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F Kern

Publications and source records attributed to F Kern.

At least 91 records · Page 5Linked to original sources
PubMed1982

A method for the accurate measurement of isotope ratios of chenodeoxycholic and cholic acids in serum.

A method for the extraction of bile acids from serum is described that enables the stable isotopic content of chenodeoxycholic acid and cholic acid to be determined accurately to levels as low as the natural 13C abundance. The method uses Sep-Pak C18 reverse phase cartridges both for extraction and purification procedures. Free bile acids, bile acid conjugates, and 3-monosulfated bile acid conjugates are recovered in high yield from the Sep-Pak in methanol-water 75:25 after first removing impurities with hexane and methanol-water 40:60 washes. Other important features of the method include the use of enzymatic rather than alkaline hydrolysis of bile acid conjugates, the use of ammonia as the reagent gas for chemical ionization mass spectrometric measurement of isotopic ratios, and the exclusion of all extraneous components in the final sample from the ion source. This method should be applicable to kinetic studies of bile acids using bile acids labeled with stable isotopes and serum measurements, and provides an alternative sampling point in the enterohepatic circulation to conventional duodenal bile samples requiring intubation.

Acetylation↗
PubMed1982

Gallbladder function in the human female: effect of the ovulatory cycle, pregnancy, and contraceptive steroids.

We have previously shown that in pregnancy fasting gallbladder volume is increased and emptying after a small volume liquid meal is incomplete. In this study we measured gallbladder volume throughout day and night in healthy women ingesting regular meals. Pregnant women, postpartum women, contraceptive-steroid users, and controls in both phases of the ovulatory cycle were studied. After an overnight fast gallbladder volume was measured by realtime ultrasonography in the fasting state and every 5-10 min for 90 min after breakfast. Residual volume was the lowest volume achieved and the rate constant of gallbladder emptying was calculated from the ln/linear regression of gallbladder volume vs. time. Gallbladder volume was also measured hourly from 11 AM to midnight while subjects ate regular, standard meals, allowing the determination of an average hourly volume. There was no effect of phase of the ovulatory cycle on any measure of gallbladder function. Fasting, residual, and average hourly volume were increased in all trimesters of pregnancy, but tended to return to normal in the postpartum period. Women taking contraceptive steroids had an increased fasting volume. Two distinct rates of emptying after breakfast, an early and a late one, were identified. The early rate was the same in all groups. Pregnant women had a slower late rate of emptying, but women taking contraceptive steroids had emptying rates similar to controls. Retention of bile in the gallbladder may be one reason for the increased risk of cholesterol cholelithiasis in pregnant women and in those taking contraceptive steroids.

Adult↗
PubMed1982

Biliary lipids, bile acids, and gallbladder function in the human female: effects of contraceptive steroids.

Individuals who take contraceptive steroids or estrogens are at increased risk of developing cholesterol gallstones. The mechanisms of the increased stone formation are incompletely understood. In this study we report biliary lipid composition and secretion, bile acid composition and kinetics, and gallbladder function in a group of healthy, nonobese women taking a contraceptive steroid preparation. A comparable group of healthy women served as controls. Bile-rich duodenal fluid was obtained after stimulation of gallbladder contraction; bile acid, phospholipid, and cholesterol concentrations were determined. Biliary lipid secretion rate was measured by the marker perfusion technique. Bile acid distribution was determined by gas-liquid chromatography. The pool size, FTR, and synthesis rate of each bile acid were measured by using CA and CDCA labeled with the stable isotope of carbon, 13C. In some of the subjects gallbladder storage and emptying were measured during the kinetic study, by real-time ultrasonography. Contraceptive steroid use was associated with a significant increase in biliary cholesterol saturation and in the lithogenic index of bile. The rate of cholesterol secretion in the contraceptive steroid group was 50% greater than in the control (p much less than 0.001) and the rate of bile acid secretion was reduced (p less than 0.02). The total bile acid pool size was significantly increased by contraceptive steroids. The major increase occurred in the CA pool (p less than 0.04). The daily rate of enterohepatic cycles of the bile acid pool was decreased by contraceptive steroids from 6.6 to 4.3 (p less than 0.01). The only effect of contraceptive steroids on gallbladder function was a slower emptying rate in response to intraduodenal amino acid infusion. No index of gallbladder function correlated significantly with any parameter of bile acid kinetics in this small group of subjects. The findings confirm the lithogenic effect of contraceptive steroids and indicate that its causes are an increase in cholesterol secretion and a decrease in bile acid secretion.

Bile↗
PubMed1981

Biliary lipids, bile acids, and gallbladder function in the human female. Effects of pregnancy and the ovulatory cycle.

To study the events that might lead to an increased risk of cholesterol gallstones, we examined biliary lipid composition and secretion and bile acid composition and kinetics at different stages of pregnancy or ovulation in young, nonobese, healthy women. Lipid composition and bile acid distribution were determined in duodenal fluid obtained in the fasting state and after stimulation of the gallbladder. Biliary lipid secretion was measured by the marker-perfusion technique. Bile acid kinetics were determined with cholic and chenodeoxycholic acids labeled with carbon13, by measuring the relative abundance of 13C in duodenal bile acids for 4--5 d. In a subset of patients we measured gallbladder storage and emptying during the kinetic study. The phase of the ovulatory cycle had no effects, but there were significant changes during pregnancy. The lithogenic or cholesterol saturation index of fasting hepatic and gallbladder bile increased during the second and third trimesters. The mean secretion rate of biliary lipids was not altered, but in the last two-thirds of pregnancy, cholesterol secretion increased in relation to bile acid and phospholipid secretion. There was a progressive decrease in the percentage of chenodeoxycholic acid and a similar increase in the percentage of cholic acid. The pool size of each major bile acid increased in the first trimester. Chenodeoxycholic acid and deoxycholic acid pools, but not cholic acid pools, subsequently decreased. The fractional turnover rate of both primary bile acids was slower during pregnancy. The synthesis rate of chenodeoxycholic but not cholic acid decreased in a linear manner during the first 20 wk of pregnancy. The rate of enterohepatic cycling of the bile acid pool was reduced throughout pregnancy. The volume of the fasting gallbladder and the residual volume after a physiologically stimulated contraction were directly correlated with bile acid pool size. The residual volume was also directly related to total bile acid synthesis.

Adult↗
PubMed1980

Effects of pregnancy and contraceptive steroids on gallbladder function.

We used real-time ultrasonography to study gallbladder kinetics in 11 nonpregnant women, 17 women using steroid contraceptives, and 33 pregnant women. Gallbladder volume was determined after an overnight fast and serially for 90 minutes after a standard liquid meal. After the first trimester of pregnancy, gallbladder volume during fasting and residual volume after contraction were twice as large as in control subjects. The rate of emptying and the percentage emptied were reduced. In early pregnancy the only important abnormality was a 30 per cent decrease in emptying rate. Gallbladder function was not affected by contraceptive steroids. Incomplete empyting of the gallbladder in late pregnancy leaves a large residual volume and may cause retention of cholesterol crystals, a prerequisite for cholesterol-gallstone formation. These findings are consistent with the view that pregnancy increases the risk of cholesterol gallstones. The increased incidence of gallstones associated with contraceptive steroids does not involve abnormal gallbladder kinetics.

Bile↗
PubMed1980

Effect of antral instillation of bile salts on fasting serum gastrin levels.

There have been several reports that bile salts instilled into a dog's alkalinized antral pouch cause acid secretion in a denervated fundic pouch. Antral gastrin release was assumed, but serum gastrin levels were not measured. In a randomized crossover study, serum gastrin levels were measured by radioimmunoassay during the infusion of a solution of bile salts (5 mM, pH 5.5, 280 mOsm, 37 degrees C), or an identical saline solution without bile salts, into the pH-controlled (5.5) antrum of 8 volunteers. The mean baseline serum gastrin level (+/- SE) was 18.7 +/- 1.0 and 20.5 +/- 0.9 pg/ml for the bile salt and control periods, respectively (NS). The serum gastrin rose promptly after bile salt infusion, but not after saline. The mean (+/- SE) integrated gastrin response was 81 +/- 17 pg . min/ml during the bile salt infusions, but essentially zero (-3.3 +/- 22 pg . min/ml) during control infusions (P less than 0.02). The 40% rise in serum gastrin in the initial 15-min bile salt period was higher than in the control period (P = 0.016). Thus we have shown, for the first time, an increase in serum gastrin during the antral instillation of bile salts in man. The potential physiologic and/or pathologic importance of this finding has not been established.

Adult↗
PubMed1980

Drug-induced pancreatitis: a critical review.

We critically reviewed the English language literature pertaining to drug-induced pancreatitis and attempted to determine whether the reported association between each drug and pancreatitis was valid. The following drugs seem to cause pancreatitis: azathioprine, thiazides, sulfonamides, furosemide, estrogens, and tetracycline. Less convincing, but suggestive evidence exists for: 1-asparaginase, iatrogenic hypercalcemia, chlorthalidine, corticosteroids, ethacrynic acid, phenformin, and procainamide. Evidence implicating other drugs is either inadequate or contradictory. Little is known about the pathogenesis of drug-induced pancreatitis. Ethanol was not considered in this review.

Acetaminophen↗
PubMed1979

National Cooperative Crohn's Disease Study: study design and conduct of the study.

The design and execution of the National Cooperative Crohn's Disease Study are described in this paper. The Study incorporated several noteworthy features developed to meet specific demands of the disease and its therapy. A standard clinical grading system, the Crohn's Disease Activity Index (CDAI) was developed to allow uniform decentralized clinical evaluation and decision-making throughout the 5 yr of the study. All three drugs in widespread clinical use in Crohn's disease were studied both for suppressive and prophylactic efficacy and for toxicity. The study employed a scheme for double-blind evaluation of patient progress which allowed adjustment of prednisone dose according to the degree of illness and ensured continuous monitoring for serious toxicity of any study drug. Results were analyzed primarily by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. Outcome was also analyzed by life-table methods. Eleven hundred nineteen patients were entered and 604 patients were randomized at 14 study centers during the 5-yr duration of the study. Twenty patients were eliminated from analysis as not meeting diagnostic criteria for Crohn's disease, and another 15 patients were eliminated as not meeting other preestablished criteria for analysis. Nine percent of randomized patients, equally distributed in the four treatment groups, withdrew as noncompliant. Ninety percent of patients completed all or all but one protocol-specified visits, and 95% completed the final radiologic and sigmoidoscopic evaluation.

Azathioprine↗
PubMed1979

National Cooperative Crohn's Disease Study: results of drug treatment.

The response of active and quiescent Crohn's disease to prednisone, sulfasalazine, or azathioprine has been studied in 569 patients in a placebo-controlled, randomized, multicenter cooperative trial. The response of active symptomatic disease to prednisone or sulfasalazine was significantly better than to placebo. Response to azathioprine was better than to placebo, but the difference did not reach conventional levels of statistical significance. Patients with colonic involvement were especially responsive to sulfasalazine, and those with small bowel involvement were especially responsive to prednisone. Patients' drug therapy immediately before entry to the study significantly affected subsequent response. For patients with quiescent disease, none of the drugs was superior to placebo in prophylaxis against flare-up or recurrence. There is less than a 5% risk that a clinically significant prophylactic effect of any of the drug regimens was missed.

Adult↗