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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 307 records · Page 17Linked to original sources
PubMed1998

Palliative terminal cancer care in community hospitals and a hospice: a comparative study.

BACKGROUND: Despite palliative care being an accepted role of community hospitals, there is little quantitative evidence of the type of care provided. AIM: To obtain quantitative data comparing palliative cancer care provided in 12 community hospitals in 10 towns (approximately 350 medical beds) and in a consultant-led purpose-built hospice (12 beds). METHOD: Retrospective medical and nursing case note analysis over one year of cancer deaths in the former Exeter Health District. RESULTS: A total of 171 community hospital and 116 hospice casenotes were analysed. Hospice patients had significantly different reasons for admission compared with community hospital patients (P < 0.001), with pain and symptom control being more frequent and terminal nursing care less frequent reasons for admission to the hospice. Community hospital length of stay was significantly longer than hospice length of stay (P = 0.002; mean community hospital stay 16 days, mean hospice stay eight days). Symptoms on admission differed significantly. Drug prescribing on admission and at death and indications of active treatment of symptoms were broadly similar. Community hospital patients received more investigations than hospice patients, linked to the observation that around one in ten community hospital patients were admitted for investigation and active treatment. Community hospital medical notes were significantly less likely to meet minimum quality standards than were hospice notes (81/171 vs. 18/116; P < 0.001), with major deficiencies in the areas of examination, progress reporting, and absence of confirmation of death. CONCLUSIONS: This study confirms the role of community hospitals in palliative terminal cancer care. Differences in care between community hospitals and a hospice have been demonstrated that may reflect either different admission populations to each setting or differences in the way care was delivered.

Hospices↗
PubMed1998

Dying from cancer in community hospitals or a hospice: closest lay carers' perceptions.

BACKGROUND: Despite there being around 400 community hospitals in the United Kingdom, there is little published research on the quality of service provided by these hospitals. AIM: To compare the quality of terminal cancer care in community hospitals with a hospice as assessed by patients' closest lay carer (relative or friend). METHOD: Structured interview (or questionnaire based on the interview proforma) with closest lay carers of all patients dying over one year in 12 community hospitals in east Devon and a purpose-built hospice in the city of Exeter. RESULTS: A total of 292 cases (176 in community hospitals and 116 in a hospice) were identified, resulting in 238 carers being eligible for interview or questionnaire survey. Overall, 106 successful interviews and 55 questionnaires were completed, giving a response rate of 67.6%. Carers gave a near unanimous vote of excellence for the total care given by the hospice, while around 40% of carers of patients in community hospitals considered that improvements were possible. Community hospitals attracted more negative comments than hospices, with criticism being directed at problems of communication, lack of nursing staff, and lack of support in bereavement. Carers of hospice patients were significantly more likely to be present at the time of death than those of community hospital patients [45/70 (64%) vs. 31/89 (35%); chi 2 = 13.6, P < 0.001], an observation possibly because nursing staff in community hospitals are less experienced at dealing with terminally ill patients and such hospitals have fewer adequate facilities. CONCLUSIONS: Lay carers indicated great satisfaction with care given in the hospice and less satisfaction with care given in the community hospitals. However, the community hospitals are non-specialist units with far lower levels of trained staff. Improvements in terms of the communication skills of doctors and nurses, specific training for nurses in palliative care, and structured bereavement care could be made without necessarily increasing staffing numbers.

Attitude to Health↗
PubMed1998

An organizational model of choice: a theoretical analysis differentiating choice, personal control, and self-determination.

Individuals experience choice when they select one option from among meaningful alternatives that possess relatively equal attractiveness and some degree of indeterminacy. Choice has been found to influence important psychological and behavioral outcomes. After differentiating among choice, personal control, and self-determination, the author offers a model of choice, with self-determination as the key mechanism regulating how choice influences intrinsic motivation. The model suggests specific types of choice-relevant information that should affect whether choice results in an internal (self-determined) or external (controlled) locus of causality. The individual characteristics of locus of control, self-presentation, self-esteem, and Type A personality are suggested as possible moderators of the effects of choice. Finally, the implications of the choice model for organizations and further areas of research are discussed.

Choice Behavior↗
PubMed1997

Fast events in protein folding: relaxation dynamics and structure of the I form of apomyoglobin.

The fast relaxation dynamics of the acid destabilized I form of apomyoglobin (pH* 3, 0.15 M NaCl; apoMb-I) following a laser-induced temperature-jump have been probed using time-resolved infrared spectroscopy. Only a fast, single exponential phase is observed (bleach centered at v = 1633 cm-1 and transient absorbance at 1666 cm-1) with relaxation times of 38 ns at 30 degrees C and 36 ns at 57 degrees C; no additional slow (microsecond) phase is observed as previously found in the native form of apomyoglobin. Folding times of approximately 66 ns are derived from the observed rates based on a simple two-state model. The equilibrium melting of the 1633 cm-1 component shows noncooperative linear behavior over the temperature range studied (10-60 degrees C). The low amide I' frequency, the fast relaxation dynamics, and the noncooperative melting behavior are characteristic of isolated solvated helix. The analysis of the amide-I' band reveals another major component at 1650 cm-1 assigned to native-like structure stabilized by tertiary contacts involving the AGH core, which does not show dynamic or static melting under our conditions. ApoMb-I has generally been taken to be a "molten globule" species. The present results indicate a heterogeneous structure consisting of separate regions of native-like unit(s), solvated helices, and disordered coil, excluding a homogeneous molten globule as a model for apoMb-I. From the current studies and other results, a detailed model of the folding of apomyoglobin is presented.

Apoproteins↗
PubMed1997

Evidence for multiple promoters of the human IL-5 receptor alpha subunit gene: a novel 6-base pair element determines cell-specific promoter function.

In addition to a previously characterized promoter (P1), we now show the existence of a second promoter for the human IL-5Ralpha gene. Initially, a genomic region (P2) 5' upstream of human IL-5Ralpha exon 2 was cloned by an inverted PCR. The transcriptional start site was then mapped to a deoxycytidine (C) residue within P2 by analyzing cellular mRNA with both the 5' rapid amplification of cDNA end-PCR and S1 nuclease protection assays. Transfection of eosinophilic HL-60 cells with reporter gene constructs in which either P1 or P2 was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene resulted in CAT expression; little or no CAT expression occurred in other myeloid and nonmyeloid cell lines. Deletion studies showed that a 66-bp region, ranging from -31 to +35, was sufficient to promote CAT expression in eosinophilic HL-60 cells. Analysis of linker-scanning mutants identified a novel 6-bp element (5' CTAATT 3') spanning -19 to -14 that was essential for P2 promoter activity. In electrophoretic mobility shift assays, a P2 region from -31 to +1 containing the unique 6-bp element, when used as a probe, formed a complex with a protein(s) that was found only in the eosinophilic cell line. This binding activity was lost upon replacement of the 6-bp element with a 6-bp linker, suggesting that this element likely serves as the binding site for an eosinophilic HL-60 cell-specific transcription factor(s). Together, these data suggest an important role for P2 promoter in the regulation of eosinophil-specific expression of the human IL-5 receptor alpha gene.

Base Sequence↗
PubMed1997

Family history and risk of breast cancer in New Zealand.

A national population-based case-control study was used to assess the influence on breast cancer risk of a family history of the disease and the possibility of an interaction with reproductive risk factors. A total of 891 women aged 25-54 years with a first diagnosis of breast cancer and 1,864 control subjects randomly selected from the electoral rolls were interviewed. Age-adjusted relative risks (RR) of breast cancer were similar for mothers (RR = 2.3) and sisters (RR = 2.7) but somewhat higher for first-degree (RR = 2.6) than for second-degree (RR = 1.7) relatives. Cases reporting a first- or second-degree relative with breast cancer were no more likely to be diagnosed at an early age than those with no family history. With regard to the age at diagnosis of the relative, the RR was higher if breast cancer had been diagnosed before the age of 45 years than later; this was true for first-degree as well as for second-degree relatives. In women with no family history, the falling RRs with increasing age at menarche reflected the usual pattern, but no such trend was apparent in those reporting a mother or sister with breast cancer. For age at first full-term pregnancy, parity, breast-feeding, menopausal status, infertility, history of benign breast disease and body mass index, no evidence was seen of effect modification by a family history of breast cancer. Mothers of cases had about twice the cumulative rate of breast cancer as mothers of controls, a similar difference being seen between sisters of cases and sisters of controls.

Adult↗
PubMed1997

Charter mark.

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Health Care Reform↗
PubMed1997

Distinct contributions of high- and low-voltage-activated calcium currents to afterhyperpolarizations in cholinergic nucleus basalis neurons of the guinea pig.

The contributions made by low- (LVA) and high-voltage-activated (HVA) calcium currents to afterhyperpolarizations (AHPs) of nucleus basalis (NB) cholinergic neurons were investigated in dissociated cells. Neurons with somata >25 microM were studied because 80% of them stained positively for choline acetyltransferase and had electrophysiological characteristics identical to those of cholinergic NB neurons previously recorded in basal forebrain slices. Calcium currents of cholinergic NB neurons first were dissected pharmacologically into an amiloride-sensitive LVA and at least five subtypes of HVA currents. Approximately 17% of the total HVA current was sensitive to nifedipine (3 microM), 35% to omega-conotoxin-GVIA (200-400 nM), 10% to omega-Agatoxin-IVA (100 nM), and 20% to omega-Agatoxin-IVA (300-500 nM), suggesting the presence of L-, N-, P-, and Q-type channels, respectively. A remaining current (R-type) resistant to these antagonists was blocked by cadmium (100-200 microM). We then assessed pharmacologically the role that LVA and HVA currents had in activating the apamin-insensitive AHP elicited by a long train of action potentials (sAHP) and the AHP evoked either by a short burst of action potentials or by a single action potential (mAHP) that is known to be apamin-sensitive. During sAHPs, approximately 60% of the hyperpolarization was activated by calcium flowing through N-type channels and approximately 20% through P-type channels, whereas T-, L-, and Q-type channels were not involved significantly. In contrast, during mAHPs, N- and T-type channels played key roles (approximately 60 and 30%, respectively), whereas L-, P-, and Q-type channels were not implicated significantly. It is concluded that in cholinergic NB neurons various subtypes of calcium channels can differentially activate the apamin-sensitive mAHP and the apamin-insensitive sAHP.

Action Potentials↗
PubMed1997

Sequencing of the cholesteryl ester transfer protein 5' regulatory region using artificial transposons.

We have isolated and sequenced genomic clones encompassing more than 5 kb of the 5' flanking region of the cholesteryl ester transfer protein gene. This region contains multiple Alu repeats, a Mermaid repeat, and an extensive GA repeat, which made sequencing exceedingly difficult. To circumvent the problems that these repeats posed to traditional sequencing methodologies, we employed a novel transposon-facilitated technique, which greatly simplified sequencing of regions that had been difficult to accomplish otherwise. We utilized the artificial transposon, AT-2, a Bluescript derivative containing the dhfr gene and unique primer sites at both ends of the insertion DNA. Integration of the transposon occurred efficiently and covered the entire region of interest. Analysis of the sequence indicates a number of potential regulatory factor binding sites upstream of the previously characterized minimal promoter. The 5.7-kb regulatory region confers significant transcriptional activation in a conditionally transformed mouse hepatocyte line as compared to a minimal 137-bp promoter fragment. In addition, a tetranucleotide repeat of variable length that may provide a useful genetic marker has been identified 2 kb upstream of the CETP transcriptional start site.

Animals↗
PubMed1997

Application of asthma action plans to childhood asthma: a national survey.

AIM: To determine the frequency of asthma action plan use by doctors in the management of childhood asthma in New Zealand, and their recommendations about the application of an increased dose of inhaled steroids in those plans. METHODS: A postal survey was sent to all 236 paediatricians and paediatric registrars and to a random sample of 500 general practitioners (GPs) in New Zealand. Questions related to asthma action plan use, the inclusion of an increased dose of inhaled steroid in those plans and details of the way the inhaled steroid dose is adjusted. RESULTS: Valid responses were received from 168 (71%) paediatricians and paediatric registrars and 340 (68%) GPs. The majority (92.6%) of GPs and paediatricians and paediatric registrars used action plans and 83.6% included a step involving an increased dose of inhaled steroids. Compared with paediatricians and paediatric registrars, GPs gave action plans to a smaller proportion of asthmatic children in their care and included an increased dose of inhaled steroid more often (GPs = 94.5%, paediatricians and paediatric registrars = 57%). CONCLUSION: In New Zealand the use of asthma action plans is inconsistent with the recommendations contained in published consensus documents in that not all asthmatic children are advised about an action plan. Specific issues relating to this and to the use of an increased dose of inhaled steroids in action plans require clarification and further research.

Administration, Inhalation↗
PubMed1997

Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants.

OBJECTIVES: To determine the extent to which plasma antioxidant concentrations in people with habitual low intake of fruit and vegetables respond to increased intakes of these foods. To examine whether advice to increase fruit and vegetables will result in reduction of concentrations of total and low density lipoprotein cholesterol. DESIGN: Randomised controlled trial in which intervention and control groups were followed up for eight weeks. The intervention group was asked to consume eight servings of fruit and vegetables a day. SETTING: Dunedin, New Zealand. SUBJECTS: Eighty seven subjects with normal lipid concentrations who ate three or fewer servings of fruit and vegetables daily. MAIN OUTCOME MEASURES: Plasma concentrations of vitamin C, retinol, alpha and beta carotene, alpha tocopherol, lipids, and lipoproteins. Dietary intake assessed with diet records over four days. RESULTS: The mean plasma vitamin C, alpha carotene, and beta carotene concentrations increased in parallel with increased dietary intake of fruit and vegetables in the intervention group. Concentrations of retinol, alpha tocopherol, lipids, and lipoproteins remained unchanged despite some increase in dietary vitamin E and a small reduction in saturated fat intake. CONCLUSIONS: Following a recommendation to increase fruit and vegetable consumption produces change in plasma concentrations of vitamin C, alpha carotene, and beta carotene likely to reduce incidence of cancer. More specific dietary advice to modify fat intake may be necessary to reduce the risk of cardiovascular disease mediated by lipoprotein and vitamin E.

Adult↗
PubMed1997

Role of Tyr518 and Tyr519 in the regulation of catalytic activity and substrate phosphorylation by Syk protein-tyrosine kinase.

The Syk protein-tyrosine kinase is expressed in many hematopoietic cells and is involved in signaling from various receptors for antigen and Fc portions of IgG and IgE. After cross-linking of these receptors, Syk is rapidly phosphorylated on tyrosine residues. We have previously reported that Syk expressed in COS cells is predominantly phosphorylated at both Tyr518 and Tyr519 at its putative autophosphorylation site. In this study, we have examined the role of each of these two residues for the catalytic activity of Syk in vitro and for the Syk-induced phosphorylation of cellular proteins in intact cells. Mutation of either residue had minor effects on the catalytic activity of Syk, and even the double mutant [F518, F519]Syk was about 60% as active as the wild-type enzyme. In intact cells, however, all three mutants consistently failed to induce the extensive tyrosine phosphorylation of cellular proteins typically observed with wild-type Syk. We have recently shown that the doubly phosphorylated Y518/Y519 site is also the site for association of Syk with the SH2 domain of the Lck kinase, which suggests that although phosphates at Y518/Y519 may enhance the catalytic activity of Syk, its interaction with Src family protein-tyrosine kinases is at least equally important for the induction of downstream substrate phosphorylation.

Amino Acid Sequence↗
PubMed1997

Fast events in protein folding: relaxation dynamics of secondary and tertiary structure in native apomyoglobin.

We report the fast relaxation dynamics of "native" apomyoglobin (pH 5.3) following a 10-ns, laser-induced temperature jump. The structural dynamics are probed using time-resolved infrared spectroscopy. The infrared kinetics monitored within the amide I absorbance of the polypeptide backbone exhibit two distinct relaxation phases which have different spectral signatures and occur on very different time scales (nu = 1633 cm(-1),tau = 48 ns; nu = 1650 cm(-1),tau = 132 micros). We assign these two spectral components to discrete substructures in the protein: helical structure that is solvated (1633 cm(-1)) and native helix that is protected from solvation by interhelix tertiary interactions (1650 cm(-1)). Folding rate coefficients inferred from the observed relaxations at 60 degrees C are k(f)(solvated) = (7 to 20) x 10(6) s(-1) and k(f)(native) = 3.6 x 10(3) s(-1), respectively. The faster rate is interpreted as the intrinsic rate of solvated helix formation, whereas the slower rate is interpreted as the rate of formation of tertiary contacts that determine a native helix. Thus, at 60 degrees C helix formation precedes the formation of tertiary structure by over three orders of magnitude in this protein. Furthermore, the distinct thermodynamics and kinetics observed for the apomyoglobin substructures suggest that they fold independently, or quasi-independently. The observation of inhomogeneous folding for apomyoglobin is remarkable, given the relatively small size and structural simplicity of this protein.

Animals↗