tbuckley/cabot-search huggingface dataset:
General Anaesthesia for Tracheostomy in Acute Laryngeal Obstruction in Children
Authors: E. H. Seward, R. A. Fraser
Journal: BMJ (1961)

The commonest forms of acute inflammatory laryngeal obstruction in childhood are acute laryngitis and acute laryngo-tracheo-bronchitis.Both infections are of remarkably sudden onset, though there may be a history of an insignificant infection of the upper respiratory tract.In both conditions there is rapidly increasing respiratory embarrassment, with inspiratory stridor, a harsh irritating cough, a hoarse muffled cry, intercostal recession, cyanosis, and a very considerable fear and distress.Signs of increasing obstruction are a rising pulse rate and restlessness.In acute laryngitis the epiglottis and the subglottic region are particularly inflamed and swollen, because in these areas the submucosa is lax.Acute epiglottitis has been described as a separate entity.In such cases, once the obstruction has been bypassed by tracheostomy, recovery should be uneventful.It is often possible to remove the tube within three days.In acute laryngo-tracheo-bronchitis the inflammation of the larynx may not be so severe, but an inflammatory oedema with exudation affects the whole lower respiratory tract.The problem here is to provide for the removal of somewhat viscid secretions in a child with a cough that is inefficient because of laryngeal inflamma- tion.Tracheostomy not only affords a way of bypassing the inflamed larynx but also allows for aspiration of the secretions from trachea and bronchi and reduction of dead space.Recovery is not usually as rapid as in the first group.It may be a week or more before the tracheostomy tube can be removed.
ABC of arterial and vascular disease: Vasculitis
Authors: C O S Savage
Journal: BMJ (2000)

Vasculitis is inflammation of blood vessel walls. The clinical and pathological features are variable and depend on the site and type of blood vessels that are affected. Diseases in which vasculitis is a primary process are called primary systemic vasculitides. 


The main types of vasculitides can be described using clinical features and pathological findings according to the Chapel Hill Consensus Conference. These names and definitions will be followed in this article. Definitive classification of systemic vasculitis is unsatisfactory since aetiology and pathogenesis are rarely known, and clinical and histological features overlap. Vasculitis may also occur as a secondary feature in other diseases, such as systemic lupus erythematosus and rheumatoid arthritis. 


Definitions of large vessel vasculitis
Giant cell arteritis (temporal arteritis)


Granulomatous arteritis of aorta and its major branches, especially extracranial branches of carotid artery


Often affects temporal artery


Usually occurs in patients older than 50 years


Often associated with polymyalgia rheumatica





Takayasu's arteritis


Granulomatous inflammation of aorta and its major branches


Usually occurs in patients younger than 50 years








Fever, night sweats, malaise, myalgia, and arthralgia are common in all types of vasculitis. Active vasculitis is usually associated with an acute phase response with an increase in C reactive protein concentration, erythrocyte sedimentation rate, or plasma viscosity.
Blood vessels and lymphatics.
Authors: Edward A. Edwards
Journal: JAMA (1963)

This is a most exciting and informative large work on the basic considerations bearing on blood vessels in general and in specific areas, as well as on lymphatics. Under the capable editorship of Dr. Abramson, 52 scientists have collaborated on details of the embryology, anatomy, physiology, pharmacology, biochemistry, and pathology of the blood vessels and lymphatics. Clinical entities are mentioned, but this is not a work on clinical medicine per se. Instead, the purpose of the work is to enable physicians to understand the pathologic physiology of diseases encountered and to render support and encouragement to those engaged in research on almost any phase of the blood vessels and lymphatics. The authorities have been well chosen. Their work has been presented concisely and clearly in a well coordinated fashion. The format of the book is excellent, with classification of subject matter clearly given. In addition, both subject matter and references
The Soluble Serum Protein Gas6 Bridges Virion Envelope Phosphatidylserine to the TAM Receptor Tyrosine Kinase Axl to Mediate Viral Entry
Authors: Kouki Morizono, Yiming Xie, Tove Olafsen, Benhur Lee, Asim Dasgupta, Anna M. Wu, Irvin S.Y. Chen
Journal: Cell Host & Microbe (2011)
Airway remodelling in children with cystic fibrosis
Authors: T. N Hilliard, N. Regamey, J. K Shute, A. G Nicholson, E. W F W Alton, A. Bush, J. C Davies
Journal: Thorax (2007)

<h3>Background:</h3> The relationship between airway structural changes and inflammation is unclear in early cystic fibrosis (CF) lung disease. A study was undertaken to determine changes in airway remodelling in children with CF compared with appropriate disease and healthy controls. <h3>Methods:</h3> Bronchoalveolar lavage and endobronchial biopsy were performed in a cross-sectional study of 43 children with CF (aged 0.3–16.8 years), 7 children with primary ciliary dyskinesia (PCD), 26 with chronic respiratory symptoms (CRS) investigated for recurrent infection and/or cough and 7 control children with no lower airway symptoms. Inflammatory cells, cytokines, proteases and matrix constituents were measured in bronchoalveolar lavage fluid (BALF). Reticular basement membrane (RBM) thickness was measured on biopsy specimens using light microscopy. <h3>Results:</h3> Increased concentrations of elastin, glycosaminoglycans and collagen were found in BALF from children with CF compared with the CRS group and controls, each correlating positively with age, neutrophil count and proteases (elastase activity and matrix metalloproteinase-9 (MMP-9) concentration). There were significant negative correlations between certain of these and pulmonary function (forced expiratory volume in 1 s) in the CF group (elastin: <i>r</i> = −0.45, p&lt;0.05; MMP-9:TIMP-1 ratio: <i>r</i> = −0.47, p&lt;0.05). Median RBM thickness was greater in the CF group than in the controls (5.9 μm vs 4.0 μm, p&lt;0.01) and correlated positively with levels of transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>; <i>r</i> = 0.53, p = 0.01), although not with other inflammatory markers or pulmonary function. <h3>Conclusions:</h3> This study provides evidence for two forms of airway remodelling in children with CF: (1) matrix breakdown, related to inflammation, proteolysis and impaired pulmonary function, and (2) RBM thickening, related to TGF-β<sub>1</sub> concentration but independent of other markers of inflammation.
Relation between inflammation and symptoms in asthma
Authors: I. Tillie‐Leblond, D. Montani, B. Crestani, J. De Blic, M. Humbert, M. Tunon‐de‐Lara, A. Magnan, N. Roche, J. Ostinelli, P. Chanez
Journal: Allergy (2009)

Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids.
Mechanisms of clonal abortion tolerogenesis. I. Response of immature hapten- specific B lymphocytes
Authors: GJV Nossal, BL Pike
Journal: The Journal of Experimental Medicine (1978)

B lymphocytes with receptors specific for the hapten fluorescein (FLU) were prepared from the spleens of mice of various ages. For most experiments, a one-step fractionation procedure based on the adherence of FLU-specific cells to FLU-gelatin was used. For some experiments, a subset of higher FLU-binding capacity was prepared from the FLU-gelatin binding population through the use of the fluorescence-activated cell sorter (FACS). FLU-specific B cells were placed into microculture with either FLU(3.6)-human gamma globulin (FLU(3.6)HGG) or FLU(12)HGG usually for 24 h at 37 degrees C. The tolerogen was then removed and 0.1 mug/ml of a T-independent antigen, FLU-polymerized flagellin, was substituted. 3 days later, cells were harvested from the microcultures and assayed for FLU-specific plaque-forming cells to determine any reduction in clonable hapten-specific B cells which the tolerogenesis treatment might have induced. The results showed that with FLU(3.6)HGG, hapten-specific newborn B cells could be tolerized at 1,000-fold lower tolerogen concentrations than adult splenic B cells of equal antigen-binding capacity. The high-avidity subset was even more susceptible to tolerance induction. Tolerance could be induced within 8 but not within 2 h, and at lower tolerogen concentrations, longer periods of tolerogenesis were required for a given effect. Using a 24-h tolerogenesis phase, 50 percent reduction in clone frequency among newborn FLU-gelatin fractionated cells was achieved at 0.08 mug/ml of FLU(3.6)HGG. Tolerance induction in immature B cells was inhibited by the concomitant presence of a polyclonal B-cell activator, Escherichia coli lipopolysaccharide (LPS) but tolerance once induced, was stable to challenge with LPS. Tolerogenesis was hapten specific. The proportion of tolerizable cells in spleens decreased with increasing age, reaching 50 percent at around 9 days. FLUI(12)HGG proved a more powerful tolerogen than FLU(3.6)HGG. It had an effect on adult cells, 50 percent reduction in clone frequency being noted at around 1 mug/ml. However, and in contrast to results claimed for other T- independent systems, there still was a major difference between immature and mature B cells, the immature cells displaying much greater sensitivity to tolerogenesis.
Acute Granulomatous Hepatitis
Authors: Herbert L. Bonkowsky
Journal: JAMA (1975)

Two previously healthy adults with acute granulomatous hepatitis attributable to cytomegalovirus (CMV) mononucleosis had prolonged fever, heterophil-negative lymphocytosis with numerous atypical forms, minor alterations in hepatic function, and evidence on biopsy, of a nonspecific acute hepatitis with granulomata. Infection with CMV was corroborated by a rising titer of complement-fixing antibody in case 1 and by a high titer of antibody that later fell in case 2. It is important to exclude CMV infection as an etiologic factor in cases of acute granulomatous hepatitis and fever of unknown origin. (<i>JAMA</i>233:1284-1288, 1975)
Praziquantel: a new schistosomicide against Schistosoma haematobium.
Authors: J E McMahon, N Kolstrup
Journal: BMJ (1979)

The effectiveness of the new schistosomicide praziquantel was assessed in African schoolchildren infected with Schistosoma haematobium. They were stratified according to the severity of their infection and were then randomly allocated to treatment with two single-dose regimens (30 and 40 mg/kg) and a split regimen of two doses of 20 mg/kg given four hours apart. All three regimens were highly effective and produced few side effects. Children who initially had very high pretreatment egg loads showed a poorer therapeutic response at all dose levels, and further investigations are necessary to find the optimum dose. Because of its effectiveness in a single dose and lack of toxicity, praziquantel may prove to be the ideal schistosomicide.
Low density lipoprotein subfractions and [Ca2+]i in vascular smooth muscle cells.
Authors: B Weisser, R Locher, J de Graaf, W Vetter
Journal: Circulation Research (1993)

Several studies have established that plasma low density lipoprotein (LDL) consists of various discrete subfractions. Using a variety of techniques (analytical ultracentrifugation, equilibrium density gradient ultracentrifugation, and gradient gel electrophoresis), LDL has been fractionated into a maximum of seven subclasses that differ in particle size, density, and physiochemical composition. Recently, a predominance of smaller denser LDL particles has been associated with an increased risk of coronary artery disease. However, other lipoprotein changes, such as elevated triglycerides and lower HDL cholesterol levels, have been shown in patients with a predominance of the smaller denser LDL subfractions. Thus, it is unclear whether the enhanced atherogenic potential is induced by the LDL subfraction pattern per se or by concomitant lipoprotein changes. Because intracellular free Ca2+ is an important second messenger involved in atherogenesis and regulation of vascular tone, we studied the influence of three LDL subfractions (very light [LDL1], 1.030 to 1.033 g/mL; light [LDL2], 1.033 to 1.040 g/mL; and dense [LDL3], 1.040 to 1.045 g/mL) on [Ca2+]i in vascular smooth muscle cells (VSMCs) cultured from rat aorta. LDL subfractions were isolated by density gradient ultracentrifugation from human EDTA-plasma (n = 15). [Ca2+]i was measured by fura 2 fluorescence. Basal [Ca2+]i was 77 +/- 6 nmol/L. Stimulation of VSMCs with dense LDL3 caused a significantly (P < .05) more pronounced increase (+71 +/- 13 nmol/L) compared with LDL1 (+38 +/- 8 nmol/L) and LDL2 (+36 +/- 9 nmol/L). To further investigate the mechanisms leading to the stimulation of [Ca2+]i by LDL subfractions, we incubated VSMCs with the Ca2+ antagonists nifedipine, diltiazem, and verapamil in concentrations up to 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by Vβ CDR3 spectratyping and flow cytometry
Authors: Antonio M. Risitano, Hoon Kook, Weihua Zeng, Guibin Chen, Neal S. Young, Jaroslaw P. Maciejewski
Journal: Blood (2002)
Echocardiographic measurements in normal subjects. Growth-related changes that occur between infancy and early adulthood.
Authors: W L Henry, J Ware, J M Gardin, S I Hepner, J McKay, M Weiner
Journal: Circulation (1978)

Echocardiographic measurements of the left ventricular dimensions and wall thicknesses at end diastole and end systole, aortic root and left atrial dimensions, mitral valve E-F slope, left ventricular ejection fraction, percent fractional shortening of the left ventricular internal dimension, estimated left ventricular mass and percentage systolic thickening of the ventricular septum and left ventricular free wall were obtained in 105 normal subjects ranging from one day to 23 years of age. Each parameter was found to follow a linear regression upon one of three functions of the body surface area. The internal dimensions of left ventricle, the left atrium, and the aortic root, and the mitral valve E-F slope varied in a linear relation to the cube root of the body surface area. Thickness of the ventricular septum and left ventricular free wall varied in a linear relation to the square root of the body surface area. Estimated left ventricular mass varied linearly with the direct measurement of body surface area. Ejection fraction, percent fractional shortening of the left ventricle and percent systolic thickening of the ventricular septum and left ventricular free wall were independent of body surface area despite a marked increase in the size of the left ventricle during normal growth and development.
P218 Predicting pneumothorax outcome by air leak measurement: Pilot using digital suction device
Authors: RJ Hallifax, JP Corcoran, NM Rahman
Journal: Thorax (2013)

<h3>Introduction</h3> Spontaneous pneumothorax (SP) is common, with an estimated incidence of 5,000 per year in the UK. Primary spontaneous pneumothorax (PSP) can be managed with needle aspiration initially but those who fail to re-expand, and the majority of secondary SP (SSP), require admission to hospital, insertion of a chest drain and connexion to a bulky underwater drainage system. Patients with SSP have greater co-morbidities; have a long hospital stay (14–16 days) and a mortality of ~16%. There are no good predictors of outcome for patients with pneumothorax: those who will respond to drainage, those who have persistent air leak and those who will require surgery. Significant early air leak could be indicative of those patients who will not resolve spontaneously and will require surgery. <h3>Aim</h3> To determine whether air leak measurement can predict patient outcome (surgical referral rate). <h3>Methods</h3> Between December 2012 and June 2013, patients with pneumothorax managed on the Respiratory Ward of a tertiary referral centre had their “air leak” measured using a digital suction device (Thopaz, Medela UK). <h3>Results</h3> A total of nine patients (6 SSP, 2 PSP, and 1 iatrogenic) were investigated. Air leak was measured during their in-patient stay: median of 3.5 days after admission (range 1–16 days). Three (33%) were referred for surgical intervention for continued air leak and pneumothorax: their average air leak was 504ml/min (range 222–952 ml/min) compared to 77 ml/min (range 1–225 ml/min) for the six patients not referred. The 427ml/min difference was not statistically significant (p = 0.2) with this sample size. <h3>Conclusion</h3> At present, there are no good predictors of outcome for patients with pneumothorax. Air leak measurement post-drain insertion may be useful surrogate marker for on-going leak and hence non-resolving pneumothorax. This pilot study showed a difference in early leak measurement between those patients who were ultimately referred for surgery and those spontaneously resolving, and further larger studies are now warranted, comparing air leak to clinically important outcomes in pneumothorax.
Should we use regulation to demand improved public health outcomes from industry? Yes
Authors: S. D Sugarman
Journal: BMJ (2008)

Preventable chronic diseases are a major threat to health worldwide. <b>Stephen Sugarman</b> argues that setting targets for companies will produce innovative solutions, but <b>Stig Pramming</b> (doi:10.1136/bmj.a1761) believes collaboration is the best way to improve health
Sodium channel mutations in epilepsy and other neurological disorders
Authors: M. H. Meisler
Journal: Journal of Clinical Investigation (2005)

Since the first mutations of the neuronal sodium channel SCN1A were identified 5 years ago, more than 150 mutations have been described in patients with epilepsy. Many are sporadic mutations and cause loss of function, which demonstrates haploinsufficiency of SCN1A. Mutations resulting in persistent sodium current are also common. Coding variants of SCN2A, SCN8A, and SCN9A have also been identified in patients with seizures, ataxia, and sensitivity to pain, respectively. The rapid pace of discoveries suggests that sodium channel mutations are significant factors in the etiology of neurological disease and may contribute to psychiatric disorders as well.
Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
Authors: Mark G. Kris, Bruce E. Johnson, Lynne D. Berry, David J. Kwiatkowski, A. John Iafrate, Ignacio I. Wistuba, Marileila Varella-Garcia, Wilbur A. Franklin, Samuel L. Aronson, Pei-Fang Su, Yu Shyr, D. Ross Camidge, Lecia V. Sequist, Bonnie S. Glisson, Fadlo R. Khuri, Edward B. Garon, William Pao, Charles Rudin, Joan Schiller, Eric B. Haura, Mark Socinski, Keisuke Shirai, Heidi Chen, Giuseppe Giaccone, Marc Ladanyi, Kelly Kugler, John D. Minna, Paul A. Bunn
Journal: JAMA (2014)

Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials.To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival.From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival.Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies.Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival.From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006).Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival.clinicaltrials.gov Identifier: NCT01014286.
Vacuum‐assisted delivery is associated with late‐onset asthma
Authors: L. Keski‐Nisula, M. Harju, M.‐R. Järvelin, J. Pekkanen
Journal: Allergy (2009)

Perinatal factors during delivery might modulate fetal immunological development and thereby be associated with the development of allergic diseases and asthma later.Perinatal data was recorded during pregnancy and at the time of delivery in regard to 5823 children who were born in Northern Finland in 1985-1986. Data from self-administered questionnaires were available at the ages of 7 and 15-16 years and skin prick tests for four main allergens were carried out at the age of 15-16 years. Only singletons delivered by the vaginal route were analyzed.There was a higher prevalence of doctor-diagnosed asthma at any time of life among children who were delivered by vacuum extraction (RR 1.80, 95% CI 1.27-2.56; P < 0.001) in comparison with spontaneously delivered children. In particular, this risk was increased as regards late-onset asthma (RR 2.41, 95% CI 1.52-3.81; P < 0.001). Perinatal effects had less impact on the development of other asthma, atopy or hay fever.The delivery by vacuum extraction had significant impact on the development of late-onset asthma compared with spontaneously delivered children.