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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 55 records · Page 3Linked to original sources
PubMed1996

Use of maltose hydrolysis measurements to characterize the interaction between the aqueous diffusion barrier and the epithelium in the rat jejunum.

Rates of intestinal absorption and surface hydrolysis are determined by the interaction of two barriers: poorly stirred fluid adjacent to the mucosa, and the epithelial cell. These two barriers commonly are modeled as a fixed, flat layer of epithelium covered by a fixed thickness of unstirred fluid. To more accurately simulate these barriers in a villous mucosa, maltase activity (measured in vitro) was distributed over an anatomically correct model of rat jejunal villi. We then determined what interaction of the aqueous and epithelial barriers best predicted in vivo maltose hydrolysis rates measured over a broad range of infusate concentrations. Hydrolysis was accurately predicted by a model in which unstirred fluid extended from 20 microm over the villous tips throughout the intervillous space. In this model, the depth of diffusion into the intervillous space is inversely proportional to the efficiency of epithelial handling of the solute. As a result, both the aqueous barrier and the functional surface area are variables rather than constants. Some implications of our findings (relative to the conventional model) include: higher predicted Vmax, efficient handling of low concentrations of a solute at the villous tips while high concentrations must penetrate thick aqueous barriers, and sensitive regulation of transport rates via ease of access to the intervillous space.

Animals↗
PubMed1996

The relation of passage of gas an abdominal bloating to colonic gas production.

OBJECTIVE: To determine the relation of gas passage and abdominal bloating to the production of gas in the colon. DESIGN: Randomized, double-blind, crossover study of gaseous symptoms during a 1-week period. SETTING: A Veterans Affairs medical center. PARTICIPANTS: 25 healthy medical center employees. INTERVENTION: Participants' diets were supplemented with either a placebo (10 g of lactulose, a nonabsorbable sugar), psyllium (a fermentable fiber), or methylcellulose (a nonfermentable fiber). MEASUREMENTS: All participants were polled for gaseous symptoms (including number of gas passages, impression of increased rectal gas, and abdominal bloating), and five were examined for breath hydrogen excretion. RESULTS: Participants passed gas 10 +/- 5.0 times per day (mean +/- SD) during the placebo period. A significant increase in gas passages (to 19 +/- 12 times per day) and a subjective impression of increased rectal gas were reported with lactulose but not with either of the two fiber preparations. Breath hydrogen excretion, an indicator of hydrogen production in the colon, did not increase after ingestion of either of the fibers. However, a statistically significant (P < 0.05) increase in feelings of abdominal bloating (which the participants perceived as excessive gas in the bowel) was reported with both fiber preparations and with lactulose. CONCLUSIONS: The physician should distinguish between excessive gas (which indicates excessive gas production) and feelings of bloating (which are usually unrelated to excessive gas production). Treatment of the former consists of limiting the supply of fermentable material to the colonic bacteria. Symptoms of bloating usually indicate the irritable bowel syndrome, and therapy should be directed accordingly.

Adult↗
PubMed1996

Factors influencing frequency of flatus emission by healthy subjects.

The purpose of the present study was to measure the frequency of flatus emission by 25 healthy subjects and to determine if factors commonly thought to influence flatulence actually correlate with the frequency of gas passage. Over a one-week period on their usual diet, subjects passed gas 10 +/- 1 times/day [upper limit of normal (mean + 2 SD): 20 times/day]. The addition of the nonabsorbable disaccharide lactulose (10 g/day) to the diet significantly (P < 0.01) increased flatus frequency to 19 +/- 2.4 times per day. Gender, age, and the ability of an individual's colonic flora to produce methane had no significant influence on flatus frequency either on the basal or lactulose-supplemented diets. Some subjects consistently passed gas more often than did others. These individual differences appeared to result, in part, from differences in the ability of the flora to produce gas from a given quantity of fermentable material.

Adult↗
PubMed1996

Ashkenazi Jews, sulfur gases, and ulcerative colitis.

Fecal pathogens have been suspected to cause ulcerative colitis, yet none have been identified. Meanwhile, the 400 species comprising normal colonic flora have received little attention as potential pathogens. Sulfate-reducing bacteria (SRB), a frequent colonic commensal, have been identified in greater numbers in people with ulcerative colitis. The bacteria produce hydrogen sulfide, a toxic compound with the potential to cause colonic injury and possibly ulcerative colitis. If these bacteria are pathogenic, high-risk populations may harbor greater numbers of these organisms in their colons. We compared a group with a high incidence of ulcerative colitis, Ashkenazi Jews, to a control population to assess carriage rates for SRB. Breath samples were collected to indirectly determine colonic conditions. No difference was found between the two groups studied.

Adolescent↗
PubMed1996

Measurements of the jejunal unstirred layer in normal subjects and patients with celiac disease.

Normal intestinal absorption of nutrients requires efficient luminal mixing to deliver solute to the brush border. Lacking such mixing, the buildup of thick unstirred layers over the mucosa markedly retards absorption of rapidly transported compounds. Using a technique based on the kinetics of maltose hydrolysis, we measured the unstirred layer thickness of the jejunum of normal subjects and patients with celiac disease, as well as that of the normal rat. The jejunum of humans and rats was perfused with varying maltose concentrations, and the apparent Michaelis constant (Km) and maximal velocity (Vmax) of maltose hydrolysis were determined from double-reciprocal plots. The true Km of intestinal maltase was determined on mucosal biopsies. Unstirred layer thickness was calculated from the in vivo Vmax and apparent Km and the in vitro Km of maltase. The average unstirred layer thickness of 11 celiac patients (170 micron) was seven times greater than that of 3 controls (25 micron). The unstirred layer of each celiac exceeded that of the controls. A variety of factors could account for the less efficient luminal stirring observed in celiacs. Although speculative, villous contractility could be an important stirring mechanism that would be absent in celiacs with villous atrophy. This speculation was supported by the finding of a relatively thick unstirred layer (mean: 106 micron) in rats, an animal that lacks villous contractility. Because any increase in unstirred layer slows transport of rapidly absorbed compounds, poor stirring appears to represent a previously unrecognized defect that could contribute to malabsorption in celiac disease and, perhaps, in other intestinal disorders.

Animals↗
PubMed1995

A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance.

BACKGROUND: Ingestion of a large dose of the milk sugar lactose--for example, the 50-g load in 1 liter of milk--causes symptoms such as abdominal pain, diarrhea, bloating, and flatulence in the majority of people with lactose malabsorption. It is uncertain whether the ingestion of more common doses of lactose, such as the amount in 240 ml (8 oz) of milk, causes symptoms. Some people insist that even smaller quantities of milk, such as the amount used with cereal or coffee, cause severe gastrointestinal distress. METHODS: In a randomized, double-blind, crossover trial, we evaluated gastrointestinal symptoms in 30 people (mean age, 29.4 years; range, 18 to 50) who reported severe lactose intolerance and said they consistently had symptoms after ingesting less than 240 ml of milk. The ability to digest lactose was assessed by measuring the subjects' end-alveolar hydrogen concentration after they ingested 15 g of lactose in 250 ml of water. Subjects then received either 240 ml of lactose-hydrolyzed milk containing 2 percent fat or 240 ml of milk containing 2 percent fat and sweetened with aspartame to approximate the taste of lactose-hydrolyzed milk; each type of milk was administered daily with breakfast for a one-week period. Using a standardized scale, subjects rated the occurrence and severity of bloating, abdominal pain, diarrhea, and flatus and recorded each passage of flatus. RESULTS: Twenty-one participants were classified as having lactose malabsorption and nine as being able to absorb lactose. During the study periods, gastrointestinal symptoms were minimal (mean symptom-severity scores for bloating, abdominal pain, diarrhea, and flatus between 0.1 and 1.2 [1 indicated trivial symptoms; and 2, mild symptoms]). When the periods were compared, there were no statistically significant differences in the severity of these four gastrointestinal symptoms. For the lactose-malabsorption group, the mean (+/- SEM) difference in episodes of flatus per day was 2.5 +/- 1.1 (95 percent confidence interval, 0.2 to 4.8). Daily dietary records indicated a high degree of compliance, with no additional sources of lactose reported. CONCLUSIONS: People who identify themselves as severely lactose-intolerant may mistakenly attribute a variety of abdominal symptoms to lactose intolerance. When lactose intake is limited to the equivalent of 240 ml of milk or less a day, symptoms are likely to be negligible and the use of lactose-digestive aids unnecessary.

Abdominal Pain↗
PubMed1995

Carbon monoxide generation from hydrocarbons at ambient and physiological temperature: a sensitive indicator of oxidant damage?

This paper shows that a variety of carbon-containing materials (wool, cotton, wood, paper, latex, Tygon) release CO during incubation at ambient temperature. This CO production was enhanced by aerobic versus anaerobic incubation, increasing temperature, and exposure to fluorescent light. CO production from glucose solutions was enhanced by alkaline pH or prior boiling or autoclaving and reduced by the presence of superoxide dismutase or catalase. We conclude that a variety of materials are constantly undergoing oxidation at ambient or physiological temperature as evidenced by the release of CO. Measurements of this CO production could provide a simple, rapid and sensitive means of assessing oxidative damage.

Carbon Monoxide↗
PubMed1995

Paracellular intestinal transport of six-carbon sugars is negligible in the rat.

BACKGROUND & AIMS: Active D-glucose absorption has been theorized to increase convective flow and enhance tight junction permeability such that paracellular transport becomes the major mechanism of D-glucose absorption. This concept was tested in rats by measuring the absorption of four gavaged, nonmetabolizable six-carbon sugars (L-glucose, L-galactose, L-mannose, and D-mannitol) thought to be absorbed solely by the paracellular route. METHODS: Uptake of gavaged probes was measured by recovery in 24-hour urine specimen collections. RESULTS: L-glucose (71.2% +/- 2.4%) absorption exceeded that of the other probes (1.4%-9%). Coadministration of 3.0 mol/L D-glucose, 0.22 mol/L D-glucose, or chow significantly reduced the absorption of L-glucose to 38.1% +/- 7.2%, 61% +/- 3.3%, and 53.6% +/- 3.5%, respectively, but did not influence the absorption of the other six-carbon probes. CONCLUSIONS: (1) L-glucose seems to have a weak affinity for a D-glucose carrier and is not a marker of paracellular transport, and (2) paracellular transport accounts for a minimal fraction of D-glucose uptake; this fraction is not enhanced by ingestion of D-glucose or chow.

Animals↗
PubMed1995

Pneumatosis cystoides intestinalis and high breath H2 excretion: insights into the role of H2 in this condition.

Patients with pneumatosis cystoides intestinalis have been reported to excrete excessive H2 because of a lack of H2-consuming intestinal bacteria. This study describes a patient with bacterial overgrowth and pneumatosis of the small intestine whose colonic flora avidly consumed H2 but whose small bowel flora produced but did not consume H2. There is no commonly accepted mechanism whereby excessive luminal H2 causes intramural gas. An explanation is proposed in which an initial, transitory source of intramural gas is distinguished from the mechanism that results in the persistence of the gas. Independent of the initial source of gas, rapid diffusion of H2 from the lumen into an intramural gas bubble would cause N2, O2, and CO2 to diffuse from the blood into the bubble. As a result, the bubble would expand and then persist indefinitely as long as H2 continued to diffuse from the lumen to the intramural gas collection.

Aged↗
PubMed1995

Review article: the treatment of lactose intolerance.

While about 50 million Americans malabsorb lactose, the colonic metabolism of this disaccharide may prevent the symptomatic state known as lactose intolerance. Elucidation of the clinical importance of lactose malabsorption requires comparison of symptoms after ingestion of lactose with those following an identical appearing lactose-free control. This paper reviews the extensive literature concerning lactose-induced symptoms and the value of lactose digestive aids. Poorly controlled studies have suggested that a cup of milk results in appreciable symptoms in the majority of lactase-deficient subjects. In contrast, controlled trials in unselected lactose malabsorbers of subjects claiming severe lactose intolerance indicate that symptoms from a cup of milk are no greater than that with a lactose-hydrolyzed control. An increasing fraction of subjects experience symptoms as the lactose load is increased, with the majority having symptoms when the equivalent of 1 L of milk is ingested as a single dose. Further studies are required to determine the tolerance to several cups of milk taken throughout the day. Available digestive aids include pre-hydrolyzed milk and lactase preparations that can be added to milk (which is then incubated) or ingested with milk. While these products are effective in reducing symptoms, it should be emphasized that there appears to be no need for these preparations when the dosage of milk is limited to one cup per day.

Humans↗
PubMed1995

High dose loperamide suppositories: a novel approach for improving clinical function after restorative proctocolectomy.

The effect of loperamide suppositories on patients following restorative proctocolectomy was studied by means of a randomized, double-blind, crossover trial comparing active suppositories (20 mg b.d. x 1 week) with placebo. Ten patients (8 male, 2 female; 7 J pouch, 3 W pouch; 8 ulcerative colitis, 2 familial adenomatous polyposis) were studied 3-60 months (median, 31.5) after ileostomy closure. Ages ranged from 24 to 63 years (medium, 41.5). All patients kept a diary of their bowel habits and eight underwent a standardized test of pouch compliance. Urgency volume (UV) and maximum tolerable volumes (MTV) and the volume at onset of large isolated pouch contractions (LIC) were recorded. Statistical analysis was by the Wilcoxon test for paired data. Mean daily stool frequency during the placebo phase ranged from 3.7 to 7.8. It was reduced during the active phase in only seven patients (P > 0.1) but was reduced in all six patients whose placebo phase stool frequency was five or more. Urgency volume was increased by use of active suppositories in six of the eight patients tested (P > 0.01). There was no consistent effect on MTV. Large isolated pouch contractions were not seen in either test in one patient. In all of the remaining seven patients LIC were recorded after the placebo phase. After the active phase LIC first appeared at higher volumes in three but were not seen at all in four patients. High dose loperamide suppositories suppress pouch contractions and tend to lower stool frequency especially when high initially. They represent a novel therapeutic approach to high stool frequency in pouch patients.

Adult↗
PubMed1995

Sensitivity of HPLC and conventional bilirubin measurements in the detection of early cholestasis.

Recent studies using very sensitive high-performance liquid chromatography (HPLC) techniques have shown that conjugated bilirubin concentrations in normal human serum are about 0.006 mg/dl, much lower than the direct-reacting bilirubin concentrations reported by typical clinical laboratory techniques (up to 0.3 mg/dl). In animal models of cholestasis, we tested the concept that HPLC measurements of true serum conjugated bilirubin would provide a more sensitive indicator of cholestasis than does the conventional measurement. Serum conjugated bilirubin was not detectable (< 0.006 mg/dl) in untreated rats and guinea pigs. After bile duct ligation, the true serum conjugated bilirubin concentration in rats was significantly elevated by 10 minutes, whereas the conventional bilirubin measurement did not become significantly elevated until 120 minutes; comparable values for the guinea pig were 30 and 240 minutes, respectively. Studies of two rat models of drug-induced cholestasis, cyclosporine A and 17 alpha-ethynylestradiol, showed that measurable levels of true conjugated bilirubin appeared in the serum of cyclosporine A-treated rats but not in the estrogen-treated animals. We conclude that true serum conjugated bilirubin concentrations measured by HPLC provide an extremely sensitive means of detecting cholestasis and that such measurements could have clinical utility in detecting very early or minimal liver dysfunction.

Animals↗
PubMed1994

Use of alveolar carbon monoxide measurements to assess red blood cell survival in hemodialysis patients.

We recently described a simple technique for measuring RBC survival based on measurements of the concentration of carbon monoxide (CO) in alveolar air, corrected for environmental CO using a device that equilibrates with atmospheric CO at the same rate as does the patient. The purpose of the present report is to demonstrate the clinical utility of this method via measurements of RBC turnover in hemodialysis patients. Prior to dialysis, the mean RBC survival of 9 chronic dialysis patients was 70 +/- 9 days, about 50% shorter than that of 32 healthy subjects. During the dialysis, the endogenous PCO increased by 14% (P < 0.05) while subjects not undergoing dialysis had a 6% fall in endogenous PCO over this same time period. Thus, this technique demonstrated that the hemodialysis procedure resulted in about a 20% increase in RBC destruction. This increased RBC destruction has not been detectable with previous methodologies (including conventional measurements of CO production) due to the insensitivity and lack of reproducibility of conventional techniques. We conclude that the simple, non-invasive measurement of endogenous PCO provides the most accurate available means of assessing the influence of a variety of acute manipulations on RBC survival.

Breath Tests↗
PubMed1994

Ambulatory pouch and anal motility in patients with ileo-anal reservoirs.

Twelve patients were studied for a median of 18 hours (range 8.5-21.5 hr) by continuous, ambulatory, simultaneous pouch and anal manometry 10-85 months after restorative proctocolectomy. Two main patterns of motility were observed: (1) Large isolated contractions up to 68 cm H2O in amplitude and up to 67 seconds in duration were present in ten patients. These were often associated with the urge to defaecate and were more frequent before defaecation than after but did not appear to be associated with expulsion of faeces from the pouch. In two patients atypical large isolated contractions up to 378 cm H2O in amplitude were observed. (2) Rhythmic contractions at a frequency of 7-11 per minute and amplitude of 24-330 cm H2O, occurred for a duration of 18 seconds to 18 minutes in six patients. In the other six patients this motility pattern was not seen. Of the 12 patients nine were considered to have good function (five or less bowel actions per 24 hours) and three poor function (ten or more bowel actions per 24 hours). Rhythmic activity was the predominant motility pattern in all three with poor function whereas large isolated contractions predominated in those with good function, although there was considerable overlap in the types of motility observed between patients with good and poor function. Mean pouch pressure tended to be higher in patients with poor function than in those with good function both throughout the entire recording and during sleep. In a number of patients simultaneous anal recordings revealed the presence of slow waves and falls in pressure, some of which were associated with a simultaneous rise in pouch pressure.

Adult↗
PubMed1994

Study of constancy of hydrogen-consuming flora of human colon.

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H2-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.

Bacteria↗