tbuckley/cabot-search huggingface dataset:
Health secretary calls on GPs to accept new contract
Authors: I. Haivas
Journal: BMJ (2003)

Health Secretary Alan Milburn has called on GPs to endorse the proposed new GPs contract, issued last month (1 March, 465).

Speaking at the National Association of Primary Care Conference held on 5 March, Mr Milburn emphasised the benefits of the new contract. “It will help GPs better manage workload, in particular the burden of out of hours care,” he said. “It will support the desire many practices have to deliver a greater range of new and …
Genetic Viability and Population History of the Giant Panda, Putting an End to the “Evolutionary Dead End”?
Authors: Baowei Zhang, Ming Li, Zejun Zhang, Benoît Goossens, Lifeng Zhu, Shanning Zhang, Jinchu Hu, Michael W. Bruford, Fuwen Wei
Journal: Molecular Biology and Evolution (2007)

The giant panda (Ailuropoda melanoleuca) is currently threatened by habitat loss, fragmentation, and human persecution. Its dietary specialization, habitat isolation, and reproductive constraints have led to a perception that this is a species at an "evolutionary dead end," destined for deterministic extinction in the modern world. Here we examine this perception by a comprehensive investigation of its genetic diversity, population structure, and demographic history across its geographic range. We present analysis of 655 base pairs of mitochondrial (mt) control region (CR) DNA and 10 microsatellite loci for samples from its 5 extant mountain populations (Qinling, Minshan, Qionglai, Liangshan, and Lesser Xiangling). Surprisingly, extant populations display average to high levels of CR and microsatellite diversity compared with other bear species. Genetic differentiation among populations was significant in most cases but was markedly higher between Qinling and the other mountain ranges, suggesting, minimally, that the Qinling population should comprise a separate management unit for conservation purposes. Recent demographic inference using microsatellite markers demonstrated a clear genetic signature for population decline starting several thousands years ago or even futher back in the past, and being accelerated and enhanced by the expansion of human populations. Importantly, these data suggest that the panda is not a species at an evolutionary "dead end," but in common with other large carnivores, has suffered demographically at the hands of human pressure. Conservation strategies should therefore focus on the restoration and protection of wild habitat and the maintenance of the currently substantial regional genetic diversity, through active management of disconnected populations.
Efficacy of Glyburide in Diabetics Poorly Controlled on First-Generation Oral Hypoglycemics
Authors: Kenneth L Cohen, Susanne Harris
Journal: Diabetes Care (1987)

Twenty-four type II (non-insulin-dependent) diabetic patients poorly controlled on maximum doses of first-generation oral hypoglycemic agents were switched to glyburide. There was a significant decrease in glycosylated hemoglobin, but the level was normalized in only four patients; there was no correlation with age, weight, or duration of diabetes. The best predictor for improvement was initial failure on tolbutamide, as opposed to the other first-generation drugs. Patients not controlled with 500 mg/day of chlorpropamide were less likely to benefit from glyburide therapy.
Functional KCa3.1 K+ channels are required for human lung mast cell migration
Authors: G Cruse
Journal: Thorax (2006)

<b>Background:</b> Mast cell recruitment and activation are critical for the initiation and progression of inflammation and fibrosis. Mast cells infiltrate specific structures in many diseased tissues such as the airway smooth muscle (ASM) in asthma. This microlocalisation of mast cells is likely to be key to disease pathogenesis. Human lung mast cells (HLMC) express the Ca<sup>2+</sup> activated K<sup>+</sup> channel K<sub>Ca</sub>3.1 which modulates mediator release, and is proposed to facilitate the retraction of the cell body during migration of several cell types. A study was undertaken to test the hypothesis that blockade of K<sub>Ca</sub>3.1 would attenuate HLMC proliferation and migration. <b>Methods:</b> HLMC were isolated and purified from lung material resected for bronchial carcinoma. HLMC proliferation was assessed by cell counts at various time points following drug exposure. HLMC chemotaxis was assayed using standard Transwell chambers (8 μm pore size). Ion currents were measured using the single cell patch clamp technique. <b>Results:</b> K<sub>Ca</sub>3.1 blockade with triarylmethane-34 (TRAM-34) did not inhibit HLMC proliferation and clotrimazole had cytotoxic effects. In contrast, HLMC migration towards the chemokine CXCL10, the chemoattractant stem cell factor, and the supernatants from tumour necrosis factor α stimulated asthmatic ASM was markedly inhibited with both the non-selective K<sub>Ca</sub>3.1 blocker charybdotoxin and the highly specific K<sub>Ca</sub>3.1 blocker TRAM-34 in a dose dependent manner. Although K<sub>Ca</sub>3.1 blockade inhibits HLMC migration, K<sub>Ca</sub>3.1 is not opened by the chemotactic stimulus, suggesting that it must be involved downstream of the initial receptor-ligand interactions. <b>Conclusions:</b> Since modulation of K<sub>Ca</sub>3.1 can inhibit HLMC chemotaxis to diverse chemoattractants, the use of K<sub>Ca</sub>3.1 blockers such as TRAM-34 could provide new therapeutic strategies for mast cell mediated diseases such as asthma.
Abstract 2720: Cidofovir modulates HPV E6 and E7 as well as p53, Rb and MDM2 in HPV16 naturally transformed head and neck squamous cell carcinoma and enhances chemosensitivity to Cisplatin
Authors: Jung Je Park, Pavan K Kommareddi, Thankam S. Nair, Ji Hyun Seo, Sea-Yuong Jeon, Sang Yoon Kim, Mark E. Prince, Carol R. Bradford, Thomas E. Carey
Journal: Cancer Research (2011)

Abstract Purpose: The increasing incidence of oropharyngeal head and neck squamous cell carcinoma (HNSCC) is largely associated with sexually transmitted infection with high risk human papillomavirus (HPV), particularly HPV16. Cidofovir is an acyclic nucleoside phosphate that has broad antiviral activity against DNA viruses and is used clinically in recurrent respiratory papillomatosis. It is not known whether Cidofovir has any therapeutic effects on naturally transformed and non-transformed HNSCC cell lines. Experimental Design: We investigated the effects of Cidofovir on naturally HPV16 transformed HNSCC cell lines, and compared these with the effects on non-transformed HNSCC cell lines from similar tumor sites. We performed RT-PCR in HPV16 transformed cell lines to evaluate the effect of Cidofovir on HPV16 E6 and E7 gene transcription. Modulation of p53, Rb, MDM2, p21(WAF1), and p16 protein levels were studied by Western blot analysis. To evaluate chemosensitivity in the cells, we pretreated the tumor cell with Cidofovir followed by Cisplatin and then assessed cell cycle by FACS analysis, and survival by clonogenic, cell viability, and MTT assays. Results: HPV16 transformed cell lines exhibited decreased E6 and E7 expression after treatment with Cidofovir. This treatment also increased p53 and Rb as well as MDM2, and p21(WAF1) in HPV16 transformed cell lines. We demonstrated that the combination of Cidofovir and Cisplatin treatment enhanced chemosensitivity in HPV16 transformed cell lines, but the effect in HPV negative tumor cells was less pronounced. Conclusion: Our results suggest that Cidofovir may have a role in senisitizing HPV16 naturally transformed HNSCC to conventional treatment and could reduce unwanted toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2720. doi:10.1158/1538-7445.AM2011-2720
Autologous Transplantation of Granulocyte Colony–Stimulating Factor–Mobilized Peripheral Blood Mononuclear Cells Improves Critical Limb Ischemia in Diabetes
Authors: Bin Zhou, Pingping Huang, Zhong Chao Han
Journal: Diabetes Care (2006)

Recently, our pilot study provided evidence that autologous transplantation of granulocyte colony–stimulating factor–mobilized peripheral blood mononuclear cells (PBMNCs) may represent a simple, safe, effective, and novel therapeutic approach for diabetic critical limb ischemia (CLI) (1). In our study, we chose diabetic patients with proven CLI, but without hypercoagulable states and/or severe coronary, cerebral, and renal vascular disease. As pointed out by Fadini and Avogaro (2), poor blood vessel growth in ischemic hearts and limbs and increased angiogenesis …
Tackling the political determinants of global health
Authors: Ilona Kickbusch
Journal: BMJ (2005)

eight specific substantial doubts. 13It did this partly because Chandra's university was unable to investigate further when Chandra failed to provide raw data and then resigned. 12But doubts now remain about Chandra's other studies, and the fact that these have not been resolved has already caused problems to meta-analysts. 14These papers exist in scientific limbo.The stories of Singh and Chandra are sorry tales, with no clear resolution.What more can journals do when their attempts to get someone else to investigate fail?Some researchers and editors argue that journals should keep collective confidential "black lists" of suspected papers and authors.But the sheer number of journals makes this unreliable; more seriously, it would imply someone was guilty until proven innocent-with a worrying lack of due process.Others suggest that journals should ask authors to deposit a copy of their dataset in a secure archive so that data could be audited if questions arise.But that too demands an infrastructure that doesn't exist.Perhaps rather than waiting for definitive proof, journals should in future be more ready to share their concerns about published papers, using the mechanism we use today-the publication of an expression of concernwhere they have reasonable grounds to believe that serious questions exist about a paper.The expression of concern does not resolve the suspicions but it alerts researchers, and in particular systematic reviewers, to doubts about the studies.And it may in turn prompt an organisation with the capacity and standing to take the action necessary to do the necessary investigations.
P671Sex-specific response to ischemia and reperfusion in hearts with different predisposition to hypertension exposed to social stress
Authors: V Ledvenyiova, I Bernatova, I Gablovsky, S Carnicka, T Ravingerova
Journal: Cardiovascular Research (2014)

Genetic predisposition and social stress may represent important risk factors in etiology of hypertension associated with impaired myocardial response to ischemia and reperfusion (I/R) in male and female heart. Sex is an important determinant of cardiovascular morbidity and mortality in human population, where men are at higher risk than age-matched premenopausal women. The capability for activation of intrinsic tolerance to I/R injury observed in females as well as in males may persist even in the hearts of animals with genetic predisposition to hypertension and may be modified by long-lasting cardiac adaptation to stressful conditions. For this reason, we aimed to test the impact of chronic stress on the response to sustained I/R in borderline/spontaneously hypertensive rats (BHR/SHR) in comparison with its effects in normotensive Wistar Kyoto (WKY) counterparts. Male and female 5-week-old BHR (offspring of Wistar mothers and SHR fathers), SHR (offspring of SHR mothers and fathers) and age-matched WKY rats were exposed to 2-week crowding stress (CS), which was induced by caging five rats per cage in a cage for two (200 cm2/rat), while controls (C) were kept four rats per cage in cages for six animals (480 cm2/rat). Langendorff-perfused hearts of stressed and non-stressed WKY, BHR and SHR animals were exposed to 30-min global ischemia and 2-h reperfusion for the evaluation of reperfusion-induced ventricular arrhythmias and size of myocardial infarction (IS, TTC staining). Female WKY hearts exhibited greater tolerance to reperfusion arrhythmias as compared to males. CS impaired postischemic recovery of contractile function with stronger effect in males. On the other hand, CS decreased the total duration of a more severe form of ventricular arrhythmias - ventricular tachycardia (VT) only in females. BHR animals of both sexes were markedly more prone to VT, while SHR hearts exhibited increased resistance to VT when compared to normotensives and BHRs. We observed dramatically decreased of VT duration in BHR-CS but not in SHR-CS males and females. Interestingly, IS was not affected by CS in normotensives as well as in BHR and SHR hearts. Social stress modifies parameters of I/R injury in a distinct way. Inherited predisposition to hypertension may be responsible for changes in cardiac ischemic tolerance of animals exposed to social stress, which appears to be sex-dependent.
Childhood Vaccinations: Are Rates Really Declining?
Authors: Paul A. Stehr-Green
Journal: JAMA (1993)

To the Editor.  —The health objectives of the United States for the year 2000 established the goal of completing the basic vaccination series in at least 90% of 2-year-olds. 1 However, coverage rates among preschool-aged children in the United States remain relatively low. Recently, 45 states and the District of Columbia estimated preschool coverage levels by examining the vaccination histories of children who entered school in 1991 and 1992; two additional states conducted surveys of children who were 2 years old in 1991. These assessments showed that median coverage rates at 2 years of age were 59.9% for four doses of diphtheria-tetanus-pertussis (DTP) vaccine, 74.4% for three doses of polio vaccine, and 78.2% for one dose of measles-containing vaccine (Centers for Disease Control and Prevention, unpublished data, 1992). Results from similar assessments conducted in more than 20 urban areas showed that complete coverage rates of the vaccine series were 10%
Notch promotes vascular maturation by inducing integrin-mediated smooth muscle cell adhesion to the endothelial basement membrane
Authors: Lea Scheppke, Eric A. Murphy, Alessandro Zarpellon, Jennifer J. Hofmann, Alona Merkulova, David J. Shields, Sara M. Weis, Tatiana V. Byzova, Zaverio M. Ruggeri, M. Luisa Iruela-Arispe, David A. Cheresh
Journal: Blood (2011)
A case of murder and the BMJ
Authors: M. B Pillai
Journal: BMJ (2002)

Editor—Meadow has sought to overcome criticism of the misapplied statistics in the trial of Sally Clark by his own version of the evidence.1 He has missed the point. His belief in her guilt does not justify misplaced evidence. Watkins addressed the issue of presenting statistical evidence fairly.2

He concluded that doctors should not use techniques without acquainting themselves with the principles underlying them. Meadow blames biased media reporting while advancing his own interpretation of the prosecution evidence in a manner that leaves little room for doubt. Yet such a strong bid to minimise the influence flawed statistics may have had betrays certainty in a field where there should be considerable room for doubt. I do not know the details of the case, but the mere fact that many medical witnesses were called by both the prosecution and the defence indicates the evidence was not clear cut. Unless Meadow is the victim of some conspiracy by the press, the edition of the Observer published the day after the BMJ gives details of the defence evidence, suggesting his paper is anything but a balanced interpretation.3

The power of medical opinion in judgments is quite profound, so it is not possible to know what influence the misleading information had on the outcome of the trial. It is crucial that opinion must at all times be accurate and evidence based if miscarriages of justice are to be avoided. Essential criteria have been set down for expert opinion,4 and require the expert to:



Provide a straightforward and not misleading opinion


Be objective and not omit factors which do not support their opinion


Be properly researched.




When belief systems become rigid to a degree where perceived guilt is put forward as justifying bad evidence, the concept of an independent and impartial adviser to the court is lost. This undermines the court process and the principles of natural justice as required under article 6 of the Human Rights Act.
Agonistic CD40 antibody induces immune-mediated liver damage and modulates tumor-induced myeloid suppressive cells
Authors: Jose Medina-Echeverz, Chi Ma, Austin Duffy, David E Kleiner, Tim F Greten
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Immune stimulatory monoclonal antibodies are currently evaluated as anti/cancer agents in clinical trials. While overall toxicity seems to be moderate, liver toxicities have been reported and are not completely understood. Based on the observation that CD11b+Gr-1+ MDSC accumulate
Book Review Postmortem: How Medical Examiners Explain Suspicious Deaths (Fieldwork Encounters and Discoveries.) By Stefan Timmermans. 367 pp. Chicago, University of Chicago Press, 2006. $30 (cloth); $18 (paper). 978-0-226-80398-2 (cloth); 978-0-226-80399-9 (paper).
Authors: Yale H. Caplan
Journal: New England Journal of Medicine (2007)
Another ANN model for the Miyashita experiments
Authors: Masahiko Morita
Journal: Behavioral and Brain Sciences (1995)

Abstract The Miyashita experiments are very interesting and the results should be examined from a viewpoint of attractor dynamics. Amit's target article shows a path toward realistic modeling by artificial neural networks (ANN), but it is not necessarily the only one. I introduce another model that can explain a substantial part of the empirical observations and makes an interesting prediction. This model consists of such units that have nonmonotonic input-output characteristics with local inhibition neurons.
The Need to Explicate the Ethical Evaluation Tools to Avoid Ethical Inflation
Authors: Rosemarie D. C. Bernabe, Ghislaine J. M. W. van Thiel, Jan A. M. Raaijmakers, Johannes J. M. van Delden
Journal: The American Journal of Bioethics (2009)

Click to increase image sizeClick to decrease image size Acknowledgment This study was performed in the context of the Escher project (T6-202), a project of the Dutch Top Institute Pharma.
Diaphragmatic Hernia
Authors: Farouk A. Pirzada
Journal: JAMA (1970)

Traumatic diaphragmatic hernia may cause symptoms and diagnostic difficulty long after the original injury. A Vietnam veteran had abdominal pain and subsequent serosanguineous pleural effusion 29 months after he sustained a battle wound. At operation, a traumatic diaphragmatic hernia with strangulation of the omentum was found and repaired. Omental strangulation appears to have been the factor common to all reported cases in which pleural effusion was a complication.
Confounding in air pollution epidemiology: when does two-stage regression identify the problem?
Authors: A H Marcus, S R Kegler
Journal: Environmental Health Perspectives (2001)

A two-stage approach has recently been proposed to assess confounding by copollutants or other variables in time-series epidemiology studies for airborne particulate matter (PM), using independent series from different cities. In the first stage of the proposed method, two regression models are fitted for each city in the analysis. The first relates the health effect to the putative causal variable such as PM without including any copollutant or confounder. The other first-stage model relates a putative confounding variable to PM. In the second stage of the analysis, the estimated city-specific regression slopes for the health-effect-versus-PM model are regressed against the estimated city-specific regression slopes for the confounder-versus-PM model. Under the proposed method, a nonzero intercept estimate in the second-stage regression would be interpreted as indicating a direct pathway from PM to the health effect, and a nonzero slope estimate would be interpreted as indicating at least partial confounding of PM with the putative confounder. A simple counterexample using an additional copollutant variable shows that inferences based on this method could be misleading.
Rehabilitation of amputees.
Authors: S. Muthu
Journal: BMJ (1992)

drugs should aim at an even larger number of patients and continue longer.The planning of this study started in 1985 after our first results2 were available; at this time there were no human data suggesting a renal protective effect of angiotensin converting enzyme inhibitors.Peter T Sawicki and Michael Berger seem to recommend a comparison of enalapril and metoprolol treatments during the follow up period from six months onwards, and that only patients with follow up times of one year or more be included.A total of 18 patients treated with enalapril and 13 treated with metoprolol are evaluable in this respect.During this period the mean (SD) rate of change in glomerular filtration rate was 0-8 (4 7) ml/min/year in the enalapril treated and -3 3 (4 2) ml/min/year in the metoprolol treated patients (p= 0 016).The mean arterial blood pressures (mean of supine and standing pressures) were 102 (5) mm Hg and 103 (4) mm Hg, respectively.Multiple regression analysis shows that enalapril or metoprolol treatment was correlated to the rate of fall in glomerular filtration rate (p=002) but mean arterial blood pressure was not (p=0 8).If supine or standing mean arterial blood pressure is used, neither result is significant (p=026 and 0-4, respectively).Thus, in our enalapril treated patients there was no fall in glomerular filtration rate after the first six months.Blood pressure was less important for the prognosis of renal function than type of antihypertensive treatment in these patients with well controlled blood pressure.