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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 37 records · Page 2Linked to original sources
PubMed1999

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa.

Colonic bacteria liberate large quantities of the highly toxic gases hydrogen sulfide (H(2)S) and methanethiol (CH(3)SH). The colonic mucosa presumably has an efficient means of detoxifying these compounds, which is thought to occur through methylation of H(2)S to CH(3)SH and CH(3)SH to dimethylsulfide (CH(3)SCH(3)). We investigated this detoxification pathway by incubating rat cecal mucosal homogenates with gas containing H(2)S, CH(3)SH, or CH(3)SCH(3). Neither CH(3)SH nor CH(3)SCH(3) was produced during H(2)S catabolism, whereas catabolism of CH(3)SH liberated H(2)S but not CH(3)SCH(3). Thus, H(2)S and CH(3)SH are not detoxified by methylation to CH(3)SCH(3). Rather, CH(3)SH is demethylated to H(2)S, and H(2)S is converted to nonvolatile metabolites. HPLC analysis of the homogenate showed the metabolite to be primarily thiosulfate. Analysis of cecal venous blood obtained after intracecal instillation of H(2)(35)S revealed that virtually all absorbed H(2)S had been oxidized to thiosulfate. The oxidation rate of H(2)S by colonic mucosa was 10,000 times greater than the reported methylation rate. Conversion to thiosulfate appears to be the mechanism whereby the cecal mucosa protects itself from the injurious effects of H(2)S and CH(3)SH, and defects in this detoxification possibly could play a role in colonic diseases such as ulcerative colitis.

Animals↗
PubMed1998

Rectal washout eliminates exfoliated malignant cells.

PURPOSE: Irrigation of the rectal stump before anastomosis after resection for carcinoma is accepted colorectal surgical practice. However, not all surgeons perform this routinely, and it has never been established conclusively that irrigation of the rectal stump eliminates exfoliated malignant cells or even reduces local recurrence. The patients of a surgeon whose standard surgical practice involved rectal irrigation were compared with those of a surgeon who does not routinely practice rectal irrigation. METHOD: Ten patients were given rectal washout with 200 to 500 ml of normal saline introduced via a Foley catheter per rectum. Ten patients were not given rectal washout. In both groups the anastomosis was performed with a circular stapler, and the stapler and donuts were rinsed in 200 ml of normal saline. The saline was sent for cytologic examination and classified as malignant cells seen or no malignant cells seen. The cytopathologist was blinded to the washout status. RESULTS: Of the ten patients who had rectal washout performed, none had malignant cells seen. Of the ten patients who did not have rectal washout performed, eight had malignant cells seen in the cytology (P = 0.007; two-tailed Fisher's exact probability test). CONCLUSION: Rectal washout eliminates exfoliated malignant cells in the rectum in the vicinity of the anastomosis.

Aged↗
PubMed1998

The physiology of ileo-anal pouch function.

Even excellent clinical function after ileo-anal pouch construction is associated with a variety of physiological abnormalities. Small bowel intestinal motility is essentially normal but the ileal reservoir serves to markedly suppress the ileal motor response both to progressive distension by intestinal contents and to transmitted myoelectrical complexes. As a result, the healthy pouch can accommodate a large volume of intestinal content before the rising baseline pressure and the appearance of large isolated contraction waves produce an urge to defecate. Evacuation in the normal pouch patient is rapid and highly efficient and is achieved by means of the Valsalva maneuver without any evidence of significant intestinal propulsion. External anal sphincter function is fully preserved but internal anal sphincter function is significantly impaired in the immediate postoperative period. Recovery occurs over the next 6 to 12 months but is often incomplete. Bacterial overgrowth in the pouch and prepouch ileum is almost universal and results in the premature deconjugation of primary bile salts and accumulation of secondary bile salts within the pouch. These produce morphologic changes in the ileal mucosa, and their excretion in pouch effluent gradually depletes the bile salt pool. Anerobic organisms also bind with vitamin B12 and the vitamin B12-intrinsic factor complex, resulting in subtle but measurable reductions in vitamin B12 levels in pouch patients. Finally, anerobic fermentation of mucus and undigested carbohydrate results in excessive quantities of short chain fatty acids within the pouch lumen. The clinical significance of these substances is unclear, but they may have an adverse action on both ileal mucosal and smooth muscle function. In essence, however, the pouch surgeon can maximize the likelihood of good clinical function by constructing a large capacity pouch, by avoiding surgery in patients with clearly deficient anal sphincter mechanisms, and by careful attention to pouch-anal anastomotic technique.

Anal Canal↗
PubMed1998

Bismuth subsalicylate markedly decreases hydrogen sulfide release in the human colon.

BACKGROUND & AIMS: Hydrogen sulfide is one of the main malodorous compounds in human flatus. This toxic gas also has been implicated in the pathogenesis of ulcerative colitis. Therefore, a treatment that reduces colonic H2S levels could be clinically useful in the treatment of flatus odor and of ulcerative colitis. In this study the ability of bismuth subsalicylate, a compound that binds H2S, to reduce H2S release in the colon, was tested. METHODS: Homogenates made from human and rat feces were incubated with and without bismuth subsalicylate, and gas production was measured. Fecal samples from 10 healthy subjects were analyzed before and after ingestion of bismuth subsalicylate (524 mg four times a day) for 3-7 days. RESULTS: Fecal homogenates showed a dose-dependent relationship between the concentration of bismuth subsalicylate and H2S release. Treatment of subjects with bismuth subsalicylate produced a >95% reduction in fecal H2S release. CONCLUSIONS: The ability of bismuth subsalicylate to dramatically reduce H2S could provide a clinically useful means of controlling fecal and/or flatus odor and of decreasing the putative injurious effects of H2S on the colonic mucosa.

Adult↗
PubMed1998

Influence of method of alveolar air collection on results of breath tests.

The influence of the method alveolar air collection on measurements of trace gas concentration has received little attention. We measured the concentrations of H2, CH4, CO, and CO2 in sequential fractions of alveolar air collected with and without breath-holding. Without breath-holding, the concentration of these gases increased appreciably as increasing quantities of alveolar air were expelled. Twenty seconds of breath-holding markedly reduced this nonhomogeneity of alveolar air. Prediction of the excretion rate of trace gases from measurements of their concentration relative to CO2 and literature values for resting CO2 excretion underestimated the true excretion rate. We conclude that breath-holding prior to sample collection enhances the reproducibility of trace gas measurements. When calculating the rate of excretion of trace gases, the use of literature values for resting ventilation or CO2 excretion may result in appreciable underestimations of the true rate.

Adult↗
PubMed1998

Lactose maldigestion is not an impediment to the intake of 1500 mg calcium daily as dairy products.

BACKGROUND: A National Institutes of Health consensus conference concluded that a daily calcium intake of 1500 mg reduces the severity of osteoporosis. Because dairy products are the main natural source of dietary calcium, a diet providing 1500 mg Ca must contain large quantities of dairy products. However, it is widely believed that the lactose content of these products will not be tolerated by persons with lactose maldigestion (approximately 30% of the adult US population). OBJECTIVE: We evaluated the symptoms of lactose maldigestion and digestion when the diet was supplemented with dairy products providing 1300 mg Ca/d. DESIGN: Sixty-two women (31 with lactose maldigestion and 31 without) were studied in a double-blind, randomized protocol. Symptoms were compared during 1-wk periods when the diet was supplemented with 480 mL (2 cups) milk, 56 g cheese, and 240 mL yogurt provided as conventional products (34 g lactose/d) or as lactose-hydrolyzed products (2 g lactose/d). RESULTS: Women who digested lactose reported no significant difference in symptoms between the 2 treatment periods. Women with lactose maldigestion reported significantly increased flatus frequency and subjective impression of rectal gas during the period of high lactose intake; however, bloating, abdominal pain, diarrhea, and the global perception of overall symptom severity were not significantly different between the 2 treatment periods. CONCLUSION: The symptoms resulting from lactose maldigestion are not a major impediment to the ingestion of a dairy-rich diet supplying approximately 1500 mg Ca/d.

Adult↗
PubMed1998

Evaluation of an extremely flatulent patient: case report and proposed diagnostic and therapeutic approach.

We recently encountered a patient with severe flatulence who previously had been subjected to innumerable diagnostic tests and ineffective therapies based on the belief that his rectal gas was produced in the colon. Analysis of three flatus samples demonstrated that nitrogen (N2) was the predominant flatus gas whereas the three gases produced in the gut (CO2, H2 [hydrogen], and CH4 [methane]) comprised <16% of rectal gas. This result plus a series of other diagnostic tests clearly indicated that the patient's flatus was derived almost entirely from swallowed air. Based on this case, the present report summarizes available data on excessive flatulence and suggests a rational approach to the patient complaining of this problem. Particular emphasis is placed upon a sequential strategy consisting of: 1) a count of flatus passages to determine if the subject truly is abnormal (normal: <20 passages/day); 2) an analysis of flatus to determine if the flatus originates from swallowed air (predominantly nitrogen) or intraluminal production (predominantly CO2, H2, and CH4); and 3) treatment based upon the origin of the rectal gas.

Adult↗
PubMed1998

Fecal hydrogen sulfide production in ulcerative colitis.

OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p < 0.003 at 24 h). The only other significant difference was increased CO2 release by ulcerative colitis feces at 1 h. Supplementation of fecal homogenates with sulfur-containing substrates showed that organic compounds (mucin, cysteine, taurocholate) provided more readily utilizable substrate for H2S production than did sulfate. CONCLUSIONS: Increased H2S release is a relatively localized metabolic aberration of ulcerative colitis feces. This increased H2S may reflect abnormalities of the fecal bacteria and/or substrate availability.

Adolescent↗
PubMed1998

Identification of gases responsible for the odour of human flatus and evaluation of a device purported to reduce this odour.

BACKGROUND/AIMS: While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour. METHODS: Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus output. The concentrations of sulphur-containing gases in each passage were correlated with odour intensity assessed by two judges. Odour intensity was also determined after treatment of flatus samples with zinc acetate, which binds sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal. Utilising gastight Mylar pantaloons, the ability of a charcoal lined cushion to adsorb sulphur-containing gases instilled at the anus of eight subjects was assessed. RESULTS: The main sulphur-containing flatus component was hydrogen sulphide (1.06 (0.2) mumol/l), followed by methanethiol (0.21 (0.04) mumol/l) and dimethyl sulphide (0.08 (0.01) mumol/l) (means (SEM)). Malodour significantly correlated with hydrogen sulphide concentration (p < or = 0.001). Zinc acetate reduced sulphur gas content but did not totally eliminate odour, while activated charcoal removed virtually all odour. The cushion absorbed more than 90% of the sulphur gases. CONCLUSION: Sulphur-containing gases are the major, but not the only, malodorous components of human flatus. The charcoal lined cushion effectively limits the escape of these sulphur-containing gases into the environment.

Adolescent↗
PubMed1998

Use of a two-compartment model to assess the pharmacokinetics of human ethanol metabolism.

The relationship between blood ethanol concentration and hepatic ethanol metabolism commonly is calculated using the Michaelis-Menten equation and a one-compartment model that assumes equality of blood and hepatic ethanol concentrations. However, at low blood concentrations, most of the ethanol arriving at the liver is metabolized, and hepatic ethanol concentrations may fall far below that of the entering blood. We have developed a two-compartment model of ethanol metabolism that accounts for the fall in ethanol concentration that may occur as blood traverses the liver and used this model to make predictions concerning ethanol metabolism at various blood ethanol concentrations. The two-compartment model predicts that near-complete saturation will occur more abruptly and at a lower blood concentration (approximately 3 mM) than is the case with the one-compartment model. Thus, the two-compartment model predicts a near-constant ethanol elimination rate for blood ethanol concentrations above 3 mM (as commonly observed in human subjects), whereas the one-compartment model predicts an increasing elimination rate over the range of concentrations observed in experimental studies. In agreement with observed data, the two-compartment model predicts that first-pass metabolism should be extremely sensitive to the rate of ethanol absorption. Application of this model to previously published data indicated that, when absorption was slowed via concomitant food ingestion, first-pass metabolism accounts for approximately 50% and 10% of ethanol dosages of 0.15 g/kg and 0.3 g/kg, respectively. When ingested without food, there is negligible first-pass metabolism of even very small ethanol dosages (0.15 g/kg). These findings suggest that first-pass metabolism is an unimportant determinant of the blood ethanol response to ingestion of potentially inebriating doses of ethanol.

Alcohol Drinking↗
PubMed1997

Fecal hydrogen production and consumption measurements. Response to daily lactose ingestion by lactose maldigesters.

The alteration of hydrogen (H2) metabolism, which accounts for the large decrease in breath H2 excretion following prolonged ingestion of malabsorbed carbohydrate (lactulose, lactose in lactose maldigesters) was studied in six lactose-maldigesting adults. Metabolic inhibitors of the three main H2-consuming reactions (methanogenesis, sulfate reduction, and acetogenesis) were used to independently measure H2 production and consumption in fecal samples obtained after 10 days of either dextrose or lactose feeding. Absolute fecal H2 production (net of production minus consumption) after 3 hr of incubation with lactose was approximately threefold lower after lactose adaptation (242 +/- 54 microliters) compared to dextrose adaptation (680 +/- 79 microliters, P = 0.006). Fecal H2 consumption was not affected by either feeding period. We conclude that decreased absolute H2 production, rather than increased H2 consumption, is responsible for the decrease in breath H2 observed with lactose feeding.

Adult↗
PubMed1997

Absence of gaseous symptoms during ingestion of commercial fibre preparations.

BACKGROUND: While fibre is believed to cause gaseous symptoms, a study in healthy volunteers showed no increase in flatulence when the diet was supplemented with fermentable (psyllium) or non-fermentable (methylcellulose) fibre. However, extrapolation of this observation to subjects who use fibre is arguable since these individuals may have a propensity to gaseousness. In the present study, gaseous complaints during fibre ingestion were assessed in subjects who believed that a previous exposure to fibre induced gas. METHODS: In a double-blind protocol, subjects were randomized to one of four treatment periods, during which the regular diet was supplemented for 1-week periods with two daily doses of: placebo 10 g, psyllium 3.4 g, methylcellulose 2 g or lactulose 5 g. A symptom diary was maintained for 1-week periods on or off treatment. RESULTS: During treatment, the lactulose group passed gas significantly more often than did the psyllium or the methylcellulose group (P = 0.01). No other symptom was significantly different among the treatment groups. CONCLUSIONS: (1) psyllium and methylcellulose did not cause greater gaseous symptomatology than did placebo in subjects who believed that these preparations caused gas; and (2) subjects commonly misidentify dietary components that cause gaseous symptoms.

Adolescent↗
PubMed1997

Tolerance to the daily ingestion of two cups of milk by individuals claiming lactose intolerance.

We reported previously that consumption of one cup of milk (240 mL) per day produced negligible symptoms in lactase-nonpersistent (LNP) individuals self-described as being severely lactose intolerant. We hypothesized that such LNP individuals could also tolerate two cups of milk per day if taken in two widely divided doses with food, and that psychologic factors play a role in perceptions of lactose intolerance. The Minnesota Multiphasic Personality Inventory 2 (MMPI-2) was administered to 19 LNP subjects self-described as markedly lactose intolerant (S-LNP), 13 LNP subjects who denied lactose intolerance (A-LNP), and 10 lactase-persistent individuals who believed they were lactose intolerant (S-LP). Symptoms were recorded when LNP subjects ingested 240 mL regular or lactose-hydrolyzed milk twice daily for 7 d in a double-blind crossover study. The results showed that neither LNP group had a significant increase in symptoms (P < 0.05) during the regular compared with the lactose-hydrolyzed milk periods. However, S-LNP subjects reported significantly greater gaseous symptoms than did the A-LNP subjects during both treatment periods. The MMPI-2 showed a high score on the "lie" validity scale for S-LNP subjects. We conclude that LNP subjects tolerate two cups of milk per day without appreciable symptoms. S-LNP subjects have underlying flatulence that is misattributed to lactose intolerance. MMPI-2 results were of questionable validity because of the high rate of dissimulation by LNP subjects.

Abdominal Pain↗
PubMed1997

Use of measurements of ethanol absorption from stomach and intestine to assess human ethanol metabolism.

Controversy exists concerning the site (stomach vs. liver) and magnitude of first-pass metabolism of ethanol. We quantitated gastric and total ethanol absorption rates in five male subjects and utilized these measurements to evaluate first-pass metabolism. Gastric emptying of ethanol (0.15 g/kg) was determined via a gamma camera and gastric absorption from the ratio of gastric ethanol to [14C]polyethylene glycol. Gastric absorption accounted for 30% and 10% of ethanol administered with food and water, respectively. With food, estimated gastric mucosal ethanol concentrations fell from 19 to 5 mM over 2 h. Calculations using these concentrations and kinetic data for gastric alcohol dehydrogenase showed <2% of the dose underwent gastric metabolism. Application of observed ethanol absorption rates to a model of human hepatic ethanol metabolism indicated that only 30% and 4% of the dose underwent first-pass metabolism when administered with food and water, respectively. We conclude that virtually all first-pass ethanol metabolism occurs in the liver and first-pass metabolism accounts for only a small fraction of total clearance.

Absorption↗
PubMed1997

Influence of a methanogenic flora on the breath H2 and symptom response to ingestion of sorbitol or oat fiber.

BACKGROUND AND OBJECTIVES: We investigated the possibility that a variant of the normal colonic flora, a high concentration of methanogens, influences the host's response to ingestion of nonabsorbable, fermentable materials. METHODS: To better evaluate symptomatic and breath H2 and methane (CH4) responses, subjects were placed on a basal diet (primarily rice and hamburger) that contained minimal amounts of nonabsorbable, fermentable substrate. A breath CH4/H2 ratio of greater or less than 1 on the second day of the basal diet was used to categorize subjects as high (N = 9) or low (N = 25) CH4 producers. After stabilization of the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested either sorbitol (8.8 g) or oat fiber (10.2 g). RESULTS: The low CH4 producers had a significantly higher (p < 0.05) breath H2 concentration than the high producers on the basal diet and after ingestion of sorbitol (27.1 +/- 2.7 ppm vs 15.8 +/- 3.6 ppm) or oat fiber (13.1 +/- 0.08 ppm vs 9.6 +/- 1.2 ppm). Low producers of methane reported significantly increased bloating and cramping after sorbitol ingestion and increased bloating after fiber ingestion, whereas high CH4 producers reported no significant increase in these symptoms. CONCLUSION: The presence of a methanogenic flora is associated with a reduced symptomatic response to ingestion of nonabsorbable, fermentable material in healthy subjects. Manipulation of the normal flora could be of therapeutic value in nonmethanogenic patients with irritable bowel syndrome.

Avena↗
PubMed1997

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

Controversy exists concerning whether first-pass metabolism of imbibed ethanol occurs in the gastric mucosa or liver. We assessed ethanol metabolism in rat gastric mucosa by determining to what extent intact [14C]ethanol in body water plus hepatic metabolism could account for [14C]ethanol absorbed from the pylorus-ligated stomach. Intact [14C]ethanol in systemic body water accounted for 84 +/- 1.9% of the [14C]ethanol absorbed from the stomach over a 30-min period. Assuming a 15 ml/min hepatic blood flow, the predicted hepatic metabolism of [14C]ethanol over the 30 min of the study was 18% of the dose. The sum of intact [14C]ethanol and predicted hepatic metabolism accounted for 100% of the ethanol absorbed from the stomach. We conclude that negligible metabolism of ethanol occurred in the gastric mucosa.

Alcohol Dehydrogenase↗