tbuckley/cabot-search huggingface dataset:
Joint erosion in rheumatoid arthritis: interactions between tumour necrosis factor , interleukin 1, and receptor activator of nuclear factor B ligand (RANKL) regulate osteoclasts
Authors: D O' Gradaigh
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Osteoclasts, specialised bone resorbing cells regulated by RANKL and M-CSF, are implicated in rheumatoid joint erosion. Lymphocyte-monocyte interactions activate bone resorption, this being attributed to tumour necrosis factor α (TNFα) and interleukin 1 β (IL1β) enhanced osteoblast expression of RANKL. In animal studies, TNF potently increases osteoclast formation in the presence of RANKL. RANKL-independent osteoclastogenesis also occurs, though IL1 is required for resorptive function in most studies. These inflammatory cytokines have a pivotal role in rheumatoid arthritis, <b>Objective:</b> To study the interactions of TNFα and IL1β with RANKL, particularly the time course of the interactions and the role of lymphocytes. <b>Method:</b> Cultures of lymphocytes and monocytes (osteoclast precursors) or of purified CD14<sup>+</sup> cells alone (osteoclast precursors) were exposed to various combinations of TNFα, RANKL, and IL1β or the inhibitors osteoprotegerin, IL1 receptor antagonist, or neutralising antibodies to RANKL or to IL1. Osteoclastogenesis and resorptive activity were assessed on microscopy of dentine slices. <b>Results:</b> TNFα potently increased osteoclast proliferation/differentiation in the presence of RANKL. This effect was greatest when RANKL was present before but not after exposure of osteoclast precursor cells to TNFα. The resorptive activity of osteoclasts generated by TNFα in the absence of RANKL was critically dependent upon IL1, which was expressed by lymphocyte-monocyte interaction. <b>Conclusion:</b> TNFα potently enhances RANKL mediated osteoclast activity. Interactions between TNFα and IL1 also result in osteoclastic activity independently of RANKL. These findings will inform therapeutic approaches to the prevention of joint erosion in rheumatoid arthritis.
A diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection
Authors: Sandra Beinhardt, Berit Anna Payer, Christian Datz, Michael Strasser, Andreas Maieron, Livia Dorn, Evelyn Grilnberger-Franz, Emina Dulic-Lakovic, Rudolf Stauber, Hermann Laferl, Judith H. Aberle, Heidemarie Holzmann, Christoph Krall, Wolfgang Vogel, Peter Ferenci, Harald Hofer
Journal: Journal of Hepatology (2013)
Adenoviral dominant-negative soluble PDGFRβ improves hepatic collagen, systemic hemodynamics, and portal pressure in fibrotic rats
Authors: V. Reichenbach, G. Fernández-Varo, G. Casals, D. Oró, J. Ros, P. Melgar-Lesmes, R. Weiskirchen, M. Morales-Ruiz, W. Jiménez
Journal: Journal of Hepatology (2012)
Asthma therapy modulates priming-associated blood eosinophil responsiveness in allergic asthmatics
Authors: J.C. Grutters, L. Brinkman, M.m Aslander, J.M.m van den Bosch, L Koenderman, J-W.j Lammers
Journal: European Respiratory Journal (1999)

Eosinophils play an important role in the pathogenesis of asthma. Several pro-inflammatory responses of eosinophils are primed in vivo in this disease. The aim of the present study was to investigate whether regular antiasthma treatment could modulate priming-sensitive cytotoxic mechanisms of human eosinophils. In a randomized, two-centre, double-blind parallel group study, the effect of 8 weeks of treatment with salmeterol xinafoate 50 microg b.i.d., beclomethasone dipropionate 400 microg b.i.d. or both on pulmonary function and the activation of priming-sensitive cytotoxic mechanisms of eosinophils, i.e. degranulation of eosinophil cationic protein (ECP) in serum, and activation of isolated eosinophils in the context of induction of the respiratory burst and release of platelet-activating factor (PAF) were tested. These effects were evaluated in 40 allergic asthmatics before and 24 h after allergen inhalation challenge. Whereas baseline forced expiratory volume in one second (FEV1) improved in all treatment groups, only treatment with a combination of salmeterol and beclomethasone significantly inhibited the allergen-induced increase in serum ECP, and (primed/unprimed) PAF-release, suggesting inhibition of eosinophil priming after allergen challenge. In contrast to the combination therapy, monotherapy with beclomethasone had no influence on allergen-induced PAF-release, suggesting an additional anti-inflammatory effect of salmeterol during combination therapy. Monotherapy with beclomethasone inhibited the prechallenge serum-treated zymosan (STZ) (0.1 mg mL(-1))-induced respiratory burst and the allergen-induced increase in serum ECP levels, reflecting pre- and postchallenge anti-inflammatory effects. During monotherapy with salmeterol, an allergen-induced increase in serum ECP concentration and STZ (0.1 mg x mL(-1))-induced respiratory burst was observed, suggesting that treatment with salmeterol alone had no effect on priming-sensitive eosinophil cytotoxic mechanisms. In conclusion, this study shows that standard asthma therapy leads to inhibition of eosinophil priming of cytotoxic mechanisms in vivo.
High prevalence of antibodies against beta1- and beta2-adrenoceptors in patients with primary electrical cardiac abnormalities
Authors: Pablo A. Chiale, Mauricio B. Rosenbaum, Marcelo V. Elizari, Ake Hjalmarson, Yvonne Magnusson, Gerd Wallukat, Johan Hoebeke
Journal: Journal of the American College of Cardiology (1995)
The Accuracy of Substituted Judgments in Patients with Terminal Diagnoses
Authors: Daniel P. Sulmasy
Journal: Annals of Internal Medicine (1998)

Background: Patients' loved ones often make end-of-life treatment decisions, but the accuracy of their substituted judgments and the factors associated with accuracy are poorly understood. Objective: To assess the accuracy of judgments made by surrogate decision makers; ascertain the beliefs, practices, and clinical and sociodemographic factors associated with accuracy of surrogates' decisions; assess the preferences of patients for life-sustaining treatments; and compare differences in accuracy across diagnoses. Design: Cross-sectional paired interviews. Setting: Outpatient practices of three university hospitals. Patients: 250 patients with terminal diagnoses of congestive heart failure, AIDS, amyotrophic lateral sclerosis, lung cancer, and chronic obstructive pulmonary disease (50 patient-surrogate pairs in each group) and 50 general medical patients and their surrogates. Measurements: The accuracy of surrogate predictions was measured by using scales based on 10 potential treatments in each of three hypothetical clinical scenarios. Results: Preferences varied according to mode of treatment and scenario. On average, surrogates made correct predictions in 66% of instances. Accuracy was better for the permanent coma scenario than for the scenarios of severe dementia or coma with a small chance of recovery (P < 0.001). In a binary logit model, the accuracy of substituted judgments was positively associated with the patient having spoken with the surrogate about end-of-life issues (odds ratio [OR], 1.9 [95% CI, 1.6 to 2.3]), the patient having private insurance (OR, 1.4 [CI, 1.1 to 1.7]), the surrogate's level of education (OR, 1.5 [CI, 1.2 to 1.9]), and the patient's level of education (OR, 1.7 [CI, 1.4 to 2.2]). Accuracy was negatively associated with the patient's belief that he or she would live longer than 10 years (OR, 0.6 [CI, 0.5 to 0.7]), surrogate experience with life-sustaining treatment (OR, 0.4 [CI, 0.3 to 0.5]), surrogate participation in religious services (OR, 0.67 [CI, 0.50 to 0.91]), and a diagnosis of heart failure (OR, 0.6 [CI, 0.5 to 0.8]). Age, ethnicity, marital status, religion, and advance directives were not associated with accuracy. Conclusions: The accuracy of substituted judgments is associated with multiple clinically apparent patient and surrogate factors. This information can help clinicians identify conditions under which substituted judgments are likely to be accurate or inaccurate and can help target populations for education designed to improve the accuracy of surrogate decision making.
Bone Scan Cold Spot from Separation of Osseous Fragments in Pathologic Fracture
Authors: JAMES D. SLAVIN, ZAHIDA YOOSUFANI, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1987)

An initial bone scan of the upper iliac crest region did not reveal any defects; a repeat study several weeks later showed a cold area (without a change on the radiograph taken two days previously). One week after the bone scan, an x-ray demonstrated a pathologic fracture of the region and separation of the fragments.
Abstract 4520: Inhibition of melanoma growth by small molecules that attenuate PI3K/PDK1 signaling and promote ATF2 mitochondrial localization
Authors: Tal Varsano, Yongmei Feng, Giuseppina Claps, Marzia Scortegagna, Eric Lau, Marilyn Leonard, Anthony Pinkerton, Maurizio Pellecchia, Michael Davies, Marcus Bosenberg, Ze'ev Ronai
Journal: Cancer Research (2014)

Abstract Phosphoinositide-dependent kinase-1 (PDK-1) phosphorylates members of the AGC kinase superfamily, including AKT and PKC. We recently demonstrated the importance of PDK1 in melanoma development and progression (Oncogene 2013). Genetic ablation of PDK1 in melanocytes effectively delayed melanoma development and inhibited metastasis in a Braf/Cdkn2a model with WT or mutant Pten. In an effort to identify small molecule inhibitors that could affect the PDK1 signaling we characterized SBI-0089410, a small molecule identified in a screen for nuclear exclusion of the transcription factor ATF2, which attenuates its oncogenic activity while enabling its function at the mitochondrial membrane to promote apoptosis. SBI-0089410 reduced melanoma cell viability, inhibited colony formation and spheroid growth, decreased mitochondrial membrane permeability, decreased ATF2 phosphorylation by PKCϵ and altered ATF2 transcriptional activity. Notably, the effect of SBI-0089401 was attenuated by the overexpression of constitutively active PKCϵ or ATF2T52E, which carries a phosphomimetic mutation at the PKCϵ phosphorylation site. Reverse phase protein array (RPPA), validated by western blot analysis, revealed that SBI-408910 attenuates PI3K/AKT/PDK1 signaling pathways. In vivo, SBI-089410 attenuated the growth of Braf/Cdkn2a/Pten tumors in a syngeneic B6 mouse model, as well as prevented their resistance to BRAFi. Our studies substantiate the importance of targeting PI3K/PDK1 signaling in melanoma as a means for effective therapy and prevention of chemoresistance. Citation Format: Tal Varsano, Yongmei Feng, Giuseppina Claps, Marzia Scortegagna, Eric Lau, Marilyn Leonard, Anthony Pinkerton, Maurizio Pellecchia, Michael Davies, Marcus Bosenberg, Ze'ev Ronai. Inhibition of melanoma growth by small molecules that attenuate PI3K/PDK1 signaling and promote ATF2 mitochondrial localization. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4520. doi:10.1158/1538-7445.AM2014-4520
Cases Illustrative of the Influence of Belladonna
Authors: Richard Hughes
Journal: BMJ (1860)

of the first class, and gastric irritation from irritating matters and worms, and painful menstruation on the other.For spinal irritation, therefore, a term wlhich should pro- bably be expunged altogether from medical etiology, we may, I think, substitute peripheral irritation of one kind or other-a really intelligible and meaning term-in some if not many of the cases sought to be explained by the former.Then we have p)aralysis agitans, in some persons with semi- worn-out cerebral power, evidently one phase of the choreal or clonic state of the muscles.From a careful examination of this subject, I find it difficlult to conclude that any more direct relation exists between chorea and carditis than the one now explained; and I do riot tliiik it at all niecessary to this inquiry, eveni if it were possible to attempt anything in the way of explanation as to that myssterious connexion between the cardiac and other ganglia of the sympathetic anid the cerebral anid true spinal system, nor of the moduts operandi of the influence which anl intlamed heart woiuld exercise through this relation upon the braini and nervous systemu.
Monitoring changes in hospital standardised mortality ratios
Authors: Brian Jarman, Alex Bottle, Paul Aylin, Mike Browne
Journal: BMJ (2005)

Dr Foster's case notesMonitoring changes in hospital standardised mortality ratios Hospital medical care has become more complex than it was in the days when there were few effective treatments available.Now many more healthcare professionals may be involved in the increasingly complex care of an individual patient, but the possibilities for error have increased.The Bristol Inquiry, w2 Harvard medical practice study, w3 and the Institute of Medicine's report To Err Is Human w4 have all drawn attention to the level of adverse events in hospitals and the need to avoid unnecessary deaths.Since January 2001 Dr Foster has published hospital standardised mortality ratios (HSMRs) based on routinely collected hospital episode statistics (HES) for the major acute hospitals in England.In 2000 Walsall Hospitals NHS Trust had an HSMR of 130, the highest of all main acute hospitals in England (30% above the value for England as a whole, which is 100).Its medical director and others formed seven clinical governance groups to implement changes in clinical disease areas: heart, malignant, gastrointestinal, respiratory, renal, diabetes, other vascular groups, trauma and
Hyperprolactinemia and Psychological Distress in Women Undergoing Chronic Hemodialysis
Authors: Maurizio Fava, Emanuela Serafini, Leopoldo De Besi, Alberto Adami, Ismaele Mastrogiacomo
Journal: Psychotherapy and Psychosomatics (1988)

In order to investigate the possible relationship of hyperprolactinemia to psychological distress in patients undergoing chronic hemodialysis, 19 uremic women were evaluated by a semistructured interview and administered the Kellner Symptom Questionnaire. Group A (10 uremic women with hyperprolactinemia) did not differ significantly in anxiety, depression, somatization and hostility from group B (9 normoprolactinemic uremic women). Both groups rated themselves more depressed and hostile than a normal control group of 10 women, and hyperprolactinemic patients were also significantly more anxious than the normal controls.
Genome-wide profiling reveals epigenetic inactivation of the PU.1 pathway by histone H3 lysine 27 trimethylation in cytogenetically normal myelodysplastic syndrome
Authors: J X Cheng, J Anastasi, K Watanabe, E L Kleinbrink, E Grimley, R Knibbs, Q J Shen, J W Vardiman
Journal: Leukemia (2013)
An Outbreak of Hepatitis Traced to Food Contamination
Authors: P. R. Joseph, J. D. Millar, D. A. Henderson, R. D. Naumann, Carter S. Bagley, H. A. Schlang, G. A. Shaw
Journal: New England Journal of Medicine (1965)

DURING a month's period in late 1961, 23 cases of hepatitis occurred among personnel at a Navy air station. The outbreak was characteristic of a common-source epidemic with a single wave of illness and was clearly related to exposure at the dining room of the Bachelor Officers' Quarters. An investigation, greatly facilitated by detailed military records, permitted the incrimination of a single food as the vehicle of infection.Few food-borne epidemics of hepatitis have, to date, been documented. Because of the extended incubation period of the disease, suspected food-borne epidemics have resisted investigation by conventional technics. In this study an . . .
Microcirculation of left atrial muscle, cerebral cortex and mesentery of the cat. A comparative analysis.
Authors: B L Chang, T Yamakawa, J Nuccio, R Pace, R J Bing
Journal: Circulation Research (1982)

By means of transillumination (microtransilluminator and light pipe), comparative analyses were carried out on geometry, topography, and morphometry of microcirculation in the cerebral cortex, left atrial muscle, and mesentery of the cat using computer analysis. In addition, specific types of capillary distribution (concurrent, countercurrent, and asymmetric distribution) in these three organs were ascertained from images visualized on films. These parameters were related to their role in tissue oxygen supply. It was found that mean capillary diameter, mean intercapillary distance, total capillary length, and total capillary surface area differed significantly among the three organs. Differences in mean capillary tortuosity between cerebral and left atrial muscle and between left atrial muscle and mesentery also were significant. Mean capillary tortuosity in mesentery and cerebral cortex was of equal magnitude. In the cerebral cortex, a high degree of tortuosity and asymmetric capillary distribution favor tissue oxygenation. A similar situation exists in left atrial muscle, although some concurrent and countercurrent distribution could be detected. In the mesentery, the combination of high capillary tortuosity and concurrent capillary arrangement is unfavorable for tissue oxygenation.
Central Nervous System Infection in Congenital Syphilis
Authors: Ian C. Michelow, George D. Wendel, Michael V. Norgard, Fiker Zeray, N. Kristine Leos, Rajiha Alsaadi, Pablo J. Sánchez
Journal: New England Journal of Medicine (2002)

Identification of infants with Treponema pallidum infection of the central nervous system remains challenging.
Superoxide production by human umbilical vein endothelial cells in an anoxia-reoxygenation model
Authors: M. L. SCHINETTI, R. SBARBATI, M. SCARLATTINI
Journal: Cardiovascular Research (1989)

Ischaemia/reperfusion of cardiac tissue has been claimed to be associated with the production of oxygen free radicals, which can contribute to severe membrane damage and tissue injury. We investigated the effects of anoxia/reoxygenation treatment on superoxide radical production in an in vitro system consisting of preconfluent and confluent human endothelial cell monolayers. The influence of varying the anoxia and reoxygenation phases on superoxide production was studied. As a test of cytotoxicity, the release of the cytosolic enzyme lactate dehydrogenase in the culture medium was measured before and at 0, 24 and 48 h after anoxia-reoxygenation. Cellular damage was monitored by microscopic examination of the cultures during and after the experiments and by the expression of the von Willebrand protein and of the membrane glycoprotein IIa by indirect immunofluorescence with specific monoclonal antibodies. Our results show that the endothelial cells subjected to anoxia-reoxygenation release superoxide anions, as revealed by superoxide dismutase inhibitable cytochrome C reduction. Free radical production is dependent on cell confluent or preconfluent state and on both anoxia and reoxygenation duration. Free radical release does not seem to be accompanied by manifest cellular alteration.
Attitudes to mouthguards and prevalence of orofacial injuries in four teams competing at the second Rugby World Cup.
Authors: P J Chapman, B P Nasser
Journal: British Journal of Sports Medicine (1993)

The opportunity was taken to conduct a questionnaire survey of the members of four competing countries at the second Rugby World Cup tournament (Australia, Ireland, Scotland, Wales) regarding the prevalence of orofacial injuries and attitudes to mouthguards. The results show that while all players in each team believed that mouthguards provided local protection, approximately one in five of each team did not wear one. The average age when players first started wearing mouthguards varied from 12.7 years for Australia to 18.1 years for Wales, while the percentage of wearers willing to play without their mouthguard ranged from only 4.6% for Australia to 15.8% for Wales. Just less than half of the total group had previously sustained an orofacial injury playing rugby.
Pathophysiological correlates of thallium-201 myocardial uptake in experimental infarction
Authors: V. C. DiCOLA, S. E. DOWNING, R. K. DONABEDIAN, B. L. ZARET
Journal: Cardiovascular Research (1977)

The pathophysiological correlates of thallium-201 (201T1) myocardial uptake were studied in a 24-hour-old closed-chest canine infarct model. Reduction in regional 201T1 uptake correlated well with the magnitude of tissue creatine phosphokinase depletion and microsphere estimates of transmural blood flow. In low flow endocardial regions 201T1 occasionally underestimated the magnitude of flow reduction. Even slight reductions of 201T1 uptake (<0.86 of normal) were associated with histopathological and histochemical evidence of necrosis.
International conference calls for better prevention to contain spread of AIDS
Authors: Henry Wasswa
Journal: BMJ (2008)

Three million people in poor and middle income countries were taking drugs to treat AIDS at the end of 2007, a conference of 1700 doctors and health experts in Kampala heard last week.

The 2008 HIV/AIDS Implementers’ Meeting also heard that the world population of people with HIV fell from 39.5 to 33.2 million between 2006 and 2007. The number of newly infected people in 2007 was 2.5 million, down from 3.2 million in 1998.

These figures were in a report produced jointly …
Prevention of Doxorubicin-Induced Hair Loss with Scalp Hypothermia
Authors: Judith C. Dean, Sydney E. Salmon, Katherine S. Griffith
Journal: New England Journal of Medicine (1979)

THE psychological impact of chemotherapy-induced alopecia represents one of the more devastating side effects of cancer chemotherapy and, in some instances, leads patients to refuse potentially curative chemotherapy. The problem of alopecia is severe when patients are treated with the anthracycline antibiotic, doxorubicin (adriamycin), which is beneficial in many types of cancer (e.g., breast, lung, ovary, sarcomas, lymphomas, and leukemias).1 2 3 4 5 6 In 1973, Luce and his co-workers achieved good protection against doxorubicin-induced alopecia in 12 of 15 patients by means of regional direction of chilled air to the scalp.7 More recently, Edelstyn's group used cryogel packs held on the scalp with . . .
TCT-303 Predictors Of Acute And Late Persistent Stent Malapposition After Percutaneous Coronary Intervention: A Follow-up Optical Coherence Tomography Study
Authors: Eui Im, Byeong-Keuk Kim, Jung-Sun Kim, Dong-Ho Shin, Young-Guk Ko, Donghoon Choi, Yang-Soo Jang, Myeong-Ki Hong
Journal: Journal of the American College of Cardiology (2012)