tbuckley/cabot-search huggingface dataset:
Alveolar-like Stem Cell–derived <i>Myb</i><sup><i>−</i></sup> Macrophages Promote Recovery and Survival in Airway Disease
Authors: Michael L. Litvack, Theodore J. Wigle, Joyce Lee, Jinxia Wang, Cameron Ackerley, Eyal Grunebaum, Martin Post
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Abnormal alveolar macrophages (AM) are found in chronic obstructive pulmonary disease, asthma, cystic fibrosis, and adenosine deaminase deficiency (ADA(-/-)). There is no specific treatment strategy to compensate for these innate immune abnormalities. Recent findings suggest AMs are of early embryonic or fetal origin. Pluripotent stem cells (PSCs) as a source of embryonic-derived AMs for therapeutic use in acute and chronic airway diseases has yet to be investigated.To determine if embryonic Myb(-/-) alveolar-like macrophages have therapeutic value on pulmonary transplantation in acute and chronic airway diseases.Directed differentiation of murine PSCs was used in factor-defined media to produce expandable embryonic macrophages conditioned to an alveolar-like phenotype with granulocyte-macrophage colony-stimulating factor. AMs were partially depleted in mice to create an acute lung injury. To model a chronic lung disease, ADA(-/-) mice were used. Alveolar-like macrophages were intratracheally transplanted to the injured animals and therapeutic potential was determined.The differentiation protocol is highly efficient and adaptable to human PSCs. The PSC macrophages are phenotypically like AMs both functionally and by ligand marker characterization. They engulf bacteria and apoptotic cells and are better phagocytes than bone marrow-derived macrophages. In vivo, these macrophages remain in healthy airways for at least 4 weeks, can engulf neutrophils during acute lung injury, enhance pulmonary tissue repair, and promote survival in ADA(-/-) mice. Animals receiving the macrophages do not develop abnormal pathology or teratomas.PSCs are a reliable source to produce therapeutically active alveolar-like macrophages to treat airway disease.
Incomplete Estrogen Suppression With Gonadotropin-Releasing Hormone Agonists May Reduce Clinical Efficacy in Premenopausal Women With Early Breast Cancer
Authors: Mitch Dowsett, Per E. Lønning, Nancy E. Davidson
Journal: Journal of Clinical Oncology (2016)

Background Oophorectomy was the first endocrine therapy for breast cancer but has been largely superseded by gonadotropin-releasing hormone agonists (GnRHas) as a result of their reversible, less invasive suppression of ovarian function. The concept was developed more than two decades ago that GnRHa efficacy in treating estrogen receptor–positive breast cancer in premenopausal women might be improved by combination with an antiestrogen or aromatase inhibitor (AI) to antagonize or inhibit the synthesis of the residual nongonadal estrogen. Now, the results of three phase III studies comparing ovarian function suppression (OFS) with and without tamoxifen or comparing OFS plus tamoxifen with OFS plus AI are available; however, the results are conflicting. Here we consider the endocrine pharmacology of these combination therapies and provide potential explanations for the variable clinical findings as well as a possible means of improving combination therapy involving OFS.
Dependence of malignant proliferation associated with loss of PTEN on glucose concentration in the hyperglycemic range: Relevance to population studies linking hyperglycemia to unfavorable cancer prognosis
Authors: M. N. Pollak, M. Blouin, M. Zakikhani, Y. Zhao, C. Algire
Journal: Journal of Clinical Oncology (2009)

11113 Background: Loss of function of the tumor suppressor PTEN enhances malignant proliferation, but effects on cellular energy metabolism are less well characterized. Population studies show that the metabolic syndrome (characterized by hyperglycemia, hyperinsulinism, and obesity) is increasingly prevalent in affluent societies and is associated with adverse outcome of many cancers, but the molecular basis for this is poorly understood. Methods: We used a tetracycline-inducible PTEN expression vector in the PTEN-null U251 glioma cell line to characterize effects of PTEN on cellular energy metabolism. Results: Forced expression of PTEN led to decreased phospho-AKT Ser473 , decreased hexokinase II and HIF-1 alpha levels, and increased p53 levels. While proliferation of PTEN-positive cells was insensitive to variation in glucose concentration at levels higher than 2.5 mM, PTEN-null cells significantly increased proliferation with increasing glucose concentration across normal physiologic range to ∼10 mM. PTEN-null cells consumed more glucose than PTEN-positive cells (17.2 ± 2.0 vs. 8.8 ± 1.5 mM/million cells/48 hrs) and produced more lactate (35.9 ± 4.8 vs. 10.7 ± 2.3 mM/million cells/48 hrs). When cells were incubated in presence of 2-deoxy-glucose (2-DG), growth inhibition was greater for PTEN-null cells (47.4% inhibition relative to control without 2-DG) compared with PTEN-positive cells (10.8% inhibition relative to control without 2-DG). Conclusions: Loss of function of PTEN leads to increased glycolysis, and increased dependence on glucose availability. Only in the presence of glucose in the hyperglycemic range are maximal adverse effects of loss of PTEN on cellular proliferation and survival seen. This provides a novel mechanism to explain at least in part the relationship between hyperglycemia and cancer mortality observed in several large population studies. The data also suggest that PTEN status is relevant to selection of tumors likely to respond to experimental therapies that exploit glucose dependency. No significant financial relationships to disclose.
Most US patients continue to be prescribed opioids after overdose
Authors: Jacqui Wise
Journal: BMJ (2016)

More than 90% of US patients who survive an overdose of prescribed opioids continue to be prescribed opioids, usually by the same prescriber, shows a retrospective cohort study published in Annals of Internal Medicine .1

The researchers used a commercial insurance database with data on 50 million people to identify 2848 patients who had a non-fatal overdose while taking opioids prescribed for chronic pain between 2000 and …
Cisplatin, Gemcitabine, and Paclitaxel in Locally Advanced or Metastatic Non–Small-Cell Lung Cancer: A Phase I-II Study
Authors: Giuseppe Frasci, Nicola Panza, Pasquale Comella, Gianpaolo P. Nicolella, Michele Natale, Luigi Manzione, Domenico Bilancia, Riccardo Cioffi, Luigi Maiorino, Giuseppe De Cataldis, Mario Belli, Enrico Micillo, Vittorio Mascia, Bruno Massidda, Vito Lorusso, Mario De Lena, Francesco Carpagnano, Antonio Contu, Guido Pusceddu, Giuseppe Comella
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Because both cisplatin-paclitaxel and cisplatin-gemcitabine combinations are generally considered to be among the most active regimens in non–small-cell lung cancer (NSCLC) patients, this study aimed to determine the maximum-tolerated dose (MTD) of paclitaxel when combined with fixed doses of cisplatin and gemcitabine in advanced NSCLC patients and aimed to define the therapeutic activity of this new regimen. PATIENTS AND METHODS: From October 1996 to September 1998, 75 patients with stage IIIB-IV NSCLC, who were either chemotherapy-naive (65 patients) or who had been pretreated (10 patients), received fixed doses of cisplatin (50 mg/m 2 ) and gemcitabine (1,000 mg/m 2 ) and escalating doses of paclitaxel in a 1-hour infusion, all on days 1 and 8, every 3 weeks. RESULTS: Five different paclitaxel doses were tested, for a total of 275 cycles delivered. The escalation was stopped at the paclitaxel dose of 75 mg/m 2 in pretreated patients, whereas it continued to 150 mg/m 2 in chemotherapy-naive patients. A total of 65 chemotherapy-naive patients were treated. A paclitaxel dose of 125 mg/m 2 was recommended for phase II, and a total of 39 patients were treated at this level, for a total of 158 cycles delivered. No treatment-related deaths occurred. Five patients were hospitalized because of sepsis, and packed RBC transfusion was required in 13 patients. Grade 4 neutropenia and thrombocytopenia occurred in 23 (31%) and eight (11%) patients, respectively. Overall, 74 of the 75 patients were assessable for response. Four complete (CR) and 38 partial (PR) responses were recorded, for an overall response rate (ORR) of 57%. Three of the ten pretreated patients achieved a PR, compared with four CRs and 35 PRs in the 64 chemotherapy-naive patients (ORR, 61%). Thirty-eight of 39 patients included in phase II were assessable for response and quality of life (QOL) (one patient's disease was not measurable). Two CRs and 24 PRs were recorded in this group, for an ORR of 68% (95% confidence interval, 51% to 82%). The QOL score improved in 27 of 38 (71%) patients. The median survival time was 15 months in the 65 chemotherapy-naive patients, but it had not yet been reached in the 39 patients included in phase II, for whom the 1-year projected survival was 70%. CONCLUSION: The cisplatin-gemcitabine-paclitaxel combination is a feasible and well-tolerated approach in advanced NSCLC patients. Both a major response and a QOL improvement can be obtained in a high proportion of patients, with a median survival time exceeding 1 year. A phase III trial comparing this combination with other effective regimens is under way.
PROCUREMENT OF PHYSICIANS FOR THE ARMED FORCES
Authors: R H WHITHAM
Journal: JAMA (1942)

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
<i>Annals</i> Graphic Medicine - She Never Woke Up
Authors: William Doan
Journal: Annals of Internal Medicine (2016)

Web Exclusives5 January 2016Annals Graphic Medicine - She Never Woke UpFREEWilliam DoanWilliam DoanSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G15-0014 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G15-0014.Author/Artist Information: William J. Doan, BA, MFA, PhD, is a Professor of Theatre at The Pennsylvania State University and a past president of the Association for Theatre in Higher Education, and his whose works include published books and plays. His work may be seen at http://driftingplay.weebly.com/. (E-mail, [email protected]edu.)Author Contributions: Conception and design: W. Doan. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe Art and Science of Nursing 5 January 2016Volume 164, Issue 1Page: W1-W9KeywordsConflicts of interestDisclosureHealth care ePublished: 5 January 2016 Issue Published: 5 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Study of Tamoxifen and Raloxifene (STAR): Change in patient-reported outcomes (PROs) after the end of treatment
Authors: P. A. Ganz, S. R. Land, D. L. Wickerham, M. Lee, M. Ritter, V. Vogel, J. P. Costantino, N. Wolmark
Journal: Journal of Clinical Oncology (2007)

1506 Background: STAR is a double-blind, placebo controlled, randomized phase III prevention trial to evaluate the efficacy of 5 years of raloxifene (R) compared to tamoxifen (T) in reducing the incidence of breast cancer in high-risk postmenopausal women. STAR was unblinded on 3/30/2006. Primary clinical outcomes, quality of life (QOL) and symptoms (SXs) were reported (JAMA, 6/2006). We now describe changes in QOL and SXs post-treatment. Methods: Endpoints for QOL were the MOS SF-36 physical (PCS) and mental (MCS) component scales and the CES-D. SXs were measured using a modified checklist from the NSABP BCPT. Questionnaires were administered before treatment, every 6 months until 60 months, and then at 66 or 72 months. Participants enrolled in QOL study at selected sites from 1/4/2000–5/31/2001. SX data were collected on all participants in the main trial. The change in PCS, MCS and SX scales after the end of treatment was analyzed with linear regression. Results: From 7/1/1999–11/4/2004, 19,747 participants enrolled in STAR and were eligible for the SX assessment; 4,338 completed both on- and post-treatment assessments. The QOL study enrolled 1983 participants; 400 completed both on- and post-treatment assessments. CES-D scores improved significantly from on- to off-treatment (p=.007), but less so for those stopping treatment early (p=.03). The MCS and CES-D returned to pre-treatment levels; the PCS remained below (p=0.02). These endpoints did not differ by treatment group. Forgetfulness (p=.01), musculoskeletal (p=.01), vasomotor (p&lt;.0001), dyspareunia (p&lt;.0001), bladder (p=.0002), weight gain (p&lt;.0001), gynecological (p&lt;.0001), and leg cramp (p&lt;.0001) scales decreased in severity after treatment. Those who stopped treatment early had a greater decrease in vasomotor SXs (p=.01) but a lesser decrease in gynecological SXs (p=.02). Patients on T had a greater decrease in the vasomotor (p=.02) and bladder (p=.009) scales and a lesser decrease in weight gain (p=.04). Compared to pre-treatment levels, post-treatment vasomotor SXs decreased (p=0.009) and leg cramps increased (p&lt;.0001). Conclusions: QOL and SXs changed significantly after treatment, largely returning to pre-treatment levels. No significant financial relationships to disclose.
Detection of 14q32 translocations in B-cell malignancies by in situ hybridization with yeast artificial chromosome clones containing the human IgH gene locus
Authors: M Taniwaki, F Matsuda, A Jauch, K Nishida, T Takashima, S Tagawa, H Sugiyama, S Misawa, T Abe, K Kashima
Journal: Blood (1994)
Sorafenib in patients with platinum (plat) treated extensive stage small cell lung cancer (E-SCLC): A SWOG (S0435) phase II trial
Authors: B. J. Gitlitz, B. S. Glisson, J. Moon, H. Reimers, D. R. Gandara
Journal: Journal of Clinical Oncology (2008)

8039 Background: Sorafenib is a multikinase inhibitor affecting pathways involved in tumor progression and angiogenesis. We conducted a phase II trial of Sorafenib in plat-treated E-SCLC patients (pts) to determine the tumor response rate, toxicity and overall survival. Methods: Pts with histologically confirmed SCLC, measurable disease, Zubrod performance status 0–1 and no more than 1 prior plat- based treatment were eligible. Pts were stratified by platinum-sensitivity status: sensitive (progression >90 days after plat) or refractory (progression during or ≤90 days after plat). Pts were treated with sorafenib 400mg PO BID continuously on a 28 day cycle. Results: Of 89 pts registered; 81 are evaluable for toxicity assessment and 79 were evaluable for response. Across all pts, there were 3 (4%) partial responses (PR) and 25 (32%) with stable disease (SD). There were no complete responses. Two of the PR’s (5%) were in the plat-sensitive group, while 1 PR (2%) was in the plat-refractory group. Both groups had similar SD rates (12 [32%] and 13 [31%]) in the plat- sensitive and plat-refractory groups, respectively. Median survival: 7 mo (plat sensitive) and 5 mo (plat refractory). Median progression free survival estimates are the same for both strata: 2 months. Major toxicities included: Twenty pts (25%) with grade (gr) 3 dermatologic; Eleven (14%) with gr 3/4 flu-like and nine (11%) with gr 3/4 metabolic. Eighteen pts discontinued treatment due to adverse events or side effects from therapy. Conclusions: Sorafenib induced response and SD in 35% of plat treated E-SCLC. Median survival in this study was comparable to historic controls receiving salvage chemotherapy. Further study is warranted in combination with chemotherapy. (Supported by SWOG grant CA 30102) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer
Lorazepam: a randomized, double-blind, crossover study of a new antiemetic in patients receiving cytotoxic chemotherapy and prochlorperazine.
Authors: J F Bishop, I N Olver, M M Wolf, J P Matthews, M Long, J Bingham, B L Hillcoat, I A Cooper
Journal: Journal of Clinical Oncology (1984)

Lorazepam was compared to placebo to assess its control of nausea and vomiting in patients receiving cytotoxic chemotherapy and prochlorperazine. The study design was a randomized, double-blind crossover in which three consecutive chemotherapy courses were compared so that each patient acted as his or her own control. Of 107 patients entered, 80 were evaluable for analysis. Lorazepam significantly reduced the severity and duration of nausea, the severity of vomiting, and the number of vomiting episodes when compared to placebo. Anxiety was reduced during lorazepam courses but not significantly when compared to placebo. There was significantly more sedation with lorazepam courses. Overall, patients preferred lorazepam courses although this preference was significant only in the patient subset receiving doxorubicin and cyclophosphamide. Lorazepam is a useful adjunct to prochlorperazine in patients receiving cytotoxic chemotherapy.
Micro‐ and Nanostructured Biomaterials for Sutureless Tissue Repair
Authors: Samuel J. Frost, D. Mawad, J. Hook, Antonio Lauto
Journal: Advanced Healthcare Materials (2016)

Sutureless procedures for wound repair and closure have recently integrated nanostructured devices to improve their effectiveness and clinical outcome. This review highlights the major advances in gecko‐inspired bioadhesives that relies mostly on van der Waals bonding forces. These are challenged by the moist environment of surgical settings that weaken adherence to tissue. The incorporation of nanoparticles in biomatrices and their role in tissue repair and drug delivery is also reviewed with an emphasis on procedures involving adhesives that are laser‐activated. Nanostructured adhesive devices have the advantage of being minimally invasive to tissue, can seal wounds, and deliver drugs in situ. All these tasks are very difficult to accomplish by sutures or staples that are invasive to host organs and often cause scarring.
Ifosfamide (IFO) and doxorubicin (DOX) dose-intensities seem related to overall survival in adult soft-tissue sarcoma (STS) patients
Authors: G. F. Almeida, G. Castro, I. M. Snitcovsky, A. C. Bassani, M. E. Diz, M. H. Federico
Journal: Journal of Clinical Oncology (2006)

9581 Background: IFO/DOX dose intensities (DI) seem to impact on the outcome of STS. We explored retrospectively the relationship between DI and overall survival (OS) in STS. Methods: From Jan/00 to Jun/05, 70 untreated STS pts received IFO/DOX, 32 as neo/adjuvant and 38 in the palliative setting at our outpatient unit. Filgrastin was not mandatory. Median age 47 y (17–74 y), 44 male; mean tumor size 13.6 cm in the neo/adjuvant and 16.5 cm in the palliative group (p=0.202, t-test). Most frequent histologies: leiomyo (16 pts), synovial (13), malignant fibrous histiocytoma (8) and liposarcoma (8). 28 pts had lower/ 9 upper limb tumors, 9 retroperitoneal, 9 trunk, 6 mediastinal, 5 visceral and 4 head and neck. Kaplan-Meier survival curves were considered from diagnosis and compared by log-rank test. Results: For the 70 pts, the mean DI for IFO and DOX were 2.5±0.9 mg/m 2 /wk and 18.8±6.0 mg/m 2 /wk, respectively. There was no difference between neo/adjuvant and palliative IFO/DOX DI (p=0.314/p=0.247, respectively). With 19-mo median f-up, the median OS (mOS) was 43 mo in the neo/adjuvant group with an advantage for pts submitted to conservative surgeries (46.5 mo vs. 16.8 mo; HR 0.185, 95%CI 0.003–0.399, p=0.007) as well as in those diagnosed with tumors with less than 3 mitoses/10 HPF (48.3 mo vs. 18.8 mo; HR 0.272, 95%CI 0.058–0.871, p=0.031). No differences in mOS related to tumor size, margin status or primary sites were found. According to IFO DI, the mOS were 46.5 mo, not reached (NR), 14.5 mo and 43 mo for pts in the 1 st and subsequent DI quartiles (chi-square test for trend, p=0.004). In the median f-up of 9.8 mo, pts in the palliative setting presented mOS 21.8 mo, superior in the lower grade subgroup (NR vs. 11.1 mo; HR 0.130, 95%CI 0.076–0.746, p=0.014) and in the STS not from extremities (40.9 mo vs. 10.8 mo; HR 2.152, 95%CI 0.959–5.137, p=0.063). According to IFO DI quartiles, we also found a direct correlation between mOS (11.3 mo, 19 mo, 45.1 mo, and NR) and DI (p=0.052), and similar trend was shown for DOX DI, with 11.3 mo, 10.3 mo, NR, and 40.9 mo mOS for the 1 st , 2 nd , 3 rd and 4 th quartiles (p=0.018). Conclusions: In these STS adult pts, we have found a relationship between IFO and DOX DI and OS. Further evaluations of more intensive chemotherapy schedules are warranted. No significant financial relationships to disclose.