Measurement of mass and radioactivity of 14CO using a reduction detector.
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Animals↗
Biomedical subjects
M D Levitt
Publications and source records attributed to M D Levitt.
Non-seminomatous germ cell testicular tumours: residual masses after chemotherapy.
Twenty-three consecutive patients with metastatic non-seminomatous germ cell testicular tumours were treated with a combination of cisplatinum, vinblastine and bleomycin. Nineteen had elevated serum tumour marker levels (alpha-fetoprotein and beta-subunit HCG) prior to chemotherapy. In 11 of the 19, residual masses were present on the completion of induction chemotherapy despite normal serum tumour marker levels (residual mass after chemotherapy). The management of these 11 patients was based on a policy of observation rather than routine resection of residual deposits and all are currently alive (32-58 months) with ten free of active disease. Two of the eleven required additional chemotherapy when serial tumour marker levels became elevated during follow-up. Another six have been observed without further intervention and have remained well with stable or diminishing deposits. The remaining three have required resection of residual masses, in each case because of mass enlargement despite persistently negative tumour marker levels. None of the masses showed histological evidence of malignancy. A more selective approach to resection of residual masses after chemotherapy is advocated.
Antineoplastic Combined Chemotherapy Protocols↗
Absorption of calcium from milk and yogurt.
An increased prevalence of osteoporosis has been observed in lactase-deficient subjects. This association has been attributed to an avoidance of calcium-containing dairy products by lactase-deficient subjects and/or an adverse affect of lactose malabsorption on calcium absorption. Because the lactose in yogurt can be digested and absorbed by hypolactasic subjects, we tested the ability of lactase-deficient subjects and controls to absorb calcium from milk and yogurt. Subjects ingested 270 mg of Ca plus 45Ca in 250 g of milk or 147 g of commercial, unflavored yogurt, and blood radioactivity was assessed at intervals over 24 h. Based on the areas under the blood radioactivity curves, lactase-deficient subjects and controls absorbed calcium equally well from yogurt and milk. Lactase-deficient subjects absorbed 45Ca from both sources at least as well as did the controls. While we found no evidence to indicate that calcium in yogurt is better absorbed than calcium in milk, yogurt remains an excellent source of calcium because this fermented product is well tolerated by lactase-deficient subjects.
Adult↗
Tin protoporphyrin inhibits carbon monoxide production in adult mice.
We studied the effect of tin protoporphyrin, a potent inhibitor of heme oxygenase (EC 1.14.99.3), on carbon monoxide (CO) production in mature mice. Measurements of CO production provide a sensitive, noninvasive means of quantitating heme catabolism. CO accumulation in the gas space of closed chambers was decreased by about 25% for mice treated with two 50 nmol/g doses of tin protoporphyrin as compared to saline-treated controls. Calculated rates of CO production were 0.28 +/- 0.07 and 0.40 +/- 0.05 nmol X g-1 X h-1 for mice injected with tin protoporphyrin and saline, respectively (p less than 0.01). When hemin (125 nmol/g) was administered to simulate hemolysis, CO production increased markedly in both saline- and tin protoporphyrin-treated mice. However, the rate of CO production in tin protoporphyrin-treated mice was only 44% that of saline-treated animals (p less than 0.0001). These studies demonstrate that tin protoporphyrin inhibits heme catabolism in both the basal- and heme-loaded states and confirm that this inhibition is at the heme oxygenase step in the heme to bilirubin pathway.
Animals↗
Serum tests for pancreatitis in patients with abdominal pain.
Though the serum total amylase test has been used for the diagnosis of pancreatitis for over 50 years, both its clinical sensitivity and specificity are far from perfect. We first present the results of serial serum total amylase, pancreatic isoamylase, lipase, and immunoreactive trypsin tests in nine patients during the week after their admission to the hospital with a diagnosis of acute pancreatitis, and then compare the serum total amylase, lipase, and immunoreactive trypsin levels in the initial serum submitted for amylase analysis from 100 patients because of the clinical suspicion of acute pancreatitis. In the former group of patients, the serum total amylase test was the least sensitive of the tests for pancreatitis after the first hospital day. In the latter group of patients, the largest discordance was found in patients with elevated serum total amylase levels, but normal lipase and immunoreactive trypsin levels. In 90% of these discordant cases, the elevation of serum total amylase was due to salivary amylase, yielding a maximum clinical specificity of only 71% for serum total amylase. Based on these data, we conclude that alternate tests deserve careful consideration as replacements for the serum total amylase test.
Abdomen↗
Yogurt--an autodigesting source of lactose.
Large quantities of yogurt are consumed by some lactase-deficient population groups. We used breath hydrogen measurements to determine whether lactase-deficient subjects absorbed lactose in yogurt better than lactose in milk. Ingestion of 18 g of lactose in yogurt resulted in only about one third as much hydrogen excretion as a similar load of lactose in milk or water, indicating a much better absorption of lactose in yogurt. Ingestion of yogurt also resulted in fewer reports of diarrhea or flatulence than did a similar quantity of lactose ingested in milk or a water solution. The enhanced absorption of lactose in yogurt appeared to result from the intraintestinal digestion of lactose by lactase released from the yogurt organisms. This autodigesting feature makes yogurt a well-tolerated source of milk for lactase-deficient persons and may explain the widespread consumption of yogurt by lactase-deficient population groups.
Adult↗
Comparison of serum amylase pancreatic isoamylase and lipase in patients with hyperamylasemia.
We compared results of measurements of total serum amylase, pancreatic isoamylase, and lipase measurements in patients with hyperamylasemia. Serial measurements of these three enzyme levels in patients recovering from acute pancreatitis indicated that pancreatic isoamylase and lipase were elevated above normal to a greater extent and remained elevated much longer than did the total amylase. This finding indicates an appreciable sensitivity advantage of the pancreatic isoamylase and lipase over total amylase measurement during the recovery phase of pancreatitis. Comparison of pancreatic isoamylase and lipase levels in selected sera indicated a good correlation (r = 0.84) between these two measurements in patients who did not have macroamylasemia. Lipase was normal in sera with amylase elevations due solely to salivary isoamylase. Thus, in nonmacroamylsemic sera, pancreatic isoamylase and lipase appear to be roughly interchangeable markers of the level of pancreatic enzymes in the blood. An advantage of the lipase assay is that this enzyme is normal in hyperamylasemia caused by macroamylasemia, whereas the inhibitor assay indicates that the pancreatic isoamylase is elevated. Development of automated assays for either pancreatic isoamylase or lipase should lead to the routine use of one of these assays in place of the present reliance on total amylase measurements in the diagnosis of pancreatitis.
Acute Disease↗
Lactose malabsorption from yogurt, pasteurized yogurt, sweet acidophilus milk, and cultured milk in lactase-deficient individuals.
The use of fermented dairy foods is common in areas of the world where lactase deficiency is prevalent. Recently, we have shown that the digestion of lactose from yogurt is enhanced as compared to that from milk. This enhanced digestion is apparently due to inherent B-galactosidase in yogurt which is active in the gastrointestinal tract after consumption of the yogurt. Furthermore, yogurt is well tolerated by lactase-deficient subjects resulting in little or no gastrointestinal distress. Since other fermented and microbial-containing dairy foods are consumed worldwide and may also contain some "lactase" activity, we chose to evaluate the digestion of lactose from three of these products: pasteurized yogurt, cultured milk (buttermilk), and sweet acidophilus milk. Breath hydrogen techniques were used to evaluate lactose malabsorption in nine lactase-deficient subjects. The studies demonstrated that yogurt is unique among the products tested in enhancing the digestion of lactose. Furthermore, pasteurization of yogurt eliminated the enhanced digestion of lactose, reduced the inherent lactase activity of the yogurt by 10-fold and reduced cell counts by 100-fold. Interestingly, eight of nine subjects fed cultured milk experienced gastrointestinal distress, whereas all subjects fed pasteurized yogurt were symptom free, even though the amount of malabsorbed lactose was similar.
Adult↗
Role of gas in functional abdominal pain.
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Abdomen↗
Use of carbon monoxide to measure luminal stirring in the rat gut.
We used carbon monoxide (CO) as a probe to quantitatively measure intestinal unstirred water layers in vivo. CO has several features that make it uniquely well suited to measure the unstirred layer in that its tight binding to hemoglobin makes uptake diffusion limited, and its relatively high lipid solubility renders membrane resistance negligible relative to the water barriers of the unstirred layer and epithelial cell. The unique application of CO was the measurement of the absorption rate of CO both from the gas phase as well as a solute dissolved in saline. Several lines of evidence showed that a gut stripped free of saline and then filled with gas contained a negligible unstirred layer. Thus, absorption of CO from the gas phase measured resistance of just the epithelial cell. Subtraction of this value from the resistance of CO absorption from saline provided a direct measure of unstirred layer resistance. Studies in the rat showed for a 3-min absorption period that the conventionally calculated apparent unstirred layer for the jejunum was 411 micron and for the colon was 240 micron. However, this conventionally calculated unstirred layer resistance did not truly depict the situation in the rat gut, since there was a continuing depletion of CO from outer surfaces of luminal contents throughout the experiment period. This produced a continually increasing diffusion barrier with time. Calculation of expected absorption rate from unstirred cylinders with the dimensions of the rat gut indicated that there was virtually no stirring in the small intestine and minimal stirring in the colon. The technique described in this paper appears to be simpler and to require fewer assumptions for validity than other techniques previously used to measure unstirred layers in vivo.
Animals↗
Carbohydrate malabsorption and intestinal gas production.
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Adult↗
Gas chromatographic method for the determination of the lower volatile alcohols in rat blood and in human stool specimens on a fused silica capillary column.
A method is described for the simultaneous quantitation of the lower volatile alcohols in stool specimens and rat blood. The addition of potassium carbonate to the assay mixture markedly increased the sensitivity in the detection of these compounds. The method is shown to be simple and reproducible and is suitable for following the metabolism of ethanol in human stool specimens.
Alcohols↗
Malabsorption of starch: a normal phenomenon.
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Colon↗
Evaluation of an inhibitor assay to determine serum isoamylase distribution.
We tested a technique to distinguish salivary from pancreatic isoamylase using a wheat protein which inhibits salivary isoamylase. The inhibitor technique accurately reflected the preponderance of pancreatic or salivary isoamylase in sera which had been "spiked" with human pancreatic or salivary isoamylase. Comparison of the results of either cellulose acetate electrophoresis or isoelectric focusing showed an excellent correlation (r = 0.99) in 43 hyperamylasemic sera which did not contain macroamylase. Normal values obtained in 160 healthy subjects indicated that pancreatic isoamylase comprised 41 +/- 21% (1 SD) of total serum amylase activity and the upper limit of normal for serum pancreatic isoamylase was 166 IU/liter. The inhibitor assay provides a simple and accurate means of differentiating salivary from pancreatic hyperamylasemia.
Amylases↗
Diagnostic value of routine isoamylase assay of hyperamylasemic serum.
The purpose of this study was to determine if routine isoamylase assay would provide valuable diagnostic information in patients with hyperamylasemia. Isoamylase distribution was determined in sera of 37 consecutive hyperamylasemic patients. The attending physicians (without knowledge of the isoamylase level) had considered acute pancreatitis to be "probable" in 19, "possible" in 4, and "unlikely" in 14 of these 37 patients. Three of the patients considered probably to have pancreatitis and 3 thought possibly to have pancreatitis had normal serum pancreatic isoamylase levels. Knowledge of the normal pancreatic isoamylase level in these 6 patients probably would have changed the clinical diagnosis to some condition other than pancreatitis. Of the 14 hyperamylasemic patients thought "unlikely" to have pancreatitis, 7 had an elevation of just pancreatic isoamylase and 3 additional patients had elevation of both pancreatic and salivary isoamylases. It seems likely that knowledge of these elevated pancreatic isoamylase levels would have changed the clinical diagnosis to "probable" pancreatitis for many of these patients. We conclude that routine isoamylase assay provides diagnostic information that might change the clinical diagnosis in 20%--40% of hyperamylasemic patients.
Acute Disease↗
A rapid and simple assay to determine if macroamylase is the cause of hyperamylasemia.
Macromolecules are known to precipitate selectively in concentrated solutions of polyethylene glycol. This report describes the use of polyethylene glycol 6000 to distinguish macroamylase from normal-sized serum amylase. Preliminary studies indicated that a PEG concentration of 12% and a 10-min incubation at 37 degrees C separated normal serum amylase from macroamylase. Using these conditions, study of 18 macroamylase-containing sera showed precipitation of at least 73% of the amylase activity. In contrast, in 46 normal sera and 16 hyperamylasemic (but not macroamylasemic) sera, less than 52% of the amylase activity was precipitated by polyethylene glycol. This test provides a rapid, simple, and accurate means of determining if macroamylasemia is the cause of hyperamylasemia.
Amylases↗
Metabolism of carbon monoxide by the colonic flora of humans.
The metabolism of carbon monoxide by the colonic flora was investigated using human fecal homogenates. During anaerobic incubation, these homogenates rapidly consumed added carbon monoxide reducing the PCO level to a minimum of about 0.2 ppm. In the presence of glucose, carbon monoxide consumption averaged about 0.7 ml/h . g feces and without glucose about 0.2 ml/h . g feces. This consumption was not observed if the homogenates were autoclaved, passed through a bacterial filter, or cultured aerobically, indicating that the carbon monoxide was removed by the metabolism of fecal anaerobes. Aerobic incubation of fecal homogenates resulted in slow but definite release of carbon monoxide. While bacterial carbon monoxide consumption probably does not play an appreciable role in the turnover of carbon monoxide that is inhaled or exogenously produced, it is possible that carbon monoxide uptake by colonic flora protects other fecal organisms and possibly the host from carbon monoxide liberated in the gut.
Aerobiosis↗