tbuckley/cabot-search huggingface dataset:
Differentiation of neurogenic and myocardial angiotensin II receptors in isolated rabbit atria.
Authors: A L Blumberg, J A Ackerly, M J Peach
Journal: Circulation Research (1975)

The effect of angiotensin on the action of tyramine was studied in isolated rabbit left atria paced by point and field stimulation to more clearly define the interaction of angiotensin with the sympathetic nervous system. Administration of angiotensin resulted in similar increases in contractility in both point- and field-stimulated atria. In point-stimulated preparations only the muscle is stimulated to contract, whereas in field-stimulated preparations both nerve and muscle are stimulated. 1-Sar-8-Ala-angiotensin II completely blocked the direct inotropic effect of angiotensin in a molar dose ratio of 3:1 in both point- and field-stimulated preparations. However, angiotensin (0.05-10 ng/ml) potentiated the inotropic effect of tyramine in field-stimulated atria only. This facilitatory effect was not inhibited by 1-Sar-8-Ala-angiotensin II at a molar dose ratio of 3:1; indeed, a ratio of 500:1 was necessary for complete blockade of this angiotensin-induced potentiation. This antagonist in odses of 0.1-1000 ng/ml was without contractile effect in any preparation, regardless of whether tyramine was present. The data suggest the presence of (1) a presynaptic angiotensin receptor that, in the presence of sympathetic nerve stimulation, modulates the release of norepinephrine and (2) a second angiotensin receptor in cardiac tissue that directly influences myocardial contractility.
Low levels of tissue factor lead to alveolar haemorrhage, potentiating murine acute lung injury and oxidative stress
Authors: Julie A Bastarache, Sara C Sebag, Jennifer K Clune, Brandon S Grove, William E Lawson, David R Janz, L Jackson Roberts, Ryszard Dworski, Nigel Mackman, Lorraine B Ware
Journal: Thorax (2012)

<h3>Background</h3> Systemic blockade of tissue factor (TF) attenuates acute lung injury (ALI) in animal models of sepsis but the effects of global TF deficiency are unknown. We used mice with complete knockout of mouse TF and low levels (∼1%) of human TF (LTF mice) to test the hypothesis that global TF deficiency attenuates lung inflammation in direct lung injury. <h3>Methods</h3> LTF mice were treated with 10 μg of lipopolysaccharide (LPS) or vehicle administered by direct intratracheal injection and studied at 24 h. <h3>Results</h3> Contrary to our hypothesis, LTF mice had increased lung inflammation and injury as measured by bronchoalveolar lavage cell count (3.4×10<sup>5</sup> wild-type (WT) LPS vs 3.3×10<sup>5</sup> LTF LPS, p=0.947) and protein (493 μg/ml WT LPS vs 1014 μg/ml LTF LPS, p=0.006), proinflammatory cytokines (TNF-α, IL-10, IL-12, p&lt;0.035 WT LPS vs LTF LPS) and histology compared with WT mice. LTF mice also had increased haemorrhage and free haemoglobin in the airspace accompanied by increased oxidant stress as measured by lipid peroxidation products (F<sub>2</sub> isoprostanes and isofurans). <h3>Conclusions</h3> These findings indicate that global TF deficiency does not confer protection in a direct lung injury model. Rather, TF deficiency causes increased intra-alveolar haemorrhage following LPS leading to increased lipid peroxidation. Strategies to globally inhibit TF may be deleterious in patients with ALI.
Activation of Fc receptor-bearing lymphocytes by immune complexes. II. Killer lymphocytes mediate Fc ligand-induced lymphokine production.
Authors: M E Neville, H W Lischner
Journal: The Journal of Experimental Medicine (1981)

Cells that participate in immune complex-induced production of leukocyte migration inhibitory factor (LIF) activity can be concentrated in a population making up 2-4% of human peripheral blood lymphocytes in which greater than 90% of the cells are active in a single cell antibody-dependent cellular cytotoxicity assay. When so concentrated, such killer (K) cell preparations are as efficient in producing LIF activity as mitogen activated T lymphocytes. Other Fc receptor (FcR)-bearing lymphocytes, including natural killer (NK) cells, do not produce measurable LIF activity when incubated with immune complexes (additional evidence that the K and NK cells among ligands to the FcR of the appropriate lymphocytes, possibly without need for exogenous receptor bridging, is the only requirement for their activation to immune complex-induced lymphokine production (ICLP). It is probable that ICLP by K cells palays a role in antibody-mediated effector functions in vivo.
THE CLINICAL INVESTIGATION AND DIFFERENTIAL MEASUREMENT OF ANXIETY
Authors: RENATUS HARTOGS
Journal: American Journal of Psychiatry (1950)

1. Four clinical methods for rapid psychiatric evaluation and measurement of anxiety have been presented. 2. These methods investigate the effects of anxiety upon visuo-motor control, self-concept, level of aspiration, and body-image. 3. Typical results and differential trends obtained through these short procedures in psychiatric syndromes, characterized etiologically or symptomatically by anxiety, have been presented. We conclude that in view of the primary importance of anxiety as psychopathogenic factor psychiatrists and medical students should acquaint themselves with objective, experimental methods, which can be used in the course of a clinical interview for the differential measurement and analysis of anxiety.
Surrogate End Points for the Treatment of Diabetic Neuropathic Foot Ulcers
Authors: David J. Margolis, Joel M. Gelfand, Ole Hoffstad, Jesse A. Berlin
Journal: Diabetes Care (2003)

OBJECTIVE—The goal of this study was to determine whether surrogate markers based primarily on changes in the size of a wound can be used to correctly predict which individuals with diabetic neuropathic foot ulcers will heal after 12 or 20 weeks of care. RESEARCH DESIGN AND METHODS—This is a retrospective cohort study using the Curative Health Services database. As many as 39,918 neuropathic wounds on 20,213 individuals with diabetes were evaluated. Seven surrogates based on changes in wound size were evaluated. RESULTS—Surrogates measured after 2, 4, or 8 weeks of care and based on percentage change in area, log healing rate, and log area ratio discriminated well with respect to differentiating between those wounds that healed and those that did not heal by the 12th or 20th week of care. For example, after 4 weeks of care, the percentage change in area can be used to correctly discriminate 76% of the time between those that healed and those that did not by the 20th week of care. CONCLUSIONS—The surrogate markers can be used in clinical trials such that shorter and smaller trials can be conducted with reasonable accuracy in order to determine which potential new therapeutics should be studied in larger, longer trials. In addition, the surrogates may also benefit clinicians when they are trying to decide whether a wound care therapy will ultimately be successful.
Genetic variants regulating insulin receptor signalling are associated with the severity of liver damage in patients with non-alcoholic fatty liver disease
Authors: P Dongiovanni, L Valenti, R Rametta, A K Daly, V Nobili, E Mozzi, J B S Leathart, A Pietrobattista, A D Burt, M Maggioni, A L Fracanzani, E Lattuada, M A Zappa, G Roviaro, G Marchesini, C P Day, S Fargion
Journal: Gut (2010)

Background/aims The aim of this study was to assess the effect of functional ENPP1(ectoenzyme nucleotide pyrophosphate phosphodiesterase 1)/PC-1 (plasma cell antigen-1) and IRS-1 (insulin receptor substrate-1) polymorphisms influencing insulin receptor activity on liver damage in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, whose progression is associated with the severity of insulin resistance. Patients and methods 702 patients with biopsy-proven NAFLD from Italy and the UK, and 310 healthy controls. The Lys121Gln ENPP1/PC-1 and the Gly972Arg IRS-1 polymorphisms were evaluated by restriction analysis. Fibrosis was evaluated according to Kleiner. Insulin signalling activity was evaluated by measuring phosphoAKT levels by western blotting in a subset of obese non-diabetic patients. Results The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively. The ENPP1 121Gln allele was significantly associated with increased prevalence of fibrosis stage &gt;1 and &gt;2, which was higher in subjects also positive for the 972Arg IRS-1 polymorphism. At multivariate analysis, the presence of the ENPP1 121Gln and IRS-1 972Arg polymorphisms was independently associated with fibrosis &gt;1 (OR 1.55, 95% CI 1.24 to 1.97; and OR 1.57, 95% CI 1.12 to 2.23, respectively). Both polymorphisms were associated with a marked reduction of ∼70% of AKT activation status, reflecting insulin resistance and disease severity, in obese patients with NAFLD. Conclusions The ENPP1 121Gln and IRS-1 972Arg polymorphisms affecting insulin receptor activity predispose to liver damage and decrease hepatic insulin signalling in patients with NAFLD. Defective insulin signalling may play a causal role in the progression of liver damage in NAFLD.
REMARKABLE CASE OF INCONTINENCE OF URINE
Authors: J. Z. Laurence
Journal: BMJ (1854)

As to tX bomeer, wO find that from the 25th Luguatto the end of September, it stood obstinately at 30, mer or lss-that is,fair.The disse this ear seems to have been of a peculiarly fatal desciption.In the Dobrudscha (Daily New8, Oct. 2),
Post subthalamic area deep brain stimulation for tremors: a mini-review
Authors: Tao Xie, Jacqueline Bernard, Peter Warnke
Journal: Translational Neurodegeneration (2012)

Deep brain stimulation (DBS) in the thalamic ventrointermediate nucleus (VIM) is the traditional target for the surgical treatment of pharmacologically refractory essential tremor or parkinsonian tremor. Studies in recent years on DBS in posterior subthalamic area (PSA), including the zona incerta and the prelemniscal radiation, have shown promising results in tremor suppression, particularly for those tremors difficult to be well controlled by VIM DBS, such as the proximal postural tremor, distal intention tremor and some cerebellar outflow tremor in various diseases including essential tremor and multiple sclerosis. The adverse effect profile of the PSA DBS is mild and transient, without lasting or striking dysarthria, disequilibrium or tolerance, in contrast to VIM DBS, particularly bilateral DBS. However, the studies on PSA DBS so far are still limited, with a handful of studies on bilateral PSA, and a short follow up duration compared to VIM. More studies are needed for direct comparison of these targets in the future. A review here would help to gain more insight into the benefits and limits of the PSA DBS compared to that in VIM in the clinical management of various tremors, particularly for those difficult to be well controlled by traditional VIM DBS.
Correlation of O<sup>6</sup>-Methylguanine Methyltransferase (MGMT) Promoter Methylation With Clinical Outcomes in Glioblastoma and Clinical Strategies to Modulate MGMT Activity
Authors: Monika E. Hegi, Lili Liu, James G. Herman, Roger Stupp, Wolfgang Wick, Michael Weller, Minesh P. Mehta, Mark R. Gilbert
Journal: Journal of Clinical Oncology (2008)

Resistance to alkylating agents via direct DNA repair by O 6 -methylguanine methyltransferase (MGMT) remains a significant barrier to the successful treatment of patients with malignant glioma. The relative expression of MGMT in the tumor may determine response to alkylating agents, and epigenetic silencing of the MGMT gene by promoter methylation plays an important role in regulating MGMT expression in gliomas. MGMT promoter methylation is correlated with improved progression-free and overall survival in patients treated with alkylating agents. Strategies to overcome MGMT-mediated chemoresistance are being actively investigated. These include treatment with nontoxic pseudosubstrate inhibitors of MGMT, such as O 6 -benzylguanine, or RNA interference-mediated gene silencing of MGMT. However, systemic application of MGMT inhibitors is limited by an increase in hematologic toxicity. Another strategy is to deplete MGMT activity in tumor tissue using a dose-dense temozolomide schedule. These alternative schedules are well tolerated; however, it remains unclear whether they are more effective than the standard dosing regimen or whether they effectively deplete MGMT activity in tumor tissue. Of note, not all patients with glioblastoma having MGMT promoter methylation respond to alkylating agents, and even those who respond will inevitably experience relapse. Herein we review the data supporting MGMT as a major mechanism of chemotherapy resistance in malignant gliomas and describe ongoing studies that are testing resistance-modulating strategies.
Erlotinib and chemoradiation in patients with surgically resected locally advanced squamous cell carcinoma of the head and neck: a GICOR phase I trial
Authors: F. Arias de la Vega, J. Contreras, M. de las Heras, A. de la Torre, V. Arrazubi, I. Herruzo, I. Prieto, J.A. García-Saenz, J. Romero, F.A. Calvo
Journal: Annals of Oncology (2011)
Validation of the Mexican-Spanish version of the EORTC QLQ-C15-PAL questionnaire for the evaluation of health-related quality of life in patients on palliative care
Authors: L. F. Onate-Ocana, Y. Suárez-del-Real, S. Allende-Pérez, A. Alférez-Mancera, R. B. Rodríguez, S. Jiménez- Toxtle, M. Gasca-Castro, A. Mohar-Betancourt
Journal: Journal of Clinical Oncology (2009)

e20557 Background: Health-related quality of life (HRQL) is a fundamental outcome in oncology and this is particularly important in the palliative care setting. Our aim was to validate the Mexican-Spanish version of the EORTC QLQ-C15-PAL questionnaire, which is a brief version of QLQ-C30, for the measure of HRQL in terminal patients with cancer. Methods: Patients attending the Palliative Care Unit at the Hospital from July to October 2008 with terminal cancer, diagnosed by biopsy and without any active anti-neoplasic treatment were included in this study. Mexican-Spanish version of the EORTC QLQ-C15-PAL questionnaire was used to measure HRQL. Linear transformation of scale scores were done after EORTC guidelines. Correlation analysis was done obtaining the Spearman correlation coefficient and the Cochran alpha. Association of clinical parameters and scale scores were analyzed using one-way ANOVA and Chi-squared test. Test-retest comparison was tested using ANOVA for repeated measurements. Survival analysis was performed using the Kaplan-Meier and Cox's methods. Results: Eighty-three patients were enrolled in this study (mean age of 61.2 years). Compliance rates were high; all patients answered the questionnaire in less than 20 minutes and it was well-accepted. Five missing values in five different items were found. Scales in the QLQ-C15 distinguished between other clinically distinct groups of patients. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Cronbach's alpha coefficients were &gt;0.7 in three of four multi-item scales. Test-retest scores were obtained from 25 patients and scores were consistent. Emotional function, Dyspnea, Insomnia and Appetite scales demonstrated an important association with overall survival by multivariate analysis (p&lt;0.05). Conclusions: The Mexican-Spanish version of EORTC QLQ-C15-PAL questionnaire is reliable and valid for HRQL measurement in terminal patients with cancer, and appropriate for its use in clinical trials in Mexican patients. No significant financial relationships to disclose.
Drug Abuse in Athletes Anabolic Steroids and Human Growth Hormone
Authors: George M. Bohigian
Journal: JAMA (1988)

This report, the first in a three-part series on drug abuse by athletes, responds to adopted Resolution 4 (1984 Annual Meeting) and to Resolution 57 (1986 Annual Meeting), "Human Growth Hormone," which was referred to the Board of Trustees for action. Subsequent reports will cover other classes of abused drugs. (<i>JAMA</i>1988;259:1703-1705)
One More Prediction Rule: Has Anything New Been Added?
Authors: Surya Prakash Bhatt
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

In their recent article, Espana and colleagues have made an effort to derive an easily calculable predictive score for severe community acquired pneumonia (SCAP) (1). The study population appears to be fairly general with the exclusion of immunocompromised patients. Whether diabetics and patients with chronic renal failure were included is not clear. How many patients had evidence of infection in respiratory secretions or the bloodstream is not evident. After defining septic shock as a criterion for the presence of SCAP, the authors go on to state that a systolic blood pressure less than 90 mm Hg was contributory in 32 false-positive cases. Though the rule does help triage by achieving a good negative predictive value (NPV), what rankles is the low positive predictive value (PPV). Contrary to what the authors claim, a low PPV precludes the rule from identifying patients at risk for an adverse outcome. If triaging patients at risk for SCAP means admission to intermediate or intensive care, the cost of 414 false-positive cases would be enormous. It would be interesting to see how many patients were in septic shock or needed mechanical ventilation (MV) at arrival since they were treated as endpoints rather than being logically weighted as was done in the m-ATS score (2). By using shock and MV as endpoints rather than emergency department (ED) variables, other parameters expected to be more frequent in these patients are given greater weight than they probably deserve. It would be interesting to see the R for the stepwise multivariate models. The basis for concluding that this rule could identify at admission patients who subsequently develop SCAP within and beyond the first 24 hours is unclear. The sensitivity, specificity, PPV, and NPV can change depending on the cutoff chosen. There is an inherent bias in comparing the scores within the population from which the rule is derived, thereby putting other scores at a disadvantage. On closer look, though, it is evident that this rule did no better than the other scores in the internal and external validation groups. In the face of such bias, a comparison of the calibration of the four rules would have been more informative, proving more useful for the individual patient, rather than the original cohort as a whole. Also, some of the other scores are simpler (3, 4). Though the authors have made a commendable effort, this rule at best adds to the plethora of derived scores.
Immunoendocrine Communication via the Hypothalamo-Pituitary-Adrenal Axis in Autoimmune Diseases*
Authors: G. WICK, Y. HU, S. SCHWARZ, G. KROEMER
Journal: Endocrine Reviews (1993)

THE interrelationship between the neuroendocrine and the immune systems has long been a neglected subject of study. In spite of the pioneering work of the group of Besedovsky and Sorkin (1), this area was apparently deemed too suspicious of polypragmatism for most neurologists, endocrinologists, and immunologists. Only after scientists from all of these fields decided to combine their expertise, immunoendocrinology became a discipline of its own, and the last decade has experienced an explosive growth of the number of papers dealing with physiological and pathological immunoendocrine interactions. Many excellent reviews on this topic have appeared (2–5). Several of these also appeared in Endocrine Reviews, specifically some classics on the subject of the physiological and pharmacological effects of glucocorticoid hormones (GC) in stress and aging (6, 7), and also on the immunoendocrine dialogue via the hypothalamo-pituitary-adrenal (HPA) axis (8). The potential modulatory role of this feedback regulation in the pathogenesis of autoimmune disease has only been suggested recently (9–13). It is the aim of this review to summarize and discuss the present state of knowledge of alterations of the immunoendocrine circuit along the HPA axis in various autoimmune diseases in experimental animals and man. However, while most of the previous reviews cited above were mainly written from an endocrinologist's standpoint, the present one is presented from an immunologist's view. Therefore, a certain amount of immunological background information is always provided for the more endocrinologically oriented reader.
Personal Experiences with Anticoagulants for Coronary Atheroselerosis
Authors: E. STERLING NICHOL
Journal: Circulation (1959)

by Wright and Prail- (lollii s lecture at the New York Academy of Medicine.These authors discussed the use of l)icuniarol inl venous thrombosis, pulmonary embolism, rlheuniiatic heart disease, and pe- riphlleral arteriopathies.During 1942 at vari- ous times I talked about the possibility of utilizinog Dicumnarol ini acute coronary throm- I)osis with iivo(car(lial infarctioni with Nelson Barker, Wilbur Duryve, Irvinog Wright, and others.Considerable doubt was expressed as to the likely results, but it was agreed that a (linical trial would be worthwhile.About this tile, Claremmee de la Chappelle noted aim incileiic e of 12 per cent thromboembolismi follow- hicr acute infarction and stated, 'Some day it iay be demiiomlstralted that [mural thrombi] ,-ill be prevented by the use of anl anticoagul it such as heparin or dicoumarin." In June 1943, after hundreds of patients with thromem"( iiibolismn had beeen treated with Dicumarol various workers, I gave Dicumarol to my first patient with acute corollary thrombosis.After this initial venture, I ('ontinued to use Dicumnarol routinely in acute myocardial ill- faretion.No data onl the use of Dicumarol ill acute coronami-thrombosis were available, but Barker had told me of its trial in a few cases, and after mn study began, Wright and Duryee informed me that they had successfully used I)ieumnarol ill 9 cases of corollary thrombosis.During 1944, casual references to the use of I)ictimarol ill acute coronary thrombosis ap- I)eared ill papers describing its gene ral use, Lam listing 3 cases, Evanis 1 case, Gefter et al. 1 fatality, Townshend and HIonigngman 3 cases, and LeFevre mentioned 7 cases ill 1945.
Maternal and infant antiretroviral regimens to prevent postnatal HIV-1 transmission: 48-week follow-up of the BAN randomised controlled trial
Authors: Denise J Jamieson, Charles S Chasela, Michael G Hudgens, Caroline C King, Athena P Kourtis, Dumbani Kayira, Mina C Hosseinipour, Deborah D Kamwendo, Sascha R Ellington, Jeffrey B Wiener, Susan A Fiscus, Gerald Tegha, Innocent A Mofolo, Dorothy S Sichali, Linda S Adair, Rodney J Knight, Francis Martinson, Zebrone Kacheche, Alice Soko, Irving Hoffman, Charles van der Horst
Journal: The Lancet (2012)