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Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 55 records · Page 3Linked to original sources
PubMed2004

Safety of telephone consultation for "non-serious" emergency ambulance service patients.

OBJECTIVE: To assess the safety of nurses and paramedics offering telephone assessment, triage, and advice as an alternative to immediate ambulance dispatch for emergency ambulance service callers classified by lay call takers as presenting with "non-serious" problems (category C calls). DESIGN: Data for this study were collected as part of a pragmatic randomised controlled trial reported elsewhere. The intervention arm of the trial comprised nurse or paramedic telephone consultation using a computerised decision support system to assess, triage, and advise patients whose calls to the emergency ambulance service had been classified as "non-serious" by call takers applying standard priority dispatch criteria. A multidisciplinary expert clinical panel reviewed data from ambulance service, accident and emergency department, hospital inpatient and general practice records, and call transcripts for patients triaged by nurses and paramedics into categories that indicated that dispatch of an emergency ambulance was unnecessary. All cases for which one or more members of the panel rated that an emergency ambulance should have been dispatched were re-reviewed by the entire panel for an assessment of the "life risk" that might have resulted. SETTING: Ambulance services in London and the West Midlands, UK. STUDY POPULATION: Of 635 category C patients assessed by nurses and paramedics, 330 (52%) cases that had been triaged as not requiring an emergency ambulance were identified. MAIN OUTCOME MEASURES: Assessment of safety of triage decisions. RESULTS: Sufficient data were available from the routine clinical records of 239 (72%) subjects to allow review by the specialist panel. For 231 (96.7%) sets of case notes reviewed, the majority of the panel concurred with the nurses' or paramedics' triage decision. Following secondary review of the records of the remaining eight patients, only two were rated by the majority as having required an emergency ambulance within 14 minutes. For neither of these did a majority of the panel consider that the patient would have been at "life risk" without an emergency ambulance being immediately dispatched. However, the transcripts of these two calls indicated that the correct triage decision had been communicated to the patient, which suggests that the triage decision had been incorrectly entered into the decision support system. CONCLUSIONS: Telephone advice may be a safe method of managing many category C callers to 999 ambulance services. A clinical trial of the full implementation of this intervention is needed, large enough to exclude the possibility of rare adverse events.

Ambulances↗
PubMed2004

Insulin-like growth factor-I receptor signalling and acquired resistance to gefitinib (ZD1839; Iressa) in human breast and prostate cancer cells.

De novo and acquired resistance to the anti-tumour drug gefitinib (ZD1839; Iressa), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been reported. We have determined whether signalling through the IGF-I receptor (IGF-1R) pathway plays a role in the gefitinib-acquired resistance phenotype. Continuous exposure of EGFR-positive MCF-7-derived tamoxifen resistant breast cancer cells (TAM-R) to 1 microM gefitinib resulted in a sustained growth inhibition (90%) for 4 months before the surviving cells resumed proliferation. A stable gefitinib-resistant subline (TAM/TKI-R) was established after a further 2 months and this showed no detectable basal phosphorylated EGFR activity. Compared with the parental TAM-R cells, the TAM/ TKI-R cells demonstrated (a) elevated levels of activated IGF-1R, AKT and protein kinase C (PKC)delta, (b) an increased sensitivity to growth inhibition by the IGF-1R TKI AG1024 and (c) an increased migratory capacity that was reduced by AG1024 treatment. Similarly, the EGFR-positive androgen-independent human prostate cancer cell line DU145 was also continuously challenged with 1 microM gefitinib and, although substantial growth inhibition (60%) was seen initially, a gefitinib-resistant variant (DU145/TKI-R) developed after 3 months. Like their breast cancer counterparts, the DU145/TKI-R cells showed increases in the levels of components of the IGF-1R signalling pathway and an elevated sensitivity to growth inhibition by AG1024 compared with the parent DU145 cell line. Additionally, DU145/TKI-R cell migration was also decreased by this inhibitor. We have therefore concluded that in breast and prostate cancer cells acquired resistance to gefitinib is associated with increased signalling via the IGF-1R pathway, which also plays a role in the invasive capacity of the gefitinib-resistant phenotype.

Antineoplastic Agents↗
PubMed2004

Pulpitis induction in baboon primary teeth using carious dentine or Streptococcus mutans.

The objective of this equivalency study was to see if a colony of Streptococcus mutans placed into cavities in primary molar teeth produced pulpitis similar to an established pulpitis induction method using carious dentine. In two juvenile baboons (Papio ursinus), occlusal cavities were cut in all 16 primary molar teeth, followed by making a small pulpal exposure after which the cavity was swabbed with 37 per cent phosphoric acid. In one half of the teeth, fresh soft human carious dentine was placed over the pulpal exposure; in the remaining teeth the exposure was covered with a colony of Streptococcus mutans in agar. All the cavities were restored with unlined light-cured composite resin. After 14 days specimens were harvested and examined under the light microscope with the examiner blind to the induction method. In both groups of teeth there was recognisable pulp, hyperaemia, micro-abscesses in the pulp and peri-apical abscesses. Reactions to soft caries were more severe than to Streptococcus mutans. The results show that Streptococcus mutans placed in a cavity with an exposure produces comparable pulpitis to fresh soft human carious dentine in the same type of cavity and that both methods produce pulpitis suitable for testing pulpotomy or pulpectomy treatments.

Abscess↗
PubMed2004

Zinc oxide-eugenol and calcium hydroxide pulpectomies in baboon primary molars: histological responses.

AIM: To compare histological responses to zinc oxide-eugenol (ZOE) and calcium hydroxide (CH) pulpectomies in primary molar teeth with inflamed pulps. STUDY DESIGN: This was an experimental study in 17 juvenile baboons (Papio ursinus). METHODS: Pulpitis was induced with fresh human carious dentine or Streptococcus mutans placed into occlusal cavities in 78 primary molars; after 14 days a pulpectomy was performed on the same primary molars with the two root fillings randomly allocated. The root canal openings were then covered with IRM and the cavity filled with amalgam. After 90 days specimens were harvested and examined under the light microscope with the examiner blind to the treatment. RESULTS: Reaction frequencies in the ZOE-treated versus CH-treated teeth were: no recognisable pulp 89% and 82%, internal root resorption 0% and 1%, external root resorption 11% and 24%, presence of bacteria 5% and 18%, periapical abscesses 24% and 52%. STATISTICS: Fisher's exact probability test showed a statistically significant higher prevalence of periapical abscesses in the CH-treated group (P=0.03, relative risk 2.2). CONCLUSIONS: ZOE pulpectomy is preferred to CH for the treatment of infected pulps in primary molars.

Animals↗
PubMed2003

Widely expressed transcripts for chemokine receptor CXCR1 in identified glutamatergic, gamma-aminobutyric acidergic, and cholinergic neurons and astrocytes of the rat brain: a single-cell reverse transcription-multiplex polymerase chain reaction study.

Increasing evidence suggests that the chemokine interleukin (IL)-8/CXCL8 plays important roles in CNS development, neuronal survival, modulation of excitability, and neuroimmune response. Recently, we have shown that CXCL8 can acutely modulate ion channel activity in septal neurons expressing receptors CXCR1 and/or CXCR2. This was a surprising finding, insofar as CXCR1 expression had not been described for the mammalian brain. Here we investigated whether CXCR1 transcripts are present in other brain regions, whether they are expressed at the single-cell level in molecularly identified neurons and astrocytes, and how they are regulated during early postnatal development. In addition, possible cellular colocalization of CXCR1 and CXCR2 transcripts was examined. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that CXCR1 mRNAs were expressed in the septum, striatum, hippocampus, cerebellum, and cortex (temporoparietal and entorhinal) at different levels and appeared to be regulated independently from CXCR2 during development. By using RT multiplex PCR on acutely dissociated cells from these brain regions, we show that CXCR1 transcripts were expressed in 83% of 84 sampled neurons displaying cholinergic (choline acetyltransferase mRNAs), gamma-aminobutyric acidergic (glutamic acid decarboxylases 65 and 67 mRNAs), or glutamatergic (vesicular glutamate transporters 1 and 2 mRNAs) phenotypes. CXCR1 and CXCR2 transcripts were colocalized in 45% of neurons sampled and also were present in some glial fibrillary acidic protein mRNA-expressing astrocytes. This is the first study to demonstrate the widespread expression of CXCR1 transcripts in the brain and suggests that CXCR1 may have hitherto unsuspected roles in neuromodulation and inflammation.

Acetylcholine↗
PubMed2003

Identification of risk factors for future fracture in patients following distal forearm fracture.

The challenge for healthcare systems around the world is delivering timely preventative strategies to subjects most likely to develop fragility fractures. The success or failure of national campaigns will be determined at local level, and many studies to date have found under-utilization of osteoporosis treatment strategies due to reduced public and healthcare professional awareness. An important link between the at-risk patients and their appropriate therapy is their identification and assessment. In the context of a medium sized secondary care provider, this study examined the efficiency of a nurse-led service for assessing women following distal forearm fracture, looking for additional risk factors for future fracture and also looking at uptake of the assessment programme among the target population. Two hundred and two women, median (range) age 69 (50-91) years presented with distal forearm fracture over a 9-month period. Fifty-four subjects did not participate in the study: they were significantly older than those who did ( P<0.002). One hundred and forty-eight subjects underwent assessment of falls risk, future hip fracture risk and calcaneal ultrasound attenuation measurement: 107 attended for assessment at the hospital and 41 required a health professional to visit at their place of residence-the latter group were significantly older ( P<0.0002). Of 148 subjects assessed, 76 (51%) had one or more risk factors for a fall: these subjects were significantly older ( P<0.0002) and more likely to have required a home visit ( P<0.002). Twenty-seven (18%) were considered at risk of a future hip fracture: again they were older and more likely to have required a home visit ( P<0.0005). Ninety-one subjects (61%) had a calcaneal ultrasound attenuation T-score below -2.0, and were referred for bone densitometry: again, they were older ( P<0.0002) and more likely to have required a home visit ( P<0.05). Bone densitometry demonstrated osteoporosis in 47 (52%) of those with low attenuation, osteopenia in 31 and normal bone density in 13. Of 76 subjects deemed to be at risk of falls, 31 (41%) had osteoporosis demonstrated on bone densitometry and of those at risk of future hip fracture, 12 (44%) had osteoporosis. Only nine (22%) subjects who received home visits had no risk factors for falls or hip fracture and normal bone density, compared to 45 (42%) of those who attended hospital. This study has demonstrated that the efficiency of a program to assess additional risk of future fracture in a population who have already fractured may be influenced by where the assessment is delivered: it may be that the patients at greatest risk did not avail of the service.

Accidental Falls↗
PubMed2003

Distinct electrophysiological properties of glutamatergic, cholinergic and GABAergic rat septohippocampal neurons: novel implications for hippocampal rhythmicity.

The medial septum-diagonal band complex (MSDB) contains cholinergic and non-cholinergic neurons known to play key roles in learning and memory processing, and in the generation of hippocampal theta rhythm. Electrophysiologically, several classes of neurons have been described in the MSDB, but their chemical identity remains to be fully established. By combining electrophysiology with single-cell RT-PCR, we have identified four classes of neurons in the MSDB in vitro. The first class displayed slow-firing and little or no Ih, and expressed choline acetyl-transferase mRNA (ChAT). The second class was fast-firing, had a substantial Ih and expressed glutamic acid decarboxylase 67 mRNA (GAD67), sometimes co-localized with ChAT mRNAs. A third class exhibited fast- and burst-firing, had an important Ih and expressed GAD67 mRNA also occasionally co-localized with ChAT mRNAs. The ionic mechanism underlying the bursts involved a low-threshold spike and a prominent Ih current, conductances often associated with pacemaker activity. Interestingly, we identified a fourth class that expressed transcripts solely for one or two of the vesicular glutamate transporters (VGLUT1 and VGLUT2), but not ChAT or GAD. Some putative glutamatergic neurons displayed electrophysiological properties similar to ChAT-positive slow-firing neurons such as the occurrence of a very small Ih, but nearly half of glutamatergic neurons exhibited cluster firing with intrinsically generated voltage-dependent subthreshold membrane oscillations. Neurons belonging to each of the four described classes were found among septohippocampal neurons by retrograde labelling. We provide results suggesting that slow-firing cholinergic, fast-firing and burst-firing GABAergic, and cluster-firing glutamatergic neurons, may each uniquely contribute to hippocampal rhythmicity in vivo.

Acetylcholine↗
PubMed2003

Comparison of the cytotoxicity of clinically relevant cobalt-chromium and alumina ceramic wear particles in vitro.

Concern over polyethylene wear particle induced aseptic loosening of metal-on-polyethylene hip prostheses has led to renewed interest in alternative materials such as metal-on-metal and alumina ceramic-on-alumina ceramic for total hip replacement. This study compared the effects of clinically relevant cobalt-chromium and alumina ceramic wear particles on the viability of U937 histiocytes and L929 fibroblasts in vitro. Clinically relevant cobalt-chromium wear particles were generated using a flat pin-on-plate tribometer. The mean size of the clinically relevant metal particles was 29.5+/-6.3 nm (range 5-200 nm). Clinically relevant alumina ceramic particles were generated in the Leeds MkII anatomical hip simulator from a Mittelmieier prosthesis using micro-separation motion. This produced particles with a bimodal size distribution. The majority (98%) of the clinically relevant alumina ceramic wear debris was 5-20 nm in size. The cytotoxicity of the clinically relevant wear particles was compared to commercially available cobalt-chromium (9.87 microm+/-5.67) and alumina ceramic (0.503+/-0.19 microm) particles. The effects of the particles on the cells over a 5 day period at different particle volume (microm(3)) to cell number ratios were tested and viability determined using ATP-Lite(TM). Clinically relevant cobalt-chromium particles 50 and 5 microm(3) per cell reduced the viability of U937 cells by 97% and 42% and reduced the viability of L929 cells by 95% and 73%, respectively. At 50 microm(3) per cell, the clinically relevant ceramic particles reduced U937 cell viability by 18%. None of the other concentrations of the clinically relevant particles were toxic. The commercial cobalt-chromium and alumina particles did not affect the viability of either the U937 histiocytes or the L929 fibroblasts.Thus at equivalent particle volumes the clinically relevant cobalt-chromium particles were more toxic then the alumina ceramic particles. This study has emphasised the fact that the nature, size and volume of particles are important in assessing biological effects of wear debris on cells in vitro.

Aluminum↗
PubMed2003

Evaluating the influence of implicit models of mental disorder on processes of shared decision making within community-based multi-disciplinary teams.

This paper reports findings from a qualitative study concerning the influence of implicit models of mental disorder on shared decision making within community-based mental health teams. One-hundred participants representing five distinct multi-agency groups: psychiatrists, community psychiatric nurses, approved social workers, patients and informal carers operating within Leicestershire, England were interviewed using a standard case vignette describing a person whose behaviour suggests he may have schizophrenia. The results showed that each of the study's multi-agency groups implicitly supports a complex range of model dimensions regarding the nature of schizophrenia, the appropriateness of specific forms of treatment and care, and their respective rights and obligations towards each other. The influence of these implicit model patterns on processes of shared decision making are discussed through evaluating their contribution to our understanding of the power relationships existing between various practitioner groups (including informal carers), and between practitioners and patients during clinical encounters.

Attitude of Health Personnel↗
PubMed2003

Syngeneic hematopoietic stem cell transplantation for women with metastatic breast cancer.

Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graft contamination with tumor. We describe 14 women with metastatic breast cancer transplanted between 1991 and 1998 with hematopoietic cells from identical twins. Median age was 41 y (range 34-50). Most women (12 of 14) were treated with mastectomy, and all received anthracycline-based regimens in their pretransplant course; nine women also received a taxane, seven radiotherapy and three hormonal therapy. Four women were in complete remission (one CR, three CRU) at transplant, five were in partial remission, two had stable disease and two had progressive disease. Eight women have died, one of treatment-related causes and seven of progressive breast cancer. Three-year survival was 48% (21-71%) and 3-year PFS was 21% (5-45%). Although the number of patients is small, outcomes for women transplanted with syngeneic grafts are similar to those of women receiving autologous grafts. This suggests that residual cancer in the patient is the major contributor to relapse after transplantation for breast cancer.

Adult↗
PubMed2003

Socio-economic inequalities in diabetes complications, control, attitudes and health service use: a cross-sectional study.

AIMS: To investigate socio-economic inequalities in diabetes complications, and to examine factors that may explain these differences. METHODS: Cross-sectional questionnaire survey of 770 individuals with diabetes among 40 general practices in Avon and Somerset. General practice, optometrist and eye hospital records over time (median 7 years) were analysed. Slope indices of inequality, odds ratios and incidence rate ratios were calculated to estimate the magnitude of inequality between the most and least educated, and the highest and lowest earning patients, adjusted for age, sex and type of diabetes, and clustering of outcomes within practices. RESULTS: The least educated patients were more likely than the most educated patients to have diabetic retinopathy [adjusted odds ratio (OR) 4.3; 95% confidence interval 0.8, 23.7] and heart disease (adjusted OR 3.6; 1.1, 11.8), had higher HbA1c levels (adjusted slope index of inequality 0.9; 0.3, 1.5), felt that diabetes more adversely affected their social and personal lives (adjusted slope index of inequality 0.8; 0.5, 1.1 Diabetes Care Profile units), were more likely to be recorded as non-compliant by their health professionals, and had lower rates of hospital attendance (adjusted rate ratio 0.43; 0.26, 0.71). However, they did not see themselves as less compliant, and had higher general practice attendance rates (adjusted rate ratio 1.5; 1.1, 2.2). CONCLUSIONS: Less educated and lower earning individuals with diabetes bear a larger burden of morbidity but use hospital care less. Health service resource allocation should reflect the distribution of chronic illness.

Aged↗
PubMed2003

Computer assisted assessment and advice for "non-serious" 999 ambulance service callers: the potential impact on ambulance despatch.

OBJECTIVE: To investigate the potential impact for ambulance services of telephone assessment and triage for callers who present with non-serious problems (Category C calls) as classified by ambulance service call takers. DESIGN: Pragmatic controlled trial. Calls identified using priority dispatch protocols as non-serious were allocated to intervention and control groups according to time of call. Ambulance dispatch occurred according to existing procedures. During intervention sessions, nurses or paramedics within the control room used a computerised decision support system to provide telephone assessment, triage and, if appropriate, offer advice to permit estimation of the potential impact on ambulance dispatch. SETTING: Ambulance services in London and the West Midlands. SUBJECTS: Patients for whom emergency calls were made to the ambulance services between April 1998 and May 1999 during four hour sessions sampled across all days of the week between 0700 and 2300. MAIN OUTCOME MEASURES: Triage decision, ambulance cancellation, attendance at an emergency department. RESULTS: In total, there were 635 intervention calls and 611 controls. Of those in the intervention group, 330 (52.0%) were triaged as not requiring an emergency ambulance, and 119 (36.6%) of these did not attend an emergency department. This compares with 55 (18.1%) of those triaged by a nurse or paramedic as requiring an ambulance (odds ratio 2.62; 95% CI 1.78 to 3.85). Patients triaged as not requiring an emergency ambulance were less likely to be admitted to an inpatient bed (odds ratio 0.55; 95% CI 0.33 to 0.93), but even so 30 (9.2%) were admitted. Nurses were more likely than paramedics to triage calls into the groups classified as not requiring an ambulance. After controlling for age, case mix, time of day, day of week, season, and ambulance service, the results of a logistic regression analysis revealed that this difference was significant with an odds ratio for nurses:paramedics of 1.28 (95% CI 1.12 to 1.47). CONCLUSIONS: The findings indicate that telephone assessment of Category C calls identifies patients who are less likely to require emergency department care and that this could have a significant impact on emergency ambulance dispatch rates. Nurses were more likely than paramedics to assess calls as requiring an alternative response to emergency ambulance despatch, but the extent to which this relates to aspects of training and professional perspective is unclear. However, consideration should be given to the acceptability, reliability, and cost consequences of this intervention before it can be recommended for full evaluation.

Adolescent↗
PubMed2003

Reducing work related psychological ill health and sickness absence: a systematic literature review.

A literature review revealed the following: key work factors associated with psychological ill health and sickness absence in staff were long hours worked, work overload and pressure, and the effects of these on personal lives; lack of control over work; lack of participation in decision making; poor social support; and unclear management and work role. There was some evidence that sickness absence was associated with poor management style. Successful interventions that improved psychological health and levels of sickness absence used training and organisational approaches to increase participation in decision making and problem solving, increase support and feedback, and improve communication. It is concluded that many of the work related variables associated with high levels of psychological ill health are potentially amenable to change. This is shown in intervention studies that have successfully improved psychological health and reduced sickness absence.

Burnout, Professional↗
PubMed2003

Wear and deformation of ceramic-on-polyethylene total hip replacements with joint laxity and swing phase microseparation.

Wear of polyethylene and the resulting wear debris-induced osteolysis remains a major cause of long-term failure in artificial hip joints. There is interest in understanding engineering and clinical conditions that influence wear rates. Fluoroscopic studies have shown separation of the head and the cup during the swing phase of walking due to joint laxity. In ceramic-on-ceramic hips, joint laxity and microseparation, which leads to contact of the head on the superior rim of the cup, has led to localized damage and increased wear in vivo and in vitro. The aim of this study was to investigate the influence of joint laxity and microseparation on the wear of ceramic on polyethylene artificial hip joints in an in vitro simulator. Microseparation during the swing phase of the walking cycle produced contact of the ceramic head on the rim of the polyethylene acetabular cup that deformed the softer polyethylene cup. No damage to the alumina ceramic femoral head was found. Under standard simulator conditions the volume change of the moderately crosslinked polyethylene cups was 25.6 +/- 5.3 mm3/million cycles and this reduced to 5.6 +/- 4.2 mm3/million cycles under microseparation conditions. Testing under microseparation conditions caused the rim of the polyethylene cup to deform locally, possibly due to creep, and the volume change of the polyethylene cup when the head relocated was substantially reduced, possibly due to improved lubrication. Joint laxity may be caused by poor soft tissue tension or migration and subsidence of components. In ceramic-on-polyethylene acetabular cups wear was decreased with a small degree of joint laxity, while in contrast in hard-on-hard alumina bearings, microseparation accelerated wear. These findings may have significant implications for the choice of fixation systems to be used for different types of bearing couples.

Ceramics↗