tbuckley/cabot-search huggingface dataset:
Increased airway inflammation in asymptomatic older teenagers with previous well characterised childhood wheeze
Authors: Lucy Marshall, Caroline Beardsmore, Will Montero, Aniña Pescatore, Claudia Kuehni, Erol Gaillard
Journal: European Respiratory Journal (2013)

Background: Many children with preschool wheeze become asymptomatic only for asthma to be diagnosed in adulthood. Persistent ‘multiple trigger’ wheeze (PW) is thought to be more closely associated with ‘true’ asthma than transient viral wheeze (TW). A previous study showed persistent eosinophilic airway inflammation in children with remitted wheezing [Warke T ERJ 2002]. Whether this inflammation persists in older teenagers and whether this differs between wheeze phenotypes is unknown.

Aims: We compared total and differential sputum inflammation cell counts in asymptomatic teenagers from the Leicester Respiratory Cohort, who had TW, PW or no wheeze during preschool years.

Methods: 29 subjects (range: 16-17 years) participated: 9 with PW; 10 with TW; and 10 healthy controls. We induced sputum with nebulised hypertonic saline and processed samples as previously described [Pin I Thorax 1992].

Results: Median % eosinophils for PW and TW were significantly higher than controls (figure 1). Total cell counts were significantly greater in PW only.

Discussion: We found increased airway inflammation (both total inflammatory cell load and eosinophilic inflammation) in sputum of adolescents with childhood wheezing after a symptom free interval. Eosinophilic inflammation was not different between PW and TW. These findings have implications for the understanding of the natural history of childhood wheeze.

![Figure][1]  [1]: pending:yes
Pharmacokinetics of paclitaxel and three major metabolites in patients with advanced breast carcinoma refractory to anthracycline therapy treated with a 3-hour paclitaxel infusion: A European Cancer Centre (ECC) trial
Authors: M.T. Huizing, J.B. Vermorken, H. Rosing, W.W. ten Bokkel Huinink, I. Mandjes, H.M. Pinedo, J.H. Beijnen
Journal: Annals of Oncology (1995)
Quantification and Longitudinal Trends of Kidney, Renal Cyst, and Renal Parenchyma Volumes in Autosomal Dominant Polycystic Kidney Disease
Authors: BERNARD F. KING, JUDD E. REED, ERIK J. BERGSTRALH, PATRICK F. SHEEDY, VICENTE E. TORRES
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The aims of this study were to assess the accuracy and reproducibility of volumetric determinations of total kidney, renal cyst, and renal parenchymal volumes, using fast electron-beam computerized tomography scanning, and to determine the rate of change of these volumes. Nine patients with autosomal dominant polycystic kidney disease (ADPKD) and serum creatinine ≤ 1.3 mg/dl and/or an initial iothalamate clearance ≥ to 60 ml/min per 1.73 m 2 were imaged weekly over a 3-wk period (total of 3 times). Approximately 8 yr later, they returned for follow-up studies. The kidney volume estimation technique involved a manual segmentation (perimeter drawing) of the kidneys and a semiautomatic threshold approach, using a histogram analysis of the peak densities of renal parenchyma and renal cysts. At entry, total kidney and renal cyst volumes correlated positively with age, while renal parenchymal volumes and GFR correlated negatively with age. The average coefficient of variation values for the three initial consecutive measurements of total kidney, renal cyst (actual and as a percent of total volume), and renal parenchymal volume were 3.4, 7.2, 5.3, and 5.6%, respectively. During the 8 yr of follow-up, total kidney and renal cyst volumes increased, while renal parenchymal volumes and GFR declined. The rate of increase in total kidney and renal cyst volumes varied markedly from patient to patient. There was a significant correlation between rate of increase in renal cyst volume and the rate of decline in GFR. The patients with an initial urine protein/osmolality ratio &gt;0.13 mg/L per mosmol per kg had a significantly higher increase in renal volume and decline in GFR than those with a lower ratio. In summary, the results of this pilot study suggest that: ( 1 ) electron-beam computerized tomography is capable of measuring total kidney, renal cyst, and renal parenchymal volumes reproducibly; ( 2 ) total kidney and renal cyst volumes increase, while parenchymal volumes decrease with time; ( 3 ) the increase in cyst volume correlates best with the decline in renal function; and ( 4 ) renal volumes appear to be good surrogate markers for disease progression in ADPKD.
Mechanisms for Activation and Antagonism of an AMPA-Sensitive Glutamate Receptor
Authors: Neali Armstrong, Eric Gouaux
Journal: Neuron (2000)

Crystal structures of the GluR2 ligand binding core (S1S2) have been determined in the apo state and in the presence of the antagonist DNQX, the partial agonist kainate, and the full agonists AMPA and glutamate. The domains of the S1S2 ligand binding core are expanded in the apo state and contract upon ligand binding with the extent of domain separation decreasing in the order of apo > DNQX > kainate > glutamate ≅ AMPA. These results suggest that agonist-induced domain closure gates the transmembrane channel and the extent of receptor activation depends upon the degree of domain closure. AMPA and glutamate also promote a 180° flip of a trans peptide bond in the ligand binding site. The crystal packing of the ligand binding cores suggests modes for subunit–subunit contact in the intact receptor and mechanisms by which allosteric effectors modulate receptor activity.
Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group.
Authors: R I Jakacki, P M Zeltzer, J M Boyett, A L Albright, J C Allen, J R Geyer, L B Rorke, P Stanley, K R Stevens, J Wisoff
Journal: Journal of Clinical Oncology (1995)

To describe the biologic and clinical features of children with primitive neuroectodermal tumors (PNETs) arising in the pineal region (pineoblastomas) and evaluate prospectively the efficacy of radiation therapy (RT) and/or chemotherapy.Between 1986 and 1992, 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study. Eight infants less than 18 months of age were nonrandomly treated with eight-drugs-in-1-day chemotherapy without RT. The remaining 17 patients were treated with craniospinal RT and randomized to receive either vincristine, lomustine (CCNU), and prednisone or the eight-drugs-in-1-day regimen.Of 24 completely staged patients, 20 (83%) had localized disease at diagnosis. All infants developed progressive disease a median of 4 months from the start of treatment. Of the 17 older patients treated with RT and chemotherapy, the Kaplan-Meier estimate of progression-free survival (PFS) at 3 years is 61% +/- 13%. This is superior to the PFS of children with other supratentorial PNETs (P = .026). Following RT, 12 of 17 patients (70.6%) had a residual pineal region mass, which persisted for as long as 5 years before resolving; only four subsequently developed progressive disease.(1) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region. (2) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy, the PFS is superior to that of children with other supratentorial PNETs. (3) A residual enhancing mass following RT is not predictive of treatment failure.
Antigenic Properties of Experimental Leukemias. II. Immunological Studies &lt;italic&gt;In Vivo&lt;/italic&gt; With C57BL/6 Radiation-Induced Leukemias&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Edward A. Boyse, Lloyd J. Old, Silvi Luell
Journal: JNCI Journal of the National Cancer Institute (1963)

The serum of C57BL/6 mice immunized against an A strain TL+(thymus leukemia antigen) spontaneous leukemia was highly cytotoxic for the cells of several C57BL/6 leukemias. Paradoxically, this was not associated with resistance in vivo to the inoculation of 2 TL+ C57BL/6 radiation-induced leukemias highly sensitive to TL antisera in vitro. Leukemia cells recovered after their outgrowth in immunized C57BL/6 mice lost their sensitivity to TL antisera in vitro and their ability to absorb specific cytotoxic activity from TL antisera. A single further passage of these cells in normal untreated C57BL/6 hosts was accompanied by complete restoration of sensitivity, even after 3 consecutive passages in immunized hosts. Immunoselection, inadequate complementation, or interference by blocking antibody might account for the outgrowth of TL+ leukemia cells in immunized hosts, but the present evidence does not favor these interpretations. More probably the temporary changes in antigenicity reflect an adaptational alteration affecting the entire population of leukemia cells.
You Never Arrive
Authors: Maggie R. Salinger
Journal: Annals of Internal Medicine (2015)

On Being a Doctor19 May 2015You Never ArriveMaggie R. Salinger, BAMaggie R. Salinger, BAFrom Emory University School of Medicine, Atlanta, Georgia.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M14-2648 Audio Reading - “You Never Arrive” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "You Never Arrive," by M.R. Salinger. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The sun sank behind the Atlanta skyline as I drove to my first Alcoholics Anonymous meeting. It was an assignment for my psychology module, a chance to observe a small wedge of an addict's existence beyond sterile hospital walls. At this particular alcoholic refuge, where none of us wore starched white coats or latex gloves, I found it impossible to maintain the role of an inquisitive onlooker. Instead, I became immersed in a rite of passage where old and young, suited and tattered, tattooed and straight-laced voluntarily surrendered to the same vulnerable status. We each had separated ourselves from bustling ... Author, Article, and Disclosure InformationAffiliations: From Emory University School of Medicine, Atlanta, Georgia.Corresponding Author: Maggie R. Salinger, BA, 240 Renaissance Parkway NE, Apartment 307, Atlanta, GA 30308; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “You Never Arrive” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "You Never Arrive," by M.R. Salinger. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 19 May 2015Volume 162, Issue 10Page: 733KeywordsAlcoholicsEmotionsGraduate medical educationGratitudeHand strengthLatexPostural controlPsychologyShouldersStarvation ePublished: 19 May 2015 Issue Published: 19 May 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Chemotherapeutic Implications of Early Tumor Cell Growth in an Animal BrainTumor Model&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Barker, T Hoshino, K T Wheeler, C B Wilson
Journal: JNCI Journal of the National Cancer Institute (1975)

The onset of tumor cell proliferation was determined in an animal brain-tumor model in which tumor cells had been injected into the cerebrum of rats through a hollow stainless steel screw implanted stereotactically. Tritiated thymidine uptake in the DNA at various periods after injection of tumor cells indicated no significant proliferation of tumor cells until 168-192 hours post implantation, after which tritium uptake increased exponentially. Control rats with screws alone or screws through which balanced salt solution had been injected showed an increased uptake at 72 hours, a phenomenon not observed in animals given tumor cells. Our findings suggested that, in the tumor model described, experimental chemotherapy tests should be deferred until at least 7 days post implantation.
Abstract 2346: Stenting of Pulmonary Artery Branch Stenosis Alleviates Pulmonary Valve Insufficiency in a Swine Model of Repaired Tetralogy of Fallot
Authors: Christopher J Petit, Matthew J Gillespie, Matthew A Harris, Travis L Seymour, Timothy Y Liu, Azeem R Khan, Richard Kim, Evelio Rodriguez, J. W Gaynor, Jonathan J Rome
Journal: Circulation (2007)

Introduction : Pulmonary insufficiency-induced right ventricular volume overload in adults with repaired tetralogy of Fallot (TOF) is associated with reduced exercise tolerance, ventricular arrhythmias and sudden cardiac death. Studies have shown that the severity of pulmonary insufficiency (PI) predicts these symptoms. There has been indirect evidence that pulmonary artery branch stenosis (PABS) exacerbates PI in adults with repaired TOF. However the impact of treatment of PABS on PI has not been evaluated. Hypothesis : Relief of unilateral PABS in the setting of PI alleviates the severity of PI. Methods : Newborn piglets (n=9) underwent pulmonary valve resection with transannular patch and left pulmonary artery (LPA) banding. Between 10 to 16 weeks later, a cardiac catheterization was performed with hemodynamic evaluation and stenting of the banded LPA. Immediately prior to catheterization, and then 1 week following intervention, a cardiac MRI was performed. MRI data obtained included main and branch pulmonary arterial forward and reverse flow, and right and left ventricular volume. Results: Six animals survived the protocol. At time of catheterization, the LPA had a discrete stenosis, with a mean gradient of 11.6 mmHg (range 9 –16.1) across the banded region. The mean diameter of the LPA at the banded region was 3.4 mm (range 3.1– 4.2) and 10.8 mm distally (range 9.6 –14) at baseline, compared with a mean right pulmonary artery diameter of 20.2 mm. The banded region was stented to a mean diameter of 10.4 mm (range 8 –12.6). The main pulmonary artery regurgitant fraction (RF) at baseline was a mean of 38.2%; after stenting of the LPA, the RF decreased to 29.6% (p=0.02). Flow into the LPA improved in all animals, from a mean of 12.2% of total at baseline to 33.6% following stenting (p&lt;0.01). While the total RF decreased following LPA stenting, the branch pulmonary arterial RF did not change significantly for either pulmonary artery. Right ventricular volume did not change significantly after stenting of the LPA. Conclusions: In the setting of unilateral PABS, stenting alleviates the severity of PI in an animal model of repaired TOF. Though clinical studies are required, these findings should be considered in decisions regarding treatment of PABS after repair of TOF.
Increased in vitro fitness of multi- and extensively drug-resistant F15/LAM4/KZN strains of Mycobacterium tuberculosis
Authors: C.C. Naidoo, M. Pillay
Journal: Clinical Microbiology and Infection (2013)

The role of fitness in transmission of drug-resistant strains has been explored in previous studies; but has not been established for F15/LAM4/KZN strains, which were responsible for the extensively drug-resistant tuberculosis (XDR-TB) outbreak in Tugela Ferry, South Africa. The biological fitness of 15 clinical strains representing the F15/LAM4/KZN, Beijing, F11 and F28 families was determined by growth, viability and competition assays and correlated with DNA sequencing of eight genes associated with drug resistance and putative compensatory mechanisms. Similar growth rates were observed among susceptible, multidrug-resistant (MDR) and XDR strains of the KZN and F28 genotypes. In contrast, Beijing and F11 MDR strains demonstrated significantly reduced fitness. Resistant strains exhibited heterogeneous fitness profiles in competition with different susceptible strains, suggesting strain dependence. In addition, co-culture growth rates were consistently higher than independent growth rates in 13/14 competition pairs. All 14 drug-resistant strains retained viability, at a low CFU/mL, when paired with susceptible strains. The persistence of such resistant strains could consequently support the acquisition of additional drug-resistance-conferring mutations and/or the evolution of compensatory mechanisms. Frequently occurring mutations were detected in KZN and F28 resistant strains whereas, the Beijing MDR strain harboured a less common katG mutation and the F11 MDR strain had no katG mutation. Contrary to drug-resistant Beijing and F11 strains, the successful transmission of KZN strains, particularly during the outbreak, may be attributed to the presence of drug-resistance-conferring mutations associated with little or no associated fitness costs. Amplified growth in co-culture may be suggestive of in vivo trans-complementation.
Rapid improvement of SLE-specific cutaneous lesions by C1q immunoadsorption
Authors: B Berner, A K Scheel, V Schettler, K M Hummel, M A Reuss-Borst, G A Müller, E Oestmann, H P Leinenbach, M Hepper
Journal: Annals of the Rheumatic Diseases (2001)

C1q is thought to play a crucial part in the pathogenesis of systemic lupus erythematosus (SLE).1-3 C1q deficiency and the presence of C1q autoantibodies are associated with increased disease activity in SLE.1 Therefore, C1q is a promising candidate for adsorption of pathogenetic relevant molecules from the plasma of patients with SLE. A C1q immunoadsorbent was developed in 19904 and has been used in several patients.5 

Our patient, a 25 year old woman, had a relapsing malar and discoid rash, which extended to almost the whole integument, since January 1999. Accompanying oral and genital ulcers, polyarthritis, and lupus nephritis (histological membranous glomerulonephritis, WHO Va), as well as laboratory abnormalities, led to the diagnosis, SLE.6 Despite treatment with chloroquine (400 mg/day) initially and methotrexate (7.5–15 mg/week) since August 1999 in combination with prednisone (10 …
Childhood Risk Factors for Adults With Medically Unexplained Symptoms: Results From a National Birth Cohort Study
Authors: Matthew Hotopf, Richard Mayou, Michael Wadsworth, Simon Wessely
Journal: American Journal of Psychiatry (1999)

The purpose of this study was to test the hypothesis that the prior experience of physical illness in childhood is associated with later experience of medically unexplained symptoms.A nested case-control study was performed within a prospective birth cohort study: the Medical Research Council National Survey of Health and Development. The 5% most symptomatic individuals at age 36 years were identified and screened for physical illness. Subjects without defined physical diagnoses (N = 191) were compared with the remainder of the sample (N = 3,107) for childhood exposures.There was a powerful relationship between poor reported health of the parents when subjects were aged 15 years and symptoms at age 36; the relationship was independent of current psychiatric disorder. Medically unexplained symptoms were associated with abdominal pain in childhood but not with defined childhood diseases.Medically unexplained symptoms appear to be related to prior experience of illness in the family and previous unexplained symptoms in the individual. This may reflect a learned process whereby illness experience leads to symptom monitoring.
Modification of Oncogenic Effects of S-Polyoma Virus by “Attenuated“ M-Polyoma Virus
Authors: L.W. Law, A.S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1963)

An “attenuated” polyoma-virus variant (M polyoma) was used to modify the response of C3Hf/Bi mice to the highly oncogenic variant (S polyoma) of identical origin but maintained on P388 D1 cells under different culture conditions. When C3Hf/Bi mice less than 24 hours old received M virus, followed by S virus at 10 days of age, only 3 of 37 (8%) developed polyoma-type tumors. Few primary sites of tumor induction were observed. In contrast, recipients of control tissue culture medium on the day of birth, followed by S-polyoma virus on the 10th day, had a high frequency of polyoma-type tumors, 47.5 percent (19 of 40), appearing as early as 3 months. Many primary sites of induction were seen. Lesions of the renal-cortical tubules were more common and more severe in this group. Neutralizing and hemagglutination-inhibiting-antibody titers were observed at low levels in C3Hf/Bi mice at the time of introduction of S virus and reached high levels by the 20th to 30th day. Although the suppression of oncogenicity of S virus may therefore be the result of viral antibody produced by infection with M virus, the possible effects of viral interference or “interferon” production must also be considered.
Attitudes and Practices Among Pediatric Oncologists Regarding End-of-Life Care: Results of the 1998 American Society of Clinical Oncology Survey
Authors: Joanne M. Hilden, Ezekiel J. Emanuel, Diane L. Fairclough, Michael P. Link, Kathleen M. Foley, Brian C. Clarridge, Lowell E. Schnipper, Robert J. Mayer
Journal: Journal of Clinical Oncology (2001)

PURPOSE: In 1998, the American Society of Clinical Oncology (ASCO) surveyed its membership to assess the attitudes, practices, and challenges associated with end-of-life care of patients with cancer. In this report, we summarize the responses of pediatric oncologists and the implications for care of children dying from cancer. METHODS: The survey consisted of 118 questions, covering eight categories. All ASCO members in the United States, Canada, and the United Kingdom were mailed a survey, which was completed by 228 pediatric oncologists. Predictors of particular attitudes and practices were identified using stepwise logistic regression analysis. Potential predictors were age, sex, religious affiliation, importance of religious beliefs, recent death of a relative, specialty, type of practice (rural or urban, academic or nonacademic), amount of time spent in patient care, number of new patients in the past 6 months, and number of patients who died in the past year. RESULTS: Pediatric oncologists reported a lack of formal courses in pediatric palliative care, a strikingly high reliance on trial and error in learning to care for dying children, and a need for strong role models in this area. The lack of an accessible palliative care team or pain service was often identified as a barrier to good care. Communication difficulties exist between parents and oncologists, especially regarding the shift to end-of-life care and adequate pain control. CONCLUSION: Pediatric oncologists are working to integrate symptom control, psychosocial support, and palliative care into the routine care of the seriously ill child, although barriers exist that make such comprehensive care a challenge.