tbuckley/cabot-search huggingface dataset:
The laryngeal pathology in early childhood
Authors: Elena Radtsig, Anna Vasina, Mikhail Bogomilsky
Journal: European Respiratory Journal (2014)

Introduction and background. There are two main laryngeal functions: breathing and phonation. The main laryngeal diseases symptoms (dysphonia/aphonia and breathlessness) are connected with them. In early childhood we meet with another one important symptom- stridor. This symptoms are not specific and can be part of a variety of illnesses.  Aims and objectives. To analyze structural laryngeal pathology in babies and toddlers.  Methods. The results of endoscopic examination (with flexible and rigid optic systems) were estimated in 135 patients in the age from 6 day to 3 year old.  Results/ Indications for endoscopic laryngeal examination were stridor (37,8%), hoarseness (25,2%), breathlessness (12,6%) and cough (9,6%). In 24 (17,8%) cases laryngeal pathology was found unexpectedly. Endoscopic examination revealed laryngeal trauma in 1 case (0,7%), acute laryngitis in 10 (7%), hemangioma of larynx in 10 (7%), vocal nodules in 18 (12%), laryngeal paresis in 11 (7,3%), laryngomalacia in 30 (20%), aspiration syndrome in 9 (6%), cicatricial stenosis of the larynx in 4 (2,6%), papillomatosis in 2 (1,3%). Combined pathology of the larynx was observed in 39 (28,9%) children.  Conclusions/ The complains are not specific and can be seen with different pathology. Only an endoscopic examination can help in diagnosing and identify the right way of treatment (conservative (medicine) or surgical).
Thrombin Generation in Normal Subjects and Cardiac Patients
Authors: KURT N. VON KAULLA, EDITH VON KAULLA
Journal: Circulation Research (1964)

A refined, reliable thrombin generation test with good sensitivity for both hypo- and hypercoagulability is described. When serial thrombin generation curves were obtained in cardiac patients subjected to standardized treadmill stress, fluctuations of the clotting system were observed in some and a marked tendency to hypercoagulability in others. The relationship of in vitro hypercoagulability as reflected by thrombin generation to an increased tendency to thrombosis remains to be determined.
CQC says it is improving despite massive failings in the past
Authors: A. O'Dowd
Journal: BMJ (2012)

The NHS’s main regulator the Care Quality Commission (CQC) has promised MPs that it is getting its act together after a “tough year” and several bad mistakes.

During an angry session of the parliamentary health select committee on 11 September at its annual accountability hearing on the commission, MPs tackled the leaders of the commission over its failings as a regulator.

Parts of the discussion focused particularly on the case of Winterbourne View private hospital near Bristol, where physical abuse of residents by staff there went unnoticed until the BBC’s Panorama programme broadcast undercover filming.1

Stephen Dorrell, committee chair and Conservative MP for Charnwood, said: “The organisation has been subject to …
Will Blocking the Platelet Save the Diabetic?
Authors: Spencer B. King, Ehtisham Mahmud
Journal: Circulation (1999)

iabetic patients with atherosclerotic heart disease are more likely to develop complications, whether treated medically, surgically, or with interventional techniques.Among the risks diabetics face is an apparent increase in restenosis after coronary stenting.This issue is addressed in this issue of Circulation by Marso et al. 1 They suggest that although use of the IIb/IIIa antibody fragment abciximab will not solve the restenosis problem for patients undergoing balloon angioplasty or for patients without diabetes mellitus undergoing stenting, its use does in fact reduce the indices of restenosis in diabetic patients undergoing stenting.This finding, if corroborated, will have a significant impact on the medical care of diabetic patients. See p 2477In recent years, enthusiasm for performing interventional procedures in patients with diabetes has decreased, especially if those patients have multivessel disease.The National Heart, Lung, and Blood Institute-sponsored multicenter randomized trial comparing coronary angioplasty with bypass surgery (the Bypass Angioplasty Revascularization Investigation [BARI]) clearly demonstrated that patients randomized to surgery had a superior survival rate at 5 years compared with patients randomized to angioplasty. 2 The Emory Angioplasty vs Surgery Trial, which initially showed no difference in a smaller cohort, now at 8 years shows the same trend as the BARI trial. 3Analysis of the survival curves in these trials leads to the conclusion that much more than simply early restenosis after angioplasty is responsible for this difference.Events continue to occur over many years, undoubtedly reflecting the development and progression of new lesions.Diabetic patients followed up in observational databases also had reduced survival after interventional procedures.This difference is much weaker than in the randomized trials but is borne out in the BARI registry 4 and in a large database from Emory University Hospital. 5ost of these trials and the observational studies were performed with balloon angioplasty as the predominant interventional technique.Currently, tremendous enthusiasm exists for the use of stents during percutaneous coronary interventions, especially in large vessels.Will the outcome of
Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro
Authors: FM Spoelstra, C Berends, B Dijkhuizen, JG de Monchy, HF Kauffman
Journal: European Respiratory Journal (1998)

The nonspecific phosphodiesterase inhibitor theophylline, widely used in asthma therapy, may cause a decrease in inflammatory responses of airways. In asthma, eosinophils migrate to the airway wall and become activated. Activated eosinophils are characterized by low cell density, as well as increased expression of CD11b and reduced expression of L-selectin, two adhesion molecules involved in transendothelial migration. To study the anti-inflammatory effect of theophylline on granulocyte adhesion molecules in vitro, the platelet-activating factor (PAF)-induced density shift was determined by density centrifugation and the modulation of CD11b and L-selectin expression by flow cytometry on eosinophils and neutrophils in human whole blood. A relatively high concentration of theophylline (10(-3) M) inhibited the increase in the percentage of hypodense eosinophils and neutrophils in whole-blood samples after PAF stimulation in vitro. A more pharmacological concentration (10(-4) M) inhibited the CD11b upregulation and L-selectin shedding induced by PAF (10(-7) M) on both eosinophils and neutrophils. The effect of isoproterenol on the inhibitory effect of theophylline was mainly additive, but a small synergistic effect could not be excluded. In conclusion theophylline can attenuate eosinophil and neutrophil activation in vitro at the level of adhesion molecule expression and changes in cell density. This may have implications for transendothelial migration of these cells in asthma.
Targeted Deletion of Dicer from Proximal Tubules Protects against Renal Ischemia-Reperfusion Injury
Authors: Qingqing Wei, Kirti Bhatt, Hong-Zhi He, Qing-Sheng Mi, Volker H. Haase, Zheng Dong
Journal: Journal of the American Society of Nephrology (2010)

MicroRNAs are endogenous, noncoding, small RNAs that regulate expression and function of genes, but little is known about regulation of microRNA in the kidneys under normal or pathologic states. Here, we generated a mouse model in which the proximal tubular cells lack Dicer, a key enzyme for microRNA production. These mice had normal renal function and histology under control conditions despite a global downregulation of microRNAs in the renal cortex; however, these animals were remarkably resistant to renal ischemia-reperfusion injury (IRI), showing significantly better renal function, less tissue damage, lower tubular apoptosis, and improved survival compared with their wild-type littermates. Microarray analysis showed altered expression of specific microRNAs during renal IRI. Taken together, these results demonstrate evidence for a pathogenic role of Dicer and associated microRNAs in renal IRI.
Autoantibodies in Prediction of the Development of Rheumatoid Arthritis Among Healthy Relatives of Patients With the Disease
Authors: Cesar Ramos‐Remus, Jose Dionisio Castillo‐Ortiz, Luis Aguilar‐Lozano, Jorge Padilla‐Ibarra, Carlos Sandoval‐Castro, Cesar Omar Vargas‐Serafin, Hector de la Mora‐Molina, Ariadna Ramos‐Gomez, Adriana Sanchez‐Ortiz, Hilario Avila‐Armengol, Francisco Javier Aceves‐Avila
Journal: Arthritis & Rheumatology (2015)

Objective Although blood bank–based studies have shown that rheumatoid arthritis (RA)–related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5‐year PPV of serum IgM rheumatoid factor (IgM‐RF) and anti–cyclic citrullinated peptide (anti‐CCP) for the development of RA among healthy relatives of patients with RA. Methods Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants’ medical history was obtained, and serum levels of IgM‐RF and anti‐CCP antibodies were determined (by nephelometry and second‐generation anti‐CCP enzyme‐linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in‐office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA. Results Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti–CCP‐2 and RF, 12 (1.5%) only for anti–CCP‐2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5‐year followup (3,313 person‐years for the seronegative group and 60.8 person‐years for the anti–CCP‐2–positive group). The PPV was 64% when both anti–CCP‐2 and RF were positive and 58% when only anti–CCP‐2 was positive. Offspring of patients with RA had an independent 3‐fold increased risk of developing RA. Conclusion Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.
Metabolic Modulation With Perhexiline in Chronic Heart Failure
Authors: Leong Lee, Ross Campbell, Michaela Scheuermann-Freestone, Rachel Taylor, Prasad Gunaruwan, Lynne Williams, Houman Ashrafian, John Horowitz, Alan G. Fraser, Kieran Clarke, Michael Frenneaux
Journal: Circulation (2005)

Background— Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. Methods and Results— In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (V̇ o 2 max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31 P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in V̇ o 2 max (16.1±0.6 to 18.8±1.1 mL · kg −1 · min −1 ; P &lt;0.001), quality of life (Minnesota score reduction from 45±5 to 34±5; P =0.04), and left ventricular ejection fraction (24±1% to 34±2%; P &lt;0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. Conclusions— In patients with CHF, metabolic modulation with perhexiline improved V̇ o 2 max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.
Stable Prediction of Mood and Anxiety Disorders Based on Behavioral and Emotional Problems in Childhood: A 14-Year Follow-Up During Childhood, Adolescence, and Young Adulthood
Authors: Sabine J. Roza, Marijke B. Hofstra, Jan van der Ende, Frank C. Verhulst
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The goal of this study was to predict the onset of mood and anxiety disorders from parent-reported emotional and behavioral problems in childhood across a 14-year period from childhood into young adulthood. METHOD: In 1983, parent reports of behavioral and emotional problems were obtained with the Child Behavior Checklist for children and adolescents 4–16 years of age from the Dutch general population. At follow-up 14 years later, lifetime mood and anxiety diagnoses were obtained by a standardized DSM-IV interview for 1,580 subjects. Cox proportional hazards models were used to predict the incidence of mood and anxiety disorders from childhood problems and demographic covariates. RESULTS: Mood disorders were significantly predicted by high scores on the anxious/depressed scale and on the internalizing composite (withdrawn, somatic complaints, and anxious/depressed). Anxiety disorders were significantly predicted by the social problems scale and the externalizing composite (delinquent behavior and aggressive behavior). Anxiety disorders predominantly started in childhood and early adolescence, whereas the incidence of mood disorders increased sharply in adolescence and young adulthood. CONCLUSIONS: These results suggest different developmental pathways for mood and anxiety disorders. The predictions based on problem behavior remained stable during the 14-year period across adolescence and young adulthood. The results therefore underline the importance of early intervention and prevention of behavioral and emotional problems in childhood.
The regulatory content of intergenic DNA shapes genome architecture
Authors: Craig E Nelson, Bradley M Hersh, Sean B Carroll
Journal: Genome biology (2004)

Factors affecting the organization and spacing of functionally unrelated genes in metazoan genomes are not well understood. Because of the vast size of a typical metazoan genome compared to known regulatory and protein-coding regions, functional DNA is generally considered to have a negligible impact on gene spacing and genome organization. In particular, it has been impossible to estimate the global impact, if any, of regulatory elements on genome architecture. To investigate this, we examined the relationship between regulatory complexity and gene spacing in Caenorhabditis elegans and Drosophila melanogaster. We found that gene density directly reflects local regulatory complexity, such that the amount of noncoding DNA between a gene and its nearest neighbors correlates positively with that gene's regulatory complexity. Genes with complex functions are flanked by significantly more noncoding DNA than genes with simple or housekeeping functions. Genes of low regulatory complexity are associated with approximately the same amount of noncoding DNA in D. melanogaster and C. elegans, while loci of high regulatory complexity are significantly larger in the more complex animal. Complex genes in C. elegans have larger 5' than 3' noncoding intervals, whereas those in D. melanogaster have roughly equivalent 5' and 3' noncoding intervals. Intergenic distance, and hence genome architecture, is highly nonrandom. Rather, it is shaped by regulatory information contained in noncoding DNA. Our findings suggest that in compact genomes, the species-specific loss of nonfunctional DNA reveals a landscape of regulatory information by leaving a profile of functional DNA in its wake.
Bridge Experience With Long-term Implantable Left Ventricular Assist Devices
Authors: MehmetC. Oz, Michael Argenziano, Katharine A. Catanese, Michael T. Gardocki, Daniel J. Goldstein, Robert C. Ashton, Annetine C. Gelijns, Eric A. Rose, Howard R. Levin
Journal: Circulation (1997)

If long-term use of left ventricular assist devices (LVADs) as bridges to transplantation is successful, the issue of permanent device implantation in lieu of transplantation could be addressed through the creation of appropriately designed trials. Our medium-term experience with both pneumatically and electrically powered ThermoCardiosystems LVADs is presented to outline the benefits and limitations of device support in lieu of transplantation.Detailed records were kept prospectively for all patients undergoing LVAD insertion. Fifty-eight LVADs were inserted over 5 years, with a survival rate of 74%. Mean patient age was 50 years, and duration of support averaged 98 days. Although common, both preexisting infection and infection during LVAD support were not associated with increased mortality or decreased rate of successful transplantation. Thromboembolic complications were rare, occurring in only three patients (5%) despite the absence of anticoagulation. Ventricular arrhythmias were well tolerated in all patients except in cases of early perioperative right ventricular failure, with no deaths. Right ventricular failure occurred in one third of patients and was managed in a small percentage by right ventricular assist device (RVAD) support and/or inhaled nitric oxide therapy. There were no serious device malfunctions, but five graft-related hemorrhages resulted in two deaths. Finally, a variety of noncardiac surgical procedures were performed in LVAD recipients, with no major morbidity and mortality.Over all, our medium-term experience with implantable LVAD support is encouraging. Although additional areas of investigation exist, improvements in patients selection and management together with device alterations that have reduced the thromboembolic incidence and facilitated patient rehabilitation lead us to believe that a prospective, randomized trial is indicated to study the role that LVADs may have as an alternative to medical management.
Potential Role of a Membrane-Bound NADH Oxidoreductase in Nitric Oxide Release and Arterial Relaxation to Nitroprusside
Authors: Kamal M. Mohazzab-H., Pawel M. Kaminski, Ritu Agarwal, Michael S. Wolin
Journal: Circulation Research (1999)

Abstract —The site of metabolism in vascular smooth muscle responsible for the release of nitric oxide (NO) from nitroprusside is not well established. In this study we observed that a membrane-bound NADH oxidoreductase in the pulmonary artery activates nitroprusside to release NO, and we examined whether this process could potentially participate in relaxation to nitroprusside. Relaxation to nitroprusside in bovine calf pulmonary artery is inhibited by a scavenger of NO and by an antagonist of NO stimulation of guanylate cyclase. A flavoprotein probe that inhibits pulmonary artery NADH oxidoreductase (1 μmol/L diphenyliodonium) and electron acceptors for NADH oxidoreductase (0.3 mmol/L nitroblue tetrazolium and 0.1 mmol/L ferricyanide) inhibited pulmonary artery relaxation to nitroprusside, but not to nitroglycerin. Pulmonary arteries were observed to promote the release of NO from nitroprusside in vitro, and NO release was inhibited by the presence of nitroblue tetrazolium, ferricyanide, and diphenyliodonium. In homogenates of pulmonary arteries, NADH (0.1 mmol/L) increased the release of NO from nitroprusside by ≈6-fold, whereas NADPH, mitochondrial substrates, and other redox cofactors had minimal effects on NO release, and the action of NADH on nitroprusside was inhibited by nitroblue tetrazolium, ferricyanide, and diphenyliodonium. A membrane fraction enriched in NADH oxidoreductase activity showed a NADH-dependent release of NO from nitroprusside; nitroprusside caused NADH consumption, and it also inhibited the NADH-dependent reduction of nitroblue tetrazolium. Thus, a membrane-bound NADH oxidoreductase appears to contribute to the release of NO from nitroprusside, but not nitroglycerin, in calf pulmonary artery.
Acute Liver Carnitine Palmitoyltransferase I Overexpression Recapitulates Reduced Palmitate Oxidation of Cardiac Hypertrophy
Authors: E. Douglas Lewandowski, Susan K. Fischer, Matthew Fasano, Natasha H. Banke, Lori A. Walker, Alda Huqi, Xuerong Wang, Gary D. Lopaschuk, J. Michael O’Donnell
Journal: Circulation Research (2012)

Rationale: Muscle carnitine palmitoyltransferase I is predominant in the heart, but the liver isoform (liver carnitine palmitoyltransferase I [L-CPT1]) is elevated in hearts with low long chain fatty acid oxidation, such as fetal and hypertrophied hearts. Objective: This work examined the effect of acute L-CPT1 expression on the regulation of palmitate oxidation and energy metabolism in intact functioning rat hearts for comparison with findings in hypertrophied hearts. Methods and Results: L-CPT1 was expressed in vivo in rat hearts by coronary perfusion of Adv.cmv.L-CPT1 (L-CPT1, n=15) vs phosphate-buffered saline (PBS) infusion (PBS, n=7) or empty virus (empty, n=5). L-CPT1 was elevated 5-fold at 72 hours after Adv.cmv.L-CPT1 infusion ( P &lt;0.05), but muscle carnitine palmitoyltransferase I was unaffected. Despite similar tricarboxylic acid cycle rates, palmitate oxidation rates were reduced with L-CPT1 (1.12 ± 0.29 μmol/min per gram of dry weight, mean±SE) vs PBS (1.6 ± 0.34). Acetyl CoA production from palmitate was reduced with L-CPT1 (69 ± 0.02%; P &lt;0.05; PBS=79 ± 0.01%; empty=81 ± 0.02%), similar to what occurs in hypertrophied hearts, and with no difference in malonyl CoA content. Glucose oxidation was elevated with L-CPT1 (by 60%). Surprisingly, L-CPT1 hearts contained elevated atrial natriuretic peptide, indicating induction of hypertrophic signaling. Conclusions: The results link L-CPT1 expression to reduced palmitate oxidation in a nondiseased adult heart, recapitulating the phenotype of reduced long chain fatty acid oxidation in cardiac hypertrophy. The implications are that L-CPT1 expression induces metabolic remodeling hypertrophic signaling and that regulatory factors beyond malonyl CoA in the heart regulate long chain fatty acid oxidation via L-CPT1.
Heterosexual Transmission of HIV: The Role of Other Sexually Transmitted Infections and Behavior in Its Epidemiology Prevention and Control
Authors: S O Aral
Journal: Annual Review of Public Health (1993)

This paper focuses on heterosexual transmission the largest and fastest growing component of HIV spread. Its properties associated risk factors and the effects of societal context on these factors are reviewed. The methodological difficulties involved in establishing causal links between potential risk factors and HIV transmission and in evaluating the efficacy and population impact of alternative prevention and control strategies are summarized and a consideration of available strategies for the prevention and control of heterosexually transmitted HIV is outlined.  (excerpt)
A PP4 Holoenzyme Balances Physiological and Oncogenic Nuclear Factor-Kappa B Signaling in T Lymphocytes
Authors: Markus Brechmann, Thomas Mock, Dorothee Nickles, Michael Kiessling, Nicole Weit, Rebecca Breuer, Wolfgang Müller, Guido Wabnitz, Felice Frey, Jan P. Nicolay, Nina Booken, Yvonne Samstag, Claus-Detlev Klemke, Marco Herling, Michael Boutros, Peter H. Krammer, Rüdiger Arnold
Journal: Immunity (2012)