tbuckley/cabot-search huggingface dataset:
Soundings: Quackery, flummery, and fleas
Authors: Kevin Barraclough
Journal: BMJ (1999)

“I've been to my cranial osteopath and she assures me that she can cure my asthma. But then, you won't believe any of that, anyway.”

I make no comment, as always. It is assumed that I, a member of a conservative profession, will hold a bigoted opinion about any form of alternative treatment.

But I do not respond. I fear the branding of intolerance. As though I, like some religious zealot, hold an intransigent belief that I proclaim through a megaphone, inciting fear and loathing with a rising cadence.

And yet, when my patient leaves, I find myself wondering at the widespread distrust of conventional medicine.

I suspect that the answer lies in the wider question of the distrust of science. We seem to be living in the backlash of the technological age. People were led to believe that science, through technology, was the route to untold riches. But what they fail to realise is that the aim of science is not to open the door on everlasting wisdom or wealth: it is to set a limit on everlasting error.

And yet these strains of antirational and quasireligious movements are unquestionably a rising tide of our times. We are witness to an alienation of people from a scientific movement that seems to them to be nihilistic. They are confronted with a scientific world view, by polemists such as Richard Dawkins and Lewis Wolpert, which presents mankind as merely a rather tragic epiphenomenon of Darwinian theory. And so we see the public desert in droves to the ranks of crystal gazers and astrologers. And yet surely this nihilism itself can be seen as the result of an extrapolation of a theory beyond the realms of its legitimate domain.

I am reminded of the professor of logic who wished to establish a link between cause and effect. He placed a flea on the table in front of the auditorium.

“Jump!” he commanded. And it jumped.

Next he produced a scalpel and chopped off the flea's back legs.

“Now, jump!” he commanded. The flea remained stationary.

He rounded triumphantly on the audience.

“My dear friends,” he announced, “we have conclusively proved that when a flea's back legs are amputated the creature is rendered completely deaf.”
A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu–Expressing Tumor in HLA-A2 Transgenic Mice
Authors: Thi Tran, Mariana O. Diniz, Estelle Dransart, Alain Gey, Nathalie Merillon, Yu Chun Lone, Sylvie Godefroy, Craig Sibley, Luis CS Ferreira, Jacques Medioni, Stephane Oudard, Ludger Johannes, Eric Tartour
Journal: Clinical Cancer Research (2016)

Abstract Purpose: E75, a peptide derived from the Her2/neu protein, is the most clinically advanced vaccine approach against breast cancer. In this study, we aimed to optimize the E75 vaccine using a delivery vector targeting dendritic cells, the B-subunit of Shiga toxin (STxB), and to assess the role of various parameters (Her2/neu expression, combination with trastuzumab) in the efficacy of this cancer vaccine in a relevant preclinical model. Experimental Design: We compared the differential ability of the free E75 peptide or the STxB-E75 vaccine to elicit CD8+ T cells, and the impact of the vaccine on murine HLA-A2 tumors expressing low or high levels of Her2/neu. Results: STxB-E75 synergized with granulocyte macrophage colony-stimulating factors and CpG and proved to be more efficient than the free E75 peptide in the induction of multifunctional and high-avidity E75-specific anti-CD8+ T cells resulting in a potent tumor protection in HLA-A2 transgenic mice. High expression of HER2/neu inhibited the expression of HLA-class I molecules, leading to a poor recognition of human or murine tumors by E75-specific cytotoxic CD8+ T cells. In line with these results, STxB-E75 preferentially inhibited the growth of HLA-A2 tumors expressing low levels of Her2/neu. Coadministration of anti-Her2/neu mAb potentiated this effect. Conclusions: STxB-E75 vaccine is a potent candidate to be tested in patients with low Her2/neu–expressing tumors. It could also be indicated in patients expressing high levels of Her2/neu and low intratumoral T-cell infiltration to boost the recruitment of T cells—a key parameter in the efficacy of anti-Her2/neu mAb therapy. Clin Cancer Res; 22(16); 4133–44. ©2016 AACR.
681 ASSOCIATION OF POLYMORPHISMS OF TUMOR NECROSIS FACTOR LOCUS WITH DISEASE SEVERITY AND INCREASED HEPATOCELLULAR CARCINOMA RISK
Authors: J.-F. Tsai, Z.-Y. Lin, S.-C. Chen, W.-L. Chuang, L.-Y. Wang, M.-L. Yu, C.-Y. Dai
Journal: Journal of Hepatology (2013)
Abstract 4420: Generating preclinical models to assess bone marrow toxicity induced by the PARP inhibitor olaparib in combination with chemotherapy.
Authors: Mark J. O'Connor, Helen Mason, Steve Horner, Ian Slater, Alan Lau, Elaine Cadogan, Lenka Oplustilova
Journal: Cancer Research (2013)

Abstract Inhibitors of the DNA damage response (DDR) provide an exciting opportunity as new anti-cancer therapies. A prominent example is olaparib, an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), that has shown potential as a monotherapy for tumours bearing BRCA1/2 defects in clinical trials. Apart from monotherapy based on the concept of synthetic lethality, PARP inhibitors also have the potential to provide additional benefit when used in combination with DNA damage-inducing chemotherapies. In the clinic, however, this approach has been challenging due to enhanced bone marrow toxicity. Our aim is to generate preclinical models to provide a better understanding of the mechanisms for this limiting bone marrow toxicity. We characterized in vitro responses to DNA damage induced by IR and chemotherapy in human hematopoietic multipotent progenitors and mesenchymal stem cells, both components of bone marrow. In parallel, we modelled the effects of a platinum chemotherapy (carboplatin) in combination with olaparib in wild type rats with the aim of reproducing the clinical combination-induced bone marrow toxicity. We will present data that provide initial insights into the suitability of the rat pre-clinical model to guide combination dose and schedules with olaparib and an assessment of the ability of different bone marrow and peripheral blood cell populations to act as useful biomarkers to guide better tolerated combination schedules. Citation Format: Mark J. O'Connor, Helen Mason, Steve Horner, Ian Slater, Alan Lau, Elaine Cadogan, Lenka Oplustilova. Generating preclinical models to assess bone marrow toxicity induced by the PARP inhibitor olaparib in combination with chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4420. doi:10.1158/1538-7445.AM2013-4420
Abstract 3807: Gugulipid-induced apoptosis in human prostate cancer cells is regulated by Bax/Bak and Bcl-xL
Authors: Yan Zeng, Vladmir Badmaev, Shivendra V. Singh, Dong Xiao
Journal: Cancer Research (2010)

Abstract Indian Ayurvedic medicinal plant Commiphora mukul has been safely used for treatment of different disorders for thousands of years. Our previous studies have shown that the extract of Commiphora mukul, gugulipid (GL), inhibits growth of human prostate cancer (Pca) cells, but not a normal prostate epithelial cell line (PrEC), by causing apoptosis. We also showed that GL-mediated inhibition of Pca cell proliferation correlated with reactive oxygen species (ROS) production. The present study was designed to gain insight into the mechanism of GL-induced apoptosis downstream of ROS production. We found that the GL-induced apoptosis correlated with induction of proapoptotic proteins Bax and Bak and down-regulation of antiapoptotic proteins Bcl-2 and Bcl-xL in LNCaP and PC-3 cells. The SV40-immortalized mouse embryonic fibroblasts derived from Bax and Bak double knockout mice were significantly more resistant to GL-induced apoptotic cell death (DNA fragmentation and cleavage of PARP) compared with wild-type mouse embryonic fibroblasts. Bcl-xL overexpression in PC-3 cells conferred protection against GL-induced apoptotic cell death. The GL treatment caused activation of c-Jun-N-terminal kinase (JNK), which functions upstream of Bax activation in apoptotic response to various stimuli. Pharmacological inhibition of JNK conferred partial yet significant protection against GL-induced apoptosis. The GL-mediated apoptosis and conformational change of Bax was markedly suppressed by ectopic expression of catalytically inactive mutant of JNK kinase JNKK2 (AA) in LNCaP cells. In conclusion, the present study indicates that Bax/Bak and Bcl-xL regulate GL-induced apoptosis in human prostate cancer cells. This investigation was supported by USPHS grant R21 CA143104-01. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3807.
NOVEL ASSOCIATION OF POLYMORPHIC GENETIC VARIANTS WITH PREDICTORS OF OUTCOME OF CATHETER ABLATION IN ATRIAL FIBRILLATION: NEW DIRECTIONS FROM A PROSPECTIVE STUDY (DECAF)
Authors: Sanghamitra Mohanty, Amelia W. Hall, Prasant Mohanty, Sameer Prakash, Chintan Trivedi, Luigi Di Biase, Pasquale Santangeli, Carola Gianni, Rong Bai, John Burkhardt, Joe Gallinghouse, Rodney Horton, Javier Sanchez, Patrick Hranitzky, Amin Al-Ahmad, Viswanath R. Iyer, Andrea Natale
Journal: Journal of the American College of Cardiology (2015)
AB0965 Multicentre randomized clinical study of aceclofenac versus diclofenac in the treatment of knee osteoarthritis
Authors: E.P. Sharapova, E.A. Taskina, D.A. Gukasyan, O.N. Ivanova, T.A. Raskina, L.I. Menshikova, I.A. Vinogradova, L.I. Alekseeva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To assess the efficacy and safety of Rceclofenac (200mg/day) versus Diclofenac (100mg/day) therapy during three month in patients with knee osteoarthritis (OA). <h3>Methods</h3> 200 outpatients (each group consists of 100 patients) with knee OA (mean age 62,6±7,1), with Kelgren and Lawrence radiograhic grade II-III, pain &gt;40mm at a 100mm visual analog scale (VAS) were studied. WOMAC and EQ-5D questionnairies, and "stand up and go" test were served as criteria of treatment efficacy. <h3>Results</h3> There was no difference between groups regarding baseline characteristics. The significant decrease of pain and joint function improvement was observed in both groups after the first month of each treatment. This was maintained during the whole period of the follow-up. Significant decrease in stiffness was observed after one month of Aceclofenac and after two months of Diclofenac treatments. Significant improvement of general health and EQ-5D questionnaire results as well as decreased "stand up and go" test accomplishment time were observed in both groups after one month of treatment. After the first month significant "improvement" was observed in 86.3% in Aceclofenac patients and in 66% patients from Diclofenac group and after three month of treatment, in 95.8% and 76.2% patients, respectively (p&lt;0.05). Therapy tolerance was satisfactory. Adverse effects were noted in 3% of Aceclofenac treated OA patients and in 12% subjects treated with Diclofenac. <h3>Conclusions</h3> Our results show that both drugs were effective in the treatment of OA. Rceclofenac is capable of decreasing pain faster than Diclofenac. In addition Rceclofenac use is associated with a decreased risk of gastroenterological side effects. <h3>Disclosure of Interest</h3> None Declared
PTH-066 Cholangioscopy-Assisted Electrohydraulic Lithotripsy is Highly Effective in the Management of Difficult Bile Duct Stones
Authors: V P K Lekharaju, O Noorullah, M Kumar, C A Wadsworth, C Kaltsidis, E S Shearer, L Dwyer, G J M Webster, R Sturgess
Journal: Gut (2013)

<h3>Introduction</h3> Although conventional endoscopic techniques for the removal of stones from the biliary tree are highly effective, they fail in up to 10% of patients with choledocholithiasis. With the introduction of single operator peroral cholangioscope (POC), the SpyGlass<sup>®</sup> System, stone fragmentation under direct visual control has proven to be highly effective and is now emerging as an important endoscopic therapy. We describe the characteristics and outcomes of patients undergoing POC directed electrohydraulic lithotripsy (POC-EHL) in two tertiary Hepatobiliary units in England. <h3>Methods</h3> Details of all patients undergoing POC-EHL at Aintree University Hospital and University College London Hospitals were prospectively recorded. Data collected included demographics, number of ERCPs, site of the stone, number of POC-EHL sessions, success of stone clearance and complications. <h3>Results</h3> A total of 93 patients were referred for POC-EHL. There were 25 males (27%) and 68 females (73%). The median age was 65 (20–92) years. 71 (76%) patients were tertiary referrals. 62 (67%) patients had at least two or more endoscopic attempts at stone removal prior to referral for POC-EHL. In six patients POC-EHL was not required because at ERCP prior to POC, the ducts could be cleared with conventional techniques. In five patients EHL was not attempted due to the size, configuration and quantity of stones. With the knowledge that these patients were fit for cholecystectomy, they were referred for cholecystectomy and bile duct exploration as a one-stage procedure. All POC-EHL sessions were performed under general anaesthesia. Of the 82 patients undergoing POC-EHL 61 (75%) patients needed one POC-EHL session and 10 (12%) required two sessions and 6 (7%) required three sessions for complete stone extraction. In 5/82 (6%) complete stone extraction was not possible despite POC-EHL and these patients were referred for surgery. The sites of stones were common bile duct in 48%, cystic duct and CBD in 20%, cystic duct in 4%, common hepatic duct in 10% and intra-hepatic ducts in 18%. Three patients developed cholangitis post POC-EHL, responding to antimicrobial therapy. Two patients experienced post-procedure bleeding, only one patient required endoscopic intervention. <h3>Conclusion</h3> On an intention to treat basis, 89% of patients referred for POC-EHL were treated successfully. Successful POC-EHL frequently requires combination with other stone removal techniques including mechanical lithotripsy. POC-EHL appears to be a safe and effective technique in the clearance of refractory biliary stones. <h3>Disclosure of Interest</h3> None Declared.
European regulator is urged to release data on drugs approved in past 10 years
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The European drug regulator should be more radical in demanding full disclosure of clinical trial data from drug companies, four groups representing the interest of patients have said.

The European Medicines Agency (EMA) should make available all data on the drugs it has approved in the last 10 years and not just from March 2014 as the agency has proposed, the campaigners say.

Since June this year the agency has been consulting on who should have access to what data when it begins publishing in January 2014 …
THU0303 The efficacy and safety of ibandronic acid for intravenous administration for treatment of severe systemic osteoporosis in patients with juvenile arthritis
Authors: S. Valiyeva, E. Alexeeva, T. Bzarova, R. Denisova, K. Isayeva, T. Sleptsova, E. Mitenko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile arthritis (JA) is one of the most common and disabling rheumatic disease in children. Severe manifestation of juvenile arthritis is a systemic osteoporosis. There is currently no developed approaches to the treatment of children with systemic osteoporosis. In adult patients with rheumatoid arthritis the first-line treatment drug for osteoporosis is bisphosphonates <h3>Objectives</h3> To evaluate the efficacy and safety of ibandronic acid for intravenous administration for treatment of severe systemic osteoporosis in patients with juvenile arthritis. <h3>Methods</h3> The study included 25 patients with juvenile arthritis at the age of 7 to 17 years (10 girls, 15 boys), including 20 patients with systemic arthritis, 3 - with polyarthritis, 2 - with ankylosing spondylitis. The mean age was 12.5 (10.5, 14.0) years. Was allocated to 2 groups: 17 children treated with glucocorticoids (GC) and 8 - not receiving GC.Children of the first group had 12 vertebral fractures and patients of the 2-d group - 1. Ibandronic acid was administered intravenously at a dose of 3 mg every 12 weeks. Evaluation of treatment efficacy was conducted by a combined index of bone mineral density of tissue Z-score, assessing the patient/parent to the severity of pain on a visual analog scale, serum markers of bone resorption C-terminal telopeptide. <h3>Results</h3> The treatment of ibandronic acid in children of both groups increased the bone mineral density. In patients treated with GC, a statistically significant increase was registered in 76 weeks of therapy (p&lt;0.01), while the second group of children - through 46 and 76 weeks (p&lt;0.05). Within 6 months of treatment in both groups of ibandronic acid was a statistically significant reduction in pain index (p&lt;0.05), after a year of treatment with this trend persisted (p&lt;0.001). In both groups, reducing the concentration of C-terminal telopeptide in serum were detected through 52 weeks of reatment (p&lt;0.05). After 76 weeks of treatment new vertebral fractures and fractures of the peripheral skeleton are not fixed. Tolerability of therapy ibandronic acid in patients was satisfactory. <h3>Conclusions</h3> In the course of the study has identified high efficacy and an acceptable tolerability ibandronic acid for treatment of severe systemic osteoporosis in patients with juvenile arthritis <h3>Disclosure of Interest</h3> None Declared
P22 Gall bladder length on ultrsonography as a screening tool in identification of auto immune sclerosing cholangitis
Authors: P. McKiernan, A. Batra, K. Au-Yong, D. A. Kelly, H. Alton
Journal: Gut (2011)

<h3>Introduction</h3> Autoimmune liver disease (AILD) in children encompasses Autoimmune Hepatitis (AIH), Autoimmune sclerosing Cholangitis (ASC) or, where there are features of both, overlap syndrome (OS). Differentiating between these entities requires cholangiography. The gold standard for the diagnosis of ASC is Endoscopic Retrograde Cholangiopancreaticography which is invasive. Magnetic Resonance Cholangiopancreaticography can be used as an alternative but is not universally available and may require anaesthesia in young children. Anecdotally, we had found increased gall bladder (GB) length on ultrasound to be a useful marker of bile duct involvement in AILD. <h3>Aim</h3> Our aim was to study the role of ultrasound measurement of Gall Bladder length as a screening tool for identifying ASC in children with AILD. <h3>Method</h3> Children, under the age of 18 years at the time of presentation, diagnosed with AILD were identified from the departmental database. Cases for whom a fasting ultrasound at the time of presentation, was available on our radiology department9s digital imaging system were included. Cases were categorised using established criterion into 2 groups; those with AIH and those with ASC with or without OS. A retrospective case notes review was performed on all eligible children, their ultrasound scans were reviewed by a single radiologist and GB length measured. <h3>Results</h3> 50 cases were included. 32/50 (64%) had AIH type1 and 6/50 (12%) had AIH type2. 12/50 (24%) had ASC and 6/12 (50%) of these had OS. The average age at presentation was 10.18 years (range 1.3–16 years). The age at presentation was similar for both groups (AIH 10.1 yrs; ASC 10.2 yrs). Overall there were 22 males and 28 females but among the group with ASC there were 8 males and 4 females. The duration of symptoms before diagnosis was 5 months and was similar in both groups. The median (25th, 75th centile) GB length in children with ASC was 9.75 cm (7.2 cm, 10.6 cm) and in children with AIH was 6.8 cm (5.5 cm, 7.9 cm) [p value 0.003]. The normal GB length in children older than 1 year is up to 7 cm. GB length &gt;7 cm was seen in 9/12 (75%) children with ASC compared to 15/38 (39.5%) of children with AIH (p=0.04). GB length &gt;9 cm was seen in 7/12 (58.3%) children with ASC and 4/38 (10.5%) children with AIH (p=0.005). <h3>Conclusion Summary:</h3> In AILD GB length is significantly increased in children with ASC. GB length &gt;9 cm has 90% specificity for the diagnosis of ASC. GB length &lt;7 cm is 88% exclusive of ASC. <h3>Conclusion:</h3> GB length measurement is a useful screening test for ASC in children with AILD. We would recommend a further study with greater number of patients.
AB0379 Subclinical atherosclerosis in the femoral arteries: similar prevalence in rheumatoid arthritis and diabetes mellitus in a case control study
Authors: A. Protogerou, E. Zampeli, N. Tentolouris, K. Makrilakis, G.D. Kitas, P.P. Sfikakis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with increased coronary artery disease (CAD) and subclinical carotid atherosclerosis, both reported to equal diabetes mellitus (DM), a CAD equivalent. On the other hand, the presence of CAD in the general population has been strongly associated with subclinical atherosclerosis in the femoral arteries. <h3>Objectives</h3> To compare the presence of atheromatic plaques in femoral arteries in RA versus DM patients. <h3>Methods</h3> Femoral plaques were identified by ultrasonography in non-diabetic RA patients matched 1:1 for age, gender and disease duration with diabetic patients. All were asymptomatic and free of CAD. <h3>Results</h3> Twenty-one middle aged (11 men, age: 41.9±11 years, disease duration: 10.6±7.4years) and 29 elderly RA patients (14 men, age: 62.8±7.9 years, disease duration: 10.5±7.6years) were matched with DM patients type 1 or 2, respectively. Prevalence of hypertension, dyslipidemia and obesity was higher in DM. The number of femoral plaques per subject was identical between RA and DM subjects (0.68±0.84 <i>vs</i> 0.68±0.87 respectively); numbers of patients with femoral plaque were also similar (middle-aged RA <i>vs</i> DM type 1: p=0.955; elderly RA <i>vs</i> DM type 2: p=0.559). As expected, elderly RA patients had more femoral plaques by 3-fold than middle-aged patients (p=0.034). <h3>Conclusions</h3> Despite the higher burden of classical cardiovascular disease risk factors in DM, subclinical femoral atherosclerosis in RA is similar to DM of equal disease duration, further confirming the territorial unrestricted acceleration of the atheromatic process in these patients. The issue of cardiovascular risk stratification based on both carotid and femoral plaques detection in RA should be addressed prospectively. <h3>Disclosure of Interest</h3> None Declared