53 research outputs found
Outcome from balloon induced coronary artery dissection after intracoronary beta radiation
OBJECTIVE: To evaluate the healing of balloon induced coronary artery
dissection in individuals who have received beta radiation treatment and
to propose a new intravascular ultrasound (IVUS) dissection score to
facilitate the comparison of dissection through time. DESIGN:
Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 31
patients with stable angina pectoris, enrolled in the beta energy
restenosis trial (BERT-1.5), were included. After excluding those who
underwent stent implantation, the evaluable population was 22 patients.
INTERVENTIONS: Balloon angioplasty and intracoronary radiation followed by
quantitative coronary angiography (QCA) and IVUS. Repeat QCA and IVUS were
performed at six month follow up. MAIN OUTCOME MEASURES: QCA and IVUS
evidence of healing of dissection. Dissection classification for
angiography was by the National Heart Lung Blood Institute scale. IVUS
proven dissection was defined as partial or complete. The following IVUS
defined characteristics of dissection were described in the affected
coronary segments: length, depth, arc circumference, presence of flap, and
dissection score. Dissection was defined as healed when all features of
dissection had resolved. The calculated dose of radiation received by the
dissected area in those with healed versus non-healed dissection was also
compared. RESULTS: Angiography (type A = 5, B = 7, C = 4) and IVUS proven
(partial = 12, complete = 4) dissections were seen in 16 patients
following intervention. At six month follow up, six and eight unhealed
dissections were seen by angiography (A = 2, B = 4) and IVUS (partial = 7,
complete = 1), respectively. The mean IVUS dissection score was 5.2 (range
3-8) following the procedure, and 4.6 (range 3-7) at follow up. No
correlation was found between the dose prescribed in the treated area and
the presence of unhealed disse
Presence and utility of electrocardiographic abnormalities in long-term childhood cancer survivors
Background: We assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors. Methods: In this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor Study part 2 and 272 siblings underwent a long-term follow-up ECG and echocardiography. We compared ECG abnormality prevalences using the Minnesota Code between survivors and siblings, and within biplane left ventricular ejection fraction (LVEF) categories. Among 880 survivors who received anthracycline, mitoxantrone or heart radiotherapy, logistic regression models using least absolute shrinkage and selection operator identified ECG abnormalities associated with three abnormal LVEF categories (<52% in male/<54% in female, <50% and <45%). We assessed the overall contribution of these ECG abnormalities to clinical regression models predicting abnormal LVEF, assuming an absence of systolic dysfunction with a <1% threshold probability. Results: 16% of survivors (52% female, mean age 34.7 years) and 14% of siblings had major ECG abnormalities. ECG abnormalities increased with decreasing LVEF. Integrating selected ECG data into the baseline model significantly improved prediction of sex-specific abnormal LVEF (c-statistic 0.66 vs 0.71), LVEF <50% (0.66 vs 0.76) and LVEF <45% (0.80 vs 0.86). While no survivor met the preset probability threshold in the first two models, the third model used five ECG variables to predict LVEF <45% and was applicable for ruling out (sensitivity 93%, specificity 56%, negative predictive value 99.6%). Calibration and internal validation tests performed well. Conclusion: A clinical prediction model with ECG data (left bundle branch block, left atrial enlargement, left heart axis, Cornell's criteria for left ventricular hypertrophy and heart rate) may aid in ruling out LVEF <45%.</p
Presence and utility of electrocardiographic abnormalities in long-term childhood cancer survivors
Background: We assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors. Methods: In this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor Study part 2 and 272 siblings underwent a long-term follow-up ECG and echocardiography. We compared ECG abnormality prevalences using the Minnesota Code between survivors and siblings, and within biplane left ventricular ejection fraction (LVEF) categories. Among 880 survivors who received anthracycline, mitoxantrone or heart radiotherapy, logistic regression models using least absolute shrinkage and selection operator identified ECG abnormalities associated with three abnormal LVEF categories (<52% in male/<54% in female, <50% and <45%). We assessed the overall contribution of these ECG abnormalities to clinical regression models predicting abnormal LVEF, assuming an absence of systolic dysfunction with a <1% threshold probability. Results: 16% of survivors (52% female, mean age 34.7 years) and 14% of siblings had major ECG abnormalities. ECG abnormalities increased with decreasing LVEF. Integrating selected ECG data into the baseline model significantly improved prediction of sex-specific abnormal LVEF (c-statistic 0.66 vs 0.71), LVEF <50% (0.66 vs 0.76) and LVEF <45% (0.80 vs 0.86). While no survivor met the preset probability threshold in the first two models, the third model used five ECG variables to predict LVEF <45% and was applicable for ruling out (sensitivity 93%, specificity 56%, negative predictive value 99.6%). Calibration and internal validation tests performed well. Conclusion: A clinical prediction model with ECG data (left bundle branch block, left atrial enlargement, left heart axis, Cornell's criteria for left ventricular hypertrophy and heart rate) may aid in ruling out LVEF <45%.</p
Gene Expression Responses Linked to Reproduction Effect Concentrations (EC10,20,50,90) of Dimethoate, Atrazine and Carbendazim, in Enchytraeus albidus
BACKGROUND: Molecular mechanisms of response to pesticides are scarce and information on such responses from soil invertebrates is almost inexistent. Enchytraeus albidus (Oligochaeta) is a standard soil ecotoxicology model species for which effects of many pesticides are known on survival, reproduction and avoidance behaviour. With the recent microarray development additional information can be retrieved on the molecular effects. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed to investigate the transcription responses of E. albidus when exposed to three pesticides - dimethoate (insecticide), atrazine (herbicide) and carbendazim (fungicide) - in a range of concentrations that inhibited reproduction by 10%, 20%, 50% and 90% (EC(10), EC(20), EC(50) and EC(90), respectively). The goal of this study was to further identify key biological processes affected by each compound and if dose-related. All three pesticides significantly affected biological processes like translation, regulation of the cell cycle or general response to stress. Intracellular signalling and microtubule-based movement were affected by dimethoate and carbendazim whereas atrazine affected lipid and steroid metabolism (also by dimethoate) or carbohydrate metabolism (also by carbendazim). Response to DNA damage/DNA repair was exclusively affected by carbendazim. CONCLUSIONS: Changes in gene expression were significantly altered after 2 days of exposure in a dose-related manner. The mechanisms of response were comparable with the ones for mammals, suggesting across species conserved modes of action. The present results indicate the potential of using gene expression in risk assessment and the advantage as early markers
Enchytraeus albidus Microarray: Enrichment, Design, Annotation and Database (EnchyBASE)
Enchytraeus albidus (Oligochaeta) is an ecologically relevant species used as standard test organisms for risk assessment. Effects of stressors in this species are commonly determined at the population level using reproduction and survival as endpoints. The assessment of transcriptomic responses can be very useful e.g. to understand underlying mechanisms of toxicity with gene expression fingerprinting. In the present paper the following is being addressed: 1) development of suppressive subtractive hybridization (SSH) libraries enriched for differentially expressed genes after metal and pesticide exposures; 2) sequencing and characterization of all generated cDNA inserts; 3) development of a publicly available genomic database on E. albidus. A total of 2100 Expressed Sequence Tags (ESTs) were isolated, sequenced and assembled into 1124 clusters (947 singletons and 177 contigs). From these sequences, 41% matched known proteins in GenBank (BLASTX, e-value≤10-5) and 37% had at least one Gene Ontology (GO) term assigned. In total, 5.5% of the sequences were assigned to a metabolic pathway, based on KEGG. With this new sequencing information, an Agilent custom oligonucleotide microarray was designed, representing a potential tool for transcriptomic studies. EnchyBASE (http://bioinformatics.ua.pt/enchybase/) was developed as a web freely available database containing genomic information on E. albidus and will be further extended in the near future for other enchytraeid species. The database so far includes all ESTs generated for E. albidus from three cDNA libraries. This information can be downloaded and applied in functional genomics and transcription studies
Gene transcription and higher-level effects of multigenerational Zn exposure in Daphnia magna
A biology-based approach for mixture toxicity of multiple endpoints over the life cycle
The use of biomarkers in Daphnia magna toxicity testing, I: the digestive physiology of daphnids exposed to toxic stress
We investigated the effect of short-term exposure to cadmium and 2,3-dichlorophenoxy acetic acid on the digestive physiology of Daphnia magna and the consequences for the bioenergetics of the organism. In both cases, ingestion was more drastically reduced compared to digestive enzyme activity. Furthermore a differential shift in catabolism was noted: in general polysaccharidases were less affected than the enzymes responsible for protein and lipid digestion. Comparison of the '1 h in vivo fluorescence' criterion (Janssen gr Persoone, 1993) with the ingestion and digestive enzyme activity revealed that this rapid screening assay should be considered as a quantification of ingestion inhibition rather than a methodology assessing digestive enzyme inhibition
A multivariate biomarker-based model predicting population-level responses of Daphnia magna
A multivariate model is proposed relating short-term biomarker measurements, in Daphnia magna to chronic effects (21-d exposure) occurring at the population level (time to death, mean brood size, mean total young per female, intrinsic rate of natural increase, net reproductive rate, and growth). The results of the short-term exposure (48h-96 h) to eight model toxicants (cadmium. chromium, mercury, tributyl tin, linear alkylsulfonic acid, sodium pentachlorophenolate, lindane. and 2,4-dichlorophenoxyacetic acid) on the following biomarkers were used for the multivariate model: digestive enzymes (amylase, cellulase, beta-galactosidase, trypsin, and esterase), enzymes of the intermediary metabolism (glycogen phosphorylase, glucose-6-phosphate dehydrogenase, pyruvate kinase, lactate dehydrogenase, and isocitrate dehydrogenase), cellular energy allocation (CEA) (protein, carbohydrate. and lipid content and electron transport activity), and DNA damage and antioxidative stress activity. Using partial least squares to latent structures (PLS), a two-component model was obtained with R-2 of 0.68 and a Q(2) value of 0. 30 based on the combined analysis of a limited number of the 48- and 96-h biomarker responses. For the individual population-level responses, the R-2 values varied from 0.66 to 0.77 and the Q(2) values from 0.52 to 0.69. Energy-related biomarkers (cellular energy allocation, lipid contents, anaerobic metabolic activity-pyruvate kinase, and lactate dehydrogenase), combined with parameters related to oxidative stress (catalase) and DNA damage measured after 48 and 96 h of exposure, were able to predict long-term effects at higher levels of biological organization
The use of biomarkers in Daphnia magna toxicity testing, IV: cellular energy allocation: a new methodology to assess the energy budget of toxicant-stressed Daphnia populations
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