The choices, choosing model of quality of life: clinical evaluation and intervention.

Two previous papers presented a conjectured model of quality of life featuring the personal management of accessing choices and choosing among them (the c-c process). Those papers made the case that this model unifies the pathways leading to impaired quality of life, especially with regard to age associated multiple co-morbidities, changes in perception and functioning, and the effects of long term care environments; it also introduces a science base for understanding and guiding interventions that can assist people to achieve their quality-of-life goals. Our aim in this paper is to outline interprofessional strategies that could relieve restrictions or distortions of the c-c process imposed by aging, ill-health, or a restricting environment. We do so by outlining potential deficits in the c-c process and matching these with restorative person-centered interprofessional interventions including interprofessional teamwork. Findings suggest that interprofessional assessment and team work is well suited to assisting the c-c process. We conclude that the groundwork has been prepared for developing training programs and clinical trials for interprofessional interventions targeting the c-c process.

The choices, choosing model of quality of life: linkages to a science base.

BACKGROUND: A previous paper began with a critical review of current models and measures of quality of life and then proposed criteria for judging the relative merits of alternative models: preference was given to finding a model with explicit mechanisms, linkages to a science base, a means of identifying deficits amenable to rational restorative interventions, and with embedded values of the whole person. A conjectured model, based on the processes of accessing choices and choosing among them, matched the proposed criteria. The choices and choosing (c-c) process is an evolved adaptive mechanism dedicated to the pursuit of quality of life, driven by specific biological and psychological systems, and influenced also by social and environmental forces. OBJECTIVE: In this paper the c-c model is examined for its potential to strengthen the science base for the field of quality of life and thus to unify many approaches to concept and measurement. CONCLUSIONS: A third paper in this set will lay out a guide to applying the c-c model in evaluating impairments of quality of life and will tie this evaluation to corresponding interventions aimed at relieving restrictions or distortions of the c-c process; thus helping people to preserve and improve their quality of life. The fourth paper will demonstrate empirical analyses of the relationship between health imposed restrictions of options for living and conventional indicators of diminished quality of life.

The choices, choosing model of quality of life: description and rationale.

AIM: This introductory paper offers a critical review of current models and measures of quality of life, and describes a choices and choosing (c-c) process as a new model of quality of life. METHOD: Criteria are proposed for judging the relative merits of models of quality of life with preference being given to explicit mechanisms, linkages to a science base, a means of identifying deficits amenable to rational restorative interventions, and with embedded values of the whole person. RESULT: A conjectured model, based on the processes of gaining access to choices and choosing among them, matches the proposed criteria. The c-c process is an evolved adaptive mechanism dedicated to the pursuit of quality of life, driven by specific biological and psychological systems, and influenced by social and environmental forces. CONCLUSIONS: This model strengthens the science base for the field of quality of life, unifies approaches to concept and measurement, and guides the evaluation of impairments of quality of life. Corresponding interventions can be aimed at relieving restrictions or distortions of the c-c process; thus helping people to preserve and improve their quality of life. RELATED WORK: Companion papers detail relevant aspects of the science base, present methods of identifying deficits and distortions of the c-c model so as to open opportunities for rational restorative interventions, and explore empirical analyses of the relationship between health imposed restrictions of c-c and conventional indicators of diminished quality of life. [corrected]

Gene therapy of ovarian cancer with IFN-alpha-producing fibroblasts: comparison of constitutive and inducible vectors.

Ovarian cancer represents a malignancy suitable for cell and gene therapy approaches owing to its containment within the peritoneal cavity, even at advanced tumor stages. As regulation of transgene expression would be preferable for conducting clinical trials for reasons of safety, we investigated whether intraperitoneal (i.p.) administration of retroviral vector-transduced fibroblasts encoding murine interferon-alpha (IFN-alpha) could have therapeutic activity, and compared its effect with the antitumor effects of fibroblasts producing IFN-alpha under a rapamycin analogue (AP21967)-inducible promoter. Human and murine fibroblasts were recruited into the solid component of transplantable ovarian cancer-grown i.p. in severe combined immunodeficiency mice. Multiple administrations of fibroblasts producing IFN-alpha in a constitutive manner showed therapeutic efficacy, leading to significant prolongation of survival in the majority of animals, associated with inhibition of tumor angiogenesis. Compared to cells transduced by the constitutive vector, fibroblasts transduced by the inducible vector released twofold higher IFN-alpha levels in vitro, following induction by AP21967, and production of the cytokine was under pharmacologic control both in vitro and in vivo. However, these cells elicited only modest therapeutic effects in vivo. Overall, these findings indicate that intracavitary IFN-alpha gene therapy using engineered fibroblasts requires sustained production of IFN-alpha to achieve durable antitumor effects.

Comparison between cachaça and rum using pattern recognition methods.

The differentiation between cachaça and rum using analytical data referred to alcohols (methanol, propanol, isobutanol, and isopentanol), acetaldehyde, ethyl acetate, organic acids (octanoic acid, decanoic acid, and dodecanoic acid), metals (Al, Ca, Co, Cu, Cr, Fe, Mg, Mn, Ni, Na, and Zn), and polyphenols (protocatechuic acid, sinapaldehyde, syringaldehyde, ellagic acid, syringic acid, gallic acid, (-)-epicatechin, vanillic acid, vanillin, p-coumaric acid, coniferaldehyde, coniferyl alcohol, kaempferol, and quercetin) is described. The organic and metal analyte contents were determined in 18 cachaça and 21 rum samples using chromatographic methods (GC-MS, GC-FID, and HPLC-UV-vis) and inductively coupled plasma atomic emission spectrometry, respectively. The analytical data of the above compounds, when treated by principal component analysis, hierarchical cluster analysis, discriminant analysis, and K-nearest neighbor analysis, provide a very good discrimination between the two classes of beverages.

Differential effects of angiostatin, endostatin and interferon-alpha(1) gene transfer on in vivo growth of human breast cancer cells.

The administration of different angiogenesis inhibitors by gene transfer has been shown to result in inhibition of tumor growth in animal tumor models, but the potency of these genes has been only partially evaluated in comparative studies to date. To identify the most effective anti-angiogenic molecule for delivery by retroviral vectors, we investigated the effects of angiostatin, endostatin and interferon(IFN)-alpha(1) gene transfer in in vivo models of breast cancer induced neovascularization and tumor growth. Moloney leukemia virus-based retroviral vectors for expression of murine angiostatin, endostatin and IFN-alpha(1) were generated, characterized, and used to transduce human breast cancer cell lines (MCF7 and MDA-MB435). Secretion of the recombinant proteins was confirmed by biological and Western blotting assays. Their production did not impair in vitro growth of these breast cancer cells nor their viability, and did not interfere with the expression of angiogenic factors. However, primary endothelial cell proliferation and migration in vitro were inhibited by supernatants of the transduced cells containing angiostatin, endostatin, and IFN-alpha(1). Stable gene transfer of the IFN-alpha(1) cDNA by retroviral vectors in both MCF7 and MDA-MB435 cells resulted in a marked and long-lasting inhibition of tumor growth in nude mice that was associated with reduced vascularization. Endostatin reduced the in vivo growth of MDA-MB435, but not MCF7 cells, despite similar levels of in vivo production, and angiostatin did not impair the in vivo growth of either cell line. These findings indicate heterogeneity in the therapeutic efficacy of angiostatic molecules delivered by viral vectors and suggest that gene therapy with IFN-alpha(1) and endostatin might be useful for treatment of breast cancer.

Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes.

In this paper we addressed the expression of the HIV co-receptors CXCR-4 and CCR-5 in human thymocytes by phenotypic, molecular and functional approaches. Cytofluorimetric analysis disclosed that CXCR-4 was constitutively expressed by freshly isolated thymocytes (~10 000 molecules/cell in about 30% of thymocytes); the receptor was endowed with functional activity, as it mediated polarization, migration and intracellular Ca2+ increase in response to its ligand, SDF-1. On the contrary, CCR-5 expression in freshly isolated thymocytes was significantly lower (<4000 molecules/cell in less than 5% of the cells), and no functional response to CCR-5 agonists could be documented. Northern blot analysis of freshly isolated thymocytes showed high CXCR-4 mRNA levels, whereas the message for CCR-5 was barely detectable. On the other hand, a modest increase in the expression of CCR-5 was associated with in vitro thymocyte stimulation, and CCR-5 density at the cell surface attained CXCR-4 figures in most cases. None the less, no functional response to CCR-5 agonists could be documented in in vitro stimulated thymocytes. In vitro infection of thymocytes by CAT-expressing recombinant HIV bearing the envelope glycoproteins from different isolates showed that T-tropic strains, which use CXCR-4 as a co-receptor, were more efficient in infecting thymocytes than M-tropic strains, which preferentially use CCR-5. Altogether, these data indicate that expression of the major co-receptors involved in infection by M-tropic HIV strains is very poor in human thymocytes, and would suggest that thymocyte infection by M-tropic HIV strains may be a rare event in vivo.