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.     

Distribution and kinetics of 3-O-methyl-6-[18F]fluoro-L-dopa in the rhesus monkey brain

Most attempts to model accurately [18F]-DOPA imaging of the dopamine system are based on the assumptions that its main peripheral metabolite, 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]3-OM-DOPA), crosses the blood-brain barrier but is present as a homogenous distribution throughout the brain, in part because it is not converted into [18F]DOPA in significant quantities. These assumptions were based mainly on data in rodents. Little information is available in the primate. To verify the accuracy of the above assumptions, we administered 18F-labeled 3-OM-DOPA to normal rhesus monkeys and animals with lesions of the DA nigrostriatal system. No selective 18F regional accumulation in brain was apparent in normal or lesioned animals. The plasma metabolite analysis revealed that only the negatively charged metabolites (e.g., sulfated conjugates) that do not cross the blood-brain barrier were found in significant quantities in the plasma. A one-compartment, three-parameter model was adequate to describe the kinetics of [18F]3-OM-DOPA. In conclusion, assumptions concerning [18F]3-OM-DOPA's behavior in brain appear acceptable for [18F]DOPA modeling purposes.     

Trust, but verify. The accuracy of references in four anesthesia journals.

To determine the accuracy of bibliographic citation in the anesthesia literature, we reviewed all 1988 volumes of ANESTHESIOLOGY, Anesthesia and Analgesia, British Journal of Anaesthesia, and Canadian Journal of Anaesthesia and sequentially numbered all references appearing in that year (n = 22,748). One hundred references from each of the four journals were randomly selected. After citations to nonjournal articles (i.e., books or book chapters) were excluded, the remaining 348 citations were analyzed in detail. Six standard bibliographic elements--authors' names, article title, journal title, volume number, page numbers, and year--were examined in each selected reference. Primary sources were reviewed, unless our institution did not own the source or could not obtain it through interlibrary loan, in which case standard indexes, abstracting services, and computerized databases were consulted. Each element was checked for accuracy, and references were classified as either correct or incorrect. A reference was correct if each element of the citation was identical to its source. Of the examined references, more than half (50.3%) contained an error in at least one element. The elements most likely to be inaccurate were, in descending order, article title, author, page numbers, journal title, volume number, and year. No significant differences (P = 0.283) existed in the error rates of the four journals; the percentage of citations containing at least one error ranged from 44% (Anesthesia and Analgesia) to 56% (British Journal of Anaesthesia). The citation error rate of anesthesia journals is similar to that reported in other specialties, where error rates ranging from 38% to 54% have been documented.     

Pulmonary artery catheterization: a modified technique

A modified technique for catheterization of the pulmonary artery was developed. It involves the passage of a tapered, movable-core, J-tipped guide wire across the right ventricle into the pulmonary artery followed by the advancement of a straightened Grollman pigtail catheter. The technique was successful in 34 of 34 pulmonary artery catheterizations. The method avoids prolonged catheter manipulation within the right ventricle. In addition, since the catheter does not cross the tricuspid valve until the guide wire has been advanced, the occasional complication of the pigtail "hooking" on a tricuspid valve leaflet or chordae tendineae during catheter withdrawal and manipulation is prevented.     

A reassessment of the role of arteriography in penetrating proximity extremity trauma: a prospective study

Penetrating proximity extremity trauma (PPET) was prospectively studied to clarify the role of routine arteriographic evaluation (AG). Over a 24-month period, 135 patients were identified with 152 injuries from PPET. All patients underwent AG and were randomized to either immediate or delayed timing. There were 27 arteriographic abnormalities from these 152 wounds, of which 16 (10.5%) were in major arteries. One acute arteriovenous fistula underwent immediate surgery. The remaining 15 major vessel injuries were nonoperatively observed, including seven cases of segmental arterial narrowing, six intimal flaps, and two small pseudoaneurysms (one of which enlarged and underwent surgical repair after 10 weeks of followup). Nine of the remaining 14 lesions resolved; two improved and three remained clinically unchanged over a mean followup interval of 2.7 months. Shotgun trauma was the mechanism which carried the greatest risk of significant vascular injury. Although "soft" clinical signs were significantly more predictive of vascular injury following PPET than proximity alone (p less than 0.0005), 50% of all injuries to major arteries did not manifest soft signs. No extremity morbidity resulted from delayed AG or from vascular injury management. We conclude from our study population: 1) the natural history of clinically occult arterial injuries was predominantly benign; 2) AG could be safely delayed up to 24 hours; 3) "soft" signs were not clinically useful predictors of vascular injury; and 4) with the exception of shotgun wounds, AG did not appear to be a cost effective screening modality, since detection of a single vascular injury requiring surgery cost $66,420.00.     

Acute lymphocytosis after trauma--early recognition of the high-risk patient?

An absolute lymphocyte count is included in the routine results provided by most automated blood cell counters, providing a prompt indication of peripheral blood lymphocytosis. Transient lymphocytosis is seen in many acutely ill patients, including those with multiple injuries. We have observed a significantly higher death rate among trauma patients with lymphocytosis at presentation; patients with lymphocytosis, on subsequent assessment of injury, proved to have higher Injury Severity Scores than those without lymphocytosis. Investigation of lymphocyte subsets in nine patients with lymphocytosis showed an increase in T cells, reversal of the CD4:CD8 ratio, and, in seven patients, an increase in "natural killer" cells. The presence of lymphocytosis and its early detection as part of a routine blood count may supply a readily available means of identifying a high-risk trauma patient.     

Oligoclonal analysis of the atopic T cell response to the group 1 allergen of Cynodon dactylon (bermuda grass) pollen: pre- and post-allergen-specific immunotherapy

BACKGROUND: Bermuda grass pollen (BGP) is an increasingly important seasonal aeroallergen in Australia and other subtropical and temperate regions. BGP shares minimal allergenic cross-reactivity with pollens of rye grass or other Pooideae grasses often used for desensitization regimens in grass pollen allergy. Current allergen immunotherapy is seldom used in asthmatic patients due to IgE-mediated side effects. Since clinically effective immunotherapy is linked with altered allergen-specific T cell response, characterisation of human T cell reactivity to Cyn d 1, the major B cell allergen of BGP, should permit the design of effective and safe immunotherapy for BGP allergy. METHODS: Short-term BGP-specific CD4+ T cell lines were established from peripheral blood of 14 BGP-sensitive patients before and after conventional 50% BGP and 50% 7-grass mix subcutaneous specific allergen immunotherapy (SIT). T cell diversity of antigen specificity and function was assessed by proliferation and cytokine production to BGP, Cyn d 1 and Cyn d 1 peptides. RESULTS: Three highly immunogenic regions of Cyn d 1 were identified in 13/14 patients pre-SIT: Cyn d 1 (109-128), (181-209) and (217-241). The SIT regimen was clinically efficacious. Following SIT, decreased proliferation to BGP, Cyn d 1 and Cyn d 1 peptides was observed with a marked decrease in the IL-5:IFN-gamma ratio. CONCLUSIONS: Cyn d 1 is a major T cell allergen of BGP. Decreased Cyn d 1-specific IL-5 dominant T cell responses were observed in association with clinically effective treatment with the 50% BGP and 50% 7-grass mix. Identified dominant T cell regions of Cyn d 1 should facilitate safer vaccine development for BGP-induced asthma in addition to rhinitis.     

Antibodies against listerial protein 60 act as an opsonin for phagocytosis of Listeria monocytogenes by human dendritic cells

Human-monocyte-derived dendritic cells (MoDC) are very efficient in the uptake of Listeria monocytogenes, a gram-positive bacterium which is an important pathogen in humans and animals causing systemic infections with symptoms such as septicemia and meningitis. In this work, we analyzed the influence of blood plasma on the internalization of L. monocytogenes into human MoDC and compared the uptake of L. monocytogenes with that of Salmonella enterica serovar Typhimurium and Yersinia enterocolitica. While human plasma did not significantly influence the uptake of serovar Typhimurium and Y. enterocolitica by human MoDC, the efficiency of the uptake of L. monocytogenes by these phagocytes was strongly enhanced by human plasma. In plasma-free medium the internalization of L. monocytogenes was very low, whereas the addition of pooled human immunoglobulins resulted in the internalization of these bacteria to a degree comparable to the highly efficient uptake observed with human plasma. All human plasma tested contained antibodies against the 60-kDa extracellular protein of L. monocytogenes (p60), and anti-p60 antibodies were also found in the commercially available pooled immunoglobulins. Strikingly, in contrast to L. monocytogenes wild type, an iap deletion mutant (totally deficient in p60) showed only a minor difference in the uptake by human MoDC in the presence or the absence of human plasma. These results support the assumption that antibodies against the listerial p60 protein may play an important role in Fc-receptor-mediated uptake of L. monocytogenes by human MoDC via opsonization of the bacteria. This process may have a major impact in preventing systemic infection in L. monocytogenes in immunocompetent humans.