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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 199 records · Page 11Linked to original sources

Mechanism of increased renal clearance of amylase/creatinine in acute pancreatitis.

We investigated three possible causes of the increased ratio of amylase/creatinine clearance observed in acute pancreatitis. The presence of rapidly cleared isoamylase was excluded by studies of serum and urine, which demonstrated no anomalous isoamylases. In pancreatitis, the ratios (+/-1 S.E.M.) of both pancreatic isoamylase (9.2+/-0.6 per cent) and salivary isoamylase (8.6+/-1.6 per cent) were significantly (P less than 0.01) elevated over respective control values (2.4+/-0.2 and 1.8+/-0.2 per cent). Increased glomerular permeability to amylase was excluded by the demonstration of normal renal clearance of dextrans. We tested tubular reabsorption of protein by measuring the renal clearance of beta2-microglobulin, which is relatively freely filtered at the glomerulus and then avidly reabsorbed by the normal tubule. During acute pancreatitis the ratio of the renal clearance of beta2-microglobulin to that of creatinine was 1.22+/-0.52 per cent, an 80-fold increase over normal (0.015+/-0.002 per cent), with a rapid return toward normal during convalescence. Presumably, this reversible renal tubular defect also reduces amylase reabsorption and accounts for the elevated renal clearance of amylase/creatinine observed in acute pancreatitis.

Acute Disease↗

Intestinal villus blood flow measured with carbon monoxide and microspheres.

The purpose of the present study was to compare the small intestinal blood flow that equilibrates with luminal CO (FLco) with simultaneous determinations of villus blood flow measured by a recent modification of the microsphere technique. These studies, carried out in rabbits, showed that FLco closely correlated (r = 0.83) with villus flow measured with microspheres over a three-fold range of flows, and the mean rate of flow to the villi by both techniques was about 0.08 ml/min X g of intestine. Thus, FLco appears to be a measure of villus blood flow. Based on previous studies of inert gas uptake from the rabbit small intestine, it appears that absorption of readily diffusible substances in the rabbit can be represented by a simple two-component model: a flow-limited component in which substances equilibrate with villus blood flow and are carried away without subsequent countercurrent exchange, and a diffusion-limited component which presumably represents uptake by the blood flow of the crypt region or submucosa.

Animals↗

Fate of soluble carbohydrate in the colon of rats and man.

The fate of glucose in the colon of rats and man was investigated by measuring breath 14CO2 and fecal 14C after direct instillation of 14C-labeled glucose, acetate, and lactate into the cecum. For the 6 h after administration of as much as 400 mg of [U-14C]-glucose to the rat and 12.5 g to man, 14CO2 excretion was as rapid after intracecal as after intragastric instillation. Less than 20% of 14C instilled into the cecum as glucose was recovered in feces and only about 15% of this fecal 14C was in a dialyzable form. The conversion of intracecally administered glucose to CO2 was dependent upon the presence of the colonic flora, as evidenced by the minimal excretion of 14CO2 after administration of [14C]glucose to germ-free rats. In contrast, acetate and lactate, fermentation products of glucose, were converted to CO2 as rapidly in germ-free rats as in their conventional counterparts. Measurement of O2 availability in the colonic lumen indicated that insufficient O2 was available for the aerobic metabolism of glucose by the colonic bacteria. These experiments suggest that the colon bacteria anaerobically metabolize most of the glucose to short-chain fatty acids, which are absorbed and oxidized by the host. Most of the remaining fecal glucose is converted to a larger molecular form that has limited osmotic activity. Thus, the colonic flora benefits the host by reducing the osmotic load of nonabsorbed carbohydrate and by making possible the salvage of a large percentage of the calories of carbohydrate, which is not absorbed in the small bowel.

Acetates↗

Quantitative measurement of lactose absorption.

The quantity of lactose not absorbed by 4 normal and 6 lactase-deficient subjects was determined by three indirect methods which involved: (1) measurement of pulmonary hydrogen (H2) excretion, (2) pulmonary (14)CO2 excretion, and (3) stool (14)C excretion, after ingestion of 12.5 g of 1-(14)C-lactose and 4 g of polyethylene glycol (PEG). Results were compared with absorption determined directly from the (14)C:PEG ratio of multiple terminal ileal aspirates. The fraction of lactose not absorbed determined by ileal aspiration ranged from 0 to 8% in normals and 42 to 75% in mild-intolerant subjects. Whereas all three indirect methods were useful in qualitatively separating normal from deficient subjects, the quantity of lactose absorbed as determined by H2 excretion correlated most closely with ileal measurements (r = 0.94). Pulmonary (14)CO2 excretion for 24 hr after (14)C-lactose ingestion did not distinguish normal (17 +/- 4% (SEM) of ingested (14)C per 24 hr) from lactase-deficient subjects (21.1 +/- 3%). Likewise, stool (14)C:PEG ratios grossly underestimated malabsorption with less than one-quarter of the nonabsorbed (14)C appearing in the stool. This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon. Analysis of ileal fluid collected during passage of the lactose meal indicated that about two-thirds of the osmotic load delivered to the colon consists of endogenous electrolytes. Thus the water load delivered to the colon is about 3 times that calculated to be osmotically held by the nonabsorbed sugar.

Carbon Dioxide↗

The role of intestinal gas in functional abdominal pain.

A washout technic with intestinal infusion of an inert gas mixture was used to study the relation of gas to functional abdominal symptoms. The volume of gas in the intestinal tract (176 plus or minus 28 ml S.E.M.) of 12 fasting patients with chronic complaints of excess gas did not differ significantly (P greater than 0.10) from that of 10 controls (199 plus or minus 31 ml). Similarly, there was no difference in the composition or accumulation rate of intestinal gas. However, more gas tended to reflux back into the stomach in patients who complained of abdominal pain during infusion of volumes of gas well tolerated by controls. Six patients with severe pain during the study had intestinal transit times of gas (40 plus or minus 6 minutes S.E.M.) that were significantly (P less than 0.05) longer than those of the control group (22 plus or minus 3 minutes). Thus, complaints of bloating, pain and gas may result from disordered intestinal motility in combination with an abnormal pain response to gut distention rather than from increased volumes of gas.

Abdomen↗

Failure to demonstrate degradation of (4-14C) cholesterol to volatile hydrocarbons in rats and in human fecal homogenates.

The inability of previous workers to recover completely the radioactivity from ingested [4-14C] cholesterol has led to the hypothesis that the colonic flora of some individuals degrade the sterol nucleus to volatile hydrocarbons, particularly CH4. In the present investigation, the production of radioactive volatiles was measured following incubation of [4-14C] cholesterol with 8 human fecal homogenates or after instillation of the labeled sterol into the cecum of 3 rats housed in a closed rebreathing system. Three of the 8 homogenates and each of the 3 rats produced copious CH4. However, analysis by combustion demonstrated no radioactivity above background in the volatile headspace of the homogenates or the gas space of the closed system housing the rats, indicating that less than 0.001% of the number 4 carbon of [4-14C] cholesterol could have been converted to volatile hydrocarbons. This study, therefore, provides no support for the concept that volatile products account for the incomplete recovery of ingested sterols observed in certain subjects. However, this hypothesis can not be excluded entirely until similar results are obtained with subjects who can be shown to degrade cholesterol.

Animals↗

Intestinal gas.

Patients with functional bowel disease commonly complain of abdominal pain, bloating, and excessive flatulence and eructation. Pain and bloating may be primarily caused by abnormal intestinal motility rather than by excessive intestinal gas. As yet there are no data available that prove excessive flatulence is actually caused by the presence of excessive intestinal gas. A study of the composition of intestinal gas provides insight into whether it is derived from swallowed air or from intraluminal metabolism. Therapy aims primarily at excluding the presence of organic disease as a cause and reassuring the patient that the disorder is functional in nature. Dietary manipulation, changing the habit of aerophagia, exercise, and pressure and heat applied to be abdominal area are all possibilities to be tried.

Aerophagy↗

Intestinal gas.

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Animals↗

Factors affecting the concentration of combustible gases in the colon during colonoscopy.

The colonic concentrations of the combustible gases, H2 and CH4, were well below hazardous levels in 60 consecutive patients at the time of colonoscopy. Independent analysis of the effect of a low residue liquid diet, a 12-hr fast, and bowel cleansing on the pulmonary excretion of these gases suggest that the low colonic concentrations encountered were largely the result of our patient preparation procedure. Both ingestion of the liquid diet and fasting decreased the pulmonary excretion of H2 markedly but caused only a slight fall in CH4 excretion. Thus H2, but not CH4, production appears to depend on the delivery to the colonic bacteria of exogenous fermentable substrate. Bulk removal of bacteria from the colon resulted in about a 10-fold reduction in the excretion of both gases. The results of these studies do not support the need for routine CO2 insufflation prior to colonoscopic electrosurgical polypectomy.

Cathartics↗

Investigation of small bowel transit time in man utilizing pulmonary hydrogen (H2) measurements.

Pulmonary H2 excretion was used to quantitate the small bowel transit time in man. This technique is based on the observation that H2 is produced when carbohydrate is fermented by colonic bacteria and that this H2 production is reflected by a concomitant increase in breath H2 excretion. The time, therefore, between ingestion of the unabsorbable disaccharide, lactulose, and the rise in breath H2 represents the small intestinal transit time of the head of the lactulose load as it passes through the gut. Following ingestion of a mixture of polyethylene glycol (PEG) and lactulose by 9 subjects, transit time measured by H2 excretion correlated closely with the simultaneously determined time for PEG to reach the distal ileum (r equals 0.97). The ileal appearance of PEG preceded the rise in H2 excretion by a mean of 7.6 minutes. Transit time of 19 Gm. of lactulose in 40 healthy subjects averaged 72 minutes (range 25 to 118). Studies repeated 3 to 5 times in 6 subjects showed good individual reproducibility with subsequent measurements differing from initial by a mean of plus or minus 14 per cent. There was an inverse relation between transit time and dose of lactulose ingested by 9 subjects with 5, 10 and 20 Gm. of lactulose having mean transit times of 128 plus or minus 19, 94 plus or minus 15, and 40 plus or minus 8 (S$M.) minutes, respectively. This technique appears to provide a simple, safe, and noninvasive means of studying small bowel transit time in man.

Adolescent↗

Use of inert gases and carbon monoxide to study the possible influence of countercurrent exchange on passive absorption from the small bowel.

The purpose of the present study was to quantitate the influence of countercurrent exchange on passive absorption of highly diffusible substances from the small intestine of the rabbit. The absorption of carbon monoxide, which is tightly bound to hemoglobin and therefore cannot exchange, was compared to the absorption of four unbound gases (H(2), He, CH(4), and (133)Xe), which should exchange freely. The degree to which the observed absorption of the unbound gases falls below that predicted from CO absorption should provide a quantitative measure of countercurrent exchange.CO uptake at high luminal Pco is flow-limited and, assuming that villus and central hemoglobin concentrations are equal, the flow that equilibrates with CO (F(co)) was calculated to equal 7.24 ml/min/100 g. The observed absorption rate of the unbound gases was from two to four times greater than would have been predicted had their entire uptake been accounted for by equilibration with F(co). This is the opposite of what would occur if countercurrent exchange retarded absorption of the unbound gases. The unbound gases have both flow- and diffusion-limited components, and F(co) should account for only the fraction of absorption that is flow limited. A simple model of perfusion and diffusion made it possible to calculate the fraction of the total uptake of unbound gases that was flow limited. This fraction of the total observed absorption rate was still about 1.8 times greater than predicted by CO absorption. A possible explanation for this discrepancy is that plasma skimming reduces the hemoglobin of villus blood to about 60% of that of central blood. Thus, F(co) is actually about 1.7 times greater than initially calculated, and with this correction, there is close agreement between the predicted and observed rates of absorption of each of the unbound gases. We conclude that countercurrent exchange does not influence passive absorption under the conditions of this study.

Animals↗