tbuckley/cabot-search huggingface dataset:
Can we manage sport related concussion in children the same as in adults?: Figure 1
Authors: P McCrory, A Collie, V Anderson, G Davis
Journal: British Journal of Sports Medicine (2004)

Evidence based guidelines are required for the management of concussive injury in children

Consensus guidelines for managing sport related concussion in adults have been increasingly widely implemented.1 So far, there are no guidelines that enable clinicians to manage similar sporting concussive injuries in children. Furthermore, there are a number of important anatomical, physiological, and behavioural differences between adults and children that suggest that adult guidelines will need to be either modified or rewritten to manage injuries in this age group.

The annual incidence of traumatic brain injury (TBI) in adults is remarkably constant worldwide and has been estimated at between 180 and 300 cases per 100 000 population.2–5 This is believed to be an underestimate of the true incidence as an equivalent number of mild injuries are treated by general practitioners and do not result in hospital admission.6 Direct sport participation accounts for approximately 15–20% of all such TBI3,7 and in children a further smaller percentage of TBI is associated with play activities.8

In children aged 15 years and under, the estimated incidence rate of TBI is 180 per 100 000 children per year of which approximately 85% are categorised as mild injuries.7 In the US, it has been estimated that more than 1 million children sustain a TBI annually and that TBI accounts for more than 250 000 paediatric hospital admissions as well as more than 10% of all visits to emergency service settings.9

In child and adolescent populations, few well controlled studies exist to identify the age specific frequency and outcome of sport related concussive injuries.

The most common cognitive sequelae of concussive injuries in children are the same as for adults, namely reduced speed of information processing, poor attention, and impaired executive function.10–14 Concussion may also have a significant …
Haemochromatosis: A Report on Three Cases
Authors: R. M. M. Lyon
Journal: BMJ (1936)

Haemochromatosis is a disease of sufficient rarity for three new cases to warrant publication.Sheldon in his recent monograph has only been able to find in the literature 311 cases which he could accept as authen- ticated instances of the condition.The following three cases were all followed up to necropsy and the diagnosis verified by the typical post-mortem findings.Case I Male aged 27, tailor's trimmer.The patient was in apparent good health until the end of January, when he began to suffer from abdominal pain and distension.The pain was dull, intermittent, and not related to the taking of food.Shortly after this he began to complain of thirst and polyuria.A month after the onset of his symptoms he developed a brownish pigmentation of the skin, which grew steadily worse, and was remarked on by his friends.At this time, also, he noticed an increasing sleepiness, which became so marked that he actually fell asleep on his feet whilst at his work.Weakness and loss of weight became so marked that he could not continue at his work, and so he reported to his doctor, who sent him to hospital on April 8th, a little over two months after the first appearance of any symptoms.On admission he was found to be well developed but undernourished.His height was 5 ft. 5 in., and weight 8 stone.There was a generalized greyish-brown pigmentation of the skin, most marked in the mammae and arms and hands.On physical examination nothing of note was found in any of the systems.There was no enlargement of liver or spleen.The blood Wassermann reaction was negative.A sugar-tolerance test with 50 grams of glucose gave a moderately severe diabetic curve, with considerable glycosuria.Fasting level ... hour ... .
Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells
Authors: Amélie Rebillard, Xavier Tekpli, Olivier Meurette, Odile Sergent, Gwenaëlle LeMoigne-Muller, Laurent Vernhet, Morgane Gorria, Martine Chevanne, Markus Christmann, Bernd Kaina, Laurent Counillon, Erich Gulbins, Dominique Lagadic-Gossmann, Marie-Thérèse Dimanche-Boitrel
Journal: Cancer Research (2007)

Abstract We have previously shown that cisplatin triggers an early acid sphingomyelinase (aSMase)-dependent ceramide generation concomitantly with an increase in membrane fluidity and induces apoptosis in HT29 cells. The present study further explores the role and origin of membrane fluidification in cisplatin-induced apoptosis. The rapid increase in membrane fluidity following cisplatin treatment was inhibited by membrane-stabilizing agents such as cholesterol or monosialoganglioside-1. In HT29 cells, these compounds prevented the early aggregation of Fas death receptor and of membrane lipid rafts on cell surface and significantly inhibited cisplatin-induced apoptosis without altering drug intracellular uptake or cisplatin DNA adducts formation. Early after cisplatin treatment, Na+/H+ membrane exchanger-1 (NHE1) was inhibited leading to intracellular acidification, aSMase was activated, and ceramide was detected at the cell membrane. Treatment of HT29 cells with Staphylococcus aureus sphingomyelinase increased membrane fluidity. Moreover, pretreatment with cariporide, a specific inhibitor of NHE1, inhibited cisplatin-induced intracellular acidification, aSMase activation, ceramide membrane generation, membrane fluidification, and apoptosis. Finally, NHE1-expressing PS120 cells were more sensitive to cisplatin than NHE1-deficient PS120 cells. Altogether, these findings suggest that the apoptotic pathway triggered by cisplatin involves a very early NHE1-dependent intracellular acidification leading to aSMase activation and increase in membrane fluidity. These events are independent of cisplatin-induced DNA adducts formation. The membrane exchanger NHE1 may be another potential target of cisplatin, increasing cell sensitivity to this compound. [Cancer Res 2007;67(16):7865–74]
Five‐year risk of incident disease following a diagnosis of chronic rhinosinusitis
Authors: A. G. Hirsch, X. S. Yan, A. S. Sundaresan, B. K. Tan, R. P. Schleimer, R. C. Kern, T. L. Kennedy, J. S. Greene, B. S. Schwartz
Journal: Allergy (2015)

Abstract Background Chronic rhinosinusitis ( CRS ) has a broad range of comorbidities. Due to a lack of longitudinal studies, it is not known whether these comorbidities cause CRS , are promoted by CRS , or share a systemic disease process with CRS . Objective The objective of this study was to determine the risk of incident disease within 5 years after a new diagnosis of CRS with nasal polyps ( CRS w NP ) and without nasal polyps ( CRS s NP ). Methods We conducted a case–control study nested within the longitudinal cohort of primary care patients in the Geisinger Clinic using electronic health record data. We evaluated incident disease over 5 years in newly diagnosed CRS w NP and CRS s NP cases compared to controls using multivariable Cox regression models. Results CRS s NP ( n = 3612) cases were at greater risk ( HR , 95% confidence interval) than controls for incidence of: upper airway diseases, including adenotonsillitis (3.29, 2.41–4.50); lower aerodigestive tract diseases, including asthma (2.69, 2.14–3.38); epithelial conditions, including atopic dermatitis (2.75, 1.23–6.16); and hypertension (1.38, 1.19–1.61). CRS w NP ( n = 241) cases were at greater risk for obesity than controls (1.74, 1.08–2.80), but CRS w NP was not associated with other diseases. Conclusion The risk of other diseases associated with CRS adds to the burden of an already highly burdensome condition, and suggests either that CRS promotes onset of other diseases or is an indicator of systemic disease processes. Different patterns of association with diseases by CRS phenotype may be due to CRS w NP sample size limitations or reflect a different pattern of disease onset by phenotype. These findings have implications for screening guidelines and care of CRS patients.
Improving rate of decline of FEV1 in young adults with cystic fibrosis
Authors: C Que
Journal: Thorax (2005)

CF is characterised by a progressive decline in lung function; reductions in this decline are often used as a measure of success in clinical trials. With improvements in treatment it may be that there has been a temporal shift in the pattern of the disease.318 patients born in five successive cohorts and attending a specialist clinic with at least two routine measurements of lung function made between the ages of 18 and 22 were included. The declines in their lung function were estimated and compared.The mean (SE) slopes for percentage predicted forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were -1.53 (0.36)% and -1.27 (0.34)%, respectively (NS). The annual deterioration in FEV(1) was -2.49%, -1.99% -2.20%, -1.65%, and -0.65% from the earliest to the most recent birth cohort; a similar pattern was observed for changes in FVC. There were no differences between male and female patients. Patients infected with Pseudomonas had a greater average decline in FEV(1) (-1.6% v -1.1%).The rates of decline in lung function in young adults with CF have diminished with successive birth cohorts. This has important implications for the design of clinical studies in this disease.
Hereditary Angioneurotic Edema: Report of a Large Kindred with Defect in C′1 Esterase Inhibitor.
Authors: John J. Dennehy
Journal: Annals of Internal Medicine (1969)

s1 May 1969Hereditary Angioneurotic Edema: Report of a Large Kindred with Defect in C′1 Esterase Inhibitor.John J. Dennehy, M.D.John J. Dennehy, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1088_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOf 39 individuals in a family with hereditary angioneurotic edema 15 are clinically affected in 4 generations, with 2 deaths from laryngeal edema. Acute attacks of nonallergic edema of the skin, intestines, and larynx have been recognized as an hereditary entity since Osler's description in 1888. In 1963 a defect in the inhibitor of the first component of complement was reported in this disease. Low or absent levels of C′1-esterase inhibitor have been demonstrated in members of this family, including some not as yet clinically affected. The complement system and pertinent literature are reviewed.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Danville, Pennsylvania PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1088-1088KeywordsComplement systemEdemaEsterasesLarynx Issue Published: 1 May 1969 PDF DownloadLoading ...
Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia
Authors: Xinmin Xie, Jonathan P. Wisor, Junko Hara, Tara L. Crowder, Robin LeWinter, Taline V. Khroyan, Akihiro Yamanaka, Sabrina Diano, Tamas L. Horvath, Takeshi Sakurai, Lawrence Toll, Thomas S. Kilduff
Journal: Journal of Clinical Investigation (2008)

Stress-induced analgesia (SIA) is a key component of the defensive behavioral "fight-or-flight" response. Although the neural substrates of SIA are incompletely understood, previous studies have implicated the hypocretin/orexin (Hcrt) and nociceptin/orphanin FQ (N/OFQ) peptidergic systems in the regulation of SIA. Using immunohistochemistry in brain tissue from wild-type mice, we identified N/OFQ-containing fibers forming synaptic contacts with Hcrt neurons at both the light and electron microscopic levels. Patch clamp recordings in GFP-tagged mouse Hcrt neurons revealed that N/OFQ hyperpolarized, decreased input resistance, and blocked the firing of action potentials in Hcrt neurons. N/OFQ postsynaptic effects were consistent with opening of a G protein-regulated inwardly rectifying K+ (GIRK) channel. N/OFQ also modulated presynaptic release of GABA and glutamate onto Hcrt neurons in mouse hypothalamic slices. Orexin/ataxin-3 mice, in which the Hcrt neurons degenerate, did not exhibit SIA, although analgesia was induced by i.c.v. administration of Hcrt-1. N/OFQ blocked SIA in wild-type mice, while coadministration of Hcrt-1 overcame N/OFQ inhibition of SIA. These results establish what is, to our knowledge, a novel interaction between the N/OFQ and Hcrt systems in which the corticotropin-releasing factor and N/OFQ systems coordinately modulate the Hcrt neurons to regulate SIA.
Characterization of european ancestry nonalcoholic fatty liver disease-associated variants in individuals of african and hispanic descent
Authors: Nicholette D. Palmer, Solomon K. Musani, Laura M. Yerges-Armstrong, Mary F. Feitosa, Lawrence F. Bielak, Ruben Hernaez, Bratati Kahali, Jeffrey J. Carr, Tamara B. Harris, Min A. Jhun, Sharon L.R. Kardia, Carl D. Langefeld, Thomas H. Mosley, Jill M. Norris, Albert V. Smith, Herman A. Taylor, Lynne E. Wagenknecht, Jiankang Liu, Ingrid B. Borecki, Patricia A. Peyser, Elizabeth K. Speliotes
Journal: Hepatology (2013)

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African- and/or Hispanic-Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African American (n = 3,124) and one Hispanic American (n = 849) cohorts. All analyses controlled for variation in age, age 2 , gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR , and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9 kg/m 2 , respectively. Hepatic steatosis was 0.20-0.34 heritable in African- and Hispanic-American families ( P &lt; 0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1 . Conclusion: Multiple genetic variants are associated with hepatic steatosis across ancestries. This explains a substantial proportion of the genetic predisposition in African- and Hispanic-Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. (Hepatology 2013;53:966–975)
Mechanisms of genetic resistance to Friend virus leukemia. III. Susceptibility of mitogen-responsive lymphocytes mediated by T cells.
Authors: V Kumar, T Caruso, M Bennett
Journal: The Journal of Experimental Medicine (1976)

Friend leukemia virus (FV) suppressed the proliferative responses of spleen, lymph node, marrow, and thymus cell populations to various T- and B-cell mitogens. Cells taken from mice, e.g. BALB/c genetically susceptible to leukemogenesis in vivo were much more susceptible to suppression of mitogenesis in vitro than similar cells from genetically resistant mice, e.g., C57BL/6. Nylon wool-purified splenic T cells from BALB/c and C3H mice lost susceptibility to FV-induced suppression of mitogenesis but became suppressible by addition of 10% unfiltered spleen cell. Thus, FV mediates in vitro suppression of lymphocyte proliferation indirectly by "activating" a suppressor cell. The suppressor cell adhered to nylon wool but not to glass wool or rayon wool columns. Pretreatment of spleen cells with carbonyl iron and a magnet did not abrogate the suppressor cell function. Suppressor cells were not eliminated by treatment with rabbit antimouse immunoglobulin (7S) and complement (C). However, high concentrations of anti-Thy-1 plus C destroyed suppressor cells of the spleen; thymic suppressor cells were much more susceptible to anti-Thy-1 serum. Nude athymic mice were devoid of suppressor cells and their B-cell proliferation was relatively resistant to FV-induced suppression in vitro. The suppressor cells in the thymus (but not in the spleen) were eliminated by treatment of mice with cortisol. Thus, FV appears to mediate its suppressive effect on mitogen-responsive lymphocytes by affecting "T-suppressor cells." Spleen cells from C57BL/6 mice treated with 89Sr to destroy marrow-dependent (M) cells were much more suppressible by FV in virto than normal C57BL/6 spleen cells. However, nylon-filtered spleen cells of 89Sr-treated C57BL/6 mice were resistant to FV-induced suppression in vitro, indicating that the susceptibility of spleen cells from 89Sr-treated B6 mice is also mediated by suppressor cells. Normal B6 splenic T cells were rendered susceptible to FV-induced suppression of mitogenesis by addition of 10% spleen cells from 89Sr-treated B6 mice. Thus, M cells appear to regulate the numbers and/or functions of T-suppressor cells which in turn mediate the immunosuppressive effects of FV in vitro. Neither mitogen-responsive lymphocytes nor T-suppressor cells are genetically resistant or susceptible to FV. The genetic resistance to FV is apparently a function of M cells, both in vitro as well as in vivo.
Pharmacogenomic Prediction of Anthracycline-Induced Cardiotoxicity in Children
Authors: Henk Visscher, Colin J.D. Ross, S. Rod Rassekh, Amina Barhdadi, Marie-Pierre Dubé, Hesham Al-Saloos, George S. Sandor, Huib N. Caron, Elvira C. van Dalen, Leontien C. Kremer, Helena J. van der Pal, Andrew M.K. Brown, Paul C. Rogers, Michael S. Phillips, Michael J. Rieder, Bruce C. Carleton, Michael R. Hayden
Journal: Journal of Clinical Oncology (2011)

Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug reaction limiting anthracycline use and causing substantial morbidity and mortality. Our aim was to identify genetic variants associated with ACT in patients treated for childhood cancer.We carried out a study of 2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug biotransformation genes in a discovery cohort of 156 anthracycline-treated children from British Columbia, with replication in a second cohort of 188 children from across Canada and further replication of the top SNP in a third cohort of 96 patients from Amsterdam, the Netherlands.We identified a highly significant association of a synonymous coding variant rs7853758 (L461L) within the SLC28A3 gene with ACT (odds ratio, 0.35; P = 1.8 × 10(-5) for all cohorts combined). Additional associations (P < .01) with risk and protective variants in other genes including SLC28A1 and several adenosine triphosphate-binding cassette transporters (ABCB1, ABCB4, and ABCC1) were present. We further explored combining multiple variants into a single-prediction model together with clinical risk factors and classification of patients into three risk groups. In the high-risk group, 75% of patients were accurately predicted to develop ACT, with 36% developing this within the first year alone, whereas in the low-risk group, 96% of patients were accurately predicted not to develop ACT.We have identified multiple genetic variants in SLC28A3 and other genes associated with ACT. Combined with clinical risk factors, genetic risk profiling might be used to identify high-risk patients who can then be provided with safer treatment options.
High-risk patients following hospitalisation for an acute exacerbation of COPD
Authors: Jacques Piquet, Jean-Michel Chavaillon, Philippe David, Francis Martin, François Blanchon, Nicolas Roche
Journal: European Respiratory Journal (2013)

The aim of this study was to assess long-term mortality and predictive factors of death after hospital admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). 1824 patients (23.2% female; mean age 70.3±11.3 years) consecutively admitted for acute exacerbation of COPD in the respiratory medicine departments of 68 general hospitals between October 2006 and June 2007 were prospectively enrolled in a follow-up cohort. Their vital status was documented between October 2010 and April 2011. Vital status was available for 1750 patients (95.9%), among whom 787 (45%) died during follow-up. Multivariate analysis found that age (60–80 years and ≥80 years versus &lt;60 years, relative risk 2.99, 95% CI 2.31–3.89), lower body mass index (25–30 kg·m −2 versus ≤20 kg·m −2 , relative risk 0.80, 95% CI 0.66–0.97), lung cancer (relative risk 2.08, 95% CI 1.43–3.01), cardiovascular comorbidity (relative risk 1.35, 95% CI 1.16–1.58), previous hospital admissions for acute exacerbation of COPD (four or more versus none, relative risk 1.91, 95% CI 1.44–2.53), use of accessory respiratory muscles (relative risk 1.19, 95% CI 1.01–1.40) or lower-limb oedema (relative risk 1.74, 95% CI (1.44–2.12)) at admission and treatment by long-term oxygen therapy at discharge (relative risk 2.09, 95% CI 1.79–2.45) were independent risk factors of death. Mortality rate during the 4 years following hospital admission for acute exacerbation of COPD was high (45%). Simple clinical information relating to respiratory and general status can help in identifying high-risk patients and targeting more intensive follow-up and care. Interestingly, cardiovascular comorbidities and past hospitalisations for acute exacerbation of COPD, but not forced expiratory volume in 1 s, independently predicted the risk of death.
Atypical Measles in Adolescent Siblings 16 Years After Killed Measles Virus Vaccine
Authors: Vincent A. Fulginiti
Journal: JAMA (1980)

The history of killed and live measles vaccine administration and exposure to natural disease is detailed in four adolescent siblings over a 16-year period. In two of these siblings, atypical measles developed 16 years after killed measles virus vaccine was administered, despite intercurrent doses of live measles virus vaccine.
Interaction of drug molecules with carrier systems as studied by parelectric spectroscopy and electron spin resonance
Authors: C. Braem, T. Blaschke, G. Panek-Minkin, W. Herrmann, P. Schlupp, T. Paepenmüller, C. Müller-Goyman, W. Mehnert, R. Bittl, M. Schäfer-Korting, K.D. Kramer
Journal: Journal of Controlled Release (2007)