tbuckley/cabot-search huggingface dataset:
Mechanisms of action of mifepristone and levonorgestrel when used for emergency contraception
Authors: K. Gemzell-Danielsson
Journal: Human Reproduction Update (2004)

An emergency contraceptive method is used after coitus but before pregnancy occurs. The use of emergency contraception is largely under-utilized worldwide. One of the main barriers to widespread use is concern about the mechanism of action. Recently, treatment with either 10 mg mifepristone or 1.5 mg of levonorgestrel has emerged as the most effective hormonal method for emergency contraception with very low side-effects. However, the knowledge of the mechanism of action of mifepristone and levonorgestrel in humans, when used for contraceptive purposes and especially for emergency contraception, remains incomplete. The objective of this review is to summarize available data on the effects of mifepristone and levonorgestrel on female reproductive functions relevant to the emergency use of the compounds. When summarized, available data from studies in humans indicate that the contraceptive effects of both levonorgestrel and mifepristone, when used in single low doses for emergency contraception, involve either blockade or delay of ovulation, due to either prevention or delay of the LH surge, rather than to inhibition of implantation.
Whole Body <sup>18</sup>FDG-PET and the Response of Esophageal Cancer to Induction Therapy: Results of a Prospective Trial
Authors: Robert J. Downey, Tim Akhurst, David Ilson, Robert Ginsberg, Manjit S. Bains, Mithat Gonen, Heng Koong, Marc Gollub, Bruce D. Minsky, Maureen Zakowski, Alan Turnbull, Steven M. Larson, Valerie Rusch
Journal: Journal of Clinical Oncology (2003)

Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy.Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months.PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P =.055 and P =.088, respectively).Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted.
Immunotherapy for Brain Cancer: Recent Progress and Future Promise
Authors: Christopher M. Jackson, Michael Lim, Charles G. Drake
Journal: Clinical Cancer Research (2014)

Immunotherapy is emerging as the newest pillar of cancer treatment, with the potential to assume a place alongside surgical debulking, radiotherapy, and chemotherapy. Early experiences with antitumor vaccines demonstrated the feasibility and potential efficacy of this approach, and newer agents, such as immune checkpoint blocking antibodies and modern vaccine platforms, have ushered in a new era. These efforts are headlined by work in melanoma, prostate cancer, and renal cell carcinoma; however, substantial progress has been achieved in a variety of other cancers, including high-grade gliomas. A recurrent theme of this work is that immunotherapy is not a one-size-fits-all solution. Rather, dynamic, tumor-specific interactions within the tumor microenvironment continually shape the immunologic balance between tumor elimination and escape. High-grade gliomas are a particularly fascinating example. These aggressive, universally fatal tumors are highly resistant to radiotherapy and chemotherapy and inevitably recur after surgical resection. Located in the immune-privileged central nervous system, high-grade gliomas also use an array of defenses that serve as direct impediments to immune attack. Despite these challenges, vaccines have shown activity against high-grade gliomas, and anecdotal, preclinical, and early clinical data bolster the notion that durable remission is possible with immunotherapy. Realizing this potential, however, will require an approach tailored to the unique aspects of glioma biology.
Childhood obstructive sleep apnoea: Hypertension was not mentioned
Authors: Daniel K Ng, Chung-hong Chan, Ka-li Kwok, Lettie C Leung, Pok-yu Chow
Journal: BMJ (2005)

Timing of tracheostomy in adult patients Potential ramifications are alarmingEditor-In their systematic review and meta-analysis Griffiths et al conclude that tracheostomies should be performed earlier in critically ill patients. 1As ear, nose, and throat surgeons we find the potential ramifications quite alarming, primarily as undertaking this major operation is not without potential morbidity in patients who are already systemically unwell. 2 3 These patients are often anaemic and have coagulopathies and sepsis among other comorbidities-points that we thought the authors had not discussed, and factors that have implications for the surgical procedure.In our experience, many patients listed for tracheostomy from intensive care units are extubated or sometimes die while waiting for their procedure; if tracheostomy were performed immediately these patients would be subjected to unnecessary procedures.The postoperative sequelae of tracheostomy are a slow weaning process before patients can be decannulated, followed by potential tracheal stenosis. 4hese patients may be able to leave intensive care earlier, but Griffiths et al do not say how long they then remain inpatients before discharge because of problems with rehabilitation with a tracheostomy tube in situ.Interestingly, although duration of ventilation and stay in the intensive care unit were shortened by an earlier tracheostomy, mortality was not altered and inpatient stay was likely to have been lengthened. 5he authors divided timing of tracheostomy into two groups, demarcated by seven days after intubation, making an artificial separation that seems invalid.It would have been more interesting to see whether increasing number of days have a proportional relation to the duration of ventilation and stay in intensive care on a linear scale.We advise great caution in interpreting the findings of Griffiths et al and about its impact on the delivery of the tracheostomy service in hospitals.
INSTEAD: a randomised switch trial of indacaterol <i>versus</i> salmeterol/fluticasone in moderate COPD
Authors: Andrea Rossi, Thys van der Molen, Ricardo del Olmo, Alberto Papi, Luis Wehbe, Matthew Quinn, Chengxing Lu, David Young, Ray Cameron, Enrica Bucchioni, Pablo Altman
Journal: European Respiratory Journal (2014)

The Indacaterol: Switching Non-exacerbating Patients with Moderate COPD From Salmeterol/Fluticasone to Indacaterol (INSTEAD) study investigated the effect of switching patients at low risk of chronic obstructive pulmonary disease (COPD) exacerbations from salmeterol/fluticasone (SFC; inhaled corticosteroid (ICS) regimen) to indacaterol monotherapy (non-ICS regimen). This 26-week, double-blind, double-dummy, parallel-group, phase IV study, randomised 581 patients with moderate COPD to indacaterol 150 μg once daily or SFC 50/500 μg twice daily. Patients had been receiving SFC 50/500 μg for ≥3 months, with no COPD exacerbations for more than a year before the study (patients for whom ICS is not recommended). The primary objective was to demonstrate non-inferiority of indacaterol to SFC, measured by trough forced expiratory volume in 1 second (FEV 1 ) after 12 weeks (non-inferiority margin of 0.06 L). The primary objective was met, with a mean treatment difference of 9 mL (95% CI -45–26 mL). There were no significant differences between treatments in terms of breathlessness (transition dyspnoea index) or health status (Saint George’s Respiratory Questionnaire) at weeks 12 or 26, or rescue medication use or COPD exacerbation rates over 26 weeks. Safety profiles of both treatments were as expected. This study demonstrated that patients with moderate COPD and no exacerbations in the previous year can be switched from SFC to indacaterol 150 μg with no efficacy loss.
Hereditary Hemochromatosis
Authors: Wylie Burke, Elizabeth Thomson, Muin J. Khoury, Sharon M. McDonnell, Nancy Press, Paul C. Adams, James C. Barton, Ernest Beutler, Gary Brittenham, Allen Buchanan, Ellen Wright Clayton, Mary E. Cogswell, Eric M. Meslin, Arno G. Motulsky, Lawrie W. Powell, Elliott Sigal, Benjamin S. Wilfond, Francis S. Collins
Journal: JAMA (1998)

Objective.—To evaluate the role of genetic testing in screening for hereditary hemochromatosis to help guide clinicians, policymakers, and researchers.Participants.—An expert panel was convened on March 3, 1997, by the Centers for Disease Control and Prevention (CDC) and the National Human Genome Research Institute (NHGRI), with expertise in epidemiology, genetics, hepatology, iron overload disorders, molecular biology, public health, and the ethical, legal, and social implications surrounding the discovery and use of genetic information.Evidence.—The group reviewed evidence regarding the clinical presentation, natural history, and genetics of hemochromatosis, including current data on the candidate gene for hemochromatosis (HFE) and on the ethical and health policy implications of genetic testing for this disorder.Consensus Process.—Consensus was achieved by group discussion confirmed by a voice vote. A draft of the consensus statement was prepared by a writing committee and subsequently reviewed and revised by all members of the expert group over a 1-year period.Conclusions.—Genetic testing is not recommended at this time in population-based screening for hereditary hemochromatosis, due to uncertainties about prevalence and penetrance of HFE mutations and the optimal care of asymptomatic people carrying HFE mutations. In addition, use of a genetic screening test raises concerns regarding possible stigmatization and discrimination. Tests for HFE mutations may play a role in confirming the diagnosis of hereditary hemochromatosis in persons with elevated serum iron measures, but even this use is limited by uncertainty about genotype-phenotype correlations. To address these questions, the expert group accorded high priority to population-based research to define the prevalence of HFE mutations, age and sex-related penetrance of different HFE genotypes, interactions between HFE genotypes and environmental modifiers, and psychosocial outcomes of genetic screening for hemochromatosis.
Impact of Exposure Measurement Error in Nutritional Epidemiology
Authors: Victor Kipnis, Laurence S. Freedman
Journal: JNCI Journal of the National Cancer Institute (2008)

For the past several decades, observational studies of diet and cancer have yielded many inconsistent results ( 1 ). Given the limited variation in dietary intakes within many study populations and the seemingly modest diet – cancer associations, results of such studies depend critically on an accurate assessment of the dietary exposure ( 2 ). Measurement error in exposure leads to seriously biased relative risks of cancer for dietary intakes and substantially reduces the statistical power to detect existing relationships ( 2 ). The international consortium of cohort studies known as the Pooling Project ( 3 ) aims to gain precision in relative risk estimates and overcome this loss of statistical power by combining analyses of individual data from multiple studies that examine associations between diet and cancer. In this issue of the Journal, Lee et al. ( 4 ) report the results of an analysis of fat, protein, and meat consumption in relation to the risk of renal cell cancer in 13 cohorts within the Pooling Project. Using multivariable models, they obtained null results for all of the associations they considered. In this editorial, we comment on the impact of exposure measurement error on the estimated associations between diet and disease in this and other studies. Exposure measurement error in prospective studies can usually be assumed to be nondifferential with respect to disease, that is, the relationship between the reported diet and the true diet is the same for the case subjects and the control subjects. When the exposure, but none of the confounders, is measured with error, this error attenuates the relative risk (ie, biases the relative risk toward no effect). Although statistical tests for the association remain valid, that is, they preserve the nominal statistical signifi cance level ( 5 ), the measurement error reduces the statistical power to detect the association. Consequently, the number of cases required to maintain the nominal statistical power is increased by a factor equal to the inverse-squared correlation between the reported exposure and the true exposure ( 6 ). Moreover, although adjustment for measurement error can remove existing bias in estimated relative risks, it cannot compensate for the loss of statistical power. Within the Pooling Project, the main dietary assessment instruments were study-specifi c food-frequency questionnaires (FFQs) and closely related diet histories. Most studies also included validation subsamples with multiple food records or 24-hour
Posterior mediastinal teratoma with abdominal extension.
Authors: S el Kalla, M Abdul-Hameed, A al Ashbal, N Menon
Journal: Thorax (1990)

Posterior mediastinal benign teratomas are uncommon neoplasms in infancy; nine cases have been reported so far. A one month old baby was found to have a benign posterior mediastinal teratoma infiltrating the lower oesophagus from the level of the carina through the oesophageal hiatus into the upper abdomen. Partial oesophagectomy provided a successful outcome.
Increased Glioma Growth in Mice Depleted of Macrophages
Authors: Hugo Galarneau, Jérôme Villeneuve, Geneviève Gowing, Jean-Pierre Julien, Luc Vallières
Journal: Cancer Research (2007)

Abstract Macrophages can promote the growth of some tumors, such as those of the breast and lung, but it is unknown whether this is true for all tumors, including those of the nervous system. On the contrary, we have previously shown that macrophages can slow the progression of malignant gliomas through a tumor necrosis factor–dependent mechanism. Here, we provide evidence suggesting that this antitumor effect could be mediated by T lymphocytes, as their number was drastically reduced in tumor necrosis factor–deficient mice and inversely correlated with glioma volume. However, this correlation was only observed in allogeneic recipients, prompting a reevaluation of the role of macrophages in a nonimmunogenic context. Using syngeneic mice expressing the herpes simplex virus thymidine kinase under the control of the CD11b promoter, we show that macrophages can exert an antitumor effect without the help of T lymphocytes. Macrophage depletion achieved by ganciclovir treatment resulted in a 33% increase in glioma volume. The antitumor effect of macrophages was not likely due to a tumoricidal activity because phagocytosis or apoptosis of glioma cells, transduced ex vivo with a lentiviral vector expressing green fluorescent protein, was rarely observed. Their antitumor effect was also not due to a destructive action on the tumor vasculature because macrophage depletion resulted in a modest reduction in vascular density. Therefore, this study suggests that macrophages can attenuate glioma growth by an unconventional mechanism. This study also validates a new transgenic model to explore the role of macrophages in cancer. [Cancer Res 2007;67(18):8874–81]
SIGNIFICANCE OF THE HEMOSIDEROSIS OF PERNICIOUS ANEMIA
Authors: Philip D. McMaster, Peyton Rous, Louise C. Larimore
Journal: The Journal of Experimental Medicine (1922)

The selective deposition of hemosiderin in the liver parenchyma during pernicious anemia does not constitute evidence that there is a hemolytic cause for the disease located in the portal region. The repeated introduction of small amounts of free hemoglobin into the general circulation, by the subcutaneous route, leads, as we have shown, to an identical siderosis. Larger amounts of hemoglobin cause a renal pigmentation equalling or exceeding the hepatic, a fact that is in keeping with what is known of the physiology of hemoglobin excretion and of the findings in human beings afteroutspoken hemolysis.
The Automated External Defibrillator: Critical Link in the Chain of Survival
Authors: Karthik Ramaswamy, Richard L. Page
Journal: Annual Review of Medicine (2003)

Sudden death due to ventricular fibrillation (VF) is the leading cause of death in the United States. Early defibrillation is the most important determinant of survival and is the key element in cardiopulmonary resuscitation. Obstacles to rapid defibrillation by trained emergency personnel persist, but the development of the automated external defibrillator (AED) promises to realize the goal of widespread early defibrillation and translate to an improved chance for survival for the cardiac arrest victim. Technological advancements have made the AED safe, easy to use, accurate, and effective in terminating VF. Use of the AED by trained nontraditional first responders (e.g., firefighters, police officers, flight crews) has improved survival rates in a variety of settings and forms the basis for public-access defibrillation.
Similarities and differences in structure, expression, and functions of VLDLR and ApoER2
Authors: Sunil S Reddy, Teal E Connor, Edwin J Weeber, William Rebeck
Journal: Molecular Neurodegeneration (2011)

Very Low Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2) are important receptors in the brain for mediating the signaling effects of the extracellular matrix protein Reelin, affecting neuronal function in development and in the adult brain. VLDLR and ApoER2 are members of the low density lipoprotein family, which also mediates the effects of numerous other extracellular ligands, including apolipoprotein E. Although VLDLR and ApoER2 are highly homologous, they differ in a number of ways, including structural differences, expression patterns, alternative splicing, and binding of extracellular and intracellular proteins. This review aims to summarize important aspects of VLDLR and ApoER2 that may account for interesting recent findings that highlight the unique functions of each receptor.
Endothelium-dependent hyperpolarization in small gastric arteries
Authors: B VANHEEL
Journal: Cardiovascular Research (2004)

In many blood vessels, stimulation of the endothelium with various vasoactive substances induces, besides the nitric oxide (NO) and prostacyclin pathways, a third mechanism evoking dilatation. It is based on hyperpolarization of the vascular smooth muscle cell membrane. In the present study, we investigated the existence of endothelium-dependent hyperpolarization in small gastric arteries of the rat and explored its underlying mechanism.Membrane potentials were recorded by conventional microelectrode techniques in isolated segments of small gastric arteries, the normalized diameter of which was determined from the passive wall tension-internal circumference characteristics as measured with a myograph.After blocking NO and prostaglandin synthesis, application of acetylcholine (3 x 10(-7) M) resulted in a membrane hyperpolarization in endothelium intact but not in endothelium-denuded arteries. This membrane potential change was increased by pre-exposure to a low concentration (30 microM) of Ba2+, which selectively inhibits inward rectifying potassium channels. Moreover, the acetylcholine-induced hyperpolarization was unaffected by additional pre-exposure to high concentrations (0.5 mM) of the Na/K-ATPase inhibitor ouabain, which by itself caused a secondary slow endothelium-independent hyperpolarization after an initial peak depolarization.We conclude that acetylcholine produces endothelium-dependent hyperpolarization in gastric small arteries, which does not rely on activation of smooth muscle cell inward rectifying K+ channels or Na/K pumps, and might prove to be another important regulator of gastric mucosal blood flow.
Enzyme-Catalyzed Activation of Anticancer Prodrugs
Authors: Martijn Rooseboom, Jan N. M. Commandeur, Nico P. E. Vermeulen
Journal: Pharmacological Reviews (2004)

The rationale for the development of prodrugs relies upon delivery of higher concentrations of a drug to target cells compared to administration of the drug itself. In the last decades, numerous prodrugs that are enzymatically activated into anti-cancer agents have been developed. This review describes the most important enzymes involved in prodrug activation notably with respect to tissue distribution, up-regulation in tumor cells and turnover rates. The following endogenous enzymes are discussed: aldehyde oxidase, amino acid oxidase, cytochrome P450 reductase, DT-diaphorase, cytochrome P450, tyrosinase, thymidylate synthase, thymidine phosphorylase, glutathione <i>S</i>-transferase, deoxycytidine kinase, carboxylesterase, alkaline phosphatase, β-glucuronidase and cysteine conjugate β-lyase. In relation to each of these enzymes, several prodrugs are discussed regarding organ- or tumor-selective activation of clinically relevant prodrugs of 5-fluorouracil, axazaphosphorines (cyclophosphamide, ifosfamide, and trofosfamide), paclitaxel, etoposide, anthracyclines (doxorubicin, daunorubicin, epirubicin), mercaptopurine, thioguanine, cisplatin, melphalan, and other important prodrugs such as menadione, mitomycin C, tirapazamine, 5-(aziridin-1-yl)-2,4-dinitrobenzamide, ganciclovir, irinotecan, dacarbazine, and amifostine. In addition to endogenous enzymes, a number of nonendogenous enzymes, used in antibody-, gene-, and virus-directed enzyme prodrug therapies, are described. It is concluded that the development of prodrugs has been relatively successful; however, all prodrugs lack a complete selectivity. Therefore, more work is needed to explore the differences between tumor and nontumor cells and to develop optimal substrates in terms of substrate affinity and enzyme turnover rates for prodrug-activating enzymes resulting in more rapid and selective cleavage of the prodrug inside the tumor cells.
Programs Against Micronutrient Malnutrition: Ending Hidden Hunger
Authors: G F Maberly, F L Trowbridge, R Yip, K M Sullivan, C E West
Journal: Annual Review of Public Health (1994)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Engaging the private sector to increase tuberculosis case detection: an impact evaluation study
Authors: Aamir J Khan, Saira Khowaja, Faisal S Khan, Fahad Qazi, Ismat Lotia, Ali Habib, Shama Mohammed, Uzma Khan, Farhana Amanullah, Hamidah Hussain, Mercedes C Becerra, Jacob Creswell, Salmaan Keshavjee
Journal: The Lancet Infectious Diseases (2012)