tbuckley/cabot-search huggingface dataset:
Temperature Management After Cardiac Arrest
Authors: Michael W. Donnino, Lars W. Andersen, Katherine M. Berg, Joshua C. Reynolds, Jerry P. Nolan, Peter T. Morley, Eddy Lang, Michael N. Cocchi, Theodoros Xanthos, Clifton W. Callaway, Jasmeet Soar, Mayuki Aibiki, Bernd W. Böttiger, Steven C. Brooks, Charles D. Deakin, Saul Drajer, Walter Kloeck, Laurie J. Morrison, Robert W. Neumar, Tonia C. Nicholson, Brian J. O’Neil, Edison F. Paiva, Michael Parr, Tzong-Luen Wang, Jonathan Witt
Journal: Circulation (2015)

For more than a decade, mild induced hypothermia (32 °C-34 °C) has been standard of care for patients remaining comatose after resuscitation from out-of-hospital cardiac arrest with an initial shockable rhythm, and this has been extrapolated to survivors of cardiac arrest with initially nonshockable rhythms and to patients with in-hospital cardiac arrest. Two randomized trials published in 2002 reported a survival and neurological benefit with mild induced hypothermia. One recent randomized trial reported similar outcomes in patients treated with targeted temperature management at either 33 °C or 36 °C. In response to these new data, the International Liaison Committee on Resuscitation Advanced Life Support Task Force performed a systematic review to evaluate 3 key questions: (1) Should mild induced hypothermia (or some form of targeted temperature management) be used in comatose post-cardiac arrest patients? (2) If used, what is the ideal timing of the intervention? (3) If used, what is the ideal duration of the intervention? The task force used Grading of Recommendations Assessment, Development and Evaluation methodology to assess and summarize the evidence and to provide a consensus on science statement and treatment recommendations. The task force recommends targeted temperature management for adults with out-of-hospital cardiac arrest with an initial shockable rhythm at a constant temperature between 32 °C and 36 °C for at least 24 hours. Similar suggestions are made for out-of-hospital cardiac arrest with a nonshockable rhythm and in-hospital cardiac arrest. The task force recommends against prehospital cooling with rapid infusion of large volumes of cold intravenous fluid. Additional and specific recommendations are provided in the document.
Deleterious systemic effects of OSA: how much evidence do we need?
Authors: Malcolm Kohler
Journal: Thorax (2015)

There is accumulating evidence from well-designed observational cohort studies and randomised controlled trials suggesting that obstructive sleep apnoea syndrome (OSAS) may independently add to vascular risk and increased mortality. Major biological mechanisms underpinning the association between OSAS and systemic consequences such as cardiovascular disease are thought to include intermittent hypoxia leading to increased oxidative stress and sympathetic activity, intrathoracic pressure changes leading to excessive mechanical stress on the heart and large artery walls and arousal-induced reflex sympathetic activation with resultant repetitive large blood pressure rises.1 The nocturnal sympathetic nervous system activation and consequent elevation of blood pressure diminish its usual physiological nocturnal dipping. Augmented sympathetic activation in patients with OSAS has also been shown to be associated with blunted baroreflex sensitivity, increased arterial stiffness and impaired endothelial function, all of which contribute to the development of arterial hypertension and consecutive vascular disease.2 ,3

Treatment with CPAP and mandibular advancement devices (MAD) have been shown to effectively abolish apnoeas and oxygen desaturations, and to prevent arousals; thus, obviate acute blood pressure swings. More than 40 randomised controlled trials looking at the effect of CPAP or MAD therapy on blood pressure have been conducted in the past and the findings of these trials have established that CPAP treatment of patients with OSAS lowers blood pressure between 2 and 10 mm Hg after several weeks of CPAP therapy.2 ,4 ,5

What do the three papers published in the …
Deficiencies in services for acute upper gastrointestinal bleeding
Authors: Alan J Lobo, Simon M Greenfield, Ian Forgacs
Journal: BMJ (2015)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Deficiencies in services for acute upper gastrointestinal bleeding Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Characterization of Staphylococcus aureus Cas9: a smaller Cas9 for all-in-one adeno-associated virus delivery and paired nickase applications
Authors: Ari E. Friedland, Reshica Baral, Pankhuri Singhal, Katherine Loveluck, Shen Shen, Minerva Sanchez, Eugenio Marco, Gregory M. Gotta, Morgan L. Maeder, Edward M. Kennedy, Anand V. R. Kornepati, Alexander Sousa, McKensie A. Collins, Hari Jayaram, Bryan R. Cullen, David Bumcrot
Journal: Genome biology (2015)

CRISPR-Cas systems have been broadly embraced as effective tools for genome engineering applications, with most studies to date utilizing the Streptococcus pyogenes Cas9. Here we characterize and manipulate the smaller, 1053 amino acid nuclease Staphylococcus aureus Cas9.We find that the S. aureus Cas9 recognizes an NNGRRT protospacer adjacent motif (PAM) and cleaves target DNA at high efficiency with a variety of guide RNA (gRNA) spacer lengths. When directed against genomic targets with mutually permissive NGGRRT PAMs, the S. pyogenes Cas9 and S. aureus Cas9 yield indels at comparable rates. We additionally show D10A and N580A paired nickase activity with S. aureus Cas9, and we further package it with two gRNAs in a single functional adeno-associated virus (AAV) vector. Finally, we assess comparative S. pyogenes and S. aureus Cas9 specificity using GUIDE-seq.Our results reveal an S. aureus Cas9 that is effective for a variety of genome engineering purposes, including paired nickase approaches and all-in-one delivery of Cas9 and multiple gRNA expression cassettes with AAV vectors.
IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury
Authors: Carmen Lefaucheur, Denis Viglietti, Carol Bentlejewski, Jean-Paul Duong van Huyen, Dewi Vernerey, Olivier Aubert, Jérôme Verine, Xavier Jouven, Christophe Legendre, Denis Glotz, Alexandre Loupy, Adriana Zeevi
Journal: Journal of the American Society of Nephrology (2015)

Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA showing C1q positivity. The distribution of iDSA IgG1–4 subclasses among the population was 75.2%, 44.0%, 28.0%, and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (P<0.001), increased microcirculation injury (P=0.002), and C4d capillary deposition (P<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (P<0.001 for all comparisons). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury.
Plasma pharmacokinetics and pharmacodynamics of a new prodrug N-l-leucyldoxorubicin and its metabolites in a phase I clinical trial.
Authors: J de Jong, G J Geijssen, C N Munniksma, J B Vermorken, W J van der Vijgh
Journal: Journal of Clinical Oncology (1992)

PURPOSE N-l-leucyldoxorubicin (Leu-Dox) was developed as a prodrug of doxorubicin (Dox) to circumvent the cardiotoxicity associated with repeated administration of Dox. Our purpose was to assess the pharmacokinetics of Leu-Dox, Dox, doxorubicinol (Dol) and four other metabolites for pharmacokinetically guided dose-escalation and to verify the prodrug character of Leu-Dox. PATIENTS AND METHODS Blood and urine of 14 patients were sampled during the phase I clinical trial and analyzed by high-performance liquid chromatography. Dose levels of Leu-Dox ranged from 18 mg/m2 to 225 mg/m2, the maximum-tolerated dose (MTD). Hematologic parameters were monitored regularly in each patient. RESULTS Leu-Dox was rapidly distributed (half-life at alpha phase [t1/2 alpha] = 2.5 +/- 0.6 minutes) followed by a biphasic elimination (half-life at beta phase [t1/2 beta] = 17.4 +/- 7.3 minutes; half-life at gamma phase [t1/2 gamma] = 1.5 +/- 0.5 hours), as measured over the first 12 hours after administration. In three patients, in whom Leu-Dox was found in the plasma for up to 48 hours after injection, a final elimination half-life (t1/2,elim) of 16 hours was observed. The t1/2,elim of Leu-Dox was short (0.6 to 16.5 hours) compared with the t1/2,elim of Dox (38 +/- 11 hours). The mean residence time and apparent volume of distribution were 23 +/- 5 minutes and 19 +/- 6 L/m2, respectively. Only 1.5% to 5% of the dose was excreted in the urine over 48 hours, with Dox as major constituent. Dox was rapidly formed, reaching its maximum concentration within 10 minutes after the end of Leu-Dox infusion. Areas under the plasma concentration versus time curve (AUC infinity, mean +/- SD, n = 16) of Leu-Dox, Dox, and Dol were 115 +/- 27 mumol.min/L, 41 +/- 12 mumol.min/L, and 33 +/- 14 mumol.min/L after a dose of 60 mg/m2 Leu-Dox (= 86 mumol/m2). After the same molar dose of Dox (50 mg/m2 = 86 mumol/m2), the AUC infinity of Dox was 179 mumol.min/L, indicating that Leu-Dox was converted into Dox for 23% in the plasma compartment. The AUCs infinity of Leu-Dox, Dox, and Dol increased linearly with the dose. Negligible AUCs were observed for the other four metabolites. The AUCs infinity of Leu-Dox and Dox at the MTD (517 and 145 mumol.min/L, respectively) were lower than those in mice at the LD10 (1,930 and 798 mumol.min/L, respectively), which means that the MTD could not be predicted from the preclinical pharmacokinetics in mice. Hematologic toxicity, especially the WBC count, appeared to correlate much better with the AUC of Dox (r = .91) than with the AUC of Leu-Dox (r = .74), thus confirming the prodrug character of Leu-Dox. CONCLUSIONS Dox is rapidly formed from Leu-Dox, and seems causative in the observed myelotoxicity. The MTD could not be predicted from the AUC at the LD10 in mice.
Hearing Mechanisms in Vertebrates.
Journal: Annals of Internal Medicine (1969)

at the price of three dollars.The wide scope of the symposia is shown by their titles.There were two on clinical genetics and one each on cytogenetics, biochemical genetics, immunogenetics, population genetics, human evolution and computer methods.It would be invidious to select a few papers for special mention, but the general standard is high and the volume is a most useful and up-to-date review of recent progress in many diverse fields.It can be thoroughly recommended.
Relationships Between Platelets and Coagulation Factors in Hemostasis
Authors: P W Majerus, J P Miletich
Journal: Annual Review of Medicine (1978)

In this review the relations between platelets and coagulation factors in hemo­ stasis are considered. The traditional view of hemostasis implies that platelets aggregate to form a hemostatic plug in wounds prior to the coagulation reactions which lead to fibrin formation. In this view the platelet plug merely provides a phospholipid surface on which the coagulation reactions take place. In contrast, we present findings that suggest much closer interactions. between platelets and coagulation factors. For example, thrombin is formed very early in hemostasis; thus a coagulation factor may be involved in early reactions of platelet aggre­ gation. Also, activation of coagulation factors may take place on the platelet surface on specific sites or receptors that direct the coagulation reactions; that is, platelets may provide more than a simple phospholipid surface to the coag­ ulation sequence.
Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration
Authors: Charles C. Wykoff, Daniel E. Croft, David M. Brown, Rui Wang, John F. Payne, Lloyd Clark, Nizar Saleh Abdelfattah, SriniVas R. Sadda
Journal: Ophthalmology (2015)

To assess prospectively a treat-and-extend (TREX) management strategy compared with monthly dosing of intravitreal ranibizumab in treatment-naïve neovascular age-related macular degeneration (AMD) patients.Phase IIIb, multicenter, randomized, controlled clinical trial.Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX management.Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) from 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or according to a TREX protocol. The TREX patients were treated monthly for at least 3 doses, until resolution of clinical and spectral-domain optical coherence tomography evidence of exudative disease activity; the interval between visits then was individualized according to a strict prospective protocol.Mean ETDRS BCVA change from baseline.At baseline, mean age was 77 years (range, 59-96 years), mean BCVA was 20/60 (Snellen equivalent), and mean central retinal thickness (CRT) was 511 μm. Fifty-seven eyes (95%) completed month 12, at which point mean BCVA improved by 9.2 and 10.5 letters in the monthly and TREX cohorts, respectively (P = 0.60). The mean number of injections administered through month 12 was 13.0 and 10.1 (range, 7-13) in the monthly and TREX cohorts, respectively (P < 0.0001). Among TREX patients, 7 (18%) were maximally extended, 4 (10%) demonstrated fluid at every visit, and at month 12, 18 (45%) had achieved an extension interval of 8 weeks or more; the mean maximum extension interval between injections after the first 3 monthly doses was 8.4 weeks (range, 4-12 weeks). Most TREX patients who demonstrated recurrent exudative disease activity (17/24 [71%]) were unable to extend beyond their initial maximum extension interval.The TREX neovascular AMD management strategy used in this prospective, randomized, controlled trial resulted in visual and anatomic gains comparable with those obtained with monthly dosing.
Is education a demographic dividend? The role of cognitive reserve in dementia-related cognitive decline: a comparison of six longitudinal studies of ageing
Authors: Dorina Cadar, Blossom C M Stephan, Carol Jagger, Nikhil Sharma, Carole Dufouil, Wendy P J den Elzen, Jacobijn Gussekloo, Marja Aartsen, Martijn Huisman, Doorly Deeg, Boo Johansson, Nicole Kochan, Simone Reppermund, Perminder Sachdev, Henry Brodaty, Scott M Hofer, Andrea M Piccinin, Graciela Muniz-Terrera
Journal: The Lancet (2015)
Localization of Parathyroid Glands
Authors: Kenneth E. Levin, Orlo H. Clark
Journal: Annual Review of Medicine (1988)

Parathyroid localization tests are helpful for all patients with primary hyperparathyroidism before parathyroid exploration, and they are essential for patients who have had previous parathyroid or thyroid operations. The selection of specific localization tests depends on whether the patient is undergoing an initial or a reoperative procedure, as well as on the availability of the specialized equipment and expertise of the physicians and technicians performing and interpreting these studies.
Perceptual Neural Organization: Some Approaches Based on Network Models and Information Theory
Authors: R Linsker
Journal: Annual Review of Neuroscience (1990)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties
Authors: T R Mosmann, R L Coffman
Journal: Annual Review of Immunology (1989)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Guanylyl Cyclase-Linked Receptors
Authors: P S T Yuen, D L Garbers
Journal: Annual Review of Neuroscience (1992)

Cyclic GMP was identified as a component of urine in 1 963 (Ashman et al) shortly after the classical works of Sutherland & RaIl had proposed the second messenger hypothesis (RaIl et al 1 957, Rall & Sutherland 1 958, Sutherland & RaIl 1957, 1 958, 1 960). Guanylyl cyclase and cyclic nucleo­ tide phosphodiesterase activities were subsequently reported to exist in virtually all tissues (Appleman et al 1973, Hardman et al 1 97 1 , Hardman & Sutherland 1969, Ishikawa et al 1969, Schultz et al 1 969, White & Aurbach 1 969), and cyclic GMP concentrations were shown to change in response to a wide variety of different agents, including hormones and neurotransmitters (Goldberg & Haddox 1 977). Progress in understanding the mechanisms by which cellular cyclic GMP concentrations were elevated in response to these various agents moved rather slowly, however, in part, because guanylyl cyclase (enzyme activity is found in both soluble and particulate fractions of most tissue homogenates) could not be activated in broken cell preparations (Murad et al 1979). That guanylyl cyclases in both particulate and soluble fractions of tissue homogenates serve as receptors for a variety of different and specific ligands has become realized over the last ten years. This review con­ centrates on the guanylyl cyclase/receptor family and the nature of the ligands that specifically bind and activate these receptors. Other recent reviews that address this topic include Brenner et al ( 1 990), Chinkers & Garbers ( 199 1), Garbers ( 1 989a,b), and Inagami ( 1989).
Infectious Granulomas: Exposit from the Leprosy Model
Authors: O K Skinsnes
Journal: Annual Review of Medicine (1982)

Understanding the immunopathology of leprosy has depended largely on our understanding of other diseases, notably tuberculosis. Thus, Danielssen and Boeck's 1847 Atlas de Colode de Spedalskhed followed on an under­ standing of the pathology of tuberculosis derived from the work of Richard Morton, Matthew Baillie, Gaspard-Laurent Bayle, and Rene Laennec. Hansen's recognition of the Bacillus leprae as leprosy's etiologic agent cautiously antedated Koch's announcement concerning the tubercle bacil­ lus, but followed Marten's 1720 astute speculations regarding the causation of infectious disease and Villemin's experiments (1865 and 1868) demon­ strating that human tuberculosis could be transmitted to experimental ani­ mals. Mitsuda and Hayashi's development of the lepromin test was patterned after Koch's work on the tuberculin test. Just as Koch's efforts were initially directed at developing an immunizing, rather than a diagnos­ tic, procedure, so also were Mitsuda and Hayashi's efforts regarding lep­ rosy. The very term tuberculoid, first used definitively in 1898 in reference to leprosy by Jadassohn, by itself speaks to this interrelationship and derivative understanding. A number of remarkable features of leprosy may now contribute to a more general understanding of other infectious granulomas (I, 2). The intergraded and graded histopathologic and immunologic responses pre­ sented by leprosy flow from tuberculoid to lepromatous via a range of
An EORTC Gastrointestinal Group phase III evaluation of combinations of methyl-CCNU, 5-fluorouracil, and adriamycin in advanced gastric cancer.
Authors: A Lacave, J Wils, H Bleiberg, E Diaz-Rubio, N Duez, O Dalesio
Journal: Journal of Clinical Oncology (1987)

In a prospective phase III multicenter trial, 189 patients with advanced measurable and nonmeasurable gastric cancer were randomized to receive 5-fluorouracil (5-FU) combined with Adriamycin (FA) or FA plus methyl-CCNU (MeFA). The response rate in patients with measurable disease was 10% (three of 29), and 18% (five of 28), respectively. No difference in the duration of survival was detected (P = .14; log rank test). Median survivals were 21 and 32 weeks, respectively. Toxicity was moderate, but there have been two toxic deaths among the patients who received FA. Because of the low response rate and the short survival, neither regimen can be recommended for the treatment of advanced gastric cancer.
Medical centers: source for training future oncologists.
Authors: L H Einhorn
Journal: Journal of Clinical Oncology (1985)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1985.3.7.1040 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 4020399 Medical centers: source for training future oncologists. L H EinhornxL H EinhornSearch for articles by this author https://doi.org/10.1200/JCO.1985.3.7.1040 PDF "Medical centers: source for training future oncologists.." Journal of Clinical Oncology, 3(7), p. 1040© 1985 by American Society of Clinical Oncology