tbuckley/cabot-search huggingface dataset:
International Infectious Disease Law
Authors: Lawrence O. Gostin
Journal: JAMA (2004)

The International Health Regulations (IHR), the only global regulations for infectious disease control, have not been significantly changed since they were first issued in 1951. The World Health Organization (WHO) is currently engaged in a process to modernize the IHR. This article reviews WHO's draft revised IHR and recommends new reforms to improve global health, which include (1) a robust mission, emphasizing the WHO's core public health purposes, functions, and essential services; (2) broad scope, flexibly covering diverse health threats; (3) global surveillance, developing informational networks of official and unofficial data sources; (4) national public health systems, setting performance criteria, measuring outcomes, and holding states accountable; (5) human rights protection, setting science-based standards and fair procedures; and (6) good governance, adopting the principles of fairness, objectivity, and transparency. The WHO should ensure state compliance with health norms and generous economic and technical assistance to poorer countries. An important issue for the international community is how sovereign countries can join together to make global health work for everyone, the poor and the wealthy alike.
A memorable patient
Authors: M. Gerard Baggot
Journal: BMJ (2005)

The war bride was born about 1920 and raised in Rumania or thereabouts. When she was 3 years old, she swallowed lye, which scarred her esophagus, making deglutition almost impossible. Fortunately, a master surgeon took her case and devised an extraordinary practical solution.

At that time, an Irishman, Dr Ivor Magill and his British associates working in London were introducing endotracheal anesthesia for plastic surgery. Their work would eventually advance surgery and critical care therapies, but it did not reach continental Europe until much later.

Meanwhile, for endothoracic operations, German surgeons were experimenting with “negative …
Interspecific Variation in Rx1 Expression Controls Opsin Expression and Causes Visual System Diversity in African Cichlid Fishes
Authors: Jane E Schulte, Conor S O'Brien, Matthew A Conte, Kelly E O'Quin, Karen L Carleton
Journal: Molecular Biology and Evolution (2014)

The mechanisms underlying natural phenotypic diversity are key to understanding evolution and speciation. Cichlid fishes are among the most speciose vertebrates and an ideal model for identifying genes controlling species differences. Cichlids have diverse visual sensitivities that result from species expressing subsets of seven cichlid cone opsin genes. We previously identified a quantitative trait locus (QTL) that tunes visual sensitivity by varying SWS2A (short wavelength sensitive 2A) opsin expression in a genetic cross between two Lake Malawi cichlid species. Here, we identify Rx1 (retinal and anterior neural fold homeobox) as the causative gene for the QTL using fine mapping and RNAseq in retinal transcriptomes. Rx1 is differentially expressed between the parental species and correlated with SWS2A expression in the F2 progeny. Expression of Rx1 and SWS2A is also correlated in a panel of 16 Lake Malawi cichlid species. Association mapping in this panel identified a 413-bp deletion located 2.5-kb upstream of the Rx1 translation start site that is correlated with decreased Rx1 expression. This deletion explains 62% of the variance in SWS2A expression across 53 cichlid species in 29 genera. The deletion occurs in both the sand and rock-dwelling cichlid clades, suggesting that it is an ancestral polymorphism. Our finding supports the hypothesis that mixing and matching of ancestral polymorphisms can explain the diversity of present day cichlid phenotypes.
Is Passive Diagnosis Enough?
Authors: David W. Dowdy, Sanjay Basu, Jason R. Andrews
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited.To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease.We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active").If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase.Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection.
Substance P Autocrine Signaling Contributes to Persistent HER2 Activation That Drives Malignant Progression and Drug Resistance in Breast Cancer
Authors: Susana Garcia-Recio, Gemma Fuster, Patricia Fernandez-Nogueira, Eva M. Pastor-Arroyo, So Yeon Park, Cristina Mayordomo, Elisabet Ametller, Mario Mancino, Xavier Gonzalez-Farre, Hege G. Russnes, Pablo Engel, Domiziana Costamagna, Pedro L. Fernandez, Pedro Gascón, Vanessa Almendro
Journal: Cancer Research (2013)

Abstract ERBB receptor transmodulation by heterologous G-protein–coupled receptors (GPCR) generates functional diversity in signal transduction. Tachykinins are neuropeptides and proinflammatory cytokines that promote cell survival and cancer progression by activating several GPCRs. In this work, we found that the pain-associated tachykinin Substance P (SP) contributes to persistent transmodulation of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R were highly expressed in HER2+ primary breast tumors (relative to the luminal and triple-negative subtypes) and were overall correlated with poor prognosis factors. In breast cancer cell lines and primary cultures derived from breast cancer samples, we found that SP could activate HER2. Conversely, RNA interference-mediated attenuation of NK-1R, or its chemical inhibition, or suppression of overall GPCR-mediated signaling, all strongly decreased steady-state expression of EGFR and HER2, establishing that their basal activity relied upon transdirectional activation by GPCR. Thus, SP exposure affected cellular responses to anti-ERBB therapies. Our work reveals an important oncogenic cooperation between NK-1R and HER2, thereby adding a novel link between inflammation and cancer progression that may be targetable by SP antagonists that have been clinically explored. Cancer Res; 73(21); 6424–34. ©2013 AACR.
VMP (Bortezomib, Melphalan, and Prednisone) Is Active and Well Tolerated in Newly Diagnosed Patients With Multiple Myeloma With Moderately Impaired Renal Function, and Results in Reversal of Renal Impairment: Cohort Analysis of the Phase III VISTA Study
Authors: Meletios A. Dimopoulos, Paul G. Richardson, Rudolf Schlag, Nuriet K. Khuageva, Ofer Shpilberg, Efstathios Kastritis, Martin Kropff, Maria T. Petrucci, Michel Delforge, Julia Alexeeva, Rik Schots, Tamás Masszi, Maria-Victoria Mateos, William Deraedt, Kevin Liu, Andrew Cakana, Helgi van de Velde, Jesús F. San Miguel
Journal: Journal of Clinical Oncology (2009)

Purpose To assess bortezomib plus melphalan and prednisone (VMP) and melphalan and prednisone (MP) in previously untreated patients with multiple myeloma (MM) with renal impairment enrolled on the phase III VISTA study, and to evaluate renal impairment reversibility. Patients and Methods Patients received nine 6-week cycles of VMP (bortezomib 1.3 mg/m 2 , melphalan 9 mg/m 2 , prednisone 60 mg/m 2 ) or MP. Patients with serum creatinine higher than 2 mg/dL were excluded. Results In the VMP/MP arms, 6%/4%, 27%/30%, and 67%/66% of patients had baseline glomerular filtration rate (GFR) of ≤ 30, 31 to 50, and higher than 50 mL/min, respectively. Response rates were higher and time to progression (TTP) and overall survival (OS) longer with VMP versus MP across renal cohorts. Response rates with VMP and TTP in both arms did not appear significantly different between patients with GFR ≤ 50 or higher than 50 mL/min; OS appeared somewhat longer in patients with normal renal function in both arms. Renal impairment reversal (baseline GFR &lt; 50 improving to &gt; 60 mL/min) was seen in 49 (44%) of 111 patients receiving VMP versus 40 (34%) of 116 patients receiving MP. By multivariate analysis, younger age (&lt; 75 years; P = .006) and less severe impairment (GFR ≥ 30 mL/min; P = .027) were associated with higher reversal rates. In addition, treatment with VMP approached significance (P = .07). In both arms, rates of grade 4 and 5 adverse events (AEs) and serious AEs appeared higher in patients with renal impairment; with VMP, rates of discontinuations/bortezomib dose reductions due to AEs did not appear affected. Conclusion VMP is a feasible, active, and well-tolerated treatment option for previously untreated patients with MM with moderate renal impairment, resulting in 44% renal impairment reversal.
Femtosecond Laser–Assisted Cataract Surgery with Integrated Optical Coherence Tomography
Authors: Daniel V. Palanker, Mark S. Blumenkranz, Dan Andersen, Michael Wiltberger, George Marcellino, Phillip Gooding, David Angeley, Georg Schuele, Bruce Woodley, Michael Simoneau, Neil J. Friedman, Barry Seibel, Juan Batlle, Rafael Feliz, Jonathan Talamo, William Culbertson
Journal: Science Translational Medicine (2010)

An image-guided, femtosecond laser can create precisely placed, accurate cuts in the eye to improve cataract surgery.
More Things in Heaven and Earth
Authors: J. O. Ballard
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification
Authors: L R Lundell, J Dent, J R Bennett, A L Blum, D Armstrong, J P Galmiche, F Johnson, M Hongo, J E Richter, S J Spechler, G N J Tytgat, L Wallin
Journal: Gut (1999)

BACKGROUND Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of disease chronicity. However, there is a serious lack of agreement about how to describe and classify the appearance of reflux oesophagitis AIMS To examine the reliability of criteria that describe the circumferential extent of mucosal breaks and to evaluate the functional and clinical correlates of patients with reflux disease whose oesophagitis was graded according to the Los Angeles system. METHODS Forty six endoscopists from different countries used a detailed worksheet to evaluate endoscopic video recordings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clinical trials of omeprazole treatment (277 patients). RESULTS Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended between the tops of mucosal folds, gave acceptable agreement (mean κ value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0–25%, 26–50%, 51–75%, 76–99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean κ values 0–0.15) for all but the lowest category of extent (mean κ value 0.4). Severity of oesophageal acid exposure was significantly (p&lt;0.001) related to the severity grade of oesophagitis. Preteatment oesophagitis grades A–C were related to heartburn severity (p&lt;0.01), outcomes of omeprazole (10 mg daily) treatment (p&lt;0.01), and the risk for symptom relapse off therapy over six months (p&lt;0.05). CONCLUSIONS Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis.
Inhibition of the checkpoint kinase Chk1 induces DNA damage and cell death in human Leukemia and Lymphoma cells
Authors: Christopher Bryant, Kirsten Scriven, Andrew J Massey
Journal: Molecular Cancer (2014)

Chk1 forms a core component of the DNA damage response and small molecule inhibitors are currently being investigated in the clinic as cytotoxic chemotherapy potentiators. Recent evidence suggests that Chk1 inhibitors may demonstrate significant single agent activity in tumors with specific DNA repair defects, a constitutively activated DNA damage response or oncogene induced replicative stress.Growth inhibition induced by the small molecule Chk1 inhibitor V158411 was assessed in a panel of human leukemia and lymphoma cell lines and compared to cancer cell lines derived from solid tumors. The effects on cell cycle and DNA damage response markers were further evaluated.Leukemia and lymphoma cell lines were identified as particularly sensitive to the Chk1 inhibitor V158411 (mean GI50 0.17 μM) compared to colon (2.8 μM) or lung (6.9 μM) cancer cell lines. Chk1 inhibition by V158411 in the leukemia and lymphoma cell lines induced DNA fragmentation and cell death that was both caspase dependent and independent, and prevented cells undergoing mitosis. An analysis of in vitro pharmacodynamic markers identified a dose dependent decrease in Chk1 and cyclin B1 protein levels and Cdc2 Thr15 phosphorylation along with a concomitant increase in H2AX phosphorylation at Ser139 following V158411 treatment.These data support the further evaluation of Chk1 inhibitors in hematopoietic cancers as single agents as well as in combination with standard of care cytotoxic drugs.
Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis
Authors: Ludwig Kappos, David Moeri, Ernst Wilhelm Radue, Andreas Schoetzau, Kati Schweikert, Frederik Barkhof, David Miller, Charles RG Guttmann, Howard L Weiner, Claudio Gasperini, Massimo Filippi
Journal: The Lancet (1999)
Corrigendum to: Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure
Authors: G. K.R. Soppa, J. Lee, M. A. Stagg, L. E. Felkin, P. J.R. Barton, U. Siedlecka, S. Youssef, M. H. Yacoub, C. M.N. Terracciano
Journal: Cardiovascular Research (2008)

[ Cardiovascular Research, Volume 77, Issue 4, 1 March 2008, Pages 695–706 ]

When this article was originally published, it should have been published as an open access article with the following copyright line:

Published on …
Desperately seeking synapses
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

![Graphic][1] 

LFA-1 (red) molecules surround central TCRs (green) in a live synapse. Signaling between a T cell and an antigen-presenting cell (APC) is orchestrated through a bull's eye–like structure known as the immunological synapse. But no one had ever spotted these structures
Tadalafil Augments Tumor Specific Immunity in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Joseph A. Califano, Zubair Khan, Kimberly A. Noonan, Lakshmi Rudraraju, Zhe Zhang, Hao Wang, Steven Goodman, Christine G. Gourin, Patrick K. Ha, Carole Fakhry, John Saunders, Marshall Levine, Mei Tang, Geoffrey Neuner, Jeremy D. Richmon, Ray Blanco, Nishant Agrawal, Wayne M. Koch, Shanthi Marur, Donald T. Weed, Paolo Serafini, Ivan Borrello
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells (MDSC). Experimental Design: We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma (HNSCC). Results: Tadalafil augmented immune response, increasing ex vivo T-cell expansion to a mean 2.4-fold increase compared with 1.1-fold in control patients (P = 0.01), reducing peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change in control patients (P = 0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P = 0.002). Tumor-specific immunity in response to HNSCC tumor lysate was augmented in tadalafil-treated patients (P = 0.04). Conclusions: These findings demonstrate that tadalafil augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application. Clin Cancer Res; 21(1); 30–38. ©2015 AACR.
The electromotive force of the ventricular free wall and papillary muscle preparations.
Authors: S Mashima, K Takayanagi, G Schmidt, A Nozaki
Journal: Circulation Research (1985)

The electromotive force of the ventricular tissues with different anatomy and activation patterns was studied. The left ventricular wall was perfused with Tyrode's solution from the circumflex branch of the left coronary artery and was stimulated first at an epicardial and then endocardial site to induce ectopic beats. The early QRS voltage was compared with the activated area at the same instant. In other experiments, the whole heart was perfused from the aorta, and the anterior papillary muscle of the right ventricle was introduced into a small separate chamber. Different locations were stimulated to induce longitudinal and transverse activation, and the remote potential was measured with leads in both directions. By means of a calibration system with artificial dipoles, the strength of the double layer was expressed in terms of mA X cm per unit area of the activation wave front. The results indicated that epicardial stimulation of the left ventricular wall produced voltage proportional to the activated area; the average moment was found to be 0.11 mA X cm per unit area. The potential curve produced by endocardial stimulation of the same preparation was characterized by an initial low-voltage phase, followed by a sharp upstroke. The right ventricular papillary muscle produced a larger double layer moment during activation in the longitudinal direction, but voltage due to transverse activation was several times smaller.
IMMUNOLOGICAL REACTIONS WITH A VIRUS CAUSING PAPILLOMAS IN RABBITS
Authors: John G. Kidd
Journal: The Journal of Experimental Medicine (1938)

The antigen that binds complement in the presence of sera neutralizing the Shope papilloma virus can be readily extracted from papillomas yielding infectious virus, but not from the normal skin of rabbits bearing the growths. The virus and the complement-binding antigen appear to have the same particle size, as determined by filtration, and they are thrown down together in the centrifuge. They are destroyed by the same amounts of heating and, in general, by the same changes in pH. It is possible, nevertheless, by irradiation with ultraviolet light, or by treatment with weak alkali, to render papilloma extracts non-pathogenic without diminishing their capacity to bind complement when mixed with immune serum.
Skin testing in patients with hypersensitivity reactions to iodinated contrast media – a European multicenter study
Authors: K. Brockow, A. Romano, W. Aberer, A. J. Bircher, A. Barbaud, P. Bonadonna, E. Faria, G. Kanny, M. Lerch, W. J. Pichler, J. Ring, J. Rodrigues Cernadas, E. Tomaz, P. Demoly, C. Christiansen
Journal: Allergy (2009)

Iodinated contrast media cause both immediate and nonimmediate hypersensitivity reactions. The aim of this prospective study was to determine the specificity and sensitivity of skin tests in patients who have experienced such reactions.Skin prick, intradermal and patch tests with a series of contrast media were conducted in 220 patients with either immediate or nonimmediate reaction. Positive skin tests were defined according to internationally accepted guidelines. Seventy-one never-exposed subjects and 11 subjects who had tolerated contrast medium exposure, served as negative controls.Skin test specificity was 96-100%. For tests conducted within the time period from 2 to 6 months after the reaction, up to 50% of immediate reactors and up to 47% of nonimmediate reactors were skin test positive. For immediate reactors, the intradermal tests were the most sensitive, whereas delayed intradermal tests in combination with patch tests were needed for optimal sensitivity in nonimmediate reactors. Contrast medium cross-reactivity was more common in the nonimmediate than in the immediate group. Interestingly, 49% of immediate and 52% of nonimmediate symptoms occurred in previously unexposed patients. Many of these patients were skin test positive, indicating that they were already sensitized at the time of first contrast medium exposure.These data suggest that at least 50% of hypersensitivity reactions to contrast media are caused by an immunological mechanism. Skin testing appears to be a useful tool for diagnosis of contrast medium allergy and may play an important role in selection of a safe product in previous reactors.