tbuckley/cabot-search huggingface dataset:
Sources of bias in randomised controlled trials II
Authors: P. Sedgwick
Journal: BMJ (2010)

Previous questions described a cluster randomised controlled trial that assessed the long term effects of an obesity prevention programme in schools.1 2 The intervention was a focused education programme delivered over one school year that promoted a healthy diet and discouraged consumption of carbonated drinks. The control treatment was no intervention.3

The clusters were classes of children aged 7-11 years within schools. Classes were allocated to a treatment group by using a random sequence generated by a researcher not involved in recruitment. A second researcher who was unaware of the sequence recruited 29 classes from six schools. As classes were recruited they were allocated to the next treatment in the sequence. Fifteen classes totalling 325 children were randomised to the active intervention and 14 classes totalling 319 children to the control. 

The main outcome measures were change in anthropometric measures such as height, weight, and waist circumference. Three years after baseline, outcome measures were obtained for 219 (67.4%) children …
Lifestyle factors and sensitization in children - the ALADDIN birth cohort
Authors: F. Stenius, J. Swartz, G. Lilja, M. Borres, M. Bottai, G. Pershagen, A. Scheynius, J. Alm
Journal: Allergy (2011)

To cite this article: Stenius F, Swartz J, Lilja G, Borres M, Bottai M, Pershagen G, Scheynius A, Alm J. Lifestyle factors and sensitization in children – the ALADDIN birth cohort. Allergy 2011; 66: 1330–1338. Background: Several cross-sectional studies indicate that an anthroposophic lifestyle reduces the risk of allergy in children. We initiated the Assessment of Lifestyle and Allergic Disease During Infancy (ALADDIN) birth cohort to elucidate the role of specific factors supposed to mediate this effect. The aims of this study are to describe the ALADDIN cohort and to report patterns of exposure and allergic sensitization during the first years of life. Methods: The ALADDIN study is a prospective birth cohort study of 330 children from families with an anthroposophic, partly anthroposophic, or nonanthroposophic lifestyle. The children and their parents were following an extensive data collection scheme, including repeated questionnaires and biological samples. Blood samples were collected from the parents and from the child at birth as well as at 6, 12, and 24 months of age. Results: Several lifestyle factors differed between the groups, such as diet, medication, and place of delivery. Children of families with an anthroposophic lifestyle had a markedly decreased risk of sensitization during the first 2 years of life compared with children of nonanthroposophic families with adjusted OR 0.25 (95% CI 0.10–0.64) and P-value 0.004. A similar situation held true for children from families with a partly anthroposophic lifestyle, adjusted OR 0.31 (95% CI 0.15–0.54), and P-value 0.002. Conclusions: The anthroposophic lifestyle comprises several factors of interest for allergy development and is here shown to be associated with reduced risk of IgE sensitization already in infancy. Identifying the factors responsible for this association would be of significant clinical importance.
Cancers as Wounds that Do Not Heal: Differences and Similarities between Renal Regeneration/Repair and Renal Cell Carcinoma
Authors: Joseph Riss, Chand Khanna, Seongjoon Koo, Gadisetti V.R. Chandramouli, Howard H. Yang, Ying Hu, David E. Kleiner, Andreas Rosenwald, Carl F. Schaefer, Shmuel A. Ben-Sasson, Liming Yang, John Powell, David W. Kane, Robert A. Star, Olga Aprelikova, Kristin Bauer, James R. Vasselli, Jodi K. Maranchie, Kurt W. Kohn, Ken H. Buetow, W. Marston Linehan, John N. Weinstein, Maxwell P. Lee, Richard D. Klausner, J. Carl Barrett
Journal: Cancer Research (2006)

Abstract Cancers have been described as wounds that do not heal, suggesting that the two share common features. By comparing microarray data from a model of renal regeneration and repair (RRR) with reported gene expression in renal cell carcinoma (RCC), we asked whether those two processes do, in fact, share molecular features and regulatory mechanisms. The majority (77%) of the genes expressed in RRR and RCC were concordantly regulated, whereas only 23% were discordant (i.e., changed in opposite directions). The orchestrated processes of regeneration, involving cell proliferation and immune response, were reflected in the concordant genes. The discordant gene signature revealed processes (e.g., morphogenesis and glycolysis) and pathways (e.g., hypoxia-inducible factor and insulin-like growth factor-I) that reflect the intrinsic pathologic nature of RCC. This is the first study that compares gene expression patterns in RCC and RRR. It does so, in particular, with relation to the hypothesis that RCC resembles the wound healing processes seen in RRR. However, careful attention to the genes that are regulated in the discordant direction provides new insights into the critical differences between renal carcinogenesis and wound healing. The observations reported here provide a conceptual framework for further efforts to understand the biology and to develop more effective diagnostic biomarkers and therapeutic strategies for renal tumors and renal ischemia. (Cancer Res 2006; 66(14): 7216-24)
Endometrial leukocytes and menstruation
Authors: L. A. Salamonsen
Journal: Human Reproduction Update (2000)

This review examines evidence supporting the concept that menstruation occurs as a result of an inflammatory process. In the endometrium, leukocyte numbers rise in the late secretory phase following the fall in serum progesterone concentrations. It is postulated that products released following activation of these leukocytes are critically important for menstruation. Mast cells, eosinophils, neutrophils and macrophages in particular are involved. Endometrial granular lymphocytes may also play a role, although their increase in numbers is somewhat earlier during the menstrual cycle than that of the others, suggesting perhaps a primary role in embryo implantation. Leukocyte products include a range of proteases, chemokines and cytokines which in concert result in focal production and activation of matrix metalloproteinases by endometrial cells and the subsequent breakdown of tissue that characterizes menstruation. Regulation of leukocyte entry, proliferation, differentiation and activation within the endometrium is not yet well understood, although both chemokines and cytokines produced locally by endometrial cells are clearly implicated. The role of progesterone in regulating these events is still not understood although the lack of progesterone receptors on endometrial leukocytes suggests indirect actions.
Evidence in Support of a Back-to-Basics Approach in Out-of-Hospital Cardiopulmonary Resuscitation vs "Advanced" Treatment
Authors: Michael Callaham
Journal: JAMA Internal Medicine (2014)

A man clutches his chest and collapses on the sidewalk. Call 911. Surely we want the most advanced life support (ALS) available—paramedics capable of intubating, administering intravenous medications, and managing complex arrhythmias, as well as transport to the hospital. Or do we?
Expression and Sequence Evolution of Aromatase cyp19a1 and Other Sexual Development Genes in East African Cichlid Fishes
Authors: Astrid Böhne, Corina Heule, Nicolas Boileau, Walter Salzburger
Journal: Molecular Biology and Evolution (2013)

Sex determination mechanisms are highly variable across teleost fishes and sexual development is often plastic. Nevertheless, downstream factors establishing the two sexes are presumably conserved. Here, we study sequence evolution and gene expression of core genes of sexual development in a prime model system in evolutionary biology, the East African cichlid fishes. Using the available five cichlid genomes, we test for signs of positive selection in 28 genes including duplicates from the teleost whole-genome duplication, and examine the expression of these candidate genes in three cichlid species. We then focus on a particularly striking case, the A- and B-copies of the aromatase cyp19a1, and detect different evolutionary trajectories: cyp19a1A evolved under strong positive selection, whereas cyp19a1B remained conserved at the protein level, yet is subject to regulatory changes at its transcription start sites. Importantly, we find shifts in gene expression in both copies. Cyp19a1 is considered the most conserved ovary-factor in vertebrates, and in all teleosts investigated so far, cyp19a1A and cyp19a1B are expressed in ovaries and the brain, respectively. This is not the case in cichlids, where we find new expression patterns in two derived lineages: the A-copy gained a novel testis-function in the Ectodine lineage, whereas the B-copy is overexpressed in the testis of the speciest-richest cichlid group, the Haplochromini. This suggests that even key factors of sexual development, including the sex steroid pathway, are not conserved in fish, supporting the idea that flexibility in sexual determination and differentiation may be a driving force of speciation.
Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA)
Authors: A. Schneeweiss, S. Chia, T. Hickish, V. Harvey, A. Eniu, R. Hegg, C. Tausch, J.H. Seo, Y.-F. Tsai, J. Ratnayake, V. McNally, G. Ross, J. Cortés
Journal: Annals of Oncology (2013)
Insulin Resistance, Hyperinsulinemia, Hypertriglyceridemia, and Hypertension: Parallels Between Human Disease and Rodent Models
Authors: Gerald M Reaven
Journal: Diabetes Care (1991)

There is considerable evidence that abnormalities of glucose, insulin, and lipoprotein metabolism occur more frequently in untreated hypertensive patients than in normotensive control subjects. More recently, it has also become apparent that similar metabolic abnormalities occur in rodent models of hypertension. One purpose of this article is to review the experimental data that have led to the above generalizations. The second goal is to address the significance of these findings, which is certainly not clear. For example, it could be argued that the relationship between high blood pressure and the associated metabolic defects is incidental. On the other hand, there is evidence that the changes in glucose, insulin, and lipoprotein metabolism may play a role in the etiology and/or clinical course of patients with high blood pressure. Although it is impossible at this point to definitively choose between these possibilities, an effort is made to marshal the evidence in support of the latter alternative.
Elevated cyclic adenosine monophosphate phosphodiesterase activity in peripheral blood mononuclear leucocytes from children with atopic dermatitis
Authors: T. SAWAI, K. IKAI, M. UEHARA
Journal: British Journal of Dermatology (1995)

We examined peripheral blood mononuclear leucocyte cyclic adenosine monophosphate phosphodiesterase (cAMP‐PDE) activity in 80 children (aged 2‐12 years) with atopic dermatitis. The enzyme activity (35.1 ± 18.6U) in children with atopic dermatitis was significantly higher than that (19.1 ± 12.6U) in age‐matched non‐atopic controls. There was no significant difference in the cAMP‐PDE activity between children with mild atopic dermatitis and children with severe atopic dermatitis. These findings support the view that elevation of peripheral mononuclear leucocyte cAMP‐PDE actvity in patients with atopic dermatitis is a gene‐associated abnormality.
In vivo electrophysiological effects of a selective slow delayed-rectifier potassium channel blocker in anesthetized dogs: potential insights into class III actions
Authors: H Nakashima
Journal: Cardiovascular Research (2004)

This study evaluated the in vivo electrophysiological effects of a highly selective slow delayed-rectifier K+-current blocker, HMR 1556, to gain insights into the consequences of selectively inhibiting the slow delayed-rectifier current in vivo.Atrial and ventricular effective refractory periods, sinus node recovery time, Wenckebach cycle-length, atrial fibrillation duration and electrocardiographic intervals were measured before and after intravenous HMR 1556.HMR 1556 increased atrial and ventricular refractory periods (e.g. by 6 +/- 4% and 27 +/- 6% at cycle lengths of 360 and 400 ms, respectively), QT intervals and sinus-node recovery times. Beta-adrenoceptor blockade with nadolol abolished all effects except those on ventricular refractoriness and changed positive use-dependent effects on refractoriness to reverse use-dependent ones. In the presence of dofetilide to block rapid delayed-rectifier current, HMR 1556 effects were potentiated (e.g. atrial and ventricular refractory periods increased by 26 +/- 3% and 34 +/- 3% at cycle lengths of 360 and 400 ms, respectively). HMR 1556 reduced vagal atrial fibrillation duration from 1077 +/- 81 to 471 +/- 38 s, an effect abolished by nadolol and greatly potentiated by dofetilide (duration 77 +/- 30 s). HMR 1556 increased Wenckebach cycle length only in the presence of dofetilide.Slowed delayed-rectifier current inhibition affects atrial repolarization, sinus node function and atrial fibrillation in vivo, but only in the presence of intact beta-adrenergic tone, and delays ventricular repolarization even when beta-adrenoceptors are blocked. The slow delayed-rectifier current is particularly important when rapid delayed-rectifier current is suppressed, illustrating the importance of repolarization reserve.
Pathologic Complete Response After Neoadjuvant Chemotherapy Plus Trastuzumab Predicts Favorable Survival in Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: Results From the TECHNO Trial of the AGO and GBG Study Groups
Authors: Michael Untch, Peter A. Fasching, Gottfried E. Konecny, Stephan Hasmüller, Annette Lebeau, Rolf Kreienberg, Oumar Camara, Volkmar Müller, Andreas du Bois, Thorsten Kühn, Elmar Stickeler, Nadia Harbeck, Cornelia Höss, Steffen Kahlert, Thomas Beck, Werner Fett, Keyur M. Mehta, Gunter von Minckwitz, Sibylle Loibl
Journal: Journal of Clinical Oncology (2011)

Purpose To evaluate efficacy and safety of epirubicin and cyclophosphamide followed by paclitaxel and trastuzumab as neoadjuvant treatment in patients with human epidermal growth factor receptor 2 (HER2)–overexpressing breast cancer. Patients and Methods Patients with centrally confirmed HER2-overexpressing breast cancer (≥ 2 cm or inflammatory) received four 3-week cycles epirubicin and cyclophosphamide (90/600 mg/m 2 ) followed by four 3-week cycles paclitaxel (175 mg/m 2 ) and trastuzumab (6 mg/kg) before surgery. Trastuzumab was continued after surgery to complete 1 year of treatment. Primary end point was pathologic complete response (pCR) defined as no residual invasive tumor in breast and lymphatic tissue. Results Thirty-nine percent of 217 enrolled patients achieved a pCR. Breast conservation was possible in 64% of patients. Three-year disease-free survival (DFS) was 88% in patients with pCR compared to 73% in patients without pCR (P = .01). Three-year overall survival (OS) was 96% in patients with pCR compared to 86% in patients without pCR (P = .025). pCR was the only significant prognostic factor for DFS (hazard ratio [HR] 2.5; 95% CI, 1.2 to 5.1; P = .013) and OS (HR, 4.9; 95% CI, 1.4 to 17.4; P = .012) in multivariable analysis. Cardiac toxicity was reported in eight patients (3.7%) of whom six presented with an asymptomatic left ventricular ejection fraction decrease and two with symptomatic chronic heart failure. Conclusion Neoadjuvant combination of trastuzumab and chemotherapy resulted in a high pCR rate in HER2-overexpressing primary breast cancer. Patients with a pCR after neoadjuvant anti-HER2 therapy in combination with chemotherapy followed by maintenance trastuzumab have an improved long-term outcome. Patients without a pCR had an increased risk for relapse and death.
Prostaglandins, Leukotrienes, and Platelet-Activating Factor in Shock
Authors: G Feuerstein, J M Hallenbeck
Journal: The Annual Review of Pharmacology and Toxicology (1987)

Three major lines of evidence support a role of eicosanoids and PAF in shock. Formation of each of the cyclooxygenase metabolites of arachidonate is enhanced at some point during the shock; these metabolites include PGE2, PGF2 alpha, PGI2, and TXA2. Enhanced formation of 5-HETE and the cysteinyl-LTs provides evidence for activation of the 5-lipoxygenase pathway of arachidonate metabolism, and preliminary biochemical evidence suggests that formation of PAF in anaphylactic and endotoxic shock is also enhanced. Second, TXA2, cysteinyl-leukotrienes, and, to an even greater extent, PAF are able to produce shock and death in intact animals. Third, pharmacological studies show that selective antagonists or synthesis inhibitors modify the course of the shock. While any of these lines of evidence may not by itself provide proof for a cause-effect relationship, the data taken together strongly suggest that vasoactive lipids might be involved in fundamental processes in the pathophysiology of shock. However, the role of vasoactive lipids might vary in different shock paradigms, change at various time points during the evolution of the shock, and depend on the species studied. Moreover, while the majority of the reports tend to focus on a specific substance, the metabolism of all of the eicosanoids mentioned, as well as PAF and probably other arachidonate metabolites (e.g. 15-lipoxygenase products such as lipoxins), changes during shock states. This fact probably causes most of the discrepancies in studies using specific antagonists or synthesis inhibitors to modify the state of shock. Thus, while blockade of one mediator might provide some protection, it might not be sufficient to halt or reverse the main course of the pathophysiological process. For example, the increase in vascular permeability, a fundamental phenomenon in trauma, anaphylaxis, or endotoxemia, might be mediated by PAF, LTs, PGs, peptides (e.g. kinins, substance P, CGRP) and amines (e.g. histamine in some species). Attempting to reverse such a complex phenomenon by blocking one specific factor might not be productive unless the specific substance played a key role in generation of the other factors. It seems, however, that while interactions between PGs, LTs, and PAF do occur (31, 32, 70), none of the shock states are crucially dependent on one class of the vasoactive lipids. Therefore, the therapeutic strategy should be based on multiple sites of action, either by drug combinations or multiple actions of a specific drug.(ABSTRACT TRUNCATED AT 400 WORDS)
Randomized, controlled trial of resistance training in breast cancer patients receiving adjuvant radiotherapy: results on cancer-related fatigue and quality of life
Authors: K. Steindorf, M.E. Schmidt, O. Klassen, C.M. Ulrich, J. Oelmann, N. Habermann, P. Beckhove, R. Owen, J. Debus, J. Wiskemann, K. Potthoff
Journal: Annals of Oncology (2014)
Liver Cancer: Connections with Obesity, Fatty Liver, and Cirrhosis
Authors: Andrea Marengo, Chiara Rosso, Elisabetta Bugianesi
Journal: Annual Review of Medicine (2015)

The burden of hepatocellular carcinoma (HCC), the most common form of liver cancer, is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The most worrisome aspects of these new risk factors are their large spread in the general population and their link with HCC arising in noncirrhotic livers. HCC may be the presenting feature of an asymptomatic nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. The HCC risk connected to metabolic factors has been underestimated so far, and a poorer surveillance has prevented an adequate treatment. Systemic and hepatic molecular mechanisms involved in obesity- and NAFLD-induced hepatocarcinogenesis as well as potential early markers of HCC are being extensively investigated. This review summarizes current evidence linking obesity, NAFLD and liver cancer, discusses its clinical impact and describes the main mechanisms underlying this complex relationship.
The Clinical Significance of Hypouricemia
Authors: C. MICHAEL RAMSDELL
Journal: Annals of Internal Medicine (1973)

Hypouricemia (serum urate, < 2 mg/100 ml) was noted in 0.97% of 6629 consecutive serum urate measurements done at two large hospitals. In two thirds of the hypouricemic patients drugs, including aspirin, allopurinol, X-ray contrast agents, and glyceryl guaiacholate, seemed to be responsible for the decreased serum urate concentration; disseminated carcinomas were noted in nine more hypouricemic patients. In many of these subjects an alteration in the renal tubular handling of uric acid seemed to cause the development of hypouricemia. Poor dietary intake of protein and purines and hypo-osmolality were common findings that may have contributed to the development of hypouricemia in some patients. Although hypouricemia has been reported as a common manifestation of several relatively rare diseases, these illnesses are unusual causes of the hypouricemia found in a general hospital population.
Know it, check it, treat it – COPD consumer mobilisation campaign. A pilot study
Authors: June Roberts, Helena Cullen, Nawar Diar Bakerly
Journal: European Respiratory Journal (2011)

Background:  COPD is under diagnosed and awareness amongst the public is low.   Aims:  To develop and pilot a consumer mobilisation campaign* to increase public awareness of COPD and encourage the undiagnosed local population to recognise symptoms and present for further assessment.   Methods:  Insights into attitudes to COPD and motivators/barriers to health messages were collected through focus groups with local clinicians and members of the public. Key messages were communicated using a variety of media over a 3-month period. Pre and post campaign awareness amongst clinicians and the public was measured using market research techniques.   Results:  Key insights from focus groups:  Don9t focus on smoking - “We don9t like anti-smoking messages”  Get people to join the dots between their symptoms and COPD - “It9s only just dawned on me that my cough is not normal”  Make the message personal - “COPD may mean you become dependent on others” was a message that shocked people and would more likely prompt action  Make statistics real – “1 in 7” people registered more with the target audience than “3.7 million people have the disease”  Of 75 people surveyed post launch:  Prompted awareness of COPD increased by 24% and its symptoms by 9%  Of 25 general practices surveyed post launch:  Awareness of the campaign amongst clinicians was high (80% unprompted)  There was an average increase in diagnosis rates of 2 patients per practice prompted by the campaign (range 0-15)   Conclusion:  COPD consumer mobilisation campaigns can increase public awareness and diagnosis rates. Further work is needed.  *Campaign developed and funded by Boehringer Ingelheim Ltd and Pfizer Ltd in collaboration with NHS Salford