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.     

Traumatic injuries associated with horseback riding.

BACKGROUND: According to the Center for Disease Control and Prevention (CDC), an estimated 30 million people ride horses each year in the United States. Horseback riding related injuries are common, with an estimated 50,000 emergency room visits annually. The popularity of recreational horseback riding has increased in South Florida and the incidence of associated traumatic injuries is a reflection of this. MATERIAL AND METHODS: Retrospective review of patients admitted to a state designated Level I trauma center that sustained horseback riding associated injuries between January 2000 and December 2003. Information extracted from the Trauma Center's data base included demographics, mechanism of injury and toxicology screening. RESULTS: During the review period, twenty-seven patients were identified. There were 12 men and 15 women. The average age was 36 years. The injuries occurred during pleasure riding in 23 patients and thoroughbred related activities in 4 patients. Multiple severe injuries were common and documented in 24 patients. All patients required hospitalization with an average stay of 5 days. Five patients had a positive toxicology screen on admission. No deaths were documented in this review. CONCLUSION: Horseback riding related injuries tends to be serious. Alcohol and recreational drugs may contribute to exacerbate the extent of these injuries. The use of proper protective equipment, instructions for safe riding, and discouraging drug and alcohol use during riding activities should be emphasized.     

Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity.

The intracellular pathway of human angiogenin incalf pulmonary artery endothelial (CPAE) cells has been studied byimmunofluorescence microscopy. Proliferating CPAE cells specifically endocytosenative angiogenin and translocate it to the nucleus, where it accumulates in thenucleoli. Nuclear translocation of angiogenin does not occur innonproliferative, confluent CPAE cells. These cells were previously found toexpress an angiogenin-binding protein (AngBP) that was identified as smoothmuscle alpha-actin. Exogenous actin, an anti-actin antibody, heparin, andheparinase treatment all inhibit the internalization of angiogenin, suggestingthe involvement of cell surface AngBP/actin and heparan sulfate proteoglycans inthis process. It has been established that two regions of angiogenin areessential for its angiogenic activity, one is its endothelial cell binding siteand the other its catalytic site capable of cleaving RNA. CPAE cells do notinternalize four enzymatically active angiogenin derivatives whose cell bindingsite is modified, but they do internalize two enzymatically inactive mutantswhose cell binding site is intact. Thus, the putative cell binding site ofangiogenin is necessary for both endocytosis and nuclear translocation, but thecatalytic site is not. Three other angiogenic molecules are also translocated tothe nucleus of growing CPAE cells. Overall, the results suggest that nucleartranslocation of angiogenin and other angiogenic molecules is a critical step inthe process of angiogenesis.     

Bacterial meningitis in the first three months of life.

A retrospective study of infants with bacterial meningitis admitted to our hospital during 1949-52, highlighted the lack of ''classical'' signs of meningitis in these infants. We carried out a similar review of 44 infants aged less than three months, admitted during 1982-91. We also determined the causative organisms and their antibiotic sensitivities. Symptoms and signs were similar in the two series. Forty infants in the later series were either febrile, irritable or had seizures on the day of admission. Overall mortality fell from 30% to 11%. Between 1982 and 1991 Group B Streptocococcus and Neisseria meningitidis were the commonest causes of meningitis. All organisms, except one, were sensitive to ampicillin and/or cefotaxime. Bacterial meningitis should be suspected in young infants who are febrile, irritable or having seizures. Initial treatment with ampicillin and cefotaxime is appropriate.     

Relationship between respiratory symptoms and cough receptor sensitivity.

The relationship was studied between preschool and current respiratory symptoms and cough receptor sensitivity in children. Forty six white children aged 7 years were investigated. They were divided into three groups: (i) healthy children; (ii) children with a history of idiopathic cough; and (iii) children with a history of wheezing. Cough receptor sensitivity was assessed by the inhalation of serially increasing concentrations of nebulised citric acid. The concentration which first induced a cough was the cough threshold and was taken as a measure of cough receptor sensitivity. The cough threshold was unrelated to respiratory symptoms, bronchial responsiveness, parental smoking, and atopic status. A wide variation in cough threshold was seen. Although these results suggest that idiopathic cough is unrelated to cough receptor sensitivity as assessed by the citric acid cough threshold, it is unclear whether threshold measurements are an accurate reflection of receptor sensitivity.     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.