tbuckley/cabot-search huggingface dataset:
THERAPEUTICS OF INSANITY.
Authors: ORPHEUS EVERTS
Journal: JAMA (1904)

Since the insane of Christian countries were rescued by the hand of science from the despotic barbarism of superstition, they have been treated rationally, if not successfully, as persons suffering bodily infirmities. The therapeutics of such treatment may be classified, for convenience, as medical, hygienic and disciplinary. Medical therapeutics consists of the administration of materials supposed to be curative of diseased conditions. That medicines administered to the insane are not always, but are, indeed, seldom curative, is a "huge criticism" of present states of knowledge respecting both disease and medicine. Were man a rational as well as a reasoning being, it might not be exacting to require of physicians prescribing medicine for the insane to have some knowledge of the more intimate relation of function and manifestation to structure, in conditions of both health and disease, as well as a clear perception of the relation of drug-energy to physiologic
Cooperation not confrontation: the imperative of a nuclear age.
Authors: J Dyer
Journal: BMJ (1985)

Health needs and the costs of confrontation * 40000 children die in the world daily from preventable diseases and malnutrition, and the same number are per- manently disabled.In terms of loss of life this equals a new Hiroshima every three days.* World spending on arms in 1985 will be over $800 billion.WHO's entire budget ($250m) is equivalent to three hours of this spending.* 4-5 million children die in the world each year from diseases that can be prevented by immunisation.* Spending on medical research is less than 20% of spending on military research world wide.* Life expectancy at birth is 30 years shorter in Africa than in Europe.* A cut of 10% in the military budget of developed countries could almost triple economic aid to underdeveloped countries.
Family trends in psychotropic and antibiotic prescribing in general practice
Authors: C Bridges-Webb
Journal: BMJ (1980)

Size of tumour and operation performed in relation to length of history, 1979 Short* Intermediate Longt history history history No of inoperable tumours 1 2 7 Average tumour diameter (cm) 16 2-6 3-1 No of mastectomies 19 29 8 No of wide local excisions 16 22 1 Total No of patients 36 53 16*Short history .onemonth.tLong history-one year.radiotherapy.The selection of patients for conservative surgery is on the basis of the relative volume of the tumour to the breast and on its position.Patients with central tumours still undergo mastectomy but patients with relatively small medial or lateral tumours have wide local excision.If wide local excision and postoperative radiotherapy can control local disease as effectively as mastectomy, then our message to the public is not that shorter delay neces- sarily means longer survival but that shorter delay means less radical surgery.
Beta-blockers in the treatment of myocardial infarction.
Authors: J Seldrup, D Burley
Journal: BMJ (1980)

to medical schools should include measures to detect vulnerability, and the curriculum should embody programmes which will help the student to cope with later professional stresses.Faculty advisors, tutors, and organised peer groups should be aware of their duty to recognise and intervene at an early stage rather than to wait for the GMC to take action when problems may be ineradicably established.
Abstract LB-48: Non-invasive imaging of response to MEK Inhibition with AZD6244 (ARRY-142886) in a human melanoma xenograft monitored by diffusion-weighted MRI
Authors: Mounia Beloueche-Babari, Yann Jamin, Vaitha Arunan, Simon Walker-Samuel, Paul D. Smith, John C. Waterton, Jane Halliday, Paul Workman, Martin O. Leach, Simon P. Robinson
Journal: Cancer Research (2010)

Abstract Background: Non-invasive imaging biomarkers are key to the development and evaluation of novel targeted anti-cancer drugs. The MEK inhibitor, AZD6244 (ARRY-142886), is one such agent that is now undergoing clinical testing. This drug causes inhibition of growth and induction of apoptosis in a range of pre-clinical tumor models. We therefore reasoned that such effects could translate to changes in tumor tissue cellular density that may be detectable by diffusion-weighted magnetic resonance imaging (DW-MRI). Here we test this hypothesis in a human melanoma xenograft model. Methodology: Female nude mice bearing V600E BRAF WM266.4 melanoma sub-cutaneous xenografts (∼550 mm3 volume) were treated twice daily for 3 days by gavage with vehicle (n=9) or 75mg/kg AZD6244 (n=9). DW-MRI data were acquired pre- and 3h post the last dose, and correlated with phosphorylated (P-) ERK1/2 and the necrotic tumor fraction by histological analysis of excised tumors. Results: Our results show that AZD6244-treated tumors were not significantly different in size compared to day 0 (100±6%) while the vehicle treated-tumors had grown by ∼ 1.4-fold (p=0.001). Relative to day 0, the mean values of the apparent diffusion coefficient (ADC), a parameter that is inversely related to tissue cellularity, were not changed in the control group (109±12%, p=0.45) but increased significantly to 160±20% (p=0.01) in the AZD6244-treated group. This effect correlated with substantially reduced P-ERK1/2 levels and increased tumor necrosis from 10± 10% in the vehicle group to 60±9% in the drug-treated group (p=0.036). Conclusions: This study highlights changes in ADC that follow treatment with a MEK signaling inhibitor, and which precede tumor shrinkage. Our data support the use of ADC as a non-invasive pharmacodynamic biomarker for early assessment of response to AZD6244 and other therapies targeted at MEK-ERK1/2 signaling during clinical trials. Acknowledgements: This work was funded by Cancer Research UK [CUK] project grant C1060/A6916, AstraZeneca and The Royal Society. We acknowledge the support received from the CRUK and EPSRC Cancer Imaging Centre in association with the MRC and Department of Health (England) grant C1060/A10334, also NHS funding to the NIHR Biomedical Research Centre. 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 LB-48.
Chronic Discoid Lupus Erythematosus in Children
Authors: R. K. Winkelmann
Journal: JAMA (1968)

In five cases of chronic discoid lupus erythematosus which began in childhood and lasted into adulthood no systemic disease was present, and long follow-up confirmed the cutaneous localization of the disease. This syndrome in children is comparable to the continuing, recurrent nature of chronic discoid lupus erythematosus in adults.
Alteration of pulmonary immunity to Listeria monocytogenes by diesel exhaust particles (DEPs). I. Effects of DEPs on early pulmonary responses.
Authors: Xue-Jun Yin, Rosana Schafer, Jane Y C Ma, James M Antonini, David D Weissman, Paul D Siegel, Mark W Barger, Jenny R Roberts, Joseph K-H Ma
Journal: Environmental Health Perspectives (2002)

It has been hypothesized that diesel exhaust particles (DEPs) aggravate pulmonary bacterial infection by both innate and cell-mediated immune mechanisms. To test this hypothesis, we investigated the effects of DEP exposure on the functions of alveolar macrophages (AMs) and lymphocytes from lung-draining lymph nodes using a rat Listeria monocytogenes infection model. In the present study, we focused on the effects of DEP exposure on AM functions, including phagocytic activity and secretion of proinflammatory cytokines. The Listeria infection model was characterized by an increase in neutrophil count, albumin content, and acellular lactate dehydrogenase activity in the bronchoalveolar lavage (BAL) fluid at 3 and 7 days postinfection. Short-term DEP inhalation (50 and 100 mg/m(3), 4 hr) resulted in a dose-dependent suppression of lung clearance of Listeria, with the highest bacteria count occurring at day 3. This aggravated bacterial infection was consistent with the inhibitory effect of DEPs on macrophage functions. DEPs suppressed phagocytosis and Listeria-induced basal secretion of interleukin-1ss (IL-1ss) and IL-12 by AMs in a dose-dependent manner. The amount of IL-1ss and IL-12 in the BAL fluid was also reduced by DEP exposure. In addition, DEPs decreased Listeria-induced lipopolysaccharide-stimulated secretion of tumor necrosis factor-alpha (TNF-alpha), IL-1ss, and IL-12 from AMs. These results suggest that DEPs retard bacterial clearance by inhibiting AM phagocytosis and weaken the innate immunity by inhibiting AM secretion of IL-1ss and TNF-alpha. DEPs may also suppress cell-mediated immunity by inhibiting AM secretion of IL-12, a key cytokine for the initiation of T helper type 1 cell development in Listeria infection.
Pressure-induced myogenic activation of cat cerebral arteries is dependent on intact endothelium.
Authors: D R Harder
Journal: Circulation Research (1987)

These studies were designed to determine the role of cerebral vascular endothelium in the "myogenic" depolarization and contraction observed in isolated cat middle cerebral arteries exposed to high transmural pressures. With intact endothelial cells we observed, on elevation of transmural pressure in cannulated isolated arteries, significant membrane depolarization, action potential generation, and reduction in internal diameter. After perfusion of the same vessels with collagenase and elastase for short periods of time to disrupt the endothelial layer, all previous responses to elevation of transmural pressure were no longer seen. Even though enzyme perfusion had no effect on membrane potential at "control" levels of transmural pressure, it abolished the pressure-dependent depolarization, action potential generation, and constriction. Furthermore, the contractile response to agonist stimulation was maintained after endothelial disruption via enzymes, showing that this method of endothelial disruption did not appreciably damage muscle cells. The data document a dependence of an intact endothelium in mediating the activation of isolated cat cerebral arteries in response to a changing transmural pressure. Thus, it is possible that the endothelial cell may serve as a transducer in the autoregulatory response to pressure.
Development of a High-Value Care Subscore on the Internal Medicine In-Training Examination
Authors: Kira L. Ryskina, Deborah Korenstein, Arlene Weissman, Philip Masters, Patrick Alguire, Cynthia D. Smith
Journal: Annals of Internal Medicine (2014)

Although high-value care (HVC) that balances benefits of tests or treatments against potential harms and costs has been a recently emphasized competency for internal medicine (IM) residents, few tools to assess residents' knowledge of HVC are available.To describe the development and initial results of an HVC subscore of the Internal Medicine In-Training Examination (IM-ITE).The HVC concepts were introduced to IM-ITE authors during question development. Three physicians independently reviewed each examination question for selection in the HVC subscore according to 6 HVC principles. The final subscore was determined by consensus. Data from the IM-ITE administered in October 2012 were analyzed at the program level.U.S. IM residency programs.362 U.S. IM residency programs with IM-ITE data for at least 10 residents.Program-level performance on the HVC subscore was compared with performance on the overall IM-ITE, the Dartmouth Atlas hospital care intensity (HCI) index of the program's primary training hospital, and residents' attitudes about HVC assessed with a voluntary survey.The HVC subscore comprised 38 questions, including 21 (55%) on managing conservatively when appropriate and 14 (37%) on identifying low-value care. Of the 362 U.S. IM programs in the sample, 41% were in a different quartile when ranked based on the HVC subscore compared with overall IM-ITE performance. Rankings by HVC subscore and HCI index were modestly inversely associated, with 30% of programs ranked in the same quartile based on both measures.Knowledge of HVC assessed from examination vignettes may not reflect practice of HVC.Although the HVC subscore has face validity and can contribute to evaluation of residents' HVC knowledge, additional tools are needed to accurately measure residents' proficiency in HVC.None.
Immunologist accused of misconduct is allowed to relocate
Authors: C. Zinn
Journal: BMJ (2004)

<h3>ABSTRACT</h3> SARS-CoV-2 has recently been detected in feces, which indicates that wastewater may be used to monitor viral prevalence in the community. Here we use RT-qPCR to monitor wastewater for SARS-CoV-2 RNA over a 52-day time course. We show that changes in SARS-CoV-2 RNA concentrations correlate with local COVID-19 epidemiological data (R<sub>2</sub>=0.9), though detection in wastewater trails symptom onset dates by 5-8 days. We determine a near complete (98.5%) SARS-CoV-2 genome sequence from the wastewater and use phylogenic analysis to infer viral ancestry. Collectively, this work demonstrates how wastewater can be used as a proxy to monitor viral prevalence in the community and how genome sequencing can be used for high-resolution genotyping of the predominant strains circulating in a community.
Abstract 4366: miR-126 reduces the tumorigenicity of melanoma cells <i>in vitro</i> and alters the melanoma microenvironment
Authors: Gabriela Gremel, Laoighse Mulrane, Toby Paul, Vivienne Williams, William M. Gallagher, Fredrik Pontén
Journal: Cancer Research (2012)

Abstract The microRNA (miRNA) miR-126 is highly expressed in endothelial cells and often reported as down-regulated in cancer. The present study thoroughly examines the functional relevance of miR-126 in melanoma progression and suggests a central role of this miRNA as prognostic marker and modulator of the melanoma microenvironment. Initially, the expression of miR-126 was quantified in two independent, isogenic cell line model series of melanoma progression. To further explore its functional role, two stable over-expression cell lines were generated and subjected to an extensive series of in vitro assays. Subsequently, the prognostic relevance of miR-126 was assessed via in situ hybridization on a large melanoma tissue microarray cohort. In both melanoma cell line systems, miR-126 expression was inversely correlated with the level of tumorigenicity. Over-expression of miR-126 in vitro resulted in a significant decrease in colony formation, both in the presence and absence of anchorage, while cell viability remained unaffected. Using a three-dimensional spheroid invasion assay, over-expression of miR-126 significantly reduced cell invasiveness. In addition, a substantial reduction in tumor cell adhesion to VCAM-1 coated micro-channels was observed when the adhesive capacity of miR-126 over-expressing cells was examined under shear stress using the Cellix's Microfluidic Platform. Using in situ hybridization on tissue microarrays containing melanoma tissue, miR-126 expression was evident in the tumor vasculature whereas melanoma cells did not appear to express miR-126. Analysis of the degree of vascular staining revealed a significant association between lower vascular miR-126 expression and lower T-stage. In addition, high vascular miR-126 scores were significantly associated with prolonged overall survival, in particular in high grade tumors (T-stages 3 and 4). Overall, miR-126 over-expression was shown to trigger a less aggressive phenotype in melanoma cells in vitro. Nonetheless, its clinical relevance in melanoma may primarily be mediated by the tumor vasculature. Depletion of miR-126 has previously been linked to a number of tumor relevant phenotypes, including inflammation. Vascular up-regulation of the miR-126 target protein VCAM-1 may mediate increased tumor infiltration of lymphocytes and macrophages, which are known to play a crucial role in tumor development and prognosis. This renders miR-126 an exciting target for closer investigation with regard to its role in the melanoma microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4366. doi:1538-7445.AM2012-4366
AML1 mutations induced MDS and MDS/AML in a mouse BMT model
Authors: Naoko Watanabe-Okochi, Jiro Kitaura, Ryoichi Ono, Hironori Harada, Yuka Harada, Yukiko Komeno, Hideaki Nakajima, Tetsuya Nosaka, Toshiya Inaba, Toshio Kitamura
Journal: Blood (2008)
Better Service for Our Overseas Subscribers
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1982)

English has become the lingua franca of medicine, and any major English-language medical journal is now likely to have a substantial international readership. This journal is no exception. Approximately 20 per cent of our subscribers live outside North America, and our overseas circulation has grown rapidly in recent years. Not surprisingly, about the same fraction of our manuscripts and letters come from overseas. Our current subscription lists include physicians and medical institutions from over 130 countries, and the national origins of our contributors are almost as far-flung.We are naturally very pleased to be of interest to such a broad . . .
The Use of Placebos in Controlled Trials
Authors: Michael Phillips
Journal: Annals of Internal Medicine (1992)

Letters1 February 1992The Use of Placebos in Controlled TrialsMichael Phillips, MDMichael Phillips, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-116-3-265 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:In a discussion of the rational use of the placebo, Bourne (1) has observed that "In some cases no 'placebo group' may be necessary at all. If one mode of therapy has definitely been shown to have genuine benefit, that therapy, not placebo, should be the 'control.' For example, in testing new drugs for symptomatic relief in rheumatoid arthritis, a demonstrated superiority to placebo medication is worse than useless, since (1) the placebo group has been deprived of active medication (aspirin) and (2) the real question, 'Is new drug X superior to conventional therapy?' has not been...References1. Bourne H. Rational use of placebo. In: Clinical Pharmacology; 2d edition. Melmon KL, Morrelli HF; eds. New York: Macmillan; 1972:1052-62. Google Scholar2. SninskyCortShanahanPowersSessionsPruitt CDFBJR. Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. Ann Intern Med. 1991;115:350-5. LinkGoogle Scholar1. Placebo-controlled clinical trials in gastroenterology—a position paper of the American College of Gastroenterology. Am J Gastroenterol. 1984;79(12):913-7. MedlineGoogle Scholar2. SninskyCortShanahanPowersSessionsPruitt CDFBJR. Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis. Ann Intern Med. 1991;115:350-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: St. Vincent's Medical Center New York Medical College Staten Island, NY 10310 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1992Volume 116, Issue 3Page: 265-265KeywordsAspirinDrug regulationDrug therapyRheumatoid arthritis Issue Published: 1 February 1992 PDF DownloadLoading ...
New Evidence about an Old Drug — Risk with Codeine after Adenotonsillectomy
Authors: Judith A. Racoosin, David W. Roberson, Michael A. Pacanowski, David R. Nielsen
Journal: New England Journal of Medicine (2013)

In response to reports of respiratory depression and death in young children who had received codeine after tonsillectomy, adenoidectomy, or both, the FDA initiated a safety evaluation. The result is a boxed warning on the labels of all codeine-containing products.
Three-dimensional optical coherence tomography of Barrett’s esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation
Authors: D. Adler, C. Zhou, T.-H. Tsai, H.-C. Lee, L. Becker, J. Schmitt, Q. Huang, J. Fujimoto, H. Mashimo
Journal: Endoscopy (2009)

Ablative therapies including photodynamic therapy, argon plasma coagulation, and radiofrequency ablation (RFA) are increasingly performed for Barrett's esophagus. Residual Barrett's esophagus from incomplete ablation and buried Barrett's esophagus glands beneath regenerative neosquamous epithelium are often found, to varying degrees, on follow-up [1]. While neosquamous epithelium indicates successful therapy, detection of residual disease is important for guiding additional treatments. Due to their diminutive or subsurface nature, detection of residual Barrett's esophagus, buried glands, and neosquamous epithelium can be challenging using conventional endoscopy alone [1].
Pulmonary and urinary clearance of atrial natriuretic factor in acute congestive heart failure in dogs.
Authors: M A Perrella, K B Margulies, C M Wei, L L Aarhus, D M Heublein, J C Burnett
Journal: Journal of Clinical Investigation (1991)

Atrial natriuretic factor (ANF) is a peptide hormone of cardiac origin elevated in acute congestive heart failure (CHF), which is degraded by the enzyme neutral endopeptidase 24.11 (NEP). This study was designed to investigate the pulmonary and urinary clearance of ANF before and after the initiation of acute experimental CHF in dogs, and to assess the contribution of enzymatic degradation to these clearances in CHF. This study demonstrated a significant clearance of plasma ANF across the pulmonary circulation at baseline, and a tendency for pulmonary clearance to decrease in CHF (1115 +/- 268 to 498 +/- 173 ml/min, NS). The pulmonary extraction of ANF present at baseline was not altered with acute CHF (36.0 +/- 7.8 to 34.9 +/- 12.1%, NS). NEP inhibition (NEPI) abolished both the clearance and extraction of plasma ANF across the lung in CHF. Similarly, significant urinary clearance of ANF was present at baseline, and in acute CHF the urinary clearance of ANF decreased (0.14 +/- 0.02 to 0.02 +/- 0.01 ml/min, P less than 0.05). NEPI prevented the decrease in the urinary clearance of ANF, and enhanced the renal response to endogenous ANF, independent of further increases in plasma ANF during CHF. This study supports an important role for NEP in the pulmonary and urinary metabolism of endogenous ANF during acute CHF.