tbuckley/cabot-search huggingface dataset:
A Suicide Prevention Center on an Indian Reservation
Authors: JAMES H. SHORE, JOHN F. BOPP, THELMA R. WALLER, JAMES W. DAWES
Journal: American Journal of Psychiatry (1972)

The authors describe the background and development of a suicide prevention service on an Indian reservation and emphasize the importance of community acceptance and involvement. Characteristics of the patient population are analyzed; most of the patients were young males. For mental health consultants the importance of timing and an understanding of the complexities of the sociopolitical milieu are essential in supporting the development of such a community-sponsored project.
Prospective study of healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infants
Authors: S Broughton
Journal: Thorax (2005)

Background: A study was undertaken to determine the impact of respiratory syncytial virus (RSV) infection, both in hospital and the community, on healthcare utilisation and respiratory morbidity in prematurely born infants and to identify risk factors for symptomatic RSV infection. Methods: A hospital and community follow up study was undertaken of 126 infants born before 32 weeks of gestational age. Healthcare utilisation (hospital admissions and general practitioner attendances) in the first year, respiratory morbidity at follow up (wheeze and cough documented by parent completed diary cards), and RSV positive lower respiratory tract infections (LRTIs) were documented. Nasopharyngeal aspirates were obtained for immunofluorescence and culture for RSV whenever the infants had an LRTI, either in the community or in hospital. Results: Forty two infants had an RSV positive LRTI (RSV group), 50 had an RSV negative LRTI (RSV negative LRTI group), and 32 infants had no LRTI (no LRTI group). Compared with the RSV negative LRTI and the no LRTI groups, the RSV group required more admissions (p = 0.392, p<0.001) and days in hospital (p = 0.049, p = 0.006) and had more cough (p = 0.05, p = 0.038) and wheeze (p = 0.003, p = 0.003) at follow up. Significant risk factors for symptomatic RSV LRTI were number of siblings (p = 0.035) and maternal smoking in pregnancy (p = 0.005), for cough were number of siblings (p = 0.002) and RSV LRTI (p = 0.02), and for wheeze was RSV LRTI (p = 0.019). Conclusion: RSV infection, even if hospital admission is not required, is associated with increased subsequent respiratory morbidity in prematurely born infants.
Microscopic conduction in cultured strands of neonatal rat heart cells measured with voltage-sensitive dyes.
Authors: V G Fast, A G Kléber
Journal: Circulation Research (1993)

Microscopic discontinuities in electrical activation were assessed in synthetic strands of neonatal rat myocytes cultured on a growth-directing matrix. An optical method using voltage-sensitive dye (RH-237) and a photodiode technique was used for recordings of membrane potential changes with subcellular resolution. Spatial resolution of the method (diameter of measurement area, 5.5 microns; interdiode distance, 30 microns) allowed for simultaneous measurements of cytoplasmic conduction time within a single cell and junctional conduction time across the cell border. In one-dimensional cell chains, where cells were juxtaposed by end-to-end connections but devoid of lateral connections, propagation of the excitation wave was strongly nonuniform: cytoplasmic conduction time was 38 +/- 30 (mean +/- SD) microseconds (n = 37), whereas junctional conduction time was 118 +/- 40 microseconds (n = 27, P < .0001). A mean delay introduced by a single junction was 80 microseconds, or 51% of conduction time. In two-dimensional strands consisting of several cells in width, which exhibited lateral as well as end-to-end connections, inhomogeneity of conduction was smaller: the cytoplasmic and junctional conduction times were 57 +/- 30 (n = 46) and 89 +/- 40 (n = 48) microseconds, respectively (P < .0001); mean junctional conduction delay was 32 microseconds (22% of conduction time). Mathematical modeling suggested that the averaging effect of lateral connections is caused by lateral convergence of local excitatory current beyond and lateral divergence before end-to-end connections. Our results demonstrate that the current flow through lateral cell-to-cell connections smooth the excitation wave front during longitudinal conduction in myocardial tissue.
ANTIARRHYTHMIC DRUG SELECTION
Authors: P J Podrid
Journal: Annual Review of Medicine (1987)

The selection of an effective and well-tolerated antiarrhythmic drug requires a systematic approach. Two methods for evaluating drug effect are routinely used--noninvasive techniques involving monitoring and exercise testing, and an invasive approach utilizing electrophysiologic testing. Each method has strengths and weaknesses and they must be applied to the appropriate patient. The evaluation of drug effect involves two types of testing. The acute drug test is a rapid screening of drug action, while a short-term maintenance period confirms drug efficacy and permits exposure of side effects. One of the most serious toxic effects is drug-induced aggravation of arrhythmia. An additional benefit of a systematized protocol is the identification of several effective agents that may be administered in combination to enhance antiarrhythmic drug effect. If an effective and well-tolerated drug is prescribed, recurrent malignant arrhythmia can be prevented.
Signaling Intricacies Take Center Stage in Cancer Cells
Authors: Rakesh Kumar, Mien-Chie Hung
Journal: Cancer Research (2005)

Abstract After many years of productive study on the signaling networks, posttranslational regulatory control of effector molecules remains an intensely investigated and continuously evolving field of research to connect signaling with phenotypic changes. In recent years, there have been intriguing results on the interaction of critical molecules to control the growth of cancer cells. This review article will focus on two critical convergence signaling nodules, Akt and p21-activated kinase, two integral components of phenotypic signaling during tumorigenesis. Here we will summarize the recent findings on how these master signaling nodules regulate their targets and alter the subcellular localization of their effectors to control their functionality. Based on the laboratory advances in the Akt and p21-activated kinase signaling pathways, it is conceivable to start defining novel avenues to develop targeted anticancer therapies.
Preparation of Nitrous Oxide
Authors: A. R. Leeds
Journal: BMJ (1868)

twitl?As far as my own xptience goes, I bilieve Chat generally inm tefewee is prejudicial inwhattever stage-of -the'labour the-convulsions may occur.Most assuredly, during gestation, and before labour has c~iuseoced, it will be universally conceded as admitting of no dispute,
Pathogenesis of the Viral Hemorrhagic Fevers
Authors: Slobodan Paessler, David H. Walker
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Four families of enveloped RNA viruses, filoviruses, flaviviruses, arenaviruses, and bunyaviruses, cause hemorrhagic fevers. These viruses are maintained in specific natural cycles involving nonhuman primates, bats, rodents, domestic ruminants, humans, mosquitoes, and ticks. Vascular instability varies from mild to fatal shock, and hemorrhage ranges from none to life threatening. The pathogenic mechanisms are extremely diverse and include deficiency of hepatic synthesis of coagulation factors owing to hepatocellular necrosis, cytokine storm, increased permeability by vascular endothelial growth factor, complement activation, and disseminated intravascular coagulation in one or more hemorrhagic fevers. The severity of disease caused by these agents varies tremendously; there are extremely high fatality rates in Ebola and Marburg hemorrhagic fevers, and asymptomatic infection predominates in yellow fever and dengue viral infections. Although ineffective immunity and high viral loads are characteristic of several viral hemorrhagic fevers, severe plasma leakage occurs at the time of viral clearance and defervescence in dengue hemorrhagic fever.
Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer
Authors: Martin Peifer, Lynnette Fernández-Cuesta, Martin L Sos, Julie George, Danila Seidel, Lawryn H Kasper, Dennis Plenker, Frauke Leenders, Ruping Sun, Thomas Zander, Roopika Menon, Mirjam Koker, Ilona Dahmen, Christian Müller, Vincenzo Di Cerbo, Hans-Ulrich Schildhaus, Janine Altmüller, Ingelore Baessmann, Christian Becker, Bram de Wilde, Jo Vandesompele, Diana Böhm, Sascha Ansén, Franziska Gabler, Ines Wilkening, Stefanie Heynck, Johannes M Heuckmann, Xin Lu, Scott L Carter, Kristian Cibulskis, Shantanu Banerji, Gad Getz, Kwon-Sik Park, Daniel Rauh, Christian Grütter, Matthias Fischer, Laura Pasqualucci, Gavin Wright, Zoe Wainer, Prudence Russell, Iver Petersen, Yuan Chen, Erich Stoelben, Corinna Ludwig, Philipp Schnabel, Hans Hoffmann, Thomas Muley, Michael Brockmann, Walburga Engel-Riedel, Lucia A Muscarella, Vito M Fazio, Harry Groen, Wim Timens, Hannie Sietsma, Erik Thunnissen, Egbert Smit, Daniëlle A M Heideman, Peter J F Snijders, Federico Cappuzzo, Claudia Ligorio, Stefania Damiani, John Field, Steinar Solberg, Odd Terje Brustugun, Marius Lund-Iversen, Jörg Sänger, Joachim H Clement, Alex Soltermann, Holger Moch, Walter Weder, Benjamin Solomon, Jean-Charles Soria, Pierre Validire, Benjamin Besse, Elisabeth Brambilla, Christian Brambilla, Sylvie Lantuejoul, Philippe Lorimier, Peter M Schneider, Michael Hallek, William Pao, Matthew Meyerson, Julien Sage, Jay Shendure, Robert Schneider, Reinhard Büttner, Jürgen Wolf, Peter Nürnberg, Sven Perner, Lukas C Heukamp, Paul K Brindle, Stefan Haas, Roman K Thomas
Journal: Nature Genetics (2012)
Liver X receptors and regulate renin expression in vivo
Authors: F. Morello
Journal: Journal of Clinical Investigation (2005)

The renin-angiotensin-aldosterone system controls blood pressure and salt-volume homeostasis. Renin, which is the first enzymatic step of the cascade, is critically regulated at the transcriptional level. In the present study, we investigated the role of liver X receptor α (LXRα) and LXRβ in the regulation of renin. In vitro, both LXRs could bind to a noncanonical responsive element in the renin promoter and regulated renin transcription. While LXRα functioned as a cAMP-activated factor, LXRβ was inversely affected by cAMP. In vivo, LXRs colocalized in juxtaglomerular cells, in which LXRα was specifically enriched, and interacted with the renin promoter. In mouse models, renin-angiotensin activation was associated with increased binding of LXRα to the responsive element. Moreover, acute administration of LXR agonists was followed by upregulation of renin transcription. In LXRα–/– mice, the elevation of renin triggered by adrenergic stimulation was abolished. Untreated LXRβ–/– mice exhibited reduced kidney renin mRNA levels compared with controls. LXRα–/–LXRβ–/– mice showed a combined phenotype of lower basal renin and blunted adrenergic response. In conclusion, we show herein that LXRα and LXRβ regulate renin expression in vivo by directly interacting with the renin promoter and that the cAMP/LXRα signaling pathway is required for the adrenergic control of the renin-angiotensin system.
<i>Helicobacter pylori</i> Infection Is Associated With an Increased Rate of Diabetes
Authors: Christie Y. Jeon, Mary N. Haan, Caroline Cheng, Erin R. Clayton, Elizabeth R. Mayeda, Joshua W. Miller, Allison E. Aiello
Journal: Diabetes Care (2012)

Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998-1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10-6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
Genetically Determined Heterogeneity in Hemoglobin Scavenging and Susceptibility to Diabetic Cardiovascular Disease
Authors: Rabea Asleh, Stuart Marsh, Mark Shilkrut, Ofer Binah, Julia Guetta, Flavio Lejbkowicz, Ben Enav, Naim Shehadeh, Yoram Kanter, Orit Lache, Osher Cohen, Nina S. Levy, Andrew P. Levy
Journal: Circulation Research (2003)

A major function of haptoglobin (Hp) is to bind hemoglobin (Hb) to form a stable Hp-Hb complex and thereby prevent Hb-induced oxidative tissue damage. Clearance of the Hp-Hb complex can be mediated by the monocyte/macrophage scavenger receptor CD163. We recently demonstrated that diabetic individuals homozygous for the Hp 2 allele (Hp 2-2) were at 500% greater risk of cardiovascular disease (CVD) compared with diabetic individuals homozygous for the Hp 1 allele (Hp 1-1). No differences in risk by Hp type were seen in individuals without diabetes. To understand the relationship between the Hp polymorphism and diabetic CVD, we sought to identify differences in antioxidant and scavenging functions between the Hp types and to determine how these functions were modified in diabetes. The scavenging function of Hp was assessed using rhodamine-tagged and 125 I-Hp in cell lines stably transfected with CD163 and in macrophages expressing endogenous CD163. We found that the rate of clearance of Hp 1-1–Hb by CD163 is markedly greater than that of Hp 2-2–Hb. Diabetes is associated with an increase in the nonenzymatic glycosylation of serum proteins, including Hb. The antioxidant function of Hp was assessed with glycosylated and nonglycosylated Hb. We identified a severe impairment in the ability of Hp to prevent oxidation mediated by glycosylated Hb. We propose that the specific interaction between diabetes, CVD, and Hp genotype is the result of the heightened urgency of rapidly clearing glycosylated Hb-Hp complexes from the subendothelial space before they can oxidatively modify low-density lipoprotein to atherogenic oxidized low-density lipoprotein.
Prescribing Amiodarone
Authors: Patricia Vassallo, Richard G. Trohman
Journal: JAMA (2007)

ContextAlthough amiodarone is approved by the US Food and Drug Administration only for refractory ventricular arrhythmias, it is one of the most frequently prescribed antiarrhythmic medications in the United States.ObjectiveTo evaluate and synthesize evidence regarding optimal use of amiodarone for various arrhythmias.Evidence AcquisitionSystematic search of MEDLINE to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. The search was limited to human-participant, English-language reports published between 1970 and 2007. Amiodarone was searched using the terms adverse effects, atrial fibrillation, atrial flutter, congestive heart failure, electrical storm, hypertrophic cardiomyopathy, implantable cardioverter-defibrillator, surgery, ventricular arrhythmia, ventricular fibrillation, and Wolff-Parkinson-White. Bibliographies of identified articles and guidelines from official societies were reviewed for additional references. Ninety-two identified studies met inclusion criteria and were included in the review.Evidence SynthesisAmiodarone may have clinical value in patients with left ventricular dysfunction and heart failure as first-line treatment for atrial fibrillation, though other agents are available. Amiodarone is useful in acute management of sustained ventricular tachyarrythmias, regardless of hemodynamic stability. The only role for prophylactic amiodarone is in the perioperative period of cardiac surgery. Amiodarone may be effective as an adjunct to implantable cardioverter-defibrillator therapy to reduce number of shocks. However, amiodarone has a number of serious adverse effects, including corneal microdeposits (&gt;90%), optic neuropathy/neuritis (≤1%-2%), blue-gray skin discoloration (4%-9%), photosensitivity (25%-75%), hypothyroidism (6%), hyperthyroidism (0.9%-2%), pulmonary toxicity (1%-17%), peripheral neuropathy (0.3% annually), and hepatotoxicity (elevated enzyme levels, 15%-30%; hepatitis and cirrhosis, &lt;3% [0.6% annually]).ConclusionAmiodarone should be used with close follow-up in patients who are likely to derive the most benefit, namely those with atrial fibrillation and left ventricular dysfunction, those with acute sustained ventricular arrhythmias, those about to undergo cardiac surgery, and those with implantable cardioverter-defibrillators and symptomatic shocks.
Subcutaneous or intrahepatic injection of suicide gene modified tumour cells induces a systemic antitumour response in a metastatic model of colon carcinoma in rats
Authors: V Pierrefite-Carle
Journal: Gut (2002)

Background: Suicide gene therapy consists of the transfer into tumour cells of a "suicide" gene that can convert a non-toxic compound into a lethal drug. Expression of the cytosine deaminase gene leads to the conversion of the non-toxic compound 5-fluorocytosine to 5-fluorouracil. We have recently shown that "suicide cell based vaccination" consisting of intrahepatic injection of cytosine deaminase expressing colon cancer cells followed by 5-fluorocytosine treatment induces regression of a distant wild-type liver tumour in rats. Aims: This study was conducted to test if (i) a distant bystander effect on a liver tumour can be induced after subcutaneous suicide cell based vaccination and (ii) suicide cell based vaccination is efficient in limiting tumour dissemination to extrahepatic compartments. Methods: An aggressive variant of rat colon carcinoma cells was selected after successive passages in vitro. Rats carrying an experimental liver "metastasis" generated by injection of these cells were vaccinated by subcapsular or subcutaneous injection of cytosine deaminase expressing cells followed by 5-fluorocytosine treatment. Results: Subcutaneous and subcapsular vaccination induced 70% regression in the median volume of the pre-established liver tumour (p=0.001) and abolished tumour dissemination compared with control animals. Conclusions: This study has compared for the first time the efficiency of subcutaneous and intrahepatic suicide cell based vaccination in a metastatic colorectal carcinoma model in rats. The results indicate that both modes of vaccination are equally efficient in inducing a systemic antitumour response, suggesting that this strategy is a powerful approach against the development and dissemination of metastatic colon carcinoma.
Staging of lung cancer: the role of noninvasive, minimally invasive and invasive techniques
Authors: Georgios Stamatis
Journal: European Respiratory Journal (2015)

Accurate staging and restaging of primary tumour and mediastinal nodes in patients with lung cancer is of significant importance. For primary tumours, computed tomography (CT) scans of the chest are recommended. Positron emission tomography (PET) imaging should be used in patients with curative intent treatment to evaluate metastatic disease. Diagnosis of the primary tumour should be performed using bronchoscopy or CT-guided transthoracic needle aspiration. In patients with enlarged mediastinal nodes and no distant metastasis, invasive staging of the mediastinum is required. For suspicious N2 or N3 disease, endoscopic needle techniques, such as endobronchial ultrasound and transbronchial needle aspiration, oesophageal ultrasound and fine needle aspiration, or a combination of both, are preferred to any surgical staging technique. In cases of suspicious nodes and negative results using needle aspiration techniques, invasive surgical staging using mediastinoscopy or video-assisted thoracic surgery should be performed. In central tumours or N1 nodes, preoperative invasive staging is indicated. Restaging after induction therapy remains a controversial topic. Today, neither CT, PET nor PET/CT scans are accurate enough to make final further therapeutic decisions for mediastinal nodal involvement. An invasive technique providing cytohistological information is still recommended.
Strong correlation between 18F-FDG PET positive bone involvement and increased IL-2R levels in patients with untreated sarcoidosis under surveillance (Preliminary results)
Authors: Alexandros Kalkanis, Dimitrios Kalkanis, Dimitrios Drougas, Napoleon Karagiannidis, Dimitrios Exarhos, Ioannis Datseris, Vlassios Polychronopoulos
Journal: European Respiratory Journal (2012)

Introduction:  F-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) has been shown to be able to detect osseous involvement in patients with sarcoidosis.   Aim:  To use FDG PET/CT to assess bone involvement in therapy-naive sarcoid patients and determine if FDG-avid bone involvement correlates with biochemical markers.   Methods:  All patients with a diagnosis of sarcoidosis were identified from a local database in our hospital. Therapy-naive patients under routine surveillance were enrolled in this study, and prospectively underwent a whole-body combined FDG PET/CT scan, as well as biochemical lab tests at the same day, which included interleukin-2 receptor (IL-2R), C-reactive protein (CRP), serum angiotensin-I converting enzyme (SACE), serum calcium and urine calcium levels.   Results:  23 patients (7 male, 49.6 ±10.4 years) were included. PET(+) bone lesions were identified in 26.1% of the patients (6/23), and all were negative on corresponding CT. SUVmax of the most FDG-avid bone lesion was 9.3 ±3.4. In patients with PET(+) bone involvement IL-2R was 3000 ±1588, while in the rest was 982 ±649. Significant correlation was found between PET(+) bone involvement and increased IL-2R levels only (Spearman9s rho=0.621, p=0.002).   Conclusions:  The prevalence of FDG PET(+) bone involvement in untreated sarcoidosis is 26.1% in this preliminary series. There is strong correlation between PET(+) bone involvement and increased IL-2R levels and no correlation with abnormal CRP, SACE, serum or urine calcium levels in patients with untreated sarcoidosis.