tbuckley/cabot-search huggingface dataset:
Tuberculosis Mortality in the United States, 1900 to 1960
Authors: Theodore C. Doege
Journal: JAMA (1965)

Tuberculosis mortality in the United States has undergone a progressive decline during the past century. Decreases in mortality rates among whites and nonwhites have been of similar magnitude, but nonwhite death rates have remained two to three times higher than white death rates. Mortality has generally been higher in males than in females, and the male-female ratio of deaths has risen steadily. Age distribution of fatal cases has changed, from infants, young adults, and the elderly, to the elderly alone. Past progress foreshadows eventual eradication of tuberculosis in the United States, especially if public health, social, economic, and educational measures are directed towards groups at greatest risk.
OBSERVATIONS ON THE USE OF CHLOROFORM AS AN ANAeSTHETIC
Authors: A. B. Steele
Journal: BMJ (1856)

M. LLoYD, at St. Bartholomew's, often mentions to his class that the application he finds most effectual in private practice, in effecting the radical cure of bydrocele, is a small quantity of red precipitate on a probe or director in- troduced into the sac subsequent to its evacuation by the trocar.In a recent case at St. Bartholomew's, accordingly, the application was tried with very good effects.Mr.ILoyd believes it seldom or never fails.It requires no specific apparatus; it produces a certain amount of inflam- mation of the common kind in the serous lining of the sac, which effectually blocks up the cavity, and no ill effects of any kind are produced.NEW OPERATION FOR PARACENTESIS IN DROPSY.A new mode of "tapping", or performing the ordinary operation of paracentesis abdominis, recently adopted by Mr. BIRKETT, deserves a word of notice.Every surgical practitioner must be aware how commonplace and unin- teresting this operation has become, and how very like the analogous process as regards a beer barrel; thus justifying in some measure the association of ideas with which the literal acceptation of the term, the process of "tapping", has come to be regarded by students and surgeons in on 12 July
Abstract 5681: Modulation of Wnt/β-catenin signaling by niclosamide and related derivatives.
Authors: Robert A. Mook, Minyong Chen, Jiuyi Lu, Larry S. Barak, H. Kim Lyerly, Wei Chen
Journal: Cancer Research (2013)

Abstract The Wnt signal transduction pathway is dysregulated in many cancers, including colorectal cancer (CRC) where activating mutations in this pathway occur in over 80% of sporadic colorectal cancers. As a result, drugs that inhibit the pathway are highly sought-after as the basis of a new generation of innovative therapeutic agents. Unfortunately, a gap exists in the ability to target the pathway with small, drug-like molecules, a gap that is the barrier to discovering drugs targeting defects in this pathway. Recently, we reported the FDA-approved anthelmintic drug niclosamide inhibits Wnt/β-catenin signaling via a novel mechanism that internalizes Frizzled receptors and leads to decreases in Dishevelled and β-Catenin proteins, even in cells harboring mutations in APC and β-catenin. The biological target driving inhibition of Wnt signaling by niclosamide is unknown. To support efforts to translate these findings in clinical trials and assist target identification efforts, we interrogated the mechanism and structure-activity relationships. We will present our findings indicating inhibition of Wnt signaling by niclosamide appears unique among the structurally-related anthelmintic agents tested and that Wnt/β-catenin activity was dependent on small changes in the chemical structure of niclosamide - including the ability to convert inhibition to activation. Overall, the findings support efforts to identify the target of niclosamide inhibition of Wnt/β-catenin signaling and the discovery of novel inhibitors of Wnt/β-catenin signaling to treat cancer, and thus accelerate the translational application of niclosamide and its derivatives to improve patient survival from cancer. Citation Format: Robert A. Mook, Minyong Chen, Jiuyi Lu, Larry S. Barak, H. Kim Lyerly, Wei Chen. Modulation of Wnt/β-catenin signaling by niclosamide and related derivatives. [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 5681. doi:10.1158/1538-7445.AM2013-5681
Lymphoscintigraphic Findings in Chylous Reflux in a Lower Extremity
Authors: Gholam R. Berenji, Emily Iker, Edwin C. Glass
Journal: Clinical Nuclear Medicine (2007)

Lymphoscintigraphy is a useful and safe tool for the diagnostic evaluation of a swollen extremity. Unilateral leg swelling with cutaneous chylous vesicles is a common manifestation of chylous reflux. The authors present a case of chylous reflux in an 11-year-old boy who presented with swelling and skin lesions of the left lower extremity.
Excess Iron Storage in Patients with Type 2 Diabetes Unrelated to Primary Hemochromatosis
Authors: Guiomar Pérez de Nanclares, Luis Castaño, Sonia Gaztambide, Jose Ramón Bilbao, Javier Pi, Maria Luisa González, Jose Antonio Vázquez
Journal: New England Journal of Medicine (2000)

To the Editor: We care for many patients with Parkinson's disease who are more concerned with hypokinesia than with dyskinesia of a tolerable degree.The most difficult adverse event is hallucination rather than dyskinesia.So Rascol et al. could have drawn the opposite conclusion: early Parkinson's disease can be managed successfully, with a reduced risk of hallucinations, with levodopa alone.Although the authors state that hallucinations were mild and easily managed in most of their patients, the same might have been true of dyskinesia.
Pilot Study on Patients' and Spouses' Attitudes Toward Potential Genetic Testing for Bipolar Disorder
Authors: Carol Lynn Trippitelli, Kay R. Jamison, Marshal F. Folstein, John J. Bartko, J. Raymond DePaulo
Journal: American Journal of Psychiatry (1998)

The purpose of this pilot study was to gain information about attitudes of individuals with bipolar disorder and their spouses toward some of the ethical and social issues arising from rapidly advancing genetic research on bipolar disorder.Patients with bipolar disorder and their unaffected spouses were asked to answer questionnaires assessing their knowledge and attitudes about treatment response rates for bipolar disorder, probability of inheritance, genetic testing, disclosure of genetic information, abortion, marriage, and child-bearing.The overwhelming majority of the patients and spouses said that they would take advantage of genetic tests for bipolar disorder if such tests were to become available. Most patients and spouses agreed that the benefits of knowing whether one carries a gene for bipolar disorder would outweigh the risks. The decisive majority of respondents also felt that they would not abort a fetus that carried a gene for bipolar disorder. Furthermore, most patients and spouses agreed that the knowledge that one of them carried a gene for bipolar disorder would not have deterred them from marriage or childbearing.The results of this study suggest that most individuals believe that they would benefit from the use of genetic testing for bipolar disorder if it were to become available. Follow-up studies using a broader patient sample and nonclinical control groups would be useful in further evaluating the issues addressed in this pilot study.
Intravenous Drug Therapy of Stokes-Adams Disease
Authors: PAUL M. ZOLL, ARTHUR J. LINENTHAL, WILLIAM GIBSON, MILTON H. PAUL, LEONA R. NORMAN
Journal: Circulation (1958)

In the treatment of Stokes-Adams disease emergency resuscitation from cardiac arrest can be effected by external electric stimulation or countershock. For the acute problems of persistent ventricular standstill and frequently recurrent seizures, which often appear immediately after resuscitation, intrinsic ventricular pacemakers must be aroused, accelerated, and maintained. In the treatment of these problems the effects of drugs on ventricular rhythmicity and atrioventricular conduction were evaluated. We have found the slow intravenous administration of dilute solutions of sympathomimetic amines to be an effective and safe technic. Epinephrine and isoproterenol were the most useful agents and were comparable in efficacy and toxicity.
Superiority of Pentazocine in Myocardial Infarction
Authors: Jacobus W. Mostert
Journal: JAMA (1974)

<h3>To the Editor.—</h3> Although all the evidence in his review points in the opposite direction, Dr. Alderman concludes that "morphine remains the analgesic of choice during the acute phase of myocardial infarction" (229:1646, 1974). He also overlooks the advantage that pentazocine is not listed on the Controlled Substances Act because it has not been found to have potential for abuse to date. A source of amazement to the anesthesiologist is the continuing preference of morphine by cardiologists at this time when comparatively ultrashort-acting narcotics that do not release significant amounts of histamine are available. There is no question of the greater safety of fentanyl citrate (Sublimaze) among anesthesiologists. Thus, the originator of neuroleptanalgesia, De Castro, routinely administers 3 mg of fentanyl as part of the symptomatic treatment of shock,<sup>1</sup>which is the equianalgesic dose of at least 300 mg of morphine. However, as anesthesiologists who provide analgesia and anesthesia to
Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioassays, and monoclonal antibodies.
Authors: H M Cherwinski, J H Schumacher, K D Brown, T R Mosmann
Journal: The Journal of Experimental Medicine (1987)

Lymphokine synthesis patterns of a panel of 19 T cell clones have been evaluated, using mRNA hybridization methods to examine 11 different mRNAs induced by Con A. The two types of CD4+ Th cell clone described previously were clearly distinguished by this procedure, and the differences between the two types have now been extended to six induced products. With minor exceptions, only Th1 clones synthesized mRNA for IL-2, IFN-gamma, and lymphotoxin, and only Th2 clones synthesized mRNA for IL-4, IL-5, and another induced gene, P600. Four more induced products were expressed preferentially but not uniquely by one or another type of clone: mRNAs for GM-CSF, TNF, and another induced, secreted product (TY5) were produced in larger amounts by Th1 clones, whereas preproenkephalin was preferentially expressed by Th2 clones. IL-3 was produced in similar amounts by both types of clone. mAbs were used to establish three bioassays that were functionally monospecific for IL-2, IL-3, and IL-4, and a new anti-IFN gamma mAb, XMG1.2, was used to establish an ELISA for IFN-gamma. These four assays were used to show that secreted protein and mRNA levels correlated well for all cell lines. The implications of these findings for normal T cells are discussed.
Abstract B36: Identification of carboxylesterase 2 as a hydrolase that cleaves the prodrug of gemcitabine LY2334737
Authors: Susan E. Pratt, Sara Durland-Busbice, Robert L. Shepard, Harry B. Harlow, Darryl Ballard, Kathleen M. Heinz-Taheny, Anne H. Dantzig
Journal: Clinical Cancer Research (2010)

Abstract Gemcitabine hydrochloride is a nucleoside anticancer agent registered for the treatment of pancreatic, NSCLC, breast, and ovarian cancers. A prodrug of gemcitabine (LY2334737) was prepared that is a gemcitabine analog with an amide-linked valproate. This prodrug is noncytotoxic and must be hydrolyzed to release gemcitabine. In man, the prodrug is orally absorbed intact and converted to gemcitabine systemically. This study was undertaken to identify the enzyme responsible for hydrolysis of the prodrug to gemcitabine. The NCI-60 cell line panel was screened for prodrug sensitivity and microarray data were used to evaluate the expression of hydrolase enzymes in responsive and unresponsive cell lines. Cell extracts and candidate enzymes were tested for LY hydrolysis using HPLC and cell lines were evaluated for enzyme expression using qRT-PCR and Western methods. Screening of the NCI-60 panel demonstrated that LY was not cytotoxic to the majority of cell lines, however sensitivity was observed in a few cell lines such as SK-OV-3 and COLO205. Other cell lines were also evaluated. Extracts of drug sensitive cell lines hydrolyzed LY to gemcitabine and its inactive metabolite 2',2'-difluorodeoxyuridine (dFdU), indicating that LY hydrolysis was necessary for activity. Analysis of the expression of known hydrolases in the NCI-60 microarray data identified the serine ester hydrolase, carboxylesterase 1 (CES1) among the top candidates. In humans, there are 3 CESs and these are known to hydrolyze other prodrugs. Human recombinant protein of each CES was tested for LY cleavage. With long incubation periods, only CES2 hydrolyzed the drug. Loperamide is an inhibitor of CES1 and CES2 that is permeable to cells and noncytotoxic. At low micromolar concentrations this inhibitor only affects CES2, therefore cytotoxicity assays were conducted with SK-OV-3 in the presence and absence of 10 µM loperamide. The cytotoxicity of LY was decreased with loperamide CES2 inhibition without effect on gemcitabine cytotoxicity. Expression of CES2 was evaluated in drug-sensitive and -insensitive cell lines by qRT-PCR and Western analysis; LY sensitive lines expressed CES2 while insensitive lines did not. An immunohistochemical assay was developed that showed expression of CES2 to be heterogeneously expressed in these cell lines. Taken together, these data indicate that CES2 hydrolyzes the prodrug. Cancer cells that express CES2 may have an enhanced response to treatment with the prodrug LY2334737. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B36.
EVALUATION OF FUNCTIONAL LIMITATIONS IN FEMALE SOCCER PLAYERS AND THEIR RELATIONSHIP WITH SPORTS LEVEL – A CROSS SECTIONAL STUDY
Authors: M Grygorowicz, T Piontek, W Dudzinski
Journal: British Journal of Sports Medicine (2014)

Background Little is known about the impact of functional muscle restrictions on the level of functional performance among female soccer players. Objective The aim of this study was to analyze: a) abnormalities in the length of lower limb muscles, b) the correctness of movement patterns, and c) the impact of functional limitations of muscles on the correctness of fundamental movement patterns in a group of female soccer players, in relation to their skill level. Design Cross Sectional Study. Setting Elite and sub-elite division. Participants 21 female soccer players from Polish Ekstraklasa (PE) and 22 players from the 1st Division (1D). Interventions All participants were tested for lower limb muscle length restrictions and level of fundamental movement skills (with the Fundamental Movement Screen TM test). Chi-square test was used for categorical unrelated variables. Differences between groups in absolute point values were analyzed using the non-parametric Mann-Whitney U test. Statistical significance was set at P&lt;.05. Main outcome measurements Lower leg muscle length, FMS TM score. Results Significantly higher number of abnormal rectus femoris length in the 1D (P=.0433) and abnormal hamstring results (P=.0006) in the PE was observed. PE scored higher in the trunk rotational stability test (P=.0008), the 1D players scored higher in the deep squat (P=.0220), in-line lunge (P=.0042) and active straight leg raise (P=.0125) tests. The results suggest that there are different functional reasons affecting point values obtained in the FMS TM tests in both groups. Conclusions The differences in the rectus femoris and hamstring muscle flexibility observed between female soccer players with different levels of training may result from a long-term impact of soccer training on the muscle-tendon system and articular structures. Different causes of abnormalities in fundamental movement patterns in both groups suggest the need for tailoring prevention programs to the level of sport skills represented by the players.
Heart Rate Recovery Following Maximal Exercise Testing as a Predictor of Cardiovascular Disease and All-Cause Mortality in Men With Diabetes
Authors: Yiling J. Cheng, Michael S. Lauer, Conrad P. Earnest, Timothy S. Church, James B. Kampert, Larry W. Gibbons, Steven N. Blair
Journal: Diabetes Care (2003)

OBJECTIVE—Heart rate recovery (HRR) is an independent prognostic indicator for cardiovascular disease (CVD) and all-cause mortality in healthy men. We examined the association of HRR to CVD-related and all-cause mortality in men with diabetes. RESEARCH DESIGN AND METHODS—In this cohort study we examined 2,333 men with documented diabetes (mean age 49.4 years) that had baseline 5-min HRR measurement following maximal exercise (heart ratepeak − heart rate5 min of recovery) at The Cooper Clinic, Dallas, TX. We identified HRR quartiles as quartile 1 &amp;lt;55, quartile 2 55–66, quartile 3 67–75, and quartile 4 &amp;gt;75 bpm. Hazard ratios (HRs) for cardiovascular and all-cause death were adjusted for age, cardiorespiratory fitness, resting heart rate, fasting blood glucose, BMI, smoking habit, alcohol consumption, total cholesterol, triglyceride, and history of CVD at baseline. RESULTS—During a median of 14.9 years follow-up, there were 142 deaths that were considered CVD related and 287 total deaths. Compared with men in the highest quartile of HRR, adjusted HRs in the first, second, and third quartiles were 2.0 (95% CI 1.1–3.8), 1.5 (0.8–2.7), and 1.5 (0.9–2.8), respectively, for cardiovascular death (P for trend &amp;lt; 0.001). Similarly, for all-cause death, adjusted HRs in the first, second, and third quartiles were 2.0 (1.3–3.2), 1.5 (1.0–2.3), and 1.5 (1.1–2.3) (P for trend &amp;lt; 0.001). CONCLUSIONS—Among men with diabetes, a decreased HRR, even measured as long as 5 min after recovery, was independently predictive of cardiovascular and all-cause death.
Smoking and blood pressure in 15 year olds in Dunedin, New Zealand.
Authors: I. M. St George, S. Williams, W. R. Stanton, P. A. Silva
Journal: BMJ (1991)

Among the immediate effects of inhaling cigarette smoke is a rise in heart rate and blood pressure as a result of the action of nicotine at a number of sites effecting neurocardiovascular control.Many studies - for example, that by Simpson et al'-have found lower average systolic and diastolic blood pressures in adults who smoked than in non-smokers.
ACTH and Cortisone in the Treatment of Ocular Disease
Authors: Richmond W. Smith, Ellis H. Steffensen
Journal: New England Journal of Medicine (1951)

OPHTHALMOLOGY has witnessed a wide-spread clinical trial of cortisone and adrenocorticotrophic hormone (ACTH) during the past two years, and the results have opened an entirely new approach to the treatment of certain ophthalmologic conditions. At present, although the number of publications on the subject is not extensive, it seems appropriate to review the available literature and to call attention to the current concepts of both etiology and therapy that have emerged from the use of these agents, particularly in the inflammatory ocular lesions. It was apparent initially that considerable enthusiasm was to be associated with the early experiences; although more . . .
BMA proposes range of measures to tackle alcohol misuse
Authors: Roger Dobson
Journal: BMJ (2008)

Routine screening in primary care for alcohol misuse, reduced opening hours of licensed premises, higher taxes on alcohol, a lowering of the drink driving limit, random roadside breath testing, and tobacco style health warnings on bottles are all urged in a new report from the BMA’s board of science.

The board’s evidence based recommendations for change aim to tackle the burden of alcohol misuse in the United Kingdom and are targeted at policy makers.

“The levels of alcohol related disorder, crime, morbidity, and premature mortality in the UK are unacceptably high,” said Charles George, the board’s chairman. “It is essential that the UK governments implement alcohol control policies that are evidence …
A NEW ASEPTIC THROAT MIRROR.
Authors: ALLEN T. HAIGHT
Journal: JAMA (1902)

In presenting this aseptic throat mirror, made out of polished metal, it seems like a return to the time of flourishing Pompeii, when highly polished brass was used for hand-mirrors. The instrument is manufactured from German silver, highly nickel-plated. The handle is universal, is made out of steel, and the joint between the mirror and the handle is a spring ball and socket, allowing mirrors of different sizes to be used. Being of solid metal, it can be rendered thoroughly aseptic by carbolizing or boiling without any deteriorating effect upon its polished surface. The mirror being nickel-plated, no acid will attack or corrode it provided the mirror is quickly cleansed after using. Moist chromic acid, to the surface of the nickel-plate, has absolutely no effect. A metal throat mirror was first used by Dr. von Stein, of Moscow, in his clinic and private practice, his instrument being of polished steel.
ACUTE YELLOW ATROPHY OF THE LIVER.
Authors: H. GIDEON WELLS
Journal: JAMA (1905)

During the past few years, there have been studied either tissues or organs from four cases of acute yellow atrophy of the liver, in the pathological laboratories of the University of Chicago and Rush Medical College, and on account of the relative infrequence of this disease it has seemed advisable to place the records of these cases in the literature where they may be available for investigators of this condition, even though not all of our reports can be as complete as we could desire. Osler's estimate that there are 250 cases on record up to 1894 inclusive, 50 of these being added by Hunter from 1880 to 1894, is possibly based on the estimate of Thierfelder in 1878 that there were 200 cases in the literature at that time. If we accept this latter as true there are at least 450 on record at the present time, as
A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis
Authors: Andrea Alimonti, Caterina Nardella, Zhenbang Chen, John G. Clohessy, Arkaitz Carracedo, Lloyd C. Trotman, Ke Cheng, Shohreh Varmeh, Sara C. Kozma, George Thomas, Erika Rosivatz, Rudiger Woscholski, Francesco Cognetti, Howard I. Scher, Pier Paolo Pandolfi
Journal: Journal of Clinical Investigation (2010)

Irreversible cell growth arrest, a process termed cellular senescence, is emerging as an intrinsic tumor suppressive mechanism. Oncogene-induced senescence is thought to be invariably preceded by hyperproliferation, aberrant replication, and activation of a DNA damage checkpoint response (DDR), rendering therapeutic enhancement of this process unsuitable for cancer treatment. We previously demonstrated in a mouse model of prostate cancer that inactivation of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (Pten) elicits a senescence response that opposes tumorigenesis. Here, we show that Pten-loss–induced cellular senescence (PICS) represents a senescence response that is distinct from oncogene-induced senescence and can be targeted for cancer therapy. Using mouse embryonic fibroblasts, we determined that PICS occurs rapidly after Pten inactivation, in the absence of cellular proliferation and DDR. Further, we found that PICS is associated with enhanced p53 translation. Consistent with these data, we showed that in mice p53-stabilizing drugs potentiated PICS and its tumor suppressive potential. Importantly, we demonstrated that pharmacological inhibition of PTEN drives senescence and inhibits tumorigenesis in vivo in a human xenograft model of prostate cancer. Taken together, our data identify a type of cellular senescence that can be triggered in nonproliferating cells in the absence of DNA damage, which we believe will be useful for developing a “pro-senescence” approach for cancer prevention and therapy.