tbuckley/cabot-search huggingface dataset:
Prospective, randomised study to compare empirical treatment versus targeted treatment on the basis of the urine antigen results in hospitalised patients with community-acquired pneumonia
Authors: M. Falguera, A. Ruiz-Gonzalez, J. A. Schoenenberger, C. Touzon, I. Gazquez, C. Galindo, J. M. Porcel
Journal: Thorax (2009)

<h3>Background</h3> Recommendations for diagnostic testing in hospitalised patients with community-acquired pneumonia remain controversial. The aim of the present study was to evaluate the impact of a therapeutic strategy based on the microbiological results provided by urinary antigen tests for <i>Streptococcus pneumoniae</i> and <i>Legionella pneumophila</i>. <h3>Methods</h3> For a 2-year period, hospitalised patients with community-acquired pneumonia were randomly assigned to receive either empirical treatment, according to international guidelines, or targeted treatment, on the basis of the results from antigen tests. Outcome parameters, monetary costs and antibiotic exposure levels were compared. <h3>Results</h3> Out of 194 enrolled patients, 177 were available for randomisation; 89 were assigned to empirical treatment and 88 were assigned to targeted treatment. Targeted treatment was associated with a slightly higher overall cost (€1657.00 vs €1617.20, p=0.28), reduction in the incidence of adverse events (9% vs 18%, p=0.12) and lower exposure to broad-spectrum antimicrobials (154.4 vs 183.3 defined daily doses per 100 patient days). No statistically significant differences in other outcome parameters were observed. Oral antibiotic treatment was started according to the results of antigen tests in 25 patients assigned to targeted treatment; these patients showed a statistically significant higher risk of clinical relapse as compared with the remaining population (12% vs 3%, p=0.04). <h3>Conclusions</h3> The routine implementation of urine antigen detection tests does not carry substantial outcome-related or economic benefits to hospitalised patients with community-acquired pneumonia. Narrowing the antibiotic treatment according to the urine antigen results may in fact be associated with a higher risk of clinical relapse.
He's Not Going to Talk About In Vitro Predictive Assays Again, Is He?
Authors: D. D. Von Hoff
Journal: JNCI Journal of the National Cancer Institute (1990)

It is difficult for anyone to determine why oncologists have not paid more attention to the use of in vitro predictive tests in the care of their patients. A review of already completed in vitro-in vivo othocorrelative trials in 2, 300 patients indicates percentages of 69 for true positives and 91 for true negatives from predictive assays. These percentages are as good as or better than those seen with already accepted tests, such as estrogen receptor assays or bacterial sensitivity testing systems. Results of a randomized trial of single-agent chemotherapy selections based on a capillary cloning assay versus a clinician's choice indicate the response rate is significantly higher when single-agent chemotherapy is selected by the cloning assay than when it is selected by a clinician (21%vs. 3%). An ongoing randomized trial in which investigators are attempting to corroborate these results in patients with previously untreated small cell lung cancer has been so slow to accrue patients that it is unlikely these trials and others will ever be completed. The usefulness, if any, of these assays and their potential to provide answers to important questions will never be determined unless attitudes are changed about participation in trials. A tool with potential for helping oncologists select patient therapy could be lost unless participation in these trials is obtained. [J Natl Cancer Inst 82: 96–101, 1990]
Development of motor abilities of trained Indian boys of 9-16 years of age.
Authors: H Singh, D S Joon, K Kooner
Journal: British Journal of Sports Medicine (1987)

A study was conducted on 294 north Indian boys of 9-16 years of age. The boys were studying in a sports school and were doing systematic sports training twice a day. The following tests were conducted on the subjects: Standing broad jump, standing shot put (4 kg), 40 m sprint, zig-zag run, forward bend and reach and endurance run. The results indicated that the spurt in height, weight and motor abilities of Indian boys is less pronounced than in boys of Europe and America.
Preventing Depression
Authors: Pim Cuijpers, Aartjan T. F. Beekman, Charles F. Reynolds
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Adjuvant therapy in pancreatic cancer: historical and current perspectives
Authors: J.P. Neoptolemos, D. Cunningham, H. Friess, C. Bassi, D.D. Stocken, D.M. Tait, J.A. Dunn, C. Dervenis, F. Lacaine, H. Hickey, M.G.T. Raraty, P. Ghaneh, M.W. Büchler
Journal: Annals of Oncology (2003)
Analysis of surgically-induced right bundle branch block pattern using intracardiac recording techniques.
Authors: R J Sung, D M Tamer, O L Garcia, A Castellanos, R J Myerburg, H Gelband
Journal: Circulation (1976)

Using intracardiac recording techniques, His bundle (H) and right ventricular apical (RVA) electrograms were recorded in 16 patients with a postoperative electrocardiographic pattern of right bundle branch block (RBBB). Their ages ranged from 5 to 12 years (mean 6.9 years) at surgery and the follow-up period was 1 to 7 years (mean 2.7 years). All were asymptomatic and in sinus rhythm at the time of study. The P-A interval was normal in all and the A-H, H-V, and V-RVA intervals were prolonged in one, one, and six patients, respectively. The V-RNA interval was normal (less than or equal to 30 msec) in ten out of the 11 patients (91%) without associated left anterior hemiblock (LAH), indicating a physiologically intact main right bundle branch, and was abnormally lengthened (45-62 msec) in all five patients (100%) with associated LAH. These findings suggest that there are two subgroups of patients with surgicall-induced RBBB pattern and the measurement of the V-RVA interval in conjunction with the H-V interval may be of ultimate importance in understanding the long-term prognostic implication of surgically-induced RBBB pattern with or without LAH.
Early fluid resuscitation in severe trauma
Authors: T. Harris, G. O. R. Thomas, K. Brohi
Journal: BMJ (2012)

#### Summary points

Trauma is a global health problem that affects patients in both rich and poor countries and accounts for 10 000 deaths each day.1 2 Trauma is the second leading cause of death after HIV/AIDS in the 5-45 year old age group.w1 w2 Early triage and resuscitation decisions affect outcome in trauma situations.w3 w4 The two leading causes of mortality in trauma are neurological injury and blood loss.3 4 w5 w6 There has been considerable improvement in our understanding of trauma resuscitation in the past 20 years, and data from databases and observational trials suggests outcomes are improving.w7 For patients with severe traumatic injuries (defined as <15 by the injury severity score, an anatomical scoring system), the high volume fluid resuscitation promoted by early advanced trauma life support manuals,5 followed by definitive surgical care, has given way to a damage …
The development of parent-infant attachment through dynamic and interactive signaling loops of care and cry
Authors: James Edward Swain, Linda C. Mayes, James F. Leckman
Journal: Behavioral and Brain Sciences (2004)

In addition to the infant cry being a signal for attention, it may also be a critical component of the early formation of attachments with caregivers. We consider the complex development of that attachment, which involves reciprocal interactive signaling and a host of evolutionarily conserved caregiver factors.
Lysophosphatidylcholine Promotes P-Selectin Expression in Platelets and Endothelial Cells
Authors: Toyoaki Murohara, Rosario Scalia, Allan M. Lefer
Journal: Circulation Research (1996)

Abstract Lysophosphatidylcholine (LysoPC), an atherogenic lysophospholipid contained in oxidized low-density lipoprotein (LDL), has been shown to stimulate protein kinase C (PKC). Since PKC activators are suggested to elicit rapid P-selectin expression in platelets and endothelial cells, we examined whether LysoPC promotes P-selectin expression in platelets and P-selectin–mediated leukocyte adherence to endothelial cells via a mechanism involving PKC activation. LysoPC, but not phosphatidylcholine (PC), which is a major phospholipid component in native LDL, significantly upregulated P-selectin on cat platelets by flow cytometric analysis. This P-selectin upregulation by LysoPC was significantly attenuated by two PKC inhibitors, 7-hydroxystaurosporine (UCN-01) and N,N,N -trimethylsphingosine, and by two NO donors, CAS1609 and sodium nitroprusside. Submicellar concentrations of LysoPC significantly activated PKC in platelets, and this was inhibited by either UCN-01 or CAS1609. LysoPC, but not PC, significantly increased adherence of autologous cat polymorphonuclear leukocytes to coronary vascular endothelium, which was also markedly attenuated by UCN-01 and by CAS1609. LysoPC induced P-selectin expression on the surface of cat coronary vascular endothelium as assessed by immunohistochemical analysis. These results suggest that LysoPC, an atherogenic lysophospholipid contained in oxidized LDL, rapidly induces P-selectin expression in both platelets and endothelial cells at least partially via PKC activation. Furthermore, NO-generating agents may inhibit P-selectin upregulation by LysoPC. Since P-selectin may play an important role in initiating atherosclerosis, our data provide further insight into the mechanism of early stages of atherogenesis and of NO-mediated inhibition of atherosclerosis.
Cognitive Therapy versus Fluvoxamine as a Second-Step Treatment in Obsessive-Compulsive Disorder Nonresponsive to First-Step Behavior Therapy
Authors: Anton J.L.M. van Balkom, Paul M.G. Emmelkamp, Merijn Eikelenboom, Adriaan W. Hoogendoorn, Johannes H. Smit, Patricia van Oppen
Journal: Psychotherapy and Psychosomatics (2012)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; To compare the effectiveness of second-step treatment with cognitive therapy (CT) versus fluvoxamine in patients with obsessive-compulsive disorder (OCD) who are nonresponsive to exposure in vivo with response prevention (ERP). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A 12-week randomized controlled trial at an outpatient clinic in the Netherlands comparing CT with fluvoxamine in OCD. Of 118 subjects with OCD treated with 12 weeks of ERP, 48 appeared to be nonresponders (Y-BOCS improvement score of less than one third). These nonresponders were randomized to CT (n = 22) or fluvoxamine (n = 26). The main outcome measure was the Y-BOCS severity scale. Statistical analyses were conducted in the intention-to-treat sample (n = 45) on an ‘as randomized basis’ and in the per-protocol sample (n = 30). Due to selective dropout in the fluvoxamine group, two additional sensitivity analyses were performed. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Complete data could be obtained from 45 subjects (94%) after 12 weeks. Fifty percent of the patients refused fluvoxamine after randomization compared to 13% who refused CT [χ&lt;sup&gt;2&lt;/sup&gt;(1) = 7.10; p = 0.01]. CT as a second-step treatment did not appear to be effective in this sample of nonresponders. Fluvoxamine was significantly superior to CT in the intention-to-treat sample, in the per-protocol sample and in the two separately defined samples in which the sensitivity analyses were performed. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; OCD patients who are nonresponsive to ERP may benefit more from a switch to treatment with an antidepressant instead of switching to CT. In clinical practice, it may be important to motivate this subgroup of patients to undergo psychopharmacological treatment, as this may improve their outcome considerably.
Molecular Mediators Governing Iron-Copper Interactions
Authors: Sukru Gulec, James F. Collins
Journal: Annual Review of Nutrition (2014)

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states.
Function of monocytes and monocyte-derived macrophages in α<sub>1</sub>-antitrypsin deficiency
Authors: Emily F.A. van’t Wout, Annemarie van Schadewijk, David A. Lomas, Jan Stolk, Stefan J. Marciniak, Pieter S. Hiemstra
Journal: European Respiratory Journal (2014)

α 1 -antitrypsin deficiency is the most widely recognised genetic disorder causing chronic obstructive pulmonary disease (COPD). Mutant Z α 1 -antitrypsin expression has previously been linked to intracellular accumulation and polymerisation of this proteinase inhibitor. Subsequently, this has been described to underlie an exaggerated endoplasmic reticulum stress response and enhanced nuclear factor-κB signalling. However, whether monocyte-derived macrophages display the same features remains unknown. Monocytes from homozygous PiZZ α 1 -antitrypsin deficiency patients and PiMM controls were cultured for 6 days in the presence of granulocyte-macrophage or macrophage colony-stimulating factor to obtain pro- and anti-inflammatory macrophages (mφ-1 and mφ-2, respectively). We first showed that, in contrast to monocytes, pre-stressed mφ-1 and mφ-2 from healthy blood donors display an enhanced endoplasmic reticulum stress response upon a lipopolysaccharide trigger ( XBP1 splicing, CHOP , GADD34 and GRP78 mRNA). However, this endoplasmic reticulum stress response did not differ between monocyte-derived macrophages and monocytes from ZZ patients compared to MM controls. Furthermore, these ZZ cells do not secrete higher cytokine levels, and α 1 -antitrypsin polymers were not detectable by ELISA. These data suggest that monocyte-derived macrophages are not the local source of Z α 1 -antitrypsin polymers found in the lung and that endoplasmic reticulum stress and pro-inflammatory cytokine release is not altered.
Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival
Authors: Aurélie Ernst, Stefanie Hofmann, Rezvan Ahmadi, Natalia Becker, Andrey Korshunov, Felix Engel, Christian Hartmann, Jörg Felsberg, Michael Sabel, Heike Peterziel, Moritz Durchdewald, Jochen Hess, Sebastian Barbus, Benito Campos, Anna Starzinski-Powitz, Andreas Unterberg, Guido Reifenberger, Peter Lichter, Christel Herold-Mende, Bernhard Radlwimmer
Journal: Clinical Cancer Research (2009)

Glioblastoma spheroid cultures are enriched in tumor stem-like cells and therefore may be more representative of the respective primary tumors than conventional monolayer cultures. We exploited the glioma spheroid culture model to find novel tumor-relevant genes.We carried out array-based comparative genomic hybridization of spheroid cultures derived from 20 glioblastomas. Microarray-based gene expression analysis was applied to determine genes with differential expression compared with normal brain tissue and to nonneoplastic brain spheroids in glioma spheroid cultures. The protein expression levels of three candidates were determined by immunohistochemistry on tissue microarrays and correlated with clinical outcome. Functional analysis of PDPN was done.Genomic changes in spheroid cultures closely resembled those detected in primary tumors of the corresponding patients. In contrast, genomic changes in serum-grown monolayer cultures established from the same patients did not match well with the respective primary tumors. Microarray-based gene expression analysis of glioblastoma spheroid cultures identified a set of novel candidate genes being upregulated or downregulated relative to normal brain. Quantitative real-time PCR analyses of 8 selected candidate genes in 20 clinical glioblastoma samples validated the microarray findings. Immunohistochemistry on tissue microarrays revealed that expression of AJAP1, EMP3, and PDPN was significantly associated with overall survival of astrocytic glioma patients. Invasive capacity and RhoA activity were decreased in PDPN-silenced spheroids.We identified a set of novel candidate genes that likely play a role in glioblastoma pathogenesis and implicate AJAP1, EMP3, and PDPN as molecular markers associated with the clinical outcome of glioma patients.
Where is the pain coming from in tendinopathy? It may be biochemical, not only structural, in origin
Authors: K M Khan, J L Cook, N Maffulli, P Kannus
Journal: British Journal of Sports Medicine (2000)

Traditional dogma would have it that pain in tendinopathy arises through one of two mechanisms. Firstly, it may result from inflammation in “tendinitis”. Secondly, it may be due to separation of collagen fibres in more severe forms of tendinopathy. The latter situation parallels the mechanism of pain with collagen separation after an acute grade I or II ligament injury (fig 1).

Despite the wide acceptance of these two classical models of pain production, a number of studies provide data inconsistent with either theory. Consider first the inflammation mechanism. Histopathological examination of surgical specimens from patients with chronic tendon pain are devoid of inflammatory cells.1 This applies to tissue from the Achilles, patellar, lateral elbow, medial elbow, and rotator cuff tendons. Furthermore, prostaglandin E2 (a marker of the inflammatory process) is no more abundant in patients with Achilles tendon pain than in normal controls.2

Unfortunately, the collagen separation theory does not hold up under scrutiny either. The following five observations about pain and collagen in the patellar tendon are inexplicable. ( a ) Patients who have patellar tendon allograft anterior cruciate ligament reconstruction have minimal donor site knee pain, yet …
Dermatological complications of etanercept therapy for rheumatoid arthritis
Authors: L. Misery, J-L. Perrot, A. Gentil-Perret, B. Pallot-Prades, F. Cambazard, C. Alexandre
Journal: British Journal of Dermatology (2002)

Sir, Etanercept is a fusion protein consisting of the extracellular ligand‐binding domain of the 75‐kDa receptor for tumour necrosis factor (TNF)‐α and the constant domain of human IgG1. This new drug is administrated by subcutaneous injection for the treatment of rheumatoid arthritis and will be probably used in other autoimmune diseases such as psoriasis, and even in chronic heart failure.1 Until now, the known adverse events have mainly been infections (of the upper respiratory tract in particular) and injection‐site reactions.1, 2 We report new dermatological adverse events. Patient 1. A 57‐year‐old woman suffering from rheumatoid arthritis was treated with etanercept (Enbrel®; Immunex Corp., Seattle, WA, U.S.A.). She developed a rash after her second injection. A patch of erythema with follicular hyperkeratosis occurred at the injection site, and other similar lesions developed at non‐injection sites. Skin biopsy revealed discoid lupus‐like lesions of folliculitis. The patient had no history of lupus. Antinuclear antibodies were present (1 : 40) but there were no anti‐DNA antibodies. Treatment with etanercept was not discontinued. The lesions did not disappear but were greatly attenuated. The titre of antinuclear antibodies did not increase after 6 months of treatment.
Disease Flare after Tyrosine Kinase Inhibitor Discontinuation in Patients with <i>EGFR</i>-Mutant Lung Cancer and Acquired Resistance to Erlotinib or Gefitinib: Implications for Clinical Trial Design
Authors: Jamie E. Chaft, Geoffrey R. Oxnard, Camelia S. Sima, Mark G. Kris, Vincent A. Miller, Gregory J. Riely
Journal: Clinical Cancer Research (2011)

Treatment of patients with oncogene-addicted cancers with tyrosine kinase inhibitors (TKI) is biologically and clinically different than with cytotoxic chemotherapy. We have observed that some patients with EGFR-mutant lung cancer and acquired resistance to erlotinib or gefitinib (RECIST progression after initial benefit) have accelerated progression of disease after discontinuation of TKI. To examine this observation and define the course of patients following TKI discontinuation, we systematically evaluated patients enrolled on clinical trials of agents to treat acquired resistance to erlotinib or gefitinib.We evaluated patients with EGFR-mutant lung cancer who participated in trials for patients with acquired resistance that mandated TKI discontinuation before administration of study therapy. Disease flare was defined as hospitalization or death attributable to disease progression during the washout period.Fourteen of 61 patients (23%; 95% CI: 14-35) experienced a disease flare. The median time to disease flare after TKI discontinuation was 8 days (range 3-21). Factors associated with disease flare included shorter time to progression on initial TKI (P = 0.002) and the presence of pleural (P = 0.03) or CNS disease (P = 0.01). There was no association between disease flare and the presence of T790M at the time of acquired resistance.In patients with EGFR-mutant lung cancer and acquired resistance to epidermal growth factor receptor TKIs, discontinuation of erlotinib or gefitinib before initiation of study treatment is associated with a clinically significant risk of accelerated disease progression. Clinical trials in this patient population must minimize protocol-mandated washout periods.