tbuckley/cabot-search huggingface dataset:
Preliminary Results of a Phase II Trial of Proton Radiotherapy for Pediatric Rhabdomyosarcoma
Authors: Matthew M. Ladra, Jackie D. Szymonifka, Anita Mahajan, Alison M. Friedmann, Beow Yong Yeap, Claire P. Goebel, Shannon M. MacDonald, David R. Grosshans, Carlos Rodriguez-Galindo, Karen J. Marcus, Nancy J. Tarbell, Torunn I. Yock
Journal: Journal of Clinical Oncology (2014)

This prospective phase II study was designed to assess disease control and to describe acute and late adverse effects of treatment with proton radiotherapy in children with rhabdomyosarcoma (RMS).Fifty-seven patients with localized RMS (age 21 years or younger) or metastatic embryonal RMS (age 2 to 10 years) were enrolled between February 2005 and August 2012. All patients were treated with chemotherapy based on either vincristine, actinomycin, and cyclophosphamide or vincristine, actinomycin, and ifosfamide-based chemotherapy and proton radiation. Surgical resection was based on tumor site and accessibility. Common Terminology Criteria for Adverse Events, Version 3.0, was used to assess and grade adverse effects of treatment. Concurrent enrollment onto Children's Oncology Group or European Pediatric Sarcoma Study Group protocols was allowed. All pathology and imaging were reviewed at the treating institution.Median follow-up was 47 months (range, 14 to 102 months) for survivors. Five-year event-free survival (EFS), overall survival (OS), and local control (LC) were 69%, 78%, and 81%, respectively, for the entire cohort. The 5-year LC by risk group was 93% for low-risk and 77% for intermediate-risk disease. There were 13 patients with grade 3 acute toxicity and three patients with grade 3 late toxicity. There were no acute or late toxicities higher than grade 3.Five-year LC, EFS, and OS rates were similar to those observed in comparable trials that used photon radiation. Acute and late toxicity rates were favorable. Proton radiation appears to represent a safe and effective radiation modality for pediatric RMS.
Farm exposure and time trends in early childhood may influence <scp>DNA</scp> methylation in genes related to asthma and allergy
Authors: S. Michel, F. Busato, J. Genuneit, J. Pekkanen, J.‐C. Dalphin, J. Riedler, N. Mazaleyrat, J. Weber, A. M. Karvonen, M.‐R. Hirvonen, C. Braun‐Fahrländer, R. Lauener, E. von Mutius, M. Kabesch, J. Tost
Journal: Allergy (2013)

Abstract Background Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases. Methods We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes ( ORMDL 1 , ORMDL 2 , ORMDL 3 , CHI 3L1 , RAD 50 , IL 13, IL 4 , STAT 6 , FOXP 3, and RUNX 3 ) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon–Mann–Whitney tests. Results In cord blood, regions in ORMDL 1 and STAT 6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD 50 and IL 13 were hypermethylated (lowest P ‐value ( STAT 6 ) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P ‐value ( IL 13 ) = 1.57*10 −8 ). Interestingly, these differences clustered in the genes highly associated with asthma ( ORMDL family) and IgE regulation ( RAD 50 , IL 13, and IL 4 ), but not in the T‐regulatory genes ( FOXP 3 , RUNX 3 ). Conclusions In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma‐ and allergy‐related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes.
Autoreactive B Cell Regulation: Peripheral Induction of Developmental Arrest by Lupus-Associated Autoantigens
Authors: Sandra Santulli-Marotto, Marc W Retter, Renelle Gee, Mark J Mamula, Stephen H Clarke
Journal: Immunity (1998)

Anti-Sm and anti-ssDNA transgenic (Tg) mice were generated using the VH-D-JH rearrangement of an anti-Sm hybridoma of MRL/Mp-lpr/lpr origin. B cells of each specificity account for 15%–35% of the splenic repertoire, but no circulating anti-Sm or anti-ssDNA antibodies are detected. Most autoreactive cells exhibit an immature B cell phenotype and have short half-lives equivalent to those of non-Tg immature B cells. However, at least some anti-Sm B cells are functional, because immunization with murine snRNPs induces anti-Sm secretion. We propose that anti-Sm and anti-ssDNA are eliminated during the transition to mature B cells and that this late stage of tolerance induction is consequential to their spontaneous activation in murine lupus.
Report on Clinical Use of BRL 1241 in Children with Staphylococcal and Streptococcal Infections
Authors: G. T. Stewart, H. H. Nixon, H. M. T. Coles, C. W. Kesson, D. Lawson, R. G. Thomas, J. N. Mishra, M. E. Mitchell, J. M. Semmens, T. H. H. Wade
Journal: BMJ (1960)

<h3>Abstract</h3> Every living cell is composed of macromolecules such as proteins, DNA, RNA and pigments. The ratio between these macromolecular pools depends on the allocation of resources within the organism to different physiological requirements, and in turn affects biogeochemical cycles of elements such as carbon, nitrogen and phosphorus. Here, we present detailed measurements of the macromolecular composition of <i>Prochlorococcus</i> MIT9312, a representative strain of a globally abundant marine primary producer, as it grows and declines due to nitrogen starvation in laboratory batch cultures. As cells reached stationary stage and declined, protein per cell decreased by ∼30% whereas RNA per cell and pigments per cell decreased by ∼75%. The decline stage was associated with the appearance of chlorotic cells which had higher forward scatter (a proxy for cell size) but lower chlorophyll autofluorescence, as well as with changes in photosynthetic pigment composition. Specifically, during culture decline divinyl-chlorophyll-like pigments emerged, which were not observed during exponential growth. These divinyl-chlorophyll-like pigments were also observed in natural samples from the Eastern Mediterranean. Around &gt;80% of the carbon fixed by <i>Prochlorococcus</i> MIT9312 (but not of a different strain, NATL2A) was released into the growth media as dissolved organic carbon under these laboratory conditions. Variations in RNA/protein indicate that, broadly defined, the macromolecular composition of <i>Prochlorococcus</i> MIT9312 is more similar to eukaryotic phytoplankton than to marine heterotrophic bacteria, possibly due to the significant investment in photosynthetic machinery of phototrophs.
Defense of Tracheostomy in Children
Authors: Cedric J. Priebe
Journal: JAMA (1975)

To the Editor.—  I read with concern the CLINICAL NOTE, Death Precipitated by Tracheostomy in a Child (231:277, 1975) by Drs. Schmidt, Bennett, and Dalai.  The pneumomediastinum in the 12-month-old drowning victim was most likely secondary to pulmonary interstitial emphysema due to high mechanical ventilating pressures of 70 to 80 cm H 2 O combined with 8 cm of positive end expiratory pressure, as may be seen in the newborn with the respiratory distress syndrome. Mediastinal air under tension usually decompresses spontaneously by rupturing into the pleural cavity, producing a treatable pneumothorax and relieving venous air block. 1 Cardiac air tamponade due to intrapericardial air may also develop and is improved by pericardiocentesis. 2 We have also successfully aspirated other localized collections of extrapleural air with small plastic catheters, but have not considered it wise to attempt decompression by surgical incision. As stated by the authors, a tracheostomy with its
Human right ventricular end-systolic pressure-volume relation defined by maximal elastance.
Authors: K A Brown, R V Ditchey
Journal: Circulation (1988)

This study was undertaken to determine 1) whether a combined radionuclide-hemodynamic technique could define the right ventricular end-systolic pressure-volume relation (RV ESPVR) in the clinical setting, 2) whether the human RV ESPVR defined by maximal elastance is linear and responsive to inotropic interventions, and 3) whether more easily measured modifications of the ESPVR are reliable substitutes as an index of RV function. Eight patients with normal RV function were studied with simultaneous micromanometer RV pressure measurements and radionuclide ventriculography to construct RV pressure-volume loops. Data were collected at baseline and after at least two alterations in loading conditions with nitroglycerin, phenylephrine, or saline. End systole was defined by maximal elastance (E(t) = P(t)/[V(t) - V0]). Data were also obtained during administration of dobutamine in four patients and after atrial pacing tachycardia in one patient. The RV ESPVR defined by maximal elastance was highly linear (r = 0.988-0.999) throughout the range of pressures and volumes tested. Furthermore, the linear correlations were significantly higher (p less than 0.005), and the linear regression standard error of the estimate (SEE) was significantly lower (p less than 0.005) for the RV ESPVR defined by maximal elastance compared with modifications of the ESPVR with the ratio of pulmonary artery-dicrotic notch pressure or RV peak pressure to end-ejection volume. Dobutamine or atrial pacing tachycardia produced a leftward shift of the entire RV pressure-volume loop, and in each patient (five of five), the point of maximal elastance fell outside the 95% confidence interval defined by the baseline ESPVR. However, because of the larger SEE, the leftward shift with modifications of the ESPVR was not statistically significant in any patient by the pulmonary artery-dicrotic notch pressure: end-ejection volume ratio and was significant in only one of five patients by the RV peak pressure: end-ejection volume ratio (p less than 0.03). Therefore, it appears that the steady-state RV ESPVR defined by maximal elastance in patients with normal RV function is responsive to alterations in inotropic state and is more sensitive to alterations in RV function than the frequently used, more easily measured modifications of the RV ESPVR.
Lessons from measles vaccination in developing countries.
Authors: A J Hall, F T Cutts
Journal: BMJ (1993)

and 33% of patients treated with the new regimen.'"The authors concluded that outcome in control patients was significantly improved compared with historical experience and that the new treatment regimen including extracorporeal carbon dioxide removal conferred no extra survival benefit.'2The conditions that must be met before further trials of extrapulmonary gas exchange can begin are daunting and make the prospect of randomised, controlled evaluation remote.Technology and clinical practice should be stable and standardised; trial protocols should direct patient selection and timing of intervention and dictate end points for failure and stopping treatment."The emergence of alternative treatments such as inhaled nitric oxide and exogenous sur- factant preparations will limit recruitment ofpatients.Centres would need experience of applying new treatments in such critically ill patients, yet be prepared to forgo their use in control patients even when conventional management is obviously failing, thereby giving rise to the same ethical dilemmas that affected assessment of these techniques in neonates.'Further studies are now required to define maximal conventional treatment and its outcome in patients meeting accepted criteria for treatment with extracorporeal membrane oxygenation, particularly as more sophisticated mechanical ventilatory support is evolving, thereby rendering historical controls invalid.A European registry of all forms of extrapulmonary lung support in adults should be established.Emphasis should be given to developing severity scoring systems in acute lung injury, which would provide advanced warning of deterioration and poor prognosis.Responsibility lies with regional referral centres to identify and transfer patients likely to benefit from adjuvant support treatments.More widespread application of these invasive techniques in the primary admitting units cannot be recommended until the technology has stabilised and the place of less invasive alternative treatments becomes clearer.
Live viruses to treat cancer
Authors: Oliver Donnelly, Kevin Harrington, Alan Melcher, Hardev Pandha
Journal: Journal of the Royal Society of Medicine (2013)

Viruses that selectively replicate in cancer cells, leading to the death of the cell, are being studied for their potential as cancer therapies. Some of these viruses are naturally occurring but cause little if any illness in humans; others have been engineered to make them specifically able to kill cancer cells while sparing normal cells. These oncolytic viruses may be selective for cancer cells because viral receptors are over-expressed on the surface of cancer cells or because antiviral pathways are distorted in cancer cells. Additionally, when oncolytic viruses kill cancer cells, it can stimulate an antitumour immune response from the host that can enhance efficacy. Numerous early phase trials of at least six oncolytic viruses have been reported with no evidence of concerning toxicity either as single agents or in combination with chemotherapies and radiotherapy. Three oncolytic viruses have reached randomized testing in cancer patients; reolysin in head and neck cancer and JX594 in hepatocellular cancers, while results from the first-phase III trial of T-vec in metastatic melanoma are expected shortly.
Specificity of small bowel biopsy findings in coeliac disease Reply
Authors: J C YARZE, J METCALF
Journal: Gut (1998)

Editor,—I read Dr Metcalf’s recent commentary ( Gut 1998; 42 :9–10) on the association between coeliac disease and primary biliary cirrhosis, with much enthusiasm. Her editorial was both succinct and insightful. My concern relates to the author’s suggestion that for coeliac disease, “endoscopic small bowel biopsy is specific.” Unfortunately, this statement is incorrect. Specifically, a …
Safety and efficacy of immunotherapy with <i>Polistes dominulus</i> venom: results from a large Italian database
Authors: M. Severino, P. Bonadonna, M. B. Bilò, G. Cortellini, M. Mauro, M. Schiappoli, D. Macchia, P. Campi, M. Manfredi, G. Passalacqua
Journal: Allergy (2009)
CELL SURFACE IMMUNOGLOBULIN
Authors: Ellen S. Vitetta, Jonathan W. Uhr
Journal: The Journal of Experimental Medicine (1972)

Turnover and release of cell surface Ig and secretion of total intracellular Ig has been studied in small lymphocytes from normal mouse spleen. The major findings to emerge are: (a) small lymphocytes secrete 8S IgM and IgG. A small portion of the 8S IgM, but virtually none of the IgG appears to have a cell surface phase. (b) Cell surface IgM is actively turned over with a half-life of 6-8 hr, and turnover can be accounted for by release into the incubation medium. Release is temperature dependent. (c) Released cell surface Ig is noncovalently bound to a fragment of plasma membrane. (d) H-2 antigens are not released during short-term incubation. Based on the above findings, we propose a model for the transport and release of both cell surface and conventionally secreted Ig.
Mental disorder and delinquency.
Authors: J. S. Bearcroft
Journal: BMJ (1967)

Antenatal Care in the Tropics-Haroon BIinSUIAL 619 a distance from the home.When an unstable lie is recurrent and the patient refuses admission she should be instructed to report in early labour.Careful explanation will avoid cases of obstructed labour and ruptured uterus in labours conducted outside hospital.Breech Presentation.-Whenfacilities are available x-ray pelvimetry should be done for primigravidae, though the results should not have precedence over clinical assessment and a short trial of labour.Precious Caesarean Section.--Early in pregnancy the need for hospital confinement should be stressed, with the explana-
SAFETY THRESHOLD FOR CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA IN CHILDHOOD UNDER BETABLOCKER TREATMENT
Authors: Fernando Wangüemert Pérez, Pablo Ruiz Hernandez, Carmelo Perez Rodriguez, Cristina Bosch Calero, Oscar Campuzano, Guillermo J. Perez, Pedro Suarez Cabrera, Joseph Brugada, Ramon Brugada-Terradellas
Journal: Journal of the American College of Cardiology (2014)
Absence of Hepatitis after Treatment with a Pasteurized Factor VIII Concentrate in Patients with Hemophilia and No Previous Transfusions
Authors: Schimpf K, Mannucci Pm, Kreutz W, Brackmann Hh, Auerswald G, Ciavarella N, Mösseler J, DeRosa, Kraus B, Brueckmann C
Journal: New England Journal of Medicine (1987)

Post-transfusion hepatitis is frequent among patients with hemophilia who are treated with concentrated factor VIII prepared from pooled plasma, especially if it is obtained from paid donors. In 26 patients with hemophilia A or von Willebrand's disease who had not been treated with blood or any blood product and hence were highly susceptible to the development of post-transfusion hepatitis, we infused 32 batches of a factor VIII concentrate that had been produced from large pools of human plasma (collected from paid plasmapheresis donors) and then heated in solution at 60°C for 10 hours before final lyophilization. Patients were examined clinically and serologically over a period of 12 months after the first infusion of the pasteurized concentrate. Neither hepatitis nor serologic signs of other viral infections were observed. The hemostatic effectiveness of the concentrate appeared to be satisfactory relative to untreated concentrates. (N Engl J Med 1987;316:918–22.)
Preoperative diagnosis of a pulmonary artery sarcoma.
Authors: V Velebit, J T Christenson, F Simonet, J Maurice, M Schmuziger, H Hauser, D Didier
Journal: Thorax (1995)

A pulmonary artery sarcoma was diagnosed preoperatively by magnetic resonance imaging enhanced with gadolinium and confirmed by percutaneous computed tomographic guided needle biopsy. Accurate preoperative diagnosis allowed planned curative surgery with removal of the right ventricular outflow tract and reconstructive surgery using a cryopreserved homograft.
Comparison of physiotherapy, manipulation, and corticosteroid injection for treating shoulder complaints in general practice: randomised, single blind study
Authors: J. C Winters, J. S Sobel, K. H Groenier, H. J Arendzen, B. Meyboom-de Jong
Journal: BMJ (1997)

To compare the efficacy of physiotherapy, manipulation, and corticosteroid injection for treating patients with shoulder complaints in general practice.Randomised, single blind study.Seven general practices in the Netherlands.198 patients with shoulder complaints, of whom 172 were divided, on the basis of physical examination, into two diagnostic groups: a shoulder girdle group (n = 58) and a synovial group (n = 114).Patients in the shoulder girdle group were randomised to manipulation or physiotherapy, and patients in the synovial group were randomised to corticosteroid injection, manipulation, or physiotherapy.Duration of shoulder complaints analysed by survival analysis.In the shoulder girdle group duration of complaints was significantly shorter after manipulation compared with physiotherapy (P < 0.001). Also the number of patients reporting treatment failure was less with manipulation. In the synovial group duration of complaints was shortest after corticosteroid injection compared with manipulation and physiotherapy (P < 0.001). Drop out due to treatment failure was low in the injection group (17%) and high in the manipulation group (59%) and physiotherapy group (51%).For treating shoulder girdle disorders, manipulation seems to be the preferred treatment. For the synovial disorders, corticosteroid injection seems the best treatment.
Environmental degradation risks undermining development progress, warns report
Authors: P. Moszynski
Journal: BMJ (2011)

Developmental progress in the world’s poorest countries could be halted or even reversed by mid-century unless bold steps are taken now to slow climate change, prevent further environmental damage, and reduce deep inequalities within and among nations, predicts the United Nations’ 2011 report on human development.

The report, launched in Copenhagen on 2 November by the administrator of the UN Development Programme, Helen Clark, and Denmark’s prime minister, Helle Thorning-Schmidt, argues that environmental sustainability can be most fairly and effectively achieved by tackling health, education, income, and sex disparities together with global action on energy production and protection of the ecosystem.

As …
THE EFFECT OF CRT THERAPY ON RV FUNCTION IN PATIENTS WITH SEVERE LV DYSFUNCTION: A MATCHED CONTROL STUDY
Authors: Haissam Haddad, Girish Dwivedi, Tony Haddad, Rami Abo-Shasha, B. Mcardle, RG Wells, Taylor Dowsley, Lisa Mielniczuk, Terrence Ruddy, Rob Beanlands, Martin Green, Benjamin Chow
Journal: Journal of the American College of Cardiology (2013)
Congenic BB.SHR rat provides evidence for effects of a chromosome 4 segment (D4Mit6-Npy ∼1 cm) on total serum and lipoprotein lipid concentration and composition after feeding a high-fat, high-cholesterol diet
Authors: Peter Kovács, Jens van den Brandt, Anita C.M. Bonné, L.F.M. van Zutphen, Hein A. van Lith, Ingrid Klöting
Journal: Metabolism (2001)
Experimental induction of isolated lower esophageal sphincter relaxation in anesthetized opossums.
Authors: W G Paterson, S Rattan, R K Goyal
Journal: Journal of Clinical Investigation (1986)

Isolated lower esophageal sphincter (LES) relaxation, defined as a transient sphincteric relaxation unaccompanied by esophageal peristalsis, has been shown to precede most episodes of gastroesophageal reflux in humans. We studied the genesis of isolated LES relaxation in anesthetized opossums by observing the response of four components of the deglutition reflex (mylohyoid electrical activity, pharyngeal contraction, esophageal peristalsis, and LES relaxation) to pharyngeal tactile stimulation, electrical stimulation of superior laryngeal nerve (SLN) afferents or cervical vagal efferents, and to balloon distention of the esophageal body. A single pharyngeal stroking evoked isolated LES relaxation in 56% of 160 instances. The proportion of isolated relaxations in response to SLN electrical stimulation varied inversely with the stimulus frequency, occurring in 64% of the responses at 5 Hz and 4% of the responses at 30 Hz. A full four-component deglutition sequence was most likely to occur at the higher frequencies of SLN electrical stimulation. Esophageal balloon distention elicited isolated LES relaxations or no response at low distending volumes, whereas at higher volumes LES relaxation and esophageal contraction predominated. Isolated LES relaxation had significantly less magnitude than relaxations accompanied by esophageal contractions. Bilateral cervical vagotomy abolished all LES and esophageal body responses induced by pharyngeal stroking and SLN stimulation, and rendered the esophageal body and LES less responsive to small volumes of distention. Vagal efferent stimulation produced isolated LES relaxation at lower frequency stimulation and LES relaxation with esophageal contractions at higher frequency stimulation. These studies show that isolated LES relaxation represents incomplete expression of either the deglutitive reflex or the peripheral reflex mediating secondary peristalsis.