tbuckley/cabot-search huggingface dataset:
Formal Discussion of “Breast Cancer Incidence and Nutritional Status with Particular Reference to Body Weight and Height”
Authors: Brian MacMahon
Journal: Cancer Research (1975)

Dr. de Waard and his colleagues in Utrecht were among the first to bring together epidemiological and endocrino logical expertise in the investigation of cancer of the breast. From its beginning their work has included consideration of the relationship of the disease to body form and nutrition. Anything they had told us would therefore have been of interest and relevance to this conference. It is, however, not sufficient for Dr. de Waard to be of historical interest. He has, once again, put new data before us that require us to look at our old concepts from a new perspective, and just when the old concepts seemedto be falling neatly into place. In the 1974 analysis of their prospective study, de Waard and Halewijn (I) pointed once again to high body weight as a risk factor for breast cancer in postmenopausal women. While such a relationship had been demonstrated previously in several case-control studies, there are also several studies in which it had not been found. In addition, even in those studies in which the association was found, it seemed generally less strong than in the Dutch material. It seemed reasonable to take into consideration the fact that in most previous studies the women against whom the cases were compared were patients with other diseases, a group in which overweight women might well be overrepresented, therefore dampening any real difference existing between breast cancer cases and normal women of comparable age. Belief that the risk associated with overweight had been underestimated in the past was strengthened by the fact that knowledge was being developed of a mechanism that might account for the relationship. Most of the components of this knowledge have been referred to by Dr. de Waard in his present paper; these include the role of estrogens in breast cancer and specifically their role around the time of menopause as evidenced in the protective effect of surgical castration and the high risk associated with late menopause, de Waard's own work on the persistence of estrogenic cervical smears in overweight women, the demonstration of the production of estrone in adipose tissue of postmenopau sal women, and the probable role of this process in the etiology of endometrial cancer. However, de Waard's recent analysis suggestedthat the whole story did not lie in obesity or overweight. Indeed, although independent effects were found for both height and
Abstract 19452: Cost-Effectiveness of Single-Chamber Compared with Dual-Chamber and Single-Lead with Atrial Sensing Implantable Cardioverter Defibrillators
Authors: David W Hutton, Michael J Harvey, Jay P Thaker, James V Freeman
Journal: Circulation (2014)

Introduction:  In patients receiving primary or secondary prevention implantable cardioverter defibrillators (ICDs) without pacing indications, dual-chamber devices may increase perioperative risks compared with single-chamber devices, yet they may also detect atrial fibrillation (AF) and prevent inappropriate shocks.   Hypothesis:  Dual-chamber and single-lead with atrial sensing ICDs may be a cost-effective alternative to single-chamber ICDs.   Methods:  We used a Markov decision model to evaluate the costs, quality adjusted life expectancy and incremental cost-effectiveness of single-chamber, dual-chamber, and single-lead with atrial sensing ICDs. Our base case was a 65 year-old patient receiving a primary or secondary prevention ICD without pacing indications. The model included perioperative adverse events and long-term inappropriate shocks, AF detection, AF treatment, and stroke.   Results:  When compared to the single-chamber ICD, the dual-chamber ICD had an incremental-cost-effectiveness ratio (ICER) of $44,087 per quality-adjusted life-year (QALY) gained (Table). When the new single-lead ICD with atrial sensing was added as an alternative therapy, it had an ICER of $23,904 per QALY compared to the single-chamber device. These results were sensitive to the patient’s age, and the ability of the atrial sensing devices to detect atrial fibrillation and avoid inappropriate shocks.   Conclusions:  For patients receiving primary or secondary prevention ICDs without pacing indications, dual-chamber ICDs may be cost-effective relative to single-chamber devices and a new single-lead with atrial sensing ICD is likely a very cost-effective alternative.
LACK OF CORRELATION BETWEEN SYMPTOMS AND DEGREE OF RENAL IMPAIRMENT
Authors: L H NEWBURGH, A A CAMARA
Journal: Annals of Internal Medicine (1951)

Article1 July 1951LACK OF CORRELATION BETWEEN SYMPTOMS AND DEGREE OF RENAL IMPAIRMENTL. H. NEWBURGH, F.A.C.P., AUGUSTO A. CAMARAL. H. NEWBURGH, F.A.C.P.Search for more papers by this author, AUGUSTO A. CAMARASearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-35-1-39 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a recent publication from this laboratory1 the work of Sirota, Baldwin and Villarreal,2 showing that the 24-hourly volume of glomerular filtrate can be measured satisfactorily, was confirmed. In the course of our studies it became evident that the disturbances from which the patients were suffering bore no close relationship to the degree of functional impairment of the glomeruli.It is not uncommon for the initial stages of glomerular nephritis to be wholly symptomless and its presence to be detected solely by the characteristic findings in the urine. In such instances, the patient may continue to be unaware that he...Bibliography1. CamaraNewburgh AALH: The 24-hour endogenous creatinine clearance as a clinical measure of the functional state of the kidneys, J. Lab. and Clin. Med. 37: 743, 1951. MedlineGoogle Scholar2. SirotaBaldwinVillarreal JHDSH: Diurnal variations of renal function in man, J. Clin. Investigation 29: 187, 1950. CrossrefMedlineGoogle Scholar3. Newburgh LH: The significance of the extracellular fluid in clinical medicine, 1946, Edwards Bros., Ann Arbor, Mich., p. 46. Google Scholar4. LeafCamara AAA: Renal tubular secretion of potassium in man, J. Clin. Investigation 28: 1526, 1949. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ann Arbor, Michigan*Received for publication March 24, 1950.From the Department of Internal Medicine, The Medical School, University of Michigan, Ann Arbor, Michigan.Aided by a grant from the United States Public Health Service. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byOn the pathogenesis of uremiaDie NiereninsuffizienzDisorders of renal functionManagement of chronic renal failureSome Therapeutic Dilemmas in Chronic Bright's Disease 1 July 1951Volume 35, Issue 1Page: 39-44KeywordsMedical servicesNephritisUrine ePublished: 1 December 2008 Issue Published: 1 July 1951 PDF downloadLoading ...
Abstract 13915: Atrial Fibrillation Begets Atrial Fibrillation in Cryptogenic Stroke Patients: Results from the Crystal-AF Trial
Authors: Rod S Passman, Jodi L Koehler, Paul D Ziegler
Journal: Circulation (2014)

Introduction: Initial episodes of atrial fibrillation (AF) detected following a cryptogenic stroke (CS) may be brief in duration and the clinical relevance of such episodes is uncertain. Hypothesis: We investigated whether an initial brief episode of AF was predictive of subsequent long duration AF episodes in CS patients (pts) with an insertable cardiac monitor (ICM). Methods: CS pts (n=208, age 61.6±11.3 years, 66% male) randomized to the ICM arm of the CRYSTAL-AF study and inserted with a device (Reveal® XT) were followed for 21±9 months. AF episodes (&gt;30 seconds) were independently adjudicated and the first adjudicated AF episode was classified as brief (&lt;1 hour) or long (≥1 hour). The incidence of subsequent long duration AF episodes among pts with an initially brief episode was computed. The impact of episode duration on prescription of oral anticoagulation (OAC) therapy was also assessed. Results: Among 36 pts with an adjudicated AF episode for which duration information was available, the initial episode was classified as brief in 18 (50%) pts and long in 18 (50%) pts. Among those with initially brief episodes, 10 (56%) experienced only subsequent brief episodes while 8 (44%) went on to experience at least one long AF episode. The median time between the initial brief episode and first long AF episode was 75 days [interquartile range: 27-624 days]. OAC was prescribed in 7/10 pts (70%) with only brief AF episodes compared to 26/26 pts (100%) with at least one long episode of AF (p=0.017). Conclusion: Initial AF episodes in pts with CS are equally likely to be of short or long duration. However, nearly half of CS pts with initially brief episodes of AF subsequently have long duration episodes detected much later via prolonged monitoring with ICMs. Therefore, early detection of brief AF episodes may merit more rigorous monitoring of AF with ICMs since physicians were significantly more likely to prescribe OAC for secondary stroke prevention in response to longer duration episodes.
Competitive Repopulation Assay of Two Gene-Marked Cord Blood Units in NOD/SCID/γcnull Mice
Authors: Takashi Yahata, Kiyoshi Ando, Hiroko Miyatake, Tomoko Uno, Tadayuki Sato, Mamoru Ito, Shunichi Kato, Tomomitsu Hotta
Journal: Molecular Therapy (2004)

In multiunit cord blood transplantation, hematopoietic stem cells from each unrelated cord blood (UCB) unit competitively reconstitute the hematopoietic system in a recipient. To evaluate the fate of the progeny of each UCB unit and to determine the effects of graft-versus-graft reaction, we established a novel competitive repopulation assay using NOD/SCID/γcnull mice in which human T lymphocytes develop from CD34+ cells. CD34+ cells from each UCB unit were labeled with recombinant lentivirus vectors carrying genes encoding either enhanced green fluorescent protein (EGFP) or enhanced yellow fluorescent protein (EYFP). Hematopoietic chimerism composed of both EGFP+ and EYFP+ cells was stably maintained up to 6 months after transplantation with purified CD34+ cells; the ratio of EGFP+ to EYFP+ cells in peripheral blood and bone marrow posttransplantation was equivalent to the ratio of these cells at transplantation. However, when mononuclear cells from two UCB units were cotransplanted with CD34+ cells, engraftment was highly competitive, with cells from only one or the other of the two UCB units surviving. Further subfractionations of mononuclear cells indicate that the skewed chimerism that is often observed in clinical multiunit cord blood transplantation may be mediated by the cooperation of both CD4+ and CD8+ T cells. The assay established here will be a useful tool for analyzing hematopoietic reconstitution in clinical multiunit cord blood transplantation.
Abstract 16732: Urinary 11-Dehydro-Thromboxane B2 is Associated With Vascular and Non-Vascular Events in Atrial Fibrillation Patients
Authors: Daniele Pastori, Pasquale Pignatelli, Roberto Cangemi, William Hiatt, Alessio Farcomeni, Simona Bartimoccia, Tommasa Vicario, Tommaso Bucci, Roberto Carnevale, Gregory Lip, Francesco Violi
Journal: Circulation (2014)

Introduction: Non-Valvular Atrial Fibrillation (AF) patients show high residual cardiovascular risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of cardiovascular events, but its predictive value in anticoagulated AF patients is unknown. Hypothesis: Aim of this was to assess whether urinary 11-dehydro-TxB2 is a predictor of cardiovascular events in anticoagulated patients with AF. Methods: Prospective single-center cohort study, including 864 consecutive AF patients. Mean time of follow-up was 30.0 months yielding 2062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end-point was the composite of myocardial infarction, ischemic stroke, cardiac revascularization, cardiovascular death and deaths from any cause. Results: Cardiovascular events occurred in 98 (11.3%), whilst 81 patients died (9.4%), including 55 from cardiovascular and 26 from non-cardiovascular causes. At baseline, urinary 11-dehydro-TxB2 levels were higher in patients who experienced a cardiovascular event (p&lt;0.001). An increased rate of cardiovascular events, cardiovascular death and all-cause death was observed across tertiles of 11-dehydro-TxB2 (p&lt;0.001). On Cox proportional hazards analysis, CHA2DS2-VASc score, second and third tertile of 11-dehydro-TxB2, compared to the first tertile, were significant predictors of vascular and non-vascular events. On a logistic regression analysis, 11-dehydro-TxB2 levels progressively increase with increasing CHA2DS2-VASc scores. Conclusions: Urinary 11-dehydro-TxB2 predicts residual risk of cardiovascular events in anticoagulated atrial fibrillation patients. Urinary 11-dehydro-TxB2 progressively increases with increasing CHA2DS2-VASc score suggesting that anticoagulated patients with high CHA2DS2-VASc score may need additional antithrombotic strategies.
An Effective Approach to High Blood Pressure Control
Authors: Alan S. Go, Mary Ann Bauman, Sallyann M. Coleman King, Gregg C. Fonarow, Willie Lawrence, Kim A. Williams, Eduardo Sanchez
Journal: Journal of the American College of Cardiology (2013)

Cardiovascular diseases, including heart disease, hypertension, and heart failure, along with stroke, continue to be leading causes of death in the United States [(1,2)][1]. Hypertension currently affects nearly 78 million[∗][2] adults in the United States and is also a major modifiable risk
74. Factors Affecting Long Terminal Repeat (LTR)-Driven Gene Expression Using VL30 Retro-Vectors and DNA Plasmid Vectors
Authors: Jim Williams, Jeremy Luke, Clague Hodgson
Journal: Molecular Therapy (2004)

Retro-vectors can be used to drive expression of foreign genes by a variety of mechanisms, including: the long terminal repeat (LTR) promoter; internal promoter; spliced message; and use of internal ribosome entry sites (IRES). However, the confines of the baggage space between LTRs (~8 kb) can create difficulties due to promoter cross-talk, processing anomalies, and adventitious start codons, among other things. Starting with the mouse VL30 retrotransposon NVL-3 vector, pVLTRAP, we created a series of modifications, designed to test effects on green fluorescent protein (GFP) expression, in the context of a retro-vector. Expression was enhanced by three of the modifications, including: 1) use of a short, synthetic IRES sequence to drive selectable marker expression (in place of the SV40 early promoter); 2) use of an SV40 early region enhancer sequence to boost LTR expression; and 3) deletion of non-essential stuffer sequences of the 5'-untranslated region (which contained ATG codons). These modifications improved GFP protein expression approximately 1 fold, 2 fold, and 1.4 fold, respectively, compared to the basic vector. Experiments are in progress to determine whether these design elements can now be combined to achieve an additive effect. We also examined several modifications that could be used in a DNA plasmid (vaccine) vector bearing the same (NVL-3) promoter, but which could not easily be incorporated into a retro-vector backbone. By combining favorable 5'- and 3'-untranslated sequences, intron, and polyadenylation signal, cumulative expression was increased by 5-6 fold compared to the basic VLTRAP vector. This improved backbone expressed GFP, in PA317 cells, comparably to the optimized vector bearing the SV40-enhanced CMV promoter in place of the NVL-3 promoter, and is currently being developed as an alternative DNA vaccine platform.
Time to register randomised trials
Authors: R. Horton, R. Smith
Journal: BMJ (1999)

The case for registering all clinical trials—first advanced a decade ago1—is now unanswerable The public has the right to know what research is being funded Researchers and research funders don't want to waste resources repeating trials already under way. And those conducting systematic reviews need to be able to identify all trials begun on a subject to avoid the problem of publication bias. Otherwise, clinicians may be deceived on what the evidence shows. Next week the Lancet , the Association of the British Pharmaceutical Industry, and the BMJ Publishing Group will hold a joint conference to promote the registering of trials.

Each year a vast financial investment is made by national funding agencies, medical research charities, and drug and device manufacturers in randomised controlled trials. Unfortunately the process is chaotic and takes little account of concurrent research. Several case studies have shown how the manipulation of trial data can provide a seriously misleading picture of an intervention's effectiveness. In a systematic review of trials using ondansetron to treat postoperative nausea and vomiting …
756. Distinct Classes of Proteasome-Modulating Agents Cooperatively Augment Recombinant Adeno-Associated Virus Type 2 and Type 5-Mediated Transduction from the Apical Surface of Human Airway Epithelia
Authors: Ziying Yan, Roman Zak, Yulong Zhang, Wei Ding, Simon Godwin, Keith Munson, Richard Peluso, John F. Engelhardt
Journal: Molecular Therapy (2004)

Top of pageAbstract
Tripeptidyl aldehyde proteasome inhibitors have been shown to effectively increase viral capsid ubiquitination and transduction of recombinant adeno-associated virus (rAAV) type 2 and 5 serotypes. In the present study, we have characterized a second class of proteasome-modulating agents (anthracycline derivatives) for their ability to induce rAAV transduction. The anthracycline derivatives doxorubicin and aclarubicin were chosen for analysis because they have been shown to interact with the proteasome through a mechanism distinct from that of tripeptidyl aldehydes. Our studies demonstrated that doxorubicin and aclarubicin also significantly augmented rAAV transduction in airway cell lines and polarized human airway epithelia, human bronchial xenografts, and mice lungs. Both tripeptidyl aldehyde and anthracycline proteasome-modulating agents similarly augmented nuclear accumulation of rAAV in A549 and IB3 airway cell lines but did not directly enhance the efficiency of second- strand synthesis for AAV genome conversion. However, these two cell types demonstrated cell specificity in terms of the ability of LLnL or doxorubicin to augment rAAV transduction. Interestingly, the combined administration of LLnL and doxorubicin resulted in substantially increased transduction (>2000 fold) following apical infection of human polarized epithelia with either rAAV-2 or rAAV-5. In summary, the cell-type specificity of LLnL and doxorubicin to induce rAAV transduction, together with the ability of these compounds to synergistically enhance rAAV transduction in polarized airway epithelial induction, suggest that these two classes of compounds likely modulate different proteasome functions that affect rAAV transduction. Findings from this study provide new insights into how modulation of the proteasome function can be used to augment rAAV transduction in airway epithelia for gene therapy of cystic fibrosis.
Thalidomide for treatment of patients with chronic graft-versus-host disease
Authors: Sibel Koc, Wendy Leisenring, Mary E. D. Flowers, Claudio Anasetti, H. Joachim Deeg, Richard A. Nash, Jean E. Sanders, Robert P. Witherspoon, Frederick R. Appelbaum, Rainer Storb, Paul J. Martin
Journal: Blood (2000)
HISTOPLASMOSIS OF DARLING: REVIEW AND CASE REPORT WITH AUTOPSY
Authors: E E ZIEGLER
Journal: Annals of Internal Medicine (1946)

ExcerptHistoplasmosis is an acute, subacute or chronic; localized or systemic; sporadic, granulomatous, infectious, fatal disease, caused by the fungus, Histoplasma capsulatum. It is spreading quite rapidly or being recognized more frequently, or both.In 1906, Richard P. Strong1published a paper on the etiology of some tropical ulcerations of the skin. He found in material curetted from a skin lesion, oval bodies, which resembled cockleshells, with a sharp outline, measuring about three to four micra in diameter; many of them contained particles of chromatin. They were found in large numbers, both free and enclosed in phagocytic endothelioid cells. He wrote,...
Systemic therapy with immunosuppressive agents and retinoids in hidradenitis suppurativa: a systematic review
Authors: J.L. Blok, S. van Hattem, M.F. Jonkman, B. Horváth
Journal: British Journal of Dermatology (2012)

Hidradenitis suppurativa (HS) is a difficult disease to treat. Although the pathogenesis of this inflammatory skin disease is largely unknown, the important role of the immune system has been demonstrated in both experimental and clinical studies. Clinicians are therefore increasingly prescribing systemic treatments with immunosuppressive agents, but the more traditionally used systemic retinoids, especially isotretinoin, also remain relatively common therapies. In order to provide an overview of all currently available systemic immunosuppressive agents and retinoids for the treatment of HS, a systematic search was performed using the Medline and Embase databases. All published papers concerning systemic retinoids or immunosuppressive treatments for HS in adults were included. The primary endpoints were the percentages of significant responders, moderate responders and nonresponders. Other endpoints were the relapse rate and adverse events. In total 87 papers were included, comprising 518 patients with HS who were treated with systemic retinoids, biological agents or another immunosuppressive agents, including colchicine, ciclosporin, dapsone or methotrexate. The highest response rates were observed with infliximab, adalimumab and acitretin. Overall, the quality of evidence was low and differed between the agents, making direct comparisons difficult. However, based on the amount of evidence, infliximab and adalimumab were the most effective agents. Acitretin was also effective in HS, although the quality of the evidence was low. The therapeutic effect of isotretinoin is questionable. Randomized controlled trials are needed to confirm the effectiveness of acitretin, and to identify the most effective immunosuppressive agents in HS.
Environmental management for vector control
Authors: D. Brewster
Journal: BMJ (1999)

This article reports a seven-fold increase in the incidence of malaria among children living close to small dams in the Tigray region of northern Ethiopia compared with children in villages distant from the dams. Despite the weakness of a case-control design, the authors of this study convincingly addressed the issue of confounders such as altitude, seasonality, and use of antimalarials. Intensity of malaria transmission does not correlate directly with morbidity and mortality because of the modulating effects of immunity and other factors. Nevertheless, increased malarial infection is likely to constitute a serious health risk to children, particularly in the region of Ethiopia. Some of the environmental management strategies for vector control, which may be applied to dam projects include locating dams at high altitude, using insecticide-treated beds for personal protection, and adopting a range of environmental manipulations. These measures, which incorporate local knowledge and fit local circumstances, are more likely to succeed than adhering to traditional methods. It is in this situation that governments and aid agencies need to make a policy commitment to minimize the adverse health risks of dam projects through the adoption of environmental management strategies for vector control and effective public interventions as part of community development activities.