Search

Folates are essential for cell survival and are required for numerous biochemical processes. The human alpha isoform folate receptor (alphahFR) has a very high affinity for folic acid and is considered an essential component in the cellular accumulation of folates and folate analogues used in chemotherapy. The expression of alphahFR is not detected inmost normal tissues. In contrast, high levels of the expression of alphahFR have been reported in a variety of cancer cells. The significance of alphahFR overexpression in malignant tissues has not been elucidated, but it is possible that it promotes cell proliferation not only by mediating folate uptake but also by generating other regulatory signals. The purpose of the present study was to evaluate alphahFR as a potential target for the treatment of breast cancer. Initial studies were done in nasopharyngeal carcinoma (KB) cells, which express high levels of alphahFR. In KB cells, antisense oligodeoxyribonucleotides (ODN) complementary to the alphahFR gene sequences were found to reduce newly synthesized alphahFR protein up to 60%. To examine the effect of alphahFR antisense ODNs in a panel of cultured human breast cancer cell lines, we used a tumor cell-targeted, transferrin-liposome-mediated delivery system. The data show that alphahFR antisense ODNs induced a dose-dependent decrease in cell survival. Finally, we determined that alphahFR antisense ODNs sensitized MDA-MB-435 breast cancer cells by 5-fold to treatment with doxorubicin. The data support the application of alphahFR antisense ODNs as a potential anticancer agent in combination with doxorubicin.

Background: Investigating older acutely ill hospitalized patients' nursing needs and quality of care is paramount, given the growing pressure on nurses to provide increasingly intensive levels of care to a growing older population while at the same time working with reduced staffing levels., Aims: The aims of this study were to determine: (1) important aspects of nursing care as perceived by older patients, their family member/carer who observed care during hospitalization, and nurses; (2) satisfaction levels of patients, family/carers and nurses on nursing care received; and (3) mismatches between nursing care priorities and satisfaction with nursing care., Methods: Two hundred and thirty-two acutely ill patients aged over 65 years, 99 carers/family members and 90 nurses completed the Caregiving Activities Survey, which measures importance of and satisfaction with various aspects of nursing care. Qualitative data, which qualified responses to survey items, were also obtained from participants., Results: Patients, carers and nurses perceived that carrying out doctors' orders was the most important aspect of nursing care, followed by physical care, psychosocial care and discharge planning. Nurses and carers rated physical care, psychosocial care and discharge planning more highly than patients. Physical care was rated highly by patients in terms of importance, but rated moderately in terms of satisfaction. Carers' and patients' ratings of satisfaction with physical care were lower than nurses' ratings of opportunities to provide it. The importance of discharge planning was rated highly by nurses but all groups were only moderately satisfied with this aspect of care., Study Limitations: The findings do not apply to acutely ill older patients with confusion, mental illness or more than early stage dementia., Conclusions: Patients, nurses and family/carers were generally in agreement about the relative importance of particular aspects of nursing care. Nurses may need to communicate more effectively with older patients and their family carers about the particular roles they will play during the patient's hospital episode, the expectations they have of patients in the process of healing and recovery, and the reasons for the actions they take in aiding this process. The findings are useful in making nurses more aware of the expectations and needs of older hospital patients and their carers. They provide evidence for developing both new models of nursing care for this patient group, and nursing education programmes.

The older population is the largest consumer of health care, yet little is known about their nursing needs during acute hospitalization. In undertaking a study to address this issue, the researchers faced many challenges that were related to the complexities of researching acutely ill hospitalized older patients. The purpose of the present discussion paper is to present some of the methodological and pragmatic factors that were encountered so that health professionals and researchers can be aware of the potential obstacles when researching this important area, and plan research accordingly. Potential barriers included the complexity of illness in the older person as a result of comorbidity and iatrogenesis; fatigue; normal age-related processes such as visual/hearing impairment; frequent ward transfer or early discharge; delirium or dementia; and high staff turnover resulting in difficulties in coordinating the study. This paper raises the importance of balancing the need to maximize the rigor of research and the needs of participants. Recommendations for future research are made.

Existing HER-2 targeted therapies for human head and neck cancers, usually administered in combination with chemotherapeutic drugs or irradiation, include monoclonal antibodies to HER-2, receptor tyrosine kinase inhibitors and HER-2 specific immunotoxins. Instead of targeting the existing protein, interference with HER-2 mRNA translation by antisense oligonucleotides may be a more efficient method to downregulate levels of HER-2 protein for combination therapy. To test this hypothesis we have used a phosphorothioate pentadecamer, complementary to the HER-2 mRNA initiation codon region (AS HER-2 ODN), to increase sensitivity to four chemotherapeutic agents in human head and neck cancer cell lines, all of which express low levels of the HER-2 protein. To improve delivery into tumor cells, the AS HER-2 ODN was complexed with our previously established folate-liposome delivery system. Cell survival assays and Western blot analysis data demonstrated that folate-liposome mediated AS HER-2 oligonucleotide treatment inhibited cell growth and HER-2 expression, and induced apoptosis in SCC-25CP cells. Moreover, there was a synergistic effect on the percent of apoptotic cells. Additionally, the combination of folate-liposome-AS HER-2 ODN and CDDP had a synergistic effect on the induction of apoptosis. Using confocal microscopy, FITC labeled ODN (FITC-ODN) in complex with folate-liganded, rhodamine (Rh) labeled, cationic liposomes was observed to enter SCC-25CP head and neck tumor cells within 3 to 6 h. Intracellularly, the FITC-ODN separated from the Rh-folate-liposomes, and FITC-ODN accumulated in the nucleus while Rh-liposomes remained in punctate cytoplasmic structures. Thus, folate-liposome-mediated delivery of AS HER-2 ODN has potential as a new means of increasing the responsiveness of head and neck cancer to conventional chemotherapy.

The proportion of older adults is increasing in Australia, and the proportion of older adults requiring medical care is expected to increase in the future. At the same time, budget restrictions are a reality for Australia's health system. Increasing need and decreasing resources suggest the need to focus on the quality aspect of treatment and care for older adults. Little research has been conducted in the area of perceived nursing needs of elderly patients during hospitalization. This is an important area of research because it is increasingly recognized that elderly patients have specialized needs and are the major consumers of health care. Even less research has compared patient and carer perceptions with those of nursing staff. This article is a literature review and an investigation of the quality of care elderly patients receive, and of patient and nurse perceptions of the importance of various nursing activities. Quality of care is reviewed in terms of perceptions of nursing care priorities and elderly patients' satisfaction with the quality of nursing care they receive. Research examining nurses' perceptions related to why they are unable to consistently provide quality nursing care to all elderly patients is also reviewed. By identifying the nursing needs of elderly patients and educating nursing staff about these needs, professional practice can be guided and improvements in quality of care, patient satisfaction, and patient outcomes may occur.

The first few months of nursing have the potential to be the most challenging and stressful for new nursing graduates. The purpose of the present study was to examine sources of, and changes in, role stress 2-3 months after employment, and 11-12 months later in new graduate nurses. This study also investigated the relationship between job satisfaction and role stress. A factor analysis demonstrated that role ambiguity was the most salient feature of role stress in the first few months, while 10 months later, role overload was the most important factor explaining variance in role stress scores. There was no significant change in role stress scores over time. For the first survey, job satisfaction was significantly negatively correlated with role ambiguity and role stress. In the second survey there was still a significant negative correlation between role ambiguity and job satisfaction, but no significant correlation between role overload and job satisfaction. The findings are discussed in terms of implications for nursing education, practice and future research.

This article reports on a study designed to determine whether demographic characteristics of patients such as age, gender and cultural background were associated with different perceptions of the importance of and satisfaction with various aspects of nursing care. In addition, patients, their family/carer and nurses from wards specializing in aged care were compared with general medical wards to determine if there were differences in these perceptions. Results demonstrated that patients who were older (aged > 80 years), female and from aged care wards perceived that physical aspects of nursing care were more important than did patients who were younger (aged 65-80 years), male and from medical wards. Older patients and those from aged care wards were more satisfied with physical care. Nurses need to be aware of these differences and focus on physical aspects of care to ensure patient satisfaction better health outcomes.

At a time of ever increasing mental health problems in Australian society, the nursing profession is beset by problems of an insufficient workforce specialising in this area. Not only is there a shortage of suitable trained specialist mental health nurses, but undergraduate nursing programs inadequately prepare students for practical mental health nursing. Fewer students are enrolling in mental health nursing, and many nurses are leaving the workforce. A particular problem in rural Australia is that there is a lack of specialist mental health services, and nurses are being increasingly relied upon to perform the role of mental health nurse despite lacking the necessary qualifications and experience.This paper aims to describe the development, implementation and evaluation of a mental health continuing education program for nurses employed in rural and remote areas of New South Wales (NSW), Australia. This was a collaborative educational initiative mounted by the NSW Health Department (who funded the project), a rural university and a number of regional health service partners. The paper includes information on how this program was conceived, developed and conducted through distance education mode. It also evaluates the efficacy of this program as perceived by 202 out of 303 participants. Overall the project was rated very favourably, and represents a cost-effective, convenient method of enabling rural and regional nurses to update and improve their skills in mental health nursing.

Background: The burden of illness associated with Coronary Heart Disease (CHD) has determined this as a key focus for research at a basic science, individual and population level. Although considerable research has been conducted on specific aspects of the experience of CHD, such as anxiety or depression, there is a lack of research investigating the global aspects of the illness experience from the individual's perspective. Furthermore, there is a paucity of research examining the cross-cultural experiences of patients from Non-English Speaking Backgrounds (NESB). Given the multicultural nature of Australian society, and that health and illness are culturally constructed experiences (Manderson 1990), it is important to include the perspectives of people from minority cultures in health related research in order to provide culturally sensitive and appropriate health care and information during an illness. Further, the potential to prevent and modulate the course of CHD, by strategies such as smoking cessation and lipid management, mandate a health promotion agenda based on equity and access for all members of society., Aims: This article discusses cultural aspects of CHD in relation to nursing and allied health care during the recovery phase of an acute cardiac event. It reviews the research that has been conducted in this area, focusing on the Chinese-Australian population., Literature Search: The CINAHL, MEDLINE, FAMILY (Australian Family and Society Abstracts Database), PsychINFO, and Multicultural Australian and immigration Studies (MAIS) databases were searched, identifying literature published from 1982. Keywords used were Chin* (Chinese, China), Asia* (Asia, Asian), experience, adjustment, psychological, heart, coronary, cardiac, health and services. Reports not written in English were excluded. Australian Government reports were also searched, as well as hand searching of nursing and medical textbooks. These searches resulted in over 1000 articles. However, only around 50 were relevant for this review., Implications: Chinese-Australians are one of the fastest growing populations in Australia, and are at increased risk of CHD upon settling to Australia. Recommendations for future research and for the practice of nursing are provided.

An ideal therapeutic for cancer would be one that selectively targets to tumor cells, is nontoxic to normal cells, and that could be systemically delivered, thereby reaching metastases as well as primary tumor. Immunoliposomes directed by monoclonal antibody or its fragments are promising vehicles for tumor-targeted drug delivery. However, there is currently very limited data on gene delivery using these vehicles. We have recently described a cationic immunoliposome system directed by a lipid-tagged, single-chain antibody Fv fragment (scFv) against the human transferrin receptor (TfR) that shows promising efficacy for systemic p53 tumor suppressor gene therapy in a human breast cancer metastasis model. However, the extremely low yield of this lipid-tagged scFv limited further downstream development and studies. Here we report a different expression strategy for the anti-TfR scFv, which produces high levels of protein without any tags, and a different approach for complexing the targeting scFv to the liposomes. This approach entails covalently conjugating the scFv to the liposome via a cysteine at the 3'-end of the protein and a maleimide group on the liposome. Our results show that this conjugation does not impair the immunological activity or targeting ability of the scFv. The scFv-cys targets the cationic liposome-DNA complex (lipoplex) to tumor cells and enhances the transfection efficiencies both in vitro and in vivo in a variety of human tumor models. This scFv-immunoliposome can deliver the complexed gene systemically to tumors in vivo, where it is efficiently expressed. In comparison with the whole antibody or transferrin molecule itself, the scFv has a much smaller size for better penetration into solid tumors. It is also a recombinant protein rather than a blood product; thus, large scale production and strict quality control are feasible. This new approach provides a promising system for tumor-targeted gene delivery that may have potential for systemic gene therapy of various human cancers.