3% in triglycerides. EFA deficiency occurred similarly during the nasogastric feeding. In Study II a subject received the same diet continuously by the nasogastric route for 10 days followed by a 24-h fast. He was then given the fat-free diet intermittently in three meals per day for 3 days. Finally, he was repleted with a diet containing 2.6% linoleic acid. By the 3rd day of the continuous nasogastric feeding, linoleic acid had fallen significantly and eicosatrienoic acid had appeared in plasma lipid fractions as in Study I. These findings were accentuated by day 10. Adipose tissue fatty acid composition did not change. Free fatty acid outflow from adipose tissue was presumably suppressed during the 10 days of continuous feeding. With increased free fatty acid outflow during fasting and intermittent feeding, linoleic acid rose and eicosatrienoic acid decreased. After 13 days of repletion with dietary linoleic acid, the EFA deficiency readily develops when fat-free diets containing glucose are given intravenously or orally as constant 24-h infusions. These diets are similar to the hyperalimentation formulas now being used clinically.

Adipose Tissue↗

Cholecystokinin cholangiography and analysis of duodenal bile in the investigation of pain in the right upper quadrant of the abdomen without gallstones.

Thirty-one patients with recurrent symptoms of the biliary tract and repeated normal oral cholecystograms were studied by a combination of cholecystokinin cholangiography and biliary drainage. Ten patients had reduplication of their symptons because of dyskinetic contractions or obstruction of the cystic duct, and seven patients had delayed gallbladder emptying without pain due to hypokinetic contractions. Five patients had abnormal duodenal bile characterized by supersaturation and the presence of crystals or bacteria. Based upon these studies, 22 patients had cholecystectomy and 20 were cured, while two showed improvement. There were no therapeutic failures. Cholecystokinin cholangiography capably detects the presence of neuromuscular disease of the gallbladder wall, whereas the oral cholecystogram tests for mucosal function or the presence of filling defects. An additional group of patients who have cholesterosis, cholecystitis, or cholelithiasis missed by the oral cholecystogram will not be diagnosed by cholecystokinin cholangiography unless the duodenal bile is also examined.

Abdomen↗