tbuckley/cabot-search huggingface dataset:
Lessons learned from the casualties of war: battlefield medicine and its implication for global trauma care
Authors: Catherine Chatfield-Ball, Peter Boyle, Philippe Autier, Sibylle Herzig van Wees, Richard Sullivan
Journal: Journal of the Royal Society of Medicine (2015)

Summary According to the Global Burden of Disease, trauma is now responsible for five million deaths each year. High-income countries have made great strides in reducing trauma-related mortality figures but low–middle-income countries have been left behind with high trauma-related fatality rates, primarily in the younger population. Much of the progress high-income countries have made in managing trauma rests on advances developed in their armed forces. This analysis looks at the recent advances in high-income military trauma systems and the potential transferability of those developments to the civilian health systems particularly in low–middle-income countries. It also evaluates some potential lifesaving trauma management techniques, proven effective in the military, and the barriers preventing these from being implemented in civilian settings.
Identification of Brain-Derived Neurotrophic Factor as a Novel Functional Protein in Hepatocellular Carcinoma
Authors: Zhen Fan Yang, David W. Ho, Chi Tat Lam, John M. Luk, Ching Tung Lum, Wan Ching Yu, Ronnie T. Poon, Sheung Tat Fan
Journal: Cancer Research (2005)

This study aims to identify a novel molecule that may contribute to hepatocarcinogenesis in a rat orthotopic hepatocellular carcinoma model. The hepatocellular carcinoma model was generated by injection of tumor cells into the left lobe of the liver. Proteomic approaches, including ProteinChip and two-dimensional electrophoresis, were used to identify proteins from serially collected rat serum samples. By both ProteinChip and two-dimensional electrophoresis techniques, the level of a 27-kDa protein was found to be augmented in serum samples during tumor development, decreased after left lobectomy, and reincreased at the time of tumor recurrence. The protein was identified to be brain-derived neurotrophic factor (BDNF). By using specific primers and monoclonal antibody, the expression pattern of BDNF was confirmed in tumor tissue but not in the adjacent nontumorous liver tissue. In addition, the truncated isoform of BDNF receptor-tyrosine protein kinase receptor B was only found in tumor tissue. An in vitro study showed that exogenous BDNF could induce tumor cell proliferation predominantly in relatively small numbers of inoculated cells. Administration of BDNF to tumor cell lines induced significantly increased expression of heat shock protein 90 (Hsp90) and cyclin D1, and blocking the activity of Hsp90 could reverse the up-regulation of cyclin D1 induced by BDNF. The present study revealed that BDNF and its receptor were uniquely expressed in tumor tissue and cell lines of hepatocellular carcimona but not in nontumorous liver tissue and normal cell line. BDNF could stimulate tumor cell proliferation in a Hsp90-dependent manner.
In vitro and in vivo activities of an oncolytic adenoviral vector designed to express GM-CSF
Authors: J.Andrew Bristol, Mingzhu Zhu, Hong Ji, Mervat Mina, Yuefeng Xie, Lori Clarke, Suzanne Forry-Schaudies, David L Ennist
Journal: Molecular Therapy (2003)

Oncolytic adenoviruses are being tested as biological cancer therapeutics. Ar6pAE2fF (E2F vector) contains the E2F-1 promoter to regulate the expression of the E1a gene in cells with a disregulated retinoblastoma pathway. Ar6pAE2fmGmF (E2F-GM vector) includes the murine granulocyte–macrophage colony-stimulating factor (GM-CSF) transgene to enhance anti-tumor activity. Both vectors selectively killed human tumor cells in vitro. The E2F-GM vector expressed biologically active murine GM-CSF in vitro and GM-CSF was detected for several days in serum and tumor extracts following injections of established human xenograft tumors. In vivo, both vectors showed significant dose-dependent anti-tumor responses. The E2F-GM vector elicited greater efficacy compared to the E2F vector, demonstrating that GM-CSF enhanced the anti-tumor activity, even in immunodeficient nude mice. Histological analysis showed that both vectors induced necrosis and mononuclear cell infiltration, but only the E2F-GM vector resulted in eosinophil infiltration. Vector replication in vivo was demonstrated. The data showed that intratumoral injection of a GM-CSF-armed oncolytic vector induced potent anti-tumor responses in xenograft tumor models, likely as the result of both oncolytic vector activity and the induction of GM-CSF-mediated inflammation and innate immunity.
A high-throughput single-cell analysis of human CD8+ T cell functions reveals discordance for cytokine secretion and cytolysis
Authors: Navin Varadarajan, Boris Julg, Yvonne J. Yamanaka, Huabiao Chen, Adebola O. Ogunniyi, Elizabeth McAndrew, Lindsay C. Porter, Alicja Piechocka-Trocha, Brenna J. Hill, Daniel C. Douek, Florencia Pereyra, Bruce D. Walker, J. Christopher Love
Journal: Journal of Clinical Investigation (2011)

CD8+ T cells are a key component of the adaptive immune response to viral infection. An inadequate CD8+ T cell response is thought to be partly responsible for the persistent chronic infection that arises following infection with HIV. It is therefore critical to identify ways to define what constitutes an adequate or inadequate response. IFN-γ production has been used as a measure of T cell function, but the relationship between cytokine production and the ability of a cell to lyse virus-infected cells is not clear. Moreover, the ability to assess multiple CD8+ T cell functions with single-cell resolution using freshly isolated blood samples, and subsequently to recover these cells for further functional analyses, has not been achieved. As described here, to address this need, we have developed a high-throughput, automated assay in 125-pl microwells to simultaneously evaluate the ability of thousands of individual CD8+ T cells from HIV-infected patients to mediate lysis and to produce cytokines. This concurrent, direct analysis enabled us to investigate the correlation between immediate cytotoxic activity and short-term cytokine secretion. The majority of in vivo primed, circulating HIV-specific CD8+ T cells were discordant for cytolysis and cytokine secretion, notably IFN-γ, when encountering cognate antigen presented on defined numbers of cells. Our approach should facilitate determination of signatures of functional variance among individual effector CD8+ T cells, including those from mucosal samples and those induced by vaccines.
H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy
Authors: J.-F. Rahier, P. Papay, J. Salleron, S. Sebastian, M. Marzo, L. Peyrin-Biroulet, V. Garcia-Sanchez, W. Fries, D. P. van Asseldonk, K. Farkas, N. K. de Boer, T. Sipponen, P. Ellul, E. Louis, S. T. C. Peake, U. Kopylov, J. Maul, B. Makhoul, G. Fiorino, Y. Yazdanpanah, M. Chaparro
Journal: Gut (2011)

Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy.The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded.Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%).Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.
Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial
Authors: J. Duran-Cantolla, F. Aizpuru, J. M. Montserrat, E. Ballester, J. Teran-Santos, J. I. Aguirregomoscorta, M. Gonzalez, P. Lloberes, J. F. Masa, M. De La Pena, S. Carrizo, M. Mayos, F. Barbe
Journal: BMJ (2010)

To assess the effect of continuous positive airway pressure (CPAP) on 24 hour ambulatory blood pressure monitoring values in a large number of patients with untreated systemic hypertension of new onset and obstructive sleep apnoea.Multicentre, double blind, randomised, placebo controlled trial.Eleven general hospitals in Spain between 2004 and 2007.340 patients recently diagnosed as having systemic hypertension by a general practitioner (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or both) and an apnoea-hypopnoea index per hour of sleep of >15 events/hour.Patients were assigned to CPAP (n=169) or sham CPAP (n=171) for three months. Main outcome measurements Net changes in the different 24 hour ambulatory blood pressure monitoring values from baseline to three months of optimal or sham CPAP.277 (81%) of the 340 patients randomised were men; the patients had a mean age of 52.4 (SD 10.5) years, a body mass index of 31.9 (5.7), an Epworth sleepiness scale score of 10.1 (4.3), an apnoea-hypopnoea index of 43.5 (24.5). No differences between groups were seen at baseline. Compared with placebo and analysed by intention to treat, the mean 24 hour ambulatory blood pressure of the CPAP group decreased by 1.5 (95% confidence interval: 0.4 to 2.7) mm Hg (P=0.01). The mean 24 hour ambulatory blood pressure monitoring measures decreased by 2.1 mm Hg (0.4 to 3.7) mm Hg (P=0.01) for systolic pressure and 1.3 (0.2 to 2.3) mm Hg (P=0.02) for diastolic blood pressure. Mean nocturnal blood pressure decreased by 2.1 (0.5 to 3.6) mm Hg (P=0.01).CPAP produced a statistically significant reduction in blood pressure in patients with systemic hypertension and obstructive sleep apnoea. This reduction is small and did not achieve the 3 mm Hg drop in mean 24 hour ambulatory blood pressure that the trial was powered to detect. Consequently, these results may have uncertain clinical relevance. However, taking into account the prevalence of hypertension and the likelihood of comorbidities, the decrease in blood pressure, although minimal, may be beneficial.Clinical trials NCT00202527.
Red Meat Enhances the Colonic Formation of the DNA Adduct <i>O</i>6-Carboxymethyl Guanine: Implications for Colorectal Cancer Risk
Authors: Michelle H. Lewin, Nina Bailey, Tanya Bandaletova, Richard Bowman, Amanda J. Cross, Jim Pollock, David E.G. Shuker, Sheila A. Bingham
Journal: Cancer Research (2006)

Abstract Red meat is associated with increased risk of colorectal cancer and increases the endogenous formation of N-nitrosocompounds (NOC). To investigate the genotoxic effects of NOC arising from red meat consumption, human volunteers were fed high (420 g) red meat, vegetarian, and high red meat, high-fiber diets for 15 days in a randomized crossover design while living in a volunteer suite, where food was carefully controlled and all specimens were collected. In 21 volunteers, there was a consistent and significant (P &amp;lt; 0.0001) increase in endogenous formation of NOC with the red meat diet compared with the vegetarian diet as measured by apparent total NOC (ATNC) in feces. In colonic exfoliated cells, the percentage staining positive for the NOC-specific DNA adduct, O6-carboxymethyl guanine (O6CMG) was significantly (P &amp;lt; 0.001) higher on the high red meat diet. In 13 volunteers, levels were intermediate on the high-fiber, high red meat diet. Fecal ATNC were positively correlated with the percentage of cells staining positive for O6CMG (r2 = 0.56, P = 0.011). The presence of O6CMG was also shown in intact small intestine from rats treated with the N-nitrosopeptide N-acetyl-N′-prolyl-N′-nitrosoglycine and in HT-29 cells treated with diazoacetate. This study has shown that fecal NOC arising from red meat include direct acting diazopeptides or N-nitrosopeptides able to form alkylating DNA adducts in the colon. As these O6CMG adducts are not repaired, and if other related adducts are formed and not repaired, this may explain the association of red meat with colorectal cancer. (Cancer Res 2006; 66(3): 1859-65)
Cognitive Enhancement Treatment for People With Mental Illness Who Do Not Respond to Supported Employment: A Randomized Controlled Trial
Authors: Susan R. McGurk, Kim T. Mueser, Haiyi Xie, Jason Welsh, Susan Kaiser, Robert E. Drake, Deborah R. Becker, Edward Bailey, Ginnie Fraser, Rosemarie Wolfe, Gregory J. McHugo
Journal: American Journal of Psychiatry (2015)

Objective: Cognitive impairment presents a serious and common obstacle to competitive employment for people with severe mental illness, including those who receive supported employment. This study evaluated a cognitive enhancement program to improve cognition and competitive employment in people with mental illness who had not responded to supported employment. Method: In a randomized controlled trial, 107 people with severe mental illness (46% with schizophrenia or schizoaffective disorder) who had not obtained or kept competitive work despite receiving high-fidelity supported employment were assigned to receive either enhanced supported employment (with specialized cognitive training of employment specialists) or enhanced supported employment plus the Thinking Skills for Work program, a standardized cognitive enhancement program that includes practice of computer cognitive exercises, strategy coaching, and teaching of coping and compensatory strategies. Research assistants tracked competitive employment weekly for 2 years, and assessors blind to treatment assignment evaluated cognitive functioning at baseline, at the end of cognitive enhancement training, and 12 and 24 months after baseline. Results: Participants in the Thinking Skills for Work group improved more than those in the enhanced supported employment only group on measures of cognitive functioning and had consistently better competitive employment outcomes during the follow-up period, including in jobs obtained (60% compared with 36%), weeks worked (23.9 compared with 9.2), and wages earned ($3,421 compared with $1,728). Conclusions: The findings suggest that cognitive enhancement interventions can reduce cognitive impairments that are obstacles to work, thereby increasing the number of people who can benefit from supported employment and competitive work.
A Regional System to Provide Timely Access to Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction
Authors: Timothy D. Henry, Scott W. Sharkey, M. Nicholas Burke, Ivan J. Chavez, Kevin J. Graham, Christopher R. Henry, Daniel L. Lips, James D. Madison, Katie M. Menssen, Michael R. Mooney, Marc C. Newell, Wes R. Pedersen, Anil K. Poulose, Jay H. Traverse, Barbara T. Unger, Yale L. Wang, David M. Larson
Journal: Circulation (2007)

Background— Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is superior to fibrinolysis when performed in a timely manner in high-volume centers. Recent European trials suggest that transfer for PCI also may be superior to fibrinolysis and increase access to PCI. In the United States, transfer times are consistently long; therefore, many believe a transfer for PCI strategy for STEMI is not practical. Methods and Results— We developed a standardized PCI-based treatment system for STEMI patients from 30 hospitals up to 210 miles from a PCI center. From March 2003 to November 2006, 1345 consecutive STEMI patients were treated, including 1048 patients transferred from non-PCI hospitals. The median first door-to-balloon time for patients &lt;60 miles (zone 1) and 60 to 210 miles (zone 2) from the PCI center was 95 minutes (25th and 75th percentiles, 82 and 116 minutes) and 120 minutes (25th and 75th percentiles, 100 and 145 minutes), respectively. Despite the high-risk unselected patient population (cardiogenic shock, 12.3%; cardiac arrest, 10.8%; and elderly [≥80 years of age], 14.6%), in-hospital mortality was 4.2%, and median length of stay was 3 days. Conclusions— Rapid transfer of STEMI patients from community hospitals up to 210 miles from a PCI center is safe and feasible using a standardized protocol with an integrated transfer system.
Photodynamic therapy: where do we go from here?
Authors: D. Moro-Sibilot, C. Brambilla
Journal: European Respiratory Journal (2003)

Photodynamic therapy (PDT) involves the use of photosensitising agents that are selectively retained within tumour cells. The agents remain inactive until exposed to light of the proper wavelength. When activated by light, these compounds generate toxic oxygen radicals that result in tumour necrosis. In the current issue of the European Respiratory Journal , Moghissi et al. 1 have provided an exhaustive review of PDT and lung cancer. PDT appears to be a therapeutic technique, with a low toxicity profile and photosensitising agents, such as sodium porfimer, that have been approved by the Food and Drug Administration and European Agencies for the photodynamic treatment of early and late stage lung cancer.

However, despite 2 decades of basic research and clinical experience, only a few centres have regular experience of PDT. Furthermore, several issues remain as yet unresolved, such as the best indications of PDT, the use of photosensitising agents other than sodium porfimer, or the comparison ofPDT and other endobronchial therapies, such as electrocautery, Neodymium-doped Yttrium …
Cell cycle–dependent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity
Authors: Paola Romagnani, Francesco Annunziato, Laura Lasagni, Elena Lazzeri, Chiara Beltrame, Michela Francalanci, Mariagrazia Uguccioni, Grazia Galli, Lorenzo Cosmi, Lucia Maurenzig, Marco Baggiolini, Enrico Maggi, Sergio Romagnani, Mario Serio
Journal: Journal of Clinical Investigation (2001)

Endothelial cell receptors for the angiostatic chemokines IFN-γ–inducible protein of 10 kDa (IP-10) and monokine induced by IFN-γ (Mig) have not yet been identified, and the mechanisms responsible for the effects of these chemokines on angiogenesis are still unclear. IP-10 and Mig share a common functional receptor on activated T lymphocytes, named CXC chemokine receptor 3 (CXCR3). Using in situ hybridization and immunohistochemistry, we show that CXCR3 is expressed by a small percentage of microvascular endothelial cells in several human normal and pathological tissues. Primary cultures of human microvascular endothelial cells (HMVECs) likewise express CXCR3, although this expression is limited to the S/G2-M phase of their cell cycle. Both IP-10 and Mig, as well as the IFN-γ–inducible T-cell α chemoattractant (I-TAC), which all share high-affinity binding for CXCR3, block HMVEC proliferation in vitro, an effect that can be inhibited by an anti-CXCR3 antibody. These data provide definitive evidence of CXCR3 expression by HMVEC and open new avenues for therapeutic interventions in all conditions in which an angiostatic effect may be beneficial.
A Qualitative Distinction between the Beta-Receptor-Blocking and Local Anesthetic Actions of Antiarrhythmic Agents
Authors: ELLIOT SHINEBOURNE, ROGER WHITE, JOHN HAMER
Journal: Circulation Research (1969)

Fragmented cardiac sarcoplasmic reticulum was isolated by differential centrifugation from canine myocardium. The effects of propranolol, quinidine, lidocaine (lignocaine) and tetracaine (amethocaine) on calcium uptake in sarcoplasmic reticulum in vitro were then measured. All the drugs are antiarrhythmic agents with local anesthetic activity, but propranolol and quinidine are known also to have beta-receptor-blocking actions in that they can prevent the cardiac effects of isoprenaline and depress the myocardium. Lidocaine and tetracaine do not generally depress the heart and had no effect on the calcium uptake, but propranolol and quinidine both significantly inhibited it. It was concluded that the antiarrhythmic actions of propranolol (and quinidine) may be independent of beta-receptor-blocking activity, and that the safety of lidocaine as an antiarrhythmic agent may be related to a lack of effect on the sarcoplasmic reticulum.
Impairment of Cd4+ T Cell Responses during Chronic Virus Infection Prevents Neutralizing Antibody Responses against Virus Escape Mutants
Authors: Adrian Ciurea, Lukas Hunziker, Paul Klenerman, Hans Hengartner, Rolf M. Zinkernagel
Journal: The Journal of Experimental Medicine (2001)

We have shown previously that neutralizing antibodies (nAbs) are important contributors to the long-term immune control of lymphocytic choriomeningitis virus infection, particularly if cytotoxic T cell responses are low or absent. Nevertheless, virus escape from the nAb response due to mutations within the surface glycoprotein gene may subsequently allow the virus to persist. Here we show that most of the antibody-escape viral mutants retain their immunogenicity. We present evidence that the failure of the infected host to mount effective humoral responses against emerging neutralization-escape mutants correlates with the rapid loss of CD4+ T cell responsiveness during the establishment of viral persistence. Similar mechanisms may contribute to the persistence of some human pathogens such as hepatitis B and C viruses, and human immunodeficiency virus.