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Biomedical subjects

J C Kolars

Publications and source records attributed to J C Kolars.

26 records · Page 2Linked to original sources

The erythromycin breath test as a predictor of cyclosporine blood levels.

The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients. Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine. Accordingly, the [14C-N-methyl] erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis. We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed. Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient. We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.

Adult↗

Pancreatic pseudocysts: clinical and endoscopic experience.

Records of 51 patients with proven pancreatic pseudocyst (PC) were retrospectively reviewed to assess clinical and endoscopic variables. Thirty-nine had surgery after preoperative endoscopic retrograde cholangiopancreatography (ERCP), six patients had ERCP only, and six patients had surgery without prior ERCP. Forty-two pancreatograms were obtained, and all were abnormal. PC communication with the pancreatic duct was present in 29 and ductal obstruction downstream from the PC was shown in 11 studies. Thirty-five cholangiograms were obtained and 19 were abnormal, including ductal narrowing in 16 and biliary calculi in three. PC contents were cultured intraoperatively in 29 patients, and 17 were positive. PC infection was highly correlated with the incidence of recurrent hospitalizations and with PC recurrence. PC infection did not occur significantly more often in patients with communicating PC or in those with preoperative ERCP. Factors that did not influence outcome included PC size, multiplicity, anatomic location, and PC communication with the pancreatic duct. Results from both ERCP and culture of PC contents add significantly to our knowledge of PC disease.

Adult↗

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↗

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↗

Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test.

The CYP3A subfamily of cytochromes P450 metabolize many medications and environmental contaminants. CYP3A4 and, in 25% of patients, CYP3A5 seem to be the major CYP3A genes expressed in adult liver. Hepatic levels of CYP3A4 can be estimated by the erythromycin breath test and vary at least 10-fold among patients. CYP3A4 has also been shown to be present in small bowel where it is responsible for significant "first-pass" metabolism of orally administered substrates. However, it is not known whether there is significant interindividual variability in the intestinal expression of CYP3A4, or whether the liver and intestinal catalytic activities of CYP3A4 correlate within an individual. It is also not known whether CYP3A5 is expressed in the small intestine. To address these questions, we administered the erythromycin breath test to 20 patients and obtained biopsies from their small bowel. There was a 6-fold variation in CYP3A catalytic activity (midazolam hydroxylation), an 11-fold variation in CYP3A4 protein content, and an 8-fold variation in CYP3A4 mRNA content in intestinal biopsies. There was an excellent correlation between intestinal CYP3A4 protein level and catalytic activity (r = 0.86; p = 0.0001); however, neither parameter significantly correlated with hepatic CYP3A4 activity as measured by the erythromycin breath test result (r = 0.27; p = 0.24 and r = 0.33; p = 0.15, respectively). We also found that CYP3A5 protein was readily detectable in biopsies from 14 (70%) of the patients, indicating that CYP3A5 is commonly expressed in human small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗