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Biomedical subjects

P Edwards

Publications and source records attributed to P Edwards.

At least 55 records · Page 3Linked to original sources

Monitor: molecules and profiles.

Monitor provides an insight into the latest developments in drug discovery through brief synopses of recent presentations and publications together with expert commentaries on the latest technologies. There are two sections: Molecules summarizes the chemistry and the pharmacological significance and biological relevance of new molecules reported in the literature and on the conference scene; Profiles offers commentary on promising lines of research, emerging molecular targets, novel technology, advances in synthetic and separation techniques and legislative issues.

Journal Article↗

Size and quality of randomised controlled trials in head injury: review of published studies.

OBJECTIVE: To assess whether trials in head injury are large enough to avoid moderate random errors and designed to avoid moderate biases. DESIGN: All randomised controlled trials on the treatment and rehabilitation of patients with head injury published before December 1998 were surveyed. Trials were identified from electronic databases, by hand searching journals and conference proceedings, and by contacting researchers. Data were extracted on the number of participants, quality of concealment of allocation, use of blinding, loss to follow up, and types of participants, interventions, and outcome measures. RESULTS: 279 reports were identified, containing information on 208 separate trials. The average number of participants per trial was 82, with no evidence of increasing size over time. The total number of randomised participants in the 203 trials in which size was reported was 16 613. No trials were large enough to detect reliably a 5% absolute reduction in the risk of death or disability, and only 4% were large enough to detect an absolute reduction of 10%. Concealment of allocation was adequate in 22 and inadequate or unclear in 25 of the 47 (23%) in which it was reported. Of 126 trials assessing disability, 111 reported the number of patients followed up, and average loss to follow up was 19%. Of trials measuring disability, 26 (21%) reported that outcome assessors were blinded. CONCLUSIONS: Randomised trials in head injury are too small and poorly designed to detect or refute reliably moderate but clinically important benefits or hazards of treatment. Limited funding for injury research and unfamiliarity with issues of consent may have been important obstacles.

Bias↗

Fibroblast growth factor signalling and cyclin D1 function are necessary for normal mammary gland development during pregnancy. A transgenic mouse approach.

A number of growth factors, growth factor receptors and cell cycle regulatory proteins have been implicated in the genesis of mammary carcinomas both in animal models as well as in human breast tumour samples. Studies on the development of the mammary gland has revealed that several of the proto-oncogenes, or their closely related gene-family members, have a function in the normal growth and differentiation of the gland. In this review the role of fibroblast growth factor signalling and the critical requirement for the cell cycle regulator, cyclin D1 is discussed with respect to their normal function in mammary gland development and abnormal role in mammary carcinogenesis.

Animals↗

The distribution of caprylate, caprate and laurate in lipids from developing and mature seeds of transgenic Brassica napus L.

The composition and positional distribution of lipids in developing and mature transgenic Brassica napus seeds accumulating up to 7 mol% of caprylate (8:0), 29 mol% caprate (10:0) or 63 mol% of laurate (12:0) were examined. The accumulation of 8:0 and 10:0 resulted from over-expression of the medium-chain-specific thioesterase (Ch FatB2) alone or together with the respective chain-length-specific condensing enzyme (Ch KASIV). Seeds containing high levels of 12:0 were obtained from plants expressing bay thioesterase (BTE) alone or crossed with a line over-expressing the coconut lysophosphatidic acid acyltransferase (LPAAT), an enzyme responsible for the increase in acylation of 12:0 at the sn-2 position. In all instances, 10:0 and 12:0 fatty acids were present in substantial amounts in phosphatidylcholine during seed development with a drastic decrease of 80-90% in mature seeds. At all stages of seed development however, 8:0 was barely detectable in this membrane lipid. Altogether, these results indicate that these transgenic seeds exclude and/or remove the medium-chain fatty acids from their membrane and that this mechanism(s) is more effective with the shorter-chain fatty acids. Furthermore, seeds of 8:0- and 10:0-producing lines had only negligible levels of these fatty acids present in the sn-2 position of the triacylglycerols. In contrast, all 12:0-producing seeds had a substantial amount of this fatty acid in the sn-2 position of the triacylglycerols, suggesting that the endogenous LPAAT is able to acylate 12:0 if no other acyl-CoA species are available.

Brassica↗

Urban residential fire and flame injuries: a population based study.

BACKGROUND: Fires are a leading cause of death, but non-fatal injuries from residential fires have not been well characterised. METHODS: To identify residential fire injuries that resulted in an emergency department visit, hospitalisation, or death, computerised databases from emergency departments, hospitals, ambulance and helicopter services, the fire department, and the health department, and paper records from the local coroner and fire stations were screened in a deprived urban area between June 1996 and May 1997. RESULT: There were 131 fire related injuries, primarily smoke inhalation (76%), an incidence of 36 (95% confidence interval (CI) 30 to 42)/100,000 person years. Forty one patients (32%) were hospitalised (11 (95% CI 8 to 15)/100,000 person years) and three people (2%) died (0.8 (95% CI 0.2 to 2.4)/100,000 person years). Injury rates were highest in those 0-4 (68 (95% CI 39 to 112)/100,000 person years) and > or = 85 years (90 (95% CI 29 to 213)/100,000 person years). Rates did not vary by sex. Leading causes of injury were unintentional house fires (63%), assault (8%), clothing and nightwear ignition (6%), and controlled fires (for example, gas burners) (4%). Cooking (31%) and smoker's materials (18%) were leading fire sources. CONCLUSIONS: Because of the varied causes of fire and flame injuries, it is likely that diverse interventions, targeted to those at highest risk, that is, the elderly, young children, and the poor, may be required to address this important public health problem.

Accidents, Home↗

Do British travel agents provide adequate health advice for travellers?

Travel-related illness is a burden for primary care, with more than two million travellers consulting a general practitioner each year. The annual cost of travel-related illness in the United Kingdom is 11 million Pounds. Travel agents are in a unique position to influence this burden as the most common and most serious problems are preventable with simple advice and/or immunisation. This study, using covert researchers, suggests this potential is not being fully utilised.

Female↗

Why the government was right to change the 'Our Healthier Nation' accidental injury target.

We congratulate the current UK Government on their inclusion of accidental injury as one of the national targets in the White Paper: Saving Lives-Our Healthier Nation (OHN). We had concerns about the particular target that was proposed in the Green Paper: 'ellipsisto reduce the rate of accidents-here being defined as those which involve a hospital visit or consultation with a family doctor-by at least a fifthellipsis'. The limitations of this target were: firstly, it would focus attention on minor injury and so not reflect the main burden of injury; and secondly, that ascertainment of cases would be influenced by social factors as well as provision of service and access factors. The new target stated in Saving Lives also has its limitations since it will be influenced by service factors. This target is to reduce by 10% the rate of serious injury, defined as injury resulting in four or more days in hospital. We have proposed the use of an alternative indicator of unintentional injury occurrence, based on serious long bone fracture admitted to the hospital. This alternative indicator is based on the occurrence of serious rather than minor injury. It is likely that a high proportion of cases of these injuries can be identified from existing data sources. Ascertainment of cases is likely to be independent of social, service or access factors. Finally, these injuries are associated with significant long term outcomes including disablement, reduced functional capacity and reduced quality of life. It does have the limitation that it does not measure all serious injury. Such a measure is much more difficult to achieve. Further improvements to our proposed indicator could be made in a number of ways, through investigating an extended definition of the indicator to include a range of other serious injuries, improving the quality of existing data, making other data sources available, including outpatient data, and making serious injury a notifiable disease.

Accident Prevention↗

Abnormalities of adherent layers grown from bone marrow of patients with myelodysplasia.

Myelodysplastic syndromes (MDS) are characterized by a clonal disorder of haemopoiesis with defective growth in vitro. The long-term culture system was used to examine aspects of stromal function in MDS patients. Primary long-term cultures of MDS bone marrow showed poor myelopoiesis with progenitors being detected for a median 3.5 weeks (n = 12) compared with 18 weeks in cultures of normal marrow (n = 10; P < 0.0001). The haemopoietic function of adherent layers was assessed in secondary co-cultures seeded with 5 x 10(6) cord blood mononuclear cells on irradiated normal (n = 27; aged 38-82 years) or MDS (n = 32; aged 41-86 years) adherent layers (> 60% confluent). The median myeloid progenitor number/cord blood co-culture was 135 in 5-week-old cultures with normal adherent layers and 22 in those with MDS layers (P < 0.0001). Myeloid colonies were detectable for a median 11 weeks with normal adherent layers and 6 weeks with MDS adherent layers (P < 0.0001); erythroid colonies were detectable for 7 weeks (normal) compared with 5 weeks (MDS) (P < 0.01). The differences in granulocyte-macrophage colony forming unit (CFU-GM) generation were not related to patient age. Cells from adherent layers of at least half of the primary normal (n = 48) and MDS (n = 26) long-term cultures expressed cytokines [interleukin (IL)-3, IL-1 beta, thrombopoietin (Tpo) and erythropoietin (Epo)] and receptors for retinoic acid (RAR alpha) [IL-2, IL-3, macrophage colony stimulating factor (M-CSF) (Fms) and Tpo (Mpl)]. Only IL-1 beta expression was reduced in week-5 MDS cultures compared with those from normal marrows (P < 0.05). There was also a highly significant decline in IL-1 beta expression in normal (but not MDS) adherent layers between week 5 and week 10. Thus, the adherent layers in cultures grown from MDS patients were haemopoietically defective and showed abnormal IL-1 beta expression.

Adult↗

Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.

In the biosynthesis of fatty acids, the beta-ketoacyl-acyl carrier protein (ACP) synthases catalyze chain elongation by the addition of two-carbon units derived from malonyl-ACP to an acyl group bound to either ACP or CoA. The enzyme is a possible drug target for treatment of certain cancers and for tuberculosis. The crystal structure of the complex of the enzyme from Escherichia coli, and the fungal mycotoxin cerulenin reveals that the inhibitor is bound in a hydrophobic pocket formed at the dimer interface. Cerulenin is covalently attached to the active site cysteine through its C2 carbon atom. The fit of the inhibitor to the active site is not optimal, and there is thus room for improvement through structure based design.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Chronic compartment syndrome affecting the lower limb: MIBI perfusion imaging as an alternative to pressure monitoring: two case reports.

Intracompartmental pressure monitoring remains the primary method of diagnosing chronic compartment syndrome. MIBI perfusion imaging is widely available and offers a radionuclear imaging technique for diagnosing this condition. Although the results are not identical with those from pressure monitoring, MIBI may offer a useful screening test for this condition.

Adult↗