Toxicological profiling of sediments using in vitro bioassays, with emphasis on endocrine disruption

In vitro bioassays are valuable tools for screening environmental samples for the presence of bioactive (e.g., endocrine-disrupting) compounds. They can be used to direct chemical analysis of active compounds in toxicity identification and evaluation (TIE) approaches. In the present study, five in vitro bioassays were used to profile toxic potencies in sediments, with emphasis on endocrine disruption. Nonpolar total and acid-treated stable extracts of sediments from 15 locations in the Rhine Meuse estuary area in The Netherlands were assessed. Dioxin-like and estrogenic activities (using dioxin-responsive chemical-activated luciferase gene expression [DR-CALUX] and estrogen-responsive chemical-activated luciferase gene expression [ER-CALUX] assays) as well as genotoxicity (UMU test) and nonspecific toxic potency (Vibrio fischeri assay) were observed in sediment extracts. For the first time, to our knowledge, in vitro displacement of thyroid hormone thyroxine (T4) from the thyroid hormone transport protein thransthyretin by sediment extracts was observed, indicating the presence of compounds potentially able to disrupt T4 plasma transport processes. Antiestrogenic activity was also observed in sediment. The present study showed the occurrence of endocrine-disrupting potencies in sediments from the Dutch delta and the suitability of the ER- and DR-CALUX bioassays to direct endocrine-disruption TIE studies.     

Self‐care in Preserving the Vascular Network: Old Problem,New Challenge for the Medical Staff

Teaching/educating patients with end stage renal disease (ESRD) and identifying their self‐care behaviors for vascular network preservation are very important. However, the self‐care behaviors regularly performed by patients are still unknown. We compared self‐care behaviors for vascular network preservation performed by patients who are/are not followed‐up by the nephrologist. The study design was a prospective, observational and comparative study. Inclusion criteria were as follows: ESRD patients (at stages 4 or 5); at least 18 years old; in pre‐dialysis with at least a 6‐month follow‐up period by the nephrologist or who started dialysis in emergency and were not followed‐up by the nephrologist; with no memory problems; and medically stable. Primary outcome was the frequency of self‐care behaviors for vascular network preservation. Secondary outcome was the comparison between self‐care behaviors by ESRD patients who were/were not followed‐up by the nephrologist. The study involved 145 patients, 64.1% were female, the mean age was 69.5 years and the self‐care behaviors mean score was 36.8% (with a SD of 39.8%). The number of patients followed‐up and not followed‐up by the nephrologist was 109 (group 1) and 36 (group 2), respectively. Social characteristics were similar in the two groups (P > 0.05). The mean self‐care behaviors were 29.4% and 59.2% in groups 1 and 2, respectively (P = 0.000). Patients performed self‐care behaviors for vascular network preservation with a relatively low frequency (the mean score was 36.8% only). Patients not followed by the nephrologist performed self‐care behaviors more often than those who were followed (59.2% vs. 29.4% respectively, P = 0.000).     

De novo “pure” partial trisomy (6)(p22.1→pter) in a chromosome 15 with an enlarged satellite,identified by microdissection

We report on a newborn boy with a congenital heart defect, severe pre‐ and postnatal growth retardation, feeding problems, facial anomalies and unilateral hydronephrosis. Cytogenetic analysis showed extra chromosomal material on the short arm of one chromosome 15 that at first sight could be mistaken for a chromosomal variant and could not be identified with conventional banding techniques. Chromosome analysis of the parents showed that both had a normal karyotype. Microdissection of five copies of the aberrant chromosome 15, amplification of the dissected chromosomal material by DOP‐PCR and subsequent reverse painting was performed and disclosed that the patient had a de novo 46,XY,der(15)(6pter→6p22.1::15p12→15qter) karyotype with a “pure” trisomy of chromosome region 6p22.1→6pter. The associated phenotypic anomalies are compared with other reported cases with a distal duplication of chromosome 6p. © Wiley‐Liss. Inc.     

The effect of paracetamol, fentanyl, and systematic assessments on children's pain after tonsillectomy and adenoidectomy

Various clinical protocols are used to manage early postoperative tonsillectomy and/or adenoidectomy (T&A) pain in children. Although believed to be effective, these protocols are not evidenced-based. Therefore, a double-blind, randomized, placebo controlled (2 x 2) factorial design was used (1) to evaluate the effectiveness of 2 pain protocols used interchangeably to manage early postoperative T&A pain and (2) to investigate whether nurses' systematic pain assessments improve pain management. In the first protocol children receive a loading dose (30 to 50 mg/kg) of paracetamol (acetaminophen) Formularium der Nederlandse Apothekers (Formulary of the Dutch Royal Society for the Advancement of Pharmacy) intraoperatively, followed by regular doses (70 to 100 mg/kg/24 hours) of paracetamol. In the second protocol children receive the first protocol, plus intramuscular fentanyl citrate (1 microgram/kg) intraoperatively. Subjects were 83 healthy children between the ages of 3 and 12 years, admitted for T&A as an outpatient procedure. The child's pain was measured using observation scales (Children's Hospital of Eastern Ontario Pain Scale and Face Legs Activity Cry Consolability Scale), a visual analogue scale, and self-report measures (Faces Pain Scale and Oucher). Neither pain protocol sufficiently relieved early postoperative T&A pain, and systemic pain assessments did not improve the effectiveness of analgesics. Further research evaluating the effectiveness of pain management protocols is needed.     

Characterization of a de novo unbalanced translocation t(14q18q) using microdissection and fluorescence in situ hybridization

We report on a patient with a de novo translocation between the long arms of chromosomes 14 and 18. The translocation was studied using microdissection in combination with fluorescence in situ hybridization (micro-FISH). Five copies of the chromosomes involved in the translocation were isolated by microdissection and amplified by means of degenerate oligonucleotide primed-polymerase chain reaction (DOP-PCR). Reverse chromosome painting with the biotin-labeled PCR product showed that part of the q-arm of chromosome 18 had no signal. The deletion was characterized further by FISH with band-specific probes and it was concluded that the rearrangement was unbalanced: 46,XY,t(14;18)(14pter→4q22::18q21.1→18qter)(18pter→18q12.2::14q22→14qter). The patient, who presented with psychomotor retardation, mild obesity, pes equinovarus, strabismus, and facial anomalies, is compared with previously reported patients with an interstitial deletion of band 18q12. Am. J. Med. Genet. 75:409-413, 1998. © 1998 Wiley-Liss, Inc.     

'Mind and Body': a lifestyle programme for people on antipsychotic medication

Rationale  Psychiatric illnesses such as schizophrenia and their treatments have consequences in terms of lifestyle, diet and weight.
Aims and objectives  'Mind and Body' is a 10-week programme of weekly sessions aimed to improve the health status of people treated with second generation antipsychotic medications.
Methods  The programme focuses on a range of lifestyle strategies including diet and exercise and was conducted at a Community Health Centre by professionally qualified staff. Between 2002 and 2006, 50 participants enrolled in, and 30 completed the programme. Measures of body weight, health status (Short Form-36) and blood markets (plasma glucose, haemoglobin A1c and lipid profile) were collected at commencement and completion of the programme.
Results  A modest improvement was demonstrated in mean values for the majority of measures collected.
Conclusions  A lifestyle program for people treated with antipsychotic medications is achievable and may be worthwhile although gains may be modest.     

Upregulation of B50/GAP-43 protein mRNA in rat dorsal root ganglia during cisplatin intoxication

Expression of the growth-associated protein B50 (GAP-43) mRNA in dorsal root ganglia (DRG) of rats was studied by in situ hybridization. In response to treatment with the neurotoxic agent cisplatin, B50 mRNA expression was significantly enhanced following a cumulative cisplatin dose of 14 mg/kg. In the untreated age-matched control animals, only half of the ganglion cells exhibited expression of B50 mRNA (mean hybridization signal, 10 times background), whereas at a cumulative cisplatin dose of 14 mg cisplatin every neuron exhibited well above background expression (mean hybridization signal, 34 times background). Cotreatment with a neuroprotective ACTH_4–9 analog known to prevent cisplatin neuropathy in rats did not affect the overall expression of B50 mRNA. However, in the subpopulation of large sensory neurons, B50 mRNA content was significantly higher in the group cotreated with the ACTH_4–9 analog as compared with the saline-cotreated group after 14 mg/kg of cisplatin. We conclude that in analogy with the well-known upregulation of B50 mRNA following mechanical nerve lesions, treatment with the neurotoxic drug cisplatin also leads to an increase in B50 mRNA expression. This observation lends strength to the hypothesis that in neuropathies an imbalance between regenerative and degenerative mechanisms exists. The ability of the larger sensory neurons to retain an increased B50 mRNA expression better after cotreatment with the peptide than without may be related to stimulation of regenerative processes by this ACTH_4–9 analog. © 1996 Wiley-Liss, Inc.     

Design of the DIRECT-project: interventions to increase job resources and recovery opportunities to improve job-related health,well-being,and performance outcomes in nursing homes

Background  

Because of high demands at work, nurses are at high risk for occupational burnout and physical complaints. The presence of job resources (such as job autonomy or social support) and recovery opportunities could counteract the adverse effect of high job demands. However, it is still unclear how job resources and recovery opportunities can be translated into effective workplace interventions aiming to improve employee health, well-being, and performance-related outcomes. The aim of the current research project is developing and implementing interventions to optimize job resources and recovery opportunities, which may lead to improved health, well-being and performance of nurses.