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Biomedical subjects

C Christiansen

Publications and source records attributed to C Christiansen.

At least 19 recordsLinked to original sources

Effect of salcatonin given intranasally on bone mass and fracture rates in established osteoporosis: a dose-response study.

OBJECTIVE: To study the dose related response of salmon calcitonin (salcatonin) given intranasally on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Outpatient clinic for research into osteoporosis. SUBJECTS: 208 healthy women aged 68-72 years who had a bone mineral content of the distal forearm on average 30% below the mean value for healthy premenopausal women. INTERVENTIONS: The 208 women were allocated randomly in blocks of four to two years of treatment with either salcatonin 50 IU, 100 IU, or 200 IU given intranasally or placebo. All groups received a calcium supplement of 500 mg. 32 of the women left the study before its end and 164 women complied with the study criteria throughout. MAIN OUTCOME MEASURES: Bone mineral content of the distal forearm and lumbar spine and rates of vertebral and peripheral fractures after two years of treatment. RESULTS: The average changes in bone mineral content of the spine showed positive outcomes of 1% (95% confidence interval -0.1% to 1.5%) in the group treated with calcium (placebo) and 3% (1.8% to 4.2%) in the group treated with salcatonin 200 IU. There was a significant dose related response to salcatonin, manifested by an increase of 1.0%/100 IU (0.2% to 1.7%, p = 0.008). The rate of patients with new fractures was reduced significantly in the women treated with salcatonin to about one third of that in the non-salcatonin treated women (relative risk 0.23 (0.07 to 0.77)). CONCLUSION: The results suggest that, compared with calcium alone, salcatonin given intranasally reduces the rates of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.

Administration, Intranasal

Nucleotide sequence, organization and characterization of the atp genes and the encoded subunits of Mycoplasma gallisepticum ATPase.

The nucleotide sequence of a 7.8 kbp DNA fragment from the genome of Mycoplasma gallisepticum has been determined. The fragment contains a cluster of nine tightly linked genes coding for the subunits of the M. gallisepticum ATPase. The gene order is I (I-subunit), B (a-subunit), E (c-subunit), F (b-subunit), H (delta-subunit), A (alpha-subunit), G (gamma-subunit), D (beta-subunit) and C (epsilon-subunit). Two open reading frames were identified in the flanking regions; one (ORFU), preceding the I gene, encodes at least 110 amino acids and the other (ORFS), following the C gene, encodes at least 90 amino acids. The deduced amino acid sequences of the various subunits are presented and discussed with regard to the structure, function and differing sensitivity of the M. gallisepticum enzyme to dicyclohexylcarbodiimide and aurovertin. The alpha- and beta-subunits of the F1 portion are well conserved (51% and 65% identity with those of Escherichia coli), whereas the gamma-, delta- and epsilon-subunits, as well as the F0-subunits, show a low percentage identity. Nonetheless, the secondary structure of the F0-subunits show a high degree of similarity to the corresponding subunits of E. coli. Two very strong potential amphipathic alpha-helices are predicted in the delta-subunit and the N-terminus of the b-subunit contains two hydrophobic helical stretches. The possible roles of these structural properties in the close association of the F1 and F0 multisubunit complexes among mycoplasmas are discussed.

Adenosine Triphosphatases

Is heritability a risk factor for postmenopausal osteoporosis?

We investigated heritability as a risk factor for the development of osteoporosis in two randomly selected populations of postmenopausal women and their premenopausal daughters. We determined the familial resemblance in bone mass at three sites; the distal forearm, lumbar spine, and proximal femur, premenopausally and with increasing maternal postmenopausal age. We also examined the bone mass of daughters in relation to mothers with and without osteoporotic fractures. Peak bone mass among premenopausal siblings was significantly correlated at all sites (r = 0.30-0.42, p less than 0.001). The same levels of resemblance were found between early postmenopausal mothers and premenopausal daughters. There was no significant difference in bone mass at any skeletal site between daughters of women with either peripheral or spinal fractures and daughters of women without fractures. We also examined familial resemblance with four biochemical markers of bone turnover (fasting urinary calcium and hydroxyproline, both corrected for creatinine, serum alkaline phosphatase, and plasma bone Gla protein). A generally significant resemblance were seen in premenopausal siblings (r = 0.25-0.39, hydroxyproline NS), but not between premenopausal daughters and postmenopausal mothers. We conclude that peak bone mass is hereditary in the distal forearm, lumbar spine, and proximal femur, but the mother-daughter resemblance explains only about 16% of the variability in daughters' bone mass. Furthermore, daughters of women with a moderate state of osteoporotic fractures are not substantially at an increased risk of having a low peak bone mass compared to the daughters of women without fractures.

Absorptiometry, Photon

Diurnal variation in serum markers of type I collagen synthesis and degradation in healthy premenopausal women.

There are several indications that the functions of human osteoblasts and osteoclasts have circadian rhythms with peak activities occurring at night. It is not known, however, whether the principal function of these cells, namely synthesis and degradation of the organic matrix of bone, of which about 90% is type I collagen, also has a circadian rhythm. This was therefore investigated for both the formation of type I collagen and the degradation of type I collagen in bone using two newly developed serum markers: the serum concentration of the carboxy-terminal propeptide of type I procollagen (PICP) as a marker of formation and the serum concentration of the carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) as a marker of degradation. PICP and ICTP were measured by RIA in samples taken every 3 h over a 24 h period in 12 healthy premenopausal women (age 32 +/- 5 years, mean +/- SD). Both PICP (p = 0.003) and ICTP (p = 0.00003) showed a significant circadian rhythm, with about 20% higher values at night than in the afternoon. We conclude that serum markers of both the formation of new type I collagen and the degradation of old type I collagen in bone exhibit a clear circadian rhythm, with increased activity of both osteoblasts and osteoclasts at night. The etiology of this circadian rhythm is still unknown.

Adult

Rectal salmon calcitonin for the treatment of postmenopausal osteoporosis.

In a 2-year study, we examined bone mass and calcium metabolism in 36 elderly women with moderate osteoporosis. The study period comprised 1 year of observation, during which the women received no treatment affecting calcium metabolism, and 1 year of treatment, during which all participants received daily salmon calcitonin (sCT) 100 IU rectally and calcium 500 mg. During the observational period a significant bone loss of 1.5% was seen in the forearm (P less than 0.01), whereas the spinal bone mass was virtually unchanged. After institution of treatment, the bone loss was arrested in the forearm and a significant increase of about 2% was seen in the spine (P less than 0.01). The net effect of treatment revealed a positive outcome in both bone compartments (1.9% and 2.9%, P less than 0.05-0.01). Correspondingly, the parameters of bone turnover (serum alkaline phosphatase, plasma bone Gla protein, and fasting urinary hydroxy-proline/creatinine) did not change during the observational period, but significantly declined, 10-30%, during sCT treatment (P less than 0.01-0.001). Tolerance was generally good, although in one woman, anoscopy revealed irritative changes in the rectal mucosa. We conclude that, given rectally, sCT is well absorbed and well tolerated and that it has a beneficial effect on calcium metabolism in moderately osteoporotic women.

Administration, Rectal

No secular increase in the prevalence of vertebral fractures due to postmenopausal osteoporosis.

We examined whether the prevalence of vertebral fractures in otherwise healthy, 70-year-old Danish women had increased during an interval of 10 years. The population-based epidemiological study included two age-matched groups of postmenopausal women. Group 1 consisted of 70-year-old women (n = 386) living in a defined area of suburban Copenhagen recruited in 1979 for an epidemiological study. Of the 285 women who were entered, 173 were judged healthy, without secondary causes of osteoporosis. Group 2 was recruited by sending questionnaires to all women aged 68-72 years living in the same area in 1989. Of the 512 women who attended a medical screening, 387 were found to be without secondary causes of osteoporosis and had a spinal radiograph. Radiographs of the thoracolumbar spine were assessed for vertebral fracture by five radiological methods. There was no significant difference between the two groups in the prevalence of vertebral fractures and the 95% confidence intervals overlapped completely in all methods. The prevalence rates varied by method from about 35% to more than 80% but the distribution of fracture types was similar in the two groups. We conclude that the prevalence of vertebral fractures due to postmenopausal osteoporosis has not increased since 1979 in otherwise healthy women residing in suburban Copenhagen, and that comparison of prevalences between studies requires that they use the same method of radiological assessment.

Aged

Secretory endometrial protein PP14 in serum from post-menopausal women receiving continuous combined oestradiol-cyproterone acetate: correlation with serum hormone concentrations and bleeding patterns.

The secretory endometrial protein PP14 was measured in serum from 49 healthy, early post-menopausal women receiving continuous combined oestradiol valerate/cyproterone acetate (2 mg E2V + 1 mg CPA daily) or placebo over a period of 2 years. In the hormone group, serum PP14 increased from 2.1 micrograms/l to a maximum of 8.1 micrograms/l after 1 month of treatment, then fell after 3 months to 3.8 micrograms/l and remained at that level for the rest of the 2-year period. After the first month, the occurrence of uterine bleeding was associated with significantly increased serum PP14 levels. Bleeding was not correlated with the serum concentration of 17 beta-oestradiol (E2) or CPA, or the CPA/E2 ratio. Serum PP14 was significantly dependent on the serum concentration of E2, but not on that of CPA. The present data confirm that serum PP14 levels reflect the secretory phase of the endometrium and that bleeding during continuous combined hormone replacement therapy is probably caused by a sub-optimal hormonal balance.

Androgen Antagonists

Serum placental protein 14 (PP14) reflects endometrial status during hormone replacement therapy.

Healthy post-menopausal women were randomly assigned to treatment groups receiving 28 day treatment cycles of oestradiol valerate (2 mg, days 1-28) sequentially combined with levonorgestrel (75 micrograms, days 17-28) (n = 19); oestradiol valerate (2 mg, days 1-28) continuously combined with cyproterone acetate (1 mg, days 1-28) (n = 18), or placebo (n = 22). Treatment continued for 2 years. After therapy, the women receiving the sequential combination had an early secretory phase (74%) or atrophic endometrium (26%). All women receiving the continuous combination or placebo had inactive or atrophic endometrium, or the tissue was inadequate for assessment. Biochemical parameters of endometrial secretion [oestradiol dehydrogenase (EDH), isocitrate dehydrogenase (ICDH)] measured in endometrial tissue and placental protein (PP14) measured in serum were all low in the groups receiving the continuous combination and placebo. During sequential treatment, all biochemical parameters showed significantly higher mean values. Serum PP14 accurately reflected this pattern. Furthermore, in the sequentially treated group, serum PP14 correlated highly significantly with EDH (r = 0.70; P less than 0.001) and ICDH (r = 0.57; P = 0.01). These correlations were of the same magnitude as the correlations between the endometrial markers, which indicates that serum PP14 reflects the endometrial status. Furthermore, serum PP14 measurements at 3 months and at 2 years of treatment were highly correlated, reflecting the long-term validity of the measurement. The present data suggest that PP14 measured in serum may be used to assess endometrial status. Further studies are required to determine whether serum PP14 will discriminate pathological endometrial conditions.

Cyproterone Acetate

Effect of menopause and hormone replacement therapy on urinary excretion of pyridinium cross-links: a longitudinal and cross-sectional study.

OBJECTIVE: To study longitudinally the effect of the menopause and hormone replacement therapy on the new markers of bone resorption: urinary excretion of pyridinoline and deoxypyridinoline. DESIGN AND PATIENTS: Urinary pyridinoline and deoxypyridinoline were measured every 3 months for 2-3 years in 15 healthy women aged 45-54 years. Nine remained premenopausal and six became post-menopausal during the study. Urinary pyridinoline and deoxypyridinoline were also measured before and after 3 months of either placebo or hormone replacement therapy in 65 post-menopausal women, aged 45-54 years, who were participating in a double-blind study. MEASUREMENTS: Urinary pyridinoline and deoxypyridinoline were measured in fasting urine samples by spectrofluorometry after high performance liquid chromatography and corrected for creatinine excretion. RESULTS: Urinary pyridinoline and deoxypyridinoline remained almost constant during the premenopausal period. Both started to increase 6 months after the last menstrual bleeding and the mean post-menopausal values were 30-50% higher than the premenopausal values in the same subjects (values in nmol/mmol creatinine given as mean +/- SEM: urinary pyridinoline (premenopausal) = 29 +/- 2 vs urinary pyridinoline (post-menopausal) = 38 +/- 6, P < 0.05; urinary deoxypyridinoline (premenopausal) = 8 +/- 1 vs urinary deoxypyridinoline (post-menopausal) = 12 +/- 1, P < 0.05). Three months of post-menopausal hormone replacement therapy decreased (P < 0.001) both to premenopausal levels. CONCLUSION: Urinary pyridinoline and deoxypyridinoline, new markers of bone resorption, remain fairly constant in the years before the menopause and start to increase about 6 months after the last menstrual bleeding. This increase is reversed by hormone replacement therapy.

Amino Acids

Changes in calcanean bone mineral occurring spontaneously and during hormone replacement therapy in early post-menopausal women.

The spontaneous calcanean bone loss occurring in healthy early post-menopausal women and the effect of two hormone replacement therapies (HRT's) were investigated in a longitudinal study. There was no difference between the right and left calcanean BMC or BMD (p > 0.15). The spontaneous bone loss was similar at all the skeletal sites measured, with a mean spontaneous loss in calcanean BMD of 1.6% over one year. Both HRT's significantly (p < 0.01) prevented the bone loss from all skeletal sites irrespective of the weight-bearing or content of trabecular bone, and (for the weight-bearing bones) there was even a gain in calcanean BMC and BMD and spinal BMD (p < 0.01). Bone mineral of the calcaneus and the spine correlated equally to body weight (r approximately 0.4, p < 0.001), whereas bone mineral in the forearm was not correlated to body weight. The correlations between the changes in bone mineral at the sites measured were all significant (r approximately 0.2-0.4).

Bone Density

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density

Treatment-induced cyclic variations in serum lipids, lipoproteins, and apolipoproteins after 2 years of combined hormone replacement therapy: exaggerated cyclic variations in smokers.

OBJECTIVE: To study the long-term effect of cigarette smoking on cyclic variations in serum lipids, lipoproteins, and apolipoproteins following combined hormone replacement therapy. METHODS: One hundred eighteen healthy, early postmenopausal women were followed for 2 years in a randomized, placebo-controlled study. Four treatment groups received estradiol, either sequentially combined with levonorgestrel (75 micrograms), medroxyprogesterone acetate (10 mg), or desogestrel (150 micrograms), or continuously combined with cyproterone acetate (1 mg). Two groups received placebo. Serum lipids, lipoproteins, and apolipoproteins were measured at well-defined times. Information on smoking habits was elicited by questionnaire. RESULTS: We found statistically significant cyclic variations in apolipoprotein A1 in the levonorgestrel group (6.7%; 95% confidence interval [CI] 1.1-12.7%) and the desogestrel group (7.4%; 95% CI 2.9-12.1%). The cyclic variations in high-density lipoprotein (HDL) cholesterol were highly statistically significant in the levonorgestrel group (24.9%; 95% CI 10.2-39.2%). When women from sequential regimens were combined, further analysis showed that smokers had significantly larger cyclic variations in HDL cholesterol (P less than .01) and apolipoprotein A1 (P less than .05) than non-smokers. CONCLUSIONS: Sequentially combined hormone replacement therapy produces cyclic variations in HDL cholesterol and apolipoprotein A1 for at least 2 years. In addition, cigarette smoking is associated with an exaggeration of the cyclic effect of treatment on these indices.

Androgen Antagonists

Gross errors made by routine blood sampling from two sites using a tourniquet applied at different positions.

Tourniquet application in routine blood sampling procedures may induce considerable haemoconcentration and thereby augment the concentration of serum protein and protein-bound substances. To evaluate this effect serum protein, calcium and magnesium were measured in 31 healthy persons before and after 3-min venous stasis induced by a standardized tourniquet. Four sites of tourniquet and two sampling sites on the arm were compared. The concentration of measured serum constituents rose after the stasis period (5--13% rise in serum protein), the changes being similar at all tourniquet positions. However, blood sampled from a cubital arm vein showed significantly larger haemoconcentration than samples obtained simultaneously more distally on the arm. Taking three samples in a series, the serum concentration of protein, calcium and magnesium rose from tube to tube (5--10% change). The study demonstrates that neither use of a standardized tourniquet nor release of the tourniquet before blood sampling eliminates the errors inherent in routine venepuncture. Adjustment to a constant serum protein level minimizes these errors.

Adolescent

Solubilization and molecular weight determination of the (Na+ + K+)-ATPase from rectal glands of Squalus acanthias.

The membrane-bound (Na+ + K+)-activated ATPase (ATP phosphohydrolase, EC 3.6.1.3) system was treated with the nonionic detergent octaethylene-glycoldodecyl ether, yielding a transparent supernatant after centrifugation. The supernatant was highly active with both ATPase and p-nitrophenylphosphatase, with initial specific activities of 2300 mumol Pi released . mg-1 protein. h-1 and 350 mumol p-nitrophenol released.mg-1 protein.h-1, respectively. The supernatant was purified to 95--100%, with respect to the 96 000 dalton and the 56 000 dalton peptides. The solubilized enzyme was gel filtered in Sepharose 4B-Cl and displayed 2 peaks, both with catalytic activity. The low molecular weight particles eluted at Kav = 0.54, corresponding to a molecular weight of approximately 500 000 daltons and the particles had a specific activity of 2100 mumol Pi.mg-1 protein.h-1. Both peaks contained phospholipid with 60 mol phospholipid bound per 300 000 g protein. The low molecular weight particles had a molecular weight of 276 000 as determined by sedimentation equilibrium analysis.

4-Nitrophenylphosphatase