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Biomedical subjects

P Williams

Publications and source records attributed to P Williams.

At least 109 records · Page 6Linked to original sources
PubMed2000

Early discharge following breast surgery: assessing care, support, and informational needs of women with early breast cancer in Australia.

BACKGROUND: The overall aims of the present study were to identify differences among women with early breast cancer who were discharged early from the hospital (within 48 h) and those who remained for routine admission in relation to demographic variables, informational needs, supportive needs, complications and satisfaction with care. METHODS: A random sample of 544 women diagnosed with early breast cancer was recruited to participate in a telephone survey via State and Territory cancer registries. RESULTS: Findings revealed little significant difference among women participating in early discharge and routine care in relation to demographics variables, informational needs, complication and satisfaction with care. Women participating in early discharge, however, were significantly less likely to be seen by a specialist breast care nurse or a volunteer with breast cancer. CONCLUSIONS: Prior to establishing early discharge as routine care, it is essential to establish clear health policy relating to early discharge and adequate follow-up services for women with breast cancer.

Aftercare↗
PubMed2000

Goals and strategies for teaching death and dying in medical schools.

Teaching medical students to respond to needs of the dying represents an important challenge for medical educators. This article describes the goals and objectives that should be identified before medical schools can meet this challenge, as well as strategies that, when implemented, will provide students with the necessary knowledge, skills, and attitudes to meet the needs of the dying patients. The goals and objectives were identified through a modified group consensus process developed during Choice In Dying's 5-year project "Integrating Education on Care of the Dying into Medical Schools." The authors have diverse experiences and backgrounds and are actively involved in death and dying teaching at 11 medical schools. They conclude that after accepting the goals and objectives, key medical school faculty can work cooperatively to develop strategies to integrate them into the school's curriculum. Without first establishing a set of goals and objectives and developing evaluation methods, medical schools could miss their mark in fostering the student's ability to care for the dying.

Journal Article↗
PubMed2000

How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)

OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives. METHODS: The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease-modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work. RESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0). CONCLUSIONS: Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.

Adult↗
PubMed2000

Viewpoint dependence and object discriminability.

In an attempt to reconcile results of previous studies, several theorists have suggested that object recognition performance should range from viewpoint invariant to highly viewpoint dependent depending on how easy it is to differentiate the objects in a given recognition situation. The present study assessed recognition across depth rotations of a single general class of novel objects in three contexts that varied in difficulty. In an initial experiment, recognition in the context involving the most discriminable object differences was viewpoint invariant, but recognition in the least discriminable context and recognition in the intermediate context were equally viewpoint dependent. In a second experiment, utilizing gray-scale versions of the same stimuli, almost identical viewpoint-cost functions were obtained in all three contexts. These results suggest that differences in the geometry of stimulus objects, rather than task difficulty, lie at the heart of previously discrepant findings.

Adult↗
PubMed2000

Aboriginal deaths in Western Australia: 1985-89 and 1990-94.

OBJECTIVE: To examine death data for Aboriginal and non-Aboriginal persons in Western Australia (WA) in 1985-89 and 1990-94. METHODS: Population estimates were provided by the Health Information Centre of the WA Health Department based on data from the Australian Bureau of Statistics (ABS). Death data came from the WA Registrar-General's Office. Standard methods were used to obtain rates and levels of significance. RESULTS: Main causes of deaths among Aboriginal males in 1990-94 were circulatory conditions, respiratory, injury and poisoning, neoplasms and endocrine diseases; in Aboriginal females they were circulatory, neoplasms, endocrine diseases, respiratory diseases, and injury and poisoning. From 1985-89 to 1990-94, the Aboriginal male all-cause age-standardised death rates fell 3% (ns) while the non-Aboriginal male rate fell 11% (p < 0.05). The Aboriginal female all-cause death rate rose 11% (ns) while the non-Aboriginal rate fell 5% (p < 0.05). The all-cause death rate ratio (Aboriginal:non-Aboriginal) changed from 2.4 to 2.6 (males) and 2.5 to 2.9 (females). There was a major increase in deaths from endocrine diseases among Aborigines and non-Aborigines. This increase was proportionally much greater among Aborigines. In non-Aborigines there was a significant decrease in deaths from circulatory diseases (mainly ischaemic heart disease); this did not occur among Aborigines. CONCLUSIONS: Over the study period, Aboriginal health standards, as reflected by death rates, apparently worsened relative to non-Aboriginal standards. IMPLICATIONS: Better health promotion, disease prevention and disease care are required to help achieve acceptable health standards among Aboriginal peoples.

Adolescent↗
PubMed2000

Molecular cloning and analysis of a putative siderophore ABC transporter from Staphylococcus aureus.

From a mass-excised Staphylococcus aureus lambdaZapII expression library, we cloned an operon encoding a novel ABC transporter with significant homology to bacterial siderophore transporter systems. The operon encodes four genes designated sstA, -B, -C, and -D encoding two putative cytoplasmic membrane proteins (sstA and sstB), an ATPase (sstC), and a membrane-bound 38-kDa lipoprotein (sstD). The sst operon is preceded by two putative Fur boxes, which indicated that expression of the sst operon was likely to be iron dependent. SstD was overexpressed in Escherichia coli, purified by Triton X-114 phase partitioning, and used to generate monospecific antisera in rats. Immunoblotting studies located SstD in the membrane fraction of S. aureus and showed that expression of the lipoprotein was reduced under iron-rich growth conditions. Triton X-114 partitioning studies on isolated membranes provided additional biochemical evidence that SstD in S. aureus is a lipoprotein. Immunoreactive polypeptides of approximately 38 kDa were detected in a wide range of staphylococcal species, but no antigenic homolog was detected in Bacillus subtilis. Expression of SstD in vivo was confirmed by immunoblotting studies with S. aureus recovered from a rat intraperitoneal chamber implant model. To further define the contribution of SstD in promoting growth of S. aureus in vitro and in vivo, we used antisense RNA technology to modulate expression of SstD. Expression of antisense sstD RNA in S. aureus resulted in a decrease in SstD expression under both iron-rich and iron-restricted growth conditions. However, this reduction in SstD levels did not affect the growth of S. aureus in vitro in an iron-limited growth medium or when grown in an intraperitoneal rat chamber implant model in vivo.

ATP-Binding Cassette Transporters↗
PubMed2000

The Pseudomonas aeruginosa lectins PA-IL and PA-IIL are controlled by quorum sensing and by RpoS.

In Pseudomonas aeruginosa, many exoproduct virulence determinants are regulated via a hierarchical quorum-sensing cascade involving the transcriptional regulators LasR and RhlR and their cognate activators, N-(3-oxododecanoyl)-L-homoserine lactone (3O-C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL). In this paper, we demonstrate that the cytotoxic lectins PA-IL and PA-IIL are regulated via quorum sensing. Using immunoblot analysis, the production of both lectins was found to be directly dependent on the rhl locus while, in a lasR mutant, the onset of lectin synthesis was delayed but not abolished. The PA-IL structural gene, lecA, was cloned and sequenced. Transcript analysis indicated a monocistronic organization with a transcriptional start site 70 bp upstream of the lecA translational start codon. A lux box-type element together with RpoS (sigma(S)) consensus sequences was identified upstream of the putative promoter region. In Escherichia coli, expression of a lecA::lux reporter fusion was activated by RhlR/C4-HSL, but not by LasR/3O-C12-HSL, confirming direct regulation by RhlR/C4-HSL. Similarly, in P. aeruginosa PAO1, the expression of a chromosomal lecA::lux fusion was enhanced but not advanced by the addition of exogenous C4-HSL but not 3O-C12-HSL. Furthermore, mutation of rpoS abolished lectin synthesis in P. aeruginosa, demonstrating that both RpoS and RhlR/C4-HSL are required. Although the C4-HSL-dependent expression of the lecA::lux reporter in E. coli could be inhibited by the presence of 3O-C12-HSL, this did not occur in P. aeruginosa. This suggests that, in the homologous genetic background, 3O-C12-HSL does not function as a posttranslational regulator of the RhlR/C4-HSL-dependent activation of lecA expression.

Adhesins, Bacterial↗
PubMed2000

Ultra-low wear rates for rigid-on-rigid bearings in total hip replacements.

With the increased clinical interest in metal-on-metal and ceramic-on-ceramic total-hip replacements (THRs), the objective of this hip simulator study was to identify the relative wear ranking of three bearing systems, namely CoCr-polyethylene (M-PE), CoCr-CoCr (M-M) and ceramic-on-ceramic (C-C). Volumetric wear rates were used as the method of comparison. The seven THR groupings included one M-PE study, two M-M studies and four C-C studies. Special emphasis was given to defining the 'run-in' phase of accelerated wear that rigid-on-rigid bearings generally exhibit. The hypothesis was that characterization of the run-in and steady state wear phases would clarify not only the tribological performance in vitro but also help correlate these in vitro wear rates with the 'average' wear rates measured on retrieved implants. The implant systems were studied on multichannel hip simulators using the Paul gait cycle and bovine serum as the lubricant. With 28 mm CoCr heads, the PE (2.5 Mrad/N2) wear rates averaged 13 mm3/10(6) cycles duration. This was considered a low value compared with the clinical model of 74 mm3/year (for 28 mm heads). Our later studies established that this low laboratory value was a consequence of the serum parameters then in use. The mating CoCr heads (with PE cups) wore at the steady state rate of 0.028 mm3/10(6) cycles. The concurrently run Metasul M-M THRs wore at the steady state rate of 0.119 mm3/10(6) cycles with high-protein serum. In the second Metasul M-M study with low-protein serum, the THR run-in rate was 2.681 mm3/10(6) cycles and steady state was 0.977 mm3/10(6) cycles. At 10 years, these data would predict a 70-fold reduction in M-M wear debris compared with the clinical PE wear model. All M-M implants exhibited biphasic wear trends, with the transition point at 0.5 x 10(6) cycles between run-in and steady state phases, the latter averaging a 3-fold decrease in wear rate. White surface coatings on implants (coming from the serum solution) were a confounding factor but did not obscure the two orders of magnitude wear performance improvement for CoCr over PE cups. The liners in the alumina head-alumina cup combination wore at the steady state rate of 0.004 mm3/10(6) cycles over 14 x 10(6) cycles duration (high-protein serum). The zirconia head-alumina cup THR combination wore at 0.174 and 0.014 mm3/10(6) cycles for run-in and steady state rates respectively (low-protein serum). The zirconia head and cup THR combination wore slightly higher initially with 0.342 and 0.013 mm3/10(6) cycles for run-in and steady state rates respectively. Other wear studies have generally predicted catastrophic wear for such zirconia-ceramic combinations. It was noted that the zirconia wear trends were frequently masked by the effects of tenacious white surface coatings. It was possible that these coatings protected the zirconia surfaces somewhat in this simulator study. The experimental ceramic Crystaloy THR had the highest ceramic run-in wear at 0.681 mm3/10(6) cycles and typical 0.016 mm3/10(6) cycles for steady state. Since these implants represented the first Crystaloy THR sets made, it was likely that the surface conditions of this high-strength ceramic could be improved in the future. Overall, the ceramic THRs demonstrated three orders of magnitude wear performance improvement over PE cups. With zirconia implants, while the cup wear was sometimes measurable, head wear was seldom discernible. Therefore, we have to be cautious in interpreting such zirconia wear data. Identifying the run-in and steady state wear rates was a valuable step in processing the ceramic wear data and assessing its reliability. Thus, the M-M and C-C THRs have demonstrated two to three orders of reduction in volumetric wear in the laboratory compared with the PE wear standard, which helps to explain the excellent wear performance and minimal osteolysis seen with such implants at retrieval operations.

Aluminum Oxide↗
PubMed2000

A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma.

The use of interleukin-2 (IL-2) and interferon-alpha (IFNalpha) in combination with chemotherapy for the treatment of advanced malignant melanoma has generated considerable interest. In particular, the relatively high number of durable complete responses has suggested this may be a significant advance in the treatment of malignant melanoma. We report our experience at the University of Colorado in 43 patients, including many with poor prognostic factors. Patients received cisplatin 20 mg/m2 on days 1-4, vinblastine 1.6 mg/m2 on days 1-4, dacarbazine 800 mg/m2 on day 1, IL-2 9 x 10(6) IU/m2 per day intravenously over 24h on days 1-4 and IFNalpha 5 x 10(6) IU/m2 per day subcutaneously on days 1-5 every 3 weeks. The median follow-up for all patients was 34 months. Responses were seen in 20 patients (47%, 95% confidence interval 31-62%) and comprised five complete responses (CRs) (12%) and 15 partial responses (PRs) (35%). Two patients achieving a CR remain disease free at 45 and 47 months follow-up. In addition three patients who obtained a surgical CR and another with only minor residual changes on computed tomography scan have not progressed at 27, 30, 40 and 27 months, respectively. Toxicity was manageable, but all patients had at least one grade 3 or 4 toxicity, predominantly hypotension and neutropenia. There were no treatment-related deaths. In conclusion, the response rate and duration is within the range previously reported for biochemotherapy. The results of ongoing randomized studies are awaited to better define the value of biochemotherapy in the treatment of advanced melanoma.

Abdominal Neoplasms↗
PubMed2000

Repeat prescribing: a role for community pharmacists in controlling and monitoring repeat prescriptions.

BACKGROUND: Traditional systems of managing repeat prescribing have been criticised for their lack of clinical and administrative controls. AIM: To compare a community pharmacist-managed repeat prescribing system with established methods of managing repeat prescribing. METHOD: A randomised controlled intervention study (19 general medical practices, 3074 patients, 62 community pharmacists). Patients on repeat medication were given sufficient three-monthly scripts, endorsed for monthly dispensing, to last until their next clinical review consultation with their general practitioner (GP). The scripts were stored by a pharmacist of the patient's choice. Each monthly dispensing was authorised by the pharmacist, using a standard protocol. The cost of the drugs prescribed and dispensed was calculated. Data on patient outcomes were obtained from pharmacist-generated patient records and GP notes. RESULTS: A total of 12.4% of patients had compliance problems, side-effects, adverse drug reactions, or drug interactions identified by the pharmacist. There were significantly more problems identified in total in the intervention group. The total number of consultations, deaths, and non-elective hospital admissions was the same in both groups. Sixty-six per cent of the study patients did not require their full quota of prescribed drugs, representing 18% of the total prescribed costs (estimated annual drug cost avoidance of 43 Pounds per patient). CONCLUSION: This system of managing repeat prescribing has been demonstrated to be logistically feasible, to identify clinical problems, and to make savings in the drugs bill.

Adolescent↗
PubMed2000

Pressure support and pressure assist/control: are there differences? An evaluation of the newest intensive care unit ventilators.

BACKGROUND: Pressure support (PS) has been widely studied in both patients and lung models, but there is little data available evaluating pressure assist/control (P A/C, frequently referred to as PCV) and no data comparing the operational capabilities of these two modes on the newest generation of ICU ventilators. We used a spontaneously breathing lung model to evaluate the response of the following new generation ventilators to varying inspiratory demand in both PS and P A/C: Bear 1000, Dräger Evita 4, Hamilton Galileo, Nellcor Puritan-Bennett 840 and 740, Siemens Servo 300A, TBird AVS. METHODS: A bellows-in-a-box lung model was set at a respiratory rate of 12 breaths/min, inspiratory time of 1.0 second, and peak inspiratory flows (modified square wave) of 40, 60, and 80 L/min. Each ventilator was set at three levels of PS and P A/C: 10, 15, and 20 cm H(2)O. On all ventilators, flow-triggering was set as sensitive as possible without causing self-triggering. RESULTS: Trigger pressure, trigger pressure-time product, inspiratory trigger time delay, ventilator-delivered peak flow, inspiratory area as a percent of the ideal inspiratory area, expiratory time delay, supraplateau expiratory pressure change, and expiratory area all varied among ventilators and at different lung model peak flows (p < 0.01 and >/= 10% difference). However, PS and P A/C on a given ventilator only differed with regard to expiratory variables (p < 0. 01 and >/= 10% difference). CONCLUSION: In a given ventilator little difference exists in gas delivery and response variables between PS and P A/C, but performance differences do exist among the ventilators evaluated. Ventilator performance is diminished at high lung model peak flows and low pressure settings. (I)), whereas PS gives control over ending inspiration to the patient. What has not been clearly defined is the gas delivery and ventilator response differences, if any, between these two (PS and P A/C) pressure targeted assist modes. Most new generation intensive care unit (ICU) ventilators provide both pressure support (PS) and pressure assist/control (P A/C) ventilation.19,20 The specific operational difference between these two modes is the mechanism that transitions inspiration to expiration. With pressure support the primary mechanism is a decrease in peak inspiratory flow to a predetermined level, whereas with P A/C mechanical T(I) is preset.19,20 We compared the operation of seven of the newest generation ICU ventilators in a spontaneously breathing lung model in both PS and P A/C. We hypothesized that there would be no difference in variables assessed between PS and P A/C except for the transition to expiration and that there would be no difference in response among ventilators evaluated.

Equipment Safety↗
PubMed1999

Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors.

OBJECTIVE: To summarise quantitatively the association between moderate alcohol intake and biological markers of risk of coronary heart disease and to predict how these changes would lower the risk. DESIGN: Meta-analysis of all experimental studies that assessed the effects of moderate alcohol intake on concentrations of high density lipoprotein cholesterol, apolipoprotein A I, fibrinogen, triglycerides, and other biological markers previously found to be associated with risk of coronary heart disease. PARTICIPANTS: Men and women free of previous chronic disease and who were not dependent on alcohol. Studies were included in which biomarkers were assessed before and after participants consumed up to 100 g of alcohol a day. INTERVENTIONS: Alcohol as ethanol, beer, wine, or spirits. MAIN OUTCOME MEASURES: Changes in concentrations of high density lipoprotein cholesterol, apolipoprotein A I, Lp(a) lipoprotein, triglycerides, tissue type plasminogen activator activity, tissue type plasminogen activator antigen, insulin, and glucose after consuming an experimental dose of alcohol for 1 to 9 weeks; a shorter period was accepted for studies of change in concentrations of fibrinogen, factor VII, von Willebrand factor, tissue type plasminogen activator activity, and tissue type plasminogen activator antigen. RESULTS: 61 data records were abstracted from 42 eligible studies with information on change in biological markers of risk of coronary heart disease. An experimental dose of 30 g of ethanol a day increased concentrations of high density lipoprotein cholesterol by 3.99 mg/dl (95% confidence interval 3.25 to 4.73), apolipoprotein A I by 8.82 mg/dl (7.79 to 9.86), and triglyceride by 5.69 mg/dl (2.49 to 8.89). Several haemostatic factors related to a thrombolytic profile were modestly affected by alcohol. On the basis of published associations between these biomarkers and risk of coronary heart disease 30 g of alcohol a day would cause an estimated reduction of 24.7% in risk of coronary heart disease. CONCLUSIONS: Alcohol intake is causally related to lower risk of coronary heart disease through changes in lipids and haemostatic factors.

Alcohol Drinking↗
PubMed1999

Regulation of learning by EphA receptors: a protein targeting study.

EphA family receptor tyrosine kinases and their ephrin-A ligands are involved in patterning axonal connections during brain development, but until now a role for these molecules in the mature brain had not been elucidated. Here, we show that both the EphA5 receptor and its ephrin-A ligands (2 and 5) are expressed in the adult mouse hippocampus, and the EphA5 protein is present in a phosphorylated form. Because there are no pharmacological agents available for EphA receptors, we designed recombinant immunoadhesins that specifically bind to the receptor binding site of the ephrin-A ligand (antagonist) or the ligand binding site of the EphA receptor (agonist) and thus target EphA function. We demonstrate that intrahippocampal infusion of an EphA antagonist immunoadhesin leads to impaired performance in two behavioral paradigms, T-maze spontaneous alternation and context-dependent fear conditioning, sensitive to hippocampal function, whereas activation of EphA by infusion of an agonist immunoadhesin results in enhanced performance on these tasks. Because the two behavioral tasks have different motivational, perceptual, and motor requirements, we infer the changes were not caused by these performance factors but rather to cognitive alterations. We also find bidirectional changes in gene expression and in electrophysiological measures of synaptic efficacy that correlate with the behavioral results. Thus, EphA receptors and their ligands are implicated as mediators of plasticity in the adult mammalian brain.

Animals↗
PubMed1999

Effect of rate of distraction on loss of range of joint movement, muscle stiffness, and intramuscular connective tissue content during surgical limb-lengthening: a study in the rabbit.

Surgical lengthening of limbs often results in loss of range of joint movement and this has been shown to be associated with an increase in passive tension and an increase in collagen content of the muscles. In this study, we have investigated the length/tension properties and the connective tissue component of muscle distracted at three different rates in order to determine whether low rates of distraction would enable the connective tissue component, as well as the contractile component (number of serial sarcomeres), to adapt more completely to the increased functional length of the muscle and thus lead to improved range of joint movement. It was found that loss of range of movement varied with rate of distraction. At the low rate, there was no change in the passive tension or collagen content compared to muscles from sham-operated animals, and range of movement was significantly greater than at the other rates. At the medium rate, although the muscles showed good adaptation in terms of serial sarcomere number, passive tension and collagen content was increased and range of movement reduced, indicating that changes in the connective tissue component are important factors in loss of joint movement. In the case of muscle distracted at a high rate, failure of the muscle fibres to add on sufficient sarcomeres, combined with changes in the connective tissue, resulted in almost total loss of joint movement.

Animals↗