Publications

960 Publications visible to you, out of a total of 960

Abstract

Not specified

Authors: Dirk Hasenclever, Markus Scholz

Date Published: 2013

Publication Type: Journal article

Abstract (Expand)

BACKGROUND\backslashr\backslashnHematopoiesis is a complex process involving different cell types and feedback mechanisms mediated by cytokines. This complexity stimulated various models with different scopes and applications. A combination of complementary models promises to provide their mutual confirmation and to explain a broader range of scenarios. Here we propose a combination of an ordinary differential equation (ODE) model of human granulopoiesis and an agent-based model (ABM) of hematopoietic stem cell (HSC) organization. The first describes the dynamics of bone marrow cell stages and circulating cells under various perturbations such as G-CSF treatment or chemotherapy. In contrast to the ODE model describing cell numbers, our ABM focuses on the organization of individual cells in the stem population.\backslashr\backslashnRESULTS\backslashr\backslashnWe combined the two models by replacing the HSC compartment of the ODE model by a difference equation formulation of the ABM. In this hybrid model, regulatory mechanisms and parameters of the original models were kept unchanged except for a few specific improvements: (i) Effect of chemotherapy was restricted to proliferating HSC and (ii) HSC regulation in the ODE model was replaced by the intrinsic regulation of the ABM. Model simulations of bleeding, chronic irradiation and stem cell transplantation revealed that the dynamics of hybrid and ODE model differ markedly in scenarios with stem cell damage. Despite these differences in response to stem cell damage, both models explain clinical data of leukocyte dynamics under four chemotherapy regimens.\backslashr\backslashnCONCLUSIONS\backslashr\backslashnABM and ODE model proved to be compatible and were combined without altering the structure of both models. The new hybrid model introduces model improvements by considering the proliferative state of stem cells and enabling a cell cycle-dependent effect of chemotherapy. We demonstrated that it is able to explain and predict granulopoietic dynamics for a large variety of scenarios such as irradiation, bone marrow transplantation, chemotherapy and growth factor applications. Therefore, it promises to serve as a valuable tool for studies in a broader range of clinical applications, in particular where stem cell activation and proliferation are involved.

Authors: Axel Krinner, Ingo Roeder, Markus Loeffler, Markus Scholz

Date Published: 2013

Publication Type: Journal article

Abstract (Expand)

BACKGROUND\backslashr\backslashnIn Germany, about 59 000 thyroid operations are performed each year for uni- or multinodular goiter, most of them for diagnostic purposes. The rate of detection of thyroid cancer in such operations is relatively low, at 1:15. Evidence suggests that the preoperative tests recommended in guidelines for estimating the risk of cancer are not being performed as often as they should. In the present study, we determined the measures that were actually taken to diagnose and treat thyroid nodules and compared the findings with the guideline recommendations.\backslashr\backslashnMETHOD\backslashr\backslashnWe retrospectively analyzed data from a single, large statutory healthinsurance carrier in Germany (AOK), determining the diagnostic and therapeutic measures that were reimbursed for 25 600 patients in whom a uni- or multinodular goiter was newly diagnosed in the second quarter of 2006 (none of these patients had carried such a diagnosis 1 year previously). We recorded the diagnostic measures performed in the preceding 9 months and all other tests and treatments, including surgery and radioactive iodine treatment, in the 2 years thereafter.\backslashr\backslashnRESULTS\backslashr\backslashnAmong patients who underwent surgery for uninodular goiter, the preoperative diagnostic studies included ultrasonography (in 100% of patients), scintigraphy (94%), measurement of thyroid-stimulating hormone (95%), measurement of calcitonin (9%), and fine-needle aspiration cytology (FNAC)(21%). An ultrasonographic examination was billed for only 28% of patients with uninodular goiter in the two years after the diagnosis was made. 13% of patients with uninodular goiter who were not operated on were given L-thyroxine, even though this is against guideline recommendations.\backslashr\backslashnCONCLUSION\backslashr\backslashnInadequate preoperative risk stratification of thyroid nodules may explain the large number of thyroid operations that are performed for diagnostic purposes, resulting in a low percentage of malignancies detected. Preoperative FNAC and calcitonin measurement should be used in the diagnostic evaluation of thyroid nodules far more often than this is now done. As a rule, follow-up ultrasonography should be performed for all thyroid nodules that are not operated on. Patients with non-operated thyroid nodules should not be given thyroxine. A limitation of this study is that diagnostic measures were only recorded if they were performed in the 9 months before surgery, with earlier diagnostic measures (if any) being missed.

Authors: Romy Wienhold, Markus Scholz, Jürgen-Bernhard Adler, Christian Günster, Ralf Paschke

Date Published: 2013

Publication Type: Journal article

Abstract

Not specified

Authors: Alfred Winter, R. -D Hilgers, R. Hofestädt, Petra Knaup-Gregori, C. Ose, A. Timmer

Date Published: 2013

Publication Type: Journal article

Abstract

Not specified

Authors: Alfred Winter, Michael Marschollek

Date Published: 2013

Publication Type: Journal article

Abstract

Not specified

Authors: Alfred Winter, Reinhold Haux, H. Bickeboller

Date Published: 2013

Publication Type: Journal article

Abstract (Expand)

PURPOSE: Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6. PATIENTS AND METHODS: Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk. RESULTS: The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers. CONCLUSION: The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.

Authors: C. Engel, M. Loeffler, V. Steinke, N. Rahner, E. Holinski-Feder, W. Dietmaier, H. K. Schackert, H. Goergens, M. von Knebel Doeberitz, T. O. Goecke, W. Schmiegel, R. Buettner, G. Moeslein, T. G. Letteboer, E. Gomez Garcia, F. J. Hes, N. Hoogerbrugge, F. H. Menko, T. A. van Os, R. H. Sijmons, A. Wagner, I. Kluijt, P. Propping, H. F. Vasen

Date Published: 10th Dec 2012

Publication Type: Not specified

Human Diseases: colon cancer

Powered by
(v.1.13.0-master)
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies