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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 181 records · Page 10Linked to original sources

Bile acid metabolism in the cirrhotic rat.

Bile acid metabolism was studied in rats with cirrhosis induced by carbon tetrachloride (CCl4). Although the typical histologic features of cirrhosis were seen, cholestasis was not present in these animals as evidenced by a normal total serum bilirubin concentration and by a normal hepatic capacity to remove taurocholate infused intravenously. The cirrhotic rats also secreted taurocholate into bile at a normal rate. The total bile salt pool size in the cirrhotic rats was not significantly different from the pool size in normal rats (10.59 +/- 1.19 mumoles per gm. of liver (+/- 1 standard error of the mean) and 10.43 +/- 0.92 mumoles per gm. of liver, respectively). When the bile was drained externally through a chronic bile fistula, the normal rats increased the bile salt synthetic rate approximately 3-fold after 48 hours of drainage. However, the cirrhotic rats failed to significantly increase the synthetic rate for bile salts in response to biliary drainage. The normal rats also had a significant increase in cholic acid synthesis at the maximal synthetic rate, whereas the cirrhotic rats did not. These findings indicate that (when feedback inhibition is removed) CCl4 cirrhotic rats lack the ability to normally increase the activity of 7 alpha-hydroxylase and 12 alpha-hydroxylase, rate-limiting enzymes in the synthesis of bile salts.

Animals↗

Serum isoamylase measurements in pancreatitis complicating chronic renal failure.

This investigation was designed to determine whether serum isoamylase measurements can aid in establishing the diagnosis of acute pancreatitis in renal failure patients. Twenty-two hemodialysis patients were studied, four of whom had documented acute pancreatitis. Total serum amylase and pancreatic isoamylase concentrations were significantly higher (p less than 0.02) in the pancreatitis patients than in the 18 patients without pancreatitis, but there was appreciable overlap between these two groups. In each of the four patients with pancreatitis, the percentage of serum amylase derived from the pancreas (range, 80% to 90%) was well above the highest value (67%) observed in the patients without pancreatitis. These results suggest that determination of the percentage of serum amylase represented by pancreatic isoamylase is of assistance in establishing the diagnosis of acute pancreatitis in renal failure patients.

Acute Disease↗

Relation between serum pancreatic isoamylase concentration and pancreatic exocrine function.

Serum pancreatic isoamylase concentrations were compared to secretory and clinical evidence of pancreatic insufficiency in 19 consecutive alcoholic patients undergoing pancreatic stimulation testing for suspected pancreatic insufficiency. In patients with normal total serum amylase levels, there was a good correlation (r = 0.83) between serum pancreatic isoamylase activity and stimulated pancreatic secretion of amylase and the 8 patients with a low pancreatic isoamylase concentration had markedly diminished pancreatic secretion of amylase, lipase, and bicarbonate. However, patients with elevated total serum amylase activity frequently had extremely poor pancreatic exocrine function despite normal or elevated levels of pancreatic serum isoamylase. Thus, the finding of a subnormal serum concentration of pancreatic isoamylase provides strong evidence for pancreatic exocrine insufficiency; however, a normal or elevated serum pancreatic isoamylase activity cannot be used as evidence for normal pancreatic exocrine function.

Adult↗

Effect of dietary fiber on intestinal gas production and small bowel transit time in man.

The influence of dietary fiber on intestinal gas production and on small bowel transit time was studied in eight healthy subjects using breath H2 excretion as an indicator of colonic gas production. Hydrogen excretion following ingestion of bran was substantially less than that following ingestion of lactulose, a nonabsorbable fermentable sugar. Likewise, human fecal homogenates produced only about 10% as much H2 and CO2 during incubation with bran as with glucose or lactulose. Thus, the polysaccharides in bran appear to be relatively poor substrate for colonic bacterial gas production, and reported gas-related symptoms after bran ingestion may be due to some other mechanism. The small bowel transit time of bran was greater than that of lactulose; however, addition of bran to lactulose did not slow lactulose transit.

Breath Tests↗

Influence of high luminal PO2 on the anaerobic bacteria of the rat colon.

The influence of high luminal PO2 on colonic anaerobes was investigated by chronically perfusing the colon of unrestrained rats with O2 or N2. A luminal PO2 of approximately 700 mm Hg did not significantly influence the fecal concentration of total anaerobes recovered on rabbit blood agar or of Bifidobacterium sp. and Bacteroides sp. recovered on selective media. However, the O2 infusion reduced the rat's excretion of CH4 (a metabolic product of anaerobic bacteria) to about 5% of the control value, although the feces of O2-treated rats produced CH4 normally. This study suggests that the production of metabolites by the colonic bacteria may sometimes be more accurately studied in situ rather than in culture. Measurement of volatile bacterial metabolites in breath may provide a simple means of studying the in situ metabolism of a variety of colonic bacteria in man.

Actinomycetales↗

Quantitation of countercurrent exchange during passive absorption from the dog small intestine: evidence for marked species differences in the efficiency of exchange.

The present investigation was designed to quantitatively assess the possible influence of countercurrent exchange on passive absorption from the small intestine of the dog. Villus blood flow was measured with a modification of the microsphere method. Simultaneously, the absorption from the gut lumen of five diffusible gases (H2, He, CH4, 133Xe, and CO) was determined. Villus blood flow averaged 0.247 +/- 0.03 (SEM) ml/min per g. The observed absorption of H2, He, CH4, and 133Xe was only 16.2 +/- 1.8, 12.8 +/- 2.3, 12.0 +/- 1.8, and 15.8 +/- 1.4 %, respectively, of what this villus blood flow could carry away if it reached perfect equilibrium with the luminal gases. This low absorption rate could result from diffusion limitation to absorption or countercurrent exchange. The diffusive permeability of the barrier seperating the luminal gases and villus blood flow was assessed by measuring the absorption rate of CO. Because absorbed CO binds tightly to hemoglobin, it cannot exchange, and when present in low concentrations its uptake is entirely diffusion limited. Knowledge of the diffusion rate through tissue of the unbound gases relative to that of CO made it possible to calculate the degree to which each of the unbound gases should equilibrate with villus tip blood. The percentage equilibration between lumen and blood at the villus tip for H2, He, CH4, and 133Xe was 99.7, 99.9, 75.6, and 36.0% , respectively. Each of these values greatly exceeded the percentage equilibration of blood leaving the villus (calculated from the observed absorption rate and villus blood flow) and indicated an exchange of 83.8, 87.2, 84.1, and 56.1% of initially absorbed H2, He, CH4, and 133Xe. This result is in accord with theoretical calculations which suggest that countercurrent exchange should be exceedingly efficient in the dog. The striking effect of countercurrent exchange on passive absorption in the dog differs from our previous studies in the rabbit where no exchange was demonstrated. This marked species difference may result from anatomical differences in villus architecture. The dog has long, densely packed villi while the rabbit has broad, widely spaced villi. In the dog, only the villus tips may equilibrate with the lumen, hence a countercurrent gradient may be established in the villus. The entire villus of the rabbit may equilibrate with the lumen and no gradient for countercurrent exchange can therefore be established.

Animals↗

Influence of amylase assay technique on renal clearance of amylase-creatinine ratio.

The influence of amylase assay technique on the renal amylase/creatinine clearance measurement was determined by analysis of serum and urine specimens obtained from 10 normal subjects. CAm/CCr averaged 2.19 +/- 0.18% with a saccharogenic technique, 1.52 +/- 0.2% with an iodometric technique, and 0.80 +/- 0.08% with a chromogenic technique. Each of these values differed significantly (P less than 0.05) from the other two. Recovery studies were carried out by adding partially purified human salivary or pancreatic amylase to human newborn serum or urine (which contain minimal endogenous amylase). Equal amylase activity was recovered from serum and urine by the saccharogenic technique whereas recovery from urine was less than 50% of that from serum using the iodometric and chromogenic techniques. The accuracy of the chromogenic technique is markedly improved by the addition of albumin to the urine assay system. Although it appears that only the saccharogenic method provides an accurate estimate of CAm/CCr, each assay technique distinguished the elevated CAm/CCr of patients with pancreatitis from the normal range established for that technique. Accurate clinical interpretation of CAm/CCr measurment requires knowledge of the amylase assay technique used.

Amylases↗

Use of breath hydrogen (H2) to quantitate small bowel transit time following partial gastrectomy.

The relation between small intestinal transit time and postgastrectomy diarrhea was investigated with a technique which employs the measurement of pulmonary H2 excretion after ingestion of the nonabsorbable sugar, lactulose. Ten postgastrectomy patients with persistent diarrhea had an average small bowel transit time of 35.2 +/- 3 min (S.E.M.), which was significantly (p less than 0.05) shorter than either that of 10 patients without diarrhea (74.6 +/- 5 min) or 40 healthy controls (72.6 +/- 5 min). These decreased transit times appeared to be due to rapid gastric emptying rather than to a primary intestinal abnormality, since the transit of lactulose instilled directly into the jejunum was equally rapid in patients and controls. All postgastrectomy patients with diarrhea failed to absorb a portion of a 100 gm dose of glucose (quantitated by pulmonary H2 measurements), but all patients without diarrhea and 10 healthy control subjects absorbed the entire dose. Constant perfusion studies of the terminal ileum in two patients indicated that glucose absorption was least efficient from the most rapidly moving front of the ingested bolus of glucose. These studies suggest that the diarrhea observed in some postgastrectomy patients is, in part, the result of malabsorption of carbohydrate due to excessively rapid small bowel transit which is secondary to rapid gastric emptying.

Breath Tests↗