tbuckley/cabot-search huggingface dataset:
Guidelines on the use of oesophageal dilatation in clinical practice
Authors: S A Riley
Journal: Gut (2004)

Oesophageal dilators or bougies have been used since the Middle Ages. Early bougies were made of natural materials and were used to disimpact food boluses by pushing them “blindly” into the stomach. The technique of oesophageal dilatation has evolved considerably in recent years. A range of purpose built dilators is now available, and with present day diagnostic techniques it is possible to select a dilator and dilatation technique appropriate to the clinical setting.

The relatively low morbidity and mortality of oesophageal dilatation has encouraged its widespread use. Despite this wealth of clinical experience however, the practice of oesophageal dilatation has been subject to surprisingly few controlled studies. The purpose of these guidelines is to highlight areas of good practice and promote the use of standardised protocols within and between centres.

These guidelines have been produced to conform to the North of England evidence based guidelines development project.12 They are based on a Medline literature search using the search term “oesophageal dilatation” and on expert opinion and review. Although oesophageal dilatation may be performed during rigid oesophagoscopy and under radiological screening, this guidance relates primarily to oesophageal dilatation performed during flexible upper gastrointestinal endoscopy. Oesophageal dilatation in the paediatric population is considered outside the scope of these guidelines.

### 2.1 Categories of evidence

The strength of evidence used to formulate these guidelines was graded according to the following system:





The …
Are There Answers?
Authors: Louis C. Charland
Journal: The American Journal of Bioethics (2003)

The Question In an innovative discussion Jason Scott Robert and Francoise Baylis (2003) argue that “the creation of novel beings that are part human and part nonhuman animal is sufciently threatening to the social order that for many this is a sufcient reason to prohibit any crossing of species boundaries involving human beings.” The “hypothesis” they propose is that “the issue at the heart of the matter is the threat of moral confusion.” They also argue that we cannot resolve this moral confusion by turning to science and appealing to the notion of species identity. This is because “there is no one authoritative denition of species.” Consequently, there is “no consensus on what exactly is being breached with the creation of interspecies beings.” So how are we supposed to go about answering this question about cross-species transgression? Curiously, this intriguing interdisciplinary discussion might say more about the intractable scale and complexity of bioethical inquiry in this domain than it does about the specic question it sets out to address. It boldly raises all the right issues in all their interdisciplinary splendor. But at the same time it invites the question how this multiplicity of interdisciplinary premises and arguments is supposed to lead to an answer. Bioethical discussions of this sort seem to promise answers, even if they do not provide them; they raise questions that are presumed to have answers. Yet this particular discussion left me wondering whether there really are answers of the expected sort to be had. In this commentary I explore this methodological worry by discussing two of the article’s central themes: species identity and moral confusion.
Increased Erythrocyte Cation Permeability in Thalassemia and Conditions of Marrow Stress
Authors: J. S. Wiley
Journal: Journal of Clinical Investigation (1981)

Calcium and sodium permeability of erythrocytes from patients with untransfused α- or β- thalassemia major has been studied and compared to mature erythrocytes or control cells with comparable reticulocytosis. Isotopic Na+ influx was increased a mean fourfold greater than normals and threefold greater than reticulocyte rich control. Passive net leak of Na+ into thalassemic cells incubated with ouabain was also increased corresponding to their greater 22Na+ influx. Erythrocyte Na+ and K+ concentrations and cell water content per unit volume of cells were normal. Quantitation of active cation pumps in the cell membrane by the technique of [3H]ouabain binding showed a 2.6- to 9.9-fold increase above normal. Inward Ca2+ movement was studied in cells with absent Ca2+ pumping produced by depletion of either ATP or Mg2+-ions. Calcium uptake by ATP depleted thalassemic cells was increased 12-fold above normals and 3.6-fold above reticulocyte-rich controls. The Ca2+ uptake by Mg2+-depleted thalassemic cells was also increased above normal confirming that erythrocyte Ca2+ permeability is increased in this disease. Osmotic fragility measurements show that the surface area to volume ratio of thalassemic erythrocytes was increased by 15 to 25% above mature erythrocytes. The increased passive cation permeability of thalassemic erythrocytes cannot be explained by either reticulocytosis or an increased surface area to volume ratio of these cells. Moreover, erythrocyte Na+ and Ca2+ influxes in congenital dyserythropoietic anemia (CDA type 2) were increased 2- and 14-fold, respectively, above normal. The increased cation fluxes and cation pump numbers in thalassemic and congenital dyserythropoietic anemia erythrocytes are consistent with the hypothesis of membrane immaturity arising from rapid marrow transit times, a concept previously advanced to explain the persistence of i-antigen on these cells.
Variation in Evolutionary Processes at Different Codon Positions
Authors: L. Bofkin, N. Goldman
Journal: Molecular Biology and Evolution (2006)

Evolutionary studies commonly model single nucleotide substitutions and assume that they occur as independent draws from a unique probability distribution across the sequence studied. This assumption is violated for protein-coding sequences, and we consider modeling approaches where codon positions (CPs) are treated as separate categories of sites because within each category the assumption is more reasonable. Such "codon-position" models have been shown to explain the evolution of codon data better than homogenous models in previous studies. This paper examines the ways in which codon-position models outperform homogeneous models and characterizes the differences in estimates of model parameters across CPs. Using the PANDIT database of multiple species DNA sequence alignments, we quantify the differences in the evolutionary processes at the 3 CPs in a systematic and comprehensive manner, characterizing previously undescribed features of protein evolution. We relate our findings to the functional constraints imposed by the genetic code, protein function, and the types of mutation that cause synonymous and nonsynonymous codon changes. The results increase our understanding of selective constraints and could be incorporated into phylogenetic analyses or gene-finding techniques in the future. The methods used are extended to an overlapping reading frame data set, and we discover that overlapping reading frames do not necessarily cause more stringent evolutionary constraints.
Effect of nedocromil sodium and sodium cromoglycate against bronchoconstriction induced by inhaled adenosine 5'-monophosphate
Authors: GD Phillips, VL Scott, R Richards, ST Holgate
Journal: European Respiratory Journal (1989)

In this randomized, double-blind, placebo controlled study, the effect of prior inhalation of nebulized sodium cromoglycate (SCG) (7.3 +/- 0.6 mg) and nedocromil sodium (NED) (7.5 +/- 0.6 mg) was observed on adenosine 5'-monophosphate (AMP)-induced bronchoconstriction in 11 non-atopic asthmatic subjects. The geometric mean provocation doses of methacholine and AMP required to produce a 20% decrease in forced expiratory volume in one second (FEV1) (PD20FEV1) were 0.6 (0.1-18.8) and 5.1 (0.8-130.7) mumole respectively. The repeatability of the AMP challenge procedure for PD20FEV1 was within one doubling dose difference. SCG and NED, administered 30 min prior to bronchoprovocation with AMP, displaced the AMP dose-response curve to the right by 9.6 (1.5-41.6) (p less than 0.01) and 22.2 (3.7-89.1) (p less than 0.01)-fold, respectively, the difference between the two drugs being significant (p less than 0.05). There was a significant correlation (r = 0.7, p = 0.02) between the log dose ratios for PD20FEV1 for SCG and NED. We conclude that both SCG and NED protect against AMP-induced bronchoconstriction, NED being at least 2.3 (0.7-11.5)-fold more potent than SCG, and that they achieve this effect by a similar mechanism(s).
Simultaneous Assessment of Fractional and Coronary Flow Reserves in Cardiac Transplant Recipients
Authors: William F. Fearon, Mamoo Nakamura, David P. Lee, Mehrdad Rezaee, Randall H. Vagelos, Sharon A. Hunt, Peter J. Fitzgerald, Paul G. Yock, Alan C. Yeung
Journal: Circulation (2003)

The utility of measuring fractional flow reserve (FFR) to assess cardiac transplant arteriopathy has not been evaluated. Measuring coronary flow reserve (CFR) as well as FFR could add information about the microcirculation, but until recently, this has required two coronary wires. We evaluated a new method for simultaneously measuring FFR and CFR with a single wire to investigate transplant arteriopathy.In 53 cases of asymptomatic cardiac transplant recipients without angiographically significant coronary disease, FFR and thermodilution-derived CFR (CFRthermo) were measured simultaneously with the same coronary pressure wire in the left anterior descending artery and compared with volumetric intravascular ultrasound (IVUS) imaging. The average FFR was 0.88+/-0.07; in 75% of cases, the FFR was less than the normal threshold of 0.94; and in 15% of cases, the FFR was < or =0.80, the upper boundary of the gray zone of the ischemic threshold. There was a significant inverse correlation between FFR and IVUS-derived measures of plaque burden, including percent plaque volume (r=0.55, P<0.0001). The average CFRthermo was 2.5+/-1.2; in 47% of cases, CFRthermo was < or =2.0. In 14%, the FFR was normal (> or =0.94) and the CFR was abnormal (<2.0), suggesting predominant microcirculatory dysfunction.FFR correlates with IVUS findings and is abnormal in a significant proportion of asymptomatic cardiac transplant patients with normal angiograms. Simultaneous measurement of CFR with the same pressure wire, with the use of a novel coronary thermodilution technique, is feasible and adds information to the physiological evaluation of these patients.
The phantom array
Authors: Wayne A. Hershberger, J. Scott Jordan
Journal: Behavioral and Brain Sciences (1996)

The array seen when saccading across a point light source blinking in the dark is displaced in the direction of the saccade. This displacement reflects an abrupt shift of spatiotopic coordinates that precedes the actual eye movement. The extraretinal signal mediating this discrete shift appears to be an oculomotor reference signal, specifying intended eye orientation, that changes discretely before saccades.
An Exponential Core in the Heart of the Yeast Protein Interaction Network
Authors: José B. Pereira-Leal, Benjamin Audit, José M. Peregrin-Alvarez, Christos A. Ouzounis
Journal: Molecular Biology and Evolution (2004)

Protein interactions in the budding yeast have been shown to form a scale-free network, a feature of other organized networks such as bacterial and archaeal metabolism and the World Wide Web. Here, we study the connections established by yeast proteins and discover a preferential attachment between essential proteins. The essential-essential connections are long ranged and form a subnetwork where the giant component includes 97% of these proteins. Unexpectedly, this subnetwork displays an exponential connectivity distribution, in sharp contrast to the scale-free topology of the complete network. Furthermore, the wide phylogenetic extent of these core proteins and interactions provides evidence that they represent the ancestral state of the yeast protein interaction network. Finally, we propose that this core exponential network may represent a generic scaffold around which organism-specific and taxon-specific proteins and interactions coalesce.
Descriptive and Longitudinal Observations on the Relationship of Borderline Personality Disorder and Bipolar Disorder
Authors: John Gunderson
Journal: American Journal of Psychiatry (2006)

Objective: The purpose of this study was to test whether borderline personality disorder is a variant of bipolar disorder by examining the rates of co-occurrence in both disorders, the effects of co-occurrence on a longitudinal course, and whether the presence of either disorder confers the risk for new onsets of the other. Method: A prospective repeated-measures design with reliable independent diagnostic measures and 4 years of follow-up was used to assess 196 patients with borderline personality disorder and 433 patients with other personality disorders. Results: Patients with borderline personality disorder had a significantly higher co-occurrence of bipolar disorder (19.4%) than did patients with other personality disorders. However, this co-occurrence did not appear to affect the subsequent course of borderline personality disorder. Although only 8.2% of the borderline personality disorder patients developed new onsets of bipolar disorder, this rate was higher than in patients with other personality disorders. Patients with other personality disorders with co-occurring bipolar disorder generally had more new onsets of borderline personality disorder (25%) than did patients with other personality disorders without co-occurring bipolar disorder (10%). Conclusions: A modest association between borderline personality disorder and bipolar disorder is reported.
Scholastic Achievements of Childhood Leukemia Patients: A Nationwide, Register-Based Study
Authors: Arja H. Harila-Saari, Päivi M. Lähteenmäki, Eero Pukkala, Pentti Kyyrönen, Marjatta Lanning, Risto Sankila
Journal: Journal of Clinical Oncology (2007)

Purpose Studies concerning the scholastic achievement of survivors of childhood leukemia have yielded controversial results. We studied the school marks of childhood leukemia survivors in a register-based study. Patients and Methods Three hundred seventy-one patients with a diagnosis of leukemia before the age of 16 years who were born between 1974 and 1986 and alive on their 16th birthday were identified from the Finnish Cancer Registry. Five matched controls were sought for each patient from the Population Register Center of Finland. Information on the ninth-grade school report was obtained from Statistics Finland. The overall mark average and the marks (scale 4 to 10) for mother tongue, foreign language, mathematics, and physical education were compared between the patients and controls. Results The ninth-grade school report was obtained by 97.6% of the patients and 98.5% of the controls. The patients whose treatment included cranial irradiation had a lower overall mark average (mean difference, −0.24; 95% CI, −0.33 to −0.15) and lower marks for all assessed school subjects compared with their controls. Of the patients treated with chemotherapy alone, only the females with leukemia diagnosed before 7 years of age had lower school marks than their controls. The biggest difference was observed in the marks for foreign language among the irradiated females diagnosed at a young age (mean difference, −1.0; 95% CI, −1.25 to −0.74). Conclusion Leukemia treatment that includes cranial irradiation impairs scholastic achievement. It is noteworthy that treatment of leukemia with chemotherapy alone impairs school performance only in females diagnosed before school age.
Carbohydrate-specific signaling through the DC-SIGN signalosome tailors immunity to Mycobacterium tuberculosis, HIV-1 and Helicobacter pylori
Authors: Sonja I Gringhuis, Jeroen den Dunnen, Manja Litjens, Michiel van der Vlist, Teunis B H Geijtenbeek
Journal: Nature Immunology (2009)
Ultrasound and Doppler micro-imaging in a model of rheumatoid arthritis in mice
Authors: G Clavel, C Marchiol-Fournigault, G Renault, M-C Boissier, D Fradelizi, N Bessis
Journal: Annals of the Rheumatic Diseases (2008)

The evaluation of joints in arthritis using conventional ultrasonography is not really feasible in mice because of the small size of the animal. However, compared with classical analysis (clinical and histological examination) it is a non-invasive method that allows follow-up of the same animal throughout the whole experiment. Moreover, power Doppler allows the study of blood flow that reflects inflammatory activity within the synovium of arthritic joints. Our aim was to determine whether ultrasonography analysis could accurately detect arthritis lesions in a mouse model of rheumatoid arthritis, namely collagen-induced arthritis.Collagen-induced arthritis was induced in 28 mice by immunising with collagen type II. Every week for 8 weeks, ultrasonography and Doppler analysis were performed on knees and ankles of all mice using the ultrasound biomicroscope (UBM), which is particularly dedicated to studying the mouse. Clinical and histological evaluations were performed as usual.We established a semiquantitative analysis by setting an UBM scoring. UBM grades were correlated to clinical and histological scores of arthritis. Vascularisation within the synovium could be estimated by power Doppler analysis and a semiquantitative vascularisation scale was established, which allowed us to show a good correlation between vascularisation scores and histological or clinical scores of arthritis.This is one of the first studies that shows it is possible to visualise a selected set of joints in a small animal using UBM analysis. It provides new perspectives in evaluating experimental models of rheumatoid arthritis and other joint diseases.
Identification of leukemia-associated inhibitory activity as acidic isoferritins. A regulatory role for acidic isoferritins in the production of granulocytes and macrophages.
Authors: H E Broxmeyer, J Bognacki, M H Dorner, M de Sousa
Journal: The Journal of Experimental Medicine (1981)

Acidic isoferritins have been identified as leukemia-associated inhibitory activity (LIA), which suppresses colony and cluster formation of colony-forming unit-granulocyte macrophages from normal donors but not from patients with leukemia. LIA was detected in all ferritin preparations tested, including ferritin isolated from normal heart, spleen, liver, and placental tissues, and from the spleens of patients with chronic myelogenous leukemia and Hodgkin's disease. Purified preparations of LIA were composed almost entirely of acidic isoferritins, as determined by immunoassay, radioimmunoassay, and isoelectric focusing. The inhibitory activity in the LIA and ferritin samples was inactivated by a battery of antisera specific for ferritin, including those prepared against acidic isoferritins from normal heart and spleen tissues from patients with Hodgkin's disease, and those previously absorbed with basic isoferritins. Antisera absorbed with acidic isoferritins did not inactivate the inhibitory activity. Separation of LIA and chronic myelogenous leukemia and normal spleen ferritin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing confirmed that the regions of peak inhibitory activity corresponded in each to an apparent molecular weight of approximately 550,000 and to a pI value of 4.7. Similar physicochemical characteristics included inactivation by methods that dissociate ferritin molecules into subunits and by treatment with trypsin, chymotrypsin, pronase, and periodate. The purified preparations were extremely stable to heat treatment. The glycoprotein nature of the inhibitory activity was substantiated because it bound to concanavalin A-Sepharose and was eluted off by alpha-methyl mannose. Inhibitory activity of the activity of the acidic isoferritins was detected at concentrations as low as 10(-17)-10(-19) M and iron saturation did not appear to be necessary for its action. These results implicate acidic isoferritins in the regulation of normal myelopoiesis and suggest a role for them in the progression of leukemia.
Dynamic interactions and mutual synchronization of sinoatrial node pacemaker cells. A mathematical model.
Authors: D C Michaels, E P Matyas, J Jalife
Journal: Circulation Research (1986)

Dynamic interactions and mutual entrainment of coupled sinoatrial pacemaker cells with different intrinsic frequencies were investigated using a computerized mathematical model. Transmembrane potentials were simulated using equations of individual membrane currents based on voltage clamp data for the sinoatrial node. The intrinsic frequency of a given cell was altered by applying bias hyperpolarizing current, or by changing the amount of slow inward current. Cells were coupled through simple ohmic resistances to form linear arrays of two or more cells. Simulations closely reproduced previous experimental work showing that the mutual interactions between pacemakers are mediated electrotonically and show phase dependence. Results from the present simulations provide an explanation for the ionic basis of these phase-dependent interactions. In addition, it is demonstrated that the mutual entrainment of coupled pacemakers can lead to their coordinated behavior (synchronization). Two pacemaker cells can synchronize at simple harmonic (i.e., 1:1, 2:1, etc.) or more complex ratios (3:2, 5:3, etc.), depending on the differences in intrinsic frequencies and the degree of electrical coupling between cells. Simulations using larger numbers of linearly connected cells yielded various patterns of pacemaker activity including 2:1 sinoatrial block and complex dysrhythmic activity. The overall results may be used to predict higher order interactions of thousands of cells comprising the sinus node. Under such a scheme, synchronization occurs not by the conducted influence of a dominant pacemaker cell, but by the mutual "democratic" interaction of individual pacemaker cells.
Detection of Telomerase Expression in Mediastinal Lymph Nodes of Patients with Lung Cancer
Authors: Michael B. Wallace, Mark Block, Brenda J. Hoffman, Robert H. Hawes, Gerard Silvestri, Carolyn E. Reed, Michael Mitas, James Ravenel, Mostafa Fraig, Scott Miller, Edward T. Jones, Alice Boylan
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Mediastinal lymph nodes are the most common site of tumor spread in non-small cell lung cancer (NSCLC). We hypothesized that micrometastatic disease could be detected by reverse transcription-polymerase chain reaction (RT-PCR) for expression of human telomerase reverse transcriptase (hTERT) in mediastinal lymph nodes and that a minimally invasive technique (endoscopic ultrasound-guided fine-needle aspiration [EUS-FNA]) is capable of sampling lymph nodes for PCR analysis without surgery. Mediastinal lymph nodes were sampled with EUS-FNA in patients with NSCLC and negative control subjects undergoing EUS for benign disease. Total RNA was harvested from samples, and RT-PCR was performed to detect telomerase gene expression. RNA was available from 87 of 100 lymph node aspirates from 39 patients with NSCLC and from 12 negative control patients. hTERT was expressed in 0 of 14 negative control lymph nodes in 18 of 57 pathologically negative lymph nodes from cancer patients and in 10 of 16 pathologically positive lymph nodes (p < 0.05). Five of 18 (28%) patients with no pathologically evident mediastinal disease expressed telomerase in at least one lymph node. Minimally invasive EUS-FNA with RT-PCR is capable of detecting expression of cancer specific mRNA in lymph nodes. Approximately one-third of pathologically negative mediastinal lymph nodes in NSCLC patients express hTERT mRNA. The clinical significance of this observation is yet to be determined.