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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

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

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↗
PubMed1979

Follow-up of a flatulent patient.

This paper describes a low-flatulence diet developed by an extremely flatulent patient. Based on meticulous recording of each passage of flatus, the patient employed an elimination diet to determine what foods were responsible for his gas production. The diet reduced the frequency of his gas passage from 34 +/- 7 to 17 +/- 5 times per day (normal: 14 +/- 6) and similar reductions were observed by two other flatulent patients during adherence to the diet. The rectal gas of each of these subjects largely consisted of two gases (CO2 and H2) which result from bacterial fermentation of carbohydrates. The diet, which is low in lactose and wheat products, presumably minimizes the quantity of carbohydrates delivered to the colonic bacteria.

Adult↗
PubMed1979

Use of microspheres to measure small intestinal villus blood flow in the dog.

The accuracy of using 7- to 10-micron microspheres to measure blood flow to dog small intestinal villi was studied. These spheres appear to pass unimpeded through the afferent arterioles of the villus and lodge at the villus tip because 1) virtually all villus spheres were located at the tip, 2) flow determined by visually counting spheres did not differ significantly from flow determined from radioactivity of the sheared-off villus layer, 3) the size distribution of spheres in the villus and subvillus layers was virtually identical to that administered, indicating no premature impaction of the larger spheres, and 4) spheres lodging in the submucosa during vasoconstriction did not subsequently migrate to the villi during vasodilatation. Studies with 25-micron spheres indicated that 28% of the 7- to 10-micron spheres shunted through vessels greater than 10 micron. Double isotope studies showed that lodges spheres do not migrate and that the injection of 2--4 X 10(6) spheres does not alter villus flow. Thus, 7- to 10-micron microspheres pass to and lodge in villus vessels in proportion to capillary flow and should provide an accurate estimate of villus nutrient blood flow.

Animals↗
PubMed1979

Clinical use of amylase clearance and isoamylase measurements.

Isoamylase determinations and measurements of the ratio of the renal clearance of amylase relative to creatinine (CAm/CCr) were employed in an attempt to improve the diagnostic accuracy of the standard amylase measurement. An elevated CAm/CCr reflects defective proximal tubular reabsorption of amylase which occurs in virtually all patients with clear-cut acute pancreatitis. However, other conditions that apparently are associated with acute defective tubular function, such as burns and diabetic acidosis, may cause an elevated ratio. Thus, elevations of CAm/CCr cannot be considered to be specific for acute pancreatitis. Pancreatic isoamylase represents, on the average, about 33% of the normal serum amylase activity, whereas about 66% is salivary-type isoamylase. Isoamylase measurements are useful in determining whether an elevated value for serum amylase activity is of pancreatic origin. However, this measurement is not useful for determining whether patients with normal serum amylase activity have pancreatitis.

Amylases↗
PubMed1979

Postoperative elevation of amylase/creatinine clearance ratio in patients without pancreatitis.

An elevated CAm/CCr ratio has been used as evidence for the frequent occurrence of acute pancreatitis in the postoperative period. We measured CAm/CCr pre and postoperatively in 28 patients undergoing extraperitoneal surgical procedures. None of the patients had clinical evidence of pancreatitis, although 2 of the 28 patients had elevated CAm/CCr ratios preoperatively. Mean CAm/CCr rose from a preoperative level of 2.3 +/- 0.3% (1 SE) to 3.2 +/- 0.3% on the first postoperative day (P less than 0.001). Of the 26 patients with normal preoperative CAm/CCr, 12% (3 of 26) developed a clearly abnormal ratio and 12% (3 of 26) developed borderline elevated values. An elevated CAm/CCr appears to be a nonspecific postoperative finding and cannot be used as evidence of acute pancreatitis during this period.

Amylases↗