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Biomedical subjects

J Hall

Publications and source records attributed to J Hall.

At least 37 records · Page 2Linked to original sources

Randomized double-blind trial of sotalol versus lignocaine in out-of-hospital refractory cardiac arrest due to ventricular tachyarrhythmia.

AIM: We aimed to compare the efficacy of sotalol versus lignocaine for the treatment of patients with out-of-hospital ventricular fibrillation refractory to > or = 4 defibrillatory shocks. BACKGROUND: The outcome of patients in ventricular fibrillation refractory to > or = 4 defibrillatory shocks is poor. In a previous randomized trial, sotalol was superior to lignocaine for acute termination of ventricular tachycardia not causing loss of consciousness. METHODS: Patients of the Ambulance Service of New South Wales treated by paramedics with continued ventricular fibrillation despite standard resuscitation and > or = 4 defibrillatory monophasic shocks were eligible. Drug doses were sotalol 100 mg or lignocaine 100 mg, given as i.v. boluses. A further 2 min of cardiopulmonary resuscitation was given and then defibrillation was repeated twice. If this failed, half the initial dose of the trial drug was repeated and a further > or = 2 shocks were given. RESULTS: Sixty patients were randomized to sotalol and 69 randomized to lignocaine. There was no significant difference between the two groups in the clinical characteristics of the patients or in the number of shocks received. Outcomes in the sotalol and lignocaine groups were survival to hospital admission in 7 (12%) and 16 (23%), respectively (P = 0.09), and survival to hospital discharge in 2 (3%) and 5 (7%), respectively (P = 0.33). CONCLUSIONS: Sotalol is not superior to lignocaine for treatment of ventricular fibrillation refractory to multiple shocks. The overall outcome of this group of patients is poor regardless of the pharmacological intervention (lignocaine or sotalol).

Aged↗

Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study.

It is unclear whether a random plasma cortisol measurement and the corticotropin (ACTH) test adequately reflect glucocorticoid secretory capacity in critical illness. This study aimed to determine whether these tests provide information representative of the 24 hour period. Plasma cortisol was measured hourly for 24 hours in 21 critically ill septic patients followed by a corticotropin test with 1 microg dose administered intravenously. Serum and urine were analysed for ACTH and free cortisol respectively. Marked hourly variability in plasma cortisol was evident (coefficient of variation 8-30%) with no demonstrable circadian rhythm. The individual mean plasma cortisol concentrations ranged from 286 +/- 59 nmol/l to 796 +/- 83 nmol/l. The 24 hour mean plasma cortisol was strongly correlated with both random plasma cortisol (r2 0.9, P < 0.0001) and the cortisol response to corticotropin (r2 0.72, P < 0.001). Only nine percent of patients increased their plasma cortisol by 250 nmol/l after corticotropin (euadrenal response). However, 35% of non-responders had spontaneous hourly rises > 250 nmol/l thus highlighting the limitations of a single point corticotropin test. Urinary free cortisol was elevated (865 +/- 937 nmol) in both corticotropin responders and non-responders suggesting elevated plasma free cortisol. No significant relationship was demonstrable between plasma cortisol and ACTH. We conclude that although random cortisol measurements and the low dose corticotropin tests reliably reflect the 24 hour mean cortisol in critical illness, they do not take into account the pulsatile nature of cortisol secretion. Consequently, there is the potential for erroneous conclusions about adrenal function based on a single measurement. We suggest that caution be exercised when drawing conclusions on the adequacy of adrenal function based on a single random plasma cortisol or the corticotropin test.

APACHE↗

Ammonia emission and deposition in Scotland and its potential environmental impacts.

The main source of atmospheric ammonia (NH3) in Scotland is livestock agriculture, which accounts for 85% of emissions. The local magnitude of emissions therefore depends on livestock density, type, and management, with major differences occurring in various parts of Scotland. Local differences in agricultural activities therefore result in a wide range of NH3 emissions, ranging from less than 0.2 kg N ha(-1) year(-1) in remote areas of the Scottish Highlands to over 100 kg N ha(-1) year-1 in areas with intensive poultry farming. Scotland can be divided loosely into upland and lowland areas, with NH3 emission being less than and more than 5 kg N ha(-1) year(-1), respectively. Many semi-natural ecosystems in Scotland are vulnerable to nitrogen deposition, including bogs, moorlands, and the woodland ground flora. Because NH3 emissions occur in the rural environment, the local deposition to sensitive ecosystems may be large, making it essential to assess the spatial distribution of NH3 emissions and deposition. A spatial model is applied here to map NH3 emissions and these estimates are applied in atmospheric dispersion and deposition models to estimate atmospheric concentrations of NH3 and NH4+, dry deposition of NH3, and wet deposition of NHx. Although there is a high level of local variability, modelled NH3 concentrations show good agreement with the National Ammonia Monitoring Network, while wet deposition is largest at high altitude sites in the south and west of Scotland. Comparison of the modelled NHx deposition fields with estimated thresholds for environmental effects ("critical loads") shows that thresholds are exceeded across most of lowland Scotland and the Southern Uplands. Only in the cleanest parts of the north and west is nitrogen deposition not a cause for concern. Given that the most intense effects occur within a few kilometres of sources, it is suggested that local spatial abatement policies would be a useful complement to traditional policies that mitigate environmental effects based on emission reduction technologies.

Ammonia↗

ATM polymorphisms as risk factors for prostate cancer development.

The risk of prostate cancer is known to be elevated in carriers of germline mutations in BRCA2, and possibly also in carriers of BRCA1 and CHEK2 mutations. These genes are components of the ATM-dependent DNA damage signalling pathways. To evaluate the hypothesis that variants in ATM itself might be associated with prostate cancer risk, we genotyped five ATM variants in DNA from 637 prostate cancer patients and 445 controls with no family history of cancer. No significant differences in the frequency of the variant alleles at 5557G>A (D1853N), 5558A>T (D1853V), ivs38-8t>c and ivs38-15g>c were found between the cases and controls. The 3161G (P1054R) variant allele was, however, significantly associated with an increased risk of developing prostate cancer (any G vs CC OR 2.13, 95% CI 1.17-3.87, P=0.016). A lymphoblastoid cell line carrying both the 3161G and the 2572C (858L) variant in the homozygote state shows a cell cycle progression profile after exposure to ionising radiation that is significantly different to that seen in cell lines carrying a wild-type ATM gene. These results provide evidence that the presence of common variants in the ATM gene, may confer an altered cellular phenotype, and that the ATM 3161C>G variant might be associated with prostate cancer risk.

Adult↗

The impact of course attendance on the practice of dentists.

INTRODUCTION: This paper reports the impact of course attendance on the practice of dentists. METHOD: Phase One: A survey sent to all general dental practitioners (GDPs) in three deaneries in England. The survey included self-ratings of the impact of course attendance on practice. Phase Two: Interviews with 20 dentists before and two to three months after they had participated in a self-selected course. The response rate to the survey was 54% (n = 2082). Comparisons with national data showed no notable bias in the sample for gender, owners/partners and age/experience. An ordered logit model was used to explore the net effect of factors (including years' experience in general dental practice and gender) on dentists' ratings of course impact. RESULTS: Course attendance was judged to impact on practice. Impact rating was affected by participation rate and years' experience. Barriers to implementation included cost, time, NHS constraints and personal or staff issues. Impact was enhanced when selection of courses was based on learning needs although courses may also serve usefully to confirm current practice. CONCLUSION: There is much that dentists themselves can do to enhance the impact of courses, principally by reflecting on learning needs. They should be supported in the development of personal learning plans.

Education, Dental, Continuing↗

The effects of network structure on the resistance of silane coupling agent layers to water-assisted crack growth.

Silane adhesion promoters are commonly used to improve the adhesion, durability, and corrosion resistance of polymer-oxide interfaces. The current study investigates a model interface consisting of the natural oxide of(100) Si and an epoxy cured from diglycidyl ether ofbisphenol A (DGEBA) and triethylenetetraamine (TETA). The thickness of (3-glycidoxypropyl)trimethoxysilane (GPS) films placed between the two materials provided the structural variable. Five surface treatments were investigated: a bare interface, a rough monolayer film, a smooth monolayer film, a 5 nm thick film, and a 10 nm thick film. Previous neutron reflection experiments revealed large extension ratios (>2) when the 5 and 10 nm thick GPS films were exposed to deuterated nitrobenzene vapor. Despite the larger extension ratio for the 5 nm thick film, the epoxy/Si fracture energy (Gc) was equal to that of the 10 nm thick film under ambient conditions. Even the smooth monolayer exhibited the same Gc. Only when the monolayer included a significant number of agglomerates did the Gc drop to levels closer to that of the bare interface. When immersed in water at room temperature for 1 week, the threshold energy release rate (Gth) was nearly equal to Gc for the smooth monolayer, 5 nm thick film, and 10 nm thick film. While the Gth for all three films decreased with increasing water temperature, the Gth of the smooth monolayer decreased more rapidly. The bare interface was similarly sensitive to temperature; however, the Gth of the rough monolayer did not change significantly as the temperature was raised. Despite the influence of pH on hydrolysis, the Gth was insensitive to the pH of the water for all surface treatments.

Journal Article↗

Cellular responses to ionising radiation of AT heterozygotes: differences between missense and truncating mutation carriers.

It has been estimated that approximately 1% of the general population are ataxia telangiectasia (AT) mutated (ATM) heterozygotes. The ATM protein plays a central role in DNA-damage response pathways; however, the functional consequences of the presence of either heterozygous truncating or missense mutations on ATM expression and the ionising radiation (IR)-induced cellular phenotype remain to be fully determined. To investigate this relationship, the ATM mRNA and protein levels and several cellular end points were characterised in 14 AT heterozygote (AT het) lymphoblastoid cell lines, compared to normal and AT homozygote lines. The AT het cell lines displayed a wide range of IR-induced responses: despite lower average levels of ATM mRNA and protein expression compared to normal cells, 13 out of 14 were capable of phosphorylating the ATM substrates p53-ser15 and Chk2, leading to a normal cell cycle progression after irradiation. However, cell survival was lower than in the normal cell lines. The presence of a missense compared to a truncating mutation was associated with lower cell survival after exposure to 2 Gy irradiation (P=0.005), and a higher level of ATM mRNA expression (P=0.047). Our results underline the difficulty in establishing a reliable test for determining ATM heterozygosity.

Ataxia Telangiectasia Mutated Proteins↗

Identification of chicken lysozyme g2 and its expression in the intestine.

Lysozyme is an important component of the innate immune system, protecting the gastrointestinal tract from infection. The aim of the present study was to determine if lysozyme is expressed in the chicken ( Gallus gallus) intestine and to characterise the molecular forms expressed. Immunohistochemical staining localised lysozyme to epithelial cells of the villous epithelium along the length of the small intestine. There was no evidence for lysozyme expression in crypt epithelium and no evidence for Paneth cells. Immunoblots of chicken intestinal protein revealed three proteins: a 14-kDa band consistent with lysozyme c, and two additional bands of approximately 21 and 23 kDa, the latter consistent with lysozyme g. RT-PCR analyses confirmed that lysozyme c mRNA is expressed in 4-day, but not older chicken intestine and lysozyme g in 4- to 35-day chicken intestine. A novel chicken lysozyme g2 gene was identified by in silico analyses and mRNA for this lysozyme g2 was identified in the intestine from chickens of all ages. Chicken lysozyme g2 shows similarity with fish lysozyme g, including the absence of a signal peptide and cysteines involved in disulphide bond formation of the mammalian and bird lysozyme g proteins. Analyses using SecretomeP predict that chicken lysozyme g2 may be secreted by the non-classical secretory pathway. We conclude that lysozyme is expressed in the chicken small intestine by villous enterocytes. Lysozyme c, lysozyme g and g2 may fulfil complimentary roles in protecting the intestine.

Amino Acid Sequence↗

Effectiveness of topical chlorhexidine powder as an alternative to hexachlorophane for the control of Staphylococcus aureus in neonates.

We routinely phage-type Staphylococcus aureus isolates from high-risk inpatients each week. This surveillance approach previously identified a five-year outbreak of a methicillin-susceptible S. aureus strain (MSSA, PT 53,85), which affected 202 babies on a regional neonatal unit. We previously reported this outbreak and the multiple staged infection control measures that were required to end it. These included strict emphasis on hand hygiene, environmental and staff surveillance sampling, application of topical triclosan solution and hexachlorophane powder, aseptic handling of a skin protectant material, and use of topical mupirocin for staff nasal carriers of the endemic MSSA strain and for babies colonized or infected with S. aureus. In summer 2000 topical hexachlorophane powder became unavailable and we therefore substituted topical 1% chlorhexidine powder as part of routine umbilical decontamination. We have continued prospective S. aureus surveillance for the past five years to monitor the effect of this practice change. We observed a continued decline in the numbers of monthly MSSA isolates from neonatal unit babies. Since the substitution of chlorhexidine for hexachlorophane, the median monthly number of MRSA isolates has been 0.5 (range 0-4). Only sporadic S. aureus PT 53,85 isolates were recovered. Control of S. aureus in our regional neonatal unit, in particular an endemic MSSA strain, was maintained when topical umbilical hexachlorophane powder was substituted with 1% chlorhexidine powder.

Administration, Topical↗

Provision of safe potable water for immunocompromised patients in hospital.

We conducted a survey of hospital drinking water provision for patients with immunocompromising conditions in 15 Trusts in the north of England. Ten trusts replied, reporting on provision of drinking water in 14 separate units. Of these, nine provided only tap water to all patients, irrespective of underlying condition. In two units, iced water, with ice from commercially available makers, was used. Five units distinguished between neutropenic and non-neutropenic patients, with the former group receiving cooled, boiled water (three units), sterile water and sterile water or carbonated water (one unit each). No unit provided filtered water. Water in jugs was changed daily, twice daily or only when empty in seven, three and four units, respectively. On 10 units, patients were allowed to provide their own drinking water, but no unit provided written advice to patients on potable water. A survey within our own Trust revealed similar inter-unit disparity. The options for potable water provision were reviewed, taking into account: microbiological quality, organoleptic (perceived taste/smell) acceptability, cost and factors relating to staff safety and patient confidentiality [as it was possible for human immunodeficiency virus (HIV) seropositive patients on some wards to be identified because they were provided with cooled, boiled water]. It concluded that end-line commercially available water filters were the optimal way to provide drinking water to immunocompromised patients in hospital.

Cross Infection↗

A risk-based methodology for deriving quality standards for organic contaminants in sewage sludge for use in agriculture--Conceptual Framework.

This paper describes a systematic methodology (Conceptual Framework) to derive quality standards for organic (anthropogenic) contaminants in sewage sludge added to agricultural land, in the context of revision of EU Sludge Directive 86/278/EEC and the broader Soil Thematic Strategy. The overall objective is to ensure, based on a risk assessment approach, a sustainable use of sludge over a long time horizon. ILSI-Europe's Conceptual Framework is in essence consistent with the EU Technical Guidance Document (TGD) for Environmental Risk Assessment of Chemicals in the soil compartment, or US-EPA's Sewage Sludge Use and Disposal Regulations, Part 503 Standards. A 'checklist' of different exposure pathways and transfer processes for organic contaminants needs to be considered, and the most sensitive relevant toxicological endpoint and its PNEC need to be identified. The additional complexity specific to deriving Sludge Quality Standards (SQS) is that the toxicity results may need-e.g., for (indirect) human toxicity-to be related back to maximum acceptable soil exposure levels (PEC(soil)). In turn, the latter need to be back-calculated to the maximum acceptable levels in sewage sludge (PEC(sludge)) at the time of application. Finally, for a sustainable sludge use, the exposure from repeated addition and potential chemical build-up over time (e.g., 100 years) needs to be assessed. The SQS may therefore vary with the (local) sludge application regime, and/or sludge pretreatment processes.

Agriculture↗

Key skills for newly qualified dentists: an evaluation of a West Midlands initiative.

INTRODUCTION: This paper reports an evaluation of the West Midlands Key Skills initiative that provides a framework for learning during vocational training (VT). METHOD: The 48 vocational dental practitioners (VDPs) who began their VT in August 2001 in the West Midlands were surveyed at the start and end of training (45 completed both surveys). They rated their confidence and experience in the 31 components of the Six Key Skills on visual analogue scales. Views were elicited in a survey of both VDPs (47 returns) and their general practice trainers (44 returns). Semi-structured interviews were also held with a stratified sample of 9 trainers and all four VT advisors. RESULTS: In terms of VDP progress, a statistically significant increase in confidence and experience was found in each of the 31 components. Six themes were identified in the views data. (i) Supporting the development of Key Skills; (ii) workload implications; (iii) the "right" six? (iv) links with the advanced diploma (MFGDP(UK)); (v) assessment of VT; and, (vi) consistency and quality assurance. CONCLUSION: VT successfully develops the confidence and experience of newly qualified dentists in the Six Key Skills and has been well received by the majority of VDPs, trainers and advisors in the West Midlands.

Clinical Competence↗

Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: (1) Describe the self-care, productivity and leisure problems identified by individuals with a spinal cord injury (SCI) during rehabilitation, (2) describe the perceived level of satisfaction and performance with self-care, productivity and leisure activities following an SCI, (3) quantify the relationship between the Canadian occupational performance measure (COPM), a client-centred, individualized measure of function, and the functional independence measure (FIM). SETTING: Tertiary rehabilitation centre, spinal cord injury unit, GF Strong Rehabilitation Centre, Vancouver, Canada. METHODS: Health records from 41 individuals with an SCI admitted between 2000 and 2002 were reviewed. Information was obtained from assessments performed on admission and discharge. Self-care, productivity and leisure problems identified by individuals with an SCI were described and their perceived level of performance and satisfaction was calculated. The relationship between the COPM and the FIM was measured by the Pearson product correlation. RESULTS: Self-care goals were identified most frequently (79%) followed by productivity (12%) and leisure (9%) goals. The top three problems identified by individuals with an SCI were functional mobility (including transfers and wheelchair use), dressing and grooming. A fair relationship was found between the COPM and the FIM (r between 0.351 and 0.514, P<0.05). CONCLUSIONS: The results highlight the importance of including a client-centred outcome measure in the assessment of individuals with an SCI. Initial support is provided for use of the COPM in individuals with an SCI.

Activities of Daily Living↗

Expression of ATM, p53, and the MRE11-Rad50-NBS1 complex in myoepithelial cells from benign and malignant proliferations of the breast.

AIMS: To analyse the expression of proteins involved in DNA double strand break detection and repair in the luminal and myoepithelial compartments of benign breast lesions and malignant breast tumours with myoepithelial differentiation. METHODS: Expression of the ataxia telangiectasia (ATM) and p53 proteins was immunohistochemically evaluated in 18 benign and malignant myoepithelial tumours of the breast. Fifteen benign breast lesions with prominent myoepithelial compartment were also evaluated for these proteins, in addition to those in the MRE11-Rad50-NBS1 (MRN) complex, and the expression profiles were compared with those seen in eight independent non-cancer (normal breast) samples and in the surrounding normal tissues of the benign and malignant tumours examined. RESULTS: ATM expression was higher in the myoepithelial compartment of three of 15 benign breast lesions and lower in the luminal compartment of eight of these lesions compared with that found in the corresponding normal tissue compartments. Malignant myoepithelial tumours overexpressed ATM in one of 18 cases. p53 was consistently negative in benign lesions and was overexpressed in eight of 18 malignant tumours. In benign breast lesions, expression of the MRN complex was significantly more reduced in myoepithelial cells (up to 73%) than in luminal cells (up to 40%) (p=0.0005). CONCLUSIONS: Malignant myoepithelial tumours rarely overexpress ATM but are frequently positive for p53. In benign breast lesions, expression of the MRN complex was more frequently reduced in the myoepithelial than in the luminal epithelial compartment, suggesting different DNA repair capabilities in these two cell types.

Acid Anhydride Hydrolases↗

Serum procalcitonin and C-reactive protein as markers of sepsis and outcome in patients with neurotrauma and subarachnoid haemorrhage.

This prospective study evaluated serum procalcitonin (PCT) and C-reactive protein (CRP) as markers for systemic inflammatory response syndrome (SIRS)/sepsis and mortality in patients with traumatic brain injury and subarachnoid haemorrhage. Sixty-two patients were followed for 7 days. Serum PCT and CRP were measured on days 0, 1, 4, 5, 6 and 7. Seventy-seven per cent of patients with traumatic brain injury and 83% with subarachnoid haemorrhage developed SIRS or sepsis (P=0.75). Baseline PCT and CRP were elevated in 35% and 55% of patients respectively (P=0.03). There was a statistically non-significant step-wise increase in serum PCT levels from no SIRS (0.4+/-0.6 ng/ml) to SIRS (3.05+/-9.3 ng/ml) to sepsis (5.5+/-12.5 ng/ml). A similar trend was noted in baseline PCT in patients with mild (0.06+/-0.9 ng/ml), moderate (0.8+/-0.7 ng/ml) and severe head injury (1.2+/-1.9 ng/ml). Such a gradation was not observed with serum CRP There was a non-significant trend towards baseline PCT being a better marker of hospital mortality compared with baseline CRP (ROC-AUC 0.56 vs 0.31 respectively). This is the first prospective study to document the high incidence of SIRS in neurosurgical patients. In our study, serum PCT appeared to correlate with severity of traumatic brain injury and mortality. However, it could not reliably distinguish between SIRS and sepsis in this cohort. This is in part because baseline PCT elevation seemed to correlate with severity of injury. Only a small proportion of patients developed sepsis, thus necessitating a larger sample size to demonstrate the diagnostic usefulness of serum PCT as a marker of sepsis. Further clinical trials with larger sample sizes are required to confirm any potential role of PCT as a sepsis and outcome indicator in patients with head injuries or subarachnoid haemorrhage.

APACHE↗

Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in hypogonadal men.

OBJECTIVE: A phase I single centre, open label study of the pharmacokinetics and tolerability of a buccal testosterone tablet (COL 1621) was carried out. DESIGN: Twelve testosterone-deficient males were treated with the buccal tablet twice daily for 7 consecutive days. Multiple blood samples were drawn for testosterone, dihydrotestosterone (DHT), bioavailable testosterone and sex hormone-binding globulin (SHBG). RESULTS: After COL 1621, means+/-S.D. serum testosterone level increased to a peak concentration of 26.6+/-5.8 nmol/l (7.7+/-1.7 ng/ml) at 4.8+/-5.8 h and stayed in the eugonadal range. Steady state was achieved within the first 24 h and was maintained in the normal range. The bioavailable testosterone, DHT and free testosterone index followed a pattern very similar to that of testosterone. The mean serum testosterone to DHT ratio was within the normal male range throughout treatment. There was only one treatment-related adverse event (headache). Two-thirds of patients indicated that treatment with COL 1621 was acceptable and that the tablet was convenient to use. Six patients (50.0%) preferred COL 1621 to their previous testosterone replacement therapy, two patients gave preference to their previous treatment and three patients found both treatments to be equally acceptable. Data for one patient was not available. CONCLUSION: We conclude that COL 1621 can efficiently elevate serum testosterone and DHT levels in hypogonadal men within the first day of application, achieve a steady state within 24 h and maintain serum testosterone in the normal range with a twice-daily treatment regimen. COL 1621 provides an effective alternative oral testosterone replacement therapy that gives physiological levels of testosterone and is well tolerated by the patients.

Administration, Buccal↗