tbuckley/cabot-search huggingface dataset:
Evaluating complementary medicine: methodological challenges of randomised controlled trials
Authors: Su Mason, Philip Tovey, Andrew F Long
Journal: BMJ (2002)

Complementary medicine is increasingly popular for treating many different problems. Doctors and patients need evidence about complementary treatments, but randomised controlled trials need to be carefully designed to take holism into account and avoid invalid results 

You think that by understanding one, you can understand two, for one and one is two. But to understand two, you must first understand “and.” Sufi saying1

Complementary medicine should be evaluated as rigorously as conventional medicine to protect the public from charlatans and unsafe practices,2–5 but many practitioners of complementary medicine are reticent about evaluation of their practice. Sceptics maintain that this is because of fear that investigations will find treatments ineffective and threaten livelihoods. In defence, many practitioners argue that research methods dissect their practice in a reductionist manner and fail to take into account complementary medicine's holistic nature leading to invalid evaluation.

#### Summary points

Complementary medicine comprises many different disciplines, a wide spectrum of practices and philosophies which differ from conventional medicine. Conventional medicine traditionally aims to diagnose illness and treat, cure, or alleviate symptoms. Many complementary disciplines aim not only to relieve symptoms and restore wellness but also to help individuals in a process of self healing within a holistic view of health. In this view, individuals are more than just mind, body, and spirit in a social—family …
Impaired IFN-α Production by Plasmacytoid Dendritic Cells Favors Regulatory T-cell Expansion That May Contribute to Breast Cancer Progression
Authors: Vanja Sisirak, Julien Faget, Michael Gobert, Nadège Goutagny, Nelly Vey, Isabelle Treilleux, Sarah Renaudineau, Gaelle Poyet, Sana Intidhar Labidi-Galy, Sophie Goddard-Leon, Isabelle Durand, Isabelle Le Mercier, Agathe Bajard, Thomas Bachelot, Alain Puisieux, Isabelle Puisieux, Jean-Yves Blay, Christine Ménétrier-Caux, Christophe Caux, Nathalie Bendriss-Vermare
Journal: Cancer Research (2012)

Abstract Infiltration and dysfunction of immune cells have been documented in many types of cancers. We previously reported that plasmacytoid dendritic cells (pDC) within primary breast tumors correlate with an unfavorable prognosis for patients. The role of pDC in cancer remains unclear but they have been shown to mediate immune tolerance in other pathophysiologic contexts. We postulated that pDC may interfere with antitumor immune response and favor tolerance in breast cancer. The present study was designed to decipher the mechanistic basis for the deleterious impact of pDC on the clinical outcome. Using fresh human breast tumor biopsies (N = 60 patients), we observed through multiparametric flow cytometry increased tumor-associated (TA) pDC (TApDC) rates in aggressive breast tumors, i.e., those with high mitotic index and the so-called triple-negative breast tumors (TNBT). Furthermore, TApDC expressed a partially activated phenotype and produced very low amounts of IFN-α following toll-like receptor activation in vitro compared with patients' blood pDC. Within breast tumors, TApDC colocalized and strongly correlated with TA regulatory T cells (TATreg), especially in TNBT. Of most importance, the selective suppression of IFN-α production endowed TApDC with the unique capacity to sustain FoxP3+ Treg expansion, a capacity that was reverted by the addition of exogenous IFN-α. These findings indicate that IFN-α–deficient TApDC accumulating in aggressive tumors are involved in the expansion of TATreg in vivo, contributing to tumor immune tolerance and poor clinical outcome. Thus, targeting pDC to restore their IFN-α production may represent an attractive therapeutic strategy to overcome immune tolerance in breast cancer. Cancer Res; 72(20); 5188–97. ©2012 AACR.
Overreaction to the Paddington rail disaster may not be beneficial in the long run
Authors: C K Connolly
Journal: BMJ (1999)

EDITOR—Years ago I remember Lord Rothschild in his Reith lecture describing how public opinion cannot put disasters into their proper context, resulting in distortion of expenditure on accident prevention. The Paddington rail disaster was tragic, but public response was the overreaction he might have predicted, particularly in view of the fire and initial overestimation of casualties. The editorial by Cocks does nothing to redress the balance.1

The uninitiated reader could not guess that current systems require more than the mere missing …
Effects of Quinidine and Verapamil on Human Cardiovascular α <sub>1</sub> -Adrenoceptors
Authors: Katsushi Shibata, Akira Hirasawa, Rudolf Foglar, Satoshi Ogawa, Gozoh Tsujimoto
Journal: Circulation (1998)

Background —The antiarrhythmic drugs quinidine and verapamil are known to block α 1 -adrenoceptors (α 1 ARs). α 1 ARs are a heterogeneous family of three subtypes (α 1A , α 1B , and α 1D ), and little is known about the effects of quinidine and verapamil on the different human α 1 AR subtypes. Methods and Results —Reverse transcriptase–polymerase chain reaction showed that all α 1 AR subtypes are expressed in both human heart (atrium and ventricle) and the mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on the α 1 AR subtypes were characterized with Chinese hamster ovary cells stably expressing cloned human α 1 AR subtypes. Radioligand binding studies showed that quinidine and verapamil had high affinities for all α 1 AR subtypes. Also, both drugs synergistically inhibited α 1 AR-mediated inositol 1,4,5-triphosphate production at the clinical effective concentration range (1 μmol/L quinidine and 0.1 μmol/L verapamil). Conclusions —The results show that all α 1 AR subtypes are expressed in the human cardiovascular system and that quinidine and verapamil may have a potent, synergistic inhibitory effect on the α 1 ARs. Clinically observed hypotension after quinidine plus verapamil can be explained by their synergistic inhibitory effects on human α 1 ARs.
Effects of vasoactive intestinal peptide and pancreatic polypeptide in rabbit intestine.
Authors: M Camilleri, B T Cooper, T E Adrian, S R Bloom, V S Chadwick
Journal: Gut (1981)

The effects of porcine vasoactive intestinal peptide (VIP) and bovine pancreatic polypeptide (PP) on jejunal, ileal, and colonic fluid transport were studied in the rabbit. VIP produced secretion in the small intestine (jejunum greater than ileum) but did not affect absorption in the colon. PP had no secretory effects in jejunum, ileum, or colon. The small intestinal secretion induced by VIP was not associated with raised cAMP concentrations in the mucosa; this suggests that the secretory effects of VIP in vivo are mediated by a mechanism other than stimulation of adenylate cyclase.
The Presence of a Haloarchaeal Type Tyrosyl-tRNA Synthetase Marks the Opisthokonts as Monophyletic
Authors: Jinling Huang, Ying Xu, Johann Peter Gogarten
Journal: Molecular Biology and Evolution (2005)

Lateral gene transfer plays an important role in the evolution of life. Events of ancient gene transfer can transmit genetic novelties to descendent lineages and subsequently shape their genetic systems. We here present the analyses of the gene encoding tyrosyl-tRNA synthetase (tyrRS), which reveal two eukaryotic tyrRS lineages, one including the opisthokonts and the other the remaining eukaryotes. The different origins of tyrRS lineages between the opisthokonts and the remaining eukaryotes indicate a likely case of ancient lateral gene transfer of tyrRS from an archaeon to the opisthokonts, which lends further support for the monophyly of the latter group. Ancient paralogy followed by differential gene loss is an alternative, albeit less parsimonious explanation for the distribution of the two eukaryotic tyrRS types. In either case, the presence of a haloarchaeal tyrRS type in the opisthokonts marks this group as monophyletic. This finding also points to the potential utility of ancient gene transfer events as molecular markers for major organismal lineages.
Effects of rider position on continuous wave Doppler responses to maximal cycle ergometry.
Authors: W D Franke, C B Betz, R H Humphrey
Journal: British Journal of Sports Medicine (1994)

Using 10 well-trained (VO2peak = 60.6 ml kg-1min-1) college age cyclists and continuous wave Doppler echocardiography, peak acceleration (PkA) and velocity (PkV) of blood flow in the ascending aorta, and the stroke velocity integral (SVI) were assessed to determine if rider position influenced the central haemodynamic responses to graded maximal cycle ergometry. Cyclist position was determined by hand placement on the uprights (UPRI) or drops (DROP) of conventional handlebars or using aerodynamic handlebars (AHB). All subjects consistently achieved a peak workload of 300 W. The Doppler variables did not differ significantly between rider positions at each stage of the maximal exercise tests but did change in response to increasing workloads. PkA was significantly (P < 0.05) greater at workloads > or = 240 W versus < or = 120 W. PkV increased significantly (P < 0.05) up to 180 W and then reached a plateau. SVI increased to a workload of 120 W and then progressively declined, becoming significantly (P < 0.05) less at 300 W. For each stage, neither submaximal VO2, VI nor heart rate (HR) differed significantly between each trial. These results suggest that rider position does not affect the physiological response to maximal bicycle ergometry as responses to each position are similar.
In and Out, Good and Bad News, of Generalizability of SWOG Treatment Trial Results
Authors: A. Bleyer
Journal: JNCI Journal of the National Cancer Institute (2014)

The issue of generalizability of clinical trial results has challenged researchers and practitioners of adult cancer patients for years. It is one reason why the adult cancer cooperative group enterprise in the United States is undergoing yet another transformation (1). Figure 1 may capture the essence of the situation. Its foreground shows the most recent data available to this commentator on the estimated proportion of cancer patients in the United States entered onto cooperative group treatment trials as a function of individual year of patient age. The background shows the rest of the United States. With only 2% to 4% of adults aged 20 to 65 years entered onto clinical trials, how can we rely on such a small sample size to be applicable to the general population? In a comparison of survival outcomes among cancer patients treated in and out of clinical trials published in this issue of the Journal, Unger and colleagues analyzed 21 SWOG treatment trials enrolled during the period from 1986 to 2007 with comparable patients in the US Surveillance, Epidemiology and End Results (SEER) database (2). Their primary subset analysis was good- vs poor-prognosis trials defined by a 2-year average study-specific survival rate of greater than 50% or less than or equal to 50%, respectively. The former had 11 trials that included melanoma, myeloma, and carcinoma of the breast, bladder, uterine cervix, and prostate. The latter had 10 trials that included acute myelogenous leukemia, brain tumors, lung cancer, and pancreatic carcinoma. The results may be interpreted as a series of good- vs bad-news scenarios (Table 1), with several advantages as a source of disadvantage and vice versa. Among the best news is that patients in SWOG trials had a survival benefit, albeit only in poor-prognosis trials. The bad news for them was that it “endured for only 1 year” (2). However, according to Supplementary Figure 2 in the Unger et al. report (2), which shows the SWOG and SEER survival curves for each of 10 poor-prognosis trials, the survival benefit is better than the authors concluded, lasting at least 5 years in two trials, 3 years in three trials, and 2 years in two trials. In only two of the 10 trials was it less than 1 year. Whether or not the apparent benefit of the SWOG trial in patients with a poor prognosis is more durable than concluded, the striking difference between the broad categories of good and poor prognosis as defined has major implications for the interpretation of cancer clinical trial outcomes and application to the general population:
Continuous Subcutaneous Insulin Infusion Is Better Than Multiple Daily Insulin Injections in Reducing Glucose Variability Only in Type 1 Diabetes With Good Metabolic Control
Authors: Giuseppe Lepore, Anna Corsi, Alessandro R. Dodesini, Italo Nosari, Roberto Trevisan
Journal: Diabetes Care (2010)

A possible advantage of continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes is the decrease of glucose excursions with respect to multiple daily injections (MDI) of insulin. Few studies investigated this aspect of insulin treatment using continuous glucose monitoring systems (1).

The aim of our study was to evaluate whether CSII reduces glucose variability with respect to MDI, in patients with comparable A1C levels. The analysis was conducted in 36 type 1 diabetic patients, treated with CSII (15 male and 21 female subjects, aged 35 ± 12 years, duration of diabetes 16 ± 11 years, A1C 8.3 ± 1.5%) and 77 patients treated with MDI (35 male and 42 female subject, aged 40 ± 15 years, duration of …
Hepatorenal syndrome, MELD score and liver transplantation: An evolving issue with relevant implications for clinical practice
Authors: Paolo Angeli, Pere Gines
Journal: Journal of Hepatology (2012)

Hepatorenal syndrome (HRS) is a severe complication of cirrhosis that is associated with poor survival. A rapid diagnosis of HRS and a prompt initiation of the treatment with terlipressin and albumin are mandatory because this leads to an improvement of prognosis. This review covers the predictive value of HRS on 3-month mortality beyond the MELD score and its consequential impact on the prioritization policy to liver transplantation (LT). Moreover, it analyzes the impact of the response to pharmacological treatment on the MELD score, its possible delaying effect on the timing of LT, and suggests a way of overcoming the paradoxical effect of terlipressin and albumin on the priority to LT in responders. Finally, the review discusses the appropriate use of combined liver-kidney transplantation (CLKT) in patients with HRS who do not respond to treatment with terlipressin and albumin.
Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801)
Authors: O. Bouché, M. Ychou, P. Burtin, L. Bedenne, M. Ducreux, G. Lebreton, J. Baulieux, B. Nordlinger, C. Martin, J.F. Seitz, J.M. Tigaud, E. Echinard, N. Stremsdoerfer, C. Milan, P. Rougier
Journal: Annals of Oncology (2005)
White Matter Hyperintensities and Cerebral Amyloidosis
Authors: Frank A. Provenzano, Jordan Muraskin, Giuseppe Tosto, Atul Narkhede, Ben T. Wasserman, Erica Y. Griffith, Vanessa A. Guzman, Irene B. Meier, Molly E. Zimmerman, Adam M. Brickman, for the Alzheimer's Disease Neuroimaging Initiative
Journal: JAMA Neurology (2013)

<h3>Importance</h3>Current hypothetical models emphasize the importance of β-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation.<h3>Objective</h3>To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography–derived amyloid positivity on the clinical expression of AD.<h3>Design</h3>Baseline PIB–positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59).<h3>Setting</h3>The Alzheimer's Disease Neuroimaging Initiative public database.<h3>Participants</h3>The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database.<h3>Main Outcome Measures</h3>Clinical AD diagnosis and WMH volume.<h3>Results</h3>Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD.<h3>Conclusions and Relevance</h3>White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.
Insight into the molecular requirements for pathogenicity of Fusarium oxysporum f. sp. lycopersici through large-scale insertional mutagenesis
Authors: Caroline B Michielse, Ringo van Wijk, Linda Reijnen, Ben JC Cornelissen, Martijn Rep
Journal: Genome biology (2009)

Abstract Background Fusarium oxysporum f. sp. lycopersici is the causal agent of vascular wilt disease in tomato. In order to gain more insight into the molecular processes in F. oxysporum necessary for pathogenesis and to uncover the genes involved, we used Agrobacterium -mediated insertional mutagenesis to generate 10,290 transformants and screened the transformants for loss or reduction of pathogenicity. Results This led to the identification of 106 pathogenicity mutants. Southern analysis revealed that the average T-DNA insertion is 1.4 and that 66% of the mutants carry a single T-DNA. Using TAIL-PCR, chromosomal T-DNA flanking regions were isolated and 111 potential pathogenicity genes were identified. Conclusions Functional categorization of the potential pathogenicity genes indicates that certain cellular processes, such as amino acid and lipid metabolism, cell wall remodeling, protein translocation and protein degradation, seem to be important for full pathogenicity of F. oxysporum . Several known pathogenicity genes were identified, such as those encoding chitin synthase V, developmental regulator FlbA and phosphomannose isomerase. In addition, complementation and gene knock-out experiments confirmed that a glycosylphosphatidylinositol-anchored protein, thought to be involved in cell wall integrity, a transcriptional regulator, a protein with unknown function and peroxisome biogenesis are required for full pathogenicity of F. oxysporum .
Outcomes of Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention With Drug-Eluting Stents for Patients With Multivessel Coronary Artery Disease
Authors: Aamir Javaid, Daniel H. Steinberg, Ashesh N. Buch, Paul J. Corso, Steven W. Boyce, Tina L. Pinto Slottow, Probal K. Roy, Peter Hill, Teruo Okabe, Rebecca Torguson, Kimberly A. Smith, Zhenyi Xue, Natalie Gevorkian, William O. Suddath, Kenneth M. Kent, Lowell F. Satler, Augusto D. Pichard, Ron Waksman
Journal: Circulation (2007)

Advances in coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) with drug-eluting stents have dramatically improved results of these procedures. The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospective, randomized data reflecting current practice. This study represents a "real-world" evaluation of current technology in the treatment of multivessel coronary artery disease.A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified. Of these, 1080 patients were treated for 2-vessel disease (196 CABG and 884 PCI) and 600 for 3-vessel disease (505 CABG and 95 PCI). One-year mortality, cerebrovascular events, Q-wave myocardial infarction, target vessel failure, and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts. Outcomes were adjusted for baseline covariates and reported as hazard ratios. The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease (9.7% CABG versus 21.2% PCI; P<0.001) and 3-vessel disease (10.8% CABG versus 28.4% PCI; P<0.001). Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel (hazard ratio 2.29; 95% CI 1.39 to 3.76; P=0.01) and 3-vessel disease (hazard ratio 2.90; 95% CI 1.76 to 4.78; P<0.001). Adjusted outcomes for the nondiabetic subpopulation demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel (hazard ratio 1.77; 95% CI 0.96 to 3.25; P=0.07) and 3-vessel disease (hazard ratio 1.70; 95% CI 0.77 to 3.61; P=0.19).Compared with PCI with drug-eluting stents, CABG resulted in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease, primarily in those with underlying diabetes. Coronary artery bypass surgery may be the preferred revascularization strategy in diabetic patients with multivessel coronary artery disease.
Modelling a dream: the molecular prevention of pancreatic cancer
Authors: E. Hawk, S. Patterson
Journal: Gut (2010)

Pancreatic cancer is a frequent and devastating cause of morbidity and mortality in many parts of the world with a 5 year survival of only 5%.1 Unfortunately, these dismal statistics have not improved appreciably over the last 30 years despite an explosive growth in our understanding of the disease's pathogenesis. Indeed, a recent model of human pancreatic cancer provides important histological and molecular insights,2 but for the most part, these insights await translation into improved markers for risk assessment, new agents for prevention and therapy, as well as intermediate endpoints that could prove useful in guiding intervention trials.

Despite these translational limitations, our growing knowledge of human cancer development has stimulated the development of many new, genetically driven rodent models that promise to provide novel mechanistic insights into cancer development and progression, and/or serve as improved preclinical systems in which to evaluate promising preventive or therapeutic agents. Of course, the relevance of these models to human applications depends on several factors.3 4 Fundamentally, the most promising new animal models should: (1) employ genetic manipulations that mimic key molecular determinants of human disease—optimally, in nature, magnitude, timing, and frequency; (2) reflect histopathological and phenotypic features of human disease that evolve over time; and (3) offer reproducible results across time and various laboratories. Additional desirable features of somewhat lesser importance include: (1) ready public access, (2) efficiency of use (eg, regarding the frequency and timing of meaningful endpoints), (3) modest cost, (4) breeding efficiencies (eg, for generation and maintenance of the colony), and (5) an intact immune system. When an animal model is used to …