"Fighting the system": Families caring for ventilator-dependent children and adults with complex health care needs at home

<p>Abstract</p> <p>Background</p> <p>An increasing number of individuals with complex health care needs now receive life-long and life-prolonging ventilatory support at home. Family members often take on the role of primary caregivers. The aim of this study was to explore the experiences of families giving advanced care to family members dependent on home mechanical ventilation.</p> <p>Methods</p> <p>Using qualitative research methods, a Grounded Theory influenced approach was used to explore the families' experiences. A total of 15 family members with 11 ventilator-dependent individuals (three children and eight adults) were recruited for 10 in-depth interviews.</p> <p>Results</p> <p>The core category, "fighting the system," became the central theme as family members were asked to describe their experiences. In addition, we identified three subcategories, "lack of competence and continuity", "being indispensable" and "worth fighting for". This study revealed no major differences in the families' experiences that were dependent on whether the ventilator-dependent individual was a child or an adult.</p> <p>Conclusions</p> <p>These findings show that there is a large gap between family members' expectations and what the community health care services are able to provide, even when almost unlimited resources are available. A number of measures are needed to reduce the burden on these family members and to make hospital care at home possible. In the future, the gap between what the health care can potentially provide and what they can provide in real life will rapidly increase. New proposals to limit the extremely costly provision of home mechanical ventilation in Norway will trigger new ethical dilemmas that should be studied further.</p

Cationic Poly-l-lysine Dendrimer Complexes Doxorubicin and Delays Tumor Growth in Vitro and in Vivo

We report in this study the complexation of the chemotherapeutic drug doxorubicin (DOX) with the novel sixth-generation cationic poly-l-lysine dendrimer (DM) (MW 8149 kDa), which we previously reported to exhibit systemic antiangiogenic activity in tumor-bearing mice. DOX–DM complexation was confirmed by florescence polarization measurement, proton nuclear magnetic resonance spectroscopy, and molecular modeling. Enhanced penetration of DOX–DM (at 1:10 molar ratio), compared to the free DOX, into prostate 3D multicellular tumor spheroids (MTS) was confirmed by confocal laser scanning microscopy. Furthermore, DOX–DM complexes achieved a significantly higher cytotoxicity in DU145 MTS system compared to the free drug, as shown by growth delay curves. Incubation of MTS with low DOX concentration (1 μM) complexed with DM led to a significant delay in MTS growth compared to untreated MTS or MTS treated with free DOX. DOX–DM complex retention was also achieved in a Calu-6 lung cancer xenograft model in tumor-bearing mice, as shown by live whole animal fluorescence imaging. Therapeutic experiments in B16F10 tumor bearing mice have shown enhanced therapeutic efficacy of DOX when complexed to DM. This study suggests that the cationic poly-l-lysine DM molecules studied here could, in addition to their systemic antiangiogenic property, complex chemotherapeutic drugs such as DOX and improve their accumulation and cytotoxicity into MTS and solid tumors in vivo. Such an approach offers new capabilities for the design of combinatory antiangiogenic/anticancer therapeutics.Peer reviewe

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate

A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [&lt;sup&gt;131&lt;/sup&gt;1]meta- iodobenzylguanidine ([&lt;sup&gt;131&lt;/sup&gt;1]MIBG), would restrict the effects of radiotherapy to malignant cells, thereby increasing efficacy and decreasing morbidity of radiotherapy. Prostate cancer cells were transfected with a transgene encoding the noradrenaline transporter (NAT) under the control of tumour-specific telomerase promoters, enabling them to actively take up [&lt;sup&gt;131&lt;/sup&gt;1]MIBG. This led to tumour-specific cell kill. This strategy has the advantage of generating a radiological bystander effect, leading to the destruction of neighbouring tumour cells that have escaped transfection. This targeted approach could be a promising tumour-specific treatment option for prostate cancer