Heterogeneous response of disseminated human ovarian cancers to cytostatics in vitro

Cell suspensions from nine human ovarian primary cancers, their metastases and ascitic cells were treated in vitro with amethopterin and melphalan. Effects were measured by incorporation of H3-TdR or H3-UdR into the cells. There was significant heterogeneity of cytostatic effects on cells from the three sources in a given patient. Ascitic cells did nt represent a "mean" of the cancer cell clones. The implications of these findings should be considered if cytostatic in vitro prediction tests are used to guide cytostatic treatment of patients.     

Häufigkeit und kleinräumige Variabilität von Operationen

On the basis of the claims data of the statutory health insurance funds, surgery rates and small-area variations within the catchment area of the AOK Magdeburg were examined for the year 1997. Substantial variation can be constantly seen. The extremal quotient at the 30 most frequent ICPM groups ranged from 2 to 5. Generally, the extent of the variation was larger with elective procedures than with acute. Correlation analyses do not show clear associations with hospital bed supply and physician density in primary sectors. The extent of the small-area variation requires further research to evaluate possible determinants of surgery rates. Criteria for hospital admission and indications for surgery should be made explicit.     

Regulation of p53R2 and its role as potential target for cancer therapy

p53R2, a recently discovered small subunit of human ribonucleotide reductase, is believed to play essential roles in DNA repair, mtDNA synthesis, and protection against oxidative stress. Because of the positive correlation between the level of this protein and drug sensitivity and tumor invasiveness, it constitutes a potential target for anticancer drugs as well as a diagnostic marker in cancer.     

Evidence-based medication and revascularization: powerful tools in the management of patients with diabetes and coronary artery disease: a report from the Euro Heart Survey on diabetes and the heart

BACKGROUND: Patients with diabetes mellitus (DM) and coronary artery disease (CAD) have a poor prognosis. Underutilization and reduced efficacy of evidence-based medications (EBM) or revascularization are among suggested explanations. This report compares the impact of EBM and revascularization on mortality and cardiovascular events (CVE=mortality, myocardial infarction or stroke) in CAD patients with and without DM. DESIGN: Between February 2003 and January 2004 the Euro Heart Survey on Diabetes and the Heart recruited patients with CAD at 110 centers in 25 European countries. The patients were followed with respect to one-year CVE. METHODS: The study population included a total of 3488 patients: 2063 (59%) in the non-DM and 1425 (41%) in the DM group. EBM was defined as the combined use of renin-angiotensin-aldosterone system inhibitors, beta blockers, antiplatelets and statins while revascularization comprised thrombolysis, percutaneous coronary intervention or coronary artery bypass grafting. RESULTS: Of the eligible patients, 44% with DM and 43% of those without DM received EBM, while 34 and 40% were revascularized. In patients with DM both EBM (0.37, 95% confidence interval (CI), 0.20-0.67, P=0.001) and revascularization (0.72, 95% CI, 0.39-1.32, P=0.275) had an independent protective effect as regards one-year mortality and as regards CVE (0.61, 95% CI, 0.40-0.91, P=0.015 and 0.61, 95% CI, 0.39-0.95, P=0.025, respectively) in patients with DM compared with the impact of these two approaches in those without DM. CONCLUSION: The systematic use of EBM and revascularization has a highly rewarding, favorable impact on one-year prognosis of DM patients with CAD.     

New p53-based anti-cancer therapeutic strategies

Thep53 gene is frequently mutated in human tumours and therefore an important target for therapeutic intervention. Several p53-based strategies for treatment of cancer are currently under development.p53 gene therapy has resulted in tumour regression in patients with lung cancer. A mutant adenovirus can obliterate tumour cells carrying mutant p53 or lacking p53, but is unable to replicate in normal cells. Furthermore, current studies suggest that reactivation of mutant p53 proteins in tumours using small p53-activating molecules may initiate p53-dependent apoptosis and thus eliminate the tumour.     

Strong interference of hemoglobin concentration on CSF total protein measurement using the trichloroacetic acid precipitation method.

BACKGROUND: Among other methods, trichloroacetic acid precipitation is used to quantify total protein in cerebrospinal fluid (CSF). METHODS: We analyzed the influence of hemoglobin on total protein concentration assayed by the trichloroacetic acid method and compared the results to the benzethonium chloride method. RESULTS: Four CSF samples were spiked with different amounts of hemoglobin, leading to overestimation of protein concentration when assayed by the trichloroacetic acid method. Using the benzethonium chloride method, measurement of protein concentration was minimally disturbed. In addition, albumin and total protein concentrations were measured in 135 clinical samples. The total protein/albumin ratio remained constant when protein was measured with the benzethonium chloride method, while ratios increased when protein was assayed by the trichloroacetic acid method. CONCLUSIONS: Strong interference by hemoglobin leads to overestimation of the total protein concentration in CSF when assayed by the trichloroacetic acid method and may lead to false conclusions when evaluating the blood-brain barrier.     

Systematic review of organisation‐wide,trauma‐informed care models in out‐of‐home care (OoHC) settings

Trauma in early childhood has been shown to adversely affect children's social, emotional, and physical development. Children living in out‐of‐home care (OoHC) have better outcomes when care providers are present for children, physically, psychologically, and emotionally. Unfortunately, the high turnover of out‐of‐home carers, due to vicarious trauma (frequently resulting in burnout and exhaustion) can result in a child's trauma being re‐enacted during their placement in OoHC. Organisation‐wide therapeutic care models (encompassing the whole organisation, from the CEO to all workers including administration staff) that are trauma‐informed have been developed to respond to the complex issues of abuse and neglect experienced by children who have been placed in OoHC. These models incorporate a range of therapeutic techniques, and provide an overarching approach and common language that is employed across all levels of the organisation. The aim of this study was to investigate the current empirical evidence for organisation‐wide, trauma‐informed therapeutic care models in OoHC. A systematic review searching leading databases was conducted for evidence of organisation‐wide, trauma‐informed, out‐of‐home care studies, between 2002 and 2017. Seven articles were identified covering three organisational models. Three of the articles assessed the Attachment Regulation and Competency framework (ARC), one study assessed the Children and Residential Experiences programme (CARE), and three studies assessed The Sanctuary Model. Risk of bias was high in six of the seven studies. Only limited information was provided on the effectiveness of the models identified through this systematic review, although the evidence did suggest that trauma‐informed care models may have significantly positive outcomes for children in OoHC. Future research should focus on evaluating components of trauma‐informed care models and assessing the efficacy of the various organisational care models currently available.     

Active video gaming improves body coordination in survivors of childhood brain tumours

Purpose: We investigated whether active video gaming (AVG) could bring about regular, enjoyable, physical exercise in children treated for brain tumours, what level of physical activity could be reached and if the children’s physical functioning improved.

Methods: Thirteen children, aged 7–17 years, were randomised to either AVG or waiting-list. After 10–12 weeks they crossed-over. Weekly Internet coaching sessions were used to sustain motivation and evaluate enjoyment. Energy expenditure (EE) levels were measured as Metabolic Equivalent of Task (MET), using a multisensory activity monitor. Single-blinded assessments of physical functioning were done, using the Bruininks–Osteretsky Test of Motor Performance, second edition, evaluating participants before and after the intervention period, as well as comparing the randomisation groups after the first period.

Results: All patients completed the study. AVG sessions (mean duration 47?minutes) were performed on 72% of all days. Mean EE level during AVG sessions was 3.0 MET, corresponding to moderate physical activity. The Body Coordination score improved by 15% (p?=?0.021) over the intervention period.

Conclusions: In this group of childhood brain tumour survivors, home-based AVG, supported by a coach, was a feasible, enjoyable and moderately intense form of exercise that improved Body Coordination.

• Implications for Rehabilitation

• Childhood brain tumour survivors frequently have cognitive problems, inferior physical functioning and are less physically active compared to their healthy peers.

• Active video gaming (AVG), supported by Internet coaching, is a feasible home-based intervention in children treated for brain tumours, promoting enjoyable, regular physical exercise of moderate intensity.

• In this pilot study, AVG with Nintendo Wii improved Body Coordination.

     

The growth hormone secretagogue hexarelin increases cell proliferation in neurogenic regions of the mouse hippocampus

ObjectiveRadiation therapy (RT) to the brain is often used in the treatment of children with different types of malignant diseases affecting the brain. However, RT in childhood may also have severe side effects including impaired brain maturation and intellectual development. For childhood cancer survivors these adverse effects of RT can cause lifelong disability and suffering. Therefore, there is an unmet need to limit late effects after RT. Precursor cells in the subgranular zone of the dentate gyrus (DG) in the hippocampus are particularly sensitive to irradiation (IR). This may be of significance as newly generated neurons in the DG are important for memory and learning. GH secretagogues (GHS) have previously been shown to promote neurogenesis and to have neuroprotective effects. In addition, several parts of the brain, including the hippocampus, have been shown to express the GHS receptor 1a (GHS-R1a). The aim of this study was to evaluate the potential effect of the GHS hexarelin on proliferation and survival of progenitor cells in the hippocampus after brain IR in a mouse model.DesignIn the present study, 10-day-old male mice received 6 Gy cranial IR. Non-irradiated sham animals were used as controls. We treated one group of irradiated and one sham group with hexarelin (100 μg/kg/day) for 28 days and used immunohistochemical labeling of bromo-deoxy uridine (BrdU) and phospho-histone H3 of the granular cell layer of the DG to evaluate proliferation and cell survival after IR at postnatal day ten.ResultsOur results show that hexarelin significantly increased the number of BrdU-positive cells in the granule cell layer by approximately 50% compared to controls.ConclusionThe increased number of BrdU-positive cells in the granule cell layer suggests a partial restoration in the pool of proliferating cells by hexarelin after IR.     

Quantitative effects of diet on fecal corticosterone metabolites in two strains of laboratory mice

The analysis of glucocorticoids excreted in feces is becoming a widespread technique for determining animal wellbeing in a wide variety of settings. In the present study an extraction protocol and an ELISA assay for quantifying fecal corticosterone metabolites (FCM) in BALB/c and C57bl/6 mice were validated. Lower ratios of solvent (ethanol) to mass of fecal sample were found to be sufficient in extracting FCM compared to what has been reported previously. Feeding mice a high energy diet, high in fat content (60% of calories from fat), significantly lowered the FCM excretion, approximately halving the FCM output. This diet also reduced the fecal mass voided to approximately a third of that of the regular diet. The two reductions were not correlated. A difference in defecation pattern was seen between the two strains, with the BALB/c mice having a more pronounced diurnal rhythm compared to the C57bl/6 mice. Furthermore, throughout the experiment, the C57bl/6 mice excreted significantly higher levels of FCM compared to the BALB/c mice. The mice were also challenged with synthetic adrenocorticotropic hormone (ACTH) and dexamethasone (DEX). The effect of the challenges could readily be detected, but had a considerably lesser impact on data than did the difference in diet. The study demonstrates some problematic consequences of expressing FCM excretion as a measure of fecal dry mass. The study also serves to emphasize the caution that must be exercised when interpreting FCM excretion in conjunction with an uncontrolled or varied diet, or perturbations of gastro-intestinal functioning.