tbuckley/cabot-search huggingface dataset:
Limitations of the Human Organism
Authors: Albert B. Craig
Journal: JAMA (1968)

World records in a number of different sports constitute a large volume of extremely reliable and accurate data. As Hill<sup>1</sup>indicated, "Some of the most consistent physiological data are contained, not in books on physiology, not even in books on medicine, but in world records for running different horizontal distances." Analysis of running records has been attempted from several different points of view. Recently, Lloyd<sup>2</sup>discussed world marks of male runners in terms of available energy required to run from 50 yards to 623 miles. Lietske<sup>3</sup>introduced the idea that one could make a prediction of future running records from analysis of the present velocityduration curves, as discussed later in this communication. As indicated in another article,<sup>4</sup>Lietske's short-range forecasts proved amazingly accurate. Similar methods have been used to examine records in swimming<sup>4</sup>and weight lifting.<sup>5</sup> Particularly suitable for examination are athletic events in which
THE VALUE AND LIMITATIONS OF FUNCTIONAL RENAL TESTS
Authors: J. T. GERAGHTY
Journal: JAMA (1913)

essential hematuria does not support any nephritic eti- ology.F.our of the patients operated on and three of those not operated on gave histories of hematuria of fifteen years or more prior to examination.If the hema- turia were one of the earliest symptoms of nephritis the progress has been rather slow.Furthermore, the number of patients who have been entirely well five years or more since nephrectomy is not in keeping with the usual course of a patient suffering with chronic nephri- tis from whom one of two diseased kidneys are removed.Whatever the cause of the hematuria may be, if systemic, it.apparently does not tend to shorten life, al least to any great extent.In support of the nephritic theory it has been advanced that many cases show traces of albu- min or occasional casts in the urine in the interval when no hematuria is present.The routine examinai ion of the urine of five thousand patients examined consecu- tively at the Mayo clinic during the past year shows a trace of albumin in 1,450, or 29 per cent.Less than a hundred of these patients had any clinical evidence of nephritis and none of them had essential hematuria.The overwhelming proportion of patients with albuminuria as compared with those Buffering from hematuria demands further explanation than that of nephritic change.Furthermore, the term "nephritic" is an unfor- tunate one for this type of hematuria now called "essen- tial," and tends to confuse it with the hematuria accom- panying acute and chronic nephritis, which is clinically quite distinct.
Abstract 5386: Disrupting p53:Mdm2 and p53:Mdm4 - Comparative cell-based assays for drug screening
Authors: Larisa Yurlova, Christopher J. Brown, Maarten Derks, Farid John Ghadessy, Ian Hickson, David P. Lane, Eberhard Krausz, Kourosh Zolghadr
Journal: Cancer Research (2014)

Abstract The important interconnected protein-protein interactions between the tumor suppressor p53 and its regulatory binding partners Mdm2 and Mdm4 (= MdmX/ HdmX) are implicated in pathogenesis of various cancers. However, until now there is a lack of reversible cell-based assays for concurrent analysis for both PPIs: p53/Mdm2 and p53/Mdm4. Our aim was to develop two comparative assays based on the Fluorescent 2-Hybrid (F2H) assay principle, which enable side-by-side analysis of antagonistic compounds. The F2H assay is a fully reversible microscopy-assisted assay for the direct intracellular analysis of PPIs. It offers a fast and straight-forward readout: an interaction-dependent co-localization of two fluorescent signals at a defined spot in the nucleus of mammalian cells. With these assays we analyzed a set of newly developed stapled peptides as potent p53:Mdm2 and/ or p53:Mdm4 inhibitors. Live cell data generated by the F2H assays enabled us to discriminate and describe the peptides according to their ability to penetrate into the cells, their efficacy on the PPIs and their cytotoxic side effects in one single assay. In parallel we performed a pilot F2H screen with a sub-set or 20 small molecule compounds (including Nutlin-3) that exhibited activity against one or both interactions at various potencies in ELISAs before. We could identify 5 potent compounds, which were dramatically reducing the number of p53:Mdm2 interactions. However, none of the small molecules, but only the stapled peptides exhibited an intracellular activity on p53:Mdm4. Furthermore, we were able to expand these assays and to identify mutants of Mdm2 resistant to Nutlin inhibition. In summary, we show that the p53:Mdm2 and p53:Mdm4 F2H assays described here, - enable side-by-side analysis of substances' dual Mdm2-Mdm4 activity - are suitable for screening and testing various types of compounds, such as peptidic inhibitors or small molecules - concurrently provide initial data on compound cell-permeability and cytotoxicity - allow real-time visualization of PPI dynamics in living cells. Citation Format: Larisa Yurlova, Christopher J. Brown, Maarten Derks, Farid John Ghadessy, Ian Hickson, David P. Lane, Eberhard Krausz, Kourosh Zolghadr. Disrupting p53:Mdm2 and p53:Mdm4 - Comparative cell-based assays for drug screening. [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 5386. doi:10.1158/1538-7445.AM2014-5386
Medical Emigration Figures
Authors: J. Seale
Journal: BMJ (1967)

Antisera to three human amyloid preparations were used to study antigenic relations between seven purified amyloid fibril proteins and 49 human Bence Jones proteins. Two of the amyloid proteins were antigenically similar to each other and shared antigenic determinants with 23 of 26 kappa light polypeptide chains. The other five amyloid proteins shared antigenic determinants among themselves and with 7 of 23 lambda light polypeptide chains. There was no evidence for either the presence or absence of an amyloid-specific antigenic determinant. These immunochemical data support the concept that the amyloid fibril proteins examined derive primarily from immunoglobulin light chains.
Children's consent to treatment
Authors: J P H Shield, J D Baum
Journal: BMJ (1994)

mendations regarding the safety of magnetic resonance imaging that are included in a recent publication of the Medical Devices Directorate.' Non-magnetic dental implants are harmless, as are intra- uterine and diaphragm contraceptive devices.Some penile and inflatable breast implants may, however, be hazardous.'Prosthetic heart valves are compatible with magnetic resonance imaging,5 although they were originally believed not to be so.Metal fragments introduced accidentally, including pellets, bullets, or shrapnel, may be a contraindication, particularly soon after introduction.6This applies particularly to intraocular foreign bodies, and permanent loss of vision in one eye due to preretinal haemorrhage has been reported.7The risk with intraocular fragments is greater with high field magnets, but exposing any patient with a suspected orbital foreign body is unwise; metal workers may not know that they are at risk.Metal detectors similar to those in airports may be too insensitive, but if an orbital foreign body is invisible in a high quality radiograph then probably no appreciable risk exists.8Most retinal tacks (excluding the martensitic steel Western European model)9 and intraocular lens mounts'0 seem safe, but eyelid springs are not.4This list of contraindications to magnetic resonance imaging is not exhaustive, and anything not included here is not necessarily innocuous.Confusion is exacerbated by anecdotal horror stories (from which even official hazard notices'I may not be immune), and full details of any disaster should be widely and responsibly circulated.
Researchers Probe the Aging Brain in Health and Disease
Authors: M. J. Friedrich
Journal: JAMA (2014)

San Diego—“By the time you’re 80 years old, you’ve learned everything.Youonlyhave to remember it,” quipped comedianGeorgeBurns at various points throughout his lengthy career. Holdingon tomemorieswithage is fundamental to one’s sense of well-being. But although aging is a risk factor for dementias that bring about serious and disabling memory decline, a good portion of older adults remain sharp and quick-witted into their 90s and beyond, experiencing perhaps only minor or annoying alterations in memory and cognitive function. So what distinguishes a healthy aging brain from one in the grips of a dementing illness? Researchers at the annual 2013 Society forNeurosciencemeetingheldhere in November presented insights into how the brain ages normally across a life span and howthosealterationscomparewithchanges thatoccur inbrainsaffectedby injuryorneurodegeneration.
TEACHER AND LEARNER IN MEDICINE
Authors: FREDERICK H. PRATT
Journal: JAMA (1913)

We are to-day in the midst of a great unrest in American medical education, and the movement for a true teaching spirit in medicine is now irresistible. How shall we meet it, how help it on its course? I propose to assemble what seem to be the chief factors in our problem as teachers and learners, setting aside formal administrative questions, and dealing largely with the more personal and fundamental. Let us try, on the threshold of a new year of work, to catch this true spirit, in order that it may permeate all our coming endeavors. In reviewing the experience of a student of twenty, fifteen, or even ten years ago, one is forced to wonder that medical teaching has lagged so far behind medical knowledge. When Vesalius struck down the centuriesold authority of Galen, and made anatomy a fabric of thought and action, he surely laid therewith the
Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the ?- blocker alone
Authors: C Merkel, D Sacerdoti, M Bolognesi, E Enzo, R Marin, G Bombonato, P Angeli, A Gatta
Journal: Hepatology (1997)

The association β-blockers plus isosorbide-5-mononitrate (I5M) has been proposed for the treatment of portal hypertension in patients with insufficient response to β-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with cirrhosis and esophageal varices were evaluated by hepatic venous pressure gradient (HVPG) measurement and duplex-Doppler ultrasonography before and after 1 month of treatment with nadolol. Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor responders, and were studied again with the same methodology after 3 months of chronic administration of nadolol + I5M 20 mg twice per day. In poor responders, mean HVPG decrease after nadolol was 8.9% ± 2.8%, and after the combination, it was 25.7% ± 1.7% (P = .004). All patients except one became good responders to the association. Portal blood flow (PBF) decreased significantly after nadolol (P = .004), and remained unchanged after the addition of nitrates. Resistance to portal blood flow (RPBF) increased after nadolol (P = .02) and returned to baseline values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P = .06) but no change in RPBF. A wide spectrum of combined changes in PBF and in RPBF after nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbalanced by a marked increase in RPBF. The addition of I5M was followed in most cases by larger effects on resistance than on flow. Doppler parameters were not significantly correlated with the HVPG response to nadolol alone or associated with I5M. It is concluded that good hemodynamic responders to nadolol differ from poor responders in the lack of increase in RPBF after the drug. The addition of nitrates to nadolol is effective in decreasing portal pressure in most poor responders to nadolol alone. A decrease in outflow resistance is the main mechanism involved.
On the Chemical Control of Cellular Growth
Authors: Michael Young
Journal: New England Journal of Medicine (1969)

When the lobster loses a claw, it will grow a new one; when a peripheral nerve is cut, it can regenerate; and as discussed by Malt in the current issue, when one kidney is removed, the remaining member of the pair grows to compensate for the loss. One of the exciting problems of modern biology is to understand in molecular terms how these changes take place and what the chemical machinery is that drives them. Over the past decade, advances in the molecular biology of enzyme catalysis and of genetic expression have furnished us with a framework within which some . . .
<i>ASH1</i> Gene Is a Specific Therapeutic Target for Lung Cancers with Neuroendocrine Features
Authors: Hirotaka Osada, Yoshio Tatematsu, Yasushi Yatabe, Yoshitsugu Horio, Takashi Takahashi
Journal: Cancer Research (2005)

Abstract Lung cancers with neuroendocrine features are usually aggressive, although the underlying molecular mechanisms largely remain to be determined. The basic helix-loop-helix protein, achaete-scute complex-like 1/achaete-scute homologue 1 (ASH1), is expressed in normal fetal pulmonary neuroendocrine cells and lung cancers with neuroendocrine elements and is suggested to be involved in lung carcinogenesis. In the present study, we show inhibition of ASH1 expression by plasmid-based RNA interference (RNAi) to significantly suppress growth of lung cancer cells with ASH1 expression through G2-M cell cycle arrest and accumulation of sub-G1 populations, possibly linked to cleavage of caspase-9 and caspase-7. However, lung cancer cell lines without ASH1 expression and immortalized normal BEAS2B bronchial epithelial cells were not affected. The RNAi-resistant mutant ASH1 clearly induced rescue from G2-M arrest, suggesting a target-specific effect of RNAi. An ASH1-RNAi adenovirus was also established and significantly inhibited not only in vitro cell proliferation but also in vivo xenograft growth of ASH1-positive NCI-H460 cells. Elevated levels of apoptosis were also observed in NCI-H460 xenografts with the ASH1-RNAi adenovirus. The present study therefore suggests that ASH1 plays a crucial role in lung cancer development and may be an effective therapeutic target in lung cancers with neuroendocrine features.
Valvular Heart Disease in Pregnancy
Authors: Sharon C. Reimold, John D. Rutherford
Journal: New England Journal of Medicine (2003)

A 29-year-old woman with a history of mitral stenosis who has a St. Jude Medical mitral-valve prosthesis presents for evaluation before attempting to conceive. She is concerned about the risks that pregnancy will confer on her and her child. How should she be evaluated and followed?
Imiquimod 5% cream for treatment of HIV-negative Kaposi's sarcoma skin lesions: A phase I to II, open-label trial in 17 patients
Authors: Noël Emile Célestin Schartz, Sylvie Chevret, Carolina Paz, Delphine Kerob, Olivier Verola, Patrice Morel, Céleste Lebbé
Journal: Journal of the American Academy of Dermatology (2008)
T cell–specific T-box transcription factor haplotype is associated with allergic asthma in children
Authors: Monica Cheng Munthe-Kaas, Kai Håkon Carlsen, Geir Håland, Chandra Sekhar Devulapalli, Kristina Gervin, Thore Egeland, Karin Lødrup Carlsen, Dag Undlien
Journal: Journal of Allergy and Clinical Immunology (2007)
Coagulation changes in individuals with sickle cell trait
Authors: M.P. Westerman, D. Green, A. Gilman‐Sachs, K. Beaman, S. Freels, L. Boggio, S. Allen, R. Schlegel, P. Williamson
Journal: American Journal of Hematology (2002)

Sickle cell disorders, such as Hb SS and Hb SC, are associated with a hypercoagulable state that may contribute to the vaso-occlusive episodes observed in the disorders. To what extent increased coagulation activity occurs in individuals with sickle cell trait has had limited study. Because such information may help clarify clinical and pathologic findings that may occur in these individuals and may be useful in clarifying the hypercoagulable state in sickle cell disease, we have examined individuals with Hb AS to determine the extent that increased coagulation activity does occur. We measured d-dimers, thrombin-antithrombin (TAT) complexes, prothrombin fragment 1.2 (F1.2), absolute blood monocyte levels, proteins C and S, and isotypes of antiphospholipid antibodies in individuals with Hb AS and in matched controls (Hb AA). Results showed that d-dimers, TAT, and F1.2 were increased significantly above normal levels. Absolute blood monocyte levels were increased. The d-dimers, TAT, F1.2, and monocyte counts showed significant increasing trends through groups of increasing severity (Hb AA, Hb AS, Hb SC, and Hb SS). Our study shows that individuals with Hb AS have increased coagulation activity, with d-dimers, TAT, and F1.2 being consistent indicators. The measures of coagulation activity in Hb AS are lower than in patients with Hb SC and Hb SS disease. These results extend our previous observation that the degree of coagulation activation parallels the degree of disease severity among sickle cell genotypes. The findings suggest that monocytosis, with the possible expression of monocyte-derived tissue factor, and the associated hypercoagulable state are driven by disease severity.
False-Positive PET Scan in a Patient With Lipoid Pneumonia Simulating Lung Cancer
Authors: Arunabh Talwar, Ross Mayerhoff, Darrin London, Rakesh Shah, Albert Stanek, Marcia Epstein
Journal: Clinical Nuclear Medicine (2004)

Purpose: Lipoid pneumonia usually presents with alveolar infiltrates or as a nonresolving process. We report a case of lipoid pneumonia that presented as a solitary pulmonary nodule and had a high standard uptake value on PET scan, thereby mimicking a malignant process. This case highlights the presence of false-positive PET imaging in a patient with lipoid pneumonia and Mycobacterium chelonae infection. Materials and Methods: The patient was examined using CT scanning. The nodule was further investigated with a PET scan using F-18 FDG and the standard uptake value was determined. Results: Histopathology following removal of the nodule confirmed the diagnosis of lipoid pneumonia, and the bronchoalveolar lavage (BAL) was reported as M. chelonae, a rapidly growing mycobacterium (RGM). Conclusion: Lipoid pneumonia can present as a PET-positive lung nodule and should be considered in the differential diagnosis and workup of a solitary pulmonary nodule.
Persistent parvovirus B19 related anemia of seven years' duration in an HIV-infected patient: Complete remission associated with highly active antiretroviral therapy
Authors: Eleftherios Mylonakis, Brian P. Dickinson, Maria D. Mileno, Timothy Flanigan, Fred J. Schiffman, Anthony Mega, Josiah D. Rich
Journal: American Journal of Hematology (1999)

A human immunodeficiency virus (HIV)-infected individual was first diagnosed with red blood cell aplasia due to B19 parvovirus infection in late 1989. Over the subsequent seven-year period, he received a total of 119 units of red blood cells (RBCs) and intravenous immunoglobulin every 2–3 weeks. In 1996 combination antiretroviral treatment with a protease inhibitor was initiated. He received four more units during the following two months and then required no more transfusions for the subsequent 24 months of follow-up. His CD4 count progressively increased and DNA polymerase chain reaction for parvovirus B19 became undetectable. Aggressive antiretroviral treatment may effectively diminish transfusion requirements among HIV-infected individuals with pure RBC aplasia resulting from parvovirus B19 infection. Am. J. Hematol. 60:164–166, 1999. © 1999 Wiley-Liss, Inc.
The Second Career, With Other Essays and Addresses
Authors: John H. Raach
Journal: JAMA (1964)

To have an avocation which affords pleasure and satisfaction is everyone's desire, but to be able to share this avocation with others for their pleasure is rare indeed. The essays and addresses which are included in this book mark the author as one of those unusual people who not only have pleasant avocations but also have succeeded in sharing them with others. The selections are well chosen. They reveal Dr. Penfield's catholicity of interest in the course of his "second career" and, at the same time, offer the reader many provocative thoughts. As bedside browsing for the profession or as reading during lonely vigils that are sometimes necessary, each of these writings offers excellent diversion. The topics covered include historical narratives, some autobiography, observations made in connection with the author's work on the brain, and personal reminiscences about his experiences with Osler, Ramón y Cajal, Sir Charles Sherrington, and others.
The Changing Demography of the Medical Profession
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1989)

Nearly 10 years ago I called attention to the rapid increase in the number of women entering U.S. medical schools and speculated on the changes in the medical profession that might ensue if this trend were to continue.1 Since then, the increase in the number of women medical students has continued,2 but it is now clear that this change is occurring against a background of declining numbers of white male applicants. We seem to be witnessing the beginnings of a demographic revolution of major proportions, which is bound to have great importance for the future of our health care system. . . .
Variables and parameters
Authors: P. Sedgwick
Journal: BMJ (2010)

Researchers investigated the influence of body mass index and alcohol consumption on the incidence of liver cirrhosis in middle aged women.1 They used data from the Million Women Study,2 a prospective cohort study based in the United Kingdom. At recruitment and follow-up, the measurements for each woman included body mass index, age, smoking, and self reported alcohol consumption.

Which one of …
Is Alcoholism a Disease?-Reply
Authors: Thomas V. Seessel
Journal: JAMA (1989)

In Reply.—  Dr Borelli misses the point of both my July 8, 1988, JAMA editorial 1 and my reply to Mr Schaler on the Supreme Court case involving recovering alcoholic veterans ( Traynor v Turnag e, 108 S Ct 1372 [1988]).  The Supreme Court did not rule on whether alcoholism is a disease, the topic that Mr Schaler pursues and whose views Dr Borelli apparently supports. Rather, the court found only that Congress had failed to pass clear-cut legislation instructing the Veterans Administration to put recovering alcoholic veterans on an equal footing with other disabled veterans in determining eligibility for a time extension to use their entitlement to education benefits.  My editorial urged that Congress take this step by legislating that the Veterans Administration could no longer characterize alcoholism as willful misconduct in making this determination. Congress did enact such legislation only 6 months after the Supreme Court decision.  As the Supreme
The Health Economy
Authors: David Hemenway
Journal: JAMA (1987)

I don't like to do book reviews, but when I was asked to review<i>The Health Economy</i>, I readily agreed. Before the book arrived, I had already written my first paragraph. "Victor Fuchs is one of the few economists who can write really well. It is always a pleasure to read his books. This one is no exception." Now I've read the book. While the above is literally true, this review will be more mixed than I would have expected. <i>The Health Economy</i>is a collection of 17 articles written by Fuchs published between 1967 and 1986. Health is considered in broad perspective. Although much of the book is on medical care, there are chapters on topics such as motor vehicle inspection, low-level radiation, and cigarette smoking. Fuchs uses economic theory to help frame the issues and identify the most relevant variables. The book is packed with insights. A few