tbuckley/cabot-search huggingface dataset:
Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial
Authors: J H Scholefield
Journal: Gut (2002)

<b>Background:</b> Three large randomised trials have shown that screening for colorectal cancer using faecal occult blood (FOB) tests can reduce the mortality from this disease. Two national pilot studies have recently been launched in the UK to investigate the feasibility of population screening for colorectal cancer in the National Health Service. The largest of the randomised trials was conducted in Nottingham and randomised 152 850 individuals between the ages of 45 and 74 years to receive biennial Haemoccult (FOB) test kit (intervention group) or to a control group. <b>Aims:</b> We have compared the mortality in the intervention group compared with the control group. <b>Methods:</b> The 152 850 randomised individuals were followed up through local health records and central flagging (Office for National Statistics) over a median follow up period of 11 years. <b>Results:</b> At a median follow up of 11 years there was a 13% reduction in colorectal cancer mortality (95% confidence interval 3–22%) in the intervention group despite an uptake at first invitation of only approximately 50%. The mortality reduction for those accepting screening was 27%. The reduction in mortality was independent of sex and site of tumour. There was no significant difference in mortality from causes other than colorectal cancer between the intervention and control groups. <b>Conclusions:</b> Although the reduction in colorectal cancer mortality was sustained, further follow up of this population is required to determine whether a significant reduction in the incidence of colorectal cancer will be achieved.
UK launches panel to tackle research misconduct
Authors: Andrew Cole
Journal: BMJ (2006)

A new independent body to tackle biomedical research misconduct in the United Kingdom was launched this week—but its powers will be limited to providing advice and promoting good practice.

The UK Panel for Health and Biomedical Research Integrity has been initially set up as a three year project, and its first priority will be to develop a code of practice applicable to universities, the NHS, and industry.

The panel will also support whistleblowers reporting cases of alleged research fraud in addition to offering training, seminars, and advice on …
Effects of Different Oxygen and Carbon Dioxide Concentrations on the Activity of the Embryonic Chick Heart
Authors: GEORGE H. PAFF, ROBERT J. BOUCEK
Journal: Circulation Research (1958)

The 72 hour chick embryo heart reacts to progressive hypoxia by the appearance of arrhythmias and asystole. In the presence of 4 per cent CO 2 , complete anoxia is tolerated for a period of 30 min. with carbon dioxide apparently augmenting the buffering capacity of the plasma clot which supports the heart. A gaseous environment of 4 per cent O 2 /4 per cent CO 2 /92 per cent N 2 induced a steady and entirely reversible state of cardiac stress.
Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat
Authors: Gerard F Curley, Mairead Hayes, Bilal Ansari, Georgina Shaw, Aideen Ryan, Frank Barry, Timothy O'Brien, Daniel O'Toole, John G Laffey
Journal: Thorax (2011)

<h3>Background</h3> Bone-marrow derived mesenchymal stem cells (MSCs) reduce the severity of evolving acute lung injury (ALI), but their ability to repair the injured lung is not clear. A study was undertaken to determine the potential for MSCs to enhance repair after ventilator-induced lung injury (VILI) and elucidate the mechanisms underlying these effects. <h3>Methods</h3> Anaesthetised rats underwent injurious ventilation which produced severe ALI. Following recovery, they were given an intravenous injection of MSCs (2×10<sup>6</sup> cells) or vehicle immediately and a second dose 24 h later. The extent of recovery following VILI was assessed after 48 h. Subsequent experiments examined the potential for non-stem cells and for the MSC secretome to enhance VILI repair. The contribution of specific MSC-secreted mediators was then examined in a wound healing model. <h3>Results</h3> MSC therapy enhanced repair following VILI. MSCs enhanced restoration of systemic oxygenation and lung compliance, reduced total lung water, decreased lung inflammation and histological lung injury and restored lung structure. They attenuated alveolar tumour necrosis factor α concentrations while increasing concentrations of interleukin 10. These effects were not seen with non-stem cells (ie, rat fibroblasts). MSC-secreted products also enhanced lung repair and attenuated the inflammatory response following VILI. The beneficial effect of the MSC secretome on repair of pulmonary epithelial wounds was attenuated by prior depletion of keratinocyte growth factor. <h3>Conclusion</h3> MSC therapy enhances lung repair following VILI via a paracrine mechanism that may be keratinocyte growth factor-dependent.
Effects of graded increases in pulmonary vascular pressures on lung fluid balance in unanesthetized sheep.
Authors: R E Parker, R J Roselli, T R Harris, K L Brigham
Journal: Circulation Research (1981)

Fourteen experiments were conducted on 12 chronically instrumented unanesthetized sheep in which we monitored pulmonary arterial, left atrial, and aortic pressures, lung lymph flow, and lymph-to-plasma ratios (L/P) of total proteins and four endogenous protein fractions during baseline and progressive elevations of left atrial pressure. We found that L/P for total proteins decreased as lung lymph flow increased until lymph flow exceeded four to five times baseline and thereafter remained nearly constant (filtration independent) at 0.26. The four protein fractions exhibited a filtration independent L/P that was related to the effective molecular radius of the protein fraction. The minimal L/P were 0.36, 0.28, 0.18, and 0.09 for the protein fractions that had effective molecular radii of 36, 38.5, 59, and 101 A, respectively. In addition, we found no evidence supporting a stretched pore phenomenon over the pressure range utilized in this investigation.
Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients
Authors: A. Campo, G. Frühbeck, J. J. Zulueta, J. Iriarte, L. M. Seijo, A. B. Alcaide, J. B. Galdiz, J. Salvador
Journal: European Respiratory Journal (2007)

Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance to leptin has been consistently associated with obesity. Raised leptin levels have been reported in subjects with sleep apnoea or obesity-hypoventilation syndrome. The aim of the present study was to assess, by multivariate analysis, the possible association between respiratory centre impairment and levels of serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2)) underwent the following tests: sleep studies, respiratory function tests, baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute ventilation), fasting leptin levels, body composition and anthropometric measures. Subjects with airways obstruction on spirometry were excluded. Out of the 346 subjects undergoing testing, 245 were included in the current analysis. Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension, percentage body fat and minimal nocturnal saturation were predictors for baseline P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin levels were predictors for hypercapnic response in males, but not in females. Hyperleptinaemia is associated with a reduction in respiratory drive and hypercapnic response, irrespective of the amount of body fat. These data suggest the extension of leptin resistance to the respiratory centre.
Impact of Metaiodobenzylguanidine Scintigraphy on Assessing Response of High-Risk Neuroblastoma to Dose-Intensive Induction Chemotherapy
Authors: Brian H. Kushner, Samuel D.J. Yeh, Kim Kramer, Steven M. Larson, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2003)

The International Neuroblastoma Response Criteria (INRC) recommend, but do not make mandatory, metaiodobenzylguanidine (MIBG) scans. We present the first report on the effect of MIBG scans on the classification of response to dose-intensive induction therapy.After dose-intensive induction and before consolidative therapy, 162 Memorial Sloan-Kettering Cancer Center (MSKCC) patients with high-risk neuroblastoma (NB) had MIBG scans (99 with (131)I, 63 with (123)I), computed tomography, (99m)Tc-bone scan, bone marrow (BM) tests, and urine catecholamine measurements. Induction included high-dose cyclophosphamide (140 mg/kg) plus other agents and high-dose cisplatin (200 mg/m(2))/etoposide (600 mg/m(2)).In 90 patients treated with dose-intensive therapy from diagnosis at MSKCC, the use of MIBG scintigraphy increased the incomplete response numbers from 14 (15.5%) to 20 (22%), giving a complete remission/very good partial remission (CR/VGPR) rate of 78%. In 72 patients treated before referral to MSKCC for intensified therapy, MIBG findings changed the response classification of one patient; the CR/VGPR rate was 43%. MIBG scans showed no BM disease in 15 of 38 patients with histologically evident NB in BM but did show uptake consistent with BM involvement in five patients who had no NB observed in BM tests.With the less effective therapy consequent to the intensification of induction only after initial exposure to standard-dose chemotherapy, MIBG scintigraphy merely confirms the findings of other staging modalities for detection of relatively widespread residual NB. However, when dose-intensive therapy is initiated at diagnosis, the reliable achievement of major disease responses makes extensive BM testing and MIBG scintigraphy prerequisites for accurate determination of disease status.
A Direct Comparison of Intravascular Ultrasound and Quantitative Coronary Arteriography
Authors: B. Greg Brown
Journal: Circulation (2007)

everal established methods for the imaging of atherosclerosis (quantitative coronary arteriography [QCA], 1,2 carotid intima-medial thickness, 3,4 magnetic resonance imaging, 5 and intravascular ultrasound [IVUS]) 6,7 have been used in clinical trials to determine whether defined therapeutic interventions slow the rate of progression of plaque size or composition, or reduce severity of luminal obstruction, and whether change in these measures predicts in-trial or future cardiovascular (CV) events.The report by Berry et al 8 in this issue of Circulation, which compares simultaneously-obtained QCA measures of luminal obstruction with IVUS measures of plaque and luminal volume or percent plaque volume and their in-trial changes is a timely comparison between IVUS and QCA.The present editorial comment addresses the emerging evidence on the relative utility of measurements by these 2 techniques for use as surrogates for efficacy in clinical trials.
Effect of Nicotine Replacement Therapy on Agitation in Smokers With Schizophrenia: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: Michael H. Allen, Martin Debanné, Coralie Lazignac, Eric Adam, L. Miriam Dickinson, Cristian Damsa
Journal: American Journal of Psychiatry (2011)

The authors conducted a randomized, placebo-controlled study of nicotine replacement therapy for the reduction of agitation and aggression in smokers with schizophrenia.Participants were 40 smokers 18-65 years of age admitted to a psychiatric emergency service with a diagnosis of schizophrenia confirmed by the Mini International Neuropsychiatric Interview. Patients were screened for agitation with the excited component subscale of the Positive and Negative Syndrome Scale (PANSS) and for nicotine dependence with the Fagerström Test for Nicotine Dependence. A score of at least 14 on the PANSS excited component subscale and at least 6 on the Fagerström test were required for study eligibility. Participants in the nicotine replacement group received a 21-mg nicotine transdermal patch, and those in the placebo group were treated with a placebo patch. Participants received usual care with antipsychotics. The Agitated Behavior Scale and other agitation measures were administered at baseline and again at 4 and 24 hours.At baseline, participants were at least moderately agitated, and 28% reported aggressive behavior in the previous week. The mean Agitated Behavior Scale score for the nicotine replacement group was 33% lower at 4 hours and 23% lower at 24 hours than for the placebo group. Participants with lower levels of nicotine dependence responded better than those with higher levels of dependence.The drug-placebo difference in this study was similar to that obtained in trials of parenteral antipsychotics in similar populations. This finding suggests that in patients with schizophrenia, smoking status should be included in the assessment of agitation and nicotine replacement included in the treatment of those who are smokers.
Identifying genetic networks underlying myometrial transition to labor.
Authors: Nathan Salomonis, Nathalie Cotte, Alexander C Zambon, Katherine S Pollard, Karen Vranizan, Scott W Doniger, Gregory Dolganov, Bruce R Conklin
Journal: Genome biology (2005)

Early transition to labor remains a major cause of infant mortality, yet the causes are largely unknown. Although several marker genes have been identified, little is known about the underlying global gene expression patterns and pathways that orchestrate these striking changes.We performed a detailed time-course study of over 9,000 genes in mouse myometrium at defined physiological states: non-pregnant, mid-gestation, late gestation, and postpartum. This dataset allowed us to identify distinct patterns of gene expression that correspond to phases of myometrial 'quiescence', 'term activation', and 'postpartum involution'. Using recently developed functional mapping tools (HOPACH (hierarchical ordered partitioning and collapsing hybrid) and GenMAPP 2.0), we have identified new potential transcriptional regulatory gene networks mediating the transition from quiescence to term activation.These results implicate the myometrium as an essential regulator of endocrine hormone (cortisol and progesterone synthesis) and signaling pathways (cyclic AMP and cyclic GMP stimulation) that direct quiescence via the transcriptional upregulation of both novel and previously associated regulators. With term activation, we observe the upregulation of cytoskeletal remodeling mediators (intermediate filaments), cell junctions, transcriptional regulators, and the coordinate downregulation of negative control checkpoints of smooth muscle contractile signaling. This analysis provides new evidence of multiple parallel mechanisms of uterine contractile regulation and presents new putative targets for regulating myometrial transformation and contraction.
Palliative Care Programs Still Face Obstacles in Mainstream Cancer Care
Authors: S. Benowitz
Journal: JNCI Journal of the National Cancer Institute (2013)

accidently discovered a new form of extracellular membrane vesicles. “Examining biopsy tissue from glioblastoma patients from the operating room, we saw their cells were covered with vesicles that contained tumor RNA that was protected from rapid degradation in the bloodstream. When these glioblastoma vesicles were added to human brain endothelial cells, they started forming tubules before our eyes within a day. We had found a very potent mechanism of promoting tumor growth that we hadn’t even known existed,” said Breakefield. The Breakefield laboratory’s findings, published in the December 2008 Nature Cell Biology, raised new questions. Could they pick out glioblastoma extracellular vesicles in blood samples? Examining blood serum from 25 glioblastoma patients confirmed tumor vesicles in all patients by virtue of a glioblastoma-specific activating mutation for the epidermal growth factor
Differing Src Signaling Levels Have Distinct Outcomes in <i>Drosophila</i>
Authors: Marcos Vidal, Stephen Warner, Renee Read, Ross L. Cagan
Journal: Cancer Research (2007)

Abstract High levels of Src activity are found in a broad spectrum of cancers. The roles of Src and its negative regulator Csk have been extensively studied, although results have often proved contradictory or the relevance to whole organisms is unclear. In Drosophila, overexpression of either Src orthologue resulted in apoptotic cell death, but paradoxically, reducing dCsk activity led to over-proliferation and tissue overgrowth. Here, we show that in Drosophila epithelia in situ, the levels of Src signaling determine the cellular outcome of Src activation. Apoptotic cell death was triggered specifically at high Src signaling levels; lower levels directed antiapoptotic signals while promoting proliferation. Furthermore, our data indicate that expression of kinase-dead Src isoforms do not necessarily act as dominant-negative factors, but can instead increase Src pathway activity, most likely by titrating Csk activity away from endogenous Src. The importance of Src activity levels was emphasized when we examined oncogenic cooperation between Src and Ras: malignant overgrowth was observed specifically when high Src signaling levels were achieved. We propose a model in which low levels of Src signaling promote survival and proliferation during early stages of tumorigenesis, whereas strong Src signaling, coupled with antiapoptotic signals, directs invasive migration and metastasis during advanced tumor stages. [Cancer Res 2007;67(21):10278–85]
The BTB–zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions
Authors: Damian Kovalovsky, Olisambu U Uche, Sonia Eladad, Robin M Hobbs, Woelsung Yi, Eric Alonzo, Kevin Chua, Maggie Eidson, Hye-Jung Kim, Jin S Im, Pier Paolo Pandolfi, Derek B Sant'Angelo
Journal: Nature Immunology (2008)
31P magnetic resonance spectroscopy detects a functional abnormality in liver metabolism after acetaminophen poisoning
Authors: Ruth M. Dixon, Peter W. Angus, Bheeshma Rajagopalan, George K. Radda
Journal: Hepatology (1992)

Eighteen patients with acetaminophen poisoning were studied with 31P magnetic resonance spectroscopy to measure phosphorus-containing metabolites in their livers. The concentrations of all magnetic resonance—detectable metabolites fell in parallel with a decrease in the synthetic ability of the liver, indicated by the prothrombin time ratio (international normalized ratio). In particular, ATP fell to about 20% of its normal concentration in severely affected patients, as did the phosphodiester signal, which is thought to arise mainly from the endoplasmic reticulum in the liver. The correlation between ATP levels and international normalized ratio suggests that the international normalized ratio is a more accurate measure of the number of viable hepatocytes than are other biochemical tests. (HEPATOLOGY 1992;16:943–948.)
Results of a Pivotal Phase II Study of Brentuximab Vedotin for Patients With Relapsed or Refractory Hodgkin's Lymphoma
Authors: Anas Younes, Ajay K. Gopal, Scott E. Smith, Stephen M. Ansell, Joseph D. Rosenblatt, Kerry J. Savage, Radhakrishnan Ramchandren, Nancy L. Bartlett, Bruce D. Cheson, Sven de Vos, Andres Forero-Torres, Craig H. Moskowitz, Joseph M. Connors, Andreas Engert, Emily K. Larsen, Dana A. Kennedy, Eric L. Sievers, Robert Chen
Journal: Journal of Clinical Oncology (2012)

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. In phase I studies, brentuximab vedotin demonstrated significant activity with a favorable safety profile in patients with relapsed or refractory CD30-positive lymphomas.In this multinational, open-label, phase II study, the efficacy and safety of brentuximab vedotin were evaluated in patients with relapsed or refractory Hodgkin's lymphoma (HL) after autologous stem-cell transplantation (auto-SCT). Patients had histologically documented CD30-positive HL by central pathology review. A total of 102 patients were treated with brentuximab vedotin 1.8 mg/kg by intravenous infusion every 3 weeks. In the absence of disease progression or prohibitive toxicity, patients received a maximum of 16 cycles. The primary end point was the overall objective response rate (ORR) determined by an independent radiology review facility.The ORR was 75% with complete remission (CR) in 34% of patients. The median progression-free survival time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months. After a median observation time of more than 1.5 years, 31 patients were alive and free of documented progressive disease. The most common treatment-related adverse events were peripheral sensory neuropathy, nausea, fatigue, neutropenia, and diarrhea.The ADC brentuximab vedotin was associated with manageable toxicity and induced objective responses in 75% of patients with relapsed or refractory HL after auto-SCT. Durable CRs approaching 2 years were observed, supporting study in earlier lines of therapy.
GOLD COPD classification and prognostic pessimism regarding ICU admission
Authors: Andrea Collins, Andrew Walden, Robert Parker
Journal: Thorax (2011)

Incorporation of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of severity of expiratory airflow limitation in chronic obstructive pulmonary disease (COPD) into the recent National Institute for Health and Clinical Excellence (NICE) guidelines is welcome and sensible.1 Describing a forced expiratory volume in one second (FEV1) of 51% predicted as ‘mild disease’ fails to capture the loss of lung function and irreversible damage done. Recognition and optimal early management of COPD cannot be overemphasised to limit its long-term health …
BOTOXR delivery by iontophoresis
Authors: G.M. Kavanagh, C. Oh, K. Shams
Journal: British Journal of Dermatology (2004)

We report two patients with severe palmar hyperhidrosis who responded to BOTOX delivered not by injection, the usual method of delivery, but by iontophoresis. The Botulinum molecule has been considered too large for delivery into the skin this way. However, other large peptides, both non-ionic and cationic, have been delivered successfully by this method, so we suspected that BOTOX could in fact be iontophoresed. Our saline-controlled treatment of these two patients with a small iontophoresis unit (Iomed Phoresor II) allowed small volumes of standard BOTOX dilutions to be used, and demonstrates that iontophoresis can indeed deliver BOTOX successfully. This has important therapeutic potential for the large number of patients with focal hyperhidrosis. They may be spared painful injections, and in more severe cases, invasive surgery.