tbuckley/cabot-search huggingface dataset:
Acute-Phase Markers of Inflammation and Glomerular Structure in Patients with Type 2 Diabetes
Authors: Michele Dalla Vestra, Michele Mussap, Pietro Gallina, Marino Bruseghin, Anna Maria Cernigoi, Alois Saller, Mario Plebani, Paola Fioretto
Journal: Journal of the American Society of Nephrology (2005)

Type 2 diabetes is frequently associated with an inflammatory status; the relationships between low-grade inflammation and diabetic nephropathy are still unclear. The aim of this study was to evaluate the relationships between acute-phase markers of inflammation, glomerular structure, and albumin excretion rate (AER) in type 2 diabetes. In 74 patients with type 2 diabetes (23 normoalbuminuric, 30 microalbuminuric, and 21 proteinuric) fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP), and IL-6 were determined. AER was measured on three 24-h urine collections; GFR was measured by 51Cr EDTA plasma clearance. A kidney biopsy was performed, and mesangial fractional volume [Vv(mes/glom)] and glomerular basement membrane (GBM) width were estimated by electron microscopic morphometric analysis. CRP, fibrinogen, SAA, and IL-6 differed among groups, with proteinuric patients having the highest levels. SAA and fibrinogen correlated with AER (P < 0.03 and P < 0.001, respectively). GBM width and Vv(mes/glom) increased from normoalbuminuric to proteinuric patients [P < 0.005 normoalbuminuric and microalbuminuric versus proteinuric for GBM, P < 0.01 normoalbuminuric versus proteinuric for Vv(mes/glom)]. In patients with increased GBM width (>396 nm), CRP, SAA, and IL-6 were higher than in patients with normal GBM width (P < 0.003, P < 0.004, and P < 0.0004, respectively). GBM width was directly correlated with fibrinogen (r = 0.33, P < 0.002) and IL-6 (r = 0.25 P < 0.05). In conclusion, this study demonstrates that acute-phase markers of inflammation are associated with nephropathy status and GBM thickening, suggesting a role for inflammation in the pathogenesis of diabetic glomerulopathy.
CHRONIC KIDNEY DISEASE-INDUCED CARDIAC FIBROSIS IS AMELIORATED BY REDUCING CIRCULATING LEVELS OF A NON-DIALYSABLE UREMIC TOXIN, INDOXYL SULFATE
Authors: Suree Lekawanvijit, Andrew Kompa, Minako Manabe, Darren J. Kelly, Henry Krum
Journal: Journal of the American College of Cardiology (2011)
MODIFIED ETHER MASK FOR SIMULTANEOUS ADMINISTRATION OF ETHER, AIR, AND OXYGEN
Authors: Bernard Stodsky
Journal: JAMA (1953)

Significant reduction in oxygen saturation of arterial blood by the application of an ether mask to the patient's face and further reduction by the application of ether to the mask have been demonstrated by Faulconer and Latterell.1 They showed that addition of 500 cc. of oxygen per minute to the ether and air mixture under the mask would restore the arterial oxygen saturation to normal levels and suggested that this procedure be practiced routinely in semiopen ether-air administration. Acting on this suggestion, I devised a modification of the standard Yankauer ether mask that provides a simple, dependable, and unencumbered method for addition of oxygen. As shown in the figure, shower curtain eyelets, or grommets (Dot eyelets no. 659), are riveted in place through the screening on the right and left sides of the mask (to accommodate right-handed and left-handed anesthetists). The evelet of this size accommodates a no. 14F red
Haploinsufficiency of an RB–E2F1–Condensin II Complex Leads to Aberrant Replication and Aneuploidy
Authors: Courtney H. Coschi, Charles A. Ishak, David Gallo, Aren Marshall, Srikanth Talluri, Jianxin Wang, Matthew J. Cecchini, Alison L. Martens, Vanessa Percy, Ian Welch, Paul C. Boutros, Grant W. Brown, Frederick A. Dick
Journal: Cancer Discovery (2014)

Abstract Genome instability is a characteristic of malignant cells; however, evidence for its contribution to tumorigenesis has been enigmatic. In this study, we demonstrate that the retinoblastoma protein, E2F1, and Condensin II localize to discrete genomic locations including major satellite repeats at pericentromeres. In the absence of this complex, aberrant replication ensues followed by defective chromosome segregation in mitosis. Surprisingly, loss of even one copy of the retinoblastoma gene reduced recruitment of Condensin II to pericentromeres and caused this phenotype. Using cancer genome data and gene-targeted mice, we demonstrate that mutation of one copy of RB1 is associated with chromosome copy-number variation in cancer. Our study connects DNA replication and chromosome structure defects with aneuploidy through a dosage-sensitive complex at pericentromeric repeats. Significance: Genome instability is inherent to most cancers and is the basis for selective killing of cancer cells by genotoxic therapeutics. In this report, we demonstrate that instability can be caused by loss of a single allele of the retinoblastoma gene that prevents proper replication and condensation of pericentromeric chromosomal regions, leading to elevated levels of aneuploidy in cancer. Cancer Discov; 4(7); 840–53. ©2014 AACR. See related commentary by Hinds, p. 764 This article is highlighted in the In This Issue feature, p. 745
Cardiovascular events in patients with COPD: TORCH Study results
Authors: P. M. A. Calverley, J. A. Anderson, B. Celli, G. T. Ferguson, C. Jenkins, P. W. Jones, C. Crim, L. R. Willits, J. C. Yates, J. Vestbo
Journal: Thorax (2010)

<h3>Background</h3> Previous studies have suggested that long-term use of β agonists to treat chronic obstructive pulmonary disease (COPD) may increase the risk of cardiovascular adverse events. In this post hoc analysis, data from the TOwards a Revolution in COPD Health (TORCH) study were used to investigate whether use of the long-acting β<sub>2</sub> agonist salmeterol over 3 years increased the risk of cardiovascular adverse events in patients with moderate to severe COPD. <h3>Methods</h3> TORCH was a randomised, double-blind, placebo controlled study conducted at 444 centres in 42 countries. Patients (n=6184; safety population) received twice daily combined salmeterol 50 μg plus fluticasone propionate 500 μg (SFC), either component alone, or placebo. Adverse events were recorded every 12 weeks for 3 years. <h3>Results</h3> The probability of having a cardiovascular adverse event by 3 years was 24.2% for placebo, 22.7% for salmeterol, 24.3% for fluticasone propionate and 20.8% for SFC. Although a history of myocardial infarction doubled the probability of cardiovascular adverse events, the event rates remained similar across treatment groups. <h3>Conclusion</h3> Post hoc analysis of the 3-year TORCH dataset showed that salmeterol alone or in combination (SFC) did not increase the risk of cardiovascular events in patients with moderate to severe COPD.
TREATMENT OF HOMOSEXUALITY BY INDIVIDUAL AND GROUP PSYCHOTHERAPY
Authors: SAMUEL B. HADDEN
Journal: American Journal of Psychiatry (1958)

From my experience I have concluded that homosexuals can be treated more effectively by group psychotherapy when they are started in groups made up exclusively of homosexuals. In such groups the rationalization that homosexuality is a pattern of life they wish to follow is destroyed by their fellow homosexuals. This breaking down of their rationalization activates anxiety and a desire to change is created. Obvious ego-strength is gained by identification with others who are also seeking socially acceptable goals. Identification with a group that has a healthy motivation soon banishes the feelings of isolation from which they suffer. When members reach the point where their homosexual drives have diminished or disappeared and they must completely reject all homosexual identifications and identify with heterosexuality they are aided in final commitment by fellow members. The group convinces its members that their homosexuality is not an affliction or trick of fate but a pattern of inadequate behaviour which can be changed.
A Nonsteroidal Glucocorticoid Receptor Agonist Inhibits Allergen-induced Late Asthmatic Responses
Authors: Gail M. Gauvreau, Louis-Philippe Boulet, Richard Leigh, Donald W. Cockcroft, Kieran J. Killian, Beth E. Davis, Francine Deschesnes, Richard M. Watson, Veronica Swystun, Carina Kärrman Mårdh, Peter Wessman, Carin Jorup, Magnus Aurivillius, Paul M. O’Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Effective antiinflammatory therapies are needed for the treatment of asthma, but preferably without the systemic adverse effects of glucocorticosteroids.Objectives: We evaluated the effect of an inhaled nonsteroidal glucocorticoid receptor agonist, AZD5423, on allergen-induced responses.Methods: Twenty subjects with mild allergic asthma were randomized to receive 7 days of treatment with nebulized AZD5423 (75 or 300 μg) once daily, budesonide 200 μg twice daily via Turbuhaler, or placebo in a double-blind, four-period, crossover design study. Allergen challenge was performed on Day 6.Measurements and Main Results: FEV1 was measured repeatedly for 7 hours after allergen challenge for early and late asthmatic responses. Sputum inflammatory cells was measured before and at 7 and 24 hours after allergen challenge, and methacholine airway responsiveness was measured before and 24 hours after allergen challenge. AZD5423 significantly attenuated the fall in FEV1 during the late asthmatic response (both doses led to an 8.7% fall) versus placebo (14% fall) (P < 0.05) with no effect of budesonide (12.5% fall) versus placebo (P > 0.05). There was no effect on the fall in FEV1 during early asthmatic response. AZD5423 300 and 75 μg significantly attenuated allergen-induced sputum eosinophilia by 63 and 61% at 7 hours, respectively, and by 46 and 34% at 24 hours after allergen challenge, respectively, versus placebo (all P < 0.05). Budesonide did not reduce allergen-induced sputum eosinophilia versus placebo. AZD5423 at 300 μg significantly attenuated allergen-induced airway hyperresponsiveness at 24 hours after allergen challenge versus placebo (P < 0.05). Both doses of AZD5423 were well tolerated.Conclusions: Seven-day treatment with inhalation of the nonsteroidal glucocorticoid receptor agonist AZD5423 effectively reduced allergen-induced responses in subjects with mild allergic asthma.Clinical trial registered with www.clinicaltrials.gov (NCT01225549).
Comparative Cardiovascular Effects of Tyramine, Ephedrine, and Norepinephrine in Man
Authors: JAY N. COHN
Journal: Circulation Research (1965)

The systemic hemodynamic and forearm vascular effects of tyramine, ephedrine, and norepinephrine were studied in normal male subjects. The pressor effect of tyramine was associated usually with bradycardia, unchanged cardiac output, and moderate arteriolar constriction in the forearm. A similar pressor effect of ephedrine was characterized by an increase of heart rate and output, with a slight fall in forearm vascular resistance. Occasional subjects responded to tyramine with an increase of cardiac output and a fall in forearm vascular resistance, and to ephedrine, with a marked increase of vascular resistance. The pressor effect of norepinephrine was associated always with bradycardia and with marked arteriolar and venous constriction in the forearm. Brachial arterial infusions of the drugs in nonpressor doses confirmed the vascular effects. Norepinephrine produced dose-dependent forearm constriction in all subjects, while vasodilatation was observed occasionally with tyramine and frequently with ephedrine. The demonstrated differences in local vascular and systemic hemodynamic effects of these drugs suggest some inconsistency in the hypothesis that the effect of either ephedrine or tyramine is mediated exclusively by norepinephrine release.
Health should be seen as a human right, global campaign says
Authors: Sophie Arie
Journal: BMJ (2005)

A campaign backed by politicians, pop stars, and medical and religious leaders was launched last week to urge the world to recognise health as a human right on a par with the right to a fair trial or to freedom of expression.

“It is time for the world to come to its senses and call health a human right,” said Mary Robinson, the …
Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local Central Nervous System Tumor Microenvironment
Authors: Linda M. Liau, Robert M. Prins, Sylvia M. Kiertscher, Sylvia K. Odesa, Thomas J. Kremen, Adrian J. Giovannone, Jia-Wei Lin, Dennis J. Chute, Paul S. Mischel, Timothy F. Cloughesy, Michael D. Roth
Journal: Clinical Cancer Research (2005)

Abstract Purpose: We previously reported that autologous dendritic cells pulsed with acid-eluted tumor peptides can stimulate T cell–mediated antitumor immune responses against brain tumors in animal models. As a next step in vaccine development, a phase I clinical trial was established to evaluate this strategy for its feasibility, safety, and induction of systemic and intracranial T-cell responses in patients with glioblastoma multiforme. Experimental Design: Twelve patients were enrolled into a multicohort dose-escalation study and treated with 1, 5, or 10 million autologous dendritic cells pulsed with constant amounts (100 μg per injection) of acid-eluted autologous tumor peptides. All patients had histologically proven glioblastoma multiforme. Three biweekly intradermal vaccinations were given; and patients were monitored for adverse events, survival, and immune responses. The follow-up period for this trial was almost 5 years. Results: Dendritic cell vaccinations were not associated with any evidence of dose-limiting toxicity or serious adverse effects. One patient had an objective clinical response documented by magnetic resonance imaging. Six patients developed measurable systemic antitumor CTL responses. However, the induction of systemic effector cells did not necessarily translate into objective clinical responses or increased survival, particularly for patients with actively progressing tumors and/or those with tumors expressing high levels of transforming growth factor β2 (TGF-β2). Increased intratumoral infiltration by cytotoxic T cells was detected in four of eight patients who underwent reoperation after vaccination. The magnitude of the T-cell infiltration was inversely correlated with TGF-β2 expression within the tumors and positively correlated with clinical survival (P = 0.047). Conclusions: Together, our results suggest that the absence of bulky, actively progressing tumor, coupled with low TGF-β2 expression, may identify a subgroup of glioma patients to target as potential responders in future clinical investigations of dendritic cell–based vaccines.
The Downside of a Drug-Crazed World
Authors: Eric G. Neilson
Journal: Journal of the American Society of Nephrology (2006)

In a world where patients are exposed to countless prescription drugs, it is amazing that more humans do not develop autoimmune drug reactions that lead to tissue injury. Of course, the chance of drug-related inflammation rises in proportion to use, but it still seems most of us are comfortably protected from such events by the high activation threshold of our immune systems. Genetic polymorphisms that modulate the initiation of antigen-specific immune responses, particularly in the MHC, are a determining influence, but the whole story is more complicated. Drugs in body fluids or their metabolites often form adducts (hapten protein carrier) that modify their physical structures, occasionally making them immunogenic and prone to drug reactions (1). These adducts can be taken up by macrophages or dendritic cells and presented on the cell surface to attract the surveillance arm of the immune system. Sometimes a drug without a carrier also can interact directly with T cell receptors within the nao ¨ve repertoire or be processed by antigen-presenting cells for potential simulation of new T cells. Some of these drug reactions are influenced by changes in metabolism induced by other drugs taken simultaneously; some are modified by the variability in local cytokine expression or the polymorphisms of enzymes that affect levels of metabolites, particularly cytochrome P-450; and in some cases, the inflammatory state depresses normal drug metabolism (2).
Assaying the regulatory potential of mammalian conserved non-coding sequences in human cells
Authors: Catia Attanasio, Alexandre Reymond, Richard Humbert, Robert Lyle, Michael S Kuehn, Shane Neph, Peter J Sabo, Jeff Goldy, Molly Weaver, Andrew Haydock, Kristin Lee, Michael Dorschner, Emmanouil T Dermitzakis, Stylianos E Antonarakis, John A Stamatoyannopoulos
Journal: Genome biology (2008)

Conserved non-coding sequences in the human genome are approximately tenfold more abundant than known genes, and have been hypothesized to mark the locations of cis-regulatory elements. However, the global contribution of conserved non-coding sequences to the transcriptional regulation of human genes is currently unknown. Deeply conserved elements shared between humans and teleost fish predominantly flank genes active during morphogenesis and are enriched for positive transcriptional regulatory elements. However, such deeply conserved elements account for <1% of the conserved non-coding sequences in the human genome, which are predominantly mammalian. We explored the regulatory potential of a large sample of these 'common' conserved non-coding sequences using a variety of classic assays, including chromatin remodeling, and enhancer/repressor and promoter activity. When tested across diverse human model cell types, we find that the fraction of experimentally active conserved non-coding sequences within any given cell type is low (approximately 5%), and that this proportion increases only modestly when considered collectively across cell types. The results suggest that classic assays of cis-regulatory potential are unlikely to expose the functional potential of the substantial majority of mammalian conserved non-coding sequences in the human genome.
Heart adaptation to acute pressure overload: an involvement of endogenous prostaglandins.
Authors: E I Chazov, V D Pomoinetsky, N G Geling, T R Orlova, A A Nekrasova, V N Smirnov
Journal: Circulation Research (1979)

The purpose of this investigation was to study the relationships between the contractile behavior of the heart and myocardial prostaglandins. Using an open-chest model in rabbits, we assayed the left ventricular tissue content to prostaglandins (PG) E and F2 alpha at various intervals following acute pressure overload created by graduated aortic stenosis. The results suggest that the rabbits could be divided into two distinct groups based on specific hemodynamic changes following coarctation (systolic and diastolic pressure, dP/dt, and contractility index). The first group included rabbits whose adaptation to pressure overload was expressed as a gradual increase in the contractility index. The second group was comprised of rabbits that developed heart failure following coarctation. The increase in contractility in response to overload in the first group was paralleled by an increase in the content of PGE and PGF 2 alpha in the left ventricle, whereas, in rabbits with heart failure, the prostaglandin level did not rise above that of the control hearts. It is suggested that an increased endogenous prostaglandin content may be an important factor in adaptation to acute overload.
Cardiac Symptoms in Women and Men—Reply
Authors: Catherine Kreatsoulas, James L. Velianou, Sonia S. Anand
Journal: JAMA Internal Medicine (2013)

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Efficacy of ablative fractional laser-assisted photodynamic therapy for the treatment of actinic cheilitis: 12-month follow-up results of a prospective, randomized, comparative trial
Authors: S.H. Choi, K.H. Kim, K.-H. Song
Journal: British Journal of Dermatology (2014)

Early identification and treatment of actinic cheilitis (AC) is recommended. Although photodynamic therapy (PDT) is an attractive therapeutic option for AC, PDT for AC does not result in the same satisfactory outcomes as in actinic keratosis (AK). The aim of our study was to compare efficacy, recurrence rate, cosmetic outcome and safety between erbium:yttrium–aluminium–garnet ablative fractional laser‐assisted methyl aminolaevulinate–PDT (Er:YAG AFL MAL‐PDT) and standard MAL‐PDT. Thirty‐three patients with histologically confirmed AC randomly received either one session of Er:YAG AFL MAL‐PDT or two sessions of MAL‐PDT. In the MAL‐PDT group, the second session of MAL‐PDT was administered 7 days later. Patients were followed up at 1 week and 3 and 12 months, and biopsies were taken from all patients at 3 and 12 months after the last treatment session. At the final 12‐month follow‐up, cosmetic outcomes were assessed. Adverse events were assessed at week 1 of the treatment phase and every subsequent follow‐up visit. In the per‐protocol (PP) population, Er:YAG AFL MAL‐PDT was significantly more effective (92% complete response rate) than MAL‐PDT (59%; P =0·040) at the 3‐month follow‐up, and differences in efficacy remained significant at the 12‐month follow‐up (85% in Er:YAG AFL MAL‐PDT and 29% in MAL‐PDT). The recurrence rate was significantly lower for Er:YAG AFL MAL‐PDT (8%) than for MAL‐PDT (50%) group at 12 months (P =0·029). No significant difference in cosmetic outcome or safety was observed between Er:YAG AFL MAL‐PDT and MAL‐PDT. Ablative fractional laser pretreatment has significant benefit for the treatment of AC with PDT.