tbuckley/cabot-search huggingface dataset:
Affluent Drowning Victims; Manacled Minds
Authors: A. G. Gordon
Journal: JAMA (1988)

<h3>To the Editor.—</h3> Dr Orlowski<sup>1</sup>endorses the claim by Bolte et al<sup>2</sup>that 66 minutes is the longest submersion followed by full neurological recovery on record. However, Rowland Jackson<sup>3</sup>reviewed several reports claiming much longer intervals. They contain some surprising and convincing details, some confirmed by later accounts. Cold water or ice was often implicated. Consciousness was retained.<sup>4</sup>Several survivors experienced excessive noise while immersed, either tinnitus or amplified environmental noises, a fact known to Shakespeare.<sup>4</sup>It is hard to see why this symptom would be mentioned by frauds or malingerers or be invented in fanciful accounts. For those who will scoff, Jackson has a Warning<sup>3</sup>: <i>Credulity</i>is fatal to Truth, yet we observe in the Minds of some Men, an arrogant and presumptuous<i>scepticism</i>, which, admitting nothing but what is easy to the Conception of its possessors, is no less prejudicial to the
FURTHER STUDIES ON THE NATURE OF THE PHENOMENON OF LOCAL SKIN REACTIVITY TO BACTERIAL FILTRATES: TOXIC FACTORS DERIVED FROM THE BLOOD SERUM
Authors: Gregory Shwartzman
Journal: The Journal of Experimental Medicine (1932)

Observations reported here seem to demonstrate the liberation or formation of a toxic principle in blood serum through a colloidal disturbance in the latter. The principle is able to elicit severe injury in tissues made vulnerable by a bacterial filtrate.
Cellular and Ionic Basis for T-Wave Alternans Under Long-QT Conditions
Authors: Wataru Shimizu, Charles Antzelevitch
Journal: Circulation (1999)

T-wave alternans (TWA), an ECG phenomenon characterized by beat-to-beat alternation of the morphology, amplitude, and/or polarity of the T wave, is commonly observed in the acquired and congenital long-QT syndromes (LQTS). This study examines the cellular and ionic basis for TWA induced by rapid pacing under conditions mimicking the LQT3 form of the congenital LQTS in an arterially perfused canine left ventricular wedge preparation.Transmembrane action potentials from epicardial, M, and endocardial cells and 6 to 8 intramural unipolar electrograms were simultaneously recorded together with a transmural ECG and isometric tension development. In the presence of sea anemone toxin (ATX-II; 20 nmol/L), an increase in pacing rate (from a cycle length [CL] of 500 to 400 to 250 ms) produced a wide spectrum of T-wave and mechanical alternans. Acceleration to CLs of 400 to 300 ms produced mild to moderate TWA principally due to beat-to-beat alternation of repolarization of cells in the M region. Transmural dispersion of repolarization during alternans was exaggerated during alternate beats. Acceleration to CLs of 300 to 250 ms caused more pronounced beat-to-beat alternation of action potential duration (APD) of the M cell, resulting in a reversal of repolarization sequence across the ventricular wall, leading to alternation in the polarity of the T wave. The peak of the negative T waves coincided with repolarization of the M region, whereas the end of the negative T wave coincided with the repolarization of epicardium. In almost all cases, electrical alternans was concordant with mechanical alternans. Torsade de pointes occurred after an abrupt acceleration of CL, which was associated with marked TWA. Both ryanodine and low [Ca2+]o completely suppressed alternans of the T wave, APD, and contraction, suggesting a critical role for intracellular Ca2+ cycling in the maintenance of TWA.Our results suggest that TWA observed at rapid rates under long-QT conditions is largely the result of alternation of the M-cell APD, leading to exaggeration of transmural dispersion of repolarization during alternate beats, and thus the potential for development of torsade de pointes. Our data also suggest that unlike transient forms of TWA that damp out quickly and depend on electrical restitution factors, the steady-state electrical and mechanical alternans demonstrated in this study appears to be largely the result of beat-to-beat alternans of [Ca2+]i.
Abstract 4028: A consolidated microplate-based workflow for monitoring intracellular calcium mobilization and mitochondrial membrane potential changes
Authors: Dee Shen, Wayne Patton
Journal: Cancer Research (2010)

Abstract The interactions between mitochondrial function and Ca2+ homeostasis are very complex. Mitochondria are known to serve as dynamic calcium storage compartments, and also form intimate contacts with other calcium-handling organelles, such as the endoplasmic reticulum. Calcium enters mitochondria, not only during pathological processes, but also during physiological calcium responses. This organelle does not simply passively buffer excessive calcium but actively utilizes calcium signals to regulate integral cell activities, such as oxidative phosphorylation and the Kreb's cycle. A consolidated microplate-based workflow is described for assessing the relationship between mitochondria and global calcium responses. Two novel small molecule probes were implemented in the assay. Mitochondrial membrane potential was monitored using a dual-emission fluorescent probe that is roughly 10-25-fold more sensitive than the conventional carbocyanine dye, JC-1. Calcium mobilization was examined using a novel fluorescent calcium indicator dye that is significantly brighter than Fluo-4 AM dye. The assay is readily performed using a fluorescence microplate reader equipped with a dual-reagent dispenser. Proof-of-principle studies were performed by evaluating cell response to two agents, diazoxide, a putative opener of the potassium-ATP channel, and BML-258, a novel sphingosine kinase-1 inhibitor. The assay workflow is suitable for monitoring calcium mobilization and mitochondrial membrane potential changes across a broad spectrum of biological targets. The easy-to-use protocol is automation-friendly and can be performed in a convenient 96-well or 384-well microplate format. The assay should provide insight into the interaction between calcium signaling and mitochondrial energetic status, relevant to a range of phenomena, including ischemia/reperfusion injury. It should also serve as a high-throughput approach for identifying specific small molecule pharmacological agents targeted to this complex interrelationship. 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 4028.
Attitudinal Barriers to Physician Involvement With Drug Abusers
Authors: John N. Chappel
Journal: JAMA (1973)

The statement, "Once an addict always an addict," typifies the hopeless and the negative attitudes that interfere with the treatment of drug dependence. Myths and stereotypes permeate the attitudes of both patients and physicians. These attitudes interfere with physician-patient involvement on at least three levels. First, patients with drugabuse problems are reluctant to seek medical help. When they do, there is very little revelation of the full details of their drug abuse. Bakewell and Ewing have commented on the number of physicians' wives whose undiagnosed illnesses led to psychiatric referral and the discovery of drug dependence.<sup>1</sup>Second, physicians, including psychiatrists, are reluctant to participate personally in the treatment of drug dependence.<sup>2</sup>Physicians report that management of alcoholics is difficult, time consuming, and unrewarding, and that drug-dependent patients are unwilling to participate in treatment or to follow advice.<sup>3</sup>Finally, hospitals often refuse to admit or treat recognized cases
Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression
Authors: Roberto Ferrarese, Griffith R. Harsh, Ajay K. Yadav, Eva Bug, Daniel Maticzka, Wilfried Reichardt, Stephen M. Dombrowski, Tyler E. Miller, Anie P. Masilamani, Fangping Dai, Hyunsoo Kim, Michael Hadler, Denise M. Scholtens, Irene L.Y. Yu, Jürgen Beck, Vinodh Srinivasasainagendra, Fabrizio Costa, Nicoleta Baxan, Dietmar Pfeifer, Dominik von Elverfeldt, Rolf Backofen, Astrid Weyerbrock, Christine W. Duarte, Xiaolin He, Marco Prinz, James P. Chandler, Hannes Vogel, Arnab Chakravarti, Jeremy N. Rich, Maria S. Carro, Markus Bredel
Journal: Journal of Clinical Investigation (2014)

Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones.
Clinical Potential of Chlorophenoxyisobutyrate (CPIB: Clofibrate) in the Management of Hypercholesterolemia—A Preliminary Report.
Authors: Garfield G. Duncan
Journal: Annals of Internal Medicine (1967)

s1 May 1967Clinical Potential of Chlorophenoxyisobutyrate (CPIB: Clofibrate) in the Management of Hypercholesterolemia—A Preliminary Report.Garfield G. Duncan, M.D., F.A.C.P., Frank A. Elliott, M.D., Theodore G. Duncan, M.D., F.A.C.P., Joseph Schatanoff, M.D.Garfield G. Duncan, M.D., F.A.C.P.Search for more papers by this author, Frank A. Elliott, M.D.Search for more papers by this author, Theodore G. Duncan, M.D., F.A.C.P.Search for more papers by this author, Joseph Schatanoff, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-5-1058_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPreliminary clinical observations of clofibrate A therapy in 24 patients—obese and nonobese, diabetic and nondiabetic—exhibiting hypercholesterolemia with and without an associated hypertriglyceridemia and blood sludging in conjunctival vessels have shown with remarkable consistency a precipitous reduction in both serum cholesterol and triglycerides, a marked amelioration of blood sludging in the conjunctival vessels, reduced stickiness of the blood platelets, subsiding evidences of coronary insufficiency in five successive patients, subjective improvement in intractable cases of diabetic neuropathy, and a prompt reversal of the hyperlipidemia upon withdrawal of the clofibrate. No unfavorable effects on diabetes nor other untoward manifestations have been detected. This... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Garfield G. Duncan, M.D., F.A.C.P.; Frank A. Elliott, M.D.; Theodore G. Duncan, M.D., F.A.C.P.; Joseph Schatanoff, M.D.Affiliations: Philadelphia, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTREATMENT OF DIABETIC NEUROPATHY WITH CLOFIBRATE 1 May 1967Volume 66, Issue 5Page: 1058-1058KeywordsBlood vesselsCholesterolHyperlipidemiaNeuropathyPlatelets ePublished: 1 December 2008 Issue Published: 1 May 1967 PDF downloadLoading ...
Review: Bariatric surgery improves weight and glycemia in nonmorbidly obese adults with diabetes
Authors: Raj Padwal
Journal: Annals of Internal Medicine (2013)

Source Citation Maggard-Gibbons M, Maglione M, Livhits M, et al. Bariatric surgery for weight loss and glycemic control in nonmorbidly obese adults with diabetes: a systematic review. JAMA. 2013;309:2250-61. 23736734
Role of Anti-Phospholipase A(2) Receptor Antibodies in the Differential Diagnosis of Diabetic and Membranous Nephropathy
Authors: Mirjam Pocivalnik, Oleksiy Tsybrovskyy, Christoph Schwarz, Alexander R. Rosenkranz, Kathrin Eller, Philipp Eller
Journal: Diabetes Care (2013)

Diabetic nephropathy and membranous nephropathy can both present with nephrotic syndrome. Here, we report on a 43-year-old female patient suffering from type 1 diabetes, diabetic retinopathy, arterial hypertension, and nephrotic syndrome. Blood glucose levels were poorly controlled by a basal-bolus insulin regimen as shown by an HbA1c of 15.9% (150 mmol/mol). The concomitant antihypertensive medication consisted of an angiotensin-2 receptor blocker, a β-blocker, a calcium antagonist, and furosemide. In March 2012, her serum creatinine and urine albumin-to-creatinine ratio were 1.06 mg/dL and 7 g/g, respectively. Until December 2012, both serum creatinine and albuminuria increased to 1.9 mg/dL and 11 g/g urinary creatinine, respectively. The estimated glomerular filtration rate via the MDRD-2 formula (Modification of Diet in Renal Disease) declined from 56 to 28 mL/min/1.73 m2. Furthermore, she presented with aggravated leg oedemas, hypoalbuminemia of 2.4 mg/dL, hypertriglyceridemia, and hypertension reflecting nephrotic syndrome. …
Staff cuts would leave CMO stranded in a crisis
Authors: H. Bower
Journal: BMJ (1998)

Dramatic cuts in staff reporting to the chief medical officer (CMO) for England over the past decade have undermined the role to such an extent that effective action in a health crisis--such as occurred over bovine spongiform encephalopathy (BSE)--would now be almost impossible, a senior health administrator said last week. The warning came just before the announcement that Professor Liam Donaldson is to be the next CMO for England (see p 233).

Presenting evidence to the BSE inquiry, Dr Hilary Pickles, who was lead principal medical officer on BSE from 1988 to 1990, said that the past 10 years had seen senior and middle ranking medical staff dramatically reduced, promotion prospects for senior staff disappear, …
Exposure to chemicals may contribute to risk of breast cancer, report says
Authors: Rory Watson
Journal: BMJ (2008)

Breast cancer is not simply a lifestyle and genetic disease but can be the result of environmental factors, noticeably exposure to chemicals, says a report published last week.

Commissioned by the Health and Environment Alliance, a European network of non-governmental organisations, and the Chem Trust, the report coordinates the findings of several international research projects between 2002 and 2007 on chemicals that disrupt the endocrine system.

Commenting on the results, the author, Andreas Kortenkamp, the head of the centre for toxicology at London University’s school of pharmacy, said, “Good laboratory and epidemiological evidence exists suggesting that manmade chemicals that …
Alexithymia, Clinical and Therapeutic Aspects
Authors: H. Warnes
Journal: Psychotherapy and Psychosomatics (1986)

The clinical observations on alexithymia which were initiated by Sifneos and Nemiah in the earlier 1970s have given rise to a host of studies with implications beyond the psychosomatic field of enquiry. Is alexithymia a pathology of affect or a character neurosis; is it primary or secondary; genetic or developmental? Is it an adaptational deformation related to social class and low psychological sophistication, a life style or a cerebral deficit? Is it global and consistent (trait) or partial and temporary (state)? Is it part of the necessary and sufficient condition for the development of a psychosomatic symptom or is it a nonspecific autoplastic alteration? It is quite possible that alexithymia is one of several mediating processes between stress and disease along with genetic susceptibility, developmental variables, context and reaction to untoward life events, coping dispositions, psychosocial support and sociocultural factors. Therapeutic approaches would depend on whether we are dealing with a primary affectless condition or a secondary one. A differential diagnosis is essential since self-numbing following psychic trauma or a pathological grief, masked and atypical depression are treatable. Blocking of affect may have dire effects on the psychosomatic economy and on the capacity for intimacy. Muscular and psychological rigidity, weariness, ennui and anhedonia may be the only clues to the presence of alexithymia. Since we may be dealing with a spectrum disorder, there is no single treatment modality. There are no controlled studies on the use of psychotropic drugs and psychoanalytic-oriented and behavioral approaches have been shown to be of some benefit.
Limitations of Angiography for Analyzing Coronary Atherosclerosis Progression or Regression
Authors: Mun K. Hong
Journal: Annals of Internal Medicine (1994)

Purpose: To analyze the utility and limitations of serial coronary angiography for determining atherosclerosis progression and regression. Data Sources: A MEDLINE search of the English-language literature (1966 to January 1994) using the keywords atherosclerosis regression, atherosclerosis progression, lipid reduction therapy, and coronary angiography. Study Selection: Selected articles on the effects of cholesterol reduction and lifestyle modification on angiographic coronary artery disease, on the animal models of atherosclerosis progression and regression, and on the limitations of coronary angiography. Data Extraction: Independent extraction by two authors. Results: Although several studies have reported that the rate of atherosclerosis progression, defined by serial coronary angiography, can be reduced and that luminal diameter can be improved somewhat by aggressive lipid modification, the reported changes are small (0.3 mm or 10% change) and have required a prolonged study duration (range, 1 to 10 years). More importantly, angiography simply does not measure atherosclerosis and cannot assess lesion composition. Angiography also underestimates the extent of atherosclerosis, especially in angiographically normal segments. In addition, difficulties with data acquisition, such as substantial variabilities in serial measurements of percent diameter stenosis and minimal luminal diameters, require large sample sizes to show statistically significant regression, even with computerized quantification. Conclusions: Given its current limitations, serial coronary angiography is not a satisfactory means of detecting atherosclerosis progression or regression.
Urinary candidiasis after renal transplantation.
Authors: R Y Cartwright, C Shaldon, G H Hall
Journal: BMJ (1972)

dilettante and will only discover something new by accident.Your "single brilliant or lucky scientist" is my man from the start, provided that he will allow for the fact that years and years of conscientious painstaking endeavour are almost certain to result in a prejudiced approach.The whole history of the progress of mankind is witness to the fact that where a breakthrough has been made, it has come about through a combination of fortuitous circumstance and insight.For this reason I cannot agree that to confirm researchers for life in a career struc- ture would be an advance.In fact I believe that because "doctors and scientists under- take research during their progress to other posts" they are much more likely to have new ideas than those who enter research as a life-time occupation.There are plenty of these devoted workers who today can look back on 30 or 40 years of conscientious endeavour without having had a single new idea.This situation is inevitable if research is conducted by a vertical approach alone.-
NHS looks set to save 20m as antipsychotic drug comes off patent
Authors: N. Hawkes
Journal: BMJ (2012)

1,25-Dihydroxyvitamin D<sub>3</sub> [1,25(OH)<sub>2</sub>D<sub>3</sub>], the active form of vitamin D, exerts potent effects on several tissues including cells of the immune system, where it affects T cell activation, differentiation and migration. The circulating, inactive form of vitamin D, 25(OH)D<sub>3</sub>, is generally used as an indication of vitamin D status. However, use of this precursor depends on its uptake by cells and subsequent conversion by the enzyme 25(OH)D<sub>3</sub>-1α-hydroxylase (CYP27B1) into active 1,25(OH)<sub>2</sub>D<sub>3</sub>. Using human T cells, we show in this study that addition of inactive 25(OH)D<sub>3</sub> is sufficient to alter T cell responses only when dendritic cells (DCs) are present. Mechanistically, CYP27B1 is induced in DCs upon maturation with LPS or upon T cell contact, resulting in the generation and release of 1,25(OH)<sub>2</sub>D<sub>3</sub>, which subsequently affects T cell responses. In most tissues, vitamin D binding protein acts as a carrier to enhance the use of vitamin D. However, we show that vitamin D binding protein modulates T cell responses by restricting the availability of inactive 25(OH)D<sub>3</sub> to DC. These data indicate that the level of free 25(OH)D<sub>3</sub> available to DCs determines the inflammatory/regulatory balance of ensuing T cell responses.
Imatinib and Regression of Type 2 Diabetes
Authors: Dino Veneri, Massimo Franchini, Enzo Bonora
Journal: New England Journal of Medicine (2005)

To the Editor: We report the case of a nulliparous, 70-year-old woman with long-standing type 2 diabetes mellitus who had regression of the disease during treatment of chronic myeloid leukemia with...