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Biomedical subjects

H Waterman

Publications and source records attributed to H Waterman.

At least 19 recordsLinked to original sources
PubMed2004

'Finding the person the disease has'--the case for multisensory environments.

Education about, and exposure to, the utilization of a multisensory environment (MSE) was provided to clinical staff as a response to findings from the problem identification stage of an action research study. Feedback was obtained about their experience and perceptions of its use. Through the auspices of focus groups and one-to-one interviews, respondents commented on the impact that using the MSE had on their perception of their clients and on subsequent care. The case is made that MSEs afford an opportunity to impact on care through their mediating influence on formal carers' perceptions of their clients and, as such represent a significant but as yet unrealized potential for improving the quality of care of older people with dementia.

Alzheimer Disease↗
PubMed2002

An evaluation of the administration of sub-Tenon local anaesthesia by a nurse practitioner.

AIM: To evaluate the administration of sub-Tenon local anaesthesia (LA) by a nurse practitioner. METHODS: 106 consecutive patients listed for cataract surgery were given sub-Tenon's anaesthesia by a nurse practitioner. The surgical procedure was performed within 15 minutes of the administration of the LA. Pain, state and adequacy of anaesthesia, appearance of the eye, and patient anxiety were measured. Patients' experiences of this new nursing role were gained through interview. RESULTS: At the beginning of surgery, few patients showed eye movement in any of the four quadrants and the surgeons reported that akinesia was inadequate in only seven (7.1%) cases. Three patients (3.3%) gave a pain score of 3 out of 10 or above during surgery whereas the surgeons assessed the pain relief to be inadequate in eight (8.1%) cases. Five (5.3%) patients required a top up of anaesthesia and 51 (39.8%) patients developed conjunctival chemosis in two or more quadrants. Overall, patients' comments indicate that they were pleased with the new service. CONCLUSION: The results suggest that nurse practitioner delivered sub-Tenon LA is an effective and safe method of LA administration for cataract surgery.

Adult↗
PubMed2001

Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases.

The major process that regulates the amplitude and kinetics of signal transduction by tyrosine kinase receptors is endocytic removal of active ligand-receptor complexes from the cell surface, and their subsequent sorting to degradation or to recycling. Using the ErbB family of receptor tyrosine kinases we exemplify the diversity of the down regulation process, and concentrate on two sorting steps whose molecular details are emerging. These are the Eps15-mediated sorting to clathrin-coated regions of the plasma membrane and the c-Cbl-mediated targeting of receptors to lysosomal degradation. Like in yeast cells, sorting involves not only protein phosphorylation but also conjugation of ubiquitin molecules. The involvement of other molecules is reviewed and recent observations that challenge the negative regulatory role of endocytosis are described. Finally, we discuss the relevance of receptor down regulation to cancer therapy.

Adaptor Protein Complex alpha Subunits↗
PubMed2001

Ethnic variation in fluorescein angiography induced nausea and vomiting.

PURPOSE: A prospective survey was undertaken to investigate ethnic variations in the frequency of nausea and vomiting after fundus fluorescein angiography (FFA). METHOD: Between May and September 1998, 197 adult patients were recruited to the study. A questionnaire containing closed-ended questions was completed by nurses after each FFA and a questionnaire was given to patients to complete 5 hours after the procedure at home. Patients' anxiety level was measured before FFA using a 5-item ordinal response scale. RESULTS: Results indicate that patients from black, Asian, Chino-Asian and mixed ethnic origins are significantly more likely to vomit and feel nauseous immediately after the administration of fluorescein dye. Patients with a history of nausea after FFA are significantly more likely to feel nauseous again after repeat FFA. CONCLUSION: Ethnic origin and a previous history of nausea and vomiting appear to be important factors in FFA-induced nausea and vomiting. The results of this study have led the investigators to develop a protocol for the prophylactic treatment of nausea and vomiting following FFA.

Adult↗
PubMed2001

Randomised controlled trial of an integrated versus an optometric low vision rehabilitation service for patients with age-related macular degeneration: study design and methodology.

A number of studies have measured the outcomes of low vision care but these have usually been longitudinal case series, thus constituting very low quality of evidence for effectiveness. To date, there have been no randomised controlled trials (RCTs) which have evaluated the effectiveness and cost effectiveness of different models of care in low vision. The size of the low vision population and the paucity of systematic evaluation have created a pressing need for evidence about cost-effectiveness in order to inform service developments for low vision rehabilitation. This paper describes the study design and methodology of a three-arm RCT currently under way in Manchester. The baseline population recruited is also described. A traditional hospital-based optometric service is being compared with an integrated service (comprising the addition of community-based rehabilitation officer input) and with more generic community input (which is non-integrated and is not vision specific). A wide range of outcome measures are being assessed at recruitment and 12 months post-intervention, including low vision specific and generic quality of life measures, patterns of low vision aid use, and task performance. The rationale for the trial is discussed and the main study outcomes are described.

Aged↗
PubMed2000

Threonine phosphorylation diverts internalized epidermal growth factor receptors from a degradative pathway to the recycling endosome.

Transregulation of the epidermal growth factor receptor (EGFR) by protein kinase C (PKC) serves as a model for heterologous desensitization of receptor tyrosine kinases, but the underlying mechanism remained unknown. By using c-Cbl-induced ubiquitination of EGFR as a marker for transfer from early to late endosomes, we provide evidence that PKC can inhibit this process. In parallel, receptor down-regulation and degradation are significantly reduced. The inhibitory effects of PKC are mediated by a single threonine residue (threonine 654) of EGFR, which serves as a major PKC phosphorylation site. Biochemical and morphological analyses indicate that threonine-phosphorylated EGFR molecules undergo normal internalization, but instead of sorting to lysosomal degradation, they recycle back to the cell surface. In conclusion, by sorting EGFR to the recycling endosome, heterologous desensitization restrains ligand-induced down-regulation of EGFR.

Animals↗
PubMed2000

Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2.

Overexpression of HER-2/ErbB-2, a homologue of the epidermal growth factor receptor, is associated with poor prognosis, and an ErbB-2-specific antibody is therapeutic when administered to patients with metastatic breast cancer. To understand the mechanism underlying immunotherapy, we concentrated on antibody- and epidermal growth factor-induced degradation of ErbB-2. We show that enhanced degradation is preceded by poly-ubiquitination of ErbB-2. This process necessitates recruitment of the c-Cbl ubiquitin ligase to tyrosine 1112 of ErbB-2. Consequently, mutagenesis of this site retards antibody-induced degradation. Thus, the therapeutic potential of certain antibodies may be due to their ability to direct ErbB-2 to a c-Cbl-regulated proteolytic pathway.

Amino Acid Sequence↗
PubMed2000

Molecular requirements for the effect of neuregulin on cell spreading, motility and colony organization.

Neuregulin can trigger morphogenetic signals in cells both in vivo and in culture through the activation of receptors from the ErbB family. We have ectopically expressed various ErbB-receptors in 32D myeloid cells lacking endogenous ErbB-proteins, and in CHO cells, which express only ErbB-2. We show here that activation of ErbB-3/ErbB-2 heterodimeric receptors triggers PI3-kinase-dependent lamellipodia formation and spreading, while individual ErbB-receptor homodimers as well as ErbB-3/ErbB-1 heterodimers are much less effective. CHO cells expressing ErB-3/ErbB-2 together with N-cadherin, an adhesion receptor, form epithelioid colonies. Neuregulin activates cell motility leading to transition of these colonies into ring-shaped multicellular arrays, similar to those induced by neuregulin in epithelial cells of different types (Chausovsky et al., 1998). This process requires both PI3-kinase and MAP kinase kinase activity and depends on coordinated changes in the actin- and microtubule-based cytoskeleton. Transactivation of ErbB-2 is not sufficient for the activation of cell motility and ring formation, and the C-terminal domain of ErbB-3 bearing the docking sites for the p85 subunit of PI3-kinase is essential for these morphogenetic effects. Thus, ErbB-3 in conjunction with ErbB-2 mediates, via its C-terminal domain, cytoskeletal and adhesion alterations which activate cell spreading and motility, leading to the formation of complex structures such as multicellular rings. Oncogene (2000) 19, 878 - 888.

Animals↗
PubMed1999

The RING finger of c-Cbl mediates desensitization of the epidermal growth factor receptor.

Ligand-induced activation of surface receptors, including the epidermal growth factor receptor (EGFR), is followed by a desensitization process involving endocytosis and receptor degradation. c-Cbl, a tyrosine phosphorylation substrate shared by several signaling pathways, accelerates desensitization by recruiting EGFR and increasing receptor polyubiquitination. Here we demonstrate that the RING type zinc finger of c-Cbl is essential for ubiquitination and subsequent desensitization of EGFR. Mutagenesis of a single cysteine residue impaired the ability of c-Cbl to enhance both down-regulation and ubiquitination of EGFR in living cells, although the mutant retained binding to the activated receptor. Consequently, the mutant form of c-Cbl acquired a dominant inhibitory function and lost the ability to inhibit signaling downstream to EGFR. In vitro reconstitution of EGFR ubiquitination implies that the RING finger plays an essential direct role in ubiquitin ligation. Our results attribute to the RING finger of c-Cbl a causative role in endocytic sorting of EGFR and desensitization of signal transduction.

Down-Regulation↗
PubMed1999

The C-terminus of the kinase-defective neuregulin receptor ErbB-3 confers mitogenic superiority and dictates endocytic routing.

Signaling by the epidermal growth factor (EGF) family and the neuregulin group of ligands is mediated by four ErbB receptor tyrosine kinases, that form homo- and heterodimeric complexes. Paradoxically, the neuregulin receptor ErbB-3 is devoid of catalytic activity, but its heterodimerization with other ErbBs, particularly the ligand-less ErbB-2 oncoprotein of carcinomas, reconstitutes superior mitogenic and transforming activities. To understand the underlying mechanism we constructed a chimeric EGF-receptor (ErbB-1) whose autophosphorylation C-terminal domain was replaced by the corresponding portion of ErbB-3. Consistent with the possibility that this domain recruits a relatively potent signaling pathway(s), the mitogenic signals generated by the recombinant fusion protein were superior to those generated by ErbB-1 homodimers and comparable to the proliferative activity of ErbB-2/ErbB-3 heterodimers. Upon ligand binding, the chimeric receptor recruited an ErbB-3-specific repertoire of signaling proteins, including Shc and the phosphatidylinositol 3-kinase, but excluding the ErbB-1-specific substrate, phospholipase Cgamma1. Unlike ErbB-1, which is destined to lysosomal degradation through a mechanism that includes recruitment of c-Cbl and receptor poly-ubiquitination, the C-terminal tail of ErbB-3 shunted the chimeric protein to the ErbB-3-characteristic recycling pathway. These observations attribute the mitogenic superiority of ErbB-3 to its C-terminal tail and imply that the flanking kinase domain has lost catalytic activity in order to restrain the relatively potent signaling capability of the C-terminus.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1.

Receptor desensitization is accomplished by accelerated endocytosis and degradation of ligand-receptor complexes. An in vitro reconstituted system indicates that Cbl adaptor proteins directly control downregulation of the receptor for the epidermal growth factor (EGFR) by recruiting ubiquitin-activating and -conjugating enzymes. We infer a sequential process initiated by autophosphorylation of EGFR at a previously identified lysosome-targeting motif that subsequently recruits Cbl. This is followed by tyrosine phosphorylation of c-Cbl at a site flanking its RING finger, which enables receptor ubiquitination and degradation. Whereas all three members of the Cbl family can enhance ubiquitination, two oncogenic Cbl variants, whose RING fingers are defective and phosphorylation sites are missing, are unable to desensitize EGFR. Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways.

Caenorhabditis elegans Proteins↗
PubMed1999

Management of day-surgery patients with cataract attending a peripheral ophthalmic clinic.

PURPOSE: To compare two organisational models of management for patients with cataract referred to a peripheral ophthalmic clinic who underwent day-surgery at a main eye hospital. METHOD: Patients were randomised into two groups. The experimental group (n = 25) received pre-operative assessment by a trained ophthalmic nurse at the peripheral clinic immediately following diagnosis of cataract and diary-booking for surgery. The control group (n = 24) received a separate appointment for pre-operative assessment at the main hospital. For all patients, the first review appointment (3 or 5 days post-operatively) and all subsequent review was at the peripheral clinic. Outcome measures included: visual acuity, subjective visual function (VF-14), anxiety and depression (HADS), semi-structured interviews to ascertain patient satisfaction, and a cost-benefit analysis. RESULTS: There were no significant differences at any time between the experimental and control groups with respect to visual acuity, subjective visual function or anxiety and depression. The experimental model was found to be more cost-effective and provided a less fragmented means of care delivery. The majority of patients in both groups expressed satisfaction with their care but, overall, the experimental model was preferred. CONCLUSIONS: Nurse-led pre-operative assessment of patients with cataract at a peripheral ophthalmic clinic is safe, cost-effective and is preferred by patients.

Aged↗
PubMed1999

Post-operative pain, nausea and vomiting: qualitative perspectives from telephone interviews.

Previous studies on post-operative pain, nausea and vomiting tend to be quantitative in method and focus on in-patient or day case surgery. The objectives of this study carried out in one specialist eye hospital in England were to consider post-operative pain, nausea and vomiting from a qualitative perspective. Fifty-five patients undergoing general anaesthetic short-stay ophthalmic surgery (orbital hydroxyapatite implantation) consented to participate in telephone interviews 8 days post-surgery. The interviews lasted between 20 and 60 minutes. Data were analysed thematically and offer insight into varying experiences of pain, nausea and vomiting in hospital, on discharge and at home. Results indicate that not all patients were discharged home in optimum condition. The needs of post-operative short-stay patients should come before financial imperatives to vacate beds. Patient education and information giving is discussed in the light of the findings.

Adult↗
PubMed1999

Planning and managing research into day-surgery for cataract.

Between 1995 and 1997, a randomized controlled study, funded by the Department of Health, was carried out into the management of patients with cataract attending a peripheral ophthalmic clinic and who had been assessed as suitable for day-surgery. The research took place in a clinical setting and it was accepted from the outset that, while such studies have the power to give information about the real clinical world, this also means that the research is potentially at the mercy of events within that world. The purpose of this paper is to report how the study was set up and integrated into the clinic. First, a literature review was undertaken in order to focus the aims of the study more clearly. Second, drawing on principles of action research, clinical and research staff worked together to implement the study. This strategy allowed a flexible approach to the research which enabled problems to be handled as they arose.

Ambulatory Surgical Procedures↗
PubMed1999

The effect of foot massage on patients' perception of care following laparoscopic sterilization as day case patients.

This randomized-controlled study examined the effects of foot massage on patients' perception of care received following surgery. The sample of 59 women who underwent laparoscopic sterilization as day case patients were randomly allocated into two groups. The experimental group received a foot massage and analgesia post-operatively, whilst the control group received only analgesia post-operatively. Each participant was asked to complete a questionnaire on the day following surgery. This examined satisfaction, memory and analgesia taken. The 76% response rate was comparable with other patient satisfaction studies following day-case surgery. Statistical analysis showed no overall significant difference in the pain experienced by the two groups; however, the mean pain scores recorded following surgery showed a significantly different pattern over time, such that the experimental group consistently reported less pain following a foot massage than the control group. This study has attempted to explore the use of foot massage in a systematic way and is therefore a basis for further study.

Ambulatory Surgical Procedures↗
PubMed1999

Trends in ophthalmology services, nursing skill-mix and education: 2nd national survey.

This paper reports on a replication study of the first national survey commissioned by the RCN Ophthalmic Nursing Forum to assess the changing skill-mix of staff caring for ophthalmic patients and the nature of ophthalmic services. After minor modifications to the original questionnaire, it was circulated to the total population of ophthalmic units and hospitals in the United Kingdom (n=181). Following quantitative data analysis, it was found that the numbers of nurses holding ophthalmic nursing qualifications has risen to almost 50%, although this did not reach statistical significance. This increase has occurred alongside a significant rise in numbers of institutions offering ophthalmic nurse education and the expansion of day case surgery. Regional variations exist, however, to the extent that the increase in ophthalmic nurses and provision of ophthalmic nurse education has not been reflected nearly as much in Scotland as the rest of the UK. Overall, it was also found that the proportion of C, G and I grade nurses has fallen significantly, whilst the numbers of nurses graded D and F has risen. The implications of the results are discussed and recommendations for future research made.

Humans↗
PubMed1999

Blood gas analysis: a study of blood loss in intensive care.

This paper describes a quantitative study conducted on an intensive care unit in the north of England. It involved the collection of data from the existing records of 65 patients consecutively sampled from a predetermined date provided that they stayed more than 24 hours and had an arterial line in situ. As patient records were used, ethical approval was not necessary. The objectives of the study were to quantify the mean number of blood gas samples taken per patient and estimate the mean blood loss resulting from this, including discard volume. Limitations include reliance on records and lack of an economic evaluation. The results show that blood loss in this study was greater than that reported elsewhere. Patients who were ventilated for 24 hours or more had a statistically significant greater blood loss when compared to those who were not (P < 0.001). A subgroup of patients undergoing renal replacement therapy had the greatest blood loss (mean 55.18 ml per day). This loss was statistically significant when compared to patients not in acute renal failure (P=0.007). When patients undergoing multiple therapies normally associated with increased sampling were compared to patients not receiving such therapies, there was no statistically significant difference in blood loss. The need to change current nursing practice to reduce iatrogenic anaemia is emphasized.

APACHE↗