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  • 1
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: carteolol ; beta-blockade ; dose-response relation ; duration of action ; plasma level-effect relation ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration-beta blocking effect and time-effect relationships of carteolol were examined in eight normal adults given 15 mg i.v. and 20 mg orally on separate occasions. Resting and post-exercise blood pressures and heart rates were assessed before and at various times up to 48 h after each dose. Carteolol, a β-blocker with some partial agonist activity, produced an insignificant, transient increase in heart rate 2 to 6 h after both doses, and a fall (p〈0.05) in diastolic blood pressure 4 and 6 h after the intravenous dose and 6 h after the oral dose in the resting supine position, as compared to the corresponding baseline values. All values of the post-exercise heart rate and the double product after each of the doses were significantly (p〈0.001) below the baseline values for the entire period (48 h) of observation. A significant correlation between the log plasma carteolol concentration (log C) and its beta-blocking effect (E: p〈0.001, r=0.508 i.v.; p〈0.001, r=0.626, p.o.) was found. The r-values for individuals were higher (0.852 to 0.977, intravenous; 0.817 to 0.981, oral) than for the group as a whole. The slope (m) of the relationship, E=m·log C+r, showed a certain variance within and between individuals. When the absolute reduction in exercise-induced heart rate was plotted against time and the rate of decline of effect (Rd) and duration of action were estimated from the time-effect relationship, the mean Rd values were 0.655 and 0.462 beats/min per h, and for the duration of action they were 83.8 and 123.9 h after the intravenous and oral doses, respectively. The effect declined at a slower rate (p〈0.02) and the duration of beta-blockade was longer (p〈0.01) after the oral dose.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1433-2965
    Keywords: Key words:Bone architecture – Osteoporosis – Peripheral quantitative computed tomography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: We assessed the volumetric bone mineral density (vBMD) and cross-sectional architecture of cortical bone at the distal radius by peripheral quantitative computed tomography (pQCT). The volumetric bone mineral density [integral bone mineral density (BMDi), trabecular bone mineral density (BMDt) and cortical with subcortical bone mineral density (BMDsc)] and the architectural parameters [cortical bone area (CBA), cortical thickness (C-th), moment of inertia (Im) and polar moment of inertia (Ip)] were measured in 115 healthy premenopausal women, 48 osteoporotic postmenopausal women and 78 age-matched healthy postmenopausal women. Age-matched healthy women had higher values of vBMD and architectural parameters at the distal radius than osteoporotic women. Premenopausal women had higher values of vBMD and architectural parameters at the distal radius than postmenopausal women. The differences in the architectural parameters between age-matched healthy women and osteoporotic women were more pronounced when only the high density area (threshold 0.70 cm–1) was included. However, the differences in architectural parameters between premenopausal women and postmenopausal women were significant using even the lowest threshold value of 0.50 cm–1 in the calculation. Receiver operating characteristic (ROC) curves were constructed and the areas under the curves calculated to evaluate the discriminating power of vBMD and architectural parameters. Comparison of the different ROC curves showed no statistical significance. In conclusion, our results suggest that both the density and mass distribution of the radius were clearly different between the healthy women and osteoporotic women. The differences in architectural parameters were more useful for studying the pathopysiology of osteoporosis than for contributing to the diagnosis. Determination of the cross-sectional mass distribution of bone combined with BMD should offer more information than BMD alone in the study of the pathophysiology of osteoporosis.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1433-2965
    Keywords: Key words:Biochemical markers – Bone resorption – Longitudinal study – Menopause – Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: The aim of this longitudinal study was to investigate the changes in the levels of biochemical markers and ultrasound indices of os calcis across the menopausal transition. One hundred and ten healthy women (age 35–59 years at the 1992 baseline) participated in this 4-year population-based longitudinal study. Serum intact osteocalcin (IOC), urinary pyridinoline (Pyr), urinary deoxypyridinoline (Dpyr) and ultrasound indices were measured at baseline and after 4 years. The percentage changes in biochemical markers (%DIOC, %DPyr and %DDpyr) and the percentage decreases in the ultrasound indices (%DSOS, %DBUA and %DStiffness) were calculated. The values of %DIOC and %DDpyr in the perimenopausal subgroup (−4 to−3 years since menopause) and the values of %DSOS and %DStiffness in the perimenopausal subgroup (−2 to 0 years since menopause) were significantly higher than those in other groups. Pyr was significantly correlated with %DSOS (r=−0.467, p〈0.01) and %DStiffness (r = −0.330, p〈0.05) and Dpyr was significantly correlated with %DSOS (r=−0.390, p〈0.05), %DBUA (r=−0.353, p〈0.05) and %DStiffness (r = −0.454, p〈0.05), while %DIOC was significantly correlated with %DSOS (r=−0.278, p〈0.05), %DBUA (r=−0.369, p〈0.01) and %DStiffness (r = −0.383, p〈0.01) in the peri- and postmenopausal groups. These results indicate that the increase in bone turnover occurs 4 years before menopause. However, the correlations between biochemical markers and ultrasound indices were too low to allow prediction of bone change in the individual patient.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1433-2965
    Keywords: Key words:Alendronate – Alfacalcidol – Bone mineral density – Double-masked comparative study – Osteoporosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: To evaluate the efficacy and safety of alendronate, a double-masked, active (alfacalcidol) controlled comparative study for 48 weeks was carried out in a total of 210 Japanese patients with osteoporosis. The doses of alendronate and alfacalcidol were 5 mg/day and 1 μg/day, respectively. The lumbar bone mineral density (LBMD) values observed at 12, 24, 36 and 48 weeks after the initiation of alendronate treatment were 3.53 ± 0.53%, 5.37 ± 0.62%, 5.87 ± 0.74% and 6.21 ± 0.59% (mean ± SE), respectively, higher than the baseline value. Corresponding values in the alfacalcidol group were 1.50 ± 0.43%, 0.69 ± 0.63%, 1.12 ± 0.60% and 1.36 ± 0.63%, respectively. There was a significant difference between the two groups at each time point (p〈0.05 or p〈0.001). The bone turnover markers were depressed during treatment in the alendronate group: −32.2% for alkaline phosphatase, −53.7% for N-terminal osteocalcin and −45.0% for urinary deoxypyridinoline compared with the corresponding baseline values. On the contrary, no notable changes in these parameters were observed in the alfacalcidol group. Treatment with alendronate caused a transient decrease in serum calcium concentrations associated with an increase in the serum level of intact parathyroid hormone. In contrast, treatment with alfacalcidol resulted in a tendency of these parameters to change in the opposite direction. No difference in fracture incidence between the two groups was observed. The overall safety of alendronate was comparable to that of alfacalcidol. In conclusion, although it was a relatively short-term study of 48 weeks, the results of the present study indicate that alendronate at the daily dose of 5 mg was effective in increasing LBMD and that no serious drug-related adverse events were observed in the alendronate-treated patients. Alendronate is more efficacious than alfacalcidol in increasing bone mineral density, although the mechanisms of the actions of the two drugs are apparently different.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1433-2965
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Our experimental and clinical studies lead to the following conclusions: 1. The amount of exercise that has a favorable effect on bone tissue differs between males and females among individuals. 2. An appropriate amount of exercise has a favorable influence not only on weight-bearing bone but also on non-weight-bearing bone, provided there is a sufficient intake of calcium. 3. Exercise may prevent the bone loss in osteoporosis, but an increase in bone mass cannot be expected. The major aim is to increase bone mass before the achievement of peak bone mass in order to prevent osteoporosis. However, suitable weight-bearing exercise in osteoporosis is useful for the prevention of falls which may result in fractures, to increase muscle strength, to improve walking balance and coordination, and to prevent orthostatic hypotension.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1433-2965
    Keywords: Calcaneus ; Dual X-ray absorptiometry ; Menopause ; Osteoporosis ; Ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The velocity (SOS), attenuation slope (BUA) and stiffness index in the os calcis were measured using the ‘Achilles’ ultrasound bone densitometer (Lunar, Madison, WI). We evaluated the basic attributes of this ultrasound bone densitometer, and showed the age-related changes in ultrasound values in normal Japanese women. The precision was measured in vivo on ten occasions over a 2-week period in 5 subjects. The short-term precision errors (CVs) in vivo were 0.6% for stiffness index, 0.3% for SOS and 1.0% for BUA. Spine, femur neck and total body BMD using dual X-ray absorptiometry (DXA) were highly correlated with stiffness index (r=0.80, 0.77 and 0.78, respectively) in 194 subjects. Ultrasound values for patients with osteoporosis were significantly lower than those for the normal controls. TheZ-score compared with young normals was significantly higher for spine bone mineral density (−4.4) than for stiffness index (−3.5); BUA and SOS gave significantly lowerZ-scores −2.9 and −3.0, respectively). Ultrasound values were also lower compared with age-matched normal controls. TheZ-score for stiffness index (−2.1) was significantly superior to that for either SOS or BUA (−1.5). Age-related change in ultrasound values was evaluated in 842 normal women. There was a decline in stiffness index of about 24% from the values in young adulthood to those of women in their seventies, about 75% of which occurred from age 44–49 years onward. These findings seem to indicate that the menopause affected the change in ultrasound values. In conclusion, ultrasound bone densitometry may not be as useful as DXA of the spine for screening for osteoporosis, since theZ-score for DXA is excellent. However, ultrasound bone densitometry appears potentially to be applicable to problems in the diagnosis and management of osteoporosis when used in association with DXA.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1433-2965
    Keywords: Bone mineral density ; Osteoporosis ; Quantitative computed tomography ; Radius
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study evaluated a commercial device for peripheral quantitative computed tomography (pQCT) and examined the age-related changes in normal Japanese women. The volumetric bone mineral density (vBMD) of the distal radius [integral bone mineral density (BMDI), trabecular bone mineral density (BMDT) and cortical with subcortical bone mineral density (BMDSC)] was measured using pQCT (Norland-Stratec XCT960) in 617 healthy women aged 20–79 years and 75 subjects with osteoporosis aged 60–89 years who exhibited at least one vertebral fracture. The short-term precision errors in vivo (CV, %) were 1.1% for BMDI 1.1% for BMDT and 1.2% for BMDSC. The correlations between pQCT and dual-energy X-ray absorptiometry measurements (Lunar DPX) of the lumbar spine werer∼0.8 (BMDI, BMDT and BMDSC). The maximal mean vBMD values were observed between 20 and 49 years; BMDI BMDT and BMDSC all showed a linear postmenopausal decline averaging 1.1% per year. The overall decreases in vBMD from the peak values in those 70–79 years were 34%, 32% and 33% in BMDI, BMDT and BMDSC, respectively. The diagnostic sensitivity of osteoporosis was expressed as aT-score.T-scores using pQCT were −3.0 (BMDI), −2.4 (BMDT) and −2.9 (BMDSC). Bone mineral measurement of the distal radius may be useful in the evaluation of age-related bone loss and for the diagnosis of osteoporosis.
    Type of Medium: Electronic Resource
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