tbuckley/cabot-search huggingface dataset:
Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study
Authors: G. Holzer, E. Riegler, H. Hönigsmann, S. Farokhnia, B. Schmidt
Journal: British Journal of Dermatology (2005)

Journal Article Effects and side‐effects of 2% progesterone cream on the skin of peri‐ and postmenopausal women: results from a double‐blind, vehicle‐controlled, randomized study Get access G. Holzer, G. Holzer Division of Special and Environmental Dermatology, Medical University of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria *Pharmacy Department, General Hospital of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Dr Gregor Holzer. E‐mail: gregor.holzer@meduniwien.ac.at Search for other works by this author on: Oxford Academic Google Scholar E. Riegler, E. Riegler Division of Special and Environmental Dermatology, Medical University of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria *Pharmacy Department, General Hospital of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar H. Hönigsmann, H. Hönigsmann Division of Special and Environmental Dermatology, Medical University of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria *Pharmacy Department, General Hospital of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar S. Farokhnia, S. Farokhnia Division of Special and Environmental Dermatology, Medical University of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria *Pharmacy Department, General Hospital of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar B. Schmidt B. Schmidt Division of Special and Environmental Dermatology, Medical University of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria *Pharmacy Department, General Hospital of Vienna, Währinger Gürtel 18–20, A‐1090 Vienna, Austria Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 3, 1 September 2005, Pages 626–634, https://doi.org/10.1111/j.1365-2133.2005.06685.x Published: 01 September 2005 Article history Accepted: 12 January 2005 Published: 01 September 2005
The Carcinogenicities of Fluoro Derivatives of 10-Methyl-1,2-benzanthracene II. Substitution of the K Region and the 3′-, 6-, and 7-Positions
Authors: James A. Miller, Elizabeth C. Miller
Journal: Cancer Research (1963)

Substitution of fluorine in the 4 position of the K region of 10-methyl-1,2-benzanthracene had little effect on the carcinogenic activity of this hydrocarbon toward mouse skin and the subcutaneous tissues of rats and mice. These results are in great contrast to our previously reported data on the lack of carcinogenic activity in the same tests of the 3-fluoro derivative which contains the fluorine substituent on the other carbon atom of the K region. Each of the 3′-, 6-, and 7-fluoro derivatives of 10-methyl-1,2-benzanthracene had considerable carcinogenic activity in two or more of the four tests employed, and therefore these positions do not appear to be directly involved in the carcinogenic activity of this hydrocarbon. 1,2-Benzanthracene and its 3-fluoro derivative exhibited little or no activity in these tests. 4′-Fluoro-1,2-benzanthracene had considerable carcinogenic activity toward the subcutaneous tissue of rats.

The role of the K region in carcinogenesis by the polycyclic aromatic hydrocarbons has been reviewed. Where adequate tests have been made, the 3-substituted compounds have generally had little or no activity, whereas the 4-substituted compounds are, in some cases, relatively active. These data and the carcinogenic activities of some sulfur isosters which do not appear to contain a K region (Waravdekar and Ranadive; Tilak) clearly indicate the need for further studies in this area.
Abstract 1651: Profiling immune cells within the tumor microenvironment for optimal model selection for pre-clinical investigations
Authors: Andrew Leishman, Olivia Harris, Jane Coates Ulrichsen, James Harper, Amy Popple, Marianna Papaspyridonos, Geoff Williams, Stefanie Mullins, Viia Valge-Archer, Ross Stewart, Richard Sainson, Michelle Morrow, Robert Wilkinson
Journal: Cancer Research (2014)

Abstract Infiltrating host immune cells can have a significant impact on the growth and outcome of many tumor types. Several leukocyte populations have been implicated in establishing an immune suppressive microenvironment (e.g. myeloid derived suppressor cells [MDSCs) and regulatory T cells [Treg cells]) and thus making it harder for anti-tumor immune effector cells to function (e.g. CD8 cytotoxic T cells). Immune-Mediated Therapy (IMT) is emerging as a key strategy for the treatment of cancer through by enhancing a patient's anti-tumor immune response. In order to maximise the potential of IMT strategies it is important to understand the immune status within the tumor microenvironment as well as systemically. Therefore, fully immune-competent preclinical models are valuable tools to enable the study of the immune system, both locally within the tumor and systemically, to understand the mechanism of action of IMT monotherapies and combination therapies in vivo. Consequently, we have profiled the immune status of a panel of syngeneic mouse tumor models to assist optimal model selection to aid these investigations. We developed multi-parameter flow cytometry techniques to identify specific immune subsets in both the tumor microenvironment and the periphery. These investigations revealed a number of tumor infiltrating immune cell end-points that can be used to correlate with response to IMT depending on the syngeneic model being used. For example, we observed differences in the MDSC and Treg cell populations across the models investigated, which will influence optimal model selection depending on the mechanism of action of the IMT being tested. Citation Format: Andrew Leishman, Olivia Harris, Jane Coates Ulrichsen, James Harper, Amy Popple, Marianna Papaspyridonos, Geoff Williams, Stefanie Mullins, Viia Valge-Archer, Ross Stewart, Richard Sainson, Michelle Morrow, Robert Wilkinson. Profiling immune cells within the tumor microenvironment for optimal model selection for pre-clinical investigations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1651. doi:10.1158/1538-7445.AM2014-1651
Abstract 13292: A Novel Reproducible Noninvasive Imaging Approach to Quantify Nitric Oxide-mediated Coronary Endothelial Function in Humans
Authors: Micaela Iantorno, Allison G Hays, Sahar Soleimanifard, Angela Steinberg, Michael Schar, Gary Gerstenblith, Matthias Stuber, Robert G Weiss
Journal: Circulation (2014)

Endothelial release of nitric oxide (NO) is a defining characteristic of non-diseased vascular tissue. Healthy coronary arteries respond to endothelial-dependent stressors with vasodilatation but those with endothelial dysfunction respond with paradoxical vasoconstriction. The combination of new non-invasive 3T coronary MRI methods and isometric handgrip exercise (IHE), has been suggested as a means to noninvasively quantify coronary endothelial function (CEF). However, IHE may trigger neural, neuro-hormonal and other vasoreactive responses; thus, it is unknown whether the IHE-induced coronary response is, in fact, primarily mediated by NO. Furthermore, it is not known whether the MRI-IHE test is reproducible over time.To test the hypothesis that the IHE-induced coronary response is NO-mediated, we performed MRI-IHE studies before and during the infusion of monomethyl-L-arginine (L-NMMA, 0.3mg/kg/min), a NO synthase inhibitor in 8 healthy subjects. To study reproducibility we performed 2 MRI-IHE studies ~8 weeks apart in 8 coronary artery disease (CAD) patients and 9 healthy subjects. Changes from rest to IHE in coronary cross-sectional area (%CSA) and coronary blood flow (%CBF) were measured with cine MRI. L-NMMA completely blocked coronary vasodilation during IHE (%CSA change 15.4%±2.8% with placebo vs -1.6%±1.3% with L-NMMA; p&lt;0.0001) and the normal increase in coronary blood flow (%CBF change 50.2%±6.7% with placebo vs -2.1%±6.7% with L-NMMA; p&lt; 0.0001). Moreover, there was a strong correlation between repeated measures for %CSA change with IHE at the two exams (R=0.91, p&lt;0.0001) and %CBF change with IHE (R=0.80; p&lt;0.001). Bland-Altman analysis and intra-class correlation coefficients for %CSA and %CBF change with IHE (0.90 and 0.80, respectively) indicated good agreement and little variability between repeated measures. In summary the coronary response to IHE is largely mediated by endothelial-derived NO and is reproducible over several weeks. Thus MRI-IHE is a noninvasive, reproducible tool to assess CEF, arguably the first to noninvasively measure macro- and micro-vascular NO-mediated coronary responses. This noninvasive tool may be useful in future studies of the impact of interventions on CAD pathogenesis.
A retrospective cost-effectiveness analysis of the treatment of onychomycosis in general practice
Authors: None Humphrey, None Cork, None Haycox
Journal: British Journal of Dermatology (1998)

Analysis of the computer records of 100 general practices from the CompuFile Doctors Independent Network revealed 1492 patients receiving treatment for onychomycosis in the first 6 months of 1994 with terbinafine, tioconazole, amorolfine or griseofulvin. These records indicated the average treatment time for each agent, number of general practitioner consultations and incidence of hospital referrals and minor surgery. Applying standard costs to this resource consumption gave the direct costs for each of these four agents. Published clinical and mycological cure rates allowed a cost per success to be calculated. These were as follows: terbinafine (n = 511) £258, amorolfine (n = 315) £312, griseofulvin (n = 196) £356 and tioconazole (n = 470) £520. Sensitivity analysis showed that terbinafine remained the most cost-effective option despite variations in resource costs. The cost impact on a typical practice for switching from a less to a more cost-effective treatment is discussed.
Abstract 8688: Incident Stroke and Mortality Associated with First-detected Atrial Fibrillation in Patients Hospitalized with Severe Sepsis
Authors: Allan J Walkey, Renda S Wiener, Joanna M Ghobrial, Lesley H Curtis, Emelia J Benjamin
Journal: Circulation (2011)

Introduction: First-detected fibrillation (AF) has been reported in 6-20% of patients with severe sepsis. Whereas chronic AF is a known risk factor for stroke and death, the clinical significance of first-detected AF in the setting of sepsis is uncertain. Our objective was to determine the in-hospital stroke and in-hospital mortality risks associated with first-detected AF in patients with severe sepsis. Hypothesis: First-detected AF during severe sepsis is associated with increased risk for in-hospital stroke and in-hospital mortality. Methods: Retrospective population-based cohort derived from 2007 California State Inpatient Database administrative claims data. Data was available from 3,147,787 hospitalized adults. Severe sepsis [N=49,082 (1.56%)] was defined by validated ICD-9-CM code 995.92. First-detected AF was defined as AF that occurred during the hospital stay, after excluding AF cases present at admission. A priori outcome measures were in-hospital ischemic stroke ( ICD-9-CM 433, 434, or 436) and mortality. Analyses of stroke and mortality outcomes were adjusted for demographics, comorbidities, and acute factors. Results: Patients with severe sepsis were 69±16 years old and 48% were women. First-detected atrial fibrillation occurred in 5.9% of patients with severe sepsis versus 0.6% of patients without severe sepsis [multivariable-adjusted odds ratio (OR), 6.82; 95% confidence interval (CI), 6.54-7.11; P &lt;0.001]. Severe sepsis was present in 14% of all first-detected AF in hospitalized adults. Participants with severe sepsis and first-detected AF had in-hospital ischemic stroke at a rate of 34.5 (95% CI, 27.2-43.3) strokes/100 patient-years. Compared with severe sepsis patients without first-detected AF, patients with first-detected AF during sepsis had greater risks of in-hospital stroke (0.6% vs. 2.6%, adjusted OR 2.70; 95% CI, 2.05-3.57; P &lt;0.0001) and in-hospital mortality (39% vs. 56%, adjusted relative risk, 1.07; 95% CI, 1.04-1.11; P &lt;0.0001). Conclusion: First-detected AF during severe sepsis is associated with clinically significant adverse outcomes including higher risk of stroke and death. Investigation of strategies to decrease risks associated with incident AF during severe sepsis are warranted.
EUS-FNA as staging tool in resectable pleural mesothelioma
Authors: S. A. Burgers, K. G. Tournoy, M. Smits, H. M. Klomp, J. T. Annema, J. P. Van Meerbeeck, P. Baas
Journal: Journal of Clinical Oncology (2008)

7606 Background: Patients with limited (cT1–3N0–1) malignant pleural mesothelioma (MPM) are potential candidates for trimodality therapy with induction chemotherapy, extrapleural pneumonectomy and hemithoracic irradiation. Since invasion of the mediastinal lymph nodes (MLN) is a negative prognostic factor, cervical mediastinoscopy has been recommended for staging. Transesophageal endoscopic ultrasound (EUS) and real-time guided fine needle aspiration (FNA) enables MLN staging in lung cancer patients with high accuracy. This study determined the feasibility and diagnostic yield of EUS-FNA in MPM, in comparison to the gold standard surgical-pathological staging. Methods: In this prospective two-center study, eligible patients had pathologically confirmed and potentially resectable MPM. Staging was performed by spiral-CT, PET, EUS-FNA and, irrespective of the EUS-FNA results, by cervical mediastinoscopy. Subsequently, patients had cisplatin and pemetrexed chemotherapy, which was in case of response or stable disease, followed by extrapleural pneumonectomy and MLN dissection. Results: Thirty-two consecutive patients (26 males; 25 right-sided) were registered from June 2004 until January 2007. Median age was 59 years (range 40–67). There were 2 sarcomatous, 26 epithelial and 4 biphasic subtypes. EUS was performed in all patients, in 7/32 without FNA since no lymph nodes > 5 mm were seen. EUS-FNA showed malignant cells amid a lymphocyte background in 4 (19%). Cervical mediastinoscopy was subsequently performed in 27 (84%) patients, which revealed no additional patients with MLN metastasis. In 11 patients, negative EUS-FNA was not confirmed by thoracotomy, mainly due to disease progression and clinical deterioration. Thoracotomy revealed a single level MLN metastasis at Naruke 4R in one patient, which was detected by neither EUS-FNA nor mediastinoscopy. Sensitivity of EUS- FNA for MLN metastases was 80% (95%-confidence limit 28–99%), specificity 95% (79–100%), NPV 94% (71–99%) and PPV 100% (39–100%). Conclusions: This is the first prospective study of EUS-FNA in MPM. EUS-FNA seems both a feasible and reliable tool for mediastinal staging in patients with potentially resectable MPM. Cervical mediastinoscopy in addition to EUS-FNA did not contribute to the detection of MLN metastases. No significant financial relationships to disclose.
Tumor Formation With Transplants of Spleen or Liver From Mice With Virus-Induced Leukemia&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Charlotte Friend, Jamil R. Haddad
Journal: JNCI Journal of the National Cancer Institute (1960)

Solid tumors were established from grafts of both the spleen and liver of a strain DBA/2 mouse with a virus-induced leukemia. The tumors, composed of the large, undifferentiated mononuclear cells characteristic of this virus leukemia, were serially transplantable to 100 percent of DBA/2 mice. Thus far, after 21 serial generations the tumors contain appreciable amounts of virus. The course of the disease was more rapid in mice implanted with local tumors than in those inoculated intraperitoneally with the virus. Tumor-bearing mice succumbed with generalized leukemia within approximately 35 days in contrast to those injected with virus, which had an average survival time of about 70 days. However, when transplantation to the randombred Swiss mice was attempted, tumors rarely developed.
Abstract 18482: Pharmacokinetics and Pharmacodynamics of Dabigatran Etexilate in Adolescents: An Open-label Phase IIa Study
Authors: Maximilian T Lobmeyer, Thorsten Lehr, Jacqueline M Halton, Lisa Cronin, Sebastian Haertter, Lesley Mitchell
Journal: Circulation (2014)

Introduction: Dabigatran etexilate (DE) is an oral direct thrombin inhibitor. It is approved for multiple indications in adults. HYPOTHESIS: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran in adolescents with venous thromboembolism (VTE). METHODS: Patients aged 12-< 18 years, who had completed anticoagulation treatment with low molecular weight heparin or an oral anticoagulant for VTE as required for clinical management, received DE twice daily for 3 days at exploratory doses targeting 1.71 mg/kg for the first dose, followed by 5 doses of 2.14 mg/kg, if there were no safety concerns. Blood samples for PK/PD purposes were taken at peak (2 h after morning dose) and trough (12 h after the evening dose). Observed plasma concentrations of total dabigatran were compared to simulated concentrations based on a population-pharmacokinetic (PopPK) model. The PK/PD relationships between total dabigatran plasma concentrations and activated partial thromboplastin (aPTT), diluted thrombi...
Man whose tumour went untreated loses negligence battle
Authors: Dyer Clare
Journal: BMJ (2005)

A man with non-Hodgkin's lymphoma whose tumour spread and went untreated for nine months—after a GP had negligently diagnosed a lipoma and failed to refer him to hospital—lost a long legal battle in the House of Lords last week.

The Medical Defence Union, which fought the case on behalf of the doctor, hailed the result as a “landmark victory.” Had it not won, the union said, “the case would have seen the erosion of a fundamental principle in clinical negligence law, with serious implications for UK clinicians.” It might have led to a massive increase in compensation claims, they warned.

In November 1994 the patient, Malcolm Gregg, …
Malaria Vaccine Shows Promise
Authors: Tracy Hampton
Journal: JAMA (2004)

THE LARGEST MALARIA VACCINE EFficacy trial ever conducted in Africa has proven that a candidate vaccine is safe in children aged 1 to 4 years and can protect a significant proportion of them against uncomplicated malaria, infection, and severe forms of the disease for at least 6 months. “This is clearly the best result we’ve ever seen with a candidate malaria vaccine,” said Pedro Alonso, MD, PhD, principal investigator of the study and head of the Center for International Health of the Hospital Clinic at the University of Barcelona, in Spain. “All the results point in the same direction with great consistency and substantial precision. So we’re quite certain not only that the vaccine has been safe and immunogenic but that we’ve seen clear efficacy of this vaccine.” The double-blind, randomized controlled phase 2 trial conducted by Alonso and colleagues involved 2022 children in southern Mozambique (Lancet. 2004;364:1411-1420). The vaccine (designated RTS,S/AS02A) involved a recombinant protein that fuses a part of a Plasmodium falciparum protein with a hepatitis B surface antigen molecule. P falciparum is the parasite that causes the greatest number of cases of malaria in Africa. Vaccine RTS,S/AS02A has been under development by GlaxoSmithKline Biologicals, in Rixensart, Belgium, for more than 15 years, but researchers stress that further studies are needed, particularly in infants younger than 12 months. Therefore, a licensed malaria vaccine is not expected to be available before 2010. P falciparum is a parasite that goes through different life stages in the human host. This particular vaccine is
Trajectory of Cognitive Decline After Incident Stroke
Authors: Deborah A. Levine, Andrzej T. Galecki, Kenneth M. Langa, Frederick W. Unverzagt, Mohammed U. Kabeto, Bruno Giordani, Virginia G. Wadley
Journal: JAMA (2015)

<h3>Importance</h3> Cognitive decline is a major cause of disability in stroke survivors. The magnitude of survivors' cognitive changes after stroke is uncertain. <h3>Objective</h3> To measure changes in cognitive function among survivors of incident stroke, controlling for their prestroke cognitive trajectories. <h3>Design, Setting, and Participants</h3> Prospective study of 23 572 participants 45 years or older without baseline cognitive impairment from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, residing in the continental United States, enrolled 2003-2007 and followed up through March 31, 2013. Over a median follow-up of 6.1 years (interquartile range, 5.0-7.1 years), 515 participants survived expert-adjudicated incident stroke and 23 057 remained stroke free. <h3>Exposure</h3> Time-dependent incident stroke. <h3>Main Outcomes and Measures</h3> The primary outcome was change in global cognition (Six-Item Screener [SIS], range, 0-6). Secondary outcomes were change in new learning (Consortium to Establish a Registry for Alzheimer Disease Word-List Learning; range, 0-30), verbal memory (Word-List Delayed Recall; range, 0-10), and executive function (Animal Fluency Test; range, ≥0), and cognitive impairment (SIS score &lt;5 [impaired] vs ≥5 [unimpaired]). For all tests, higher scores indicate better performance. <h3>Results</h3> Stroke was associated with acute decline in global cognition (0.10 points [95% CI, 0.04 to 0.17]), new learning (1.80 points [95% CI, 0.73 to 2.86]), and verbal memory (0.60 points [95% CI, 0.13 to 1.07]). Participants with stroke, compared with those without stroke, demonstrated faster declines in global cognition (0.06 points per year faster [95% CI, 0.03 to 0.08]) and executive function (0.63 points per year faster [95% CI, 0.12 to 1.15]), but not in new learning and verbal memory, compared with prestroke slopes. Among survivors, the difference in risk of cognitive impairment acutely after stroke, compared with immediately before stroke, was not statistically significant (odds ratio, 1.32 [95% CI, 0.95 to 1.83];<i>P</i> = .10); however, there was a significantly faster poststroke rate of incident cognitive impairment compared with the prestroke rate (odds ratio, 1.23 per year [95% CI, 1.10 to 1.38];<i>P</i> &lt; .001). For a 70-year-old black woman with average values for all covariates at baseline, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference of 4.0% (95% CI, −1.2% to 9.2%) at year 3 and 12.4% (95% CI, 7.7% to 17.1%) at year 6. <h3>Conclusions and Relevance</h3> Incident stroke was associated with an acute decline in cognitive function and also accelerated and persistent cognitive decline over 6 years.
HIV/antiretroviral therapy–related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma
Authors: J Peraire, M López-Dupla, V Alba, R Beltrán-Debón, E Martinez, P Domingo, V Asensi, M Leal, C Viladés, M-I Inza, X Escoté, M Arnedo, G Mateo, E Valle-Garay, S Ferrando-Martinez, S Veloso, J Vendrell, J Ma Gatell, F Vidal
Journal: Clinical Microbiology and Infection (2015)