Orthogonal polarization spectroscopy (OPS) is a technique for taking images to finally characteri... more Orthogonal polarization spectroscopy (OPS) is a technique for taking images to finally characterise microcirculation. Current image analysis algorithms have limitations when applied to image sequences obtained from the liver. We developed an automatic analysis tool which enables detection of liver vessels, measurement of vessel diameters, and determination of blood flow velocities with sparse user interactions. For validation purpose, data was analysed with our proposed algorithm and compared with manual results by experienced users. Related to commercial products, the needed time for analysis is reduced from more than 30 minutes to less than 2 minutes with comparable results for accuracy.
Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FL... more Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FLR) in patients with primarily irresectable liver tumor. However, regeneration of the FLR is not always sufficient to allow curative resection of the portally-deprived tumor-bearing liver lobe. We hypothesize that simultaneous hepatectomy (PHx) and PVL augments regeneration of the FLR and that the effect is related to the extent of the additional resection. Seventy-two Lewis rats were enrolled into 3 groups: 20%PVL + 70%PHx; 70%PVL + 20%PHx; 90%PVL. Animals were observed for 1, 2, 3 and 7 days postoperatively (n = 6/time point). Liver enzymes, caudate liver/body-weight-ratio, BrdU-proliferation-index (PI), proliferating-cell-nuclear-antigen (PCNA)-mRNA-expression level and autophagy-related-proteins were evaluated. Compared with 90% PVL, additional PHx induced significantly more hypertrophy during the observation time, which was confirmed by significantly higher PI and higher level of PCN...
The aim of this study was to establish a procedure for blood progenitor cell graft processing in ... more The aim of this study was to establish a procedure for blood progenitor cell graft processing in rats. As a first step the mobilization protocol was optimized. The second step was dedicated to define the optimal source for subsequent graft manufacturing: either peripheral blood or spleen. The third step was designed to establish a protocol for purification of stem cells. The best mobilization results in terms of white blood cell count, granulocyte colony forming units (CFUG) and CD90 positive progenitor cells were obtained after pre-treatment of the donors for 5 days with recombinant human granulocyte colony stimulating factor (100 I¼g/kg) in combination with murine stem cell factor (33 I¼g/kg). Splenectomy prior to mobilization increased the yield of stem cells from peripheral blood. The numbers of CD90-positive progenitor cells recovered from the spleen of one rat after stem cell mobilization were sufficient to generate one stem cell graft. Grafts containing ...
Aging is a natural life process which leads to a gradual decline of essential physiological proce... more Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS...
Decellularized tissue is an important source for biological tissue engineering. Evaluation of the... more Decellularized tissue is an important source for biological tissue engineering. Evaluation of the quality of decellularized tissue is performed using scanned images of hematoxylin-eosin stained (H&E) tissue sections and is usually dependent on the observer. The first step in creating a tool for the assessment of the quality of the liver scaffold without observer bias is the automatic segmentation of the whole slide image into three classes: the background, intralobular area, and extralobular area. Such segmentation enables to perform the texture analysis in the intralobular area of the liver scaffold, which is crucial part in the recellularization procedure. Existing semi-automatic methods for general segmentation (i.e., thresholding, watershed, etc.) do not meet the quality requirements. Moreover, there are no methods available to solve this task automatically. Given the low amount of training data, we proposed a two-stage method. The first stage is based on classification of simpl...
Inflammation, which is induced by the immune response, is recognized as the driving factor in man... more Inflammation, which is induced by the immune response, is recognized as the driving factor in many diseases, including infections and inflammatory diseases, metabolic disorders and cancers. Genetic variations in pivotal genes associated with the immune response, particularly single nucleotide polymorphisms (SNPs), may account for predisposition and clinical outcome of diseases. Lipopolysaccharide (LPS)-binding protein (LBP) functions as an enhancer of the host response to LPS, the main component of the outer membrane of gram-native bacteria. Given the crucial role of LBP in inflammation, we will review the impact of SNPs in the LBP gene on infections and inflammatory diseases, metabolic disorders and cancers.
Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie
Zusammenfassung Hintergrund Die Verwendung videobasierter Analysekonzepte gewinnt in der medizini... more Zusammenfassung Hintergrund Die Verwendung videobasierter Analysekonzepte gewinnt in der medizinischen Ausbildung zunehmend an Bedeutung. In erster Linie dienen diese Tools dazu, Informationen über die individuelle Performance eines Kandidaten zu bekommen und Feedback zu geben. Die vorliegende Studie untersucht, ob die Videoanalyse praktischer Fertigkeiten auch für die Weiterentwicklung des chirurgischen Unterrichts genutzt werden kann. Material und Methoden Zunächst wurde die Durchführung einer chirurgischen Nahtübung (Dauer: 3 min) bei Studierenden des 10. Semesters (n = 38) videobasiert dokumentiert. Im Anschluss folgte die Analyse des Videomaterials anhand von 10 spezifischen Kriterien. Die Analyse diente dann als Grundlage für die Entwicklung fehlerpräventiver Übungen. Nachfolgend wurden die Effekte der fehlerpräventiven Übungen auf die Ergebnisqualität der Nahtübung im Rahmen eines Pilotversuchs in einem 2-Gruppen-Vergleich untersucht. Ergebnisse Die Videosequenzen wurden von ...
In-vivo liver decellularization has become a promising strategy to study in-vivo liver engineerin... more In-vivo liver decellularization has become a promising strategy to study in-vivo liver engineering. However, long term survival after in-vivo liver decellularization has not yet been achieved due to anatomical and technical challenges. This study aimed to establish a survival model of in-vivo partial liver lobe perfusion-decellularization in rat. We compared three decellularization protocols (1%Triton X100 followed by 1%SDS, 1%SDS versus 1%Triton X100, n=6/group). Using the optimal one as judged by macroscopy, histology and DNA-content, we characterized the structural integrity and matrix-proteins using histology, scanning electron microscopy (SEM), Computed Tomography (CT) scanning and immunohistochemistry. We prevented contamination of the abdominal cavity with the corrosive detergents by using polyvinylidene chloride (PVDC) film + dry gauze in comparison to PVDC-film + dry gauze + aspiration tube (n=6/group). Physiological reperfusion was assessed by histology. Survival rate was determined after a 7 d observation period. Only perfusion with 1% SDS resulted in an acellular scaffold (fully translucent without histologically detectable tissue remnants, DNA concentration is less than 2% of that in native lobe) with remarkable structural and ultrastructural integrity as well as preservation of main matrix proteins (immunohistochemically positive for collagen IV, laminin, and elastin). Contamination of abdominal organs with the potentially toxic SDS-solution was achieved by placing a suction tube in addition to the PDVC-film + dry gauze and allowed 7d-survival of all animals without severe postoperative complications. Upon reperfusion, the liver turned red within sec without any leakage from the surface of the liver. About 12 h after reperfusion, blood cells but also some clots were visible in the portal vein (PV), sinusoidal matrix network and central vein (CV), suggesting physiological perfusion. In conclusion, our results study shows the first available data on generation of a survival model of in-vivo parenchymal organ decellularization, creating a critical step towards in-vivo organ engineering.
Background: Medical schools globally now use objective structured clinical examinations (OSCEs) f... more Background: Medical schools globally now use objective structured clinical examinations (OSCEs) for assessing a student's clinical performance. In Germany, almost all of the 36 medical schools have incorporated at least one summative OSCE into their clinical curriculum. This nationwide study aimed to examine whether the introduction of OSCEs shifted studying time. The authors explored what resources were important for studying in preparation for OSCEs, how much time students spent studying, and how they performed; each compared to traditionally used multiple choice question (MCQ) tests. Methods: The authors constructed a questionnaire comprising two identical sections, one for each assessment method. Either section contained a list of 12 study resources requesting preferences on a 5-point scale, and two open-ended questions about average studying time and average grades achieved. During springtime of 2015, medical schools in Germany were asked to administer the web-based questionnaire to their students in years 3-6. Statistical analysis compared the responses on the open-ended questions between the OSCE and MCQs using a paired t-test. Results: The sample included 1131 students from 32 German medical schools. Physical examination courses were most important in preparation for OSCEs, followed by class notes/logs and the skills lab. Other activities in clinical settings (e.g. medical clerkships) and collaborative strategies ranked next. Conversely, resources for gathering knowledge (e.g. lectures or textbooks) were of minor importance when studying for OSCEs. Reported studying time was lower for OSCEs compared to MCQ tests. The reported average grade, however, was better on OSCEs. Conclusions: The study findings suggest that the introduction of OSCEs shifted studying time. When preparing for OSCEs students focus on the acquisition of clinical skills and need less studying time to achieve the expected level of competence/performance, as compared to the MCQ tests.
Background: Given the expected increase in those entering retirement, the number of practising ph... more Background: Given the expected increase in those entering retirement, the number of practising physicians is predicted to decrease. Conversely, the number of physicians needed is set to increase, due to higher demands resulting from the increasing average age of the German population. This may cause a deficit in the availability and accessibility of medical care for the population in Germany, as well as in other countries. As such, there needs to be a specific focus on the next generation of physicians. Will they fill the gap in those medical specialties where it is most needed? This study aims to investigate (a) preferences for medical specialties over time and (b) the reasoning behind these preferences among students. Methods: Over three subsequent years, all medical students from the Jena Faculty of Medicine were repeatedly invited to participate in an online survey. The questionnaire consisted of three parts to explore the students' (1) preferred postgraduate specialty, (2) the reasons for their decision and (3) socio-demographic data. Data analysis was performed using Fisher's exact tests and logistic regression analysis. Results: The number of students completing the questionnaire in a given year ranged from 180 to 320, resulting in a total number of 720 completed questionnaires. Between 40 and 50% of the students preferred internal medicine as postgraduate specialty. About 25% of the students were interested in a surgical specialty. Diagnostics and psychiatric medical fields were preferred by about 10% of all students for each field in each year of the survey. A large percentage (about 18%) of the students remained undecided. The factors influencing the students' specialty preferences were most frequently reconciliation of work and family life, career goals as well as predicted workload. The factors depended on the preferred medical specialty. Conclusion: The influencing factors should be taken into account for recruiting prospective residents. Doing so could increase the chance to attract the number of physicians needed to ensure adequate medical care in the field of interest, according to the growing health needs of the population.
Multimodal treatment concepts including liver transplantation for hepatocellular carcinoma (HCC),... more Multimodal treatment concepts including liver transplantation for hepatocellular carcinoma (HCC), extended resection methods and neoadjuvant chemotherapy for colorectal liver metastasis significantly improve patients' outcome. However, surgery-induced hepatic ischemia-reperfusion injury (IRI) and chemotherapy-associated hepatotoxicity result in hepatocellular damage and compromised liver function. Activation of common key pathways in ischemic liver and hepatotoxic injury results in oxidative stress, inflammatory responses and apoptosis causing organ damage. Controlling liver damage before and during surgery is essential for the postoperative outcome. Nigella sativa has a long tradition as a natural remedy. In the essential oil, Thymoquinone (TQ) was identified as the main component and responsible for most of the therapeutic effects. Therefore, this systematic review aimed to summarize the hepatoprotective effects of TQ and its potential suitability to improve surgical outcome by reducing surgical ischemic injury and hepatotoxicity of neoadjuvant chemotherapy. The key findings can be summarized as TQ having strong antioxidant, anti-inflammatory, antifibrotic, anti-/proapoptotic and anticarcinogenic effects. Almost no side effects were reported irrespective of a large dose range, suggesting a wide therapeutic window. These results give rise to the expectation that TQ could evolve to a novel powerful drug to reduce hepatic injury.
Ventral or incisional hernia are a common disease pattern in general surgery. Mostcommonly, a mes... more Ventral or incisional hernia are a common disease pattern in general surgery. Mostcommonly, a mesh repair is used for reconstruction, whereby the mesh itself might causecomplications, like infections or adhesions. Biological materials, like biocellulose, might reducethese clinical problems substantially. In this prospective rodent study, a biocellulose mesh(produced by Gluconacetobacter xylinus) was implanted either by a sublay technique or assupplementation of the abdominal wall. After an observation period of 90 days, animals weresacrificed. The adhesions after the reconstruction of the abdominal wall were moderate. Thehistologic investigations revealed that the biocellulose itself was inert, with a minimal regenerativeresponse surrounding the mesh. The explanted mesh showed a minimal shrinkage (around 15%) aswell as a minimal loss of tear-out force, which might be without clinical relevance. This is the firstin vivo study describing biocellulose as a suitable mesh for the repair ...
Journal of visualized experiments : JoVE, Jan 6, 2018
Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be... more Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be used in transplantation. Recently, in vivo liver engineering, including in vivo organ decellularization followed by repopulation, has emerged as a promising approach over ex vivo liver engineering. However, postoperative survival was not achieved. The aim of this study is to develop a novel surgical technique of in vivo selective liver lobe perfusion in rats as a prerequisite for in vivo liver engineering. We generate a circuit bypass only through the left lateral lobe. Then, the left lateral lobe is perfused with heparinized saline. The experiment is performed with 4 groups (n = 3 rats per group) based on different perfusion times of 20 min, 2 h, 3 h, and 4 h. Survival, as well as the macroscopically visible change of color and the histologically determined absence of blood cells in the portal triad and the sinusoids, is taken as an indicator for a successful model establishment. After...
Automated image analysis enables quantitative measurement of steatosis in histological images. Ho... more Automated image analysis enables quantitative measurement of steatosis in histological images. However, spatial heterogeneity of steatosis can make quantitative steatosis scores unreliable. To improve the reliability, we have developed novel scores that are "focused" on steatotic tissue areas. Focused scores use concepts of tile-based hotspot analysis in order to compute statistics about steatotic tissue areas in an objective way. We evaluated focused scores on three data sets of images of rodent liver sections exhibiting different amounts of dietary-induced steatosis. The same evaluation was conducted with the standard steatosis score computed by most image analysis methods. The standard score reliably discriminated large differences in steatosis (intraclass correlation coefficient ICC = 0.86), but failed to discriminate small (ICC = 0.54) and very small (ICC = 0.14) differences. With an appropriate tile size, mean-based focused scores reliably discriminated large (ICC = ...
Background: High levels of serum lipopolysaccharide (LPS) were observed in sepsis patients with l... more Background: High levels of serum lipopolysaccharide (LPS) were observed in sepsis patients with liver injury and high mortality. However, the role of liver in modulation LPS induced inflammatory injury was ill investigated. In the present study, the severity of LPS induced inflammatory response was observed after liver resection or portal branch occlusion to decreasing functional liver mass. The local and systemic damage was observed to investigate the role of liver in modulation inflammatory injury. Methods: First, 30%, 70%, and 90% partial hepatectomy (PH) were performed, and serum TNF-α, survival rate, and hepatic LPS uptake was observed. Second, LPS-exposure of the functional liver mass was decreased by selectively blocking the RL prior to LPS-injection, which was given 30 min before a 70% PH, and the inflammatory response was compared in the occluded and the non-occluded liver. The control group was subjected to LPS injection 30 min prior to liver resection without blocking the RL transiently. The serum TNF-α, ALT, AST, creatinine levels, and urea levels, survival rate, hepatic LPS uptake, and hepatic inflammatory cytokines was observed. Results: The decreasing of functional liver mass after 90%, 70%, and 30% PH was associated with decreased serum TNF-α, survival rate, and increased hepatic LPS uptake after LPS injection. Occluding the right lobes (RL) prior to LPS administration reversed the liver injury caused by 70% PH, indicated by 100% survival rate and decreased liver and kidney injury, and systemic inflammatory response. The induction of inflammatory response in occluding liver lobes were lower than un-occluding liver lobes. Conclusions: The severity of the LPS-induced systemic inflammatory injury is determined by functional liver volume. This observation suggests that the liver is the central organ for the initiation of the inflammatory response, and is involved in causing a severe SIRS with systemic damage and death.
Introduction. Sepsis is the primary cause of death from infection. We wanted to improve the outco... more Introduction. Sepsis is the primary cause of death from infection. We wanted to improve the outcome of sepsis by stimulating innate immunity in combination with modulating the severity of inflammatory responses in rats. Method. Sepsis was induced by the injection of feces suspension (control). A 5-day course of G-CSF treatment was given before the septic insult (G-CSF). The inflammatory response was decreased using various doses of the LPS-blocking peptide LBPK95A (5 mg/kg=100% Combi group, 0.5 mg/kg=10% Combi group, and 0.05 mg/kg=1% Combi group). Survival rates were observed. Bacterial clearance, neutrophil infiltration, tissue damage, and the induction of hepatic and systemic inflammatory responses were determined 2 h and 12 h after the septic insult. Results. High-dose LBPK95A (100% Combi) reduced the survival rate to 10%, whereas low-dose LBPK95A (10% and 1% Combi) increased the survival rates to 50% and 80%, respectively. The survival rates inversely correlated with multiorgan...
Orthogonal polarization spectroscopy (OPS) is a technique for taking images to finally characteri... more Orthogonal polarization spectroscopy (OPS) is a technique for taking images to finally characterise microcirculation. Current image analysis algorithms have limitations when applied to image sequences obtained from the liver. We developed an automatic analysis tool which enables detection of liver vessels, measurement of vessel diameters, and determination of blood flow velocities with sparse user interactions. For validation purpose, data was analysed with our proposed algorithm and compared with manual results by experienced users. Related to commercial products, the needed time for analysis is reduced from more than 30 minutes to less than 2 minutes with comparable results for accuracy.
Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FL... more Portal vein ligation (PVL) has been adopted to induce hypertrophy of the future liver remnant (FLR) in patients with primarily irresectable liver tumor. However, regeneration of the FLR is not always sufficient to allow curative resection of the portally-deprived tumor-bearing liver lobe. We hypothesize that simultaneous hepatectomy (PHx) and PVL augments regeneration of the FLR and that the effect is related to the extent of the additional resection. Seventy-two Lewis rats were enrolled into 3 groups: 20%PVL + 70%PHx; 70%PVL + 20%PHx; 90%PVL. Animals were observed for 1, 2, 3 and 7 days postoperatively (n = 6/time point). Liver enzymes, caudate liver/body-weight-ratio, BrdU-proliferation-index (PI), proliferating-cell-nuclear-antigen (PCNA)-mRNA-expression level and autophagy-related-proteins were evaluated. Compared with 90% PVL, additional PHx induced significantly more hypertrophy during the observation time, which was confirmed by significantly higher PI and higher level of PCN...
The aim of this study was to establish a procedure for blood progenitor cell graft processing in ... more The aim of this study was to establish a procedure for blood progenitor cell graft processing in rats. As a first step the mobilization protocol was optimized. The second step was dedicated to define the optimal source for subsequent graft manufacturing: either peripheral blood or spleen. The third step was designed to establish a protocol for purification of stem cells. The best mobilization results in terms of white blood cell count, granulocyte colony forming units (CFUG) and CD90 positive progenitor cells were obtained after pre-treatment of the donors for 5 days with recombinant human granulocyte colony stimulating factor (100 I¼g/kg) in combination with murine stem cell factor (33 I¼g/kg). Splenectomy prior to mobilization increased the yield of stem cells from peripheral blood. The numbers of CD90-positive progenitor cells recovered from the spleen of one rat after stem cell mobilization were sufficient to generate one stem cell graft. Grafts containing ...
Aging is a natural life process which leads to a gradual decline of essential physiological proce... more Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS...
Decellularized tissue is an important source for biological tissue engineering. Evaluation of the... more Decellularized tissue is an important source for biological tissue engineering. Evaluation of the quality of decellularized tissue is performed using scanned images of hematoxylin-eosin stained (H&E) tissue sections and is usually dependent on the observer. The first step in creating a tool for the assessment of the quality of the liver scaffold without observer bias is the automatic segmentation of the whole slide image into three classes: the background, intralobular area, and extralobular area. Such segmentation enables to perform the texture analysis in the intralobular area of the liver scaffold, which is crucial part in the recellularization procedure. Existing semi-automatic methods for general segmentation (i.e., thresholding, watershed, etc.) do not meet the quality requirements. Moreover, there are no methods available to solve this task automatically. Given the low amount of training data, we proposed a two-stage method. The first stage is based on classification of simpl...
Inflammation, which is induced by the immune response, is recognized as the driving factor in man... more Inflammation, which is induced by the immune response, is recognized as the driving factor in many diseases, including infections and inflammatory diseases, metabolic disorders and cancers. Genetic variations in pivotal genes associated with the immune response, particularly single nucleotide polymorphisms (SNPs), may account for predisposition and clinical outcome of diseases. Lipopolysaccharide (LPS)-binding protein (LBP) functions as an enhancer of the host response to LPS, the main component of the outer membrane of gram-native bacteria. Given the crucial role of LBP in inflammation, we will review the impact of SNPs in the LBP gene on infections and inflammatory diseases, metabolic disorders and cancers.
Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie
Zusammenfassung Hintergrund Die Verwendung videobasierter Analysekonzepte gewinnt in der medizini... more Zusammenfassung Hintergrund Die Verwendung videobasierter Analysekonzepte gewinnt in der medizinischen Ausbildung zunehmend an Bedeutung. In erster Linie dienen diese Tools dazu, Informationen über die individuelle Performance eines Kandidaten zu bekommen und Feedback zu geben. Die vorliegende Studie untersucht, ob die Videoanalyse praktischer Fertigkeiten auch für die Weiterentwicklung des chirurgischen Unterrichts genutzt werden kann. Material und Methoden Zunächst wurde die Durchführung einer chirurgischen Nahtübung (Dauer: 3 min) bei Studierenden des 10. Semesters (n = 38) videobasiert dokumentiert. Im Anschluss folgte die Analyse des Videomaterials anhand von 10 spezifischen Kriterien. Die Analyse diente dann als Grundlage für die Entwicklung fehlerpräventiver Übungen. Nachfolgend wurden die Effekte der fehlerpräventiven Übungen auf die Ergebnisqualität der Nahtübung im Rahmen eines Pilotversuchs in einem 2-Gruppen-Vergleich untersucht. Ergebnisse Die Videosequenzen wurden von ...
In-vivo liver decellularization has become a promising strategy to study in-vivo liver engineerin... more In-vivo liver decellularization has become a promising strategy to study in-vivo liver engineering. However, long term survival after in-vivo liver decellularization has not yet been achieved due to anatomical and technical challenges. This study aimed to establish a survival model of in-vivo partial liver lobe perfusion-decellularization in rat. We compared three decellularization protocols (1%Triton X100 followed by 1%SDS, 1%SDS versus 1%Triton X100, n=6/group). Using the optimal one as judged by macroscopy, histology and DNA-content, we characterized the structural integrity and matrix-proteins using histology, scanning electron microscopy (SEM), Computed Tomography (CT) scanning and immunohistochemistry. We prevented contamination of the abdominal cavity with the corrosive detergents by using polyvinylidene chloride (PVDC) film + dry gauze in comparison to PVDC-film + dry gauze + aspiration tube (n=6/group). Physiological reperfusion was assessed by histology. Survival rate was determined after a 7 d observation period. Only perfusion with 1% SDS resulted in an acellular scaffold (fully translucent without histologically detectable tissue remnants, DNA concentration is less than 2% of that in native lobe) with remarkable structural and ultrastructural integrity as well as preservation of main matrix proteins (immunohistochemically positive for collagen IV, laminin, and elastin). Contamination of abdominal organs with the potentially toxic SDS-solution was achieved by placing a suction tube in addition to the PDVC-film + dry gauze and allowed 7d-survival of all animals without severe postoperative complications. Upon reperfusion, the liver turned red within sec without any leakage from the surface of the liver. About 12 h after reperfusion, blood cells but also some clots were visible in the portal vein (PV), sinusoidal matrix network and central vein (CV), suggesting physiological perfusion. In conclusion, our results study shows the first available data on generation of a survival model of in-vivo parenchymal organ decellularization, creating a critical step towards in-vivo organ engineering.
Background: Medical schools globally now use objective structured clinical examinations (OSCEs) f... more Background: Medical schools globally now use objective structured clinical examinations (OSCEs) for assessing a student's clinical performance. In Germany, almost all of the 36 medical schools have incorporated at least one summative OSCE into their clinical curriculum. This nationwide study aimed to examine whether the introduction of OSCEs shifted studying time. The authors explored what resources were important for studying in preparation for OSCEs, how much time students spent studying, and how they performed; each compared to traditionally used multiple choice question (MCQ) tests. Methods: The authors constructed a questionnaire comprising two identical sections, one for each assessment method. Either section contained a list of 12 study resources requesting preferences on a 5-point scale, and two open-ended questions about average studying time and average grades achieved. During springtime of 2015, medical schools in Germany were asked to administer the web-based questionnaire to their students in years 3-6. Statistical analysis compared the responses on the open-ended questions between the OSCE and MCQs using a paired t-test. Results: The sample included 1131 students from 32 German medical schools. Physical examination courses were most important in preparation for OSCEs, followed by class notes/logs and the skills lab. Other activities in clinical settings (e.g. medical clerkships) and collaborative strategies ranked next. Conversely, resources for gathering knowledge (e.g. lectures or textbooks) were of minor importance when studying for OSCEs. Reported studying time was lower for OSCEs compared to MCQ tests. The reported average grade, however, was better on OSCEs. Conclusions: The study findings suggest that the introduction of OSCEs shifted studying time. When preparing for OSCEs students focus on the acquisition of clinical skills and need less studying time to achieve the expected level of competence/performance, as compared to the MCQ tests.
Background: Given the expected increase in those entering retirement, the number of practising ph... more Background: Given the expected increase in those entering retirement, the number of practising physicians is predicted to decrease. Conversely, the number of physicians needed is set to increase, due to higher demands resulting from the increasing average age of the German population. This may cause a deficit in the availability and accessibility of medical care for the population in Germany, as well as in other countries. As such, there needs to be a specific focus on the next generation of physicians. Will they fill the gap in those medical specialties where it is most needed? This study aims to investigate (a) preferences for medical specialties over time and (b) the reasoning behind these preferences among students. Methods: Over three subsequent years, all medical students from the Jena Faculty of Medicine were repeatedly invited to participate in an online survey. The questionnaire consisted of three parts to explore the students' (1) preferred postgraduate specialty, (2) the reasons for their decision and (3) socio-demographic data. Data analysis was performed using Fisher's exact tests and logistic regression analysis. Results: The number of students completing the questionnaire in a given year ranged from 180 to 320, resulting in a total number of 720 completed questionnaires. Between 40 and 50% of the students preferred internal medicine as postgraduate specialty. About 25% of the students were interested in a surgical specialty. Diagnostics and psychiatric medical fields were preferred by about 10% of all students for each field in each year of the survey. A large percentage (about 18%) of the students remained undecided. The factors influencing the students' specialty preferences were most frequently reconciliation of work and family life, career goals as well as predicted workload. The factors depended on the preferred medical specialty. Conclusion: The influencing factors should be taken into account for recruiting prospective residents. Doing so could increase the chance to attract the number of physicians needed to ensure adequate medical care in the field of interest, according to the growing health needs of the population.
Multimodal treatment concepts including liver transplantation for hepatocellular carcinoma (HCC),... more Multimodal treatment concepts including liver transplantation for hepatocellular carcinoma (HCC), extended resection methods and neoadjuvant chemotherapy for colorectal liver metastasis significantly improve patients' outcome. However, surgery-induced hepatic ischemia-reperfusion injury (IRI) and chemotherapy-associated hepatotoxicity result in hepatocellular damage and compromised liver function. Activation of common key pathways in ischemic liver and hepatotoxic injury results in oxidative stress, inflammatory responses and apoptosis causing organ damage. Controlling liver damage before and during surgery is essential for the postoperative outcome. Nigella sativa has a long tradition as a natural remedy. In the essential oil, Thymoquinone (TQ) was identified as the main component and responsible for most of the therapeutic effects. Therefore, this systematic review aimed to summarize the hepatoprotective effects of TQ and its potential suitability to improve surgical outcome by reducing surgical ischemic injury and hepatotoxicity of neoadjuvant chemotherapy. The key findings can be summarized as TQ having strong antioxidant, anti-inflammatory, antifibrotic, anti-/proapoptotic and anticarcinogenic effects. Almost no side effects were reported irrespective of a large dose range, suggesting a wide therapeutic window. These results give rise to the expectation that TQ could evolve to a novel powerful drug to reduce hepatic injury.
Ventral or incisional hernia are a common disease pattern in general surgery. Mostcommonly, a mes... more Ventral or incisional hernia are a common disease pattern in general surgery. Mostcommonly, a mesh repair is used for reconstruction, whereby the mesh itself might causecomplications, like infections or adhesions. Biological materials, like biocellulose, might reducethese clinical problems substantially. In this prospective rodent study, a biocellulose mesh(produced by Gluconacetobacter xylinus) was implanted either by a sublay technique or assupplementation of the abdominal wall. After an observation period of 90 days, animals weresacrificed. The adhesions after the reconstruction of the abdominal wall were moderate. Thehistologic investigations revealed that the biocellulose itself was inert, with a minimal regenerativeresponse surrounding the mesh. The explanted mesh showed a minimal shrinkage (around 15%) aswell as a minimal loss of tear-out force, which might be without clinical relevance. This is the firstin vivo study describing biocellulose as a suitable mesh for the repair ...
Journal of visualized experiments : JoVE, Jan 6, 2018
Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be... more Organ engineering is a novel strategy to generate liver organ substitutes that can potentially be used in transplantation. Recently, in vivo liver engineering, including in vivo organ decellularization followed by repopulation, has emerged as a promising approach over ex vivo liver engineering. However, postoperative survival was not achieved. The aim of this study is to develop a novel surgical technique of in vivo selective liver lobe perfusion in rats as a prerequisite for in vivo liver engineering. We generate a circuit bypass only through the left lateral lobe. Then, the left lateral lobe is perfused with heparinized saline. The experiment is performed with 4 groups (n = 3 rats per group) based on different perfusion times of 20 min, 2 h, 3 h, and 4 h. Survival, as well as the macroscopically visible change of color and the histologically determined absence of blood cells in the portal triad and the sinusoids, is taken as an indicator for a successful model establishment. After...
Automated image analysis enables quantitative measurement of steatosis in histological images. Ho... more Automated image analysis enables quantitative measurement of steatosis in histological images. However, spatial heterogeneity of steatosis can make quantitative steatosis scores unreliable. To improve the reliability, we have developed novel scores that are "focused" on steatotic tissue areas. Focused scores use concepts of tile-based hotspot analysis in order to compute statistics about steatotic tissue areas in an objective way. We evaluated focused scores on three data sets of images of rodent liver sections exhibiting different amounts of dietary-induced steatosis. The same evaluation was conducted with the standard steatosis score computed by most image analysis methods. The standard score reliably discriminated large differences in steatosis (intraclass correlation coefficient ICC = 0.86), but failed to discriminate small (ICC = 0.54) and very small (ICC = 0.14) differences. With an appropriate tile size, mean-based focused scores reliably discriminated large (ICC = ...
Background: High levels of serum lipopolysaccharide (LPS) were observed in sepsis patients with l... more Background: High levels of serum lipopolysaccharide (LPS) were observed in sepsis patients with liver injury and high mortality. However, the role of liver in modulation LPS induced inflammatory injury was ill investigated. In the present study, the severity of LPS induced inflammatory response was observed after liver resection or portal branch occlusion to decreasing functional liver mass. The local and systemic damage was observed to investigate the role of liver in modulation inflammatory injury. Methods: First, 30%, 70%, and 90% partial hepatectomy (PH) were performed, and serum TNF-α, survival rate, and hepatic LPS uptake was observed. Second, LPS-exposure of the functional liver mass was decreased by selectively blocking the RL prior to LPS-injection, which was given 30 min before a 70% PH, and the inflammatory response was compared in the occluded and the non-occluded liver. The control group was subjected to LPS injection 30 min prior to liver resection without blocking the RL transiently. The serum TNF-α, ALT, AST, creatinine levels, and urea levels, survival rate, hepatic LPS uptake, and hepatic inflammatory cytokines was observed. Results: The decreasing of functional liver mass after 90%, 70%, and 30% PH was associated with decreased serum TNF-α, survival rate, and increased hepatic LPS uptake after LPS injection. Occluding the right lobes (RL) prior to LPS administration reversed the liver injury caused by 70% PH, indicated by 100% survival rate and decreased liver and kidney injury, and systemic inflammatory response. The induction of inflammatory response in occluding liver lobes were lower than un-occluding liver lobes. Conclusions: The severity of the LPS-induced systemic inflammatory injury is determined by functional liver volume. This observation suggests that the liver is the central organ for the initiation of the inflammatory response, and is involved in causing a severe SIRS with systemic damage and death.
Introduction. Sepsis is the primary cause of death from infection. We wanted to improve the outco... more Introduction. Sepsis is the primary cause of death from infection. We wanted to improve the outcome of sepsis by stimulating innate immunity in combination with modulating the severity of inflammatory responses in rats. Method. Sepsis was induced by the injection of feces suspension (control). A 5-day course of G-CSF treatment was given before the septic insult (G-CSF). The inflammatory response was decreased using various doses of the LPS-blocking peptide LBPK95A (5 mg/kg=100% Combi group, 0.5 mg/kg=10% Combi group, and 0.05 mg/kg=1% Combi group). Survival rates were observed. Bacterial clearance, neutrophil infiltration, tissue damage, and the induction of hepatic and systemic inflammatory responses were determined 2 h and 12 h after the septic insult. Results. High-dose LBPK95A (100% Combi) reduced the survival rate to 10%, whereas low-dose LBPK95A (10% and 1% Combi) increased the survival rates to 50% and 80%, respectively. The survival rates inversely correlated with multiorgan...
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Papers by Uta Dahmen