tbuckley/cabot-search huggingface dataset:
Ancel Keys Lecture.
Authors: G Rose
Journal: Circulation (1991)

W hen I was a young doctor, we used to explain to our patients with atherosclerotic problems that unfortunately their arteries were wearing out: We did not need to seek causes because it was a result of old age.We were vaguely aware that the incidence rate varied in different populations, but no one saw this as an intellectual challenge; we were fatalists.It is to the Framingham group that we owe our understanding that this disease does not strike indi- viduals haphazardly like lightning; rather, it strikes very selectively and is drawn by identifiable risk factors.But it was Ancel Keys who led us to confront the more fundamental question, namely, why did the western epidemic of heart disease occur in the first place?Why do population incidence rates vary?Keys raised the debate regarding these questions in cardiology and preventive medicine to a new level.He did not merely provide some of the main answers; he also taught us to investigate the problems of a mass disease from a new viewpoint -that of the sick population.To honor his achievement by giving this first Ancel Keys Lecture is a weighty and anxious responsibility.My qualification for attempting the task is simply a keen awareness of the importance of his contribution.I shall first examine the preventive approach to individuals based on identifying and correcting their risk factors; then, I shall turn to the more basic and powerful population approach, which tackles the underlying causes of high incidence rates, and I shall explore the implications of some new data.My principal conclusion is that the two approaches are neither opposite nor even independent but rather highly interactive. Prevention in IndividualsMedicine is concerned primarily with patients, and preventive medicine is concerned with preventing people from becoming patients.Our profession is strongly oriented toward the problems of individuals and a wish to prevent them from changing from normal, healthy people into sick people.This leads us to think of the sick as a distinct group and of disease as a defined entity that is separate from normalcy.Indeed, the basis of clinical diagnosis is the assump- tion that with respect to each disease, the world is divided into just two classes -those who have it and those who do not.
Health in Africa: Medical brain drain is a consequence of bad policy
Authors: Gbola O Sangosanya
Journal: BMJ (2005)

EDITOR—The medical brain drain is not new.1 During my undergraduate medical education in Africa, most of our lecturers had at some stage trained abroad. Our impression was that standards were better in Europe and America. Attached to this was a clear message that if you wanted to be the best, experience abroad was crucial. …
301 HEDGEHOG PATHWAY EXPRESSION IN PROGRESSIVE LIVER INJURY
Authors: C.A. Grzelak, K. Ajami, M.A. Eckersley-Maslin, B. Patkunanathan, S.R. Richardson, C. Wicking, G.W. McCaughan, N.A. Shackel, F.J. Warner
Journal: Journal of Hepatology (2009)
The Risk of AIDS After Hepatitis Vaccination-Reply
Authors: henry Sacks
Journal: JAMA (1985)

<h3>In Reply.—</h3> Mr Upfal seems to have placed more emphasis on our maximum estimate for the rate of AIDS induced by hepatitis B vaccination than on our best estimate. Our best estimate of the rate of AIDS from the vaccine was, and remains, zero. While it is possible that currently available vaccine was prepared from plasma with a higher likelihood of containing the AIDS agent, there are no data to support the contention that the infectious AIDS agent escaped the purification and inactivation procedures. In fact, since our article was submitted, more evidence on the safety of the vaccine has appeared. Vaccine recipients have normal T-cell subsets<sup>1</sup>and have not been found to have increased rates of antibody to human T-cell leukemia Virus-III.<sup>2</sup>Sensitive procedures have failed to find material derived from this virus in vaccine.<sup>3</sup>Thus, we are even more convinced now than when we prepared our
Abstract 5612: Pretreatment with chemotherapy can enhance the immunogenicity of tumors by promoting adaptive immune responses
Authors: Wai M. Liu, Daniel W. Fowler, Peter Smith, Angus G. Dalgleish
Journal: Cancer Research (2010)

Abstract Cancer patients are typically immuno-compromised, and it has been long felt that immune-intervention is not compatible with standard chemotherapies. However, evidence suggests that standard chemotherapy drugs may stimulate beneficial changes in both the immune system and tumour. We have assessed the impact of chemotherapy agents (cyclophosphamide, oxaliplatin and gemcitabine (GEM)) on the potential immunogenicity of tumour cells (A549, Caki2, HCT116, MCF7 and PC3), and investigated the interactions between supernatants derived from these stressed cells and cells of the immune system, by studying the activities between dendritic cells and T-cells. Results showed that some chemotherapy agents can increase total MHC class I expression on tumour cells, even when expression is low. For example, expression on MCF7 cells was increased by ∼4-fold upon treatment with GEM (133 ± 31 vs. 33 ± 7.8 in untreated cells; p&amp;lt;0.001). The increases in expression were associated with enhanced killing by cytotoxic T-cells (e.g. in HCT116, the MTT reading for GEM pre-treated tumour cells cultured with T-cells was 0.17 ± 0.011 vs. 0.12 ± 0.0096 in untreated tumour cells with T-cells added; p=0.007), which were negated by HLA1-blockade. Results also showed that the supernatants derived from tumours treated with chemotherapy augmented DC-maturation as indicated by increases in the maturation markers CD80/CD83/CD86. Furthermore, DC function was enhanced as confirmed by an increase in DC-mediated proliferation of CFSE-loaded T-cells. For example, the percentage of CD3+/CD4+ cells with a reduced CFSE content (indicating proliferation) was higher in cells exposed to supernatants derived from GEM treated A549 cells (12 ± 2.1% vs. 5.2 ± 1.4% in controls where the supernatant was from untreated tumours; p=0.028). In summary, there is evidence that a facet of immune surveillance can be restored by appropriate chemotherapy agents. Also, tumours exposed to some chemotherapy may deliver signals that can mature DCs, which ultimately enhances T-cell responses. This work was supported by the Cancer Vaccine Institute. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5612.
A chromosomal translocation in cyclin D1–negative/cyclin D2–positive mantle cell lymphoma fuses the CCND2 gene to the IGK locus
Authors: Stefan Gesk, Wolfram Klapper, José I. Martín-Subero, Inga Nagel, Lana Harder, Kai Fu, Heinz-Wolfram Bernd, Dennis D. Weisenburger, Reza Parwaresch, Reiner Siebert
Journal: Blood (2006)
Growth and Bone-Age Retardation in Cystic Fibrosis
Authors: James L. Dennis
Journal: JAMA (1965)

Children with cystic fibrosis respond to anabolic steroids with increments in height and weight; a regression of clubbing and cyanosis of digits; increased muscle tone, physical tolerance, and cheerfulness; enlargement of the phallus; and advances in skeletal maturation. In contrast to normal children who have been given anabolic steroids, the height gain in children with cystic fibrosis was relatively greater than the weight gain; increments in bone age were slightly greater than either. The degree of bone-age deficit present appears to correlate with the severity of the disease, hence patients with severe disease can be treated with steroids for longer periods of time than those who have minimal involvement. Anabolic steroids did not alter sweat chloride patterns. Anabolic steroid therapy for cystic fibrosis must be considered palliative, temporary, and still somewhat experimental. Only prolonged studies of a longitudinal nature can determine whether such therapy will affect the ultimate stature of these patients.
N-Acetyl-cysteine modulates inducible nitric oxide synthase gene expression in human hepatocytes
Authors: Pedro Lorenzo Majano, Jesús Medina, Itxaso Zubı́a, Lourdes Sunyer, Enrique Lara-Pezzi, Alejandra Maldonado-Rodrı́guez, Manuel López-Cabrera, Ricardo Moreno-Otero
Journal: Journal of Hepatology (2004)
Femtosecond Lasers for LASIK Flap Creation
Authors: Ayad A. Farjo, Alan Sugar, Steven C. Schallhorn, Parag A. Majmudar, David J. Tanzer, William B. Trattler, John B. Cason, Kendall E. Donaldson, George D. Kymionis
Journal: Ophthalmology (2012)
Responding to Adolescent Needs
Authors: Maria C. Morgan
Journal: JAMA (1981)

This slim volume highlights interesting topics of particular relevance to adolescence—family, schools, law, health, sex, and work—written by prestigious and distinguished authors of national renown. Although Dr Daniel Offer, in the foreword, states: "It is a book full of facts and figures, which present unique suggestions to the professional working with adolescents," the reader may find the scope of the suggestions variable and the strengths of the book uneven. This may be a result of the diversity of chapter authors, with little flow from one chapter to another. The first chapter, "Family Maladaptation Reflected in Drug Abuse and Delinquency" details the interweaving in the relationship between family dynamics and the evolution of drug misuse and delinquent behavior. Family situations are presented in a clear, factual, and insightful manner. The chapter entitled "Families, Communities and Rebellious Adolescents" is equally remarkable. One finds eloquent statements like "Where the dominant strain in the
Four Years of Replacing Ailing Hearts: Surgeons Assess Data, Questions Remain
Authors: Helene M. Cole
Journal: JAMA (1986)

The author reviews the clinical course of those patients in the United States who have received permanent or temporary artificial hearts and presents their physicians' assessments of the failures and successes of the devices. Several transplant surgeons offer their opinions on the controversial issue of the prioritization in selection for a human heart transplant of patients maintained on a temporary artificial heart (bridge-to-transplantation) and on the Food and Drug Administration's criteria for centers permitted to use the bridge-to-transplantation procedure. Cole concludes that, despite the optimism of some investigators, the risks associated with either temporary or permanent artificial hearts may be too great to justify further use. Still unanswered are the public policy issues of payment for these programs and of equitable allocation of donor organs.
Prevention of Bioprosthetic Heart Valve Calcification by Ethanol Preincubation
Authors: Narendra Vyavahare, Danielle Hirsch, Eyal Lerner, Jonathan Z. Baskin, Frederick J. Schoen, Richard Bianco, Howard S. Kruth, Robert Zand, Robert J. Levy
Journal: Circulation (1997)

Background Calcification of the cusps of bioprosthetic heart valves fabricated from either glutaraldehyde cross-linked porcine aortic valves or bovine pericardium frequently causes the clinical failure of these devices. Our investigations studied ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valves as a new approach to prevent cuspal calcification. The hypothesis governing this approach holds that ethanol pretreatment inhibits calcification resulting from protein structural alterations and lipid extraction. Methods and Results Results demonstrated complete inhibition of calcification of glutaraldehyde-pretreated porcine bioprosthetic aortic valve cusps by 80.0% ethanol in rat subdermal implants (60-day ethanol-pretreated calcium level, 1.87±0.29 μg/mg tissue compared with control calcium level, 236.00±6.10 μg/mg tissue) and in sheep mitral valve replacements (ethanol-pretreated calcium level, 5.22±2.94 μg/mg tissue; control calcium level, 32.50±11.50 μg/mg tissue). The mechanism of ethanol inhibition may be explained by several observations: ethanol pretreatment resulted in an irreversible alteration in the amide I band noted in the infrared spectra for both purified type I collagen and glutaraldehyde cross-linked porcine aortic leaflets. Ethanol pretreatment also resulted in nearly complete extraction of leaflet cholesterol and phospholipid. Conclusions Ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valve bioprostheses represents a highly efficacious and mechanistically based approach and may prevent calcific bioprosthetic heart valve failure.
Abstract 2716: Tailored-dose capecitabine chemotherapy as adjuvant treatment in elderly colon cancer patients
Authors: Hye Jung Chang, Keun-Wook Lee, In Sil Choi, Yu Jung Kim, Jee Hyun Kim, Soo-Mee Bang, Jong-Seok Lee
Journal: Cancer Research (2010)

Abstract Backgrounds Elderly patients with curatively resected colon cancer (CC) receive adjuvant chemotherapy less frequently and show poorer compliance than young patients. The dosage of capecitabine in elderly patients is still controversial. Although the capecitabine dosage of 2000 mg/m2/day (days 1∼14, every 3 weeks) is commonly used in elderly patients with various solid tumors, fixed-dose reduction in all patients may compromise the effect of adjuvant treatment. Therefore, in this study, we analyzed the feasibility of tailored-dose capecitabine therapy, and clinical parameters associated with dose reduction of capecitabine and toxicities in elderly CC patients. Methods Elderly CC patients (≥70 years) with high risk stage II or stage III who had received adjuvant capecitabine monotherapy were prospectively enrolled. Eight cycles of capecitabine was planned. The starting dosage of capecitabine was 2000 mg/m2/day (days 1∼14, every 3 weeks). On the second cycle, the dosage was escalated to 2500 mg/m2/day if the patient was tolerable to the first cycle. Results Eighty-two patients were enrolled and 582 cycles of capecitabine were administered. Median age was 74.5 years (range: 70-90 years). Fifty-six patients (68%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0/1 and 26 patients (32%) had ECOG PS grade 2, respectively. Sixty-seven patients (82%) completed 8 cycles of chemotherapy. Fifty-six patients (68%) could receive the escalated dose of capecitabine at the second cycle and 24 patients (29%) could complete the 8 cycles at escalated dose (2500 mg/m2/day). The mean relative dose intensity (RDI) of capecitabine was 81.3% compared with escalated dose (2500 mg/m2/day). Creatinine clearance (Ccr) &amp;lt; 50 mL/min and Charlson Age Comorbidity Index (CACI) ≥ 8 were independent predictive factors for reduced administration of capecitabine dosage in multivariate analysis (P = 0.02 and 0.03, respectively). Severe hematologic toxicities (per cycle) included grade 3/4 neutropenia (0.9%) and thrombocytopenia (0.3%). Severe non-hematologic toxicities (per patient) included grade 3/4 hand-foot syndrome (26%), anorexia (6%) and diarrhea (6%). Conclusion The tailored-dose for elderly CC patients receiving adjuvant capecitabine therapy is feasible and may be an appropriate approach to avoid unnecessarily uniform dose reduction and increased toxicities. When determining adequate dosage for elderly patients, Ccr and CACI should be considered as predictive factors for capecitabine dose reduction. 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 2716.
Transthoracic three dimensional echocardiography: Defining requirements for rapid and accurate left ventricular volumes and ejection fraction measurements
Authors: Youssef F.M. Nosir, Wim B. Vletter, Eric Boersma, Folkert J. Ten Cate, Paolo M. Fioretti, Jos R.T.C. Roelandt
Journal: Journal of the American College of Cardiology (1996)
756 QUASISPECIES CHANGES DETECTED IN HYPERVARIABLE REGION 1 OF HEPATITIS C GENOME WITH HIGH-RESOLUTION DNA MELTING ANALYSIS IN TREATED AND UNTREATED CHRONIC HEPATITIS C PATIENTS
Authors: I. Hrstic, B. Grahovac, B. Mohar, B. Kolaric, R. Ostojic, B. Vucelic
Journal: Journal of Hepatology (2010)
Potential health implications for acid precipitation, corrosion, and metals contamination of drinking water.
Authors: W E Sharpe, D R DeWalle
Journal: Environmental Health Perspectives (1985)

Potential health effects of drinking water quality changes caused by acid precipitation are presented. Several different types of water supply are discussed and their roles in modifying acid rain impacts on drinking water are explained. Sources of metals contamination in surface water supplies are enumerated. The authors present some results from their research into acid rain impacts on roof-catchment cisterns, small surface water supplies, and lead mobilization in acid soils. A good correlation was obtained between cistern water corrosivity as measured by the Ryznar Index (RI) values and standing tapwater copper concentrations. However, lead concentrations in tapwater did not correlate well with cistern water RI. A modified linear regression model that accounted for Ryznar Index change during storage in vinyl-lined cisterns was used to predict the Ryznar Index value at a copper concentration of 1000 micrograms/L. The predicted RI was greater than the RI of precipitation with a pH of 5.3, indicating that anthropogenically acidified precipitation may result in cistern tapwater copper concentrations in excess of the 1000 micrograms/L suggested drinking water limit. Good correlations between tapwater Ryznar Index and tapwater copper and lead concentrations were not obtained for the small surface water supply. Aluminum concentrations in reservoir water were similar to those in stream source water. Limited data were also presented that indicated lead was present in acid forest soil leachate and streams draining such soils in relatively small concentrations. Where appropriate, recommendations for future research are included with the discussions of research results.
Immunotherapy with PI3K Inhibitor and Toll-Like Receptor Agonist Induces IFN-γ+IL-17+ Polyfunctional T Cells That Mediate Rejection of Murine Tumors
Authors: Neil A. Marshall, Karen C. Galvin, Anna-Maria B. Corcoran, Louis Boon, Rowan Higgs, Kingston H.G. Mills
Journal: Cancer Research (2011)

Abstract The immunosuppressive microenvironment in tumors hampers the induction of antitumor immunity by vaccines or immunotherapies. Toll-like receptor (TLR) ligands have the potential to treat tumors, but they can exert a mixture of positive and negative effects on inflammation in the tumor microenvironment. In this study, we show that specific small molecule inhibitors of phosphoinositide 3-kinase (PI3K) relieve immunosuppression to heighten the proinflammatory effects of TLR ligands that support antitumor immunity. Multiple strategies to inhibit PI3K in dendritic cells (DC) each led to suppression of interleukin (IL)-10 and TGF-β but did affect IL-12 or IL-1β induction by the TLR5 ligand flagellin. In three different mouse models of cancer, combining flagellin with a class I PI3K inhibitor, either with or without a DC vaccine, delayed tumor growth and increased survival, with some animals exhibiting complete rejection and resistance to secondary challenge. Tumor growth suppression was associated with increased accumulation of polyfunctional T cells that secreted multiple effector cytokines, including IFN-γ, IL-17, and IL-2. Therapeutic protection was abolished in mice deficient in IL-17 or deprived of IFN-γ. Together, our results indicate that PI3K inhibition heighten the antitumor properties of TLR ligands, eliciting tumor regression directly but also indirectly by relieving suppressive signals that restrict potent antitumor T-cell responses. These findings suggest important uses for PI3K inhibitors in heightening responses to cancer immunotherapy and immunochemotherapy. Cancer Res; 72(3); 581–91. ©2011 AACR.
Circus movement in rabbit atrial muscle as a mechanism of tachycardia. II. The role of nonuniform recovery of excitability in the occurrence of unidirectional block, as studied with multiple microelectrodes.
Authors: M A Allessie, F I Bonke, F J Schopman
Journal: Circulation Research (1976)

Periods of tachycardia were induced in isolated segments (15 X 15 mm) of rabbit left atrium by local application of a properly timed premature stimulus. We used a special device for multiple synchronous microelectrode recordings of responses of more than 100 fibers during the initiation of tachycardia. We clearly demonstrated circus movement of the impulse through a small area of atrial muscle as the underlying mechanism. The premature impulse was conducted antegrade in only one direction, whereas in the other directions antegrade conduction failed. The local responses of the fibers in the blocked area served as a temporary obstacle for return of the premature impulse. When these fibers recovered their excitability before extinction of the premature impulse, they were reentered in a retrograde direction, and the impulse traveled in a circular route. During the propagation of a premature beat, local block, which set the stage for circus movement, was caused by nonuniform recovery of excitability of the atrium. We related the spread of activation of a premature impulse to the naturally occurring spatial dispersion in refractory periods and found that local conduction block invariably was associated with an area of delayed restoration of excitability. Artificial induction of differences in refractory periods by regional application of carbamylcholine made it clear that a disparity in refractory periods of only 11-6 msec between adjacent areas may be sufficient to cause local conduction block of a properly timed premature impulse.
A memorable patient: Ward cleaner's clinical observation
Authors: V M Sethukumar
Journal: BMJ (1997)

It was a busy evening in the casualty department in India, where I was the medical student shadowing a senior doctor.

We were interrupted by the domestic cleaner, who ran up to us asking us to see a patient on the trolley rather urgently. Not waiting for an answer she took the senior doctor by the hand across the room to the patient. …