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Biomedical subjects

G W Hepner

Publications and source records attributed to G W Hepner.

At least 37 records · Page 2Linked to original sources
PubMed1977

The effect of pelvic irradiation on ileal function.

Thirty-three patients with gynecological neoplasms undergoing radiotherapy to the pelvis had cholyl[1-14C]glycine breath tests to assess ileal function. Breath tests were performed on each patient in the first and fifth weeks of treatment and 19 of the patients had a third test three months post-treatment. In the first test, 29.9+/-16.8% (mean+/-SD) of the administered dose was excreted in breath 14C in 24 hours. This rose to 47.3+/-15.9% (t=6.08; p less than .001) in the fifth week and fell to 36.6+/-16% (t=2.29; p less than .05) at three months post-treatment. Eight patients had breath tests performed one year post-treatment and the test percentages were 32.7+/-7.8% (t=1.19; p less than .10). The increase in 14CO2 excretion in the fifth week of treatment occurred at a time when most patients were having diarrhea. The data suggest that bile acid malabsorption due to ileal dysfunction may be a factor in radiation-induced diarrhea which occurs in nearly all patients during pelvic irradiation.

Adult↗
PubMed1977

Dynamics of the enterohepatic circulation of the glycine conjugates of cholic, chenodeoxycholic, deoxycholic, and sulfolithocholic acid in man.

Highly sensitive and specific radioimmunoassays for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine have been used to study the kinetics of the enterohepatic circulation of these conjugated bile acids in 8 healthy subjects. Venous blood samples were collected over a 32-hr period, during which time the subjects ate three meals. Serum levels of cholylglycine and chenodeoxycholylglycine rose after each meal, and reached their maximum level within 30 to 60 min. A second chenodeoxycholylglycine peak occurred 2 to 3 hr after the first two meals in all subjects; a second peak was also found for cholylglycine in 3 of the 8 subjects. Serum deoxycholylglycine levels also rose postprandially; the peak level generally occurred 30 min later than that of cholylglycine. Serum sulfolithocholylglycine levels did not alter significantly after meals. The data indicate that the dynamics of the enterohepatic circulation of individual serum bile acids differ both quantitatively and qualitatively.

Adult↗
PubMed1976

Abnormal aminopyrine metabolism in patients with hepatic neoplasm. Detection by breath test.

Aminopyrine metabolism was assessed by the aminopyrine breath test (ABT) in 153 patients with malignant disease, of whom 75 had hepatic neoplasm and 78 had none. Radioactive carbon dioxide (14CO2) exhalation was measured two hours after oral administration of a trace dose of carbon-14 labeled aminopyrine. The ABT was correct in 62 of 75 (83%) patients with hepatic neoplasm and in 73 of 78 (94%) patients without. It was correct in 16 of 22 (73%) patients who had hepatic neoplasm without abnormal serum biochemistry. Aminopyrine metabolic clearance rate (AMCR) was 32.4 ml/min in patients with hepatic neoplasm and 103.4 +/- 18.8 ml/min in the patients without. There was a highly significant correlation between ABT and AMCR (r =.76, P less than .01). We conclude that aminopyrine metabolism is depressed in most patients with hepatic neoplasm and that the ABT affords a useful method for detecting malignant tumors of the liver.

Administration, Oral↗
PubMed1976

Aminopyrine disposition: studies on breath, saliva, and urine of normal subjects and patients with liver disease.

To investigate aminopyrine disposition, breath, saliva, and urine were collected from 25 control patients, 15 patients with hepatocellular disease, and 26 patients with hepatic neoplasm after oral administration of 2 muCi [14C]aminopyrine. The percentage 14C excreted in breath 14CO2 in 2 hr (aminopyrine breath test, ABT) correlated with the breath 14CO2 elimination rate (r = 0.92, p less than 0.01), with the aminopyrine metabolic clearance rate (MCR) (r = 0.85, p less than 0.01), and with the plasma half-life of 4-aminoantipyrine (r = -0.54, p less than 0.05). The ABT permits study of aminopyrine disposition with simplicity, accuracy, and safety.

Adult↗
PubMed1976

Interaction between antipyrine and aminopyrine.

Aminopyrine administered to normal human volunteers in an oral dose of either 9 mg/kg or 4.5 mg/kg prolonged the plasma half-life and reduced the metabolic clearance rate of antipyrine (18 mg/kg, orally) without changing its apparent volume of distribution. By contrast, this same oral dose of antipyrine given simultaneously with 9 mg/kg aminopyrine failed to alter aminopyrine disposition. Thus, antipyrine and aminopyrine should not be administered simultaneously to measure different steps in hepatic drug oxidation, although in man aminopyrine can be given for this purpose 24 hr after antipyrine. Antipyrine elimination was prolonged to the same extent when aminopyrine was given 5 hr before antipyrine as when the drugs were given simultaneoulsy. Since in man aminopyrine has a biologic halic-life of approximately 2.7 hr, the marked inhibitory effects observed 5 hr after aminopyrine administration may be due to its major metabolite, 4-aminoantipyrine. To define mechanism by which aminopyrine affects antipyrine disposition in vivo, hepatic microsomes were prepared from rats, mice, and dogs, and rates of antipyrine hydroxylation were measured in vitro both in the absence and in the presence of aminopyrine. In these species in vitro inhibition of antipyrine hydroxylation by 4-aminoantipyrine was of a mixed type; antipyrine inhibited competitively aminopyrine N-demethylation in vitro in rats, mice, and dogs. There were some sex and species differences in the Km' V max' and Ki for aminopyrine and antipyrine.

Adult↗
PubMed1976

The effect of phenobarbital on biliary lipid metabolism and hepatic microsomal drug metabolism in patients with cholesterol cholelithiasis.

Six patients with cholesterol cholelithiasis were studied before and after 3 weeks treatment with phenobarbital, 120 mg/day. The kinetics of cholic and chenodeoxycholic acid and biliary lipid composition were not significantly affected by phenobarbital treatment although hepatic mixed-function oxidase was stimulated by the treatment as shown by increased breath output of 14CO2 after administration of (14C)aminopyrine. It is concluded that treatment with phenobarbital is unlikely to be effective therapy for patients with cholesterol cholelithiasis.

Adult↗
PubMed1976

Abnormal vitamin D metabolism in patients with cirrhosis.

To assess the role of hepatic function and alcohol on vitamin D metabolism, serum 25-hydroxyvitamin D (25-OHD) levels were measured in 20 healthy nonalcoholic control subjects, 31 "inactive" cirrhotics whose alcoholism was in remission, 8 alcoholic cirrhotics, and 15 alcoholics with normal liver function. Cirrhosis but not alcoholism, was assoicated with low serum 25-OHD levels. The aminopyrine breath test (ABT) was performed because aminopyrine, like vitamin D3, is metabolized by hepatic microsomes; the ABT correlated highly (r = 0.74, rho less than 0.01) with serum 25-OHD in the inactive cirrhotics. After an intravenous injection of 120 mug vitamin D3, serum 25-OHD rose significantly within 24 hr in 6 healthy controls and 2 patients with celiac disease but not in 6 inactive cirrhotics. The data suggest impaired 25-hydroxylation of vitamin-D impaired in patients with cirrhosis, related predominantly to the degree of hepatic dysfunction.

Adult↗
PubMed1976

Levels of immunoreactive glycine-conjugated bile acids in health and hepatobiliary disease.

A sensitive radioimmunoassay for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine was established using antibodies obtained from rabbits injected with albumin conjugates of these bile acids. Glycine-conjugated bile acid levels were measured in sera from 25 control subjects and 110 patients who had hepatic disease (alcoholic cirrhosis, hepatitis, cholestasis, and hepatic malignancy). Sulfolithocholylglycine was elevated in the sera of all 110 patients with hepatic disease. Cholylglucine was within normal range in only three. Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy. It was normal in most sera of patients who had alcoholic cirrhosis, suggesting that chenodeoxycholic acid may be subject to further biotransformations in these patients. Deoxycholylglycine was elevated in a minority of patients, none of whom had cholestasis. The data suggest that serum bile acids, particularly sulfolithocholylglycine, are a highly sensitive index for hepatic dysfunction.

Alcoholism↗
PubMed1976

The effect of prednisone and irradiation on the rectum in dogs.

In an attempt to diminish the severity of the acute and late effects of irradiation to the rectum of dogs, oral prednisone was administered to 10 dogs for 1 week prior to, during, and for 1 month following a 3-week fractionated course of 60Co exposures to the pelvis. A control group of 10 dogs received irradiation alone. The dogs were observed clinically, serial rectal biopsies were done during and following the acute reaction, and the rectum was studied following sacrifice. Observations suggest that prednisone has no beneficial effect on the acute inflammatory reaction, and increases the severity of the late tissue damage.

Animals↗
PubMed1975

Altered bile acid metabolism in vegetarians.

Bile acid kinetics were studied in a group of healthy vegetarians and a matched group of healthy control subjects. The daily fractional turnover rate of cholic acid was significantly smaller in the vegetarians than in the controls and deoxycholic acid pool size was significantly smaller in the vegetarians than in the controls. The data suggest that enterohepatic conservation of cholic acid is more efficient in vegetarians than in control subjects resulting in decreased deoxycholic acid input in vegetarian subjects. The possible significance of these data to intestinal oncogenesis is discussed.

Adult↗
PubMed1975

Normal antipyrine metabolism in patients with cholesterol cholelithiasis. Evidence that the disease is not due to generalized hepatic microsomal dysfunction.

Plasma antipyrine half-lives and metabolic clearances were measured after a single oral dose of antipyrine in 10 control subjects, 12 patients with gallstones, and 9 patients having undergone cholecystectomy for cholesterol cholelithiasis, to determine whether impairment of hepatic antipyrine metabolism occurs in patients with cholesterol cholelithiasis. The plasma antipyrine half-life and metabolic clearances in the control subjects were 11.7 plus or minus 1.3 hours and 42.5 plus or minus 3.3 ml/min, respectively; in patients with gallstones, 12.3 plus or minus 1.3 hours and 36.0 plus or minus 3.2 ml/min, respectively; and in patients having undergone cholecystectomy, 13.2 plus or minus 1.8 hours and 33.8 plus or minus 4.2 ml/min, respectively. Values for antipyrine half-life and metabolic clearance were not statistically different in these three groups. This study suggests the presence of normal hepatic antipyrine metablosim in patients with cholesterolcholelithiasis.

Adult↗
PubMed1975

Metabolism of [35S]taurine in man.

Taurine metabolism in man was defined by an isotope dilution technique during normal taurine intake (five subjects) or increased taurine intake (two subjects). A tracer dose of [35S]taurine was administered intravenously, and the amount and chemical form of radioactivity were determined in blood, urine, bile, and feces. Analysis of plasma specific activity decay curves indicated that taurine metabolism can be described by two exchangeable pools: a small (2 mmoles), rapidly exchanging pool (t1/2 approximately equal to 0.1 hour); and a large (98 mmoles), very slowly exchanging pool (t1/2 approximately equal to 70 hours). A small amount of [35S]isethionic acid was detected in urine, possibly the result of deamination of taurine by tissues; but otherwise no evidence of tissue biotransformation was obtained. Taurine was excreted predominantly (95%) in urine, about 70% as taurine and 25% as sulfate. The sulfate was considered to be formed in the intestine by bacterial degradation of taurine and then absorbed. Supplemental taurine (given orally) was well absorbed, caused a transient increase in plasma taurine levels, was excreted in urine without equilibration with the slowly exchangeable pool, and caused only a modest increase in total body taurine. Thus, taurine resembles other amino acids in having large tissue pools but differs strikingly in being metabolically inert with an extremely slow turnover rate.

Adult↗
PubMed1975

Effect of bile acids on electrical properties of rat colon: evaluation of an in-vitro model for secretion.

A preparation of rat colon mucosa has been evaluated as a useful model to study effects of bile acids on the changes in short-circuit current and transmural electrical potential difference (pd) which others have associated with alterations in electrolyte transport. Using this preparation, it was found that bile acids were effective in increasing short-circuit current and pd when applied to the serosal, but not the mucosal, surface of the tissue. Furthermore, taurine-conjugated cholic acid, which has no demonstrable effect on the colon in vivo, was found to increase short-circuit current and pd significantly in the in-vitro preparation. These data indicate the limitations of the in-vitro model in studying the mechanism of bile acid-stimulated intestinal secretion.

Animals↗
PubMed1975

Quantitative assessment of hepatic function by breath analysis after oral administration of (14C)aminopyrine.

The rate of hepatic metabolism of dimethylaminoantipyrine (aminopyrine), which occurs primarily through N-demethylation, was assessed by measurement of the specific activity of 14CO2 excreted in breath samples obtained 2 hours after oral administration of a trace dose of [14C]aminopyrine. The percentage of administered 14C excreted in 14CO2 in 2 hours was 7.0 +/- 1.3 (SD)% in control patients, and significantly less (P less than 0.01) in patients with portal cirrhosis (2.6 +/- 1.2%), fatty liver (4.7 +/- 1.1%), hepatitis (2.6 +/- 1.4%), and hepatic malignancy (3.5 +/- 1.8%). In 16 of 24 subjects with cholestasis not caused by malignant disease the mean 14CO2 excretion was normal. The 14CO2 excretion in patients with portal cirrhosis correlated highly with aminopyrine metabolic clearance rate (r equals 0.92), serum albumin (r equals 0.75), and retention of bromsulphalein (r equals 0.73). Abnormal 14CO2 excretion returned to normal in patients with hepatitis, when the hepatitis resolved. The data suggest that the aminopyrine breath test is a safe, simple, qualitative and quantitative liver function test.

Administration, Oral↗
PubMed1975

Increased sensitivity of the cholylglycine breath test for detecting ileal dysfunction.

Deconjugation of bile salts was assessed by measuring the rate of appearance of 14-CO2 in the breath after the administration of cholyl [1-14-C]glycine to patients with ileal dysfunction (ileitis or ileal resection), cholesterol cholelithiasis with or without cholecystectomy, and control subjects (healthy or with diarrhea). Vitamin B12 absorption was also measured in many of the patients with ileal dysfunction by determining the recovery of 57-Co in the urine (Schilling test). The percentage of administered 14-C excreted in breath 14-CO2 was increased in the patients with ileal dysfunction, but there was considerable overlap between the patients with ileal dysfunction and the control subjects. Breath 14-CO2 was excreted more rapidly in all the patients with ileal dysfunction than in the control subjects. Of the calculated 24-hr breath excretion 78.3 plus or minus 8.9% SD of administered 14-C was excreted in 12 hr in the patients with ileal dysfunction, compared to 39.1 plus or minus 13.1% in the control subjects; only 1 of the 19 patients with ileal dysfunction overlapped with the control subjects. The Schilling test was normal orequivocal in 5 of 14 patients with ileal dysfunction. The percentage of administered 14-C excreted in breath 14-CO2 was increased in patients with cholecystectomy, but excretion was not more rapid than in the control subjects. The data suggest that the sensitivity of the breath test for diagnosing ileal dysfunction may be usefully increased by determining the rate of excretion of breath 14CO2.

Adult↗
PubMed1975

Effect of decreased gallbladder stimulation on enterohepatic cycling and kinetics of bile acids.

The effect of diet on the rate of enterohepatic recycling and bile acid kinetics was studied in groups of human subjects by reducing dietary protein and fat. The effect on enterohepatic cycling was assessed indirectly in control subjects, in patients with cholesterol cholelithiasis, and in patients with cholecystectomy by comparing output of breath 14-CO2 after the administration of a trace of cholyl [1-14-C]glycine during two periods: a control period when three meals containing protein and fat were eaten daily and a diet period, when protein and fat were excluded from the diet. Breath 14-CO2 output was not altered by diet in the patients with cholecystectomy. In the healthy subjects and in the patients with cholesterol cholelithiasis breath 14-CO2 output fell by approximately 50%, indicating that decreased endogenous cholecystokinin-pancreozymin stimulation had reduced but not eliminated enterohepatic recycling. Bile acid kinetics after administration of [2,4-3-H]cholic acid and [24-14-C]chenodeoxycholic acid were measured in 6 healthy subjects during a control period, when they ate a diet containing three daily meals containing fat and protein, and again not less than 4 months later during the 4th week of a diet during which they ate only one meal containing fat and protein every other day. tthe pool size of cholic and chenodeoxycholic acid rose significantly during the diet as did the total bile acid pool size. The daily fractional turnover rate of both primary bile acids fell significantly during the diet, but their synthesis rate was not significantly changed. It is concluded that (1) significant enterohepatic circulation of bile acids occurs even in the absence of dietary stimuli for gallbladder contraction; and (2) diet may significantly affect bile acid pool size and fractional turnover, while bile acid synthesis remains essentially unchanged.

Adult↗