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959 Publications visible to you, out of a total of 959
Modelling chemotherapy effects on granulopoiesis.
GLA - German Lymphoma Alliance, Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND: Although the growth-factor G-CSF is widely used to prevent granulotoxic side effects of cytotoxic chemotherapies, its optimal use is still unknown since treatment outcome depends on many … parameters such as dosing and timing of chemotherapies, pharmaceutical derivative of G-CSF used and individual risk factors. We showed in the past that a pharmacokinetic and -dynamic model of G-CSF and human granulopoiesis can be used to predict the performance of yet untested G-CSF schedules. However, only a single chemotherapy was considered so far. RESULTS: Model assumptions proved to be feasible in explaining granulotoxicity of 10 different chemotherapeutic drugs or drug-combinations applied in 33 different schedules with and without G-CSF. Risk groups of granulotoxicity were traced back to differences in toxicity parameters. CONCLUSION: We established a comprehensive model of combined G-CSF and chemotherapy action in humans which allows us to predict and compare the outcome of alternative G-CSF schedules. We aim to apply the model in different clinical contexts to optimize and individualize G-CSF treatment.

Authors: S. Schirm, C. Engel, M. Loeffler, M. Scholz

Date Published: 24th Dec 2014

Publication Type: Not specified

Human Diseases: leukopenia

Elevated HbA1c is associated with increased risk of incident dementia in primary care patients.
LIFE Adult

Abstract (Expand)

Type 2 diabetes mellitus (T2DM) is a risk factor of dementia. The effect of T2DM treatment quality on dementia risk, however, is unclear. 1,342 elderly individuals recruited via general practitioner … registries (AgeCoDe cohort) were analyzed. This study analyzed the association between HbA1c level and the incidence of all-cause dementia (ACD) and of Alzheimer's disease dementia (referred to here as AD). HbA1c levels >/=6.5% were associated with 2.8-fold increased risk of incident ACD (p = 0.027) and for AD (p = 0.047). HbA1c levels >/=7% were associated with a five-fold increased risk of incident ACD (p = 0.001) and 4.7-fold increased risk of incident AD (p = 0.004). The T2DM diagnosis per se did not increase the risk of either ACD or AD. Higher levels of HbA1c are associated with increased risk of ACD and AD in an elderly population. T2DM diagnosis was not associated with increased risk if HbA1c levels were below 7%.

Authors: A. Ramirez, S. Wolfsgruber, C. Lange, H. Kaduszkiewicz, S. Weyerer, J. Werle, M. Pentzek, A. Fuchs, S. G. Riedel-Heller, T. Luck, E. Mosch, H. Bickel, B. Wiese, J. Prokein, H. H. Konig, C. Brettschneider, M. M. Breteler, W. Maier, F. Jessen, M. Scherer

Date Published: 20th Dec 2014

Publication Type: Not specified

Human Diseases: diabetes mellitus, dementia, Alzheimer's disease

Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group.
GLA - German Lymphoma Alliance

Abstract (Expand)

PURPOSE: To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: In the SMARTE-R-CHOP-14 … trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6xR-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6xR-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial. RESULTS: The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients. CONCLUSION: Extended rituximab exposure compared with eight 2-week applications in combination with 6xR-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6xR-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.

Authors: M. Pfreundschuh, V. Poeschel, S. Zeynalova, M. Hanel, G. Held, N. Schmitz, A. Viardot, M. H. Dreyling, M. Hallek, C. Mueller, M. H. Wiesen, M. Witzens-Harig, L. Truemper, U. Keller, T. Rixecker, C. Zwick, N. Murawski

Date Published: 20th Dec 2014

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma, diffuse large B-cell lymphoma

Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating serum chemerin
Genetical Statistics and Systems Biology

Abstract (Expand)

Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis … of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p\textless5.0\times10-8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8\times10-14, beta = -0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2 = 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p\textless0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations.

Authors: Anke Tönjes, Markus Scholz, Jana Breitfeld, Carola Marzi, Harald Grallert, Arnd Gross, Claes Ladenvall, Dorit Schleinitz, Kerstin Krause, Holger Kirsten, Esa Laurila, Jennifer Kriebel, Barbara Thorand, Wolfgang Rathmann, Leif Groop, Inga Prokopenko, Bo Isomaa, Frank Beutner, Jürgen Kratzsch, Joachim Thiery, Mathias Fasshauer, Nora Klöting, Christian Gieger, Matthias Blüher, Michael Stumvoll, Peter Kovacs

Date Published: 18th Dec 2014

Publication Type: Journal article

Monitoring Motor Skills of Children and Adolescents in LIFE Child
LIFE - Leipzig Research Center for Civilization Diseases

Abstract (Expand)

Life Child is an epidemiological study running at the LIFE Research Center for Civilization Diseas-es (University of Leipzig) since 2011. It aims at monitoring the development in children and adolescents … by examining thousands of children in and around Leipzig. Of particular interest in this study are motor skills and physical activities of children between 6 and 18 years. There are multiple examinations including interviews, self-completed questionnaires and physical examinations (e.g., sport tests) to generate data describing the determined child as well her lifestyle and environment. The goal is to find causes for low to non physical activity and unincisive motor skills and capabilities since they are commonly attended with diseases, such as obesity and diabetes. As a first step in this direction, we analyzed data of specific sport tests, such as pushups, side steps and long jumps, according to the body mass index (BMI) of participants. We found that participants with high BMI achieve a similar number of pushups in early years like the normal BMI group, while in later years the pushup number of participants with normal BMI exceeds the pushup number of high BMI group. Surprisingly, the number of side steps is indifferent over age categories (6-18, yearly) between both groups. Conversely, the normal BMI group achieve higher distances through-out all age categories than the high BMI group. In future, we will associate these results with socio-economic and lifestyle indicators, e.g., interest in sport and physical activities of child and parents.

Authors: J. Lang, C. Warnatsch, M. Vogel, Toralf Kirsten, W. Kiess

Date Published: 17th Dec 2014

Publication Type: Not specified

Soziodemographische Merkmale und soziökonomischer Status der Teilnehmer in der LIFE Child Kohorte im nationalen Vergleich
LIFE Child

Abstract (Expand)

Soziodemographische Merkmale gelten in den Humanwissenschaften als globale Einflussfaktoren in fast allen Forschungsgebieten und bilden das Basiselement von Kohortenstudien. Darüber hinaus wurde in … vielen Bereichen ein direkter Zusammenhang zwischen sozialen Faktoren und Gesundheit nachgewiesen. Insbesondere im Kindes- und Jugendalter nimmt der sozioökonomische Status einer Familie entscheidenden Einfluss auf die physische sowie mentale Entwicklung. Derartige und weitere Forschungsfragen stehen im Blickpunkt des Projektes LIFE Child.

Authors: L. Meißner, C. Bucher, M. Vogel, Toralf Kirsten, S. Nerlich, U. Igel, W. Kiess, A. Hiemisch

Date Published: 17th Dec 2014

Publication Type: Not specified

Obesity Associated Cerebral Gray and White Matter Alterations Are Interrelated in the Female Brain.
LIFE Adult

Abstract (Expand)

Obesity is known to affect the brain's gray matter (GM) and white matter (WM) structure but the interrelationship of such changes remains unclear. Here we used T1-weighted magnetic resonance imaging … (MRI) in combination with voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) with tract-based spatial statistics (TBSS) to assess the relationship between obesity-associated alterations of gray matter density (GMD) and anisotropic water diffusion in WM, respectively. In a small cohort of lean to obese women, we confirmed previous reports of obesity-associated alterations of GMD in brain regions involved in executive control (i.e., dorsolateral prefrontal cortex, DLPFC) and habit learning (i.e., dorsal striatum). Gray matter density alterations of the DLPFC were negatively correlated with radial diffusivity in the entire corpus callosum. Within the genu of the corpus callosum we found a positive correlation with axial diffusivity. In posterior region and inferior areas of the body of the corpus callosum, axial diffusivity correlated negatively with altered GMD in the dorsal striatum. These findings suggest that, in women, obesity-related alterations of GMD in brain regions involved in executive control and habit learning might relate to alterations of associated WM fiber bundles within the corpus callosum.

Authors: K. Mueller, A. Horstmann, H. E. Moller, A. Anwander, J. Lepsien, M. L. Schroeter, A. Villringer, B. Pleger

Date Published: 11th Dec 2014

Publication Type: Not specified

Human Diseases: obesity

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