tbuckley/cabot-search huggingface dataset:
Major and Minor Tranquilizers
Authors: Frank M. Berger
Journal: JAMA (1965)

<h3>To the Editor:—</h3> The 1965 edition of "<i>New Drugs</i>" classifies tranquilizers as "minor" and "major." This division appears to me unfortunate because it seems to imply that these drugs may be of value in the treatment of the same conditions and differ from each other only in the intensity of effect they produce. It is well known that tranquilizers useful in the treatment of psychoneurotic conditions are ineffective in the treatment of the major symptoms of psychosis, while the so-called major tranquilizers often are effective in the relief of psychotic symptoms but of little or no value in psychoneurotic and psychosomatic conditions. The division of tranquilizers into "minor" and "major" also implies that psychoneurotic conditions are milder than psychotic states. This is not necessarily the case. A severe psychoneurotic may be more severely ill than a psychotic and may require hospitalization while an ambulatory schizophrenic may be socially well adjusted
An Integrated Hypothesis That Considers Drusen as Biomarkers of Immune-Mediated Processes at the RPE-Bruch's Membrane Interface in Aging and Age-Related Macular Degeneration
Authors: Gregory S. Hageman, Phil J. Luthert, N.H. Victor Chong, Lincoln V. Johnson, Don H. Anderson, Robert F. Mullins
Journal: Progress in Retinal and Eye Research (2001)
T-type Ca2+ signalling regulates aldosterone-induced CREB activation and cell death through PP2A activation in neonatal cardiomyocytes
Authors: Laurent Ferron, Yann Ruchon, Jean-François Renaud, Véronique Capuano
Journal: Cardiovascular Research (2010)

We have investigated Ca2+ signalling generated by aldosterone-induced T-type current (ICaT), the effects of ICaT in neonatal cardiomyocytes, and a putative role for ICaT in cardiomyocytes during cardiac pathology induced by stenosis in an adult rat. Neonatal rat cardiomyocytes treated with aldosterone showed an increase in ICaT density, principally due to the upregulation of the T-type channel Cav3.1 (by 80%). Aldosterone activated cAMP-response element-binding protein (CREB), and this activation was enhanced by blocking ICaT or by inhibiting protein phosphatase 2A (PP2A) activity. Aldosterone induced PP2A activity, an induction that was prevented upon ICaT blockade. ICaT exerted a negative feedback regulation on the transcription of the Cav3.1 gene, and the activation of PP2A by ICaT led to increased levels of the pro-apoptotic markers caspase 9 and Bcl-xS and decreased levels of the anti-apoptotic marker Bcl-2. These findings were corroborated by flow cytometry analysis for apoptosis and necrosis. Similarly, in a rat model of cardiac disease, ICaT re-emergence was associated with a decrease in CREB activation and was correlated with increases in caspase 9 and Bcl-xS and a decrease in Bcl-2 levels. Our findings establish PP2A/CREB as targets of ICaT-generated Ca2+ signalling and identify an important role for ICaT in cardiomyocyte cell death.
Selective Constraints on Codon Usage of Nuclear Genes from Arabidopsis thaliana
Authors: B. R. Morton, S. I. Wright
Journal: Molecular Biology and Evolution (2006)

Highly expressed nuclear genes from Arabidopsis thaliana show an increased frequency of codons that match abundant tRNAs, and it has been suggested that this reflects a selective pressure to increase translation efficiency. Here we explore the possibility that the difference in codon usage between highly expressed genes and other Arabidopsis genes is not the result of selection but, rather, arises from mutation biases. Specifically, we explore the possibility that an influence of transcription level on mutational properties coupled with a context dependency of mutations, both of which have been observed in various organisms, contribute to variation in codon-usage bias across genes. Using noncoding sites immediately flanking both high- and low-expression-coding sequences to infer context-dependent composition biases, we analyze codon-usage bias across genes. The data show that mutation bias cannot explain codon usage of high-expression genes in Arabidopsis and, surprisingly, also indicate that even low-expression genes are under selective constraints. In addition, the data indicate that the general preference for certain codons is context dependent; the composition of the 3' nucleotide, that is, the first position of the next codon, is correlated with what codon is found at an increased frequency in highly expressed genes. This context dependency indicates that selective pressure on codon usage is more complex than previously thought. Overall, the study supports previous suggestions that selection plays a significant role in determining codon usage of nuclear genes in A. thaliana.
A Guide to Medical Publishing and Writing
Authors: Marios C Papadopoulos
Journal: Journal of the Royal Society of Medicine (2002)

Medical schools do not teach much on the processes of medical writing and publishing. Newly qualified doctors, whatever their specialty, soon discover that a poorly presented curriculum vitae can lose them the job they want. Most senior house officers and registrars must also generate peer-reviewed publications if they are to progress in their chosen specialties. The most important thing when writing a book about medical publishing and writing is to avoid dullness. Peter Richardson and his contributors have succeeded in this respect. The major strengths of his Guide are that it is short and easy to read. Despite being small enough to fit in a pocket to be read on a train, it contains contributions from 14 experts and covers a wide variety of topics such as scientific papers, case reports and books. I liked the way key points are highlighted at the end of each chapter, with references for further reading. Some relevant topics are not covered. A chapter on how to write a research grant application would have been welcome. Also a chapter on journal impact factors would have been useful to explain what they are, their advantages and disadvantages. The downside of including more chapters, however, is an increase in size.

No book, of course, can convey the full art of writing research papers, case reports, peer reviews, critical letters and so on. There is a useful parallel here with surgery: one will not learn how to perform an operation just by reading about it. The best way to start is under the guidance of somebody more experienced.
Prevalence of urinary and faecal incontinence in hospitals and residential and nursing homes for older people
Authors: S M Peet, C M Castleden, C W McGrother
Journal: BMJ (1995)

Studies of older people in long term care have shown that urinary and faecal incontinence are more prevalent in this group than among older people in the community.1 2 3 However, data describing the size of the problem in all types of long term care are lacking. We determined the prevalence of incontinence to assess the use of aids among older people in long term care.

In November 1990 a census of all people aged 65 years and over in long term care was carried out in Leicestershire.4 Data were collected on health, dependency, and the use of continence aids. Residents experiencing at least one incontinent episode weekly were defined as being incontinent …
Terminal Transferase Activity and Lymphoblastic Neoplasms
Authors: Sharon Murphy, Elaine S. Jaffe
Journal: New England Journal of Medicine (1984)

Terminal deoxynucleotidyl transferase (TdT), an enzyme normally present in the human thymus and in a subpopulation of marrow cells, has the unique ability to catalyze the addition of deoxynucleoside triphosphates onto the single-strand, free end of DNA in a template-independent fashion.1 The presence of TdT within the lymphoblasts of a child with acute lymphoblastic leukemia was first noted 10 years ago.2 Since then, the detection of TdT has become a conventional laboratory aid to morphologic studies for the classification of leukemia, the enzyme being present in nearly every case of acute lymphoblastic leukemia examined.1 , 3 , 4 Several years ago, Donlon and co-workers . . .
Do selective serotonin reuptake inhibitors cause suicide?: Risk of suicide should be assessed for whole class of antidepressants
Authors: François Curtin, Pierre Schulz
Journal: BMJ (2005)

Do selective serotonin reuptake inhibitors cause suicide? Risk of suicide should be assessed for whole class of antidepressantsEditor-Gunnell et al's report on suicide risk with selective serotonin reuptake inhibitors (SSRIs) raises several issues. 1 Firstly, clinicians have observed that the first weeks of treatment of severe depression with an antidepressant are accompanied by a higher risk of suicide because of a drug induced motor disinhibition that is not yet accompanied by mood improvement. 2 Secondly, the authors' finding of a trend towards a protective effect of SSRIs against suicidal thoughts (odds ratio 0.77) compared with a trend towards an increased risk of self harm (odds ratio 1.57) is paradoxical.More surprising is the heterogeneity of results among SSRIs.Why would sertraline show a protective effect for suicidal thoughts and simultaneously increase the risk of self harm?The risk difference between citalopram and its active S-enantiomere, escitalopram, is also strange.No strong biological rationale can explain such heterogeneity among drugs with the same mechanism of action.Thirdly, the authors mention that the Medicine and Healthcare products Regulatory Agency found little evidence for a risk difference between SSRIs and the other antidepressants.The two accompanying papers show that the suicidal risk seems similar for serotoninergic and tricyclic antidepressants. 3 4The risk of suicide must be assessed for the whole class of antidepressants.The next stage would be to measure the risk of suicide according to the time since starting an antidepressant.Initially, the risks are higher than the benefits.To confirm old clinical observations by evidence based methods would be interesting and useful.
A Response to Commentators on “Universal and Uniform Protections of Human Subjects in Research”
Authors: Adil E. Shamoo, Jack Schwartz
Journal: The American Journal of Bioethics (2008)

We thank the commentators for their thoughtful and very useful comments. We agree with many of them. Our intention in writing the article, however, was not to address all issues of concern about the system of human subjects’ protections in research but rather to emphasize an important shortfall in the scope of the current system and suggest a remedy for this problem. More specifically, we would like to respond and comment on the following:
Impact of C-Reactive Protein Kinetics on Survival of Patients with Metastatic Renal Cell Carcinoma
Authors: Kazutaka Saito, Manabu Tatokoro, Yasuhisa Fujii, Yasumasa Iimura, Fumitaka Koga, Satoru Kawakami, Kazunori Kihara
Journal: European Urology (2008)
Delay in Passage of a Ryle Tube Ingested Accidentally
Authors: W. Wilson
Journal: BMJ (1955)

Cuthbertson and his colleagues (1954) described a method of estimating isonicotinic acid hydrazide (I.N.H., isoniazid) in blood plasma and urine that marked a considerable advance on previous methods.Their method, however, requires about 10 ml. of blood and is rather elaborate for routine purposes.Our interest in the subject has been confined to blood and cerebrospinal fluid (C.S.F.), for which it has been possible to shorten the procedure in a manner that may be of interest to others.Method for Serum and C.S.F.Reagents.-Aceticacid, 0.OSN.Phosphate buffer pH 6.5: 3 vol.M/S Na2HPO4 and 7 vol.M/5 KH2PO4.Picryl chloride solution: 35 mg.(B.D.H.) in 10 ml.ethanol.Acetic acid, SN. n-Butanol.Pr-otein Precipitation (in test-tube, 16 by 125 mm.).Seruim.-To 1.25 ml. of serum add 7.5 ml. of water and
Abstract CT330: Adjusting for confounding effects of treatment crossover in a randomized phase 2 study of dabrafenib plus trametinib in <i>BRAF</i> V600+ metastatic melanoma
Authors: Nicholas Latimer, Mayur Amonkar, Ceilidh Stapelkamp, Peng Sun
Journal: Cancer Research (2014)

Abstract In a randomized phase 2 study (BRF113220), dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) improved progression-free survival (HR=0.39; 95% CI, 0.25-0.62; P&amp;lt;.001) vs dabrafenib alone. 54 patients were randomized to each arm. At the most recent data cut (March 2013), median duration of follow-up was 24 months and 52% of patients had died. ITT analyses of overall survival (OS) are likely to underestimate the true benefit of treatment because patients in the control arm (83%) were able to cross over to combination treatment upon progression. ITT median OS, a secondary endpoint, was 23.8 vs 20.2 months (HR=0.73; 95% CI, 0.43-1.24). We adjusted for confounding due to this crossover using randomization-based crossover adjustment methods: the rank-preserving structural failure time model (RPSFTM) and iterative parameter estimation (IPE) algorithm. Different assumptions about the durability of treatment effect were tested: “treatment group” analyses allow for a treatment effect that continues beyond treatment discontinuation, while “on treatment_observed” analyses assumed that the treatment effect disappears upon discontinuation. Results are presented in the Table. Reestimation of median OS following adjustment with both RPSFTM and IPE (possible only for the treatment group analyses) suggested an OS gain of 9.1 months with combination treatment vs dabrafenib alone (compared with a 3.6-month gain under ITT assumptions). The RPSFTM estimation method performed marginally better than the IPE analyses and may provide more robust results. After adjusting for the effect of crossover, the reduction in HRs to 0.47-0.50 suggests that the ITT analysis underestimates the effect of dabrafenib plus trametinib on OS. Results are uncertain due to the limiting assumptions associated with the RPSFTM and IPE methodology, small trial size, low number of observed deaths, and low number of control group patients who did not cross over. Crossover Adjustment MethodAssumptionOS HR (95% CI)None (ITT analysis unadjusted for crossover)0.73 (0.43-1.24)RPSFTMTreatment group0.47 (0.13-1.66)On treatment–observed analyses0.49 (0.15-1.63)IPETreatment group0.50 (0.16-1.54)On treatment–observed analyses0.47 (0.14-1.61) Citation Format: Nicholas Latimer, Mayur Amonkar, Ceilidh Stapelkamp, Peng Sun. Adjusting for confounding effects of treatment crossover in a randomized phase 2 study of dabrafenib plus trametinib in BRAF V600+ metastatic melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT330. doi:10.1158/1538-7445.AM2014-CT330
Genetic testing and informed consent
Authors: D. L. Page
Journal: JAMA (1997)

<h3>In Reply.</h3> —The purpose of our article was not to advance the debate about informed consent for the use of stored DNA. Our goal was to outline what should be done prospectively when obtaining informed consent for nonanonymous cancer susceptibility tests when the results will be disclosed to individual patients. Drs Page and Jensen overlook 2 important distinctions: one between existing samples and those being obtained in new projects, and the other between identifiable and "anonymized" samples. Are Page and Jensen suggesting that genetic testing on identifiable samples be permitted without specific consent? The authors support institutional review board review of protocols as an alternative to the guidelines emerging from multidisciplinary panels. However, the Office of Protection From Research Risks 1993 guidelines for institutional review boards states in the "Human Genetic Research" section: "Particular attention should be paid to protecting the confidentiality of the data and obtaining consent from the participants for
Alcohol and Heart Disease
Authors: Lawrence D. Horwitz
Journal: JAMA (1975)

TESTIMONIALS such as the Latin proverb, "In vino veritas," or the more modern, but equally immortal, lines by Ogden Nash: Candy Is dandy But liquor Is quicker attest to the popularity of alcoholic beverages. Cardiac patients who subscribe to these views often ask their physician whether they should continue to imbibe. Unfortunately, many physicians are unaware that alcohol may have detrimental effects on the heart. This is not surprising since for centuries there has been a widespread misconception, promulgated in textbooks of medicine, that alcohol is a cardiac "stimulant." In fact, there is strong evidence that ethanol is a myocardial depressant. When isolated rat atria are exposed to concentrations of 100 mg/ 100 ml, or more, developed tension is reduced, a finding indicative of impaired contractile function. In conscious dogs, ethanol in an intravenous dose equivalent to a human drinking 120 to 150 ml (4 to 5 oz) of 90-proof
HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients
Authors: Anne Hosmalin, Assia Samri, Marie-Jeanne Dumaurier, Yasmine Dudoit, Eric Oksenhendler, Marina Karmochkine, Brigitte Autran, Simon Wain-Hobson, Rémi Cheynier
Journal: Blood (2001)
Nephelometry compared with differential antibody titre in routine rheumatoid factor measurements.
Authors: R K Knight, M H Pritchard
Journal: Annals of the Rheumatic Diseases (1982)

The comparative merits of agglutination techniques (differential agglutination titre (DAT)/latex slide test) and nephelometry for the routine measurements of IgM rheumatoid factors have been studied in this 2-part paper. The first part investigates the errors inherent in standard DAT measurements, and the second determines the rate of false positive results in an elderly nonrheumatoid population. It was found that the errors in agglutination techniques are due to differences in setting up the tests rather than in interpreting the results, and that the coefficient of variance was consistently around 20%. Approximately 1 in 5 of DAT results have such a high error as to be clinically valueless. The false positive rate in the elderly nonrheumatoid population was only 2% with nephelometry compared with 9% on the latex slide test. A previous study had demonstrated the advantages of nephelometry over DAT in routine rheumatological use, showing not only greater reproducibility but also a more accurate positive detection rate than the DAT in rheumatoid arthritis. The results also suggest that the traditional spectrum of rheumatoid factors of low titre detectable in the general population is probably an artefact inherent in agglutination techniques and that a definitive cut-off point is more likely. As nephelometers are generally available in biochemistry laboratories there is much to recommended their routine use for the measurement of IgM rheumatoid factors.
NO Balance
Authors: Cornel Badorff, Stefanie Dimmeler
Journal: Circulation (2003)

ongestive heart failure is a leading cause of cardiovascular mortality in the United States and Europe. 1 Clinically, this syndrome is characterized by water retention and often left ventricular dilatation with poor systolic contractility.Etiologically, congestive heart failure can be of genetic or acquired origin.In 1993, 2 groups independently reported mutations in the cytoskeletal protein dystrophin as the cause of X-linked dilated cardiomyopathy, a rare inheritable disease that leads to enlargement of ventricular dimensions and to congestive heart failure. 1 Over the last decade, the pathophysiological relevance of the cardiac myocyte cytoskeleton for the development of congestive heart failure is being increasingly recognized.
THE ANALYSIS OF STREPTOCOCCAL INFECTIONS
Authors: S. P. Halbert, R. Bircher, E. Dahle
Journal: The Journal of Experimental Medicine (1961)

1. The rapid death which occurred after intravenous injection of activated streptolysin O from. Group A or Group C streptococci was always preceded by profound electrocardiographic alterations. After several multiples of the LD50 doses, cardiac electrical arrest or fibrillation could occur within 2 to 4 seconds after completion of the injection. 2. The streptolysin O preparations used were rather highly purified, but were known to be contaminated with small amounts of one or two other immunologically distinct components. Evidence that the observed results were due to streptolysin O was obtained by tests of the reversibly oxidized materials, and by cholesterol inactivation, as well as by in vivo protection with human gamma globulin rich in antistreptolysin antibodies. 3. Four non-streptolysin streptococcal antigens, partially or highly purified, failed to produce similar electrocardiographic changes, and were much less toxic. One of these was 3 X recrystallized and 1 X rechromatographed streptococcal proteinase. Shigella paradysenteriae type III endotoxin also did not produce striking electrocardiographic abnormalities. 4. A working hypothesis has been developed implicating streptolysin O as the etiological streptococcal factor responsible for the pathogenesis of rheumatic fever, which seems to account for the principal features of this illness.
A Weighty Matter — Lifting after Breast Cancer
Authors: Wendy Demark-Wahnefried
Journal: New England Journal of Medicine (2009)

In 1996, the Canadian Medical Association Journal featured a cover story entitled “Breast-cancer survivors begin to challenge exercise taboos.”1 This story appeared during an era when lymphedema was reported in up to 62% of women treated for breast cancer, and patients were cautioned against making repetitive arm movements and lifting more than 10 to 15 lb (4.5 to 6.8 kg). The article also chronicled the fledgling research efforts of a group of Canadian investigators who were exploring progressive resistance training (exercise regimens that promote gradual increases in intensity, frequency, and load to improve muscle strength) as a means to improve . . .