tbuckley/cabot-search huggingface dataset:
Modification of Ochsner and Mahorner Test for Patency of Deep Veins of Calf
Authors: J. R. Belcher
Journal: BMJ (1946)

MEICA JOUINAL etc.) ; and as a stimulant in all cases of indolent wounds.In the surgical and therapeutical clinics of the Academy Profs.H. H. Vlados and V. I. Kazansky have made over 700 injections of colloidal infusin.Patients have proved able to withstand large doses of the solution, and its value as a substitute and a stimu- laint has been proved.
5-hydroxytryptamine and neurotransmitter release in canine blood vessels. Inhibition by low and augmentation by high concentrations.
Authors: M A McGrath
Journal: Circulation Research (1977)

Experiments were designed to determine the effect of 5-hydroxytryptamine on adrenergic neurotransmission in blood vessels.Strips from canine saphenous veins and tibial arteries were incubated in norepinephrine|7-3 H] and mounted for supervision and isometric tension recording.The superfusate was collected for estimation of total radioactivity and for column chromatographic separation of norepinephrine[7-3 H] and its metabolites.5-Hydroxytryptamine (5-HT), 10 8 M and 10~7 M, inhibited the increase in smooth muscle tension and the release of norepinephrine|7-3 H] caused by transmural electric stimulation of the sympathetic nerve endings.By contrast, the increase in tension caused by direct stimulation of the smooth muscle with norepinephrine was either unchanged or augmented.In addition, 5-HT augmented the increase in tension with tyramine but did not affect the release of radiolabeled compounds by this substance.In unstimulated preparations low concentrations of 5-HT (10~7 M) caused contraction but did not affect the release of norepinephrine[7-3 H].With a higher concentration (10~5 M) the release of neurotransmitter was markedly increased.This response was inhibited by cocaine.Whereas 5-HT-induced contractions were inhibited by phentolamine and methysergide, these antagonists had no effect on its inhibitory action at the sympathetic nerve ending.Hence, low concentrations of 5-HT depress sympathetic tone by inhibiting the release of transmitter during nerve depolarization.At higher concentrations 5-HT has a direct excitatory effect on vascular smooth muscle together with an indirect effect which involves the uptake of 5-HT into the sympathetic nerve ending via the cocaine-sensitive mechanism and the release of norepinephrine.
Tumour necrosis factor and lymphotoxin A polymorphisms and lung function in smokers
Authors: G. Tanaka, A. J. Sandford, K. Burkett, J. E. Connett, N. R. Anthonisen, P. D. Paré, J-Q. He
Journal: European Respiratory Journal (2006)

Genetic variants in the tumour necrosis factor ( TNF ) gene have been investigated in chronic obstructive pulmonary disease (COPD). However, there are many instances of nonreplication of these associations due to insufficient power or other factors. In this study, a large number of subjects were examined to elucidate whether genetic variations of TNF and/or lymphotoxin A ( LTA ), which is clustered with TNF , are associated with variations in lung function among smokers. The present authors designed two nested case–control studies in the National Heart, Lung, and Blood Institute Lung Health Study (LHS), which enrolled 5,887 smokers. The first design included continuous smokers who had the fastest (n = 279) and the slowest (n = 304) decline of lung function during the 5-yr follow-up period, and the second included the subjects who had the lowest (n = 533) and the highest (n = 532) post-bronchodilator % predicted forced expiratory volume in one second at the start of the LHS. Within the TNF and LTA region, 10 tagging single-nucleotide polymorphisms were selected and genotyped. Unlike the previous associations between TNF -308 and COPD in Asians, the current study found no association between either of the two phenotypes and the LTA and TNF polymorphisms. In conclusion, these results support the findings of previous studies in late-onset chronic obstructive pulmonary disease in Caucasian populations.
A Mouse to Human Search for Plasma Proteome Changes Associated with Pancreatic Tumor Development
Authors: Vitor M Faca, Kenneth S Song, Hong Wang, Qing Zhang, Alexei L Krasnoselsky, Lisa F Newcomb, Ruben R Plentz, Sushma Gurumurthy, Mark S Redston, Sharon J Pitteri, Sandra R Pereira-Faca, Renee C Ireton, Hiroyuki Katayama, Veronika Glukhova, Douglas Phanstiel, Dean E Brenner, Michelle A Anderson, David Misek, Nathalie Scholler, Nicole D Urban, Matt J Barnett, Cim Edelstein, Gary E Goodman, Mark D Thornquist, Martin W McIntosh, Ronald A DePinho, Nabeel Bardeesy, Samir M Hanash
Journal: PLoS Medicine (2008)

Background The complexity and heterogeneity of the human plasma proteome have presented significant challenges in the identification of protein changes associated with tumor development. Refined genetically engineered mouse (GEM) models of human cancer have been shown to faithfully recapitulate the molecular, biological, and clinical features of human disease. Here, we sought to exploit the merits of a well-characterized GEM model of pancreatic cancer to determine whether proteomics technologies allow identification of protein changes associated with tumor development and whether such changes are relevant to human pancreatic cancer. Methods and Findings Plasma was sampled from mice at early and advanced stages of tumor development and from matched controls. Using a proteomic approach based on extensive protein fractionation, we confidently identified 1,442 proteins that were distributed across seven orders of magnitude of abundance in plasma. Analysis of proteins chosen on the basis of increased levels in plasma from tumor-bearing mice and corroborating protein or RNA expression in tissue documented concordance in the blood from 30 newly diagnosed patients with pancreatic cancer relative to 30 control specimens. A panel of five proteins selected on the basis of their increased level at an early stage of tumor development in the mouse was tested in a blinded study in 26 humans from the CARET (Carotene and Retinol Efficacy Trial) cohort. The panel discriminated pancreatic cancer cases from matched controls in blood specimens obtained between 7 and 13 mo prior to the development of symptoms and clinical diagnosis of pancreatic cancer. Conclusions Our findings indicate that GEM models of cancer, in combination with in-depth proteomic analysis, provide a useful strategy to identify candidate markers applicable to human cancer with potential utility for early detection.
Bronchial cartilage in chronic bronchitis
Authors: M. K. Tandon, A. H. Campbell
Journal: Thorax (1969)

An examination has been made of the amount of bronchial cartilage in the subsegmental bronchi of nine chronic bronchitics and seven controls. The axial pathway in four or five representative bronchopulmonary segments were carefully dissected in each lung. In each segment the mean extent of cartilage arranged circumferentially in the walls of the bronchi was significantly less in the chronic bronchitic patient than in the controls. Of the 42 specimens from the various bronchopulmonary segments of the controls, the cartilage was arranged circumferentially to the fifth generation or further in 33, but extended this far in only 14 of the 50 specimens from the chronic bronchitics. Using certain defined criteria, deficiency of cartilage was found in 25 of 50 specimens from 11 lungs of the chronic bronchitics and in only one of 42 specimens from nine control lungs. There was a negative correlation between the degree of bronchial gland enlargement, as measured by the gland/wall ratio, and the average extent of circumferentially arranged cartilage along the bronchi (r=−0·8, p&lt;0·01). Similarly, the number of bronchopulmonary segments affected increased and the average extent of circumferentially arranged cartilage decreased with increase in severity of the bronchitis. We think that the deficiency of bronchial cartilage in chronic bronchitics would favour collapse of the affected bronchi during forceful expiration or cough.
Greater epitope recognition of shrimp allergens by children than by adults suggests that shrimp sensitization decreases with age
Authors: Rosalía Ayuso, Silvia Sánchez-Garcia, Jing Lin, Zhiyan Fu, María Dolores Ibáñez, Teresa Carrillo, Carlos Blanco, Marina Goldis, Ludmila Bardina, Joaquín Sastre, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2010)
Guidelines for the management of inflammatory bowel disease in adults
Authors: C. Mowat, A. Cole, A. Windsor, T. Ahmad, I. Arnott, R. Driscoll, S. Mitton, T. Orchard, M. Rutter, L. Younge, C. Lees, G.-t. Ho, J. Satsangi, S. Bloom
Journal: Gut (2011)

The management of inflammatory bowel disease represents a key component of clinical practice for members of the British Society of Gastroenterology (BSG). There has been considerable progress in management strategies affecting all aspects of clinical care since the publication of previous BSG guidelines in 2004, necessitating the present revision. Key components of the present document worthy of attention as having been subject to re-assessment, and revision, and having direct impact on practice include: The data generated by the nationwide audits of inflammatory bowel disease (IBD) management in the UK in 2006, and 2008. The publication of ‘Quality Care: service standards for the healthcare of people with IBD’ in 2009. The introduction of the Montreal classification for Crohn9s disease and ulcerative colitis. The revision of recommendations for the use of immunosuppressive therapy. The detailed analysis, guidelines and recommendations for the safe and appropriate use of biological therapies in Crohn9s disease and ulcerative colitis. The reassessment of the role of surgery in disease management, with emphasis on the importance of multi-disciplinary decision-making in complex cases. The availablity of new data on the role of reconstructive surgery in ulcerative colitis. The cross-referencing to revised guidelines for colonoscopic surveillance, for the management of metabolic bone disease, and for the care of children with inflammatory bowel disease. Use of the BSG discussion forum available on the BSG website to enable ongoing feedback on the published document http://www.bsg.org.uk/forum (accessed Oct 2010). The present document is intended primarily for the use of clinicians in the United Kingdom, and serves to replace the previous BSG guidelines in IBD, while complementing recent consensus statements published by the European Crohn9s and Colitis Organisation (ECCO) https://www.ecco-ibd.eu/index.php (accessed Oct 2010).
A causal relationship between LTP and learning? Has the question been answered by genetic approaches?
Authors: Robert Gerlai
Journal: Behavioral and Brain Sciences (1997)

Gene targeting has generated a great deal of data on the molecular mechanisms of long-term potentiation and its potential role in learning and memory. However, the interpretation of some results has been questioned. Compensatory mechanisms and the contribution of genetic background may make it difficult to unequivocally prove the existence of a causal (genetic) link between LTP and learning.
Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate
Authors: G. Gasparini, R. Sarmiento, S. Amici, R. Longo, D. Gattuso, M. Zancan, M. Gion
Journal: Annals of Oncology (2005)

Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer.Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR.At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment.The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.
Reducing Treatment Decision Conflict Difficulties in Breast Cancer Surgery: A Randomized Controlled Trial
Authors: Wendy W.T. Lam, Miranda Chan, Amy Or, Ava Kwong, Dacita Suen, Richard Fielding
Journal: Journal of Clinical Oncology (2013)

Purpose Breast cancer (BC) decision aid (DA) randomized studies are limited to DA use in consultations among Western populations and for primary surgery. Their effectiveness beyond consultations, for reconstructive surgery and in other populations, has not been evaluated. We developed a DA administered after consultation for Chinese women deciding on BC surgery and, where relevant, immediate breast reconstruction, which was evaluated in this randomized controlled trial (RCT). Patients and Methods Overall, 276 women considering BC surgery for early-stage BC were randomly assigned to receive a DA (take-home booklet) or the standard information booklet (control condition) after the initial consultation, wherein surgeons disclosed the diagnosis and discussed treatment options with patients. Using block random assignment by week, 138 women were assigned to the DA arm and 138 to the control arm. Participants completed interview-based questionnaires 1 week after consultation and then 1, 4, and 10 months after surgery. Primary outcome measures were decisional conflict, decision-making difficulties, BC knowledge 1 week after consultation, and decision regret 1 month after surgery. Secondary outcome measures were treatment decision, decision regret 4 and 10 months after surgery, and postsurgical anxiety and depression. Results The DA group reported significantly lower decisional conflict scores 1 week after consultation (P = .016) compared with women in the control arm. Women receiving the DA had significantly lower decision regret scores 4 (P = .026) and 10 months (P = .014) after surgery and lower depression scores 10 months after surgery (P = .001). Conclusion This RCT demonstrated DAs may benefit Chinese patients in Hong Kong by reducing decisional conflict and subsequent regret and enhance clinical services for this population.
Inhibition of Tumor Necrosis Factor-α Improves Postischemic Recovery of Hypertrophied Hearts
Authors: C Stamm, I Friehs, D B Cowan, A M Moran, H Cao-Danh, L F Duebener, P J del Nido, F X McGowan
Journal: Circulation (2001)

Tumor necrosis factor (TNF)-alpha has been implicated in the pathogenesis of heart failure and ischemia-reperfusion injury. Effects of TNF-alpha are initiated by membrane receptors coupled to sphingomyelinase signaling and include altered metabolism and calcium cycling, contractile dysfunction, and cell death. We postulate that pressure-overload hypertrophy results in increased myocardial TNF-alpha expression and that it contributes to decreased contractility in hypertrophied infant hearts subjected to ischemia-reperfusion.Neonatal rabbits underwent aortic banding to induce LV hypertrophy. Myocardial TNF-alpha protein expression increased progressively with LV hypertrophy. Serum TNF-alpha was detected only after the onset of heart failure. Before onset of ventricular dilatation and heart failure (determined by serial echocardiograms), hearts from aortic banded and age-matched control rabbits were perfused in the Langendorff mode and subjected to 45 minutes of ischemia and 30 minutes of reperfusion. Postischemic recovery was impaired in hypertrophied hearts, but addition of neutralizing anti-rabbit TNF-alpha antibody to cardioplegia and perfusate solutions restored postischemic function. This effect was mimicked by treatment with the ceramidase inhibitor N-oleoyl ethanolamine. TNF-alpha inhibition also was associated with faster postischemic recovery of phosphocreatine, ATP, and pH as assessed by (31)P nuclear magnetic resonance spectroscopy. Intracellular calcium handling, measured by Rhod 2 spectrofluorometry, demonstrated lower diastolic calcium levels and higher systolic calcium transients in anti-TNF-alpha treated hearts.TNF-alpha is expressed in myocardium during compensated pressure-overload hypertrophy and contributes to postischemic myocardial dysfunction. Inhibition of TNF-alpha signaling significantly improves postischemic contractile function, myocardial energetics, and intracellular calcium handling.
Modulation of Lymphocyte Regulation for Cancer Therapy: A Phase II Trial of Tremelimumab in Advanced Gastric and Esophageal Adenocarcinoma
Authors: Christy Ralph, Eyad Elkord, Deborah J. Burt, Jackie F. O'Dwyer, Eric B. Austin, Peter L. Stern, Robert E. Hawkins, Fiona C. Thistlethwaite
Journal: Clinical Cancer Research (2010)

Cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T-cell activation, is targeted by the antibody tremelimumab to release potentially useful antitumor activity.This phase II trial investigated tremelimumab as a second-line treatment for patients with metastatic gastric and esophageal adenocarcinomas. Tremelimumab was given every 3 months until symptomatic disease progression. Safety, clinical efficacy, and immunologic activity were evaluated.Eighteen patients received tremelimumab. Most drug-related toxicity was mild; however, there was a single death due to bowel perforation that complicated colitis. Four patients had stable disease with clinical benefit; one patient achieved a partial response after eight cycles (25.4 months) and remains well on study at 32.7 months. Markers of regulatory phenotype, forkhead box protein 3 and CTLA4, doubled transiently in CD4(+)CD25(high) lymphocytes in the first month after tremelimumab before returning to baseline. In contrast, CTLA4 increased in CD4(+)CD25(low/negative) lymphocytes throughout the cycle of treatment. De novo proliferative responses to tumor-associated antigens 5T4 (8 of 18 patients) and carcinoembryonic antigen (5 of 13) were detected. Patients with a posttreatment carcinoembryonic antigen proliferative response had median survival of 17.1 months compared with 4.7 months for nonresponders (P = 0.004). Baseline interleukin-2 release after T-cell activation was higher in patients with clinical benefit and toxicity.Despite the disappointing response rate of tremelimumab, one patient had a remarkably durable benefit for this poor-prognosis disease. In vitro evidence of enhanced proliferative responses to relevant tumor-associated antigens suggests that combining CTLA4 blockade with antigen-targeted therapy may warrant further investigation.
The role of vasoactive agents in the resuscitation of microvascular perfusion and tissue oxygenation in critically ill patients
Authors: E. Christiaan Boerma, Can Ince
Journal: Intensive Care Medicine (2010)

The clinical use of vasoactive drugs is not only intended to improve systemic hemodynamic variables, but ultimately to attenuate derangements in organ perfusion and oxygenation during shock. This review aims (1) to discuss basic physiology with respect to manipulating vascular tone and its effect on the microcirculation, and (2) to provide an overview of available clinical data on the relation between vasoactive drugs and organ perfusion, with specific attention paid to recent developments that have enabled direct in vivo observation of the microcirculation and concepts that have originated from it.A MedLine search was conducted for clinical articles in the English language over the last 15 years pertainig to shock, sepsis, organ failure, or critically ill patients in combination with vasoactive drugs and specific variables of organ perfusion/oxygenation (e.g., tonometry, indocyanine clearance, laser Doppler, and sidestream dark field imaging).Eighty original papers evaluating the specific relationship between organ perfusion/oxygenation and the use of vasoactive drugs were identified and are discussed in light of physiological theory of vasomotor tone.Solid clinical data in support of the idea that increasing blood pressure in shock improves microcirculatory perfusion/oxygenation seem to be lacking, and such a concept might not be in line with physiological theory of microcirculation as a low-pressure vascular compartment. In septic shock no beneficial effect on microcirculatory perfusion above a mean arterial pressure of 65 mmHg has been reported, but a wide range in inter-individual effect seems to exist. Whether improvement of microcirculatory perfusion is associated with better patient outcome remains to be elucidated.
Validation of a Pretransplant Risk Score for New-Onset Diabetes After Kidney Transplantation
Authors: Harini A. Chakkera, Yu-Hui Chang, Asad Ayub, Thomas A. Gonwa, E. Jennifer Weil, William C. Knowler
Journal: Diabetes Care (2013)

Identification of patients at high risk for new-onset diabetes after kidney transplantation (NODAT) will facilitate clinical trials for its prevention.We previously described a pretransplant predictive risk model for NODAT using seven pretransplant variables (age, planned use of maintenance corticosteroids, prescription for gout medicine, BMI, fasting glucose, fasting triglycerides, and family history of diabetes). We have now applied the initial model to a cohort of 474 transplant recipients from another center for validation. We performed two analyses in the validation cohort. The first was a standard model with variables derived from the original study. The second was a summary score model, in which the sum of dichotomized variables (all the variables dichotomized at clinically relevant cut points) was used to categorize, individuals into low (0-1), intermediate (2, 3), or high (4-7) risk groups. We also conducted a combined database analyses, merging the initial and validation cohorts (n=792) to obtain better estimates for a prediction equation.Although the frequency of several risk factors differed significantly between the two cohorts, the models performed similarly in each cohort. Using the summary score model, incidences of NODAT in low-risk, medium-risk, and high-risk groups in the initial cohort were 12, 29, and 56%, and in the validation cohort incidences were 11, 29, and 51%.A pretransplant model for NODAT, including many type 2 diabetes risk factors, predicted NODAT in the validation cohort.