123 research outputs found
The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.
No full textBACKGROUND Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed.
OBJECTIVE Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients.
DESIGN Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars (30,830. The incremental cost of giving TXA compared with not giving TXA was 64.
CONCLUSIONS Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/).
TRIAL REGISTRATION Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919.
FUNDING The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information
An investigation of fludarabine as a potential radiation sensitizer of human prostate cancer cells in vitro
No full textAim: Patient relapse following radiotherapy for prostate cancer is of major concern to oncologists. As chemotherapeutic agents have shown promise as radiation sensitizers, we investigated the use of fludarabine monophosphate as a radiation enhancement agent in human LNCaP-LN3, PC3 and LNCaP prostate carcinoma cell lines with different sensitivities to fludarabine and ionizing radiation. Methods: Cells were treated with non-cytotoxic doses of fludarabine for 16 h pre-irradiation or 5 days post-irradiation; survival fractions were determined by clonogenic assay. Cell cycling was also assessed. Results: LNCaP-LN3 cells incubated with 1 μmol/L fludarabine for 5days post-irradiation were slightly sensitized (1.18 times, P =0.029), whilst 16 h pre-incubation had no effect on the radiation response. PC3 cells incubated with 10μmol/L fludarabine for 16h pre-irradiation were sensitized to ionizing radiation (1.61 times, P < 0.0001), but treatment for 5days post-irradiation with fludarabine had no effect on their radiosensitivity. Neither fludarabine incubation had any effect on the sensitivity of LNCaP cells to ionizing radiation. A characterization of the cell cycle following 16h exposure to fludarabine demonstrated that enhanced radiosensitivity of PC3 cells is independent of cell cycle. Conclusion: PC3, but not LN3 or LNCaP cells, were sensitized to ionizing radiation by pre-incubation with 10 μmol/L fludarabine for 16h (1.61 times, P < 0.0001) but not by post-irradiation exposure to the drug. The enhanced radiosensitivity of PC3 cells is independent of cell cycle. Further studies are required to elucidate the mechanism of fludarabine mediated sensitization in these cells. © 2008 The Authors Journal Compilatio
Emergency care research priorities in South Africa
No full textCITATION: Van Hoving, D.J., Barnetson, B.K. & Wallis, L. 2015. Emergency care research priorities in South Africap. South African Medical Journal, 105(3):202-208, doi:10.7196/SAMJ.8967.The original publication is available at http://www.samj.org.za/index.php/samj/indexENGLISH SUMMARY : Background. Emergency care research is rarely undertaken in low- and middle-income countries. A manageable ‘road map’ for research in South African (SA) emergency care is needed to address research gaps.
Objective. To identify, collate and prioritise research topics from identified knowledge gaps in emergency care in SA.
Methods. Seventy-six individuals were invited to participate in a modified Delphi study. Participants were requested to suggest important
research topics before rating them. Consensus was achieved when >75% of participants strongly agreed or disagreed. Participants then
ranked the agreed statements before selecting the most appropriate methodology relating to study design, funding and collaboration.
Results. Three hundred and fifty topics were suggested by 31 participants. Topics were collated into 123 statements before participants rated them. Consensus was achieved for 39 statements. The highest-ranked priority in the prehospital group was to determine which prehospital interventions improve outcomes in critically ill patients. The competence of emergency care providers in performing common lifesaving skills was deemed the most important in clinical emergency care. Implementing and reviewing quality improvement systems scored the highest under general systems and safety management. Only 22 statements achieved consensus regarding study design. The National Department of Health was the preferred funding source, while private organisations and emergency care societies were identified as possible collaborative partners.
Conclusion. This study provides expert consensus on priority research areas in emergency care in SA as a guide for emergency care providers to ensure evidence-based care that is relevant to the SA population.Publishers versio
Genetic heterogeneity in heterocellular hereditary persistence of fetal hemoglobin
No full textCraig, J E ; Rochette, J ; Sampietro, M ; Wilkie, A O ; Barnetson, R ; Hatton, C S ; Demenais, F ; Thein, S
Supplementary Data from Docetaxel-Resistant Prostate Cancer Cells Remain Sensitive to <i>S</i>-Trityl-l-Cysteine–Mediated Eg5 Inhibition
No full textSupplementary Data from Docetaxel-Resistant Prostate Cancer Cells Remain Sensitive to S-Trityl-l-Cysteine–Mediated Eg5 Inhibitio
Sunscreens - Which and what for?
No full textIt is well established that sun exposure is the main cause for the development of skin cancer. Chronic continuous UV radiation is believed to induce malignant melanoma, whereas intermittent high-dose UV exposure contributes to the occurrence of actinic keratosis as precursor lesions of squamous cell carcinoma as well as basal cell carcinoma. Not only photocarcinogenesis but also the mechanisms of photoaging have recently become apparent. In this respect the use of sunscreens seemed to prove to be more and more important and popular within the last decades. However, there is still inconsistency about the usefulness of sunscreens. Several studies show that inadequate use and incomplete UV spectrum efficacy may compromise protection more than previously expected. The sunscreen market is crowded by numerous products. Inorganic sunscreens such as zinc oxide and titanium oxide have a wide spectral range of activity compared to most of the organic sunscreen products. It is not uncommon for organic sunscreens to cause photocontact allergy, but their cosmetic acceptability is still superior to the one given by inorganic sunscreens. Recently, modern galenic approaches such as micronization and encapsulation allow the development of high-quality inorganic sunscreens. The potential systemic toxicity of organic sunscreens has lately primarily been discussed controversially in public, and several studies show contradictory results. Although a matter of debate, at present the sun protection factor (SPF) is the most reliable information for the consumer as a measure of sunscreen filter efficacy. In this context additional tests have been introduced for the evaluation of not only the protective effect against erythema but also protection against UV-induced immunological and mutational effects. Recently, combinations of UV filters with agents active in DNA repair have been introduced in order to improve photoprotection. This article reviews the efficacy of sunscreens in the prevention of epithelial and nonepithelial skin cancer, the effect on immunosuppression and the value of the SPF as well as new developments on the sunscreen market. Copyright (C) 2005 S. Karger AG, Basel
Nitric Oxide Appears to Be a Mediator of Solar-Simulated Ultraviolet Radiation-Induced Immunosuppression in Humans
No full textTopical application of NG-methyl-L-arginine and 2,2′-dipyridyl were used to examine the respective roles of nitric oxide and reactive oxygen species in solar-simulated ultraviolet radiation-induced immunosuppression in humans in vivo. Immunosuppression was studied using a nickel contact hypersensitivity recall model. Ultraviolet radiation dose–responses were generated to determine the extent to which NG-methyl-L-arginine and 2,2′-dipyridyl affected the immune response. NG-methyl-L-arginine but not 2,2′-dipyridyl protected the immune system from ultraviolet radiation-induced suppression. Both NG-methyl-L-arginine and 2,2′-dipyridyl inhibited nitrite production. Nitrite is a degradation product of peroxynitrite, a cytotoxic mediator resulting from reactions between nitric oxide and reactive oxygen species. This suggests that nitric oxide, not its downstream product peroxynitrite, was likely to be responsible for solar-simulated ultraviolet radiation-induced immunosuppression. In contrast, both nitric oxide and reactive oxygen species were mediators of solar-simulated ultraviolet radiation-induced apoptosis and loss of dendritic S-100+ cells (probably Langerhans cells) from the epidermis. It is likely that different mechanisms are involved in these ultraviolet-induced endpoints and that events in addition to Langerhans cell depletion are important for local immune suppression to recall antigens in humans. Understanding the mechanisms of cutaneous ultraviolet-induced oxidative stress will assist in the future design of novel products that protect skin from photoaging and skin cancer
Regulation of the Skin Immune System by Retinoids During Carcinogenesis
No full textOne of the immunosuppressive effects of both ultraviolet (UV) light and chemical carcinogens is to deplete Langerhans cells (LC) from the epidermis, suggesting that these cells play an important role in inducing immune responses to developing tumors during the early phases of carcinogenesis. Retinoids such as all-trans-retinoic acid (PA) are natural or synthetic derivatives of vitamin A; RA binds to nuclear receptors in the skin, effecting transcription of a wide range of genes. Topical application of PA prevents the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) from depleting the density of LC in murine epidermis. In contrast, topical RA did not itself alter the normal LC density. PA also inhibited the development of TPA-induced immunosuppression to a locally applied contact sensitizer. Topical RA also prevented UV light from reducing the density of both LC and Thy-l+dendritic epidermal cells (Thy-l+dEC). However, the RA treatment did not prevent local immunosuppression to the contact sensitizer from developing in response to UV irradiation. The reasons for this are unclear; however, it is possible that PA does not inhibit some other immunosuppressive effect of UV light. Temarotene, a recently developed synthetic retinoid also inhibited UV light from reducing the LC and Thy-1+dEC density from murine epidermis. Thus part of the anti-carcinogenic activity of retinoids may be due to their ability to protect LC during the early stages of carcinogenesis
Sunscreens Protect Epidermal Langerhans Cells and Thy-1+ Cells But Not Local Contact Sensitization from the Effects of Ultraviolet Light
No full textThis study compares the ability of two commonly used sunscreens–octyl dimethyl para-aminobenzoate (Padimate O) and 2-ethylhexyl-p-methoxycinnamate (2-EHMC) to protect Langerhans cells (LC), Thy-1+ dendritic epidermal cells (Thy-1+dEC), and local contact sensitivity (CS) from the effects of ultraviolet (UV) light. Chronic exposure of mice 5 d per week for 4 Weeks with an intermediate dose of solar-simulated sunlight from which any UVC had been filtered reduced the LC and Thy-1+ dEC density of murine epidermis. This irradiation procedure was designed to simulate closely the daily exposure of humans to sunlight. This effect on LC and Thy-1+dEC occurred in both albino and pigmented mice that develop a tan during the irradiation procedure, indicating that a tan does not protect these cells from the effects of UV light. Sunscreen preparations with Padimate O and 2-EHMC, both of which also contained benzophenone-3, as well as Padimate O or 2-EHMC in organic solvent, inhibited UV light from depleting LC from the epidermis of both mouse strains. Padimate O and 2EHMC in organic solvent were used to ensure that these were the active ingredients in the sunscreen preparations. In contrast to the effects on LC, Padimate O, but not 2-EHMC, protected Thy-l+dEC from UV exposure in both mouse strains, but neither protected against the development of local immunosuppression using a contact sensitivity model. Thus, even in a mouse strain that is sensitive to UV-induced immunosuppression, local immunosuppression can occur in the presence of normal densities of LC and Thy-l+ dEC
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