tbuckley/cabot-search huggingface dataset:
Treatment of torsade de pointes with magnesium sulfate.
Authors: D Tzivoni, S Banai, C Schuger, J Benhorin, A Keren, S Gottlieb, S Stern
Journal: Circulation (1988)

Twelve consecutive patients who developed torsade de pointes (polymorphous ventricular tachycardia with marked QT prolongation, TdP) over a 4 year period were treated with intravenous injections of magnesium sulfate. In nine of the patients a single bolus of 2 g completely abolished the TdP within 1 to 5 min, and in three others complete abolition of the TdP was achieved after a second bolus was given 5 to 15 min later. Nine of the patients also received continuous infusion of MgSO4 (3 to 20 mg/min) for 7 to 48 hr until the QT interval was below 0.50 sec. In nine of the 12 patients the TdP was induced by antiarrhythmic agents. The QT interval preceding TdP ranged from 0.54 to 0.72 sec. After the MgSO4 bolus, which prevented the recurrence of TdP, no significant changes were observed in the QT interval. There were no side effects of this treatment. In eight of the 12 patients potassium levels before the TdP were below 3.5 meq/liter; magnesium levels were available in eight patients before TdP, and were normal in all. Five additional patients with polymorphous ventricular tachycardia but normal QT intervals (non-TdP patients) received two to three boluses of MgSO4. This treatment was ineffective in all, but they responded to conventional antiarrhythmic therapy. Thus, MgSO4 is a very effective and safe treatment for TdP, and its application is rapid and simple. Its use is therefore recommended as the first line of therapy for TdP.
Cognitive Bias Modification Approaches to Anxiety
Authors: Colin MacLeod, Andrew Mathews
Journal: Annual Review of Clinical Psychology (2012)

Clinical anxiety disorders and elevated levels of anxiety vulnerability are characterized by cognitive biases, and this processing selectivity has been implicated in theoretical accounts of these conditions. We review research that has sought to evaluate the causal contributions such biases make to anxiety dysfunction and to therapeutically alleviate anxiety using cognitive-bias modification (CBM) procedures. After considering the purpose and nature of CBM methodologies, we show that variants designed to modify selective attention (CBM-A) or interpretation (CBM-I) have proven capable of reducing anxiety vulnerability and ameliorating dysfunctional anxiety. In addition to supporting the causal role of cognitive bias in anxiety vulnerability and dysfunction and illuminating the mechanisms that underpin such bias, the findings suggest that CBM procedures may have therapeutic promise within clinical settings. We discuss key issues within this burgeoning field of research and suggest future directions CBM research should take to maximize its theoretical and applied value.
Systemic effects, bioavailability, and pharmacokinetics of fluticasone propionate (FP) diskus and mometasone furoate (MF) twisthaler in healthy and asthmatic subjects
Authors: M.G.M. Derks, A.T. Weeks, R.S. Mehta, M. Beerahee, A. Sousa, P.T. Daley-Yates
Journal: Journal of Allergy and Clinical Immunology (2005)
Interpreting Trial Results in Light of Conflicting Evidence: A Bayesian Analysis of Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer
Authors: Rebecca A. Miksad, Mithat Gönen, Thomas J. Lynch, Thomas G. Roberts
Journal: Journal of Clinical Oncology (2009)

Purpose When successive randomized trials contradict prior evidence, clinicians may be unsure how to evaluate them: Does accumulating evidence warrant changing practice? An increasingly popular solution, Bayesian statistics quantitatively evaluate new results in context. This study provides a clinically relevant example of Bayesian methods. Methods Three recent non–small-cell lung cancer adjuvant chemotherapy trials were evaluated in light of prior conflicting data. Results were used from International Adjuvant Lung Trial (IALT), JBR.10, and Adjuvant Navelbine International Trialist Association (ANITA). Prior evidence was sequentially updated to calculate the probability of each survival benefit level (overall and by stage) and variance. Sensitivity analysis was performed using expert opinion and uninformed estimates of survival benefit prior probability. Results The probability of a 4% survival benefit increased from 33% before IALT to 64% after IALT. After sequential updating with JBR.10 and ANITA, this probability was 82% (hazard ratio = 0.84; 95% CI, 0.77 to 0.91). IALT produced the largest decrease in variance (61%) and decreased the chance of survival decrement to 0%. Sensitivity analysis did not support a survival benefit after IALT. However, sequential updating substantiated a 4% survival benefit and, for stage II and III, more than 90% probability of a 6% benefit and 50% probability of a 12% benefit. Conclusion When evaluated in context with prior data, IALT did not support a 4% survival benefit. However, sequential updating with JBR.10 and ANITA did. A model for future assessments, this study demonstrates the unique ability of Bayesian analysis to evaluate results that contradict prior evidence.
Total Mortality by Elevated Transferrin Saturation in Patients With Diabetes
Authors: Christina Ellervik, Henrik Ullits Andersen, Anne Tybjærg-Hansen, Merete Frandsen, Henrik Birgens, Børge G. Nordestgaard, Thomas Mandrup-Poulsen
Journal: Diabetes Care (2013)

It is not known to what extent iron overload predicts prognosis in patients with diabetes after diagnosis or whether iron overload is a risk factor independent of the HFE genotype. We investigated total and cause-specific mortality according to increased transferrin saturation (≥ 50 vs. <50%), whether mortality is driven by the HFE genotype, and whether early measurement of transferrin saturation helps to predict mortality outcome.Cohort 1 included patients with late-onset type 1 diabetes (n = 716) with a cross-sectional measurement of transferrin saturation and HFE genotype. Cohort 2 included consecutively recruited patients with any diabetes (n = 6,120), transferrin saturation measurement at referral, and HFE genotype if transferrin saturation was above 50%.In cohort 1, the hazard ratio for total mortality was 2.3 (95% CI 1.3-3.9; P = 0.002) and for cause-specific mortality by neoplasms was 5.8 (2.4-14; P = 0.00007) in patients with transferrin saturation ≥ 50 vs. <50%. Excluding genotypes C282Y/C282Y and C282Y/H63D gave similar results. The hazard ratio for total mortality was 4.0 (1.2-13; P = 0.01) and for cause-specific mortality by neoplasms was 13 (3.6-49; P = 0.0001) in patients with C282Y/C282Y versus wild type. In cohort 2, total mortality was not different in patients with transferrin saturation ≥ 50 vs. <50%. In patients with late-onset type 1 diabetes and transferrin saturation ≥ 50%, the hazard ratio for total mortality was 0.4 (0.2-0.9; P = 0.03) in cohort 2 versus cohort 1.Increased transferrin saturation and HFE genotype C282Y/C282Y predict total mortality in patients with late-onset type 1 diabetes, and increased transferrin saturation after diagnosis is an independent risk factor. Early measurement of transferrin saturation in these patients leading to early intervention improves life expectancy.
Survival and Hospitalization for Intensive Home Hemodialysis Compared with Kidney Transplantation
Authors: Karthik K. Tennankore, S. Joseph Kim, Heather J. Baer, Christopher T. Chan
Journal: Journal of the American Society of Nephrology (2014)

Canadian patients receiving intensive home hemodialysis (IHHD; ≥16 hours per week) have survival comparable to that of deceased donor kidney transplant recipients in the United States, but a comparison with Canadian kidney transplant recipients has not been conducted. We conducted a retrospective cohort study of consecutive, adult IHHD patients and kidney transplant recipients between 2000 and 2011 at a large Canadian tertiary care center. The primary outcome was time-to-treatment failure or death for IHHD patients compared with expanded criteria, standard criteria, and living donor recipients, and secondary outcomes included hospitalization rate. Treatment failure was defined as a permanent switch to an alternative dialysis modality for IHHD patients, and graft failure for transplant recipients. The cohort comprised 173 IHHD patients and 202 expanded criteria, 642 standard criteria, and 673 living donor recipients. There were 285 events in the primary analysis. Transplant recipients had a reduced risk of treatment failure/death compared with IHHD patients, with relative hazards of 0.45 (95% confidence interval [95% CI], 0.31 to 0.67) for living donor recipients, 0.39 (95% CI, 0.26 to 0.59) for standard criteria donor recipients, and 0.42 (95% CI, 0.26 to 0.67) for expanded criteria donor recipients. IHHD patients had a lower hospitalization rate in the first year of treatment compared with standard criteria donor recipients and in the first 3 months of treatment compared with living donor and expanded criteria donor recipients. In this cohort, kidney transplantation was associated with superior treatment and patient survival, but higher early rates of hospitalization, compared with IHHD.
Gene Flow-Dependent Genomic Divergence between Anopheles gambiae M and S Forms
Authors: D. Weetman, C. S. Wilding, K. Steen, J. Pinto, M. J. Donnelly
Journal: Molecular Biology and Evolution (2011)

Anopheles gambiae sensu stricto exists as two often-sympatric races termed the M and S molecular forms, characterized by fixed differences at an X-linked marker. Extreme divergence between M and S forms at pericentromeric "genomic islands" suggested that selection on variants therein could be driving interform divergence in the presence of ongoing gene flow, but recent work has detected much more widespread genomic differentiation. Whether such genomic islands are important in reproductive isolation or represent ancestral differentiation preserved by low recombination is currently unclear. A critical test of these competing hypotheses could be provided by comparing genomic divergence when rates of recent introgression vary. We genotyped 871 single nucleotide polymorphisms (SNPs) in A. gambiae sensu stricto from locations of M and S sympatry and allopatry, encompassing the full range of observed hybridization rates (0–25%). M and S forms were readily partitioned based on genomewide SNP variation in spite of evidence for ongoing introgression that qualitatively reflects hybridization rates. Yet both the level and the heterogeneity of genomic divergence varied markedly in line with levels of introgression. A few genomic regions of differentiation between M and S were common to each sampling location, the most pronounced being two centromere–proximal speciation islands identified previously but with at least one additional region outside of areas expected to exhibit reduced recombination. Our results demonstrate that extreme divergence at genomic islands does not simply represent segregating ancestral polymorphism in regions of low recombination and can be resilient to substantial gene flow. This highlights the potential for islands comprising a relatively small fraction of the genome to play an important role in early-stage speciation when reproductive isolation is limited.
Long-term safety of pegloticase in chronic gout refractory to conventional treatment
Authors: Michael A Becker, Herbert S B Baraf, Robert A Yood, Aileen Dillon, Janitzia Vázquez-Mellado, Faith D Ottery, Dinesh Khanna, John S Sundy
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To evaluate the long-term safety (up to 3 years) of treatment with pegloticase in patients with refractory chronic gout. <h3>Methods</h3> This open-label extension (OLE) study was conducted at 46 sites in the USA, Canada and Mexico. Patients completing either of two replicate randomised placebo-controlled 6-month trials received pegloticase 8 mg every 2 weeks (biweekly) or every 4 weeks (monthly). Safety was evaluated as the primary outcome, with special interest in gout flares and infusion-related reactions (IRs). Secondary outcomes included urate-lowering and clinical efficacy. <h3>Results</h3> Patients (n=149) received a mean±SD of 28±18 pegloticase infusions and were followed for a mean of 25±11 months. Gout flares and IRs were the most frequently reported adverse events; these were least common in patients with a sustained urate-lowering response to treatment and those receiving biweekly treatment. In 10 of the 11 patients with a serious IR, the event occurred when uric acid exceeded 6 mg/dl. Plasma and serum uric acid levels remained &lt;6 mg/dl in most randomised controlled trial (RCT)-defined pegloticase responders throughout the OLE study and were accompanied by sustained and progressive improvements in tophus resolution and flare incidence. <h3>Conclusions</h3> The safety profile of long-term pegloticase treatment was consistent with that observed during 6 months of RCT treatment; no new safety signals were identified. Improvements in clinical status, in the form of flare and tophus reduction initiated during RCT pegloticase treatment in patients maintaining goal range urate-lowering responses were sustained or advanced during up to 2.5 years of additional treatment.
Induced tolerance in F1 rats to anti-major histocompatibility complex receptors on parental T cells. Implications for self tolerance.
Authors: D Bellgrau, D Smilek, D B Wilson
Journal: The Journal of Experimental Medicine (1981)

The immunogenicity of cell surface markers associated with specific anti-major histocompatibility complex (MHC) alloreactivity of rat peripheral T lymphocyte subpopulations has been demonstrated in the past by the ability of such cell populations to induce a profound and specific resistance to systemic graft-vs.-host (GVH) disease in adult rats. Our studies demonstrate that these specificity-associated anti-MHC parental strain T cell markers are also tolerogenic; if small numbers of parental strain T cells are administered to newborn F1 rats, they result in the specific inability to induce GVH resistance later on in adult life. Moreover, unlike normal animals, these F1 rats are extremely sensitive to systemic GVH disease caused by T cells from the original donor parental strain.
THE SURVIVAL OF POLIOMYELITIS AND COXSACKIE VIRUSES FOLLOWING THEIR INGESTION BY FLIES
Authors: Joseph L. Melnick, Lawrence R. Penner
Journal: The Journal of Experimental Medicine (1952)

Poliomyelitis virus and Coxsackie (or C) virus were quantitatively fed to blowflies, Phormia regina and Phaenicia sericata, and to houseflies, Musca domestica. Naturally infectious human stools were the source of virus. Poliomyelitis virus can be almost quantitatively recovered from flies and from their excreta collected over a period of several days following the feeding. C virus can also be recovered but in lesser yields. No conclusive evidence for virus multiplication in these laboratory-bred insects was obtained. Poliomyelitis virus from human sources could be detected in flies between the 5th and 17th day and in the excreta between the 4th and 10th day. Murine-adapted strains of poliomyelitis virus and murine encephalomyelitis virus could not be detected beyond the 5th day, even though comparable amounts of virus were fed. The persistence of C virus excretion (2 to 12 days) varied directly with the amount of virus fed. Poliomyelitis virus, as present in human stools, survived drying and storage at room temperature for at least 3 days and at 4° for 3 weeks. C virus from human stools under the same circumstances was detected for 15 days at room temperature (with marked drop in titer after the 3rd day) and for 21 days at 4° with little loss in titer. When stool samples were fed to flies and the dried excreta of the insects examined, it was found that (a) poliomyelitis virus persisted for at least 1 to 2 days at room temperature and for 3 to 4 days at 4°, and (b) C virus persisted for 1 day at room temperature and for 5 days at 4°. Poliomyelitis virus could be carried through only two serial passages in adult flies. Flies emerging from maggots fed virus were free from the agent.
The Role of Nonhemoglobin Proteins and Reduced Glutathione in the Protection of Hemoglobin from Oxidation In Vitro*
Authors: A. S. Hill, A. Haut, G. E. Cartwright, M. M. Wintrobe
Journal: Journal of Clinical Investigation (1964)

human erythrocytes by Allen and Jandl (10) led these authors to conclude that GSH per se pro- tects hemoglobin from oxidation and that no ad- ditional factors are required; conversely, Szein- berg and Marks (11) found that GSH affords no protection to human hemoglobin against oxidative changes.The earlier report of Foulkes and Lemberg (12) that GSH might oxidize hemo- globin, along with
Phase III Randomized Trial of Very Accelerated Radiation Therapy Compared With Conventional Radiation Therapy in Squamous Cell Head and Neck Cancer: A GORTEC Trial
Authors: Jean Bourhis, Michel Lapeyre, Jacques Tortochaux, Michel Rives, Mehdi Aghili, Sylvain Bourdin, François Lesaunier, Toufik Benassi, Claire Lemanski, Lionel Geoffrois, Antoine Lusinchi, Pierre Verrelle, Etienne Bardet, Morbize Julieron, Pierre Wibault, Monique Luboinski, Ellen Benhamou
Journal: Journal of Clinical Oncology (2006)

With the aim to increase the dose intensity of radiation therapy (RT), and subsequently the locoregional control rate, a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma (HNSCC).Between 1994 and 1998, 268 patients with T3 or T4, N0 to N3 HNSCC (staged by 1997 International Union Against Cancer criteria) that was not eligible for surgery were randomly assigned to receive either conventional RT, delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days, or to receive very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days (2 Gy/fraction bid).The most common tumor site was the oropharynx and most of the patients (70%) had T4 and N1 to N3 tumors in 72% of patients. The main patient and tumor characteristics were well-balanced between the two arms. The median total doses were 63 Gy (accelerated) and 70 Gy (conventional), with a median overall time of 22 days and 48 days, respectively. Acute mucositis was markedly increased in the accelerated-RT arm (P < .001). The locoregional control rate was improved by 24% at 6 years with accelerated RT. In contrast, disease-free survival and overall survival were not significantly different between the two arms. There was no difference in late effects between the two arms.The very accelerated RT regimen was feasible and provided a major benefit in locoregional control but had a modest effect on survival.
Ultraviolet Irradiation Represses <b> <i>PATCHED</i> </b> Gene Transcription in Human Epidermal Keratinocytes through an Activator Protein-1-Dependent Process
Authors: Florence Brellier, Claire Marionnet, Odile Chevallier-Lagente, Rune Toftgard, Alain Mauviel, Alain Sarasin, Thierry Magnaldo
Journal: Cancer Research (2004)

Abstract Basal cell carcinoma (BCC) is one of the major types of skin cancer arising from keratinocytes. The SONIC HEDGEHOG pathway is deregulated in 100% of sporadic BCCs, as indicated by the overexpression of PATCHED, whose product encodes the receptor of SONIC HEDGEHOG, in 100% of analyzed BCCs. Reverse transcription-PCR analysis revealed that exposure to UVB irradiation, which is a risk factor known to contribute to BCC development, induces a strong and sharp decrease of PATCHED mRNA level both in vitro and ex vivo. Transcription of a reporter gene driven by the 4.4-kb 5′-regulatory region of the human PATCHED gene was shown to be down-regulated after UVB irradiation. Furthermore, overexpression of c-JUN, a member of the activator protein (AP)-1 family, induced repression of the PATCHED promoter. The role of AP-1 in UVB-induced PATCHED repression was confirmed in mouse embryonic fibroblasts knocked out for c-JUN NH2-terminal protein kinase. This study thus provides the first evidence of UV-induced down-regulation at the transcriptional level of the BCC-associated tumor suppressor PATCHED relying on activation of the AP-1 oncogenic pathway.
A Randomized Controlled Trial of a Phytotherapic Compound Containing Boswellia Serrata and Bromeline for Seasonal Allergic Rhinitis Complicated By Upper Airways Recurrent Respiratory Infections
Authors: Maurizio Marogna, Carol Braidi, Chiara Colombo, Fausto Colombo, Loredana Palumbo
Journal: Journal of Allergy and Clinical Immunology (2015)
Neuropharmacology of Amino Acid Inhibitory Transmitters
Authors: G A R Johnston
Journal: The Annual Review of Pharmacology and Toxicology (1978)

In the three years since the review on amino acids as central neurotransmitters by DeFeudis (1) there has been a profusion of neurophysiological, neuropharmacologi­ cal, and neurochemical studies concerned with simple amino acids and the eNS. While y-aminobutyric acid (GABA) and glycine are generally accepted as inhibi­ tory transmitters of major significance, there are some problems regarding possible functions of the excitatory amino acids, glutamate and aspartate (2). Glutamate may well be the major excitatory transmitter in the brain but it does appear to be a somewhat gregarious substance being involved in much, e.g. y-glutamyl compounds (3), that is not directly related to excitatory transmission. Some other amino acids, including taurine (4, 5) and proline (6), may function as inhibitory transmitters. Major activities in the field of amino acid transmitters during the past three years might be grouped into several general areas. There has been continued and wide­ spread use of postsynaptic antagonists such as bicuculline and strychnine to study synaptic inhibitions, and a thus far unsuccessful search for suitably selective antago­ nists of synaptic excitations that might be mediated by amino acid excitants (7). Neurochemical studies on the localization of amino acid transmitters have been greatly aided by the development of immunocytochemical techniques for specific enzymes and the increasing use of degeneration experiments (8). Studies of the binding of amino acid agonists and antagonists to synaptic membrane fractions have opened up new vistas and greatly accelerated investigations of isolated receptors that exhibit many of the properties anticipated from in vivo studies (9). Much work has been devoted to studies of amino acid compartmentation (10), of the processes whereby amino acids are taken up into, and released from, the various compart­ ments that include glial as well as neuronal elements (11-14) and of the active transport processes involved in synaptic transmission mediated by amino acids. There has been some progress in our understanding of the effects of some widely used centrally active drugs, and in the development of new agents that may lead to
Why do residents choose the medical oncology specialty? Implications for future recruitment—results of the 2007 French Association of Residents in Oncology (AERIO) Survey
Authors: Y. Loriot, L. Albiges-Sauvin, D. Dionysopoulos, A. Bouyon-Monteau, H. Boyle, B. You, C. Massard, T. de La Motte Rouge
Journal: Annals of Oncology (2009)
More improvements are needed at troubled trust that faces legal conditions
Authors: A. O'Dowd
Journal: BMJ (2010)

Slow progress at a troubled trust that has been criticised for inadequate maternity services means that it has little time to improve before a new registration regime for all trusts begins.

A progress report on Milton Keynes Hospital NHS Foundation Trust published on 18 January by the health service regulator the Care Quality Commission shows that despite improvements at the trust progress on some of its problems has been too slow.

The commission’s system of registration for all NHS trusts, under which they will be allowed to operate, is due to begin in April, and the trust is now under pressure to improve or face having legal requirements placed on it or have some of its services suspended.

The new …