Breast cancer is a multifactorial disease with the highest incidence rates amongst all cancer typ... more Breast cancer is a multifactorial disease with the highest incidence rates amongst all cancer types. Further, high levels of circulating tumour cells are a characteristic of breast cancer patients demonstrating a particular predisposition to the development of breast cancer metastatic disease. Actual diagnostic approaches are frequently unable to recognise early stages of tumour development which impairs individual outcomes. In contrast, predictive and preventive risk assessment and early diagnosis may lead to full recovery after surgical resection. Recently, the authors have reported about the construction of diagnostic windows, which could influence the molecular diagnostics of breast cancer. In a previous study, diagnostic windows for breast cancer risk assessment were analysed. Women with non-malignant breast diseases demonstrating molecular profiles similar to those of breast cancer patients were enrolled into this follow-up study. In the interviews, for patients identified as predisposed to cancer, a specialised questionnaire has been set up to characterise individual risk factors and estimate their potential impacts on cancer onset and progression. By utilising the technological tool of diagnostic windows, 13 individuals have been identified demonstrating molecular profiles typical for patients diagnosed with breast cancer. The current paper summarises the analytical results and makes statements to the application of the pathology-specific molecular profiles recognised as the technological tool for improved diagnostic approach, breast cancer risk assessment and preventive health care management. The necessity to create individual patient profiles and analyse the evolution of the molecular signature is justified for advanced medical services. Expert recommendations are provided to promote further developments in the field of advanced breast cancer management.
ABSTRACT Aim: Breast cancer is the most common cause of cancer-related death among women. Delayed... more ABSTRACT Aim: Breast cancer is the most common cause of cancer-related death among women. Delayed diagnosis leads to development of metastasis and impairs the outcome. This study was designed to utilize subcellular DNA imaging by 'comet assay' and determine pathology-specific comet patterns as the robust biomarker to distinguish between high and low risk for breast cancer development among predisposed individuals with benign breast alterations. Materials & methods: A total of 161 patients were grouped as follows: benignancy, premenopause (n = 59); benignancy, postmenopause (n = 20); breast cancer, premenopause (n = 19); breast cancer, postmenopause (n = 63). On average, 800-1000 comets were evaluated per patient. Results & conclusion: The qualitative comet assay is an innovative approach for breast cancer risk assessment that can be utilized for the screening of highly predisposed individuals among patients with benign breast alterations. Pathology-specific comet patterns have been identified as the robust biomarker for breast cancer risk. Mathematic model-based diagnostic windows have been constructed for their clinical application.
Journal of Vascular and Interventional Radiology, 2014
To investigate passive transjugular intrahepatic portosystemic shunt (TIPS) stent expansion in pa... more To investigate passive transjugular intrahepatic portosystemic shunt (TIPS) stent expansion in patients with intentional "underdilation" (eg, 10-mm stent, 8-mm balloon) during TIPS creation. Custom in-house software was developed for objective quantification of cross-sectional stent area from computed tomography (CT) data. The technique was validated by in vitro experiments. The study included 39 patients (22 men; mean age, 59.2 y) who underwent TIPS creation (VIATORR stent graft [W. L. Gore & Associates, Flagstaff, Arizona]; n = 29; WALLSTENT endoprosthesis [Boston Scientific, Marlborough, Massachusetts], n = 10) with stent underdilation. Follow-up CT data of the patients were used to quantify in vivo stent area changes. Data were analyzed by variance analysis and entered into a general linear model to test for interrelations between stent area changes and clinical (eg, cirrhosis grade) and procedural parameters. In vitro validation of the in-house software showed good agreement and reproducibility without overestimation of stent area. Mean clinical follow-up time in patients was 787 days (range, 7-2,450 d). At the time of intervention, VIATORR stent grafts and WALLSTENT endoprostheses were dilated to an average of 64.4% ± 2.3% and 65.63% ± 8.52% of nominal area, respectively. At the last imaging follow-up evaluation, this value had increased in all stents to a mean of 87.8% ± 7.9% (VIATORR) and 82.34% ± 19.6% (WALLSTENT) in the TIPS tract (P…
The purpose of this analysis was to evaluate the impact of preoperative magnetic resonance imagin... more The purpose of this analysis was to evaluate the impact of preoperative magnetic resonance imaging (MRI) on management in patients with locoregional recurrent breast cancer. Forty-three patients who underwent treatment for locoregional relapse of breast cancer from 2008 through 2012 were analyzed. All patients underwent both conventional surveillance by mammography, ultrasound, and clinical examination and subsequent bilateral breast MRI. Preoperative MRI detected additional tumor foci in 15 of 43 patients (34.9%). In two cases (4.7%), the diagnosis of occult sites had no influence on the subsequent treatment. Two patients (4.7%) had an unfavorable change of surgical management with unnecessary additional resection of benign foci. Eleven patients benefited from the MRI scan detecting malignant occult lesions (25.6%) resulting in either additional surgical resection or radiotherapy. Patient and tumor characteristics in primary disease did not differ significantly between patients with a favorable impact on surgical management and patients who experienced either no benefit or even disadvantage from MRI scan. Preoperative breast MRI has a strong impact on the management of locoregional recurrent breast cancer. This study demonstrates that breast MRI is a powerful supplement to conventional diagnostic work-up, both during follow-up or preoperative treatment planning in recurrent disease.
Mapping of the great saphenous vein is very important for planning of peripheral and coronary byp... more Mapping of the great saphenous vein is very important for planning of peripheral and coronary bypass surgery. This study investigated mapping of the great saphenous vein as an adjunct to peripheral MR angiography using a blood pool contrast agent in patients who were referred for evaluation of peripheral arterial occlusive disease and bypass surgery. 38 patients with peripheral arterial occlusive disease (21 men; mean age: 71 years, range, 44-88 years) underwent peripheral MR angiography using the blood pool contrast agent Gadofosveset trisodium. Apart from primary arterial assessment images were evaluated in order to determine great saphenous vein diameters at three levels: below the saphenofemoral junction, mid thigh and 10 cm above the knee joint (usability: diameter range: >3 and <10 mm at one level and >3.5 and <10 mm at a neighboring level). Duplex ultrasound was performed by an independent examiner providing diameter measurements at the same levels. Additionally, vessel usability was determined intraoperatively by the vascular surgeon during subsequent bypass surgery. Mean venous diameters for MR angiography/duplex ultrasound were 5.4±2.6/5.5±2.8 mm (level 1), 4.7±2.7/4.6±2.9 mm (level 2) and 4.4±2.2/4.5±2.3 mm (level 3), respectively, without significant differences between the modalities (P = 0.207/0.806/0.518). Subsequent surgery was performed in 27/38 patients. A suitable saphenous vein was diagnosed in 25 and non-usability was diagnosed in 2 of the 27 patients based on MR angiography/duplex ultrasound, respectively. Usability was confirmed by intraoperative assessment in all of the 24 patients that received a venous bypass graft in subsequent bypass surgery. In 1 case, in which the great saphenous vein was assessed as useable by both MR angiography and duplex ultrasound, it was not used during subsequent bypass surgery due to the patients clinical condition and comorbidities. Simultaneous mapping of the great saphenous vein as an imaging adjunct to peripheral MR angiography with a blood pool contrast agent is an alternative to additive duplex ultrasound in patients undergoing subsequent peripheral bypass grafting.
Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one pati... more Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxifica...
The International Journal of Neuropsychopharmacology, 2008
Various lines of research suggest that neurotrophic processes in the hippocampus are key mechanis... more Various lines of research suggest that neurotrophic processes in the hippocampus are key mechanisms in major depressive disorder and are of relevance for response to antidepressive treatment. We performed proton magnetic resonance spectroscopy (1H-MRS) of the hippocampus at 3 T in 18 unmedicated subjects with unipolar major depressive episodes and in 10 age- and gender-matched healthy volunteers. Thirteen patients underwent a second examination after 8 wk treatment with either citalopram (n=7) or nortriptyline (n=6). Of these patients, 11 MRS datasets could be used for the assessment of treatment correlates. In the cross-sectional comparison, we observed a significant reduction of the metabolic ratios Glx/Cr (Glx=glutamine, glutamate and gamma-aminobutyric acid) and glutamine (Gln)/Cr in the patient group. The Gln/Glx ratio also showed a trend towards significant reduction. The individual effect of treatment correlated with an increase in the absolute concentrations of N-acetylaspartate (NAA) and of choline compounds (Cho). Low baseline NAA and Cho levels predicted positive treatment effects. There was no difference in any clinical or metabolic measure, either at baseline or at follow-up between the two treatment groups (citalopram, nortriptyline). Our data provide first evidence for a reduction of Gln in the hippocampus of subjects with major depression. Furthermore, we provide first evidence in patients with major depression for neurorestorative effects in the hippocampus by pharmacological treatment expressed by a correlation of NAA and Cho increases with treatment response. This accounts in particular for those patients with low NAA and Cho baseline levels.
The International Journal of Neuropsychopharmacology, 2010
FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested... more FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested to play a role in the regulation of the hypothalamic-pituitary-adrenocortical system and the pathophysiology of depression. Previously, three studies identified single nucleotide polymorphisms (SNPs) in the FKBP5 gene associated with response to antidepressants, and one study found an association with diagnosis of depression. We selected five markers from the region of interest. A case-control sample comprising 268 German in-patients with recurrent unipolar depression, and 284 German controls recruited from the general population were available. Association of the selected FKBP5 sequence variants with clinical depression were analysed. In addition, we explored association with treatment response by (a) the Hamilton Depression Rating Scale and (b) the dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test, as well as association with hippocampal volumes in a subpopulation of 110 patients. For three of the five investigated SNPs we were able to show association with the diagnosis of depression. In the subpopulation of 110 patients, diagnosis-related alleles were also associated with the reduction of cortisol secretion in the Dex/CRH test during a 4-wk treatment period, while psychopathological changes were not associated. Furthermore, diagnosis-related alleles were associated with reduction of the hippocampal volume. This study extends the replicated association of a promoter SNP with antidepressant response on a biological level by demonstrating normalization of the cortisol response under Dex/CRH stimulation during treatment. Furthermore, several of the investigated SNPs were associated with the disease status and the intermediate phenotype of hippocampal volume.
RöFo : Fortschritte auf dem Gebiete der Röntgenstrahlen und der Nuklearmedizin, 2014
In the first decade of the twenty-first century, whole-body magnetic resonance scanners with high... more In the first decade of the twenty-first century, whole-body magnetic resonance scanners with high field strengths (and thus potentially better signal-to-noise ratios) were developed. At the same time, parallel imaging and "echo-sharing" techniques were refined to allow for increasingly high spatial and temporal resolution in dynamic magnetic resonance angiography ("time-resolved" = TR-MRA). This technological progress facilitated tracking the passage of intra-venously administered contrast agent boluses as well as the acquisition of volume data sets at high image refresh rates ("4D-MRA"). This opened doors for many new applications in non-invasive vascular imaging, including simultaneous anatomic and functional analysis of many vascular pathologies including arterio-venous malformations. Different methods were established to acquire 4D-MRA using various strategies to acquire k-space trajectories over time in order to optimize imaging according to clinic...
To compare intraindividually the nerve conspicuity of the brachial and lumbosacral plexus on diff... more To compare intraindividually the nerve conspicuity of the brachial and lumbosacral plexus on diffusion-weighted (DW) MR neurography (MRN) at two different field strengths. 16 healthy volunteers were investigated at 3.0T and 1.5T applying optimized variants of a DW spin-echo echo-planar imaging sequence with short TI inversion recovery fat suppression. Full-volume (FV) and curved sub-volume (CSV) maximum intensity projection (MIP) images were reconstructed and nerve conspicuity was visually assessed. Moreover, visible length and sharpness of the nerves were quantitatively analyzed. On FV MIP images, nerve conspicuity at 3.0T compared to 1.5T was worse for brachial plexus (P=0.00228), but better for lumbosacral plexus (P=0.00666). On CSV MIP images, nerve conspicuity did not differ significantly for brachial plexus, but was better at 3.0T for lumbosacral plexus (P=0.00091). The visible length of the analyzed nerves did not differ significantly with the exception of some lumbosacral ne...
Zusammenfassung Fragestellung Wichtige, für eine erneute Herzoperation notwendige Informationen... more Zusammenfassung Fragestellung Wichtige, für eine erneute Herzoperation notwendige Informationen, welche durch die Koronarangiographie nur eingeschränkt geliefert werden können, beinhalten Angaben zum genauen Verlauf etwaiger Bypässe und ihre Beziehung zum Sternum. Ziel war es herauszufinden inwieweit man mittels einer EGK-getriggerten MSCT Untersuchung den anatomischen Verlauf, sowie Verschlüsse oder Stenosen von vorhandenen Bypässen darstellen und Aussagen über arteriosklerotische Wandveränderungen in venösen Bypässen machen kann, welche unter Umständen zur Embolisation infolge der Reoperation führen können. Material und Methoden Zwischen September 2003 und Juni 2005 wurden 40 Patienten (34 Männer/6 Frauen), die nach vorangegangener Bypassoperation nun zur erneuten Herzoperation eingewiesen wurden, mittels MSCT untersucht. Alle Patienten hatten im Vorfeld eine Koronarangiographie und wurden mittels eines 16-Slice MSCT (Phillips Mx8000 Brilliance) mit einer Schichtdicke von 0,75...
To analyze results of intensity-modulated radiotherapy after cryotherapy ablation for adenocarcin... more To analyze results of intensity-modulated radiotherapy after cryotherapy ablation for adenocarcinoma of the prostate. Patients were either treated adjuvantly after targeted cryotherapy or treated for salvage after local failure of standard whole-prostate cryotherapy. Patients were treated with intensity-modulated radiotherapy to a minimum dose of 73 Gy (mean dose, >75Gy). Prostate-specific antigen (PSA) failure was defined according to the Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology 2006 consensus definition. Late gastrointestinal and genitourinary toxicity were graded according to the Radiation Therapy Oncology Group late toxicity scale and the Late Effects of Normal Tissue-Subjective, Objective, Management, and Analytic scale. A total of 16 patients were treated from 1997 to 2007. Three patients were treated adjuvantly, and 13 patients were treated for local failure. The mean pre-cryotherapy PSA value was 8.7 ng/mL. The mean PSA value before irradiation was 6.0 ng/mL. Most patients were intermediate to high risk (8 intermediate risk, 7 high risk). Median follow-up was 33 months. No grade 3 or greater toxicity was seen. Biochemical (PSA) control was achieved in 12 of the 16 patients at last follow-up. Full-dose intensity-modulated radiotherapy after cryotherapy is well tolerated, without excess late morbidity. This study supports the use of radiation for cryotherapy failure salvage. Furthermore, the combination of cryotherapy and irradiation may be considered in a phase II trial.
Concomitant disease of the supra-aortic arteries can influence the outcome of surgical treatment ... more Concomitant disease of the supra-aortic arteries can influence the outcome of surgical treatment of carotid artery stenosis. However, sensitivity and specificity data of noninvasive contrast-enhanced 3-dimensional (3D) magnetic resonance angiography (CE MRA) for the detection of steno-occlusive disease of the entire supra-aortic arteries including the circle of Willis remain unclear. We aimed to intra-individually compare high-spatial-resolution CE 3D MRA and digital subtraction angiography (DSA) for the assessment of steno-occlusive vascular disease of the supra-aortic arteries. CE MRA and DSA of the supra-aortic arteries were prospectively performed in 50 consecutive patients. Intra-individual comparison of CE MRA and DSA was available in 833 arteries. High-spatial-resolution CE MRA comprised a measured voxel size of 0.81 mm x 0.81 mm x 1 mm (0.66 mm3). Steno-occlusive vascular disease of the 833 arteries was assessed independently by 2 radiologists according to the NASCET criteria. CE MRA had a sensitivity of 100% (73/73), a specificity of 99.3% (760/765), a positive predictive value of 93.6% (73/78), and a negative predictive value of 100% (760/760) by using a 70% to 99% threshold of arterial diameter stenosis. For detection of occlusion, sensitivity, specificity, PPV, and NPV value of CE MRA were 100%, respectively. Noninvasive high-spatial-resolution CE MRA is suited to replace diagnostic DSA for the detection of steno-occlusive disease of the supra-aortic arteries.
Breast cancer is a multifactorial disease with the highest incidence rates amongst all cancer typ... more Breast cancer is a multifactorial disease with the highest incidence rates amongst all cancer types. Further, high levels of circulating tumour cells are a characteristic of breast cancer patients demonstrating a particular predisposition to the development of breast cancer metastatic disease. Actual diagnostic approaches are frequently unable to recognise early stages of tumour development which impairs individual outcomes. In contrast, predictive and preventive risk assessment and early diagnosis may lead to full recovery after surgical resection. Recently, the authors have reported about the construction of diagnostic windows, which could influence the molecular diagnostics of breast cancer. In a previous study, diagnostic windows for breast cancer risk assessment were analysed. Women with non-malignant breast diseases demonstrating molecular profiles similar to those of breast cancer patients were enrolled into this follow-up study. In the interviews, for patients identified as predisposed to cancer, a specialised questionnaire has been set up to characterise individual risk factors and estimate their potential impacts on cancer onset and progression. By utilising the technological tool of diagnostic windows, 13 individuals have been identified demonstrating molecular profiles typical for patients diagnosed with breast cancer. The current paper summarises the analytical results and makes statements to the application of the pathology-specific molecular profiles recognised as the technological tool for improved diagnostic approach, breast cancer risk assessment and preventive health care management. The necessity to create individual patient profiles and analyse the evolution of the molecular signature is justified for advanced medical services. Expert recommendations are provided to promote further developments in the field of advanced breast cancer management.
ABSTRACT Aim: Breast cancer is the most common cause of cancer-related death among women. Delayed... more ABSTRACT Aim: Breast cancer is the most common cause of cancer-related death among women. Delayed diagnosis leads to development of metastasis and impairs the outcome. This study was designed to utilize subcellular DNA imaging by 'comet assay' and determine pathology-specific comet patterns as the robust biomarker to distinguish between high and low risk for breast cancer development among predisposed individuals with benign breast alterations. Materials & methods: A total of 161 patients were grouped as follows: benignancy, premenopause (n = 59); benignancy, postmenopause (n = 20); breast cancer, premenopause (n = 19); breast cancer, postmenopause (n = 63). On average, 800-1000 comets were evaluated per patient. Results & conclusion: The qualitative comet assay is an innovative approach for breast cancer risk assessment that can be utilized for the screening of highly predisposed individuals among patients with benign breast alterations. Pathology-specific comet patterns have been identified as the robust biomarker for breast cancer risk. Mathematic model-based diagnostic windows have been constructed for their clinical application.
Journal of Vascular and Interventional Radiology, 2014
To investigate passive transjugular intrahepatic portosystemic shunt (TIPS) stent expansion in pa... more To investigate passive transjugular intrahepatic portosystemic shunt (TIPS) stent expansion in patients with intentional "underdilation" (eg, 10-mm stent, 8-mm balloon) during TIPS creation. Custom in-house software was developed for objective quantification of cross-sectional stent area from computed tomography (CT) data. The technique was validated by in vitro experiments. The study included 39 patients (22 men; mean age, 59.2 y) who underwent TIPS creation (VIATORR stent graft [W. L. Gore & Associates, Flagstaff, Arizona]; n = 29; WALLSTENT endoprosthesis [Boston Scientific, Marlborough, Massachusetts], n = 10) with stent underdilation. Follow-up CT data of the patients were used to quantify in vivo stent area changes. Data were analyzed by variance analysis and entered into a general linear model to test for interrelations between stent area changes and clinical (eg, cirrhosis grade) and procedural parameters. In vitro validation of the in-house software showed good agreement and reproducibility without overestimation of stent area. Mean clinical follow-up time in patients was 787 days (range, 7-2,450 d). At the time of intervention, VIATORR stent grafts and WALLSTENT endoprostheses were dilated to an average of 64.4% ± 2.3% and 65.63% ± 8.52% of nominal area, respectively. At the last imaging follow-up evaluation, this value had increased in all stents to a mean of 87.8% ± 7.9% (VIATORR) and 82.34% ± 19.6% (WALLSTENT) in the TIPS tract (P…
The purpose of this analysis was to evaluate the impact of preoperative magnetic resonance imagin... more The purpose of this analysis was to evaluate the impact of preoperative magnetic resonance imaging (MRI) on management in patients with locoregional recurrent breast cancer. Forty-three patients who underwent treatment for locoregional relapse of breast cancer from 2008 through 2012 were analyzed. All patients underwent both conventional surveillance by mammography, ultrasound, and clinical examination and subsequent bilateral breast MRI. Preoperative MRI detected additional tumor foci in 15 of 43 patients (34.9%). In two cases (4.7%), the diagnosis of occult sites had no influence on the subsequent treatment. Two patients (4.7%) had an unfavorable change of surgical management with unnecessary additional resection of benign foci. Eleven patients benefited from the MRI scan detecting malignant occult lesions (25.6%) resulting in either additional surgical resection or radiotherapy. Patient and tumor characteristics in primary disease did not differ significantly between patients with a favorable impact on surgical management and patients who experienced either no benefit or even disadvantage from MRI scan. Preoperative breast MRI has a strong impact on the management of locoregional recurrent breast cancer. This study demonstrates that breast MRI is a powerful supplement to conventional diagnostic work-up, both during follow-up or preoperative treatment planning in recurrent disease.
Mapping of the great saphenous vein is very important for planning of peripheral and coronary byp... more Mapping of the great saphenous vein is very important for planning of peripheral and coronary bypass surgery. This study investigated mapping of the great saphenous vein as an adjunct to peripheral MR angiography using a blood pool contrast agent in patients who were referred for evaluation of peripheral arterial occlusive disease and bypass surgery. 38 patients with peripheral arterial occlusive disease (21 men; mean age: 71 years, range, 44-88 years) underwent peripheral MR angiography using the blood pool contrast agent Gadofosveset trisodium. Apart from primary arterial assessment images were evaluated in order to determine great saphenous vein diameters at three levels: below the saphenofemoral junction, mid thigh and 10 cm above the knee joint (usability: diameter range: >3 and <10 mm at one level and >3.5 and <10 mm at a neighboring level). Duplex ultrasound was performed by an independent examiner providing diameter measurements at the same levels. Additionally, vessel usability was determined intraoperatively by the vascular surgeon during subsequent bypass surgery. Mean venous diameters for MR angiography/duplex ultrasound were 5.4±2.6/5.5±2.8 mm (level 1), 4.7±2.7/4.6±2.9 mm (level 2) and 4.4±2.2/4.5±2.3 mm (level 3), respectively, without significant differences between the modalities (P = 0.207/0.806/0.518). Subsequent surgery was performed in 27/38 patients. A suitable saphenous vein was diagnosed in 25 and non-usability was diagnosed in 2 of the 27 patients based on MR angiography/duplex ultrasound, respectively. Usability was confirmed by intraoperative assessment in all of the 24 patients that received a venous bypass graft in subsequent bypass surgery. In 1 case, in which the great saphenous vein was assessed as useable by both MR angiography and duplex ultrasound, it was not used during subsequent bypass surgery due to the patients clinical condition and comorbidities. Simultaneous mapping of the great saphenous vein as an imaging adjunct to peripheral MR angiography with a blood pool contrast agent is an alternative to additive duplex ultrasound in patients undergoing subsequent peripheral bypass grafting.
Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one pati... more Global figures clearly demonstrate inadequacy of current diabetes care: every 10 seconds one patient dies of diabetes-related pathologies. Nephropathy is the leading secondary complication of the disease. Nutritional supplement by chromium-picolinate is assumed to have beneficial therapeutic effects. However, potential toxic effects reported increase concerns about safety of chromium-picolinate. The experimental design aimed at determining, whether the treatment with clinically relevant doses of chromium-picolinate can harm through DNA damage and extensive alterations in central detoxification / cell-cycle regulating pathways in treatment of diabetes. Well-acknowledged animal model of db/db-mice and clinically relevant doses of chromium-picolinate were used. As an index of DNA-damage, measurement of DNA-breaks was performed using "Comet Assay"-analysis. Individual and group-specific expression patterns of SOD-1 and P53 were evaluated to give a clue about central detoxifica...
The International Journal of Neuropsychopharmacology, 2008
Various lines of research suggest that neurotrophic processes in the hippocampus are key mechanis... more Various lines of research suggest that neurotrophic processes in the hippocampus are key mechanisms in major depressive disorder and are of relevance for response to antidepressive treatment. We performed proton magnetic resonance spectroscopy (1H-MRS) of the hippocampus at 3 T in 18 unmedicated subjects with unipolar major depressive episodes and in 10 age- and gender-matched healthy volunteers. Thirteen patients underwent a second examination after 8 wk treatment with either citalopram (n=7) or nortriptyline (n=6). Of these patients, 11 MRS datasets could be used for the assessment of treatment correlates. In the cross-sectional comparison, we observed a significant reduction of the metabolic ratios Glx/Cr (Glx=glutamine, glutamate and gamma-aminobutyric acid) and glutamine (Gln)/Cr in the patient group. The Gln/Glx ratio also showed a trend towards significant reduction. The individual effect of treatment correlated with an increase in the absolute concentrations of N-acetylaspartate (NAA) and of choline compounds (Cho). Low baseline NAA and Cho levels predicted positive treatment effects. There was no difference in any clinical or metabolic measure, either at baseline or at follow-up between the two treatment groups (citalopram, nortriptyline). Our data provide first evidence for a reduction of Gln in the hippocampus of subjects with major depression. Furthermore, we provide first evidence in patients with major depression for neurorestorative effects in the hippocampus by pharmacological treatment expressed by a correlation of NAA and Cho increases with treatment response. This accounts in particular for those patients with low NAA and Cho baseline levels.
The International Journal of Neuropsychopharmacology, 2010
FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested... more FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested to play a role in the regulation of the hypothalamic-pituitary-adrenocortical system and the pathophysiology of depression. Previously, three studies identified single nucleotide polymorphisms (SNPs) in the FKBP5 gene associated with response to antidepressants, and one study found an association with diagnosis of depression. We selected five markers from the region of interest. A case-control sample comprising 268 German in-patients with recurrent unipolar depression, and 284 German controls recruited from the general population were available. Association of the selected FKBP5 sequence variants with clinical depression were analysed. In addition, we explored association with treatment response by (a) the Hamilton Depression Rating Scale and (b) the dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test, as well as association with hippocampal volumes in a subpopulation of 110 patients. For three of the five investigated SNPs we were able to show association with the diagnosis of depression. In the subpopulation of 110 patients, diagnosis-related alleles were also associated with the reduction of cortisol secretion in the Dex/CRH test during a 4-wk treatment period, while psychopathological changes were not associated. Furthermore, diagnosis-related alleles were associated with reduction of the hippocampal volume. This study extends the replicated association of a promoter SNP with antidepressant response on a biological level by demonstrating normalization of the cortisol response under Dex/CRH stimulation during treatment. Furthermore, several of the investigated SNPs were associated with the disease status and the intermediate phenotype of hippocampal volume.
RöFo : Fortschritte auf dem Gebiete der Röntgenstrahlen und der Nuklearmedizin, 2014
In the first decade of the twenty-first century, whole-body magnetic resonance scanners with high... more In the first decade of the twenty-first century, whole-body magnetic resonance scanners with high field strengths (and thus potentially better signal-to-noise ratios) were developed. At the same time, parallel imaging and "echo-sharing" techniques were refined to allow for increasingly high spatial and temporal resolution in dynamic magnetic resonance angiography ("time-resolved" = TR-MRA). This technological progress facilitated tracking the passage of intra-venously administered contrast agent boluses as well as the acquisition of volume data sets at high image refresh rates ("4D-MRA"). This opened doors for many new applications in non-invasive vascular imaging, including simultaneous anatomic and functional analysis of many vascular pathologies including arterio-venous malformations. Different methods were established to acquire 4D-MRA using various strategies to acquire k-space trajectories over time in order to optimize imaging according to clinic...
To compare intraindividually the nerve conspicuity of the brachial and lumbosacral plexus on diff... more To compare intraindividually the nerve conspicuity of the brachial and lumbosacral plexus on diffusion-weighted (DW) MR neurography (MRN) at two different field strengths. 16 healthy volunteers were investigated at 3.0T and 1.5T applying optimized variants of a DW spin-echo echo-planar imaging sequence with short TI inversion recovery fat suppression. Full-volume (FV) and curved sub-volume (CSV) maximum intensity projection (MIP) images were reconstructed and nerve conspicuity was visually assessed. Moreover, visible length and sharpness of the nerves were quantitatively analyzed. On FV MIP images, nerve conspicuity at 3.0T compared to 1.5T was worse for brachial plexus (P=0.00228), but better for lumbosacral plexus (P=0.00666). On CSV MIP images, nerve conspicuity did not differ significantly for brachial plexus, but was better at 3.0T for lumbosacral plexus (P=0.00091). The visible length of the analyzed nerves did not differ significantly with the exception of some lumbosacral ne...
Zusammenfassung Fragestellung Wichtige, für eine erneute Herzoperation notwendige Informationen... more Zusammenfassung Fragestellung Wichtige, für eine erneute Herzoperation notwendige Informationen, welche durch die Koronarangiographie nur eingeschränkt geliefert werden können, beinhalten Angaben zum genauen Verlauf etwaiger Bypässe und ihre Beziehung zum Sternum. Ziel war es herauszufinden inwieweit man mittels einer EGK-getriggerten MSCT Untersuchung den anatomischen Verlauf, sowie Verschlüsse oder Stenosen von vorhandenen Bypässen darstellen und Aussagen über arteriosklerotische Wandveränderungen in venösen Bypässen machen kann, welche unter Umständen zur Embolisation infolge der Reoperation führen können. Material und Methoden Zwischen September 2003 und Juni 2005 wurden 40 Patienten (34 Männer/6 Frauen), die nach vorangegangener Bypassoperation nun zur erneuten Herzoperation eingewiesen wurden, mittels MSCT untersucht. Alle Patienten hatten im Vorfeld eine Koronarangiographie und wurden mittels eines 16-Slice MSCT (Phillips Mx8000 Brilliance) mit einer Schichtdicke von 0,75...
To analyze results of intensity-modulated radiotherapy after cryotherapy ablation for adenocarcin... more To analyze results of intensity-modulated radiotherapy after cryotherapy ablation for adenocarcinoma of the prostate. Patients were either treated adjuvantly after targeted cryotherapy or treated for salvage after local failure of standard whole-prostate cryotherapy. Patients were treated with intensity-modulated radiotherapy to a minimum dose of 73 Gy (mean dose, >75Gy). Prostate-specific antigen (PSA) failure was defined according to the Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology 2006 consensus definition. Late gastrointestinal and genitourinary toxicity were graded according to the Radiation Therapy Oncology Group late toxicity scale and the Late Effects of Normal Tissue-Subjective, Objective, Management, and Analytic scale. A total of 16 patients were treated from 1997 to 2007. Three patients were treated adjuvantly, and 13 patients were treated for local failure. The mean pre-cryotherapy PSA value was 8.7 ng/mL. The mean PSA value before irradiation was 6.0 ng/mL. Most patients were intermediate to high risk (8 intermediate risk, 7 high risk). Median follow-up was 33 months. No grade 3 or greater toxicity was seen. Biochemical (PSA) control was achieved in 12 of the 16 patients at last follow-up. Full-dose intensity-modulated radiotherapy after cryotherapy is well tolerated, without excess late morbidity. This study supports the use of radiation for cryotherapy failure salvage. Furthermore, the combination of cryotherapy and irradiation may be considered in a phase II trial.
Concomitant disease of the supra-aortic arteries can influence the outcome of surgical treatment ... more Concomitant disease of the supra-aortic arteries can influence the outcome of surgical treatment of carotid artery stenosis. However, sensitivity and specificity data of noninvasive contrast-enhanced 3-dimensional (3D) magnetic resonance angiography (CE MRA) for the detection of steno-occlusive disease of the entire supra-aortic arteries including the circle of Willis remain unclear. We aimed to intra-individually compare high-spatial-resolution CE 3D MRA and digital subtraction angiography (DSA) for the assessment of steno-occlusive vascular disease of the supra-aortic arteries. CE MRA and DSA of the supra-aortic arteries were prospectively performed in 50 consecutive patients. Intra-individual comparison of CE MRA and DSA was available in 833 arteries. High-spatial-resolution CE MRA comprised a measured voxel size of 0.81 mm x 0.81 mm x 1 mm (0.66 mm3). Steno-occlusive vascular disease of the 833 arteries was assessed independently by 2 radiologists according to the NASCET criteria. CE MRA had a sensitivity of 100% (73/73), a specificity of 99.3% (760/765), a positive predictive value of 93.6% (73/78), and a negative predictive value of 100% (760/760) by using a 70% to 99% threshold of arterial diameter stenosis. For detection of occlusion, sensitivity, specificity, PPV, and NPV value of CE MRA were 100%, respectively. Noninvasive high-spatial-resolution CE MRA is suited to replace diagnostic DSA for the detection of steno-occlusive disease of the supra-aortic arteries.
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Papers by Hans Schild