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Biomedical subjects

F Kern

Publications and source records attributed to F Kern.

At least 37 records · Page 2Linked to original sources
PubMed1987

Cholesterol synthesis in the perfused liver of pregnant hamsters.

Pregnancy is a risk factor for the development of cholesterol gallstones. In pregnant women, biliary cholesterol saturation and secretion are increased. To investigate whether this was due to increased cholesterol synthesis, we studied hepatic cholesterol synthesis in Syrian Golden hamsters. Female controls and animals 10- to 14-days pregnant were studied. The studies were performed in the in situ perfused hamster liver. Cholesterol synthesis was determined by measuring the incorporation of 3H2O added to the perfusate into hepatic, perfusate, and bile cholesterol during a 90-min period. In both pregnant groups, bile flow decreased significantly, but biliary cholesterol concentration increased only in the 14-day pregnant group. The cholesterol synthesis rate averaged (mean +/- SD) 172 +/- 27, 127 +/- 37, and 552 +/- 79 nmol X hr-1 X g liver-1 in controls, 10-day, and 14-day pregnant animals, respectively. The 14-day pregnant animals secreted a markedly higher fraction (47.3 +/- 11.3 vs. 11.1 +/- 13.4%; P less than 0.01) of newly synthesized cholesterol into bile but not into perfusate. Chenodeoxycholate, but not cholate, synthesis rate was decreased in both pregnant groups. We conclude from our studies that hepatic cholesterol synthesis increases towards the end of pregnancy in the hamster and that more newly synthesized cholesterol is secreted into bile at that time. This could at least partially explain the increased biliary cholesterol saturation and secretion observed in women in the third trimenon, and explain pregnancy as a risk factor in the development of cholesterol gallstones.

Animals↗
PubMed1987

Contraceptive steroids increase cholesterol in bile: mechanisms of action.

Contraceptive steroids increase the risk of acquiring cholesterol gallstones. The factors responsible include an increase in cholesterol saturation of bile and an increase in rate of secretion of cholesterol into bile. The goal of this study was to investigate the mechanism(s) of these increases in biliary cholesterol. During the use of contraceptive steroids, cholesterol saturation of gallbladder bile and the amount of cholesterol secreted per mole of bile acid increased (P less than 0.05 and P less than 0.02, respectively). Cholesterol absorption, cholesterol synthesis, chylomicron remnant clearance, and the concentration of plasma and lipoprotein lipids were not altered by contraceptive steroids. Despite this apparent lack of effect, important correlations were present during steroid use. LDL (low density lipoprotein) cholesterol increased as dietary cholesterol increased (r = 0.58, P less than 0.025). Cholesterol synthesis correlated directly with VLDL cholesterol concentration (r = 0.64, P less than 0.01), biliary cholesterol secretion (r = 0.68, P less than 0.01) and with molar percent cholesterol in bile (r = 0.49, P = 0.06). Chylomicron remnant clearance also correlated with cholesterol secretion (r = 0.85, P less than 0.001). As either remnant uptake or synthesis increased, the effect of the other source of hepatic cholesterol on biliary cholesterol secretion diminished. These relationships were not observed in the same subjects when they were not taking the hormones. The findings suggest that both newly synthesized and dietary cholesterol contribute to the cholesterol secreted in bile. This is consistent with the hypothesis that cholesterol for secretion into bile and VLDL is derived from a common metabolic pool of free cholesterol. It is proposed that contraceptive steroids exert their effect on biliary cholesterol by increasing cholesterol entering the pool and/or by inhibiting hepatic ACAT (acylcoenzyme A:cholesterol acyltransferase) activity, a known effect of progesterone, so that an increase in free cholesterol entering the pool leads to an increase in output.

Absorption↗
PubMed1986

Regulation of bile acid synthesis via direct effects on the microsomal membrane.

Rats treated with ethinylestradiol (5 mg kg-1 day-1 for 5 days) secrete de novo synthesized bile acids at a markedly reduced rate (-57%). Administration of the nonionic detergent Triton WR-1339 to estradiol-treated rats rapidly restored the rate of secretion of de novo synthesized bile acids to control levels. In contrast, when Triton was administered to control rats, the secretion rate of bile acids was unaffected. The reduction in bile acid synthesis displayed by estradiol-treated rats was similar to the 50% decrease in the activity of hepatic microsomal 7 alpha-hydroxylase. The activity of 7 alpha-hydroxylase was also restored to control levels by the administration of Triton to estradiol-treated rats. We examined the possibility that estradiol acts directly on the hepatic microsomes. Adding increasing amounts of estradiol to microsomes obtained from control rats resulted in decreasing activities of 7 alpha-hydroxylase. The inhibition by estradiol of 7 alpha-hydroxylase obtained in vitro occurred with amounts of estradiol that were found to accumulate in the liver via in vivo treatment. Double-reciprocal analysis showed that at and below 50 micrograms of estradiol/0.5 mg of protein uncompetitive inhibition was displayed. Additional experiments showed that adding Triton to microsomes obtained from estradiol-treated rats increased the activity of 7 alpha-hydroxylase to control levels. In contrast, Triton did not increase the activity of 7 alpha-hydroxylase when it was added to control microsomes. These data show for the first time that the estrogenic steroid estradiol acts directly on the microsomes and inhibits both the activity of 7 alpha-hydroxylase and the rate of bile acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Obstructive cholangitis secondary to mucus secreted by a solitary papillary bile duct tumor.

A middle-aged woman had repeated episodes of common bile duct obstruction and cholangitis caused by profuse secretion of mucus by a solitary papillary tumor in the left hepatic duct. This complication usually occurs only with papillomatosis. The tumor initially appeared to be benign but subsequently was proven to be an invasive adenocarcinoma. Although the tumor recurred after surgical resection, her course remained uneventful without spread of the neoplasm for 3 yr.

Adenocarcinoma↗
PubMed1986

Contraceptive steroids increase hepatic uptake of chylomicron remnants in healthy young women.

In an investigation of alterations in cholesterol metabolism during contraceptive steroid use, we studied plasma clearance of chylomicron remnants. Six healthy women were studied on and off contraceptive steroid therapy. Remnant clearance was measured from the disappearance of retinyl palmitate administered intravenously in plasma endogenously labeled with retinyl palmitate. We also measured cholesterol in HDL and its subfractions and postheparin lipoprotein lipase and hepatic triglyceride lipase activities. Plasma decay of retinyl palmitate was biexponential. The rapid component, reflecting chylomicron remnant removal, accounted for about 90% of the total clearance in all studies. During contraceptive steroid intake, both rapid and slow decay constants and the calculated plasma clearance rates were significantly increased (mean values: rapid decay constant, control 0.048 versus treated 0.101 min-1, P less than 0.05; slow decay constant, 0.004 versus 0.014 min-1, P less than 0.01; plasma clearance 74 versus 115 ml/min, P less than 0.025) indicating enhanced hepatic uptake of chylomicron remnants and probably an increased hepatic uptake of higher density lipoproteins (d greater than 1.006 g/ml). Total postheparin lipolytic activity and lipoprotein lipase activity were depressed in all six women (P less than 0.05) and hepatic triglyceride lipase activity was increased in four of five subjects. Contraceptive steroids also caused a decrease in the HDL2/HDL3 cholesterol ratio (P less than 0.05), implying impaired peripheral lipoprotein triglyceride hydrolysis and/or increased HDL2 clearance by hepatic triglyceride lipase. In conclusion, during intake of contraceptive steroids, the plasma clearance of chylomicron remnants and higher density lipoproteins was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Gastrointestinal transit time in human pregnancy: prolongation in the second and third trimesters followed by postpartum normalization.

Fifty-nine studies of gastrointestinal transit time were performed in 27 healthy women during pregnancy and postpartum. Gastrointestinal transit time was defined as the time of the first sustained rise in breath hydrogen concentration after ingestion of 10 g of lactulose. Gastrointestinal transit time was significantly prolonged in both the second and third trimesters of pregnancy (125 +/- 48 min and 137 +/- 58 min, respectively) when compared with either the first trimester of pregnancy or the postpartum period (99 +/- 39 min and 75 +/- 33 min, respectively). Transit times measured in the first trimester were not significantly different from those postpartum. Because the prolongation of transit time in late pregnancy is transient, it is probably due to hormones (perhaps progesterone) or other metabolic effects of pregnancy.

Adolescent↗
PubMed1985

[Success and failure rate in peridural anesthesia. A 1-year study].

The real significance of epidural anaesthesia is determined by its practicability in the daily routine. The present paper shows, that about 20% of all operations which will be anaesthetized by a large anaesthesia department can be done under epidural anaesthesia. In 84,6% of all patients under epidural anaesthesia, anaesthesia was satisfactory; 4.7% of epidural anaesthesias were failures. The difficulty of epidural puncture and of advancing the epidural catheter were examined, as well as the degree of the necessary sedation. The main complication is puncture of the dura, in our series in 1,7% of the cases. We also examined the results achieved in relation to the state of training and in special cases of epidural anaesthesia. In the most interesting special case, namely patients requiring repeated epidural anaesthesia the success rate decreased significantly and the number of complications increased. The dosage-scheme for local anaesthetic given by Bromage has been confirmed in our patients. A simplified diagram and an approximate formula for calculation of dosage are given.

Adolescent↗
PubMed1985

Plasma decay of chylomicron remnants is not affected by heparin-stimulated plasma lipolytic activity in normal fasting man.

In an earlier study it was shown that retinyl palmitate appeared to be a satisfactory label for the core of chylomicrons and their remnants. When chylomicrons were endogenously labeled with retinyl palmitate and pulse-injected into healthy donors, retinyl palmitate was cleared from plasma by a first order process. Its fractional decay constant was very similar to the fractional catabolic rate of VLDL triglycerides, a lipoprotein lipase-dependent process, and 2-3 times slower than hepatic chylomicron remnant uptake in experimental animals. We, therefore, investigated whether plasma clearance of retinyl palmitate-labeled chylomicrons is accelerated by enhanced plasma triglyceride hydrolysis produced by heparin administration. Five healthy subjects took retinyl palmitate by mouth and 5-6 hr later two units of plasma were obtained by plasma-pheresis. After storage for 42 hr, the units were pooled and separated into two equal volumes. The first half was injected into the donor and plasma retinyl palmitate and chylomicron triglyceride were measured for 3.5 hr (control study). Heparin was then given intravenously as a bolus followed by an infusion for 7 hr. A second retinyl palmitate clearance (postheparin study) was performed during the heparin infusion. Plasma lipolytic activity and retinyl palmitate and chylomicron triglyceride concentrations were measured serially. Total plasma lipolytic activity and hepatic triglyceride lipase activity were increased approximately 500-fold during postheparin studies, enhancing triglyceride decay 2.5- to 3-fold. Retinyl palmitate plasma decay, however, was unaffected. Retinyl palmitate plasma decay was a biexponential concentration-dependent function in eighty of ten pre- and postheparin studies with the first, rapid exponential accounting for 90 +/- 4% of total plasma retinyl palmitate decay.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Controlled trial of medical therapy for active upper gastrointestinal bleeding and prevention of rebleeding.

UNLABELLED: This multicentered, placebo-controlled trial evaluated the efficacy of medical therapy to stop bleeding in 285 patients with active upper gastrointestinal bleeding (bleeding phase) and 194 patients who had ceased gastrointestinal bleeding and in whom therapy was instituted to prevent rebleeding during the same hospitalization (prevention phase). Patients in the bleeding phase were given cimetidine (300 mg every six hours) or intravenous placebo. There was no significant overall difference between intravenous cimetidine (71 percent) and placebo (77 percent) in stopping acute upper gastrointestinal bleeding. There was also no significant difference noted between intravenous cimetidine and placebo when specific bleeding lesions were evaluated. Once gastrointestinal bleeding had stopped, recurrence of bleeding while receiving prevention therapy (cimetidine tablets 300 mg one three times a day and at bedtime, or Mylanta II liquid 30 ml every hour, or cimetidine plus hourly antacids, or placebo) was evaluated in 194 of the patients in the bleeding phase. Twenty-four percent (12 of 51 patients) rebled while receiving cimetidine, 13 percent (five of 39 patients) rebled while receiving hourly antacids, 11 percent (six of 54 patients) rebled while receiving cimetidine plus hourly antacids, and 26 percent (13 of 50 patients) rebled while receiving placebo. None of these prevention regimens reached statistical significance (p = 0.13). Evaluation of specific bleeding lesions within this group also failed to show any significant value of prevention therapy. IN CONCLUSION: (1) intravenous cimetidine offers no advantage over placebo in stopping active upper gastrointestinal bleeding; (2) the occurrence of rebleeding during the same hospitalization does not appear to be significantly affected by any of the medical regimens used for prevention. These findings would suggest that the cessation of active bleeding and the prevention of recurrent upper gastrointestinal bleeding during a single hospitalization appear to be unaffected by therapy directed at acid neutralization or reduction.

Adult↗
PubMed1984

Plasma clearance of chylomicrons labeled with retinyl palmitate in healthy human subjects.

To estimate hepatic uptake of chylomicron remnants in humans, chylomicrons and intestinal very low density lipoproteins (VLDL) were endogenously labeled with retinyl esters, harvested by plasmapheresis, and pulse-injected into the donor 44 hr after plasmapheresis. Plasma decay of retinyl palmitate was measured in eight healthy volunteers. Retinyl palmitate plasma disappearance obeyed an apparent first order function in seven studies and, in one study, a biexponential function with the second, slow exponential accounting for only 13% of the retinyl palmitate plasma decay. The mean fractional removal of rate was 0.037 +/- 0.037 min-1 (mean +/- SD) in a one-compartment model. The apparent volume of distribution, Vd, was 109 +/- 25% of the estimated plasma volume. Plasma clearance of retinyl palmitate was 130 +/- 97 ml/min calculated as Vd x Ke. Mean T 1/2 was 29 +/- 16 min. Both in vitro and in vivo the retinyl palmitate remained largely within chylomicrons and intestinal VLDL. Only 4.3% was transferred from chylomicrons to other lipoprotein classes during in vitro incubation for 5 hr. After plasma was stored for 42 hr, 5% was transferred to higher density lipoproteins. During 12 hr after a test meal containing retinyl palmitate, only 6.4 +/- 1.5% of the retinyl palmitate absorbed was found in the LDL fraction and 3.1 +/- 3.8% in the d 1.063 g/ml lipoproteins. We conclude that retinyl palmitate is a useful marker for chylomicrons and their remnants in humans and that the plasma clearance of retinyl palmitate-labeled chylomicrons is probably an estimate of chylomicron remnant plasma clearance in man.

Adult↗
PubMed1983

Gallbladder and small intestinal regulation of biliary lipid secretion during intraduodenal infusion of standard stimuli.

The gallbladder and small intestine are reservoirs for the bile acid pool during its enterohepatic circulation and, as such, may regulate biliary secretion of bile acid. During studies of biliary bile acid secretion, a stimulus to gallbladder contraction is continuously infused into the duodenum. Under these conditions, it is assumed that the gallbladder is tonically contracted and that the rate of bile acid secretion into the duodenum equals the hepatic bile acid secretion rate. However, secretion rates vary by as much as 100%, depending upon which of two standard stimuli is used. Therefore, we studied the role of gallbladder emptying and small intestinal transit in determining biliary lipid secretion rate and composition during infusion of these stimuli in five healthy subjects. Each subject was studied with a liquid formula containing 40% of calories as fat, and with an amino acid solution for 10 h. Bile acid, phospholipid, cholesterol, and markers were measured in duodenal bile and hourly secretion rates were calculated by marker dilution technique. Real-time gallbladder sonographs and serum pancreatic polypeptide levels were obtained every 30 min. Small bowel transit time was estimated levels were obtained every 30 min. Small bowel transit time was estimated by the breath hydrogen response after giving lactulose intraduodenally.During liquid formula infusion, gallbladder emptying was more complete, small intestinal transit was faster, and pancreatic polypeptide levels were higher. Secretion rates of all lipids were greater and molar percent cholesterol was lower. For the combined data from both infusions, the secretory relationships of cholesterol to bile acid, cholesterol to phospholipid, and phospholipid to bile acid were curvilinear. We conclude that more complete gallbladder emptying and faster intestinal transit increase the enterohepatic cycling of bile acids and lower the molar percent cholesterol of bile. Some of the fluctuation observed in biliary lipid secretion rates, especially during amino acid infusion, is due to gallbladder refilling and emptying.

Adult↗
PubMed1983

[Epidural buprenorphine for postoperative analgesia after hip operations].

Two groups of 20 patients each were given immediately after hip-operation an epidural injection of 0,15 or 0,3 mg buprenorphine. Effects and side effects are compared with those observed in two groups of patients having the same type of operation, and given either 4 mg of morphine or saline (placebo) by epidural injection. Buprenorphine in both doses produced a shorter duration of analgesia than 4 mg of morphine. In no case did respiratory depression occur. Urinary retention after buprenorphine was barely more frequent than in the placebo group. Nausea and vomiting occurred in 35-45% of patients. We do not see an advantage in replacing morphine by buprenorphine for epidural opiate-analgesia, because the same high rate of nausea/vomiting is associated with a significantly shorter duration of analgesia after buprenorphine. We are convinced that epidural opiate-analgesia is most valuable for postoperative pain relief but should be reserved for selected cases.

Aged↗
PubMed1983

The biliary tract in inflammatory bowel disease.

In summary, the biliary tract seems particularly vulnerable to damage in patients with chronic inflammatory bowel diseases. The intrahepatic histological features of the common entity, pericholangitis, and the uncommon lesion, sclerosing cholangitis, overlap and, some feel, may be different manifestations of the same hepatobiliary insult. The potentially important role for cholangiography in distinguishing between usually banal and frequently serious disease is evident. Not knowing the cause of either lesion, appropriate preventive measures or treatment are not available. The role of the inflammatory disease in the potential development of cholangiocarcinoma is not clear. Cholelithiasis secondary to ileal dysfunction is usually independent of the other three processes.

Adult↗
PubMed1983

Coordination of gastric and gallbladder emptying after ingestion of a regular meal.

The relationship of gallbladder emptying and refilling to gastric emptying of solids, gastrointestinal transit time, and human pancreatic polypeptide response was examined after ingestion of a standard breakfast (40% fat) in 12 healthy men and women. Gallbladder volume, emptying, and refilling was measured by real-time ultrasonography, and gastric emptying of solids was measured scintigraphically by the disappearance from the stomach of egg labeled with 99mTc-sulfur colloid. Gastrointestinal transit time was defined as the time of initial rise in breath hydrogen following ingestion of 10 g of lactulose. Serum human pancreatic polypeptide level was measured by radioimmunoassay. Gallbladder emptying was biphasic, initially 0.015 +/- 0.003 min-1 and later 0.005 +/- 0.001 min-1, and gallbladder volume remained small until refilling began at 249 +/- 67 min. Gallbladder refilling was 70% complete at 335 +/- 57 min. The slower rate of gallbladder emptying and tonic gallbladder contraction occurred during gastric emptying of solids. Gallbladder refilling began when approximately 13% of solids remained in the stomach. Serum human pancreatic polypeptide showed the expected biphasic response to the meal and returned to basal levels at approximately the time of initiation of gallbladder refilling. The gastrointestinal transit time of women was twice that of men (73.6 +/- 20.2 vs. 37.5 +/- 22.7, p = 0.025). No other sex-related differences were detected. We conclude that gastric emptying of the solid portion of a meal containing fat maintains tonic gallbladder contraction through continued release of humoral mediators from small bowel and pancreas. When gastric emptying nears completion, humoral stimulation ceases and the gallbladder refills. Human pancreatic polypeptide does not appear to be responsible for gallbladder refilling.

Adult↗
PubMed1982

[Postoperative analgesia with epidural morphine after hip operations (author's transl)].

80 patients undergoing hip surgery under lumbar epidural block have been studied (double blind) for postoperative analgesia. There were 4 groups, of 20 patients each, who received a single epidural injection of 0 mg, 2 mg or 4 mg morphine in 1 ml of saline added to 6 ml bupivacaine 0.5% or 4 mg morphine in 6 ml saline. In the morphine groups analgesia lasted between 37 and 50 hours. No neurological side-effects or severe respiratory depression have was observed; but a significant rise of paCO2 was found. Other side-effects were nausea/vomiting and the need for catheterisation in about 50% of patients. We conclude, that the indications for epidural analgesia with morphine have to be chosen carefully.

Aged↗
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↗