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Dominant/nondominant differences in bone mineral density (BMD) have been observed in the upper extremities. However for the proximal femur, the distinction between dominant and nondominant hips is not clear. The purpose of this study is to evaluate left/right variations in femoral BMD and hip axis length (HAL) in both single beam and fan beam dual x-ray absorptiometry (DXA) scans. A total of 36 women aged 41-76 years (average age 60 +/- 10 years) received single beam and fan beam DXA scans of both proximal femora with a Hologic QDR-2000 scanner. Femoral BMD and hip axis length were determined for each scan. Left/right and single beam/fan beam correlations were determined and differences were evaluated using a two-way analysis of variance. Femoral BMD at corresponding measurement regions in opposing femora were highly correlated (r = 0.81-0.96). No significant left/right differences were detected. At the femoral neck, the mean BMD difference (+/- standard deviation) was 1.5% +/- 4.7% in a single beam mode and -0.6% +/- 6.3% in fan beam mode. Though mean values of femoral BMD were equivalent, the observed individual left/right differences were occasionally large (as high as 26% in the femoral neck). The hip axis length of the left and right hips were highly correlated and statistically equivalent. However, hip axis length using fan beam was significantly larger (7.5%) than the single beam measurement with a larger observed variation. We conclude that measurement of a single proximal femur will usually be sufficient for clinical evaluation of BMD and/or hip axis length.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Though spinal and femoral measurements are typically preferred for evaluating skeletal density, an abundance of forearm data exists, primarily from single photon absorptiometry (SPA) devices. Most dual X-ray absorptiometry (DXA) scanners are capable of scanning the forearm and provide analysis tools to duplicate conventional SPA measurements. In this study, we have compared the radius density measurements from three commonly available densitometers: a Norland 278 SPA, a Lunar DPX-L, and a Hologic 1000/W. Radius bone mineral density (BMD) on the nondominant forearm was measured in 28 volunteers (21 women and 7 men) aged 24-78, with an average age of 51 +/- 17 years. Values were compared and regression relationships derived at corresponding measurement sites. SPA and DXA BMD values were found to be highly correlated (r = 0.99) with small standard errors (0.014 g/cm2-0.021 g/cm2), though significant absolute differences were observed at most measurement regions. Correlation slopes ranged from 0.85 to 1.04, with intercepts from 0.01 to 0.08 g/cm2. Using the resultant regression equations, SPA BMD values can be converted to DXA values with an expected error of roughly 3%. DXA BMD can also be interconverted between Lunar and Hologic with a similar expected error. In situations where this level of imprecision is acceptable, patient forearm measurements obtained on different systems can be interconverted. [ABSTRACT FROM AUTHOR]

Background:The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening.Methods:We measured if the relative risk of cervical cancer in younger women (20-29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20 yrs.Results:Cervical cancer incidence in women aged 20-29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30-39 was less steep (3.5%/year) but no significant rise was observed in women aged 40-49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results.Conclusion:The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25-29 years are recommended. [ABSTRACT FROM AUTHOR]

Many falls occur among older adults with no traditional risk factors. We examined potential independent effects of lifestyle on fall risk. Not smoking and going outdoors frequently or infrequently were independently associated with more falls, indicating lifestyle-related behavioral and environmental risk factors are important causes of falls in older women. Physical and lifestyle risk factors for falls and population attributable risks (PAR) were examined. We conducted a 4-year prospective study of 8,378 community-dwelling women (mean age = 71 years, SD = 3) enrolled in the Study of Osteoporotic Fractures. Data on number of falls were self-reported every 4 months. Fall rates were calculated (# falls/woman-years). Poisson regression was used to estimate relative risks (RR). Physical risk factors ( p ≤ 0.05 for all) included tall height (RR = 0.89 per 5 in.), dizziness (RR = 1.16), fear of falling (RR = 1.20), self-reported health decline (RR = 1.19), difficulty with Instrumental Activities of Daily Living (IADLs) (RR = 1.12, per item), fast usual-paced walking speed (RR = 1.18, per 2 SD), and use of antidepressants (RR = 1.20), benzodiazepines (RR = 1.11), or anticonvulsants (RR = 1.62). Protective physical factors ( p ≤ 0.05 for all) included good visual acuity (RR = 0.87, per 2 SD) and good balance (RR = 0.85 vs. poor). Lifestyle predicted fewer falls including current smoking (RR = 0.76), going outdoors at least twice weekly but not more than once a day (RR = 0.89 and vs. twice daily). High physical activity was associated with more falls but only among IADL impaired women. Five potentially modifiable physical risk factors had PAR ≥ 5%. Fall interventions addressing modifiable physical risk factors with PAR ≥ 5% while considering environmental/behavioral risk factors are indicated. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to examine the relationships of vitamin D supplementation and serum concentrations of vitamin D metabolites and parathyroid hormone (PTH) with neuromuscular function and falls in older community-dwelling women. Methods: We examined these relationships using a 4-year prospective multi-center study among 9,526 community-dwelling women enrolled in the Study of Osteoporotic Fractures (median age: 70 years; interquartile range: 67-75) and a subset of 389 women (97%) out of 400 who were randomly selected from the entire cohort for serum measures. Measurements included: vitamin D supplementation, serum 25-hydroxyvitamin D3 [25(OH)D3], serum 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and serum intact parathyroid hormone (iPTH); grip and quadriceps strength, chair-stand time, walking speed, reaction time, and balance-walk time (including changes in grip strength, chair-stand time, walking speed and balance-walk time over approximately 3.7 years); and incident fall rates (number of falls/woman-years). Results: In 9,526 women, vitamin D supplementation was not associated with any measures of neuromuscular function, change in neuromuscular function, or fall rates (p>0.01 for all). In a subgroup of 389 women, there was a trend of higher 25(OH)D3 concentration with slightly weaker grip strength (p=0.007), and women in the fourth quartile of 1,25(OH)2D3 had a faster chair-stand time (p=0.017) than women in the first quartile; still, in general, concentrations of 25(OH)D3, 1,25(OH)2D3, and iPTH were not associated with either neuromuscular function or changes in neuromuscular function (p>0.05 for all). However, higher 1,25(OH)2D3 concentration was associated with lower fall rates (p=0.039). Conclusions: Higher 1,25(OH)2D3 concentration is associated with a lower fall risk in older community-dwelling women, but vitamin D supplementation, and 25(OH)D3 and iPTH concentrations are not associated with either neuromuscular function or falls. [ABSTRACT FROM AUTHOR]

Introduction: Proximal femoral bone strength is not only a function of femoral bone mineral density (BMD), but also a function of the spatial distribution of bone mass intrinsic in structural geometric properties such as diameter, area, length, and angle of the femoral neck. Recent advancements in bone density measurement include software that can automatically calculate a variety of femoral structural variables that may be related to hip fracture risk. The purpose of this study was to compare femoral bone density, structure, and strength assessments obtained from dual-energy X-ray absorbtiometry (DXA) measurements in a group of women with and without hip fracture. Methods: DXA measurements of the proximal femur were obtained from 2,506 women 50 years of age or older, 365 with prior hip fracture and 2,141 controls. In addition to the conventional densitometry measurements, structural variables were determined using the Hip Strength Analysis program, including hip axis length (HAL), cross-sectional moment of inertia (CSMI), and the femur strength index (FSI) calculated as the ratio of estimated compressive yield strength of the femoral neck to the expected compressive stress of a fall on the greater trochanter. Results: Femoral neck BMD was significantly lower and HAL significantly higher in the fracture group compared with controls. Mean CSMI was not significantly different between fracture patients and controls after adjustment for BMD and HAL. FSI, after adjustment for T score and HAL, was significantly lower in the fracture group, consistent with a reduced capacity to withstand a fall without fracturing a hip. Conclusion: We conclude that BMD, HAL, and FSI are significant independent predictors of hip fracture. [ABSTRACT FROM AUTHOR]

PurposeTo describe the strategy used for large-scale ophthalmological monitoring in the clinical development of the novel anticancer agent gefitinib (‘Iressa’, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, which had demonstrated ocular effects in preclinical animal models.MethodsIn this extensive clinical trial programme, patients in Phase I and II trials underwent frequent and intensive ophthalmological monitoring at baseline and during the trials. Data were reviewed by an external independent Ophthalmology Advisory Board.ResultsOphthalmological data for 221 patients in Phase I trials of gefitinib and 425 patients in Phase II trials revealed no evidence of any consistent or drug-related ophthalmological toxicity. Interestingly, the baseline data revealed that, in an asymptomatic population, transient ophthalmological events are identified during monitoring.ConclusionsThis study reports the methodology and normative data in an ophthalmological screening programme that should prove useful for future studies.Eye (2005) 19, 729–738. doi:10.1038/sj.eye.6701630 Published online 28 January 2005 [ABSTRACT FROM AUTHOR]

This article describes the European DIMOND approach to defining reference levels (RLs) for radiation doses delivered to patients during two types of invasive cardiology procedures, namely coronary angiography (CA) and percutaneous transluminal coronary angioplasty (PTCA). Representative centres of six European countries recorded patients' doses in terms of dose-area product (DAP), fluoroscopy time and number of radiographic exposures, using X-ray equipment that has been subject to constancy testing. In addition, a DAP trigger level for cardiac procedures which should alert the operator to possible skin injury, was set to 300 Gyxcm2. The estimation of maximum skin dose was recommended in the event that a DAP trigger level was likely to be exceeded. The proposed RLs for CA and PTCA were for DAP 45 Gyxcm2 and 75 Gyxcm2, for fluoroscopy time 7.5 min and 17 min and for number of frames 1250 and 1300, respectively. The proposed RLs should be considered as a first approach to help in the optimisation of these procedures. More studies are required to establish certain "tolerances" from the proposed levels taking into account the complexity of the procedure and the patient's size. [ABSTRACT FROM AUTHOR]

Broccoli florets contain low levels of 3-methylsuphinylpropyl and 4-methylsulphinylbutyl glucosinolates. Following tissue disruption, these glucosinolates are hydrolysed to the corresponding isothiocyanates (ITCs), which have been associated with anticarcinogenic activity through a number of physiological mechanisms including the induction of phase II detoxification enzymes and apoptosis. In this paper, we describe the development of ITC-enriched broccoli through the introgression of three small segments of the genome of Brassica villosa, a wild relative of broccoli, each containing a quantitative trait locus (QTL), into a broccoli genetic background, via marker-assisted selection and analysis of glucosinolates in the florets of backcross populations. Epistatic and heterotic effects of these QTLs are described. The ITC-enriched broccoli had 80-times the ability to induce quinone reductase (a standard assay of phase II induction potential) when compared to standard commercial broccoli, due both to an increase in the precursor glucosinolates and a greater conversion of these into ITCs. [ABSTRACT FROM AUTHOR]

In the absence of reliable supplies of X-ray film, direct fluoroscopy is still extensively used in Albania, with chest radiology a particularly common application. This paper aims to quantify both patient skin dose and the risk-related quantity effective dose for direct fluoroscopy units based in seven different Albanian X-ray departments. A standard Quality Assurance (QA) protocol was used to assess tube potential accuracy, half value layer and X-ray tube output of these units. Three groups of X-ray beam parameters were defined from the QA results, covering the range of chest posteroanterior (PA) fluoroscopy technique factors seen during the study. Organ-equivalent doses were then measured for a nominal PA chest fluoroscopy examination using a Rando anthropomorphic phantom loaded with lithium fluoride thermoluminescent dosimeter chips. Normalised organ dose factors are listed for the three groups of beam conditions simulated. Using these factors, effective dose for the seven systems surveyed was found to be between 0.06 and 0.42 mSv for a 20 s PA chest fluoroscopy examination. Mean effective dose for this group of systems was 0.22 mSv which is a factor of 13 greater than mean effective dose for film/screen PA chest radiography in the UK, whereas entrance surface dose was a factor of 50 greater than the current EU reference level. [ABSTRACT FROM AUTHOR]

Many studies have shown the high correlation between Lunar and Hologic DXA bone mineral density (BMD) measurements despite differences in absolute calibration. However, in clinical practice, raw BMD values (in g/cm) are not normally used for assessing skeletal status and fracture risk. Instead, the BMD values are expressed in terms of the number of standard deviations above or below the young normal value (commonly referred to as the T-score). If the normative populations of the various systems are consistent, the standard deviation scores should also be consistent. For this reason, the World Health Organization (WHO) recently established diagnostic criteria for osteoporosis based on T-scores and not BMD. However, few studies have compared the instruments in terms of their standard deviation scores. In this study, we used linear regression to compare T-scores in 83 women at L1-4 and 120 women at the femoral neck obtained on a Lunar DPX and a Hologic QDR-1000/W system. Patient BMD and T-score measurements were highly correlated between the two systems ( r>0.95). No clinically significant difference in L1-4 T-scores was seen (less than 0.1 SD). However, linear regression analysis confirmed a systematic difference of 0.9 SD between the femoral neck T-scores. This discrepancy is caused by: (1) differences in the normal populations, and (2) differences in statistical models used to determine the young normal mean and standard deviation. In an attempt to correct the discrepancy, the female young normal mean and standard deviation were recalculated for the femoral neck using published epidemiological data from NHANES and existing DXA cross-calibration equations. The Hologic young normal value (mean ± SD) was redefined as 0.85±0.11 g/cm, while the Lunar value was redefined as 1.00±0.11 g/cm. When the femoral neck T-scores for the study population were recalculated on the basis of these new values, the results were equivalent between manufacturers, effectively eliminating the discrepancy. However, the revised values should be confirmed by additional measurements in young normal adults. [ABSTRACT FROM AUTHOR]

Dual-energy X-ray absorptiometry (DXA) has become the measurement of choice for multicenter trials with bone density endpoints. When performing DXA measurements with several different systems, it is important to implement a quality assurance program to guarantee that any observed density changes are real and not due to machine and/or operator variability. In this study, we present a series of procedures based on phantom measurements designed to monitor DXA instrument stability. Techniques for longitudinal evaluation of machine performance and cross-calibration of instruments are described. These procedures are then demonstrated using quality assurance data collected from a number of different DXA scanners. Together these methods provide a defined approach to instrument quality control. Though based primarily on the use of spinal phantoms, these procedures can be generalized for use in any multicenter DXA study. [ABSTRACT FROM AUTHOR]

Compared with white women, Asian women have about a 40%-50% and blacks a 50%-60% lower risk of hip fracture, but the reason for this racial difference is not known. Women with a shorter hip axis have a lower risk of hip fracture. To test the hypothesis that a shorter hip axis length could account for the lower risk of hip fracture among Asian and black women, we measured hip axis length in 135 Caucasian, 74 Asian and 50 black women. The mean hip axis lengths of Asian and black women were significantly shorter (1.2 and 0.7 standard deviations, respectively) than that of the whites ( p<0.0001). We estimate that, compared with white women, Asians would have a 47% lower risk (95% confidence interval: 32%-63%) and blacks would have a 32% (15%-45%) lower risk of hip fracture because of their shorter hip axis. We conclude that a shorter hip axis length might be a major factor accounting for Asian women's lower risk of hip fracture and might contribute to the lower risk in black women. [ABSTRACT FROM AUTHOR]

A concept for quality assurance (QA) in bone densitometry has been developed for clinical multicenter studies. Major elements provided by a coordinating center comprise (1) consulting services and certification of participating centers in the start-up phase of the study, (2) review of scan data acquired on QA standards for cross-calibration and longitudinal assessment of scanner stability, (3) review of selected patient data as well as of problem cases during the study, and (4) comprehensive review and correction of patient results based on QA data after conclusion of the study. Limitations of phantom-based QA data should be acknowledged. Typical problems encountered during research studies and guidelines for solutions are presented. Successful implementation of QA measures may yield substantial enhancement of statistical power. Depending on the study design and the variability of response within patient groups, improvement in precision due to QA measures may reduce the smallest detectable difference between subject groups or, alternatively, sample size by a few to more than 50%, and thus may contribute to a substantial reduction in study cost. Formulae for calculation of the magnitude of these effects are presented. To maximize the net benefit, QA efforts have to be limited to levels that assure reliability of the data at acceptable QA cost. While QA programs at individual clinical sites or for local practitioners may not need to be as extensive as for multicenter clinical trials, awareness of the potential problems and implementation of basic QA measures will help in obtaining high-quality bone densitometry results. [ABSTRACT FROM AUTHOR]

To assess the utility of quantitative ultrasound (QUS) of the heel for osteoporosis screening, we studied a group of 170 early postmenopausal women using both QUS of the heel and dual-energy X-ray absorptiometry (DXA) at the spine, hip, forearm, and whole body. On the basis of the linear regression results between QUS and DXA, a 95% bone mineral density (BMD) estimate confidence range was defined. Correlation coefficients between the QUS measurements and DXA ranged from 0.26 to 0.63. The confidence ranges for the estimated BMD based on a QUS measurement of the heel were large, such that an estimation of skeletal BMD at any of the DXA sites measured was not possible. For example, an estimate of the normative anteroposterior spine BMD (i.e. the T-score or the Z-score) based on a calcaneal ultrasound reading would have an error of ±1.9 standard deviations. Results for predicting the normative BMD of the other DXA regions were similar, with expected errors ranging from ±1.4 to ±2.0 standard deviations. We therefore conclude that QUS is not suited for the screening of early postmenopausal women for low axial or peripheral BMD. However, QUS may have a role as an independent predictor of fracture by measuring skeletal properties in addition to bone density. [ABSTRACT FROM AUTHOR]

Noninvasive measurements of bone mineral density allow the assessment of skeletal integrity, both centrally and peripherally, with high precision and accuracy and with relatively low radiation dose. When estimating skeletal status, it may be important to measure bone mineral density at more than one site to assess differential skeletal responses related to disease or therapy and to assess differential fracture risk. Due to technical differences between the various methods of bone mineral measurement, the quantitative results are typically expressed with differing calibration standards, such that direct comparisons must be carefully made. SPA measurements have been shown in several prospective studies to aid in the assessment of osteoporotic fracture risk. Limited data to date have shown spinal DPA to be at least comparable to peripheral SPA for fracture risk assessment, and current research with DXA indicates promising results for the X-ray-based bone densitometers. DXA has seen rapid growth in recent years, with current scanners able to measure the spine, hip, forearm and total body bone mineral density with a speed and precision previously unattainable with the isotope-based DPA systems. Longitudinal studies have shown QCT to be highly sensitive for detecting early and rapid bone loss and cross-sectional studies have shown QCT's capacity for separating normal and osteoporotic patient populations. though prospective studies are needed to confirm the latter result. QCT has the disadvantage of higher cost and radiation dose compared with the other methods currently in use, but it is the only noninvasive modality able preferentially to measure trabecular, cortical, or integral bone density at any skeletal site. All of the techniques in current clinical use, specifically SPA, DPA, DXA and QCT, represent major advances for the noninvasive measurement of bone mineral density at radiation doses significantly less than those due to yearly exposure from normal background radiation. [ABSTRACT FROM AUTHOR]

Quantitative computed tomography (QCT) has been shown to be a precise and sensitive method for evaluating spinal bone mineral density (BMD) and skeletal response to aging and therapy. Precise and accurate determination of BMD using QCT requires a calibration standard to compensate for and reduce the effects of beam-hardening artifacts and scanner drift. The first standards were based on dipotassium hydrogen phosphate (KHPO) solutions. Recently, several manufacturers have developed stable solid calibration standards based on calcium hydroxyapatite (CHA) in water-equivalent plastic. Due to differences in attenuating properties of the liquid and solid standards, the calibrated BMD values obtained with each system do not agree. In order to compare and interpret the results obtained on both systems, cross-calibration measurements were performed in phantoms and patients using the University of California San Francisco (UCSF) liquid standard and the Image Analysis (IA) solid standard on the UCSF GE 9800 CT scanner. From the phantom measurements, a highly linear relationship was found between the liquid- and solid-calibrated BMD values. No influence on the cross-calibration due to simulated variations in body size or vertebral fat content was seen, though a significant difference in the cross-calibration was observed between scans acquired at 80 and 140 kVp. From the patient measurements, a linear relationship between the liquid (UCSF) and solid (IA) calibrated values was derived for GE 9800 CT scanners at 80 kVp (IA=[1.15×UCSF]-7.32). The UCSF normative database for women and men obtained with the liquid standard was corrected for use with the solid standard. Proper procedures for cross-calibrating QCT measurements and the appropriate uses of normative data are discussed. [ABSTRACT FROM AUTHOR]

In this study, the cross-calibration of a fan beam DXA system (Hologic QDR-2000) to a pencil beam scanner from the same manufacturer (Hologic QDR-1000/W) is described. The scanners were calibrated by the manufacturer using the same anthropomorphic spine phantom at installation. To verify consistent machine calibration, a group of 69 female subjects, aged 46-75, had anteroposterior (AP) spine and proximal femur scans on the QDR-1000/W followed by pencil and array scans of the same sites on the QDR-2000 during the same visit. Many of the subjects had bilateral examinations of the proximal femur for a total of 123 hip scans. Pencil and array area, bone mineral content (BMC), and bone mineral density (BMD) from the QDR-2000 were compared with the values obtained on the QDR-1000/W, and linear regression equations were derived for relating the two instruments. At the spine, no differences were found between the QDR-1000/W BMD values and the QDR-2000 array BMD values. A slight difference between pencil beam modes was detected but was not deemed clinically significant. Linear regression models relating the QDR-2000 and QDR-1000/W AP spine BMD measurements showed correlation coefficients greater than 0.99, with slopes of 1.00, intercepts equivalent to zero, and small root mean square errors. Comparisons at the proximal femur showed equivalency at the femoral neck and trochanter regions for the two machines in pencil mode, but slight increases in BMC and BMD at the other femoral sites on the QDR-2000 in both pencil and array mode. Correlation coefficients were 0.97-0.99 for all measurement regions except for Ward's.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]