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  • 1
    Digitale Medien
    Digitale Medien
    Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Journal of the European Academy of Dermatology and Venereology 11 (1998), S. 0 
    Details
    ISSN: 1468-3083
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Background The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus.Aim We compared the number of Wood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate.Study design Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA (n= 21) or etretinate (n= 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0–3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters.Results After CyA treatment the PASI-score amounted to 24 ± 4%, after etretinate to 56 ± 6% of the initial values (mean ± SEM). One week after CyA treatment, esosinophils dropped from 190 ± 21 to 137 ± 16/μ (P= 0.038, Wilcoxon test), after 10 weeks to 127 ± 18/μ (P= 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 ± 1.30 (CyA) and 15.3 ± 5.53 μg/1 (etretinate) were measured (normal range 3–16 /μg/1), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional.Outcome We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1468-3083.1998.tb00975.x
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  • 2
    Digitale Medien
    Digitale Medien
    Gaucher's disease: therapy by intravenous infusions of modified glucocerebrosidase (1993)
    Springer
    Journal of molecular medicine 71 (1993), S. 78-78 
    Details
    ISSN: 1432-1440
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00210974
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  • 3
    Digitale Medien
    Digitale Medien
    Magnetic resonance imaging of trabecular bone structure in the distal radius: Relationship with X-ray tomographic microscopy and biomechanics (1996)
    Springer
    Osteoporosis international 6 (1996), S. 376-385 
    Details
    ISSN: 1433-2965
    Schlagwort(e): Architecture ; Magnetic resonance ; Microscopy ; Osteoporosis ; Trabecular bone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The contribution of trabecular bone structure to bone strength is of considerable interest in the study of osteoporosis and other disorders characterized by changes in the skeletal system. Magnetic resonance (MR) imaging of trabecular bone has emerged as a promising technique for assessing trabecular bone structure. In this in vitro study we compare the measures of trabecular structure obtained using MR imaging and higher-resolution X-ray tomographic microscopy (XTM) imaging of cubes from human distal radii. The XTM image resolution is similar to that obtained from histomorphometric sections (18 µm isotropic), while the MR images are obtained at a resolution comparable to that achievable in vivo (156×156×300 µm). Standard histomorphometric measures, such as trabecular bone area fraction (synonymous with BV/TV), trabecular width, trabecular spacing and trabecular number, texture-related measures and three-dimensional connectivity (first Betti number/volume) of the trabecular network have been derived from these images. The variation in these parameters as a function of resolution, and the relationship between the structural parameters, bone mineral density and the elastic modulus are also examined. In MR images, because the resolution is comparable to the trabecular dimensions, partial volume effects occur, which complicate the segmentation of the image into bone and marrow phases. Using a standardized thresholding criterion for all images we find that there is an overestimation of trabecular bone area fraction (∼3 times), trabecular width (∼3 times), fractal dimension (∼1.4 times) and first Betti number/ volume (∼10 times), and an underestimation of trabecular spacing (∼1.6 times) in the MR images compared with the 18-µm XTM images. However, even for a factor of 9 difference in spatial resolution, the differences in the morphological trabecular structure measures ranged from a factor of 1.4 to 3.0. We have found that trabecular width, area fraction, number, fractal dimension and Betti number/volume measured from the XTM and MR images increases, while trabecular spacing decreases, as the bone mineral density and elastic modulus increase. A preliminary bivariate analysis showed that in addition to bone mineral density alone, the Betti number, trabecular number and spacing contributed to the prediction of the elastic modulus. This preliminary study indicates that measures of trabecular bone structure using MR imaging may play a role in the study of osteoporosis.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01623011
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  • 4
    Digitale Medien
    Digitale Medien
    Effekte der frühen Östrogenersatztherapie auf die Knochenstabilität von ovarektomierten Ratten (2000)
    Springer
    Der Orthopäde 29 (2000), S. 1082-1087 
    Details
    ISSN: 1433-0431
    Schlagwort(e): Schlüsselwörter Tiermodell ; Östrogenersatztherapie ; Mikroarchitektur ; Röntgentomographische Mikroskopie ; Biomechanische Tests ; Keywords Animal model ; Estrogen replacement ; Microarchitecture ; X-ray tomographic microscopy ; Mechanical testing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Abstract Postmenopausal osteoporosis leads to a significant increase in bone fragility. In this study we used the rat tibia plateau fracture model to investigate the efficiency of estrogen replacement therapy (ERT) to mitigate the post-ovariectomy decrease in fracture load. A total of 73 virgin Sprague Dawley rats had been ovariectomized and 26 animals underwent sham operation. The ovariectomized animals were either untreated (n=35) or treated with estrogen injections (10 μg/kg per day 3 days a week until sacrifice), starting treatment at either 0, 5, 8, or 13 days post surgery. Before starting ERT and at 50 days post surgery, the trabecular structure of the right proximal tibial metaphysis of each animal was imaged non-invasively using high resolution X-ray topography. The animals were then sacrificed and the right knee from each animal was harvested and mounted into a servo-hydraulic materials testing system so that the distal femoral condyle could be forced into the proximal tibial plateau until fracture occurred. The failure load (F) of the ovariectomized group without estrogen administration was significantly less than that for the sham group. The mean stiffness (K) of the ovariectomized group was 22 percent less than that of the sham group, though this difference did not reach statistical significance. Across all groups, the failure load and stiffness were significantly correlated with the trabecular bone volume. Our data suggest that prompt ERT can increase the fracture load and stiffness of trabecular bone by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which estrogen and other antiresorptive agents increase bone mass, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.
    Notizen: Zusammenfassung Postmenopausalbedingte Osteoporose kann zu einer signifikanten Zunahme der Knochenbrüchigkeit führen. In der vorliegenden Studie wurde das Tibiaplateaufrakturmodell an der ovarektomierten Ratte eingesetzt, um die Wirkung der Östrogenersatztherapie (ÖET) sowohl biomechanisch als auch radiologisch zu untersuchen; 73 “Virgin-Sprague-Dawley-Ratten” wurden ovarektomiert und 26 Tiere wurden einer Scheinoperation unterzogen. Die ovarektomierten Tiere wurden entweder mit Östrogeninjektionen (n=38) oder mit Placebo (n=35) behandelt. Die Behandlung begann entweder am Tag der Ovarektomie oder am 5., 8. bzw. 13. Tag nach Ovarektomie. Vor Ovarektomie und am 50. Tag danach wurde die Trabekelstruktur der proximalen Tibiamethaphyse in jedem Versuchstier mit Hilfe hochauflösender, dreidimensionaler, röntgentomographischer Mikroskopie gemessen. Die Tiere wurden anschließend getötet und die Hinterläufe biomechanisch getestet. Die Bruchlast (N) der ovarektomierten Ratten ohne Östrogengabe war signifikant kleiner als die der Tiere aus der scheinovarektomierten Gruppe. Die Steifigkeit (N/mm) der ovarektomierten Tiere war 22% kleiner als die der nichtovarektomierten Tiere. Die Tibiae ovarektomierter Tiere mit Östrogenbehandlung zeigten im Vergleich zu den Tieren ohne Östrogenbehandlung eine signifikante Zunahme der Bruchlast zu allen 4 Zeitpunkten des Beginns der Östrogenbehandlung und eine signifikante Zunahme in Steifigkeit in den Tieren, bei denen mit der Östrogentherapie am 5. und 8. postoperativen Tag begonnen wurde. Die Veränderungen des Trabekelvolumens waren signifikant bei den ovarektomierten Tieren ohne Östrogentherapie im Vergleich zu den Tieren aus der scheinovarektomierten Gruppe. Die Veränderungen des Trabekelvolumens zwischen den ovarektomierten Tieren ohne Östrogenbehandlung und Tieren aus allen 4 Gruppen mit Östrogenbehandlung waren ebenfalls signifikant. In allen Gruppen korrelierte die Bruchlast und die Steifigkeit signifikant mit dem Trabekelvolumen. Unsere Ergebnisse zeigen, dass eine rasch eingeleitete ÖET die Bruchlast und Steifigkeit in trabekulärem Knochen erhöhen kann. Dies geschieht wahrscheinlich durch Zunahme der Trabekeldicke, was letztlich zu einer Erhöhung des Gesamttrabekelvolumens führt und dadurch zu einer Reduzierung des Risikos von osteoporosebedingten Frakturen.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s001320050563
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  • 5
    Digitale Medien
    Digitale Medien
    Stress distributions within the proximal femur during gait and falls: Implications for osteoporotic fracture (1995)
    Springer
    Osteoporosis international 5 (1995), S. 252-261 
    Details
    ISSN: 1433-2965
    Schlagwort(e): Fall ; Finite element analysis ; Gait ; Hip fracture ; OsteoporosisStress
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The rates of fracture at sites with different relative amounts of cortical and trabecular bone (hip, spine, distal radius) have been used to make inferences about the pathomechanics of bone loss and the existence of type I and type II osteoporosis. However, fracture risk is directly related to the ratio of tissue stress to tissue strength, which in turn is dependent not only on tissue composition but also tissue geometry and the direction and magnitude of loading. These three elements determine how the load is distributed within the tissue. As a result, assumptions on the relative structural importance of cortical and trabecular bone, and how these tissues are affected by bone loss, can be inaccurate if based on regional tissue composition and bone density alone. To investigate the structural significance of cortical and trabecular bone in the proximal femur, and how it is affected by bone loss, we determined the stress distributions in a normal and osteoporotic femur resulting from loadings representing: (1) gait; and (2) a fall to the side with impact onto the greater trochanter. A three-dimensional finite element model was generated based on a representative femur selected from a large database of femoral geometries. Stresses were analyzed throughout the femoral neck and intertrochanteric regions. We found that the percentage of total load supported by cortical and trabecular bone was approximately constant for all load cases but differed depending on location. Cortical bone carried 30% of the load at the subcapital region, 50% at the mid-neck, 96% at the base of the neck and 80% at the intertrochanteric region. These values differ from the widely held assumption that cortical bone carries 75% of the load in the femoral neck and 50% of the load at the intertrochanteric region. During gait, the principal stresses were concentrated within the primary compressive system of trabeculae and in the cortical bone of the intertrochanteric region. In contrast, during a fall, the trabecular stresses were concentrated within the primary tensile system of trabeculae with a peak magnitude 4.3 times that present during gait. While the distribution of stress for the osteoporotic femur was similar to the normal, the magnitude of peak stress was increased by between 33% and 45%. These data call into question several assumptions which serve as the basis for theories on the pathomechanics of osteoporosis. In addition, we expect that the insight provided by this analysis will result in the improved development and interpretation of non-invasive techniques for the quantification of in vivo hip fracture risk.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01774015
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  • 6
    Digitale Medien
    Digitale Medien
    Long-term metabolic effects in patients with urinary diversion (1998)
    Springer
    World journal of urology 16 (1998), S. 292-297 
    Details
    ISSN: 1433-8726
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The use of intestinal segments in genitourinary reconstruction could influence vitamin metabolism and affect the skeletal bone and its mineral content in the long term. In 137 patients, serum levels of the vitamins A, B1, B2, B6, B12, D, and E and of folic acid, bile acid, and ammonia as well as levels of intracorpuscular vitamin B12 and folic acid were examined and a red blood cell count was performed. The patients were divided into three groups (≤2 years, 〉2 to ≤4 years, and 〉4 years after surgery) as well as into children and adults. In addition, bone mineral density (dual-photon absorptiometry) was measured in 25 patients. Of these, 16 patients were ≈16.8 years s/p rectal reservoir, 6 were ≈20.5 years s/p colonic conduit, two were 6 and 8 years s/p ileocecal pouch, and one adolescent was 5 years s/p ileal bladder augmentation. In all patients the levels of vitamins A, B1, B2, B6, D, and E and of folic acid, bile acid, and ammonia as well as the red blood cell count were within normal ranges. In children (n= 51) there was no significant drop in vitamin B12 levels after the operation. In adults (n= 86), serum vitamin B12 levels dropped significantly from 402 ± 182 ng/l during the first 2 years after the operation to 292 ± 204 ng/l after the 4th year (normal range 240–1,100 ng/l). No significant increase in the intracorpuscular vitamin B12 level was observed during the same period. The bone mineral density was normal in all 25 patients with different types of urinary diversion. In addition to regular examination (sonography, creatinine levels, and base excess), vitamin B12 levels should be determined at 4 years after urinary diversion. It remains unclear whether substitution is necessary. However, substitution is easy to achieve and cheaper than the regular determination of vitamin B12. No decrease in bone mineral content was seen in the long-term follow-up with early correction of the base excess (below −2.5).
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s003450050069
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  • 7
    Digitale Medien
    Digitale Medien
    Collagen type I metabolism after bone surgery (1999)
    Springer
    Archives of orthopaedic and trauma surgery 119 (1999), S. 212-216 
    Details
    ISSN: 1434-3916
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study follows the postoperative course of serum collagen type I metabolites in patients after uncomplicated implantation of a cemented total hip endoprothesis (TEP; n = 12, mean age: 69.3 years), a cemented hemiendoprothesis (HEP; n = 13, mean age 79.7 years), a dynamic condylar or hip screw (DCS/DHS; n = 12, mean age 75.1 years) and osteosynthetic treatment of a Weber B or C fracture (OS; n = 17, mean age 54.3 years). The course of the propeptide of human type I procollagen (PICP) as an anabolic marker as well as of I-carboxyterminal telopeptide (ICTP) as a catabolic marker of bone metabolism was characterized. Measurements were done preoperatively and weekly for 3 weeks after surgery. The concentrations of both markers increased and reached a maximum in the 2nd or 3rd week after surgery. However, the PICP values differed, depending on the kind of surgical intervention and the type of bone healing. Secondary fracture healing with formation of callus occurred in the DCS/DHS group, which developed the highest median PICP concentrations (initial 83 μ g/l, second week 337 μg/l; P 〈 0.001). In contrast, the primary bone healing in the OS group showed increasing ICTP but unchanged PICP concentrations. Patients in the cemented TEP and HEP groups as a kind of artificial bone healing had comparable concentrations. To consider the effective metabolism of collagen type I, the PICP/ICTP ratio was calculated. Although the median PICP and ICTP concentrations of the studied groups differed, the PICP/ICTP ratios were similar. In comparison to 54 young and healthy volunteers (median PICP/ICTP ratio: 37), the ratios of the studied groups were still normal but low (median ratios: 〈 20). This could be an effect of decreasing collagen type I metabolism with age. Although the results are in agreement with animal studies and histomorphometric investigations, the clinical use of PICP and ICTP determination as a tool for the detection of complicated bone healing is limited by the marked interindividual variability and the uncertain bone specificity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s004020050393
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  • 8
    Digitale Medien
    Digitale Medien
    Influence of blood sampling from venipunctures and catheter systems on serial determinations of prothrombin activation fragment 1 + 2 and thrombin-antithrombin III complex (1993)
    Springer
    Annals of hematology 67 (1993), S. 121-125 
    Details
    ISSN: 1432-0584
    Schlagwort(e): Thrombin-antithrombin III complex ; Prothrombin fragment 1+2 ; Blood withdrawal technique ; Catheter ; Venipuncture
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary To evaluate the influence of different blood sampling techniques on test results of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1+2 (F1+2) serial determinations were performed. In six groups of nonrandomized patients (ten patients each) the concentrations of the coagulation markers of blood samples from central catheters (internal jugular, caval, Shaldon, pulmonary artery) and peripheral cannulas (17G and 18G) were compared with those of blood samples obtained simultaneously from direct venipunctures of the contralateral arm. Medians and 25th–75th percentiles of TAT and Fl+2 concentrations of plasmas obtained from central catheters were not different from those taken from venipunctures. When Δ mean values (catheter — venipuncture) were calculated negative results were obtained, indicating lower concentrations measured from blood sampled through central catheters with the exception of blood that taken from Shaldon catheters. Only for TAT concentrations significantly were lower values measured in blood samples taken from internal jugular catheters when compared with blood samples obtained from direct venipunctures. Significantly higher TAT concentrations were determined in blood samples obtained from Shaldon catheters. For both coagulation markers correlations were found between concentrations in blood samples from central catheters and venipunctures. In blood samples taken from peripheral venous cannulas only F1+2 concentrations correlated with the concentrations found in samples from direct venipuncture. In contrast to F1+2, TAT concentrations measured from blood samples via peripheral cannulas were determined significantly higher than those taken from direct venipunctures. Blood drawn from peripheral catheters is not suited for the determination of TAT and F1+2 due to frequently encountered activation of coagulation, while blood sampling with central catheters can be regarded as an alternative to venipuncture.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01701734
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  • 9
    Digitale Medien
    Digitale Medien
    Monitoring prothrombin fragment 1+2 during initiation of oral anticoagulant therapy after intracoronary stenting (1992)
    Springer
    Annals of hematology 65 (1992), S. 83-87 
    Details
    ISSN: 1432-0584
    Schlagwort(e): Intracoronary stenting ; Aggressive anticoagulation ; Subacute occlusion ; Bleeding complication ; Prothrombin fragment 1+2
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Patients with intracoronary stent implantation are treated with aggressive anticoagulant and antiplatelet therapy consisting of high-dose heparin, phenprocoumon, acetylsalicylic acid, dipyridamole, and the infusion of dextran to prevent a subacute thrombotic occlusion of the stented segment. In an effort to optimize this treatment by reducing both imminent bleeding complications and subacute thrombotic occlusion, the concentrations of prothrombin fragment 1+2 (F1+2) were determined after intracoronary Palmaz-Schatz stent implantation in 19 consecutive patients. The F1+2 concentrations after stent implantation and before the initiation of oral anticoagulant therapy (OAT) were 0.35 nm/l and 0.25–0.53 nm/l (median and 25th–75th percentile), versus 0.74 nm/l and 0.52–0.78 nm/l, in healthy subjects and 0.61 nm/l and 0.30–1.02 nm/l in 15 patients with ongoing proximal DVT. Nine days after initiation of OAT, F1+2 concentrations in both patient groups had not yet reached levels observed in patients with OAT in the stable state (0.16 nm/l, 0.12–0.26 nm/l;n=76;P〈0.0001 compared with healthy subjects; INR 2.0–4.5). Despite an INR greater than 2.0, accompanying heparinization was terminated on day 9. In two stented patients a minor bleeding complication arose after the removal of the arterial catheter. Subacute thrombotic occlusions were not observed. Since F1+2 concentrations did not exceed the upper limit of normal range (1.11 nm/l) in any of the 19 patients, the therapeutic regimen was not changed. Monitoring F1+2 may thus be helpful in introducing a more individual treatment if aggressive anticoagulation has to be performed.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01698135
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  • 10
    Digitale Medien
    Digitale Medien
    Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques (CSH) dans le traitement des cancers du sein métastatiques : résultats du programme national Pegase 04 (1999)
    Springer
    Hematology and cell therapy 41 (1999), S. 71-74 
    Details
    ISSN: 1279-8509
    Schlagwort(e): High dose chemotherapy ; Breast cancer ; Stem cells transplantation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients. Patients and methods:Inclusion criteria were : age 〈 60 year, PS 〈 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide 120 mg/kg, Melphalan 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response. ResultsThe median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12). Conclusion The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s00282-999-0071-1
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