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Biomedical subjects

B Lindberg

Publications and source records attributed to B Lindberg.

At least 127 records · Page 7Linked to original sources
PubMed1984

Methodological problems in studies on hypertension therapy during pregnancy.

As yet, no distinct aetiological factor underlying hypertension in pregnancy has been disclosed, and there is therefore no clearcut treatment for this condition. The lack of well-defined end-points makes it difficult to plan and evaluate the results of studies on the treatment of hypertension during pregnancy. However, we cannot await the solution to the puzzle of pre-eclampsia before providing treatment for this hypertension. Well-designed investigations to determine the most effective form of such treatment are therefore of great value and must be carried out in spite of the many problems associated with these studies. If given due consideration, as discussed in this paper, this problem can be alleviated.

Apgar Score↗
PubMed1984

Hemodynamic findings before and after resection of abdominal aortic aneurysm.

A preoperative and postoperative hemodynamic study was performed in 20 consecutive patients undergoing elective resection of abdominal aortic aneurysm. Screening for venous thrombosis and pulmonary embolism with 125I uptake test, measurements of maximal venous emptying and pulmonary perfusion scintigraphy were also done before and after the operation. Only five patients complained of intermittent claudication preoperatively, but the laboratory investigations revealed signs of peripheral arterial insufficiency in 15 cases. Maximal venous emptying from the legs was markedly decreased on the first postoperative day and remained significantly below normal on the sixth day. Signs of postoperative thromboembolism appeared in eight patients. These patients did not differ from the others in regard to the pattern of maximal venous emptying. In the three-year follow-up period, the calf blood flow and the ratio of systolic toe pressure to systemic systolic blood pressure were further decreased, despite significant rise in systemic blood pressure.

Aged↗
PubMed1984

Kinetics of 11C-labeled opiates in the brain of rhesus monkeys.

The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appeared 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.

Animals↗
PubMed1984

Comparison of different clearance estimates for metoprolol in the rhesus monkey.

After oral administration, the fraction of unchanged drug available systemically is predominantly governed by hepatic drug-metabolizing enzyme activity and/or binding to the liver. If the "well stirred" model for hepatic elimination mimics reality, the apparent oral clearance (Clo) of metoprolol, a drug which is completely absorbed and metabolized only by the liver, should reflect the intrinsic clearance (Cli), i.e., the maximum enzyme activity in absence of blood flow limitations. According to theory, the hepatic venous (hv) drug concentrations after an i.v. dose are also a function of Cli. This postulate has previously been verified in the isolated perfused rat liver by others and has now been tested by us in the intact rhesus monkey. We have compared Clo, Cli and the systemic clearance (Cls) of metoprolol in six rhesus monkeys catheterized in the hepatic and femoral veins (hv; fv). They were given simultaneously 37 to 73 micrograms of [3H]metoprolol i.v. and 9 mg of metoprolol per kg b.w. orally. Unlabeled drug was analyzed in plasma by gas chromatography and 3H-labeled metoprolol by liquid scintillation after liquid chromatography separation. The Cls [dose i.v./area under the blood concentration vs. time curve in the femoral vein (AUCs)] varied between 27 and 32 ml X kg-1 X min-1. As expected, the Clo (doseo/AUCs) was considerably higher and ranged from 89 to 147 ml X kg-1 X min-1. The Cli (dosei.v./AUChv) was in the same range as Clo (46-163 ml X kg-1 X min-1). The determined oral availability was 19 to 31% with a mean of 25.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Morphine glucuronidation in the rhesus monkey: a comparative in vivo and in vitro study.

The kinetics of morphine in the rhesus monkey after i.v. or oral administration including the hepatic extraction ratio determined directly in the portal and hepatic veins were compared with the glucuronidation of morphine in liver microsomes from the same animals. The plasma half-lives varied between 102 and 202 min and the apparent volume of distribution was 2.68 to 3.15 l X kg b.wt.-1. The systemic blood clearance (9.2-21.3 ml X min-1 X kg b.wt.-1) was in the same range as the estimated hepatic blood clearance (9.7-23.9 ml X min-1 X kg b.wt.-1). After i.v. administration, the blood concentrations of morphine-3-glucuronide ( M3G ) were 8 to 11 times higher than those of morphine. The molar blood concentration ratio between morphine-6-glucuronide and M3G was 0.04 or less. The ratio between the metabolite levels in blood was similar to the relative formation rates for M3G and morphine-6-glucuronide in liver microsomal preparations (less than .039). The intrinsic hepatic metabolic clearance of morphine as estimated from the apparent enzyme kinetic constants Vmax and Km for the formation of the major M3G metabolite was used to predict the hepatic extraction ratio. The predicted values of the hepatic extraction ratio (0.09-0.14) were, however, underestimates of the experimentally determined hepatic extraction ratio, which varied between 0.61 and 0.74. This indicates that unknown factors in the liver microsomal glucuronidation preclude the use of enzyme kinetics parameters obtained in vitro for the prediction of the hepatic extraction ratio of morphine. For some drugs that are oxidized it has been shown previously that such prediction from in vitro data is possible.

Animals↗
PubMed1983

Structural studies of the Escherichia coli O-antigen 25.

The structure of the Escherichia coli O-antigen 25 has been investigated using n.m.r. spectroscopy, methylation analysis, and various specific degradations. It is concluded that the O-antigen is composed of pentasaccharide repeating-units having the following structure.

Antigens, Bacterial↗
PubMed1983

Exchange of amino acids by muscle and liver in sepsis.

The amino acid "central fractional clearance rate" (CFCR), the ratio of the rate of amino acid entry into the extracellular pool to the size of the pool, is a measure of amino acid uptake and clearance by liver and other visceral tissues. In nine normal postabsorptive persons, the mean CFCR was 5%, compared with 21% in 31 seriously infected patients. For comparative purposes, biopsy specimens of liver and muscle were obtained for incubation. In infected patients, the rate of hepatic incorporation of tyrosine into protein was three times that in noninfected patients and correlated well with the CFCR. There was no significant difference in hepatic tyrosine oxidation. In muscle from infected patients, net protein degradation was six times that in noninfected patients. Incubated tissues from rats behaved similarly. Thus, accelerated transfer of amino acid from muscle to viscera for protein synthesis occurs in humans with sepsis, as it does in animals. The CFCR demonstrated the importance to survival of visceral amino acid uptake; it was 35% in surviving patients, and only 19% in those who died.

Amino Acids↗
PubMed1983

Cohort study of oestrogen treatment and the risk of endometrial cancer: evaluation of method and its applicability.

A Swedish study of the risk of endometrial cancer associated with oestrogen treatment was started in 1977. A prospective design was chosen and a cohort of 23,233 women receiving oestrogen medication was collected over a three-year period. Cohort members were recruited on the basis of prescription forms for oestrogens produced by all 120 pharmacies in a defined geographical region, resulting in comprehensive coverage of that region. A questionnaire study of a random sample (1/30) of the cohort permitted mapping of confounding factors, estimation of drug compliance and detailed characterization of oestrogen and progestagen exposures. Efficient follow-up of the cohort members was achieved by linkage of identity numbers of cohort members and those of all incident cases of endometrial cancer in the region. The expected outcome was calculated on the basis of accumulated person-years of observation in the entire cohort - and in subgroups - and age-specific incidence rates of endometrial cancer in the reference population. The present design may be generally useful for post-marketing studies of the association between drug use and side-effects.

Adult↗
PubMed1983

Increased oral clearance of metoprolol in pregnancy.

The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20-40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smaller during (mean 262 nmol/1 X h) than after (mean 1298 nmol/1 X h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4 times higher during (362 ml X kg-1 body-weight X min-1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.

Administration, Oral↗
PubMed1983

Styrene oxide metabolism in rhesus monkey liver: enzyme activities in subcellular fractions and in isolated hepatocytes.

The activity and the kinetic behavior of expoxide hydrolase were studied in various subcellular fractions of rhesus monkey liver isolated by differential centrifugation. The purity of the fractions was estimated by morphometric electron microscopy. Hydrolase activity was measured by a specific radiometric assay with [7-3H]styrene oxide as substrate. All isolated subcellular fractions catalyzed the hydration of styrene oxide at a significant rate. With a saturating concentration of substrate (1 mM), the enzymatic activity (nanomole of product per minute per milligram of protein; mean +/- S.E.) turned out to be 1.51 +/- 0.45 (nuclear fraction), 3.50 +/- 1.11 (mitochondrial fraction), 14.8 +/- 2.26 (microsomal fraction) and 1.69 +/- 0.37 (soluble fraction). The hydrolase obeyed Michaelis-Menten kinetics in each fraction. Vmax (nanomole per minute per milligram; mean +/- S.E.) was 1.64 +/- 0.65 (nuclear fraction) 3.87 +/- 1.71 (mitochondrial fraction), 19.8 +/- 5.4 (microsomal fraction) and 2.72 +/- 1.36 (soluble fraction). The Km (millimole; mean +/- S.E.) values in the fractions were 0.09 +/- 0.02, 0.07 +/- 0.01, 0.23 +/- 0.15 and 0.64 +/- 0.40, respectively. The metabolism of styrene oxide was also studied in isolated hepatocytes from rhesus monkey. These cells hydrated the substrate easily whereas the conjugation of styrene oxide with glutathione was not measurable. Our results show that epoxide hydrolase is present in all subcellular fractions of the rhesus monkey liver. Styrene oxide is preferentially metabolized by hydration to styrene glycol in the isolated hepatocytes of this species and no conjugation with glutathione was found under the incubation conditions used.

Animals↗
PubMed1982

Structural studies of the Vibrio cholerae O-antigen.

The dominant part of the O-antigen of Vibrio cholerae is a homopolysaccharide composed of (1 leads to 2)-linked 4-amino-4,6-dideoxy-alpha-D-mannopyranosyl (perosaminyl) residues, in amino groups of which are acylated by 3-deoxy-L-glycero-tetronic acid. Most of the amino sugar is decomposed during acid hydrolysis. Treatment of the polymer with anhydrous hydrogen fluoride, which cleaves the glycosidic linkages but does not cause N-deacylation, followed by acid hydrolysis under mild conditions, produced the monomer in good yield. Treatment of the N-deacylated polysaccharide with nitrous acid caused deamination with concomitant rearrangements, typical of 4-amino-4-deoxyhexopyranosyl residues in which the amino group occupies an equatorial position.

Carbohydrate Conformation↗
PubMed1982

A 500-MHz proton-magnetic-resonance study of several fragments of the carbohydrate-protein linkage region commonly occurring in proteoglycans.

The proton-magnetic-resonance spectra of three partial structures of the carbohydrate-protein linkage region that frequently occurs in proteoglycans, namely, beta-D-Galp-(1 leads to 3)-beta-D-Galp-(1 leads to 4)-beta-D-Xylp-(1 leads to O)-L-Ser, were recorded in 2H2O at 500 MHz; they could be completely interpreted, both for the glyco-serines and for the corresponding glyco-xylitols. The chemical shifts and the coupling constants were refined by computer simulation of the spectra. The change in the chemical shift of H-4 of a D-galactopyranosyl residue upon substitution at C-3 by a beta-D-galactopyranosyl group is proposed to be characteristic for this particular attachment, making H-4 of galactose a structural-reporter group. The three constituting monosaccharides adopt the 4C1 (D) ring conformation. The terminal galactopyranosyl group and the internal galactopyranosyl residue differ as to the population of rotamers around the C-5/C-6 axis. Concomitantly, the flexibility of their glycosidic linkages is distinct.

Carbohydrates↗
PubMed1982

Fetal jejunal atresia and intrauterine volvulus--a case report.

Ultrasonic B-scan not only confirms the clinical suspicion of polyhydramniosis, but will also in many cases diagnose the etiology. In case of a high intestinal atresia, two or more fluid-filled structures are seen in the fetal abdomen. In case of a congenital defect combination, intestinal atresia is generally associated with malrotation. This combination is frequently complicated by a midgut volvulus. The report describes a case of intrauterine volvulus with a surviving child. Repeat CTG-recordings in this case led to an acute caesarean section, when the CTG turned from normal to silent pattern.

Adult↗