Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm²) while underestimating the value at the higher value (1.5 g/cm²). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.     

A simple nutrition screening tool for hemodialysis nurses.

OBJECTIVE: To assess the reliability of a nurse-performed nutrition screening tool (NST) for hemodialysis (HD) patients to identify nutritionally at-risk patients. DESIGN: Tool reliability assessment. SETTING AND PARTICIPANTS: The setting was nine non-hospital private (n = 3) and public (n = 6) HD units in Australia (two rural and seven metropolitan). Participants were 112 HD patients. RESULTS: A total of 112 HD patients (male = 65, female = 47) from 9 non-hospital HD units in Australia (seven metropolitan and two rural) were screened with the NST and the outcome of dietitian referral compared with Standard Dietitians Assessment. The mean age of patients was 57.6 years. Overall, the NST showed a sensitivity of 0.84 (range, 0.71 to 0.94; P < .05) and a specificity of 0.9 (range, 0.82 to 0.98; P < .05). The NST was more sensitive (sensitivity, 0.93 [range, 0.87 to 0.99; P < .05]) and was more specific for men (specificity, 0.92 [range, 0.85 to 0.99; P < .05]). Specificity was very strong in metropolitan patients (specificity, 0.94 [range, 0.87 to 1.01; P < .05]). CONCLUSIONS: The tool was more sensitive and specific than the NST previously reported by the same investigators. The tool is particularly specific in that it screens those patients not requiring dietitian intervention. The use of this tool may benefit HD units that do not have on-site or regular dietetic support to prioritize patients needing dietitian intervention.     

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

Comparison of the detection of subtle changes in myocardial regional systolic function using qualitative and semi-quantitative techniques.

PURPOSE: To evaluate qualitative wall motion assessment vs. quantitative wall thickening for the assessment of subtle changes in myocardial systolic function using cine MRI. METHODS: Cine MR images were obtained in 5 canines with a significant coronary artery stenosis and in 2 controls on a 1.5T scanner. Qualitative results were obtained using a numerical scoring system; quantitative analysis was performed using a semi-automatic segmentation program. The techniques were matched and compared using Spearman correlations. RESULTS: All correlations in the experimental group revealed significant but weak to moderate relationships between the qualitative and quantitative results (e.g., at-risk tissue rho = 0.363, p < 0.0001; remote tissue rho = 0.275, p = 0.0002), with each identifying changes in regional function that ensued following creation of the stenosis. Intra-observer variability was reasonable in both methods when repeat analysis on a subset of the data was performed, with both techniques showing a significant correlation between the repeated measurements (quantitative - rho = 0.52, p < 0.0001; qualitative - rho = 0.54, p < 0.0001). CONCLUSION: Both methods were able to detect very limited wall motion abnormalities present in the canines with significant stenosis and either method gives comparable results.     

Visual acuity with reversed-contrast charts: I. Theoretical and psychophysical investigations.

When the contrast polarity of a visual acuity chart is reversed by using bright letters on a dark background instead of dark on light, the shape and height of the resolution feature in the retinal image is identical but inverted compared with the normal situation. However, the contrast is different in the two cases because the background light level, which is a dividing factor when contrast is calculated, is much less when only the letters are bright. To the extent that contrast is a limiting factor in visual acuity, reversed-contrast acuity would be expected to be better, and proportionally more so in eyes where light scatter and aberrations widen and flatten the point-spread function. In a careful psychophysical study of Landolt C resolution, the minimum angle of resolution was found to be significantly smaller for white letters on a dark background than for the traditional dark on bright situation.     

Persistent Low-frequency Spontaneous Discharge in A-fiber and C-fiber Primary Afferent Neurons during an Inflammatory Pain Condition

Background: Primary afferent nociceptor sensitization and its accompanying spontaneous discharge are believed to be the proximate cause of the spontaneous pain and hypersensitivity that follow an acute tissue injury. Evidence for this comes almost entirely from studies limited to the first few minutes to an hour or two after injury, when the inflammatory reaction to injury has just begun. However, there is evidence that inflammatory pain mechanisms differ from acute pain mechanisms and that the mechanisms that drive and modulate inflammatory pain may evolve over time.

Methods: The authors surveyed spontaneous afferent discharge in rats with hind paw inflammation evoked by complete Freund adjuvant over the entire 14 days of the inflammatory pain condition, as determined in parallel experiments assessing allodynia and hyperalgesia.

Results: Inflammation-evoked heat hyperalgesia, mechanoallodynia, and mechanohyperalgesia began within hours, persisted until at least day 7, and resolved by day 14. A large percentage (23%) of A fibers had spontaneous discharge 2 days after inflammation, but the incidence was much reduced (to 7-9%) by 7 and 14 days. At all times, the A-fiber discharge frequency was low (<3.0 Hz) or very low (<0.3 Hz). A large percentage (24%) of C fibers had spontaneous discharge 2 and 7 days after inflammation, but this also declined to near control levels by day 14; C-fiber discharge frequency was also always low (most at 0.3-1.0 Hz).