tbuckley/cabot-search huggingface dataset:
Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice
Authors: Ezequiel Ridruejo, Raúl Adrover, Marcelo O. Silva
Journal: Hepatology (2011)

We read with interest the article by Hongthanakorn et al. published in a recent issue of HEPATOLOGY.1 The authors reported a very high incidence of virological breakthrough (VBT) in patients receiving five different nucleos(t)ide analogues (NUCs) in clinical practice: 26% (39 patients). They reported that 7% of NUC-naïve patients receiving entecavir (ETV) experienced VBT, and that the cumulative probability of experiencing VBT at 3 years was 13%. The VBT rates reported by Hongthanakorn et al. are higher than described previously. In our population of 69 NUC-naïve chronic HBV patients treated in routine clinical practice with ETV, we found that 100% achieved undetectable HBV DNA after 96 weeks of treatment.2 We did not perform tests to evaluate genetic resistance, but we found no evidence of clinical resistance to treatment or VBT. Other studies in clinical practice have shown high efficacy of treatment with low rates of VBT, around 1%.3-5 In phase 3 randomized clinical trials, VBT rates with ETV treatment were 1.6%.6, 7 Hongthanakorn et al. argue that "medication adherence is likely to be lower in clinical practice than in phase 3 clinical trials, where highly motivated patients are recruited and closely monitored" and that "patients with CHB receiving NUC therapy who experienced VBT should be counseled on medication adherence."1 We agree that adherence is crucial in the efficacy of treatment, but we have demonstrated that a high adherence rate and treatment efficacy can be obtained in clinical practice. Ezequiel Ridruejo* , Raúl Adrover , Marcelo O. Silva , * Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno, Buenos Aires, Argentina, Centro de Hepatología, Buenos Aires, Argentina, Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Buenos Aires, Argentina.
Preoperative autologous blood transfusion programme.
Authors: L A Kay
Journal: BMJ (1993)

A verdict of accidental death was recorded in 31 of the 150 paracetamol deaths where an overdose was taken but death was not thought to be the intention.The most effective way of preventing these deaths would be to convince people never to exceed the manufacturers' dosage recommenda- tions.To achieve the same objective by the addition of methionine to all paracetamol products would be difficult because of formulation difficulties involving a very large number of products and different manufacturers.Furthermore, is it certain that the consumption of more than the daily requirement ofmethionine in this combination would be safe for all the more than 20 million adults in the United Kingdom who currently consume paracetamol each year without harm?Certainly it will be disappointing if the number of deaths due to paracetamol overdosage continues at the current level, but it would be wise to recognise that in 1990 in England and Wales there were a further 1593 deaths due to overdosage of medicines other than paracetamol and that the prevention of such deaths should receive at least equal attention.
Number of Circulating CD14-Positive Cells and the Serum Levels of TNF-α Are Raised in Acute Charcot Foot
Authors: Guillaume Mabilleau, N. Petrova, M.E. Edmonds, A. Sabokbar
Journal: Diabetes Care (2011)

Charcot neuro-osteoarthropathy (CNO) is a devastating complication of diabetes characterized by increased local bone resorption mediated by osteoclasts. Often CNO leads to multiple fractures and joint destruction resulting in severe deformity of the foot. Osteoclasts are multinucleated cells that have a common precursor with monocytes/macrophages (1). Previously, we reported that the number of osteoclasts generated in vitro from circulating cells was higher in acute CNO patients compared with diabetic control subjects and was partially independent from receptor activator for NF-κB (RANK)-RANK ligand (RANKL), the main osteoclastogenic mediator (2). One hypothesis could be that the number of circulating osteoclast precursors is increased in CNO. Among all monocytes subpopulations, CD14-positive cells are the most potent to transform into bone-resorbing osteoclasts (3).

We studied 11 diabetic patients with recent onset of acute CNO, 10 diabetic …
Immunotherapeutic strategies to prevent and treat human herpesvirus 6 reactivation after allogeneic stem cell transplantation
Authors: Ulrike Gerdemann, Laura Keukens, Jacqueline M. Keirnan, Usha L. Katari, Chinh T. Q. Nguyen, Anne P. de Pagter, Carlos A. Ramos, Alana Kennedy-Nasser, Stephen M. Gottschalk, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney, Ann M. Leen
Journal: Blood (2012)
Hospital Library Management
Authors: Susan Crawford
Journal: JAMA (1984)

There are approximately 7,000 hospitals in the United States and some 2,000 libraries in these hospitals. Traditionally, libraries provided for information needs of the medical staff in research, teaching, and patient care when hospitals were freestanding, acute-care institutions. In recent years, however, libraries have been caught in the great technological, economic, and organizational changes that hospitals are undergoing today. Within their own information-handling area, they are also faced with a computer and communications revolution that has required an almost completely new orientation.<i>Hospital Library Management</i>addresses these issues and has come at a time when guidelines are needed by hospital libraries. This practical, pragmatic guide to providing library service in hospitals was written by hospital librarians and superbly edited. It is divided into four sections, beginning with an overview of the functions and structure of the modern hospital and then moving to the hospital library within this setting. Subsequent sections
Abstract BSF1-2: Understanding Stem Cells To Get Abreast of Breast Cancer
Authors: GJ Lindeman
Journal: Cancer Research (2010)

Abstract Gene profiling studies have provided a basis for classifying breast cancer into at least six molecular subtypes and stimulated interest in identifying the cell type in which these distinct subtypes arise. Elucidating the normal cellular hierarchy within breast tissue is essential for identifying the ‘cell of origin’ that is targeted for neoplastic transformation. Stem cells, which lie at the apex of the normal tissue hierarchy, represent strong candidates, given that they are long-lived and capable of self-renewal. Alternatively, committed progenitor cells (stem cell descendants) or even mature progeny could also serve as cells of origin in breast cancer. Under these circumstances, cells would need to acquire certain stem cell-like properties (such as self-renewal) during tumorigenesis. Our group (and others) have isolated discrete subpopulations of mouse and human mammary epithelial cells on the basis of cell-surface markers and defined subsets that are highly enriched for basal/mammary stem cells, committed luminal progenitor cells and mature luminal cells. Gene profiling revealed remarkable similarities between their molecular signatures and certain subtypes of breast cancer. Notably, the luminal progenitor signature (and not the basal/stem cell signature) was most similar to basal-like breast cancer. Moreover, breast tissue from breast cancer prone BRCA1 mutation carriers was found to contain increased numbers of luminal progenitors, which had aberrant growth and differentiation properties. Taken together, these findings suggest that luminal progenitors (and not basal/stem cells) are the likely target that give rise to basal-like breast cancer. Key markers (such as KIT) expressed by luminal progenitor cells could serve as therapeutic targets for breast cancer prevention or therapy. The cancer stem cell (CSC) hypothesis is in many ways distinct from the ‘cell of origin’ concept. This model proposes that established tumors are hierarchically organised (like normal tissue) and contain a subpopulation of cells with tumor propagating ability. CSCs are not necessarily derived from transformed stem cells. However, CSCs do need to acquire key stem cell properties (such as self-renewal capability). Breast CSCs have now been identified by several groups using xenograft models. Our laboratory has studied syngeneic mouse models of mammary tumorigenesis and found that a subset (but not all) appear to conform to the CSC hypothesis. The luminal progenitor marker (CD61/≥3-integrin) was found to identify a CSC population in mammary tumor-prone MMTV-wnt-1 and BALB/c-p53+/−, but not in MMTV-neu/erbB2 mice. We speculate that the CSC model may not necessarily apply to all breast tumors. Rather, the conventional ‘clonal evolution’ model (or perhaps a hybrid model) may also be relevant in some cases of breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr BSF1-2.
Multifunctional nanocarriers for mammographic quantification of tumor dosing and prognosis of breast cancer therapy
Authors: Efstathios Karathanasis, Leslie Chan, Sri R. Balusu, Carl J. D'Orsi, Ananth V. Annapragada, Ioannis Sechopoulos, Ravi V. Bellamkonda
Journal: Biomaterials (2008)
Resolving Discrepancies Between a Meta-analysis and a Subsequent Large Controlled Trial
Authors: Rebecca DerSimonian
Journal: JAMA (1999)

ContextA recent meta-analysis found calcium supplementation to be highly effective in preventing preeclampsia but a large National Institutes of Health trial (Calcium for Preeclampsia Prevention [CPEP]) found no risk reduction due to calcium in healthy nulliparous women.ObjectivesTo resolve discrepancies between the results of the meta-analysis and the CPEP trial and to assess the role of effect heterogeneity in the discrepancies.Data SourcesLiterature search of English-language articles published prior to July 10, 1997, the date of publication of the CPEP trial, using MEDLINE and by a manual search of bibliographies of published articles.Study SelectionTrials were included if they reported data on preeclampsia and calcium supplementation. Fourteen trials were systematically evaluated for differences in study design and patient populations. One trial was excluded because its results were reported after publication of the major CPEP results.Data ExtractionThe sample size and number of subjects who developed preeclampsia in the calcium supplementation group vs a control group were recorded and analyzed on an intent-to-treat basis. Each author independently extracted the data.Data SynthesisSubstantial heterogeneity existed across trials (P=.001). After stratifying studies by the presence of a placebo-controlled group and by high-risk and low-risk populations, the conclusions of the meta-analysis of placebo-controlled trials enrolling a low-risk population (relative risk, 0.79; 99% confidence interval, 0.44-1.42; P=.30) were compatible with the conclusions of the CPEP trial that calcium supplementation does not prevent preeclampsia in healthy nulliparous women. In contrast, the data implied a strong beneficial calcium effect (relative risk, 0.19; 99% confidence interval, 0.08-0.46; P=.001) in healthy high-risk subject populations. However, only 225 women were analyzed and because of inconsistent data, these results remain equivocal.ConclusionsFurther studies are needed to establish the efficacy of calcium for preeclampsia prevention in healthy high-risk populations. A single summary measure does not adequately describe the findings of a meta-analysis when the observed effects in individual studies differ substantially. In such settings the primary focus should be to identify and incorporate pertinent covariates that reduce heterogeneity and allow for optimum treatment strategies.
Determinants of arrhythmic death due to coronary spasm: effect of preexisting coronary artery stenosis on the incidence of reperfusion arrhythmia.
Authors: F H Sheehan, S E Epstein
Journal: Circulation (1982)

Coronary spasm can occur in the presence or absence of coronary artery disease. We therefore determined the effect of preexisting coronary stenosis on the incidence of ventricular fibrillation during reperfusion after circumflex artery (CFX) occlusion. Twenty dogs underwent a 30-minute open-chest CFX occlusion. During reperfusion, CFX blood flow was restricted by a partial occluder. In dogs that survived reperfusion, peak CFX flow was 91 +/- 44% of baseline (mean +/- SD) compared with 163 +/- 68% in dogs that died of ventricular fibrillation (p less than 0.02). In another 17 dogs, the left anterior descending coronary artery was gradually occluded by an ameroid constrictor. After 17-39 days, the CFX was acutely occluded for 30 minutes and then reperfused. Collateral flow to the CFX, measured by microspheres, was 27.6 +/- 28.3 ml/min . 100 g-1 in dogs that died of reperfusion ventricular fibrillation, compared with 64.4 +/- 27.2 ml/min . 100 g-1 in surviving dogs (p less than 0.02). Thus, the risk of reperfusion ventricular fibrillation is greater in dogs with normal coronary arteries than in dogs with a flow-limiting partial stenosis of the artery undergoing transient occlusion, or chronic stenosis of a second coronary artery inducing collateralization to the artery subsequently undergoing transient occlusion. These results suggest that the risk of ventricular fibrillation during release of coronary spasm may be greater in patients without than in those with coronary artery disease.
1007-180 The effect of losartan versus atenolol on circulating adhesion molecules in essential hypertension: A LIFE substudy
Authors: Michael H Olsen, Peter Clausen, Kristian Wachtell, Ulrik Andersen, Keld Neland, Hans Ibsen, Harriet Dige-Pedersen
Journal: Journal of the American College of Cardiology (2004)
Myocardial Injury in Critically III Patients
Authors: Joseph Varon
Journal: JAMA (1995)

<h3>To the Editor.</h3> —We read with interest the article by Dr Guest and colleagues<sup>1</sup>documenting the presence of myocardial injury in critically ill patients. Cardiovascular dysfunction has long been recognized in critically ill patients. Parker et al2 clearly demonstrated left ventricular dysfunction in patients with septic shock in an ICU setting. It is not surprising that critically ill patients demonstrate biochemical evidence of myocardial injury, as evidenced by cardiac troponin I release as reported by Guest et al, given the high prevalence of multiorgan dysfunction among patients with critical illness. However, we take exception with the supposition of the authors that cardiac troponin I release among critically ill patients is necessarily related to ischemia. Despite considerable evidence of myocardial dysfunction, Cunnion et al<sup>3</sup>have demonstrated that among patients with septic shock, myocardial perfusion is actually increased and that there is net lactic utilization across the coronary bed. Although some
Homosexuality and Prostitution
Authors: R. Browne
Journal: BMJ (1956)

Previously, a novel series of 1<i>H</i>-4-substituted imidazole compounds were described as potent and selective histamine (HA) H<sub>3</sub> receptor ligands (Yates et al., 1999). The present studies extend the structure-activity relationships for optimal HA H<sub>3</sub> receptor affinity and central nervous system penetration by incorporation of a conformationally restricted cyclopropane nucleus. Moreover, the current studies extend our understanding of ligand-receptor interactions at the HA H<sub>3</sub> receptor with the development of high affinity HA H<sub>3</sub> receptor antagonists containing a stereochemical presentation. Structure-activity relationships were established from in vitro HA H<sub>3</sub>receptor-binding affinities using [<sup>3</sup>H]N<sup>α</sup>-methylhistamine and rat cortical tissue homogenates. Systematic optimization of multiple structural features critical for HA H<sub>3</sub> receptor affinity provided some of the most potent HA H<sub>3</sub> receptor agents described. For example, GT-2331 was determined to bind to a single population of HA H<sub>3</sub> receptors with a <i>K</i><sub>i</sub> of 0.125 nM. In vivo, GT-2331 has a favorable central nervous system penetration profile with an ED<sub>50</sub> of 0.08 mg/kg (i.p.) in rats and a long duration of action (<i>T</i><sub>1/2</sub> &gt; 4 h). In addition, GT-2331 was extremely selective for the HA H<sub>3</sub>receptor versus other HA receptors and a battery of neurotransmitter, neuropeptide, hormone, or enzyme systems. Several compounds were tested in vitro which suggested HA H<sub>3</sub> receptor heterogeneity and are discussed in terms of structure-activity relationships for the HA H<sub>3</sub> receptor.
Porous Hyaluronic Acid Hydrogels for Localized Nonviral DNA Delivery in a Diabetic Wound Healing Model
Authors: Talar Tokatlian, Cynthia Cam, Tatiana Segura
Journal: Advanced Healthcare Materials (2015)

The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect. Here, 100 and 60 μm porous and nonporous (n‐pore) hyaluronic acid‐MMP hydrogels with encapsulated reporter (pGFPluc) or proangiogenic (pVEGF) plasmids are used to investigate scaffold‐mediated gene delivery for local gene therapy in a diabetic wound healing mouse model. Porous hydrogels allow for significantly faster wound closure compared with n‐pore hydrogels, which do not degrade and essentially provide a mechanical barrier to closure. Interestingly, the delivery of pDNA/PEI polyplexes positively promotes granulation tissue formation even when the DNA does not encode for an angiogenic protein. And although transfected cells are present throughout the granulation tissue surrounding, all hydrogels at 2 weeks, pVEGF delivery does not further enhance the angiogenic response. Despite this, the presence of transfected cells shows promise for the use of polyplex‐loaded porous hydrogels for local gene delivery in the treatment of diabetic wounds.
Deactivating Implantable Cardioverter Defibrillators
Authors: Joanne Lynn
Journal: Annals of Internal Medicine (2005)

Letters1 November 2005Deactivating Implantable Cardioverter DefibrillatorsJoanne Lynn, MDJoanne Lynn, MDFrom RAND Health, Arlington, VA 22202.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-9-200511010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The need to discontinue use of an ICD is not an occasional consideration; it is a predictable part of the course of dying for any patient with an ICD who will die a natural death. With demographic analysis now showing that more than 80% of Americans die while covered by Medicare (elderly or disabled) and 90% live with serious chronic illnesses for many months before dying, recipients of ICDs will routinely be better served if they avoid the discomfort and disruption of having shocks while dying.One obvious ethical response is that patients should be aware at ...Reference1. Berger JT. The ethics of deactivating implanted cardioverter defibrillators. Ann Intern Med. 2005;142:631-4. [PMID: 15838070] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Joanne Lynn, MDAffiliations: From RAND Health, Arlington, VA 22202.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Ethics of Deactivating Implanted Cardioverter Defibrillators Jeffrey T. Berger Deactivating Implantable Cardioverter Defibrillators Jeffrey T. Berger Deactivating Implantable Cardioverter Defibrillators Heather M. Ross Deactivating Implantable Cardioverter Defibrillators James M. Beattie , Michael J. Connolly , and John E. Ellershaw Metrics 1 November 2005Volume 143, Issue 9Page: 691KeywordsArrhythmiaCaregiversConflicts of interestElderlyImplantable cardioverter defibrillatorsMedicareShock ePublished: 1 November 2005 Issue Published: 1 November 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Letter: Improving the service.
Authors: R W Griffiths
Journal: BMJ (1975)

understand immunity to erytshocytic malaria, and it is far from simple.What we just do not know is how to identify and produce in bulk the appropriate antigen(s) of experi- mental malarias, let alone of P. falciparum and other human parasites.Nor do we know -how to present these antigens in a way which stimulates the inmnune system to best advantage without using Draconian adjuvants like F.CA.When we have solved these fomidable problems a practical vaccine in- corprating blood stage antigens might become feasible.-Iam, etc.,
<i>N</i>-Benzyladriamycin-14-Valerate (AD198) Induces Apoptosis through Protein Kinase C-δ–Induced Phosphorylation of Phospholipid Scramblase 3
Authors: Yongwen He, Jihua Liu, David Durrant, Hung-Sheng Yang, Trevor Sweatman, Leonard Lothstein, Ray M. Lee
Journal: Cancer Research (2005)

Abstract Phospholipid scramblase 3 (PLS3) is an enzyme that plays a critical role in mitochondrial morphology, functions, and apoptotic response. During apoptosis, activated protein kinase C-δ (PKC-δ) translocates to mitochondria and phosphorylates PLS3. Here, we utilize an extranuclear-targeted anthracycline N-benzyladriamycin-14-valerate (AD198), a PKC-δ activator, to investigate the mechanism of PLS3 phosphorylation by PKC-δ. Overexpression of PLS3 enhanced, whereas down-regulation of PLS3 by small interfering RNA decreased, the sensitivity of AD198-induced apoptosis. Overexpression of PKC-δ, but not the kinase-defective PKC-δ, and AD198 treatment enhanced threonine phosphorylation of PLS3. The phosphorylated threonine was mapped to Thr21 of PLS3. Mutation of Thr21 to alanine did not affect mitochondrial localization of PLS3 but abolished threonine phosphorylation by PKC-δ in vitro and AD198-induced PLS3 phosphorylation in vivo. Expression of PLS3(T21A) in cells could not enhance AD198-induced apoptosis compared with expression of the wild-type PLS3. Using benzyloxycarbonyl-Val-Ala-Asp-(OMe) fluoromethyl ketone and cyclosporine A, we also showed that AD198-induced PLS3 phosphorylation occurs upstream of caspase activation and independent of mitochondrial permeability transition. These studies establish that AD198-activated PKC-δ induces phosphorylation of mitochondrial PLS3 at Thr21 and that PLS3 is a critical downstream effector of PKC-δ in AD198-induced apoptosis.
Prognostic Factors in Patients with Renal Cell Carcinoma: Retrospective Analysis of 675 Cases
Authors: Vincenzo Ficarra, Rita Righetti, Stefania Pilloni, Antonio D’amico, Nicola Maffei, Giovanni Novella, Luisa Zanolla, Gianni Malossini, Gaetano Mobilio
Journal: European Urology (2002)