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Biomedical subjects

E Schiller

Publications and source records attributed to E Schiller.

At least 19 recordsLinked to original sources
PubMed2001

Elevated DNA double strand breaks and apoptosis in the CNS of scid mutant mice.

Genetic approaches have provided evidence that DNA end-joining problems serve an essential role in neuronal survival during development of mammalian embryos. In the present study, we tested whether the DNA repair enzyme, DNA dependent protein kinase, plays an important role in the survival of cerebral cortical neurons in mice. DNA-PK is comprised of a DNA-binding subunit called Ku and a catalytic subunit called DNA-PKcs. In mice with the scid mutation, DNA-PKcs is truncated near the kinase domain, which causes loss of kinase activity. We compared the spatial and temporal aspects of neuronal cell death in scid versus isogenic wild-type embryos and found a significant increase in dying cells in scid mice, as assessed by nuclear changes, DNA fragmentation and caspase-3 activity. Additional biochemical and immunocytochemical studies indicated that of several DNA repair enzymes investigated, only PARP was increased in scid mice, possibly in response to elevated DNA strand breaks.

Animals↗
PubMed2001

Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment.

OBJECTIVES: To develop a categorical outcome measure related to clinical decisions and to perform secondary analyses to supplement the primary analyses of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA). METHOD: End-of-treatment status was summarized by averaging the parent and teacher ratings of attention-deficit/hyperactivity disorder and oppositional defiant disorder symptoms on the Swanson, Nolan, and Pelham, version IV (SNAP-IV) scale, and low symptom-severity ("Just a Little") on this continuous measure was set as a clinical cutoff to form a categorical outcome measure reflecting successful treatment. Three orthogonal comparisons of the treatment groups (combined treatment [Comb], medication management [MedMgt], behavioral treatment [Beh], and community comparison [CC]) evaluated hypotheses about the MTA medication algorithm ("Comb + MedMgt versus Beh + CC"), multimodality superiority ("Comb versus MedMgt"), and psychosocial substitution ("Beh versus CC"). RESULTS: The summary of SNAP-IV ratings across sources and domains increased the precision of measurement by 30%. The secondary analyses of group differences in success rates (Comb = 68%; MedMgt = 56%; Beh = 34%; CC = 25%) confirmed the large effect of the MTA medication algorithm and a smaller effect of multimodality superiority, which was now statistically significant (p < .05). The psychosocial substitution effect remained negligible and nonsignificant. CONCLUSION: These secondary analyses confirm the primary findings and clarify clinical decisions about the choice between multimodal and unimodal treatment with medication.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Psychosocial treatment strategies in the MTA study: rationale, methods, and critical issues in design and implementation.

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first multisite, cooperative agreement treatment study of children, and the largest psychiatric/psychological treatment trial ever conducted by the National Institute of Mental Health. It examines the effectiveness of Medication vs. Psychosocial treatment vs. their combination for treatment of ADHD and compares these experimental arms to each other and to routine community care. In a parallel group design, 579 (male and female) ADHD children, aged 7-9 years, 11 months, were randomly assigned to one of the four experimental arms, and then received 14 months of prescribed treatment (or community care) with periodic reassessments. After delineating the theoretical and empirical rationales for Psychosocial treatment of ADHD, we describe the MTA's Psychosocial Treatment strategy applied to all children in two of the four experimental arms (Psychosocial treatment alone; Combined treatment). Psychosocial treatment consisted of three major components: a Parent Training component, a two-part School Intervention component, and a child treatment component anchored in an intensive Summer Treatment Program. Components were selected based on evidence of treatment efficacy and because they address comprehensive symptom targets, settings, comorbidities, and functional domains. We delineate key conceptual and logistical issues faced by clinical researchers in design and implementation of Psychosocial research with examples of how these issues were addressed in the MTA study.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices.

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.

Attention Deficit Disorder with Hyperactivity↗
PubMed1996

Quantification of reactive oxygen species generated by alveolar macrophages using lucigenin-enhanced chemiluminescence--methodical aspects.

Alveolar macrophages lavaged from bovine lungs using Ca2(+)- and Mg2(+)-deprived saline containing EGTA for calcium chelation were cultivated in RPMI-1640 medium. The generation of reactive oxygen species (ROS) was assessed by determination of lucigenin-enhanced chemiluminescence (LUC-CL) using a LB 9505 C Biolumat. Monitoring of LUC-CL depends on various methodical parameters: besides medium constituents, the method of cell harvesting and the time-schedule of the protocol appear to be essential parameters that influence ROS-generation. In addition, the cell number (cell density) as well as the ratio of cell number to particle mass influence the amount of ROS-generation. Following exposure of cells to micronized quartz, we observed a dose-related increase in the generation of ROS.

Acridines↗
PubMed1994

[Dose intensified carboplatin monotherapy in advanced ovarian cancer].

Platinum derivatives are known as the most effective cytostatic agents in ovarian carcinoma. The steep dose-response curves described by Hryniuk and Levin [5] make them the ideal substances for dose escalation. We treated patients with advanced ovarian carcinoma with dose intensified carboplatinmonotherapy six times at AUC 5 (= +/- 400 mg/m2 in patients with normal renal function). Dose intensification was not done by increasing single doses, but by shortening the intervals between therapies (23, 21, 17, 14 days). In order to prevent leucopenia G-CSF was administered at a dose of 5 micrograms/kg s.c. Besides mild emesis no extramedullary toxicity especially no alopezia was documented. Up to an interval of 17 days therapy was safe; no thrombocytopenia < 49,000 x 10(6)/L and no leucopenia < 1000 x 10(6) was observed. With the intention to arrive at a 14-day interval and to attain further dose escalation we will treat future patients with a slightly reduced dose of carboplatin (AUC 4) in combination with escalating doses of cis-platinum, which is known for its low myelotoxicity.

Adult↗
PubMed1987

[Clinical value of determining C-reactive protein in the maternal serum in pregnancies with threatened premature labor].

In this article, because of the importance of subclinical infections for triggering premature labor, we have investigated the maternal serum levels of C-reactive protein (CRP) in 88 pregnancies with comparable gestational ages at the onset of premature birth symptoms. We found certain associations between possible prolongation of gestation by tocolysis and absence or presence of pathologic values of this acute-phase-protein. Positive CRP-values are associated with significantly lowered prolongation of pregnancy by tocolysis and subsequently lowered gestational age at birth. Though there are no correlations to maternal temperature and white blood cell counts, antenatal CTG-results, amniotic fluid properties and parameters of the neonate, we found probable relations to the detection of Ureaplasmas in the vaginal swabs. Once more we point out to possible associations between mycoplasmas and premature birth.

C-Reactive Protein↗
PubMed1985

Detection and separation of mitoxantrone and its metabolites in plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method using ion-pair chromatography on reversed-phase C18 material was developed. After sample clean-up on XAD columns, mitoxantrone at concentrations below 1 ng/ml in serum and 0.2 ng/ml in urine were measurable with a coefficient of variation of less than 9.3% at a wavelength of 658 nm. Four metabolites were separated in urine. The two major metabolites co-chromatographed with the synthesized mono- and dicarboxylic acid derivatives of mitoxantrone. The method allowed the measurement of mitoxantrone and its metabolites in serum up to more than one week and in urine up to four weeks after administration of the drug.

Anthraquinones↗
PubMed1985

The pharmacokinetics and metabolism of mitoxantrone in man.

An HPLC method using paired-ion chromatography on RP C-18 material was developed. After sample clean up on XAD columns, mitoxantrone (Novantrone; dihydroxyanthracenedione) in concentrations below 1 ng/ml in serum and 0.2 ng/ml in urine were measurable with a coefficient of variation less than 9.3% at a wavelength of 658 nm. Four metabolites were separated in urine. The major metabolite cochromatographed with the synthesized dicarboxylic acid of mitoxantrone. Within 48 hours 4.4% of the administered dose was excreted in urine as mitoxantrone, 0.5% as metabolite 1 and 0.3% as metabolite 2. The pharmacokinetic parameters are adequately described by a three-compartment model with a terminal half-life of 214.8 hours, and a volume of distribution (ss) of 3792 litres. The total body clearance was 358 ml/min and the renal clearance was 26.2 ml/min.

Anthraquinones↗
PubMed1976

Return to work after a myocardial infarction: evaluation of planned rehabilitation and of a predictive rating scale.

This paper reports the first recorded controlled trial of cardiac rehabilitation after myocardial infarction in men of working age, viewed as a team intervention effort to facilitate the patient's return to normal work. Our results show that this intervention is helpful in returning to jobs which they can handle successfully men who would otherwise be at risk of remaining unemployed. A previously developed rating scale for predicting return to work after myocardial infarction was used and reevaluated. Employment and occupational level at admission to hospital, work history, availability of the previous job, educational level, family and social stability, age at which regular cigarette smoking commenced, and level of anxiety and depression on a personality scale proved highly predictive.

Evaluation Studies as Topic↗
PubMed1976

[Chromatographic investigation of the substrate properties of 8-bromo-ATP in the nucleoside diphosphate kinase reaction (author's transl)].

8-bromo-ATP is a substrate of nucleoside diphosphate kinase. Its reactivity is similar to that of ATP, and the reaction appears to be unaffected by the different conformations of these two substrates. The nucleoside diphosphate kinase reaction with 8-bromo-ATP cannot be monitored photometrically (optical test) using an NADH/NAD+-dependent enzyme system, because the product 8-bromo-ADP is not a substrate for pyruvate kinase. Measurements of the nucleoside diphosphate kinase reaction with 8-bromo-ATP therefore, were carried out by chromatographic analysis of the nucleoside-triphosphate/diphosphate ratio.

Adenosine Triphosphate↗