tbuckley/cabot-search huggingface dataset:
Consensus guidelines for the safe prescription and administration of oral bowel-cleansing agents
Authors: Andrew Connor, Damian Tolan, Stephen Hughes, Nick Carr, Charles Tomson
Journal: Gut (2012)

Oral bowel-cleansing preparations are used before colonic surgery and endoscopic and radiological assessment of the intestine to minimise faecal contamination. In February 2009, the UK National Patient Safety Agency issued a Rapid Response Report highlighting the potential risk of harm associated with the use of these preparations and instructing local NHS Trusts to implement safeguards to reduce this risk. This guidance has been prepared to help NHS Trusts to respond to these concerns, as the risk of complications is influenced by both individual patient risk factors and the choice of bowel preparation, for which definitive guidance was not previously available. This document provides an outline of the different available oral bowel-cleansing agents and the complications that may arise. This is followed by recommendations for their use in different patient groups and circumstances. The recommendations are based on consensus between the authors, each of whom circulated drafts to members of their specialist society. The evidence for these recommendations has been assessed using the modified GRADE system. The recommendations cover the choice, administration and complications (relative and absolute) of the different oral bowel-cleansing agents, with specific guidance provided for different patient groups.
Cognitive Function and Brain Structure in Persons With Type 2 Diabetes Mellitus After Intensive Lowering of Blood Pressure and Lipid Levels
Authors: Jeff D. Williamson, Lenore J. Launer, R. Nick Bryan, Laura H. Coker, Ronald M. Lazar, Hertzel C. Gerstein, Anne M. Murray, Mark D. Sullivan, Karen R. Horowitz, Jingzhong Ding, Santica Marcovina, Laura Lovato, James Lovato, Karen L. Margolis, Christos Davatzikos, Joshua Barzilay, Henry N. Ginsberg, Peter E. Linz, Michael E. Miller
Journal: JAMA Internal Medicine (2014)

<h3>Importance</h3> Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. <h3>Objective</h3> To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. <h3>Design, Setting, and Participants</h3> A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A<sub>1c</sub>(HbA<sub>1c</sub>) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. <h3>Main Outcome Measures</h3> Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. <h3>Results</h3> Baseline mean HbA<sub>1c</sub>level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, −4.4 [95% CI, −7.8 to −1.1] cm<sup>3</sup>;<i>P</i> = .01). Fibrate therapy had no effect on TBV compared with placebo. <h3>Conclusions and Relevance</h3> In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00000620
Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA.
Authors: Y M Centifanto-Fitzgerald, T Yamaguchi, H E Kaufman, M Tognon, B Roizman
Journal: The Journal of Experimental Medicine (1982)

The pattern of ocular disease produced in the rabbit eye by HSV-1 (F) and HSV-1(MP) strains and recombinants F(MP)A, F(MP)B, F(MP)C, F(MP)D, F(MP)E, and F(MP)F was studied. The characteristics of ocular herpetic disease such as morphology of dendritic ulcers, severity of epithelial disease and incidence and duration of stromal disease produced in the rabbit eye are genetically determined by the virus strain. Our studies show that transfer of a defined part of the genome of the stromal disease-producing virus, HSV-1(MP), to the genome of an epithelial disease-producing virus, HSV-1(F), yielded recombinants with one or more of the disease characteristics of the donor strain. Specifically, recombinant F(MP)D produced lesions characteristic of the donor HSV-1(MP) strain; recombinants F(MP)C and F(MP)E produced stromal disease approaching the severity of the disease produced by the donor HSV-1(MP) strain, and only recombinants F(MP)A and F(MP)B retained the typically elongate lesions of the recipient HSV-1(F), whereas the recombinant strain F(MP)F produced no disease. The viral functions pertaining to the ocular disease pattern map between 0.70 and 0.83 map units in HSV-1 DNA within the BglII F DNA fragment. The pattern of stromal disease is independent of the production of glycoprotein C and fusion of HEp-2-infected cells. The functions relating to these aspects of ocular disease segregate but are closely linked.
High Proportions of Erectile Dysfunction in Men With the Metabolic Syndrome
Authors: Katherine Esposito, Francesco Giugliano, Emilia Martedì, Giovanni Feola, Raffaele Marfella, Massimo D’Armiento, Dario Giugliano
Journal: Diabetes Care (2005)

Erectile dysfunction is an important cause of decreased quality of life in men (1,2). Strong epidemiological evidence links the subsequent risk of erectile dysfunction to the presence of well-recognized risk factors for coronary heart disease, such as increased body weight, hypertension, and dyslipidemia (3,4). Some have suggested that a diagnosis of erectile dysfunction is a sentinel event that should prompt investigation for coronary heart disease in asymptomatic men (5). We postulated an association between erectile dysfunction and the metabolic syndrome because four of the five components of the metabolic syndrome are risk factors for erectile dysfunction and are also characterized by abnormal endothelial function (6).

Men were recruited among those attending the outpatient department for metabolic diseases of the teaching hospital at the second University of Naples, Naples, Italy. To be enrolled in the study, subjects had to have three or more of the criteria to meet the diagnosis of the metabolic syndrome, as recommended by the Adult Treatment Panel (7). Exclusion criteria were diabetes or impaired glucose tolerance, impaired renal function, pelvic trauma, prostatic disease, peripheral or autonomic neuropathy, hypertension (blood pressure >140/90 mmHg), cardiovascular disease, psychiatric problems, use of drugs or alcohol abuse, and smoking (both present and past smoking). Endocrine causes of erectile dysfunction were also excluded. A total …
Modulation by cAMP of IL-1 -induced eotaxin and MCP-1 expression and release in human airway smooth muscle cells
Authors: W.A. Wuyts, B.M. Vanaudenaerde, L.J. Dupont, M.G. Demedts, G.M. Verleden
Journal: European Respiratory Journal (2003)

Inflammatory cells, such as eosinophils, seem to be key players in the inflammatory process of asthma. These cells are attracted by chemokines, for example eotaxin and monocyte chemotactic protein (MCP‐1). In this study, the authors investigated whether eotaxin and MCP‐1 expression and release in human airway smooth muscle cells could be modulated by an increase in intracellular cyclic adenosine monophosphate (cAMP) concentration. The possible involvement of cAMP‐dependent protein kinase A (PKA) was also studied. Forskolin, a direct stimulator of adenylyl cyclase, decreased the interleukin (IL)‐1β‐induced eotaxin and MCP‐1 release by 73±8 and 65±6%, respectively. 8Bromo‐cAMP, a cAMP analogue, similarly decreased the chemokine production by 58±9 and 63±8% for eotaxin and MCP‐1, respectively. Prostaglandin E2, known as an activator of the prostanoid receptors EP 2 and EP 4 , which are positively coupled to adenylyl cyclase, also decreased the IL‐1β‐induced eotaxin and MCP‐1 production by 57±17 and 53±4%, respectively. H‐89, an inhibitor of PKA, was able to inhibit the decrease in eotaxin and MCP‐1 protein release induced by forskolin. Using Western-blot analysis, no effect of cAMP was found on the IL‐1β‐induced p38 mitogen-activated protein kinase, extracellular signal-related kinase or cJun N ‐terminal kinase activation. This study shows that an increase in intracellular cyclic adenosine monophosphate concentration may decrease the interleukin‐1β‐induced eotaxin and monocyte chemotactic protein‐1 expression and production. This can be inhibited by addition of H‐89, an inhibitor of cyclic adenosine monophosphate-dependent protein kinase. No decrease was observed in interleukin‐1β‐induced p38 mitogen-activated protein kinase, extracellular signal-related kinase or cJun N ‐terminal kinase activation. These findings may be important for the further development of new anti-inflammatory drugs.
Responsiveness of Hypercalciuria to Thiazide in Dent’s Disease
Authors: Khalid A Raja, Scott Schurman, Richard G. D’Mello, Douglas Blowey, Paul Goodyer, Scott Van Why, Robert J. Ploutz-Snyder, John Asplin, Steven J. Scheinman
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Hypercalciuria is the major risk factor promoting stone formation in Dent’s disease, also known as X-linked recessive nephrolithiasis, but the effects of diuretics on calcium excretion and other stone risk factors in this disease are unknown. This study examined urine composition in eight male patients with Dent’s disease, ages 6 to 49 yr, all of whom were hypercalciuric and had inactivating mutations of CLCN5. Eight males, ages 7 to 34 yr, with idiopathic hypercalciuria (IH) served as controls. Patients were instructed to maintain a consistent intake of sodium, potassium, calcium, and protein. Two consecutive 24-h urine collections were obtained after a baseline period and after 2 wk of chlorthalidone (25 mg), amiloride (5 mg), and the two diuretics in combination, with a week off drug separating the treatment periods in a randomized crossover design. Doses were reduced by half in boys under age 12 yr. Chlorthalidone alone (P < 0.002) and the combination of chlorthalidone and amiloride (P < 0.003) reduced calcium excretion significantly in either patient group. With chlorthalidone, calcium excretion fell to normal (<4.0 mg/kg per d) in all but one patient in each group. Amiloride alone had no significant effect on urinary calcium excretion, in either patient group. In patients with Dent’s disease during chlorthalidone therapy, the supersaturation ratios for calcium oxalate and calcium phosphate fell by 25% and 35%, respectively. Mean citrate excretion was reduced by chlorthalidone (P < .04) and by chlorthalidone in combination with amiloride (P < .02). There were no significant differences in the responses to these diuretics between the patient groups in any of the urinary parameters. The intact hypocalciuric response to a thiazide diuretic indicates that inactivation of the ClC-5 chloride channel does not impair calcium transport in the distal convoluted tubule and indicates that thiazides should be useful in reducing the risk of kidney stone recurrence in patients with Dent’s disease.
Production of Serotonin by Tryptophan Hydroxylase 1 and Release via Platelets Contribute to Allergic Airway Inflammation
Authors: Thorsten Dürk, Daniel Duerschmied, Tobias Müller, Melanie Grimm, Sebastian Reuter, Rodolfo Paula Vieira, Korcan Ayata, Sanja Cicko, Stephan Sorichter, Diego J. Walther, J. Christian Virchow, Christian Taube, Marco Idzko
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: 5-Hydroxytryptamine (5-HT) is involved in the pathogenesis of allergic airway inflammation (AAI). It is unclear, however, how 5-HT contributes to AAI and whether this depends on tryptophan hydroxylase (TPH) 1, the critical enzyme for peripheral 5-HT synthesis.Objectives: To elucidate the role of TPH1 and the peripheral source of 5-HT in asthma pathogenesis.Methods: TPH1-deficient and TPH1-inhibitor–treated animals were challenged in ovalbumin and house dust mite models of AAI. Experiments with bone marrow chimera, mast cell–deficient animals, platelets transfusion, and bone marrow dendritic cells (BMDC) driven model of AAI were performed. 5-HT levels were measured in bronchoalveolar lavage fluid or serum of animals with AAI and in human asthma.Measurements and Main Results: 5-HT levels are increased in bronchoalveolar lavage fluid of mice and people with asthma after allergen provocation. TPH1 deficiency and TPH1 inhibition reduced all cardinal features of AAI. Administration of exogenous 5-HT restored AAI in TPH1-deficient mice. The pivotal role of 5-HT production by structural cells was corroborated by bone marrow chimera experiments. Experiments in mast cell–deficient mice revealed that mast cells are not a source of 5-HT, whereas transfusion of platelets from wild-type and TPH1-deficient mice revealed that only platelets containing 5-HT enhanced AAI. Lack of endogenous 5-HT in vitro and in vivo was associated with an impaired Th2-priming capacity of BMDC.Conclusions: In summary, TPH1 deficiency or inhibition reduces AAI. Platelet- and not mast cell–derived 5-HT is pivotal in AAI, and lack of 5-HT leads to an impaired Th2-priming capacity of BMDC. Thus, targeting TPH1 could offer novel therapeutic options for asthma.
Recent changes in dental caries.
Authors: G N Jenkins
Journal: BMJ (1985)

Categorization allows organisms to efficiently extract relevant information from a diverse environment. Because of the multidimensional nature of odor space, this ability is particularly important for the olfactory system. However, categorization relies on experience, and the processes by which the human brain forms categorical representations about new odor percepts are currently unclear. Here we used olfactory psychophysics and multivariate fMRI techniques, in the context of a paired-associates learning task, to examine the emergence of novel odor category representations in the human brain. We found that learning between novel odors and visual category information induces a perceptual reorganization of those odors, in parallel with the emergence of odor category-specific ensemble patterns in perirhinal, orbitofrontal, piriform, and insular cortices. Critically, the learning-induced pattern effects in orbitofrontal and perirhinal cortex predicted the magnitude of categorical learning and perceptual plasticity. The formation of <i>de novo</i> category-specific representations in olfactory and limbic brain regions suggests that such ensemble patterns subserve the development of perceptual classes of information, and imply that these patterns are instrumental to the brain9s capacity for odor categorization. <b>SIGNIFICANCE STATEMENT</b> How the human brain assigns novel odors to perceptual classes and categories is poorly understood. We combined an olfactory-visual paired-associates task with multivariate pattern-based fMRI approaches to investigate the <i>de novo</i> formation of odor category representations within the human brain. The identification of emergent odor category codes within the perirhinal, piriform, orbitofrontal, and insular cortices suggests that these regions can integrate multimodal sensory input to shape category-specific olfactory representations for novel odors, and may ultimately play an important role in assembling each individual9s semantic knowledge base of the olfactory world.
Pupil Signs of Sympathetic Autonomic Neuropathy in Patients With Type 1 Diabetes
Authors: Daniel Pittasch, Ralf Lobmann, Wolfgang Behrens-Baumann, Hendrik Lehnert
Journal: Diabetes Care (2002)

Pupillary autonomic neuropathy is considered an early sign of the development of systemic autonomic neuropathy. Sympathetic denervation is related to the duration of diabetes and the development of systemic autonomic dysfunction. We investigated pupil responsiveness to directly and indirectly acting sympathomimetics in type 1 diabetic patients with and without long-term complications, defined as cardiac autonomic neuropathy (CAN), peripheral sensomotor neuropathy, retinopathy, and nephropathy, and in healthy subjects.A total of 47 randomly chosen type 1 diabetic patients and 20 healthy subjects were selected for this study. Patients were divided into groups determined by whether they had long-term diabetic complications. Pharmacological tests were performed with cocaine 4%, epinephrine 1%, and pholedrine 5% eye drops. Horizontal pupil diameter (HPD) was measured at the beginning of the pharmacological tests and at defined time points after instillation of the eye drops.Statistical analysis showed a significantly smaller HPD in the patients before instillating eye drops (P = 0.011). In particular, the HPD was significantly smaller in the patient group without CAN when compared with healthy subjects (P = 0.004). Maximal cocaine reaction was diminished in the complication group (P < 0.001). Epinephrine test, visual acuity, ocular pressure, and HbA(1c) did not differ in patients with or without long-term complications. The noncomplication group showed no significant differences in pupillary responses as compared with healthy subjects. The complication group showed a smaller HPD (P = 0.022), reduced pupillary responses in the cocaine (P = 0.037) and pholedrine tests (P < 0.001), and anisocor pupil sizes after instillation of the eye drops (P = 0.034).Our results clearly show that sympathetic denervation does exist in the pupil of diabetic patients and that it can be rapidly assessed using the cocaine test. These data and the results of the epinephrine test suggest a mixed pre- and postganglionic dysfunction of the sympathetic plexus. The significant smaller HPD in patients without CAN compared with that of healthy subjects could be a sign for early involvement of the pupil function before cardiac manifestation of systemic autonomic diabetic neuropathy.
Treatment of Advanced Non–Small-Cell Lung Cancer in the Elderly: Results of an International Expert Panel
Authors: Cesare Gridelli, Matti Aapro, Andrea Ardizzoni, Lodovico Balducci, Filippo De Marinis, Karen Kelly, Thierry Le Chevalier, Christian Manegold, Francesco Perrone, Rafael Rosell, Frances Shepherd, Luigi De Petris, Massimo Di Maio, Corey Langer
Journal: Journal of Clinical Oncology (2005)

The best treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) is still debated. To guide clinical management of these patients and suggest the priorities for clinical research in this field, an International Expert Panel met in Naples, Italy, on April 19 to 20, 2004. Results and conclusions based on a review of evidence available in the literature to date are presented in this article. A comprehensive geriatric assessment is recommended to better define prognosis and to predict tolerance to treatment. In the first randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine showed superiority over supportive care alone, both in terms of survival and quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed to show any advantage over either agent alone. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. These data should be interpreted cautiously because retrospective subgroup analyses are encumbered by selection bias; hence, randomized trials dedicated to platinum-based chemotherapy for nonselected elderly patients are warranted. Several promising biologic therapies are under investigation; however, with present data, target-based agents as first-line treatment for elderly NSCLC patients are not yet recommended. Clinical research, with trials specifically designed for elderly patients, is mandatory. With the current evidence, single-agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, a taxane) should be the recommended option for nonselected elderly patients with advanced NSCLC. Platinum-based chemotherapy is a viable option for fit patients with adequate organ function. Best supportive care remains important, in addition to chemotherapy or as the exclusive option for patients who are unsuitable for more aggressive treatment.
Treatment of oropharyngeal squamous cell carcinoma with IMRT: patterns of failure after concurrent chemoradiotherapy and sequential therapy
Authors: D J Sher, V Thotakura, T A Balboni, C M Norris, R I Haddad, M R Posner, J Lorch, L A Goguen, D J Annino, R B Tishler
Journal: Annals of Oncology (2012)
Reversibility of gelsolin/actin interaction in macrophages. Evidence of Ca2+-dependent and Ca2+-independent pathways.
Authors: C Chaponnier, H L Yin, T P Stossel
Journal: The Journal of Experimental Medicine (1987)

We have developed an immunoadsorption technique for quantitating EGTA-resistant gelsolin/actin complexes in macrophages extracted with Triton X-100. We report here that the proportion of gelsolin complexed irreversibly to actin is low in freshly harvested macrophages. The amount of the EGTA-resistant complex increases spontaneously during incubation of the cells in suspension at 37 degrees C, or after exposure to the Ca2+ ionophore ionomycin. On the other hand, exposure of suspended cells to the chemotactic oligopeptide, FMLP, or plating of the cells onto tissue culture dishes causes the EGTA-resistant complex to dissociate rapidly. Plating even prevents Ca2+ ionomycin-treated cells with elevated intracellular Ca2+ from inducing this complex. Therefore, our results suggest that macrophages possess a mechanism, not directly involving Ca2+, for dissociating actin/gelsolin EGTA-resistant complexes. This mechanism may be a Ca2+-independent signal for leukocyte activation.