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Biomedical subjects

A Bremmelgaard

Publications and source records attributed to A Bremmelgaard.

71 records · Page 4Linked to original sources

Analysis of plasma bile acid profiles in patients with liver diseases associated with cholestasis.

Bile acids in plasma of patients with intra- or extra-hepatic cholestasis have been analyzed by gas chromatography-mass spectrometry after fractionation into groups by mode of conjugation. During cholestasis plasma concentrations ranged from 14 to 252 mumol/l. The predominant bile acid was cholic acid, comprising 44% to 89% of total bile acids. Tetrahydroxy- and trihydroxy-cholanoates with a tentative 6-hydroxy structure were identified, whereas 1-hydroxylated bile acids were not found. 3 beta-Hydroxy-5-cholenoic acid was the most important monohydroxycholanoate, comprising up to 13% of total bile acids in serum. The ratio of cholic to chenodeoxycholic acid in patients with primary biliary cirrhosis was in all cases more than 1. With the exception of 1-hydroxylated bile acids the main bile acids in urine an plasma were the same. Renal clearance of individual conjugated and sulfated bile acids could be calculated for some of the patients, assuming insignificant metabolism of bile acids in the kidney. The renal clearance of cholic acid conjugates tended to be higher tna that of chenodeoxycholic acid conjugates, and sulfates of cholic acid conjugates tended to have a higher renal clearance than sulfates of chenodeoxycholic acid conjugates. The clearance of sulfated 3 beta-hydroxy-5-cholenoic acid was still smaller. Chenodeoxycholic acid predominated in two healthy persons. Unconjugated bile acids accounted for 30% and 53%, respectively, of total bile acids. Sulfates of lithocholic, allolithocholic, and 3 beta-hydroxy-5-cholenoic acids were found after stimulation with a test meal.

Adult↗

Hydroxylation of cholic, chenodeoxycholic, and deoxycholic acids in patients with intrahepatic cholestasis.

The metabolism of 14C-labeled chenodeoxycholic, cholic, and deoxycholic acids was studied in patients with intrahepatic cholestasis. Radioactively labeled metabolites were isolated from urine and were identified by gas-liquid chromatography-mass spectrometry. About 5% of the radioactivity was recovered in urine after administration of labeled chenodeoxycholic acid to a patient with mild intrahepatic cholestasis. In urine collected 0-24 hr after the injection, 20% of the radioactivity appeared in the combined glycine and taurine conjugate fractions, and the predominant metabolite in these fractions was identified as hyocholic acid. Eighty percent of the activity was eluted in the sulfate fraction presumably representing mainly sulfated chenodeoxycholic acid conjugates. Twenty percent of the radioactivity was recovered in urine following administration of labeled cholic acid to a patient with biliary cirrhosis and severe cholestasis. In urine collected on the fifth day, half of this radioactivity appeared in the glycine and taurine conjugate fractions, and 10% of this activity was present as tetrahydroxycholanoates. The major metabolites in this fraction were 3 alpha, 6 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta- and 1 xi, 3 alpha, 7 alpha, 12 alpha-tetrahydroxy-5 beta-cholanoic acids. The former compound constituted about 50% of the tetrahydroxycholanoates. Three additional minor tetrahydroxy bile acids were present, one of which was tentatively identified as 6 beta-hydroxycholic acid. About 5% of the radioactivity appeared in urine after oral administration of labeled deoxycholic acid to a patient with mild intrahepatic cholestasis. Twenty-two percent of the activity appeared in the glycine and taurine conjugate fractions isolated from urine collected on the second day after the administration. About 75% of this activity was associated with trihydroxycholanoates. The main metabolite was 1 beta-hydroxydeoxycholic acid with small amounts of, tentatively, 6 alpha-hydroxydeoxycholic acid.

Bile Acids and Salts↗

Acute Corynebacterium endocarditis causing aortic valve destruction. Successful treatment with antibiotics and valve replacement.

A case of acute infective endocarditis caused by diphtheroids in a healthy young male is described. The pathogenic role of the diphtheroids was verified by recognition of the same bacterium in 6 consecutive blood cultures and simultaneous rise of specific antibody titers. The infection was effectively controlled by antibiotic treatment, but destruction of the aortic valve led to progressive heart failure irresponsive to medical treatment. The affected valve was successfully replaced by a prosthetic valve, and the patient made a complete recovery. Neither congenital or acquired cardiac defects, nor signs of immunological deficiency could be detected.

Adult↗

Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatorgaphy-mass spectrometry.

A method is described for quantitative analysis of bile acids in urine. Urine is acidified and bile acids are extracted on an Amberlite XAD-2 column. Bile salts are converted to acids on an Amberlyst A-15 column and are separated into groups of unconjugated, glycine, taurine, monosulfated, and polysulfated conjugates using the lipophilic anion exchanger diethylaminohydroxypropyl Sephadex LH-20 (DEAP-LH-20). After solvolysis and hydrolysis, the deconjugated bile acids are purified on DEAP-LH-20, and are converted to methyl ester trimethylsilyl ether derivatives. Identification and quantitation of the individual bile acids is accomplished by computerized gas-liquid chromatography-mass spectrometry. The daily excretion of bile acids in urine from healthy subjects was 6.4-11 micro moles. The mixture of bile acids was quite complex and differed from that in bile. About 30 bile acids were identified or partially characterized. Three of these were monosubstituted: lithocholic, allolithocholic, and 3beta-hydroxy-5-cholenoic acids. Fourteen disubstituted bile acids included epimers of deoxycholic, allodeoxycholic, chenodeoxycholic, allochenodeoxycholic, and hyodeoxycholic acids. 3alpha-Hydroxy-12-keto-5beta-cholanoic acid was the major ketonic bile acid and 3beta,12alpha-dihydroxy-5-cholenoic acid was the major unsaturated bile acid in this group. Nine trihydroxy bile acids included cholic and allocholic acids, epimers of these compounds, hyocholic acid, and a 1-hydroxylated bile acid tentatively characterized as 1,3,12-trihydroxycholanoic acid. Cholestatic subjects excreted tetrahydroxycholanoates carrying hydroxyl groups in positions 1, 3, 6, 7, 12, or 23. All monohydroxy and the predominant part of dihydroxy bile acids were present in the monosulfate fraction. Exceptions were 3alpha,12beta-dihydroxy- and 3alpha-hydroxy-12-keto-5beta-cholanoic acids, which were found mainly in the glycine conjugate fraction. Most of the trihydroxy bile acids were nonsulfated, and cholic and norcholic acids were the major unconjugated bile acids. The tetrahydroxy bile acids and hyocholic acid were present mainly in the taurine conjugate fraction, while 1,3,12-trihydroxycholanoic acid was predominantly found in the glycine conjugate fraction. Sulfation of trihydroxy bile acids was increased in patients with marked cholestasis. All bile acids in the monosulfate fraction were conjugated and carried the sulfate ester group at C-3. Significant amounts of di- and trisulfates were not found. The results indicate selective mechanisms for sulfation, hydroxylation, and renal elimination of bile acid conjugates. Analysis of metabolic profiles of bile acids in urine may be a useful method in studies of the function of organs involved in bile acid metabolism.

Bile Acids and Salts↗

Bile acids in bile during long-term chenodeoxycholic acid treatment.

Relative concentrations of conjugated and sulfated bile acids in duodenal bile were measured in 5 patients before and during treatment with 0.50-0.75 g of chenodeoxycholic acid per day for 3-4 months. Lithocholic acid constituted 0.8-3.3% (mean 1.8%) of total conjugated and sulfated bile acids before and 0-5.4% (mean 2.6%) during treatment. Lithocholic acid was the predominant bile acid in the sulfate fraction in three patients and chenodeoxycholic acid in two. Sulfated bile acids constituted less than 1% of total bile acids and did not increase during treatment. Ursodeoxycholic acid, the other major metabolite of chenodeoxycholic acid, was found in higher amounts during therapy. The unsaturated bile acid 3beta-hydroxy-delta5-cholenic acid, which was found exclusively as its sulfate ester, showed a slight fall. The average G/T conjugation ratio rose from 2.2 to 4.5.

Bile↗

Hepatic morphology and bile acid composition of bile and urine during chenodeoxycholic acid therapy for radiolucent gallstones.

In 9 patients with radiolucent gallstones, percutanous liver biopsy was performed during treatment with chenodeoxycholic acid in a dose of 500 to 750 mg per day for 3-14 months. In 4 patients pretreatment specimens were available for comparison. No sign of hepatic cellular necrosis or bile duct proliferation was noticed in the biopsies. In 2 patients hepatic steatosis was reduced, and in one patient moderate portal tract inflammation decreased during therapy. Mean values of alkaline phosphatases, alanine aminotransferases, prothrombin, and serum lipids remained unchanged and did not exceed normal limits. In 5 patients the urinary bile acid profile was examined during therapy. Chenodeoxycholic acid constituted 27-50%, lithocholic acid 25-63%, and ursodeoxycholic acid 0-13% of total bile acids in urine. The renal excretion of total bile acids was estimated to be less than two mg per day in each patient. From 86 to 100 per cent of the bile acids in urine was sulfated.

Bile↗

Differentiation between Pseudomonas cepacia and Pseudomonas pseudomallei in clinical bacteriology.

If only conventional laboratory tests are used, the widely occurring species Pseudomonas cepacia may, due to its variability, sometimes be difficult to differentiate from the dangerous pathogen Pseudomonas pseudomallei. In a comparative study using fresh isolates it is shown that animal inoculation seems to be a useful additional method in the differentiation. Also the determination of the ability to utilize selected carbon sources such as starch, hydroxybenzoate and uracil is helpful in reaching a correct identification.

Animals↗

Infections related to the menstrual cycle. A study of five otherwise healthy women with recurrent abscesses and a review of the literature.

The purpose of the study was to investigate the in vitro bactericidal function of blood polymorphonuclear leucocytes (PMN) in various phases of the menstrual cycle from otherwise healthy women with recurrent cutaneous abscesses related to the premenstrual phase of the menstrual cycle compared with the bactericidal activity of PMN from healthy women with no inconveniences related to the menstrual cycle. The bactericidal activity against Staphylococcus aureus 502A was investigated and when possible against the patients' own strain. No variation in bactericidal activity was observed during the different phases of the menstrual cycle. PMN from five women with recurrent abscesses related to the premenstrual phase tended to kill fewer S. aureus 502A than PMN from three women in the control group. The literature of immunological defence mechanisms and the occurrence of infections related to the menstrual cycle is reviewed.

Blood Bactericidal Activity↗

In vivo flux of plasma cholesterol into human abdominal aorta with advanced atherosclerosis.

To measure the flux of free and esterified cholesterol from plasma into abdominal aortic tissue that had severe atherosclerotic lesions, we intravenously injected two autologous plasma samples containing radioactive cholesterol into patients scheduled for reconstructive arterial surgery. After the injections, blood samples were collected for calculation of the exposure of arterial tissue to labeled free and esterified plasma cholesterol. When tissue specimens were removed a few days after the injection, the aortic influx was determined by the simultaneous use of two differently labeled species of cholesterol. The flux of free and esterified cholesterol into 51 tissue specimens from the abdominal aorta of 12 normocholesterolemic patients was 41 +/- 3 and 45 +/- 3 nmol X cm-2 X day-1 (mean +/- SE), respectively, with 7% to 30% hydrolysis and 8% to 24% esterification of the labeled sterols in the atherosclerotic tissue. The influx was up to 100 times greater than the influx into nonatherosclerotic ascending aorta previously measured in other patients. The cholesterol content of the atherosclerotic tissue corresponded to 16 +/- 3 months (mean +/- SE) of continuous cholesteryl ester influx. Unless counteracted by cholesteryl ester efflux from the plaque, this influx provides enough cholesteryl ester from plasma to cause rapid lesion progression.

Aged↗