tbuckley/cabot-search huggingface dataset:
Use of placebo controls in the evaluation of surgery: systematic review
Authors: K. Wartolowska, A. Judge, S. Hopewell, G. S. Collins, B. J. F. Dean, I. Rombach, D. Brindley, J. Savulescu, D. J. Beard, A. J. Carr
Journal: BMJ (2014)

<b>Objective</b> To investigate whether placebo controls should be used in the evaluation of surgical interventions. <b>Design</b> Systematic review. <b>Data sources</b> We searched Medline, Embase, and the Cochrane Controlled Trials Register from their inception to November 2013. <b>Study selection</b> Randomised clinical trials comparing any surgical intervention with placebo. Surgery was defined as any procedure that both changes the anatomy and requires a skin incision or use of endoscopic techniques. <b>Data extraction</b> Three reviewers (KW, BJFD, IR) independently identified the relevant trials and extracted data on study details, outcomes, and harms from included studies. <b>Results</b> In 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery. In 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small. Serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%); in four trials authors did not specify in which arm the events occurred. However, in many studies adverse events were unrelated to the intervention or associated with the severity of the condition. The existing placebo controlled trials investigated only less invasive procedures that did not involve laparotomy, thoracotomy, craniotomy, or extensive tissue dissection. <b>Conclusions</b> Placebo controlled trial is a powerful, feasible way of showing the efficacy of surgical procedures. The risks of adverse effects associated with the placebo are small. In half of the studies, the results provide evidence against continued use of the investigated surgical procedures. Without well designed placebo controlled trials of surgery, ineffective treatment may continue unchallenged.
Towards greater transparency in the life sciences
Authors: R. Thompson, D. Khanna
Journal: BMJ (2012)

After the recent publication of guidance on collaboration between healthcare professionals and the drug industry,1 the BMJ printed two letters of criticism to which we would like to respond.2 3 This guidance is just the first step in a series of work by the Ethical Standards in Health and Life Sciences Group (ESHLSG) to tackle problems in the relationship between …
Canine vascular tissues are targets for androgens, estrogens, progestins, and glucocorticoids.
Authors: K B Horwitz, L D Horwitz
Journal: Journal of Clinical Investigation (1982)

Sex differences and steroid hormones are known to influence the vascular system as shown by the different incidence of atherosclerosis in men and premenopausal women, or by the increased risk of cardiovascular diseases in women taking birth control pills or men taking estrogens. However, the mechanisms for these effects in vascular tissues are not known. Since steroid actions in target tissues are mediated by receptors, we have looked for cytoplasmic steroid receptor proteins in vascular tissues of dogs. We find specific saturable receptors, sedimenting at 8S on sucrose density gradients for estrogens (measured with [3H]estradiol +/- unlabeled diethylstilbestrol), androgens (measured with [3H]R1881 +/- unlabeled R1881 and triamcinolone acetonide), and glucocorticoids (measured with [3H]dexamethasone +/- unlabeled dexamethasone); they are absent for progesterone (measured with [3H]R5020 +/- unlabeled R5020 and dihydrotestosterone). Progesterone receptors can, however, be induced by 1-wk treatment of dogs with physiological estradiol concentrations (100 pg/ml serum estrogen), indicating a functional estrogen receptor. Receptor levels range from 20 to 2,000 fmol/mg DNA. They are specific for each hormone; unrelated steroids fail to complete for binding. Low dissociation constants, measured by Scatchard analyses, show that binding is of high affinity. Steroid binding sites are in the media and/or adventitia since they persist when the intima is removed. Compared with the arteries, receptor levels are reduced 80% in inferior venae cavae of females, and are absent in the venae cavae of males. We hypothesize that steroid hormones can have direct effects on vascular tissues medicated by specific receptors present in arterial blood vessel walls.
World leaders agree to cut deaths from non-communicable diseases by a quarter by 2025
Authors: A. Gulland
Journal: BMJ (2012)

Health ministers and senior officials from 194 countries have agreed to cut the number of premature deaths from the four most prevalent non-communicable diseases by a quarter by 2025.

The voluntary target was set at the 65th World Health Assembly in Geneva last week, eight months after world leaders signed an agreement to tackle the causes of the four major non-communicable diseases—diabetes, lung disease, cancer, and cardiovascular disease—at the United Nations General Assembly.1

However, at the UN meeting leaders failed to set any targets or goals for tackling the diseases, which cause 63% of the world’s deaths, four fifths of which are in low and middle income countries.

As well as agreeing to cut …
"TUBERCULOSIS AMONG MEDICAL STUDENTS"
Authors: Earle M. Chapman
Journal: JAMA (1942)

<h3>To the Editor:—</h3> In the May 16 issue ofThe Journalappears a current comment on "Tuberculosis Among Medical Students," and in the discussion the emphasis is placed on the environment of the students. Although "contact with patients" is mentioned, it seems to me that this is the chief source of tuberculosis in students who are clumsy and careless in their first approach to the ill but undiagnosed patient. I believe that it is in the second and third years particularly that tuberculosis has its greatest incidence among medical students. It is in this period that the student is struggling to acquire a technic in physical diagnosis. As a teacher of physical diagnosis at Harvard Medical School I am amazed, startled and disgusted with the manner in which a young man with a stethoscope will allow a total stranger to cough directly into his face. Yet with each second year
Lenalidomide plus Dexamethasone for Relapsed Multiple Myeloma in North America
Authors: Donna M. Weber, Christine Chen, Ruben Niesvizky, Michael Wang, Andrew Belch, Edward A. Stadtmauer, David Siegel, Ivan Borrello, S. Vincent Rajkumar, Asher Alban Chanan-Khan, Sagar Lonial, Zhinuan Yu, John Patin, Marta Olesnyckyj, Jerome B. Zeldis, Robert D. Knight
Journal: New England Journal of Medicine (2007)

Lenalidomide, an oral immunomodulatory drug that is similar to thalidomide but has a different safety profile, has clinical activity in relapsed or refractory multiple myeloma.Patients in the United States and Canada who had received at least one previous therapy for multiple myeloma but who required additional treatment were randomly assigned to receive either 25 mg of lenalidomide or placebo on days 1 to 21 of a 28-day cycle. Both groups also received 40 mg of oral dexamethasone on days 1 to 4, 9 to 12, and 17 to 20 for the first four cycles. After the fourth cycle, 40 mg of dexamethasone was administered only on days 1 to 4. Safety, clinical response, time to progression, and overall survival were assessed.We assigned 177 patients to the lenalidomide group and 176 to the placebo group. Complete, near-complete, or partial responses occurred in 108 patients (61.0%) in the lenalidomide group and in 35 patients (19.9%) in the placebo group (P<0.001); complete responses occurred in 14.1% and 0.6%, respectively (P<0.001). The median time to progression was 11.1 months in the lenalidomide group and 4.7 months in the placebo group (P<0.001). Median overall survival times in the two groups were 29.6 months and 20.2 months, respectively (P<0.001). Grade 3 or 4 adverse events were reported in 85.3% of the lenalidomide group and in 73.1% of the placebo group; these events resulted in study discontinuation in 19.8% and 10.2%, respectively. Grade 3 or 4 neutropenia and venous thromboembolism were more common in the lenalidomide group than in the placebo group (41.2% vs. 4.6% and 14.7% vs. 3.4%, respectively; P<0.001 for both comparisons).Lenalidomide plus dexamethasone is superior to placebo plus dexamethasone in patients with relapsed or refractory multiple myeloma. (ClinicalTrials.gov number, NCT00056160 [ClinicalTrials.gov].).
Abstract 5139: Trop2 modulates beta1 integrin-mediated adhesion and migration of prostate cancer cells
Authors: Marco Trerotola, Saverio Alberti, Lucia R. Languino
Journal: Cancer Research (2010)

Abstract Trop1 and Trop2 are highly related transmembrane glycoproteins, which are overexpressed in many human carcinomas and have been suggested to contribute to cancer progression. Recently, Trop2 has been discovered as an important marker for identification of candidate tumor-initiating cells in a mouse model of prostate cancer (PrCa), suggesting that this protein is a novel regulator of PrCa progression. In this study, we show that Trop2 was expressed at high levels in aggressive human PrCa cells, and was co-localized with beta1 integrins, which are known to modulate cell adhesion and invasion and to be deregulated in PrCa. We demonstrate that Trop2 inhibited adhesion of PC3 PrCa cells on fibronectin (the major ligand for beta1), but strongly enhanced their ability to migrate on fibronectin as compared to controls. This effect was specific for cells seeded on fibronectin, since no effect was observed on vitronectin. Confocal microscopy studies using PC3 cells seeded on fibronectin showed strong co-localization of Trop2 with beta1 in leading edges. On the other hand, Trop2 did not co-localize with beta5, an integrin that did not affect migration of PC3 cells on fibronectin. We did not observe any change of beta1 expression in Trop2-overexpressing PC3 cells compared to controls, suggesting that affinity for fibronectin or clustering in focal complexes might be modulated by Trop2. Our studies on Trop2-overexpressing PC3 cells seeded on fibronectin demonstrated that beta1 was in fact displaced from focal adhesions to relocate to Trop2-containing leading edges. Our findings demonstrate a novel cross-talk between Trop2 and beta1 integrins in PrCa cells. We hypothesize that this interplay can result in destabilization of firm adhesion to fibronectin and accelerated re-organization of dynamic structures responsible for migration/invasion of PrCa cells. MT is recipient of a fellowship from the Italian Foundation for Cancer Research (FIRC). Grant Support: NIH R01 CA109874 (LRL). 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 5139.
Contact Dermatitis from Spandex Yarn
Authors: C. F. Allenby, K. D. Crow, V. Kirton, D. Munro-Ashman
Journal: BMJ (1966)

BanIBsH(and also female deaths from benign tumours) were anomalous in being considerably less frequent in spring (March-April-May) than in autumn (September-October-November).And Table III shows that this anomaly was characteristic, though unequally so, of most of the individual cancer sites.Of the very few non-neoplastic diseases which were similarly anomalous in England and Wales in 1956-633 the two with the lowest ratio of spring to autumn deaths were simple goitre, namely 0.72 (33:46), and avitaminoses (in females), namely 0.76 (121:160).In contrast, the corresponding ratio at the other extreme for thyrotoxicosis, namely 1.35 (750: 554), and for non-toxic nodular goitre, namely 1.41 (55: 39).This last was next highest to the ratio for respiratory diseases, namely 1.43 (140,512:97,999).Gereb2 found that cancer deaths were least frequent in March and April, and as a possible explanation of this he suggested vitamin lack, citing experimental evidence of the inhibiting effect of vitamin lack on tumour growth, and also evidence, consistent with this, of seasonal variation in tumour growth.Speculation as to causes, however, is likely to be unfruitful until at the least a much more extensive and sophisticated analysis has been made, not only of British and German data but also of corresponding data from other latitudes and longitudes.-Iam, etc.,.
Infantile colic and parental stress
Authors: S. Thacker
Journal: BMJ (1993)

pattern of pain is of no value in localising the site of the lesion.2We advocate consultation with a senior doctor and consideration of early computed tomography for patients with a good history of neck rotation at the time of impact.This increases the chance of bony injury,2 particularly between the occiput and C2, which is often poorly visualised in plain films.Computed tomography should also be considered in those with a fixed abnormal neck position, particularly if pain does not seem to be the restricting factor, and those with definite neurological signs and symptoms, even if their presenta- tion is delayed.
Exposure chamber for allergen challenge The development and validation of a new concept
Authors: S. M. Rønborg, H. Mosbech, C. R. Johnsen, L. K. Poulsen
Journal: Allergy (1996)

Exposure chambers have proven to be valuable tools in studying allergic diseases. The chamber provides a controlled environment and maintains conditions for measuring the amount of allergen inducing symptoms in allergic subjects. The aim of the present study was to develop and test an exposure chamber. The chamber was constructed as an airtight tent, made of transparent polyethylene, easy to adapt to the shape of an existing room, easy to clean, and providing exact allergen‐dosage control. Airflow to the interior of the tent was controlled by a variable inlet ventilator fitted with a micropore filter and balanced by a variable high‐volume air‐sampler on the outlet side. Trace material and allergen were administered as aerosols with a nebulizer connected to the inlet pipe. Samples were obtained from interior surfaces and filters at the outlet. Two different methods were used to test the concept. One method used a colored, neutral trace substance (phenol red indicator) measured photometrically on extracts from filters. Secondly, house‐dust mite allergen ( Dermatophagoides pteronyssinus ) was applied, with samples analyzed by an ELISA technique. The results demonstrated the ability of the system to administer and sample allergen with a high degree of reproducibility. A clinical pilot trial proved the capability of the system to initiate syniptoms in allergic subjects.
A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood “resident” monocytes, and embryonic macrophages suggests common functions and developmental relationships
Authors: Ferdinando Pucci, Mary Anna Venneri, Daniela Biziato, Alessandro Nonis, Davide Moi, Antonio Sica, Clelia Di Serio, Luigi Naldini, Michele De Palma
Journal: Blood (2009)
β-Adrenoceptors and Glucose Receptors in Pancreatic Beta Cells
Authors: Samuel Vaisrub
Journal: JAMA (1975)

Seven decades have elapsed since John Newport Langley<sup>1</sup>introduced the concept of drug receptors and Paul Ehrlich<sup>2</sup>endorsed it by extending his side-chain theory to include responses to drugs. Yet, the nature and interrelations of these receptors still provide material for controversy. One such lively debate currently centers on β-adrenergic receptors and their relation to postulated glucose receptors and the glucose-induced insulin response in the beta cells of the pancreas. Curiously, Langley's original conclusions were based on the study of adrenalin action and the sympathetic nervous system. The debate was initiated by Cerasi and his associates,<sup>3</sup>who reported that intravenously administered propranolol had suppressed insulin release in response to a concurrent infusion of glucose in 16 healthy subjects. As a consequence of this suppression, the level of blood glucose rose substantially—a somewhat unexpected finding in view of previously reported<sup>4,5</sup>hypoglycemic effects of propranolol, attributable to interference
Two-dimensional and pulsed Doppler echocardiography in the postoperative evaluation of total anomalous pulmonary venous connection.
Authors: J F Smallhorn, P Burrows, G Wilson, J Coles, D L Gilday, R M Freedom
Journal: Circulation (1987)

The role of combined two-dimensional and pulsed Doppler echocardiography in the postoperative assessment of patients with total anomalous pulmonary venous connection was evaluated. Twenty-two cases with a median age of 9.5 weeks at the initial examination were evaluated. Serial ultrasound examinations were performed throughout the study period. The ultrasound results were compared with chest radiographs obtained during the same period. Of the 22 patients, 16 had normal pulmonary venous flow profiles characterized by low-velocity laminar flow. Of this group 12 had persistent radiographic postoperative pulmonary edema that cleared in all by 4 months. Six patients with pulmonary venous obstruction were identified, the diagnosis being confirmed at catheterization or autopsy. The venous flow pattern in this group was uniformly high velocity and turbulent. It was possible to localize the site of obstruction in each case. Although pulmonary edema was present in each patient, the chest radiograph did not provide reliable information as to the exact site of obstruction. Combined two-dimensional and Doppler echocardiography is a useful adjunct in the postoperative evaluation of patients with total anomalous pulmonary venous connection.
The Risk of Menstrual Abnormalities after Tubal Sterilization
Authors: Herbert B. Peterson, Gary Jeng, Suzanne G. Folger, Susan A. Hillis, Polly A. Marchbanks, Lynne S. Wilcox
Journal: New England Journal of Medicine (2000)

The existence of a post–tubal-ligation syndrome of menstrual abnormalities has been debated for decades. We used data from the U.S. Collaborative Review of Sterilization to determine whether the likelihood of persistent menstrual abnormalities was greater among women who had undergone tubal sterilization than among women who had not.
Safeguarding children: a challenge to doctors
Authors: J. Thomas, S. Humphery
Journal: BMJ (2014)

Airway colonisation with Pseudomonads, especially <i>Pseudomonas aeruginosa</i>, is common in lung transplant (LTx) recipients. The current authors investigated whether pseudomonal colonisation affects the prevalence of bronchiolitis obliterans syndrome (BOS) after lung transplantation. In the present retrospective study, 92 double (SS)LTx recipients (26 cystic fibrosis (CF) and 66 non-CF patients), with at least two consecutive post-operative bronchoalveolar lavage or sputum cultures evaluated for Pseudomonads, were included. Freedom of BOS was investigated in post-operatively colonised and noncolonised patients. The current study has shown post-operative airway colonisation to be an independent risk factor for BOS stage ≥1 and to be associated with a worse BOS stage ≥1-free survival in univariate analysis, especially in CF SSLTx recipients. Multivariate analysis demonstrated a trend for colonisation only as an independent risk factor for BOS; however, this pointed to a possible role in the development of BOS. In conclusion, pseudomonal airway colonisation after lung transplantation may be associated with an increased prevalence of bronchiolitis obliterans syndrome, especially in cystic fibrosis patients. Possible pathophysiological mechanisms in the development of bronchiolitis obliterans syndrome need further investigation, although the induction of neutrophilic airway inflammation seems to be its main characteristic.
The structure of rhodopsin and mechanisms of visual adaptation
Authors: Rosalie K. Crouch, D. Wesley Corson
Journal: Behavioral and Brain Sciences (1995)

Abstract Rapidly advancing studies on rhodopsin have focused on new strategies for crystallization of this integral membrane protein for x-ray analysis and on alternative methods for structural determination from nuclear magnetic resonance data. Functional studies of the interactions between the apoprotein and its chromophore have clarified the role of the chromophore in deactivation of opsin and in photoactivation of the pigment.
Vertebrate Cone Opsins Enable Sustained and Highly Sensitive Rapid Control of G i/o Signaling in Anxiety Circuitry
Authors: Olivia A. Masseck, Katharina Spoida, Deniz Dalkara, Takashi Maejima, Johanna M. Rubelowski, Lutz Wallhorn, Evan S. Deneris, Stefan Herlitze
Journal: Neuron (2014)
Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.
Authors: N E Tawa, R Odessey, A L Goldberg
Journal: Journal of Clinical Investigation (1997)

Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P < 0.01), and this effect was rapidly reversed upon removal of the inhibitor. The peptide aldehydes did not alter protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P < 0.001). Similarly, the rise in muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.
Cascading and feedback in interactive models of production: A reflection of forward modeling?
Authors: Gary S. Dell
Journal: Behavioral and Brain Sciences (2013)

Abstract Interactive theories of lexical retrieval in language production assume that activation cascades from earlier to later processing levels, and feeds back in the reverse direction. This commentary invites Pickering &amp; Garrod (P&amp;G) to consider whether cascading and feedback can be seen as a form of forwarding modeling within a hierarchical production system.