tbuckley/cabot-search huggingface dataset:
Impact on patients' health status following early identification of a COPD exacerbation
Authors: J. Bourbeau, G. Ford, H. Zackon, N. Pinsky, J. Lee, G. Ruberto
Journal: European Respiratory Journal (2007)

The current study aimed to assess the impact on patient health status during an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). A total of 421 COPD patients were enrolled in a multicentre, single-arm study with a 6-month observational follow-up period. Patients received two inhalations of Symbicort 200 Turbuhaler® twice a day. Patients were assessed before the run-in period, at baseline and at 1, 3 and 6 months. Patients were instructed to report a change in respiratory symptoms lasting &gt;24 h. This defined an AECOPD. In addition to the initial call, the St George’s Respiratory Questionnaire (SGRQ), COPD Control Questionnaire (CCQ), Medical Research Council (MRC) dyspnoea scale and activities of daily living (ADL) were completed at 5–7 and 12–14 days. A group of 176 patients reported at least one AECOPD. Exacerbations were associated with statistically significant mean changes (worsening) in the SGRQ activity and impact domains at onset (mean± sd 12.1±18.1 and 14.0±15.2), during the first (9.8±19.0 and 9.4±16.6) and second weeks (3.1±15.5 and 3.3±14.7). Clinically significant deterioration in SGRQ impact scores was shown in 71% of patients following early identification, with 55 and 37% during the first and second weeks of an AECOPD, respectively. Acute exacerbation severely impacts on health status. The current study provides valuable information on the change in health status during an acute exacerbation of chronic obstructive pulmonary disease that can be utilised for future trials that evaluate therapeutic intervention.
Abstract 1300: Evaluating the relative bioavailability of a new formulation of navitoclax (ABT-263) in both cancer patients and healthy volunteers
Authors: Jianning Yang, Hao Xiong, Andrew Krivoshik, Kyle Holen, Rajendra Pradhan, Yi-Lin Chiu, Adel Nada, Anthony Tolcher, Walid Awni, Rod Humerickhouse
Journal: Cancer Research (2011)

Abstract INTRODUCTION: Navitoclax (ABT-263) is a novel, orally bioavailable small molecule that inhibits Bcl-2 family proteins and promotes apoptosis. The current Phase 1 formulation is a lipid solution, which has a short shelf-life. A new lipid solution with improved shelf-life was developed to support Phase 2/3 clinical development. Relative bioavailability studies in patients were expected to have large variability, which would make the interpretation challenging. Meanwhile, the toxicity profile of navitoclax limited an evaluation at the recommended phase II dose in healthy volunteers. Therefore, relative bioavailability studies for the new formulation were conducted in both healthy volunteers (at doses with minimal safety risk) and cancer patients (at therapeutic doses). METHODS: Two randomized, crossover studies were conducted to evaluate the bioavailability of the new formulation relative to that of the Phase 1 formulation. Study I was conducted in 12 healthy female subjects with non-childbearing potential at a single dose of 25 mg navitoclax. Study II was conducted in 12 cancer patients at a single dose of 250 mg navitoclax. Both studies were conducted under low-fat conditions. RESULTS: The new lipid solution was bioequivalent to the Phase 1 formulation in healthy subjects. In patients, the point estimates of the bioavailability of the new lipid solution were 30% higher than the Phase 1 formulation; nevertheless, the point estimates were associated with wide 90% confidence intervals indicating high uncertainty in the point estimate. The percent coefficient of variation for navitoclax exposure in patients (49%) was markedly higher than that in healthy subjects (25%). CONCLUSION: Relative bioavailability assessment in healthy volunteers had substantially lower variability compared to that in cancer patients, therefore served as the primary basis for decision making. However, results from patients provided supportive information at the therapeutic dose levels. Overall results from both studies in healthy subjects and patients provided strong evidence that the new lipid solution has comparable bioavailability as the Phase 1 formulation under low-fat conditions at therapeutic doses, and enabled a decision to select the new lipid formulation without dose modification for Phase 2/3 studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1300. doi:10.1158/1538-7445.AM2011-1300
Bone Marrow Mesenchymal Stem Cells Loaded With an Oncolytic Adenovirus Suppress the Anti-adenoviral Immune Response in the Cotton Rat Model
Authors: Atique U Ahmed, Cleo E Rolle, Matthew A Tyler, Yu Han, Sadhak Sengupta, Derek A Wainwright, Irina V Balyasnikova, Ilya V Ulasov, Maciej S Lesniak
Journal: Molecular Therapy (2010)

Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer. However, following intratumoral injections, oncolytic viruses fail to efficiently migrate away from the injection site and are rapidly cleared by the immune system. We have previously demonstrated enhanced viral delivery and replicative persistence in vivo using human bone marrow–derived mesenchymal stem cells (MSCs) as delivery vehicles. In this study, we evaluated the immune response to adenovirus (Ad)-loaded MSCs using the semipermissive cotton rat (CR) model. First, we isolated MSCs from CR bone marrow aspirates. Real-time quantitative PCR analysis revealed that CR MSCs supported the replication of Ads in vitro. Moreover, we observed similar levels of suppression of T-cell proliferation in response to mitogenic stimulation, by MSCs alone and virus-loaded MSCs. Additionally, we found that MSCs suppressed the production of interferon-γ (IFN-γ) by activated T cells. In our in vivo model, CR MSCs enhanced the dissemination and persistence of Ad, compared to virus injection alone. Collectively, our data suggest that the use of MSCs as a delivery strategy for oncolytic Ad potentially offers a myriad of benefits, including improved delivery, enhanced dissemination, and increased persistence of viruses via suppression of the antiviral immune response. Oncolytic adenoviral virotherapy is an attractive treatment modality for cancer. However, following intratumoral injections, oncolytic viruses fail to efficiently migrate away from the injection site and are rapidly cleared by the immune system. We have previously demonstrated enhanced viral delivery and replicative persistence in vivo using human bone marrow–derived mesenchymal stem cells (MSCs) as delivery vehicles. In this study, we evaluated the immune response to adenovirus (Ad)-loaded MSCs using the semipermissive cotton rat (CR) model. First, we isolated MSCs from CR bone marrow aspirates. Real-time quantitative PCR analysis revealed that CR MSCs supported the replication of Ads in vitro. Moreover, we observed similar levels of suppression of T-cell proliferation in response to mitogenic stimulation, by MSCs alone and virus-loaded MSCs. Additionally, we found that MSCs suppressed the production of interferon-γ (IFN-γ) by activated T cells. In our in vivo model, CR MSCs enhanced the dissemination and persistence of Ad, compared to virus injection alone. Collectively, our data suggest that the use of MSCs as a delivery strategy for oncolytic Ad potentially offers a myriad of benefits, including improved delivery, enhanced dissemination, and increased persistence of viruses via suppression of the antiviral immune response.
Genome Reduction and Co-evolution between the Primary and Secondary Bacterial Symbionts of Psyllids
Authors: Daniel B. Sloan, Nancy A. Moran
Journal: Molecular Biology and Evolution (2012)

Genome reduction in obligately intracellular bacteria is one of the most well-established patterns in the field of molecular evolution. In the extreme, many sap-feeding insects harbor nutritional symbionts with genomes that are so reduced that it is not clear how they perform basic cellular functions. For example, the primary symbiont of psyllids (Carsonella) maintains one of the smallest and most AT-rich bacterial genomes ever identified and has surprisingly lost many genes that are thought to be essential for its role in provisioning its host with amino acids. However, our understanding of this extreme case of genome reduction is limited, as genomic data for Carsonella are available from only a single host species, and little is known about the functional role of "secondary" bacterial symbionts in psyllids. To address these limitations, we analyzed complete Carsonella genomes from pairs of congeneric hosts in three divergent genera within the Psyllidae (Ctenarytaina, Heteropsylla, and Pachypsylla) as well as complete secondary symbiont genomes from two of these host species (Ctenarytaina eucalypti and Heteropsylla cubana). Although the Carsonella genomes are generally conserved in size, structure, and GC content and exhibit genome-wide signatures of purifying selection, we found that gene loss has remained active since the divergence of the host species and had a particularly large impact on the amino acid biosynthesis pathways that define the symbiotic role of Carsonella. In some cases, the presence of additional bacterial symbionts may compensate for gene loss in Carsonella, as functional gene content indicates a high degree of metabolic complementarity between co-occurring symbionts. The genomes of the secondary symbionts also show signatures of long-term evolution as vertically transmitted, intracellular bacteria, including more extensive genome reduction than typically observed in facultative symbionts. Therefore, a history of co-evolution with secondary bacterial symbionts can partially explain the ongoing genome reduction in Carsonella. However, the absence of these secondary symbionts in other host lineages indicates that the relationships are dynamic and that other mechanisms, such as changes in host diet or functional coordination with the host genome, must also be at play.
Regulations<i>Are</i>Needed for Stem Cell Tourism: Insights From China
Authors: Dominique McMahon, Halla Thorsteinsdóttir
Journal: The American Journal of Bioethics (2010)

As demonstrated in this issue of American Journal of Bioethics, stem cell tourism is a growing and highly contentious practice. The articles presented by Murdoch and Scott and by Zarzeczny and Caul...
Ten vs Five Years of Bisphosphonate Treatment for Postmenopausal Osteoporosis
Authors: Cathleen S. Colón-Emeric
Journal: JAMA (2006)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Abstract P1-06-03: Chinese Herb Fructus Cornii Exhibits Preventive Efficacy in a Cell Culture Model for Hormone Responsive Breast Cancer
Authors: NT Telang, DW Sepkovic, JL Bradlow, GYC. Wong
Journal: Cancer Research (2010)

Abstract Background: Selective estrogen receptor modulators and combination of chemotherapeutic agents represent conventional therapeutic interventional strategies for estrogen receptor positive (ER+) clinical breast cancer. Herbal medicines have been extensively used in alternative and complementary medicine for cancer of various organ sites. Concerns of adverse toxicity or acquired tumor resistance from conventional chemo-endocrine therapy, rationalizes the use of herbal medicines independently or in combination with chemo-endocrine therapy. The present study has utilized a human cell culture model for ER+ breast cancer to assess potential preventive efficacy of a popular Chinese nutritional herb Fructus Cornii (FC). Material and Methods: The ER+ human mammary carcinoma derived MCF-7 cells represented the model. Status of cellular metabolism of estradiol (E2), anchorage dependent growth and anchorage independent colony formation provided the quantitative end point biomarkers for efficacy. Results: MCF-7 cells maintained in a serum depleted medium (E2&amp;lt;1 nM) retained E2 responsiveness as evidenced by growth modulation by E2, its metabolites, anti-estrogen Tamoxifen, and by the persistence of E2 metabolism via the C17-oxidation, C2-hydroxylation and C16α-hydroxylation pathways. Treatment of E2 stimulated MCF-7 cells with FC produced cytostatic growth arrest and reduction in the number of anchorage independent colonies in a dose dependent manner. Treatment of MCF-7 cells with FC at the maximum cytostatic concentration increased anti-mitogenic 2-hydroxyestrone (2-OHE1), and decreased pro-mitogenic 16α-hydroxyestrone (16α-OHE1) formation. Discussion: These data identify a mechanistic lead for the efficacy of FC and thereby, validate a human cell culture based approach for rapid prioritization of efficacious herbal medicinal products for prevention/therapy of ER+ clinical breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-06-03.
Metapneumovirus and acute wheezing in children
Authors: Tuomas Jartti, Bernadette van den Hoogen, Roberto P Garofalo, Albert DME Osterhaus, Olli Ruuskanen
Journal: The Lancet (2002)

A new respiratory virus, human metapneumovirus, was recently identified. We detected this virus by PCR in ten (8%) of 132 consecutive children admitted to Turku Hospital, Finland, for acute expiratory wheezing (median age 7 months, range 4–25). The mean duration of hospital stay was 2·5 days (SD 1·6) and mean duration of respiratory symptoms was 19 days (8). The white blood cell count, C-reactive protein, and regulated upon activation, normal T-cell-expressed and T-cell-secreted (RANTES) concentrations in nasal secretion remained low, whereas interleukin 8 concentrations in nasal secretion were high. Human metapneumovirus is a clinically important causative agent of acute wheezing in young children.
Trimethoprim-sulphamethoxazole in Acute Osteomyelitis Due to Penicillin-resistant Staphylococci in Uganda
Authors: J. L. Craven, D. J. Pugsley, R. Blowers
Journal: BMJ (1970)

Most recent cases of staphylococcal osteomyelitis seen at Mulago Hospital, Kampala, have been due to penicillin-resistant organisms. Six severely ill patients-four with multiple bone lesions-were treated with trimethoprim-sulphamethoxazole; the response was prompt and satisfactory in all cases.
Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment.
Authors: B Waldecker, J Coromilas, A E Saltman, S M Dillon, A L Wit
Journal: Circulation (1993)

Clinical electrophysiology studies have used, for the most part, models of anatomic reentrant circuits to explain entrainment of ventricular tachycardia. Our studies use activation maps to directly determine mechanisms of entrainment of functional circuits that cause tachycardia.Electrograms were recorded from 192 sites on reentrant circuits in the epicardial border zone of canine myocardial infarcts during sustained ventricular tachycardia. Overdrive stimulation from different sites and at different cycle lengths was investigated. The reentrant circuits were shown to be functional, yet stimulated impulses could enter and repetitively reset the circuits (entrainment), demonstrating the presence of an excitable gap. Entrainment could occur from different stimulation sites with the stimulated impulses from each site activating the circuit with a different pattern. Entrainment, however, did not occur when the stimulated wave fronts obliterated the lines of functional block in the circuit. Fusion on the ECG occurred during entrainment when the stimulated impulses activated the ventricles concurrently with a previous stimulated impulse leaving the reentrant circuit at a different site. The first postpacing QRS was captured but not fused because it was caused by the last stimulated impulse emerging from the circuit. The first postpacing cycle length on the ECG was either equal to or longer than the overdrive cycle length depending on whether there was a fusion QRS during overdrive. The first postpacing cycle length at sites in the reentrant circuit equaled the pacing cycle length. At an appropriately short overdrive cycle length, stimulated impulses blocked in the circuit to terminate reentry.Functional reentrant circuits causing ventricular tachycardia can be reset and entrained. Activation maps directly show the mechanisms.
Hematopoietic Cytokine-Mediated FDG Uptake Simulates the Appearance of Diffuse Metastatic Disease on Whole-Body PET Imaging
Authors: EDWARD F. HOLLINGER, HALUK ALIBAZOGLU, AMJAD ALI, ALEXANDER GREEN, GREGORY LAMONICA
Journal: Clinical Nuclear Medicine (1998)

FDG-PET is increasingly being used to assess malignant tumors. However, leukocyte colony-stimulating factors (CSFs), which promote the expansion of hematopoietic bone marrow, have also been demonstrated to cause increased bone-marrow FDG uptake. Three hundred FDG-PET studies conducted over a 1-year period were reviewed for diffuse bone-marrow uptake. Elevated bone-marrow uptake on PET was correlated with pathological findings and courses of granulocyte-CSF (G-CSF) therapy. These results demonstrate that G-CSF mediated FDG uptake in bone marrow is often indistinguishable from that caused by disseminated metastatic disease. However, the bone-marrow response to G-CSF decreases rapidly following the last CSF administration. Therefore, FDG-PET in patients receiving G-CSF should be delayed, when possible, until 5 days after the end of G-CSF therapy.
Kupffer Cells and Not Liver Sinusoidal Endothelial Cells Prevent Lentiviral Transduction of Hepatocytes
Authors: Niek P. van Til, David M. Markusic, Roos van der Rijt, Cindy Kunne, Johan K. Hiralall, Heleen Vreeling, Wilma M. Frederiks, Ronald P.J. Oude-Elferink, Jurgen Seppen
Journal: Molecular Therapy (2004)

Lentiviral vectors can stably transduce dividing and nondividing cells in vivo and are best suited to long-term correction of inherited liver diseases. Intraportal administration of lentiviral vectors expressing green fluorescent protein (Lenti-GFP) in mice resulted in a higher transduction of nonparenchymal cells than hepatocytes (7.32 ± 3.66% vs 0.22 ± 0.08%, respectively). Therefore, various treatments were explored to increase lentiviral transduction of hepatocytes. Lenti-GFP was injected into the common bile duct, which led to transduction of biliary epithelium and hepatocytes at low efficiency. Transient removal of the sinusoidal endothelial cell layer by cyclophosphamide to increase accessibility to hepatocytes did not improve hepatocyte transduction (0.42 ± 0.36%). Inhibition of Kupffer cell function by gadolinium chloride led to a significant decrease in GFP-positive nonparenchymal cells (2.15 ± 3.14%) and a sevenfold increase in GFP-positive hepatocytes compared to nonpretreated mice (1.48 ± 2.01%). These findings suggest that sinusoidal endothelial cells do not significantly limit lentiviral transduction of hepatocytes, while Kupffer cells sequester lentiviral particles thereby preventing hepatocyte transduction. Therefore, the use of agents that inhibit Kupffer cell function may be important for lentiviral vector treatment of liver disease.
Lesson of the week: Orbital trauma: do not blow your nose
Authors: G N Shuttleworth, D B David, M J Potts, C N Bell, P G Guest
Journal: BMJ (1999)

Patients with proved or suspected orbital or sinus fractures should be told not to blow their nose and should be prescribed prophylactic antibiotics

Orbital infections may be divided into preseptal cellulitis, in which infection is located anterior to the orbital septum (a thin sheet of fibrous tissue arising from the periosteum of the orbital margin and inserting into the tarsal plates), and orbital cellulitis, in which there is infection of orbital tissues posterior to the orbital septum. Preseptal cellulitis generally responds to oral antibiotics and rarely has important sequelae. However, orbital cellulitis is a serious infection which may be complicated by abscess formation (subperiosteal, orbital, or brain), meningitis, septicaemia, cavernous sinus thrombosis, and death. Although orbital cellulitis is related to ethmoid sinusitis in 70-80% of cases,1 it may also develop after orbital or sinus trauma. 2 3Prompt and appropriate management of patients with orbital cellulitis or at risk of developing this minimises the risk of complications.

A 16 year old girl attended her local casualty department after sustaining a blow to the right side of her face. Facial radiography showed a minimally displaced fracture of her right zygoma. She was sent home and told to report three days later to the Bristol …
Contempo 1997: Dermatology
Authors: Lynn Marks
Journal: JAMA (1997)

To the Editor.  —Drs Dover and Arndt infer equivalent efficacy for topical penciclovir and acyclovir and also for famciclovir and valacyclovir in their Contempo article on dermatology. 1 These inferences are inconsistent with the results of controlled clinical trials and product labeling for these antiviral agents. The authors indicated that topical penciclovir (Denavir, Smith-Kline Beecham Pharmaceuticals, Collegeville, Pa) is no more effective than topical acyclovir (Zovirax, Glaxo Wellcome, Research Triangle Park, NC) in the management of herpes labialis. It is important to note that comparative efficacy trials have not been conducted between these 2 agents, despite the statement in the article to this effect that Mr Ziegler cited as unpublished data. However, 2 randomized, double-blind, placebo-controlled trials have documented significant reductions in the time to healing and loss of pain of herpes labialis in immunocompetent patients treated with penciclovir. 2,3 This clinical trial data supported penciclovir in becoming the