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In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients. These include general aspects (structure and process quality, primary diagnostics and therapy as well as indication for subsequent treatment; resuscitation room management; diagnostics and monitoring; general therapeutic measures; hygiene measures; and pharmacotherapy) and also specific aspects concerning angiology, endocrinology, diabetology and metabolism, gastroenterology, geriatric medicine, hematology and oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology and toxicology. Publications focussing on contents of advanced training are quoted in order to support this concept. The curriculum has primarily been written for internists for their advanced emergency training, but it may generally show practising emergency physicians the broad spectrum of internal medicine diseases or comorbidities presented by patients attending the emergency department., (© 2024. The Author(s).)

Background and Objective: Despite a measurable increase in recent years, the bystander resuscitation rate in Germany lags behind the European comparison. Special centers for the care of patients after cardiac arrest, so-called cardiac arrest centers (CAC), have been established. The aim of this work is to evaluate the role of CACs, in addition to in-hospital patient care, in improving the bystander resuscitation rate in Germany and what obstacles exist in the implementation of resuscitation training., Materials and Methods: Online survey by the working group cardiopulmonary resuscitation (AG42) of the German Society of Cardiology (DGK) and the German Resuscitation Council (GRC) RESULTS: Of the 74 participating clinics (78.4% certified as CAC), 23 (31.1%) conduct lay resuscitation training. These mainly take place within the framework of action days for resuscitation (82.6%) or in schools (39.1%). Permanent cooperation with at least one school existed in 52.2%. Basic life support (BLS) resuscitation dummies are available in 63.5% of these clinics and an automated external defibrillator (AED) demonstration device in 43.2%. According to the interviewees, the biggest obstacles to the consistent implementation of resuscitation courses in schools include lack of qualified instructors, lack of refinancing and difficulties with regard to coordinating activities between schools and providers., Conclusions: Direct training of lay rescuers by hospitals faces several obstacles. To increase the bystander resuscitation rate, focusing on targeted training of teachers as multipliers (train-the-trainer) can be a good approach for cardiac arrest centers., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Point-of-care sonography is a precondition in acute and emergency medicine for the diagnosis and initiation of therapy for critically ill and injured patients. While emergency sonography is a mandatory part of the training for clinical acute and emergency medicine, it is not everywhere required for prehospital emergency medicine. Although some medical societies in Germany have already established their own learning concepts for emergency ultrasound, a uniform national training concept for the use of emergency sonography in the out-of-hospital setting is still lacking. Experts of several professional medical societies have therefore joined forces and developed a structured training concept for emergency sonography in the prehospital setting. The consensus paper serves as quality assurance in prehospital emergency sonography., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: At the onset of the coronavirus pandemic, concerns were raised about sufficiency of available intensive care resources. In many places, routine interventions were postponed and criteria for the allocation of scarce resources were formulated. In Germany, some hospitals were at times seriously burdened during the course of the pandemic. Intensive care units in particular experienced a shortage of resources, which may have led to a restriction of services and a stricter indication setting for resource-intensive measures such as extracorporeal membrane oxygenation (ECMO). The aim of this work is to provide an overview of how these pressures were managed at large ECMO centers in Germany., Methods: One representative of each major ECMO referral center in Germany was invited to participate in an online survey in spring 2021., Results: Of 34 invitations that were sent out, the survey was answered by 23 participants. In all centers, routine procedures were postponed during the pandemic. Half of the centers increased the number of beds on which ECMO procedures could be offered. Nevertheless, in one-third of the centers, the start of at least one ECMO support was delayed because of a feared resource shortage. In 17% of centers, at least one patient was denied ECMO that he or she would have most likely received under prepandemic conditions., Conclusion: The results of this online survey indicate that the experienced pressures and resource constraints led some centers to be cautious about ECMO indications., (© 2022. The Author(s).)

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: Improved imaging modalities contributed to increasing awareness of cardiac amyloidosis. Contemporary data on frequency trends in Germany are lacking., Methods: In a retrospective study using health claims data of a German statutory health insurance, patients with diagnostic codes of amyloidosis and concomitant heart failure between 2009 and 2018 were identified., Results: Prevalence increased from 15.5 to 47.6 per 100,000 person-years, and incidence increased from 4.8 to 11.6 per 100,000 person-years, with a continuous steepening in the slope of incidence trend. In patients with amyloidosis and heart failure age and proportion of men significantly increased, whereas the frequency of myeloma and nephrotic syndrome significantly decreased over time. Median (IQR) survival time after first diagnosis was 2.5 years (0.5-6 years), with a 9% (95% CI 2-15%, p = 0.008) reduced risk of death in the second compared to the first 5 years of observation. In the 2 years prior and 1 year after diagnosis, mean total health care costs were 6568 €, 11,872 € and 21,955 € per person and year., Conclusion: The rise in cardiac amyloidosis has continuously accelerated in the last decade. Considering the adverse outcome and high health care burden, further effort should be put on early detection of the disease to implement available treatment., (© 2022. The Author(s).)

Background: Temperature control is recommended after out of hospital cardiac arrest (OHCA) by international guidelines. This survey aimed to investigate current clinical practice and areas of uncertainty., Methods: Online survey targeting members of three medical emergency and critical care societies in Germany (April 21-June 6, 2022) assessing post-cardiac arrest temperature control management., Results: Of 341 completed questionnaires 28% (n = 97) used temperature control with normothermic target and 72% (n = 244) temperature control with hypothermic target. The definition of fever regarding patients with cardiac arrest ranged from ≥ 37.7 to 39.0 °C. Temperature control was mainly started in the ICU (80%, n = 273) and most commonly core cooling (74%, n = 254) and surface cooling (39%, n = 134) with feedback were used. Temperature control was maintained for 24 h in 18% (n = 61), 48 h in 28% (n = 94), 72 h in 42% (n = 143) and longer than 72 h in 13% (n = 43). 7% (n = 24) were using different protocols for OHCA with initial shockable and non-shockable rhythm. Additional 14% (n = 48) were using different temperature control protocols after in-hospital cardiac arrest (IHCA) compared with OHCA. Overall, 37% (n = 127) changed practice after the publication of the ERC-2021 guidelines and 33% (n = 114) after the recent publication of the revised ERC-ESICM guideline on temperature control., Conclusions: One-third of the respondents changed clinical practice since recent guideline update. However, a majority of physicians further trusts in temperature control with a hypothermic target. Of interest, 14% used different temperature control strategies after IHCA compared with OHCA and 7% for shockable and non-shockable initial rhythm. A more individualized approach in post resuscitation care may be warranted., (© 2023. The Author(s).)

Health workers (HW) are at increased risk for SARS-CoV-2 infection. In order to monitor the infection dynamic on the basis of contact with patients, HW at the St. Antonius Hospital (SAH) were tested four times in one year by PCR and serology. The cumulative incidence of infection in HW was calculated. Swab and blood tests were simultaneously performed between April 2020 and April 2021. Risk factors and demographic information were assessed at the beginning of the study. The response rate was above 75% in all rounds of testing. The study comprised 1506 HW, 165 (10.6%) of which tested positive for SARS-CoV-2 infection. Working in an ICU or on wards with patient contact were risk factors (OR 4.4, 95% CI 1.73-13.6 and OR 2.9, 95% CI 1.27-8.49). At the end of the study, the majority of HW (810 of 1363 (59.4%)) had been vaccinated at least once. A total of 29.1% of unvaccinated HW and 5.3% of vaccinated HW showed an immune response typical for natural SARS-CoV-2 infection. Of the 73 HW who provided information on the course of the disease, 31.5% reported that their quality of life continued to be impaired. The cumulative incidence of infection was low in these HW, which may be attributed to vaccination and good hygiene. Nevertheless, a work-related infection risk was identified, highlighting the need to improve protection against infection. A high risk of developing long COVID was found after the infection has subsided. Special rehabilitation programs should be provided and HW should be compensated for reduced work capacity in the case that rehabilitation fails or takes a long time.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Structured sonography training in internal medicine intensive care and emergency medicine (SIN) comprises two levels and was proposed by three national societies in Germany (DGIIN, DGK and DEGUM). The curriculum consists of a basic level (SIN-I) and an expert level (SIN-II) which are consecutive levels teaching both theoretical and hands-on skills using a symptom-based approach. Competency is assessed using written, oral and practical structured assessments at the end of each level. The goal is to implement national and international recommendations regarding the use of point-of-care ultrasound into clinical practice.

Predominantly the older population is affected by a severe course of COVID-19. The mortality of hospitalized patients with COVID-19 above the age of 80 years is up to 54% in international studies. These observations indicate the necessity to highlight the geriatric perspective on this disease. The diagnostics and treatment of COVID-19 do not differ between younger and older patients but atypical symptoms should be expected more frequently in old age. Older subjects show an increased need for rehabilitation after COVID-19. Paradoxically, increasing rehabilitation demands go along with a reduced availability of geriatric rehabilitation options, the latter being a consequence of closure or downsizing of rehabilitation departments during the pandemic. In general, measures of isolation and quarantine should be diligently balanced as the health and emotional consequences of such measures may be severe in older persons. In light of the poor prognosis of older COVID-19 patients, advanced care planning becomes even more relevant. Caregivers and physicians should be encouraged to compose advanced care directives that also reflect the specific circumstances of COVID-19. Fortunately, current data suggest that the effectiveness of the vaccination with the mRNA-vaccines approved in Germany may be equally high in older compared to younger persons.

Background: We assessed the prevalence of SARS-CoV-2 in the staff of a general hospital in North-Rhine-Westphalia in a cross-sectional study., Method: Employees (n = 1363) were offered a nasopharyngeal swab and serology for SARS-CoV-2. Additionally, employees completed a questionnaire about preexisting conditions, contacts with SARS-CoV-2-positive individuals and COVID-19-specific symptoms., Results: 1212 employees participated. 19 of 1363 (1.4 %) employees tested positive by PCR (3 within and 16 before the study). 40 (3.3 %) and 105 (8.6 %) had IgG and IgA, respectively, 32 (2.6 %) both IgG and IgA. Overall, 47 employees tested positive. In this group, most frequently reported symptoms were headache (56 %), fatigue (49 %), sore throat (49 %), and cough (46 %); fever was reported by 33 %. SARS-CoV-2-positive employees reported more frequently contact with COVID-19 cases (60.5 % vs. 37.3 %, p = 0.006). Employees testing positive only for IgA reported less symptoms., Conclusion: Between 27.04. and 20.05.2020, 3.9 % of the employees working in a general hospital were tested positive for SARS-CoV-2. This proportion was lower than expected; possible explanations are the low level of endemic infection and the extensive, uniform in-house preventative measures., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Invasive mechanical ventilation can be terminated by immediate (palliative) extubation or by gradual reduction of ventilation with the ventilation access left open (terminal weaning). Both procedures are ethically equivalent and can be performed in everyday life, so that individual patient factors and the experience of the treatment team are decisive. However, the primary goal is to ensure that the patient and relatives do not suffer. This article presents step by step which aspects are relevant: communication, adjust or stop monitoring, selection and implementation of the appropriate procedure, preparatory measures, recognition and treatment of distressing symptoms by means of drug or non-drug therapy options and last but not least accurate documentation., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Since 2010, the number of organ donations has decreased by 30% in Germany; however, stricter organizational structures in clinics and improved payment for hospital services associated with organ removal should increase the current decline in the number of organ donations in Germany. In addition, the Federal Minister of Health proposed introduction of the double presumed consent solution for organ donation. This proposal is currently being discussed very controversially. Against this background, we conducted an online survey of all members of the German Society of Medical Intensive Care and Emergency Medicine (DGIIN) in order to evaluate the attitude towards organ donation., Method: The present work is an anonymous online survey among the members of DGIIN, which took place from 10-23 September 2018. In addition to a few demographic queries, the personal opinion on the regulation of organ donation was collected., Results: A total of 1019 (51.9%) of 1964 invited DGIIN members took part at the survey: 79.3% of the participants were male; average age 47.5 ± 11.2 years; 97.7% were physicians, of whom 89.2% were specialists and 62.7% had the additional degree in critical care; 20.6% voted for the current decision-making solution, 43.1% for the presumed consent, 33.1% for the double presumed consent, whereas 3.2% of the respondents were uncertain in their decision., Conclusion: A clear majority of the surveyed members of DGIIN support the concept of presumed consent.

Aims: Peripartum cardiomyopathy (PPCM) establishes late in pregnancy or in the first postpartum months. Many patients recover well within the first year, but long-term outcome studies on morbidity and mortality are rare. Here, we present 5-year follow-up data of a German PPCM cohort., Methods and Results: Five-year follow-up data were available for 66 PPCM patients (mean age 34 ± 5 years) with a mean left ventricular ejection fraction (LVEF) of 26 ± 9% at diagnosis. Ninety-eight percent initially received standard heart failure therapy (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and/or mineralocorticoid receptor antagonists), and 86% were additionally treated with dopamine D2 receptor agonists (mainly bromocriptine) and anticoagulation. After 1 year, mean LVEF had improved to 50 ± 11% (n = 48) and further increased to 54 ± 7% at 5-year follow-up with 72% of patients having achieved full cardiac recovery (LVEF >50%). At 5-year follow-up, only three patients (5%) displayed no recovery, of whom one had died. However, 20% had arterial hypertension and 17% arrhythmias, including paroxysmal supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Moreover, 70% were still on at least one heart failure drug. Subsequent pregnancy occurred in 16 patients with two abortions and 14 uneventful pregnancies. Mean LVEF was 55 ± 7% at 5-year follow-up in these patients., Conclusion: Our PPCM collective treated with standard therapy for heart failure, dopamine D2 receptor agonists, and anticoagulation displays a high and stable long-term recovery rate with low mortality at 5-year follow-up. However, long-term use of cardiovascular medication, persisting or de novo hypertension and arrhythmias were frequent., (© 2019 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Mortality in patients with out-of-hospital cardiac arrest (OHCA) remains very high despite advances in resuscitation algorithms. Most of these patients die at the scene and do not reach hospital. It is currently the subject of discussion whether transport to hospital with ongoing cardiopulmonary resuscitation (CPR) improves survival and neurological outcome in patients with OHCA., Objective: The aim of this study was to identify predictors of survival and good neurological outcome in patients after OHCA who were transported to hospital with ongoing CPR., Patients and Methods: A total of 70 consecutive patients with refractory OHCA (mean age 54.7 ± 15 years) transported to hospital with ongoing CPR were retrospectively analyzed. Neurological outcome was assessed after 30 days based on the Glasgow-Pittsburgh cerebral performance category (CPC)., Results: After 30 days 82.9% of the patients enrolled in the trial died (CPC score of 5), 8 patients (11.4%) showed a good neurological recovery with CPC scores of 1-2 and 4 patients (5.7%) had a poor neurological outcome with CPC scores of 3-4. Predictors of good neurological outcome were witnessed arrest, initial defibrillatable rhythm and serum lactate levels on admission. In all patients with good outcome, the index event for OHCA was from cardiac causes., Conclusion: Selected patient collectives can benefit from transport to hospital with ongoing cardiopulmonary resuscitation (CPR).

Purpose: The aim of the FEELING-ON-ICU study was to compare mortality estimations of critically ill patients based on 'gut feeling' of medical staff and by Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA)., Materials and Methods: Medical staff estimated patients' mortality risks via questionnaires. APACHE II, SAPS II and SOFA were calculated retrospectively from records. Estimations were compared with actual in-hospital mortality using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC)., Results: 66 critically ill patients (60.6% male, mean age 63±15years (range 30-86)) were evaluated each by a nurse (n=66, male 32.4%) and a physician (n=66, male 67.6%). 15 (22.7%) patients died on the intensive care unit. AUC was largest for estimations by physicians (AUC 0.814 (95% CI 0.705-0.923)), followed by SOFA (AUC 0.749 (95% CI 0.629-0.868)), SAPS II (AUC 0.723 (95% CI 0.597-0.849)), APACHE II (AUC 0.721 (95% CI 0.595-0.847)) and nursing staff (AUC 0.669 (95% CI 0.529-0.810)) (p<0.05 for all results)., Conclusions: The concept of physicians' 'gut feeling' was comparable to classical objective scores in mortality estimations of critically ill patients. Concerning practicability physicians' evaluations were advantageous to complex score calculation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: Besides early percutaneous coronary intervention (PCI) long-term medical treatment is crucial for outcomes after ST-elevation myocardial infarction (STEMI). The present study aimed to identify predictors of adherence to evidence-based medication in this high risk population., Methods and Results: A total of 1025 consecutive patients with adjudicated STEMI treated by primary PCI in a single centre as part of the Cologne Infarction Model (KIM) were prospectively analysed. Gender-specific multivariate predictors of long-term medication adherence were identified. Follow-up with available information on drug use was completed for 610 of 738 (82.7%) patients confirmed to be alive after a median period of 36 months. Adherence was persistently high for evidence-based medication with 90.8% for acetylsalicylic acid (ASA), 88.2% for statins, 87.5% for beta-blockers and 79.2% for ACE-inhibitors or angiotensin-receptor blockers (ARBs). Patients with a history of heart failure had a higher medication adherence to beta-blockers, ACE-inhibitors/ARBs and diuretics, whereas long-term prescription rates for calcium channel blockers (CCBs) were lower in patients with reduced versus preserved ejection fraction. Patients with a history of hypertension presented higher medication adherence to CCBs, ACE-inhibitors/ARBs and diuretics but not to beta-blockers. On multivariate analysis, age, body mass index (BMI), hypertension, chronic kidney disease and lack of PCI were independently associated with prescription of diuretics at follow-up. In women, adherence was lower to beta-blockers and higher to CCBs compared to men., Conclusion: In the high risk population of STEMI patients long-term adherence to evidence-based medication is high. The lower adherence to beta-blockers and higher prescription rate for CCBs in women needs particular attention., (© The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Phytochemical investigation of plants used in traditional Indonesian medicine (Jamu) yielded lignans (pinoresinol, 9 alpha-hydroxypinoresinol and salicifoliol), flavonoids (3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol, luteolin and apigenin) and coumarins (coumarin, 8-hydroxycoumarin and 5-hydroxycoumarin). The beneficial effects of the respective plants for human health are thought to be associated with antioxidative activity. In the present study, the antioxidative capacity of the isolated compounds was determined in an in-vitro assay. Luteolin and kaempferol (cleavage product of 3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol, which is thought to be formed in the intestine) showed strong antioxidant activity; pinoresinol and 9 alpha-hydroxypinoresinol showed only minor antioxidative effects. The coumarins, as well as apigenin and 3-O-beta-(D)-glucopyranosyl-(1-->6)-beta-(D)-glucopyranosylkaempferol were inactive. The antioxidative effects of luteolin, kaempferol and pinoresinol were further investigated in H4IIE rat hepatoma cells. A strong protective effect of kaempferol and luteolin was found against H2O2-mediated intracellular reactive oxygen species formation measured using the dichlorofluorescein assay and H2O2-mediated DNA strand breaks. Pinoresinol did not have a protective effect against H2O2-mediated DNA-damage, but in the dichlorofluorescein assay, an antioxidative effect was detectable. During studies with H4IIE cells, kaempferol, luteolin and pinoresinol were taken up by the cells within 60 min. The flavonoids were found to be relatively toxic at higher concentrations, while pinoresinol was less cytotoxic. In conclusion, kaempferol and luteolin, at low concentrations (< or = 50 microM), protect H4IIE cells against oxidative stress but are cytotoxic at higher concentrations; the biological effects of pinoresinol are less prominent in comparison. These results are important for the identification of pharmacologically active substances from traditional Indonesian medicinal plants.