Long-term ovariectomy decreases ovine compact bone viscoelasticity.

Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low-amplitude 3-point bending at frequencies of 1-20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tandelta, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tandelta at low (6-12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long-term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA).

Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

Magnetization transfer MRI: application to treatment of middle cerebral artery occlusion in rat.

The temporal profiles of MRI parameters which use quantitative estimates of magnetization transfer were measured in 22 male Wistar rats subjected to middle cerebral artery occlusion, with and without therapeutic intervention with an anti-ICAM-1 monoclonal antibody. Two measures were used: the value of a magnetization transfer-related parameter in a predetermined region of interest, and the area of damage, as measured by changes in this parameter. In both groups, the value and area of damage of the inverse of the apparent forward transfer rate for magnetization transfer (1/k(fa)) significantly increased from the preischemic values (P < 0.05), as did T1 under an off-resonance partial saturation of the macromolecular pool (T1sat), and T1 (P < 0.05). Moreover, the increase in the value and total area of damage, as measured by 1/k(fa), T1, and T1sat in the treated group, was smaller compared to that of the untreated group, with significant differences detected between groups at 5, 24, and 48 hours. Our data suggest that a quantitative measure of MT may provide a sensitive and early method to detect the efficacy of therapeutic intervention in experimental stroke.

Predictive modeling techniques in prostate cancer.

A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.

Genetic adaptive neural network to predict biochemical failure after radical prostatectomy: a multi-institutional study.

BACKGROUND AND PURPOSE: Despite many new procedures, radical prostatectomy remains one of the commonest methods of treating clinically localized prostate cancer. Both from the physician's and the patient's point of view, it is important to have objective estimation of the likelihood of recurrence, which forms the foundation for treatment selection for an individual patient. Currently, it is difficult to predict the probability of biochemical recurrence (rising serum prostate specific antigen [PSA] concentration) in an individual patient, and approximately 30% of the patients do experience recurrence. Tools predicting the recurrence will be of immense practical utility in the treatment selection and planning follow up. We have utilized preoperative parameters through a computer based genetic adaptive neural network model to predict recurrence in such patients, which can help primary care physicians and urologists in making management recommendations. PATIENTS AND METHODS: Fourteen hundred patients who underwent radical prostatectomy at participating institutions form the subjects of this study. Demographic data such as age, race, preoperative PSA, systemic biopsy based staging and Gleason scores were used to construct a neural network model. This model simulated the functioning of a trained human mind and learned from the database. Once trained, it was used to predict the outcomes in new patients. RESULTS: The patients in this comprehensive database were representative of the average prostate cancer patients as seen in USA. Their mean age was 68.4 years, the mean PSA concentration before surgery was 11.6 ng/mL, and 67% patients had a Gleason sum of 5 to 7. The mean length of follow-up was 41.5 months. Eighty percent of the cancers were clinical stage T2 and 5% T3. In our series, 64% of patients had pathologically organ-confined cancer, 33% positive margins, and 14% had seminal vesicle invasion. Lymph node positive patients were not included in this series. Progression as judged by serum PSA was noted in 30.6%. With entry of a few routinely used parameters, the model could correctly predict recurrence in 76% of the patients in the validation set. The area under the curve was 0.831. The sensitivity was 85%, the specificity 74%, the positive predictive value 77%, and the negative predictive value of 83%. CONCLUSION: It was possible to predict PSA recurrence with a high accuracy (76%). Physicians desiring objective treatment counseling can use this model, and significant cost savings are anticipated because of appropriate treatment selection and patient-specific follow-up protocols. This technology can be extended to other treatments such as watchful waiting, external-beam radiation, and brachytherapy.

Randomized trial of parathyroidectomy in mild asymptomatic primary hyperparathyroidism: patient description and effects on the SF-36 health survey.

BACKGROUND: The treatment of patients with asymptomatic primary hyperparathyroidism remains controversial despite a National Institutes of Health consensus statement. This statement also recommended a randomized clinical trial because none exists to address this issue. METHODS: Informed consent was obtained from 53 asymptomatic patients with confirmed asymptomatic primary hyperparathyroidism who participated in this randomized trial of parathyroidectomy versus observation. Patients completed the SF-36 Health Survey, an instrument that measures wellness, every 6 months for 2 years. Average annual changes were compared. RESULTS: Fifty-three patients (42 female, 11 male) with asymptomatic, mild (serum calcium level, 10.1-11.5 mg/dL) asymptomatic primary hyperparathyroidism who agreed to participate were randomized into either a surgical group or an observation group. The mean calcium level was 10.31 mg/dL. The only demographic difference between groups was age, with the operative group being older (66.7 vs 62.6 years; P <.03). The scores on 2 of the 9 domains of the SF-36 were significantly different (P <.007 and <.012, respectively); both favored the operative group. CONCLUSIONS: Improved function is seen after parathyroidectomy when compared with patients who did not undergo operation. This study supports surgical management of mild primary hyperparathyroidism at the time of diagnosis because many patients have reversible nonclassic symptoms of the disease.

Femoral structure and stiffness in patients with femoral neck fracture.

Bone morphological characteristics may relate to the risk of hip fracture. We applied finite element modeling to radiologic data for two groups of women in vivo to address two questions: (a) Do individuals who have just sustained a femoral neck fracture exhibit reduced three-dimensional structural stiffness? and (b) Are victims of hip fracture disproportionately more susceptible to loads sustained in a fall than to stance-type loads? Ten white women (age: 64-76 years) who had just sustained a femoral neck fracture and 18 female volunteers (age: 65-76 years), matched as groups for race, age. and body mass index, were evaluated. From quantitative computed tomography scans, femoral morphometric and volumetric cancellous density measurements were obtained and a finite element model was constructed. Two load conditions were simulated: single-stance phase and lateral fall. Global stiffness values were determined for each model. The cancellous bone density was significantly lower at the femoral neck and the femoral neck and head diameters were significantly larger in the women in the fracture group than in those in the control group. The stiffness of the proximal femur did not differ significantly between the groups for either load condition. An apparently linear relationship was found for stiffness at stance load compared with stiffness at fall load (r = 0.84, p < 0.001). and slopes did not differ significantly between the groups. Although cancellous density was reduced at the fracture site in patients with femoral neck fractures. this did not result in a reduction in the predicted bone stiffness. Previous studies have established a very strong relationship between the stiffness and strength of bone. Since these modeling methods were thoroughly validated ex vivo, we conclude that although decreased bone density at the femoral neck may predict where fracture initiates, the risk of hip fracture per se may be more strongly dependent on issues such as the risk of falling and fall biomechanics than on the structural characteristics of bone.

Short term in vivo precision of proximal femoral finite element modeling.

As more therapies are introduced to treat osteoporosis, precise in vivo methods are needed to monitor response to therapy and to estimate the gains in bone strength that result from treatment. A method for evaluating the strength of the proximal femur was developed and its short term reproducibility, or precision, was determined in vivo. Ten volunteer subjects aged 51-62 years (mean 55.6 years), eight women and two men, were examined using a quantitative computed tomography (QCT) protocol. They were positioned, scanned, repositioned and re-scanned. The QCT images were registered in three-dimensional space, and finite element (FE) models were generated and processed to simulate a stance phase load configuration. Stiffness was computed from each FE model, and strength was computed using a regression equation between FE stiffness and fracture load for a small set (n = 6) of experimental specimens. The coefficients of variation (COV) and repeatability (COR= 2.23* 42*COV) were determined. The COV for the FE fracture load computed was 1.85%, and the detectable limit (coefficient of repeatability) for serial measurements was 5.85%. That is, if a change of 5.85% or more in computed FE fracture load is observed, it will be too large to be consistent with measurement variation, but instead can be interpreted as a real change in the strength of the bone. The detectable limit of this method makes it suitable for serial research studies on changes in femoral bone strength in vivo.

Bone density distribution and gender dominate femoral neck fracture risk predictors.

OBJECTIVE: To determine whether regional characteristics of the proximal femur could discriminate between a group of patients who had just sustained a first low-trauma femoral neck fracture (n=50) from a group of healthy volunteers (n=123). DESIGN: The application of an integral bone measurement (dual-energy X-ray absorptiometry) in conjunction with a volumetric cancellous bone density measurement (quantitative computed tomography) to the proximal femur in vivo provided an estimate of the contribution of the spatial distribution of bone density to hip fracture risk prediction. RESULTS: The primary finding of this study was a significant difference between male and female hip fracture risk predictor variables. In men with femoral neck fracture, a significant decrease in bone density throughout the proximal femur was observed. In women with femoral neck fracture, a combination of local bone deficits (significant decrease in cancellous bone at the site of fracture, and a decrease in cortical bone at the site of impact) and significantly larger proximal femur dimensions (femoral neck and head widths) was evident. CONCLUSIONS: These results imply that effective hip fracture prevention strategies may require separate approaches for men and women. Screening programs for diminished bone density at the proximal femur have proved effective in previous studies. An approach which includes examining these local bone characteristics may further improve our ability to accurately determine hip fracture risk in vivo.

Effect of vitamin D nutrition on parathyroid adenoma weight: pathogenetic and clinical implications.

In primary hyperparathyroidism, adenoma size is a major determinant of disease severity and manner of presentation, but the reason for the large variation in size (>100-fold) is unknown. One factor could be the level of vitamin D nutrition, because in India, where vitamin D deficiency is endemic, adenomas are larger and the disease more severe than in the U.S. Accordingly, we determined the relationship between vitamin D nutrition, as measured by serum levels of 25-hydroxyvitamin D (25OHD), and parathyroid gland weight, expressed on a logarithmic scale, in 148 U.S. patients with primary hyperparathyroidism. A significant inverse relationship was found between log gland weight as dependent variable and serum 25OHD as independent variable (r = -0.365; P < 0.0001). The only other influence on gland weight was a weak inverse correlation with age. Log gland weight as an independent variable was significantly related to adjusted calcium, PTH, and alkaline phosphatase (AP) as dependent variables. In 51 patients with serum 25OHD levels less than 15 ng/mL, gland weight, PTH, AP, and adjusted calcium were each significantly higher than in 97 patients with 25OHD levels of 15 ng/mL or more, but 1,25-dihydroxyvitamin D levels were similarly increased in both groups. In the former group the response of adjusted calcium to PTH was blunted, and the response of AP was enhanced, based on significant differences in regression slopes (P = 0.0004 and 0.0022, respectively). Suboptimal vitamin D nutrition stimulates parathyroid adenoma growth by a mechanism unrelated to hypocalcemia or 1,25-dihydroxyvitamin D deficiency and reduces the calcemic response to PTH, so that a higher PTH level and more parathyroid cells are needed to raise the patient's serum calcium to the level corresponding to the increased set-point that is characteristic of the disease. Improved vitamin D nutrition in the population is partly, perhaps largely, responsible for the historical changes in disease severity and manner of presentation that have occurred over the last 50 yr.

Magnetic resonance imaging indexes of therapeutic efficacy of recombinant tissue plasminogen activator treatment of rat at 1 and 4 hours after embolic stroke.

With use of magnetic resonance imaging (MRI), the effects of early and delayed treatment of embolic stroke in rat with recombinant tissue plasminogen activator (rt-PA) were investigated. Rats with embolic stroke were treated with rt-PA at 1 (n = 9) or 4 (n = 7) hours after stroke onset or were untreated (n = 15). Diffusion-weighted imaging, perfusion-weighted imaging, and T2-weighted imaging were performed before and after embolization from 1 hour to 7 days. No significant differences were detected in the relative areas with low cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), and T2 between the 4-hour treated group and the untreated group. Significant decreases in the average relative areas with low CBF were detected in the 1-hour treated group from 4 to 48 hours after embolization as compared with the untreated group. The increase in T2 in the 1-hour treated group was significantly lower than in the untreated and 4-hour treated groups. A significant increase in ADCw was detected in the 1-hour treated group at 3 and 24 hours after embolization as compared with the untreated and 4-hour treated groups. Secondary embolization was detected by both MRI and laser scanning confocal microscopy. The data suggest that MRI can detect the efficacy of rt-PA treatment and secondary ischemic damage.

Hearing loss as a complication of Paget's disease of bone.

Hearing loss has long been known to be a complication of Paget's disease of bone. Older ideas about the mechanisms of hearing loss are being replaced by a new view based on experimental evidence from patients. Studies reviewed show no evidence of auditory nerve dysfunction and confirm a cochlear site of lesion. A loss of bone mineral density in the cochlear capsule is associated with both a high-tone hearing loss and a low-tone air-bone gap.

T1 and magnetization transfer at 7 Tesla in acute ischemic infarct in the rat.

T1 and magnetization transfer at a field strength of 7 Tesla were used to discriminate between water accumulation and protein mobilization in tissue undergoing infarction. Twelve rats subjected to acute stroke via intralumenal suture occlusion of the middle cerebral artery, and 19 controls, were studied. In MRI studies to 6 hr post-ictus, serial data acquisition allowed the measurement of cerebral blood flow (CBF), apparent diffusion coefficient of water (ADCw), equilibrium magnetization (M0) and T1, and equilibrium magnetization and T1 under an off-resonance partial saturation of the macromolecular pool (Msat and T1sat). Using these parameters, the apparent forward transfer rate of magnetization between the free water proton pool and the macromolecular proton pool, k(fa), was calculated. Regions of interest (ROIs) were chosen using depressed areas in maps of the ADCw. T1 measurements in bovine serum albumin at 7T were not affected by the mobility of the macromolecular pool (P > 0.2), but magnetization transfer between free water and protein depended strongly on the mobility of the macromolecular pool (P < 0.001). For 6 hr after ictus, k(fa) uniformly and strongly decreased in the region of the infarct (P < 0.0001). Ratios (ischemic/non-ischemic) of parameters M0, Msat, T1, and T1sat all uniformly and strongly increased in the infarct. The ratio T1/T1sat in the region of infarction showed that a progressive accumulation of free water in the region of interest was the major (>80%) contribution to the decrease in k(fa). There also existed a small contribution due to changes at the water-macromolecular interface, possibly due to proteolysis (P = 0.005).

Dialysate iron therapy: infusion of soluble ferric pyrophosphate via the dialysate during hemodialysis.

BACKGROUND: Soluble iron salts are toxic for parenteral administration because free iron catalyzes free radical generation. Pyrophosphate strongly complexes iron and enhances iron transport between transferrin, ferritin, and tissues. Hemodialysis patients need iron to replenish ongoing losses. We evaluated the short-term safety and efficacy of infusing soluble ferric pyrophosphate by dialysate. METHODS: Maintenance hemodialysis patients receiving erythropoietin were stabilized on regular doses of intravenous (i.v.) iron dextran after oral iron supplements were discontinued. During the treatment phase, 10 patients received ferric pyrophosphate via hemodialysis as monthly dialysate iron concentrations were progressively increased from 2, 4, 8, to 12 micrograms/dl and were then sustained for two additional months at 12 micrograms/dl (dialysate iron group); 11 control patients were continued on i.v. iron dextran (i.v. iron group). RESULTS: Hemoglobin, serum iron parameters, and the erythropoietin dose did not change significantly from month 0 to month 6, both within and between the two groups. The weekly dose of i.v. iron (mean +/- SD) needed to maintain iron balance during month 6 was 56 +/- 37 mg in the i.v. iron group compared with 10 +/- 23 mg in the dialysate iron group (P = 0.001). Intravenous iron was required by all 11 patients in the i.v. iron group compared with only 2 of the 10 patients receiving 12 micrograms/dl dialysate iron. The incidence of adverse effects was similar in both groups. CONCLUSIONS: Slow infusion of soluble iron pyrophosphate by hemodialysis may be a safe and effective alternative to the i.v. administration of colloidal iron dextran in maintenance hemodialysis patients.

Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of middle cerebral artery embolic stroke and recombinant tissue plasminogen activator intervention in the rat.

Thrombolysis of embolic stroke in the rat was measured using diffusion (DWI)-, T2 (T2WI)-, and perfusion (PWI)-weighted magnetic resonance imaging (MRI). An embolus was placed at the origin of the middle cerebral artery (MCA) by injection of an autologous single blood clot via an intraluminal catheter placed in the intracranial segment of internal carotid artery. Rats were treated with a recombinant tissue plasminogen activator (rt-PA) 1 hour after embolization (n = 9) or were not treated (n = 15). Diffusion-weighted imaging, T2WI, and PWI were performed before, during, and after embolization from 1 hour to 7 days. After embolization in both rt-PA-treated and control animals, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) in the ischemic region significantly declined from the preischemic control values (P < 0.001). However, mean CBF and ADCw in the rt-PA-treated group was elevated early after administration of rt-PA compared with the untreated control group, and significant differences between the two groups were detected in CBF (24 hours after embolization, P < 0.05) and ADCw (3, 4, and 24 hours after embolization, P < 0.05). T2 values maximized at 24 (control group, P < 0.001) or 48 hours (treated group, P < 0.01) after embolization. The increase in T2 in the control group was significantly higher at 24 hours and 168 hours than in the rt-PA-treated group (P < 0.05). Significant correlations (r > or = 0.80, P < 0.05) were found between lesion volume measured 1 week after embolization and CBF and ADCw obtained 1 hour after injection of rt-PA. Within a coronal section of brain, MRI cluster analysis, which combines ADCw and T2 data maps, indicated a significant reduction (P < 0.05) in the lesion 24 hours after thrombolysis compared with nontreated animals. These data demonstrate that the values for CBF and ADCw obtained 1 hour after injection of rt-PA correlate with histologic outcome in the tissue, and that the beneficial effect of thrombolysis of an intracranial embolus by means of rt-PA is reflected in an increase of CBF and ADCw, a reduction in the increase of T2, and a reduction of the ischemic lesion size measured using MRI cluster analysis.

Diffusion, perfusion, and T2 magnetic resonance imaging of anti-intercellular adhesion molecule 1 antibody treatment of transient middle cerebral artery occlusion in rat.

The effect of anti-intercellular adhesion molecule-1 (anti-ICAM-1) antibody treatment of transient (2 h) middle cerebral artery (MCA) occlusion in the rat was measured using diffusion (DWI)-, T2 (T2I)- and perfusion (PWI)-weighted magnetic resonance imaging. Rats were treated upon reperfusion with an anti-ICAM-1 monoclonal antibody (n=11) or a control antibody (n=7). DWI, T2I and PWI were performed before, during, and after induction of focal cerebral ischemia from 1 h to 7 days. In both groups, the apparent diffusion coefficient of water (ADCw) and cerebral blood flow (CBF) values in the ischemic region significantly declined from the preischemic ADCw values (p<0. 05). The post ischemic increase in T2 of the control group was significantly higher at 48 h than in the anti-ICAM-1 treated group (p<0.05). CBF was not significantly different between the two groups. The temporal profiles of MRI cluster analysis, which combines ADCw and T2 maps into a single image, was significantly different between groups. These data suggest that the neuroprotective effect of anti-ICAM-1 antibody treatment is reflected in reductions of T2 and lesion growth during reperfusion and may not be associated with increased cerebral perfusion.

Ethnic differences in the prevalence of asthma in middle class children.

BACKGROUND: Studies have shown a higher prevalence of asthma among boys compared with girls and in blacks compared with whites, but it has been difficult to separate socioeconomic from racial effects because the blacks in the studied populations were more likely to have low socioeconomic status. OBJECTIVE: To compare the prevalence of asthma in a socioeconomically homogeneous, middle class, multiethnic population of schoolchildren. METHODS: Based on a telephone survey of all families of third-graders in Southfield, Michigan, we ascertained the prevalence of physician-diagnosed asthma and probable undiagnosed asthma. One reason Southfield was chosen for study was because the city comprises an integrated middle class population with only 4% blacks and 7% whites having incomes below federal poverty limits. RESULTS: The lifetime prevalence of asthma was 9.5% (12% for blacks and 6% for whites) and higher in boys (14%) than girls (5%), a pattern that was reflected in period prevalence estimates. The lifetime prevalence of probable undiagnosed asthma was greater in blacks (16.6%) than whites (10.8%), with little sex difference. Adjusting for sex and maternal education, the prevalence of physician-diagnosed asthma and probable asthma were associated independently with black ethnicity. CONCLUSIONS: Our study is unique in the similarity of the black and white families' socioeconomic status and residence in the same middle class community. Since access to medical care and macro-environmental conditions were similar across this study population, our results are consistent with the hypothesis that differences in biologic factors between blacks and whites and boys and girls play a role in asthma risk.

Predictive value of proximal femoral bone densitometry in determining local orthogonal material properties.

Models which are based on non-invasive bone measurements may in the future be able to successfully identify individual subjects at an increased risk for hip fracture; thus, we designed a study to determine the usefulness of dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) in predicting the local material properties of human proximal femoral cancellous bone. There has been some disagreement in the scientific literature regarding appropriate predictive models for local material properties of cancellous bone. We sought to confirm that density-mechanical property relationships were consistent from subject to subject, and that three-dimensional QCT measurements were stronger predictors of mechanical properties than two-dimensional DXA results. Linear and power fit relationships between these densitometric measures and material properties were also examined to determine which were more appropriate. Bone cubes from specific regions of highly oriented trabeculae were analyzed separately to determine if cube orientation had an effect on mechanical properties independent of bone density. Ten pairs of ex vivo femurs (five male, five female; age 30-93, mean age 62) were prepared such that specific anatomic planes were visible radiographically. Both QCT and DXA measurements were made on all 20 femurs. Cancellous bone cubes were obtained proceeding along two distinct directions from the proximal end of each femur pair. Unexpectedly, the density-modulus relationships among these ten donors were found to be significantly different at p <0.01 (83 percent of the tests were different at p <0.0001). Density-strength regressions were also significantly different at p <0.01, but this effect was not as consistent nor as statistically significant. In general, the QCT method did not produce predictions of local cancellous bone material properties superior to the DXA method. The linear and power fit models appeared to produce consistent results, with neither being obviously more advantageous. These density measurements explained at best 30-40 percent of the variance in modulus and 50-60 percent of the variance in ultimate stress. The orientation of cancellous cubes in the principal compressive trabeculae region was a significant contributor to mechanical properties (p= 0.0001) independent of bone density. This finding was not as dramatic in the femoral neck cancellous bone region.

The impact of an ambulatory rotation on medical student interest in internal medicine. The Society of General Internal Medicine Task Force on Career Choice in Internal Medicine.

OBJECTIVE: To determine whether students who take ambulatory rotations in internal medicine are more likely to choose internal medicine careers. DESIGN: National survey. SETTING AND PARTICIPANTS: The intended sample was 1,650 senior U.S. medical students from 16 medical schools, of whom 1,244 (76%) responded. Representative schools nationwide were selected using a stratified, random-sampling method. MEASUREMENTS: The questionnaire asked about characteristics of the ambulatory rotation, perceptions of internal medicine, and factors influencing students toward or away from an internal medicine career. RESULTS: Ambulatory rotations were taken by 543 students (43%). Of these rotations, 73% were required, 74% were during the fourth year, 77% were in general internal medicine, 73% provided continuity of care, and 19% were during the medicine clerkship. Overall, 24% of the students chose careers in general (9%) or subspecialty internal medicine (15%). Thirty percent of the students who did ambulatory rotations planned internal medicine careers, compared with 19% of the students who had no rotation [odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.3 to 2.4, p = 0.0001]. This association was of similar magnitudes for students completing required rotations (OR = 1.6, 95% CI 1.2 to 2.2, p = 0.002) and for students completing rotations before or in proximity to when they chose careers (OR = 1.7, 95% CI 1.1 to 2.4, p = 0.01). Ninety percent of the 543 students who had ambulatory rotations were satisfied with the experience. Thirty-eight percent of the highly satisfied students chose internal medicine careers, compared with 21% of the students who had low or moderate satisfaction (p = 0.0001). CONCLUSIONS: An ambulatory rotation is strongly associated with positive perceptions of, attraction to, and choice of a career in internal medicine. Research is needed to determine specific components of an effective rotation. Further development of ambulatory rotations could help attract more students to internal medicine.

Relationship between physician specialty and the selection and outcome of ischemic stroke patients.

OBJECTIVE: This study compares the initial characteristics, in-hospital treatment, and outcomes of stroke patients managed by neurologists versus non-neurologists. DATA SOURCES/STUDY SETTING: An inception cohort of 146 patients hospitalized with their first stroke at a private, a university, or a Veterans Affairs hospital. STUDY DESIGN: A prospective, hospital-based, multisite cohort study design is used to ascertain the patients' initial 180-day in-hospital and postdischarge experience. DATA COLLECTION/EXTRACTION METHODS: Data were collected on patient demographics, disease severity, and risk factors for stroke; diagnostic tests and pharmacologic management; one-month and six-month all-cause and cause-specific mortality; and physical and functional impairment. PRINCIPAL FINDINGS: The 88 patients (60 percent) admitted to the neurology services of the study hospitals had better prognostic profiles, i.e., lower likelihood of having either completed stroke or cardiac comorbidity, and were less likely to die within one and six months of stroke onset. CONCLUSIONS: Substantial systematic differences in the types of patients managed by neurologists versus other specialists may preclude comparison of outcomes of care.