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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 19 recordsLinked to original sources
PubMed1992

Ileoanal pouch compliance and motor function.

Measurement of intrapouch pressure during continuous distension with water (pouchmetrography) was performed in ten patients with good pouch function after restorative proctocolectomy and a 'normal' baseline pressure curve was constructed from the mean pressures at 50-ml intervals. Eight other patients with poor pouch function were studied and the two groups were compared. Patients with poor function had significantly lower maximum tolerated volumes (297.5 versus 565 ml, P less than 0.02) and volumes which caused urgency (135 versus 265 ml, P less than 0.02). Baseline pressure curves were above the upper limit of the normal range (mean plus two standard deviations) for a substantial proportion of the recording in six of the patients with poor function. Large, isolated contraction waves were recorded in six of ten patients with good function and in three of those with poor function. Rhythmic waves were frequently seen in both groups but were more prominent in patients with poor function. Pouchmetrography is a provocative test of pouch motor function which may unmask abnormal muscle activity resulting from reduced compliance or a primary motility disorder.

Adult↗
PubMed1992

Effect of yogurt on clindamycin-induced Clostridium difficile colitis in hamsters.

Yogurt exhibits in vitro bactericidal activity against a variety of pathogenic microorganisms, including Clostridium difficile. In the present studies, we tested whether yogurt ingestion could prevent or ameliorate antibiotic associated colitis in the clindamycin-treated hamster model. Male golden Syrian hamsters were given 5 mg/kg clindamycin subcutaneously 24 hr before and 6 hr following inoculation with 0.5 ml of less than 10, 10(3), 10(5), or 10(6) CFU/ml of C. difficile. Hamsters in the control group ingested chow and water ad libitum, whereas the experimental group ingested chow and a 1:1 (v/v) mixture of yogurt and water ad libitum, beginning 24 hr before the first injection of clindamycin and continuing throughout the course of the study. Animals were monitored for colonization with C. difficile, pathological evidence of colitis, and death. Mortality was 100% in yogurt-treated animals, and all animals showed histological changes of severe colitis. Fecal and intestinal segment cultures were positive for C. difficile in all animals. Thus, in the hamster model, we found no evidence to support the possible efficacy of yogurt in the prevention of C. difficile colitis.

Animals↗
PubMed1992

Shaking of the intact rat and intestinal angulation diminish the jejunal unstirred layer.

A sizeable pre-epithelial diffusion barrier (unstirred layer) is present during perfusion of the rat jejunum. In the present study, three rapidly transported compounds, CO, [14C]warfarin, and glucose (5.5 mmol/L), were used as probes to assess the ability of manipulations to reduce the unstirred layer. This layer was 700-800 microns thick in a 30-cm jejunal segment perfused in conventional fashion on the abdominal wall. Placement of four sharp angulations in the segment or replacement in the abdominal cavity reduced the maximal unstirred layer to 200-400 microns. Increasingly rapid shaking of the anesthetized, intact rat on a platform shaker produced progressively thinner unstirred layers. At 250 revolutions per minute, the maximal layer ranged from 32 to 68 microns for the three probes and may have been appreciably less if the epithelium offered appreciable resistance. Shaking yields a > 15-fold reduction in unstirred layer resistance and provides a means for measuring this resistance and for obtaining more accurate assessment of the true in vivo transport Michaelis constant (Km) of any compound.

Animals↗
PubMed1992

Human jejunal unstirred layer: evidence for extremely efficient luminal stirring.

Previous studies employing the osmotic transient technique have suggested that the human jejunal lumen is poorly stirred with a resultant unstirred layer thickness of approximately 600 microns. However, assuming negligible epithelial resistance to glucose absorption, we recently estimated that the unstirred layer thickness seemingly could not exceed 48 microns in the human jejunum. Because disaccharidases are located on the brush border, the rate of disaccharide hydrolysis can be used to determine unstirred layer thickness, independent of epithelial transport. In the present report, we utilized published hydrolysis data for sucrose and maltose to calculate the unstirred layer thickness in the normal human jejunum. This calculation indicated that the unstirred layer thickness was only approximately 35 microns, less than one-fifteenth of previously reported 600-microns values obtained with the osmotic transient technique. Diffusion through a 600-microns unstirred layer would be the rate-limiting step in absorption of all rapidly transported compounds. In contrast, with a 35-microns unstirred layer, variations in epithelial function or luminal stirring could readily influence the absorption.

Diffusion↗
PubMed1992

Factors affecting hydrogen production and consumption by human fecal flora. The critical roles of hydrogen tension and methanogenesis.

We studied the influence of hydrogen tension (PH2) and methanogenesis on H2 production and consumption by human fecal bacteria. Hydrogen consumption varied directly with PH2, and methanogenic feces consumed H2 far more rapidly than did nonmethanogenic feces. At low PH2, H2 production greatly exceeded consumption and there was negligible accumulation of the products of H2 catabolism, methane and sulfide. Thus, incubation at low PH2 allowed the first reported measurements of absolute as opposed to net H2 production. Feces incubated at high and intermediate PH2 had a net H2 production of only 1/900 and 1/64 of absolute production. Glucose fermentation by fecal bacteria yielded an absolute H2 production of 80 ml/g, a value far in excess of that excreted by volunteers ingesting lactulose. We conclude that most H2 produced by colonic bacteria is consumed and methanogenesis and fecal stirring (via its influence on fecal PH2) are critical determinants of H2 consumption and, hence, net H2 production. Study of fecal samples from four subjects with low breath H2 excretion after lactulose showed that absolute H2 production was normal, and the low H2 excretion apparently reflected increased consumption due to rapid methanogenesis (two subjects) and decreased luminal stirring (two subjects).

Bacteria↗
PubMed1992

First-pass gastric mucosal metabolism of ethanol is negligible in the rat.

Ethanol metabolism by gastric alcohol dehydrogenase (ADH) is thought to be an important determinant of peripheral ethanol time-concentration curves (AUCs) in rats and humans. We quantitated this metabolism in rats by measuring the gastric absorption of oral ethanol (0.25 g/kg) and the gastric venous-arterial (V-A) difference of ethanol versus ethanol metabolites (acetate, acetaldehyde, and bicarbonate). Over 1 h, approximately 20% of the ethanol was absorbed from the stomach and 70% was emptied into the duodenum. The gastric V-A difference of ethanol metabolites was less than 4% of that of ethanol. Thus, gastric metabolism accounted for less than 1% (less than 4% of 20% absorbed) of the dose. This negligible metabolism was predictable from the low affinity of gastric ADH for ethanol. In contrast, gastric ADH has a high affinity for octanol, and 66% of this compound was metabolized during gastric absorption. Evidence supporting gastric metabolism of ethanol largely derives from the lower AUCs observed after oral than after intravenous administration; however, we observed increasingly higher AUCs with increasingly rapid portal vein infusions of identical ethanol doses. We conclude that gastric metabolism of ethanol is negligible in the rat, and differences in AUCs ascribed to gastric metabolism may reflect differences in ethanol absorption.

Absorption↗
PubMed1992

Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat.

Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity. Myoglobin is directly implicated in the pathogenesis of renal failure in rhabdomyolysis. In the glycerol model of this syndrome, we demonstrate that the kidney responds to such inordinate amounts of heme proteins by inducing the heme-degradative enzyme, heme oxygenase, as well as increasing the synthesis of ferritin, the major cellular repository for iron. Prior recruitment of this response with a single preinfusion of hemoglobin prevents kidney failure and drastically reduces mortality (from 100% to 14%). Conversely, ablating this response with a competitive inhibitor of heme oxygenase exacerbates kidney dysfunction. We provide the first in vivo evidence that induction of heme oxygenase coupled to ferritin synthesis is a rapid, protective antioxidant response. Our findings suggest a therapeutic strategy for populations at a high risk for rhabdomyolysis.

Animals↗
PubMed1992

Lack of benefit of ursodeoxycholic acid in drug-induced cholestasis in the rat.

The administration of ursodeoxycholic acid (UDCA) has been reported to improve cholestasis in patients with primary biliary cirrhosis or sclerosing cholangitis. In the present study, we tested the hypothesis that UDCA similarly might reduce cholestasis induced by drugs. Rats were treated with three different drugs reported to induce cholestasis: 17 alpha-ethynylestradiol, alpha-napthylisothiocyanate, and cyclosporine A. UDCA administration (0.4.g/day-1.k-1 before and during administration of the cholestatic drug) did not improve survival, food intake, or serum indicators of cholestasis in any of these three animal models of cholestasis. To the extent that drug-induced cholestasis in rats mimics the human situation, we conclude that UDCA probably will not be beneficial in drug-induced cholestasis in humans.

1-Naphthylisothiocyanate↗
PubMed1992

A simple carbon monoxide breath test to estimate erythrocyte turnover.

Carbon monoxide is stoichiometrically released when heme is converted to bilirubin. This report describes and validates a novel technique that permits the estimation of heme turnover and red blood cell survival from the carbon monoxide concentration of end-expiratory breath samples. The end-alveolar Pco of a subject was corrected for environmental carbon monoxide exposure with a simple device that equilibrates with atmospheric carbon monoxide at the same rate as does the subject. The resultant value (endogenous Pco) was tested for its ability to predict heme turnover and red blood cell survival. Red cell survival times of 32 healthy subjects, as calculated from the endogenous Pco, averaged 101 +/- 19 days, a value close to the expected 110-day survival time; 13 patients with clinical evidence of shortened red blood cell survival times had measured erythrocyte life spans ranging from 10 to 59 days. The endogenous Pco of each of seven patients increased after red blood cell transfusion, demonstrating that this technique detected the known rapid turnover of a small fraction of transfused cells. A good correlation (r = 0.91) was observed between heme turnover calculated from endogenous Pco and total fecal biliary pigment output. Carbon monoxide measurements reflect red blood cell destruction in both the marrow and the circulation, therefore yielding shorter life spans than did chromium 51 survival studies. This breath test appears to yield a rapid, semiquantitative assessment of heme turnover and red blood cell survival that is not provided by any other presently available technique. This simple, noninvasive carbon monoxide breath test may find widespread use in the evaluation of anemia and jaundice.

Adult↗
PubMed1991

Controlled trial of polyglycolic acid versus catgut and nylon for appendicectomy wound closure.

Six hundred and fifty patients undergoing appendicectomy were included in a prospective randomized controlled trial. At operation patients were allocated to control (chromic catgut ligatures and muscle closure, nylon skin closure) or study (polyglycolic acid ligatures and muscle and skin closure) groups. Wounds were examined by an independent observer daily in hospital and 1 month after operation. Wound infection was defined as discharge of serous or purulent material, or a grossly inflamed wound without discharging pus, or any evidence of intra-abdominal sepsis. Of the 650 patients (335 men, 315 women, age 5-80 years, median 18 years), 615 have completed follow-up. Groups were well matched for age, sex, degree of sepsis at operation, histological diagnosis and surgeon. Infection was significantly reduced in the study (polyglycolic acid) group (12.0 per cent) compared with the control (chromic catgut/nylon) group (21.2 per cent) (chi 2 = 9.3, P = 0.002). Infection was significantly reduced in the polyglycolic acid group regardless of whether the appendix was inflamed or normal. These results indicate that suture material can influence the incidence of wound infection and that this is less frequent when polyglycolic acid sutures are used.

Adolescent↗
PubMed1991

Pouch dynamics--a simple test of ileo-anal pouch evacuation.

A simple technique for quantifying ileo-anal pouch evacuation has been used to compare patients with good pouch function and fully spontaneous defaecation (n = 10) to patients with a symptomatic disorder of pouch evacuation (n = 10), usually due to a pouch-anal stricture (n = 7). Pouch emptying was significantly less efficient in those with disordered evacuation (median 54% evacuated) than in those with good function (median 98% evacuated, p = 0.02) and significantly slower (median 22.4 sec vs 5.2 sec to evacuate 75% of instilled barium, p less than 0.02) even when of comparable efficiency. Testing of four further patients with high stool frequency but neither stenosis nor symptomatic difficulty with evacuation excluded a significant disorder of evacuation in three but identified inefficient emptying in the fourth. This test may prove useful in the investigation of patients with poor pouch function of uncertain origin.

Adult↗
PubMed1991

Reproducibility of measurements of trace gas concentrations in expired air.

Measurement of the pulmonary excretion of trace gases has been used as a simple means of assessing metabolic reactions. End alveolar trace gas concentration, rather than excretory rate, is usually measured. However, the reproducibility of this measurement has received little attention. In 17 healthy subjects, duplicate collections of alveolar air were obtained within 1 minute of each other using a commercially available alveolar air sampler. The concentrations of hydrogen, methane, carbon monoxide, and carbon dioxide were measured. When the subject received no instruction on how to expire into the device, a difference of 28% +/- 19% (1SD) was found between duplicate determinations of hydrogen. Instructing the subjects to avoid hyperventilation or to inspire maximally and exhale immediately resulted in only minor reduction in variability. However, a maximal inspiration held for 15 seconds before exhalation reduced the difference to a mean of 9.6% +/- 8.0%, less than half that observed with the other expiratory techniques. Percentage difference of methane measurements with the four different expiratory techniques yielded results comparable to those obtained for hydrogen. In contrast, percentage differences for carbon monoxide measurements were similar for all expiratory techniques. When normalized to a PCO2 of 5%, the variability of hydrogen measurements with the breath-holding technique was reduced to 6.8% +/- 4.7%, a value significantly lower than that obtained with the other expiratory methods. This study suggests that attention to the expiratory technique could improve the accuracy of tests using breath hydrogen measurements.

Breath Tests↗
PubMed1991

A reappraisal of the magnitude and implications of the intestinal unstirred layer.

Until recently, a variety of studies had suggested that luminal stirring in the jejunum is relatively poor, with unstirred layers of about 600 microns reported for humans and 300-900 microns for animals. Unstirred layers of this magnitude would markedly retard the absorption of all solutes, and diffusion through this layer would be the rate-limiting step in the uptake of all rapidly absorbed compounds. As a result, luminal stirring, rather than epithelial transport, would be the major variable influencing absorption rate. However, recent studies in dogs and humans have shown that the unstirred layer has a maximal apparent thickness of only about 40 microns. This layer is far thinner than what can be achieved in vitro with vigorous stirring with a magnetic bar, suggesting that some unique stirring mechanism, perhaps villous contractions, is responsible for this extraordinarily efficient mixing. A 40-microns unstirred layer would produce only about 1/15 the resistance of the previously reported 600 microns value; with this thinner layer, alterations in either luminal stirring or epithelial function could readily influence the absorption rate of rapidly transported compounds.

Animals↗
PubMed1991

Methane production and bowel function parameters in healthy subjects on low- and high-fiber diets.

Colon cancer patients are more likely than healthy subjects to excrete breath methane, and methane production has been suggested as a screening method to predict risk of developing colon cancer. To assess whether methane production is related to fiber ingestion and bowel function, we measured end-alveolar breath methane in 126 healthy subjects; 36% produced methane (greater than 3 ppm). Fifteen methane producers and nine controls were selected to participate in a 17-day study: a self-selected diet for 7 days, followed by the same diet plus 24 g/day dietary fiber (Fiber One Cereal) for 10 days. Methane was measured three times per day on three days during each diet. Two subjects screened as methane producers stopped excreting methane during the study, and one control started to excrete methane. Radiopaque pellets were given at the start and end of each diet, and feces were collected, homogenized, and dried. Mean transit time (p less than 0.0001) and fecal pH (p less than 0.0003) were significantly decreased with fiber, whereas fecal hydration scale (p less than 0.003), fecal dry (p less than 0.0001) and wet (p less than 0.0001) weight, and frequency of defecation (p less than 0.0006) were significantly increased with fiber. No significant change in methane excretion (p less than 0.057) was seen with added fiber. Thus, in this study methane excretor status was not constant in healthy subjects and was not significantly changed by 24 g/day dietary fiber as Fiber One Cereal.

Adolescent↗
PubMed1991

Competition for hydrogen by human faecal bacteria: evidence for the predominance of methane producing bacteria.

Studies of sludge have shown that some species of sulphate reducing bacteria outcompete methane producing bacteria for the common substrate H2. A similar competition may exist in human faeces where the methane (CH4) producing status of an individual depends on the faecal concentration of sulphate reducing bacteria. To determine if non-methanogenic faeces outcompete CH4 producing faeces for H2, aliquots of each type of faeces were incubated alone or mixed together, with or without addition of 10% H2 and/or 20 mmol/l sulphate. Methane producing faeces consumed H2 significantly more rapidly and reduced faecal H2 tension to a lower value compared with non-methanogenic faeces. The mixture of the two types of faeces yielded significantly more CH4 than CH4 producing faeces alone (mean (SD) 8.5 (1.3) v 2.9 (0.45) mmol/l of homogenate per 24 hours, p less than 0.01). Faecal sulphide concentrations were similar in CH4 producing and non-producing homogenates both before and after 24 hours of incubation. The addition of sulphate to the homogenates did not significantly influence CH4 production or sulphide formation. Our results suggest that in human faeces methane producing bacteria outcompete other H2 consuming bacteria for H2.

Bacteria, Anaerobic↗
PubMed1990

Where does serum amylase come from and where does it go?

The serum amylase concentration reflects the balance between the rates of amylase entry into and removal from the blood. Hyperamylasemia can result either from an increased rate of entry of amylase into the circulation and/or a decreased metabolic clearance of this enzyme. The pancreas and salivary glands have amylase concentrations that are several orders of magnitude greater than that of any other normal tissue, and these two organs probably account for almost all of the serum amylase activity in normal persons. A variety of techniques are now available to distinguish pancreatic from salivary-type isoamylase. Pancreatic hyperamylasemia results from an insult to the pancreas, ranging from trivial (cannulation of the pancreatic duct) to severe (pancreatitis). In addition, loss of bowel integrity (infarction or perforation) causes pancreatic hyperamylasemia due to absorption of amylase from the intestinal lumen. Hyperamylasemia due to salivary-type isoamylase is observed in conditions involving the salivary glands. In addition, this type of hyperamylasemia occurs in conditions in which there is no clinical evidence of salivary gland disease, such as chronic alcoholism, postoperative states (particularly postcoronary bypass), lactic acidosis, anorexia nervosa or bulimia, and malignant neoplasms that secrete amylase. Hyperamylasemia can also result from decreased metabolic clearance of amylase due to renal failure or macroamylasemia (a condition in which an abnormally high-molecular-weight amylase is present in the serum). Patients with abdominal pain and a markedly elevated serum amylase (more than three times the upper limit of normal) usually have acute pancreatitis, and additional serum enzyme testing is not helpful. Patients with smaller elevations of serum amylase often have conditions other than pancreatitis, and measurement of a serum enzyme more specific for the pancreas (pancreatitic isoamylase, lipase or trypsin) is frequently of diagnostic value in such patients.

Amylases↗