tbuckley/cabot-search huggingface dataset:
The Bristol third stage trial: active versus physiological management of third stage of labour.
Authors: W. J. Prendiville, J. E. Harding, D. R. Elbourne, G. M. Stirrat
Journal: BMJ (1988)

OBJECTIVE--To compare the effects on fetal and maternal morbidity of routine active management of third stage of labour and expectant (physiological) management, in particular to determine whether active management reduced incidence of postpartum haemorrhage. DESIGN--Randomised trial of active versus physiological management. Women entered trial on admission to labour ward with allocation revealed just before vaginal delivery. Five months into trial high rate of postpartum haemorrhage in physiological group (16.5% v 3.8%) prompted modification of protocol to exclude more women and allow those allocated to physiological group who needed some active management to be switched to fully active management. Sample size of 3900 was planned, but even after protocol modification a planned interim analysis after first 1500 deliveries showed continuing high postpartum haemorrhage rate in physiological group and study was stopped. SETTING--Maternity hospital. PARTICIPANTS--Of 4709 women delivered from 1 January 1986 to 31 January 1987, 1695 were admitted to trial and allocated randomly to physiological (849) or active (846) management. Reasons for exclusion were: refusal, antepartum haemorrhage, cardiac disease, breech presentation, multiple pregnancy, intrauterine death, and, after May 1986, ritodrine given two hours before delivery, anticoagulant treatment, and any condition needing a particular management of third stage. INTERVENTIONS--All but six women allocated to active management actually received it, having prophylactic oxytocic, cord clamping before placental delivery, and cord traction; whereas just under half those allocated to physiological management achieved it. A fifth of physiological group received prophylactic oxytocic, two fifths underwent cord traction and just over half clamping of the cord before placental delivery. ENDPOINT--Reduction in incidence of postpartum haemorrhage from 7.5% under physiological management to 5.0% under active management. MEASUREMENTS AND MAIN RESULTS--Incidence of postpartum haemorrhage was 5.9% in active management group and 17.9% in physiological group (odds ratio 3.13; 95% confidence interval 2.3 to 4.2), a contrast reflected in other indices of blood loss. In physiological group third stage was longer (median 15 min v 5 min) and more women needed therapeutic oxytocics (29.7% v 6.4%). Apgar scores at one and five minutes and incidence of neonatal respiratory problems were not significantly different between groups. Babies in physiological group weighed mean of 85 g more than those in active group. When women allocated to and receiving active management (840) were compared with those who actually received physiological management (403) active management still produced lower rate of postpartum haemorrhage (odds ratio 2.4;95% CI1.6 to 3.7). CONCLUSIONS--Policy of active management practised in this trial reduces incidence of postpartum haemorrhage, shortens third stage, and results in reduced neonatal packed cell volume.
John Vernon Thurston
Authors: A. Thurston
Journal: BMJ (2011)

John Vernon Thurston was born in London in 1923, and was educated at Falconbury Preparatory School in Bexhill, and Haileybury College in Hertford. He went on to St Mary’s Medical School and qualified in 1945. After two years’ service in the Royal Air Force, he undertook various GP assistant posts before travelling out to Trinidad in 1950 to work as medical officer for the Shell oil company. He returned to the …
Cycle injury trends: helmets are most likely explanation
Authors: A. Cook
Journal: BMJ (2001)

EDITOR—We studied national trends in hospital admissions among English cyclists during 1991–5 and found significant reductions in admissions of cyclists with head injury.1 Data from annual surveys of cycle helmet usage during this period indicate that the proportion of children always wearing a helmet increased from 3% in 1991 to 20% in 1995,2 this last figure corresponding well with the 16% of cyclists observed wearing a helmet in a separate large survey in …
Abdominal Tuberculosis: Peritoneal Involvement Shown by F-18 FDG PET
Authors: Hiroaki Shimamoto, Kenichiro Hamada, Ichiro Higuchi, Masao Tsujihata, Norio Nonomura, Yasuhiko Tomita, Akihiko Okuyama, Katsuyuki Aozasa, Jun Hatazawa
Journal: Clinical Nuclear Medicine (2007)

We present a case of a right renal tumor associated with increased accumulation of F-18 FDG in the peritoneum and ileocecum on PET imaging. The FDG-PET images suggested peritoneal carcinomatosis, but the histopathology of the open biopsy proved tuberculous peritonitis. Tuberculous peritonitis should be considered as a potential interpretive pitfall in mimicking peritoneal carcinomatosis.
Israel prepares for "Jerusalem syndrome"
Authors: J. Siegel-Itzkovich
Journal: BMJ (1999)

<h3>Background and aims</h3> To examine the ethical, legal, and social implications (ELSI) of microdosing in exploratory paediatric research where there is exposure to background radiation and no therapeutic benefit to participants. <h3>Methods</h3> The ethical and regulatory issues encountered in the ERA-NET PRIOMEDCHILD project ‘Paediatric Accelerator Mass Spectrometry Evaluation Research Study (PAMPER)’ were analysed. These included the project design, scientific and ethical reviews, informed consent and recruitment processes. Infants 0–2 years were recruited in Estonia and the UK to study the pharmacokinetics (PK) of acetaminophen using accelerator mass spectrometry (AMS) bioanalysis. The study was considered in the context of the scientific, regulatory, and ethical frameworks guiding Phase 0 studies in adults and children. <h3>Results</h3> The science and ethics were developed in the protocol design and informed consent process, which resulted in approval of the study by research ethics committees in the UK and Estonia. Fifty-two babies were recruited into the study, with an acceptance rate of 50% among the parents approached. The study results demonstrated PK comparability between microdosing and therapeutic dosing in young children. <h3>Conclusions</h3> The PAMPER study showed the feasibility and validity of microdosing AMS PK studies in children, This methodology may provide a safer and more ethically robust approach for paediatric PK studies in certain drug models than more traditional PK study designs. The parameters and validation methods for microdosing AMS PK studies need to be reflected in regulatory guidance from the EMA, FDA and other authorities.
Victory Over Pain: Morton's Discovery of Anaesthesia
Authors: Lester S. King
Journal: JAMA (1971)

The discovery of ether as an anesthetic was an extraordinary event in medical history and one of the great turning points in the development of medicine. In this chain of events the story of William Morton is dramatic indeed. MacQuitty, aiming at a popular audience, tells the story well, in a colorful, sometimes even flamboyant style. The author contributes no new scholarship and, although she presents a substantial bibliography, relies heavily on a relatively few key sources. Various controversial features, such as Morton's search for recompense, the thorny relationships with Jackson, or the claims of Wells and Long, are treated in a somewhat partisan manner. Nevertheless, the book, in a highly readable fashion, successfully offers a dramatic narrative set against an interesting background.
Station interviews: all change?
Authors: Philip E M Smith
Journal: BMJ (2005)

I n the late 1980s it took me 10 interviews to obtain a senior registrar post in neurology. In each interview I was called before a committee and asked in a fairly unstructured way about my previous jobs, research, audit and management skills, and interests outside medicine. The panel then chose the candidate who had interviewed the best—or, more likely, the candidate who despite the interview had remained the first choice from various pre-interview discussions, recommendations, and references. A sweaty hour with fellow interviewees would end with a door being opened, the lucky name being called, and the remainder of the group hearing how close it had been and how any of us might on another day have been appointed.

Whether such a process led to the appointment of the person who could actually do the job was never questioned. The limited data available indicate that it may not have done, since clinical performance actually …
THE TREATMENT OF MALIGNANT GROWTHS BY THE ROENTGEN RAYS.
Authors: ENNION G. WILLIAMS
Journal: JAMA (1907)

In the field of Roentgen ray therapy we are still a band of pioneers endeavoring to discover the possibilities of this new and mysterious agent. Its first decade has been productive of much new and valuable knowledge concerning the therapy of those diseased conditions which have heretofore proven most obstinate to all forms of treatment. We should be slow to condemn the ray because it has not fulfilled the expectations of the early enthusiasts, or because the results and observations of different operators have varied so greatly. It is only natural that the results should differ when we consider how great are the variations in the agent itself and the methods of application. What it has undoubtedly accomplished should be our standard and the beacon light to guide us in establishing its real value. To determine the value of the ray as a therapeutic agent we have to consider, first,
Tolbutamide in Treatment of Multiple Sclerosis and Parkinsonism
Authors: Hubert C. Peltier
Journal: JAMA (1961)

<h3>To the Editor:—</h3> Since tolbutamide has attained widespread use in the treatment of diabetes, there have been several reports of its use in unrelated disorders, including schizophrenia, acne, angina pectoris, intermittent claudication, paralysis agitans, and, most recently, multiple sclerosis. The possibility that the drug might be of value in these conditions was usually suggested initially by improvement in the condition of patients who had a combination of diabetes and one of the above diseases. However, it should be noted that therapy in all of these diseases has been notoriously difficult to evaluate in the past either because of their variable course, characterized by remissions and exacerbations or because of a pronounced placebo effect. Confirmatory reports have not been forthcoming, and other investigators working in several of the above areas have not been impressed by the value of the drug. The occasional value of serendipity in medical discoveries cannot be denied.
THE EFFECT OF IODIDE ON THE RATE OF RELEASE OF I131 FROM AUTONOMOUS THYROID NODULES*
Authors: William L. Green, Sidney H. Ingbar
Journal: Journal of Clinical Investigation (1962)

1 Although a portion of the I" lost from the thyroid under these conditions actually escapes in the form of inorganic iodide (1, 2), this iodide almost certainly is drawn from organic sources, arising from the deiodina- tion of free iodotyrosines (3).2 This function has often been called the "hormonal release rate."While this term has the advantage of
Abstract 4545: Identifying neuroblastoma-specific ligands for cancer targeted therapy using a one-bead one-compound combinatorial approach.
Authors: Andy Iskandar, Connie Duong, Cathy Chen, Eduardo Sanchez, David Olivos, Kit Lam, Noriko Satake
Journal: Cancer Research (2013)

Abstract Neuroblastoma is the most common extra-cranial tumor in children, with around 700 new diagnoses each year. High-risk patients have poor outcomes and only 30% survive despite the most intensive therapies available, which can also harm healthy cells. Thus, we are developing novel targeted therapies for neuroblastoma to increase treatment efficacy and limit damage to healthy cells. We utilized the One-Bead One-Compound (OBOC) combinatorial split-mix method developed by Kit Lam (Lam et al., 1991) to identify unique ligands against neuroblastoma cells for therapeutic delivery. The OBOC libraries consist of hundreds to millions of 90 μm Tentagel beads, and each bead displays 1013 copies of a peptide on its surface. Thus, each bead has one unique compound on its exterior. Twelve random OBOC libraries with varying peptide lengths (5 to 16 amino acids) were screened against three human neuroblastoma cell lines (SK-N-BE, SK-N-DZ, and IMR-32) to determine a library for more stringent screening of ligands. 37,500 beads from each library were screened against each cell line and the libraries averaged 2 positive candidates per 18,750 beads within 2 hours of incubation. The results also suggested preference for longer peptide libraries, but an intermediate length random decamer library was chosen for further screening due to both a good yield of positive beads and convenient sequencing. Each neuroblastoma line was screened against 150,000 beads from the decamer library to identify potential ligands. Positive beads were selected, retested three times, and decoded using Edman degradation. Several cancer cell lines (A549 lung cancer, and Reh and Jurkat leukemia cell lines) were used as negative controls. Ten beads per cell line displaying high binding affinity were selected. Candidate beads with positive binding to all three neuroblastoma cell lines are currently being sequenced and the ligands will be synthesized. We plan to characterize the ligands for high affinity and specificity, as well as internalization capacity, and to identify their receptors. Currently, there are very few targeted therapies for neuroblastoma. We believe our ligand discoveries can be developed for future novel targeted therapies in neuroblastoma. Citation Format: Andy Iskandar, Connie Duong, Cathy Chen, Eduardo Sanchez, David Olivos, Kit Lam, Noriko Satake. Identifying neuroblastoma-specific ligands for cancer targeted therapy using a one-bead one-compound combinatorial approach. [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 4545. doi:10.1158/1538-7445.AM2013-4545
Mechanisms of Death in the CABG Patch Trial
Authors: J. Thomas Bigger, William Whang, Jeffrey N. Rottman, Robert E. Kleiger, Charles D. Gottlieb, Pearila B. Namerow, Richard C. Steinman, N. A. Mark Estes
Journal: Circulation (1999)

Background —The CABG Patch trial compared prophylactic implantable cardiac-defibrillator (ICD) implantation with no antiarrhythmic therapy in coronary bypass surgery patients who had a left ventricular ejection fraction &lt;0.36 and an abnormal signal-averaged ECG. There were 102 deaths among the 446 ICD group patients and 96 deaths among the 454 control group patients, a hazard ratio of 1.07 ( P =0.63). The mechanisms of death were classified, and hypotheses were tested about the effects of ICD therapy on arrhythmic and nonarrhythmic cardiac deaths in the CABG Patch Trial and the Multicenter Automatic Defibrillator Implantation Trial (MADIT). Methods and Results —The 198 deaths in the trial were reviewed by an independent Events Committee and classified by the method of Hinkle and Thaler. Only 54 deaths (27%) occurred out of hospital; 145 deaths (73%) were witnessed. Seventy-nine (82%) of the 96 deaths in the control group and 76 (75%) of the 102 deaths in the ICD group were due to cardiac causes. Cumulative arrhythmic mortality at 42 months was 6.9% in the control group and 4.0% in the ICD group ( P =0.057). Cumulative nonarrhythmic cardiac mortality at 42 months was 12.4% in the control group and 13.0% in the ICD group ( P =0.275). Death due to pump failure was significantly associated with death &gt;1 hour from the onset of symptoms, dyspnea within 7 days of death, and overt heart failure within 7 days of death. Conclusions —In the CABG Patch Trial, ICD therapy reduced arrhythmic death 45% without significant effect on nonarrhythmic deaths. Because 71% of the deaths were nonarrhythmic, total mortality was not significantly reduced.
To market, to market
Authors: F. Davidoff
Journal: BMJ (1996)

Let's face it, LaPorte and Hibbitts are talking marketplaces—not science, not intellectual freedom. Leave aside their blithe assumptions that the Beatles are “dismayed” over Michael Jackson's ownership of most of their songs; that this is an “artistic tragedy.” (The Beatles may be creative, but they're not dumb; it's just possible that they decided to take their billions in lump sums, and leave behind the hassles of dealing with copyright lawyers.) No, LaPorte and Hibbitts' real concern is with middlemen—a fantasy of Blue Meenie publishers, bloated with money (their words: “[societies] derive considerable revenue from the publication of biomedical journals”) and obsessed with power (their words: “journals have monopolised scientific communication”) who control not only the intellectual lives but also the livelihood of scientists.

Shades of the 1960s! Can it be an accident that their broadside is interlarded …
Reanalysis of alteplase for stroke stirs controversy
Authors: Jeanne Lenzer
Journal: BMJ (2004)

An independent panel, appointed by a leading US institute to reanalyse the data regarding stroke treatment, has published its findings which they say support the use of thrombolytic agent alteplase (tPA, also known as rt-PA) “to treat patients with acute ischaemic stroke within three hours of onset under the NINDS [National Institute of Neurological Disorders and Stroke] tPA trial protocol.”

Data was reanalysed after an article in the BMJ (2002;324:723-9) sparked off controversy. The original study data reviewed by the panel was published in the New England Journal of Medicine more than nine years ago (1995;333:1581-7).

Critics take issue, however, with the printed conclusions of the analysis published in this month's issue of Stroke (2004;35:2418-24).

Jerome Hoffman, professor of medicine and emergency medicine at the University of California in Los Angeles and a leading critic of calls for widespread use of thrombolysis for stroke, …
Systemic Sclerosis after Augmentation Mammoplasty with Silicone Implants
Authors: J Varga, H R Schumacher, S A Jimenez
Journal: Annals of Internal Medicine (1989)

We describe four women who presented with systemic sclerosis several years after cosmetic augmentation mammoplasty with silicone-gel implants. The interval between implantation mammoplasty and the onset of systemic sclerosis ranged from 6 to 15 years. All patients fulfilled the criteria established by the American Rheumatism Association for systemic sclerosis and had Raynaud phenomenon, arthralgia, and evidence of pulmonary or gastrointestinal involvement. Enlargement of lymph nodes draining the prostheses was noted in two patients. Antinuclear antibodies were detected in three patients and showed speckled or nucleolar patterns. Removal of the prostheses in two cases did not result in improvement of systemic sclerosis. Evidence of silicone leakage from the implants included the following: The observation by light microscopy of refractile particles in tissues distant from the prostheses, the observation by electron microscopy of electron-dense structures consistent with silica, and the definitive identification of the element silicon by energy-dispersive analysis in these electron-dense structures. A marked, chronic inflammatory infiltrate containing lymphocytes, "foamy" histiocytes, and larger numbers of multi-nucleated giant cells with vacuoles and asteroid bodies was found at the same sites. Our demonstration that silicone escapes from elastomer-silicone-gel breast implants and appears to be closely associated with a chronic inflammatory reaction suggests that silicone plays a role in the development of certain cases of systemic sclerosis.
Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers
Authors: Benjamin G Bitler, Katherine M Aird, Azat Garipov, Hua Li, Michael Amatangelo, Andrew V Kossenkov, David C Schultz, Qin Liu, Ie-Ming Shih, Jose R Conejo-Garcia, David W Speicher, Rugang Zhang
Journal: Nature Medicine (2015)
Long-Term Exposure to Environmental Concentrations of the Pharmaceutical Ethynylestradiol Causes Reproductive Failure in Fish
Authors: Jon P. Nash, David E. Kime, Leo T. M. Van der Ven, Piet W. Wester, François Brion, Gerd Maack, Petra Stahlschmidt-Allner, Charles R. Tyler
Journal: Environmental Health Perspectives (2004)

Heightened concern over endocrine-disrupting chemicals is driven by the hypothesis that they could reduce reproductive success and affect wildlife populations, but there is little evidence for this expectation. The pharmaceutical ethynylestradiol (EE2) is a potent endocrine modulator and is present in the aquatic environment at biologically active concentrations. To investigate impacts on reproductive success and mechanisms of disruption, we exposed breeding populations (n = 12) of zebrafish (Danio rerio) over multiple generations to environmentally relevant concentrations of EE2. Life-long exposure to 5 ng/L EE2 in the F1 generation caused a 56% reduction in fecundity and complete population failure with no fertilization. Conversely, the same level of exposure for up to 40 days in mature adults in the parental F0 generation had no impact on reproductive success. Infertility in the F1 generation after life-long exposure to 5 ng/L EE2 was due to disturbed sexual differentiation, with males having no functional testes and either undifferentiated or intersex gonads. These F1 males also showed a reduced vitellogenic response when compared with F0 males, indicating an acclimation to EE2 exposure. Depuration studies found only a partial recovery in reproductive capacity after 5 months. Significantly, even though the F1 males lacked functional testes, they showed male-pattern reproductive behavior, inducing the spawning act and competing with healthy males to disrupt fertilization. Endocrine disruption is therefore likely to affect breeding dynamics and reproductive success in group-spawning fish. Our findings raise major concerns about the population-level impacts for wildlife of long-term exposure to low concentrations of estrogenic endocrine disruptors.
"Citizens' jury" disagrees over whether screening leaflet should put reassurance before accuracy
Authors: N. Hawkes
Journal: BMJ (2012)

A “citizens’ jury” of 25 women, assembled this week to provide advice for the drafting of a new leaflet on breast cancer screening, has reached consensus on some of the tricky issues.

The leaflet is being rewritten after criticism that it conveyed a falsely optimistic message and in the light of the Marmot review of breast cancer screening, which found that women invited to mammographic screening were three times as likely to be “overdiagnosed” as they were to have their lives saved.1

The jury did not draft a new leaflet or the covering invitation letter that will accompany it but did consider some of the central issues to be considered by those who will draft them. For example, the jury preferred the term “overtreatment” to “overdiagnosis” by a majority of 21 to four, on the grounds that it was easier to understand, and also preferred expressing benefits in terms of lives saved rather than deaths avoided, though by a smaller majority.

One juror said that lives saved set a more upbeat message than deaths avoided. Put to the vote, 13 women favoured lives saved and three preferred …
SIRT1 Deacetylase in SF1 Neurons Protects against Metabolic Imbalance
Authors: Giorgio Ramadori, Teppei Fujikawa, Jason Anderson, Eric D. Berglund, Renata Frazao, Shaday Michán, Claudia R. Vianna, David A. Sinclair, Carol F. Elias, Roberto Coppari
Journal: Cell Metabolism (2011)