Faculty Bibliography

PURPOSE/OBJECTIVES: To apply the Hanahan and Weinberg conceptual framework for tumor development to the specific biomarkers observed or expressed in ovarian cancer. DATA SOURCES: Data-based publications, topical reviews, and book chapters. DATA SYNTHESIS: Articles specific to ovarian cancer were reviewed to examine whether the six rules from the Hanahan and Weinberg conceptual framework were applicable to biomarkers of ovarian cancer. This approach allows for the application of a general framework for the development of solid tumors to the development of ovarian cancer. CONCLUSIONS: The six rules for tumor cell development outlined in the Hanahan and Weinberg conceptual framework are applicable to biomarkers expressed or observed in patients with ovarian cancer. IMPLICATIONS FOR NURSING: Oncology nurses can enhance their clinical teaching by integrating this information into their practice. Nurses who conduct research on ovarian cancer can use this framework to guide the selection of biomarker(s) for these studies. Finally, nurse educators can use this framework when teaching students key concepts in the care of patients with cancer.

PURPOSE: The purpose of this pilot study was to examine arachidonate 5-lipoxygenase (ALOX5) and ALOX5-activating protein (ALOX5AP) gene variations in patients with and without acute coronary syndrome (ACS). METHODOLOGY: Four and six single nucleotide polymorphisms spanning the ALOX5 and ALOX5AP genes, respectively, were genotyped in 19 non-Hispanic Caucasian patients with ACS and 27 controls. RESULTS: Presence of the common allele of rs9508835 (ALOX5AP) and the minor allele of rs2029253 (ALOX5) were associated with ACS. After adjustment for age, being a carrier of the rs9508835 common allele was associated with an increased risk of ACS (odds ratio = 2.86). RELEVANCE FOR NURSING PRACTICE: Through the inhibition of the ALOX5AP gene by downregulation of the leukotriene pathway, the risk of ACS may be decreased in individuals that carry susceptibility allele(s). Knowledge of the genetic basis of treatments that downregulate the leukotriene pathway may prove essential to the care of individuals with ACS.

PURPOSE: In a sample of family caregivers (FCs) of patients with prostate cancer who were to begin radiation therapy (RT), the purposes were to determine the prevalence and severity of depression, anxiety, pain, sleep disturbance, and fatigue; determine the relationships among these symptoms and between these symptoms and functional status and quality of life (QOL); evaluate for differences in functional status and QOL between FCs with low and high levels of these symptoms; and determine which factors predicted FCs' functional status and QOL. PATIENTS AND METHODS: FCs were recruited before patients initiated RT and completed self-report questionnaires that evaluated demographic characteristics, symptoms, functional status, and QOL. RESULTS: Sixty female FCs participated in the study. On the basis of established cut point scores for each symptom questionnaire, 12.2% of the FCs had clinically meaningful levels of depression, 40.7% anxiety, 15.0% pain, 36.7% sleep disturbance, 33.3% morning fatigue, and 30.0% evening fatigue. FCs who were older and who had lower levels of state anxiety and higher levels of depression, morning fatigue, and pain reported significantly poorer functional status (R(2) = 38.7%). FCs who were younger, had more years of education, were working, and who had higher levels of depression, morning fatigue, sleep disturbance, and lower levels of evening fatigue reported significantly lower QOL scores (R(2) = 70.1%). CONCLUSION: A high percentage of FCs experienced clinically meaningful levels of a variety of symptoms. These symptoms have a negative impact on the FCs' functional status and QOL.

The aims of this replication study were to determine if subgroups of oncology outpatients receiving active treatment could be identified based on their experience with the symptoms of fatigue, sleep disturbance, depression, and pain; whether patients in these subgroups differed on selected demographic, disease, and treatment characteristics; and if patients in these subgroups differed on functional status and quality of life (QOL). A convenience sample of 228 oncology outpatients was recruited from seven outpatient settings in Israel. Patients completed a demographic questionnaire, a Karnofsky Performance Status score, the Multidimensional Quality of Life Scale-Cancer, the Lee Fatigue Scale, the General Sleep Disturbance Scale, the Center for Epidemiological Studies-Depression Scale, and a numeric rating scale of worst pain intensity. Cluster analysis was used to identify the patient subgroups based on their symptom experience. Four relatively distinct patient subgroups were identified based on their experiences with the above symptoms (i.e., low levels of all four symptoms (32.9%), low levels of pain and high levels of fatigue (18.0%), high levels of pain and moderate levels of fatigue (42.5%), and high levels of all four symptoms (6.6%). No differences were found among the four subgroups on any demographic, disease, or treatment characteristics. The subgroup of patients who reported high levels of all four symptoms reported the worst functional status and poorest QOL. In conclusion, differences in the symptom experience of oncology outpatients suggest that patients may harbor different phenotypic characteristics (e.g., environmental or physiologic) or genetic determinants for experiencing symptoms that are independent of demographic, disease, and treatment characteristics.

Hypertriglyceridemia is a hallmark of many disorders, including metabolic syndrome, diabetes, atherosclerosis and obesity. A well-known cause is the deficiency of lipoprotein lipase (LPL), a key enzyme in plasma triglyceride hydrolysis. Mice carrying the combined lipase deficiency (cld) mutation show severe hypertriglyceridemia owing to a decrease in the activity of LPL and a related enzyme, hepatic lipase (HL), caused by impaired maturation of nascent LPL and hepatic lipase polypeptides in the endoplasmic reticulum (ER). Here we identify the gene containing the cld mutation as Tmem112 and rename it Lmf1 (Lipase maturation factor 1). Lmf1 encodes a transmembrane protein with an evolutionarily conserved domain of unknown function that localizes to the ER. A human subject homozygous for a deleterious mutation in LMF1 also shows combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders. Thus, through its profound effect on lipase activity, LMF1 emerges as an important candidate gene in hypertriglyceridemia.

Although the concept of the coagulation cascade represented a significant advance in the understanding of coagulation and served for many years as a useful model, more recent clinical and experimental observations demonstrate that the cascade/waterfall hypothesis does not fully and completely reflect the events of hemostasis in vivo. The goal of this article is to review the evolution of the theories of coagulation and their proposed models to serve as a tool when reviewing the research and practice literature that was published in the context of these different theories over time.

OBJECTIVES: To examine symptom clusters in oncology patients; to determine if these symptom clusters might share a common biologic mechanism; and to describe potential biologic mechanisms that warrant investigation. DATA SOURCES: Synthesis of the theoretical and research papers on symptom clusters. CONCLUSION: Definitive conclusions about whether there is a biologic basis for the clustering of symptoms cannot be determined at this time. The animal model of sickness behavior holds promise as a potential biologic mechanism for clustering symptoms. IMPLICATIONS FOR NURSING PRACTICE: Until more definitive studies of symptom clusters are performed, clinicians need to monitor patients for the co-occurrence of multiple symptoms and develop appropriate management plans.

The majority of the research on the various aspects of symptom management has focused on individual symptoms. However, patients with cancer often experience multiple symptoms simultaneously as a result of their disease and treatment. In 2001, symptom management researchers began to study the impact of symptom clusters on patient outcomes. Over the past 6 years, a number of conceptual reviews as well as several research studies have been published on symptom clusters in oncology patients. This paper summarizes the conceptual basis for symptom cluster research, describes two conceptual approaches to symptom cluster research, and discusses the implications of symptom clusters for quality-of-life research. The paper concludes with an enumeration of the critical considerations that need to be addressed if this area of scientific inquiry is to move forward.

The most common form of von Willebrand disease (VWD) is reported to be type 1, accounting for as much as 80% of reported cases. With prevalence estimates as high as 1.6% in the general population, upwards of 4.5 million Americans may be affected. Unfortunately, VWD type 1 is also the most difficult type to diagnose. Despite the continuing progress in defining the genetic lesions responsible for VWD types 2 and 3, identification of the genetic determinants of VWD type 1 remains elusive. Herein the phenomenon known as VWD is summarized, the challenges associated with the diagnosis of type 1 VWD are described, and the role of genetic research in meeting these challenges is explored. The authors identify key gaps in the current genetics literature and suggest new avenues for future research. Lastly, they explore the role of nurses in this research and clinical endeavor. To the authors'knowledge, this review is the first to address these complex issues in nursing research.