tbuckley/cabot-search huggingface dataset:
Profound hypotension after atenolol in severe hypertension.
Authors: M. Kholeif, C. Isles
Journal: BMJ (1989)

deterioration in lung function, which has been described after nebulised asthma treatment in infancy, did not occur."4Ipratropium bromide acts on the nose by decreasing secretions but has not been shown to alter resistance in the nasal airway.As two infants with complete nasal blockage showed a 20% improvement in specific conductance we assume that the improvement seen after ipratropium bromide was due to broncho- dilatation.A Nebuhaler has been shown to be effective in giving inhaled budesonide to young children.'We used this delivery system to give budesonide and fP2 agonists to asthmatic children aged under 2 and obtained dramatic improvement in many cases (unpublished results).Though this method of delivery does not replace nebulisers in severe attacks of asthma in young children, it may enable many children without access to a nebuliser to be treated successfully at home.Handicapped patients who cannot use other inhalation devices may also benefit.
Secukinumab in psoriasis: randomized, controlled phase 3 trial results assessing the potential to improve treatment response in partial responders (STATURE)
Authors: D. Thaçi, J. Humeniuk, Y. Frambach, R. Bissonnette, J.J. Goodman, S. Shevade, Y. Gong, C. Papavassilis
Journal: British Journal of Dermatology (2015)

Secukinumab, an anti-interleukin-17A monoclonal antibody, has demonstrated rapid and sustained efficacy in phase 3 psoriasis trials.To examine whether partial responders could achieve improved responses with intravenous (IV) secukinumab vs. the same or a higher subcutaneous (SC) dose.Forty-three participants with moderate-to-severe psoriasis and partial response [Psoriasis Area and Severity Index (PASI) score improvement of ≥ 50% but < 75%] after 12 weeks of 300 or 150 mg SC secukinumab therapy were randomized 1 : 1 to secukinumab 10 mg kg(-1) IV (baseline, weeks 2 and 4, respectively) or secukinumab 300 mg SC (baseline, week 4). All participants subsequently received secukinumab 300 mg SC every 4 weeks (weeks 8-36). Co-primary end points were PASI 75 and Investigator's Global Assessment [2011 modified version (IGA mod 2011)] 0/1 response rates at week 8 (IV vs. SC).Higher IGA mod 2011 0/1 response rates (66.7% vs. 33.3%; P = 0.03) and a trend towards higher PASI 75 response rates (90.5% vs. 66.7%; P = 0.06) were observed with secukinumab IV vs. SC at week 8. The primary objective was not met, as the difference was not significant for both co-primary end points. Improved responses in both groups were maintained at week 40 in most participants. Safety profiles for IV and SC secukinumab were similar. The trial was underpowered owing to its small sample size.Improved response may be attained in patients with psoriasis achieving partial response after 12 weeks of SC secukinumab treatment by continued dosing with 300 mg SC or treatment with higher doses.
Roentgenographic Aspects of Narcotic Addiction
Authors: Melvin Hershkowitz
Journal: JAMA (1977)

<h3>To the Editor.—</h3> The article by Dr Stern (236:963, 1976) entitled "Roentgenographic Aspects of Narcotic Addiction" states that the observation of gynecomastia in an addict's chest roentgenogram may be a clue to the diagnosis of hepatitis. Although gynecomastia is widely recognized as an occasional physical sign in patients with cirrhosis, it is certainly not frequent in the type of acute hepatitis seen in drug addicts. Inability of the diseased liver to deactivate circulating estrogens would not be an acceptable pathogenetic mechanism for gynecomastia in recently acquired hepatitis, and there is some doubt, too, that it is the real explanation for gynecomastia in cirrhotic patients. The incidence of acute alcoholism and drug addiction is very high in Jersey City. We have seen many patients with hepatitis resulting from heroin use in the past five years, but I cannot recall seeing gynecomastia in the early evolutionary stage of this disease. The occurrence
HIV Drug Resistance
Authors: François Clavel, Allan J. Hance
Journal: New England Journal of Medicine (2004)

Combinations of antiretroviral drugs have proven remarkably effective in controlling the progression of HIV disease and prolonging survival, but these benefits can be compromised by the development of drug resistance. About 50 percent of patients receiving antiretroviral therapy in the United States are estimated to harbor viruses that express resistance to at least one of the available antiretroviral drugs.
Bile Acid Reflux Contributes to Development of Esophageal Adenocarcinoma via Activation of Phosphatidylinositol-Specific Phospholipase Cγ2 and NADPH Oxidase NOX5-S
Authors: Jie Hong, Jose Behar, Jack Wands, Murray Resnick, Li Juan Wang, Ronald A. DeLellis, David Lambeth, Weibiao Cao
Journal: Cancer Research (2010)

Abstract Gastroesophageal reflux disease complicated by Barrett's esophagus (BE) is a major risk factor for esophageal adenocarcinoma (EA). However, the mechanisms of the progression from BE to EA are not fully understood. Besides acid reflux, bile acid reflux may also play an important role in the progression from BE to EA. In this study, we examined the role of phosphatidylinositol-specific phospholipase C (PI-PLC) and a novel NADPH oxidase NOX5-S in bile acid–induced increase in cell proliferation. We found that taurodeoxycholic acid (TDCA) significantly increased NOX5-S expression, hydrogen peroxide (H2O2) production, and cell proliferation in EA cells. The TDCA-induced increase in cell proliferation was significantly reduced by U73122, an inhibitor of PI-PLC. PI-PLCβ1, PI-PLCβ3, PI-PLCβ4, PI-PLCγ1, and PI-PLCγ2, but not PI-PLCβ2 and PI-PLCδ1, were detectable in FLO cells by Western blot analysis. Knockdown of PI-PLCγ2 or extracellular signal-regulated kinase (ERK) 2 mitogen-activated protein (MAP) kinase with small interfering RNAs (siRNA) significantly decreased TDCA-induced NOX5-S expression, H2O2 production, and cell proliferation. In contrast, knockdown of PI-PLCβ1, PI-PLCβ3, PI-PLCβ4, PI-PLCγ1, or ERK1 MAP kinase had no significant effect. TDCA significantly increased ERK2 phosphorylation, an increase that was reduced by U73122 or PI-PLCγ2 siRNA. We conclude that TDCA-induced increase in NOX5-S expression and cell proliferation may depend on sequential activation of PI-PLCγ2 and ERK2 MAP kinase in EA cells. It is possible that bile acid reflux present in patients with BE may increase reactive oxygen species production and cell proliferation via activation of PI-PLCγ2, ERK2 MAP kinase, and NADPH oxidase NOX5-S, thereby contributing to the development of EA. Cancer Res; 70(3); 1247–55
Flashing out or fleshing out? A developmental perspective on a universal model of reading
Authors: Bruce D. Homer, Russell Miller, Seamus Donnelly
Journal: Behavioral and Brain Sciences (2012)

Abstract The principles for universal reading models proposed by Frost correspond to developmental theories, in which neurocognitive constraints and cultural experiences shape development. We question his contention that Hebrew word identification is fundamentally about roots, excluding verbal and nominal word-pattern morphemes; and we propose that readers use all information available in stimuli, adjusting for volume and usefulness.
A targeted antithrombotic conjugate with antiplatelet and fibrinolytic properties which reduces in vivo thrombus formation
Authors: R. S More, M. J Underwood, M. J Brack, S. Pringle, D. P d. Bono, A. H Gershlick
Journal: Cardiovascular Research (1993)

Objective: Potent therapy that could be locally delivered to inhibit blood factor-vessel wall interaction and which would remain localised to the site of damage may avoid the side effects of systemic drugs in the treatment of disorders such as subacute thrombosis of saphenous vein grafts and intravascular stents. We therefore assessed the feasability of developing a targeted antithrombotic conjugate by covalently cross-linking urokinase to a monoclonal antibody to platelet glycoprotein Ilb/IIIa (M735) and a monoclonal antibody against damaged endothelium (P14G11). Methods: Conjugation was carried out using N-succinimidyl-3-(2-pyridyldithio) propionate as the cross-linking reagent. The conjugate was assessed in vitro and in an in vivo model of thrombosis and local delivery. Results: The conjugate formed, ATC(3), retained specificity for damaged endothelial cells and platelets and had urokinase activity of approximately 10 000 IU·mg−1 protein. Persistence of urokinase activity on binding to intact platelets and scratch damaged endothelial monolayer preparations was confirmed. Platelet aggregation studies (using ADP and collagen) revealed complete inhibition by ATC(3) at a dose of 5 μg·ml−1 while an unconjugated mixture of M735 (20 μg·ml−1), P14G11 (20 μg·ml−1), and urokinase (200 IU·ml−1) failed to inhibit completely platelet aggregation induced by ADP. In an in vivo model of thrombosis and vascular injury, local delivery of ATC(3) significantly reduced the weight of thrombus formed [median 13 mg (interquartile range 9-20)] compared to an unconjugated mixture of M735, P14G11 and urokinase [35 mg (28-45)] and urokinase alone [41 mg (33-55)]. Conclusions: It is possible to produce a targeted antithrombotic conjugate which retains activity of all its individual components. Cardiovascular Research 1993;27:2200-2204
Hoarseness, cough and cervical lymphadenopathy
Authors: A. J. Turk, T. Brack, C. Alfaré, A. Gaspert, E. W. Russi
Journal: European Respiratory Journal (2005)

A 43-yr-old native Brazilian female complained of a sore throat, recent onset of hoarseness, progressive pain and bilateral swelling of the neck during the past 6 months, when she presented at the University Hospital of Zurich (Zurich, Switzerland) for the first time.The patient had moved to Switzerland 5 yrs before, had been a heavy smoker for the past 20 yrs and coughed chronically.She reported a short episode of minor haemoptysis 2 yrs previously that had ceased spontaneously.The patient suffered no fever or night sweats, but had lost 2 kg of weight during the past 2 months, despite a normal appetite.Five months previously, she had spent 3 months in a town south of the capital Brasilia, where she was treated with sulphamethoxazole and trimethoprim for pneumonia.After a transient recovery, the cough, sore throat and cervical swelling reappeared.
Failure of Corticosteroid Test in the Differential Diagnosis of Jaundice
Authors: George I. Loutfi
Journal: JAMA (1966)

The differential diagnosis of jaundice is often a challenge to the clinician, and in recent years numerous laboratory tests have been proposed. In an analysis of 200 cases of jaundice, Berkowitz<sup>1</sup>found an overall diagnostic accuracy of 76% with only a 33% accuracy in cases with intrahepatic obstruction. Steroids and corticotropin were found to be effective in lowering the concentration of serum bilirubin in patients with acute viral hepatitis associated with features suggesting biliary obstruction. Hence it has been suggested that these drugs can be beneficially used under such circumstances as a diagnostic test. Evaluation of the corticotropin (ACTH) test in the differential diagnosis of jaundice<sup>2</sup>indicated that this four-day test has a limited usefulness because it shows a moderate overlap between patients with medical and surgical jaundice. More recently, Summerskill et al<sup>3</sup>found that a 40% decrease in serum bilirubin concentration occurred in four to six
Website offering orthopaedic second opinions is criticised by surgeons' leaders
Authors: A. Tuffs
Journal: BMJ (2011)

Professional bodies in Germany have criticised a website that offers a second opinion, for a fee of between €200 (£180; $290) and €600, to patients who have been recommended for joint replacement surgery.

NAV-Virchowbund, an association of GPs and specialists with their own practices, has charged the 12 senior orthopaedic surgeons behind the site (www.vorsicht-operation.de) with violating professional medical regulations because they are offering diagnosis and counselling without actually seeing patients. The association has reported what it sees as professional …
Paroxysmal Nocturnal Hemoglobinuria and Cancer: High Incidence Of Cancer In a Large Series Of PNH Patients In a Single Center
Authors: Cristina Muñoz-Linares, Emilio Ojeda, Rafael Fores, Martin Cabero, Daniel Morillo, Guiomar Bautista, Belen Navarro, Isabel Krsnik, Santiago Gil, Almudena de LaIglesia, Carmen Regidor, Jose Luis Bueno, Jose A Garcia-Marco, Jose Rafael Cabrera
Journal: Blood (2013)
Comparative toxicity and tissue distribution of lead acetate in weanling and adult rats.
Authors: J I Rader, J T Peeler, K R Mahaffey
Journal: Environmental Health Perspectives (1981)

The relative toxicity of low doses of lead acetate provided steadily in drinking water or by mouth once per week was studied in weanling and adult rats. Free erythrocyte protoporphyrin and urinary delta-aminolevulinic acid levels were measured, as well as lead levels in blood and kidney. The accumulation of lead in brain tissue and in bone (femur) was measured to determine the effect of age and schedule of administration on tissue distribution and retention of lead. Total intakes of lead during the 60-week experimental period were: weanling and adult rats exposed to drinking water supplemented with 200 microgram of lead acetate/ml: 127 +/- 10 mg and 160 +/- 16 mg, respectively; weanling and adult rats dosed with lead acetate orally once per week: 132 mg and 161 mg, respectively. Increased toxic effects of lead in the weanling animals were apparent in most of the parameters measured (urinary delta-aminolevulinic acid and blood, brain, femur and kidney lead levels). This pattern was observed in weanling rats exposed to lead steadily through drinking water or dosed orally with an equivalent quantity of lead once per week. Lead levels in blood were highly correlated with the accumulation of lead in brain, femur, and kidney tissue in both groups of weanling rats. In adult rats, significant correlations between blood lead and kidney lead and between blood lead and femur lead were found only in the rats receiving lead steadily in drinking water.
Inhibition of human platelet phospholipase A2 by mono(2-ethylhexyl)phthalate.
Authors: R S Labow, E Meek, G A Adams, G Rock
Journal: Environmental Health Perspectives (1988)

There is evidence that the carcinogenic and teratogenic effects attributed to the plasticizer di(2-ethylhexyl)phthalate (DEHP) are due to its major metabolite mono(2-ethylhexyl)phthalate (MEHP). MEHP is also formed ex vivo by a plasma enzyme in blood products stored in polyvinyl chloride (PVC) DEHP plastic containers. People who receive large amounts of blood products, such as hemophiliacs or patients undergoing hemodialysis, cardiopulmonary bypass, or massive transfusion, are exposed to significant levels of plasticizer. In this study, the platelet was used to show that MEHP inhibits phospholipase A2 (PLA2), one of enzymes important in the release of arachidonic acid from membrane phospholipids. Arachidonate is the parent molecule for the synthesis of prostaglandins, thromboxanes, leukotrienes, and lipoxins that are made by a wide variety of cells. PLA2 was measured by the liberation of 14C-arachidonic acid from 1-stearoyl-2-[1-14C]arachidonyl-L-3-phosphatidylcholine. MEHP inhibits PLA2 activity noncompetitively in intact human platelets and lysates with a Ki of 3.7 x 10(-4) M. DEHP does not inhibit PLA2 in whole platelets. Inhibition of PLA2 by MEHP occurs at only three times the circulating level of MEHP measured in neonates undergoing exchange transfusion and 20-fold the levels experienced by patients during cardiopulmonary bypass. Therefore, infants and adult patients with multisystem failure who accumulate MEHP in their blood may be at risk for decreased platelet function.
EXTENDED RELEASE NIACIN IMPROVES LIPID PROFILE BUT NOT ENDOTHELIAL FUNCTION IN PATIENTS WITH CORONARY ARTERY DISEASE ON HIGH DOSE STATINS
Authors: Jaroslav Hubacek, Andrew C. Philpott, Yichun C. Sun, Vincent Lee, Darlene Hilland, Todd J. Anderson
Journal: Journal of the American College of Cardiology (2010)
Vascular Disorders of the Extremities
Authors: Geza de Takats
Journal: JAMA (1975)

According to its preface, this encyclopedia of peripheral vascular disorders is written for the family physician, the dermatologist, the orthopedist, the neurologist, and the podiatrist. It represents the lifelong involvement of the author in the physiology and clinical manifestations of peripheral circulation, with an emphasis on differential diagnosis, arterial impairment, venous disorders, and vascular injuries. Throughout the text, the author's vast knowledge of his subject is apparent, reinforced by an extensive although somewhat selective bibliography. While he discusses in detail the disadvantages of stealing blood from ischemic to normally vascularized areas by sympathectomy, he minimizes the same effect of vasodilators so widely employed in the treatment of peripheral vascular diseases. There is a wealth of valuable information scattered throughout this volume whose only real defect is the organization of the material, requiring continuous cross-references. The author seems fond of the kind of tables that are cumbersome and do not add
SYT-SSX1 and SYT-SSX2 Interfere with Repression of E-Cadherin by Snail and Slug: A Potential Mechanism for Aberrant Mesenchymal to Epithelial Transition in Human Synovial Sarcoma
Authors: Tsuyoshi Saito, Makoto Nagai, Marc Ladanyi
Journal: Cancer Research (2006)

Abstract Synovial sarcoma is a primitive mesenchymal neoplasm characterized in almost all cases by a t(X;18) fusing the SYT transcriptional coactivator gene with either SSX1 or SSX2, with the resulting fusion gene encoding an aberrant transcriptional regulator. A subset of synovial sarcoma, predominantly cases with the SYT-SSX1 fusion, shows foci of morphologic epithelial differentiation in the form of nests of glandular epithelium. The striking spontaneous mesenchymal to epithelial differentiation in this cancer is reminiscent of a developmental switch, but the only clue to its mechanistic basis has been the observation that most cases of synovial sarcoma with glandular epithelial differentiation (GED) contain SYT-SSX1 instead of SYT-SSX2. We report here that SYT-SSX1 and SYT-SSX2 interact preferentially with Snail or Slug, respectively, and prevent these transcriptional repressors from binding to the proximal E-cadherin promoter as shown by coimmunoprecipitation and chromatin immunoprecipitation. Luciferase reporter assays reveal that SYT-SSX1 and SYT-SSX2 can respectively overcome the Snail- or Slug-mediated repression of E-cadherin transcription. This provides a mechanism by which E-cadherin expression, a prerequisite of epithelial differentiation, is aberrantly derepressed in synovial sarcoma and may also explain the association of GED with the SYT-SSX1 fusion because it interferes with Snail, the stronger repressor of the E-cadherin promoter. Thus, our data provide a mechanistic basis for the observed heterogeneity in the acquisition of epithelial characteristics in synovial sarcoma and highlight the potential role of differential interactions with Snail or Slug in modulating this phenotypic transition. (Cancer Res 2006; 66(14): 6919-27)
Insulin Secretion in Diabetes Mellitus
Authors: DAVID M. KIPNIS
Journal: Annals of Internal Medicine (1968)

Measurements of the plasma immunoreactive insulin responses to various insulinogenic stimuli in prediabetic, latent, juvenile, and maturity-onset diabetics indicate that impaired insulin secretion is a characteristic feature of the diabetic state. The development of overt diabetes depends, however, on both the degree of impairment of insulin secretion and the insulin sensitivity of the individual. The maintenance of normal carbohydrate tolerance in preand latent diabetics, despite decreased insulin secretion, indicates increased endorgan responsiveness to insulin. Normal-weight, maturity-onset diabetics also exhibit increased glucose utilization per unit insulin secreted, but insulin secretion is sufficiently impaired to result in overt diabetes. In these terms conditions that increase insulin resistance—obesity, pregnancy, infection, excess glucocorticoids, and growth hormone—precipitate, and conditions that decrease insulin resistance—for example, glucocorticoid and growth hormone deficiency and unknown factors—delay the onset of overt diabetes in individuals possessing the inherited beta cell defect characteristic of diabetes mellitus.
Pneumococcal Vaccine-Reply
Authors: Carol Brignoli Gable
Journal: JAMA (1991)

<h3>In Reply.—</h3> We conducted a retrospective observational study of the effectiveness of pneumococcal vaccination by examining a "real world" cohort of vaccinated persons in the year before and after vaccination. An age- and sex-matched comparison group served only as a reference for pneumonia prevalence in the subsequent year. This design reduced the potential confounding from external factors by using persons as their own controls and objectively supports the outcomes by identifying the 2-year trend in pneumonia without vaccination.<sup>1</sup> Drs Weiss and Foy expressed concern about using persons as their own controls because the high pneumonia rate prior to vaccination might regress to the mean in the subsequent year. In general, this is a valid concern, especially in studies where subjects are selected with abnormally high or low biological variables and no comparison cohort is followed up.<sup>2</sup>However, pneumonia presents a different situation because it is a condition that
A Brief Report on Outcomes of Stereotactic Ablative Radiotherapy for a Second Primary Lung Cancer: Evidence in Support of Routine CT Surveillance
Authors: Gwendolyn H.M.J. Griffioen, Frank J. Lagerwaard, Cornelis J.A. Haasbeek, Ben J. Slotman, Suresh Senan
Journal: Journal of Thoracic Oncology (2014)