Search

Background In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab–paclitaxel in aTNBC. Patients and methods Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab–paclitaxel versus 5.7 months with placebo–paclitaxel]. In the PD-L1-positive population, atezolizumab–paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo–paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab–paclitaxel versus 28.3 months with placebo–paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov NCT03125902.

Background In the PALOMA-3 trial, palbociclib plus fulvestrant demonstrated a clinically meaningful improvement in overall survival compared with fulvestrant plus placebo in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer who had relapsed or progressed on prior endocrine therapy (Turner NC et al., NEJM 2018). Detailed analyses for first-line (1L) and second- or later- line (2L+) therapy are still limited. Methods The prospective, multicenter phase 2 INGE-B trial was designed to generate efficacy and safety data on the combination of palbociclib with letrozole (1L) or fulvestrant (1L, 2L+) in accordance with the PALOMA trials and to generate so far lacking trial data on the combination of palbociclib with anastrozole (1L), exemestane (1L) or letrozole (2L+). This pre-planned interim analysis was conducted to evaluate data on pts receiving palbociclib plus fulvestrant as 1L or 2L+ therapy. The primary endpoint was the clinical benefit rate (CBR) in pts with measurable disease according to RECIST v1.1. Key secondary endpoints included the overall response rate (ORR), the CBR for all pts, and safety. Data were analyzed with descriptive statistics. Results At the cut-off date of the interim analysis (Dec 17, 2018), 124 pts have been recruited from 03/2017 through 06/2018 at 47 sites across Germany to receive palbociclib plus fulvestrant (1L: 57 pts; 2L+: 67 pts). 57 of 67 pts treated in 2L+ were evaluable. Median age was 68.0 years, 91.2% (n = 52) of pts had an ECOG performance score of 0 or 1. 28.1% (n = 16) of pts presented with non-measurable bone-only disease. The CBR was 35% (n = 14) for the 40 pts with measurable disease (RECIST v1.1) and 51% (n = 29) for all pts (investigator assessment). The ORRs were 25% (n = 10) and 21% (n = 12), respectively. Grade 3/4 adverse events experienced by at least 10% of pts were neutropenia (n = 21, 36.8%) and leukopenia (n = 7, 12.3%). Conclusions This INGE-B interim analysis showed a remarkable clinical benefit for palbociclib plus fulvestrant as second- or later-line therapy for pts with HR+/HER2- advanced breast cancer. No new safety signals were detected. Clinical trial identification 2015-001603-32. Legal entity responsible for the study iOMEDICO AG. Funding Pfizer Pharma GmbH. Disclosure D. Luftner: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Teva; Advisory / Consultancy: Tesaro; Advisory / Consultancy: L’Oreal; Advisory / Consultancy: MSD; Advisory / Consultancy: AstraZeneca. M.K. Welslau: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: GILEAD; Honoraria (self), Advisory / Consultancy: HEXAL; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Medac; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self): Astellas; Honoraria (self): AstraZeneca. A. Welt: Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Eisai; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Amgen. M. Zaiss: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis. N.W. Marschner: Leadership role, Shareholder / Stockholder / Stock options: iOMEDICO AG; Research grant / Funding (institution): Pfizer. All other authors have declared no conflicts of interest.

Background Large-scale multi-national data are lacking on the real world use and outcomes of nivolumab for advanced non-small cell lung cancer (NSCLC). I-O Synthesise NSCLC aims to pool and collectively analyse data from independent study cohorts of real world patients treated with nivolumab for advanced NSCLC. In the present study, we evaluated the real-world benefit of nivolumab in patients with lung cancer from two prospective multi-centre observational cohorts studies [in France (EVIDENS, NCT03382496)) and Germany (ENLARGE, NCT02910999)]. Methods Individual patient data from EVIDENS and ENLARGE were pooled and harmonised in terms of inclusion criteria and variable definitions. Eligible patients had locally advanced or metastatic (stage IIIb/IV) NSCLC, were treated with nivolumab following at least one prior systemic therapy and without diagnoses of other primary cancers. Overall survival (OS) was calculated, including according to histology, using the Kaplan-Meier method from nivolumab initiation date until death or censoring on the last visit date or study withdrawal. Results Following harmonisation of inclusion criteria, 1837 patients (EVIDENS, 1209 patients; ENLARGE, 628 patients) from 225 centres across France and Germany were included in the pooled sample. Baseline characteristics were: median age 65 years, 68% male, 83% ECOG 0-1, 74% 1 prior line of therapy, 68% non-squamous histology, 94% stage IV, 22% with brain metastases (treated or untreated), and 2.8% active autoimmune disease. At the time of analysis over 90% of patients had at least six-months of follow-up. Median OS was 11.5 (10.4, 12.2) months, 10.2 (8.6, 11.5) for squamous and 12.2 (10.8, 13.2) for non-squamous disease. The one-year OS rate was 49%, 51% for non-squamous, and 45% for squamous histology. Conclusions In this large-scale study of nivolumab in pre-treated advanced NSCLC, real-world outcomes were consistent with pivotal nivolumab trials. Clinical trial identification NCT03382496; NCT02910999. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure A. Dixmier: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis. B. Asselain: Advisory / Consultancy: Bristol-Myers Squibb. D. Debieuvre: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Pierre Fabre; Research grant / Funding (institution): Mundipharma . C. Audigier Valette: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer–Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. A. Groschel: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD. S. Gutz: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda; Honoraria (self): Boehringer Ingelheim. D. Moro-Sibilot: Advisory / Consultancy: Roche; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: BMS; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Boehringer; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Takeda. M. Perol: Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Lilly; Advisory / Consultancy: BMS; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Takeda; Advisory / Consultancy: Clovis ; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. C. Schumann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche. V. Allan: Full / Part-time employment: Bristol-Myers Squibb. C.Y. Calvet: Full / Part-time employment: Bristol-Myers Squibb. K.J. Rothnie: Full / Part-time employment: Bristol-Myers Squibb. V. Wunsch: Full / Part-time employment: Bristol-Myers Squibb. M. Sebastian: Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Medio-launum; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Takeda. All other authors have declared no conflicts of interest.

Zwei entscheidende Erkenntnisse der letzten 15 Jahre haben zu einem Wandel in der Therapie primarer Magenlymphome gefuhrt: Studien haben gezeigt, dass die Operation keine therapeutische Option mehr ist und dass bei Marginalzonenlymphomen im Stadium I mit positivem Nachweis von Helicobacter pylori (H.p.) eine antibiotische Behandlung in der uberwiegenden Zahl der Falle zu einer Heilung des Lymphoms fuhrt. Fur indolente Lymphome in den Stadien I und II zeigen die Daten der Deutschen Studiengruppe Gastrointestinale Lymphome, dass die Strahlentherapie mit 40 Gy im Tumorbereich zu einer Kontrolle des Lymphoms zu uber 95% fuhrt. Standards fur lokalisierte aggressive Non-Hodgkin-Lymphome bzw. Lymphome in den Stadien III und IV sind noch nicht ausreichend definiert.

Heliox is a mixture of Oxygen and Helium. The low density of Helium allows this mixture to flow in a laminar pattern where oxygen, nitrogen or air flow would be turbulent. Therefore the force necessary to move a volume of gas (e.g. Heliox) is greatly reduced in comparison to a turbulent gas flow. In a respiratory loading experiment we investigated the effects which Heliox exerts on hemodynamic as well respiratory variables. 10 volunteers were breathing spontaneously and through three different endotracheal (ET-) tubes (ID 4.0, 4.5, 5.0 mm). The subjects were switched from room air to Heliox and differences in the variables heart rate (HR), blood pressure (BP), stroke volume (SV), stroke index (SI), peripheral vascular resistance (TPRI) and left ventricular work index (LVWI) were measured. Furthermore the (PhAng) between abdomen and thorax was detected using respiratory inductance plethysmography (n=2) and the sense of dyspnoe under the different conditions was assessed by the use of a dyspnea score (DS). The means of BP, SV, SI, TPRI and LVWI did not significantly differ between the resting and the different loading conditions irrespective of the gas that was used. The variability of hemodynamic measures was significant larger during loaded vs. unloaded breathing. Heliox could significantly reduce this degree of variability. In two subjects Heliox could also significantly reduce the PhAng as well as DS. Heliox showed effects on hemodynamic as well as respiratory and subjective variables. These effects can be interpreted as a reduction of the extent of pressure variations in the intrapleural space leading to less impact on hemodynamic variables while breathing Heliox vs. room air in a resistive loading experiment. In the future the combined measurement of hemodynmic variables as well as non-invasive assessment of respiration might shed new light on cardio-respiratory interaction and effects of Heliox during airway obstruction.

Ventrikulare Herzrhythmusstorungen konnen bei Kindern sowohl die Folge als auch der Ausloser einer myokardialen Funktkionsstorung sein. Wir berichten uber ein 2jahriges Madchen mit ventrikularer Tachykardie und Herzinsuffizienz im Sinne einer Tachykardiomyopathie. Eine Therapie mit Antiarrhythmika der Klasse I und III fuhrte zu keiner signifikanten Verbesserung der Situation. Die kardiologischen Untersuchungen zeigten eine Analogie zur verapamilsensitiven ventrikularen Tachykardie im jungen Erwachsenenalter. Die Behandlung mit Verapamil fuhrte zur vollstandigen Normalisierung der Befunde.

Mesophyll protoplasts of six lines of Silybum marianum were enzymatically isolated from young leaves, embedded in sodium alginate, and cultivated in KM-medium. Division frequencies observed after ten days were strongly influenced by the protoplast density. When 5 x 10 (4)/ml protoplasts were plated, division frequencies of about 35% were obtained, with a protoplast population density of 1 x 10 (5)/ml division frequencies of about 75% resulted. Plant regeneration experiments undertaken with the protocalluses on medium containing BAP led to shoot formation in only two lines with regeneration frequencies of less than 1% in one (M 24) and up to 7% in a second line (M 2), respectively. However, when the protocalluses from line M 2 were treated with thidiazuron (TDZ) in a first culture step, and with BAP in a second step, the shoot formation frequency rose to 22%. Shoots were rooted on hormone free MS agar medium and transferred into soil where plants grew to maturity. Similar results were obtained when protoplasts of the line M 2, isolated from a suspension culture, were cultivated.

In crossing experiments between S. marianum and S. eburneum the number of fruits produced was relatively high as compared to the two parental species. All the F(1)-plants showed the variegated leaf characteristic of S. marianum, whereas after selfing the F(2)-plants had completely green and variegated leaves in a ratio of about 3:1 indicating that the leaf colour is monofactorially inherited. This proves that the two species are only variants. Using leaf colour as the genetic marker, the outcrossing rate in field experiments was studied. Since the outcrossing rate on average is only about 2%, SILYBUM is predominantly a self-pollinator. From 11 randomly selected plants, three inbred generations were produced and their silymarin composition (silibinin, silidianin, silichristin) was studied. Two types of lines could be distinguished based on the relative values of three flavonolignans: lines with approximately 70% silibinin, 30% silichristin, and traces of silidianin in all inbred generations and those with the relative contents of the compounds 30%, 57%, and 13%, respectively.

Ein 6 1/2 Jahre altes Madchen aus Eritrea zeigte bei Zustand nach rheumatischem Fieber eine schwere Aorten- und Mitralklappeninsuffizienz. Die defekte Aortenklappe wurde durch einen Autograft, bestehend aus Pulmonalklappe mit angrenzendem Gefassaum der Pulmonalarterienwurzel, in Anlehnung an das Operationsverfahren nach Ross ersetzt. Gleichzeitig konnte die Mitralklappe rekonstruiert werden. Das Ergebnis bezuglich der Aortenklappe war exzellent. An der Mitralklappe bestand postoperativ eine leichte Insuffizienz. Schlusfolgerung: Der pulmonale Autograft kann als gute Alternative zur Implantation einer Aortenklappenprothese angesehen werden. Dieser Fallbericht ermutigt zur Anwendung der Ross-Operation bei vergleichbaren Patienten.

Heliox is a mixture of Oxygen and Helium. The low density of Helium allows this mixture to flow in a laminar pattern where oxygen, nitrogen or air flow would be turbulent. Therefore the force necessary to move a volume of gas (e.g. Heliox) is greatly reduced in comparison to a turbulent gas flow. In a respiratory loading experiment we investigated the effects which Heliox exerts on hemodynamic as well respiratory variables. 10 volunteers were breathing spontaneously and through three different endotracheal (ET-) tubes (ID 4.0, 4.5, 5.0 mm). The subjects were switched from room air to Heliox and differences in the variables heart rate (HR), blood pressure (BP), stroke volume (SV), stroke index (SI), peripheral vascular resistance (TPRI) and left ventricular work index (LVWI) were measured. Furthermore the (PhAng) between abdomen and thorax was detected using respiratory inductance plethysmography (n=2) and the sense of dyspnoe under the different conditions was assessed by the use of a dyspnea score (DS). The means of BP, SV, SI, TPRI and LVWI did not significantly differ between the resting and the different loading conditions irrespective of the gas that was used. The variability of hemodynamic measures was significant larger during loaded vs. unloaded breathing. Heliox could significantly reduce this degree of variability. In two subjects Heliox could also significantly reduce the PhAng as well as DS. Heliox showed effects on hemodynamic as well as respiratory and subjective variables. These effects can be interpreted as a reduction of the extent of pressure variations in the intrapleural space leading to less impact on hemodynamic variables while breathing Heliox vs. room air in a resistive loading experiment. In the future the combined measurement of hemodynmic variables as well as non-invasive assessment of respiration might shed new light on cardio-respiratory interaction and effects of Heliox during airway obstruction.

La repolarisation precoce est une caracteristique electro cardiographique commune (1-5 % de la population generale). Une etude recente a montre que l’incidence de la repolarisation precoce (RP) est plus elevee chez les sujets ayant presente une fibrillation ventriculaire (31 % des patients vs 5 % des controles). A ce jour, il est encore impossible de differencier les patients presentant un aspect de RP a risque parmi la population generale. L’existence de forme familiale de RP associee a des morts subites suggere un caractere hereditaire a cette pathologie. Une etude genetique a ete realisee sur une cohorte de 96 patients. Les genes majeurs des troubles du rythme cardiaque et les genes codant les canaux ioniques impliques dans la phase de repolarisation du potentiel d’action ventriculaire ont ete exclus par sequencage chez ces patients. Les canaux potassiques ATP dependant (KATP) sont fortement exprimes dans les cardiomyocytes. L’une des hypotheses emises est qu’une augmentation de 1-2 % de l’ouverture de ces canaux genererait un courant suffisant qui pourrait affecter la phase de repolarisation ventriculaire. Les canaux KATP sont composes de sous-unites canalaires Kir6.0 (KCNJ8 codant Kir6.1 ou KCNJ11 codant Kir6.2) et de recepteurs aux sulphonylurees SUR (ABCC8 codant SUR1 ou ABCC9 codant SUR2). L’approche gene-candidat a permis de mettre en evidence le variant rare p.S422L dans le gene KCNJ8 chez une jeune patiente presentant de nombreux episodes de fibrillation ventriculaire (plus de 100) et une RP dans les derivations infero-laterales. Suite a ces premiers resultats, nous avons sequences les autres sous-unites des canaux KATP. Ainsi, 5 variants ont ete identifies dans le gene ABCC9 : 4 variants faux-sens et une substitution d’un nucleotide dans un site d’epissage. L’enquete familiale et l’analyse fonctionnelle sont en cours pour ces patients. Plusieurs hypotheses physiopathologiques (augmentation du trafic membranaire, diminution de la sensibilite a l’ATP…) vont etre testees afin de comprendre l’implication de ces variants sur le potentiel d’action ventriculaire. L’identification de 6 patients sur 96 (6.25 %) porteurs de variant dans les genes codant les canaux KATP conforte l’hypothese du role de ce courant dans le syndrome de repolarisation precoce.

Ventricular arrhythmias can both result from and cause myocardial dysfunction. We report a case of a two-year-old girl with ventricular tachycardia showing signs of heart failure consisting with a tachycardiomyopathy. The therapy with class I and class III antiarrhythmic drugs did not improve the cardiac situation significantly. The cardiologic investigations were consistent with the verapamil-sensitive ventricular tachycardia in young adults. The treatment with verapamil led to a normal rhythm and function of the heart.Verapamil-type calcium channel blockers can also be used in children for the treatment of ventricular tachycardias if the corresponding investigations show characteristic findings.

breast cancer. In this patient cohort, the LYL due to late side effects appeared to be dominated by lung cancer, followed by cardiovascular disease. The combined LYL was lowest with DIBH (p < 0.0001) and the additional benefit of IMRT was not significant. Conclusions: DIBH significantly decreases the estimated risk of cardiovascular disease and lung cancer after radiation therapy for mediastinal Hodgkin lymphoma. Combined risk estimates were lowest with DIBH combined with IMRT and the results should be confirmed in a larger patient cohort. Author Disclosure: M.C. Aznar: None. M.V. Maraldo: None. P. Brodin: None. I.S. Vogelius: None. M. Josipovic: None. P.M. Petersen: None. S.M. Damkjaer: None. D. Schut: None. A.K. Berthelsen: None. L. Specht: None.

In order to investigate the possibility of isolating greater amounts of the antimalarial compound artemisinin (quinghaosu), plants of ARTEMISIA ANNUA were cultivated and analysed at different stages of development. We found the highest content just before flowering. It was also possible to correlate development of the plants with the maximum content of artemisinin. ARTEMISIA ANNUA plants cultivated from various other sources were also examine for artemisinin content. According to our results, none of these plants contained sufficient amounts of artemisinin to justify an isolation on a technical scale. Furthermore other Artemisia species were tested. We found artemisinin in only one other species. To possibly increase the amount of artemisinin during the growth period of the plant, we tested two hormone-type growth regulators on A. ANNUA strain 811. The results showed that one of them, chlormequat, was able to increase the artemisinin content by 30% over untreated plants. We also found some slight effects of the growth regulators on morphological criteria of glandular trichomes.

Fibrinogen half-life was determined in 3 healthy individuals and in 17 children with cyanotic congenital heart disease. Fibrinogen half-life was normal in the healthy individuals and shortened in 9 of the 17 patients. The simultaneously performed coagulation tests were often pathological but did not lead to a clear diagnosis of the haemostatic defect and did not correlate with the fibrinogen half-life. Significant correlations were found between fibrinogen half-life and red cell count (P

21 infants and children with proven bacterial endocarditis were observed at the Unviersity Children Hospital of Düsseldorf from January 1969 to December 1976. There was high incidence of cases in the infant group and again among the 6 to 8 years old children. Some important aspects of the disease were characteristic for the infant group (N=5): No congenital cardiac abnormality was present, but a surgical cerebro-atrial connection in two cases of hydrocephalus and a prolonged artifical respiration in a third patient could have been predisposing factors. Staphylococci were the pathologic organisms in three infants. The course of the disease consistently resembled that of septicemia and the outcome was always lethal. The diagnosis of bacterial endocarditis was disclosed only by the post mortem examination. The mitral and the tricuspid valves were affected twice respectively, the pulmonary cusps only once. In the children group (N=16) fifteen patients had a congenital malformation of the heart confirmed by previous catheterization. 8 were cyanotic and 5 of them had a tetralogy of Fallot with previous aorto-pulmonary shunting procedure (Waterston). Unlike the spectrum of micro-organisms presently found in adults, the streptococcus viridans prevailed as before, it was isolated in 11 of the 13 blood cultures which yielded positive results. The disease displayed a subacute course and mortality remained with 3 deaths relatively low. In 3 other cases a valve lesion subsisted, in two instances severe enough to necessitate surgery (aortic valve prosthesis, mitral annular narrowing). No relapse was observed during the mean follow up period of 2;8 years.

The essential oil and its main components (i.e., proazulenes) are useful taxonomic characters also in the genera Ankistrodesmus and Scenedesmus. The amounts of oil in these genera are similar to that of the genus Chlorella. A few strains of Ankistrodesmus, which are unable to synthesize proazulenes, seem to belong to other genera.