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Background: Stroke is emerging as a public health threat in sub-Saharan African countries including Ethiopia. Even though cognitive impairment is increasingly being recognized as a major cause of disability among stroke survivors there is a paucity of information on the magnitude of stroke-related cognitive dysfunction in Ethiopia. Thus, we assessed the magnitude and predictors of post-stroke cognitive impairment among Ethiopian stroke survivors. Methods: A facility-based cross-sectional study was employed to assess the magnitude and predictor of post-stroke cognitive impairment among adult stroke survivors who came for follow-up at least 3 months after the last stoke episode from February to June 2021 in three outpatient neurology clinics in Addis Ababa, Ethiopia. We used the Montreal Cognitive Assessment Scale-Basic (MOCA-B), modified Rankin Scale (mRS), and Patient Health Questionnaire-9 (PHQ-9) to assess post-stroke cognition, functional recovery, and depression, respectively. Data were entered and analyzed using SPSS software version 25. A binary logistic regression model was employed to identify the predictors of post-stroke cognitive impairment. A p-value of 0.05 was considered statistically significant. Results: Of the 79 stroke survivors approached, 67 were included. The mean (SD) age was 52.1 (12.7) years. Over half (59.7%) of the survivors were males and most (67.2%) were urban residents. The median stroke duration was 3 years ranging from 1 to 4 years. Almost half (41.8%) of stroke survivors had cognitive impairment. Increased age (AOR=0.24, 95% CI=0.07,0.83), lower education (AOR=4.02, 95% CI=1.13,14.32), and poor function recovery (mRS ³3) (AOR=0.27, 95% CI=0.08-0.81) were predictors significantly associated with post-stroke cognitive impairment. Conclusion: Nearly one in two stroke survivors had cognitive impairment. The major predictors associated with cognitive decline were age above 45 years, low literacy, and poor recovery in physical function. Although causality cannot be inferred, physical rehabilitation and better education are essential in building cognitive resilience among stroke survivors.

Background: Stroke is emerging as a public health threat to sub-Saharan African countries. Even though cognitive impairment is increasingly being recognized as a major cause of disability in stroke survivors there is no data on the burden of stroke related cognitive dysfunction from Ethiopia. In this study, we aimed to assess the frequency and predictors of post-stroke cognitive impairment in Ethiopian stroke survivors.Methods: Participants were adult stroke survivors who came for follow-up at least 3 months after the last stoke. Demographic and clinical data were collected using a structured questionnaire. We employed the Montreal Cognitive Assessment Scale-Basic (MOCA-B), modified Rankin Scale (mRS) and Patient Health Questionnaire-9 (PHQ-9) to assess post-stroke cognition, functional recovery, and depression, respectively.Results: Among 67 stroke survivors (mean age: 52.1 ± 12.7 years, females: 40.3%, low or no education: 41.8%, median stroke duration: 3 years), 28 (41.8%) had post-stroke cognitive impairment. Of these, 20 (30%) had mild cognitive impairment and 8 (12%) had post-stroke dementia. On multivariate analysis, increased age [AOR=0.24, 95% CI (0.07,0.83)], lower education [AOR=4.02, 95% CI (1.13,14.32)] and poor function recovery (mRS ³3) [AOR=0.27, 95% CI (0.08-0.81)] were independently associated with post-stroke cognitive impairment.Conclusion:Cognitive impairment is frequent among Ethiopian stroke survivors. We found that increased age, low educational attainment, and poor recovery on physical function were independently associated with cognitive decline. Although causality cannot be inferred, physical rehabilitation and better education might play a significant role in building cognitive resilience among stroke survivors.

Obstructive Sleep Apnea is emerging as a global health epidemic, particularly due to the obesity pandemic. However, comprehensive prevalence data are still lacking and global OSA research has not yet been structurally evaluated. Using the latest comprehensive age/gender-specific BMI and obesity data, a global landscape estimating the risk/burden of OSA was created. Results were presented in relation to an in-depth analysis of OSA research and countries&rsquo, socioeconomic/scientific background. While the USA, Canada, and Japan are the highest publishing countries on OSA, Iceland, Greece, and Israel appeared at the forefront when relating the scientific output to socioeconomic parameters. Conversely, China, India, and Russia showed relatively low performances in these relations. Analysis of the estimated population at risk (EPR) of OSA showed the USA, China, India, and Brazil as the leading countries. Although the EPR and OSA research correlated strongly, major regional discrepancies between the estimated demand and actual research performances were identified, mainly in, but not limited to, developing nations. Our study highlights regional challenges/imbalances in the global activity on OSA and allows targeted measures to mitigate the burden of undiagnosed/untreated OSA. Furthermore, the inclusion of disadvantaged countries in international collaborations could stimulate local research efforts and provide valuable insights into the regional epidemiology of OSA.

Background Fabry disease (FD), the second most prevalent lysosomal storage disorder, is classified as a rare disease. It often leads to significant quality of life impairments and premature death. Many cases remain undiagnosed due to the rarity and heterogeneity. Further, costs related to treatment often constitute a substantial financial burden for patients and health systems. While its epidemiology is still unclear, newborn screenings suggest that its actual prevalence rate is significantly higher than previously suspected. Methods Based on well‐established methodologies, this study gives an overview about the background of the development of FD‐related research and provides a critical view of future needs. Results On the grounds of benchmarking findings, an increasing research activity on FD can be observed. Most publishing countries are the USA, some European countries, Japan, Taiwan, and South Korea. In general, high‐income countries publish comparably more on FD than low‐ or middle‐income economies. The countries' financial and infrastructural background are unveiled as crucial factors for the FD research activity. Conclusions Overall, there is a need to foster FD research infrastructure in developing and emerging countries with focus on cost‐intensive genetic research that is independent from economic interests of big pharmaceutical companies., In general, high‐income countries publish comparably more on Fabry disease (FD) than low‐ or middle‐income economies. The countries' financial‐ and infrastructural background as well as the presence of pharmaceutical companies are unveiled as crucial factors for the FD research activity. Therefore, our findings stress that collaborative efforts should be strengthened worldwide to facilitate a better understanding of FD in terms of epidemiological background, diagnosis, and treatment and to also develop standardized guidelines to improve patient outcomes.

BACKGROUND There is evidence that time spent in patient care in between patient visits is increasing and a contributor to physician burnout. The extent of this work on providers in the field of headache medicine is unknown. OBJECTIVES To establish whether headache outpatients require a high level of care in addition to clinic visits, based on the quantity of remote encounters per patient (phone calls and secure email communication to the clinics), in comparison to other neurologic clinics. METHODS In an academic referral clinic, a total of 3164 established patients were included in this retrospective analysis, 275 from the headache clinic, the remainder from various other neurology clinics (2 physician providers per clinic except 3 physician providers in the headache clinic). Patients presenting for a follow-up visit between January 2014 and April 2016 were observed for a 12-month period during which the number of a) telephone and b) secure email (MyChart) encounters per patient was recorded, and in addition, the number of entries related to each of these encounters. This analysis did not require IRB approval as per institutional guidelines. RESULTS Headache clinic patients required a high frequency of remote encounters (composite of both telephone and email messages) per patient, second only to the MS clinic patients. Use of secure email messaging (MyChart) per patient was much higher in the headache clinic compared to all other clinics. CONCLUSION Patients in a headache clinic in an academic tertiary care setting require a high intensity of remote outpatient care, more so than patients in other neurology subspecialty clinics and general neurology clinic, with the exception of the neuroimmunology/MS clinic. This is to a large extent secondary to the very frequent use of secure email linked to the electronic medical record by headache patients.

Introduction Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage. Method Thirty-one patients with CRC age ≤ 18 years and treated between 1990 and 2012 have been identified through the structures and registries of the German Society for Pediatric Oncology and Hematology. Results The age range was 9–18 years (median 13.5 years); the median follow-up time was 43.9 months (range 1–124 months). Twenty-six patients (84%) were tested for a genetic tumor syndrome (GTS); of these, 11 patients (35% of all patients) tested positive (eight cases of Lynch syndrome, one patient with familial adenomatous polyposis, two patients with constitutional mismatch repair deficiency). An unfavorable histology was reported in 55% of the records (n = 17), a poor differentiation (grade III) in 68% of carcinoma (n = 21). Overall survival (OS) and event-free survival at 5 years was 52.0% and 65.6%, respectively. Five-year survival according to stage was 100% in stage II (n = 2), 100% in stage III (n = 13), and 12.9% in stage IV (n = 15; P < 0.001). Five-year OS in patients with and without a defined GTS was 100% and 36.5% (P = 0.019), respectively. Conclusion Children and adolescents with CRC are frequently diagnosed in advanced stages and have an unfavorable prognosis. In this study, a high percentage of pediatric CRC patients presented with a tumor predisposition syndrome and showed an especially favorable OS.

A recent report from our group described that the (serotonin receptor-3)-antagonist ondansetron exhibits antiproliferative effects in the B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cell line REH. Furthermore, after each application of ondansetron to cultured REH cells, significant increases (+23%) in the concentration of nitric oxides (NO) were observed in the cell supernatants after 72 hours incubation in standard conditions, and this effect was found to correlate with the described antiproliferative activity. This feature was further confirmed by using mRNA dot blot hybridizations with a specific gene probe for the inducible NO-synthase (iNOS), yielding significant increases (+100%) of iNOS mRNA, which were found to widely correlate with the detected increases of NO release, and also with the previously described antiproliferative effects. The presented results are the first report on high specific pro-inflammatory features of a (serotonin receptor 3)-antagonist in a BCP-ALL cell line, which are associated with previously described antiproliferative properties.

Bei Menschen in Langzeitarbeitslosigkeit stehen einer erfolgreichen Arbeitsvermittlung oft gesundheitliche Einschrankungen im Wege. In einer quasi-experimentellen, kontrollierten Studie sollten die Effekte eines zielgruppenspezifischen Gesundheitskompetenztrainings, das individuelle Beratungsgesprache nach den Prinzipien des „Motivational Interviewing“ mit partizipativen Gruppenangeboten einschlieslich Bewegungseinheiten kombiniert, untersucht werden. Im Vergleich zur Kontrollgruppe (n = 108) konnten die Teilnehmer der Interventionsgruppe (n = 179) uber einen Zeitraum von drei Monaten verstarkt zu mehr Bewegung im Alltag und einer gesunden Ernahrung motiviert werden. Sie hatten signifikant haufiger eine Handlungsintention in diesen Bereichen entwickelt (Bewegung: Odds Ratio 4,44; 95%-KI: 2,00–9,83; Ernahrung: Odds Ratio 3,94; 95%-KI: 1,55–10,00) beziehungsweise hatten signifikant haufiger bereits eine Verhaltensanderung umgesetzt (Bewegung: Odds Ratio 2,77; 95%-KI: 1,35–5,71; Ernahrung: Odds Ratio 4,34; 95%-KI: 1,92–9,78). Fur Rauchen und Alkoholkonsum wurden keine Interventionseffekte gefunden. Die Ergebnisse belegen, dass das beschriebene Gesundheitskompetenztraining das Ernahrungs- und Bewegungsverhaltens effektiv verandern kann.

SummaryIntroduction: Desmopressin (DDAVP) testing (DT) in patients (pts) with haemophilia A (HA) and carriers (CHA) is up to now not standardized. This prompted us to evaluate results of DT carried out between 1996 and 2011 in centres of the Competence Network Haemor-rhagic Diatheses East. Patients and method: An increase of the factor VIII activity (FVIII) above 50% or at least the two fold of initial values within 120 min after DDAVP was defined as complete response (CR). Data from 80 patients (31 children, 49 adults) of whom 64 suffered from HA (sub-HA: n = 48; mild: n = 14; moderate: n = 2) and 16 patients CHA were evaluated. Results: In 34 patients DDAVP was given i. v. (dose range: 0.26–0.6 μg/kg body weight, mean: 0.33), in 31 intranasally (i.n. 300–600 μg) and in 15 s. c. (15–40 μg). The maximal FVIII increase was reached 60 min after DDAVP. For i. v. application the mean FVIII increase was 3.1-fold, for i. n. 2.1-fold and for s. c. 2.4-fold. A CR was de tected in 71 patients, a non-response in 9. Mild side effects such as flush, headaches or nausea were observed in 11 patients (14%). Conclusion: For desmopressin testing in patients with haemophilia A and carriers i. v. application at 0.3 μg/kg body weight and the determination of FVIII before and 60 min after desmopressin infusion is recommended.

Im Kindesalter handelt es sich bei ungefahr der Halfte aller malignen Erkrankungen um extra- und intrakraniale solide Tumoren. Letztere [ZNS-Tumoren (ZNS: Zentralnervensystem)] bilden die groste Gruppe, gefolgt von extrakranialen embryonalen Tumoren und Sarkomen. Die Erkennung charakteristischer Krankheitssymptome und Kenntnisse uber die Altersverteilung solider Tumoren im Kindesalter sowie eine umfassende pratherapeutische Diagnostik zur Stadieneinteilung und Klassifizierung stellen essenzielle Voraussetzungen fur die Wahl der geeigneten Therapie dar. Zytogenetik und Molekulargenetik erganzen die biologische Charakterisierung der malignen Erkrankung.

Hypoxia-inducible factor 1 (HIF-1) controls angiogenesis and glycolysis, two leading characteristics of solid tumor invasion, metastasis, and lethality. Increased angiogenesis is also found in the bone marrow (BM) of leukemias. Less is known in leukemia about the role of HIF-1 and vascular endothelial growth factor (VEGF), the most important proangiogenic target gene of HIF-1. We show by immunohistochemistry that the oxygen-regulated component of HIF-1 (HIF-1alpha) is overexpressed in clusters of leukemic cells in BM specimens of childhood acute lymphoblastic leukemia (ALL) and absent in biopsies of normal BM. Half the HIF-1alpha-positive ALL biopsies exhibited VEGF coexpression. Among 96 children with relapsed ALL, diagnostic BM aspirates with high VEGF mRNA levels were associated with a significantly lower probability of event-free survival at 3 years (0.31+/-0.08 vs 0.65+/-0.07, P=0.003). Those with poor molecular response to therapy (evaluated by MRD assessment) had 2.2-fold higher VEGF levels than those responding well to chemotherapy (P=0.005). In conclusion, the data demonstrate activation of the HIF pathway in the BM of ALL patients and indicate that the expression of HIF target genes, such as VEGF, play an important role in leukemia progression, therapy response, and outcome.

Die molekularen Untersuchungen von neoplastischen Erkrankungen im Kindesalter haben erheblich zur Entdeckung von neuen Genen und zu einem besseren Verstandnis der Tumorentstehung beigetragen. Bei keiner anderen malignen Erkrankung spielen die molekularen Erkenntnisse eine so bedeutende Rolle bzgl. Diagnostik, Prognose der Erkrankung sowie Steuerung und Uberwachung der Therapie. Zunehmend werden charakteristische genetische Veranderungen in neoplastischen Zellen gefunden, deren Kenntnis einerseits eine zuverlassigere Beurteilung der Heilungschancen des einzelnen Patienten ermoglicht, andererseits einen rationalen therapeutischen Ansatz birgt. Neue genetische Techniken wie die genomweiten Expressionsprofil-Analysen werden zukunftig zur Entwicklung von innovativen Medikamenten beitragen. Das Ziel ist die Intervention in die bei neoplastischen Zellen gestorten biologischen Prozesse.

Background. Long-term unemployment is associated with poorer mental health. The aim of this study was to evaluate the effectiveness of a health promotion program using the train-the-trainer approach on health-related quality of life (HRQoL) and mental health of long-term unemployed persons.Methods. A prospective parallel-group study was conducted among 365 long-term unemployed persons. 287 participants (179 members of the intervention group IG and 108 members of the control group) were reassessed after three months. The intervention comprised both individual sessions based on Motivational Interviewing and participatory group sessions; no health promotion program was administered in the control group. The endpoints were HRQoL (SF-12), depression, and anxiety. The effect size of the change across time in the IG and CG was measured by Cohen’sd. To assess the significance of group differences in the change across time, a random effects model was used.Results. Within three months HRQoL improved and anxiety and depression decreased significantly in the IG. A significant intervention effect was observed for anxiety (p= 0.012). Effect sizes in the IG were small to moderate in terms of Cohen’sd(anxiety:d=-0.33; SF-12 mental:d=0.31; depression:d=-0.25; SF-12 physical:d=0.19).Conclusions. The health promotion program, based on a train-the-trainer approach, showed positive effects on HRQoL and mental health, especially anxiety, of long-term unemployed persons, a highly burdened target group where an improvement in mental health is a crucial prerequisite to social participation and successful reintegration into the job market.

The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Munster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD

Neurocysticercosis is the most common parasitic infection of the brain. Endemic in many regions of the world, neurocysticercosis is now showing up in nonendemic areas such as Wisconsin. We present 3 patients that illustrate features typical for neurocysticercosis in anon-endemic area, including immigrant/travel status, presentation with focal seizures, classic magnetic resonance imaging features of single enhancing lesions, and good response to treatment with anticonvulsants, anti-inflammatory agents, and cysticidal drugs. It behooves physicians involved in the care of at-risk populations to be aware of the clinical features, radiographic signs, diagnostic tests, and general principles for treating neurocysticercosis.

The clinical heterogeneity among first relapses of childhood ETV6/RUNX1-positive acute lymphoblastic leukemia indicates that further genetic alterations in leukemic cells might affect the course of salvage therapy and be of prognostic relevance. To assess the incidence and prognostic relevance of additional copy number alterations at relapse of the disease, we performed whole genome array comparative genomic hybridization of leukemic cell DNA from 51 patients with first ETV6/RUNX1-positive relapse enrolled in and treated according to the relapse trials ALL-REZ of the Berlin-Frankfurt-Munster Study Group. Within this cohort of patients with relapsed ETV6/RUNX1-positive acute lymphoblastic leukemia, the largest analyzed for genome wide DNA copy number alterations to date, alterations were present in every ETV6/RUNX1-positive relapse and a high proportion of them occurred in recurrent overlapping chromosomal regions. Recurrent losses affected chromosomal regions 12p13, 6q21, 15q15.1, 9p21, 3p21, 5q and 3p14.2, whereas gains occurred in regions 21q22 and 12p. Loss of 12p13 including CDKN1B was associated with a shorter remission duration (P=0.009) and a lower probability of event-free survival (P=0.001). Distribution of X-chromosomal copy number alterations was gender-specific: whole X-chromosome loss occurred exclusively in females, gain of Xq only in males. Loss of the glucocorticoid receptor gene NR3C1 (5q31.3) was associated with a poor response to induction treatment (P=0.003), possibly accounting for the adverse prognosis of some of the ETV6/RUNX1-positive relapses.

The sequence of application of methotrexate and histone deacetylase inhibitors determines either a synergistic or an antagonistic response in childhood acute lymphoblastic leukemia cells

A pinhole grid spectrometer is used to measure the light emission from the plasma of the pulsed arc cluster ion source (PACIS). Spectra of various metals and carbon have been measured between 20 and 100 nm. In the case of carbon the average electron temperature is estimated to about 0.69 eV. Higher temperatures up to 0.79 eV are measured when inserting seeding gas which flushes the discharge volume with approx. one atmosphere of helium. An operation under this source conditions leads to the generation of an intense charged cluster beam. The application of the source as a bright light source in the VUV region is discussed.

A controlled trial to improve perceived health in a sample of long-term unemployed persons was conducted. As primary endpoint the SF12-questionnaire was used. The intervention was tailored to the specific needs of the long-term unemployed combining individual sessions based on motivational interviewing and group sessions designed with the participation of the participants. 365 participants were enrolled in the study. 287 or, respectively, 148 unemployed persons participated at the 3-months/12-months follow-up assessments. A positive effect of the intervention in the setting of long-term unemployed persons has been shown for perceived health, mental health and changes towards more physical activity and healthier nutrition.

Purpose Paediatric solid cancers such as osteosarcoma, Ewing s sarcoma, rhabdomyosarcoma and neuroblastoma are the most common cancers in children besides leukemia. These cancers have a poor prognosis, are highly metastatic and often resistant to current therapeutic approaches. Viscum album L. (mistletoe) is one of the most widely used complementary cancer therapies in Germany but little is known about its actual effects on paediatric solid cancers. Approved Viscum album L. extracts (VAE) basically contain water soluble compounds of the plant (lectins, viscotoxins). However, mistletoe also contains triterpene acids (mainly oleanolicand betulinic acid) that are water-insoluble. The antitumorigenic properties of these solubilized triterpene acids are the subject of ongoing research. The aim of this study is to determine the effects of different VAE containing either lectins (viscum), triterpene acids (TT) or a combination thereof (viscum TT) on solid tumor models in vitro and in vivo.

Purpose Aqueous Viscum album L. extracts (VAE) are widely used in complementary cancer therapies. Due to their low solubility, triterpene acids, which are known to possess anti-cancer properties, do not occur in aqueous extracts in significant amounts. Using cyclodextrins it was possible to solubilize mistletoe triterpene acids and to determine the anti-cancer properties in different acute lymphoblastic (ALL) and myeloid leukemia cell lines (AML). Methods The experimental extracts contain either mistletoe lectin-I and viscotoxins (viscum) or solubilized oleanolicand betulinic acids (TT) and more interestingly, a combination thereof (viscumTT). The cytotoxicity of increasing concentrations of VAE preparations was tested in NALM-6, U937 and HL-60 cells in vitro. Apoptosis was determined using mitochondrial membrane potential measurement, Annexin/PI, Western blot analysis and caspase assays. A C.B-17/SCID model of pre-B ALL/NALM-6 was used to test efficacy and mechanisms of treatment with lectin- and triterpenecontaining preparations in vivo. Results All three cell lines have shown distinct apoptosis induction for viscum, TT and viscumTT. However, differences between ALL and AML cell lines toward the lectin and triterpene acids sensitivity were observed. Annexin/PI and mitochondrial membrane potential assays indicated that dose-dependent induction of apoptosis was the main mechanism. The combination (viscumTT) of lectin- (viscum) and triterpene acidscontaining (TT) extracts showed the strongest apoptosis induction. Furthermore, caspase activity demonstrated that these extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways. The in vivo experiment showed that treatment of mice with the viscumTT combination prolonged the mean survival significantly compared control group. Conclusion

Among the long-term unemployed ill health is often a hindrance to successful reintegration in the job market. In a quasi-experimental controlled study we examined the effects of a health promotion intervention program tailored to the specific needs of the long-term unemployed combining individual sessions based on motivational interviewing and participatory group sessions including physical activity. Over a period of 3 months the participants of the intervention group (n = 179) showed more improvement compared to the control group (n = 108) in terms of motivation for lifestyle changes towards more physical activity and healthier nutrition. Participants of the intervention group developed an intention to act significantly more often (active lifestyle: odds ratio 4.44; 95% CI: 2.00-9.83; healthy nutrition: odds ratio 3.94; 95% CI: 1.55-10.00) and actually implemented a behavior change significantly more often (active lifestyle: odds ratio 2.77; 95% CI: 1.35-5.71; healthy nutrition: odds ratio 4.34; 95% CI: 1.92-9.78). In terms of smoking and alcohol consumption no significant intervention effects were detected. The results of the study show the effectiveness of the described health promotion program regarding a lifestyle change towards more healthy nutrition and more physical activity.

Background: In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. Objective: The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. Data sources and methods: Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. Results: We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.

The antimutagenic potencies of the juices of 28 fruits and 34 vegetables commonly consumed in Germany were investigated with respect to the mutagenic activities induced by 2-amino-3-methyl[4,5-f]-quinoline (IQ), and in part by 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) or 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in Salmonella typhimurium TA98 and TA100. With IQ, weak to strong antimutagenic activities were found in 68% of the fruits and 73% of the vegetables that were tested. In fruits, strong antimutagenic activities were detected in bananas, blackberries, blueberries, sweet and sour cherries, blackcurrants and redcurrants, pineapple and watermelon. Moderate antimutagenic activities were detected in greengage, kiwi, mangos, honeydew melons and plums. Weak antimutagenic activities were detected in apple, apricot, mirabelle, pears, peaches and strawberries, whereas white and red grapes and raspberries were inactive, and gooseberries and citrus fruits in general possessed marginal or no antimutagenic activities. In vegetables, strong to moderate antimutagenic activities were found for all cruciferous vegetables, except Chinese cabbage, which had only weak antimutagenic activity. Other vegetables with strong antimutagenic activities were beets, chives, horseradish, onions, rhubarb and spinach. Moderate antimutagenic activities were found with green beans and tomatoes, weak activities in eggplant, garden cress, many lettuces, leeks, mangold, cucumber, pumpkin, radish and summer squash. Asparagus, carrots, fennel leaves, parsley, green peppers and radishes were inactive. When fruit and vegetable juices were heated, a considerable reduction of antimutagenic potencies was seen with apple, apricot, kiwi, pineapple, beets, cabbage (Chinese, Savoy, red and white), cauliflower, leafy lettuce, cucumber, onions, radish and rhubarb. Antimutagenic factors in blackberries, blueberries, sweet and sour cherries, honeydew melons, mirabelle, plums, strawberries, Brussels sprouts, chicory greens, eggplant, garden cress, mangold, pumpkin, lamb's lettuce and spinach were, however, remarkably heat stable. Antimutagenic potencies in bananas, blackcurrants and redcurrants, greengages, gooseberries, mangos, watermelon, green beans, kohlrabi, horseradish, tomatoes and chives were partially reduced. Antimutagenic activities in the juices of eight apple cultivars were moderate in two, weak in four, and marginal or absent in two. No major differences, however, were detected in five batches of oranges and three batches each of grapefruits, asparagus, green beans, broccoli, cauliflower, spinach and tomatoes. No (or only minor) differences were seen between IQ, MeIQ and MeIQx and tester strains TA98 and TA100. Pineapple and celeriac juices inhibited the enzymatic system responsible for the activation of IQ, but had no desmutagenic activity. Peroxidase activity found to be present in broccoli, cauliflower, green beans and tomatoes may contribute to antimutagenic activities in these vegetables.

Treatment response and residual-disease monitoring in initial and relapsed TEL-AML1 positive childhood ALL

A calculation is presented for the phase-dependent dc current induced in a semiconductor superlattice by the simultaneous application of an ac field and its phase-shifted second harmonic. The dc current is a result of the Esaki–Tsu non-ohmicity of the superlattice for the case where it Bloch oscillates. The effect provides a tool for a determination of the relaxation time of the electrons.

In a retrospective collaborative study in children with an isolated extramedullary (IEM) relapse of acute lymphoblastic leukaemia, we demonstrated that bone marrow is involved at relapse diagnosis on submicroscopic level and this submicroscopic bone marrow involvement (SBI) revealed a prognostic impact. In a current prospective study in first IEM relapses treated according to the ALL-REZ BFM 2002 trial, SBI has been observed in 72% of patients. Therefore we have been interested, how are the reduction kinetics of SBI during treatment. We have quantified the SBI at relapse diagnosis and its reduction during therapy (MRD) using T-cell receptor/immunoglobulin gene rearrangements in 43 patients (28 central nervous system/10 testicular/5 other extramedullary relapses). 76% of patients who had a positive SBI at relapse diagnosis showed a negative MRD-result after induction. However, MRD reappeared or increased at later time points in 5 patients. These MRD reappearances/increases preceded a subsequent relapse in 3/5 patients. We have developed a common database to combine our data with prospective data of international collaboration partners for a sufficiently large statistical analysis. Deutsche Kinderkrebsstiftung, Bonn Madeleine-Schickedanz Kinderkrebsstiftung, Furth-Dambach

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.