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Biomedical subjects

T Christiansen

Publications and source records attributed to T Christiansen.

At least 37 records · Page 2Linked to original sources
PubMed2002

LDL receptor mutation genotype and vascular disease phenotype in heterozygous familial hypercholesterolaemia.

Patients with homozygous familial hypercholesterolaemia (FH) caused by receptor-negative, low-density lipoprotein (LDL) receptor gene mutations have higher concentrations of LDL-cholesterol in plasma and earlier onset of cardiovascular disease (CVD) than patients homozygous for receptor-defective, LDL receptor mutations. In contrast, it is uncertain whether the severity of atherosclerotic disease differs in heterozygous FH caused by receptor-negative and receptor-defective mutations. The present authors investigated the influence of LDL receptor mutation type on the clinical phenotype in 31 patients with heterozygous FH caused by the receptor-negative, Trp23-stop mutation and in 31 patients heterozygous for the receptor defective Trp66-Gly mutation. Untreated levels of plasma LDL-cholesterol and calculated cholesterol-years score did not differ significantly between the two groups of patients. Detection of vascular disease was based on two approaches: (1) measurement of coronary calcification by spiral computed tomography (CT) scanning; and (2) ultrasonic measurement of carotid intima-media thickness (IMT). Age was significantly correlated to the presence of coronary calcification, but controlling for relevant cofactors, there was no evidence that the receptor-negative mutation caused more calcification than the receptor-defective mutation. Furthermore, carotid IMT was significantly influenced by plasma concentrations of Lp(a) and triglycerides, as well as by age, sex and smoking status, but again, there was no statistically significant effect of LDL receptor gene mutational type. The similarity in vascular phenotypes was probably caused by a similar life-long burden of LDL-cholesterol in the two groups of patients.

Adult↗
PubMed2001

Simple and robust method for estimation of the split between the oxidative pentose phosphate pathway and the Embden-Meyerhof-Parnas pathway in microorganisms.

The flux through the oxidative pentose phosphate (PP) pathway was estimated in Bacillus clausii, Saccharomyces cerevisiae, and Penicillium chrysogenum growing in chemostats with [1-(13)C]glucose as the limiting substrate. The flux calculations were based on a simple algebraic expression that is valid irrespective of isotope rearrangements arising from reversibilities of the reactions in the PP pathway and the upper part of the Embden-Meyerhof-Parnas pathway. The algebraically calculated fluxes were validated by comparing the results with estimates obtained using a numerical method that includes the entire central carbon metabolism. Setting the glucose uptake rate to 100, the algebraic expression yielded estimates of the PP pathway flux in B. clausii, S. cerevisiae, and P. chrysogenum of 20, 42, and 75, respectively. These results are in accordance with the results from the numerical method. The information on the labeling patterns of glucose and the proteinogenic amino acids were obtained using gas chromatography / mass spectrometry, which is a very sensitive technique, and therefore only a small amount of biomass is needed for the analysis. Furthermore, the method developed in this study is fast and readily accessible, as the calculations are based on a simple algebraic expression.

Bacillus↗
PubMed2001

The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days daily oral treatment with NN703 in healthy male subjects.

The aim of the present study was to assess the safety, pharmacokinetics and pharmacodynamics (including specificity) of NN703 (tabimorelin), a growth hormone (GH) secretagogue, in healthy male subjects following treatment for 7 days once-daily. This was a randomized, double-blind and placebo-controlled study with four active dose levels: 1.71, 3.0, 4.5 and 6.86 mg/kg body weight. There was a dose-related increase for GH area under the curve (AUC) (0-12 h) and GH C(max)(0--12 h); these were significantly higher on both days 1 and 7 as compared with placebo treatment (P = 0.04 to P< 0.0001); however, an overall significant decrease in GH release was found from day 1 to day 7 (P< 0.001). Insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3) increased at all dose levels (including placebo); however, a significantly higher increase as compared with placebo treatment was observed at the three highest dose levels for IGF-I (P = 0.04--0.0006) and at the highest dose level for IGFBP-3 (P = 0.03). There was no statistically significant increase in AUC (0-5 h) for follicle-stimulating hormone, luteinizing hormone and cortisol between active and placebo treatment for day 1 or 7. On day 1 only, a statistically significant increase in AUC (0--5 h) was found for prolactin at 1.71 and 6.86 mg/kg (P< 0.05), for thyroid-stimulating hormone (TSH) at 3.0 mg/kg (P< 0.01) and for adrenocorticotrophic hormone (ACTH) at 4.5 mg/kg (P< 0.05); however, no dose--response relationship was observed for TSH or ACTH. In addition, a statistically significant decrease in AUC (0--5 h) for ACTH (3.0 and 6.86 mg/kg) and cortisol (1.71 mg/kg) was observed on day 7 (P< 0.05). Thus, NN703 is a promising candidate for treatment of absolute or relative GH deficiency.

Administration, Oral↗
PubMed2000

Equity in the delivery of health care in Europe and the US.

This paper presents a comparison of horizontal equity in health care utilization in 10 European countries and the US. It does not only extend previous work by using more recent data from a larger set of countries, but also uses new methods and presents disaggregated results by various types of care. In all countries, the lower-income groups are more intensive users of the health care system. But after indirect standardization for need differences, there is little or no evidence of significant inequity in the delivery of health care overall, though in half of the countries, significant pro-rich inequity emerges for physician contacts. This seems to be due mainly to a higher use of medical specialist services by higher-income groups and a higher use of GP care among lower-income groups. These findings appear to be fairly general and emerge in countries with very diverse characteristics regarding access and provider incentives.

Data Collection↗
PubMed2000

The pharmacokinetics, pharmacodynamics, safety and tolerability of a single dose of NN703, a novel orally active growth hormone secretagogue in healthy male volunteers.

The aim of the present study was to investigate the pharmacodynamics, pharmacokinetics, safety and tolerability of a single dose of NN703 (tabimorelin), a growth hormone secretagogue in healthy male subjects. The study design was double blind, randomized and placebo-controlled, with eight escalating dose levels (0.05-12 mg/kg bodyweight (BW)). NN703 was well tolerated by the subjects. The GH area under the curve (AUC) (0-24 h) was significantly higher when compared to placebo for the three highest dose levels (3.0 mg/kg: P = 0.027, 6.0 mg/kg: P = 0.0023, 12 mg/kg: P< 0.0001), and for GH maximal concentration C(max)the four highest dose levels were also significantly higher when compared to placebo (1.5 mg/kg: P = 0.04, 3.0 mg/kg: P = 0.0143, 6.0 mg/kg: P = 0.0053, 12 mg/kg: P = 0.0007). Furthermore, there was a significant increase in IGF-1 levels when compared to placebo for the 6.0 and 12.0 mg/kg BW dose levels (P< 0. 0001). Statistical analysis comparing the AUC (0-24 h) of the NN703 (four highest dose levels) and placebo-treated groups showed no significant increases following NN703 for ACTH, LH, FSH, TSH, prolactin, and cortisol, however, subtle individual changes were noted in ACTH, cortisol and prolactin at doses above 3.0 mg/kg. In conclusion, NN703 is a promising potential candidate for treatment of GH deficiency/insufficiency.

Administration, Oral↗
PubMed2000

Ultrasound for diagnosis of scaphoid fractures.

We investigated the diagnostic value of two different ultrasound scanning methods for the early diagnosis of acute scaphoid fractures. Fifty-seven patients with ten scaphoid fractures were assessed within a week of injury. The accuracy of the ultrasound assessment was 84% and its specificity was 91%. However, its sensitivity was only 50%. We conclude that ultrasound examination is unreliable for the diagnosis of acute scaphoid fractures.

Adult↗
PubMed2000

Management guidelines for hypotensive pelvic fracture patients.

Pelvic fractures are common in blunt trauma patients and are often associated with other system injuries. Most studies describe the type of pelvic fractures and classify them by the forces creating the injury. Mortality from these fractures is due most often to other system injuries or to hemorrhage. Mortality ranges from 5 to 20 per cent depending on complexity and number of systems injured. We studied 692 cases of pelvic fractures and analyzed the seriously ill patients. They were identified by blood pressure (BP) less than 90 systolic on presentation to the trauma room and having a complex pelvic fracture. The management of these patients was by a protocol used by a group of eight trauma surgeons. This group of 75 hypotensive pelvic fracture patients were analyzed to identify significant factors in their management that predicted mortality. Patients with base excess (BE) values < or =-5 were significantly more likely to die (P<0.05). Patients with BP < or =90 on leaving the trauma room had a significantly higher mortality (P<0.01). Injury Severity Score predicted mortality and can be useful as a tool for quality assurance and process improvement. The early operative intervention to fix associated fractures within 24 hours was not detrimental to patient outcome. Overall mortality in this very sick population was 14.7 per cent. Emergent angiography was used successfully on 14 patients. Seven patients died of continued bleeding. The most important management guidelines for these seriously injured, complex patients are: 1) resuscitate with BE used as a monitor; 2) keep patient blood volume as close to normal as possible; 3) use BP, BE, and ISS to evaluate management of these patients.

Adolescent↗
PubMed1999

On-line study of growth kinetics of single hyphae of Aspergillus oryzae in a flow-through cell.

Using image analysis the growth kinetics of the single hyphae of the filamentous fungus Aspergillus oryzae has been determined on-line in a flow-through cell at different glucose concentrations in the range from 26 mg L-1 to 20 g L-1. The tip extension rate of the individual hyphae can be described with saturation type kinetics with respect to the length of the hyphae. The maximum tip extension rate is constant for all hyphae measured at the same glucose concentration, whereas the saturation constant for the hyphae varies significantly between the hyphae even within the same hyphal element. When apical branching occurs, it is observed that the tip extension rate decreases temporarily. The number of branches formed on a hypha is proportional to the length of the hypha that exceeds a certain minimum length required to support the growth of a new branch. The observed kinetics has been used to simulate the outgrowth of a hyphal element from a single spore using a Monte Carlo simulation technique. The simulations shows that the observed kinetics for the individual hyphae result in an experimentally verified growth pattern with exponential growth in both total hyphal length and number of tips.

Aspergillus oryzae↗
PubMed1999

The redistributive effect of health care finance in twelve OECD countries.

The OECD countries finance their health care through a mixture of taxes, social insurance contributions, private insurance premiums and out-of-pocket payments. The various payment sources have very different implications for both vertical and horizontal equity and on redistributive effect which is a function of both. This paper presents results on the income redistribution consequences of the health care financing mixes adopted in twelve OECD countries by decomposing the overall income redistributive effect into a progressivity, horizontal inequity and reranking component. The general finding of this study is that the vertical effect is much more important than horizontal inequity and reranking in determining the overall redistributive effect but that their relative importance varies by source of payment. Public finance sources tend to have small positive redistributive effects and less differential treatment while private financing sources generally have (larger) negative redistributive effects which are to a substantial degree caused by differential treatment.

Cross-Cultural Comparison↗
PubMed1999

Equity in the finance of health care: some further international comparisons.

This paper presents further international comparisons of progressivity of health care financing systems. The paper builds on the work of Wagstaff et al. [Wagstaff, A., van Doorslaer E., et al., 1992. Equity in the finance of health care: some international comparisons, Journal of Health Economics 11, pp. 361-387] but extends it in a number of directions: we modify the methodology used there and achieve a higher degree of cross-country comparability in variable definitions; we update and extend the cross-section of countries; and we present evidence on trends in financing mixes and progressivity.

Cross-Cultural Comparison↗
PubMed1999

Reliability of the COOP/WONCA charts. Test-retest completed by patients presenting psychosocial health problems to their general practitioner.

OBJECTIVE: To study the reliability of the COOP/WONCA charts when completed by patients who contacted their general practitioner (GP) with psychosocial health problems. DESIGN: Test-retest study. Three measures: on day 0, day 1 and day 14. Comparisons were made between measures on day 0 and day 1 (1-day test) and measures on day 1 and day 14 (13-day test). Patients reported separately if change in their health had occurred between the measurements. SETTING: General practice, Denmark. MATERIAL: 54 1-day test chart sets and 54 13-day test chart sets. METHOD: Cohen's weighted kappa was used to assess reproducibility. In the group of patients who reported health change in the 13-day test we used clinically significant changes in the individual items to assess the charts' sensitivity to changes. RESULTS: The items "overall health", "feelings", and "social activities" showed high reproducibility for patients without reported health change between the tests, and good sensitivity to reflect the reported changes for patients with change. CONCLUSION: The COOP/WONCA health status measures: "overall health", "feelings", and "social activities" are, combined with "change in health", reliable for assessing primary care patients with psychosocial health problems.

Family Practice↗
PubMed1999

Inequalities in health: evidence from Denmark of the interaction of circumstances and health-related behaviour.

It is well known that the experience of poor health depends on adverse social and material circumstances and on unhealthy behaviour. In 1990 a British study asserted that privileged people gain more health benefit from a healthy lifestyle than do deprived people. In the present study this assertion was taken as a hypothesis, assuming statistical interaction between circumstances and health behaviour. The combined effect of these variables was studied in Denmark. Data was obtained from a 1987 national Health and Morbidity Survey; variables were selected to correspond closely with those in the earlier British study. The analysis included a multivariate analysis of variance. The results show that health-related behaviour has a positive effect on health both for those who are deprived and those who are not deprived, which is at variance with the findings of the British study. It confirms earlier analyses of Danish and Dutch data.

Activities of Daily Living↗
PubMed1999

Hemorrhagic septicemia in fallow deer (Dama dama) caused by Pasteurella multocida multocida.

Four outbreaks of hemorrhagic septicemia caused by Pasteurella multocida multocida occurred in a population of 1,800 fallow deer (Dama dama) during 1992-1996. A total of 340 fallow deer were submitted for postmortem examination. Pasteurellosis was diagnosed in 273 of 312 deer suspected of having septicemia. Pasteurella multocida was isolated from 257 animals, and the diagnosis was based on typical pathologic changes alone in the other 16 animals. Pasteurella multocida was isolated in pure culture from 219 of 248 samples of cerebrospinal fluid. Eighteen animals were observed moribund with severe depression, foamy nasal discharge, and respiratory distress, and 257 were found dead. Major clinical signs and pathologic changes included extensive swelling of the head and the neck and peracute or acute septic pneumonia, petechial and ecchymotic hemorrhages on serous membranes, and severely hemorrhagic adrenal glands and abomasum. Rhinitis and necrotic pharyngeal mucosae were common. Histologically, the most advanced lesions were in the nasal mucosa and pharynx. The swelling of the head and the neck arose from a diffuse cellulitis in the subcutaneous and intermuscular tissues. The earliest lesions in the lungs included large numbers of bacteria in the pulmonary capillaries, but various degrees of fibrinous exudation to the alveoli and infiltration with heterophils usually were observed.

Age Distribution↗
PubMed1999

Typing of Pasteurella multocida from haemorrhagic septicaemia in Danish fallow deer (Dama dama).

Isolates of Pasteurella multocida ssp. multocida (n = 31) from a Danish population of fallow deer which succumbed to haemorrhagic septicaemia during 1992 1993 and isolates from the palatine tonsils of apparently healthy fallow deer from the same area (n=6) were typed and compared with P. multocida from other sources. Plasmids were net observed in the fallow deer strains and one unique pattern was observed by ribotyping using HindIII and by pulsed-field gel electrophoresis using SanlI as restriction endonuclease. All Danish fallow deer isolates belonged to serotype B:3,4. On restriction endonuclease analysis using HhaI as restriction endonuclease, all had a profile identical to that of a fallow deer isolate from the United Kingdom: profile 0033 of Wilson et al. On restriction endonuclease analysis using HpaII as restriction endonuclease, the Danish fallow deer isolates had a unique profile, designated 0062, which differed slightly from that of a fallow deer isolate from the United Kingdom. P. multocida from other animal species were genotypically different from the fallow deer isolates. It is concluded that a specific clone of P. multocida was responsible for the outbreak of haemorrhagic septicaemia among Danish fallow deer. A carrier rate of 27% was demonstrated among apparently normal animals from the same population.

Animals↗
PubMed1998

Effects of nonylphenol and 17 beta-oestradiol on vitellogenin synthesis, testicular structure and cytology in male eelpout Zoarces viviparus.

Nonylphenol has been found to be oestrogenic in fish and may influence the reproductive system of male fish. In the present study, the effects of low (10 microg g-1 week-1) and high (100 microg g-1 week-1) doses of nonylphenol and of 17 beta-oestradiol on the synthesis of vitellogenin and on testicular structure and cytology were investigated in male eelpout Zoarces viviparus during active spermatogenesis (May) and late spermatogenesis (June). Twenty-five days after injection, a significant dose-dependent increase in the plasma vitellogenin concentration, measured by enzyme-linked immunosorbent assay, was observed in the treated groups. A highly significant reduction in the gonadosomatic index was observed concomitant with the increase in the plasma vitellogenin concentration. Macroscopically, milt was observed to be present in the control fish, but was sparse or absent in the treated fish. Histological examination using light microscopy revealed severe effects of nonylphenol as well as of oestradiol treatment on testicular structure. Control fish had seminiferous lobules containing spermatogenic cysts and only a few spermatozoa (May) or had the walls of their seminiferous lobules lined with cuboidal Sertoli cells (June). In the treated fish, the seminiferous lobules were degenerated (May) or were filled with numerous spermatozoa and the Sertoli cells appeared very squamous (June). Electron microscopy revealed greater numbers of phagocytosed spermatozoa in these Sertoli cells. In rats, -glutamyl transpeptidase (-GTP) has been used as a specific marker of Sertoli cell function. In the present study, both nonylphenol and 17 beta-oestradiol treatment resulted in a reduction in the activity of this enzyme. The study provides evidence that nonylphenol is oestrogenic, as indicated by the large increase in vitellogenin synthesis, and that both nonylphenol and oestradiol have marked effects on the testicular structure and cytology of germ cells and Sertoli cells of male Z. viviparus.

Animals↗