tbuckley/cabot-search huggingface dataset:
Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK)
Authors: Liam G Heaney, Ratko Djukanovic, Ashley Woodcock, Samantha Walker, John G Matthews, Ian D Pavord, Peter Bradding, Robert Niven, Chris E Brightling, Rekha Chaudhuri, Joseph R Arron, David F Choy, Douglas Cowan, Adel Mansur, Andrew Menzies-Gow, Ian Adcock, Kian F Chung, Chris Corrigan, Peter Coyle, Timothy Harrison, Sebastian Johnston, Peter Howarth, James Lordan, Ian Sabroe, Jeannette Bigler, Dirk Smith, Matthew Catley, Richard May, Lisa Pierre, Chris Stevenson, Glenn Crater, Frank Keane, Richard W Costello, Val Hudson, David Supple, Tim Hardman
Journal: Thorax (2015)

The UK Refractory Asthma Stratification Programme (RASP-UK) will explore novel biomarker stratification strategies in severe asthma to improve clinical management and accelerate development of new therapies. Prior asthma mechanistic studies have not stratified on inflammatory phenotype and the understanding of pathophysiological mechanisms in asthma without Type 2 cytokine inflammation is limited. RASP-UK will objectively assess adherence to corticosteroids (CS) and examine a novel composite biomarker strategy to optimise CS dose; this will also address what proportion of patients with severe asthma have persistent symptoms without eosinophilic airways inflammation after progressive CS withdrawal. There will be interactive partnership with the pharmaceutical industry to facilitate access to stratified populations for novel therapeutic studies.
Transapical Minimally Invasive Aortic Valve Implantation
Authors: Thomas Walther, Paul Simon, Todd Dewey, Gerhard Wimmer-Greinecker, Volkmar Falk, Marie T. Kasimir, Mirko Doss, Michael A. Borger, Gerhard Schuler, Dietmar Glogar, Wolfgang Fehske, Ernst Wolner, Friedrich W. Mohr, Michael Mack
Journal: Circulation (2007)

To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis.TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81+/-6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27+/-14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26-mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7+/-5.9% at a follow-up interval of 110+/-77 days (range 1 to 255 days).TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied.
Basic Principles and Practices of Behavior Therapy of Neuroses
Authors: JOSEPH WOLPE
Journal: American Journal of Psychiatry (1969)

The author presents a brief review of the theory and practices of behavior therapy, describing the various methods and their usefulness. He cites several studies which indicate more consistent success for behavior therapy than for analysis, in complex as well as simple neuroses, and also very low rates of relapse or the symptom substitution so often predicted by analysts.
General practice consultations: is there any point in being positive?
Authors: K B Thomas
Journal: BMJ (1987)

A group of 200 patients who presented in general practice with symptoms but no abnormal physical signs and in whom no definite diagnosis was made were randomly selected for one of four consultations: a consultation conducted in a "positive manner," with and without treatment, and a consultation conducted in a "non-positive manner," called a negative consultation, with and without treatment. Two weeks after consultation there was a significant difference in patient satisfaction between the positive and negative groups but not between the treated and untreated groups. Similarly, 64% of those receiving a positive consultation got better, compared with 39% of those who received a negative consultation (p = 0.001) and 53% of those treated got better compared with 50% of those not treated (p = 0.5).
Transferrin receptor expression in rat liver: Immunohistochemical and biochemical analysis of the effect of age and iron storage
Authors: Raf Sciot, Guido Verhoeven, Peter van Eyken, Jean Cailleau, Valeer J. Desmet
Journal: Hepatology (1990)

Hepatic transferrin receptors were studied in normal male rats at 1 to 59 wk after weaning, using immunohistochemical and biochemical techniques. The number of transferrin receptors measured and the intensity of the staining in situ decreased rapidly during the first 10 wk of life and more slowly thereafter. Immunohistochemistry further demonstrated changes in the topographical and (sub)cellular localization of the transferrin receptor. In the young rat livers, staining was almost exclusively present on hepatocytes in acinar zone 2 + 3 in a honeycomb to sinusoidal pattern. With aging, a panacinar heterogeneous and mainly sinusoidal staining of hepatocytes was more frequent. Kupffer cell positivity was more obvious as compared with the young rat livers. The observed changes in transferrin receptor expression may partly be explained by age-dependent alterations in DNA synthesis and proliferative potential of the liver cells. A series of rats were iron loaded with carbonyl iron up to 39 wk and "unloaded" by administration of a normal diet during 20 wk. In these animals, serial histochemical studies showed predominantly parenchymal (7 to 14 wk), mixed parenchymal and reticuloendothelial (39 wk) and almost exclusive reticuloendothelial siderosis (59 wk). In the siderotic livers transferrin receptor numbers tended to be lower than in the controls with significant differences after 14 and 39 wk. Immunohistochemistry showed decreased parenchymal but increased reticuloendothelial transferrin receptor expression with iron load. After the period of unloading, parenchymal transferrin receptors were virtually absent despite the negligible siderosis of these cells. In contrast, siderotic reticuloendothelial cells were intensely positive. These findings support down-regulation of parenchymal transferrin receptor resulting from iron storage. However, the positivity of siderotic reticuloendothelial cells and the absence of re-emergence of parenchymal receptors in conditions of minimal parenchymal and prominent reticuloendothelial siderosis need further elucidation.
Cancerous Inhibitor of Protein Phosphatase 2A, an Emerging Human Oncoprotein and a Potential Cancer Therapy Target
Authors: Anchit Khanna, John E. Pimanda, Jukka Westermarck
Journal: Cancer Research (2013)

Abstract Protein phosphatase 2A (PP2A) complexes function as tumor suppressors by inhibiting the activity of several critical oncogenic signaling pathways. Consequently, inhibition of the PP2A phosphatase activity is one of many prerequisites for the transformation of normal human cells into cancerous cells. However, mechanisms for PP2A inactivation in human cancers are poorly understood. The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), a recently identified endogenous PP2A inhibitor in malignant cells, is one such mechanism. Various independent studies have validated CIP2A's role in promoting tumor growth and resistance to apoptosis and senescence-inducing therapies. Notably, high CIP2A expression predicts poor patient prognosis in several human cancer types. Among the oncogenic proteins dephosphorylated by PP2A, the MYC oncoprotein, which is phosphorylated at serine 62, has surfaced as a marker for the oncogenic activity of CIP2A. The positive-feedback loop between CIP2A and MYC augments the activity of MYC in cancer cells. In addition, CIP2A promotes the phosphorylation and activity of additional oncoproteins, including E2F1 and AKT. However, CIP2A is not essential for normal mouse growth and development. These findings indicate that CIP2A is a novel anticancer target based on PP2A reactivation and inhibition of the oncogenic activity of its downstream effectors. The potential approaches and feasibility of targeting CIP2A are discussed here. Cancer Res; 73(22); 6548–53. ©2013 AACR.
Been There, Done That, Wrote the Blog: The Choices and Challenges of Supporting Adolescents and Young Adults With Cancer
Authors: Claire L. Treadgold, Aura Kuperberg
Journal: Journal of Clinical Oncology (2010)

The purpose of this article is to review the current literature on the provision of support groups for adolescent and young adult (AYA) patients with cancer with a focus on the challenges that are faced by these initiatives. The value of group support to patients with cancer and particularly to this age group has been well documented. However, with the advent and increase in popularity of online support options, it is an opportune time to examine the options available to the AYA group and highlight areas that would benefit from further investigation. This article will review the literature on the need to provide support groups to this age group, the available options, and the challenges they face.
Estimation of Oxygen Delivery in Newborns With a Univentricular Circulation
Authors: Ofer Barnea, William P. Santamore, Anthony Rossi, Ellis Salloum, Sufan Chien, Erle H. Austin
Journal: Circulation (1998)

Background —The management of neonates with complex congenital anomalies depends on careful interpretation of arterial blood gas values. Improved interpretation of these oxygen parameters may allow clinicians to avoid unexpected cardiovascular events. This study examined whether systemic oxygen delivery (D o 2 ) can be maximized by the use of indices derived from oxygen saturation measurements in neonates with hypoplastic left heart syndrome. Methods and Results —For the single-ventricle heart with both circulations in parallel, we used a previously developed computer simulation to obtain D o 2 as a function of systemic arterial (Sa o 2 ) and venous (Sv o 2 ) oxygen saturation, arteriovenous oxygen difference (Sa-v o 2 ), or pulmonary-to-systemic flow ratio (Qp/Qs). We also examined the oxygen excess factor, Sa o 2 /Sa-v o 2 (Ω). We found that (1) slight increases in Sa o 2 may be associated with large decreases in D o 2 . (2) Low values for Sv o 2 indicate low values for D o 2 . (3) Curves for Sa-v o 2 and Qp/Qs are redundant in the data provided. (Qp/Qs, however, provides these data in more physiologically relevant terms.) (4) High values for Qp/Qs (&gt;4) are associated with low D o 2 . (5) Estimating Qp/Qs from oxygen saturation measurements may result in errors when pulmonary venous oxygen saturation is not available. (6) Maximizing D o 2 is extremely difficult using Sa o 2 , Sv o 2 , and Qp/Qs. (7) A linear relationship exists between Ω and D o 2 , and this linear relationship is not altered by changes in cardiac output. Conclusions —Patients with low Sv o 2 values require attention. Ideally, after reducing Qp/Qs to &lt;1.5, Ω might be a better index to guide further therapy and maximize D o 2 . Interventions that increased Ω would be considered beneficial, whereas interventions that decreased Ω would be considered detrimental.
Enhanced Angiotensin II Activity in Heart Failure
Authors: Lionel H. Opie, Michael N. Sack
Journal: Circulation Research (2001)

There are strong data favoring the pathogenic role of angiotensin II type 1 receptor (AT(1)) activation with subsequent promotion of myocyte growth and cardiac fibrosis in the development of cardiac hypertrophy and heart failure. An emerging hypothesis suggests that the activity of the angiotensin II type 2 receptor (AT(2)) may counterregulate AT(1) receptor effects during cardiac development and during the evolution of cardiac hypertrophy and heart failure. In this review, we examine the potential role of AT(2) activity in the context of this hypothesis. In contrast to the counterregulatory hypothesis, studies in mice with an overabundance of, or a deficiency in, the AT(2) receptor do not suggest that AT(2) signaling is essential for cardiac development. Moreover, the proposed antigrowth effects of AT(2) receptor signaling in pathological cardiac hypertrophy could not be shown in two mice models both deficient in AT(2) receptors. The role of AT(2) receptor signaling in cardiac fibrosis is, however, still debatable because of conflicting data in the same two studies. In angiotensin II-evoked apoptosis in cardiomyocytes, the proposed proapoptotic role of AT(2) activity could not be confirmed. Furthermore, in the progression from the bench to bedside, the results of two large clinical trials in heart failure, namely ELITE II and Val-HeFT, can be explained without ascribing a major protective role to the unopposed activity of the AT(2) receptor in the failing myocardium. In this review, we conclude that the collective evidence does not strongly support a net beneficial effect of AT(2) stimulation in the diseased myocardium.
Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline
Authors: J.-M. Dumonceau, M. Polkowski, A. Larghi, P. Vilmann, M. Giovannini, J.-L. Frossard, D. Heresbach, B. Pujol, G. Fernández-Esparrach, E. Vazquez-Sequeiros, A. Ginès
Journal: Endoscopy (2011)

This article is part of a combined publication that expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about endoscopic ultrasound (EUS)-guided sampling in gastroenterology, including EUS-guided fine needle aspiration (EUS-FNA) and EUS-guided trucut biopsy (EUS-TCB), of submucosal tumors, diffuse esophageal/gastric wall thickening, pancreatic solid masses and cystic-appearing lesions, mediastinal lesions unrelated to lung or esophageal cancer, cancer of the esophagus, stomach, and rectum, lymph nodes of unknown origin, adrenal gland masses, and focal liver lesions. False-positive cytopathological results and needle tract seeding are also discussed. The present Clinical Guideline describes the results of EUS-guided sampling in the different clinical settings, considers the role of this technique in patient management, and makes recommendations on circumstances that warrant its use. A two-page executive summary of evidence statements and recommendations is provided. A separate Technical Guideline describes the general technique of EUS-guided sampling, particular techniques to maximize the diagnostic yield depending on the nature of the target lesion, and sample processing. The target readership for the Clinical Guideline mostly includes gastroenterologists, oncologists, internists, and surgeons while the Technical Guideline should be most useful to endoscopists who perform EUS-guided sampling.
Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers.
Authors: A Mertz-Nielsen, J Hillingso, O Eskerod, K Bukhave, J Rask-Madsen
Journal: Gut (1995)

The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion and luminal output of PGE2 into the stomach and the duodenum of nine healthy volunteers using a new technique permitting simultaneous measurements. In the stomach modified sham feeding increased bicarbonate secretion from 382 (62) mumol/h (mean (SEM)) to 959 (224) mumol/h (p &lt; 0.02). In the duodenum modified sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p &lt; 0.02) and 634 (157) mumol/cm x h (p &lt; 0.01), respectively. Pirenzepine (10 mg/h intravenously) reduced basal and vagally stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p &lt; 0.03). In the stomach, but not the duodenum, basal and vagally stimulated PGE2 output increased significantly (p &lt; 0.05) in response to pirenzepine. In conclusion, human gastroduodenal mucosal bicarbonate secretion is regulated by a pirenzepine sensitive mechanism, which is probably cholinergic. The rise in gastric PGE2 output seen in response to M1 receptor inhibition by pirenzepine suggests the existence of a feed back loop secondary to the decrease seen in bicarbonate secretion.
The morphogenic/cytotoxic and prostaglandin-stimulating activities of interleukin-1 beta in the rat ovary are nitric oxide independent.
Authors: I Ben-Shlomo, E Y Adashi, D W Payne
Journal: Journal of Clinical Investigation (1994)

Nitric oxide (NO) has been implicated as a mediator of physiologic and pathologic cellular injury. Since the cytokine interleukin-1 beta (IL-1 beta) induces nitric oxide synthase (NOS) activity as well as effects morphogenic/cytotoxic changes and increased prostaglandin (PGE2) levels in cultured whole ovarian dispersates, we set out to determine whether these actions are interrelated. Treatment with IL-1 beta resulted in a marked increase in media nitrite and nitrate accumulation, morphological alterations, and increased release of lactate dehydrogenase (LDH) into media. Addition of IL-1 receptor antagonist (RA) eliminated these IL-1 beta effects. In contrast, specific inhibitors of NOS failed to reverse IL-1 beta-induced morphogenic changes or LDH release in spite of complete reduction of media nitrite to control levels. Similarly, treatment with transforming growth factor beta 1, inhibited IL-1 beta-induced nitrite accumulation, but had no effect on the morphologic or cytotoxic endpoints. Moreover, the addition of sodium nitroprusside, an NO generator, resulted in progressive increments in media nitrite content without a corresponding increase in the IL-1 beta-associated morphogenic changes or media LDH content. Furthermore, IL-1-induced PGE2 accumulation remained unaffected by specific NOS inhibition. These observations support the view that NO does not mediate the morphogenic/cytotoxic or inflammatory-like (e.g., PGE2 inducing) properties of IL-1 beta in cultured whole ovarian dispersates. Although the precise role of NO in ovarian physiology remains unknown, it is possible that NO participates in the periovulatory modulation of ovarian blood flow by virtue of its potent vasodilatory activity.
Radiographic assessment of patellofemoral osteoarthritis.
Authors: A C Jones, J Ledingham, T McAlindon, M Regan, D Hart, P J MacMillan, M Doherty
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--To determine the feasibility of assessing patellofemoral osteoarthritis using the 9skyline9 view and to compare its reproducibility with the standard lateral view. METHODS--Fifty patients attending a rheumatology outpatient department with osteoarthritis of the knee had standard radiographs taken of both knees: standing weightbearing anteroposterior; lateral supine radiograph in 30 degrees of flexion; and a skyline view of the patellofemoral joint. After an initial training period using 20 sets of films the remaining 30 sets were read blind by five observers. Intraobserver and interobserver variability was assessed using the kappa statistic. The minimum joint space in each compartment was measured using a ruler. Two views of a single normal subject were measured to determine the effect of knee flexion. RESULTS--The final 30 study films were from 20 women and 10 men, median age 72.5, range 18-91 years. A grading system comprising assessment of osteophytosis, joint space narrowing, sclerosis, cysts, and attrition could easily be applied to the skyline patellofemoral view. Intraobserver reproducibility was better than the interobserver reproducibility for all features. The skyline view performed more reproducibly and over a wider range of categorisation for joint space narrowing than the lateral radiograph. Measurement using a ruler was easy to perform and precise to within 1 mm for the medial tibiofemoral and lateral facet of the patellofemoral joint. In normal knees the degree of flexion significantly affected the measurement. CONCLUSIONS--Radiographic grading of the skyline patellofemoral view is readily achieved, is more reproducible than assessment of the lateral view, and allows more precise localisation of change. Such views should be considered in radiological surveys of osteoarthritis of the knee.
The logic of the sociobiological model Geary-style
Authors: Diane Proudfoot
Journal: Behavioral and Brain Sciences (1996)

Abstract Geary's is the traditional view of the sexes. Yet each part of his argument – the move from sex differences in spatial ability and social preferences to a sex difference in mathematical ability, the claim that the former are biologically primary, and the sociobiological explanation of these differences – requires considerable further work. The notion of a biologically secondary ability is itself problematic.
Preventing childhood obesity: two year follow-up results from the Christchurch obesity prevention programme in schools (CHOPPS)
Authors: Janet James, Peter Thomas, David Kerr
Journal: BMJ (2007)

<b>Objective</b> To assess the long term effects of an obesity prevention programme in schools. <b>Design</b> Longitudinal results after a cluster randomised controlled trial. <b>Setting</b> Schools in southwest England. <b>Participants</b> Of the original sample of 644 children aged 7-11, 511 children were tracked and measurements were obtained from 434 children three years after baseline. <b>Intervention</b> The intervention was conducted over one school year, with four sessions of focused education promoting a healthy diet and discouraging the consumption of carbonated drinks. <b>Main outcome measures</b> Anthropometric measures of height, weight, and waist circumference. Body mass index (BMI) converted to z scores (SD scores) and to centile values with growth reference curves. Waist circumference was also converted to z scores (SD scores). <b>Results</b> At three years after baseline the age and sex specific BMI z scores (SD scores) had increased in the control group by 0.10 (SD 0.53) but decreased in the intervention group by −0.01 (SD 0.58), with a mean difference of 0.10 (95% confidence interval −0.00 to 0.21, P=0.06). The prevalence of overweight increased in both the intervention and control group at three years and the significant difference between the groups seen at 12 months was no longer evident. The BMI increased in the control group by 2.14 (SD 1.64) and the intervention group by 1.88 (SD 1.71), with mean difference of 0.26 (−0.07 to 0.58, P= 0.12). The waist circumference increased in both groups after three years with a mean difference of 0.09 (−0.06 to 0.26, P=0.25). <b>Conclusions</b> These longitudinal results show that after a simple year long intervention the difference in prevalence of overweight in children seen at 12 months was not sustained at three years.