tbuckley/cabot-search huggingface dataset:
A RETENTIVE APPARATUS FOR FRACTURES OF THE CLAVICLE.
Authors: RAYMOND RUSS
Journal: JAMA (1905)

In the clinical work at the surgical dispensary of the University of California the Sayre adhesive plaster dressing has been used for some time as a routine treatment for fractures of the clavicle. In many cases the results attained were good, but the method of treatment failed in a number of instances. It was not until several of these failures followed closely on one another that the necessity for a better method of treatment became imperative. The mostpronounced failures were in those rare cases of fractured clavicle which presented great overlapping of the fragments and in which it was impossible to maintain reduction by the ordinary methods. A glance over the literature was not reassuring. More methods of treatment have probably been suggested for this fracture than for any other. Pilcher sums up the matter by saying: "The fact remains that those methods which are efficient are intolerable and those
Lysis of Autologous Melanoma Cells by Tumor*Infiltrating Lymphocytes: Association With Clinical Response
Authors: P. Aebersold, C. Hyatt, S. Johnson, K. Hines, L. Korcak, M. Sanders, M. Lotz, S. Topalian, J. Yang, S. A. Rosenberg
Journal: JNCI Journal of the National Cancer Institute (1991)

Tumor–infiltrating lymphocytes (TILs) can be grown in vitro in medium containing interleukin–2 (IL–2). In clinical trials at the Surgery Branch of the National Cancer Institute, patients with metastatic malignant melanomas were treated with IL–2 plus the adoptive transfer of autologous TILs. At the time of treatment, TILs were assayed for in vitro lysis of fresh autologous and allogeneic melanoma cells and Daudi cells. Patients were evaluated for clinical response 4–8 weeks later. Lysis of autologous tumor cells by TILs was significantly higher for responding than for non responding patients. Tumor cells from responding and non–responding patients were equally sensitive to lysis by allogeneic lymphokine–activated killer (LAK) cells. There was no difference between TILs from responding and non–responding patients for lysis of LAK sensitive Daudi cells, which was low in most cases and demonstrated that TIL lysis of autologous tumor cells was not due to LAK cells. The observed association of autologous tumors cell lysis by TILs with clinical response suggests that the development of culture methods to optimize lysis of autologous tumors may lead to increased response rates using this TIL treatment regimen.[J Natl Cancer Inst 83: 932–937, 1991]
787. Engineered Fok I Heterodimers for Enhanced Zinc Finger Nuclease Specificity
Authors: Jeffrey C. Miller, Michael Holmes, Jianbin Wang, Ya-Li Lee, Igor Rupniewski, Adam Waite, Dmitry Guschin, Philip Gregory, Carl O. Pabo, Edward J. Rebar
Journal: Molecular Therapy (2006)

Zinc finger nucleases have been shown to be effective tools for high-frequency genome editing with potential therapeutic applications (Urnov et al., Nature 435:646-651). Such nucleases are created by fusing the cleavage domain of the type IIs restriction enzyme Fok I to engineered zinc finger proteins. One limitation of this architecture is that the natural Fok I cleavage domain must dimerize in order to cleave DNA; therefore two different zinc finger protein-Fok I fusions are required to introduce a double-stranded break at an asymmetric target site. As a consequence, use of this technology for genome editing may expose the cell to three different nuclease species – the desired heterodimer as well as two homodimers which are irrelevant to the desired process but which may still contribute to off-target cleavage events. Creating Fok I cleavage domain variants that do not function as homodimers would eliminate the possibility of off-target cutting by these species and would also increase the availability of the desired heterodimer. In order to develop such variants, we used a process of iterative structure-based design and screening in which candidate designs were tested for their ability to cleave DNA in vitro and for their ability to potentiate gene correction in a reporter cell line. A pair of nuclease variants, each containing two mutations at the dimerization interface, were developed that worked well when paired together, but were severely impaired when paired with a second copy of themselves. These mutant cleavage domains were substituted for the wild-type FokI cleavage domains in the reagents used by Urnov et al. and tested for their ability to induce sequence alterations at the endogenous human common gamma chain gene. In this system we observed that a heterodimer of our designed cleavage domains was as active as wild type Fok I at stimulating gene correction while inducing significantly fewer overall DNA cutting events. Moreover, homodimers of the designed Fok I cleavage domain variants were completely inactive. These studies demonstrate that we have successfully developed Fok I cleavage domain variants that function as obligate heterodimers. These variants should be broadly useful for increasing the potency and specificity of designed zinc finger nucleases.
Progress in Cardiology 1/1
Authors: Samuel Zoneraich
Journal: JAMA (1988)

The first issue of<i>Progress in Cardiology</i>under the new editorship of Zipes and Rowlands continues the impressive tradition of excellence established by the previous editors Yu and Goodwin. The text focuses on a central theme, cardiac arrhythmias. The first three chapters are dedicated to mechanisms; the following three chapters deal with substrates; and the last eight chapters discuss electrophysiology, clinical presentation, therapy, and evaluation of cardiac arrhythmias. Pioneers and experts in the field reevaluate in a clear and concise language the latest techniques of investigation and methods of treatment. They indicate, for example, what was known by all clinicians but rarely brought out in discussion: that the long-term use of type I antiarrhythmic drugs is limited by their side effects. Thus, the search for newer and better drugs must go on and on. The authors are cautious in adopting new surgical techniques. Atrioventricular modifications or ablation by cryosurgical or
Hungarian doctors angered by plans to privatise hospitals
Authors: Carl Kovac
Journal: BMJ (2001)

Two Hungarian associations of health professionals have reservations about a health ministry draft bill that would turn the country's 160 hospitals, all owned by municipalities or state universities, into businesses and doctors into private contractors.

The bill, scheduled to be presented to parliament this autumn, would convert hospitals and clinics into either non-profit making or shareholding operations. It proposes that these institutions contract medical specialists as entrepreneurs who would pay their own taxes and social security contributions, as is the practice in many countries in the European Union.

The ministry contends that such moves would put hospitals in a much healthier financial position because it would make them more …
NOTES ON A CASE OF TETAN Y.Read in the Section of Diseases of Children at the Forty-first Annual Meeting of the American Medical Association, at Nashville, Tenn., May, 1890.
Authors: JACOB SCHNECK
Journal: JAMA (1890)

Under the various names of tetany, tetanella, idiopathic muscular spasm, and carpo - pedal spasm, we find described a variety of cases which have, as prominent symptoms, more or less tonic contractions of the muscles of various parts of the body, beginning usually at the extremities and passing, in somewhat regular succession, to the muscles of the body and head. The consciousness of the individual is not disturbed during the paroxysm. The symptoms of this disease trench closely on those of a number of the functional neuroses; and it is probable that many of the cases reported under this heading are really spasms due to reflex irritation, caused by teething or a disordered condition of the alimentary canal; or to irritation produced in the nerve-centres by the distal ends of nerves, leading to them, being involved in cicatrices or other inflammatory products; these cases are permanently cured by removing the
Reply to José I. Lopéz's Letter to the Editor re: Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, et al. Stage pT0 in Radical Prostatectomy with No Residual Carcinoma and with a Previous Positive Biopsy Conveys a Wrong Message to Clinicians and Patients: Why Is Cancer Not Present in the Radical Prostatectomy Specimen? Eur Urol 2009;56:272–4
Authors: Rodolfo Montironi, Liang Cheng, Antonio Lopez-Beltran, Marina Scarpelli, Roberta Mazzucchelli, Gregor Mikuz, Ziya Kirkali, Francesco Montorsi
Journal: European Urology (2009)
Nonhormonal Therapies for Menopausal Hot Flashes
Authors: Heidi D. Nelson, Kimberly K. Vesco, Elizabeth Haney, Rongwei Fu, Anne Nedrow, Jill Miller, Christina Nicolaidis, Miranda Walker, Linda Humphrey
Journal: JAMA (2006)

ContextConcern regarding the adverse effects of estrogen and other hormones for treating menopausal symptoms has led to demand for other options; however, the efficacy and adverse effects of nonhormonal therapies are unclear.ObjectiveTo assess the efficacy and adverse effects of nonhormonal therapies for menopausal hot flashes by reviewing published randomized controlled trials.Data SourcesMEDLINE (1966-October 2005), PsycINFO (1974-October 2005), and the Cochrane Controlled Clinical Trials Register Database (1966-October 2005) were searched for relevant trials that provided data on treatment of menopausal hot flashes using 1 or more nonhormonal therapies.Study SelectionAll English-language, published, randomized, double-blind, placebo-controlled trials of oral nonhormonal therapies for treating hot flashes in menopausal women measuring and reporting hot flash frequency or severity outcomes.Data ExtractionTrials were identified, subjected to inclusion and exclusion criteria, and reviewed. Data on participants, interventions, and outcomes were extracted and trials were rated for quality based on established criteria. A meta-analysis was conducted for therapies with sufficient trials reporting hot flash frequency outcomes.Data SynthesisFrom 4249 abstracts, 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. The number of daily hot flashes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) (mean difference, −1.13; 95% confidence interval [CI], −1.70 to −0.57), 4 trials of clonidine (−0.95; 95% CI, −1.44 to −0.47), and 2 trials of gabapentin (−2.05; 95% CI, −2.80 to −1.30). Frequency was not reduced in meta-analysis of trials of red clover isoflavone extracts and results were mixed for soy isoflavone extracts. Evidence of the efficacy of other therapies is limited due to the small number of trials and their deficiencies. Trials do not compare different therapies head-to-head and relative efficacy cannot be determined.ConclusionThe SSRIs or SNRIs, clonidine, and gabapentin trials provide evidence for efficacy; however, effects are less than for estrogen, few trials have been published and most have methodological deficiencies, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women.
Immune mediated therapy and MEK inhibition: preclinical assessment of immunobiology and combination activity in vitro and in vivo
Authors: Ross Stewart, Edmund Poon, Stefanie Mullins, Amanda Watkins, Paul D Smith, Robert W Wilkinson
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Immune mediated therapies (IMT), such as anti-CTLA-4 and anti-PD-1/PD-L1, are showing significant promise in the treatment of solid tumors. However, although these treatments can show significant overall benefit, a subset of patients fails to respond. It is believed that activity
952-30 Left Ventricular Ejection Performance Improves Late After Aortic Valve Replacement in Patients with Aortic Stenosis and Reduced Ejection Fraction
Authors: Paul A. Robiolio, Vera H. Rigolin, Eric B. Lieberman, John S. Wilson, Steven E. Hearne, Katherine B. Kisslo, Cynthia H. Pierce, Thomas M. Bashore, J. Kevin Harrison
Journal: Journal of the American College of Cardiology (1995)
Long-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin
Authors: John P.H. Wilding
Journal: Annals of Internal Medicine (2012)

Background: Dapagliflozin, a selective inhibitor of sodium–glucose cotransporter 2, may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin. Objective: To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs. Design: A 24-week, randomized, placebo-controlled, multicenter trial followed by a 24-week extension period. An additional 56-week extension period is ongoing. (ClinicalTrials.gov registration number: NCT00673231) Setting: 126 centers in Europe and North America from 30 April 2008 to 19 November 2009. Patients: 808 patients with inadequately controlled type 2 diabetes mellitus receiving at least 30 U of insulin daily, with or without up to 2 oral antidiabetic drugs. Intervention: Patients were randomly assigned in a 1:1:1:1 ratio and allocated with a computer-generated scheme to receive placebo or 2.5, 5, or 10 mg of dapagliflozin, once daily, for 48 weeks. Measurements: The primary outcome was change in hemoglobin A1c from baseline to 24 weeks. Secondary outcomes included changes in body weight, insulin dose, and fasting plasma glucose level at 24 weeks and during the 24-week extension period. Adverse events were evaluated throughout both 24-week periods. Results: 800 patients were analyzed. After 24 weeks, mean hemoglobin A1c decreased by 0.79% to 0.96% with dapagliflozin compared with 0.39% with placebo (mean difference, −0.40% [95% CI, −0.54% to −0.25%] in the 2.5-mg group, −0.49% [CI, −0.65% to −0.34%] in the 5-mg group, and −0.57% [CI, −0.72% to −0.42%] in the 10-mg group). Daily insulin dose decreased by 0.63 to 1.95 U with dapagliflozin and increased by 5.65 U with placebo (mean difference, −7.60 U [CI, −10.32 to −4.87 U] in the 2.5-mg group, −6.28 U [CI, −8.99 to −3.58 U] in the 5-mg group, and −6.82 U [CI, −9.56 to −4.09 U] in the 10-mg group). Body weight decreased by 0.92 to 1.61 kg with dapagliflozin and increased by 0.43 kg with placebo (mean differences, −1.35 kg [CI, −1.90 to −0.80 kg] in the 2.5-mg group, −1.42 kg [CI, −1.97 to −0.88 kg] in the 5-mg group, and −2.04 kg [CI, −2.59 to −1.48 kg] in the 10-mg group). These effects were maintained at 48 weeks. Compared with the placebo group, patients in the pooled dapagliflozin groups had a higher rate of hypoglycemic episodes (56.6% vs. 51.8%), events suggesting genital infection (9.0% vs. 2.5%), and events suggesting urinary tract infection (9.7% vs. 5.1%). Limitation: Insulin doses were not titrated to target, and the study was not designed to evaluate long-term safety. Conclusion: Dapagliflozin improves glycemic control, stabilizes insulin dosing, and reduces weight without increasing major hypoglycemic episodes in patients with inadequately controlled type 2 diabetes mellitus. Primary Funding Source: AstraZeneca and Bristol-Myers Squibb.
Urban and Social Origins of Childhood Bronchitis in England and Wales
Authors: J. R. T. Colley, D. D. Reid
Journal: BMJ (1970)

A survey of respiratory disease in over 10,000 children aged 6 to 10 years living in contrasting urban and rural areas of England and Wales showed pronounced social class gradient in the frequency of chronic cough, history of bronchitis, and also in disease of ears and nose. A consistent rise in the frequency of chest conditions with increasing local levels of air pollution was clearly seen only among the children of semi-skilled and unskilled workers. No such gradient was obvious for diseases of the ear and nose. These trends in chest disease in children paralleled similar trends in mortal and disabling bronchitis among adults in the same areas. The excess rate for bronchitis in children and adults found in South Wales could not be accounted for by local levels of air pollution.
Duodenal Ulcer: The Present Status of Definitive Surgery; The Selection and Management of Patients Undergoing Operation
Authors: John R. Brooks, Francis D. Moore
Journal: New England Journal of Medicine (1959)

Clinical Settings for the Ulcer PatientPatients Not Requiring Definitive Ulcer Surgery Young, male or female, with early, first-episode pain or nonshock-producing bleeding. There is no disagreement on treatment for the young patient in the third or fourth decade of life who has his or her first early episode of ulcer pain. Such symptoms, frequently occurring at a time of emotional stress related to study, job acquisition or real or contemplated matrimony, can be expected to subside with a properly conducted diet and medicines and with at least an attempt to remove known emotional or environmental stimuli. In females . . .
Outcomes of Cardiac Transplantation in Single-Ventricle Patients With Plastic Bronchitis: A Multicenter Study
Authors: Jeffrey G. Gossett, Christopher S. Almond, Richard Kirk, Steven Zangwill, Marc E. Richmond, Paul F. Kantor, Margaret A. Tresler, Susanna M. Lenderman, David C. Naftel, Kathleen L. Matthews, Elfriede Pahl
Journal: Journal of the American College of Cardiology (2013)
Preferential distribution of inhibitory cardiac receptors with vagal afferents to the inferoposterior wall of the left ventricle activated during coronary occlusion in the dog.
Authors: M D Thames, H S Klopfenstein, F M Abboud, A L Mark, J L Walker
Journal: Circulation Research (1978)

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by cardiac receptors during anterior as opposed to inferoposterior ischemia of the left ventricle of the dog. Cessation of perfusion (coronary "occlusion") of the circumflex coronary artery (Cx) in 29 chloralose-anesthetized dogs with common carotids ligated (group I) resulted in significant bradycardia and hypotension, but in no significant change in perfusion pressure in the gracilis muscle perfused at constant flow. Occlusion of the left anterior descending coronary artery (LAD) produced less hypotension, no change in heart rate, and vasoconstriction in the gracilis. After vagotomy and aortic nerve section, no significant change in heart rate or gracilis perfusion pressure was observed during lad or Cx occlusion, and the blood pressure responses to LAD and Cx occlusion were not different. In nine dogs with sinoaortic denervation (group II), brief Cx occlusion resulted in bradycardia, hypotension, and vasodilation in the gracilis muscle. LAD occlusion in group II dogs caused less hypotension and no change in heart rate or gracilis perfusion pressure. After vagotomy, the bradycardia and vasodilation resulting from Cx occlusion were abolished and the blood pressure responses to LAD and Cx occlusion were not different. The weights of left ventricle perfused by each occluded vessel were not different. These data show that left ventricular receptors with vagal afferents which are activated during coronary occlusion and which mediate cardioinhibitory and vasodepressor responses are located mainly in the inferoposterior left ventricle of the dog heart.
Activated Tyrosine Kinase Ack1 Promotes Prostate Tumorigenesis: Role of Ack1 in Polyubiquitination of Tumor Suppressor Wwox
Authors: Nupam P. Mahajan, Young E. Whang, James L. Mohler, H. Shelton Earp
Journal: Cancer Research (2005)

Aberrant activation of tyrosine kinases is linked causally to human cancers. Activated Cdc42-associated kinase (Ack1), an intracellular tyrosine kinase, has primarily been studied for its signaling properties but has not been linked to specific pathologic conditions. Herein, we report that expression of activated Ack1 in LNCaP cells, while minimally increasing growth in culture, enhanced anchorage-independent growth in vitro and dramatically accelerated tumorigenesis in nude mice. Molecular chaperone heat shock protein 90beta (Hsp90beta)-bound Ack1 and treatment of cells with geldanamycin, a Hsp90 inhibitor, inhibited Ack1 kinase activity and suppressed tumorigenesis. Further, we identify the tumor suppressor WW domain containing oxidoreductase (Wwox) as an Ack1-interacting protein. Activated Ack1 tyrosine phosphorylated Wwox, leading to rapid dissociation of the Ack1-Wwox complex and concomitant Wwox polyubiquitination followed by degradation. Tyrosine phosphorylation of Wwox was critical for its degradation, as splice variant WwoxDelta5-8 that was not phosphorylated by Ack1 failed to undergo polyubiquitination and degradation. It has been reported that phosphorylation of Wwox at Tyr33 stimulated its proapoptotic activity. We observed that Y33F Wwox mutant was still tyrosine phosphorylated and polyubiquitinated by Ack1 action. Site-directed mutagenesis revealed that activated Ack1 primarily phosphorylated Wwox at Tyr287, suggesting that phosphorylation of distinct tyrosine residues activate or degrade Wwox. Primary androgen-independent prostate tumors but not benign prostate showed increased tyrosine-phosphorylated Ack1 and decreased Wwox. Taken together, these data indicate that Ack1 stimulated prostate tumorigenesis in part by negatively regulating the proapoptotic tumor suppressor, Wwox. Further, these findings suggest that Ack1 could be a novel therapeutic target for prostate cancer.
IMPROVEMENT OF EARLY INVASIVE TREATMENT FOR NSTE-ACS OVER TIME IN CLINICAL PRACTICE IN EUROPE: LESSONS FROM THE EURO HEART SURVEY ACS REGISTRY
Authors: Anselm K. Gitt, Matthias Hochadel, Wojtek Wojakowski, Marek Gierlotka, Hector Bueno, Ralf Zahn, Uwe Zeymer, Jean-Pierre Bassand, Francois Schiele
Journal: Journal of the American College of Cardiology (2011)
The Diagnosis of Circulatory Shunts by the Nitrous Oxide Test
Authors: RICHARD J. SANDERS, ANDREW G. MORROW
Journal: Circulation (1958)

The nitrous oxide test for the detection and localization of left-to-right shunts has previously been studied clinically. Further experience with the method has shown that a higher N 2 O concentration and an earlier sampling period result in a larger arteriovenous N 2 O difference that increases the sensitivity of the test and further minimizes the importance of possible analytic errors. In addition, a method is described of determining the magnitude of the shunt from the results of a N 2 O test. The results of 150 N 2 O tests performed with the improved technic are presented, and compared to the results obtained with the O 2 method in a group of patients on whom both tests were carried out.
Interaction between selenium and inorganic mercury.
Authors: M Berlin
Journal: Environmental Health Perspectives (1978)

Data on mercury and selenium interaction in the mammalian body are reviewed. Experimental data from studies on rats show that selenium interacts with mercury metabolism and toxicity after exposure to mercuric mercury. Autopsy data from workers exposed to mercury vapor indicate an association between mercury and selenium retention in the central nervous system, suggesting the formation of a mercury-selenium complex. In animal experiments, mercuric mercury interferes with selenium metabolism and toxicity. Available data do not, at present, permit deduction as to whether additional selenium intake in man, exposed to mercury vapor or mercuric mercury, will have any effect, beneficial or adverse.