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  • 1
    ISSN: 1432-1440
    Keywords: Peripheral quantitative computed tomography ; Trabecular bone density ; Reference values
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is well established that measurement of bone mineral density (BMD) can estimate the risk of future fractures. To assess individual fracture risk BMD measurements are compared with a reference range provided by the manufacturer of the respective BMD technology. However, the power of trabecular bone measured by peripheral quantitative computed tomography (pQCT) to predict future fractures has not been shown up to now. We conducted measurements of trabecular bone density (TBD) at the distal radius (pQCT XCT 900, Stratec, Germany) in a sample of 506 healthy white women aged 40–60 years (mean 48) and compared the results with the manufacturer's normal range. We found a remarkable difference in TBD values between our healthy study population and the manufacturer's reference data in all age groups (e.g., age 50–54 years, 143.1 ± 43.2 mg/cm3 versus 181.1 ± 39.0 mg/cm3). Compared to the ± 2 SD limits of the manufacturer's reference range our study population showed mean TBD values that were about 1 SD below the mean of the reference range. About 50% of our healthy cohort were below the −1 SD limit of the reference range. Almost ten times as many normal subjects as expected (22.1%) were found below the −2 SD limit and therefore classified as individuals with increased fracture risk. This overestimation of fracture risk leads to discomfort of the patient, unnecessary therapeutic intervention, and significant costs to the public. This difference is probably due to the fact that the manufacturer's reference values were generated with the older device (SCT 900) using a 125I source, and that these were later used in devices with an X-ray source. Correction of the manufacturer's software is now underway; all devices with X-ray source distributed in Germany by the company must receive a new software with a generally agreed reference data-set. Our study indicates that a reliable reference database must become a prerequisite for the approvement of BMD technology prior to the use in patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1433-2965
    Keywords: Estrogen replacement therapy ; Menopause ; Osteoporosis ; Velocity of ultrasound
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Determination of apparent velocity of ultrasound (AVU) in bone has been proposed as a valuable tool for discriminating between normal and osteoporotic women. We have studied the influence of age, menopause and estrogen replacement therapy (ERT) on AVU at the patella in a large sample of pre- and postmenopausal women. Three hundred and eighteen woman aged 40–60 year participated in the study (112 women were premenopausal, 21 were perimenopausal and 185 were postmenopausal of whom 110 had received ERT for a minimum of 1 year). AVU was determined as the mean of four measurements at each patella using a Signet instrument (Osteo-Technology, Framingham, MA). An age-dependent decline in AVU was observed only after menopause (r=−0.33,p=0.0055); in premenopausal women there was a slight but not significant decrease in AVU with age (r=−0.12,p〉0.05). AVU was significantly lower in postmenopausal women compared with premenopausal women (1882±84 m/s vs 1961±73 m/s,p〈0.05). ERT prevented the menopause-related fall in AVU. There was a significant positive correlation between the duration of ERT and AVU measurements. Our findings demonstrate a pronounced influence of estrogens on AVU at the patella, supporting the concept of a protective role of ERT in bone stability. AVU measurements therefore merit further investigation as an inexpensive method for predicting fracture risk that does not expose the subject to radiation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2307
    Keywords: Megakaryocytes ; Sinus wall ; Transmural migration ; 3D-reconstruction ; Double-immunostaining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using sequential double-immunostaining and a newly-developed three-dimensional (3D-) reconstruction technique on serially cut sections from bone marrow trephines, we studied the transmural passage of megakaryocytes through the sinus wall. Biopsies derived from patients with primary (idiopathic) osteomyelofibrosis were exposed to monoclonal antibody against type IV collagen to delineate the sinus walls and also the frequently thickened basement membrane. Staining with the primary antibody was followed by Y2/51 (CD61) to identify all elements of megakaryopoiesis. In most instances serial sectioning and 3D-reconstruction revealed an amoeboid shape of megakaryocytes and a tandem-like arrangement in close spatial contact with the abluminal surface of the sinus wall. Preceded by formation of cytoplasmic processes, straight penetration of entire megakaryocytes through gaps in the sinus walls into the lumen was seen. Where collagen deposits apparently presented a barrier, a mole-like tunnelling through the basement membrane material (type IV collagen) was recognizable. Our findings are in keeping with the assumption that megakaryocyte locomotion is an essential requirement for normal thrombocytogenesis.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: CML ; Morphometry ; Immunostaining (CD61, PG-M1) ; Prognostic variables ; Cox models ; Life expectancy ; ROC analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the prognostic significance of clinical as well as histological disease features at the time of diagnosis, an immunohistochemical and morphometric study was performed on bone marrow trephine biopsies in 130 patients with Ph1+-CML. For identification of all cell elements of the megakaryocytopoiesis we used the monoclonal antibody CD61 (Y2/51) and for the macrophages, the recently characterized antibody PG-M1. Density of argyrophilic fibers was determined per fat cell-free marrow area. Based on a multivariate analysis-derived risk model, the reproducibility of the prognostic score described by Sokal and co-workers was tested, particularly with regard to histological variables. Additionally, we calculated the disease-specific loss in life expectancy. Our prognostic model (Cox model) consisted of the variables: age, spleen size, peripheral erythro-normoblasts, pseudo-Gaucher cells, and fiber density. To assess the validity of this new CML score, a receiver-operating curve (ROC) of sensitivity and specificity was constructed. The improved prognostic efficiency of this newly developed risk model in predicting death within 3 years after diagnosis of CML was demonstrated in comparison with generally accepted staging systems. Immunohistochemistry revealed that not the total number of macrophages, but only the subfraction of pseudo-Gaucher cells exerted a significant impact on survival. Furthermore, it was feasible to calculate the number of atypical micromegakaryocytes and pro-and megakaryoblasts. This abnormal and immature cell population showed a significant correlation with fiber density and prognosis. Finally, the practical value of the Hannover classification was tested. This histological classification enabled a discrimination between two groups with different survival patterns, i.e., granulocyte and/or megakaryocyte-rich subtypes versus subtypes with increase in reticulin and collagen fibers.
    Type of Medium: Electronic Resource
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