tbuckley/cabot-search huggingface dataset:
Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes
Authors: Wayne H.-H. Sheu, Ira Gantz, Menghui Chen, Shailaja Suryawanshi, Arpana Mirza, Barry J. Goldstein, Keith D. Kaufman, Samuel S. Engel
Journal: Diabetes Care (2015)

OBJECTIVE This study was conducted to determine the optimal dose of omarigliptin, a once-weekly (q.w.) dipeptidyl peptidase IV (DPP-4) inhibitor, for the treatment of patients with type 2 diabetes and evaluate the long-term safety of that dose. RESEARCH DESIGN AND METHODS In a multicenter, double-blind, 12-week, dose-range finding study, 685 oral antihyperglycemic agent-naïve or washed-out subjects with type 2 diabetes were randomized to one of five once-weekly doses of omarigliptin (0.25 mg, 1 mg, 3 mg, 10 mg, or 25 mg) or placebo. The primary efficacy end point was change from baseline in HbA1c, and secondary end points were 2-h postmeal glucose (PMG) and fasting plasma glucose (FPG). Analysis included all patients who received at least one dose of the study medication. Subjects who completed the base study were eligible to enter a 66-week extension study. RESULTS Once-weekly treatment for 12 weeks with omarigliptin provided dose-related reductions in HbA1c, 2-h PMG, and FPG. At week 12, the omarigliptin 25-mg dose provided the greatest glycemic efficacy. The placebo-adjusted least-squares mean reductions from baseline in HbA1c, 2-h PMG, and FPG were −0.72% (−7.8 mmol/mol), −2.5, and −1.3 mmol/L, respectively (all P &amp;lt; 0.001). The incidence of adverse events was similar across dose groups, with a low incidence of symptomatic hypoglycemia and no effect on body weight. Omarigliptin was generally well-tolerated throughout the base and extension studies. CONCLUSIONS Omarigliptin 25 mg q.w., compared with placebo, provided significant glucose lowering and was generally well tolerated for up to 78 weeks in patients with type 2 diabetes.
Chemodetection and Destruction of Host Urea Allows Helicobacter pylori to Locate the Epithelium
Authors: Julie Y. Huang, Emily Goers Sweeney, Michael Sigal, Hai C. Zhang, S. James Remington, Michael A. Cantrell, Calvin J. Kuo, Karen Guillemin, Manuel R. Amieva
Journal: Cell Host & Microbe (2015)
FDA Cannot Ensure Overseas Protections
Authors: Brian Vastag
Journal: JAMA (2001)

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 18069: Evaluation of Potential Antiplatelet Effects of CSL112, a Novel Formulation of Human Apolipoprotein A-I: Results From a Phase 2a Study
Authors: Paul A Gurbel, Kevin P Bliden, Denise M D’Andrea, Karen W Henderson, John H Alexander, Udaya S Tantry, Charles Shear, Pierluigi Tricoci
Journal: Circulation (2013)

Background: CSL112, a novel formulation of apoA-I purified from human plasma and reconstituted to form HDL particles, is in development for the treatment of patients with coronary artery disease. Prior data with a similar compound (CSL111) indicated a potential short-term platelet inhibitory effect. We assessed the potential antiplatelet effects of CSL112 in a phase 2a multicenter, randomized, ascending dose study in subjects with stable atherosclerotic disease. Methods: Subjects (n=44) on aspirin (75-325 mg/day) and clopidogrel (75 mg/day, n=37) or prasugrel (10 mg/day, n=7) for &gt;30 days in addition to standard of care therapy were randomized to a single dose of placebo or CSL112: 1.7, 3.4, and 6.8g. Conventional platelet aggregation in response to 2 mM arachidonic acid (AA), 5 and 10 μM adenosine diphosphate (ADP), and 4μg/mL collagen were performed at baseline and 8, 12, 24 and 48 h post-dosing. The change from baseline in maximal aggregation was determined and compared by ANOVA analysis among the treatments at any time point. Results: Baseline characteristics were well balanced across treatment groups. Compared to placebo, CSL112 did not show any time or dose dependent effects on maximum platelet aggregation in response to any agonist (p&gt;0.05 for all tests) [Table]. Conclusion: CSL112, when co-administered with dual antiplatelet therapy, does not significantly influence platelet aggregation in response to AA, ADP and collagen. Based on these data, it is anticipated that CSL112 will not affect hemostasis when administered with concomitant antiplatelet therapies.
Delivery of Instructions via Mobile Social Media App Increases Quality of Bowel Preparation
Authors: Xiaoyu Kang, Lina Zhao, Felix Leung, Hui Luo, Limei Wang, Ji Wu, Xiaoyang Guo, Xiangping Wang, Linhui Zhang, Na Hui, Qin Tao, Hui Jia, Zhiguo Liu, Zhangqin Chen, Junjun Liu, Kaichun Wu, Daiming Fan, Yanglin Pan, Xuegang Guo
Journal: Clinical Gastroenterology and Hepatology (2015)
Results of Treatment After Relapse From High-Dose Chemotherapy in Germ Cell Tumors
Authors: Pierluigi Porcu, Sumeet Bhatia, Matt Sharma, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To identify therapy-related or patient-related characteristics that predict response and long-term survival after failure of high-dose chemotherapy (HDCT) for germ cell tumors (GCT). PATIENTS AND METHODS: Between 1986 and 1997, 101 GCT patients relapsed after high-dose carboplatin and etoposide (VP-16) at Indiana University (Indianapolis, IN). Median time to relapse was 10 months (range, 1 to 17 months). HDCT was the first salvage treatment in 29 patients and second or later salvage treatment in 72 patients. RESULTS: Fifty-four of 101 patients received post-HDCT treatment. Of these, 47 received chemotherapy, alone (n = 35) or in combination with surgery (n = 12). Seven patients underwent surgery alone. There were only 12 objective responses (three complete and nine partial responses) for 66 chemotherapy regimens given to 47 patients, for an overall response rate of 18.2%. Fifteen patients received platinum-based chemotherapy, with only one objective response. Chemotherapy was discontinued in 17% of cases because of toxicity. A longer interval between HDCT and post-HDCT treatment was the only variable that was associated with response. Five patients (4.9%) are disease-free at 30, 53, 57, 85, and 93 months after relapse. Of these, three responded to oral VP-16 and underwent resection of residual mediastinal, retroperitoneal, and inguinal cancer, respectively. One had resection of residual mediastinal yolk sac tumor, followed by oral VP-16. One relapsed with teratoma and received thoracoabdominal resection without chemotherapy. CONCLUSION: Patients who experience disease progression after HDCT often receive further chemotherapy and/or surgery. Chemotherapy resulted in a response rate of less than 20%, with only three complete responses. All of the long-term survivors (4.9%) had surgery as a component of their post-HDCT regimen.
Differential characteristics of tuberculosis among immigrants
Authors: Concepción Morales-García, Jorge Parra-Ruiz, Beatriz Valero-Aguilera, Sara Sanbonmatsu-Gámez, Cintia Merinas-López, Beatriz Jiménez-Rodríguez, José Hernández-Quero
Journal: European Respiratory Journal (2013)

Background:  The incidence of tuberculosis (TB) among the native population continues to decrease, resulting in a higher proportion of foreign-born cases.  The aim of this study was to identify the differential characteristics of TB within the immigrant population with respect to natives in the Health District of South Granada (HDSG).   Methods:  This was a prospective study of all cases of TB diagnosed in the HDSG during the period 2003 to 2010. Immigration-related variables were assessed using bivariate analysis. Statistical significance was set at p   Results:  319 TB cases were diagnosed: 247 natives and 72 (22.6%) immigrants. The following variables were significantly associated with immigrant TB cases: age   The percentage of foreign-born TB cases increased from under 5% in 2003 to 50% in 2010. More than half came from either Romania (35%) or Morocco (21%).   Conclusions:  The incidence of TB has remained constant in HDSG due to the increase in cases among immigrants. Compared with native TB, immigrant TB patients were younger and had a longer diagnostic delay and more advanced disease, indicating poorer TB control. Strategies for earlier diagnosis of TB in immigrants are mandatory.
Drug-Induced Fever and Bone Marrow Suppression in a 12-Year-Old Girl with Cystic Fibrosis
Authors: Claudia Gore, T J David
Journal: Journal of the Royal Society of Medicine (2001)

A 12-year-old girl with cystic fibrosis suffered from severe chronic lower respiratory tract infection. For several years she had been treated with elective 3-monthly intravenous antibiotic therapy for persistent respiratory Staphylococcus aureus infection. She was hospitalized earlier than scheduled for an additional course of intravenous antibiotic therapy because of deterioration of her respiratory infection, as evidenced by increased cough and sputum production. The latest sputum samples had grown S. aureus. She was treated with intravenous ceftazidime (300mg/kg/day), colomycin (0.6 mega units, taken three times a day) and tobramycin (starting dose 4.5mg/kg/day, increased to 13mg/kg/day according to drug levels), a regimen that had previously been used successfully. All three drugs were given 8-hourly and a 14-day treatment course was planned. On day 12 a permanent indwelling venous access device (Port-A-Cath) was inserted surgically to assist venous access. The antibiotic therapy was continued for a further 4 days to cover the postoperative period. Due for discharge on day 16, the patient suddenly developed fever spikes of up to 41.28C, occurring every 8 h. Clinically there was no focus of infection, and between fevers she was well. Because of the possibility of ongoing respiratory infection the antibiotics were continued. This did not lead to clinical improvement, and the fever continued to spike at 8-hourly intervals. After 72 h of this febrile illness her full blood count started to show abnormalities; by day 20 her leukocyte count had dropped from 5.16109/L (day 5) and 3.86109/L (day 16) to 2.26109/L (day 20) with a neutrophil count of only 0.86109/L (day 20) (normal range leukocyte count: 53.56109/L, neutrophils 51.86109/L). Her platelet count dropped from 3146109/L (day 5) and 1986109/L (day 16) to 696109/L (day 20) (normal range 140–4006109/L). The haemoglobin fell from 12.1 g/dL (day 5) and 11.7 g/ dL (day 16) to 10.4 g/dL (day 20) (normal range 11.5– 14.5 g/dL; a decrease by 510% is significant)1. At this stage the differential diagnoses for this illness had included the following:
Associations between specific serum IgE response and 6 variants within the genes IL4, IL13, and IL4RA in German children
Authors: Xin Liu, Terri H Beaty, Philipp Deindl, Shau-Ku Huang, Susanne Lau, Christine Sommerfeld, M.Daniele Fallin, W.H.Linda Kao, Ulrich Wahn, Renate Nickel
Journal: Journal of Allergy and Clinical Immunology (2004)
Consolidation and maintenance therapy in multiple myeloma: randomized comparison of a new approach to therapy after initial response to treatment.
Authors: H J Cohen, A A Bartolucci, W B Forman, H R Silberman
Journal: Journal of Clinical Oncology (1986)

A randomized, controlled trial was initiated in 1977 to evaluate the impact of three alternative approaches to consolidation and maintenance therapy after initial maximal response for multiple myeloma. All patients were treated initially with BCNU, cyclophosphamide, and prednisone (BCP) until a designated level of response was achieved. Responders were randomly assigned to either melphalan and prednisone (MP); prednisone, Adriamycin (Adria Laboratories, Columbus, Ohio), azathioprine, and vincristine (PAIV), or no therapy until relapse, then treatment with BCP. Initial response rates were comparable with previous trials. A small number of incremental responses were observed with both MP and PAIV. Survival was the same for all three maintenance approaches and the same as that observed in our previous continuous BCP or MP therapy. Additional or consolidation/maintenance therapy of the type administered here appears to offer little advantage once an initial response has been achieved.
Clinical characteristics of chronic pulmonary aspergillosis and colonization; retrospective analysis of patients with isolation of asperguillus species from respiratory samples
Authors: Sayaka Ohara, Yoko Tazawa, Hajime Horiuchi, Kazuhiro Usui
Journal: European Respiratory Journal (2014)

Background and Aim of Study: With the advancement of anti-fungal drugs, it becomes more important to diagnose Chronic Pulmonary Aspergillosis (CPA). The aim of this study is to clarify the clinical characteristics of CPA.  Methods: We retrospectively extracted 110 patients with isolation of Aspergillus species from respiratory samples (sputum or broncho lavage fluid) between 01/2001 and 12/2011. We divided patients into three groups; CPA, ABPA, and colonization and compared the clinical characteristics of the patients with CPA to those with colonization.  Results: Median age of patients was 71 years-old (range 31-92). There were 46 women (42%). The most frequent Aspergillus species isolated was  Aspergillus fumigatus  (N=58), followed by  Aspergillus niger  (35),  Aspergillus flavus  (10),  Aspergillus terreus  (3),  Aspergillus nidulans  (1), and  Aspergillus spp  (13).  Thirty (27.4%) were diagnosed with CPA, whereas 75 (68.2%) with colonization and 5 (4.5%) with ABPA. Compared with colonization, CPA included more men (CPA vs colonization; 49.3% vs 13.3%), with low BMI (18.45kg/m2 vs 21.09kg/m2). CPA patients had a significantly higher prevalence of sequalae of pulmonary tuberculosis (40% vs 8%) and a history of thoracic surgery (43% vs 13%) than colonization. Bronchial asthma is less frequent in CPA group than colonization (0% vs 20%). Positivity of Aspergillus antigen is higher in CPA group than colonization group (64% vs 14%). CPA patients have significantly shorter survival than colonization (median survival time:1126 days vs not reached ).  Conclusion: CPA shows distinct clinical characteristics from colonization.
Effect of Zafirlukast (Accolate) on Cellular Mediators of Inflammation
Authors: WILLIAM J. CALHOUN, BERNARD J. LAVINS, MARGARET C. MINKWITZ, RHOBERT EVANS, GERALD J. GLEICH, JUDITH COHN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The effect of zafirlukast (Z) to alter the inflammatory response to segmental antigen challenge (SAC) was assessed by bronchoalveolar lavage (BAL) in this double-blind, placebo-controlled, two-period, crossover trial in 11 allergic asthmatic patients. Patients with asthma and positive skin tests to antigen received 7 d of treatment with Z (20 mg twice daily) or placebo (P) during two trial periods 14 to 21 d apart. At steady state (Day 5), patients underwent SAC followed by BAL immediately after challenge and 48 h later. Purified alveolar macrophages were analyzed ex vivo for phorbol myristate acetate (PMA)-driven superoxide release. Results were analyzed by analysis of variance (ANOVA). Forty-eight hours after SAC, Z therapy was associated with significantly reduced BAL lymphocytes and alcian blue–positive cells (presumably basophils) compared with P (p < 0.01), with a trend toward reduced numbers of alveolar macrophages (p = 0.06). PMA-driven superoxide release by purified alveolar macrophages was significantly reduced 48 h after SAC in the Z versus P arms (p < 0.05). Reduction of basophil influx, mediator release, and cellular activation may be important in attenuating the late phase of asthma. Collectively, the data suggest that zafirlukast therapy alters cellular infiltration and activation associated with antigen challenge.
Journal: PLoS Medicine
Authors: Paul Garner, Helen Smith
Journal: BMJ (2004)

“Prescription for a healthy journal: take monthly, at no cost; reaches six billion.” These are the heady first words written by the editors of PLoS Medicine, which hit our screens for the first time this month. This first issue, with its fascinating variety of commentary, essays, and original research, is about as good as it gets for a global medical journal. With science and research at the core of the journal, the editors have tackled head on the problems that cause a huge disease burden worldwide, with accessible articles about public health and the latest in molecular research in clinical disease and immunology.

Health problems and their solutions need research that ranges from the test tube to debates about the political context of care delivery. This journal encompasses them all in a truly international context. In this issue Bernard Pecoul writes about an initiative to improve the pipeline for new drugs for neglected diseases, such as sleeping sickness. Ann Taket and colleagues debate the evidence for whether health professionals screen all women for domestic violence. Dingle Spence from Kingston, Jamaica, and colleagues from Kampala and Kigali highlight the need for palliative care in Africa and the Caribbean. And Helene Arentz-Hansen and colleagues report research on the molecular basis for oat intolerance in people with coeliac disease. Other exciting columns are planned, such as “research in translation”—a refreshing innovation for a medical journal.

The internet is a great leveller. With immediate and free global access PLoS Medicine overcomes the iniquities of subscription based journals for people in developing countries. We have personal experience of this: when, with colleagues in Thailand, we were writing a systematic review on snake bite treatment we were able to access a paper in the BMJ just 10 minutes after it had been published, before anyone in the United Kingdom had woken up. Better access reduces power imbalance and helps global ownership; and open access publishing addresses head on the problem of user subscription charges. The Health InterNetwork access to research initiative has done much to overcome this problem for some journals for readers in registered institutions, but the initiative does not cover all countries and readers.

And what of connectivity? Is web access really an option for a doctor in Nigeria, for example? Over the last five years internet access in many countries has increased massively through commercial providers and institutional networks. Although connection charges can be costly, access seems to be getting better all the time and is often more certain, immediate, and cheaper than paper based distribution.

Journals are about engaging the reader, and this first issue of PLoS Medicine does just that. The journal has a clear mission to encourage research and comment that addresses the global burden of disease, the core values of medicine. Let us hope the editors and contributors ensure that subsequent issues are as good as the first.
Immune modulation by mesenchymal stem cells in a mouse model of house dust mite allergic asthma
Authors: Dorian Hassoun, David Lair, Virginie Forest, Marie-Aude Cheminant, Christine Sagan, Julie Chesné, Karine Botturi-Cavaillès, Damien Reboulleau, Patricia Lemarchand, Antoine Magnan
Journal: European Respiratory Journal (2012)

Background: Mesenchymal Stem Cells (MSCs) display immunomodulatory features in ovalbumin-induced allergic asthma models, by inducing Th1 and/or Treg polarization. However, little is known about their role in pneumallergen adjuvant free animal models.

Objectives: Our aim was to evaluate whether MSC could suppress inflammation in an adjuvant-free mouse model of house dust mite (HDM) allergic asthma. We hypothesized that alleviated inflammatory responses could trigger a decrease in airway hyper responsiveness (AHR) in treated mice.

Methods: After epicutaneous sensitization to HDM on day 0, 7, 14 and 21, mice were challenged with intranasal HDM on day 27 and 34. Asthmatic and sham non-asthmatic mice received an I.V. injection of 5.105 MSCs immediately prior first challenge. Effects on AHR, pulmonary inflammation, bronchoalveolar lavage (BAL), cytokine secretion and serum immunoglobulin were assessed on day 35 and 37.

Results: Treated asthmatic mice displayed a 1,8 fold decrease of airway resistance estimated by PENH (p<0,05) compared to controls with a return to baseline. Moreover, asthmatic mice treated with MSC had significantly fewer infiltrated cells in BAL than control mice (308±34 vs 734±119, N.103/mL, p<0.001), especially neutrophils (p<0.01), T cells (p<0,05) and B cells (p<0.05). An increase of IL-10 in BAL was observed in treated mice compared with controls (26,80±11,19 vs 10,39±2,75, pg/mL). In parallel, non-asthmatic treated mice showed neither significant pulmonary cell infiltration (227±38 vs 152±18, N.103/mL) nor development of AHR compared to controls.

Conclusions: Taken together, these results demonstrate that MSC reduced AHR in a relevant allergic model of HDM asthma.