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The responsibilities and areas of accountability of the perioperative nurse are growing. The Perioperative Education department at St Luke's Episcopal Hospital in Houston, TX has developed creative methods of orientation, critical pathways, and continuing education to meet the expectations of staff competency for all patient care.
It was only 25 years ago that the concept of cancer as a genetic disease began to gain widespread acceptance. It is encouraging to note that recurrent molecular pathways critical to the genesis and evolution of human sarcomas are being elucidated through molecular and cytogenetic techniques. It is also important to remember that molecular genetics and cytogenetics are still in their infancy. In this review, we have barely touched on the tremendous amount of information that has developed in sarcoma genetics and cytogenetics. As this synergistic evolution of genetic changes in human sarcomas becomes better understood, new and better therapeutic strategies aimed at circumventing these processes will be developed. But the biologic and genetic redundancies intrinsic to mammalian cells continue to allow tumors to adapt and resist chemotherapeutic agents. Understanding sarcoma progression at the molecular level will allow, therefore, for the identification of better diagnostic markers, the development of new therapeutic strategies, and the ability to select the most effective and least toxic combination of antitumor therapies for a patient.
Long-term care has come to include both an acute component and the more traditional chronic component. The growth in subacute care has occurred under private prepaid auspices but has also been stimulated by changes in Medicare funding for hospitals. Quality improvement techniques, such as critical pathways, have been applied to long-term care.
Nursing case management is a model of care delivery that focuses on achieving optimal patient outcomes in expected time frames while containing costs. This is accomplished through a multidisciplinary team approach, guided by a multidisciplinary care plan, called a critical pathway. This model of care meets the standards of regulatory agencies and is in line with health care reform activities at the federal level. It should be considered as an effective, new way to provide care in the NICU.
An orthopedic practice that consists mainly of total joint replacements is an ideal setting for a case manager. While fixed reimbursement demands that care be cost-effective, an older patient population presents with more complex health problems. Key factors towards achieving successful patient outcomes are thorough preoperative assessment, patient and family education, and the development of critical pathways.
Case management can reduce health care costs of the aortoiliac bypass graft surgery patient by eliminating unnecessary services, preventing duplication of services, and preventing costly readmissions in high-risk patients. This can be achieved through use of a case management plan that incorporates critical pathways, perioperative clinical nurse specialists as nurse case managers, ad hoc group practices, and patient and family participation.
A case management (CM) project was initiated for pediatric patients undergoing an outpatient endoscopy procedure. Health care professionals must meet the physical and psychological needs of the entire family unit when working with children. Meeting the needs of the child is accomplished more easily when the parents/guardians understand the process and are informed. Using a critical pathway and CM plan helps the nurse to accomplish this task. By using all members of the health care team, CM systematically moves the child and his/her parents/guardians through the hospital experience in an anticipated manner that is caring, efficient, and cost-effective.
Karen Zander, a member of the original research team at the New England Medical Center Hospital that created the first hospital case management model and critical pathways, outlines recent developments in education, automation, and research that she says point to an increasing interest in these two health care delivery strategies.
Nursing case management has been documented as one solution to the balance of cost and quality issues in healthcare. A current focus in healthcare is continuous quality improvement (CQI). CQI methods are focused on outcome measurements. Outcome research is a recent development in case management. Tracking variance, evaluating cost reduction and patient effectiveness, and determining types of patients at risk for negative variance are current case management research demands. Tracking patient comorbidities would allow for additional subset "tailoring" of existing critical pathways for specific comorbidities. Little research has been done on these issues. Few systems exist that track both variance and comorbidities. This article presents a graphic, simple, multidisciplinary tracking system that includes comorbidities and allows for individual and group patient variance analysis.
Using a systems approach, critical pathways address different types of injuries in trauma patients. A 640-bed tertiary referral center contracted with an independent consultant to evaluate its trauma program, resulting in several improvements in the delivery of services. Case management achieved the action plan goals: improved utilization of resources, improved continuity of care, and decreased length of stay.
The interaction of lead (Pb) with proteins may represent a fundamental mechanism by which Pb exerts toxicity. In this overview, various factors which influence the interaction of Pb with proteins will be discussed. Pb interacts with enzyme functional groups, and high-affinity metal-binding proteins, such as Pb-binding proteins and metallothioneins, can mediate this Pb-enzyme interaction. Many other factors influence Pb-protein interactions including ligand competition and binding affinities; protein folding and the nature of the metal-binding site; rates of protein synthesis and degradation; and intracellular localization of the ligand and metal. The remainder of this overview will focus on specific examples of important proteins known to be influenced by Pb or which hypothetically may be influenced by Pb. Gaps in knowledge and important research needs are emphasized. Many of the factors discussed play a role in the relative sensitivity of various enzymes in heme biosynthesis to Pb. Disruption of this critical pathway by Pb may result in neuropathologies and accumulation of neurotoxic heme precursors. High-affinity metal-binding proteins have been shown to play a role in mediating Pb inhibition of the octameric Zn-containing enzyme, ALA dehydratase. Knowledge of regional localization in brain and the postnatal ontogeny of the high-affinity metal-binding proteins may be pivotal in understanding Pb neurotoxicity. Other specific examples related to or potentially related to Pb toxicity which are discussed include nucleic acid binding proteins, calmodulin, protein kinase C, and carbonic anhydrase. These proteins will serve as models to understand some basic principles and differences in Pb-protein interactions.
S-Adenosylmethionine-dependent transmethylation reactions are required for many critical pathways in human cells. The enzyme S-adenosylhomocysteine hydrolase converts S-adenosylhomocysteine, a potent endogenous inhibitor of S-adenosylmethione-mediated methyltransferase reactions, to adenosine and L-homocysteine. The effects of the inhibitor of S-adenosylhomocysteine hydrolase, Z-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (MDL 28,842), on the growth of cultured keratinocytes and cutaneous squamous cell carcinoma lines were investigated. MDL 28,842 suppressed the proliferation of all cells in a dose-dependent manner, and significantly increased keratinocyte differentiation at a concentration of 1 microM. Following incubation with MDL 28,842, the methylation indices (ratio of S-adenosylmethionine/S-adenosylhomocysteine) of undifferentiated keratinocytes and squamous cell carcinoma lines were significantly decreased. These data demonstrate that the inhibitory effect of MDL 28,842 on squamous carcinoma cells and keratinocyte proliferation may result directly from inhibition of S-adenosylhomocysteine hydrolase activity. The antiproliferative activity of MDL 28,842 against squamous carcinoma cells and keratinocytes suggests a potential role for MDL 28,842 as a novel therapeutic agent for neoplastic and hyperproliferative disorders of the skin.
CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, mediates signal transduction pathways critical for immune responses. However, the mechanism of CD45-mediated signal transduction and the identity of CD45-associated proteins have remained unclear. A CD45-associated 30-kDA phosphorylated protein (CD45-AP) was purified by virtue of its specific association with CD45, and its mouse cDNA was cloned by using the internal amino acid sequence information. In vitro translated CD45-AP bound specifically to CD45. CD45-AP appears to be leukocyte-specific and shares no significant homology with presently known sequences. The predicted sequence contains no consensus tyrosine phosphorylation sites or conserved sequences of GTP-binding proteins. CD45-AP may act as an adapter molecule for CD45-mediated signal transduction.
BACKGROUND: Continuous quality improvement (CQI) techniques have been used most frequently in hospital operations such as pharmaceutical ordering, patient admitting, and billing of insurers, and less often to analyze and improve processes that are close to the clinical interaction of physicians and their patients. This paper describes a project in which CQI was implemented in a family practice setting to improve continuity of care. METHODS: A CQI study team was assembled in response to patients' complaints about not being able to see their regular physician providers when they wanted. Following CQI methods, the performance of the practice in terms of provider continuity was measured. Two "customer" groups were surveyed: physician faculty members were surveyed to assess their attitudes about continuity, and patients were surveyed about their preferences for provider continuity and convenience factors. RESULTS: Process improvements were selected in the critical pathways that influence provider continuity. One year after implementation of selected process improvements, repeat chart audit showed that provider continuity levels had improved from .45 to .74, a 64% increase from 1 year earlier. CONCLUSIONS: The project's main accomplishment was to establish the practicality of using CQI methods in a primary care setting to identify a quality issue of value to both providers and patients, in this case, continuity of provider care, and to identify processes that linked the performance of health care delivery procedures with patient expectations.
Human contact with the nontuberculous mycobacteria (NTM) is quite common, yet serious infections with these organisms were relatively infrequent until the advent of AIDS. Mycobacteria present an important window on the interaction of the innate (neutrophils, macrophages, NK cells) and acquired (T cells and B cells) immune systems. In their attempt to infect macrophages, the mycobacteria use their complex glycopeptidolipid cell wall to down-regulate macrophage responses. Once inside, mycobacteria are subject to the panoply of primary macrophage responses (e.g., vacuolar acidification, lytic enzymes). The infected macrophage produces cytokine signals (e.g., chemokines, interleukin [IL]-12] that recruit and stimulate lymphocytes from the innate (NK cell) and acquired (T and B cells) arms of the immune response to help kill the invading mycobacteria. Lymphocyte products that are central to the activation of macrophages to increased mycobacterial killing include tumor necrosis factor-alpha (TNF-alpha), interferon-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF). The precise mechanisms by which these cytokines work remains unknown. Rare patients who have refractory disseminated NTM infection without HIV infection probably have underlying immune defects in critical pathways for control of mycobacteria. We have recently characterized one such family and found abnormal IL-12 regulation. Interferon-gamma, the cytokine primarily elicited by IL-12, has been used successfully with antimycobacterials for treatment of these patients. The window on the interaction of the innate and acquired immune systems that mycobacteria afford is being opened. Understanding the cell-cell interactions and cytokines involved in NTM infections will lead to new therapeutic approaches.
The P-glycoproteins are integral membrane proteins that function as ATP-dependent transporters. The multidrug resistance genes which encode P-gp comprise a small gene family, with 2 members in humans and 3 in rodents. The P-gp encoded by the mdr1 gene functions as a drug efflux pump to remove drugs from cells and may serve as a barrier to protect cells from cytotoxic agents. In normal tissues, P-gp is localized on the luminal surface of transporting epithelia in the liver, kidney, small intestine, testes, and blood-brain barrier. Transient exposure to drugs transcriptionally increases the level of expression of the mdr1 genes, however, the cellular pathways critical to this regulation are yet unknown. This observation may have some implications on the level of expression in tumors and response to chemotherapy. Examination of the basal level of MDR expression in tumors may not be a reliable predictor of the effect of P-gp on chemotherapy. Induction of MDR transcription by drugs may further impede the effectiveness of anti-cancer agents. This is most obvious for drugs which are substrates for P-gp transport, however, it also applies significantly to compounds which are not themselves substrates but affect the response to other drugs simultaneously or subsequently administered. A clear understanding of the mechanisms that regulate basal and drug-induced mdr transcription will facilitate development of novel agents which circumvent this obstacle or permit targeted modification of mdr expression. Expressed on the bile canalicular surface of the liver, P-gps represent the first ATP-dependent biliary transporters to be characterized. The P-gp encoded by mdr2 is the major form of P-gp expressed in normal liver and transports phospholipids into bile. A defect in this protein leads to severe liver disease caused by chronic inflammation of the biliary system that results from high concentrations of free bile salts. The cellular origin and molecular basis of the ensuing liver tumors in these mice are unclear. It is possible that the chronic damage to the biliary ductules causes an increased growth rate of the surrounding cells, including putative stem cells in the liver. Thus, these mice may serve as a model for carcinogenesis in which the liver is under constant promotion placing the proliferating cells at increased risk to further genetic alterations or expansion of preexisting, but normally quiescent, mutations. Mdr2-deficient animals may also provide a model for human chronic inflammatory liver disease. Clearly, these exciting results indicate that further characterization of the P-gps as normal physiologic canalicular membrane transporters is necessary.
The 1990s will be remembered as a decade when quality assurance, evidence-based medicine and clinical quality improvement became key issues in the delivery of health care in hospitals and community settings. As public expectations of high quality health care increase in the face of diminishing resources and as accountability and standardisation of clinical practice are demanded by both consumers and professional regulatory bodies, the medical profession has responded with a proliferation of clinical practice guidelines and pathways. The efforts have been spearheaded by the various professional and academic colleges. Despite all the enthusiasm that has been created, there is still uncertainty regarding the clinical effectiveness, validity and medico-legal effects of practice guidelines and clinical pathways. This article focuses on the reasons behind the increasing popularity of clinical guidelines and pathways, a critical appraisal of their effectiveness and the medico-legal implications, effects and consequences of implementing such guidelines in clinical practice.
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent phospholipid mediators with diverse biological activities. Their appearance and functional properties suggest possible roles in development, wound healing, and tissue regeneration. The growth-stimulating and other complex biological activities of LPA and S1P are attributable in part to the activation of multiple G protein-mediated intracellular signaling pathways. Several heterotrimeric G proteins, as well as Ras- and Rho-dependent pathways play central roles in the cellular responses to LPA and S1P. Recently, several G protein-coupled receptors encoded by a family of endothelial differentiation genes (edg) have been shown to bind LPA or S1P and transduce responses of cAMP, Ca2+, MAP kinases, Rho, and gene transcription. This review summarizes our current understanding of signaling pathways critical for cellular responses to LPA and S1P and of recent progress in the molecular biological analyses of the Edg receptors.