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Biomedical subjects

M D Levitt

Publications and source records attributed to M D Levitt.

At least 127 records · Page 7Linked to original sources
PubMed1988

Physiological measurement of luminal stirring in perfused rat jejunum.

Poor stirring of intestinal contents yields a preepithelial diffusion barrier that is thought to be the rate-limiting step in absorption of many compounds. In many previous studies, the resistance of this barrier is equal to an unstirred water layer of 300-800 micron. Using three probes, CO, glucose, and [14C]warfarin, we measured the preepithelial resistance in a 30-cm segment in rats that were 1) conscious, 2) anesthetized with pentobarbital sodium, or 3) anesthetized and laparotomized. Measurements with each of the probes showed that the maximal preepithelial resistance in conscious rats was equivalent to an unstirred layer of only approximately 100 micron. Anesthesia roughly doubled this resistance, and anesthesia and laparotomy caused a sixfold increase (unstirred layer of approximately 600 micron). We conclude that the luminal stirring is much more efficient than previously has been appreciated. The very thick jejunal unstirred layers reported previously (300-800 micron) reflect the results of studies performed under nonphysiological conditions or studies employing inappropriate techniques to measure luminal stirring.

Anesthesia↗
PubMed1988

Use of laminar flow and unstirred layer models to predict intestinal absorption in the rat.

Carbon monoxide (CO) and [14C]warfarin were used to measure the preepithelial diffusion resistance resulting from poor luminal stirring (RL) in the constantly perfused rat jejunum at varying degrees of distension (0.05, 0.1, and 0.2 ml/cm). RL was much greater than epithelial cell resistance, indicating that poor stirring was the limiting factor in absorption and that an appropriate model of stirring should accurately predict absorption. A laminar flow model accurately predicted the absorption rate of both probes at all levels of gut distension, as well as the absorption of glucose when RL was the rate-limiting factor in absorption. In contrast, an unstirred layer model would not have predicted that gut distension would have little influence on absorption, and would have underestimated [14C]warfarin absorption relative to CO. We concluded that in the perfused rat jejunum, laminar flow accurately models luminal stirring and an unstirred layer should be considered to be a unit of resistance in laminar flow, rather than a model of luminal stirring.

Animals↗
PubMed1987

H2 excretion after ingestion of complex carbohydrates.

Malabsorption of fermentable material in a variety of foods was assessed by measurement of breath H2 excretion. Breath H2 increased well above that observed in fasting subjects after ingestion of 100 g of carbohydrate in oats, whole wheat, potatoes, corn, and baked beans. Rice caused only a minimal increase in H2 excretion and hamburger was associated with no increase. We estimated the malabsorption of fermentable material by comparing the H2 excretion for 9 h after ingestion of various complex carbohydrates with that after 10 g of lactulose. The mean malabsorption of fermented material after 100-g carbohydrate meals was 20 g for baked beans; 7-10 g for wheat, oats, potatoes, and corn; and 0.9 g for rice. Whole oats or whole wheat resulted in 2-5 times more H2 than did the refined flours. As purified fiber appeared to be a poor substrate for H2 production by fecal homogenates, we conclude that most complex carbohydrates, with the exception of rice, contain a good deal of fermentable material that escapes small bowel absorption and it seems likely that this fermentable material is malabsorbed starch.

Adult↗
PubMed1987

Lactose digestion by yogurt beta-galactosidase: influence of pH and microbial cell integrity.

Lactase-deficient subjects more effectively digest lactose in yogurt than lactose in other dairy products, apparently due to yogurt microbial beta-galactosidase (beta-gal) which is active in the GI tract. We evaluated the effects of buffering capacity of yogurt, gastric pH, and microbial cell disruption on beta-gal activity and lactose digestion. Three times more acid was required to acidify yogurt than to acidify milk. Yogurt beta-gal was stable at pH 4.0 but inactivated at lower pH. When yogurt was sonicated to disrupt microbial cell structure, only 20% activity remained after incubation at pH 4.0 for 60 min. In vivo gastric pH remained greater than 2.7 for 3 h after ingestion of yogurt. Acidified milk alone or with disrupted yogurt microorganisms caused twice as much lactose malabsorption as did acidified milk containing intact yogurt microorganisms. The results provide a possible explanation for the survival of beta-gal activity from yogurt in the GI tract.

Adult↗
PubMed1987

Gaseous response to ingestion of a poorly absorbed fructo-oligosaccharide sweetener.

Fructo-oligosaccharides are naturally occurring sweet substances that are poorly absorbed and have the potential to be clinically useful nonnutritive sweeteners. Because most nonabsorbed carbohydrates are fermented yielding gas, we assessed flatulent symptoms and H2 excretion during ingestion of fructo-oligosaccharide (5 g tid) for 12 d. Ten subjects had significantly greater flatulence while taking the oligosaccharide than did five subjects taking sucrose (5 g tid). Breath H2 after 10 g fructo-oligosaccharide was similar to that of 10 g lactulose, suggesting near total malabsorption of the fructo-oligosaccharide. Although previous studies found a marked diminution in breath H2 after prolonged exposure to lactulose, breath H2 response increased by 50% after a 12-d period on the oligosaccharide and gaseous symptoms did not improve. We conclude that adaptation of colonic bacteria to carbohydrate malabsorption is variable and may depend upon quantity or nature of the carbohydrate.

Adult↗
PubMed1987

Temperature dependence of macroamylase binding.

The presence of macroamylasemia can be suspected when a patient has low renal clearance of amylase relative to creatinine (Cam/Ccr). However, the Cam/Ccr is seldom reduced to the extent expected given the fraction of amylase that appears to be bound in the macroamylase complex by gel filtration studies at 3 degrees C. Therefore, we tested the possibility that the binding of amylase in macroamylase complexes was temperature dependent and that binding at physiological temperatures might be less than at 3 degrees C. Gel filtration of five macroamylase-containing sera was carried out at temperatures of 3 degrees, 25 degrees, 37 degrees, 43 degrees, and 49 degrees C. Binding of amylase in the complex decreased as the temperature increased with virtually all amylase bound at 3 degrees C and virtually no amylase bound at 49 degrees C. The fraction of the amylase that bound at 37 degrees C was approximately what would have been predicted from the Cam/Ccr of each of the five subjects. We conclude that amylase binding in macroamylase complexes is extremely temperature sensitive and appreciable changes in binding may occur over the physiological temperature range of 37-41 degrees C.

Amylases↗
PubMed1987

Quantitative assessment of luminal stirring in the perfused small intestine of the rat.

We measured the resistance (RL) to CO absorption that resulted from poor luminal stirring in the constantly perfused rat jejunum. RL or calculated unstirred layer thickness was greater for 30-cm than 10-cm long segments, indicating lack of a uniform thickness of unstirred layer. The possibility that laminar flow existed in the gut was first tested by calculating expected CO absorptions from fluid moving with laminar flow. These values agreed closely with observed absorption rates. Laminar flow also was supported by the observation that CO absorption was independent of perfusate viscosity. Lastly, after sudden addition of phenolsulfonphthalein (PSP) to the perfusate, PSP outflow concentration was similar in tygon tubing (which has laminar flow) and a gut segment of comparable dimension. We conclude that flow in the perfused gut is laminar and that this laminar flow has many implications for studies carried out with the constant-perfusion technique.

Animals↗
PubMed1987

Milk intolerance and microbe-containing dairy foods.

The relationship between primary lactase deficiency, the amount of lactose in the diet, and symptoms of intolerance continues to be debated. Primary adult lactase deficiency is common with a worldwide occurrence of near 70%. Lactase-deficient individuals malabsorb lactose but may or may not show intolerance symptoms. The development of symptoms appears to depend on the dose of lactose ingested, whether it is accompanied by a meal or other food, rate of gastric emptying, and small intestine transit time. Lactose loads of 15 g or greater produce symptoms in the majority of lactase-deficient persons. However, when lactose loads of up to 12 g are fed, symptoms can be minimal or absent. Tolerance to yogurt, acidophilus milk, and other microbe-containing dairy foods has been suggested and is thought to be due to either a low lactose content or in vivo autodigestion by microbial beta-galactosidase. Up to 20 g of lactose in yogurt is tolerated well by lactase-deficient persons. Associated with the consumption of yogurt is a three- to fourfold reduction in lactose malabsorption as compared with similar lactose consumption in milk. Improved lactose digestion appears due to autodigestion by microbial beta-galactosidase. This enzyme may be released from yogurt culture by gastric or bile acid digestion. Feeding yogurt that was pasteurized following fermentation, with only trace amounts of microbial beta-galactosidase activity, results in a threefold increase in lactose malabsorption as compared with feeding yogurt with a viable culture. However, pasteurized yogurt also is tolerated well by lactase-deficient persons, suggesting that tolerance of up to 20 g of lactose in yogurt may be independent of lactose malabsorption. The enhanced lactose absorption and tolerance observed with yogurt feeding are not apparent when unfermented acidophilus milk or cultured milk are fed.

Animals↗
PubMed1987

Hyperamylasemia in patients with eating disorders.

Hyperamylasemia, which has been reported in patients with the eating disorders anorexia nervosa and bulimia, generally has been thought to result from pancreatitis. To evaluate the mechanisms of hyperamylasemia, we measured amylase, lipase, and isoamylase activity in 17 consecutive patients admitted to the eating disorder unit. Six patients had elevated amylase activity, and 5 of these 6 had isolated increases in salivary isoamylase activity. Six other patients had normal serum total amylase activity but modest elevations in the salivary isoamylase fraction. No patient developed clinical evidence of pancreatitis during hospitalization. Thus, the hyperamylasemia in patients with anorexia and bulimia often is caused by increased salivary-type amylase activity. The appropriate diagnostic test for hyperamylasemia in patients with anorexia or bulimia is the simple measurement of serum lipase or pancreatic isoamylase activity. If these levels are found to be normal, further tests to exclude pancreatitis are unnecessary.

Adolescent↗
PubMed1986

Role of the unstirred layer in protecting the murine gastric mucosa from bile salt.

Bile salts disrupt a functional gastric mucosal barrier which normally minimizes back-diffusion of H+ into mucosa. Our previous studies have shown that ionized bile salts disrupt the barrier to H+ by dissolving membrane lipids. The presence of an unstirred water layer on the surface of the gastric mucosa could protect against bile salt injury either by creating a concentration gradient of bile salt from lumen to mucosal surface or by slowing diffusion of lipid-laden mixed micelles away from the mucosal surface. In the present study we investigated this possibility in the anesthetized rat. Measurements of H+ back-diffusion and Na+ forward-diffusion across the gastric mucosa were made before and after exposure to a bile salt solution that was either unmixed or mixed by continuous withdrawal and injection. Using carbon monoxide diffusion, we observed this method of mixing to decrease the unstirred layer thickness from 880 to 448 micron (p less than 0.02). Mixing increased mean H+ back-diffusion induced by a 10 mM mixture of six conjugated bile salts from -2.58 to -4.11 microEq/min (p less than 0.01) and increased mean forward-diffusion of Na+ from 1.81 to 3.27 microEq/min (p less than 0.01). Mixing also increased efflux of mucosal phospholipid (32.7 to 52.2 nmol/min, p less than 0.05) and of cholesterol (4.89 to 8.87 nmol/min, p less than 0.05) into the bile salt solution. Addition of saturation amounts of lecithin and cholesterol to the bile salt solution completely prevented disruption of the barrier whether the solution was mixed or not. Mixing also increased mucosal uptake of bile salt from 74.6 to 221.3 nmol/min (p less than 0.01) when no lipids were added. In the presence of lecithin and cholesterol, mixing increased absorption of bile salt from 63.5 to 165.6 (p less than 0.02). These findings further support the hypothesis that bile salts disrupt the gastric mucosal barrier by dissolution of mucosal membrane lipids, and provide evidence that the unstirred water layer helps protect the gastric mucosa from bile salt injury.

Animals↗
PubMed1986

Breath hydrogen and methane: poor indicators of apparent digestion of soy fiber.

To examine whether end-alveolar breath hydrogen and methane could be used as indicators of fiber digestion in humans, 16 male subjects were fed four fiber-free, complete liquid diets with 0, 30 g (heat processed), 30 g, and 60 g/day soy polysaccharide. Breath hydrogen was measured hourly and breath methane every 4 h on days 6 and 8 of each study period. Feces were collected, homogenized, dried, and analyzed for neutral detergent fiber (NDF). NDF in diets was determined and apparent NDF digestibility calculated. NDF from soy was extensively fermented, greater than 80%, on the fiber-containing diets. No significant relationship was found between breath-gas excretion and fiber digestion, although breath-gas values varied greatly. Breath hydrogen and methane were not significantly different when subjects consumed diets containing 0, 30, or 60 g soy polysaccharide.

Adult↗
PubMed1986

Parathyroidectomy in chronic renal failure.

Between 1978 and 1984, 19 patients at Royal Perth Hospital (RPH) underwent parathyroidectomy for secondary (renal) hyperparathyroidism. This represented 6.0% of the overall dialysis population treated at RPH during this period of time. The mean duration of pre-operative dialysis for these 19 patients was 48 months, compared with a mean duration of 30 months for the overall dialysis population. The principal indications for parathyroidectomy were symptomatic hyperparathyroid bone disease (10), hypercalcaemia (six), progressive lower limb ischaemia (two) and painful peri-articular calcification (one). The complications of chronic renal failure that were most consistently improved by parathyroidectomy were the clinical, radiological and biochemical manifestations of hyperparathyroid bone disease and hypercalcaemia. Features such as pruritus, soft tissue calcification, vessel wall calcification and peripheral ischaemia responded less predictably. Hyperparathyroid bone disease and hypercalcaemia remain the principal indications for parathyroidectomy in chronic renal failure. Profound postoperative hypocalcaemia was the major early postoperative management problem (seven patients) and was closely linked with the severity of pre-operative hyperparathyroid bone disease. It was also seen more frequently in those patients undergoing total parathyroidectomy with immediate autotransplantation of parathyroid tissue (TP-A), than in those in whom residual parathyroid tissue was left in situ (subtotal parathyroidectomy or STP). Recurrent hyperparathyroidism (four patients) was the major late postoperative complication, but was more frequently the result of a supernumerary or previously overlooked fourth parathyroid gland (three), than due to hyperplasia of residual parathyroid tissue (one). STP and TP-A were equally effective in controlling or reversing renal hyperparathyroidism, but the former was associated with a lower incidence of postoperative management problems and should be the preferred operation in this group of patients.

Adult↗
PubMed1986

Liver abscess in Western Australia (1974-1983).

Over the 10 year period 1974-1983, 91 cases of liver abscess presented to the major teaching hospitals in Perth, Western Australia. Amoebic liver abscess (ALA) accounted for 37 (or 41%) of these cases, an incidence inflated by Perth's proximity to south-east Asia where amoebiasis is endemic. This frequent recent history of contact, the availability of sensitive and specific diagnostic serology and a clinical presentation usually suggesting pathology in the right upper quadrant, accounted for the consistently short delay in diagnosis of ALA. There were no deaths from ALA and a low incidence of complications such as secondary infection or rupture into the thorax. On the other hand, pyogenic liver abscess (PLA) commonly presented in a more non-specific manner and in an older age group, contributing to a long delay in diagnosis. Despite improvements in liver imaging techniques and advances in antibiotic and general supportive therapy, mortality for PLA remains high, 20% in this series. Fatal PLA was associated with multiple abscesses not amenable to drainage, increasing age, delay in diagnosis and the presence of septicaemia.

Adolescent↗
PubMed1986

Urine protein excretion in acute pancreatitis.

The mechanism of the increased renal clearance of amylase and the amylase to creatinine clearance ratio (CAM/CCR) in acute pancreatitis remains controversial with both renal tubular dysfunction and altered glomerular permeability being invoked as explanations. To differentiate between these mechanisms, we investigated the quantity and character of protein excretion in 10 patients with pancreatitis. For a short period of time, seven of 10 patients had mild proteinuria with a mean protein excretion rate of 230 +/- 154 mg/24 hr. Proteinuria decreased in 9/9 survivors to 17 +/- 18 mg/24 hr. Albumin excretion rate initially was minimally increased in 10/10 patients with a mean of 61 +/- 40 mg/24 hr, decreasing during recovery in 8/9 survivors to 10.9 +/- 10.4 mg/24 hr (P less than 0.01). Electrophoresis of urine obtained during the acute phase consistently showed a low molecular weight proteinuria pattern that cleared with recovery. Twenty-one of 22 urinary samples with an elevated CAM/CCR had a low molecular weight protein pattern. All the above findings can be explained by alterations in renal tubular reabsorption of proteins without changes in glomerular permeability. In 2/4 patients a low molecular weight protein was present in urine specimens from the acute phase that was not present in highly concentrated urine specimens from the recovery period. This raises the possibility that an abnormal low molecular weight protein enters the serum in acute pancreatitis, which, after glomerular filtration, produces the renal tubular malfunction found in acute pancreatitis.

Albuminuria↗