tbuckley/cabot-search huggingface dataset:
Molecular Magnetic Resonance Imaging of Pulmonary Emboli with a Fibrin-specific Contrast Agent
Authors: Elmar Spuentrup, Marcus Katoh, Andrea J. Wiethoff, Edward C. Parsons, Rene M. Botnar, Andreas H. Mahnken, Rolf W. Günther, Arno Buecker
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The detection of pulmonary embolism is still challenging due to the often nonspecific clinical findings. The aim of this study was to investigate the potential of molecular targeted magnetic resonance imaging (MRI) of pulmonary emboli using low-dose application of a fibrin-specific contrast agent (EP-2104R; Epix Pharmaceuticals, Cambridge, MA).Fresh clots from human blood were engineered ex vivo and delivered in the lungs of 11 swine. Subsequently, a T1-weighted breath-hold three-dimensional gradient-echo sequence was performed before as well as 5 minutes, 1 hour, and 2 hours after systemic administration of 7.5 (n = 5) or 4 (n = 5) micromol/kg EP-2104R. One swine that did not receive any contrast agent served as a control. MR images were analyzed by two investigators and contrast-to-noise ratio between the thrombus and the surrounding tissue (blood pool and lung parenchyma) was assessed. Localization of thrombi was compared with 16-row multislice computed tomography. Finally, the animals were killed and thrombi were removed for assessment of gadolinium concentration.Before contrast media application, thrombi were not visible on MR images. At 1 and 2 hours after contrast media injection, pulmonary emboli were selectively visualized with high-signal intensity foci, independent of the dosage used. A high gadolinium concentration in thrombi was found after both dosages (83 +/- 41 microM for 4 micromol/kg and 130 +/- 57microM for 7.5 micromol/kg), resulting in a similar high contrast-to-noise ratio on MR images (between 11 and 13).Systemic low-dose application of EP-2104R allows for selective molecular MRI of fresh pulmonary thromboembolism in a swine model.
G Proteins in Rat Liver Proliferation During Cholestasis
Authors: Nieves Rodriguez-Henche, Luis G. Guijarro, Alain Couvineau, Isabel Carrero, Eduardo Arilla, Marc Laburthe, Juan C. Prieto
Journal: Hepatology (1994)

Liver proliferation appears to be dually regulated, in part by cyclic AMP levels. Here we studied the alterations in the stimulatory action of cholera toxin and other agents on the adenylyl cyclase system, as well as the status of Gs and Gi protein subunits during the liver proliferation that follows bile duct ligation in rats. The stimulatory effects of glucagon and vasoactive intestinal peptide (which act through membrane receptors) or guanosine 5′–[βγ–imido]triphosphate (which interacts with G proteins) and forskolin (which directly activates the adenylyl cyclase catalytic subunit) on liver adenylyl cyclase activity were blunted in cholestasis. The results indicated an impairment in the stimulatory interaction between the αs subunit of Gs protein and the adenylyl cyclase catalytic subunit. Indeed, we observed an important decrease in the stimulation of adenylyl cyclase activity by cholera toxin in cholestasis that was accompanied by a reduced extent of [32P]ADP ribosylation of αs protein catalyzed by cholera toxin, as revealed by the poor labeling of the 42,000 Da band in liver membranes from cholestatic rats. However, there was no change in the amount of αs or β proteins as measured with immunoblotting techniques. Experiments on [32P]ADP ribosylation of αi subunits of Gi proteins indicated an impairment in liver membranes from cholestatic rats, whereas Western blotting for the detection of αi subunits showed decreased αi3 and increased αi2 levels in this condition. Further efforts are needed to better understand the molecular mechanisms underlying the relationship between the observed divergent expression of Gs and Gi proteins and liver cell proliferation in the cholestatic liver. (Hepatology 1994;20:1041-1047).
Regulation of Cell Death and Innate Immunity by Two Receptor-like Kinases in Arabidopsis
Authors: Minghui Gao, Xia Wang, Dongmei Wang, Fang Xu, Xiaojun Ding, Zhibin Zhang, Dongling Bi, Yu Ti Cheng, She Chen, Xin Li, Yuelin Zhang
Journal: Cell Host & Microbe (2009)
THE CURE OF PSORIASIS, WITH A STUDY OF 500 CASES OF THE DISEASE, OBSERVED IN PRIVATE PRACTICE.
Authors: L. DUNCAN BULKLEY
Journal: JAMA (1906)

Psoriasis is well known to be one of the most obstinate of all diseases of the skin, discouraging alike the physician and patient, and one which often persists for many years, or recurs, in spite of various attempts at cure, While, under proper and energetic local treatment, it is often possible to remove the existing lesions in a shorter or longer time, the tendency to a recurrence of the eruption is so strong that some have regarded the disease as incurable, and too often have only attempted to give relief to the cutaneous symptoms present, principally by local means. It is to be noticed that writers who base their judgment on cases seen in public practice, and who dwell principally on the local treatment of psoriasis, speak most discouragingly in regard to the possibility of its permanent cure, while certain others, who study the disease in its broadest aspects, express
Benzodiazepine Use in the United States
Authors: Mark Olfson, Marissa King, Michael Schoenbaum
Journal: JAMA Psychiatry (2014)

Although concern exists regarding the rate of benzodiazepine use, especially long-term use by older adults, little information is available concerning patterns of benzodiazepine use in the United States.To describe benzodiazepine prescription patterns in the United States focusing on patient age and duration of use.A retrospective descriptive analysis of benzodiazepine prescriptions was performed with the 2008 LifeLink LRx Longitudinal Prescription database (IMS Health Inc), which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population.The percentage of adults filling 1 or more benzodiazepine prescriptions during the study year by sex and age group (18-35 years, 36-50 years, 51-64 years, and 65-80 years) and among individuals receiving benzodiazepines, the corresponding percentages with long-term (≥120 days) benzodiazepine use, prescription of a long-acting benzodiazepine, and benzodiazepine prescriptions from a psychiatrist.In 2008, approximately 5.2% of US adults aged 18 to 80 years used benzodiazepines. The percentage who used benzodiazepines increased with age from 2.6% (18-35 years) to 5.4% (36-50 years) to 7.4% (51-64 years) to 8.7% (65-80 years). Benzodiazepine use was nearly twice as prevalent in women as men. The proportion of benzodiazepine use that was long term increased with age from 14.7% (18-35 years) to 31.4% (65-80 years), while the proportion that received a benzodiazepine prescription from a psychiatrist decreased with age from 15.0% (18-35 years) to 5.7% (65-80 years). In all age groups, roughly one-quarter of individuals receiving benzodiazepine involved long-acting benzodiazepine use.Despite cautions concerning risks associated with long-term benzodiazepine use, especially in older patients, long-term benzodiazepine use remains common in this age group. More vigorous clinical interventions supporting judicious benzodiazepine use may be needed to decrease rates of long-term benzodiazepine use in older adults.
Obesity in Young Men after Famine Exposure in Utero and Early Infancy
Authors: Gian-Paolo Ravelli, Zena A. Stein, Mervyn W. Susser
Journal: New England Journal of Medicine (1976)

In a historical cohort study of 300,000 19-year-old men exposed to the Dutch famine of 1944-45 and examined at military induction, we tested the hypothesis that prenatal and early postnatal nutrition determines subsequent obesity. Outcomes were opposite depending on the time of exposure. During the last trimester of pregnancy and the first months of life, exposure produced significantly lower obesity rates (P less than 0.005). This result is consistent with the inference that nutritional deprivation affected a critical period of development for adipose-tissue cellularity. During the first half of pregnancy, however, exposure resulted in significantly higher obesity rates (P less than 0.0005). This observation is consistent with the inference that nutritional deprivation affected the differentiation of hypothalamic centers regulating food intake and growth, and that subsequent increased food availability produced an accumulation of excess fat in an organism growing to its predetermined maximum size.
Combined use of chondroitinase-ABC, TGF-β1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fibrocartilage repair
Authors: Eleftherios A. Makris, Regina F. MacBarb, Nikolaos K. Paschos, Jerry C. Hu, Kyriacos A. Athanasiou
Journal: Biomaterials (2014)
Reversal of bone marrow angiogenesis in chronic myeloid leukemia following imatinib mesylate (STI571) therapy
Authors: Hans Michael Kvasnicka, Juergen Thiele, Peter Staib, Annette Schmitt-Graeff, Martin Griesshammer, Jens Klose, Knut Engels, Susanne Kriener
Journal: Blood (2004)
Plasma cyclic adenosine 3':5'-monophosphate response to isoproterenol and glucagon in hyperkinetic borderline (labile) hypertension.
Authors: F H Messerli, O Kuchel, P Hamet, G Tolis, G P Guthrie, J Fraysse, W Nowaczynski, J Genest
Journal: Circulation Research (1976)

The hemodynamic changes observed in patients with the "hyperkinetic" form of borderline (labile) essential hypertension (BEH) could be related to the hyperresponsiveness of cardiac beta-adrenergic receptors to catecholamines. The isoproterenol-induced increase in plasma cyclic adenosine 3':5'-monophosphate (cAMP) reflects the response of adenylate cyclase to beta-adrenergic stimulation, whereas a non-beta-receptor-mediated increase occurs with the administration of glucagon. Both substances were infused into 13 control subjects and 14 patients with the hyperkinetic form of BEH before and after propranolol administration. Baseline plasma cAMP concentrations were comparable in both groups. After 30 minutes of isoproterenol infusion (20 ng/kg per min) a significantly higher increase in plasma cAMP and heart rate and a smaller decrease in diastolic blood pressure were seen in this type of BEH than in control subjects. The increase in plasma cAMP and in heart rate correlated positively when all subjects were considered together. Propranolol abolished hemodynamic and humoral responses to a similar degree in both groups. The plasma cAMP responses to glucagon (200 ng/kg per min) were slightly lower in our patients with BEH than in control subjects and were not suppressed by propranolol. The data are compatible with a hyperreactivity of the beta-adrenergic receptors or of the adenylate cyclase or both in hyperkinetic BEH and could correspond to the previously observed exaggerated beta-adrenergic drive to the heart in this type of hypertension. The non-beta-receptor-mediated rise in plasma cAMP (glucagon), however, remains comparable in control subjects and BEH.
Analysis of Data from Clinical Trials
Authors: Susan Ellenberg, Janet Wittes
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 December 1983Analysis of Data from Clinical TrialsSUSAN ELLENBERG, PH.D., JANET WITTES, PH.D.SUSAN ELLENBERG, PH.D.Search for more papers by this author, JANET WITTES, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-6-874 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In an indictment of classical statistical methodology, Diamond and Forrester (1) have proposed an alternative Bayesian methodology for analyzing data from clinical trials. In a subsequent correction, they pointed out a mislabeled figure and wrote that the text associated with the figure ". . . is therefore, incorrect and should be disregarded" (2). We submit that their paper is so seriously flawed that it should be disregarded in its entirety.The authors claim their figures and arguments show that highly significant results seen with small sample sizes, as well as conventionally significant results seen from large sample...References1. DIAMOND G and FORRESTER J. Clinical trials and statistical verdicts: probable grounds for appeal. Ann Intern Med. 1983;98:385-94. LinkGoogle Scholar2. DIAMOND G and FORRESTER J. Correction: figure labels in Diamond and Forrester paper. Ann Intern Med. 1983;98:1032. LinkGoogle Scholar3. LINDGREN B. Statistical Theory. New York: The MacMillan Company; 1968:318. Google Scholar4. JEFFREYS H. Theory of Probability. 3rd ed. London: Oxford University Press; 1961:272. Google Scholar5. LINDLEY D. Introduction to Probability and Statistics from a Bayesian Viewpoint; Part 2: Inference. Cambridge, England: Cambridge University Press; 1965:61-2. CrossrefGoogle Scholar6. FEINSTEIN A. Clinical Biostatistics. St. Louis: C. V. Mosby; 1977:66-70. Google Scholar1. DIAMOND G and FORRESTER J. Clinical trials and statistical verdicts: probable grounds for appeal. Ann Intern Med. 1983;98:385-94. LinkGoogle Scholar2. JEFFREYS H. Theory of Probability. 3rd ed. London: Oxford University Press; 1961. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SUSAN ELLENBERG, PH.D.; JANET WITTES, PH.D.Affiliations: Hunter College of the City University of New York New York, NY 10021 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPosterior Probability in Clinical TrialsGEORGE A. DIAMOND, M.D., JAMES S. FORRESTER, M.D.Bayesian and Non-Bayesian Methods of InferenceROBERT D. SMALL, PH.D., STANLEY S. SCHOR, PH.D. 1 December 1983Volume 99, Issue 6 Page: 874-875 Keywords Clinical trials Statistical data ePublished: 1 December 2008 Issue Published: 1 December 1983 PDF downloadLoading ...
Abnormalities in Insulin Secretion in Healthy Offspring of Indian Patients with Maturity-Onset Diabetes of the Young
Authors: Viswanathan Mohan, Chamukuttan Snehalatha, Ambady Ramachandran, Moopil Viswanathan
Journal: Diabetes Care (1986)

Serum C-peptide (CP) and immunoreactive insulin (IRI) responses were studied in 47 euglycemic offspring of patients with maturity-onset diabetes of the young (MODY). Mean IRI responses were not significantly different in nonobese offspring of MODY patients (O-MODY) but they were lower in obese O-MODY than in respective controls. Mean CP responses were low in both groups, the change being more pronounced in obese O-MODY. These findings indicate that alterations of secretion and metabolism of insulin can be detected even before glucose intolerance is seen in O-MODY.
Triggering of Transmural Infarctions, but Not Nontransmural Infarctions, by Ambient Fine Particles
Authors: David Q. Rich, Howard M. Kipen, Junfeng Zhang, Leena Kamat, Alan C. Wilson, John B. Kostis
Journal: Environmental Health Perspectives (2010)

Previous studies have reported increased risk of myocardial infarction (MI) after increases in ambient particulate matter (PM) air pollution concentrations in the hours and days before MI onset.We hypothesized that acute increases in fine PM with aerodynamic diameter < or = 2.5 microm (PM(2.5)) may be associated with increased risk of MI and that chronic obstructive pulmonary disease (COPD) and diabetes may increase susceptibility to PM(2.5). We also explored whether both transmural and nontransmural infarctions were acutely associated with ambient PM(2.5) concentrations.We studied all hospital admissions from 2004 through 2006 for first acute MI of adult residents of New Jersey who lived within 10 km of a PM(2.5) monitoring site (n = 5,864), as well as ambient measurements of PM(2.5), nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone.Using a time-stratified case-crossover design and conditional logistic regression showed that each interquartile-range increase in PM(2.5) concentration (10.8 microg/m3) in the 24 hr before arriving at the emergency department for MI was not associated with MI overall but was associated with an increased relative risk of a transmural infarction. We found no association between the same increase in PM(2.5) and nontransmural infarction. Further, subjects with COPD appeared to be particularly susceptible, but those with diabetes were not.This PM-transmural infarction association is consistent with earlier studies of PM and MI. The lack of association with nontransmural infarction suggests that future studies that investigate the triggering of MI by ambient PM(2.5) concentrations should be stratified by infarction type.
Evaluation of Exogenous Surfactant in HCl-induced Lung Injury
Authors: ANGELA M. BRACKENBURY, PRAMOD S. PULIGANDLA, LYNDA A. McCAIG, VARONA NIKORE, LI-JUAN YAO, RUUD A. W. VELDHUIZEN, JAMES F. LEWIS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The efficacy of exogenous surfactant administration is influenced by numerous factors, which has resulted in variable outcomes of clinical trials evaluating this treatment for the acute respiratory distress syndrome (ARDS). We investigated several of these factors in an animal model of acid aspiration including different surfactant preparations, and different delivery methods. In addition, high-frequency oscillation (HFO), a mode of mechanical ventilation known to recruit severely damaged lungs, was utilized. Lung injury was induced in adult rabbits via intratracheal instillation of 0.2 N HCl followed by conventional mechanical ventilation (CMV) until Pa(O2)/FI(O2) values ranged from 220 to 270 mm Hg. Subsequently, animals were given one of three surfactants administered via three different methods and physiological responses were assessed over a 1-h period. Regardless of the surfactant treatment strategy utilized, oxygenation responses were not sustained. In contrast, HFO resulted in a superior response compared with all surfactant treatment strategies involving CMV. The deterioration in physiological parameters after surfactant treatment was likely due to overwhelming protein inhibition of the surfactant. In conclusion, various surfactant treatment strategies were not effective in this model of lung injury, although the lungs of these animals were recruitable with HFO, as reflected by the acute and sustained oxygenation improvements.
Discontinuation of Antihyperlipidemic Drugs — Do Rates Reported in Clinical Trials Reflect Rates in Primary Care Settings?
Authors: Susan E. Andrade, Alexander M. Walker, Lawrence K. Gottlieb, Norman K. Hollenberg, Marcia A. Testa, Gordon M. Saperia, Richard Platt
Journal: New England Journal of Medicine (1995)

Discontinuation rates for drugs used to treat chronic conditions may affect the success of therapy. However, the discontinuation rates reported in clinical trials may not reflect those in primary care settings.
Scopulariopsosis and Hypersensitivity Pneumonitis in an Addict
Authors: HANS G. GRIEBLE
Journal: Annals of Internal Medicine (1975)

Granulomatosis caused by fungal spores of a soil saprophyte is a newly recognized pulmonary complication of intravenous drug addiction. Brown, non-budding spores were histologically identified in necrotic tissue, inside giant cells of sarcoidlike granulomata, and in the vicinity of focal angiitic lesions. The fungus was identified by culture as the dematiaceous Scopulariopsis brumptii. Cultural and histopathologic studies of lung biopsy specimens established the diagnosis. We showed precipitating antibodies to fungal antigen in the serum, prepared from the patient's isolate. Similar granulomatous pulmonary lesions were experimentally produced in mice by a single intravenous injection of spores of S. brumptii. The spores remained viable but did not show evidence of growth in the animal's tissue. Precipitating antibodies to fungal antigen and immediate wheal and late necrotizing type of skin reactions were shown in the challenged mice. The studies support the notion that pulmonary hypersensitivity to fungal spores was mediated by an Arthus'-type phenomenon.
54Detection, quantification and visualization of ryanodine receptor phosphorylation in human atrial myocytes using a novel ratiometric immunofluorescent analysis
Authors: A Vallmitjana, PE Molina, A Herraiz, J Montiel, J Cinca, R Benitez, L Hove-Madsen
Journal: Cardiovascular Research (2014)

Purpose: Calcium release through the ryanodine receptor (RyR2) plays a central role in the regulation of cardiac contraction and rhythm, and is modulated by RyR2 phosphorylation. However, little is known about the distribution of phosphorylated RyR2s in isolated cardiac myocytes and the purpose of the present study was to develop an immunofluorescent ratio-metric approach to quantify and visualize the spatial distribution of phosphorylated RyR2s.

Methods: Forty-nine human atrial myocytes from nine patients were labeled with anti-phospho Ser-2808 (Red) and anti-RyR2 (Green) antibodies and detected automatically using a custom made algorithm based on: 1) Enhancing the contrast of both green and red-labeled images using a histogram stretching intensity transformation. 2) Removing background noise by using an adaptive median filter that estimates the noise level. 3) Enhancing the location of all green-labeled RyRs with a 2D Gaussian filter with a standard deviation of 0.5 microns followed by segmentation using a multilevel watershed algorithm. 4) Eliminating non-specific staining by setting the maximal RyR diameter to 1.2 microns. 5) Detection of red-labeled ser2808 phosphorylated RyR2s by checking if a cluster of red pixels was present at the location of each green labeled RyR2. Red clusters that overlapped at least 20% of the area of a green-labeled RyR2 were accepted if the normalized intensity of the overlapping area was above 15%.

Results: Superimposing detected RyR2s on the original confocal image revealed a detection efficiency near 95%, and visual inspection of superimposed original confocal images confirmed that all red ser2808 clusters coincided with a green RyR2. Moreover, stimulation of RyR2 phosphorylation with the beta-adrenergic agonist was used as a positive control, and it significantly increased the ser2808:total RyR2 ratio from 0.32±0.03 to 0.52±0.06 (p<0.01).

Conclusion: We have developed a novel immunofluorescent ratiometric approach that allows quantifying and visualizing RyR2 phosporylation in isolated human atrial myocytes. This approach may also apply to other proteins with a punctate distribution that are modulated by phosphorylation, and should be useful to study how disease affects the distribution of such proteins under basal or phosphorylating conditions.
Endoscopic Managment of Obstructive Jaundice due to Portal Cavernoma
Authors: G. N. Yattoo, M. S. Khuroo
Journal: Endoscopy (1996)

See also: Endoscopic Management of Obstructive Jaundice due to Portal CavernomaEndoscopy 1993; 25(06): 423-425DOI: 10.1055/s-2007-1009120