tbuckley/cabot-search huggingface dataset:
If it doesn't work, stop it
Authors: Simon M Loader
Journal: BMJ (2004)

Editor—Alderson and Groves suggest that “what we don't know we don't know would be a good topic for a BMJ theme issue.”1 But, do you know what? It couldn't be done. For to write about what we don't know, we must surely know we don't know it first, otherwise how could it be an issue?

The only way it could work would be that those who know they don't know something, but think the rest of us don't know we don't know it, write about it so that the rest of us then also know we don't know it. Then everything in that issue will no longer be unknown unknowns, but known unknowns. Do you know what I mean?
The Mortality from Childhood Tuberculosis in Sheffield
Authors: J. Lorber
Journal: BMJ (1953)

The purpose of this paper is to describe the recent decline in tuberculosis mortality in children in Sheffield, to con- sider some of the factors probably responsible for that decline, and to compare the results in Sheffield with those obtained in Great Britain and her other major cities. Decline of Tuberculosis Mortality in Children SheffieldIn 1924, 82 Sheffield children under 15 years of age died of tuberculosis.In the next ten years the number of annual deaths was more than halved, and in 1934 they fell to 29.At this point the improvement was halted, and between 1934 and 1947 no significant reduc- tion occurred.The number of children who died of tuberculosis varied between 25 and 31 in the peace years, but rose higher in the war years and reached a peak of 39 in 1941.After 1947 there was a dramatic fall in the tuberculosis mortality in children.In 1948 and 1949, 18 chil- dren died each year, in 1950 12, in 1951 6, and in 1952 only 2 (Table I).The death rate per 100,000 children TABLE I.-Annutal Number of Deaths from Tubercuilosis in Children (0-14 years) in Sheffield, 1924-52 Year No. of
PULMONARY TUBERCULOSIS—ITS DIMINISHING PREVALENCE.
Authors: EDWARD F. WELLS
Journal: JAMA (1896)

In a paper presented, several months ago, to the Chicago Medical Society, I enunciated the proposition that pulmonary tuberculosis is declining in prevalence, and supported the assertion by some condensed statistical tables. The conclusions arrived at, although neither novel nor surprising, have met with no hearty acceptance. On the contrary, I have been informed that my deductions were extracted from an array of facts much too circumscribed; that a careful survey of a wider field would show other and differing premises; that my conclusions were misleading; that the prevalence of pulmonary tuberculosis has, in fact, undergone no decline. Recently I have tabulated statistics from a broader field, as suggested, with the result of confirming the opinion previously expressed. Readily accessible medical literature gives us very little information upon this subject. Weitemeyer<sup>1</sup>informs us that in Munich during the 75 years from 1814 to 1888, there were 329,862 deaths from
Consider underlying body dysmorphic disorder in users of melanotan
Authors: A. Affleck
Journal: British Journal of Dermatology (2009)

Journal Article Consider underlying body dysmorphic disorder in users of melanotan Get access A. Affleck A. Affleck Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: andrew.affleck@nhs.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 2, 1 February 2010, Pages 459–460, https://doi.org/10.1111/j.1365-2133.2009.09553.x Published: 01 February 2010
Health care in London. Playing with numbers.
Authors: M F Bush
Journal: BMJ (1993)

exploitation by the imperial powers than any population explosion.Today, as Third World countries become more marginalised in the world economy and less able to maintain debt repayments it is their desperation, poverty, and stagnation that determine their inclusion in the "developing" world.While the world economy leaves millions with no access to clean water or medical or food supplies and pays Western farmers to leave pro- ductive land fallow, Smith highlights the "evidence ... that many women are crying out for access to contraceptives."Population must be kept "on the agenda from the United Nations to the village council," but until the prevailing assumptions are replaced with critical scientific, social, and political investigation there will be no solutions.
Rights and responsibilities in HIV prevention
Authors: R. Danziger
Journal: BMJ (1996)

It is not necessary for Toozs-Hobson and Car- dozo to claim that the whole female population is diseased in order to recommend prophylaxis; we recommend supplementation with folic acid for women before conception and in the first trimester without believing that they all have a dietary deficiency.There may well be a very good argu- ment for all postmenopausal women to take hormone replacement therapy, based on evidence of a favourable ratio of benefits to risks.For the women who are being recommended lifelong hormone replacement therapy, convincing arguments of this sort will be more persuasive than labelling a universal life event as a disease.
P254 Investigating HMGB1 as a potential inflammatory mediator in brain death induced lung damage
Authors: A. E. Vallance, H. R. Walden, D. M. Karamanou, C. R. Fox, A. J. Rostron, J. A. Kirby, A. J. Simpson, J. H. Dark, A. J. Fisher
Journal: Thorax (2010)

<h3>Background</h3> Donor lungs are particularly susceptible to the haemodynamic instability and systemic inflammation which occurs following induction of brain death (BD). Increased donor lung inflammation with IL-6 or IL-8 is associated with poor post-transplant outcomes. Donor LPS pre-conditioning significantly ameliorates the lung inflammation after BD in a rat model suggesting that TLR-4 ligation following BD contributes to donor lung inflammation, even in the absence of LPS. We hypothesised that HMGB1, an alarmin released from damaged tissue and immune cells and known TLR-4 ligand, may act as an inflammatory mediator in BD induced lung injury. <h3>Methods</h3> BD was induced in a rat model using rapid intra-cranial balloon inflation and bronchoalveolar lavage (BAL), serum and lung tissue were collected and compared with sham operated controls rats. The HMGB1 concentration in the rat serum and BAL was measured by ELISA. Real-time PCR was used to assess HMGB1 mRNA expression in lung tissue following BD. HMGB1 immunolocalisation studies were performed on BD and sham rat lung tissue. Finally HMGB1 staining was assessed in lung tissue from human BD donors and normal controls. <h3>Results</h3> The BAL HMGB1 concentration was significantly higher in the BD group (965±302 ng/ml) than in the sham group (655 ± 274 ng/ml) (p=0.0172). There was however no difference in HMGB1 gene expression between the two groups. HMGB1 positive staining was visualised in a nuclear and extra-nuclear location and was dispersed throughout the rat and human lung with a greater density around the bronchioles. There was a significantly higher area of positive staining in BD rat lung tissue than sham tissue (p=0.0345). No difference was seen in the human BD lungs compared to controls (Abstract P254 Figure 1). <h3>Conclusions</h3> HMGB1 is likely to be released passively from lung cells suffering sustained damage during BD. As HMGB1 gene transcription is unchanged up to 5 h following BD, the lung tissue is most likely releasing presynthesised cellular HMGB1. This study provides evidence of the presence of an alarmin which is likely to potentiate inflammation in the donor lung <i>via</i> the TLR-4 pathway. If release occurs early following BD, HMGB1 could be an important initiating mediator in donor lung inflammation.
Pharmacokinetic significance of serum reverse T3 levels during amiodarone treatment: a potential method for monitoring chronic drug therapy.
Authors: K Nademanee, B N Singh, J A Hendrickson, A W Reed, S Melmed, J Hershman
Journal: Circulation (1982)

We studied the antiarrhythmic effects of amiodarone, 600-1400 mg/day, in 18 patients with refractory arrhythmias, and related to drug efficacy and side effects to serum levels of T4, reverse T3 (rT3) and the QTc interval. In the 11 patients with ventricular arrhythmias, premature complexes were reduced by 90-98%, and complex ectopy and runs of ventricular tachycardia were abolished; in the seven patients with paroxysmal atrial flutter, there were no recurrences on stable drug therapy. The QTc lengthened by 11.6% (p less than 0.01), T4 increased by 31.6-63.3% (p less than 0.001) and rT3 increased by 82.9-176.8% (p less than 0.001) as a function of dose and duration of amiodarone therapy. A close correlation was found between rT3 (normal up to 50 ng/dl) and drug efficacy and some of the drug side effects; arrhythmia suppression occurred at levels of 55-100 ng/dl, and some of the known side effects at levels of 100-110 ng/dl. When amiodarone was stopped in nine patients, the changes in QTc, T4 and rT3 regressed toward normal and arrhythmia recurred in eight 2-20 weeks (mean 7.4 weeks) and when rT3 levels fell below 55 ng/dl; arrhythmia resuppression was achieved 3-28 days (mean 11 days) after resumption of amiodarone therapy. The indirect therapeutic half-life of amiodarone in seven patients, computed from the semilogarithmic plots of plasma rT3 after cessation of amiodarone therapy, ranged from 25 to 55 days (mean 35 days). The data suggest that rT3 levels may be useful in monitoring the efficacy and certain side effects of amiodarone.
Binding of aromatic amines to the rat hepatic Ah receptor in vitro and in vivo and to the 8S and 4S estrogen receptor of rat uterus and rat liver.
Authors: P Cikryt, T Kaiser, M Göttlicher
Journal: Environmental Health Perspectives (1990)

Studies on structurally related aromatic amines with different carcinogenic properties have shown that 2-acetylaminofluorene (2-AAF) and 2-acetylaminophenanthrene (AAP) inhibit the binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin to the Ah receptor in vitro. The apparent inhibitor constants (Ki) are 2.3 microM for 2-AAF and 2.7 microM for AAP. In contrast, 4-acetylaminofluorene, an isomer of 2-AAF, and trans-4-acetylaminostilbene do not bind to the rat hepatic cytosolic Ah receptor. Pretreating female Wistar rats with 2-AAF or AAP leads to the induction of the P-450 isoenzymes that are under the control of the Ah receptor. Ornithine decarboxylase activity is induced by all aromatic amines tested irrespective of their Ah receptor affinity. The aromatic amines used as model compounds do not inhibit the binding of 17-beta-estradiol to the 8S and 4S estrogen receptor of rat uterus or rat liver in a competition assay analyzed using sucrose density gradient centrifugation. On the other hand, the aromatic amines bind to varying extents to another estrogen-binding protein of rat liver whose function and identity is still unknown. Our study demonstrates that structurally related aromatic amines in their unmetabolized form interact differentially with a cellular target protein, the Ah receptor, in vitro as well as in vivo. However, a relationship between these effects and the postulated promoting properties of 2-AAF remains to be established.
The effect of 60-Hz magnetic fields on co-promotion of chemically induced skin tumors on SENCAR mice: a discussion of three studies.
Authors: J R McLean, A Thansandote, D Lecuyer, M Goddard
Journal: Environmental Health Perspectives (1997)

Three independent experiments involving a total of 288 SENCAR mice were used to study the effects of 60-Hz magnetic fields on the growth and development of skin tumors. Given the constraints imposed by the experimental design, the results did not support a role for magnetic fields as a tumor co-promoter. This negative finding could also be interpreted to mean that the SENCAR mouse skin tumor model was not sensitive enough to detect the action of a weak co-promoter. The two-stage (initiation/promotion) model was used to assess the genotoxic potential of magnetic fields because it had been widely used to evaluate chemical carcinogens. This model, however, lacks the sensitivity to detect all but the most potent direct-acting carcinogens, and the tumor response to the action of low doses of promoter results in large random fluctuations in tumor incidence, yield, and multiplicity. The need to limit tumor incidence in the sham is a necessary condition to ensure that a magnetic field-induced effect on tumorigenesis would have a reasonable chance of being detected. This requirement, and the variability in tumor development between and within experiments, increases the level of uncertainty in the system and makes a weak response to the magnetic field difficult to detect and interpret.
Endomicroscopie confocale: Etude de faisabilité du système Cellvizio® GI (Mauna Kea Technologies)
Authors: C Pesenti, F Caillol, E Bories, G Monges, M Giovannini
Journal: Endoscopy (2008)

Objectif: L'endomicroscopie est l'adaptation en endoscopie digestive de la microscopie optique traditionnelle, grâce à l'intégration de microscopes miniaturisés permettant l'étude de la muqueuse digestive à l'échelon cellulaire. Il s'agit d'illuminer la muqueuse digestive préalablement marquée par une molécule fluorescente (la fluorescéine) à l'aide d'un laser argon, et de sélectionner les photons provenant du même plan focal, afin de créer une section optique de la zone étudiée. Nous avons évalué la faisabilité, la tolérance et l'efficacité de l'endomicroscopie confocale des mini-sondes du système Cellvizio® GI au cours d'endoscopies digestives hautes ou basses.
In vitro contractile effects of short chain fatty acids in the rat terminal ileum.
Authors: C Cherbut, A C Aube, H M Blottiere, P Pacaud, C Scarpignato, J P Galmiche
Journal: Gut (1996)

Short chain fatty acids (SCFAs), produced in the gut by bacterial fermentation of carbohydrates, change intestinal motility by mechanisms as yet unknown. This study examined the mechanism(s) of action of SCFAs on contractility using isolated rat terminal ileum segments and isolated ileal smooth muscle cells. Strip contractions were recorded under isometric conditions. Intracellular calcium concentration ([Ca2+]i) was measured in single cells loaded with indo-1 penta-acetoxymethyl ester (indo-1 AM). SCFAs (10(-9) to 10(-2) mol/l) induced concentration dependent contractions. The effect was not different among the individual SCFAs. Exogenous acids (namely tartaric and citric acids) caused similar responses as SCFAs, whereas sodium acetate had no effect. The contraction was not blocked by tetrodotoxin, atropine or hexamethonium, showing that it was not mediated through a cholinergic pathway. Moreover, removal of the mucosa or addition of procaine (a local anaesthetic) to the bath did not change the SCFA induced contraction, while verapamil (a calcium-channel antagonist) completely suppressed it. In addition, application of SCFAs to isolated ileal myocytes evoked peaks in [Ca2+]i inhibited by D 600 (a blocker of voltage dependent calcium channels). Taken together, these results suggest that the contractile response stimulated by SCFAs in the rat terminal ileum could result from an acid sensitive calcium dependent myogenic mechanism.
Ototoxicity caused by aminoglycosides
Authors: Maria Bitner-Glindzicz, Shamima Rahman
Journal: BMJ (2007)

Background: Since specific epidermal growth factor receptor (EGFR) somatic mutations have been demonstrated to influence the response to anti-EGFR therapy in non-small cell lung cancer, EGFR gene mutational analysis of different types of neoplasm is under investigation. Patients and Methods: EGFR protein expression and gene mutations in exons 18, 19 and 21 were investigated in 49 gastric adenocarcinomas. Results: no specific EGFR gene mutations were detected, while EGFR positive staining was detected in 6% of the cases. Conclusion: Our findings indicate that in gastric adenocarcinoma, specific EGFR gene mutations are very rare or absent and the rate of EGFR protein expression is low.
The Computer-Stored Medical Record
Authors: Clement J. McDonald
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Two diametrically opposite approaches are being marketed to solve hospitals' information-processing problems.<sup>1,2</sup>The first follows a centralized model where all processing software is purchased from a single vendor. The other follows a distributed model and interconnects the independent systems, eg, laboratory, pharmacy, and order entry systems, systems that might already exist in a hospital. We argued that the fastest way for most hospitals to create an automated hospital record system is to draw on the data that already exist, including those stored in independent laboratory and pharmacy systems when they are present. However, we were describing current opportunities, not arguing for a future reality. Whether the centralized or distributed model will be predominant in the future is not a question to argue in a learned journal; it is a question the marketplace will decide. We accept that Drs Korpman and Lincoln's persuasive arguments for a centralized,
Looking forward - what will EUS be doing in 10 years?
Authors: R. Hawes
Journal: Endoscopy (2006)

It is easy to speculate where a procedure will be in ten years time but the accuracy of such a prediction is always uncertain. It is however, an important mental exercise to consider because training and practice patterns need to evolve in parallel with the procedure and technology. In order to try to predict where EUS will be in ten years time, one needs to consider the strengths and weaknesses of EUS as well as contemplate where gastrointestinal endoscopy in general is moving. Finally, one must consider how competing technologies will evolve over the next decade.
Prevalence of antibody to human T cell leukaemia/lymphoma virus in women attending antenatal clinic in southeast London: retrospective study
Authors: M. Donati
Journal: BMJ (2000)

Infection with human T cell leukaemia/lymphoma virus (HTLV) type I occurs mainly in Japan, central and west Africa, and the Caribbean basin.Infection confers a lifetime risk of 2-4% for adult T cell leukaemia or lymphoma and 0.2-5% for tropical spastic paraparesis.However, the incubation period for these conditions after naturally acquired infection may be several decades. 1 The virus is transmitted via infected lymphocytes, and in areas of high prevalence breast feeding is an important route of transmission, particularly if continued for over six months. 2e determined the prevalence of HTLV antibody in women who had attended antenatal clinics at King's Healthcare NHS Trust, southeast London, to assess whether antenatal screening should be considered locally.
Characterization of chronic myeloid leukemia stem cells
Authors: Jonathan M. Gerber, Lu Qin, Jeanne Kowalski, B. Douglas Smith, Constance A. Griffin, Milada S. Vala, Michael I. Collector, Brandy Perkins, Marianna Zahurak, William Matsui, Christopher D. Gocke, Saul J. Sharkis, Hyam I. Levitsky, Richard J. Jones
Journal: American Journal of Hematology (2010)

Although tyrosine kinase inhibitors have redefined the care of chronic myeloid leukemia (CML), these agents have not proved curative, likely due to resistance of the leukemia stem cells (LSC). While a number of potential therapeutic targets have emerged in CML, their expression in the LSC remains largely unknown. We therefore isolated subsets of CD34(+) stem/progenitor cells from normal donors and from patients with chronic phase or blast crisis CML. These cell subsets were then characterized based on ability to engraft immunodeficient mice and expression of candidate therapeutic targets. The CD34(+)CD38(-) CML cell population with high aldehyde dehydrogenase (ALDH) activity was the most enriched for immunodeficient mouse engrafting capacity. The putative targets: PROTEINASE 3, SURVIVIN, and hTERT were expressed only at relatively low levels by the CD34(+)CD38(-)ALDH(high) CML cells, similar to the normal CD34(+)CD38(-)ALDH(high) cells and less than in the total CML CD34(+) cells. In fact, the highest expression of these antigens was in normal, unfractionated CD34(+) cells. In contrast, PRAME and WT1 were more highly expressed by all CML CD34(+) subsets than their normal counterparts. Thus, ALDH activity appears to enrich for CML stem cells, which display an expression profile that is distinct from normal stem/progenitor cells and even the CML progenitors. Indeed, expression of a putative target by the total CD34(+) population in CML does not guarantee expression by the LSC. These expression patterns suggest that PROTEINASE 3, SURVIVIN, and hTERT are not optimal therapeutic targets in CML stem cells; whereas PRAME and WT1 seem promising.
Placing Trials in Context Using Bayesian Analysis
Authors: James M. Brophy
Journal: JAMA (1995)

Standard statistical analyses of randomized clinical trials fail to provide a direct assessment of which treatment is superior or the probability of a clinically meaningful difference. A Bayesian analysis permits the calculation of the probability that a treatment is superior based on the observed data and prior beliefs. The subjectivity of prior beliefs in the Bayesian approach is not a liability, but rather explicitly allows different opinions to be formally expressed and evaluated. The usefulness of this approach is demonstrated using the results of the recent GUSTO study of various thrombolytic strategies in acute myocardial infarction. This analysis suggests that the clinical superiority of tissue-type plasminogen activator over streptokinase remains uncertain.
The Saikewicz Decision
Authors: William J. Curran
Journal: New England Journal of Medicine (1978)

AFTER a delay of some 16 months, the Massachusetts Supreme Judicial Court has issued a full opinion concerning life-death decisions on patients.1 The decision has caused great consternation among Massachusetts physicians and hospitals. Physicians involved in intensive care of infants and adults alike, physicians in burn centers and physicians and hospitals caring for terminally ill patients are frankly reacting in disbelief at the news reports about the case; lawyers representing medical clients waited to read the decision and, after reading it, could only respond that the news reports were correct. The Court really did mean that all decisions on either . . .