tbuckley/cabot-search huggingface dataset:
INCOMPLETE DILATATION OF THE LUNGS AS A FACTOR IN NEONATAL MORTALITY
Authors: YANDELL HENDERSON
Journal: JAMA (1931)

Many children now die at birth or within the neonatal period who could and should live. Among these fatalities the largest group is that which results from one or other of such related conditions as primary or secondary failure of respiration, inadequate expansion of the lungs, and pneumonia developing from atelectasis. The knowledge requisite to save a large percentage of these lives is now available. It is clear and certain. The method of its application is simple and inexpensive. It is merely an inhalation of carbon dioxide in oxygen for a few minutes several times a day during each of the first few days of life. Every new-born child, even those that appear normal, should receive this treatment as a prophylactic to insure early and complete relief of atelectasis. The hazard of neonatal pneumonia is thus largely eliminated. For the prevention of blindness, disinfection of the eyes with silver nitrate
Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial
Authors: Suresh S Ramalingam, Pasi A Jänne, Tony Mok, Kenneth O'Byrne, Michael J Boyer, Joachim Von Pawel, Adam Pluzanski, Mikhail Shtivelband, Lara Iglesias Docampo, Jaafar Bennouna, Hui Zhang, Jane Q Liang, Jim P Doherty, Ian Taylor, Cecile B Mather, Zelanna Goldberg, Joseph O'Connell, Luis Paz-Ares
Journal: The Lancet Oncology (2014)
Evidence for beta adrenoceptors in proximal tubules. Isoproterenol-sensitive adenylate cyclase in pars recta of canine nephron.
Authors: N Murayama, B T Ruggles, S M Gapstur, J L Werness, T P Dousa
Journal: Journal of Clinical Investigation (1985)

Observations in vivo suggest that catecholamines modulate reabsorptive functions of proximal tubules by acting on beta-adrenoceptors. However, beta-catecholamine binding sites or beta-adrenoceptor-sensitive adenylate cyclase (AdC) has not been found in segments of proximal tubules of rat, rabbit, or mouse kidney. In the present study, we investigated the responsiveness of AdC to catecholamines, [8-Arg]vasopressin (AVP), and to parathyroid hormone (PTH) in proximal convoluted tubules (PCT), proximal straight tubules (PST), and in late distal convoluted tubules (LDCT) microdissected from canine kidney. Isoproterenol (ISO) caused a marked and dose-dependent stimulation of AdC in PST (maximum: delta + 850%; half maximum stimulation at 10(-7) M ISO), but ISO had no effect on AdC in PCT. The AdC in both PCT and PST was markedly stimulated by PTH; AVP stimulated the AdC in LDCT but not in PST or in PCT. The stimulatory effect of 10(-5) M ISO in PST (delta + 725%) was significantly greater than in LDCT (delta + 307%); norepinephrine and epinephrine had stimulatory effects in PST similar to ISO. The stimulation of AdC in PST by ISO was blocked by propranolol and by beta 2-blocker ICI-118551. On the other hand, alpha-blocker phentolamine and beta 1-blocker metoprolol did not abolish the stimulation of AdC in PST by ISO. The accumulation of cAMP in intact PCT and PST incubated in vitro was stimulated by PTH both in PST and in PCT, but ISO elevated cAMP (delta + 683%) only in PST. Our results show that proximal tubules of canine nephron, PST but not PCT, contain beta-adrenoceptors of beta 2 subtype coupled to AdC. These observations provide direct evidence that the effects of catecholamines, either released from renal nerve endings or arriving from blood supply, can act directly on beta 2-adrenoceptors located in proximal tubules, and also suggest that at least some of the catecholamine effects in proximal tubules are mediated via cAMP generation.
Biodistribution and efficacy of donor t lymphocytes in a murine model of lysosomal storage disease
Authors: Pampee P Young, Carole Vogler, A Alex Hofling, Mark S Sands
Journal: Molecular Therapy (2003)

Lymphocyte-directed gene transfer has been proposed as potential therapy to treat certain congenital immunological deficiencies as well as other genetic diseases such as lysosomal storage diseases (LSDs). To understand better the extent to which adoptively transferred peripheral T lymphocytes (PTLs) are able to ameliorate LSDs we utilized the β-glucuronidase-deficient mouse as a model system. PTLs (1 × 107) isolated from the spleen of syngeneic mice overexpressing (∼8-fold) human β-glucuronidase (GUSB) were injected intravenously into young adult β-glucuronidase-deficient mice without myeloablative conditioning. Using biochemical and histochemical assays, we were able to track the donor lymphocytes in vivo. Donor lymphocytes were detected in relatively high numbers in liver, spleen, small intestine, mesenteric lymph node, and thymus for at least 5 months, the last time point of analysis. Although liver and spleen had the highest total GUSB activity, histopathologic analysis demonstrated minimal to no correction of lysosomal distention at all time points studied. By contrast, we have shown in earlier studies that administration of similar numbers of macrophages reduced lysosomal storage in several organs, including liver and spleen. To understand this difference in efficacy, we compared the relative level of GUSB released into the medium by nonactivated and activated PTLs as well as by macrophages. Macrophages released >50-fold excess enzyme compared to either activated or nonactivated PTLs. These data suggest that a LSD can be more effectively treated by directing a gene therapy approach to a hematopoietic lineage other than T lymphocytes.
P192 A pilot study to assess the influence of β2-adrenoceptor polymorphism on small airway function and asthma control: Abstract P192 Table 1:
Authors: A Manoharan, J Lipworth, PM Short, WJ Anderson, PA Williamson, J Berg, BJ Lipworth
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> It is increasingly recognised that small airway dysfunction is associated with suboptimal asthma control. We have previously reported that β2-adrenoreceptor polymorphism at position 16 (i.e. Arg/Gly) is not related to FEV<sub>1</sub> or airway hyper-responsiveness in persistent asthmatics.<sup>1</sup> However effects of β2-adrenoreceptor polymorphism on the small airways are not known. This pilot study in a different cohort of patients evaluated the effects of β2-adrenoreceptor polymorphism on small airway function and asthma control. Impulse oscillometry (IOS) was used to assess small airway function along with FEF<sub>25–75</sub>. IOS is an effort independent test performed during normal quiet tidal breathing and is able to discriminate between changes in central and peripheral airways. Resistance at 5 Hz (R5) and 20 Hz (R20) indicate total and central airway resistance respectively - the difference between R5 and R20 indicates peripheral airway resistance. Asthma control was assessed using the Asthma Control Questionnaire (ACQ-5). <h3>Methods</h3> We collected spirometry, IOS and ACQ data from patients attending a secondary care asthma clinic. A total of 100 patients all taking inhaled corticosteroids (20% taking long acting beta-agonists) were included with a mean: age 39.2 year FEV<sub>1 </sub>88.4%, FEF<sub>25–75</sub>% 55.5%, R5%162%, R5-R20 0.07 kPa/l/s, ACQ-5 1.70 <h3>Results</h3> 48% (n = 48) had 1 or 2 copies of the Arg allele (i.e. Arg/Arg or Arg/Gly genotypes) while 52% (n = 52) had no copies of the Arg allele (i.e. Gly/Gly genotype). There was no significant difference between genotypes in terms of FEV<sub>1</sub>, FEF<sub>25–75</sub>, R5, R5-R20 or ACQ. Furthermore there was no significant effect of LABA according to Arg/Gly polymorphism. <h3>Reference</h3> 1. Manoharan A, Anderson WJ, Lipworth BJ. Influence of β2-adrenergic receptor polymorphism on methacholine hyperresponsiveness in asthmatic patients. Ann Allergy Asthma Immunol 2013;110: 161–164
The Value of the Right Precordial Leads of the Electrocardiogram
Authors: Hein J.J. Wellens
Journal: New England Journal of Medicine (1999)

The electrocardiogram continues to be a valuable, noninvasive, easily repeatable, and inexpensive means of diagnosing many cardiac abnormalities, such as myocardial infarction, ischemia, and ventricular hypertrophy, and it is unequaled in the analysis of cardiac arrhythmias. Also, in the past few decades the clinical information that can be derived from the electrocardiogram has grown continually.1 Traditionally, 12 leads are recorded, 6 leads on the extremities and 6 on the precordium. This has been the standard approach for almost half a century. The extremity leads give a more distant image of the electrical activity of the heart. For example, leads II . . .
Validation of viscosity measurements for canine hepatic bile
Authors: David D. Wilson, Howard S. Lowensohn
Journal: Hepatology (1988)

This study developed the validated standards for a known viscosity method by obtaining consistent viscosity measurements with defined precision, reproducibility and sensitivity limits for canine hepatic bile. Size 75 Cannon-Manning semimicro viscometers yielded the most precise viscosity measurements. With the development of proper handling methods for fresh bile samples, a precision defined by a coefficient of variation of less than or equal to +/- 0.3% was obtained. To maintain viscometer constancy, the viscometers must be cleaned with chromic acid after each bile test and pass reproducibility tests using defined distilled water viscosity tests.
Genotyping Non-small Cell Lung Cancer (NSCLC) in Latin America
Authors: Oscar Arrieta, Andrés Felipe Cardona, Guillermo Federico Bramuglia, Aly Gallo, Alma D. Campos-Parra, Silvia Serrano, Marcelo Castro, Alejandro Avilés, Edgar Amorin, Ricardo Kirchuk, Mauricio Cuello, José Borbolla, Omar Riemersma, Henry Becerra, Rafael Rosell
Journal: Journal of Thoracic Oncology (2011)
Platelet function, thromboxane formation and blood pressure control during supplementation of the Western diet with cod liver oil.
Authors: R Lorenz, U Spengler, S Fischer, J Duhm, P C Weber
Journal: Circulation (1983)

Epidemiologic and experimental data suggest an antiatherothrombotic potential of omega-3 polyunsaturated fatty acids. Therefore, the Western diet, which supplies predominantly omega-6 polyunsaturated fatty acids, was supplemented with 40 ml/day of cod liver oil, which provides about 10 g of omega-3 polyunsaturated fatty acids daily, for 25 days in eight volunteers. The omega-3 polyunsaturated fatty acids were incorporated in platelet and erythrocyte membrane phospholipids at the expense of omega-6 polyunsaturated fatty acids. Bleeding time increased (p less than 0.01) and platelet count (p less than 0.05), platelet aggregation upon ADP and collagen (p less than 0.01-0.05), and associated thromboxane B2 formation (p less than 0.01) decreased. Blood pressure (p less than 0.05) and blood pressure response to norepinephrine (p less than 0.01) and angiotensin II (NS) fell, without major changes in plasma catecholamines, renin, urinary aldosterone, kallikrein, prostaglandins E2 and F2 alpha and red cell cation fluxes. Biochemical and functional changes were reversed 4 weeks after cod liver oil was discontinued. Formation of prostaglandins derived from eicosapentaenoic acid and interference of eicosapentaenoic acid with formation and action of prostaglandins derived from arachidonic acid were evident in vitro. Whatever the mechanism, this moderate supplement of omega-3 polyunsaturated fatty acids markedly changed membrane phospholipids, which was associated with a shift toward less reactive platelets and a blunted circulatory response to pressure hormones.
Diets and obesity
Authors: V. Katikireddi
Journal: BMJ (2004)

The BBC Horizon programme reviewed in this week's BMJ again raised questions about the ever popular Atkins diet. Does it work? If so, how does it work? And what are the risks?

The website of Atkins Nutritionals (http://atkins.com/) offers an overview of the science behind the diet—with summaries of articles from peer reviewed journals taken from PubMed—as well as providing many controlled carb …
Book: Cold Wars: The Fight against the Common Cold
Authors: H. Ellis
Journal: BMJ (2003)

David Tyrrell, Michael Fielder Oxford University Press, £19.99, pp 253 ISBN 0 19 263285 X Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> Who hasn't had a cold, or indeed colds, in the past 12 months? Probably no one reading this review, unless you spent the time completely isolated—for example, on an Antarctic weather station or on Tristan da Cunha. Yet the cold, the commonest of all illnesses, has no prophylaxis and no effective cure. This in spite of the longest list of suggested therapies for any disease, ranging from John Wesley's advice in 1747 to “pare very thin the yellow rind of an orange, roll it up inside and thrust a roll into … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Inlet and intrachamber concentration distributions in tracer studies of the canine central circulation and their relation to the isotope dilution residue function.
Authors: F S Castellana, S M Snapinn, S Y Tam, R B Case
Journal: Circulation Research (1980)

We analyzed the isotope dilution residue function from a single cardiac chamber for an arbitrary inlet distribution of tracer and arbitrary mixing within the chamber, and established a general relationship between cardiac output and the chamber residue function. In our experiments, we made simultaneous temperature measurements in three left ventricular chamber subregions of the dog subjected to left and right atrial injections of chilled saline. Flow-proportional tracer labeling always occurred at the left ventricular inlet when injection was into the right atrium. This state almost never obtained, however, with direct left atrial injection, although it was approximated most closely when multiple side hole cathers were used. We also demonstrated that imperfect tracer mixing in the normal ventricle can lead to significant regional temperature inequalities during tracer passage. These inequalities are more pronounced in the ventricle with compromised function, but in both normal and compromised ventricles they are minimal several beats after tracer concentration peaks if injection is into the right atrium.
Alzheimer's Disease: Treatment and Long-term Management
Authors: Edward D. Bird
Journal: JAMA (1990)

<h3>Alzheimer's Disease, edited by Richard J. Wurtman, Suzanne Corkin, John H. Growdon, and Eva Ritter-Walker (Adv Neurol, vol 51), 282 pp, with illus, $85, ISBN 0-88167-574-1, New York, NY, Raven Press, 1990.</h3> <i>Alzheimer's Disease: Treatment and Long-Term Management</i>is the fourth volume in a series that deals with therapy in neurological disorders. This is a most welcome resource for the management of Alzheimer's disease. There has not to my knowledge been a text devoted specifically to this issue; the care of the patient with Alzheimer's disease is usually left to the final chapters of publications that focus mainly on diagnosis and/or theoretical causes. The progressive deterioration that occurs in Alzheimer's disease does not make the care of such patients very exciting. However, this text includes chapters by a number of care givers from a wide range of allied health specialties who have devoted a great deal of attention to improving the
The Functional Intraoperative Pulmonary Blood Flow Study Is a More Sensitive Predictor Than Preoperative Anatomy for Right Ventricular Pressure and Physiologic Tolerance of Ventricular Septal Defect Closure After Complete Unifocalization in Patients With Pulmonary Atresia, Ventricular Septal Defect, and Major Aortopulmonary Collaterals
Authors: Osami Honjo, Osman O. Al-Radi, Cathy MacDonald, Kim-Chi D. Tran, Priya Sapra, Lisa D. Davey, Rajiu R. Chaturvedi, Christopher A. Caldarone, Glen S. Van Arsdell
Journal: Circulation (2009)

The objective was to determine if intraoperative pulmonary artery (PA) flow studies after complete unifocalization correlate with postrepair hemodynamics for pulmonary atresia (PA), ventricular septal defects (VSD), and major aortopulmonary collaterals.Twenty patients (median age, 8 months; weight, 7.9 kg) underwent unifocalization between 2003 and 2008. A functional PA flow study was achieved by cannulating the unifocalized central PA before intracardiac repair and increasing flow incrementally to 2.5 L/min per m(2). Mean PA pressure (mPAP) was measured. The intent was to close the VSD for a mPAP of <30 mm Hg. Right ventricular systolic pressure (RVSP) and systemic systolic pressure were recorded. Total incorporated pulmonary segments, pulmonary segment artery ratio (ratio of incorporated segments to 18), and total neopulmonary artery index (the sum of major aortopulmonary collaterals and native PA index) were calculated. The VSD was successfully closed in 18 patients (90%). One attempted closure required an intraoperative fenestration. The study mPAP correlated with RVSP (rho=0.72; P=0.0027) and RVSP/systemic systolic pressure (rho=0.67; P=0.0063). Total neopulmonary artery index had a nonsignificant negative correlation with RVSP (rho=-0.42; P=0.079). Total incorporated pulmonary segments and pulmonary segment artery ratio were not correlated. Flow study mPAP had the highest accuracy in predicting successful VSD closure: area under the receiver-operator curve (0.83) versus total neopulmonary artery index (0.42), pulmonary segments (0.35), and pulmonary segment artery ratio (0.33).The intraoperative pulmonary flow study predicted postoperative physiology significantly better than did standard anatomic measures. Conventional measures should be used with caution when determining the possibility for complete repair.
Interleukin‐4‐positive mast cells are highly associated with the extent of immediate allergic wheal reaction in the skin
Authors: J. V. Saarinen, R. J. Harvima, M. Horsmanheimo, I. T. Harvima, A. Naukkarinen
Journal: Allergy (2001)

Background : In addition to histamine, mast cells contain other potent mediators which can contribute to the allergic wheal reaction in the skin. Methods : To study the association of tryptase‐, chymase‐, and interleukin‐4 (IL‐4)‐positive mast cells with the size of the prick‐test wheal reaction, 50 sensitive atopic subjects were prick‐tested with the cow‐dander allergen on the forearm skin, and the wheal area was measured. A corresponding site of intact healthy‐looking skin was biopsied and examined enzyme‐histochemically for tryptase and chymase. A double‐staining method was used to demonstrate the immunoreactivity of IL‐4 and chymase inhibitors (α 1 ‐proteinase inhibitor and α 1 ‐antichymotrypsin) in mast cells. The levels of total and cow‐specific immunoglobulin E (IgE) were measured in serum. Results : The number of tryptase‐ and chymase‐positive mast cells or those containing chymase inhibitors revealed no correlation with the wheal reaction. In contrast, both the percentage and the number of IL‐4‐positive mast cells showed significant positive correlation with the wheal size per se ( P &lt;0.0001), as well as with the ratio of the wheal size by cow allergen to that by histamine control ( P &lt;0.003). In addition, tryptase‐, chymase‐, and IL‐4‐positive mast cells correlated with total IgE, but not with specific IgE, levels, and they showed no relation to the clinical manifestation of atopic disease, asthma or atopic dermatitis. Conclusions : The novel finding was that IL‐4‐positive, but not tryptase‐ and chymase‐positive, mast cells are intimately associated with the extent of the prick‐test wheal.
Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate
Authors: Gail D. Lewis Phillips, Guangmin Li, Debra L. Dugger, Lisa M. Crocker, Kathryn L. Parsons, Elaine Mai, Walter A. Blättler, John M. Lambert, Ravi V.J. Chari, Robert J. Lutz, Wai Lee T. Wong, Frederic S. Jacobson, Hartmut Koeppen, Ralph H. Schwall, Sara R. Kenkare-Mitra, Susan D. Spencer, Mark X. Sliwkowski
Journal: Cancer Research (2008)

HER2 is a validated target in breast cancer therapy. Two drugs are currently approved for HER2-positive breast cancer: trastuzumab (Herceptin), introduced in 1998, and lapatinib (Tykerb), in 2007. Despite these advances, some patients progress through therapy and succumb to their disease. A variation on antibody-targeted therapy is utilization of antibodies to deliver cytotoxic agents specifically to antigen-expressing tumors. We determined in vitro and in vivo efficacy, pharmacokinetics, and toxicity of trastuzumab-maytansinoid (microtubule-depolymerizing agents) conjugates using disulfide and thioether linkers. Antiproliferative effects of trastuzumab-maytansinoid conjugates were evaluated on cultured normal and tumor cells. In vivo activity was determined in mouse breast cancer models, and toxicity was assessed in rats as measured by body weight loss. Surprisingly, trastuzumab linked to DM1 through a nonreducible thioether linkage (SMCC), displayed superior activity compared with unconjugated trastuzumab or trastuzumab linked to other maytansinoids through disulfide linkers. Serum concentrations of trastuzumab-MCC-DM1 remained elevated compared with other conjugates, and toxicity in rats was negligible compared with free DM1 or trastuzumab linked to DM1 through a reducible linker. Potent activity was observed on all HER2-overexpressing tumor cells, whereas nontransformed cells and tumor cell lines with normal HER2 expression were unaffected. In addition, trastuzumab-DM1 was active on HER2-overexpressing, trastuzumab-refractory tumors. In summary, trastuzumab-DM1 shows greater activity compared with nonconjugated trastuzumab while maintaining selectivity for HER2-overexpressing tumor cells. Because trastuzumab linked to DM1 through a nonreducible linker offers improved efficacy and pharmacokinetics and reduced toxicity over the reducible disulfide linkers evaluated, trastuzumab-MCC-DM1 was selected for clinical development.
Physicians and the Acquired Immunodeficiency Syndrome
Authors: Dorsett D. Smith
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The editorial in the October 13 issue of<i>JAMA</i>entitled "Physicians and Acquired Immunodeficiency Syndrome: A Reply to Patients"<sup>1</sup>proposes that physicians not be required to disclose their human immunodeficiency virus (HIV) status to their patients since the risk of transmitting the disease to patients is small. This statement fails to consider the impact of the subtle development of HIV-related encephalopathy on patient care and judgment problems related to the slow and common development of dementia in HIV-infected individuals. An error in judgment can be as lethal as HIV infection, yet no consideration has been given to the impact of HIV-related dementia on patient interaction and health care. What is the medicolegal obligation of an employer who employs a physician with an HIV infection who makes a judgmental error related to HIV encephalopathy? The employer or hospital certainly would have some degree of culpability and medicolegal
OF WHAT USE IS SURGICAL TREATMENT IN OVARIAN NEUROSES?
Authors: A. F. JONAS
Journal: JAMA (1897)

The term<i>neurosis</i>, as commonly used by the profession, has an indefinite meaning. It may mean a pain, severe or slight, of a "neuralgic character.<sup>1</sup>' It is often applied to irregular functional disturbances, as for example, the gastro-intestinal functions, which may be perfect to-day, less so to-morrow, violently disturbed the next day, and normal the fourth, without any assignable cause. Neurosis may mean emotional manifestations, for example, irritability of temper, explosions of unprovoked grief, attacks of epileptiform convulsions, such psychic disturbances as melancholia and maniacal conditions. Ecstasy, delirium, hallucinations and trance have been called by that convenient term. It is often applied to that indefinite symptom-complex, known as neurasthenia, or more popularly called hysteria. In short, no matter what the train of symptoms may have been, when it seemed impossible to find structural changes due to inflammatory processes, acute or chronic, or when it could not be shown that