E-commerce turns to PriceWaterhouseCoopers.
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Biomedical subjects
Publications and source records attributed to D Hughes.
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INTRODUCTION: Point mutations in N, K and H RAS have been found in adverse haematological malignancies. The background frequency of RAS mutations in the normal population has yet to be determined. Here we report the results of a screen for RAS mutations from normal individuals. MATERIALS AND METHODS: DNA from peripheral blood or bone marrow from 115 haematologically normal individuals was screened for point mutations in N, K and H RAS, at amino acid positions 12, 13 and 61. The screening was done using polymerase chain reaction and oligonucleotide hybridisation and candidate mutations were subsequently confirmed by cloning and sequencing. RESULTS AND CONCLUSION: Point mutations were identified in DNA from two of the 115 individuals. Both mutations resulted in an amino acid substitution at position 12 in H RAS. Both individuals with detectable H RAS mutations remain haematologically normal.
Interprofessional relations between doctors and nurses: perspectives from South Wales This paper discusses findings from a study of interprofessional relationships between doctors and nurses in medical wards in three provincial general hospitals in south Wales. The aim of the research was to investigate the changing nature of doctor-nurse relations, and in particular, how far the notion of the doctor-nurse game, as developed by Leonard Stein (Stein 1967, 1990), remains relevant to contemporary hospital work. The present paper concentrates on a subset of the findings concerned with doctors' and nurses' accounts of the hospital division of labour and the extent of any overlap in their work activities. Semi-structured interviews were conducted with 20 doctors and 39 nurses in their places of work over a period of 4 months. Inductive analysis of the data indicated that, whilst doctors and nurses perceived their roles in largely traditional terms, there was some recognition of blurring of occupational boundaries, especially when considering work pressures, working at night and differences in practice in more specialized clinical areas. Although nurses were generally reluctant to challenge doctors' authority, some used the notion of patient 'advocacy' to frame and justify their questioning of particular decisions. Whilst doctors valued 'experience' in nurses and saw experienced nurses as the group who might most legitimately move into doctors' territory, nurses valued formal education and saw advanced nursing qualifications as the route to role expansion.
Reductions in growth rate caused by fusidic acid-resistant EF-G mutants in Salmonella typhimurium correlate strongly with increased mean cell size. This is unusual because growth rate and cell size normally correlate positively. The global transcription regulator molecule ppGpp has a role in co-ordinating growth rate and division, and its basal level normally correlates inversely with cell size at division. We show that fusidic acid-resistant EF-G mutants have perturbed ppGpp basal levels during steady-state growth and perturbed induced levels during starvation. One mutation, fusA1, associated with the slowest growth rate and largest cell size, causes a reduction in the basal level of ppGpp to one-third of that found in the wild-type strain. Other fusA mutants with intermediate or wild-type growth rates and cell sizes have either normal or increased basal levels of ppGpp. There is an inverse relationship between the basal level of ppGpp in vivo and the degree to which translation dependent on mutant EF-G is inhibited by ppGpp in vitro. This enhanced interaction between mutant EF-G and ppGpp correlates with an increased KM for GTP. Our results suggest that mutant EF-G modulates the production of ppGpp by the RelA (PSI) pathway. In conclusion, fusidic acid-resistant EF-G mutations alter the level of ppGpp and break the normal relationship between growth rate and cell size at division. It would not be surprising if other phenotypes associated with these mutants, such as loss of virulence, were also related to perturbations in ppGpp levels effected through altered transcription patterns.
Acquisition of vascular access in the emergent small animal patient is one of the keys to successful management of a population of patients that are often unstable with regard to their major body systems. Venous and intraosseus cannulation allow for the administration of a variety of fluids and potentially life-saving medications. In addition, central venous and arterial access also serve as conduits for atraumatic blood sampling and intravascular pressure monitoring. A thorough knowledge of vascular access theory, the dynamics of fluid flow, vascular anatomy, catheter selection criteria, and placement techniques are critical to the proper and safe use of the vascular access options available today to the small animal clinician.
Prolonged nitric oxide (NO) production by the enzyme type II nitric oxide synthase (NOS2) has been implicated in angiogenesis and metastasis of human cancers. In animal models, wild-type p53 (but not mutant) protein results in down-regulation of NOS2 expression, which reduces both tumour growth and dissemination. In the current study, we aimed to find out whether a correlation was present in oral squamous cell carcinoma. Fifty-six cases of squamous cell carcinoma were assessed immunohistochemically using antibodies to NOS2 and p53 (clone DO-7). We also confirmed NOS2 protein expression in selected cases using immunoblotting. The results were correlated with clinicopathological findings. Statistical analysis showed a significant relationship between p53 and NOS2 expression (P= 0.001). No relationship was found between size of tumour or histological degree of differentiation, and NOS2 expression in the primary tumour.
The management of a pregnant mother at 20 weeks' gestation presenting with ventricular fibrillation and her subsequent elective caesarean section at 38 weeks' gestation are described. Investigation showed the presence of coronary artery aneurysms due to Kawasaki disease. The pregnancy was further complicated by placenta praevia (grade IV).
BACKGROUND: Non-invasive assessment of inflammation is likely to be useful in the management of cystic fibrosis (CF). Exhaled carbon monoxide (CO) concentrations are increased in patients with clinically stable CF. A study was undertaken to determine whether this marker of oxidative damage is further increased during exacerbations of the disease. METHODS: Exhaled CO concentrations were measured in 12 healthy non-smoking control subjects (six men) of mean (SE) age 37 (2) years with forced expiratory volume in one second (FEV(1)) 95 (1)% predicted and in 44 patients with CF (20 men) of mean (SE) age 29 (1) years with FEV(1) 56 (3)% predicted using an on-line CO analyser. RESULTS: Twenty nine patients were in a stable condition while 15 had clinically defined respiratory exacerbations (increased cough and production of sputum, change in the quality of the sputum, shortness of breath, sensation of chest congestion, and deterioration of FEV(1)) and represented the unstable group. Exhaled CO concentrations were 2.0 (0.15) ppm in the control group, were increased in the stable CF group to 2.7 (0.13) ppm (differences between means -0.67 (0.22), 95% confidence interval (CI) 0.22 to 1.12, p<0.01) and further increased in the unstable group to 4.8 (0.3) ppm (differences between means -2.15 (0.32), 95% CI 1.50 to 2.79, p<0.001). A significant correlation was found between the deterioration in FEV(1) and exhaled CO concentrations. CONCLUSIONS: This study shows that the measurement of exhaled CO is of potential value as an indicator of exacerbations in patients with CF and could be used as a simple method to monitor the course of the disease.
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The introduction, or extension, of freedom of information legislation in Britain and other Western countries seems certain to influence the climate for health services research. However, researchers should be clear that, although such legislation may improve access to certain types of data, it will also create new problems and dilemmas. Statutory freedom of information regimes are likely to raise difficult issues of adaptation and compliance for health service bodies. Researchers may find that this translates into reluctance to agree access and accentuates difficulties in managing field relationships. They may, inter alia, face difficult dilemmas in deciding whether, or how, to report non-compliance, judging whether to extend research into areas where consent has not been obtained and weighing the benefits of using the official rules to insist on disclosure against the dis-benefits of jeopardising relationships. Health services researchers should regard freedom of information legislation, not simply as a resource, but a topic deserving study in its own right.
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A 5-month-old 22-kg (48.4-lb) sexually intact male Collie was examined after ingesting a moxidectin-containing deworming medication. The dog was comatose and had respiratory arrest after progressively worsening lethargy, ataxia, and seizures. Exposure was confirmed by isolation of moxidectin from a biopsy specimen of adipose tissue, using liquid chromatography-mass spectroscopy methods. Treatment included use of intermittent positive-pressure ventilation, activated charcoal and cathartic administered enterally, nutrients administered via nasogastric tube, and intensive supportive care. The dog was weaned from a ventilator on day 6 after ingestion and was discharged on day 10. The dog was considered clinically normal during examination 24 days after ingestion. On the basis of the dog reported here and toxicologic data provided by the manufacturer of the deworming product, some Collies may have increased susceptibility to products containing high doses of moxidectin.
OBJECTIVE: To determine relationships between plasma lactate concentration and gastric necrosis and between plasma lactate concentration and outcome for dogs with gastric dilatation-volvulus. DESIGN: Retrospective study. ANIMALS: 102 dogs. PROCEDURE: Information on signalment, history, plasma lactate concentration, medical and surgical treatment, cost of hospitalization, and outcome was retrieved from medical records. RESULTS: 69 of 70 (99%) dogs with plasma lactate concentration < 6.0 mmol/L survived, compared with 18 of 31 (58%) dogs with plasma lactate concentration > 6.0 mmol/L (1 dog euthanatized for economic reasons was not included). Gastric necrosis was identified in 38 (37%) dogs. Median plasma lactate concentration in dogs with gastric necrosis (6.6 mmol/L) was significantly higher than concentration in dogs without gastric necrosis (3.3 mmol/L). Specificity and sensitivity of using plasma lactate concentration (with a cutoff of 6.0 mmol/L) to predict which dogs had gastric necrosis were 88 and 61%, respectively. Sixty-two of 63 (98%) dogs without gastric necrosis survived, compared with 25 of 38 (66%) dogs with gastric necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative plasma lactate concentration was a good predictor of gastric necrosis and outcome for dogs with GDV. Preoperative measurement of plasma lactate concentration may assist in determining prognosis of dogs with GDV.
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A study on the use of 3'-directing groups for the synthesis of imidazole 2'-deoxy-4'-thionucleosides led to varying alpha:beta ratios in the glycosylation reaction. The para-nitrobenzoyl group gave the optimum result in the glycosylation step; therefore, this protected thiosugar 10b was used for the synthesis of a series of novel 2'-deoxy-4'-thio-imidazole nucleosides which have been evaluated for antiviral activity in vitro.
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We compared the use of sevoflurane and propofol with three different doses of rocuronium for modified rapid-sequence induction of anaesthesia. One hundred and forty adult patients were randomly allocated to have a rapid-sequence intravenous induction with propofol 2-3 mg.kg-1 (group P) or an inhalational induction with sevoflurane 8% in oxygen, using a vital capacity technique (group S). Following loss of the eyelash reflex, cricoid pressure was applied and 20 patients in each group were administered rocuronium 0.3 (groups P/0.3 and S/0.3), 0.45 (groups P/0.45 and S/0.45) or 0.6 (groups P/0.6 and S/0.6) mg.kg-1. An additional 10 patients in each group received only saline placebo in place of the muscle relaxant (groups P/Saline and S/Saline). Laryngoscopy was started 60 s later and intubating conditions evaluated by a blinded anaesthetist according to a standard scoring system. Intubating conditions were acceptable in one patient and no patient, respectively, following induction with sevoflurane and propofol without the muscle relaxant. The conditions were acceptable in 30, 55 and 90% of subjects with sevoflurane induction, and in 45, 80 and 90% of subjects with propofol induction following 0.3, 0.45 and 0.6 mg.kg-1 of rocuronium, respectively (no significant difference for each dose of rocuronium). The present study shows that intubating conditions during a rapid-sequence induction using rocuronium 0.6 mg.kg-1 following induction of anaesthesia with sevoflurane or propofol are similar.