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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 73 records · Page 4Linked to original sources
PubMed1994

Surgery for severe constipation: the use of radioisotope transit scan and barium evacuation proctography in patient selection.

Nineteen women aged 19-64 years (median 38) with intractable constipation were assessed by Indium-111 DTPA colonic transit scan and barium evacuation proctogram. Patients were classified as having an isolated (I) or predominant disorder of colonic transit (II), a mixed disorder of colonic transit and rectal evacuation (III), a predominant disorder of rectal evacuation (IV) or normal colorectal emptying (V). Twelve patients fell into categories I and II and were considered suitable for surgery. Three responded to further vigorous aperient therapy and nine (32-55 years, median 38) underwent subtotal colectomy with ileorectal anastomosis at the level of the sacral promontory. Two patients required re-operation for suspected anastomotic leak. One patient required readmission on two occasions for small bowel obstruction. Follow up has been 2-21 months (median 16). Eight of the nine patients no longer take oral aperients. Eight patients have a satisfactory stool frequency of 2-8 per 24 h; the other patient has an ileostomy and incapacitating postprandial abdominal pain. Abdominal pain is troublesome in two other patients. Two patients require antidiarrhoeal therapy but none experience faecal incontinence. In severely constipated patients with a proven disorder of colonic transit but normal or near normal rectal evacuation subtotal colectomy provides excellent symptomatic relief.

Adult↗
PubMed1994

A comparison of J and W pouches using an isolated ileal reservoir in pigs.

A new model for studying ileal reservoirs was used to compare J and W pouches. Sixteen female piglets were operated on between 62 and 67 days of age (median = 65). An approximately 50 cm vascularized segment of terminal ileum was isolated from the faecal stream and intestinal continuity restored. The distal 40 cm of the isolated loop was opened along its antimesenteric border and the pouch constructed (J = 8, W = 8). The remaining proximal length of ileum was brought out through the abdominal wall as a mucous fistula. One piglet in the W pouch group died post-operatively and in another, spontaneous closure of the mucous fistula prevented access to the W pouch for testing leaving six W and eight J pouches for comparison. Compliance was tested at 4 weeks by measuring intrapouch pressure during continuous distension by water. The volumes instilled at pressures of 20, 40, 60 and 80 cm of water were compared using the Mann-Whitney U-Test. Volumes varied widely at all pressures within both study groups although W pouches tended to be of larger volume for any given pouch pressure (P = NS). The failure of this study to demonstrate more clearly a difference between J and W pouches may be due to the small numbers involved but the wide range of volumes seen raises doubts about the usefulness of this pouch model.

Anastomosis, Surgical↗
PubMed1994

Magnitude, origin, and implications of the discrepancy between blood ethanol concentrations of tail vein and arterial blood of the rat.

The rat is widely used as an animal model for experiments involving ethanol, and alcohol concentrations in blood obtained from the tail routinely are used to monitor ethanol exposure and metabolism. The present study demonstrates that during periods of rising and declining ethanol levels, the alcohol concentrations in tail vein blood lags far behind that of arterial, jugular, or femoral vein blood. As a result, tail vein ethanol concentrations markedly underestimate the concentration in arterial blood and rapidly perfused tissue during periods of increasing body ethanol, whereas the reverse is true as body ethanol declines. This discrepancy, which appeared to result from the low blood perfusion:tissue water ratio in the tail, disappeared when the tail was heated to 37 degrees C. Compared with arterial blood, alcohol measurements performed on tail vein blood yielded a much higher apparent Km for ethanol clearance and a somewhat lower estimate of ethanol reaching the peripheral circulation. We conclude that, for a variety of studies, analyses of arterialized blood from the heated tail should yield a more accurate and reproducible measure of ethanol exposure and/or metabolism than does the conventional collection from the unheated tail.

Alcohol Drinking↗
PubMed1994

Methanogens outcompete sulphate reducing bacteria for H2 in the human colon.

Methanogens and sulphate reducing bacteria compete for H2 in the human colon, and, as a result, faeces usually contain high concentrations of just one of these two organisms. There is controversy over which of these organisms wins the competition for H2, although theoretical data suggest that sulphate reducing bacteria should predominate. To elucidate this question experiments were undertaken in which sulphate enriched homogenates of human sulphate reducing faeces and methane producing faeces were incubated separately or mixed together. Co-incubation of sulphate reducing faeces with methanogenic faeces resulted in a sixfold reduction in the activity of the sulphate reducing bacteria (measured as sulphide production), whereas methane production was not inhibited by co-incubation with sulphate reducing bacteria. Methanogenic faeces also consumed H2 more rapidly and reduced the H2 tension of the homogenate to a lower value than did sulphate reducing faecal samples. In these experiments, methanogens seem to outcompete sulphate reducing bacteria for H2.

Adult↗
PubMed1994

Can the liver account for first-pass metabolism of ethanol in the rat?

Although the liver has far more ethanol-metabolizing capacity than does the stomach, all first-pass metabolism of alcohol is said to occur in the gastric mucosa because hepatic alcohol dehydrogenase is saturated at low peripheral blood alcohol concentrations. We evaluated the ability of the liver to carry out first-pass metabolism in the rat by constructing a model of hepatic handling of ethanol based on the kinetics of ethanol clearance after intraperitoneal injection of alcohol. Because the efficiency of first-pass metabolism is influenced by the rate of delivery of ethanol, the absorption rate of oral alcohol (0.5 g/kg) was determined and applied to the model. The blood ethanol curves predicted by the model for ethanol delivered via the portal vein or via intravenous infusion were virtually identical to the ethanol curves observed in experimental animals with each of these routes of delivery. We conclude that the liver can account for all first-pass metabolism experimentally observed in the rat, and it is not necessary to postulate some extrahepatic site of first-pass metabolism, such as the stomach.

Absorption↗
PubMed1994

Factors affecting the ability of a high beta-galactosidase yogurt to enhance lactose absorption.

Lactose in yogurt is better absorbed by lactase-deficient subjects than is an equivalent quantity of lactose in milk, presumably because of the microbial activity of the beta-galactosidase present in yogurt. In this study, we describe a process that increases the beta-galactosidase of yogurt 5- to 6-fold and the ability of this high lactase yogurt to enhance lactose absorption in lactase-deficient subjects. These subjects ingested the yogurt meals after a 12-h fast, and lactose malabsorption was determined by measuring breath hydrogen. Breath hydrogen was reduced 39% following ingestion of high lactase yogurt from that after consumption of conventional yogurt, indicating that the high lactase yogurt enhanced lactose absorption. However, the reduction after high lactase yogurt was less than expected, given the 5- to 6-fold increment in beta-galactosidase measured in vitro. In vivo activity of beta-galactosidase requires that the enzyme resist acid denaturation in the stomach. The beta-galactosidase in high lactase yogurt was much less acid resistant than was the beta-galactosidase in conventional yogurt, and the relative inability of high lactase yogurt to enhance lactose absorption was likely due to the destruction of the beta-galactosidase in the stomach.

Absorption↗
PubMed1994

Pitfalls in the use of breath pentane measurements to assess lipid peroxidation.

Literature values for breath pentane, an indicator of lipid peroxidation, vary by 1,000-fold in healthy subjects. This report describes multiple technical artifacts that may explain this disparity. First, we found that a major component of human breath (probably isoprene) co-eluted with pentane on columns used by some investigators, resulting in erroneously high determinations. Second, despite washouts using pentane-free air, ambient pentane dissolved in body fat may result in breath concentrations many times greater than that due to endogenous production. True endogenous breath pentane may never have been accurately determined.

Animals↗
PubMed1994

Diurnal rhythm of heme turnover assessed by breath carbon monoxide concentration measurements.

Measurements of pulmonary carbon monoxide (CO) excretion can be used as a quantitative indicator of heme turnover. We determined whether a diurnal variation of heme turnover occurs by using a recently described technique that estimates breath CO excretion from measurements of alveolar CO concentration corrected for environmental CO to yield an endogenous PCO. This simple technique, unlike the previously employed rebreathing method, makes it possible to repeatedly measure CO excretion throughout a 24-hour period. Nine studies in seven healthy adult subjects demonstrated a diurnal rhythm of CO excretion with a peak excretion rate at about noon that was 26% greater than the nadir, which occurred at about midnight. The rhythm of CO production underlying the observed breath CO excretion was calculated to have an amplitude of about twice that of CO excretion and a phase shift relative to excretion of about 4 hours. We conclude that a diurnal variation in the rate of heme turnover occurs, and when CO determinations are used to assess minor alterations in heme turnover, consideration must be given to the time of day at which the measurements are obtained.

Aged↗
PubMed1994

The critical role of the rate of ethanol absorption in the interpretation of studies purporting to demonstrate gastric metabolism of ethanol.

The area under blood ethanol concentration-time curves may be lower after ingestion vs. intravenous infusion of similar ethanol doses, a difference that has been attributed to first-pass metabolism in the gastric mucosa. Using a model of human hepatic ethanol metabolism, we predicted the area under blood ethanol concentration-time curves and first-pass metabolism that would result from oral vs. intravenous ethanol. This model accurately predicted reported differences in AUC after oral vs. intravenous ethanol. First-pass metabolism has been shown to disappear when the stomach is bypassed via intraduodenal or portal vein infusion of ethanol. Our model predicts that the efficiency of first-pass metabolism is extremely sensitive to the hepatic delivery rate of ethanol and the rapid ethanol delivery rate in bypass studies would have eliminated hepatic first-pass metabolism. We conclude that hepatic ethanol metabolism could explain published observations concerning first-pass metabolism and it is not necessary to postulate a major role for gastric mucosal metabolism in this process. Inhibition of the liver's ability to oxidize ethanol is a necessary requirement of any theory proposing that the gastric mucosa is the primary site of first-pass ethanol metabolism.

Ethanol↗
PubMed1993

Detection of malabsorption of low doses of carbohydrate: accuracy of various breath H2 criteria.

BACKGROUND: Although the accuracy of breath H2 testing to detect malabsorption of small (< 50 g) doses of carbohydrate has never been evaluated, studies suggest that its accuracy is limited by a high prevalence of "H2 nonproducers." The aim of this study was to determine the accuracy of H2 breath testing in the detection of malabsorption of 10 g of carbohydrate. METHODS: In 55 healthy subjects, we determined the ability of breath H2 measurements to distinguish between the ingestion of 10 g of a nonabsorbable carbohydrate (lactulose) and two control meals, a nonabsorbable electrolyte solution or glucose (10 g). RESULTS: The conventional criterion of a 20 ppm increase in breath H2 had 100% specificity but failed to identify lactulose malabsorption in 47% and 24% of subjects at 4 and 8 hours of testing. In contrast, a breath H2 of > 6 ppm at 5 or 6 hours had near perfect specificity and sensitivity. A sum of breath H2 at 5, 6, and 7 hours of > 15 ppm yielded perfect separation between lactulose and control solutions. CONCLUSIONS: True "H2 nonproducers" are extremely rare. Using appropriate criteria, breath H2 testing provides a very accurate means of identifying malabsorption of low doses of carbohydrate.

Adult↗
PubMed1993

Review article: lack of clinical significance of the interaction between H2-receptor antagonists and ethanol.

It has been proposed that an appreciable fraction of ingested ethanol is metabolized in the gastric mucosa and that inhibition of this metabolism by H2-receptor antagonists produces clinically important increases in blood ethanol. This paper reviews available data concerning gastric metabolism of ethanol and the influence of H2-antagonists on ethanol metabolism. It concludes that very little, if any, metabolism of ethanol is likely to occur in the gastric mucosa, and the interaction between H2-antagonists and ethanol is clinically insignificant.

Animals↗
PubMed1993

Cholangiocarcinoma and familial adenomatous polyposis.

A case of cholangiocarcinoma occurring in a patient with familial adenomatous polyposis--only the fourth such case reported--is presented. Evidence suggests that tumours of the extrahepatic biliary tree may also be an extra-colonic manifestation of familial adenomatous polyposis.

Adenomatous Polyposis Coli↗
PubMed1993

Use of metabolic inhibitors to study H2 consumption by human feces: evidence for a pathway other than methanogenesis and sulfate reduction.

Human fecal bacteria produce and consume hydrogen, and consumption rate is a critical determinant of the volume of H2 liberated into the colonic lumen. Two bacterial reactions that have been reported to be major consumers of H2 are methanogenesis and sulfate reduction. To determine the importance of each of these reactions, we measured the disappearance of exogenous H2 during incubation with human fecal homogenates treated with 20 mmol/L 2-bromoethanesulphonic acid (BES), an inhibitor of methanogenesis, and/or 20 mmol/L sodium molybdate (Mo), an inhibitor of sulfate reduction. Four methanogenic and four nonmethanogenic samples consumed an average of 99% and 85%, respectively, of the initial H2 during 22 hours of incubation. With methanogenic homogenates, 36% of the H2 consumption persisted despite inhibition of methanogenesis. Inhibition of sulfate reduction had no effect on the rate of H2 consumption by these eight fecal specimens. The importance of fecal sulfate availability was determined in fecal samples obtained from an additional 14 randomly selected volunteers. Incubation after supplementation with 20 mmol/L sulfate was associated with an increase in sulfide production in four of the samples, and three of these four samples also demonstrated an increased rate of H2 consumption. No such evidence of sulfate reduction was observed in the other 10 homogenates. We conclude that a bacterial reaction other than methanogenesis and sulfate reduction, perhaps the recently described reduction of CO2 to acetate, represents a major metabolic route of H2 disposal in nonmethanogenic feces and a minor, but appreciable, pathway in methanogenic feces.

Feces↗
PubMed1993

Facilitated method for measurement of biliary secretion rates in healthy humans.

We have developed a facilitated method for determining secretion of constituents into bile. The ratio of constituent/bilirubin was measured in gallbladder bile and multiplied by bilirubin secretion rate, estimated by measuring endogenous production of carbon monoxide (VCO) by breath sampling. Accuracy of this method was assessed by measuring secretion rate of 99mTechnetium-labeled disofenin during steady-state constant intravenous infusion. In nine subjects, mean (+/- SEM) secretion of disofenin by the CO method was 104.2 +/- 7.2% of expected and by standard marker perfusion was 97.8 +/- 13.1% of expected. In ten subjects, secretion rate of cholesterol by the CO method averaged 103 mumol/h by the CO method compared to 113 by marker perfusion (NS). Compared to marker perfusion (which is believed to reflect 24-h secretion rate), the CO method significantly underestimated secretion rate of bile acid (1110 vs. 1332 mumol/h, P = 0.076) and lecithin (295 vs. 413 mumol/h, P = 0.01), probably because gallbladder bile contained a disproportionate amount of fasting versus postprandial bile. Thus, this new method provides an accurate secretion rate for biliary constituents secreted at a relatively constant rate, including cholesterol, with less variability than marker perfusion. However, it can be used to estimate secretion of bile acid and lecithin only when a 20-30% underestimation of 24-h secretion is acceptable.

Adult↗