Search PubMed⌕ Search

Biomedical subjects

T W Hansen

Publications and source records attributed to T W Hansen.

At least 19 recordsLinked to original sources
PubMed2004

Relation between insulin and aortic stiffness: a population-based study.

Recent studies have suggested that a high pulse wave velocity (PWV), a measure of aortic stiffness, may be a stronger risk factor for cardiovascular disease (CVD) than a high blood pressure (BP). The relation between insulin, believed to play an important role in the development and clinical course of high BP, and PWV is not yet clear. Therefore, we decided to examine the relationship between insulin and PWV in a large population-based study. The study population consisted of a random sample of 1213 women and 1207 men (age range, 41-72 years) without a history of myocardial infarction or stroke. Fasting insulin was determined together with conventional risk factors for CVD. PWV was recorded transcutaneously by a mechanical electrical principle with one transducer positioned over the left common carotid artery, and another over the left femoral artery. In univariate analysis, insulin was highly significantly related to PWV (standardized regression coefficient: 0.0669+/-0.0051; P<0.001). In multivariate analysis, controlling for all well-established predictors of PWV, such as age, systolic BP or mean BP and pulse pressure, sex, and heart rate, as well as controlling for conventional risk factors for CVD and use of BP-lowering drugs, the level of insulin remained a significant predictor of PWV (standardized regression coefficient: 0.0122+/-0.0048; P=0.012). In conclusion, the present study found that a higher insulin level was related to a higher PWV. This indicates that hyperinsulinaemia may affect BP and risk of CVD by increasing aortic stiffness.

Adult↗
PubMed2001

Atomic-resolution in situ transmission electron microscopy of a promoter of a heterogeneous catalyst.

Insight into the location, state, and function of a promoter in heterogeneous catalysis was obtained through atomic-resolution in situ transmission electron microscopy. In the most active ruthenium catalyst for ammonia synthesis known so far, the barium promoter is shown to be located in two different phases in the catalyst. The increased activity is suggested to be related to a two-dimensional barium-oxygen overlayer on the ruthenium crystals. The possibility for conducting such studies for other reactions could add substantially to our current understanding of heterogeneous catalysis. Heterogeneous catalysis plays an increasingly important role in environmental protection processes, in fuel upgrading, and in providing the majority of the chemical building blocks required by contemporary society. Most heterogeneous catalysts of industrial importance are multicomponent materials that are designed by trial-and-error experimentation. Application of even the most sophisticated physical-chemical characterization techniques is usually not sufficient to obtain a complete understanding of the structure of the active site, the reaction mechanism and kinetics, the structural dynamics, and the specific roles of all catalyst components.

Journal Article↗
PubMed2001

[Fiberoptic phototherapy of neonatal jaundice. Comments to a Cochrane report].

Twenty-four studies filled the inclusion criteria for a Cochrane report on the use of fiberoptic phototherapy for neonatal jaundice. Fiberoptic phototherapy lowers serum bilirubin and may have a place in the treatment of neonatal jaundice. In term and near-term infants fiberoptic phototherapy is inferior to conventional phototherapy, whereas in premature infants the effects are comparable. A better effect is achieved when conventional and fiberoptic phototherapy are combined as compared to conventional phototherapy alone. Fiberoptic phototherapy has not been shown to interfere less with parent-infant bonding than conventional phototherapy. There continues to be a great need for research concerning phototherapy for neonatal jaundice.

Evidence-Based Medicine↗
PubMed2001

Bilirubin brain toxicity.

Bilirubin is toxic in most biological systems tested. Several mechanisms have been suggested for this toxic effect, including inhibition of enzyme systems and inhibition of cell regulatory reactions (protein/peptide phosphorylation). The identity of the basic mechanism(s) has not been conclusively proven, but inhibition of peptide phosphorylation, perhaps mediated or modulated by lysine at the active site(s), appears to be compatible with many of the observations currently found in the literature. Bilirubin entry into brain is facilitated by drug displacement of bilirubin from its albumin binding, reduced albumin binding capacity, increased brain bloodflow, increased permeability of the blood-brain barrier, and other factors. The rate of bilirubin entry into brain, as well as the degree of retention and rate of clearance from brain, depends on which of these circumstances are operative. It is as yet unclear whether the mechanism responsible for increased brain bilirubin is important for toxicity. The mechanism for preferential localization of bilirubin to the basal ganglia in kernicterus is also not known. Bilirubin appears to distribute differentially to brain subcellular compartments and is oxidized in brain by an enzyme localized on the inner mitochondrial membrane. This enzyme is found both in neurons and in glia, but appears to be more active in the latter. The activity increases with postnatal age, and is subject to genetic variability in animals. The enzyme is cytochrome c-dependent. It is as yet not clear whether the activity of this enzyme serves a brain-protective effect in severe hyperbilirubinemia.

Animals↗
PubMed2001

Ontogeny of P-glycoprotein in mouse intestine, liver, and kidney.

BACKGROUND: P-glycoprotein (Pgp) is an ATP-dependent, integral plasma-membrane efflux pump that is constitutively expressed on (i) adult apical brush-border epithelial cells of the intestine, (ii) the bile canalicular face of hepatocytes, and (iii) the brush border epithelium of renal proximal tubules. This Pgp tissue distribution and localization affects the absorption, distribution, metabolism, and excretion of Pgp substrates. Little is known regarding the ontogeny of Pgp expression in these tissues. METHODS: Postnatal expression of Pgp on brush border membranes of small intestine, liver, and kidney as a function of maturity from birth through adulthood was determined using Western immunoblotting and immunohistochemical techniques. Tissue was isolated from FVB mice at four different ages: day of life 0 (D0), day of life 7 (D7), day of life 21 (D21), and adult (Ad). The relative expression of Pgp protein on Western immunoblots was assessed by scanning densitometry and indexed as a percentage (mean+/-SEM) of the adult levels. RESULTS: On Western immunoblots, Pgp expression was limited at birth (19+/-6% of Ad) and increased significantly with maturation in intestine (ANOVA, P<0.005). In contrast, hepatic (113+/-12% of Ad) and renal (96+/-15% of Ad) Pgp expression were at adult levels at birth. The tissue-specific developmental pattern of Pgp expression was confirmed by immunohistochemistry. CONCLUSIONS: We conclude that Pgp is expressed in a tissue-specific and developmentally regulated fashion and speculate that developmental modulation of intestine-Pgp expression may affect the oral bioavailability of Pgp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Guidelines for treatment of neonatal jaundice. Is there a place for evidence-based medicine?

UNLABELLED: Treatment of neonatal jaundice continues to be a controversial issue. Arguments that traditional practice results in over-treatment have led to the adoption of more liberal guidelines in some countries. The importation of liberal guidelines from one country to the next, however, is fraught with danger, because differences in epidemiology, sociology and healthcare delivery systems between countries may not be adequately reflected. The unreflected extension of liberalization to non-target groups of patients can expose the latter to significant risk. It is not clear that the evidence on which guidelines for treatment of neonatal jaundice are based satisfy the requirements for evidence-based medicine. Evidence of adequate quality may be hard to obtain. CONCLUSIONS: Introduction of more liberal guidelines for the treatment of neonatal jaundice, if at all contemplated, must be adapted to local circumstances, and any available evidence pertaining to local epidemiology, sociology and healthcare organization has to be carefully weighed and incorporated. The time is ripe for a joint international effort to secure adequate funding for basic and applied research within the mechanisms of bilirubin encephalopathy in the newborn.

Evidence-Based Medicine↗
PubMed2001

Spectrum of outcome in infants with extreme neonatal jaundice.

UNLABELLED: The increasing number of case reports on neurologic sequelae related to hyperbilirubinaemia may represent a re-emergence of kernicterus in the industrialized world. However, not much has been written about infants who survived extreme levels of serum bilirubin without neurologic damage. We present three cases of extreme neonatal hyperbilirubinaemia, all with peak serum bilirubin levels >600 micromol/L. Two of the infants developed neurologic sequelae, but the third infant did not. In contrast to the two with sequelae, the infant without sequelae was female, had a positive Coombs' test, less clinical signs compatible with bilirubin encephalopathy, and a shorter exposure to serum bilirubin values >400 micromol/L. CONCLUSION: The basic mechanism of bilirubin neurotoxicity remains unknown, and it is not clear why some infants do not develop neurologic injury at serum bilirubin levels at which others do. We speculate that a comparison between patients with sequelae and those without may yield important information.

Bilirubin↗
PubMed2000

Kernicterus in term and near-term infants--the specter walks again.

UNLABELLED: Diagnostic and therapeutic intervention is common in newborns with neonatal jaundice, motivated by the fear of bilirubin-associated brain damage, kernicterus. In recent years, a resurgence of kernicterus has been noted in countries in which this complication had essentially disappeared. Both early postnatal discharge and relaxation of attitudes to neonatal jaundice have been implicated. Guidelines for the management of neonatal jaundice show significant disparity, attesting to our inadequate understanding of the underlying biology. Aggressive guidelines expose infants to unnecessary risks, risks that are significant when it comes to exchange transfusion, and may also involve improper use of limited resources. Relaxed guidelines, on the other hand, may expose infants to increased risk of brain toxicity. CONCLUSION: At present we have no tools for ensuring certain identification of individuals with increased vulnerability to bilirubin toxicity. Relaxation of guidelines which have been proven safe through prolonged use should therefore be undertaken only in an atmosphere of increased vigilance. Guidelines that allow for a range of therapeutic and diagnostic options underline the need for careful assessment of each case on its individual merits.

Bilirubin↗
PubMed2000

Bilirubin oxidation by brain mitochondrial membranes is not affected by hyperosmolality.

Brain mitochondrial membranes oxidize bilirubin at a rate that may be biologically significant. Hyperosmolality delays clearance of bilirubin from rat brain. We hypothesized that this might be due to a decrease in brain bilirubin metabolism. Rats were anesthetized and infused with 75 mM/kg urea i.v. over 5 min (n = 7) and sacrificed at 1 h; control rats (n = 7) had no treatment. Crude mitochondrial membrane fractions ('P2') were produced by homogenization and differential centrifugation in sucrose. The change in optical density at 440 nM of a 10-micromol/l bilirubin solution was measured after 60 min incubation with mitochondrial membranes. Hyperosmolality did not affect bilirubin oxidation by brain mitochondrial membranes (t = 1.27, p = 0.23 by unpaired t-test). The lack of effect of hyperosmolality on bilirubin oxidation by brain mitochondrial membranes suggests that decreased clearance of bilirubin from brain in hyperosmolality may be related to changes in transfer of bilirubin across the blood-brain barrier.

Animals↗
PubMed2000

The analysis of the complement activation product SC5 b-9 is applicable in neonates in spite of their profound C9 deficiency.

Native complement factors and complement activation products were measured in healthy neonates (n = 72) and in a group of infants with premature prolonged rupture of the membranes (PPROM) without sepsis (n = 10). Vitronectin concentration in normal cord blood was not correlated with gestational age, and the median value was 86.0% of adult values. This was markedly higher than other native complement factors studied (factor B: 35.9%, C4: 45.1%, C3: 56.2%). The concentration of C9 showed a positive correlation with gestational age and was very low, 10.8% of normal adult values in cord blood and 8.3% in the patients. Fifteen percent of the neonates had C9 levels lower than 2% of adult values. The complement activation products Bb and SC5 b-9 were significantly elevated in the patients (159% and 130% of control values, respectively), indicating alternative and terminal pathway activation. In contrast, C4 bc and C3 bc levels were not increased. The maximum amount of SC5 b-9 which could be generated in the neonatal sera by cobra venom factor was highly correlated with C9 concentration (rs = 0.86, p = 0.0001) The profound C9 deficiency found in neonates is correlated with gestational age, limits the capacity to form bacteriolytic C5 b-9 (m) and may predispose for severe invasive bacterial infection. The plasma level of SC5 b-9 under normal conditions was very low, only 0.3% (0.1%-3.0%) of the values obtained after CVF activation of the same samples. Therefore, we suggest that the analysis of SC5 b-9 is applicable also in neonates, in spite of their extremely low C9 levels.

Bacteremia↗
PubMed2000

Pioneers in the scientific study of neonatal jaundice and kernicterus.

Neonatal jaundice must have been noticed by caregivers through the centuries, but the scientific description and study of this phenomenon seem to have started in the last half of the 18th century. In 1785 Jean Baptiste Thimotée Baumes was awarded a prize from the University of Paris for his work describing the clinical course in 10 jaundiced infants. The work by Jaques Hervieux, which he defended for his doctor of medicine degree in 1847, was, in many respects, a landmark. He had autopsied 44 jaundiced infants and apparently had clinical observations on many others. His descriptions of pathoanatomical findings were very detailed and systematic. A number of his clinical observations are still thought to be accurate today, such as the essentially benign nature of neonatal jaundice in most cases, the appearance of neonatal jaundice during the first 2 to 4 days of life as well as its disappearance within 1 to 2 weeks, and the cephalocaudal progression of jaundice. He described jaundice of the brain in 31 of his 44 autopsied cases, with variable intensity of staining. Johannes Orth was an assistant to the famous Virchow in Berlin, when in 1875 he published the results of an autopsy of a jaundiced term infant. The brain was notable for an intense yellow staining of the basal ganglia, the wall of the third ventricle, the hippocampus, and the central parts of the cerebellum. While the contribution of Orth was limited to this single case report, in 1903 Christian Schmorl presented the results of his autopsies of 120 jaundiced infants to the German Society for Pathology. All of these infants' brains were jaundiced, but only 6 cases demonstrated a staining phenomenon similar to that previously described by Orth. Schmorl coined the term kernicterus (jaundice of the basal ganglia) for this staining pattern. Although the following century of scientific study has added an enormous amount of information about the epidemiology and pathophysiology of neonatal jaundice and kernicterus, the contributions of Hervieux, Orth, and Schmorl will undoubtedly continue to be seen as historical landmarks in our quest for understanding of these phenomena.

France↗