tbuckley/cabot-search huggingface dataset:
Response to Kirkman and Juneja and Lorber
Authors: Abbas E. Kitabchi
Journal: Diabetes Care (2001)

Drs. Kirkman and Juneja (1) are correct in pointing out the discrepancies between the text and the algorithm figures for post hyperglycemic crises management in our articles on hyperglycemic crises (2,3). We regret the confusion surrounding this issue and have corrected this omission in Figs. 1 and 2, as described below.

As stated in the text, as soon as the patient is able to tolerate fluids and/or meals, we recommend treatment with a multidose regimen of short- and intermediate/long–acting insulin after resolution of the hyperglycemic crisis. To maintain adequate plasma insulin levels and prevent recurrence of diabetic ketoacidosis (DKA) and/or hyperglycemia, subcutaneous (SC) insulin should be given 1–2 h before the insulin infusion is discontinued.

After the resolution of DKA or hyperosmolar hyperglycemic state (HHS), some patients may be unable to take oral nourishment. While NPO (not eating), they should receive intravenous (IV) insulin infusion or be temporarily treated every 4 h with SC regular insulin based on blood glucose levels. SC regular insulin is given in 5-unit increments …
Snuffing out the cigarette habit: how about another source of nicotine?
Authors: Elizabeth Rasche González
Journal: JAMA (1980)

Nicotine is well known for its addictive properties. The exhilarating or calmative C<sub>10</sub>H<sub>14</sub>N<sub>2</sub>"high" that many cigarette users crave may help to explain why some of them will do anything to get out of a respiratory intensive care unit so as to resume puffing. People who have no comprehension of such suicidal behavior probably have never been smokers. But more and more investigators are recognizing the grip of the habit and are helping incorrigible tobacco junkies to maintain their blood nicotine levels while salvaging their lungs. The use of nicotinecontaining chewing gum, for instance, has a respectable history. Now a report in<i>The Lancet</i>(1:474-475, 1980) suggests that taking snuff (pulverized chewing tobacco) through the nose may provide a reasonable alternative to smoking. The authors, M. A. H. Russell, M. J. Jarvis, and C. Feyerabend of the Addiction Research Unit, Institute of Psychiatry, and the
Stimulation of integrin-mediated adhesion of T lymphocytes and monocytes: two mechanisms with divergent biological consequences.
Authors: R J Faull, N L Kovach, J M Harlan, M H Ginsberg
Journal: The Journal of Experimental Medicine (1994)

We show that the adhesion of T lymphoid cells to immobilized fibronectin can be increased by two distinct mechanisms. The first is by increasing the affinity of the fibronectin receptor/ligand interaction using the anti-beta 1 integrin monoclonal antibody 8A2. The second is by treating the cells with phorbol 12-myristate 13-acetate (PMA), which alters events that occur after receptor occupancy (e.g., cell spreading) without affecting receptor affinity. The effects of these two mechanisms on adhesion in the presence of physiological concentrations of soluble fibronectin suggest that they have different biological consequences. Under these conditions, the net effect of increasing the affinity of the fibronectin receptors is to decrease cell adhesion, whereas the increase in adhesion induced by PMA is unaffected. This suggests that the high affinity receptors are not primarily available for cell adhesion under these circumstances, and that they have an alternative function. We further show that high affinity binding of soluble fibronectin can be induced by either differentiation of the monocytic cell line THP-1 or by cross-linking the T cell receptor complexes on the T lymphoid cell line HUT-78. The differentiated monocytic cells express two populations of fibronectin receptors: a minority in a high affinity state, and the majority in a low affinity state. Thus they will both continue to adhere in the presence of physiological concentrations of soluble fibronectin and bind significant amounts of soluble fibronectin at the cell surface.
Book: Evidence Based Gastroenterology and Hepatology
Authors: H. F Hammer
Journal: BMJ (2000)

Eds John McDonald, Brian Feagan, Andrew Burroughs BMJ Books, £65, pp 572 ISBN 0 7279 1182 1 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> ![Graphic][4]</img> The purpose of evidence based medicine is to help doctors to keep up with the expanding scientific basis of medicine and to apply it to individual patients. In this regard Evidence Based Gastroenterology and Hepatology clearly addresses a need, especially for those who need to be at the cutting edge of medical sciences, such as scientists, teachers, … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Effect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trial
Authors: K. Johansson, M. Neovius, Y. T. Lagerros, R. Harlid, S. Rossner, F. Granath, E. Hemmingsson
Journal: BMJ (2009)

To assess the effect of weight loss induced by a very low energy diet on moderate and severe obstructive sleep apnoea in obese men. Design Single centre, two arm, parallel, randomised, controlled, open label trial. Blocked randomisation procedure used for treatment allocation. Setting Outpatient obesity clinic in a university hospital in Stockholm, Sweden. Participants 63 obese men (body mass index 30-40, age 30-65 years) with moderate to severe obstructive sleep apnoea (apnoea-hypopnoea index (AHI) >or=15), treated with continuous positive airway pressure.The intervention group received a liquid very low energy diet (2.3 MJ/day) for seven weeks to promote weight loss, followed by two weeks of gradual introduction of normal food, reaching 6.3 MJ/day at week 9. The control group adhered to their usual diet during the nine weeks of follow-up.AHI, the major disease severity index for obstructive sleep apnoea. Data from all randomised patients were included in an intention to treat analysis (baseline carried forward for missing data). Results Of the 63 eligible patients, 30 were randomised to intervention and 33 to control. Two patients in the control group were dissatisfied with allocation and immediately discontinued. All other patients completed the trial. Both groups had a mean AHI of 37 events/h (SD 15) at baseline. At week 9, the intervention group's mean body weight was 20 kg (95% confidence interval 18 to 21) lower than that of the control group, while its mean AHI was 23 events/h (15 to 30) lower. In the intervention group, five of 30 (17%) were disease free after the energy restricted diet (AHI <5), with 15 of 30 (50%) having mild disease (AHI 5-14.9), whereas the AHI of all patients in the control group except one remained at 15 or higher. In a subgroup analysis of the intervention group, baseline AHI significantly modified the effectiveness of treatment, with a greater improvement in AHI in patients with severe obstructive sleep apnoea (AHI >30) at baseline compared with those with moderate (AHI 15-30) sleep apnoea (AHI -38 v -12, P<0.001), despite similar weight loss (-19.2 v -18.2 kg, P=0.55). Conclusion Treatment with a low energy diet improved obstructive sleep apnoea in obese men, with the greatest effect in patients with severe disease. Long term treatment studies are needed to validate weight loss as a primary treatment strategy for obstructive sleep apnoea.Current Controlled Trials ISRCTN70090382.
Effect of Nicotinic Acid on the Incorporation of Radiocarbon into Cholesterol
Authors: JOSEPH M. MERRILL
Journal: Circulation Research (1958)

Nicotinic acid when fed to rats as 0.8 per cent of their diet caused an 83 per cent increase in radioactivity of liver cholesterol-digitonin precipitate. In vitro studies using rat liver slices indicated that nicotinic acid increased the incorporation of radiocarbon into cholesterol by 46 per cent.
Evidence for Molecular Differences in Prostate Cancer between African American and Caucasian Men
Authors: Francesca Khani, Juan Miguel Mosquera, Kyung Park, Mirjam Blattner, Catherine O'Reilly, Theresa Y. MacDonald, Zhengming Chen, Abhishek Srivastava, Ashutosh K. Tewari, Christopher E. Barbieri, Mark A. Rubin, Brian D. Robinson
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The aim of this study was to compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men. Experimental design: Dominant tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared with 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing. Results: ERG rearrangement was identified in 48 of 113 tumors (42.5%) in CaM and 29 of 105 tumors (27.6%) in AAM (P = 0.024). PTEN deletion was seen in 19 of 96 tumors (19.8%) in CaM and 7 of 101 tumors (6.9%) in AAM (P = 0.011). SPINK1 overexpression was present in 9 of 110 tumors (8.2%) in CaM and 25 of 105 tumors (23.4%) in AAM (P = 0.002). SPOP mutation was identified in 8 of 78 (10.3%) tumors in CaM and 4 of 88 (4.5%) tumors in AAM (P = 0.230). When adjusted for age, body mass index, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (P = 0.018 and P = 0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (P = 0.061 and P = 0.087, respectively). Conclusions: Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, whereas ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine whether these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups. Clin Cancer Res; 20(18); 4925–34. ©2014 AACR.
Untangling asthma phenotypes and endotypes
Authors: I. Agache, C. Akdis, M. Jutel, J. C. Virchow
Journal: Allergy (2012)

Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice.
A Method of Total Extirpation of the Gasserian Ganglion for Trigeminal Neuralgia
Authors: Harvey Cushing
Journal: JAMA (1983)

Of the many diseases which, on therapeutic grounds, are supposed to occupy a border-line position between the provinces of the physician and surgeon, perhaps no one more than intractable epileptiform neuralgia illustrates so well the dictim of that renowned Philadelphian and friend of many doctors, Benjamin Franklin, to the effect that "he is the best physician who knows the worthlessness of the most medicines." Granting the premise in all cases of true tic douloureux, the neuralgia quinti major of Henry Head, in which all three divisions of the trigeminal nerve are affected, that surgical measures alone can with any degree of certainty be depended on to afford relief from this horrible affliction and that the removal of the Gasserian ganglion must ultimately be contemplated, it is to be regretted that this final procedure should generally be regarded as one hazardous in its performance and uncertain in its permanent effects. Two
What is the significance of pancreatic ductal mucinous hyperplasia?
Authors: T G Allen-Mersh
Journal: Gut (1985)

The prevalence, distribution, and clinical associations of pancreatic ductal mucinous hyperplasia were studied in 102 non-malignant pancreases. Ductal mucinous hyperplasia was found in over 60% of specimens and was frequently associated with increased fibrosis--occasionally resembling pancreatitis. Significantly more ductal mucinous hyperplasia was found in pancreas from patients who were receiving corticosteroid treatment. Neither a history of hypercalcaemia in the three months before death, diabetes mellitus, alcoholism, tobacco smoking, nor the presence of gall stones was associated with an increase in ductal mucinous hyperplasia. The age of maximum prevalence, and the distribution of ductal mucinous hyperplasia in the pancreas were similar to those of pancreatic carcinoma. These similarities may be because both ductal mucinous hyperplasia and pancreatic carcinoma are proliferative responses, rather than because ductal mucinous hyperplasia is a precursor of pancreatic carcinoma.
At crossroads of biomedical research world
Authors: Kimberly Glasbrenner
Journal: JAMA (1984)

would like to say that health knows no geographical or political boundaries, says Craig Wallace, MD (CAPT, MC, USN), but we have to be aware of political situations and consider diplomacy in what we do.  In January, after many years of working in overseas medicine, Wallace left his position as commanding officer of Naval Medical Research Unit No. 3 in Cairo to begin a new career with  Public Health Service as an assistant surgeon general and as director of  Fogarty International Center. The center is  international component of what he describes as the largest biomedical research organization in  world—the NIH.  In dealing with foreign governments, Wallace says,  wouldn't be truthful if I didn't say there are politics involved. To illustrate this he refers to  recent World Health Assembly where  Iranians, seated next to  Iraqis, became engaged in a vitriolic discussion when
Imaging of plasmacytoid dendritic cell interactions with T cells
Authors: María Mittelbrunn, Gloria Martínez del Hoyo, María López-Bravo, Noa B. Martín-Cofreces, Alix Scholer, Stéphanie Hugues, Luc Fetler, Sebastián Amigorena, Carlos Ardavín, Francisco Sánchez-Madrid
Journal: Blood (2008)
Involvement of Tachykinin NK<sub>3</sub> Receptors in Citric Acid–induced Cough and Bronchial Responses in Guinea Pigs
Authors: SAMIRA DAOUI, CÉCILE COGNON, EMMANUEL NALINE, XAVIER EMONDS-ALT, CHARLES ADVENIER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Aerosolized citric acid induces several pulmonary effects including bronchoconstriction, airway inflammation, and cough. Evidence from the use of tachykinin NK1 and NK2 receptor antagonists, as well as chronic treatment with high doses of capsaicin, have suggested that these effects are mediated through the release of tachykinins from sensory nerve endings. In the present study, we have investigated the effects of a tachykinin NK3 receptor antagonist, SR 142801 (osanetant), on cough, bronchoconstriction, and bronchial hyperresponsiveness induced by aerosolized citric acid (0.4 M) in guinea pigs. SR 142801, at 0.3 and 1 mg · kg− 1 by intraperitoneal route, significantly inhibited cough in conscious guinea pigs by 57 ± 3 and 62 ± 10% (n = 8), respectively. In anaesthetized guinea pigs, it failed to inhibit the bronchoconstriction induced by citric acid when given alone but abolished it when combined with the tachykinin NK2 receptor antagonist, SR 48968 (saredutant). In guinea pigs pretreated with thiorphan (1 mg · kg− 1), aerosolized citric acid (0.4 M, 1 h) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor effect of acetylcholine. A microvascular leakage hypersensitivity also occurred and was demonstrated by a potentiation of the plasma protein extravasation from bronchial vessels induced by histamine. When given once intraperitoneally at 1 mg · kg− 1 30 min before the citric acid exposure, SR 142801 inhibited both hyperresponsiveness to acetylcholine and the potentiation of histamine-induced increase in microvascular permeability. The results suggest that tachykinin NK3 receptors are involved in citric acid–induced effects on airways.
Report of the Treatment of a very Extensive Outbreak of Ringworm of the Head, in a School: Eighty-Five out of Ninety-Two Children being Affected
Authors: A. Smith
Journal: BMJ (1882)

I 19SThe very concentrated solutions of arseniate of soda, employed in the end experiments, containing, viz., 5 per cent. of metallic arsenic, caused a certain amount of shock, following directly on the injection ; this occurred in three out of the five cases, but recovery soonfollowed, and in all a stage of comparative well-being preceded the onset of symp-
Abstract 4141: Notch signaling: A new potential target in the treatment of uveal melanoma
Authors: Laura Asnaghi, Michael L. Coonfield, Karisa C. Schreck, Eli E. Bar, James Handa, Shannath Merbs, Katy Ebrahimi, J. William Harbour, Charles G. Eberhart
Journal: Cancer Research (2010)

Abstract Uveal melanoma is the most common primary intra-ocular malignancy in adults, and causes significant mortality due to its propensity to metastasize. Our aim is to investigate the role of Notch signaling in promoting uveal melanoma proliferation and invasion. We examined five established uveal melanoma cell lines, and found using qPCR that the Notch 1-2-3 receptors, Jag1-2 ligands and the pathway target Hes1 were expressed to varying degrees in all lines. We then blocked Notch signaling using the gamma-secretase inhibitor (GSI) MRK003, and found that only three of the lines (OCM1, OCM3, OCM8) had their growth inhibited by the drug. Interestingly, these three lines had significantly higher levels of Hes1 mRNA as compared to the two lines resistant to GSI treatment (Mel 285, Mel 290). GSI treatment induced a dose-dependent reduction of anchorage-independent clonogenic growth, with 50% inhibition in OCM1, 70% in OCM3, and 40% in OCM8, as well as a significant reduction in Hes1 mRNA and protein levels. Apoptosis, as measured by cleavage and activation of caspase-9, was also induced. Finally, we observed inhibition of cellular invasion in GSI treated cultures using transwell migration and scratch assays. Preliminary studies of snap-frozen primary tumors indicate that Notch pathway components are expressed in primary uveal melanoma in vivo at levels as high or higher than those in our cell line models. In addition, oligonucleotide microarray analysis showed a significant increase in Jag2 and Notch3 expression levels in primary uveal melanomas that metastasized as compared to those that did not. Our findings suggest that the Notch pathway plays an important role in inducing cellular proliferation and invasion in uveal melanoma, and that inhibiting this pathway using pharmacological agents may be effective in preventing tumor growth and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4141.
Abstract 3193: EPHB2 expression parallels malignant behavior in mesothelioma
Authors: Chandra M. Goparaju, Jessica S. Donington, Nathalie Hirsch, Ryan G. Harrington, Harvey I. Pass
Journal: Cancer Research (2010)

Abstract Purpose: Erythropoietin-producing hepatocellular (EPH) receptors and their Ephrin (EFN) ligands are members of the transmembrane receptor tyrosine kinase (RTK) family. EPHB2 is a RTK, promotes uncontrolled cell growth, migration and tumor progression. Preliminary gene array data indicate EPHB2 overexpression in malignant pleural mesothelioma (MPM). Here, we aim to verify EPHB2 overexpression in MPM tumors and cell lines and hypothesize that EPHB2 silencing decreases malignant behavior in MPM cell lines. Methods: EPHB2 mRNA expression was evaluated by RT-PCR in eight MPM and three benign mesothelial cell lines, and seven pairs of MPM tumors and matched normal tissue. Functional significance of EPHB2 was evaluated by transfecting EPHB2-shRNA and empty vector controls into two MPM cell lines, HP-1 and H2595. Expression of EPHB2, BCL2L1, survivin, Caspase2, Caspase8, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) were evaluated by RT-PCR following silencing. Pooled populations of transfected cells were evaluated in scratch closure, cell proliferation by CellTitre BlueTM, MatrigelTM Invasion and colorimetric TUNELTM apoptotic assays. Comparisons were made between EPHB2 silenced and control cell lines. Results: EPHB2 was overexpressed in all MPM cell lines, but not in the benign mesothelial cell lines and in all tumors compared to matched normal tissue. Targeted knockdown of EPHB2 in MPM cell lines reduced its expression and subsequently reduced MMP-2, VEGF, BCL2L1 and survivin expression, and increased Caspase2 and Caspase8 expression. Inhibition of EPHB2 significantly decreased scratch closure, proliferation and invasion compared to the controls, and significantly increased apoptotic cells, likely related to Caspase2 and Caspase8 mediated cell death. Conclusion: Silencing of EPHB2 reduced the malignant behavior in MPM cell lines. EPHB2 appears to play an important role in MPM pathogenesis and could potentially serve as a novel therapeutic target for MPM treatment.Results of Functional AssaysAssayHP-1 ControlHP-1 EPHB2shRNAp ValueH2595 ControlH2595 EPHB2shRNAp ValueScratch Assay (% closure)69.237.6&amp;lt;0.00556.945.7&amp;lt;0.03Cell Proliferation Assay (OD value)9.56.4&amp;lt;0.058.75.7&amp;lt;0.05Matrigel Invasion Assay (cells invaded)14678&amp;lt;0.0057643&amp;lt;0.005TUNEL Apoptotic Assay (% apoptotic cells)074n/a088.5n/a Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3193.
Origin of error signals during cerebellar learning of motor sequences
Authors: Michel Dufossé, Arthur Kaladjian, Philippe Grandguillaume
Journal: Behavioral and Brain Sciences (1997)

Prefrontal cerebral areas project to Purkinje cells, located in the most lateral part of the cerebellum, via mossy and climbing fibers. The latter olivary error signals reflect the attentional load of the prefrontal cortex. At the cerebral level, LTP-LTD plasticity allows these Purkinje cells to adaptively reinforce the active pyramidal cells involved in the motor sequence.
Electronic preprints can be categorised
Authors: M. Choolani
Journal: BMJ (1999)

EDITOR—McConnell and Horton have put a critical issue on trial: the role of scientific journals in the age of the internet.1 Posting protocols, results, and preliminary “publications” on an individual or institutional website allows for intellectual discussion and a healthy exchange among coworkers internationally. Working by fax or email does not allow for the same level of flexibility or impact. Penalising authors for this practice by not considering for print the articles that have …