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PubMed2002

Raloxifene- and estradiol-mediated effects on uterus, bone and B lymphocytes in mice.

Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It is selective by having estrogen-agonistic effects on bone, vessels and blood lipids while it is antagonistic on mammary and uterine tissue. Our aim was to study the agonistic and antagonistic properties of the raloxifene analogue LY117018 (LY) on uterus, bone, B lymphopoiesis and B cell function. Oophorectomized and sham-operated animals were treated with s.c. injections of equipotent anti-osteoporotic doses of 17beta-estradiol (E2) (0.1 mg/kg) or LY (3 mg/kg) or vehicle as controls. Effects on bone mineral density (BMD) were studied using peripheral quantitative computed tomography, uterine weight was examined, B lymphopoiesis was examined using flow cytometry and B cell function in bone marrow and spleen was studied by the use of an ELISPOT assay. E2 and LY had similar effects on BMD and bone marrow B lymphopoiesis, while LY had a clear antagonistic effect on endogenous estrogen in uterine tissue and no stimulating effect on the frequency of Ig-producing B cells in sham-operated animals. Our results are discussed in the context of estrogen receptor biology, relations between the immune system and bone metabolism and also with respect to the estrogen-mediated effects on rheumatic diseases.

Animals↗
PubMed2005

Impaired skeletal growth in mice with haploinsufficiency of IGF-I: genetic evidence that differences in IGF-I expression could contribute to peak bone mineral density differences.

Although it is well established that there is considerable inter-individual variation in the circulating levels of IGF-I in normal, healthy individuals and that a genetic component contributes substantially to this variation, the direct evidence that inter-individual variation in IGF-I contributes to differences in peak bone mineral density (BMD) is lacking. To examine if differences in IGF-I expression could contribute to peak BMD differences, we measured skeletal changes at days 23 (prepubertal), 31 (pubertal) and 56 (postpubertal) in mice with haploinsufficiency of IGF-I (+/-) and corresponding control mice (+/+). Mice (MF1/DBA) heterozygous for the IGF-I knockout allele were bred to generate +/+ and +/- mice (n=18-20 per group). Serum IGF-I was decreased by 23% (P<0.001) in mice with IGF-I haploinsufficiency (+/-) group at day 56 compared with the control (+/+) group. Femoral bone mineral content and BMD, as determined by dual energy X-ray absorptiometry, were reduced by 20% (P<0.001) and 12% respectively in the IGF-I (+/-) group at day 56 compared with the control group. The peripheral quantitative computed tomography measurements at the femoral mid-diaphysis revealed that periosteal circumference (7%, P<0.01) and total volumetric BMD (5%, P<0.05) were decreased significantly in the +/- group compared with the +/+ group. Furthermore, serum IGF-I showed significant positive correlations with both areal BMD (r=0.55) and periosteal circumference (r=0.66) in the pooled data from the +/+ and +/- groups. Our findings that haploinsufficiency of IGF-I caused significant reductions in serum IGF-I level, BMD and bone size, together with the previous findings, are consistent with the notion that genetic variations in IGF-I expression could, in part, contribute to inter-individual differences in peak BMD among a normal population.

Absorptiometry, Photon↗
PubMed2001

Recombinant human bone morphogenetic protein-2 accelerates healing in a rabbit ulnar osteotomy model.

BACKGROUND: Approximately 5% to 20% of fractures have delayed or impaired healing. Therefore, it is desirable to develop new therapies to enhance fracture-healing that can be used in conjunction with traditional treatment methods. The purpose of this study was to evaluate the ability of a single application of recombinant human bone morphogenetic protein-2 to accelerate fracture-healing in a rabbit ulnar osteotomy that heals spontaneously. METHODS: Bilateral mid-ulnar osteotomies (approximately 0.5 to 1.0 mm wide) were created in seventy-two skeletally mature male rabbits. The limbs were assigned to one of three groups: those treated with an absorbable collagen sponge containing recombinant human bone morphogenetic protein-2, those treated with an absorbable collagen sponge containing buffer, and those left untreated. In the first two groups, an 8 20-mm strip of absorbable collagen sponge containing either 40 g of recombinant human bone morphogenetic protein-2 or buffer only was wrapped around the osteotomy site. The rabbits were killed at two, three, four, or six weeks after surgery. In addition, twenty-four age-matched rabbits were used to provide data on the properties of intact limbs. The retention of recombinant human bone morphogenetic protein-2 at the osteotomy site was determined with scintigraphic imaging of (125)I-labeled recombinant human bone morphogenetic protein-2. After the rabbits were killed, the limbs were scanned with peripheral quantitative computed tomography to assess the area and mineral content of the mineralized callus. The limbs were then tested to failure in torsion, and undecalcified specimens were evaluated histologically. RESULTS: Gamma scintigraphy of (125)I-recombinant human bone morphogenetic protein-2 showed that 73% +/- 6% (mean and standard deviation) of the administered dose was initially retained at the fracture site. Approximately 37% +/- 10% of the initial dose remained at the site one week after surgery, and 8% +/- 7% remained after two weeks. The mineralized callus area was similar in all groups at two weeks, but it was 20% to 60% greater in the ulnae treated with recombinant human bone morphogenetic protein-2 than in either the ulnae treated with buffer or the untreated ulnae at three, four, and six weeks (p < 0.05). Biomechanical properties were similar in all groups at two weeks, but they were at least 80% greater in the ulnae treated with recombinant human bone morphogenetic protein-2 at three and four weeks than in either the ulnae treated with buffer (p < 0.005) or the untreated ulnae (p < 0.01). By four weeks, the biomechanical properties of the ulnae treated with recombinant human bone morphogenetic protein-2 were equivalent to those of the intact ulnae, whereas the biomechanical properties of both the ulnae treated with buffer and the untreated ulnae had reached only approximately 45% of those of the intact ulnae. At six weeks, the biomechanical properties were similar in all groups and were equivalent to those of the intact ulnae. The callus geometry and biomechanical properties of the ulnae treated with buffer were equivalent to those of the untreated ulnae at all time-points. CONCLUSIONS AND CLINICAL RELEVANCE: These findings indicate that treatment with an absorbable collagen sponge containing recombinant human bone morphogenetic protein-2 enhances healing of a long-bone osteotomy that heals spontaneously. Specifically, osteotomies treated with recombinant human bone morphogenetic protein-2 healed 33% faster than osteotomies left untreated. The results of this study provide a rationale for testing the ability of recombinant human bone morphogenetic protein-2 to accelerate healing in patients with fractures requiring open surgical management.

Animals↗
PubMed2003

Pullout strength of suture anchors used in rotator cuff repair.

BACKGROUND: Surgical treatment of rotator cuff tears may be complicated by osteoporosis of the proximal part of the humerus. The purpose of this study was to determine whether pullout strength of suture anchors is affected by the location of the anchor placement and by bone mineral density. We hypothesized that higher bone mineral density is associated with higher pullout strength of suture anchors. METHODS: Peripheral quantitative computed tomography was used to measure total, trabecular, and cortical bone mineral density in different regions of the lesser and greater tuberosities in seventeen cadaveric humeri. Suture anchors were inserted into individual regions and subjected to cyclic loading. Repeated-measures analysis of variance was used to assess differences in bone mineral density and load to failure between regions of interest. Pearson correlation was used to determine the association between bone mineral density and pullout strength of suture anchors. RESULTS: Total, trabecular, and cortical bone mineral densities were an average of 50%, 50%, and 10% higher, respectively, in the proximal part of the tuberosities compared with the distal part (p < 0.01). Within the proximal part of the greater tuberosity, trabecular bone mineral density of the posterior region and cortical bone mineral density of the middle region were, on the average, 25% and 16% higher, respectively, than the densities in the other regions (p < 0.01). Load to failure in the proximal part of the tuberosities was an average of 53% higher than that in the distal part (p < 0.01). The lesser tuberosity showed, on the average, a 32% higher load to failure than did the greater tuberosity (p < 0.01). Within the proximal part of the greater tuberosity, loads to failure in the anterior and middle regions were, on the average, 62% higher than the load to failure in the posterior region (p < 0.01). Overall positive correlations were found between bone mineral density and load to failure (0.65 </= r </= 0.74, p < 0.01). CONCLUSIONS: We found that pullout strength of suture anchors correlates well with bone mineral density of the tuberosities. Higher loads to failure were found in regions in the proximal part of the tuberosities. Placement of anchors in these regions may prevent anchor loosening, formation of a tendon-bone gap, and failure of the rotator cuff repair.

Aged↗
PubMed2006

rhBMP-2/calcium phosphate matrix accelerates osteotomy-site healing in a nonhuman primate model at multiple treatment times and concentrations.

BACKGROUND: While recombinant human bone morphogenetic protein-2 (rhBMP-2) administered in a calcium phosphate cement accelerates osteotomy-site healing in animal models when administered three hours after surgery, definitive fracture treatment is often delayed. The present study evaluated the ability of rhBMP-2, administered in a new particulating calcium phosphate matrix, to accelerate nonhuman primate fibular osteotomy-site healing following treatment at multiple treatment times and concentrations. METHODS: The ability of 1.5-mg/mL rhBMP-2/calcium phosphate matrix to accelerate osteotomy-site healing when administered three hours, one day, one week, or two weeks after surgery was first evaluated with use of bilateral proximal and distal fibular osteotomy sites in adult male monkeys. In a second study, the healing of osteotomy sites that had been treated with the administration of calcium phosphate matrix alone and with different concentrations of rhBMP-2/calcium phosphate matrix (0.5 mg/mL, 1.5 mg/mL, or 4.5 mg/mL) seven days after surgery was compared with that of contralateral, untreated osteotomy sites. In a third study, the histologic progression of osteotomy-site healing following treatment with 1.5-mg/mL rhBMP-2/calcium phosphate matrix or calcium phosphate matrix alone, administered three hours or one week after surgery to the osteotomy site, was assessed at multiple time points for as long as twenty-four months after surgery. RESULTS: Radiographs demonstrated increased callus area and more rapid healing in response to 1.5-mg/mL rhBMP-2/calcium phosphate matrix administered over the range of treatment times after surgery as compared with the findings of previous reports on untreated osteotomy sites. Bone formation appeared at the osteotomy sites sooner following treatment at one and two weeks as compared with the findings at the earlier time-points. Scintigraphic imaging at one day and one week after surgery showed prolonged retention of rhBMP-2 at the osteotomy site following an initial burst release. In the second study, radiographic, peripheral quantitative computed tomographic, biomechanical, and microscopic evaluation demonstrated that administration of 1.5 and 4.5-mg/mL rhBMP-2/calcium phosphate matrix one week after surgery accelerated osteotomy-site healing by 40% to 50% compared with the findings in untreated controls. The magnitude of acceleration was less in response to 0.5-mg/mL rhBMP-2/calcium phosphate matrix, and calcium phosphate matrix alone did not accelerate osteotomy-site healing. Histological evaluation indicated that an increased cellular infiltrate and increased direct bone formation contributed to the accelerated osteotomy-site healing following administration of rhBMP-2/calcium phosphate matrix at one week compared with three hours after surgery. CONCLUSIONS: A single percutaneous injection of rhBMP-2/calcium phosphate matrix accelerated healing in nonhuman primate fibular osteotomy sites over a wide range of treatment times. Efficacy was optimized in association with the administration of 1.5-mg/mL rhBMP-2/calcium phosphate matrix. Delaying treatment for one week further accelerated healing because of an increase in the number of responding cells and an increase in direct bone formation.

Animals↗
PubMed1997

An analysis of users' preference on keyboards through ergonomic comparison among four keyboards.

The usability of four kinds of keyboards as regards touch and feel was evaluated by measuring the performance and eliciting the preferences of a total of 24 Japanese participants in a test that consisted of typing English text. It was found that quiet keyboards with an indistinct tactile feedback tend to give higher uncorrected error rates than keyboards with a distinct tactile feedback and clicking sound, while no significant difference in throughput was found among the four keyboards. As regards preference, the test participants were divided into two groups: those who preferred keyboards with a distinct tactile feedback and clicking sound, and those who preferred keyboards with an indistinct tactile feedback and no sound. Analysis revealed that these two groups also showed different sensations and preferences with respect to several aspects of the touch and feel of keyboards. This result suggests that suppliers of computer keyboards should provide two kinds of keyboards, with distinct and indistinct tactile key switches, in order to satisfy as many users as possible.

Computer Peripherals↗
PubMed2006

Adaptive skeletal responses to mechanical loading during adolescence.

Adolescence, defined as the period between puberty and maturity, provides a 'window of opportunity' for positive skeletal adaptations to mechanical loading unlike any other period in life. Age-related bone loss highlights the importance of accumulating sufficient bone mass during formative years. Adolescents who regularly engage in weight-bearing mechanical loading appear advantaged in site-specific markers of bone mass. The positive influence of physical activity on bone mineral accrual during growth has been extensively studied; however, few studies have examined skeletal responses to mechanical loading during adolescence. Weight-bearing physical activity, particularly high-impact sports such as gymnastics, is recognised as being more osteogenic than weight-supported activities. Unilateral loading activities such as tennis or squash provide a direct comparison of skeletal response without sampling bias or genetic confounding. Intervention and longitudinal studies show evidence of positive skeletal adaptations; however, sustainability of skeletal advantages remains unclear. Limitations inherent with single-plane dual x-ray absorptiometry technology are well recognised. The integration of densitometric data with structural responses to mechanical loading using 3-dimensional imaging technologies such as peripheral quantitative computed tomography and magnetic resonance imaging appears vital to enhancing our understanding of adolescent musculoskeletal health.

Adolescent↗
PubMed2006

Image quality of a wet laser printer versus a paper printer for full-field digital mammograms.

OBJECTIVE: The purpose of our study was to compare the image quality of a wet laser printer with that of a paper printer for full-field digital mammography (FFDM). MATERIALS AND METHODS: For both a wet laser printer and a paper printer connected to an FFDM system, image quality parameters were evaluated using a standardized printer test image (luminance density, dynamic range). The detectability of standardized objects on a phantom was also evaluated. Furthermore, 640 mammograms of 80 patients with different breast tissue composition patterns were imaged with both printers. Subjective image quality parameters (brightness, contrast, and detection of details of anatomic structures-that is, skin, subcutis, musculature, glandular tissue, and fat), the detectability of breast lesions (mass, calcifications), and the diagnostic performance according to the BI-RADS classification were evaluated. RESULTS: Both the luminance density and the dynamic range were superior for the wet laser printer. More standardized objects were visible on the phantom imaged with the wet laser printer than with the paper printer (13/16 vs 11/16). Each subjective image quality parameter of the mammograms from the wet laser printer was rated superior to those of the paper printer. Significantly more breast lesions were detected on the wet laser printer images than on the paper printer images (masses, 13 vs 10; calcifications, 65 vs 48; p < 0.05). With the paper printer images, BI-RADS 4 and 5 categories were underestimated for 10 (43.5%) of 23 patients. CONCLUSION: For FFDM, images obtained from a wet laser printer show superior objective and subjective image quality compared with a paper printer. As a consequence, the paper printer should not be used for FFDM.

Adult↗
PubMed1995

The gray-scale ink-jet printer: value in making hard copies of digital images.

Referring physicians often are supplied with copies of images to illustrate a report of the findings of a radiologic study or so that the radiologist can retain the original images. The increasing costs of production, film, and recovery of chemicals have enhanced the requirement for a clean, low-cost dry printing process. An ink-jet gray-scale paper printer (Unitone, Scitex Medical Systems, Bedford, MA) can print high-quality (300 dots per inch [dpi]) images with an effective 10-bit gray scale range by using the Hertz continuous ink-jet method [1-3], which does not require the use of a darkroom or hazardous chemicals. Several types of media (matte paper, glossy paper, transparency film) with a printing area of 26.9 x 43.7 cm (10.6 x 17.4 inches) may be used. The consumables are approximately 50-70% less expensive than the cost of silver halide film, providing a cost advantage over film for referral and archival copies. The results of an initial evaluation of the ink-jet printer at our institution are reported here.

Computer Peripherals↗
PubMed2001

Remote sonographic interpretation using a laser printer network: system performance and diagnostic accuracy in actual clinical practice.

OBJECTIVE: The purpose of our study was to evaluate the technical and clinical performance of remote sonographic interpretation using a laser printer network connecting a community-based imaging center and an academic medical center. SUBJECTS AND METHODS: During a 3-month period, 161 consecutive sonographic examinations were performed at a community-based imaging center and all 161 patients were enrolled in the study. Seventy-one (44%) of 161 examinations were interpreted on-site at the community-based imaging center, and 90 (56%) of 161 were transmitted over a T-1 line to an academic medical center where the static images were interpreted remotely. For the purposes of this study, the examination time was defined as the interval from the time the technologist started to scan the patient to the time the patient was dismissed from the radiology department. Examination times were recorded for each patient. Follow-up was available for 92 (57%) of 161 studies. Sensitivity and specificity for studies interpreted at the community-based imaging center and at the academic medical center were calculated. RESULTS: The mean examination time for pelvic sonographic examinations interpreted at the academic medical center (43 min) was significantly longer than for scans interpreted at the community-based imaging center (31 min) (p < 0.01). However, no significant difference was noted in the examination time for abdominal sonography. For all examinations interpreted on-site at the community-based imaging center for which follow-up was available, the sensitivity and specificity were 95% and 100%, respectively. For all examinations interpreted remotely at the academic medical center for which follow-up was available, the sensitivity and specificity were 93% and 90%, respectively. No significant difference was seen in the sensitivity (p = 1.00) or specificity (p = 0.24) of studies interpreted on-site versus remotely. CONCLUSION: Static sonographic images can be interpreted remotely without loss of sensitivity, but with decreased specificity. However, more time must be allotted for performing pelvic sonography when these examinations are to be interpreted remotely.

Abdomen↗
PubMed2004

Prevention of trabecular bone loss in the mandible of ovariectomized rats.

The effect of therapeutic agents on trabecular bone loss in the mandible was investigated in ovariectomized rats. Eighty-seven Wistar SPF female rats were ovariectomized (OVX) or given a sham operation (Sham), and maintained on a diet containing 0.1% calcium. Four weeks later, groups of OVX rats were treated with estriol (E3), calcitonin (CT), etidronate, or 2-carboxyethylgermanium sesquioxide (Ge-132). The Basal group was maintained on a diet containing 1.0% calcium, and the OVX and sham groups on a diet containing 0.1% calcium. The trabecular bone mineral density (BMD) and trabecular bone mineral content (BMC) in 11 mandibular slices from 0.5 mm at the mesial margin of the first molar to 0.5 mm at the distal margin of the third molar, were measured using peripheral Quantitative Computed Tomography (pQCT). The BMD in the OVX group was lower than that in the Sham group, and decreased BMC was observed only in the molar region. BMD and BMC were increased in the etidronate-treated group, but only BMC was increased in the CT group. E3 treatment increased BMD and BMC; significant increases were also observed beneath the molar. Ge-132 treatment increased both BMD and BMC, especially the latter.

Animals↗
PubMed2004

Design features of alternative computer keyboards: a review of experimental data.

Design of computer keyboards no longer is limited to the flat keyboards that are typically shipped with personal computers. Keyboards now exist that are split into halves and these halves can be slanted away from each other (creating a triangle between the halves), sloped downward toward the visual display terminal, tilted upward like a tent, or simply separated. These design features are intended to alleviate discomfort and possible musculoskeletal disorders that have been suggested to be associated with the extensive use of conventional computer keyboards. The geometry of conventional keyboards requires the wrists to be in 10 degrees to 15 degrees of ulnar deviation and 20 degrees of extension and the forearms to be nearly fully pronated while typing. A review of the available experimental data collected on 10-digit touch typists indicates that (1) keyboards with a slant angle (half of the opening angle) of 10 degrees to 12.5 degrees or keyboards with halves separated to approximately shoulder width are both effective in placing the wrist in near neutral (0 degree) ulnar/radial deviation when typing, (2) wrist extension can be reduced to near neutral (0 degrees) when a keyboard with a negative slope of 7.5 degrees is used, contingent on the wrist rest also sloping with the keyboard, and (3) tilting the keyboard halves 20 degrees to 30 degrees is effective in reducing forearm pronation to approximately 45 degrees. These studies also indicate that experienced 10-digit touch typists readily adapt (within 10 minutes) to these individual alternative keyboard features, and can type with approximately the same speed and accuracy as with the conventional keyboard. While placing the wrist and forearm in a more neutral position could, in theory, reduce the incidence of musculoskeletal disorders, randomized controlled trials are necessary before strong recommendations can be made on the effectiveness of alternative keyboards for the prevention and/or treatment of musculoskeletal disorders. In the absence of these randomized controlled trials, the information in this article provides preliminary guidance to clinicians in their evaluation of computer keyboards and workstations and their recommendations to patients.

Computer Peripherals↗
PubMed2004

Computer use associated with poor long-term prognosis of conservatively managed lateral epicondylalgia.

STUDY DESIGN: Multicenter prospective design with a cohort of patients with lateral epicondylalgia commencing physical therapy. OBJECTIVE: To identify key factors associated with long-term prognosis of conservatively managed lateral epicondylalgia. BACKGROUND: The response to conservative management of lateral epicondylalgia is inconsistent and the rate of recovery varies widely among individuals. The reasons for these discrepancies are not understood. The identification of factors associated with prognosis will aid in the prediction of patient outcomes. METHODS AND MEASURES: Sixty patients with lateral epicondylalgia, recruited from 9 sports medicine clinics and 2 hospital outpatient physical therapy departments in Ontario, Canada, were followed for 6 months. A baseline clinical assessment was conducted on each participant using standard physical therapy techniques. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and a 100-mm pain visual analog scale (VAS) were completed at baseline and 6 months later. RESULTS: The key factor associated with both 6-month DASH and pain VAS scores was repetitive-work tasks (DASH, 9.8 [P < .011; pain VAS, 13.1 mm [P = .0105]). A subanalysis indicated that women were more likely than men to have cervical joint signs and, among women, positive cervical articular signs were also associated with higher final DASH and pain VAS scores. CONCLUSIONS: Although many of the participants identified sports activities as the cause of their injury, these findings emphasize the importance that a patient's work tasks can have on recovery of lateral epicondylalgia. This would suggest that management should perhaps focus on work stations, postures, and behaviors.

Adult↗
PubMed2004

Differences in measurements of lumbar curvature related to gender and low back pain.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To test the assumption that postural alignment and gender have a bearing on the specific type of low back pain (LBP) a person manifests. BACKGROUND: Measurements of static sagittal lumbar curvature are used by clinicians in the management of patients with LBP, but no investigator has reported differences in curvature related to specific categories of LBP. METHODS AND MEASURES: We used a computer-interfaced, 3-D, electromechanical digitizer to derive curvature angles for the region of the spine between T12-L1 and S2. Trained clinicians examined the subjects and determined their LBP diagnoses. We used t tests to examine differences in curvature between women and men, those with and those without LBP, and those in 4 different categories of LBP. We used chi2 to examine the relationship between gender and LBP category. RESULTS: Lumbar curvature angle (lordosis) was 13.2 degrees larger for women than for men (t = 6.74; P<.01). There was no difference in lumbar curvature between people with undifferentiated LBP and people without LBP. There were differences in lumbar curvature between people in various categories of LBP, for example, subjects in the lumbar-rotation-with-extension category had 8.4 degrees more lumbar curvature than subjects in the lumbar-rotation-with-flexion category (t = 2.16; P<.05). Based on the frequency distributions, there was a significant relationship between gender and LBP category (chi2 = 10.19; P<.01). CONCLUSIONS: Measurements of lumbar curvature should be expected to differ between men and women and may be related to different types of low back pain.

Adult↗