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Object The conception of individual patient-adjusted treatment strategies is constantly emerging in the field of neuro-oncology. Systemic laboratory markers may allow insights into individual needs and estimated treatment benefit at an earliest possible stage. Therefore, the present study was aimed at analyzing the prognostic significance of preoperative routine laboratory values in patients with newly-diagnosed glioblastoma. Methods Between 2014 and 2019, 257 patients were surgically treated for newly-diagnosed glioblastoma at the Neuro-Oncology Center of the University Hospital Bonn. Preoperative routine laboratory values including red blood cell distribution width (RDW) and platelet count were reviewed. RDW to platelet count ratio (RPR) was calculated and correlated to overall survival (OS) rates. Results Median preoperative RPR was 0.053 (IQR 0.044–0.062). The receiver operating characteristic (ROC) curve indicated an optimal cut-off value for RPR to be 0.05 (AUC 0.62; p = 0.002, 95% CI 0.544–0.685). 101 patients (39%) presented with a preoperative RPR Conclusions The present study suggests the RPR to constitute a novel prognostic inflammatory marker for glioblastoma patients in the course of preoperative routine laboratory examinations and might contribute to a personalized medicine approach.

Zusammenfassung Hintergrund Die Mortalität bei Sepsis bleibt hoch. Verschiedene Techniken zur extrakorporalen Zytokinelimination wurden als zusätzliche therapeutische Maßnahmen bei Sepsis und septischem Schock untersucht. Ziele Zusammenfassung einer Auswahl extrakorporaler Blutreinigungstechniken und der aktuellen Erkenntnisse in der klinischen Anwendung mit besonderem Schwerpunkt auf dem therapeutischen Plasmaaustausch. Methoden Nicht systematische Literaturrecherche. Ergebnisse Verschiedene extrakorporale Blutreinigungstechniken mit unterschiedlichen Evidenzniveaus hinsichtlich Zytokinelimination, Verbesserung der Hämodynamik und Verringerung der Mortalität werden derzeit klinisch eingesetzt. Die am ausführlichsten untersuchten Modalitäten umfassen die hochvolumige Hämofiltration/Dialyse mit und ohne High-Cut-off-Filter sowie Hämoadsorptionstechniken (einschließlich CytoSorb- und Polymyxin-B-Filter). Trotz teilweise ermutigender Beobachtungen bezüglich der Entfernung proinflammatorischer Zytokine und verbesserten Hämodynamik zeigten randomisierte Studien bislang keinen positiven Einfluss auf das Überleben. Aufgrund der Verwendung von Spenderplasma als Substitutionsflüssigkeit stellt der therapeutische Plasmaaustausch das einzige Verfahren dar, das zusätzlich verbrauchte protektive Faktoren ersetzen kann. Schlussfolgerungen Die Anwendung extrakorporaler Blutreinigungsmethoden kann für Sepsispatienten außerhalb klinischer Studien bisher nicht empfohlen werden, da derzeit keine Beweise für ihre Wirksamkeit vorliegen. Zukünftige Untersuchungen sollten darauf abzielen, das untersuchte Patientenkollektiv hinsichtlich des klinischen Schweregrads, des Zeitpunkts der Intervention und verschiedener inflammatorischer (Sub-)Phänotypen zu homogenisieren.

Background A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock. Methods We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset 0.4 μg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma. Results Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41–61) vs. 63% (48–70), p = 0.029; protein C, 47% (38–60) vs. 62% (54–69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21–42) % before to 47 (38–62) % after TPE (p p p = 0.001, R2 = 0.316). Conclusions Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors. Trial registration ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.

Background Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p p p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p Conclusions Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Object: Inflammatory response is an important determinant of subsequent brain injury after deep-seated intracerebral hemorrhage (ICH). The ratio of red blood cell (RBC) distribution width to platelet count (RPR) has been established as a new index to reflect the severity of inflammation. To the best of our knowledge, no association between RPR and prognosis after spontaneous ICH has yet been reported.Methods: In all patients with deep-seated ICH treated at our Neurovascular Center from 2014 to 2020, initial laboratory values were obtained to determine RPR in addition to patient characteristics and known risk factors. Subsequent multivariate analysis was performed to identify independent risk factors for 90-day mortality after deep-seated ICH.Results: Hundred and two patients with deep-seated ICH were identified and further analyzed. Patients with an initial RPR < 0.06 exhibited significantly lower mortality rate after 90 days than those with an initial RPR ≥ 0.06 (27 vs. 57%; p = 0.003). Multivariate analysis identified “ICH score ≥ 3” (p = 0.001), “anemia on admission” (p = 0.01), and “elevated RPR ≥ 0.06” (p = 0.03) as independent predictors of 90-day mortality.Conclusions: The present study constitutes the first attempt to demonstrate that the ratio of RBC distribution width to platelets—as an independent inflammatory marker—might serve for prognostic assessment in deep-seated ICH.

ObjectIntra-tumoral hemorrhage is considered an imaging characteristic of advanced cancer disease. However, data on the influence of intra-tumoral hemorrhage in patients with brain metastases (BM) remains scarce. We aimed at investigating patients with BM who underwent neurosurgical resection of the metastatic lesion for a potential impact of preoperative hemorrhagic transformation on overall survival (OS).MethodsBetween 2013 and 2018, 357 patients with BM were surgically treated at the authors’ neuro-oncological center. Preoperative magnetic resonance imaging (MRI) examinations were assessed for the occurrence of malignant hemorrhagic transformation.Results122 of 375 patients (34%) with BM revealed preoperative intra-tumoral hemorrhage. Patients with hemorrhagic transformed BM exhibited a median OS of 5 months compared to 12 months for patients without intra-tumoral hemorrhage. Multivariate analysis revealed preoperative hemorrhagic transformation as an independent and significant predictor for worsened OS.ConclusionsThe present study identifies preoperative intra-tumoral hemorrhage as an indicator variable for poor prognosis in patients with BM undergoing neurosurgical treatment.

Background: Brain metastases (BM) indicate advanced states of cancer disease and cranial surgery represents a common treatment modality. In the present study, we aimed to identify the risk factors for a reduced survival in patients receiving a surgical treatment of BM derived from non-small cell lung cancer (NSCLC). Methods: A total of 154 patients with NSCLC that had been surgically treated for BM at the authors’ institution between 2013 and 2018 were included for a further analysis. A multivariate analysis was performed to identify the predictors of a poor overall survival (OS). Results: The median overall survival (mOS) was 11 months (95% CI 8.2–13.8). An age &gt, 65 years, the infratentorial location of BM, elevated preoperative C-reactive protein levels, a perioperative red blood cell transfusion, postoperative prolonged mechanical ventilation (&gt, 48 h) and the occurrence of postoperative adverse events were identified as independent factors of a poor OS. Conclusions: The present study identified several predictors for a worsened OS in patients that underwent surgery for BM of NSCLC. These findings might guide a better risk/benefit assessment in the course of metastatic NSCLC therapy and might help to more sufficiently cope with the challenges of cancer therapy in these advanced stages of disease.

Simple Summary Patients with brain metastasis are at a severe stage of cancer, and brain surgery can prevent neurological morbidity. However, the success of brain surgery might require a patient’s physical integrity prior to the operation. In the present study, we asked whether a preoperative physical decline affects survival in patients with brain metastasis from lung cancer. In order to measure the physical condition, we used a commonly-known index—the so-called frailty index—and additionally measured the thickness of a particular masticatory muscle as muscle loss correlates to physical decline. We found that a decreased muscle thickness was accompanied by worsened survival for patients < 65 years and an increased frailty index correlated to worsened survival for patients ≥ 65 years. These results encourage to use of the frailty index and muscle thickness as easily available parameters in order to more sufficiently estimate individual treatment success in patients with metastatic lung cancer. Abstract Neurosurgical resection represents an important therapeutic pillar in patients with brain metastasis (BM). Such extended treatment modalities require preoperative assessment of patients’ physical status to estimate individual treatment success. The aim of the present study was to analyze the predictive value of frailty and sarcopenia as assessment tools for physiological integrity in patients with non-small cell lung cancer (NSCLC) who had undergone surgery for BM. Between 2013 and 2018, 141 patients were surgically treated for BM from NSCLC at the authors’ institution. The preoperative physical condition was assessed by the temporal muscle thickness (TMT) as a surrogate parameter for sarcopenia and the modified frailty index (mFI). For the ≥65 aged group, median overall survival (mOS) significantly differed between patients classified as ‘frail’ (mFI ≥ 0.27) and ‘least and moderately frail’ (mFI < 0.27) (15 months versus 11 months (p = 0.02)). Sarcopenia revealed significant differences in mOS for the

Background Extra Corporeal Membrane Oxygenation (ECMO) has become an accepted treatment option for severely ill patients. Due to a limited availability of ECMO support therapy, patients must often be transported to a specialised centre before or after cannulation. According to the ELSO guidelines, an ECMO specialist should be present for such interventions. Here we describe the safety and efficacy of a reduced team approach involving one anaesthesiologist, experienced in specialised intensive care medicine, and a specialised critical care nurse. Methods This study is a 10 years retrospective, single institution analysis of all data collected between January 2007 and December 2016 from the medical records at the University Hospital Bonn, Germany. Results The Bonner mobile ECMO team was deployed in 170 cases for on-site evaluation for ECMO support therapy. 4 (2.4%) patients died prior to arrival or during the implementation of ECMO support. Of the remaining 166 patients, 126 were cannulated at the referring site, 40 were transported without ECMO. Of those, 21 were subsequently cannulated out our centre. 19 patients never received ECMO treatment. The primary indication for ECMO treatment was ARDS (159/166 patients). Veno-venous ECMO was initiated in 137, whilst 10 patients received veno-arterial ECMO treatment. Mean transportation time was 75 ± 36 min, and mean transport distance was 56 ± 57 km. In total, 26 complications were observed, three being directly transport-related. The overall survival was 55%. Conclusions Initiation of extracorporeal membrane oxygenation and subsequent transport can be safely and efficiently performed by a two-man team with good outcome. Electronic supplementary material The online version of this article (10.1186/s12871-019-0687-9) contains supplementary material, which is available to authorized users.

Background: The SARS-CoV-2 pandemic has challenged many of our current routine practices in the treatment and care of patients. Given the critical importance of blood donation and transfusion we analyzed 92 blood samples of individuals infected with SARS-CoV-2 stratified by symptoms. Study Design and Methods: We therefore tested blood samples for SARS-CoV-2 via RT-PCR targeting the E gene. In addition, we tested each blood sample for anti-SARS-CoV-2 IgG antibodies via ELISA and performed plaque reduction neutralization tests. Results: SARS-CoV-2 RNA was absent in the blood of mild to asymptomatic patients (57 individuals) and only detectable in individuals with severe COVID-19 who were admitted to the intensive care unit (35 individuals) (n = 6/92 [6.5%]; p = 0.023 Fisher’s exact test). Interestingly, anti-spike IgG antibodies were not significantly higher in intensive care unit patients compared to mild patients, but we found that their neutralizing capacity was disproportionately increased (p < 0.001). Conclusion: Our observations support the hypothesis that there are no potential hazards from blood or plasma transfusion of SARS-CoV-2-positive individuals with mild flu-like symptoms and more importantly of asymptomatic individuals.

Surgical resection is highly effective in the treatment of tumor-related epilepsy (TRE) in patients with brain metastases (BM). Nevertheless, some patients suffer from postoperative persistent epilepsy which negatively impacts health-related quality of life. Therefore, early identification of patients with potentially unfavorable seizure outcome after BM resection is important. Patients with TRE that had undergone surgery for BM at the authors’ institution between 2013 and 2018 were analyzed with regard to preoperatively identifiable risk factors for unfavorable seizure outcome. Tumor tissue and tumor necrosis ratios were assessed volumetrically. According to the classification of the International League Against Epilepsy (ILAE), seizure outcome was categorized as favorable (ILAE 1) and unfavorable (ILAE 2–6) after 3 months in order to avoid potential interference with adjuvant cancer treatment. Among all 38 patients undergoing neurosurgical treatment for BM with concomitant TRE, 34 patients achieved a favorable seizure outcome (90%). Unfavorable seizure outcome was significantly associated with larger tumor volumes (p = 0.012), a midline shift > 7 mm (p = 0.025), and a necrosis/tumor volume ratio > 0.2 (p = 0.047). The present study identifies preoperatively collectable risk factors for unfavorable seizure outcome in patients with BM and TRE. This might enable to preselect for highly vulnerable patients with postoperative persistent epilepsy who might benefit from accompanying neuro-oncological expertise during further systemical treatment regimes.

Background: Metastatic melanoma disease is accompanied by highly systemic inflammatory responses. The prognostic value of preoperative laboratory inflammation markers in brain metastatic melanoma patients has not been adequately investigated so far. Methods: Preoperative inflammatory blood parameters were correlated to overall survival (OS) rates in melanoma patients that underwent surgery for brain metastasis (BM) between 2013 and 2019 at the authors’ institution. Receiver operating characteristic (ROC) analyses were used for cutoff determination of routine laboratory parameters. Results: Median OS in the present cohort of 30 melanoma patients with surgically treated BM was 7 months (95% confidence interval (CI) 5.7–8.3). Initial elevated C-reactive protein (CRP) levels (&gt, 10 mg/L), neutrophil-to-lymphocyte ratio (NLR) ≥ 4, platelet-to-lymphocyte ratio (PLR) ≥ 145, and lymphocyte-to-monocyte ratio (LMR) &lt, 2 were associated with significantly reduced OS rates. Conclusions: The present study identifies several preoperative peripheral inflammatory markers as indicators for poor prognosis in melanoma patients with BM undergoing neurosurgical treatment. Elevated initial CRP values, higher NLR and PLR, and lower LMR were associated with reduced OS and, thus, might be incorporated into preoperative interdisciplinary treatment planning and counseling for affected patients.

Intracerebral hemorrhage (ICH) is a frequently disabling or fatal disease. The localizationof ICH often allows an etiological association. However, in atypical/lobar ICH, the cause of bleedingis less obvious. Therefore, we present prospective histopathological and radiological studies whichwere conducted within the diagnostic workup to identify causes for lobar ICH other than hypertension.From 2016 to 2018, 198 patients with spontaneous, non-traumatic ICH requiring neurosurgicalmonitoring were enrolled in an institutional prospective patient registry. Patients with deep-seatedICH and/or hemorrhagically transformed cerebral infarcts were excluded from further analysis.Data to evaluate the source of bleeding based on histopathological and/or radiological workup wereprospectively evaluated and analyzed. After applying the inclusion criteria and excluding patientswith incomplete diagnostic workup, a total of 52 consecutive patients with lobar ICH were furtheranalyzed. Macrovascular disease was detected in 14 patients with lobar ICH (27%). In 11 patients,diagnostic workup identified cerebral amyloid angiopathy-related ICH (21%). In addition, five patientswith tumor-related ICH (10%) and six patients with ICH based on infectious pathologies(11%) were identified. In four patients, the cause of bleeding remained unknown despite extensivediagnostic workup (8%). The present prospective registry study demonstrates a higher probabilityto identify a cause of bleeding other than hypertension in patients with lobar ICH. Therefore, athorough diagnostic work-up in patients with ICH is essential to accelerate treatment and furtherimprove outcome or prevent rebleeding

Simple Summary Meningiomas are most commonly benign intracranial tumors, and surgical resection represents the treatment modality of choice. However, especially for patients of higher age and with increasing comorbidities, brain surgery might be accompanied by the need for postoperative prolonged intensive care, which might impair intended operative benefit. In the present study, we therefore analyzed prolonged mechanical ventilation (PMV) as an indicator variable for such intensive care treatment with regard to potential effects on mortality after meningioma resection in patients aged 70 years and older. We found that patients with postoperative PMV exhibited a profoundly increased probability to die within 1 year after surgery. Based on these findings, we identified risk factors for postoperative PMV occurrence and developed an easy-to-use score which allows us to estimate the risk of PMV occurrence preliminary to the surgical resection. We believe that this score might help to more sufficiently guide patients in the course of risk–benefit assessment and preoperative counseling. Abstract Indication for surgical treatment in patients with intracranial meningioma must include both clinical aspects and an individual risk–benefit stratification, especially in geriatric patients. Prolonged mechanical ventilation (PMV) has not been investigated for its potential effects in patients with meningioma. We therefore analyzed the impact of PMV on mortality in geriatric patients who had undergone meningioma resection. Between 2009 and 2019, 261 patients aged ≥ 70 years were surgically treated for intracranial meningioma at our institution. PMV was defined as postoperative invasive ventilation of >7 days. Postoperative PMV was present in 17 of 261 geriatric meningioma patients (7%). Twenty-five geriatric patients (10%) died within 1 year after surgery. A scoring system (“ACKT”) based on the variables of age, preoperative C-reactive protein (CRP) value, Karnofsky performance scale and tumor size supports prediction of postoperative PMV (sensitivity 73%, specificity 84%). PMV is significantly associated with increased mortality after surgical treatment of meningiomas in geriatric patients. Furthermore, we suggest a novel score (“ACKT”) to preoperatively estimate the risk of PMV occurrence, which might help to guide future risk–benefit assessment and patient counseling in the geriatric meningioma population.

Objective: The need for continuous renal replacement therapy (CRRT) in patients with deep-seated intracerebral hemorrhage (ICH) requires sustained intensive care and often postpones further rehabilitation therapy. Therefore, an early identification of patients at risk is essential.Methods: From 2014 to 2019, all patients with deep-seated ICH who were admitted to intensive care for >3 days were included in the further analysis and retrospectively reviewed for the need for CRRT. All patients underwent CRRT with regional citrate anticoagulation for continuous veno-venous hemodialysis (CVVHD). Outcome was evaluated after 3 months using the modified Rankin scale. A multivariate analysis was performed to identify potential predictors for CRRT in patients with deep-seated ICH.Results: After applying the inclusion criteria, a total of 87 patients with deep-seated spontaneous ICH were identified and further analyzed. During the first 48 h after admission, 21 of these patients developed early acute kidney injury (AKI; 24%). During treatment course, CRRT became necessary in nine patients suffering from deep-seated ICH (10%). The multivariate analysis revealed “development of AKI during the first 48 h” [p = 0.025, odds ratio (OR) 6.1, 95% confidence interval (CI) 1.3–29.8] and “admission procalcitonin (PCT) value >0.5 μg/l” (p = 0.02, OR 7.7, 95% CI 1.4–43.3) as independent and significant predictors for CRRT in patients with deep-seated ICH.Conclusions: Elevated serum levels of procalcitonin on admission as well as early development of acute renal injury are independent predictors of the need for renal replacement therapy in patients with deep-seated intracerebral bleeding. Therefore, further research is warranted to identify these vulnerable patients as early as possible to enable adequate treatment.

ObjectiveAlthough the treatment of glioblastoma patients is well established in neuro-oncological surgery, precious scarce data is available on patients with glioblastoma requiring postoperative prolonged mechanical ventilation (PMV). Therefore, the aim of the present study was to determine the influence of PMV on overall survival (OS) in patients with glioblastoma.MethodsPatients with newly diagnosed glioblastoma who had undergone surgical therapy and complete subsequent neuro-oncological treatment at the authors’ neuro-oncological center from January 2013 to December 2018 were selected and included in the further analysis. PMV was defined as mechanical ventilation for more than 24 h after surgery. Survival analyses were performed, including established prognostic factors such as age, Karnofsky performance score, MGMT-promoter methylation status and extent of resection.ResultsA total of 240 patients with newly diagnosed glioblastoma and subsequent surgical treatment were identified. 13 patients (5%) suffered from PMV during the treatment course of glioblastoma. All but one patient were successfully weaned from mechanical ventilation. Patients suffering from PMV achieved significantly less often favorable functional outcome after 3, 6, 9, and 12 months compared to patients without PMV. Multivariate analysis revealed PMV to constitute a significant prognostic factor for OS, independent of other prognostic factors (pConclusionsThe present study identifies PMV as significantly associated with impaired functional outcome and poor OS in patients suffering from newly diagnosed glioblastoma. These findings encourage further efforts to investigate/assess this prognostic factor in future studies.

Background Acute respiratory distress syndrome (ARDS) is a life-threatening condition and the identification of the underlying direct (pulmonary) or indirect (non-pulmonary) cause is mandatory for a successful treatment. Intragastric balloon (IGB) therapy is a minimal invasive and supposedly harmless option to reduce body weight for the growing number of obese people. We present a case of a young patient who developed a direct ARDS due to initially undiagnosed abdominal pathologies caused by an IGB therapy. Case presentation A 23-year old woman was admitted because of a direct ARDS for extracorporeal membrane oxygenation (ECMO) therapy. Weeks before, an IGB has been removed because of abdominal pain and free intraabdominal air. Diagnostic work-up of free intraabdominal air, previous pain of the left shoulder and newly developed abscess pneumonia revealed a perforation of the posterior wall of the gastral antrum. This resulted in a left subphrenic abscess with destruction of the diaphragm, development of pneumonia per continuitatem and subsequent direct lung injury. The gastric perforation was endoscopically clipped and the ARDS was successfully treated under ECMO therapy. Conclusion This case illustrates that a patient presenting with direct ARDS may have upper abdominal pathologies caused by a rare complication of a supposedly harmless treatment.

First described in the mid-1960s, acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure with an overall mortality rate of approximately 40%. Despite significant advances in the understanding and treatment of ARDS, no substantive pharmacologic therapy has proven to be beneficial, and current management continues to be primarily supportive. Beyond their antibacterial activity, several antibiotics such as macrolides and tetracyclines exert pleiotropic immunomodulatory effects that might be able to rectify the dysregulated inflammatory response present in patients with ARDS. This review aims to provide an overview of preclinical and clinical studies that describe the immunomodulatory effects of antibiotics in ARDS. Moreover, the underlying mechanisms of their immunomodulatory properties will be discussed. Further studies are necessary to investigate their full therapeutic potential and to identify ARDS phenotypes which are most likely to benefit from their immunomodulatory effects.

(1) Background: As elements of the standard admission blood panel, lactate and glucose represent potential biomarkers for outcome prediction. In patients with intracranial hemorrhage (ICH), data on the predictive value of these blood values is exceedingly sparse. (2) Methods: Between 2014 and August 2020, all patients with deep-seated ICH referred to the neurovascular center at the authors’ institution were included in the subsequent study. Serum levels of lactate and glucose at the time of admission were compared with mortality at 90 days. In addition, a multivariate analysis was performed in order to identify independent admission predictors for 90-day mortality. (3) Results: Among the 102 patients with deep-seated ICH, elevated lactate and glucose levels on admission were significantly associated with increased mortality at 90 days. Multivariate logistic regression analysis identified “ICH score ≥3” (p = 0.004) along with “admission hyperlactatemia” (p = 0.025) and “admission hyperglycemia” (p = 0.029) as independent and significant predictors of 90-day mortality in patients with deep-seated ICH. (4) Conclusions: Initially elevated lactate and glucose levels after spontaneous intracerebral hemorrhage are associated with poor outcome, suggesting a potential application for future prognostic models when considered in conjunction with other parameters.

Sepsis, a life threating syndrome characterized by organ failure after infection, is the most common cause of death in hospitalized patients. The treatment of sepsis is generally supportive in nature, involving the administration of intravenous fluids, vasoactive substances and oxygen plus antibiotics to eliminate the pathogen. No drugs have been approved specifically for the treatment of sepsis, and clinical trials of potential therapies have failed to reduce mortality - suggesting that new approaches are needed. Abnormalities in the immune response elicited by the pathogen, ranging from excessive inflammation to immunosuppression, contribute to disease pathogenesis. Although hundreds of immunomodulatory agents are potentially available, it remains unclear which patient benefits from which immune therapy at a given time point. Results indicate the importance of personalized therapy, specifically the need to identify the type of intervention required by each individual patient at a given point in the disease process. To address this issue will require using biomarkers to stratify patients based on their individual immune status. This article reviews recent and ongoing clinical investigations using immunostimulatory or immunosuppressive therapies against sepsis including non-pharmacological and novel preclinical approaches.

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines&rsquo, recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.

Introduction: A significant increase of the p-wave of a real-time intracavitary electrocardiography is a reliable and safe method to confirm the central venous catheter tip position close to the atrium. However, conflicting data about the feasibility of electrocardiography exist in patients with atrial fibrillation. Methods: An observational prospective case–control cohort study was set up to study the feasibility and accuracy of the electrocardiography-controlled central venous catheter tip placement in 13 patients with atrial fibrillation versus 10 patients with sinus rhythm scheduled for elective surgery. Each intervention was crosschecked with ultrasound-guided positioning via right supraclavicular fossa view and chest radiography. Ultrasound-guided supraclavicular venipuncture of the right subclavian vein and guidewire advancement were performed. A B-mode view of the superior vena cava and the right pulmonary artery was obtained to visualize the J-tip of the guidewire. The central venous catheter was advanced over the guidewire and the electrocardiography was derived from the J-tip of the guidewire protruding from the central venous catheter tip. Electrocardiography was read for increased p- and atrial fibrillation waves, respectively, and insertion depth was compared with the ultrasound method. Results: Electrocardiography indicated significantly increasing fibrillation and p-waves, respectively, in all patients and ultrasound-guided central venous catheter positioning confirmed a tip position within the lower third of the superior vena cava. Conclusion: Electrocardiography-guided central venous catheter tip positioning is a feasible real-time method for patients with atrial fibrillation. Combined with ultrasound, the electrocardiography-controlled central venous catheter placement may eliminate the need for postinterventional radiation exposure.

Although pediatric emergence delirium (ED) is common, preventive and therapeutic pharmacological treatment is the matter of an international controversial discussion and evidence on different options is partially vague. We therefore examined clinical routine in prevention strategies and postoperative therapy of ED with respect to clinical experience in pediatric anesthesia. A web-based survey was developed investigating routine management (prevention and treatment) of ED, facility structure, and patient population. The link was sent to all enlisted members of the German Society of Anesthesiology. We analyzed 1229 questionnaires. Overall, 88% reported ED as a relevant clinical problem; however, only 5% applied assessment scores to define ED. Oral midazolam was reported as standard premedication by 84% of respondents, the second largest group was ‘no premedication’ (5%). The first choice prevention strategy was to perform total intravenous (propofol) anesthesia (63%). The first choice therapeutic pharmacological treatment depended on clinical experience. Therapeutic propofol was preferentially chosen by more experienced anesthesiologists (5 to >20 patients per week, n = 538), while lesser experienced colleagues (

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. Most of what we know about the deleterious effects of alcohol in vivo has been gleaned from studies in sober alcoholics recruited from substance abuse treatment programs. Little is known about effects of chronic drinking in the moderate or heavy range encountered in a much larger fraction of modern society. Extrapolation of information on the adverse effects of chronic drinking on organ function from clinical samples to social drinkers in the general population has to be met with great skepticism, as it may lead to wrong conclusions about the chronic effects of alcohol in social drinkers. Several recent studies suggest that moderate alcohol consumption has certain beneficial health effects, whereas heavy social alcohol consumption has recently been associated with organ abnormalities and cognitive deficits. These social drinking effects have attracted great public interest; reports of benefits of moderate drinking have also inspired inappropriate publications by the media, including misleading advertisements by the alcohol producing and distributing industry. Although adverse effects of moderate to heavy drinking on heart, liver, and cancer development have attracted attention by clinicians and researchers for some time, its compromising effects on brain and cognition have only recently been studied. This symposium brought together researchers from different disciplines, who reviewed and presented new data on consequences of social drinking in the areas of clinical neuropsychology and behavior (Drs. Nixon and Meyerhoff), neurophysiology (Dr. Nixon, Ms. De Bruin), neuroimaging (Ms. de Bruin, Dr. Meyerhoff), hepatic disease (Dr. Bode), and cancer (Dr. Seitz). The symposium aimed to clarify both the potential health benefits of moderate alcohol consumption and risks of moderate and heavy drinking on proper organ function and to provide insights and new data to practicing physicians and public health authorities for education on problem drinking.

BACKGROUND Epidemiologic studies found that high tomato intakes reduce the risk of colorectal cancers. This beneficial effect is assumed to be caused by high intakes of lycopene, a carotenoid with strong antioxidant activity that is present predominantly in tomatoes. OBJECTIVE We assessed the relation between plasma lycopene concentrations and colorectal adenomas, the precursors for most colorectal cancers. In addition, the concentrations of 2 other antioxidants, beta-carotene and alpha-tocopherol, were measured. DESIGN White subjects undergoing a complete colonoscopy were included in the study (73 with adenomas, 63 without any polyps, and 29 with hyperplastic polyps). A detailed dietary history and information on alcohol consumption and smoking habits were collected from all subjects. Plasma lycopene, beta-carotene, and alpha-tocopherol concentrations were measured by using HPLC. RESULTS Patients with adenomas and control subjects without polyps did not differ significantly in body mass index; intakes of energy, fat, protein, carbohydrates, fiber, beta-carotene, and alcohol; or prevalence of smoking, but patients with adenomas were slightly older. The median plasma lycopene concentration was significantly lower in the adenoma group than in the control group (-35%; P = 0.016). The median plasma beta-carotene concentration also tended to be lower in the adenoma group (-25.5%), but the difference was not significant. In the multiple logistic regression, only smoking (odds ratio: 3.02; 95% CI: 1.46, 6.25; P = 0.003) and a plasma lycopene concentration < 70 microg/L (odds ratio: 2.31; 1.12, 4.77; P = 0.023) were risk factors for adenomatous polyps. Patients with hyperplastic polyps did not differ significantly from control subjects in any variable. CONCLUSION Our findings support the hypothesis that lycopene contributes to the protective effect of high tomato intakes against the risk of colorectal adenomas.

Consumption of large quantities of alcoholic beverages leads to disturbances in the intestinal absorption of nutrients including several vitamins. The inhibition of the absorption of sodium and water caused by alcohol contributes to the tendency in alcoholics to develop diarrhoea. Excessive alcohol consumption (even a single episode) can result in duodenal erosions and bleeding and mucosal injury in the upper jejunum. An increased prevalence for bacterial overgrowth in the small intestine may contribute to functional and/or morphological abnormalities of this part of the gut and also to non-specific abdominal complaints in alcoholics. The mucosal damage caused by alcohol increases the permeability of the gut to macromolecules. This facilitates the translocation of endotoxin and other bacterial toxins from the gut lumen to the portal blood, thereby increasing the liver's exposure to these toxins and, consequently, the risk of liver injury. The results of recent experimental studies support the assumption that alcohol significantly modulates the mucosal immune system of the gut.

The objective of this study was to investigate the effect of alcohol administration on jejunoileal bypass (JIB)-induced liver dysfunction in rats resulting in abnormalities of fatty acid composition of cell membranes, and whether methionine is able to reverse these changes. Male Wistar rats were subjected to a jejunoileal bypass operation. For 12 weeks, all groups were pair-fed either an alcohol-containing (36% of total calories) liquid diet or a liquid diet in which alcohol was replaced isocalorically by starch. Methionine supplementation in three control groups was 0, 32, 160 and 224 mg/kg body weight/day and the rats in the four alcohol feeding groups received 0, 32, 160 and 224 mg/kg body weight/day. In the alcohol group without any methionine supplementation, higher proportions of oleic and linoleic acid and lower proportions of docosahexaenoic and arachidonic acid became evident in tissue samples of liver and jejunum, in comparison with the other alcohol group. A possible explanation for this reduction in tissue polyunsaturated fatty acid (PUFA) may be a decrease in the activities of delta 6-and delta 5-desaturases, and subsequently a displacement of PUFA from lipid fractions by other fatty acids. Interestingly, in the alcohol group with the highest methionine supplementation, compared to all other alcohol groups, lower proportions of oleic acid and higher proportions of docosahexaenoic acid, appeared. A possible explanation for this increase of PUFA in tissue may be increased activities of delta 6- and delta 5-desaturases.

p44/42 mitogen-activated protein kinase (MAPK) and signal transducers and activation of transcription 3 (STAT3), vascular endothelial growth factor receptor (VEGFR)-1 and -2, and platelet-derived growth factor receptor (PDGFR)and , in primary RCC specimens were measured by immunohistochemical staining. RESULTS: Of several factors examined, tumor grade and the expression level of VEGFR-2 were shown to have significant impact on response to sunitinib in these 60 patients. Progression-free survival (PFS) was significantly associated with the expression levels of VEGFR-2 in addition to tumor grade, performance status, MSKCC risk classification system and c-reactive protein level on univariate analysis. Of these significant factors, only VEGFR-2 expression appeared to be independently related to PFS by multivariate analysis. In fact, the PFS in patients with strong expression of VEGFR-2 was significantly favorable compared with that in those with weak expression of VEGFR-2. CONCLUSIONS: It would be useful to consider expression levels of potential molecular markers, particularly VEGFR-2, as well as conventional parameters to select metastatic RCC patients likely to benefit from treatment with sunitinib.

A recently developed chromogenic endotoxin assay with plasma Tween 80 pretreatment was compared with the conventional dilution and heating method. Plasma endotoxin was measured in patients with liver cirrhosis and upper gastrointestinal (GI) bleeding by these methods. Plasma endotoxin concentration was calculated from an individual internal standard curve by adding three different standard endotoxin solutions to each sample. By the conventional heating method, added standard endotoxin gave different OD values in each sample and the slope of the standard curve showed interindividual variations. When sample plasma from chronic alcoholics was pretreated with 1% Tween 80 and ultrasonification after heating, the slope of standard curves was somewhat increased and interindividual variation was minimized. Significantly higher plasma endotoxin levels in cirrhotics with upper GI bleeding compared with those without upper GI bleeding was detected by this Tween 80 method. There was a strongly positive correlation between the endotoxin levels determined by this method and those determined by the perchloric acid method and endotoxin-specific substrate in patients with upper GI bleeding. Endotoxin levels, which were elevated 1–2 days after the bleeding, tended to decrease as patients recovered. In summary, the recovery of endogenous and exogenous endotoxin from plasma sample was increased by adding Tween 80 before the chromogenic substrate assay. Transient elevation of plasma endotoxin was demonstrated by this Tween 80 method in patients with liver cirrhosis and upper GI bleeding.

Purpose IGF-I serum levels have been demonstrated as being associated with prostate cancer (PCa) and can serve as a predictive factor for the risk of PCa development. However, the role of IGF-II in PCa and its importance as a predictive marker is still unclear. Our aim was to determine PSA and IGF-II serum levels in patients with PCa and benign prostatic hyperplasia (BPH) and to analyse the value of IGF-II as an additional predictive factor in the diagnostics of PCa. Methods 112 patients who underwent surgery for BPH or PCa (no hormonal treatment, no further malignancies) were included in this study ((I) 38 PCa, PSA≤15ng/ml; (II) 34 PCa, PSA>15ng/ml; (III) 40 BPH). Preoperative serum levels of total PSA and total IGF-II were determined by ELFA and ELISA, respectively. Results PSA levels were (I) 5.7±1.9ng/ml; (II) 25.0±11.5ng/ml and (III) 4.0±2.8ng/ml. (II) was statistically associated with a high grading (2b/3; p =0.0182), a high Gleason sum score (7–10; p =0.0049) and a non-organ confined tumor (T3/4; p =0.0009) compared to (I), all Chi 2 test. IGF-II levels were significantly higher in PCa (I+II) compared to BPH (833.8±238.9ng/ml vs. 633.3±141.4ng/ml, p t -test). Both PSA and IGF-II were associated with tumor staging ( p =0.0097, p =0.0308; t -test). No significant correlation was observed between PSA and IGF-II levels. Logistic regression analysis revealed that the combination of PSA and IGF-II improves the prediction of tumor staging in PCa ( p =0.0175 and p =0.0459, Wald test). Additionally, the combination of PSA and IGF-II can significantly increase discrimination between BPH and PCa; each p Conclusions This study provides evidence that IGF-II serum levels may serve as an additional parameter for (a) improved determination of tumor staging and (b) better discrimination between BPH and PCa.

OBJECTIVES: To determine the prevalence of small bowel bacterial overgrowth (SBBO) in older adults and to assess whether SBBO is associated with abdominal complaints and nutrient intake. DESIGN: Cross-sectional survey. SETTING: Eight senior residence sites in Stuttgart, Germany. PARTICIPANTS: Older adults living independently in senior residence houses. MEASUREMENTS: The prevalence of SBBO was measured in 328 subjects, of whom 294 were aged 61 and older, by measuring hydrogen concentration (parts per million; ppm) in exhaled air after ingestion of 50 g glucose. Anthropometric data were obtained and nutritional status was recorded with a computer-aided diet history. RESULTS: The prevalence of a positive hydrogen breath test (>10 ppm increase) was 15.6% in older adults, compared with 5.9% in subjects aged 24 to 59. The intake of inhibitors of gastric acid production contributed significantly to the high prevalence of a positive breath test in older adults, which was associated with lower body weight, lower body mass index, lower plasma albumin concentration, and higher prevalence of diarrhea. Subjects with a positive hydrogen breath test consumed significantly less fiber, folic acid, and vitamins B2 and B6 than those without. No difference was observed in the intake of energy, protein, fat, or carbohydrates. CONCLUSION: Prevalence of SBBO is associated with reduced body weight, which is paralleled by reduced intake of several micronutrients. Malabsorption resulting from diarrhea might be an aggravating factor contributing to weight loss in these subjects.

Aim: While the diuretic action of acute ingestion of alcohol has been studied extensively, the effect of chronic alcohol consumption has received less attention. The aim of the present study was to investigate the effect of chronic alcohol consumption on the balance of water intake and excretion and certain renal functions in rats during a period of 12 months. Animals and Study Design: Male Wistar rats received either alcohol (15% v/v; group A, n = 65) or tap water (group C, n = 35) as drinking fluid. Urine and faeces were collected from 6 rats of each group during 7 days, at monthly intervals. In further experiments, the animals received a low-protein/high-fat diet with and without alcohol. Results: When the rats were fed the standard diet, 24-hour urine excretion was significantly reduced in group A compared with group C. This difference was even more pronounced when the animals were fed the low-protein/high-fat diet. The reduced urine excretion was not due to lower liquid consumption and the pattern of daily excretion of faeces was comparable with that observed for urine excretion. Both sodium and potassium excretion and the diuretic response to an acute water load were significantly reduced in group A compared with group C. The changes in water balance induced by chronic alcohol consumption were reversible within a few days when the rats received water instead of 15% alcohol. Conclusions: Chronic alcohol consumption has an antidiuretic effect in rats. The percentage of total ingested fluid leaving the body as hidden water loss increases after alcohol consumption by up to 25–26% over control values.

This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were J. Christian Bode and Hiroshi Fukui. The presentations were (1) Essentials and the course of the pathological spectrum of alcoholic liver disease in humans, by P. de la M. Hall; (2) Lieber-DeCarli liquid diet for alcohol-induced liver injury in rats, by C. S. Lieber and L. M. DeCarli; (3) Tsukamoto-French model of alcoholic liver injury, by S. W. French; (4) Animal models to study endotoxin-ethanol interactions, by K. O. Lindros and H. Jarvelainen; and (5) Jejunoileal bypass operation in rats-A model for alcohol-induced liver injury? by Christiane Bode, Alexandr Parlesak, and J. Christian Bode.

No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD).The permeability to polyethylene glycol Mr 400, Mr 1500, Mr 4000, and Mr 10,000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls.Permeability to polyethylene glycol Mr 400 was found to be unchanged in patients with ALD in comparison to healthy controls, whereas polyethylene glycol Mr 1500 and Mr 4000 were recovered in about twice as high concentrations in the urine of ALD patients (p0.01). Polyethylene glycol Mr 10,000 was detected significantly less frequently in urine from healthy controls (0/30) than in urine of patients with alcoholic liver disease (20/54, p0.01). Endotoxin concentrations in the plasma of alcoholics were increased more than 5-fold compared to healthy controls (p0.01).The results of this study indicate that alcohol abuse impairs the function of the intestinal barrier, which might enhance the translocation of bacterial toxins, thereby contributing to inflammatory processes in alcoholic liver disease.

Background/Aims: The proinflammatory effects of endotoxemia, which is often observed in alcohol-abusing patients with various degrees of liver disease, may be modulated by changes in the concentration of endotoxin binding factors. Therefore, the plasma endotoxin concentration and the overall endotoxin binding capacity of whole blood were measured in these patients. Methods: Patients with minor (A1: n =27), more pronounced (A2; n =13), cirrhotic alcoholic liver disease (A3; n =18), and non-alcoholic cirrhosis (NC: n =6), and 15 healthy control persons (HC) were included in the study. Endotoxin plasma levels were determined using a standardized limulus assay. A modified assay was applied to additionally detect tightly bound endotoxin. To measure the endotoxin-binding capacity, aliquots of whole blood were incubated with serial dilutions of endotoxin, supernatants were obtained, and endotoxin retrieval was estimated by addition of limulus lysate, followed by photometric measurement of the maximal reaction velocity (dOD max ). Endotoxin binding capacity equals the endotoxin concentration at which dOD max reaches a predefined threshold. Results: All groups of alcohol abusers had significantly elevated endotoxin plasma levels with a considerable portion of ‘bound' endotoxin. Conversely, the endotoxin binding capacity was markedly diminished, mainly in patients with more advanced liver disease (A1: 85.8% of the control value [non-significant vs. controls]; A2: 25.4% [ p p Conclusions: The endotoxin-binding capacity is diminished in patients with alcoholic and non-alcoholic cirrhosis, as well as in less advanced alcoholic liver disease. Reduced endotoxin binding may contribute to the adverse effects of endotoxemia.

Neovascular targeting is an established approach for the therapy of prostate cancer (PCa). Cationic liposomes have been shown to be absorbed by immature vascular endothelial cells due to negative electric charge of their outer cell membrane. We aimed to evaluate the antitumoural efficacy of paclitaxel encapsulated in cationic liposomes for the treatment of PCa. Tumours were generated by subcutaneous injection of 10(6) MatLu tumour cells into the right hind leg of 21 male Copenhagen rats. After tumour growth, the animals were treated by an i.v. infusion with either 5% glucose (Gl), paclitaxel (Pax), cationic liposomes (CL) or paclitaxel encapsulated in cationic liposomes (EndoTAG-1) on days 12, 14, 16 and 19. Treatment was initiated on day 12 after tumour inoculation at mean tumour volumes of 0.31+/-0.13 mm(3). On the last day of treatment, animals treated with EndoTAG-1 had the significantly lowest tumour volumes with 2.49+/-0.84 cm(3) vs. Pax (5.59+/-0.45 cm(3)) vs. CL (3.87+/-1.25 cm(3)) vs. GL (5.17+/-1.70 cm(3)). The quantification of MVD showed the lowest count for EndoTAG-1-treated tumours (11.78+/-2.68 vessels/mm(2)) followed by Gl (15.64+/-6.68 vessels/mm(3)), Pax (18.22+/-9.50 vessels/mm(3)) and CL (40.9+/-32.8 vessels/mm(3)). The data confirm that neovascular targeting with EndoTAG-1 is a promising new method for the treatment of PCa by reducing the primary tumour mass and demonstrating benefits in the suppression of angiogenesis in comparison with the conventional treatment.

1. In der vorliegenden Arbeit sollte gepruft werden, ob fur die Fetteinlagerung in die Leber durch akute Alkoholzufuhr vorweigend eine Neusynthese von Fettsauren in der Leber oder eine Mobilisierung von Fettsauren aus dem peripheren Fettgewebe verantwortlich ist. Hierzu wurde der Einflus von Alkohol auf den Gehalt von Metaboliten und Coenzymen des Fett- und Kohlehydratstoffwechsels unter verschiedenen Ausgangsbedingungen in der Rattenleber und auf Metabolitspiegel im Blut bei der Ratte und beim Menschen gemessen. 2. Die durch die Alkoholoxydation selbst bedingten Stoffwechselanderungen in der Leber (deutliche Zunahme der Reduktion des cytoplasmatischen NAD-Systems der Leber, gemessen an den Quotienten Lactat/Pyruvat,α-Glycerophosphat/Dihydroxyacetonphosphat, NADH/NAD und Anstieg des Acetyl-CoA-Gehaltes) sind bereits sehr fruh nach einmaliger Alkoholgabe zu beobachten. 3. Die Triglycerideinlagerung in die Leber erfolgt im Vergleich hierzu erst relativ spat und geht parallel dem Anstieg der freien Fettsauren im Plasma, die in den ersten Stunden nach der Gabe von Alkohol zunachst abfallt. 4. Unter proteinarmer Kost (0,5% Protein) nimmt die Aktivitat der Alkohol-Dehydrogenase in der Leber stark ab. Nach 3 Wochen betragt sie nur noch 15% des Wertes der Kontrolltiere. Unter diesen Bedingungen ist die Alkoholoxydation, gemessen an der Abnahme des Blutalkoholspiegels nach einmaliger Alkoholabgabe, stark verlangsamt. Hierdurch ist bei gleicher Alkoholdosis die Alkoholkonzentration im Blut eiweisarm ernahrter Ratten starker und uber langere Zeit erhoht als bei normal ernahrten Tieren. Auch beim Menschen ist der Alkoholabbau, gemessen an der Alkoholelimination im Blut, unter eiweisarmer Kost deutlich verringert. 5. Bei proteinarm ernahrten Ratten bleiben, wie bei der verminderten Oxydationskapazitat fur Alkohol zu erwarten, die Stoffwechselanderungen in der Leber durch die Athanoloxydation (Zunahme der Reduktion des cytoplasmatischen NAD-Systems, Anstieg des Acetyl-CoA-Gehaltes und derα-GP-Konzentration) aus oder sind stark reduziert. Die Triglycerideinlagerung in die Leber ist dagegen noch ausgepragter als bei den normal ernahrten Kontrollen. Auch die Ketokorperkonzentration und der Quotientβ-HOB/AcAc nehmen in der Leber und im Blut starker zu als bei Normaltieren. 6. Die Hemmung der Ausschuttung der lipolytisch wirksamen Catecholamine durch Adrenalektomie oder Gabe vonβ-Receptorenblockern vermindert die alkoholinduzierte Triglycerideinlagerung in die Leber. Stoffwechselanderungen durch die Alkoholoxydation selbst, wie der Anstieg der Quotienten Lactat/Pyruvat und NADH/NAD in der Leber entsprechen dabei den Befunden der Kontrolltiere. 7. Uber 12 Std dauernde Alkoholeinwirkung fuhrt bei Ratten, die Standardkost erhielten zu einer deutlichen Zunahme langkettiger Acyl-Co-Ester in der Leber. Bei proteinarm ernahrten Ratten ist die Akkumulation langkettiger Acyl-CoA-Ester in der Leber unter Athanol noch erheblich ausgepragter. In den beiden Fallen erfolgt die Zunahme auf Kosten von freiem CoA. Die starke Zunahme des Gehaltes an Acetyl-CoA-Ester last eine „feed-back“-Hemmung der Fettsauresynthese am Ort der Acetyl-CoA-Carboxylase vermuten. 8. Bei hyperthyreoten Ratten ist die Oxydationskapazitat furα-Glycerophosphat (α-GP) um eine Grosenordnung gegenuber Normaltieren erhoht. Diese Stoffwechselanderung bietet eine Moglichkeit, den Einflus vonα-GP auf die Triglycerideinlagerung zu untersuchen, daα-GP rascher oxydiert wird und fur die Triglyceridsynthese weniger zur Verfugung steht. Wie zu vermuten, wird der Anstieg desα-GP-Gehaltes in der Leber nach Alkoholgabe durch Hyperthyreose vermindert. Gleichzeitig ist die Triglycerideinlagerung durch Athanol deutlich geringer als bei euthyreoten Tieren. 9. Beim Menschen verhalten sich die Redoxquotienten Lactat/Pyruvat,β-HOB-AcAc, sowie weitere Stoffwechseleffekte, im Blut nach oraler Alkoholgabe analog den bei den Tierversuchen beobachteten Veranderungen. 10. Aus den Ergebnissen wird geschlossen, das akute Alkoholzufuhr nicht zu einer gesteigerten Fettsauresynthese in der Leber fuhrt. Die Fettsauren fur die akute alkoholinduzierte Triglycerideinlagerung stammen wahrscheinlich vorwiegend aus dem peripheren Fettgewebe, wo sie durch indirekte Alkoholeinwirkung vermehrt freigesetzt werden. Der starke Anstieg desα-GP-Gehaltes ist zusammen mit dem vermehrten Fettsaureangebot entscheidend fur die bevorzugte Triglyceridsynthese.

One-hundred sixty patients (81 cyanidanol, 79 placebo) were included in a double-blind placebo-controlled clinical trial to evaluate the effect of 3 gm (+)-cyanidanol-3 per day for 8 weeks on the clinical course of acute viral hepatitis and HBsAg elimination. Quantitative determination of HBsAg was performed at frequent intervals. The mean time for serum bilirubin to decrease to 1.3 mg per dl was 30.8 +/- 3.5 days in the treated group and 52.2 +/- 9.8 days in the control group, (p less than 0.025). The time for SGOT to decrease to 100 IU per liter was 17.98 +/- 1.82 in the treated group and 26.53 +/- 3.7 in the control group (p less than 0.025). No significant difference in the evolution of other laboratory values or symptoms was found. The elimination rate of HBsAg was identical in both groups. Treatment did not alter the incidence of chronicity.