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Biomedical subjects

K Kristensen

Publications and source records attributed to K Kristensen.

At least 37 records · Page 2Linked to original sources

Hormone replacement therapy affects body composition and leptin differently in obese and non-obese postmenopausal women.

Leptin and oestrogen are both involved in the regulation of adipose tissue deposition and feeding behaviour. We investigated whether 5 years of hormone replacement therapy (HRT) affected serum leptin and body composition differently in 89 postmenopausal women treated with HRT compared with 178 controls. At baseline, leptin was significantly correlated with oestradiol (r=0.13, P<0.05) and in multiple backward regression analysis including oestradiol and any estimate of body fat, oestradiol remained a significant determinant of leptin levels. In the control group, all estimates of body fat determined by dual energy X-ray absorptiometry (DEXA) or anthropometry were increased (3.6-16.9%) and leptin increased 31.3% (16.03+/-1.02 to 20.84+/-1.2 ng/ml (s.e.m.), P<0.001). In the HRT group all estimates of body composition also increased during the 5-year observation but to a lesser extent than observed in the control group (1.0-8.5%). Leptin was raised by 19.7% (17.81+/-1.32 to 20.57+/-1.65 ng/ml, P<0.001). However, the DEXA scans revealed that the control group gained 2.4-fold more fat during the 5-year observation (1.9+/-0.3 vs 0.8+/-0.4 kg, P<0.05), and especially the trunk fat increased (1.4+/-0.2 vs 0.7+/-0.3 kg, P<0.05). This was reflected in the increase in leptin levels, which were increased by 7.4% in the control group compared with the HRT group (4.81+/-0.60 vs 2.76+/-0.87 ng/ml, P<0.05). Adjusting for the difference in adipose tissue revealed that HRT had no independent effect on leptin levels. Comparisons between obese (body mass index>25 kg/m(2)) and non-obese (<25 kg/m(2)) subjects by stratifying for HRT treatment using multiple linear regression revealed that the change in fat mass was significantly less among treated subjects (P=0.038) and especially in the non-obese subjects (P=0.001). The change in trunk fat was similarly correlated with treatment status (P=0.029) and with the degree of obesity (P=0.006). In conclusion, 5 years of HRT treatment significantly reduced fat mass accumulation, especially in the trunk region. This effect of HRT was more pronounced in non-obese as compared with obese subjects. The HRT-induced reduction in fat mass seems not to be mediated by leptin.

Body Composition↗

[The auto- and endocrine function of the adipose tissue. Significance for metabolic complications in obesity].

The present review discusses recent research showing adipose tissue to be highly metabolically active, producing and releasing many different bioactive compounds besides free fatty acids (FFA) such as tumor necrosis factor alpha (TNF alpha), leptin, acetylation stimulating protein (ASP), plasminogen activator inhibitor-1 (PAI-1), cholesterol ester transfer protein (CETP), prostaglandins and oestrogens. Most of these compounds have autocrine effects on the adipose cells and they are presumably involved in the physiological regulation of blood flow, growth and metabolism of the adipose tissue. When the adipose tissue becomes enlarged, as seen in association with obesity, it has now been shown that several of the compounds produced in the adipose tissue (TNF, PAI-1, CETP etc.) may be directly involved in the pathogenesis of some of the complications commonly seen in association with obesity such as insulin resistance, hypertension, enhanced thrombogenesis, and premature atherosclerosis.

Adipose Tissue↗

Serum leptin levels and leptin expression in growth hormone (GH)-deficient and healthy adults: influence of GH treatment, gender, and fasting.

Growth hormone (GH) treatment is associated with a reduction in fat mass in healthy and GH-deficient (GHD) subjects. This is mainly mediated via a direct GH action on adipose cells and stimulation of lipolysis. Leptin is secreted from adipose tissue and may be involved in signaling information about adipose tissue stores to the brain. Hormonal regulation of leptin is still not fully elucidated, and in the present study, we investigated both the long-term (4-month) and short-term (28-hour) GH effects on serum leptin and leptin gene expression in subcutaneous adipose tissue. In GHD adults (n = 24), leptin correlated with most estimates of adiposity (r = .62 to .86), as previously found in healthy subjects. However, no correlation was observed with intraabdominal fat determined by computed tomographic (CT) scan (INTRA-CT). GH treatment for 4 months had no independent effect on either serum leptin or leptin gene expression. In a short-term study, we found that fasting gradually reduced leptin levels in both healthy men and GHD adults, with a maximum reduction of 58% to 60% (P < .01) after 31 hours. No independent effect of GH suppression or GH substitution on serum leptin was found during fasting. Adipose tissue leptin mRNA correlated with serum leptin (r = .51, P < .01) and the body mass index ([BMI] r = .55, P < .05). Serum leptin levels and gene expression were significantly higher in women compared with men (26.6 +/- 5.8 v 10.0 +/- 1.30 ng/mL, P < .05). However, in regression analysis accounting for the gender differences in subcutaneous femoral adipose tissue (FEM-CT), the difference in serum leptin disappeared, indicating that subcutaneous femoral fat or factors closely related to femoral fat (eg, sex hormones) may be causal factors for the gender difference in leptin.

Adipose Tissue↗

Epidemiology of respiratory syncytial virus infection requiring hospitalization in East Denmark.

BACKGROUND: Prophylaxis against infection caused by respiratory syncytial virus (RSV) with high titered RSV immunoglobulin or humanized antibody may soon be available in Europe. OBJECTIVE: To study the epidemiology of RSV infections requiring hospitalization in infants <6 months in East Denmark to provide a rational basis for decisions concerning prophylaxis against RSV. METHOD: Populat ion-based retrospective review of case records of infants <6 months admitted to pediatric departments with RSV infection in East Denmark from November 1, 1995, to April 30, 1996. RESULTS: Data were obtained from 459 infants. Seventy-three had predisposing conditions: prematurity, 49; pulmonary disease, 2; congenital heart disease, 7; neurologic disease, 6; others, 9. One preterm infant had bronchopulmonary dysplasia. The incidence of RSV infection requiring hospitalization in East Denmark among infants <6 months was estimated to be 34/1000/season. It was 32/1000/season among term infants and 66/ 1000/season among preterm infants (P<0.001). Infants with predisposing conditions and/or nosocomial infection (n = 24) had significantly more severe courses than otherwise healthy infants (P<0.01). One-hundred thirty infants received respiratory support by nasal continuous positive airway pressure, but only six required mechanical ventilation. No infants died. CONCLUSION: The course of RSV disease in East Denmark was milder than reported elsewhere, possibly as a result of the low prevalence of bronchopulmonary dysplasia in Denmark. However, RSV constitutes a considerable burden to the Danish pediatric health care system, and therefore prophylaxis against RSV is desirable.

Denmark↗

Systemic administration of epidermal growth factor reduces fat mass in rats: effects on the hormone-sensitive-lipase, lipoprotein lipase and leptin.

We examined whether the reduction in fat mass induced by EGF treatment in mature animals was via activation of hormone-sensitive lipase (HSL) and thereby the induction of lipolysis, or through inhibition of lipoprotein lipase activity thus reducing fat uptake in adipose tissue. Sixteen male rats were treated with placebo or EGF 150 microg/kg/day for 7 days via mini-osmotic pumps. The results demonstrate that systemic EGF treatment reduces the amount of adipose tissue, most likely due to increased lipolysis as HSL activity as well as HSL mRNA were increased. The circulating levels of free fatty acids were slightly increased and leptin levels reflected the decrease in adipose tissue mass.

Adipose Tissue↗

Major haemorrhagic complications during oral anticoagulant therapy in a Danish population-based cohort.

OBJECTIVES: To estimate the incidence of bleeding leading to death or hospital admission in out-patients treated with oral anticoagulants. DESIGN: Population-based historical cohort study 1 January 1992 to 31 September 1994. SETTING: The County of North Jutland, Denmark (488,000 inhabitants). SUBJECTS: Six hundred and eighty-two consecutive patients commencing oral anticoagulant therapy. MAIN OUTCOME MEASURES: Fatal bleeding or bleeding demanding hospital admission. RESULTS: In 756 treatment-years of follow-up, there were 45 major haemorrhagic events (6.0 per 100 treatment-years) in 42 patients, of which seven (0.9 per 100 treatment-years) were fatal. The risk of a first major haemorrhagic episode was highest during the first 90 days of treatment compared with duration above one year (incidence rate ratio, IRR, 1.9; 95% CI, 0.8-4.1). The rate was highest above the age of 60 years, 6.8 per 100 treatment-years, compared with 2.9 per 100 treatment-years below 60 years (IRR 2.3; 95% CI, 1.0-5.6). The rate for a bleeding event was slightly higher in females than in males (IRR 1.3; 95% CI, 0.7-2.3), but did not vary according to type of anticoagulant drug. CONCLUSIONS: The reported rates of major bleeding in this routine community setting implied a higher bleeding risk than was found in randomized trials or when patients are monitored in specialist anticoagulation clinics.

Adult↗

Effects of long-term total fasting and insulin on ob gene expression in obese patients.

In the present study the effect of long-term fasting (6 days) on obese (ob) gene expression was examined in nine severely obese females of 34 +/- 3 years and with a body mass index of 46.4 +/- 2.3 kg/m2. Six days of fasting induced a significant weight loss (126.8 +/- 5.3 vs 120.5 +/- 5.1 kg, P < 0.0001). Insulin-stimulated glucose uptake (hyperinsulinemic, euglycemic clamp, insulin infusion rate 1.5 mU/kg per min) was markedly reduced following fasting (M-value 5.96 +/- 0.74 vs 2.79 +/- 0.23 mg/kg per min, P < 0.0001). Ob mRNA/beta-actin concentration in fat biopsies from abdominal subcutaneous adipose tissue was unchanged after 6 days of fasting (1.50 +/- 0.40 vs 1.47 +/- 0.36 arbitrary units, not significant), whereas serum leptin levels decreased significantly from 53.8 +/- 4.7 to 30.7 +/- 2.0 ng/ml (P < 0.0001) during the same period. No significant correlations were found between insulin-stimulated glucose uptake and serum leptin concentration, either prior to the fast or after the fast. Serum leptin levels were unchanged by hyperinsulinemia for 3 h during the clamp prior to the fast, while hyperinsulinemia for 3 h after 6 days of fasting increased serum leptin by 25% (P < 0.01). In conclusion, 6 days of fasting reduced serum leptin by about 40%. In contrast, ob mRNA in abdominal subcutaneous adipose tissue was unchanged. Furthermore, after 6 days of fasting insulin was able to increase the serum level of leptin significantly, indicating that the effect of insulin on the level of leptin is dependent on the nutritional state.

Adipose Tissue↗

[Vaccination of premature infants].

The article gives a review of the literature concerning immunization of preterm infants. The initial response to diphtheria-tetanus-whole-cell-pertussis vaccine and inactivated polio vaccine may be impaired in preterms, but after two and three doses the responses to these vaccines is comparable to those of term infants of the same chronological age. Likewise, the response to oral polio vaccine is normal and independent of gestational age after two and three doses in preterm infants. After two doses, the response to Haemophilus influenzae type b conjugate vaccine is impaired in preterm infants with very low gestational age, but comparable to that of term infants in preterms with higher gestational ages. After three doses the response to this vaccine is normal and unaffected by gestational age in preterms. Recombinant hepatitis b vaccine induces a reduced response in preterm infants even after three doses, and they may therefore need an extra dose of this vaccine. Studies of diphtheria-tetanus-whole-cell-pertussis vaccine and Haemophilus influenzae type b conjugate vaccine in preterm infants do not suggest that adverse effects occur more often or are more severe than those seen in term infants. The literature provides no background for postponement of immunizations in preterm infants.

Denmark↗

Antibody response to Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid in preterm infants.

OBJECTIVE: To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. SUBJECTS: Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from 920 to 2550 g. Controls were 37 term infants. METHODS: All infants were immunized with HibCP-TT at 2, 4 and 12 months of age. Antibodies to HibCP and TT were determined at each immunization and 1 month after the second and third. RESULTS: After two doses of HibCP-TT the preterm infants with GAs < or = 30 weeks (n = 8; mean GA, 29.5 weeks) had a significantly lower HibCP antibody response than the preterm infants with GAs > 30 weeks (n = 23; mean GA, 34.2 weeks) (P = 0.004), who for their part had a response not significantly different from that of the term infants. After the third dose there were no significant differences among the groups. The response to the TT part of the vaccine showed the same pattern. CONCLUSION: Although the most immature infants may show an inadequate antibody response to the initial immunizations, many preterm infants can benefit from vaccination with HibCP-TT when starting immunization at the same chronologic age as term infants.

Antibodies, Bacterial↗

Stereoselective pharmacokinetics of methadone in chronic pain patients.

Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. The analgesically active R-methadone has a significantly longer mean elimination half-life than the optical antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total volume of distribution is 496.6 L for R-methadone and 289.1 L for S-methadone. Significant differences in the mean clearance between R- and S-methadone are seen (0.158 and 0.129 L/min, respectively). However, the lagtime after oral administration and the bioavailability did not show differences between the isomers. The data suggest that both enantiomers of methadone should be measured if correlations between pharmacodynamics and kinetics are made due to the stereoselective differences in half-life, total volume of distribution, and clearance.

Aged↗

Long-term (6 months) effect of a new fermented milk product on the level of plasma lipoproteins--a placebo-controlled and double blind study.

OBJECTIVE: We have recently demonstrated a short-term hypocholesterolemic effect (reduction of 8-10%) of a new fermented milk product taken for 6 weeks (Agerbaek et al, 1995; Richelsen et al, 1993). The present study was undertaken to investigate the more long-term (6 months) effect of this fermented product on the level of lipoproteins. DESIGN: The study was randomized, double-blind, and placebo-controlled, and performed for a period of six months. SUBJECTS: Eighty-seven non-obese and normocholesterolemic females and males, aged 50-70 y old, were included in the study. INTERVENTION: 200 ml of either the fermented milk product or placebo (chemically fermented) were given daily. The test product was fermented with a bacteria culture containing Enterococcus faecium and two strains of Streptococcus termophilus. RESULTS: After one month the total- and LDL-cholesterol were significantly reduced in the fermented milk group as compared to placebo, LDL was reduced by 0.21 mmol/l vs 0.0 mmol/1 (P < 0.02). The maximal reduction of LDL-cholesterol was reached after 3 months in the test group with a reduction of 0.32 mmol/1 of initial values (P < 0.001). In the placebo group a gradual fall of total- and LDL-cholesterol was observed from 1-6 months of the study. Thus, after six months the reduction of LDL-cholesterol was similar in the two groups (P = 0.95) even though the reduction was significant in both groups in relation to initial values (P < 0.05). No changes in HDL-cholesterol or triglyceride were observed during the study. There were no differences in the response between women and men. CONCLUSION: The fermented milk product resulted in a rapid reduction of LDL-cholesterol observed after one month but during long-term intake (6 months) the reduction of LDL-cholesterol was similar to the placebo product, indicating that low-fat milk or fermented milk products may have some hypocholesterolemic effects but the present tested product does not seem to be superior in that respect to the placebo milk product used in the present study.

Aged↗

[Use of blood products in Denmark in 1993. Regional differences and comparison with other Scandinavian and European countries].

In Denmark approximately 396,000 units of blood were collected during 1993 from among approximately 270,000 voluntary non-renumerated blood donors corresponding to about 76 donations per 100 inhabitants. Almost all units (approx. 99%) were fractionated into blood components in the blood banks. Approximately 16,000 erythrocyte units were rejected due to technical errors or quality control, while around 37,000 erythrocyte units were discarded from stock. Only 190 units were transfused as whole blood. In all 327,108 SAG-M erythrocyte suspensions, 70,971 thrombocyte concentrates, 50,161 units of fresh frozen plasma, FFP, and approximately 1700 kg albumin, 100% were transfused, corresponding to 63, 14 and 10 units and 340 g per 1000 inhabitants. When compared to other Scandinavian and European countries, Denmark has a high consumption of erythrocyte components, FFP and albumin for transfusion. The reason why cannot be clarified by available data, but it is not unlikely that Denmark has a more liberal transfusion policy than the other countries. There are considerable differences within Denmark as regards the clinical use of blood products. Counties/regions with university hospitals and regional and/or national functions tend to have a relatively high consumption. However, no information exists on consumption related to demographic parameters or related to hospitals, departments or diagnoses.

Blood Component Transfusion↗

The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine.

The binding affinities of racemic methadone and its optical isomers R-methadone and S-methadone were evaluated for the opioid receptors mu1, mu2, delta and kappa, in comparison with that of morphine. The analgesic R-methadone had a 10-fold higher affinity for mu1 receptors than S-methadone (IC50 3.0 nM and 26.4 nM, respectively). At the mu2 receptor, the IC50 value of R-methadone was 6.9 nM and 88 nM for S-methadone, respectively. As expected, R-methadone had twice the affinity for mu1 and mu2 receptors than the racemate. All of the compounds tested had low affinity for the delta and kappa receptors. This result suggests that S-methadone does not essentially contribute to opioid effect of racemic methadone. R-methadone has a receptor binding profile which resembles that of morphine.

Animals↗

Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection.

Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls once with a Haemophilus influenzae type b (Hib) conjugate vaccine. Total IgG subclasses, total antipolysaccharide Hib antibodies, and antipolysaccharide Hib antibodies of IgM, IgG, IgA, and IgG1-4 specificity were determined by ELISA. There were no significant differences between the two groups in any single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls (P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls (P = 0.005), whereas 1 month later they had significantly more IgM antibody (P = 0.038). No other significant differences were found between the groups before or after immunization with respect to antipolysaccharide Hib antibodies. Since naturally occurring IgG antibodies are thought to be acquired partly as a consequence of antigenic stimulation on mucosal surfaces, we hypothesize that the low level of specific IgG found before immunization, as well as the low total IgG in the children with RLRI, may reflect an impaired ability to prime through mucosal surfaces. This is supported by our finding of an increased IgM response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Adherence of chewing gum to dental restorative materials.

PURPOSE: To describe a method whereby chewing gum tackiness can be measured. MATERIALS AND METHODS: The chewing gum used for the experiment was V6 (Freshmint). Paladur denture base material, Silux Plus, P-50 and Heliomolar resin composites and Luxalloy amalgam were used. Squared specimens (15 x 15 x 2 mm) composed of the polymerized materials tested or set amalgam were made with a mold. As gold specimen, a gold-plated brass specimen was used, having the same dimension as specified above. A tooth enamel specimen (5 x 5 mm) was made out of flat ground human enamel from an incisor. All specimens were stored for more than 7 days in water before use, and wet ground on paper No 320 immediately before testing. The adhesion was measured by a balance equipped with a recorder and a bottom attachment, to which a chain was mounted. The end of the chain was attached to a quadratic brass plate, to which one of the above described specimen was glued by cyanoacrylate. Another brass plate, with an attached specimen of the same material, was mounted in a small vise in such way that the two specimens were parallel with and facing each other. A motor drive enabled parallel removal of the two plates from each other. The gum was chewed approximately 1 second between bites and for various periods of time. It was then pressed between the two parallel squares (mentioned above) of restorative materials or enamel, reaching a final distance of 1 mm between the plates and occupying the entire space between the plates. The study was carried out at 36 degrees C, and the two plates were wetted with fresh saliva or water immediately before placement of the chewing gum. Excess liquid was removed after the wetting, leaving a thin film. The maximal force during parallel removal of the two plates from each other was recorded. The measurements were performed eight times in each group, and the mean adhesion per surface area and SD was expressed as mN/mm(2). The measurements were repeated for some of the groups. The significance of differences between each group was tested by Newman-Keul's Multiple Range Test at a 5% level of significance. RESULTS: Adherence of chewing gum to dental restorative materials and enamel was found to decrease as follows: denture base material > resin composites = silver amalgam > gold > human enamel. The adhesion was dependent on gum base and not on the sweetening additives and reached a maximum after about 2 minutes' chewing.

Adhesiveness↗