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Biomedical subjects

H Waterman

Publications and source records attributed to H Waterman.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nurses failure to appreciate the risks of infection due to needle stick accidents: a hospital based survey.

One of the most important occupational risks to healthcare workers is exposure is to blood-borne viruses. This study examined nurses' perceptions of risk of contracting infection following single or multiple exposure to blood or body fluids. Two hundred and ninety nurses were surveyed using a questionnaire. One hundred and thirty-three responded; 85 worked in higher risk areas (ITU, Haematology, Haemodialysis and Neonatal Surgical Units) (Group A) and 48 worked in lower risk areas (medical wards, an orthopaedic and an ENT ward) (Group B). Forty-nine percent of subjects from group A and 60% of subjects from Group B believed that a needle stick injury with a needle contaminated with infected blood was an unlikely source of infection. Fifteen percent from group A and 20% from group B thought that infection with a blood-borne virus following a needle stick injury contaminated with Human Immunodeficiency Virus (HIV) infected blood was very unlikely. Twelve percent from group A and 10% from Group B did not know whether resheathing needles between use can provide protection against HIV. Sixty-seven percent from group A and 71% from group B disagreed with the statement that nurses are at higher risk of exposure to HIV/HBV than the other healthcare workers. Thirteen percent from group A and 5% from group B agreed with the statement, whereas 8% from group A and 5% from group B thought that nurses are at less risk. Only 22% from group A and 23% from group B would take more precautions if they knew that the patient had HIV/HBV infection, whilst 11% and 8% respectively admitted that they would take special precautions only when the patient has clinical symptoms of HIV/HBV infection. The findings suggest that these nurses would benefit from further education regarding infection from blood-borne viruses.

Attitude of Health Personnel↗
PubMed1998

Cellular oxygenation of 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid by 5-lipoxygenase is stimulated by 5-lipoxygenase-activating protein.

It has been proposed that 5-lipoxygenase (5-LO)-activating protein (FLAP) is an arachidonate transfer protein for leukotriene biosynthesis. Using the Spodoptera frugiperda (Sf9) insect cells, we demonstrate that FLAP causes a large stimulation (190-fold) of the conversion of 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) to 5, 12-diHETE when co-expressed with 5-lipoxygenase. We also demonstrate that FLAP can stimulate (2-2.5-fold) the oxygenation of 15(S)-HETE by 5-LO to 5,15-diHETE. The stimulation of both 12(S)-HETE and 15(S)-HETE oxygenation by 5-LO is completely inhibitable by the FLAP inhibitor, MK-886. In order to determine which residues of FLAP are important for 12(S)-HETE and arachidonic acid utilization by 5-LO, various mutants of FLAP were co-expressed with 5-LO in Sf9 cells. The FLAP deletion mutants del 37-53, del 52-58, del 106-108, and del 148-161 and the point mutant D62N were analyzed. The D62N mutation, which reduces the binding of indole inhibitors to FLAP, had no effect on the stimulation of substrate utilization by 5-LO. In contrast to wild type FLAP, the mutant proteins del 37-53, del 106-108, and del 148-161 failed to stimulate 12(S)-HETE and arachidonic acid utilization by 5-LO. Only one of the latter three mutations (del 37-53) has been shown to abolish the binding of indole inhibitors to FLAP. These results suggest that the lipid binding site of FLAP overlaps the inhibitor binding site and occupies several regions of the protein not essential for inhibitor binding. Because FLAP can stimulate the utilization of 12(S)-HETE, 15(S)-HETE, and arachidonic acid by 5-LO, FLAP may also function as a more general lipid carrier protein for the biosynthesis of multiple oxygenation products of arachidonic acid in addition to its role in leukotriene biosynthesis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1998

c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor.

Ligand-induced down-regulation of two growth factor receptors, EGF receptor (ErbB-1) and ErbB-3, correlates with differential ability to recruit c-Cbl, whose invertebrate orthologs are negative regulators of ErbB. We report that ligand-induced degradation of internalized ErbB-1, but not ErbB-3, is mediated by transient mobilization of a minor fraction of c-Cbl into ErbB-1-containing endosomes. This recruitment depends on the receptor's tyrosine kinase activity and an intact carboxy-terminal region. The alternative fate is recycling of internalized ErbBs to the cell surface. Cbl-mediated receptor sorting involves covalent attachment of ubiquitin molecules, and subsequent lysosomal and proteasomal degradation. The oncogenic viral form of Cbl inhibits down-regulation by shunting endocytosed receptors to the recycling pathway. These results reveal an endosomal sorting machinery capable of controlling the fate, and, hence, signaling potency, of growth factor receptors.

Biological Transport↗
PubMed1998

Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network.

Virulence of poxviruses, the causative agents of smallpox, depends on virus-encoded growth factors related to the mammalian epidermal growth factor (EGF). Here we report that the growth factors of Shope fibroma virus, Myxoma virus and vaccinia virus (SFGF, MGF and VGF) display unique patterns of specificity to ErbB receptor tyrosine kinases; whereas SFGF is a broad-specificity ligand, VGF binds primarily to ErbB-1 homodimers, and the exclusive receptor for MGF is a heterodimer comprised of ErbB-2 and ErbB-3. In spite of 10- to 1000-fold lower binding affinity to their respective receptors, the viral ligands are mitogenically equivalent or even more potent than their mammalian counterparts. This remarkable enhancement of cell growth is due to attenuation of receptor degradation and ubiquitination, which leads to sustained signal transduction. Our results imply that signal potentiation and precise targeting to specific receptor combinations contribute to cell transformation at sites of poxvirus infection, and they underscore the importance of the often ignored low-affinity ligand-receptor interactions.

Animals↗
PubMed1998

Differential endocytic routing of homo- and hetero-dimeric ErbB tyrosine kinases confers signaling superiority to receptor heterodimers.

Both homo- and hetero-dimers of ErbB receptor tyrosine kinases mediate signaling by a large group of epidermal growth factor (EGF)-like ligands. However, some ligands are more potent than others, although they bind to the same direct receptor. In addition, signaling by receptor heterodimers is superior to homodimers. We addressed the mechanism underlying these two features of signal tuning by using three ligands: EGF; transforming growth factor alpha (TGFalpha); and their chimera, denoted E4T, which act on cells singly expressing ErbB-1 as a weak, a strong, and a very strong agonist, respectively. Co-expression of ErbB-2, a developmentally important co-receptor whose expression is frequently elevated in human cancers, specifically potentiated EGF signaling to the level achieved by TGFalpha, an effect that was partially mimicked by ErbB-3. Analysis of the mechanism underlying this trans-potentiation implied that EGF-driven homodimers of ErbB-1 are destined for intracellular degradation, whereas the corresponding heterodimers with ErbB-2 or with ErbB-3, dissociate in the early endosome. As a consequence, in the presence of either co-receptor, ErbB-1 is recycled to the cell surface and its signaling is enhanced. This latter route is followed by TGFalpha-driven homodimers of ErbB-1, and also by E4T-bound receptors, whose signaling is further enhanced by repeated cycles of binding and dissociation from the receptors. We conclude that alternative endocytic routes of homo- and hetero-dimeric receptor complexes may contribute to tuning and diversification of signal transduction. In addition, the ability of ErbB-2 to shunt ligand-activated receptors to recycling may explain, in part, its oncogenic potential.

Animals↗
PubMed1998

Alternative intracellular routing of ErbB receptors may determine signaling potency.

The ErbB signaling module consists of four receptor tyrosine kinases and several dozen ligands that activate specific homo- and heterodimeric complexes of ErbB proteins. Combinatorial ligand/receptor/effector interactions allow large potential for signal diversification. Here we addressed the possibility that turn-off mechanisms enhance the diversification potential. Concentrating on ErbB-1 and two of its ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha), and the Neu differentiation factor (NDF/neuregulin) and one of its receptors, ErbB-3, we show that ligand binding variably accelerates endocytosis of the respective ligand-receptor complex. However, unlike the EGF-activated ErbB-1, which is destined primarily to degradation in lysosomes, NDF and TGF-alpha direct their receptors to recycling, probably because these ligands dissociate from their receptors earlier along the endocytic pathway. In the case of NDF, structural, as well as biochemical, analyses imply that ligand degradation occurs at a relatively late endosomal stage. Attenuation of receptor down-regulation by this mechanism apparently confers to both NDF and TGF-alpha more potent and prolonged signaling activity. In conclusion, alternative endocytic trafficking of ligand-ErbB complexes may tune and diversify signal transduction by EGF family ligands.

Animals↗
PubMed1998

Epiregulin is a potent pan-ErbB ligand that preferentially activates heterodimeric receptor complexes.

The ErbB signaling network consists of four transmembrane receptor tyrosine kinases and more than a dozen ligands sharing an epidermal growth factor (EGF) motif. The multiplicity of ErbB-specific ligands is incompletely understood in terms of signal specificity because all ErbB molecules signal through partially overlapping pathways. Here we addressed the action of epiregulin, a recently isolated ligand of ErbB-1. By employing a set of factor-dependent cell lines engineered to express individual ErbBs or their combinations, we found that epiregulin is the broadest specificity EGF-like ligand so far characterized: not only does it stimulate homodimers of both ErbB-1 and ErbB-4, it also activates all possible heterodimeric ErbB complexes. Consistent with its relaxed selectivity, epiregulin binds the various receptor combinations with an affinity that is approximately 100-fold lower than the affinity of ligands with more stringent selectivity, including EGF. Nevertheless, epiregulin's action upon most receptor combinations transmits a more potent mitogenic signal than does EGF. This remarkable discrepancy between binding affinity and bioactivity is permitted by a mechanism that prevents receptor down-regulation, and results in a weak, but prolonged, state of receptor activation.

Animals↗
PubMed1998

The hydroxyapatite orbital implant: post-operative pain.

PURPOSE: To compare and quantify the degree of post-operative pain experienced by patients undergoing primary and secondary hydroxyapatite orbital implantation. METHODS: A prospective survey design was employed to monitor patients' pain pre-operatively and up to 7 days post-operatively. Fifty-five consecutive patients undergoing primary and secondary hydroxyapatite orbital implantation were recruited over a period of 1 year. Standardised anaesthetic, operative and post-operative protocols were followed. During the patients' in-patient stay nurses completed a data proforma that required them to record patients' pain using an 11-item numerical rating scale. A self-completion proforma was given to patients to score their pain at home until the first post-operative out-patient appointment. RESULTS: Patients undergoing primary implant surgery tend to experience more post-operative pain than those undergoing secondary implant surgery. A small proportion of patients experience severe post-operative pain. CONCLUSION: Post-operative pain experienced by patients undergoing primary and secondary hydroxyapatite implantation has been underestimated. This study has provided the necessary data to enable such patients to be effectively counselled pre-operatively and to plan a rational discharge policy.

Adult↗
PubMed1998

Post-operative nausea and vomiting following orbital hydroxyapatite implant surgery.

Fifty-five consecutive patients undergoing a short-stay ophthalmic operation (orbital hydroxyapatite implantation) were recruited over 1 year to assess the frequency and duration of post-operative nausea and vomiting over 7 days. The incidence of nausea and vomiting in hospital was recorded. Patients scored their nausea and vomiting four times daily at home. By the end of the first day after surgery, 31 (75%) patients had experienced mild to severe nausea. Eighteen (38%) patients became nauseated on five or more occasions. Nineteen (35%) patients had vomited by the end of the first day after surgery and, over 7 days, 24 (43%) patients had vomited on one or more occasion. Three patients reported that they had vomited during the journey home. Vomiting was not correlated with pain or a past history of post-operative nausea and vomiting. However, there was a statistically significant correlation between nausea and pain. The high incidence of nausea and vomiting observed in this study appears to provide additional evidence of an oculo-emetic reflex. The timing of discharge and appropriate patient education are discussed.

Adult↗
PubMed1998

Embracing ambiguities and valuing ourselves: issues of validity in action research.

Further elucidation is required on the validity of action research. The tendency of nurse action researchers to rely on perspectives of validity from qualitative or ethnographic research only gives a partial picture. Three categories of validity regarding action research are proposed in order to develop understandings and to stimulate debate: dialectical, critical and reflexive. Tensions and processes, moral responsibilities, reflexivity and accounts of action research are discussed to illuminate the validity of action research. The complexity and contradictions inherent even when attempting to demonstrate its validity are highlighted and illustrated with reference to examples of action research.

England↗
PubMed1997

Promoting action research in healthcare settings.

To coincide with the first annual Action Research conference taking place in London this week, this article promotes the idea of using action research for health care exploration and change. It also introduces the work of the Healthcare Subgroup of the Collaborative Action Research Network, the group's aims and how practitioners can make contact and be involved with the development. The article also describes the outcomes of a research study that underpin the philosophy, process and potential benefits of the network as a means to promote practice development and change in client care.

Clinical Nursing Research↗
PubMed1997

Building a relationship: communications and relationships between staff and stroke patients on a rehabilitation ward.

Communications among staff and patients on a stroke rehabilitation ward form the focus of this article, which reports on some aspects of a larger study using a grounded theory approach. Tape-recorded interviews were transcribed and analysed concurrently according to recommendations for the approach. A main theme entitled building a relationship was identified, and this process was found to occur in a context varying from participative at one end of a continuum to hierarchical at the other. Building a relationship was found to be influenced by role, personal qualities and organizational context. Appropriate relationships between role-holders were subject to negotiation, leading to a resulting congruence or incongruence between participants' expectations of each other and their roles. Personal qualities were brought into play in the process, with patients' views of staff and staff views of patients both being influential. Some of these views seemed to parallel what has been described in earlier literature as 'the sick role' and the labelling of patients as 'good' or 'bad'. Responses to personal qualities led to nurses ascribing meaning to patients' behaviour in terms of adjustment to their stroke, giving time to them to help them to adjust, and withdrawal and handing over to other staff if this strategy failed. Organizational context also had an influence on building a relationship, with time constraints being identified particularly by nurses, and the need to fit in the most essential aspects of care. Place was also important, in that nurses were confined to the ward as a work location, whereas other therapists and doctors worked in other places and sometimes had the facility to take patients off the ward to concentrate on therapy. The findings are discussed against the background of related literature and the conclusion is drawn that the crucial role of nurses in rehabilitation is not recognized and valued, and that shortages of resources-especially suitably qualified and trained nursing staff-are a negative influence on building the relationships which are vital to successful rehabilitation.

Cerebrovascular Disorders↗
PubMed1996

Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions.

The ErbB family includes two receptors, ErbB-1 and ErbB-3, that respectively bind to epidermal growth factor and Neu differentiation factor, and an orphan receptor, ErbB-2. Unlike ErbB-1 and ErbB-2, the intrinsic tyrosine kinase of ErbB-3 is catalytically impaired. By using interleukin-3-dependent cells that ectopically express the three ErbB proteins or their combinations, we found that ErbB-3 is devoid of any biological activity but both ErbB-1 and ErbB-2 can reconstitute its extremely potent mitogenic activity. Transactivation of ErbB-3 correlates with heterodimer formation and is reflected in receptor phosphorylation and the transregulation of ligand affinity. Inter-receptor interactions enable graded proliferative and survival signals: heterodimers are more potent than homodimers, and ErbB-3-containing complexes, especially the ErbB-2/ErbB-3 heterodimer, are more active than ErbB-1 complexes. Nevertheless, ErbB-1 signaling displays dominance over ErbB-3 when the two receptors are coexpressed. Although all receptor combinations activate the mitogen-activated protein kinases ERK and c-Jun kinase, they differ in their rate of endocytosis and in coupling to intervening signaling proteins. It is conceivable that combinatorial receptor interactions diversify signal transduction and confer double regulation, in cis and in trans, of the superior mitogenic activity of the kinase-defective ErbB-3.

Animals↗
PubMed1996

The introduction of case management on a rehabilitation floor.

An exchange for 1 day a week between a clinical nurse specialist and a lecturer gave rise to the opportunity to evaluate the introduction of case management on a newly created rehabilitation floor at an elderly care hospital. The aims of the study were to examine the feelings and concerns of new case managers, their conception of case management and their perceived educational needs. Qualitative research methods were employed to achieve the aims. Rigour was addressed, in part, through concurrent analysis of data with data collection, which encouraged probing of issues important to research participants. Thematic categories are presented under the headings: 'structure' and 'process'. The data collected revealed vividly that, as with any change, the people involved experienced anxieties and/or confusion over their new roles, but that some of the problems arose from the relocation of staff when the rehabilitation floor was established. Despite these difficulties, there was general enthusiasm for the potential of case management.

Aged↗
PubMed1996

An examination of nurses' practices when performing aseptic technique for wound dressings.

The purpose of this study was to establish if nurses' actions when carrying out 'aseptic technique' using the 'gloves technique' are simple and based on up-to-date knowledge and do not incur unnecessary wastage. A sample of convenience was used involving 21 trained nurses. Observation and formal interviews were used to collect quantitative and qualitative data. Results showed that not all nurses in the sample applied a 'simple aseptic technique'. The rationale for the practice of aseptic technique was not always research based, though other aspects of wound management were derived from research findings. The study highlighted other areas of aseptic technique which require investigations.

Asepsis↗
PubMed1996

A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor.

The ErbB family includes four homologous transmembrane tyrosine kinases. Whereas ErbB-1 binds to the epidermal growth factor (EGF), both ErbB-3 and ErbB-4 bind to the Neu differentiation factors (NDFs, or neuregulins), and ErbB-2, the most oncogenic family member, is an orphan receptor whose function is still unknown. Because previous lines of evidence indicated the existence of interreceptor interactions, we used ectopic expression of individual ErbB proteins and their combinations to analyze the details of receptor cross talks. We show that 8 of 10 possible homo-and heterodimeric complexes of ErbB proteins can be hierarchically induced by ligand binding. Although ErbB-2 binds neither ligand, even in a heterodimeric receptor complex, it is the preferred heterodimer partner of the three other members, and it favors interaction with ErbB-3. Selective receptor overexpression in human tumor cells appears to bias the hierarchical relationships. The ordered network is reflected in receptor transphosphorylation, ErbB-2-mediated enhancement of ligand affinities, and remarkable potentiation of mitogenesis by a coexpressed ErbB-2. The observed superior ability of ErbB-2 to form heterodimers, in conjunction with its uniquely high basal tyrosine kinase activity, may explain why ErbB-2 overexpression is associated with poor prognosis.

Animals↗
PubMed1995

Parallels and contradictions in the theory and practice of action research and nursing.

This paper draws on the authors' experiences of nursing in general and of action research projects. Parallels will be drawn between, on the one hand, the relationship between the practice and theory of nursing and, on the other band, the relationship between the practice and theory of action research. Difficulties common to nursing and action research will be identified (e.g. between the implementation of the theory of nursing and of action research). Over- simplification, non-specificity of issues and gaps in theory are frequent but inevitable problems that hinder theoretical applications. Similarly, comparisons will be made between the problems associated with the translation of nursing practice into theory and the difficulties in transposing the experience of research into theory. The complexities of practice, whether nursing or research, and the evolutionary nature of experience inescapably give rise to dilemmas when analysing theory and practice. The concepts of theory and practice when conceived as a dichotomy present a useful overview of issues. We argue that, through a discussion of the core themes of action research, including 'knowledge in action' and 'self and group reflection', consideration should also be given to a symbiotic and complementary analysis of theory and practice. We observe that many contradictions exist within the theory and practice of action research and of nursing, and that these need to be addressed to promote theoretical and practical advances. Action research offers theoretical and practical insights that contribute to the current debate on the reciprocal relationship between theory and practice.

Diffusion of Innovation↗