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Biomedical subjects

C Willis

Publications and source records attributed to C Willis.

At least 19 recordsLinked to original sources
PubMed2006

Speed enforcement detection devices for preventing road traffic injuries.

BACKGROUND: It is estimated that by 2020, road traffic crashes will have moved from ninth to third in the world ranking of burden of disease, as measured in disability adjusted life years. The identification of effective strategies for the prevention of road traffic injuries is of global public health importance. Measures aimed at reducing traffic speed are considered essential to preventing road injuries; the use of speed enforcement detection devices (including speed cameras and radar and laser devices) is one such measure. OBJECTIVES: To assess whether the use of speed enforcement detection devices (SEDs) reduces the incidence of speeding, road traffic crashes, injuries and deaths. SEARCH STRATEGY: We searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, Science (and Social Science) Citation Index, TRANSPORT, PsycINFO, CINAHL, EconLit. We searched the websites of road safety and motoring associations, as well as general internet searches. We handsearched selected journals and conference proceedings, and contacted experts in the field. The searches were conducted during May to November 2004. SELECTION CRITERIA: Randomised controlled trials and controlled before-after studies that assessed the impact of speed enforcement detection devices on speeding, road crashes, injuries and deaths were eligible for inclusion. For studies involving co-interventions, SEDs had to be the major intervention focus of the study to be eligible. DATA COLLECTION AND ANALYSIS: We independently screened search results, assessed studies for inclusion, extracted data and assessed methodological quality. Due to variability between and within included studies, a pooled analysis was not appropriate. MAIN RESULTS: No randomised controlled trials were identified. Twenty-six studies met the inclusion criteria, of which 22 were controlled before-after trials incorporating a distinct control or comparison group(s) and four were interrupted time series designs with a comparison group(s). Fourteen studies reported speed and crash outcomes, seven reported crash outcomes only and five reported speed outcomes only. All but one study reported an absolute reduction in pre/post average speeds. A pre/post reduction in the proportion of speeding vehicles ranged across studies from 5% to 70% depending on the speed threshold set. Pre/post reductions of 50% to 65% were reported in the proportion of speeding vehicles travelling >15 km/h over the speed limit. Compared with controls, the relative improvement was from 1% to 15% for average speed and from 14% to 65% for percent speeding. All studies reporting crash outcomes reported an absolute pre/post reduction in all crashes and injury related crashes. In the vicinity of camera sites these pre/post reductions ranged from 14% to 72% for all crashes, 8% to 46% for injury crashes, and 40% to 45% for crashes resulting in fatalities or serious injuries. More generalised effects over wider areas showed an absolute pre/post crash reduction ranging from 9% to 35%, 7% to 30% for all injury crashes and 13% to 58% for crashes resulting in fatalities alone, or in combination with serious injuries. The studies of longer duration showed that these positive trends were either maintained or improved with time. Compared with controls, the relative improvement in pre/post crash numbers resulting in any type of injury ranged from 5% to 36%. AUTHORS' CONCLUSIONS: Despite the methodological limitations of the studies reviewed, the consistency of reported positive reductions in speed and crash outcomes across all studies suggest that SEDs are a promising intervention for reducing the number of road traffic injuries and deaths. More studies of a scientifically rigorous nature are necessary to provide a stronger evidence base that these interventions are worthwhile. There is a need for international harmonisation of data collection methods, including standards on how best to measure speeds and collect crash data, over lengthy intervention and follow-up periods, as well as some consensus as to the expression of outcomes in studies, so that studies can be compared.

Accident Prevention↗
PubMed2006

Bacteria-free endoscopy rinse water -- a realistic aim?

A number of outbreaks and pseudo-outbreaks have been associated with contaminated rinse water in endoscope washer-disinfectors. Health Technical Memorandum 2030 specifies that final rinse water should be 'bacteria-free'. In this study, results of rinse-water testing from 20 endoscopy units were reviewed over a 4-month period. Over 60% of samples were of an unsatisfactory quality (i.e. not bacteria-free) and none of the endoscopy units consistently achieved sterile water throughout the study period. Poor microbiology results caused anxiety to endoscopy staff and infection control teams who had to decide whether or not to take washer-disinfectors out of use, possibly resulting in delays to medical procedures. There was no common policy on how to react to poor results, with staff at each unit developing their own action levels. Here, it is suggested that future guidelines would be of more practical use if they specified a series of action levels of increasing severity based on the bacterial count in a water sample.

Bacterial Infections↗
PubMed2006

NGF receptor TrkAd5: therapeutic agent and drug design target.

Biochemical studies have shown that domain 5 of the TrkA (tropomyosin receptor kinase A) receptor is involved in the binding of NGF (nerve growth factor). Crystallographic studies have confirmed this, demonstrating that one homodimer of NGF binds to two TrkAd5 molecules. TrkAd5 has been made recombinantly in Escherichia coli, purified and shown to bind NGF with picomolar affinity. We have used the co-ordinates of the crystal structure of the NGF-TrkAd5 complex to screen approximately two million compounds in silico for the identification of small molecule agonists/antagonists. Selected hits were shown to be active in an in vitro ligand-binding assay; structure-activity relationships are now being investigated. In addition, TrkAd5 has been shown to be efficacious in preclinical models of inflammatory pain and asthma by the sequestration of excess levels of endogenous NGF, and therefore represents a novel therapeutic agent.

Alzheimer Disease↗
PubMed2006

Effects of chronic triclosan exposure upon the antimicrobial susceptibility of 40 ex-situ environmental and human isolates.

BACKGROUND: Triclosan (TCS) exposure of Escherichia coli selects for tolerant clones, mutated in their enoyl-acyl carrier protein reductase (FabI). It has been inferred that this phenomenon is widespread amongst bacterial genera and might be associated with resistance to third party agents. METHODS: Ex-situ, low passage isolates of enteric, human axilla, human oral origin and bacteria isolated from a domestic drain, together with selected type cultures were exposed to escalating concentrations of TCS over 10 passages using a gradient plate technique. One fresh faecal isolate of E. coli was included as a positive control. TCS susceptibility was determined for all strains before and after exposure, whilst enteric isolates were additionally assessed for susceptibility towards chlorhexidine, tetracycline, chloramphenicol, nalidixic acid and ciprofloxacin, and the oral isolates towards chlorhexidine, tetracycline and metronidazole. RESULTS: Triclosan exposure of E. coli markedly decreased TCS susceptibility. TCS susceptibility also decreased for Klebsiella oxytoca, Aranicola proteolyticus and Stenotrophomonas maltophilia. Susceptibility of the remaining 35 strains to TCS and the other test agents remained unchanged. CONCLUSIONS: These data suggest that selection for high level resistance by TCS exposure is not widespread and appears to be confined to certain enteric bacteria, especially E. coli. Change in TCS susceptibility did not affect susceptibility towards chemically unrelated antimicrobials. SIGNIFICANCE AND IMPACT: Acquired high-level TCS resistance is not a widespread phenomenon.

Anti-Infective Agents, Local↗
PubMed2006

Evaluation of a new chromogenic agar for the detection of Listeria in food.

AIM: Rapid identification of Listeria in food is important in protecting consumers from infection. The development of chromogenic media such as agar Listeria according to Ottaviani and Agosti (ALOA) has allowed more rapid detection of Listeria monocytogenes, with presumptive identification of this pathogenic species after only 24 h of incubation. The aim of this study was to evaluate Oxoid chromogenic Listeria agar (OCLA) in comparison with ALOA and a traditional, nonchromogenic medium, Oxford agar. METHODS AND RESULTS: Media were compared using pure cultures, spiked food samples and naturally contaminated samples. Whilst development of typical colony morphology took 48 h on Oxford agar, Listeria spp. were frequently detected after 24 h of incubation on OCLA and ALOA. There was no significant difference in recovery between the two chromogenic media. CONCLUSIONS: Results indicate that OCLA gives equivalent recovery of Listeria spp. compared with ALOA. Whilst L. monocytogenes was frequently detected after 24 h of incubation, a 48-h incubation time was necessary to ensure detection of both L. monocytogenes and other Listeria spp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has shown that a commercially available chromogenic medium other than ALOA is appropriate for use in the international standard method. The commercial availability of more than one medium will facilitate the more widespread use of the method, thus increasing confidence in the ability to detect L. monocytogenes in food in the presence of other Listeria spp.

Agar↗
PubMed2005

Evaluation of chromogenic media for the detection of Listeria species in food.

AIMS: The aim of this study was to evaluate the performance of chromogenic agars, Agar Listeria according to Ottaviani and Agosti (ALOA) and Rapid L. mono agar, compared with Oxford agar for the enumeration and detection of Listeria species in food. METHODS AND RESULTS: A total of 170 food samples were examined using the three plating media. Listeria species were isolated from 63 samples. In contrast to Oxford agar, detection of Listeria colonies on chromogenic media was as good after 24 h of incubation of plates as after 48 h. While there was no significant difference in recovery of Listeria monocytogenes on the three media, recovery of other Listeria species was significantly poorer on Rapid L. mono agar compared with Oxford and ALOA agars. Recovery of species other than L. monocytogenes was significantly improved by including a secondary enrichment stage in the detection method. CONCLUSIONS: Using chromogenic agars, presumptive identification of L. monocytogenes is possible after 24 h, compared with 3-4 days using Oxford agar. However, the poor detection of species other than L. monocytogenes on Rapid L. mono agar is a disadvantage of this medium. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides new information regarding the isolation of Listeria species other than L. monocytogenes from food using chromogenic plating media. This is important, as non-pathogenic Listeria species act as markers for the likelihood of presence of L. monocytogenes and allow preventive action to be taken to avoid its presence.

Agar↗
PubMed2004

Alcohol ignition interlock programmes for reducing drink driving recidivism.

BACKGROUND: An ignition interlock device is part of a multi-dimensional programme aimed at reducing recidivism in convicted drink drivers. To operate a vehicle equipped with an ignition interlock device, the driver must first provide a breath specimen. If the breath alcohol concentration of the specimen exceeds the predetermined level, the vehicle will not start. As a measure to reduce circumvention of the device (i.e. someone else blows into the mouthpiece), random retests are required while the vehicle is running. Other components of the drink driving programme include information seminars for the driver and downloading data from the device's data logger, which logs all test attempts and records all passes, warnings and failures. OBJECTIVES: To systematically assess the effectiveness of ignition interlock programmes on recidivism rates of drink drivers, by examining rates of recidivism while the ignition interlock device was installed in the vehicle and after removal of the device. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched, in addition to relevant electronic databases and the Internet. SELECTION CRITERIA: Controlled trials in which offenders have been charged with drink driving and have either been sentenced to participate in an ignition interlock programme or the usual punishment (either licence suspension or some form of treatment programme). This study was not restricted by language or status of publication. DATA COLLECTION AND ANALYSIS: One randomised controlled trial (RCT) and ten controlled trials were identified, and also three ongoing trials. Data regarding recidivism while the interlock is installed in the vehicle; after the interlock has been removed from the vehicle and total recidivism during the study were extracted and entered into analyses using RevMan. MAIN RESULTS: The RCT showed that the interlock programme was effective while the device was installed in the vehicle; relative risk 0.36 (95% confidence interval 0.21 to 0.63). Controlled trials support this conclusion, with a general trend - in both first-time and repeat offenders - towards lower recidivism rates when the interlock device is installed. Neither the RCT nor the controlled trials provide evidence for any effectiveness of the programmes continuing once the device has been removed. REVIEWERS' CONCLUSIONS: In order to eliminate potential selection bias, more RCTs need to be conducted in this area so that effectiveness, as well as efficacy, can be ascertained. The interlock programme appears to be effective while the device is installed in the vehicle of the offender. Studies need to address ways of improving recidivism rates in the long term, as the major challenges are participation rates, compliance and durability.

Alcohol Drinking↗
PubMed2004

Excitatory amino acid inhibitors for traumatic brain injury.

BACKGROUND: Glutamate is the principal excitatory neurotransmitter in the brain. Injury to the brain can cause an ionic imbalance in cerebral tissue, creating an excitotoxic cascade involving glutamate and other excitatory amino acids, that leads to neuronal death in the tissue surrounding the original injury site. Research has centred around inhibiting this increase in excitatory amino acid during injury either pre- or post-synaptically. Animal studies appeared promising, but as yet, those results have not been repeated in human clinical trials. OBJECTIVES: To assess systematically the efficacy of excitatory amino acid inhibitors on improving patient outcome following traumatic brain injury. SEARCH STRATEGY: Online searches of the databases; CENTRAL, MEDLINE, EMBASE, IDdb3, and Science Citation Index. Online searches of clinical trial registers. General online searches of the Internet. Authors of published works and associated pharmaceutical companies were contacted. SELECTION CRITERIA: Trials were included if they were randomised, double-blind, controlled trials where excitatory amino acid inhibitors were administered to patients with traumatic brain injury, within 24 hours of sustaining that injury, and compared to a control group. DATA COLLECTION AND ANALYSIS: Twelve trials, involving eight compounds, were identified that appeared to fit the inclusion criteria. Further investigation excluded three of these trials. Two of the remaining trials are ongoing. Of the seven included studies, one trial did not report GOS data and we were unable to acquire them. Three trials have not been published and the data were not made available to us. One trial is currently being prepared for publication, leaving two trials where data were available. Data were extracted by two independent reviewers. MAIN RESULTS: Data were available for two of the seven relevant trials identified, with 760 recruited participants. Mortality is similar between patients who receive excitatory amino acid inhibitors and those that receive placebo: odds ratio (OR) 1.11; 95% confidence interval (CI) 0.78, 1.60. Patients who have a favourable outcome six months after injury are also similar between treatment and placebo groups: OR 0.86; 95% CI 0.64, 1.16. REVIEWER'S CONCLUSIONS: The case for efficacy of excitatory amino acid inhibitor therapy remains unproven. To date, no product has proven to be efficacious (as determined by the criteria applied) for improving the outcomes of brain-injured patients. Early termination, unpublished, and underpowered studies limit a clear appreciation of the merits of this form of intervention. Additional studies, some of which remain in progress, may more clearly define the efficacy and effectiveness issues.

Brain Injuries↗
PubMed2003

Predicting survival after treatment for fracture of the proximal femur and the effect of delays to surgery.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the prognosis after treatment for femoral neck fracture, to assess the impact of delay to surgery, and to devise a clinical prediction rule and score. METHODS: A prospective observational study was conducted in which 1780 patients treated surgically in two teaching hospitals between 1 November 1997 and 31 October 1999 were followed over 12 months. Logistic regression was used to distinguish the effects of predictor variables on survival. Using a probit transformation of the predicted posterior probabilities of death, a prognostic score was devised with scores constrained so that a nominal score of approximately 90 represented a 50:50 chance of survival over 12 months. RESULTS: Mortality was 30.1% in men and 19.5% in women. Increasing age, male gender, longer pre-operative delay, a higher American Society of Anesthesiology score, a lower Mental Test score, and a lower activities of daily living (Barthel) score were associated with increased risks of death. Of those waiting between 1 and 5 days for surgery, approximately 8 medium-risk and 17 high-risk patients (with prognostic scores of 90 and 120, respectively) would have to have their delay reduced to < 24 hours to yield one additional survivor. CONCLUSION: The application of prediction rules must be guided by ethical, social, and scientific concerns.

Activities of Daily Living↗
PubMed2003

Cytokine production by peripheral blood monocytes during the normal human ovulatory menstrual cycle.

BACKGROUND: There is considerable evidence that hormone-driven changes resembling an inflammatory response occur in the vascular compartment during the menstrual cycle, and peripheral blood monocytes may be central in the process. We investigated whether there is a cyclical change in intrinsic production of pro-inflammatory cytokines by monocytes in the ovulatory menstrual cycle, and whether there is a circulating factor that influences the pattern of cytokine production in a cyclical manner. METHODS: Monocytes were purified by density-gradient centrifugation followed by countercurrent centrifugal elutriation, from the blood of normal women (n = 10) pre- and post-ovulation. Monocytes were cultured under basal conditions with bacterial lipopolysaccharide (LPS), and to determine the effects of circulating factors, incubations were also conducted in the presence of autologous serum. Concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6, tumour necrosis factor (TNF)-alpha and IL-1 receptor antagonist (IL-1Ra) were measured by sandwich ELISA. RESULTS: The majority of IL-1alpha and IL-1beta was cell associated, while the other cytokines were almost entirely secreted. Basal levels of IL-1alpha, IL-1beta, and TNF-alpha were significantly increased following ovulation, while there was no significant change in levels of secretion of IL-6 or IL-1Ra. These effects were present in unstimulated cells, suggesting prior activation in vivo. Cytokine production was increased in response to LPS; however, there was no consistent effect of autologous serum. CONCLUSIONS: Intrinsic production of pro-inflammatory cytokines by monocytes is increased following ovulation.

Adult↗
PubMed2002

Spontaneous haemopneumothorax: are guidelines overdue?

Spontaneous life threatening haemopneumothorax is an unusual but treatable cause of unexpected circulatory collapse in young patients. Two case histories are presented to illustrate the management of this condition. Diagnosis and initial management depends on early recognition of the clinical pattern by accident and emergency (A&E) staff and/or hospital physicians. Problems may arise for two reasons. Firstly, as the incidence of life threatening spontaneous haemopneumothorax is low, admitting medical staff may not have experienced this condition in the absence of trauma. Secondly, unlike surgeons, staff in these specialties are unlikely to have received training of either traumatic or spontaneous haemopneumothorax. The cases illustrate potential problems. Not only early recognition of the clinical pattern but also proactive intervention in the A&E department are necessary before referral to a cardiothoracic surgeon. Furthermore, we suggest treatment would be improved by the introduction of management guidelines.

Adult↗
PubMed2001

Errors in the estimation of the distance of fall and angles of impact blood drops.

This paper presents derived equations for the estimation of the variances in the estimated distance of fall and the estimated angle of impact for blood droplets. The derived equation for the variance of the estimated distance of fall predicts that as the blood drop size approaches that of a blood droplet falling at terminal velocity, the variance of the estimate grows without limit. The derived equation for the variance in the estimated angle of impact shows that as the angle of impact approaches 90 degrees, the variance grows without limit. The validity of the equation for the estimated variance of the angle of impact was tested for five angles of impact (15, 30, 45, 60 and 75 degrees); the equation correctly predicted the observed variance up to an angle of 60 degrees.

Blood↗
PubMed2001

Population pharmacokinetics of tacrolimus in children who receive cut-down or full liver transplants.

BACKGROUND: The aim of this study was to investigate the population pharmacokinetics of tacrolimus in pediatric liver transplant recipients and to identify factors that may explain pharmacokinetic variability. METHODS: Data were collected retrospectively from 35 children who received oral immunosuppressant therapy with tacrolimus. Maximum likelihood estimates were sought for the typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) with the program NONMEM. Factors screened for influence on the pharmacokinetic parameters were weight, age, gender, postoperative day, days since commencing tacrolimus therapy, transplant type (whole child liver or cut-down adult liver), liver function tests (bilirubin, alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT]), creatinine clearance, hematocrit, corticosteroid dose, and concurrent therapy with metabolic inducers and inhibitors of tacrolimus. RESULTS: No clear correlation existed between tacrolimus dosage and blood concentrations (r2=0.003). Transplant type, age, and liver function test values were the most important factors (P<0.01) that influenced the pharmacokinetics of tacrolimus. CL/F estimates were greater in whole liver recipients, decreased with increasing patient age and AST values, and increased with increasing GGT values. Average parameter estimates were CL/F=5.75 L/h (cut-down liver), CL/F=44 L/h (whole liver), and V/F=617 L. Marked intersubject variability (CV%=110% to 297%) and residual variability (CV%=42%) was observed. CONCLUSIONS: Pharmacokinetic information obtained in this study may assist physicians in making individualized dosage decisions in regard to tacrolimus in pediatric liver transplant recipients. Children who received a whole child's liver appeared to retain "pediatric" clearance, whereas those who received a cut-down adult liver had "adult" clearances (on average 7-fold less).

Adolescent↗
PubMed2001

Spectrum of mutations in USH2A in British patients with Usher syndrome type II.

Usher syndrome (USH) is a combination of a progressive pigmentary retinopathy, indistinguishable from retinitis pigmentosa, and some degree of sensorineural hearing loss. USH can be subdivided in Usher type I (USHI), type II (USHII) and type III (USHIII), all of which are inherited as autosomal recessive traits. The three subtypes are genetically heterogeneous, with six loci so far identified for USHI, three for USHII and only one for USHIII. Mutations in a novel gene, USH2A, encoding the protein usherin, have recently been shown to be associated with USHII. The gene encodes a protein with partial sequence homology to both laminin epidermal growth factor and fibronectin motifs. We analysed 35 British and one Pakistani Usher type II families with at least one affected member, for sequence changes in the 20 translated exons of the USH2A gene, using heteroduplex analysis and sequencing. Probable disease-causing mutations in USH2A were identified in 15 of 36 (41.7%) Usher II families. The most frequently encountered mutation (11/15 families or 11/18 mutated alleles) was del2299G in exon 13, resulting in a frameshift and premature stop codon. Other mutations include insertions and point mutations, of which two are previously unreported. Five different polymorphisms were also detected. Our results indicate that mutations in this gene are responsible for disease in a large proportion of British Usher type II patients. Moreover, if screening for mutations in USH2A is considered, it is sensible to screen for the del2299G mutation first.

Chromosome Deletion↗
PubMed2001

A retrospective analysis of mycophenolic acid and cyclosporin concentrations with acute rejection in renal transplant recipients.

OBJECTIVES: Although monitoring of cyclosporin (CsA) is standard clinical practice postrenal transplantation, mycophenolic acid (MPA) concentrations are not routinely measured. There is evidence that a relationship exists between MPA area under the concentration-time curve (AUC) and rejection. In this study, a retrospective analysis was undertaken of 27 adult renal transplant recipients. METHODS: Patients received CsA and MPA therapy and had a four-point MPA AUC investigation. The relationship between MPA AUC performed in the first week after transplantation, as well as median trough cyclosporin concentrations, and clinical outcomes in the first month posttransplant were evaluated. RESULTS: A total of 12 patients experienced biopsy proven rejection (44.4%) and 4 patients had gastrointestinal adverse events (14.8%). A statistically significant relationship was observed between the incidence of biopsy proven rejection and both MPA AUC (p = 0.02) and median trough CsA concentration (p = 0.008). No relationship between trough MPA concentration and rejection was observed (p = 0.21). Only 3 of 11 (27%) patients with an MPA AUC > 30 mg x h/L and a median trough CsA > 175 microg/L experienced acute rejection, compared with a 56% incidence of rejection for the remaining 16 patients. Patients who experienced adverse gastrointestinal events had significantly lower MPA AUC (p = 0.04), but median trough CsA concentrations were not significantly different (p = 0.24). Further, 3 of these 4 patients had rejection episodes. CONCLUSIONS: In addition to standard CsA monitoring, we propose further investigation of the use of a 4-point sampling strategy to predict MPA AUC in the first week posttransplant, which may facilitate optimization of mycophenolate mofetil dose at a time when patients are most vulnerable to acute rejection.

Adult↗