tbuckley/cabot-search huggingface dataset:
Structure-activity relationships for ulcerogenic and adrenocorticolytic effects of alkyl nitriles, amines, and thiols.
Authors: S Szabo, E S Reynolds
Journal: Environmental Health Perspectives (1975)

In rats, a single administration of acrylonitrile (vinyl cyanide) produces a rapidly occurring bilateral adrenal apoplexy. Structure-activity studies have shown that a close derivative, propionitrile (ethyl cyanide), causes duodenal ulcer without markedly affecting the adrenal glands. Prolonging the two-carbon chain of propionitrile by a methyl group (n-butyronitrile) enhances, replacing the methyl by bromide or nitrile decreases, while substitution by an amino group abolistes the ulcerogenic potency and variably affects the adrenocorticolytic action. On assaying a large number of nonnitrile compounds as well for ulcerogenic effect, such as thiols and amines, this effect was found to be related to a two-carbon structure bearing electronegative radicals on one or both ends of the chain.
Heller-type cardiomyotomy using NOTES
Authors: A. Mathew, E. Pauli, M. Moyer, R. Haluck
Journal: Endoscopy (2008)

We read with interest the article by Pasricha et al. on endoscopic myotomy [1]. It is clear that esophageal myotomy could be one of the procedures easily done using natural-orifice transluminal endoscopic surgery (NOTES). Unfortunately the described technique would not enable achievement of a complete Heller-type cardiomyotomy extending into the gastric wall. While accessing the esophageal submucosal plane and incising the muscle layer is easy, performing an adequate cardiomyotomy may be difficult using this reported technique.
The Importance of Disease Prevalence in Transporting Clinical Prediction Rules
Authors: ROY M. POSES
Journal: Annals of Internal Medicine (1986)

Because clinical prediction rules often are applied in new settings to calculate the probability of a disease, we evaluated the accuracy of three rules for predicting streptococcal pharyngitis in 310 patients. Use of the rules led to overestimations of disease probability in 47%, 82%, and 93% of the patients. When we used receiver-operating characteristic curve analysis, no rule lost power to discriminate streptococcal from nonstreptococcal causes of pharyngitis. The overestimations in disease probability likely were caused by differences in disease prevalence between our setting (5%) and the settings in which they were developed (15% to 17%). All rules led to accurate predictions when they were adjusted for the disease prevalence found in our setting using a likelihood ratio formulation of Bayes' theorem. The value of prediction rules, like that of other diagnostic tests, is affected by differences in disease prevalence in different settings. Failure to recognize and adjust for these differences may cause poor decision making or the premature dismissal of valid rules.
Regaining the initiative. Forging a new model of the patient-physician relationship
Authors: J. Balint
Journal: JAMA (1996)

The patient-physician relationship has undergone major and increasingly rapid changes in the past 40 years. It has moved from a relationship based on physician paternalism, through one of patient autonomy, to one where the patient and the physician's authority and control over the patient's care are facing significant threats from outside sources. In this article, we examine the historical and social forces that have contributed to these changes and the effects these forces have had on the traditional models of the patient-physician relationship. We present arguments to support our proposal for a patient-physician alliance in the community based on mutual education of physician and patient about health and illness, values and persons, social responsibility, beneficence, trust, and a degree of paternalism. We believe such an alliance offers the best hope for patients and their physicians to regain the initiative in guiding the evolution of health care in a way that preserves the essentials of the therapeutic relationship.
Lack of inducible nitric oxide synthase leads to increased hepatic apoptosis and decreased fibrosis in mice after chronic carbon tetrachloride administration
Authors: Ghazaleh Aram, James J. Potter, Xiaopu Liu, Michael S. Torbenson, Esteban Mezey
Journal: Hepatology (2008)

The role of nitric oxide (NO) in liver injury and fibrosis is unclear. The purpose of this study was to determine whether inducible NO synthase deficiency (iNOS−/−) affects liver injury and fibrosis produced in mice by chronic carbon tetrachloride (CCl4) administration. Wild-type (WT) or iNOS−/− mice were subjected to biweekly CCl4 injections over 8 weeks, whereas controls were given isovolumetric injections of olive oil. Serum aminotransferases were lower after CCl4 in the iNOS−/− than in the WT mice, which correlated with decreased necrosis on liver histology. There was increased apoptosis, a lower number of stellate cells, and a lesser degree of fibrosis after CCl4 in the iNOS−/− as compared with the WT mice. α1(I) collagen messenger RNA (mRNA) was markedly increased after CCl4 in the WT and to a significantly lesser extent in the iNOS−/− mice. Liver matrix metalloproteinase-9 (MMP-9) mRNA and MMP-2 mRNA were increased more in the WT than in the iNOS−/− mice after CCl4. Also tissue inhibitor metalloproteinase 1 (TIMP-1) mRNA was increased to a much greater extent in the WT than in the iNOS−/− mice after CCl4 ( P &lt; 0.05). However, MMP-9 and TIMP-1 protein, determined by western blot, were similarly increased after CCl4 in both groups of mice. Conclusion: NO protects against CCl4-induced apoptosis. In the absence of iNOS, there is decreased necrosis, increased apoptosis, and reduced liver fibrosis.
DIAZEPAM AS AN ANTI-CONVULSANT AGENT IN ECT
Authors: MEHMET EKINCI, JOHN J. HSU, MORRIS BRUCK, ROBERT A. BRAUN
Journal: American Journal of Psychiatry (1964)

Evaluation of the scales on severity of convulsions revealed a significant difference between anectine-Na pentothal on the one hand and diazepam and placebo on the other hand. Even with the highest doses of diazepam, the convulsions were as severe as with placebo while they were significantly reduced on anectine-Na pentothal. This result is confirmed by the findings of fractures following diazepam and placebo, but not following anectine-Na pentothal. There were no side effects with anectine-Na pentothal treatment, but there was ataxia and drowsiness with high doses of diazepam. It is concluded from this study that oral diazepam is not an adequate substitute for anectine-Na pentothal as pre-ECT medication for the prevention of fractures.
Association between KRAS rs61764370 and triple-negative breast cancer—a false positive? – Authors' reply
Authors: Joanne Weidhaas, Frank Slack, Nicola Miller, Lyndsay Harris, David Tuck, Yong Zhu, Daniel Zelterman, Michael Kerin, Trupti Paranjape, Helen Heneghan, Robert Lindner, Florence Keane, Jemima Dorairaj, Kimberly Geyda, Cory Pelletier, Sunitha Nallur
Journal: The Lancet Oncology (2011)
Native Medicine in the United States
Authors: Nat Kanner
Journal: JAMA (1966)

To the Editor:—  The letter Native Medicine in Viet Nam ( 197 :734, 1966) describes   for the treatment of influenza in Viet Nam. This form of therapy is not limited to the Vietnamese people. I had been cupping even before I became a physician. I still use it on occasion.  During the 1918 influenza epidemic, as a high school youth, I went from house to house cupping people with the suction cups applied to their chests, externally, front and back. None whom I cupped died, but some I knew who were not cupped died of influenza. The Yiddish name for cupping is  . To put on bonkis is cupping. In New York city there are still barbers who, as laymen, are called to homes to cup persons ill with acute upper respiratory ailments, virus infections, influenza, and the grippe.  I have had a set of 24 suction cups in
Tyrosine and serine phosphorylation of α-synuclein have opposing effects on neurotoxicity and soluble oligomer formation
Authors: Li Chen, Magali Periquet, Xu Wang, Alessandro Negro, Pamela J. McLean, Bradley T. Hyman, Mel B. Feany
Journal: Journal of Clinical Investigation (2009)

Mutations in the neuronal protein α-synuclein cause familial Parkinson disease. Phosphorylation of α-synuclein at serine 129 is prominent in Parkinson disease and influences α-synuclein neurotoxicity. Here we report that α-synuclein is also phosphorylated at tyrosine 125 in transgenic Drosophila expressing wild-type human α-synuclein and that this tyrosine phosphorylation protects from α-synuclein neurotoxicity in a Drosophila model of Parkinson disease. Western blot analysis of fly brain homogenates showed that levels of soluble oligomeric species of α-synuclein were increased by phosphorylation at serine 129 and decreased by tyrosine 125 phosphorylation. Tyrosine 125 phosphorylation diminished during the normal aging process in both humans and flies. Notably, cortical tissue from patients with the Parkinson disease–related synucleinopathy dementia with Lewy bodies showed less phosphorylation at tyrosine 125. Our findings suggest that α-synuclein neurotoxicity in Parkinson disease and related synucleinopathies may result from an imbalance between the detrimental, oligomer-promoting effect of serine 129 phosphorylation and a neuroprotective action of tyrosine 125 phosphorylation that inhibits toxic oligomer formation.
Antidepressants and risk of suicide
Authors: M. Sinyor, A. H. Cheung
Journal: BMJ (2015)

Reported differences among drugs are important to know, but hard to interpret

Suicide is recognized as one of the most urgent public health concerns of our time, with approximately 60% of such deaths attributed to mood disorders.1 Ideally, well designed randomized controlled trials would guide doctors toward the best antidepressant for reducing the risk of suicide (and away from those likely to increase it).

Despite 1.5% of the world’s population dying from suicide,2 these deaths occur throughout the lifespan so risk remains low during any brief period under study. This makes research uniquely challenging. For example, one large meta-analysis of 372 antidepressant trials and nearly 100 000 patients reported a total of just eight suicide deaths.3 Given this, large population based studies are needed to understand better the true impact of antidepressants on patients. Ultimately the combined evidence base from both clinical trials and epidemiological studies should inform clinical decision making.

In a linked paper (doi:10.1136/bmj.h517) Coupland and colleagues conducted a cohort study using a large UK primary care database to quantify associations between different antidepressants and suicide as well as deliberate self harm (including suicide attempts) during the first five years of follow-up for adults with a …
Muscle Stiffness and Vitamin C
Authors: J. L. Corbett, A. Barr
Journal: BMJ (1967)

IBrr 113 that there is a good case for the nutritional origin of these megaloblastic anaemias.The high incidence of pregnancy megaloblastic anaemias in our district, 272 over the same 71-month period, would also support the mainly dietary origin of folate deficiency megaloblastic anaemias.While in some areas it holds true that per- nicious anaemia is the predominant megalo- blastic anaemia in the elderly, this does not appear to be the case in our patient material.This does not subtract from the import- ance of the recommendation contained in the last sentence of your leading article, but underlines at the same time the necessity of an exact diagnosis of the deficiency involved in megaloblastic anaemia in any age groupeven in the elderly.-Weare, etc.,
Career structure--the modern doctors' dilemma.
Authors: G Todd, M O'Brien, D Gooding
Journal: BMJ (1985)

The changes in inumigration rules that bring overseas doctors and dentists in line with other workers' have clearly been stimulated by the view of the Advisory Committee for Medical Manpower Planning2 that any need for short term reduction in the supply of doctors will be more readily effected by a reduction in net immigra- tion than by a reduction in medical school intake.Although the changes might prove successful they will not do anything to cope with the dilemma presented by long serving registrars and senior house officers.That there is such a dilemma was shown by an earlier study in one region and is confirmed by the observations of this inquiry.Junior doctors are well aware of the problem but shy away from one of the more obvious potential solutions.4 Method and resultsDuring August and September 1984 personnel staff in district health authorities in the Northern, Trent, and Oxford regions extracted information from curricula vitae of senior house officers and registrars.This enabled the length of time in each grade to be calculated for substantive and locum posts.The age structure of the doctors in the two grades was also examined.The figure shows the age distribution of senior house officers and registrars combined for the three regions but separated to show any variance between teaching and other districts.Although most senior house officers are under 29 and registrars under 32 in the teaching 102 A 90 ,
Microspectrophotometric methods for studying the cytokinetic behaviour of the psoriatic epidermis in vivo
Authors: G. L. GROVE
Journal: British Journal of Dermatology (1984)

Journal Article Microspectrophotometric methods for studying the cytokinetic behaviour of the psoriatic epidermis in vivo Get access G. L. GROVE G. L. GROVE Simon Greenberg Foundation, Skin Study Centre at University Square, 3901 Market Street, Philadelphia, PA 19104. U. S. A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s27, 1 July 1984, Pages 188–194, https://doi.org/10.1111/j.1365-2133.1984.tb15604.x Published: 01 July 1984
Burkholderia cepacia bronchiectasis
Authors: S SURESH, I. DOULL;, M. LEDSON, M. WALSHAW
Journal: Thorax (1999)

We read with interest the case report by Ledson et al 1 describing a non-cystic fibrosis individual with chronic Burkholderia cepacia bronchiectasis. Although B cepacia most commonly affects patients with cystic fibrosis, it is also known to infect patients with chronic ventilatory requirements or immunocompromised patients.2 The immunocompromised patient population who appear most vulnerable to B cepacia infection are those with chronic granulomatous disease …
Bill to protect doctors who try experimental treatments starts journey through UK parliament
Authors: C. Dyer
Journal: BMJ (2014)

A bill that would give extra legal protection to doctors who try experimental treatments on patients who are hard to treat is expected to become law with government support.

The Medical Innovation Bill, sponsored by the Conservative peer Maurice Saatchi, is due to have its first reading in the House of Lords this week, after it was redrafted to introduce further safeguards.

Some critics of the bill have argued that it could promote quackery, while others maintained that it was unnecessary because the common law already protects doctors who act in line with a responsible body of medical opinion.

But a public consultation by the Department of Health for …
Failure of Pretreatment With Intravenous Folic Acid to Alter the Cumulative Hematologic Toxicity of Lometrexol
Authors: F. M. MUGGIA, T. W. SYNOLD, E. M. NEWMAN, S. JEFFERS, L. P. LEICHMAN, J. H. DOROSHOW, K. JOHNSON, S. GROSHEN
Journal: JNCI Journal of the National Cancer Institute (1996)

believe that this treatment schedule is worth testing in patients with other cancers in which a biologic activity of retinoids is involved.
Are we asking the right questions?
Authors: Peter-Marc Fortune
Journal: BMJ (2007)

Costeloe dismisses some of the key issues and draws attention away from the dangers and limitations of the current approach.1 I question our current interpretation of “active” and “passive” euthanasia. How exactly is extubating a child with serious pulmonary disease (which may or may not improve) different from giving him or her a lethal injection? …
Systematic Review: Opioid Treatment for Chronic Back Pain: Prevalence, Efficacy, and Association with Addiction
Authors: Bridget A. Martell, Patrick G. O'Connor, Robert D. Kerns, William C. Becker, Knashawn H. Morales, Thomas R. Kosten, David A. Fiellin
Journal: Annals of Internal Medicine (2007)

The prevalence, efficacy, and risk for addiction for persons receiving opioids for chronic back pain are unclear.To determine the prevalence of opioid treatment, whether opioid medications are effective, and the prevalence of substance use disorders among patients receiving opioid medications for chronic back pain.English-language studies from MEDLINE (1966-March 2005), EMBASE (1966-March 2005), Cochrane Central Register of Controlled Clinical Trials (to 4th quarter 2004), PsychInfo (1966-March 2005), and retrieved references.Articles that studied an adult, nonobstetric sample; used oral, topical, or transdermal opioids; and focused on treatment for chronic back pain.Two investigators independently extracted data and determined study quality.Opioid prescribing varied by treatment setting (range, 3% to 66%). Meta-analysis of the 4 studies assessing the efficacy of opioids compared with placebo or a nonopioid control did not show reduced pain with opioids (g, -0.199 composite standardized mean difference [95% CI, -0.49 to 0.11]; P = 0.136). Meta-analysis of the 5 studies directly comparing the efficacy of different opioids demonstrated a nonsignificant reduction in pain from baseline (g, -0.93 composite standardized mean difference [CI, -1.89 to -0.03]; P = 0.055). The prevalence of lifetime substance use disorders ranged from 36% to 56%, and the estimates of the prevalence of current substance use disorders were as high as 43%. Aberrant medication-taking behaviors ranged from 5% to 24%.Retrieval and publication biases and poor study quality. No trial evaluating the efficacy of opioids was longer than 16 weeks.Opioids are commonly prescribed for chronic back pain and may be efficacious for short-term pain relief. Long-term efficacy (> or =16 weeks) is unclear. Substance use disorders are common in patients taking opioids for back pain, and aberrant medication-taking behaviors occur in up to 24% of cases.
Maternal allergy increases susceptibility to offspring allergy in association with TH2-biased epigenetic alterations in a mouse model of peanut allergy
Authors: Ying Song, Changda Liu, Yiqun Hui, Kamal Srivastava, Zhenwen Zhou, Jia Chen, Rachel L. Miller, Fred D. Finkelman, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2014)
Nectin-3 links CRHR1 signaling to stress-induced memory deficits and spine loss
Authors: Xiao-Dong Wang, Yun-Ai Su, Klaus V Wagner, Charilaos Avrabos, Sebastian H Scharf, Jakob Hartmann, Miriam Wolf, Claudia Liebl, Claudia Kühne, Wolfgang Wurst, Florian Holsboer, Matthias Eder, Jan M Deussing, Marianne B Müller, Mathias V Schmidt
Journal: Nature Neuroscience (2013)
The Expansions of Medical Literature
Authors: G. G. Liddle
Journal: JAMA (1966)

<h3>To the Editor:—</h3> I am sure your readers, and your editorial board, will join with me in welcoming a new medical journal to the lists of those already in press. The importance of this occasion may not be apparent to all, wherefore this letter. Earlier in my speckled career I argued that all men and women should have a medical education. Instead of high schools and colleges devoted to teaching the liberal arts, we should have medical schools. These would teach only the amount of algebra and syntax essential to understanding the stethoscope or to grasp the import of the<i>culmen</i>of the<i>monticulus.</i>Such esoteric and recondite subjects as economics or poetry would be strictly postgraduate pursuits, outlawed for study until after the MD had been bestowed: "The dithyramb 'twere a naughty thing, Ere dunked in th'Aesculapian spring." The advantages of such a system of education, although clear to
Abstract 2766: YM155 inhibits survivin-mediated survival, migration, and tumor growth in neuroblastoma.
Authors: Heather M. McClung, Ping Zhao, Lauren Smith, Alexandra Eckardt, Giselle L. Sholler
Journal: Cancer Research (2013)

Abstract Background: Neuroblastoma is the most common extracranial solid tumor in children, with poor prognosis in children diagnosed after 12-15 months of age. Even with current multimodal therapies, the 5-year event-free survival is below 50%, necessitating the development of new, targeted therapies. Survivin is a developmentally regulated gene that is highly up-regulated in many cancers. In neuroblastoma, survivin is up-regulated by PI3Kinase-AKT signaling and its expression correlates with poor prognosis. Survivin is a member of the Inhibitor of Apoptosis family of proteins and is involved in cell survival through caspase dependent and independent pathways. Knockdown of survivin in melanoma cells reduces cell migration in vitro and its expression correlates with metastasis in Ewing's Sarcoma and Schwann cell tumors. YM155 is a transcriptional suppressor of survivin and has shown efficacy in several cancer model systems both in vivo and in vitro and is currently under clinical investigation for adult cancers. In this study, we investigate the effects of YM155 on neuroblastoma cell apoptosis and migration in vitro and on tumor growth in vivo. Methods: Four neuroblastoma cell lines were treated with YM155 and subject to cell viability and migration assays. Gene expression was investigated by microarray and signaling by Western Blotting. In vivo, effects on tumor volume were determined by xenograft implant of neuroblastoma cell lines followed by YM155 treatment and measurement by calipers. Results: Treatment with YM155 caused a dose-dependent decrease in survivin expression and reduced cell viability in neuroblastoma cell lines; however IC50 values vary by cell line. Cells treated with YM155 near the respective IC50 showed increased cleavage of Caspase 3 and PARP indicating apoptosis. Gene and protein expression changes include reduced CXCR4 and Mcl-1. Low levels of YM155 reduced cell migration by 30-50%; cytotoxicity was not observed at the lower concentrations. Treatment with YM155 reduced tumor growth in vivo by 25-70% and depended on cell line. Conclusions: YM155 inhibits survivin expression, reduces cell viability, induces apoptosis, and migration in vitro, and reduces tumor volume in vivo. Further investigation is warranted in characterization of YM155 as a possible therapeutic agent for neuroblastoma. Citation Format: Heather M. McClung, Ping Zhao, Lauren Smith, Alexandra Eckardt, Giselle L. Sholler. YM155 inhibits survivin-mediated survival, migration, and tumor growth in neuroblastoma. [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 2766. doi:10.1158/1538-7445.AM2013-2766