tbuckley/cabot-search huggingface dataset:
Incidence and aetiology of a raised hemidiaphragm after cardiopulmonary bypass.
Authors: S R Large, L J Heywood, C D Flower, R Cory-Pearce, J Wallwork, T A English
Journal: Thorax (1985)

A raised hemidiaphragm has been reported as an uncommon complication of cardiopulmonary bypass, possibly resulting from cold injury to the phrenic nerve. At Papworth Hospital myocardial protection during cardiac arrest relies in part on irrigation of the pericardial cavity with large volumes of Hartmann9s solution at 4 degrees C. Retrospective review of the chest radiographs of 100 consecutive patients undergoing cardiopulmonary bypass showed that 31 had a raised left hemidiaphragm soon after operation. The only significant correlation was with aortic cross clamp time (p less than 0.03). A prospective study of 36 consecutive patients undergoing cardiopulmonary bypass was then undertaken with diaphragmatic screening and chest radiography. Preoperative screening gave normal results in all patients. In the early postoperative period 16 (44%) had left diaphragmatic weakness or paralysis, two (5.5%) right sided weakness, and two (5.5%) bilateral weakness. Repeat screening of these patients showed resolution in all but four cases (80%) at six months and in all but two (90%) at one year. The greater number of left sided lesions than of right (8:1) is probably due to the fact that the cold jet of irrigating fluid is directed towards the left phrenic nerve. These findings have implications with regard to the optimum temperature of the irrigant fluid for myocardial protection during cardiopulmonary bypass.
Loss of MicroRNA-155 Protects the Heart From Pathological Cardiac Hypertrophy
Authors: Hee Young Seok, Jinghai Chen, Masaharu Kataoka, Zhan-Peng Huang, Jian Ding, Jinglu Yan, Xiaoyun Hu, Da-Zhi Wang
Journal: Circulation Research (2014)

Rationale: In response to mechanical and pathological stress, adult mammalian hearts often undergo mal-remodeling, a process commonly characterized as pathological hypertrophy, which is associated with upregulation of fetal genes, increased fibrosis, and reduction of cardiac dysfunction. The molecular pathways that regulate this process are not fully understood. Objective: To explore the function of microRNA-155 (miR-155) in cardiac hypertrophy and remodeling. Methods and Results: Our previous work identified miR-155 as a critical microRNA that repressed the expression and function of the myocyte enhancer factor 2A. In this study, we found that miR-155 is expressed in cardiomyocytes and that its expression is reduced in pressure overload–induced hypertrophic hearts. In mouse models of cardiac hypertrophy, miR-155 null hearts suppressed cardiac hypertrophy and cardiac remodeling in response to 2 independent pathological stressors, transverse aortic restriction and an activated calcineurin transgene. Most importantly, loss of miR-155 prevents the progress of heart failure and substantially extends the survival of calcineurin transgenic mice. The function of miR-155 in hypertrophy is confirmed in isolated cardiomyocytes. We identified jumonji, AT rich interactive domain 2 (Jarid2) as an miR-155 target in the heart. miR-155 directly represses Jarid2, whose expression is increased in miR-155 null hearts. Inhibition of endogenous Jarid2 partially rescues the effect of miR-155 loss in isolated cardiomyocytes. Conclusions: Our studies uncover miR-155 as an inducer of pathological cardiomyocyte hypertrophy and suggest that inhibition of endogenous miR-155 might have clinical potential to suppress cardiac hypertrophy and heart failure.
Habitually Higher Dietary Glycemic Index During Puberty Is Prospectively Related to Increased Risk Markers of Type 2 Diabetes in Younger Adulthood
Authors: Janina Goletzke, Christian Herder, Gesa Joslowski, Katja Bolzenius, Thomas Remer, Stefan A. Wudy, Michael Roden, Wolfgang Rathmann, Anette E. Buyken
Journal: Diabetes Care (2013)

Carbohydrate nutrition during periods of physiological insulin resistance such as puberty may affect future risk of type 2 diabetes. This study examined whether the amount or the quality (dietary glycemic index [GI], glycemic load [GL], and added sugar, fiber, and whole-grain intake) of carbohydrates during puberty is associated with risk markers of type 2 diabetes in younger adulthood.The analysis was based on 226 participants (121 girls and 105 boys) from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study (DONALD) with an average of five 3-day weighed dietary records (range 2-6) during puberty (girls, age 9-14 years; boys, age 10-15 years) and fasting blood samples in younger adulthood (age 18-36 years) (average duration of follow-up 12.6 years). Multivariable linear regression was used to analyze the associations between carbohydrate nutrition and homeostasis model assessment-insulin resistance (HOMA-IR) as well as the liver enzymes alanine aminotransferase (ALT) and γ-glutamyltransferase (GGT) (n = 214).A higher dietary GI was prospectively related to greater values of HOMA-IR (P(trend) = 0.03), ALT (P(trend) = 0.02), and GGT (P(trend) = 0.04). After adjustment for sex, adult age, baseline BMI, and early life and socioeconomic factors as well as protein and fiber intake, predicted mean HOMA-IR values in energy-adjusted tertiles of GI were 2.37 (95% CI 2.16-2.60), 2.47 (2.26-2.71), and 2.59 (2.35-2.85). The amount of carbohydrates, GL, and added sugar, fiber, and whole-grain intake were not related to the analyzed markers.Our data indicate that a habitually higher dietary GI during puberty may adversely affect risk markers of type 2 diabetes in younger adulthood.
Reproducibility of flow rates measured with low density gas mixtures in exercise-induced bronchospasm.
Authors: S G Spiro, C W Bierman, I S Petheram
Journal: Thorax (1981)

We have studied the reproducibility of the change in maximum expiratory flow rates after breathing helium/oxygen (He/O2) mixtures in 12 asthmatics at rest and after exercise. Each subject performed four identical exercise tests which caused a similar degree of exercise-induced bronchospasm (EIB) on each occasion. We compared flow rates at 50% of the vital capacity (V50) breathing He/O2 to those breathing air at rest, and with the lowest V50 on air after exercise. Those subjects showing an increase of greater than 20% in V50 with He/O2 compared to the corresponding air value were termed "responders". At rest the responder status after He/O2 was more consistent than during EIB. Six subjects were non-responders consistently on up to 12 separate measurements at rest while the other five subjects were non-responders on all but one occasion and the remaining subject a responder on seven of eight measurements. During EIB all but one subject showed a He/O2 response. A response was seen consistently in six subjects but the actual percentage change in V50 with helium varied greatly. One subject remained a non-responder after exercise and the other five were He/O2 responders after only two or three of the four test runs, and non-responders on the remainder. The lack of consistency of our data, particularly during EIB makes the interpretation of the He/O2 breathing test less useful than originally claimed.
Real-life use of long-acting antimuscarinic agents following their approval for COPD treatment
Authors: Nicolas Roche, Gilles Jebrak, Denis Caillaud, Gaetan Deslée, Graziella Brinchault, Pascal Chanez, Isabelle Court-Fortune, Roger Escamilla, Pascale Nesme-Meyer, Christophe Pinet, Philippe Carré, Jean-Louis Paillasseur, Thierry Perez, Pierre-Régis Burgel
Journal: European Respiratory Journal (2014)

Chronic obstructive pulmonary disease (COPD) pharmacological treatment aims to reduce symptoms, represented mostly by dyspnoea and its impact on daily life, and future risk, i.e. lung function decline, mortality and exacerbations [1]. Inhaled therapies, including long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS), are the main treatments recommended for COPD patients. LABD have been found not only to improve lung function, decrease dyspnoea, increase exercise tolerance and improve health status, but also to reduce the rate of exacerbations. In that respect, some studies suggested that long-acting antimuscarinic agents (LAMA) could be more effective than long-acting β2-agonists (LABA) [2]. In most countries, ICS are indicated only as part of fixed-dose combinations (FDC) with LABA and are used mostly to decrease the risk of exacerbations, which is associated with health status improvement [3]. Therefore, it appeared logical to restrict their use to patients at high risk of exacerbations. The long-term benefit of combining LAMA and FDC (triple therapy) is not strongly documented [4]. Many studies in various countries found discrepancies between guidelines and real-life practice regarding long-term maintenance treatment in patients with COPD [5–7]. Although the impact of nonadherence to guidelines on efficacy outcomes is controversial [8], it increases healthcare costs [9] and, New agents for COPD treatment appear to increase overall treatment intensity in all severity categories [http://ow.ly/BS6Wq][1] [1]: http://ow.ly/C95Ue
Neutrophil recruitment in Clostridium difficile toxin A enteritis in the rabbit.
Authors: C P Kelly, S Becker, J K Linevsky, M A Joshi, J C O'Keane, B F Dickey, J T LaMont, C Pothoulakis
Journal: Journal of Clinical Investigation (1994)

Neutrophil infiltration is a prominent feature of Clostridium difficile-associated enteritis and colitis. The aim of this study was to examine the importance of neutrophil recruitment and neutrophil-mediated tissue damage in C. difficile toxin A-induced enteritis. Competitive binding experiments using purified 3H-toxin A demonstrated the presence of a single class of medium affinity receptors on rabbit neutrophils (Kd 7 x 10(-8) M). Pertussis toxin and the nonhydrolyzable GTP analog GTPgamma S both inhibited 3H-toxin A binding (by 56 and 65%, respectively), indicating that the rabbit neutrophil toxin A receptor is G protein linked. Toxin A elicited a dose-dependent (25-200 micrograms/ml) stimulation of neutrophil migration in vitro, and this functional effect was also pertussis toxin sensitive (69% inhibition). Treatment of neutrophils with R15.7, a blocking monoclonal antibody to the leuocyte adhesion molecule CD18, inhibited toxin A-stimulated neutrophil migration by 85% in vitro. Pretreatment of rabbits with R15.7 also prevented neutrophil infiltration of toxin A-exposed ileal loops in vivo as determined by histologic examination and by ileal tissue myeloperoxidase levels. Furthermore, R15.7 effected a substantial inhibition of fluid secretion (by 65%), mannitol permeability (by 66%), and histologic damage in toxin A-exposed ileal loops. Anti-CD18 (R15.7) had no inhibitory effect on cholera toxin enterotoxicity. These data demonstrate that C. difficile toxin A is a proinflammatory toxin whose enterotoxic effects are substantially dependent upon neutrophil recruitment.
Transcriptome Profiling and the Pathogenesis of Diabetic Complications
Authors: Susan B. Connolly, Denise Sadlier, Niamh E. Kieran, Peter Doran, Hugh R. Brady
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Diabetes is an escalating problem worldwide and a major cause of vascular disease, renal failure, and blindness, among other complications. The cellular mediators of high glucose–induced injury include activation of protein kinase C, accumulation of cell sorbitol from increased flux through the aldose reductase pathway, and generation of advanced glycosylation end products and reactive oxygen species, among others. Current strategies for preventing and slowing the progression of the macrovascular and microvascular complications of diabetes include optimization of glycemic control and BP, angiotensin-converting enzyme inhibitors and angiotensin II blockers, and HMG CoA reductase inhibitors. However, there is an urgent need to develop new therapeutic strategies, as these interventions, although they may slow, rarely halt the progression of diabetic complications. Central to this process is the elucidation of the molecular events that drive this complex disease and that are potential therapeutic targets. This review discusses the promise offered in this regard by global monitoring of cellular or tissue mRNA expression (so-called transcriptomics) and illustrates the potential of this approach by focusing on recent studies on the pathogenesis of diabetic nephropathy. E-mail: deptofmedicine@mater.ie
Improvement in Cheyne-Stokes respiration following cardiac resynchronisation therapy
Authors: J. Y. Gabor
Journal: European Respiratory Journal (2005)

The effect of standard cardiac resynchronisation therapy (CRT) on the severity of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure was studied. It was hypothesised that CRT, through its known beneficial effects on cardiac function, would stabilise the control of breathing and reduce CSR. Twenty-eight patients who were eligible for CRT and receiving optimised medical treatment for congestive heart failure were referred for overnight polysomnography, including monitoring of thoracic and abdominal movements to identify CSR and obstructive sleep apnoea events. Patients underwent repeat polysomnography after 6 months of CRT to re-evaluate sleep quality and sleep-disordered breathing. Twelve of the 28 patients had significant CSR (43%); 10 patients had a successful implantation and underwent repeat polysomnography a mean+/-SD 27+/-7 weeks after continuous biventricular pacing. Six of the 10 patients experienced a significant decrease in CSR severity following CRT, associated with correction of congestive heart failure-related hyperventilation and hypocapnia. Circulation time, oxygen saturation, frequency of obstructive apnoeas and sleep quality did not change. In conclusion, cardiac resynchronisation therapy is associated with a reduction in Cheyne-Stokes respiration, which may contribute to improved clinical outcome in patients treated with cardiac resynchronisation therapy.
Mechanisms that Regulate Establishment, Maintenance, and Remodeling of Dendritic Fields
Authors: Jay Z. Parrish, Kazuo Emoto, Michael D. Kim, Yuh Nung Jan
Journal: Annual Review of Neuroscience (2007)

Although dendrite arborization patterns are hallmarks of neuronal type and critical determinants of neuronal function, how dendritic arbors take shape is still largely unknown. Transcription factors play important roles in specifying neuronal types and have a profound influence on dendritic arbor size and complexity. The space that a dendritic arbor occupies is determined largely by a combination of growth-promoting signals that regulate arbor size, chemotropic cues that steer dendrites into the appropriate space, and neurite-neurite contacts that ensure proper representation of the dendritic field and appropriate synaptic contacts. Dendritic arbors are largely maintained over the neuron's lifetime, but in some cases, dendritic arbors are refined, in large part as a result of neuronal activity. In this review, we summarize our current understanding of the cellular and molecular mechanisms that regulate dendritic field formation and influence the shaping of dendritic arbors.
Productivity and Medical Costs of Diabetes in a Large Employer Population
Authors: Scott Ramsey, Kent H. Summers, Stephanie A. Leong, Howard G. Birnbaum, Jason E. Kemner, Paul Greenberg
Journal: Diabetes Care (2002)

OBJECTIVE—The purpose of this study was to assess the economic burden of diabetes from an employer’s perspective. We analyzed the costs of diabetes, using claims data for an employed population and the prevalence of selected comorbid conditions. RESEARCH DESIGN AND METHODS—The data source is a claims database from a national Fortune 100 manufacturer. It includes medical, pharmacy, and disability claims for all beneficiaries (n &amp;gt;100,000). Both medical and work productivity costs of diabetes patients are compared by age with those of matched control subjects from the overall beneficiary population. Out-of-pocket and intangible costs are excluded. RESULTS—In 1998, the employer’s mean annual per capita costs were higher for all diabetes beneficiaries than for control subjects ($7,778 ± 16,176 vs. $3,367 ± 8,783; P &amp;lt; 0.0001), yielding an incremental cost of $4,410 ± 18,407 associated with diabetes. The medical and productivity costs for employees with diabetes were significantly (P &amp;lt; 0.0008) higher than for control subjects. The incremental cost of diabetes among employees ranged from $4,671 (aged 18–35 years) to $4,369 (aged 56–64 years). CONCLUSIONS—Diabetes imposes a significant economic burden on employers, particularly when including productivity costs. Employers should select health plans that provide enriched benefits to diabetes patients, including ready access to medical and pharmacy services as well as aggressive diabetes management programs.
Definition of arthritis candidate risk genes by combining rat linkage-mapping results with human case-control association data
Authors: L Backdahl, J P Guo, M Jagodic, K Becanovic, B Ding, T Olsson, J C Lorentzen
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To define genomic regions that link to rat arthritis and to determine the potential association with rheumatoid arthritis (RA) of the corresponding human genomic regions. <h3>Methods:</h3> Advanced intercross lines (AIL) between arthritis susceptible DA rats and arthritis resistant PVG.1AV1 rats were injected with differently arthritogenic oils to achieve an experimental situation with substantial phenotypic variation in the rat study population. Genotyping of microsatellite markers was performed over genomic regions with documented impact on arthritis, located on rat chromosomes 4, 10 and 12. Linkage between genotypes and phenotypes were determined by R/quantitative trait loci (QTL). Potential association with RA of single nucleotide polymorphisms (SNPs) in homologous human chromosome regions was evaluated from public Wellcome Trust Case Control Consortium (WTCCC) data derived from 2000 cases and 3000 controls. <h3>Results:</h3> A high frequency of arthritis (57%) was recorded in 422 rats injected with pristane. Maximum linkage to pristane-induced arthritis occurred less than 130 kb from the known genetic arthritis determinants <i>Ncf1</i> and <i>APLEC</i>, demonstrating remarkable mapping precision. Five novel quantitative trait loci were mapped on rat chromosomes 4 and 10, with narrow confidence intervals. Some exerted sex-biased effects and some were linked to chronic arthritis. Human homologous genomic regions contain loci where multiple nearby SNPs associate nominally with RA (eg, at the genes encoding protein kinase Cα and interleukin 17 receptor α). <h3>Conclusions:</h3> High-resolution mapping in AIL populations defines limited sets of candidate risk genes, some of which appear also to associate with RA and thus may give clues to evolutionarily conserved pathways that lead to arthritis.
Hypokalemia After Resuscitation From Out-of-Hospital Ventricular Fibrillation
Authors: Robert G. Thompson
Journal: JAMA (1982)

We studied serum electrolyte levels, blood gas values, and diuretic history in 115 patients immediately after resuscitation from out-of-hospital ventricular fibrillation. Comparisons were made with 84 patients admitted for acute myocardial infarction and with 88 ambulatory patients with coronary heart disease. Admission serum potassium values of 3.60 mEq/L or lower were found in 56 (49%) of the resuscitated patients, compared with 16 (19%) and eight (9%) of the comparison groups, respectively. In the resuscitated patients, the mean serum potassium level was 3.70 +/- 0.72 (SD) mEq/L, compared with 4.09 +/- 0.66 and 4.17 +/- 0.35 mEq/L in the respective comparison groups. Reduced serum potassium concentration was not related to simple extracellular alkalosis. However, the absence of a causative relationship to diuretic use suggested that it occurred during cardiac arrest and resuscitation. Rapid correction of extracellular acidosis by bicarbonate therapy and ventilation may have produced a shift of extracellular potassium into the intracellular compartment even in the absence of extracellular alkalosis.
Doctors involved at Winterbourne View hospital may face GMC hearing
Authors: A. O'Dowd
Journal: BMJ (2011)

Doctors who had dealings with a residential hospital for vulnerable adults that was the subject of a recent high profile TV expose may face disciplinary action before the General Medical Council (GMC), MPs have been told.

Possible action was mentioned during an evidence session of the parliamentary health select committee on 14 June at which MPs quizzed medical and nursing regulators as part of their inquiry into regulatory bodies.

The committee asked about the recent high profile case of alleged abuse at Winterbourne View hospital near Bristol, as highlighted in the BBC’s Panorama programme on 31 May ( BMJ 2011;342:d3482, published 3 June 2011).

Committee chair Stephen Dorrell, Conservative MP for Charnwood, said: “There must …
Symposium: reproduction in baboons. Some reproductive studies in the baboon
Authors: V. Stevens
Journal: Human Reproduction Update (1997)

A captive colony of baboons has been used for three decades for various reproductive studies where application of findings to human therapeutics was desired. The characteristics of the menstrual cycle in baboons are very similar to those of women, except that of the baboon is slightly longer and there is a lower luteal phase concentration of oestradiol. The duration of pregnancy in baboons is about two-thirds that of humans but patterns of oestrogen and progesterone secretion are virtually identical. The principal oestrogen produced by the pregnant baboon is oestrone, while oestriol is the most abundant in human pregnancies. Chorionic gonadotrophin (CG) is elevated significantly only in the first trimester of a baboon pregnancy, while human pregnancy concentrations of this hormone are about one-third of the first trimester level in the second and third trimesters. Breeding success of baboons in captivity depends on care being taken to cull infertile animals from the colony prior to commencing matings. Under optimal conditions, fertility rates can reach nearly 80%. Female baboons have been successfully used to gain insights into antifertility effects of contraceptive vaccines directed against CG, spermatozoa and ovum antigens. Extensive use of the colony for developing a human chorionic gonadotrophin (HCG) antifertility vaccine has been invaluable for progress in this field. Other pharmaceuticals and devices have been successfully tested in baboons, but costs and mandated regulations for the management of these nonhuman primates have made their current use in meaningful studies extremely difficult.