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Biomedical subjects

C Christiansen

Publications and source records attributed to C Christiansen.

At least 199 records · Page 11Linked to original sources

The diagnostic validity of urinary free pyridinolines to identify women at risk of osteoporosis.

The urinary excretion of pyridinolines either in the free form or linked to different peptide fragments of type I collagen are intensively studied as new biochemical markers of bone resorption. In the present study we compared the urinary excretion of free pyridinoline (F-Pyr) determined by enzyme-linked immunosorbent assay (ELISA) (Collagen Crosslinks Kit, Metra Biosystems) to pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) determined by high performance liquid chromatography (HPLC) in early postmenopausal women treated with either hormone replacement therapy or placebo and in healthy age-matched premenopausal women. Other markers of bone metabolism were included for comparison. Compared with the premenopausal women, the postmenopausal women had significantly increased values of the biochemical parameters. F-Pyr, Pyr, D-Pyr, and T-Pyr (= Pyr + D-Pyr) decreased during hormone therapy. D-Pyr correlated with the rate of bone loss, whereas this was not the case for F-Pyr. The correlations between the markers yielded r values of 0.71 (F-Pyr vs Pyr), 0.67 (F-Pyr vs D-Pyr), and 0.71 (F-Pyr vs T-Pyr). In conclusion, the present study shows that the newly introduced ELISA for determination of the free pyridinolines is less sensitive than pyridinium crosslinks measured by high performance liquid chromatography (HPLC) in hydrolyzed urine for the changes in calcium metabolism that occur at menopause and during hormone replacement therapy. Whether this limitation will be balanced out by avoiding the inconvenience of the complicated, expensive, and time-consuming HPLC procedure is still being debated.

Adult↗

Estimation of the effect of salmon calcitonin in established osteoporosis by biochemical bone markers.

We reviewed data on 42 postmenopausal women with established osteoporosis (forearm fracture or a low bone mass) who had been randomly treated for 1 year with either rectal salmon calcitonin (sCT), 100 IU daily (n = 25) or nasal sCT, 200 IU daily (n = 17) applying an estimation algorithm for bone loss rates. Both groups received a daily calcium supplement of 500 mg. A group of 18 age-matched women who received no treatment served as controls. The bone mineral content of the distal forearm (BMCarm) was measured every 3 months by single photon absorptiometry. The individual rates of change during the 1-year period were calculated by linear regression analysis (alpha BMCarm). Bone loss rates were estimated initially and after 1 year of therapy by measurements of serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxyproline and calcium (both corrected for creatinine excretion) according to the estimation algorithm. Both administration forms revealed significant control group-corrected decreases in serum and urine markers of bone turnover of 15-40% (P < 0.05-0.01) and positive outcomes of 2% in alpha BMCarm (P < 0.01). The estimated effect on bone mass was expressed as the difference between the bone loss estimated after 1 year and initially (delta ESTBIO). A significant correlation was seen between alpha BMCarm and delta ESTBIO (r = 0.5, P < 0.0001). We conclude that the effect of sCT on bone can be followed up by biochemical markers for bone turnover, i.e., by an annual blood and fasting urine sample, applying an estimation algorithm for the rate of bone loss.

Absorptiometry, Photon↗

The carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen in serum as a marker of bone resorption: the effect of nandrolone decanoate and hormone replacement therapy.

Carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) in serum has recently been proposed as a new biochemical marker of bone resorption. In the present study we compared serum ICTP with radiopharmaceutical and histomorphometric measurements of bone turnover in postmenopausal women with mild osteoporosis, and assessed the effect of hormone replacement therapy (HRT) (2 mg 17 beta-estradiol plus 1 mg norethisterone daily) and anabolic steroid therapy (50 mg nandrolone decanoate (ND) i.m. every 3 weeks) on serum ICTP in two double-blind placebo-controlled studies with 55 to 75-year-old women. Serum ICTP measured by radioimmunoassay (RIA) correlated significantly with the 24-hour whole body retention of 99m-technetium diphosphonate (Rho = 0.47, P < 0.001, n = 66), but not with histomorphometric measurements of bone turnover in iliac crest biopsies. One year of HRT (n = 16) versus placebo (n = 15) did not produce significant changes in serum ICTP. Compared with placebo (n = 17), 1 year of ND (n = 19) produced an increase in serum ICTP of 90 +/- 16% (P < 0.0001); 6 months after discontinuation of the treatment, serum ICTP had returned to pretreatment values. We conclude that serum ICTP does reflect bone metabolism in postmenopausal osteoporosis, but it is not a sensitive marker of the changes in bone resorption induced by hormone replacement therapy, and it does not correspond with other measures of bone resorption during anabolic steroid therapy.

Aged↗

Effect of the menopause and hormone replacement therapy on the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen.

We investigated the effect of the menopause and postmenopausal hormone replacement therapy (HRT) on the serum concentration of carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), a potential new biochemical marker of bone resorption. A group of 44 healthy postmenopausal women, aged 45-54 years, had about 19% higher serum ICTP than did a group of 42 healthy premenopausal women aged 35-50 years (3.6 +/- 0.8 micrograms/l v 3.0 +/- 0.7 micrograms/l (mean +/- SD); p < 0.01), although there was a large overlap in the values. The 44 postmenopausal women also participated in a longitudinal clinical study, in which 20 received HRT and 24 received a placebo. Compared with the placebo group, those who received HRT had a significant (p < 0.05) decrease in ICTP of about 12% at the end of 1 year of treatment, but again there was considerable overlap in the values. The menopause- and HRT-induced changes in ICTP were less than those seen in serum osteocalcin, serum total alkaline phosphatase, and fasting urinary excretion of hydroxyproline, calcium, pyridinoline and deoxypyridinoline. We conclude that the menopause increases and HRT decreases ICTP, although these changes are less pronounced than those seen in other biochemical markers of bone turnover.

Animals↗

Postmenopausal bone loss and the risk of osteoporosis.

The two most important risk factors for long-term skeletal health are the peak bone mass and the subsequent rate of bone loss. The rate of bone loss after skeletal maturity is determined by both genetic factors and environmental factors. Furthermore, all factors that impair estrogen production will increase bone loss. The present risk of developing osteoporosis and fractures may be assessed by bone mass measurements in the total skeleton, or in local parts of the skeleton such as the spine, hip and forearm, by single-photon/X-ray absorptiometry (SPA or SXA), dual-photon/energy X-ray absorptiometry (DPA or DXA), or quantitative computed tomography (QCT). Furthermore, the rate of bone loss in postmenopausal women may be assessed by means of a number of biochemical markers. The fútúre risk of developing osteoporosis may thus be determined by combining the values for bone mineral content and bone loss.

Absorptiometry, Photon↗

Non-responders to hormone replacement therapy for the prevention of postmenopausal bone loss: do they exist?

Hormone replacement therapy (HRT) prevents postmenopausal bone loss, but the prevalence of non-responders in healthy early postmenopausal women is not known. In order to study this, we reviewed data from three published studies, each carried out in a randomized, placebo-controlled, longitudinal design over 2 year, that used seven hormone replacement therapies. Bone mineral content (BMC) was measured in the distal forearm by single photon absorptiometry. A mathematical model for elimination of measurement errors was applied to published BMC data. After this correction, we found that only 1.2% of early healthy postmenopausal women who are receiving HRT in conventional doses will lose more than 1% of forearm BMC per year. In conclusion, most, if not all, healthy early postmenopausal women who might need HRT against loss of bone will respond positively in forearm BMC to such therapy.

Bone Density↗

Bleeding pattern and climacteric symptoms during different sequential combined HRT regimens in current use.

Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms. Treatment was with either 2 mg 17 beta-oestradiol with 1 mg norethisterone acetate [E2 + NETA]; 2 mg oestradiol valerate with 75 micrograms levonorgestrel [E2V + LNG]; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [E2V + MPA]; or 1.5 mg 17 beta-oestradiol with 150 micrograms desogestrel [E2 + DG]. A placebo-controlled study lasting 12-24 months was completed by 143 healthy early postmenopausal women. Bleeding lengths were not substantially different; in all regimens the majority of women were bleeding for 3-6 days. Bleeding onset showed differences when related to the 11th day of progestogen addition; in the regimen with E2V + LNG, 21% of the women women were bleeding before the 11th day of progestogen addition 26% on, and 53% after that day. In the regimen with E2V + MPA, 56% of the women were bleeding before the 11th day, 28% on, and 17% after that day, whereas in the regimen with E2 + DG, 15% of the women were bleeding before the 11th day, 5% on, and 80% after that day. All regimens reduced climacteric symptoms to the same extent. Breast tenderness occurred in all the regimens, except in the E2 + DG. Conclusively, the differences between the responses to treatment were not conspicuous. However, our data indicate that one regimen (E2 + DG) resulted in optimal bleeding control, optimal effect on climacteric symptoms, and no production of breast tenderness.

Breast↗

Precision and accuracy of analysis of air-filled albumin microspheres using Coulter Multisizer Mark II.

The suitability of the electrical sensing zone technique for routine analysis of air-filled albumin microspheres has been thoroughly investigated using three Coulter Multisizer Mark II instruments. The precision of the method, expressed as repeatability relative standard deviation (RSD), was found to be 1-2% for number distribution parameters and 3-4% for volume distribution parameters. Significant instrument-to-instrument variation as high as 11% was, however, also observed. Accuracy was evaluated from analyses of commercially available latex standards and from comparison of results from Coulter analysis with results from the following alternative techniques: light diffraction, optical microscopy and gravimetry. Accuracy, expressed as the difference from either certified values or values obtained with the alternative techniques, was found to be 100-106%.

Albumins↗

Effect of alcohol on glucose, insulin, free fatty acid and triacylglycerol responses to a light meal in non-insulin-dependent diabetic subjects.

Alcohol accounts for 4-6% of the average energy intake in most Western countries. Alcohol-induced hypoglycaemia is a well-known and feared complication in insulin-dependent diabetic subjects, but little attention has been paid to the impact of alcohol on carbohydrate metabolism in non-insulin-dependent diabetes. The aim of the present study was to investigate in non-insulin-dependent diabetic subjects the acute metabolic effects of a moderate amount of alcohol taken with a light meal, conditions chosen to mimic an everyday situation. The patients received 500 ml non-alcoholic beer with an alcohol content (ml/l) of 0 (treatment A) and 54 (treatment B) together with a light meal, implying identity of the contents of ingredients except for alcohol. We found similar serum glucose, insulin, free fatty acid and triacylglycerol responses irrespective of addition of a modern amount of alcohol. In conclusion, a moderate amount of alcohol can be taken with a meal without eliciting hypoglycaemia in non-insulin-dependent diabetic subjects.

Blood Glucose↗

Total and regional body-composition changes in early postmenopausal women: age-related or menopause-related?

Total and regional body composition were measured in 373 early postmenopausal women aged 49-60 y by dual-energy x-ray absorptiometry to evaluate whether the changes in body composition in the early postmenopausal years are related to menopause itself or merely to age. Both fat mass and fat distribution correlated with age (r = 0.12-0.21, P < 0.05-P < 0.001), but not with years since menopause (YSM). Lean tissue mass, on the other hand, decreased with YSM (r = -0.17, P < 0.001) but was not related significantly to age. Total body bone mineral density decreased with both YSM (r = -0.30, P < 0.001) and age (r = -0.21, P < 0.001). Our study suggests that postmenopausal changes in body fat and fat distribution are more dependent on age than on menopause, but we cannot exclude a separate effect of the menopause. Changes in fat-free mass, including a postmenopausal decline in both soft lean tissue mass and bone mass, are, however, mainly menopause-related

Adipose Tissue↗

Urinary excretion of pyridinium cross-links in healthy women; the long-term effects of menopause and oestrogen/progesterone therapy.

OBJECTIVES: We investigated the effect of the menopause when followed longitudinally for a decade to evaluate whether women with an increased bone loss continue to have elevated urinary excretion of pyridinium cross-links later in menopause. Furthermore, we investigated the effect of oestrogen/progesterone therapy on the urinary excretion of pyridinium cross-links. PARTICIPANTS: In the cross-sectional study: 18 healthy premenopausal, 142 healthy post-menopausal women and 41 osteopenic post-menopausal women. In the longitudinal study: 45 healthy post-menopausal women followed up for 7-10 years after the menopause; these women were further divided into two equal groups, according to their loss of forearm bone mineral content over 2 years. In the oestradiol/progesterone double-blind, placebo-controlled 2-year trial: early post-menopausal women were given either hormone replacement therapy (n = 38) or placebo (n = 16). MEASUREMENTS: The urinary excretion of pyridinoline/creatinine (Pyr/Cr) and urinary deoxypyridinoline/creatinine (D-Pyr/Cr), two new markers of bone resorption. RESULTS: Pyr/Cr and D-Pyr/Cr increased significantly after the menopause (Pyr/Cr, 77%; D-Pyr/Cr, 98%, P < 0.001). Hormone replacement therapy reversed this increase towards premenopausal levels. Both pyridinium cross-links remained fairly constant during the first decade of the menopause, when measured in the longitudinal study. When the women were divided according to loss in forearm BMC, those with a loss greater than 3.5%/2 years had significantly higher levels of pyridinium cross-links (P < 0.05-0.01). Furthermore, both Pyr/Cr and D-Pyr/Cr were significantly higher in elderly osteopenic women (aged 68-72 years) than in age-matched non-osteopenic women (P < 0.01-0.001). CONCLUSIONS: Both Pyr/Cr and D-Pyr/Cr, two new markers of bone resorption, increased significantly at the time of the menopause, thereafter remaining fairly constant during the first post-menopausal decade. Women with increased bone loss continue to have elevated urinary excretion of pyridinium cross-links during the first decade of the menopause. This post-menopausal change is reversed by hormone replacement therapy to the premenopausal level.

Adult↗

Platelet activation in major surgical stress: influence of combined epidural and general anaesthesia.

Platelets are activated in surgery releasing vasoactive substances such as serotonin and thromboxane. Platelets become temporarily hypoaggregable during surgery followed by a postoperative hyperaggregability. Local anaesthetics are known to inhibit platelet function but earlier reports are conflicting. In order to study the impact of the combined use of general and regional anaesthesia on platelet function during major surgery 16 otherwise healthy patients were randomised to either general anaesthesia (GA) (n = 8) or GA combined with epidural anaesthesia (GA+EPI) (n = 8) for elective upper abdominal surgery. Cyclic 3',5' adenosine monophosphate, plasma glucose, plasma cortisol and the rate pressure product (RPP) were markers of the stress response. ADP-induced platelet aggregation and the release products beta-thromboglobulin, serotonin and thromboxane 2 were measured in plasma before and during as well as for 3 days after surgery. A marked stress response was noted in both groups and epidural anaesthesia (EPI) only reduced the rate pressure product (RPP). Platelet aggregation was reduced during surgery, a little more so in the GA+EPI group. Postoperatively both groups showed significant hyperaggregability. The release products were not significantly influenced by regional anaesthesia. In conclusion epidural as combined with general anaesthesia affects platelet responses to major abdominal surgery only to a minor extent, although it may attenuate the haemodynamic response.

Adenosine Diphosphate↗

Lack of an immune response to Albunex, a new ultrasound contrast agent based on air-filled albumin microspheres.

Albunex is a new ultrasound contrast agent consisting of air-filled microspheres of heat-aggregated human albumin suspended in a 5% (w/v) solution of human albumin for infusion. The structural alterations induced in the albumin molecules during heat aggregation may cause the formation of new epitopes that may provoke an immunological response in recipients. To assess the possible immunogenicity of the contrast agent, 34 healthy volunteers were randomized to receive four injections of either Albunex or 5% human serum albumin (0.01 ml/kg) at 4-week intervals. Analysis of blood samples taken 3 weeks after each injection did not reveal any formation of IgE or IgG antibodies directed against the Albunex microsphere protein or albumin in any of the recipients. The evaluation of novel enzyme immunosorbent assays developed to detect the presence of these specific IgE and IgG antibodies is described. It was also investigated whether the heat-aggregated microsphere albumin was structurally altered in such a way that it could be recognized by cat albumin specific IgE, present in the sera of individuals allergic to cat albumin. 187 serum samples shown to contain elevated levels of cat albumin specific IgE were used in the study. No cross-reactive binding of the heat-aggregated human albumin to anticat albumin IgE could be detected. There is no evidence from the present studies that the heat-aggregated albumin of the Albunex microspheres will provoke an immunological reaction upon repeated injections or cause an adverse reaction when administered to allergic individuals having cat albumin as one of their allergens.

Adolescent↗

Aortic permeability to LDL during estrogen therapy. A study in normocholesterolemic rabbits.

17 beta-Estradiol has recently been found to inhibit atherogenesis by mechanisms that are in part independent of the estrogenic action on plasma lipoprotein levels. Since aortic permeability to low-density lipoprotein (LDL) in normocholesterolemic rabbits is a strong predictor for subsequent atherosclerosis during hypercholesterolemia, the present study investigated a possible influence of 17 beta-estradiol on aortic permeability to LDL. Twenty rabbits were initially ovariectomized and then fed a nonatherogenic diet for 10 weeks. One group of rabbits (n = 10) received 4 mg of 17 beta-estradiol orally per day; the other group (n = 10) received placebo. Serum concentrations of very-low-density lipoprotein cholesterol and triglycerides increased significantly more in the placebo group than in the estrogen group (P < .03), whereas there were no statistically significant differences between groups in LDL, high-density lipoprotein, or total cholesterol. At the end of the experiment, 125I-LDL was injected intravenously into each rabbit. Aortas were removed 3 hours later, and the aortic permeability to LDL was calculated from the radioactivity in the plasma and the aortic intima/inner media. The aortic permeability to LDL was virtually identical in the 17 beta-estradiol (31.6 +/- 7.2 nL.cm-2.h-1) and the placebo (36.9 +/- 7.9 nL.cm-2.h-1) groups (mean +/- SEM). The aortic cholesterol content was also similar in the two groups. These data suggest that the plasma lipid-independent antiatherogenic effect of estradiol is not mediated through an effect on aortic permeability to LDL but rather is related to the metabolism of the lipoproteins after they have entered the arterial wall.

Animals↗

Bone metabolism in premenopausal women with nontoxic goiter and reduced serum thyrotropin levels.

OBJECTIVE: To study whether premenopausal women with nontoxic goiter, but reduced serum TSH as a sign of spontaneous subclinical hyperthyroidism have decreased bone mass or other indications of increased bone turnover. DESIGN AND SUBJECTS: In a cross-sectional study, bone mass measurements were performed in the distal forearm and the lumbar spine in 11 premenopausal women with nontoxic goiter and a stable reduction in serum TSH (median (range) 8 months (6-108 months)), and in 22 matched controls. In a longitudinal study, measurements were repeated every 3 months for a maximum period of 2 years in 9 of the patients (6 completed 9 months, 4 completed 2 years follow-up). RESULTS: Serum TSH in the patients were (median (range)) 0.025 mU/l (< 0.005-0.256 mU/l). Patients had a bone mineral content of the distal forearm and a bone mineral density of the lumbar spine similar to those of controls, medians of controls: 98.4% and 93.8%, respectively. The risk of a type 2 error for over-looking a 10% difference was 2% for the distal forearm and 20% for the spine. TSH correlated negatively with marginal significance (p < 0.10) with markers of bone turnover: plasma osteocalcin, serum alkaline phosphatase, and fasting urinary hydroxyproline corrected for creatinine, although all patients had absolute values of these parameters within normal range. During follow-up bone mass measurements did not tend to decrease, but serum alkaline phosphatase and fasting urinary hydroxyproline showed increasing trends (p < 0.05). CONCLUSIONS: Premenopausal women with nontoxic goiter and reduced serum TSH do not seem to have reduced bone mass but seem to demonstrate signs of increased bone turnover.

Adult↗

The glycaemic index of spaghetti and gastric emptying in non-insulin-dependent diabetic patients.

OBJECTIVE: In the dietary treatment of non-insulin-dependent diabetes mellitus (NIDDM) great interest has been focused on foods with low glycaemic indices. Spaghetti has a low glycaemic index, but in NIDDM the underlying mechanism has not been elucidated. We investigated whether the low glycaemic index in spaghetti was the result of a retarded gastric emptying. DESIGN: Randomized study. SETTING: Department of Endocrinology & Metabolism, Aarhus County Hospital. SUBJECTS: Eight NIDDM in-patients participated without drop-outs. INTERVENTIONS: Paracetamol was used as a marker of the gastric emptying. On three different occasions the patients ingested 40 g of carbohydrate as: (1) spaghetti without paracetamol, (2) spaghetti containing 1.5 g paracetamol, and (3) mashed potatoes with 1.5 g paracetamol added. During the 4 h observation periods blood samples were drawn frequently. The spaghettis were industrially manufactured. RESULTS: The spaghetti meals induced similar glucose and insulin responses. The potato meal induced significantly higher glucose and paracetamol areas [607 +/- 108 vs 284 +/- 54 mmol/l*240 min (P = 0.02), and 18,668 +/- 999 vs 4979 +/- 369 mumol/l*240 min (P < 0.02)] as well as lower emptying index (time(peak)/peak concentration ratio of paracetamol) [2.1 +/- 0.3 vs 0.4 +/- 0.1 (P = 0.001)], as compared with the spaghetti meal. CONCLUSIONS: This study shows that the ingestion of spaghetti was associated with a slower gastrointestinal accessibility of the carbohydrates, which accounts for the low glycaemic index of spaghetti in NIDDM subjects.

Acetaminophen↗

Six months' follow-up on exercise added to a short-term diet in overweight postmenopausal women--effects on body composition, resting metabolic rate, cardiovascular risk factors and bone.

The aim of this work was to study the long-term effects of the addition of exercise to a short-term diet in overweight postmenopausal women. A follow up study was made of 118 overweight, postmenopausal women, who 6 months earlier had completed 12 weeks of randomized intervention (three groups: 4.2 MJ/d diet, 4.2 MJ/d diet with exercise, and controls). The following were measured: body composition and fat distribution (measured by dual-energy X-ray absorptiometry), resting metabolic rate, serum lipids and lipoproteins, blood pressure, and bone mineral densities. It was found that weight was still significantly reduced (by about 8 kg). HDL-C was significantly increased (10%), and triglycerides decreased (20%), whereas the initial reductions in total cholesterol and LDL-C had disappeared at the follow-up. The women from the former diet-plus-exercise group, who were current exercisers at the follow-up, had a significantly greater reduction in weight (10.9 vs 6.6 kg), fat tissue mass (10.0 vs 5.4 kg) and abdominal-to-total-body fat tissue mass (9.6 vs 4.7), and a significantly greater increase in the resting metabolic rate (11.1 vs 1.1 kJ/kg/d), as compared with the non-exercisers from this group. There were no major detrimental changes in total body, spinal, or forearm bone mineral density or in markers of bone turnover. The short-term dietary treatment in this study may have beneficial long-term effects on weight, fat tissue mass and cardiovascular risk factors with no additional benefits from added exercise, unless the exercise is continued.

Body Composition↗