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PubMed2005

Use and development of clinical pathways by registered nurses in an acute paediatric setting.

Clinical pathways are widely regarded as providing valuable knowledge about specific types of patients and their care, as well as providing direct guidance in clinical practice. In Australia, the use of care pathways has occurred with seemingly minimal professional nursing debate as to their benefits in practice. Comments supporting the introduction of pathways into clinical practice have focused on assistance to decision making, facilitation of clinical judgements about care, assistance in improving practice and utility as educational tools, particularly for new staff, new graduates and casual employees. A survey of 259 nurses working in an acute paediatric setting sought to gain their views about pathways of care with regard to satisfaction with use, content of pathway, ability to use in practice, effect on practice and commitment to use. While the most positive findings to emerge from the research indicated that nurses liked clinical pathways because they saved time and reduced documentation requirements, issues were also raised about the need for a broader, more inclusive development process for pathways, and an improved education program for staff use. The implications to arise from these findings are important for senior staff and educators who are responsible for staff orientation programs and ongoing staff development as well as for those responsible for the development and implementation of clinical pathways into practice.

Attitude of Health Personnel↗
PubMed2003

Regulation of inducible heparanase gene transcription in activated T cells by early growth response 1.

Cleavage of heparan sulfate by the beta-D-endoglucuronidase heparanase (HPSE) is a fundamental event in a number of important physiological processes including inflammation, wound healing, and angiogenesis. HPSE activity has also been directly correlated with pathological conditions such as tumor growth and metastasis and autoimmune disease. The tight regulation of HPSE expression and function is critical to ensure homeostasis of the normal physiological processes to which it contributes and to prevent imbalance toward pathological situations. Little is known about the transcriptional mechanisms that regulate HPSE expression. In this study we have shown human HPSE gene transcription in Jurkat T cells is induced upon activation. Functional analysis of the HPSE promoter has identified a 280-bp region that is highly inducible. Mutation studies together with supershift experiments have identified a 4-bp motif that binds the transcription factor early growth response-1 (Egr1) and is critical in regulating inducible HPSE gene transcription. Furthermore, the overexpression of Egr1 resulted in the enhanced activation of the HPSE promoter. By using MAPK pathway inhibitors, we have also shown that inducible expression of HPSE mRNA and the activity of the 280-bp HPSE promoter element are dependent on the ERK1/2 (MEK1/2) pathway. This pathway is critical for induction of Egr1 expression at both the mRNA and protein level in T cells, an observation that provides further support to Egr1 playing an important role as a key activator of HPSE expression. In addition, HPSE and Egr1 were shown to co-localize by immunohistochemistry to invading mononuclear leukocytes in actively induced experimental autoimmune encephalomyelitis in rats. These findings provide the first insight into the mechanisms controlling inducible transcription of the HPSE gene, and could represent an important lead into understanding how HPSE expression is deregulated in metastatic tumor cells.

Amino Acid Motifs↗
PubMed2006

Distinct biological impact of dephosphorylation vs. downregulation of p210Bcr-Abl: implications for imatinib mesylate response and resistance.

Imatinib mesylate suppresses phosphorylation of its kinase target, Bcr-Abl. We hypothesized that loss of p210Bcr-Abl (the kinase target) may lead to imatinib mesylate resistance. We studied K562 cells [chronic myelogenous leukemia (CML) blast crisis line] and MO7E/MBA-1 cells (with MBA-1 cells representing MO7E cells stably transfected with BCR-ABL). Imatinib mesylate resistance developed when p210Bcr-Abl expression was abolished. Furthermore, K562 cells were significantly more growth suppressed after imatinib mesylate exposure than after downregulation of Bcr-Abl expression. Signaling pathways which were functional in the absence of Bcr-Abl expression (NF-kappaB and mitogen-activated protein kinase activation or the growth factor pathway) were disrupted when p210Bcr-Abl was present but dephosphorylated, suggesting that an intact, but enzymatically inactive Bcr-Abl, may interfere with critical growth/signaling pathways. Downregulation of p210Bcr-Abl may be a mechanism by which imatinib mesylate resistance emerges. Samples from three of 15 patients with imatinib mesylate-resistant CML blast crisis had undetectable levels of p210Bcr-Abl. We conclude that retention of a dephosphorylated p210Bcr-Abl has a biologic impact distinct from that of downregulation/loss of p210Bcr-Abl and, in a subset of patients, loss of the target of the kinase inhibitor may lead to imatinib mesylate resistance.

Benzamides↗
PubMed1998

Enhancing clinical pathway placement.

Soaring health care costs have fueled the immense growth in managed care. To contain these costs, health care organizations have turned to clinical pathways. However, clinical pathways cannot do an effective job if health care personnel are not aware of their existence. The article presents a simple, effective, and efficient method to increase placement of clinical pathways in inpatient medical records.

Cost Control↗
PubMedDate not supplied

Knowledge-based quality management and clinical pathways.

OBJECTIVES: Although 65% of the hospitals in Taiwan claim to be applying the clinical pathway concept, most hospitals do not implement this concept effectively. The purpose of this study was to determine the reasons for the improper or inappropriate application of the clinical pathway design in hospitals. METHODS: This study differs from other studies in clinical pathway design and application in that it seeks to resolve misunderstandings of the clinical pathway analysis that may have been generated by the responses to survey questionnaires. Therefore, in-depth interviews and Senge's system archetype have been used to ascertain the reasons why the use of a clinical pathway design has been ineffective. We also used the 4 dimensions of knowledge-based management proposed by Drucker to set up the knowledge-based clinical pathway. Thirteen experts used the Delphi method to construct 20 knowledge-based clinical pathway guidelines. CONCLUSIONS: The application of knowledge- and management-based clinical pathway designs is recommended.

Critical Pathways↗
PubMed2005

Language, therapeutic relationships and individualized care: addressing these issues in mental health care pathways.

Care pathways are used extensively in inpatient medical and surgical services to facilitate the delivery of evidence-based health care. There is a growing interest in their use in the mental health arena. However, questions remain about their acceptability to service users and staff. Most current literature is aimed at communicating the value of care pathways. Consequently, issues that are particularly pertinent to mental health, like language, therapeutic relationships and individualized care have not been fully addressed. This paper reports on the development of a care pathway in residential services in Nottingham. It will illustrate how by working in multidisciplinary groups with service users and carers these issues were incorporated into a comprehensive pathway that follows the service user's journey from admission to discharge. The paper concludes by highlighting some of the challenges of care pathway implementation and suggests ways they can be overcome.

Communication↗
PubMed2004

Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression.

Toll-like receptor 4 (TLR4) has been identified as a transmembrane protein involved in the host innate immune response to gram-negative bacterial lipopolysaccharide (LPS). Upon activation by LPS recognition, the TIR domain of TLR4 signals through MyD88 to activate the nuclear factor kappa B (NF-kappa B) pathway, a critical regulator of many proinflammatory genes, including interleukin-8 (IL-8). Emerging evidence suggests that reactive oxygen species (ROS) can contribute to diverse signaling pathways, including the LPS-induced cascade. In the present study we investigated the role of ROS in TLR-mediated signaling. Purified Escherichia coli LPS, a highly specific TLR4 agonist, elicited an oxidative burst in the monocyte-like cell line THP-1 in a time- and dose-dependent manner. This oxidative burst was shown to be dependent on the presence of TLR4 through transfection studies in HEK cells, which do not normally express this protein, and with bone marrow-derived macrophages from C3H/HeJ mice, which express a mutated TLR4 protein. LPS-stimulated IL-8 expression could be blocked by the antioxidants N-acetyl-L-cysteine and dimethyl sulfoxide at both the protein and mRNA levels. These antioxidants also blocked LPS-induced IL-8 promoter transactivation as well as the nuclear translocation of NF-kappa B. These data provide evidence that ROS regulate immune signaling through TLR4 via their effects on NF-kappa B activation.

Animals↗
PubMed1997

Lap choly pathway leads to efficiency, savings.

Promina Gwinnett Health System's laparoscopic cholecystectomy pathway has allowed the system's surgery programs to standardize supplies, reduce time and paperwork, and cut costs by $200 per patient per day. Care coordinators at Promina recently implemented a perioperative pathway that will be used in conjunction with a number of outpatient surgical pathways, including lap choly. The perioperative pathway further addresses the issue of reducing paperwork. To gain acceptance for their pathways, case managers meet frequently with physicians one on one to discuss concerns. The also post a list of physicians who comply with the pathway as a means of applying peer pressure.

Case Management↗
PubMed1997

Development of an ostomy competency.

Staff educators and staff nurses developed an ostomy competency, with the guidance and expertise of the advanced practitioner and enterostomal nurse at a large teaching hospital. The competency improved the quality of care for surgical ostomy patients. Care was standardized and staff nurses' clinical knowledge was enhanced. Following the sessions, staff nurses verbalized increased confidence in working with patients with ostomies and demonstrated increased autonomy and problem-solving abilities. No variances in educational aspects of care were noted on clinical pathways.

Clinical Competence↗
PubMed2005

Regulators of angiogenesis and strategies for their therapeutic manipulation.

Angiogenesis provides a mechanism by which delivery of oxygen and nutrients is adapted to compliment changes in tissue mass or metabolic activity. However, maladaptive angiogenesis is integral to the process of several diseases common in Western countries, including tumor growth, vascular insufficiency, diabetic retinopathy and rheumatoid arthritis. Understanding the process of capillary growth, including the identification and functional analyses of key pro- and anti-angiogenic factors, provides knowledge that can be applied to improve/reverse these pathological states. Initially, angiogenesis research focused predominantly on vascular endothelial growth factor (VEGF) as a main player in the angiogenesis cascade. It is apparent now that participation of multiple angiogenic factors and signal pathways is critical to enable effective growth and maturation of nascent capillaries. The purpose of this review is to focus on recent progress in identifying angiogenesis signaling pathways that show promise as targets for successful induction or inhibition of capillary growth. The strategies applied to achieve these contradictory tasks are discussed within the framework of our existing fundamental knowledge of angiogenesis signaling cascades, with an emphasis on comparing the employment of distinctive tactics in modulation of these pathways. Innovative developments that are presented include: (1) inducing a pleiotropic response via activation or inhibition of angiogenic transcription factors; (2) modulation of nitric oxide tissue concentration; (3) manipulating the kallikrein-kinin system; (4) use of endothelial progenitor cells as a means to either directly contribute to capillary growth or to be used as a vehicle to deliver "suicide genes" to tumor tissue.

Animals↗
PubMed2000

Detection of complement alternative pathway mRNA and proteins in the Alzheimer's disease brain.

Previous research on complement activation in the Alzheimer's disease (AD) brain has focused almost exclusively on the classical complement pathway. The alternative pathway represents another important arm for complement activation, converging with the classical cascade at the C5 cleavage step. Here, we show that mRNA for a critical alternative pathway component, factor B, is present in AD frontal cortex and that the factor D cleaved split products of factor B, Bb and Ba, are significantly increased, indicating alternative pathway activation. By contrast, the two major inhibitors of alternative pathway activation, factor H and factor I, are present at the level of mRNA and protein but are not significantly upregulated. Immunohistochemical analysis reveals significant positive staining in AD sections for all three components. Taken together with previous reports demonstrating alternative pathway activation by amyloid beta peptide, these findings suggest that conditions conducive to chronic alternative pathway activation may exist in the AD brain.

Aged↗
PubMed2005

Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells.

OBJECTIVE: The aim of this study is to investigate the signaling pathways and their roles in the differentiation of immature monocyte-derived dendritic cells (MoDCs). METHODS: MoDCs were generated from peripheral blood monocytes (PBMCs) using the standard protocols. Various kinase inhibitors, including SB203580, PD98059, and LY294002 and Wortmannin, or p38 activator were added at the beginning of the cultures. After 7 days of culture, immature MoDCs were harvested and analyzed for their surface expression of relevant molecules and the fraction of apoptotic cells by flow cytometry. Western blots were used to analyze mitogen-activated protein kinase (MAPK), NF-kappaB, Raf, mitogen-induced extracellular kinase (MEK), and AKT expression by cultured cells. NF-kappaB was also analyzed by electrophoretic mobility shift assay. Allogeneic MLR was used to examine the capacity of MoDCs to activate allogeneic T cells. RESULTS: The present study shows that the differentiation of immature MoDCs was accompanied by phosphorylation of AKT, Raf, MEK, extracellular signal-related kinase (ERK), and NF-kappaB activity. Inhibiting PI3K or MEK retarded the differentiation of immature MoDCs and induced apoptosis in 10 to 30% of the cultured cells, while inhibiting both PI3K and MEK resulted in apoptosis in 70% of the cells. Surprisingly, inhibiting p38 enhanced the phosphorylation of ERK and NF-kappaB activity and led to an enhanced upregulation, compared with control cells, of expression of dendritic cell (DC)-related adhesion and costimulatory molecules and antigen presentation capacity. CONCLUSIONS: Our results indicate that the Raf/MEK/ERK and PI3K/AKT signaling pathways play critical roles in the differentiation and survival of immature MoDCs. Moreover, this study also demonstrates that activated p38 is detrimental to the differentiation of immature MoDCs.

Anisomycin↗