tbuckley/cabot-search huggingface dataset:
Potentiation of cytotoxic drugs with concomitant exposure to retinoids in neuroblastoma
Authors: Peter C. Adamson, Catherine Wilson
Journal: Cancer Research (2006)

4873  The current treatment of high-risk neuroblastoma includes dose intensive chemotherapy followed by administration of retinoids. The basis for administering retinoids following chemotherapy is largely empiric, and whether concomitant administration of retinoids with cytotoxics is superior has not been explored. METHODS: We analyzed three sequences of drug administration in two neuroblastoma cell lines (SH-SY5Y and NGP): retinoid followed by cytotoxic, cytotoxic followed by retinoid, and concomitant exposure. Each exposure block was for three days with analysis on day 7. Retinoids studied were 9-cis retinoic acid (9cRA), 13-cis retinoic acid (13cRA), all-trans retinoic acid (ATRA), and fenretinide (4-HPR); cytotoxics studied were cisplatin (CDDP), etoposide (VP16), vincristine (VCR), doxorubicin (DOX), topotecan (TOPO), and irinotecan (IRN). Cell proliferation was assessed with the SRB assay. As most retinoids do not produce cytotoxicity at pharmacologically relevant concentrations, enhancement to the effects of chemotherapy was examined through a potentiation design. Three concentrations of retinoids (1, 5 and 10 μM) were studied against a range of cytotoxic drug concentrations that yielded a concentration-response curve. Results were expressed as the log ratio of the combination to the single agent exposure [log(IC50retinoid+cytotoxic/IC50cytotoxic)]. RESULTS: Retinoids had the greatest potentiating effect on the cytotoxicity of CPPD followed by VCR; the potentiation appeared most pronounced with concomitant exposure. In SH-SY5Y cells, the IC50 log ratio of 13cRA with CPPD was -0.80 for concomitant exposure, -0.67 for cytotoxic followed by retinoid, and -0.43 for retinoid followed by cytotoxic. For 4-HPR and CPPD, the log ratio was -0.93 for concomitant exposure, -1.1 for cytotoxic followed by retinoid, and -0.63 for retinoid followed by cytotoxic. Similar trends were found with ATRA and 9cRA. Potential antagonistic effects were observed with IRN and TOPO. CONCLUSIONS: Contrary to how retinoids are currently utilized, concomitant rather than sequential exposure of retinoids and cytotoxics appeared most effective for select drugs. The addition of 13cRA or 4-HPR to CPPD resulted in an almost 10-fold increase in the cytotoxicity of CPPD. Further evaluation of select combinations in in vivo models is warranted and ongoing.
Fungal infections of skin and nails of feet
Authors: H. Williams, R. Hart, S. E M Bell-Syer, F. Crawford, P. Young, I. Russell, D. J Torgerson
Journal: BMJ (1999)

Editor—The systematic review on topical treatment for fungal infections of the feet and the accompanying editorial by Finlay illustrate the difficulties encountered when the evidence shows that an alternative treatment is both more effective and more expensive.1,2 Finlay (a member of the advisory board of Novartis, which manufactures the more expensive allylamine treatment) believes that we should give our patients the most effective (and most expensive) treatment. Hart et al provide purchasers with a more balanced view by presenting the costs of treating patients with an azole initially followed by an allylamine against the likely costs of treating all patients with allylamines from the start.

I had always been led to believe that topical terbinafine was vastly superior to azoles in tinea pedis, but the systematic review shows that cure rates were 80% and 72% respectively—not a vast difference in absolute terms. So there is at least a case for a policy of “try the cheaper one first and then the more expensive one after” in an NHS that has limited money to spend. Wider debate is needed about whether the inconvenience associated with such a policy for the 8% of patients who might have been cured if they had been given terbinafine in the first place outweighs the savings. Extrapolated on a national scale, the saving of £155 per cohort of 100 patients could save around £12.5m for the NHS as a whole, even if only a tenth of those with fungal infections of the foot sought medical care—money that arguably could be better spent.

One of the conclusions has to be that a pragmatic clinical trial is now necessary to test the model of azoles first then allylamine for treatment failures versus allylamines throughout. Finlay suggests that patients will simply not comply with four weeks’ treatment whereas they would with one week’s treatment, a hypothesis that is fully testable in a pragmatic trial. Such a trial would also answer the question of whether the 28% or so of people who do not respond to azoles initially will then respond to the allylamine or whether they represent a subset with resistant fungal species that fail to respond to anything.

Those working for the NHS have a duty not to accept automatically the most effective and expensive treatment but to question the evidence of gains and losses for competing strategies. Far from being confused by the evidence, patients and prescribers are now aware of exactly how much extra benefit they may receive from different treatment choices.
Cardiovascular pharmacology. II: The use of catecholamines, pressor agents, digitalis, and corticosteroids in CPR and emergency cardiac care.
Authors: Otto Cw
Journal: Circulation (1986)

The Cardiovascular Pharmacology II panel met during the AHA National Conference on Standards and Guidelines for CPR and emergency cardiac care to consider the use of catecholamines, pressor agents, digitalis, and corticosteroids during advanced cardiac life support. During cardiac arrest, catecholamines and pressor agents have been shown to improve the rate of success of resuscitation. The useful properties of these drugs are mediated by strong alpha-adrenergic stimulation resulting in improved coronary perfusion. beta-Adrenergic stimulation during cardiac arrest is unimportant for resuscitation and potentially harmful. Studies have not demonstrated a difference between mixed agonists and alpha-agonists with respect to overall outcome. Consequently, the panel recommended that epinephrine continue to be the primary vasopressor for use during cardiac arrest. For cardiovascular support in the hemodynamically unstable patient, the panel recommended that drugs be chosen for specific pharmacologic actions that will allow the needed physiologic manipulation guided by objective hemodynamic measurements. The panel found that digitalis preparations and corticosteroids have very limited use in emergency cardiac care.
Sequential Intravenous Oral Antibiotic Therapy for Osteomyelitis
Authors: Ian C. Michelow, Jason G. Mandell
Journal: JAMA Pediatrics (2015)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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 Pediatrics journal
Abstract 18178: Role of Mesenchymal Stem Cell SDF-1 Release and Myocardial CXCR4 Expression in Post -MI Cardiac Repair
Authors: Feng DONG, Amanda Finan, Kristal Weber, Marc Penn
Journal: Circulation (2011)

Introduction: Adult stem cell based repair of the heart is due to paracrine factor release. SDF-1 has been shown to affect multiple pathways involved in tissue repair and is secreted by mesenchymal stem cells (MSC). In this study we directly tested the importance of MSC SDF-1 release on myocardial response to MSC engraftment after myocardial infarction (MI). Methods: Cardiac myocyte (CM)-CXCR4 null mice were generated using tamoxifen inducible cardiac specific cre by crossing the CXCR4 floxed with the MCM-cre mouse. Studies were performed in littermates who did (CM-CXCR4 null) or did not (control) receive tamoxifen at least 3 weeks before MI. Mice were randomly selected to receive either 100,000 GFP positive MSC or saline 1 d after MI. Cardiac stem cells (CSC) population in the heart 7 days post MI were investigated by flow cytometry. Serial echocardiography was used to assess cardiac function. The number of TUNEL positive cardiac myocytes in the infarct border zone was quantified 4 days after AMI. Vascular density and infarct size were measured 21 d after AMI. Results: The αMHC-MerCreMer promoter is activated in both endogenous CSC and cardiac myocytes. There was a similar level of MSC engraftment in wild-type (WT) and CM-CXCR4 null mice 7 days following MSC infusion. MSC engraftment led to a significant increase of CSC recruitment (100.9%, p&lt;0.01) in the heart of WT mice 7 days after MI that was decreased to 55.4% in CM-CXCR4 null mice. MSC treatment decreased CM apoptosis by 44% in WT mice but only 23% in CM-CXCR4 null mice (p&lt;0.01). Consistent with improved CM survival, MSC infusion led to an 80% (p&lt;0.05) increase in ejection fraction in WT mice compared to a 40% (p=NS) increase in CM-CXCR4 null mice despite similar levels of an increase (16%) in vascular density in the presence or absence of CM-CXCR4. Conclusion: Our results demonstrate a specific paracrine mechanism of MSC engraftment and support an important role for SDF-1/CXCR4 in CSC recruitment and cardiac myocyte survival after AMI. Furthermore, our data demonstrate that in the absence of SDF-1 mediated increases in cardiac myocyte survival and CSC recruitment, the increase in vascular density induced by MSC engraftment is unchanged but insufficient to induce significant improvements in cardiac function after AMI.
Abstract 3062: Evaluation of Long-term Changes of Neointimal Coverage on Sirolimus-eluting Stents by Optical Coherence Tomography
Authors: Matsumoto Daisuke, Shite Junya, Shinke Toshiro, Otake Hiromasa, Ogasawara Daisuke, Tanino Yusuke, Sawada Takahiro, Yokoyama Mitsuhiro
Journal: Circulation (2006)

BACKGROUND Long term condition of neointimal coverage on Sirolimus-eluting stents (SES) remains to be clarified. Optical coherence tomography (OCT) with an excellent resolution visualizes thin neoi...
Honey, I Sequenced the Kids: Preventive Genomics and the Complexities of Adolescence
Authors: Maya Sabatello, Paul S. Appelbaum
Journal: The American Journal of Bioethics (2015)

How much control should individuals have over their genomic data? Although this question has been extensively discussed in debates about return of genomic incidental findings (IFs), Lazaro-Munoz and colleagues consider it in another putative context: population-based preventive genomic sequencing (PGS) programs that would target rare, highly penetrant, and medically actionable genetic (MAG) conditions. The authors advocate for a “menu” rather than a “panel” approach to the management of genomic information—allowing participants greater discretion regarding genes to be analyzed—because it better resonates with prevalent notions of patients’ autonomy, choice, and patient-centered decision making in medical contexts. This is an important discussion, which will likely continue. However, the article does not address the implications of either approach for minors; indeed, it does not mention minors at all. Although steering away from genomic dilemmas in minors may simplify the discussion, it misses important considerations for this substantial group of stakeholders. As genetic testing in pediatrics increases, knowledge of adolescents’ genetic propensities may have substantial positive and negative impact on their life plans, identity, and other aspects of their development. Consideration of their interests in this evolving context is consistent with the increasing recognition of children, especially adolescents, as active participants in medical decision making. In this commentary, we highlight the complexities involved with the management of genomic findings of adolescents and offer possible ways to enhance their autonomous choices in such processes.
Abstract 011: Prevalence and Control of Diabetes in Chinese Adults: The China Metabolic Risk Factor Study
Authors: Yufang Bi, Yu Xu, Mian Li, Weiqing Wang, Tiange Wang, Limin Wang, Yong Jiang, Min Xu, Jieli Lu, Jianhong Li, Shengquan Mi, Chung-Shiuan Chen, Shenghan Lai, Linhong Wang, Jiajun Zhao, Yiming Mu, Guangwei Li, Jiang He, Jialun Chen, Lingzhi Kong, Wenhua Zhao, Guang Ning
Journal: Circulation (2013)

Objective: Diabetes is a major risk factor for vascular disease in the general population. We investigated the prevalence of diabetes and glycemic control in the Chinese adult population. Methods: We conducted a cross-sectional survey in a nationally representative sample of 98,658 Chinese adults aged ≥18 years in 2010. After an overnight fast, participants without known diabetes underwent an oral glucose-tolerance test (OGTT) using 75 g anhydrous glucose dissolved in water. Previously diagnosed diabetes was determined on the basis of self-report. Undiagnosed diabetes was defined as a hemoglobin A1c (A1c) ≥ 6.5% or fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/l) or 2-h plasma glucose (2-h PG) ≥200 mg/dl (11.1 mmol/l) during an OGTT according to the 2010 American Diabetes Association criteria. Pre-diabetes was defined as FPG 100-125 mg/dl (5.6-6.9 mmol/l) or 2-h PG 140-199 mg/dl (7.8-11.0 mmol/l) or A1c 5.7-6.4%. Prevalence was calculated by weighting sampling factors derived from China population census data in 2010 to obtain national estimates. Results: Prevalence of self-reported diabetes was estimated to be 3.5% in the Chinese population aged ≥18 years (3.6% in men and 3.4% in women) or 34.2 million persons (18.0 million men and 16.3 million women). Prevalence of undiagnosed diabetes was 8.1% (8.5% in men and 7.7% in women) or 79.6 million persons (42.5 million men and 37.1 million women), and the prevalence of pre-diabetes was 50.1% (52.1% in men and 48.1% in women) or 493.4 million persons (260.1 million men and 233.3 million women). The prevalence of diabetes was higher in urban (14.3%) than in rural (10.3%) residents, and higher in persons who were older, heavier, and living in economically developed areas. The proportion of controlled (A1c &lt;7.0%) was 42.8% among self-reported diabetes (42.3% in men and 43.4% in women) in the general population in China. Conclusions: Our study shows that the prevalence of diabetes in the general population in China is much higher than previously reported. More troublesome, 7 out of every 10 diabetic patients are undiagnosed. Among self-reported diabetes, 3 out of 5 were poorly controlled. Our findings indicate that diabetes has become a major public health problem in China and suggest an urgent need to develop national strategies for prevention and treatment of diabetes.
Hypoxia But Not Inflammation Augments Glucose Uptake in Human Macrophages
Authors: Eduardo J. Folco, Yuri Sheikine, Viviane Z. Rocha, Thomas Christen, Eugenia Shvartz, Galina K. Sukhova, Marcelo F. Di Carli, Peter Libby
Journal: Journal of the American College of Cardiology (2011)
Abstract 13595: Echocardiographic Determination of Left Ventricular Diastatic Chamber Stiffness: Kinematic Modeling-Based Derivation With in-vivo Validation
Authors: Sina Mossahebi, Sandor J Kovacs
Journal: Circulation (2011)

The slope of the diastatic pressure-volume relationship (D-PVR) defines passive left ventricular (LV) stiffness K. Although K is a relative measure, an absolute measurement method (cardiac catheterization) is employed to obtain it. Echocardiography is the preferred quantitative diastolic function (DF) assessment method and Doppler E-waves can only provide relative, rather than absolute, pressure information. We hypothesized that appropriate E-wave analysis can generate the D-PVRE-wave whose slope, KE-wave, is the E-wave derived diastatic, passive chamber stiffness - a relative DF index. A validated kinematic model of filling and Bernoulli's equation were used to compute pressure and volume at diastasis, to generate D-PVRE-wave, parametrized by the kinematic model's E-wave derived indexes of stiffness (k), relaxation/viscoelasticity (c) and load (xo). For validation, simultaneous (conductance catheter) P-V and echocadiographic E-wave data from 30 subjects (444 total cardiac cycles) having normal LV ejectio...
An open-label, comparative study of the efficacy and safety of an outpatient single daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis.
Authors: E. Ramacciotti, G. R. Araujo, S. Lastoria, Francisco Humberto de Abreu Maffei, F. Dietrich
Journal: Blood (2002)
Abnormal extra heartbeats may be modifiable risk factor for heart failure, study shows:
Authors: Susan Mayor
Journal: BMJ (2015)

Having commonly occurring abnormal extra heartbeats known as premature ventricular contractions may be a modifiable risk factor for congestive heart failure, the results of a large US follow-up study have shown.1

The study, published in the Journal of the American College of Cardiology , randomly assigned 1139 people aged 65 and over to 24 hour ambulatory electrocardiography. These participants were a subgroup of the 5201 randomly selected people recruited to …
Abstract 14802: Osteoprotegerin and Osteopontin Serum Levels Are Associated With Arterial Wall Properties and Interleukin-6 Serum Levels in Patients With Coronary Artery Disease
Authors: Konstantinos Maniatis, Gerasimos Siasos, Dimitris Tousoulis, Evangelos Oikonomou, Marina Zaromitidou, Stamatios Kioufis, Eleni Kokkou, Nikolaos Gouliopoulos, Savvas Mazaris, Theodosia Konsola, Christina Kollia, Manolis Vavuranakis, Konstantinos Zisimos, Christodoulos Stefanadis
Journal: Circulation (2013)

Background: Osteoprotegerin (OPG) and osteopontin (OPN) have recently emerged as key factors in both vascular remodeling and atherosclerosis progression. Interleukin-6 is a well established inflamm...
Modeling Chronic Myelomonocytic Leukemia Through Patient-Derived Induced Pluripotent Stem Cells
Authors: Keisuke Kataoka, Kazuki Taoka, Masashi Miyauchi, Masataka Hosoi, Keiki Kumano, Shunya Arai, Kazuhiro Toyama, Genta Nagae, Wei Qu, Shinichi Morishita, Hiroyuki Aburatani, Mineo Kurokawa
Journal: Blood (2013)
Silibinin inhibits in vivo growth of colorectal cancer by inhibiting tumor cell proliferation and angiogenesis in athymic nude mice
Authors: Mallikarjuna Gu, Rana Singh, Rajesh Agarwal
Journal: Cancer Research (2007)

4966  Dietary intake of many fruits and vegetables as well as supplements has been shown to be associated with reduced risk of cancer. In this regard, chemoprevention is emerging as an alternative and effective strategy for colorectal cancer (CRC) control. Here, for the first time we investigated the in vivo efficacy and associated molecular biomarkers and mechanisms of silibinin, a naturally occurring flavanolignan, in human colorectal tumor xenograft in athymic nude mice. Mice were implanted with human colorectal HT-29 carcinoma cells, and six days later when tumors were of ~300 mm3 size, oral gavaged with vehicle (carboxymethyl cellulose) or 200 mg/kg/day (5 days/week) dose of silibinin for 32 days. Tumor size, body weight and diet consumption were monitored twice a week. At the end of experiment, tumors were analyzed for biomarkers, namely, cell proliferation, apoptosis and angiogenesis, and associated molecular alterations by immunohistochemistry (IHC) and/or western blot analysis. Our data show that silibinin feeding strongly inhibited tumor growth that accounted for 48% (P=0.002) decrease in tumor volume/mouse and 42% (P=0.012) decrease in tumor weight/mouse at the end of the experiment. A stronger antitumor effect was observed when silibinin was fed as silybin-phytosome preparation which contains silibinin and phosphatidylcholine in 1:2 ratios in order to enhance its absorption. Silibinin feeding did not show any significant change in body weight gain and diet consumption. IHC analysis of tumors showed that silibinin decreases proliferation index by 40% (P
Ceftriaxone or ciprofloxacin should be considered as first line prophylaxis
Authors: M J Martin, N A Hutchinson, I J Eltringham, P Y C Lee, K Birthistle
Journal: BMJ (1996)

EDITOR,—We disagree with several points raised by Bjorn-Erik Kristiansen and Arne-Birger Knapskog in their editorial on secondary prevention of meningococcal disease.1 Rifampicin eradicates carriage but may not prevent systemic disease. …
AMG 900, a Potent and Highly Selective Aurora Kinase Inhibitor Shows Promising Preclinical Activity Against Acute Myeloid Leukemia Cell Lines In Vitro and In Vivo
Authors: Kam Cheung, Gloria Juan, William Wayne, Kelly Hanestad, Kathleen Keegan, Justin Huard, Patricia McElroy, Mary K Stanton, Tammy L Bush, Richard L Kendall, Robert Radinsky, Steve Abella, Peter C Pieslor, Gregory Friberg, Angela Coxon, Erick Gamelin, Marc Payton
Journal: Blood (2013)
Abstract 17024: Are the Clinical Outcomes with Everolimus-eluting versus Paclitaxel-eluting Coronary Stents Different in Patients With and Without Diabetes? Insights from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE Randomized Trials
Authors: Gregg W Stone, Elvin Kedhi, Patrick W Serruys, Helen Parise, Martin Fahy, Peter C Smits, Dean J Kereiakes
Journal: Circulation (2010)

Introduction: Prior studies have been inconclusive as to whether the clinical outcomes with rapamycin analogue-eluting versus paclitaxel-eluting stents (PES) differ in pts with and without diabetes mellitus (DM), and no single trial has been adequately powered to definitively address this question. We therefore analyzed the 1-year clinical outcomes in patients randomized to XIENCE V everolimus-eluting stents (EES) compared to TAXUS Express2 or Liberte paclitaxel-eluting stents (PES) from a large pooled database of 4 randomized trials. Methods: Baseline clinical, angiographic and procedural data from the SPIRIT II, III, IV and COMPARE trials, each of which assigned pts to EES vs. PES, were pooled in a database of 6,788 randomized pts. One-year clinical event rates were calculated with Kaplan-Meier methods and compared with the log-rank test according to the presence or absence of DM. Results: DM was present in 1,869/6,780 pts (27.6%), including 494 pts (7.3%) requiring insulin (DM status was unknown in 8 ...
Second messenger systems and psychoactive drug action: focus on the phosphoinositide system and lithium
Authors: J M Baraban, P F Worley, S H Snyder
Journal: American Journal of Psychiatry (1989)

Most models of psychotropic drug action have emphasized effects on the release or uptake of neurotransmitters as well as interactions with receptors. Stimulation of neurotransmitter receptors triggers a complex array of electrical and biochemical actions. Recent experimental advances have greatly clarified the second messenger systems underlying neurotransmitter actions, suggesting novel sites of action for psychotropic agents. The authors emphasize the phosphoinositide system and the implications of its involvement for the therapeutic actions of lithium.
P0026 : The HIV infection does not have impact on survival and tumor recurrence in hepatocellular carcinoma patients treated by liver transplantation
Authors: F. Agüero, A. Forner, C. Manzardo, A. Valdivieso, M. Blanes, R. Barcena, A. Rafecas, L. Castells, A. Rimola, J.M. Miró
Journal: Journal of Hepatology (2015)