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190 Publications visible to you, out of a total of 190
Age-dependency of cardiac morphology and function: results of the LIFE-Adult-Study – analysis of the echocardiographic substudy
LIFE Adult

Abstract (Expand)

In the NORRE study (EHJCVI (2014) 15, 680 – 690) normal values determined by echocardiography were published in healthy subjects (n = 734) with mean age of 46+13 years (range: 20 – 78). Left ventricular … (LV)-volumes showed good correlations to the participants' (pts') age. LV-volumes were decreased and LV ejection fraction (EF) was increased according to the increase of the pts' age. A significant correlation between age and LV-mass was only found in women. Left atrial (LA)-volumes did not significantly change with age. Parameters of diastolic function showed a strong age-dependency (decrease of E/A-ratio; increase of E/E'-ratio). In the present LIFE-Adult analysis echocardiographic parameters were compared to the NORRE data. In 773 pts (326 males and 447 females; median age: 51 years), standardised transthoracic echocardiography was performed according to the national and international recommendations. The following parameters were analysed: LV- and LA-volume analyses by M-Mode measurements and 2D-LV planimetry, maximum E-and A-velocity, E/A-ratio and E/E'-ratio. The cohort was divided in age related subcohorts between 20 – 40, 41 – 50 and 51 – 60 years. Mean LV-diameter was 54 ± 5 mm (males) and 49 ± 4 mm (females). There was no age-dependency in males, but a tendency of LV-diameter increase in females. Mean LA diameter was 39 ± 4 mm in males and 35 ± 4 mm in females. Mean LA-diameter-index was 20 ± 2 mm/m2 (males) and 20 ± 3 mm/m2 (females) showing Age-dependency of an increasing LA-diameter in males and females. LV mass-index was 100 ± 20 g/m2 (males) and 83 ± 19 g/m2 (females) showing a tendency of increasing LV mass-index with age in males and females. Subsequently, septal and posterior wall thickness slightly increases with age. No differences of LVEF with increase of the pts' age could be observed. E/A-ratio was decreased and E/E'-ratio was increased with increase of the pts' age. The analysis of the echocardiographic parameters of the LIFE-Adult trial showed differences of the age-dependency in comparison to the NORRE data.

Authors: S. Stöbe, A. Hagendorff, S. Zeynalova, S. Tautenhahn, K. Wirkner, G. Farese, D. Jurisch, D. Pfeiffer, M. Loeffler

Date Published: 18th Aug 2016

Publication Type: Journal article

Correlation of the E/E'-ratio to NT-BNP: echocardiographic subanalysis of the LIFE-Adult-Study
LIFE Adult

Abstract (Expand)

The E/E'-ratio is used as a surrogate parameter for the estimation of the left ventricular enddiastolic pressure. It is assumed that chronic systolic and diastolic heart failure is associated with … E/E'-values of more than 15 or at least with intermediate values between 9 – 5. The aim of the present retrospective analysis of the epidemiological echocardiographic cohort of the LIFE-Adult study (Leipzig Research Centre for Civilization Diseases) was to evaluate the correlation of NT-BNP (N-terminales propeptid BNP) values to the E/E'-ratio by the assessment of left ventricular diastolic function in this cohort. In 773 participants (pts) standardised transthoracic echocardiography was performed and in 748 pts NT-BNP was analysed. The E/E'-ratio was determined according to the international recommendations by measuring the maximum velocity of the early diastolic inflow by pulsed wave Doppler echocardiography and the basal septal maximum myocardial velocity by tissue Doppler echocardiography at early diastole. NT-BNP was determined using commercially available diagnostic tests. Pathological NT-BNP levels were assumed in the range > 222pg/ml. Normal E/E'-ratios as well as normal NT-BNP levels were observed in 91% of all participants. In 1.4% of the pts elevated NT-BNP levels were found in the presence of normal E/E'-ratio. In contrast in 1.1% of the pts elevated E/E'-ratios were found in the presence of normal NT-BNP levels. Most of the pts with heart failure detected by NT-BNP vales > 222pg/ml also showed intermediate E/E'-ratios between 9 and 15 (42pts). In only 0.8% of the pts (5 pts) significantly elevated E/E'-ratios > 15 and pathological NT-BNP levels could be observed (see fig). Only 4 pts with elevated NT-BNP values showed left ventricular systolic dysfunction. E/E'-ratio has to be verified to be suitable for the detection of heart failure patients. The present data show that E/E'-ratio of > 15 is not well correlated to increased NT-BNP levels.

Authors: S. Stöbe, A. Hagendorff, S. Zeynalova, S. Tautenhahn, S. Wirkner, F. Gerardo, D. Jurisch, D. Pfeiffer, M. Loeffler

Date Published: 18th Aug 2016

Publication Type: Journal article

Novel Anthropometry Based on 3D-Bodyscans Applied to a Large Population Based Cohort.
LIFE Adult, Genetical Statistics and Systems Biology

Abstract (Expand)

Three-dimensional (3D) whole body scanners are increasingly used as precise measuring tools for the rapid quantification of anthropometric measures in epidemiological studies. We analyzed 3D whole body … scanning data of nearly 10,000 participants of a cohort collected from the adult population of Leipzig, one of the largest cities in Eastern Germany. We present a novel approach for the systematic analysis of this data which aims at identifying distinguishable clusters of body shapes called body types. In the first step, our method aggregates body measures provided by the scanner into meta-measures, each representing one relevant dimension of the body shape. In a next step, we stratified the cohort into body types and assessed their stability and dependence on the size of the underlying cohort. Using self-organizing maps (SOM) we identified thirteen robust meta-measures and fifteen body types comprising between 1 and 18 percent of the total cohort size. Thirteen of them are virtually gender specific (six for women and seven for men) and thus reflect most abundant body shapes of women and men. Two body types include both women and men, and describe androgynous body shapes that lack typical gender specific features. The body types disentangle a large variability of body shapes enabling distinctions which go beyond the traditional indices such as body mass index, the waist-to-height ratio, the waist-to-hip ratio and the mortality-hazard ABSI-index. In a next step, we will link the identified body types with disease predispositions to study how size and shape of the human body impact health and disease.

Authors: H. Loffler-Wirth, E. Willscher, P. Ahnert, K. Wirkner, C. Engel, M. Loeffler, H. Binder

Date Published: 29th Jul 2016

Publication Type: Not specified

Human Diseases: obesity

The Speaking Voice in the General Population: Normative Data and Associations to Sociodemographic and Lifestyle Factors.
LIFE Adult

Abstract (Expand)

OBJECTIVES: Normative data concerning the speaking voice in the general population were gathered with the aim to establish standard values for clinical diagnostics. Associations between the speaking … voice and sociodemographic factors were examined. STUDY DESIGN: This is a prospective cross-sectional population-based study. METHODS: Speaking voice profiles were measured for 2472 (1154 male and 1318 female) participants between the ages of 40 and 79 years, using four speaking voice intensity levels: softest speaking voice (I), conversational voice (II), classroom voice (III), and shouting voice (IV). Smoking status and socioeconomic status were assessed. Data were analyzed using multivariate regression. RESULTS: The mean voice frequencies were 111.8 Hz for male and 161.3 Hz for female participants (I), 111.9 Hz for male and 168.5 Hz for female participants (II), 130.2 Hz for male and 198.0 Hz for female participants (III), and 175.5 Hz for male and 246.2 Hz for female participants (IV). Frequencies increased significantly with age for male but not for female participants. Sound pressure levels rose significantly with age at intensity levels I-III for both sexes, but decreased at intensity level IV. Frequencies and sound pressure levels were similar between nonsmokers and former smokers. Current smokers showed significantly lower frequencies as opposed to non- and former smokers. Speaking voice range and dynamics increased with higher socioeconomic status. CONCLUSIONS: The data are suitable as age-adjusted normative values for clinical measurement of the speaking voice. The mean fundamental speaking voice frequency of female participants was six to seven semitones lower than previously described.

Authors: M. Berg, M. Fuchs, K. Wirkner, M. Loeffler, C. Engel, T. Berger

Date Published: 3rd Jul 2016

Publication Type: Journal article

A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice
Genetical Statistics and Systems Biology

Abstract (Expand)

Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due … to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

Authors: Sibylle Schirm, Peter Ahnert, Sandra Wienhold, Holger Mueller-Redetzky, Geraldine Nouailles-Kursar, Markus Loeffler, Martin Witzenrath, Markus Scholz

Date Published: 19th May 2016

Publication Type: Journal article

Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma.
GLA - German Lymphoma Alliance

Abstract (Expand)

Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study … is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

Authors: K. Hohloch, S. Zeynalova, B. Chapuy, M. Pfreundschuh, M. Loeffler, M. Ziepert, A. C. Feller, L. Trumper, D. Hasenclever, G. Wulf, N. Schmitz

Date Published: 12th May 2016

Publication Type: Not specified

Human Diseases: non-Hodgkin lymphoma

Reliability of 3D laser-based anthropometry and comparison with classical anthropometry
Genetical Statistics and Systems Biology

Abstract (Expand)

Anthropometric quantities are widely used in epidemiologic research as possible confounders, risk factors, or outcomes. 3D laser-based body scans (BS) allow evaluation of dozens of quantities in short … time with minimal physical contact between observers and probands. The aim of this study was to compare BS with classical manual anthropometric (CA) assessments with respect to feasibility, reliability, and validity. We performed a study on 108 individuals with multiple measurements of BS and CA to estimate intra- and inter-rater reliabilities for both. We suggested BS equivalents of CA measurements and determined validity of BS considering CA the gold standard. Throughout the study, the overall concordance correlation coefficient (OCCC) was chosen as indicator of agreement. BS was slightly more time consuming but better accepted than CA. For CA, OCCCs for intra- and inter-rater reliability were greater than 0.8 for all nine quantities studied. For BS, 9 of 154 quantities showed reliabilities below 0.7. BS proxies for CA measurements showed good agreement (minimum OCCC \textgreater 0.77) after offset correction. Thigh length showed higher reliability in BS while upper arm length showed higher reliability in CA. Except for these issues, reliabilities of CA measurements and their BS equivalents were comparable.

Authors: Andreas Kuehnapfel, Peter Ahnert, Markus Loeffler, Anja Broda, Markus Scholz

Date Published: 1st May 2016

Publication Type: Journal article

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