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  • 1
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    Online Resource
    SNP-Based Analysis of Genetic Substructure in the German Population
    S. Karger AG ; 2006
    In:  Human Heredity Vol. 62, No. 1 ( 2006), p. 20-29
    Details
    In: Human Heredity, S. Karger AG, Vol. 62, No. 1 ( 2006), p. 20-29
    Abstract: 〈 i 〉 Objective: 〈 /i 〉 To evaluate the relevance and necessity to account for the effects of population substructure on association studies under a case-control design in central Europe, we analysed three samples drawn from different geographic areas of Germany. Two of the three samples, POPGEN (n = 720) and SHIP (n = 709), are from north and north-east Germany, respectively, and one sample, KORA (n = 730), is from southern Germany. 〈 i 〉 Methods: 〈 /i 〉 Population genetic differentiation was measured by classical F-statistics for different marker sets, either consisting of genome-wide selected coding SNPs located in functional genes, or consisting of selectively neutral SNPs from ‘genomic deserts’. Quantitative estimates of the degree of stratification were performed comparing the genomic control approach [Devlin B, Roeder K: Biometrics 1999;55:997–1004], structured association [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945–959] and sophisticated methods like random forests [Breiman L: Machine Learning 2001;45:5–32]. 〈 i 〉 Results: 〈 /i 〉 F-statistics showed that there exists a low genetic differentiation between the samples along a north-south gradient within Germany (F 〈 sub 〉 ST 〈 /sub 〉 (KORA/POPGEN): 1.7 · 10 〈 sup 〉 –4 〈 /sup 〉 ; F 〈 sub 〉 ST 〈 /sub 〉 (KORA/SHIP): 5.4 · 10 〈 sup 〉 –4 〈 /sup 〉 ; F 〈 sub 〉 ST 〈 /sub 〉 (POPGEN/SHIP): –1.3 · 10 〈 sup 〉 –5 〈 /sup 〉 ). 〈 i 〉 Conclusion: 〈 /i 〉 Although the F 〈 sub 〉 ST 〈 /sub 〉 -values are very small, indicating a minor degree of population structure, and are too low to be detectable from methods without using prior information of subpopulation membership, such as STRUCTURE [Pritchard JK, Stephens M, Donnelly P: Genetics 2000;155:945–959], they may be a possible source for confounding due to population stratification.
    Type of Medium: Online Resource
    ISSN: 0001-5652 , 1423-0062
    URL: Article
    DOI: 10.1159/000095850
    RVK:
    WA 15000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2006
    detail.hit.zdb_id: 1482710-4
    SSG: 12
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  • 2
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    Commercially Available Gene Expression Assays as Predictive Tools for Adjuvant Radiotherapy? A Critical Review
    S. Karger AG ; 2020
    In:  Breast Care Vol. 15, No. 2 ( 2020), p. 118-127
    Details
    In: Breast Care, S. Karger AG, Vol. 15, No. 2 ( 2020), p. 118-127
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Gene expression assays are increasingly used for decision-making regarding adjuvant chemotherapy in patients with hormone receptor-positive, HER2-negative breast cancer. There are some clinical situations in which there is also a need for better prognostic and predictive markers to better estimate the amount of benefit from adjuvant radiotherapy. The rising availability of gene expression analyses prompts the question whether their results can also be used to guide clinical decisions regarding adjuvant radiation. 〈 b 〉 〈 i 〉 Summary: 〈 /i 〉 〈 /b 〉 Multiple studies suggest a correlation between results from gene expression assays and locoregional recurrence rates. Only few publications addressed the predictive value of results from gene expression analysis for the role of adjuvant radiotherapy in different settings. 〈 b 〉 〈 i 〉 Key Messages: 〈 /i 〉 〈 /b 〉 To date, the available evidence on the possible predictive value of gene expression assays for radiotherapy does not support their inclusion into the decision-making process for adjuvant radiation. This is due to methodological weaknesses and limitations regarding patient selection, the nonrandomized design of all studies in terms of radiotherapy use, and limited availability of tissue from prospective trials. Thus, utilization of the present knowledge for clinical indication of radiotherapy should be very cautious.
    Type of Medium: Online Resource
    ISSN: 1661-3791 , 1661-3805
    URL: Article
    DOI: 10.1159/000505656
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2020
    detail.hit.zdb_id: 2205941-6
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  • 3
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    Long-Term Results of the TARGIT-A Trial: More Questions than Answers
    S. Karger AG ; 2022
    In:  Breast Care Vol. 17, No. 1 ( 2022), p. 81-84
    Details
    In: Breast Care, S. Karger AG, Vol. 17, No. 1 ( 2022), p. 81-84
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a “risk-adapted” intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications. 〈 b 〉 〈 i 〉 Summary: 〈 /i 〉 〈 /b 〉 From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications. 〈 b 〉 〈 i 〉 Key Message: 〈 /i 〉 〈 /b 〉 Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: “the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery.”
    Type of Medium: Online Resource
    ISSN: 1661-3791 , 1661-3805
    URL: Article
    DOI: 10.1159/000515386
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2022
    detail.hit.zdb_id: 2205941-6
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  • 4
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    Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies
    S. Karger AG ; 2021
    In:  Transfusion Medicine and Hemotherapy Vol. 48, No. 3 ( 2021), p. 137-147
    Details
    In: Transfusion Medicine and Hemotherapy, S. Karger AG, Vol. 48, No. 3 ( 2021), p. 137-147
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Patients who had recovered from CO­VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from & #x3c;1:20 to & #x3e;1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.
    Type of Medium: Online Resource
    ISSN: 1660-3796 , 1660-3818
    URL: Article
    DOI: 10.1159/000515610
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2021
    detail.hit.zdb_id: 2100533-3
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  • 5
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    Use of Endorectal Surface Coil Magnetic Resonance Imaging for Diagnosis of a Multicystic Seminal Vesicle with Ipsilateral Renal Agenesis
    S. Karger AG ; 1996
    In:  Urologia Internationalis Vol. 57, No. 2 ( 1996), p. 115-118
    Details
    In: Urologia Internationalis, S. Karger AG, Vol. 57, No. 2 ( 1996), p. 115-118
    Type of Medium: Online Resource
    ISSN: 1423-0399 , 0042-1138
    URL: Article
    DOI: 10.1159/000282892
    RVK:
    XA 10000
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1996
    detail.hit.zdb_id: 1464417-4
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  • 6
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    Changing Characteristics of Obese Children and Adolescents Entering Pediatric Lifestyle Intervention Programs in Germany over the Last 11 Years: An Adiposity Patients Registry Multicenter Analysis of 65,453 Children and Adolescents
    S. Karger AG ; 2017
    In:  Obesity Facts Vol. 10, No. 5 ( 2017), p. 517-530
    Details
    In: Obesity Facts, S. Karger AG, Vol. 10, No. 5 ( 2017), p. 517-530
    Abstract: 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 To examine whether characteristics of children and adolescents who start lifestyle intervention (LI) for obesity in Germany changed over the last decade. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 65,453 subjects ( 〈 21 years) from the APV database (Adiposity Patients Registry) with a BMI ≥ 90th percentile were included (years 2005-2015). Logistic regression models (confounders: age, sex, migration background) were created for overweight, obesity, extreme obesity, and obesity-related comorbidities. Comorbidities were further adjusted for weight category. Results were stratified by inpatient or outpatient care. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Extreme obesity was found to be more frequent at the onset of LI (2005: 11.6; 2015: 12.7%) with a similar trend in subgroups (p 〈 0.001). Obesity increased (2005: 50.3%; 2015: 55.1%), and overweight decreased (2005: 34.1%; 2015: 29.0%) in the whole study population. Trends were similar for inpatient or outpatient care (all p 〈 0.001). Hypertension increased from 45.7% to 49.2% in the whole study population, and similar data were obtained in the subgroup of inpatients (both p 〈 0.0001). Dyslipidemia increased in all patients (2005: 21.9%; 2015: 28.0%) and in inpatients (2005: 20.2%; 2015: 25.7%; both p 〈 0.0001). Abnormal carbohydrate metabolism rose in all patients (from 5.2 to 6.4%; p = 0.0002) without significant trends in subgroups. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 During the last decade, children and adolescents presented with higher BMI SDS at the onset of LI and the proportion with obesity-related comorbidities increased. Particularly the presence of comorbidities differed between outpatients and inpatients.
    Type of Medium: Online Resource
    ISSN: 1662-4025 , 1662-4033
    URL: Article
    DOI: 10.1159/000479631
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 2455819-9
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  • 7
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    Predicting Weight Loss and Maintenance in Overweight/Obese Pediatric Patients
    S. Karger AG ; 2014
    In:  Hormone Research in Paediatrics Vol. 82, No. 6 ( 2014), p. 380-387
    Details
    In: Hormone Research in Paediatrics, S. Karger AG, Vol. 82, No. 6 ( 2014), p. 380-387
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 Pediatric lifestyle interventions have positive short-term effects on obese patients. Studies on long-term effects are still scarce in Europe. We investigated long-term weight patterns and sociodemographic predictors of a weight change in a large Central European (Germany, Austria and Switzerland) overweight pediatric cohort. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 The APV (Adiposity Patients Verlaufsbeobachtung) database was retrospectively analyzed; 157 specialized childhood obesity centers contributed standardized data of 29,181 patients [body mass index (BMI) ≥90th percentile; 5-25 years old] presenting between 2000 and 2012. BMI standard deviation scores (BMI-SDS) were analyzed in a 2-year follow-up and grouped according to BMI-SDS changes. Multiple logistic regression analyses were conducted to assess associations between sociodemographic factors and weight patterns. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 2-year follow-up data were available in 3,135 patients (54.6% female). Five distinct weight trajectories ‘rapid weight loss' (n = 735, 23.4%), ‘delayed success' (n = 697, 22.2%), ‘cycling weight' (n = 43, 1.4%), ‘initial weight loss' and ‘weight rebound' (n = 383, 12.2%) and ‘no weight loss throughout' (n = 1,277, 40.7%) best characterized long-term BMI-SDS changes. Younger and male patients were more likely to reduce weight and maintain weight loss. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our results suggest that an intervention before the onset of puberty seems promising for long-term weight maintenance in overweight children. Thus, new concepts are needed to improve long-term treatment success in patients with lower success rates.
    Type of Medium: Online Resource
    ISSN: 1663-2818 , 1663-2826
    URL: Article
    DOI: 10.1159/000368963
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
    detail.hit.zdb_id: 2540224-9
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  • 8
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    Cytoskeleton and Epithelial Polarity
    S. Karger AG ; 1993
    In:  Kidney and Blood Pressure Research Vol. 16, No. 1-2 ( 1993), p. 6-14
    Details
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 16, No. 1-2 ( 1993), p. 6-14
    Abstract: The membrane surface of polarized epithelial cells can be divided in apical and basolateral domains that differ in molecular composition and function. Components of the cytoskeleton are involved in critical steps of both generation and maintenance of cell polarity. Generation of polarity is controlled by microtubules that serve as uniformly aligned and polarized cytoplasmic guiding structures for the vectorial and selective transport of Golgi-derived carrier vesicles to the apical cell surface. Targeting of membrane proteins to the basolateral cell surface does not depend on microtubules but follows the constitutive bulk flow of membranes. Once inserted into the lipid bilayer several membrane proteins such as the kidney anion exchanger 1 (AE1) and the sodium pump become immobilized at specialized microdomains of the lateral cell surface. Evidence is provided that both membrane proteins are linked via ankyrin to the spectrin-based membrane cytoskeleton that underlies the basolateral membrane domain. Linkage of these and other integral membrane proteins to the cytoskeleton may not only place them to specialized sites of the plasma membrane but may also prevent these transporters from clustering and endocytosis, thus helping them to stay at the cell surface. In search of sequence motifs involved in binding of integral membrane proteins to components of the cytoskeleton we found that the binding interface of AE1 to protein 4.1 (an actin and spectrin cross-linking protein) consists of a cluster of five amino acid residues, namely IRRRY in AE1 and LEEDY on protein 4.1. This motif may play a more general role in cytoskeleton membrane linkages.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    URL: Article
    DOI: 10.1159/000173747
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1993
    detail.hit.zdb_id: 1482922-8
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  • 9
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    Effects of Kallikrein Inhibition with Aprotinin on Intrarenal Hemodynamics and Urinary Prostaglandin Excretion in Control and Saline-Loaded Conscious Rats
    S. Karger AG ; 1979
    In:  Kidney and Blood Pressure Research Vol. 2, No. 6 ( 1979), p. 302-310
    Details
    In: Kidney and Blood Pressure Research, S. Karger AG, Vol. 2, No. 6 ( 1979), p. 302-310
    Abstract: In conscious rats inhibition of kallikrein formation with aprotinin suppressed urinary prostaglandin (PG) E 〈 sub 〉 2 〈 /sub 〉 excretion. This was associated with a decrease in inner cortical perfusion in the absence of changes in GFR or hippuran clearance. During acute expansion of the extracellular fluid volume (ECFV) with isotonic saline PGE 〈 sub 〉 2 〈 /sub 〉 excretion significantly increased but was suppressed during stable ECFV expansion. With ECFV expansion GFR increased, while total and regional cortical perfusion remained unchanged. Aprotinin suppressed the early rise in PGE 〈 sub 〉 2 〈 /sub 〉 excretion and reduced GFR and hippuran clearance as a result of decreased outer cortical perfusion. It is suggested that integrity of the kinin-prostaglandin system represents an important prerequisite for the functional adaptation of the kidney to acute expansion of the ECFV with isotonic saline.
    Type of Medium: Online Resource
    ISSN: 1420-4096 , 1423-0143
    URL: Article
    DOI: 10.1159/000172722
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1979
    detail.hit.zdb_id: 1482922-8
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  • 10
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    Non-Invasive Monitoring of Renal Transplant Recipients: Urinary Excretion of Soluble Adhesion Molecules and of the Complement-Split Product C4d
    S. Karger AG ; 2004
    In:  Nephron Clinical Practice Vol. 94, No. 1 ( 2004-11-17), p. c19-c26
    Details
    In: Nephron Clinical Practice, S. Karger AG, Vol. 94, No. 1 ( 2004-11-17), p. c19-c26
    Abstract: 〈 i 〉 Background: 〈 /i 〉 The number of inducible adhesion molecules known to be involved in cell-mediated allograft rejection is still increasing. In addition, recent data describe complement activation during acute humoral allograft rejection. The aim of this study was to assess whether specific molecules from either pathway are excreted into urine and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. 〈 i 〉 Methods: 〈 /i 〉 Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1) and of the complement degradation product C4d were determined by standardized ELISA technique in 75 recipients of renal allografts and 29 healthy controls. Patient samples were assigned to four categories according to clinical criteria: 〈 i 〉 group 1: 〈 /i 〉 acute steroid-sensitive rejection (ASSR, n = 14), 〈 i 〉 group 2: 〈 /i 〉 acute steroid-resistant rejection (ASRR, n = 12), 〈 i 〉 group 3: 〈 /i 〉 chronic allograft dysfunction (CAD, n = 20) and 〈 i 〉 group 4: 〈 /i 〉 stable graft function (SGF, n = 29). 〈 i 〉 Results: 〈 /i 〉 All patients with rejection episodes (groups 1–3) had significantly higher values of urinary sC4d compared with healthy controls and patients with stable graft function (p 〈 0.05). The urinary levels of sVCAM-1 were significantly higher in group 2 (ASRR) compared with all other groups (p 〈 0.001). Uniformly low amounts of s-VCAM-1 and complement-split product C4d were excreted by healthy controls (group 0). In contrast, urinary sICAM-1 concentration in healthy controls was almost as high as in group 2 (ASRR) whereas patients with a stable functioning graft (group 4) excreted significantly less sICAM-1 (p 〈 0.05). 〈 i 〉 Conclusion: 〈 /i 〉 The evaluation of sVCAM-1 and sC4d excretion in urine can provide a valuable tool with regard to the severity and type of allograft rejection. With respect to long-term allograft survival, serial measurements of these markers should have the potential to detect rejection episodes and prompt immediate treatment.
    Type of Medium: Online Resource
    ISSN: 1660-2110
    URL: Article
    DOI: 10.1159/000070820
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2004
    detail.hit.zdb_id: 2098336-0
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