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Transiently increased bone density after irradiation and the radioprotectant drug amifostine in a rat model.

At therapeutic levels in pediatric patients, radiation causes damage to the growth plate and contributes to growth deformity and fractures. The purpose of this project was to examine the effects of x-ray irradiation on regional bone mineral density (BMD) and osteoclast histology of rat bone with and without radioprotectant amifostine (AMF) pretreatment. Seventy-two weanling rats had their right knee irradiated with single fraction 17.5 Gy, whereas the left leg was used as an internal control. Twelve animals were euthanized at each of 6 time periods (0.5-6 wk) after irradiation, half having received 100 mg/kg amifostine. BMD (g/cm3) was determined for both the right and left femurs using peripheral quantitative computed tomography (CT) (pQCT). Tibial sections were stained for osteoclasts/chondroclasts with tartrate-resistant acid phosphatase. Statistically significant increases in BMD within the radiation field were seen in the treatment groups' right irradiated legs over the control unirradiated left legs at all time points from 0.5 through 6 weeks. Anatomically, a peak in BMD occurs in the region immediately adjacent to the chondro-osseous junction at 2 weeks after irradiation and then moves proximally within the adjacent metaphysis after 3 weeks. Corresponding to these findings, histologically a 2-week nadir occurs after irradiation in osteoclasts/chondroclast numbers adjacent to the chondro-osseous junction with a 71.9% decrease compared with controls (p <0.05). At 3 weeks, the numbers of osteoclasts/chondroclasts in this region have increased to 47.4% greater than the control legs (p <0.03) The animals receiving amifostine had BMD that was consistently closer to controls only adjacent to the chondro-osseous junction at 0.5, 2, and 3 weeks and osteoclast/chondroclast numbers that were closer to controls only at 4 weeks.

Amifostine↗

A video-based system for acquiring biomechanical data synchronized with arbitrary events and activities.

A video-based data acquisition and interactive multimedia data extraction system are described for measuring and synchronizing large quantities of biomechanical analog data with arbitrary events and activities. Analog signals from up to 32 channels are digitized, frequency-shift key (FSK) coded, and recorded directly onto the audio tracks of a video tape in synchronization with the video information. The data acquisition system includes an A/D converter that digitizes up to 16 multiplexed channels of 8-b data at a fixed sample rate between 60 and 960 Hz, and an FSK modem that transfers the data onto one of two VHS high fidelity (20 Hz-20 kHz bandwidth) audio tracks. Twenty megabytes of digitized data and time codes, along with associated video and normal audio are contained on a conventional 120-min video tape. An analyst interactively reviews the video tape off-line using a computer-controlled VCR and identifies specific events that divide arbitrary activities into time segments. The computer automatically extracts the biomechanical data corresponding to each time segment for further processing or analysis. This system is useful for ergonomics, gait analysis, sports medicine, sleep laboratory, biomechanics, or any application where complex visual events are synchronized with low-frequency analog data.

Analog-Digital Conversion↗

Optimal character arrangements for ambiguous keyboards.

Many persons with disabilities lack the fine motor coordination necessary to operate traditional keyboards. For these individuals, ambiguous (or reduced) keyboards offer an alternative access method. By placing multiple characters on each key, the size and accessibility of the individual keys can be enhanced without requiring a larger keyboard. Using statistical disambiguation algorithms to automatically interpret each keystroke, these systems can approach the keystroke efficiency (keystrokes per character) of conventional keyboards. Since the placement of characters on each key determines the effectiveness of these algorithms, several methods of optimizing keyboard arrangements have previously been proposed. This paper presents a new method for optimizing an arbitrary set of N characters over a collection of M keys. While earlier efforts relied upon approximations of keystroke efficiency, the proposed approach optimizes the arrangement under this exact performance measure. Applied to the canonical 26 characters on a nine-key "telephone keypad" problem, this method provides an improvement in efficiency of 2.5 percentage points over previously established layouts. Using only a minimum of calculations, the proposed technique operates quickly and efficiently, deriving optimal arrangements in a matter of seconds using a personal computer. The flexible method is applicable to arbitrary disambiguation algorithms, character sets, and languages.

Algorithms↗

Autocorrelation and cepstral methods for measurement of tibial cortical thickness.

Cortical thickness of the tibia is related to stress fracture risk and overall skeletal status. Two methods are proposed for estimating tibial cortical thickness based on power spectra of ultrasonic echoes containing reflections from front and back surfaces of the cortex. The locations of the peaks in the autocorrelation function and the cepstrum are related to cortical thickness. Data were acquired on plastic plates in order to validate the methodology. These data indicate high correlations between estimated and true thickness with correlation coefficients r = 0.99, (95% confidence interval: 0.993-1.00) for the autocorrelation method and r = 0.99 (95% CI: 0.996-1.00) for the cepstral method. Data on six tibia samples in vitro indicate correlation coefficients of r = 0.92 (95% CI: 0.72-1.00) for the autocorrelation method and r = 0.85 (95% CI: 0.62-0.94) for the cepstral method. Estimates of precisions of the two methods were 0.3 +/- 0.1 mm (autocorrelation method) and 0.5 +/- 0.2 mm (cepstral method). One measurement in a human volunteer in vivo demonstrated clinical feasibility of the measurement and good agreement with cortical thickness assessed using peripheral quantitative computed tomography (QCT). This technology offers the promise of an inexpensive, fast, portable, simple, nonionizing technique for assessing skeletal status.

Algorithms↗

Changes in bone density and metabolism in pregnancy.

OBJECTIVE: The impact of pregnancy on maternal bone density remains unclear. As a prerequisite to investigate the pathophysiology of gestational bone metabolism, we sought to document the changes in bone metabolism biochemistry in conjunction with those in selective trabecular/cortical osteodensitometry between early and late pregnancy. METHODS: A prospective, controlled study in a university hospital was conducted with 43 healthy women, 34 of them during uneventful pregnancy. The main outcome measures are trabecular and cortical bone density measured in the first and third trimesters using peripheral quantitative computed tomography in conjunction with a panel of bone metabolism parameters, including blood parathyroid hormone, calcitonin, osteocalcin, skeletal alkaline phosphatase, and the urinary desoxypyridinoline/creatinine ratio. RESULTS: Cortical bone density was unaffected by pregnancy. Trabecular bone density changes showed wide interindividual variation, ranging from +1.3 to -20.7% per year, identified as fast losers (less than -3%) and slow losers (more than -3%). Serum osteocalcin levels were lower in slow versus fast bone losers in both trimesters (first: P=0.02, third: P=0.02) and were the only independent parameter to differentiate between fast and slow losers. CONCLUSIONS: Our data suggest that wide interindividual variation and the failure to provide a separate measure of trabecular bone density account for the conflicting evidence in earlier reports. Serum osteocalcin concentration during the first trimester distinguishes between fast and slow losers of trabecular bone and should be evaluated in future studies as predictor for later bone loss (osteoporosis).

Absorptiometry, Photon↗

Non-invasive measurement of haemodynamics during sleep apnoea.

Sleep apnoeas are accompanied by large variations in heart rate (HR) and blood pressure (BP). This nocturnal variability in BP may be involved in the increased cardiovascular morbidity of these patients. Due to the complex interaction between asphyxia, intrathoracic pressure, cardiac function and autonomic activation, the exact haemodynamic mechanisms are unclear. To evaluate the components of the BP surges at resumption of breathing (RB) a non-invasive beat-to-beat measurement was taken of cardiac output (CO) by the pulse contour analysis of the Finapres signal. Six male normotensive patients, free of medication (37-60 y, BMI 26.5-43.0 kg m-2) were studied during polysomnography (apnoea index: 22-69 h-1). Systolic blood pressure rose from 126.5 +/- 1.3 mmHg at beginning apnoea (P1) to 140.4 +/- 1.3 at RB (P < 0.01, ANOVA). During sleep Stages 2 and 3, stroke volume decreased during RB to 96% of P1 value (NS). Due to an opposite change in HR, CO tended to rise at RB to 106% of P1. Computed total peripheral resistance rose during RB to 105% of P1 value (P < 0.011. Therefore, it is concluded that the surge in BP at RB after apnoea is due to concomitant increases in CO and in TPR. Both rises are presumably a consequence of sympathetic nervous activation by the arterial chemoreceptors.

Journal Article↗

Differences in bone mineral content and density between male and female budgerigars (Melopsittacus undulatus) during the non-reproductive season.

It is known that female birds increase medullary mineral stores in long bones shortly before egg laying. Here, we present results from two groups of budgerigars, in both of which females had significantly higher bone mineral contents and densities, as measured by peripheral quantitative computed tomography of the tibiotarsus, during a reproductively dormant period. The results could indicate that female birds can accumulate mineral stores outside of the breeding season.

Animals↗

An analysis of the haemodynamic effects of tolbutamide in conscious dogs.

1. In conscious chronically instrumented dogs, tolbutamide (5-45 mg/kg) induced significant dose-related increases in mean arterial pressure and left ventricular end-diastolic pressure. 2. Cardiac output was decreased while heart rate, d(LVP)/dt, and regional myocardial performance at the left ventricle were not significantly affected. Computed total peripheral resistance was increased. 3. Pretreatment with the alpha-antagonist phentolamine (1-1.5 mg/kg) abolished the pressor response. Furthermore, the pressor response to norepinephrine (0.1 microgram/kg) was enhanced by pretreatment with tolbutamide (45 mg/kg). 4. In an isolated tissue preparation using ring segments of canine femoral arteries, neither tolbutamide nor its major hepatic metabolites (carboxytolbutamide, p-toluene-sulfonamide and p-toluene-sulfonylurea) caused any smooth muscle contraction. However, pretreatment of these tissues with 10(-4), 10(-3), or 10(-2) mol/l tolbutamide potentiated the contractile response to norepinephrine by up to 19% and to phenylephrine by up to 8%. 5. It was concluded that the pressor effect of tolbutamide arises by potentiating the alpha-adrenoceptor mediated vasoconstrictor action of circulating endogenous catecholamines.

Adrenergic alpha-Antagonists↗

Changes in bone structure after augmentation cystoplasty in chronic uraemic rats.

OBJECTIVE: To investigate the effect of urinary diversion using several types of intestinal segments on cortical and cancellous bone structure of growing rats with renal insufficiency. MATERIAL AND METHODS: In all, 110 female Sprague-Dawley rats (8 weeks old) had either a two-stage subtotal nephrectomy by removing five-sixths of the renal mass, or a sham operation. Except for a uraemic control group, all uraemic rats then had an enterocystoplasty using stomach, ileum or colon (20 animals per group). An additional group with colic augmentation received the bisphosphonate ibandronate. After 12 weeks, the left tibia was assessed using peripheral quantitative computed tomography and bone histomorphometry. RESULTS: After subtotal nephrectomy all groups had approximately 30% less endogenous creatinine clearance. Renal failure alone or in association with gastric or colic augmentation induced only negligible changes in the mass and structure of cortical and cancellous tibial bone. In contrast, rats after ileal augmentation and renal failure had a significant reduction in cancellous bone mineral density (P < 0.05) whereas the reduction in trabecular bone area and volume was not statistically significant. Furthermore, ileocystoplasty caused a decrease in trabecular number and perimeter, increased trabecular separation and enlarged bone marrow space, whereas ileocystoplasty had no effect on cortical bone. The changes were not associated with alterations in serum pH. Ibandronate treatment in the colonic cystoplasty group increased trabecular bone mass and structural variables over the untreated colonic cystoplasty group. CONCLUSIONS: These results suggest that cystoplasty using an ileal segment causes a decrease in bone mass and architecture in growing rats with mild uraemia. It remains open to question whether the results obtained from experimental animals can be directly extrapolated to the clinical situation.

Animals↗

A prospective study on the effects of depot medroxyprogesterone acetate on trabecular and cortical bone after attainment of peak bone mass.

OBJECTIVE: To study the annual change of bone mass in women aged 30-45 years being treated with depot medroxyprogesterone acetate (DMPA) in order to evaluate whether the bone mass depends on the duration of DMPA use or the oestradiol level. DESIGN: Prospective longitudinal study over an interval of 12 months. SETTING: A family planning centre of a university hospital. PATIENTS: Thirty-six current users of DMPA. INTERVENTIONS: Injection of 150 mg DMPA every 12 weeks. MEASUREMENTS: Bone mass was measured at the distal radius by peripheral quantitative computed tomography (reproducibility 0.3%). RESULTS: Mean annual changes (SD) in trabecular and cortical bone mass were 0.06 (1.6%) [P = 0.8] and -0.26% (0.6) [P < 0.04]. The decrease in cortical bone mass was not significant because the changes were within the precision error of the method used for the measurements. Duration of DMPA use and oestradiol levels were not associated to the bone parameters. CONCLUSION: We did not find a negative impact of DMPA on the bone mass of premenopausal women aged 30-45 years.

Adult↗

Analysis of the functional muscle-bone unit of the forearm in pediatric renal transplant recipients.

BACKGROUND: Renal transplantation in children and adolescents is associated with various skeletal complications. The incidence of spontaneous fractures appears to be increased, but the reasons for this are not entirely clear. Our objective was therefore to evaluate macroscopic bone architecture, mass, and strength by peripheral quantitative computed tomography (pQCT), a method that is not influenced by size-related artifacts. In addition, we investigated the muscle-bone relationship in these patients because under physiologic conditions bone strength continually adapts to increasing mechanical loads, that is, muscle force. METHODS: In 55 patients (41 males) aged 15.8 +/- 4.1 years, we evaluated in a cross-sectional study 4.9 +/- 3.6 years after renal grafting bone mass, density, geometry, and strength of the radius, as well as forearm muscle size and strength, using pQCT at the proximal and distal radius, radiography of the second metacarpal shaft and hand dynamometry. Data were compared to a large cohort (N= 350) of healthy children. RESULTS: Muscle mass and force were adequate for body size in pediatric renal transplant recipients. However, the radial bone was characterized by an inadequately thin cortex in relation to muscular force, as shown by a reduced height-adjusted cortical thickness both at the proximal (-0.83 +/- 1.12 SDS) and distal radius (-0.52 +/- 1.69 SDS), the metacarpal shaft (-0.54 +/- 1.35 SDS), and by a reduced relative cortical area (-0.90 +/- 1.13 SDS), while the mineralization of trabecular bone was unaltered. As a consequence of cortical thinning, the Strength-Strain Index that reflects the combined strength of trabecular and cortical bone was reduced in these patients. CONCLUSION: While bone mineral density of the forearm is not decreased in pediatric renal transplant recipients, bone strength in relation to muscular force is reduced. This alteration may contribute to the increased propensity for fractures in these patients.

Adolescent↗

Urinary calcium is a determinant of bone mineral density in elderly men participating in the InCHIANTI study.

BACKGROUND: It is generally acknowledged that calcium excretion is a determinant of bone mineral density. Since data confirming this hypothesis are not conclusive, the present study evaluates the relationship between calcium excretion and volumetric bone mineral density (vBMD) in a sample of general population mostly composed of elderly subjects. METHODS: This relationship was studied in 595 subjects in good health (M/F 302/293), selected from the InCHIANTI population, an epidemiologic survey on aging in Tuscany (Italy). Of these subjects, 432 (72.6%) were 65 years old or older. Trabecular and cortical apparent vBMDs were measured by peripheral quantitative computed tomography at right tibia and standardized to age and body mass index (BMI) in each gender (z-score). RESULTS: Men in the highest tertile of calcium excretion had significantly lower trabecular vBMD, and were more likely to have a trabecular z-score of -1 or less. These results were confirmed in men older than 64 years, but not in women and younger men. Sodium excretion and 25-hydroxycolecalciferol (25(OH)D) were greater in men and women in the highest tertile. No differences among tertiles were observed for cortical vBMD, circulating levels of interleukin-1beta and interleukin-6, and intake of principal nutrients and calcium. The lower levels of vBMD z-score were confirmed in men in the highest tertile of calcium excretion, standardized to creatinine clearance, sodium excretion, plasma calcium, and logarithm of circulating 25(OH)D, and resulted to be associated with calcium excretion at multiple regression analysis in men. CONCLUSION: High calcium excretion is associated with a decreased trabecular BMD in elderly men and may predispose men to trabecular bone loss.

Adult↗

Development of integrated electronics unit for drive and control of undulation pump-left ventricular assist device.

In this study, we have developed an implantable electronics unit (IEU) for driving an undulation pump-left ventricular assist device (UP-LVAD). The IEU consists of a pump driver, three series-connected lithium ion batteries (1800 mAh), a charger, and a transcutaneous information transmission system. These electronic subunits were encapsulated in a case (110 x approximately 80 x approximately 30 mm) made of epoxy resin. The IEU was evaluated in two animal experiments using goats implanted with the UP-LVAD. The lithium ion batteries in the IEU provided 30-min energy supply daily to the UP-LVAD. The transcutaneous information transmission system transmitted data bidirectionally between the IEU and the personal computer at the data transmission ratio of 56 kbps without any transmission error. We could obtain survival days of 27 and 28 days supporting cardiac function with the UP-LVAD system. The temperature inside the IEU case was maintained under 45 degrees C, and there was evidence of a burn on the surrounding tissue in autopsies in each experiment. Based on the results, the IEU is promising to be suitable for drive and control of an implantable UP-LVAD.

Animals↗

Disaster recovery.

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Computer Peripherals↗

Grape seed proanthocyanidins extract promotes bone formation in rat's mandibular condyle.

We studied the effect of dietary supplementation with grape seed proanthocyanidins extract (GSPE) 3 mg added in 100 g high-calcium diet with a calcium content of 1697 mg 100 g(-1) on mandibular condyle bone debility, which was induced by a low-calcium diet. Forty Wistar male rats, 5 week old, were randomly divided into control (Co), low-calcium diet (LC), low-calcium/high-calcium diet (LCH), and low-calcium/high-calcium with supplementary GSPE diet (LCHG) groups for 6 wk. Bone formation of the mandibular condyle was measured using peripheral quantitative computed tomography (pQCT). Significant differences were not seen among the four groups for body weight, measured weekly. The LCHG group scored significantly higher in cortical bone density, total bone cross-sectional area, cortical bone cross-sectional area, cortical bone mineral content, total bone density, total bone mineral content, and in the stress-strain index to the reference axis x when compared with the LCH group. We concluded that a high-calcium diet combined with GSPE supplementation is more effective in reversing mandibular condyle bone debility in rats than is a low-calcium diet, standard diet, or high-calcium diet alone.

Anatomy, Cross-Sectional↗

Cost-effectiveness of alendronate in the prevention of osteoporotic fractures in Danish women.

Pharmacological interventions for osteoporosis may reduce morbidity and mortality, but they incur additional health care costs. The aim was to quantify the additional costs and health benefits of prescribing alendronate 10 mg and calcium/vitamin D daily for 71-year-old women with a fracture risk twice that of the population average in stead of calcium/vitamin D alone. A state transition model based primarily on Scandinavian data was developed. Women were followed from age of 71 years until 100. Alendronate was assumed to reduce the fracture risk by 50%. Health benefits from the interventions were expressed in terms of life years, quality adjusted life years, and fractures avoided. Societal costs were estimated using literature estimates and Danish tariffs. All costs were measured in 2002 Danish Kroner (DKK). Future costs and benefits were discounted at 5% per year. The incremental cost per QALY gained was DKK125,000 while the cost per life year gained was DKK 374,000. The use of alendronate was cost-saving when 1) the treatment was extended to five years, 2) the risk of fracture was four times the population average, 3) the effect of alendronate was assumed to persist for three years after discontinuation of treatment, 4) a greater proportion had severe sequelae after a hip fracture, or 5) the start of therapy was delayed until age of 77 years. In conclusion, the use of alendronate compares well with other well established therapies in terms of cost-effectiveness in older women with high risk of fracture.

Aged↗

Influence of exercise on bone mineral density of immature cortical and trabecular bone of the equine metacarpus and proximal sesamoid bone.

Bone mineral density (BMD) and cross-sectional area (CSA), measured using peripheral quantitative computed tomography, were determined in the left third metacarpal bone (MCIII) and left medial proximal sesamoid bone (psb) in 3 differently exercised groups of foals. Group(box) (n = 14) was confined to a box stall from birth to age 5 months, Group(training) (n = 14) was kept in similar box stalls but additionally given a daily exercise programme consisting of an increasing number of gallop sprints and Group(pasture) (n = 15) remained at pasture. At 5 months of age, 8 foals from each group were randomly selected and subjected to euthanasia, the remaining 19 foals were given an identical light exercise regimen for an additional 6 months and were killed at age 11 months. In MCIII CSA increased with age and was also significantly (P<0.05) larger in Group(pasture) compared to Group(box) at age 5 months. At 11 months this difference had disappeared. In the dorsal cortex, BMD was significantly (P<0.05) higher in Group(box) than in both other groups. At age 11 months all significant differences had disappeared. In the psb, CSA increased with age, but there were no differences between the exercise groups. At the apical level, trabecular BMD was higher in Group(training) than in Group(box) and Group(pasture) (P<0.001 and P<0.01, respectively). At 11 months, trabecular BMD in the foals that had belonged to Group(training) was less than in the foals that had belonged to Group(box) (P<0.05). It is concluded that box-rest during the first months of life results in a retardation of normal development which is compensated for when the restriction on exercise is lifted. Exercise during the first months of life induces an increase in CSA in the third metacarpal bone. In the psb exercise increases BMD, principally in trabecular bone. There is an indication that the specific training regimen used in this study led to an overstimulation of the bone resulting in less active mineral deposition in the longer term.

Animals↗

In vivo assessment of trabecular bone structure using fractal analysis of distal radius radiographs.

Our purpose in this study was (i) to measure trabecular bone structure using fractal analysis of distal radius radiographs in subjects with and without osteoporotic hip fractures, and (ii) to compare these measures with bone mineral density (BMD) as well as with measures of trabecular bone structure derived from high resolution magnetic resonance (MR) images. Distal radius radiographs were obtained using semi-industrial films (55 kVp, 400 mAs) in 30 postmenopausal patients, who had suffered osteoporotic hip fractures (74.8+/-8.2 years) in the last 24 months and 27 postmenopausal age-matched (74.6+/-6.6 yr) normal volunteers. Radiographs were digitized at 50 microm. A Fourier power spectrum-based fractal dimension (FD) characterizing the trabecular pattern was measured in a region of interest proximal to the joint line. The fractal dimension was calculated over two spatial frequency (f) ranges: FD1 was calculated over 0.5<log(f)<l.0, FD2 over the higher range 1.0<log(f)<1.5. Trabecular BMD in the radius was obtained using peripheral quantitative computed tomography (pQCT) (Stratec GmbH, Germany). In addition BMD of the proximal femur was determined using dual x-ray absorptiometry (DXA) (QDR 2000, Hologic, MA). In a subset of patients (16 controls and 18 with hip fractures), high resolution MR imaging of the distal radius (spatial resolution of 156 x 156 x 500 microm) was used to obtain measures analogous to bone histomorphometry. There were significant differences (p<0.05) between the fracture and nonfracture groups in the total femur BMD (13%), trabecular BMD in the distal radius (4%), and the fractal dimension in the radiographs (FD2) (3%). The correlations between FD2 and the total femur BMD as well as trabecular bone BMD in the distal radius were -0.48 (p<0.006) and -0.22 (p<0.33); respectively; FD1 increased with BMD and showed lower correlations. FD2 showed good correlations with App. Tb.N (-0.71) and App. Tb.Sp (0.69) (p<0.01), moderate correlation with App BV/TV (-0.53) (p<0.05), and no significant correlation with App. Tb.Th. The correlations between structural measures and FD1 showed the inverse trend and were typically lower. The odds ratios for a hip fracture were 2.44 for total femur BMD, 1.5 for trabecular BMD (radius), and 1.5 for FD2, respectively. In summary, the fractal measures derived from radiographs of the radius show differences between subjects with and without hip fractures, the predictive power of measures in the distal radius are comparable to radial trabecular BMD but lower than that of total hip BMD.

Aged↗