tbuckley/cabot-search huggingface dataset:
Membrane-Initiated Actions of Estrogens in Neuroendocrinology: Emerging Principles
Authors: Nandini Vasudevan, Donald W. Pfaff
Journal: Endocrine Reviews (2007)

Hormonal ligands for the nuclear receptor superfamily have at least two interacting mechanisms of action: 1) classical transcriptional regulation of target genes (genomic mechanisms); and 2) nongenomic actions that are initiated at the cell membrane, which could impact transcription. Although transcriptional mechanisms are increasingly well understood, membrane-initiated actions of these ligands are incompletely understood. Historically, this has led to a considerable divergence of thought in the molecular endocrine field.
Routine Diagnosis by Computer
Authors: IVAN W. SLETTEN, HAROLD ALTMAN, GEORGE A. ULETT
Journal: American Journal of Psychiatry (1971)

A clinical computer program at the University of Missouri uses data collected by clerks, technicians, relatives, and the staff to build a data base that helps predict significant patient behavior and outcome. Computer-generated probability statements regarding diagnostic classifications are now routinely provided to clinicians. These are augmented by statistical techniques designed to help predict length of hospital stay, risk of running away, and assaultive ideation.
Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10
Authors: O. Lidegaard, L. H. Nielsen, C. W. Skovlund, E. Lokkegaard
Journal: BMJ (2012)

<b>Objective</b> To assess the risk of venous thrombosis in current users of non-oral hormonal contraception. <b>Design</b> Historical national registry based cohort study. <b>Setting</b> Four national registries in Denmark. <b>Participants</b> All Danish non-pregnant women aged 15-49 (n=1 626 158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010. <b>Main outcome measures</b> Incidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis. <b>Results</b> Within 9 429 128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10 000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10 000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7). <b>Conclusion</b> Women who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10 000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system.
The effects of a mixture of surface-active agents (Sonarex) on upper airways resistance and snoring in anaesthetized dogs
Authors: JG Widdicombe, A Davies
Journal: European Respiratory Journal (1988)

We measured upper airways resistance from the trachea and from the pharynx to the atmosphere, EMG of the genioglossus muscle and the sound of snoring, in anaesthetized greyhounds, breathing spontaneously through the upper airways. Using extra-corporeally produced continuous flow we determined flow/pressure curves for the upper airways and resistances from the trachea and from the pharynx. We tested the effects of 0.9% saline and of Sonarex (a proprietary mixture containing sodium chloride, glycerol, polysorbate 80 and benzalkonium chloride). Both saline and Sonarex decreased upper airways resistance, but the latter did so more consistently. With Sonarex, genioglossus activity increased and the sound of snoring decreased. Flow/pressure curves 5-20 min after Sonarex showed a decrease in upper airways resistance and a smoother curve, whereas those with saline showed an increase in resistance. The sound produced by continuous flow through the upper airways was decreased by Sonarex but increased by saline. Thus, both Sonarex and saline decrease upper airways resistance, but Sonarex also reduces the sound of snoring and the resistance and sound of continuous airflow through the upper airways.
Emerging Infectious Threats to the Blood Supply
Authors: Roger Y. Dodd, David A. Leiby
Journal: Annual Review of Medicine (2004)

During the past 15 years, it has become clear that new agents and new strains of existing agents continue to emerge worldwide as protagonists of infectious disease. These emerging agents pose threats not only to the general human population but also to recipients of blood transfusions. Indeed, the modern era of blood safety perhaps began with the recognition of HIV as an emerging agent transmissible by blood transfusion. Today, emerging infectious agents that pose a threat to the blood supply are not limited to viruses, but include bacterial, protozoan, and prion agents. Preventing the transmission of these new agents by blood transfusion is often problematic, as the available tools may be inadequate. It is certain, however, that new agents will continue to emerge as threats to blood safety and these agents are likely to require novel approaches to prevent their transmission.
Does guanine concentration in house-dust samples reflect house-dust mite exposure?
Authors: T.E. Hallas, Xue Yi, C. Schou
Journal: Allergy (1993)

Using specific ELISA extracts, we analyzed samples of pure mite cultures and house dust for group I allergens from Dermatophagoides pteronyssinus , D. farinae , and D. microceras . Correspondingly, we measured the concentration of guanine and xanthine by rigorous chemical methods. The pure mite cultures were used to correiate allergen levels with guanine levels. The house‐dust samples one‐sidedly contained more guanine than expected. This suggests that considerable amounts of guanine originate from non‐house‐dust mite sources and implies that guanine quantifications are of limited clinical value.
Efficacy of <i>Ipomoea batatas</i> (Caiapo) on Diabetes Control in Type 2 Diabetic Subjects Treated With Diet
Authors: Bernhard Ludvik, Beatrice Neuffer, Giovanni Pacini
Journal: Diabetes Care (2004)

OBJECTIVE—To investigate the tolerability, efficacy, and mode of action of Caiapo, an extract of white sweet potatoes, on metabolic control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A total of 61 type 2 diabetic patients treated by diet were given 4 g Caiapo (n = 30; mean age 55.2 ± 2.1 years; BMI 28.0 ± 0.4 kg/m2) or placebo (n = 31; mean age 55.6 ± 1.5 years; BMI 27.6 ± 0.3 kg/m2) once daily for 12 weeks. Each subject underwent a 75-g oral glucose tolerance test (OGTT) at baseline and after 1, 2, and 3 months to assess 2-h glucose levels. Additionally, fasting blood glucose, HbA1c, total cholesterol, and triglyceride levels were measured. RESULTS—After treatment with Caiapo, HbA1c decreased significantly (P &amp;lt; 0.001) from 7.21 ± 0.15 to 6.68 ± 0.14%, whereas it remained unchanged (P = 0.23) in subjects given placebo (7.04 ± 0.17 vs. 7.10 ± 0.19%). Fasting blood glucose levels decreased (P &amp;lt; 0.001) in the Caiapo group (143.7 ± 1.9 vs. 128.5 ± 1.7 mg/dl) and did not change in the placebo group (144.3 ± 1.9 vs. 138.2 ± 2.1 mg/dl; P = 0.052). A decrease in body weight was observed in both the placebo group (P = 0.0027) and in the Caiapo group (P &amp;lt; 0.0001), probably due to a better- controlled lifestyle. In the Caiapo group, body weight was related to the improvement in glucose control (r = 0.618; P &amp;lt; 0.0002). Two-hour glucose levels were significantly (P &amp;lt; 0.001) decreased in the Caiapo group (193.3 ± 10.4 vs. 162.8 ± 8.2 mg/dl) compared with the placebo group (191.7 ± 9.2 vs. 181.0 ± 7.1 mg/dl). Mean cholesterol at the end of the treatment was significantly lower in the Caiapo group (214.6 ± 11.2 mg/dl) than in the placebo group (248.7 ± 11.2 mg/dl; P &amp;lt; 0.05). No significant changes in triglyceride levels or blood pressure were observed, and Caiapo was well tolerated without significant adverse effects. CONCLUSIONS—This study confirms the beneficial effects of Caiapo on plasma glucose as well as cholesterol levels in patients with type 2 diabetes. For the first time, the long-term efficacy of Caiapo on glucose control was demonstrated by the observed decrease in HbA1c. Thus, the neutraceutical Caiapo seems to be a useful agent in the treatment of type 2 diabetes.
Insufficient oxygen concentration obtained at domiciliary controls of eighteen concentrators
Authors: JP Bongard, C Pahud, R De Haller
Journal: European Respiratory Journal (1989)

The oxygen concentration (O2%) produced by 12 type A concentrators, with a working time of 28-18,099 h, and 6 type B concentrators, with a working time of 0-3,033 h, was measured over a 12 month period in the user's home, at a flow rate of 2 l.min-1. One hundred and two measurements of O2% (mean 82.9), made at least once monthly by a visiting nurse, showed that type A concentrators were usually delivering less than 92% expected O2. Four concentrators were delivering less than 40% O2 after a working time of only 4,000 h. Sixty two measurements made by the manufacturer confirmed these findings (mean 86.8). The 18 measurements performed by the nurse on the type B concentrators showed expected O2% values (mean 93.1). Our study demonstrates the necessity of regular clinical and technical surveillance, at the user's home, during long-term domiciliary oxygen therapy and the need for the manufacturer to incorporate an alarm system monitoring the O2% into oxygen concentrators.
Evidence of premature immune aging in patients thymectomized during early childhood
Authors: Delphine Sauce, Martin Larsen, Solène Fastenackels, Anne Duperrier, Michael Keller, Beatrix Grubeck-Loebenstein, Christophe Ferrand, Patrice Debré, Daniel Sidi, Victor Appay
Journal: Journal of Clinical Investigation (2009)

While the thymus is known to be essential for the initial production of T cells during early life, its contribution to immune development remains a matter of debate. In fact, during cardiac surgery in newborns, the thymus is completely resected to enable better access to the heart to correct congenital heart defects, suggesting that it may be dispensable during childhood and adulthood. Here, we show that young adults thymectomized during early childhood exhibit an altered T cell compartment. Specifically, absolute CD4+ and CD8+ T cell counts were decreased, and these T cell populations showed substantial loss of naive cells and accumulation of oligoclonal memory cells. A subgroup of these young patients (22 years old) exhibited a particularly altered T cell profile that is usually seen in elderly individuals (more than 75 years old). This condition was directly related to CMV infection and the induction of strong CMV-specific T cell responses, which may exhaust the naive T cell pool in the absence of adequate T cell renewal from the thymus. Together, these marked immunological alterations are reminiscent of the immune risk phenotype, which is defined by a cluster of immune markers predictive of increased mortality in the elderly. Overall, our data highlight the importance of the thymus in maintaining the integrity of T cell immunity during adult life.
Dietary Tannins and Salivary Proline-Rich Proteins: Interactions, Induction, and Defense Mechanisms
Authors: Haile Mehansho, Larry G. Butler, Don M. Carlson
Journal: Annual Review of Nutrition (1987)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
NCCN Oncology Risk Evaluation and Mitigation Strategies White Paper: Recommendations for Stakeholders
Authors: Philip E Johnson, George Dahlman, Kirby Eng, Rekha Garg, Scott Gottlieb, James M Hoffman, Peyton Howell, Mohammad Jahanzeb, Shirley Johnson, Emily Mackler, Mark Rubino, Brenda Sarokhan, F Marc Stewart, Tim Tyler, Julie M Vose, Sharon Weinstein, Edward C Li, Jessica Demartino
Journal: Journal of the National Comprehensive Cancer Network (2010)

REMS are a particularly important issue for oncology and the National Comprehensive Cancer Network (NCCN). A disproportionate number of drugs with complex REMS are used in patients with cancer or hematologic disorders. REMS policies and processes within oncology may act as a model for other clinical areas. A breadth of experience and access to a wide knowledge base exists within oncology that will ensure appropriate development and consideration of the practical implications of REMS. NCCN is uniquely positioned to assume a leadership role in this process given its status as the arbiter of high-quality cancer care based on its world-leading institutions and clinicians. Notwithstanding the potential benefits, the successful design, implementation, and analysis of the FDA's recent requirement for REMS for some high-risk drugs and biologics will present significant challenges for stakeholders, including patients, providers, cancer centers, manufacturers, payors, health information technology vendors, and regulatory agencies. To provide guidance to these stakeholders regarding REMS challenges, the NCCN assembled a work group comprised of thought leaders from NCCN Member Institutions and other outside experts. The Work Group identified challenges across the REMS spectrum, including the areas of standardization, development and assessment of REMS programs, medication guides, provider knowledge and impact on prescribing, provider burden and compensation, and incorporation of REMS into clinical practice.
RADIOACTIVE IRON AND ITS METABOLISM IN ANEMIA
Authors: P. F. Hahn, W. F. Bale, E. O. Lawrence, G. H. Whipple
Journal: The Journal of Experimental Medicine (1939)

Artificially produced radioactive iron is an extremely sensitive agent for use in following iron in the course of its changes in body metabolism, lending itself to studies of absorption, transport, exchange, mobilization, and excretion. The need of the body for iron in some manner determines the absorption of this element. In the normal dog when there is no need for the element, it is absorbed in negligible amounts. In the anemic animal iron is quite promptly assimilated. The plasma is clearly the means of transport of iron from the gastrointestinal tract to its point of mobilization for fabrication into hemoglobin. The speed of absorption and transfer of iron to the red cell is spectacular. The importance of the liver and bone marrow in iron metabolism is confirmed.
Alzheimer and Vascular Dementias and Driving
Authors: L. Jaime Fitten
Journal: JAMA (1995)

<h3>Objective.</h3> —To characterize on-the-road, behind-the-wheel driving abilities and related laboratory performances of subjects with mild Alzheimer's disease (AD) and vascular dementia. <h3>Design.</h3> —Prospective, experimental study involving two mild dementia and three age and health control groups. Road test reliability and validity were assessed. <h3>Setting.</h3> —Greater western Los Angeles. Subjects were enrolled from the community by referral and from the Veterans Affairs dementia and diabetes clinics. <h3>Participants.</h3> —Eighty-seven driving subjects were enrolled; 83 completed the study. A sample of eligible dementia clinic subjects consisting of 15 mild AD patients met National Institute of Neurological and Communicative Disorders and Stroke— Alzheimer's Disease and Related Disorders Association probable AD criteria, while 12 met<i>Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition</i>and Hachinski diagnostic criteria for multi-infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age-matched patients with diabetes and without a history of stroke or dementia. Community controls consisted of 26 healthy, age-matched, older subjects (&gt;60 years) and 16 young subjects (20 to 35 years). <h3>Main Outcome Measures.</h3> —Drive score from the Sepulveda (Calif) road test and laboratory measures of attention, perception, and memory. <h3>Results.</h3> —The drive scores in the mild AD group (mean, 22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed significantly (<i>P</i>&lt;.001 studentized range test) from the drive scores in the diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean, 32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score among the three control groups did not vary significantly. Short-term memory (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores correlated best with drive score, with a cumulative<i>R</i><sup>2</sup>of 0.68. Drive score and number of collisions and moving violations per 1000 miles driven were negatively correlated (<i>r</i>=-0.38;<i>P</i>&lt;.02). <h3>Conclusions.</h3> —Based on this study, type and degree of cognitive impairment are better predictors of driving skills than age or medical diagnosis per se. Specific testing protocols for drivers with potential cognitive impairment may detect unsafe drivers more effectively than using age or medical diagnosis alone as criteria for license restriction or revocation. (<i>JAMA</i>. 1995;273:1360-1365)
Antigen-driven B cell differentiation in vivo.
Authors: M G McHeyzer-Williams, M J McLean, P A Lalor, G J Nossal
Journal: The Journal of Experimental Medicine (1993)

The secretion of specific antibodies and the development of somatically mutated memory B cells in germinal centers are consequences of T cell-dependent challenge with the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP). Using six-parameter flow cytometry and single cell molecular analysis we can directly monitor the extent of somatic hypermutation in individual responsive (isotype switched) antigen-specific B cells. The current study provides a direct quantitative assessment of recruitment into the antibody-secreting compartment on the one hand, and the germinal center pathway to memory on the other. Cellular expansion in both compartments is exponential and independent during the first week after challenge. The first evidence of somatic mutation, towards the end of the first week, was restricted to the germinal center pathway. Furthermore, germinal center cells express a significantly shorter third hypervariable region (CDR3), even when unmutated, than their antibody-secreting counterparts, suggesting a secondary selection event may occur at the bifurcation of these two pathways in vivo. By the end of the second week, the majority of mutated clones express a shorter CDR3 and affinity-increasing mutations as evidence of further selection after somatic mutation. These data provide evidence for substantial proliferation within germinal centers before the initiation of somatic mutation and the subsequent selection of a significant frequency of mutated clonotypes into the memory compartment.
Analysis of Gene Expression Using Gene Sets Discriminates Cancer Patients with and without Late Radiation Toxicity
Authors: J. Peter Svensson, Lukas J. A Stalpers, Rebecca E. E. Esveldt–van Lange, Nicolaas A. P Franken, Jaap Haveman, Binie Klein, Ingela Turesson, Harry Vrieling, Micheline Giphart-Gassler
Journal: PLoS Medicine (2006)

Background Radiation is an effective anti-cancer therapy but leads to severe late radiation toxicity in 5%–10% of patients. Assuming that genetic susceptibility impacts this risk, we hypothesized that the cellular response of normal tissue to X-rays could discriminate patients with and without late radiation toxicity. Methods and Findings Prostate carcinoma patients without evidence of cancer 2 y after curative radiotherapy were recruited in the study. Blood samples of 21 patients with severe late complications from radiation and 17 patients without symptoms were collected. Stimulated peripheral lymphocytes were mock-irradiated or irradiated with 2-Gy X-rays. The 24-h radiation response was analyzed by gene expression profiling and used for classification. Classification was performed either on the expression of separate genes or, to augment the classification power, on gene sets consisting of genes grouped together based on function or cellular colocalization. X-ray irradiation altered the expression of radio-responsive genes in both groups. This response was variable across individuals, and the expression of the most significant radio-responsive genes was unlinked to radiation toxicity. The classifier based on the radiation response of separate genes correctly classified 63% of the patients. The classifier based on affected gene sets improved correct classification to 86%, although on the individual level only 21/38 (55%) patients were classified with high certainty. The majority of the discriminative genes and gene sets belonged to the ubiquitin, apoptosis, and stress signaling networks. The apoptotic response appeared more pronounced in patients that did not develop toxicity. In an independent set of 12 patients, the toxicity status of eight was predicted correctly by the gene set classifier. Conclusions Gene expression profiling succeeded to some extent in discriminating groups of patients with and without severe late radiotherapy toxicity. Moreover, the discriminative power was enhanced by assessment of functionally or structurally related gene sets. While prediction of individual response requires improvement, this study is a step forward in predicting susceptibility to late radiation toxicity.