tbuckley/cabot-search huggingface dataset:
Paediatric origins of adult lung disease bullet 6: Paediatric origins of adult lung disease
Authors: E von Mutius
Journal: Thorax (2001)

There is substantial evidence that morbidity due to asthma is on the increase in western affluent countries.1 The increases in the prevalence of asthma have, however, only been reported in children and young adults, whereas no major increase in the prevalence of asthma has been found in adults. In an Australian study investigating the time trends from 1982 to 1992, a doubling both in the prevalence of wheeze and airway hyperresponsiveness was seen in children.2 In contrast, in a similar survey of adults from 1981 to 1990 the prevalence of recent wheeze increased only in subjects under 30 years of age.3 Moreover, the prevalence of airway hyperresponsiveness had not increased at all, even among atopic adults. The prevalence of asthma and airway hyperresponsiveness was higher in Australian children than in adults, and the severity of airway responsiveness was higher in atopic children than in atopic adults. Likewise, Yunginger and colleagues in the USA performed a study using a population based computer linked medical diagnosis system to identify individual medical records with diagnoses of asthma.4These authors found an increase in the incidence of asthma between 1964 and 1983 which was entirely accounted for by increased incidence rates in children and adolescents aged 1–14 years.

These observations point towards the importance of childhood years for the development of asthma. In fact, Yunginger and colleagues showed that incidence rates were highest in infants of less than one year of age, particularly in boys. Between one and four years of age the incidence rates decreased, but were still much higher than in older age groups.

The development of wheezing illnesses follows a certain pattern over the childhood years. In a prospective, longitudinal, population based survey, the Tucson Children's Respiratory Study in the USA, wheeze was reported at some time …
G‐CSF <scp>P</scp>riming, clofarabine, and high dose cytarabine (GCLAC) for upfront treatment of acute myeloid leukemia, advanced myelodysplastic syndrome or advanced myeloproliferative neoplasm
Authors: Pamela S. Becker, Bruno C. Medeiros, Anthony S. Stein, Megan Othus, Frederick R. Appelbaum, Stephen J. Forman, Bart L. Scott, Paul C. Hendrie, Kelda M. Gardner, John M. Pagel, Roland B. Walter, Cynthia Parks, Brent L. Wood, Janis L. Abkowitz, Elihu H. Estey
Journal: American Journal of Hematology (2014)

Prior study of the combination of clofarabine and high dose cytarabine with granulocyte colony‐stimulating factor (G‐CSF) priming (GCLAC) in relapsed or refractory acute myeloid leukemia resulted in a 46% rate of complete remission despite unfavorable risk cytogenetics. A multivariate analysis demonstrated that the remission rate and survival with GCLAC were superior to FLAG (fludarabine, cytarabine, G‐CSF) in the relapsed setting. We therefore initiated a study of the GCLAC regimen in the upfront setting in a multicenter trial. The objectives were to evaluate the rates of complete remission (CR), overall and relapse‐free survival (OS and RFS), and toxicity of GCLAC. Clofarabine was administered at 30 mg m −2 day −1 × 5 and cytarabine at 2 g m −2 day −1 × 5 after G‐CSF priming in 50 newly‐diagnosed patients ages 18–64 with AML or advanced myelodysplastic syndrome (MDS) or advanced myeloproliferative neoplasm (MPN). Responses were assessed in the different cytogenetic risk groups and in patients with antecedent hematologic disorder. The overall CR rate was 76% (95% confidence interval [CI] 64–88%) and the CR + CRp (CR with incomplete platelet count recovery) was 82% (95% CI 71–93%). The CR rate was 100% for patients with favorable, 84% for those with intermediate, and 62% for those with unfavorable risk cytogenetics. For patients with an antecedent hematologic disorder (AHD), the CR rate was 65%, compared to 85% for those without an AHD. The 60 day mortality was 2%. Thus, front line GCLAC is a well‐tolerated, effective induction regimen for AML and advanced myelodysplastic or myeloproliferative disorders. Am. J. Hematol. 90:295–300, 2015. © 2014 Wiley Periodicals, Inc.
Impaired elastin fiber assembly related to reduced 67-kD elastin-binding protein in fetal lamb ductus arteriosus and in cultured aortic smooth muscle cells treated with chondroitin sulfate.
Authors: A Hinek, R P Mecham, F Keeley, M Rabinovitch
Journal: Journal of Clinical Investigation (1991)

In the fetal ductus arteriosus (DA) disruption in the assembly of elastin fibers is associated with intimal thickening and we previously reported that fetal lamb DA smooth muscle cells incubated with endothelial conditioned medium produce two-fold more chondroitin sulfate (CS) compared with aorta (Ao) cells (Boudreau, N., and M. Rabinovitch. 1991. Lab. Invest. 64:187-199). We hypothesized that CS or dermatan sulfate (DS), both N-acetylgalactosamine glycosaminoglycans (GAGs), may be similar to free galactosugars in causing release of the 67-kD elastin binding protein (EBP) from the smooth muscle cell surfaces and impaired elastin fiber assembly. Using immunohistochemistry, immunoelectron microscopy, and western immunoblot we demonstrated a reduction in the 67-kD EBP in fetal lamb DA smooth muscle in tissue and in cultured cells. Also, reduced EBP was observed in fetal lamb and neonatal rat Ao smooth muscle cells incubated with N-acetylgalactosamine GAGs, CS, and DS, but not with N-acetylglucosamine containing GAGs, heparan sulfate (HS), or hyaluronan. Reduction in EBP was related to shedding from cell surfaces into the conditioned medium. This was associated with impaired elastin fiber assembly in cultured cells, assessed both morphologically and by a relative increase in tropoelastin and decrease in desmosines. The EBP extracted from smooth muscle cell membranes binds to an elastin affinity gel and can be eluted from it with CS but not with HS. Moreover, the amount of EBP extractable from smooth muscle cell membranes correlated with the morphologic assessment. We propose that increased CS or DS, may impair assembly of newly synthesized elastin in the media of the ductus arteriosus associated with the development of intimal thickening.
Acute Hypereosinophilic Syndrome
Authors: Ellis J. Van Slyck
Journal: JAMA (1979)

WE describe here a young woman with hypereosinophilic syndrome (HES) who had a high peripheral WBC count, circulating early eosinophilic forms without blast forms, mental confusion with delusions bordering on coma, and severe cardiac manifestations. She successfully responded to a single course of vincristine sulfate, cytarabine, and prednisone therapy after high-dose prednisone therapy failed. <h3>Report of a Case</h3> A 31-year-old woman had a six-week history of weakness, night sweats, intermittent fever, occipitoparietal headaches, paresthesia, and dyspnea. Confusion, emotional lability, and severe heart failure had developed over the previous four days. History disclosed allergies to penicillin and aspirin, mescaline and LSD abuse, hepatitis eight years previously, and chronic asthma controlled adequately with an epinephrine inhaler. Noteworthy findings on physical examination included marked pallor, extreme lethargy, anterior cervical adenopathy, retinal hemorrhages, engorged breasts due to lactation, and pedal edema. Vital signs were normal except for a pulse rate of 100 beats per
ADRB2 Gly16Arg polymorphism, asthma control and lung function decline
Authors: C. Rebordosa, M. Kogevinas, S. Guerra, F. Castro-Giner, D. Jarvis, L. Cazzoletti, I. Pin, V. Siroux, M. Wjst, J. M. Anto, R. de Marco, X. Estivill, A. G. Corsico, R. Nielsen, C. Janson
Journal: European Respiratory Journal (2011)

Arg/Arg homozygotes for the Gly16Arg polymorphism in the β<sub>2</sub>-adrenoreceptor gene (<i>ADRB2</i>) have a reduced response to short-acting β<sub>2</sub>-agonists but no effect has been associated with long-acting β<sub>2</sub>-agonists (LABAs). We selected 604 subjects with current asthma from the European Community Respiratory Health Study to evaluate whether asthma control and lung function decline were associated with Gly16Arg polymorphism, and to test whether LABA or inhaled corticosteroid (ICS) use modified these effects. There was an increased risk of noncontrolled asthma (OR 1.33, 95% CI 1.01–1.75; p=0.046) for each Arg allele. Among nonusers of ICS, the odds ratio of noncontrolled asthma among Arg/Arg <i>versus</i> Gly/Gly subjects was 2.73 (95% CI 1.28–5.82; p=0.009). No increased risk of noncontrolled asthma associated with the Arg allele was observed among ICS and/or LABA users. For each Arg allele, a mean±se decrease in decline in forced expiratory volume in 1 s of 7.7±2.5 mL·yr<sup>−1</sup> was found (p-value for trend 0.003), irrespective of ICS or LABA use. Arg/Arg subjects had an increased risk of bronchial hyperresponsiveness (BHR)<i> versus</i> Gly/Gly subjects, with an odds ratio of 2.51 (95% CI 1.12–5.63; p=0.025) if they did not use ICS. The Arg allele was associated with poorer asthma control, a steeper lung function decline and BHR. Absence of genotypic effects on asthma control among ICS users may be due to reversed β<sub>2</sub>-adrenoreceptor desensitisation.
Historical Comparisons of Morbidity and Mortality for Vaccine-Preventable Diseases in the United States
Authors: Sandra W Roush, Trudy V Murphy
Journal: JAMA (2007)

National vaccine recommendations in the United States target an increasing number of vaccine-preventable diseases for reduction, elimination, or eradication.To compare morbidity and mortality before and after widespread implementation of national vaccine recommendations for 13 vaccine-preventable diseases for which recommendations were in place prior to 2005.For the United States, prevaccine baselines were assessed based on representative historical data from primary sources and were compared to the most recent morbidity (2006) and mortality (2004) data for diphtheria, pertussis, tetanus, poliomyelitis, measles, mumps, rubella (including congenital rubella syndrome), invasive Haemophilus influenzae type b (Hib), acute hepatitis B, hepatitis A, varicella, Streptococcus pneumoniae, and smallpox.Number of cases, deaths, and hospitalizations for 13 vaccine-preventable diseases. Estimates of the percent reductions from baseline to recent were made without adjustment for factors that could affect vaccine-preventable disease morbidity, mortality, or reporting.A greater than 92% decline in cases and a 99% or greater decline in deaths due to diseases prevented by vaccines recommended before 1980 were shown for diphtheria, mumps, pertussis, and tetanus. Endemic transmission of poliovirus and measles and rubella viruses has been eliminated in the United States; smallpox has been eradicated worldwide. Declines were 80% or greater for cases and deaths of most vaccine-preventable diseases targeted since 1980 including hepatitis A, acute hepatitis B, Hib, and varicella. Declines in cases and deaths of invasive S pneumoniae were 34% and 25%, respectively.The number of cases of most vaccine-preventable diseases is at an all-time low; hospitalizations and deaths have also shown striking decreases.
Elevated Levels of Serum Sulfite in Patients with Chronic Renal Failure
Authors: HIROSHI KAJIYAMA, YOSHIHISA NOJIMA, HIDEKI MITSUHASHI, KAZUE UEKI, SHIGEO TAMURA, TETSUO SEKIHARA, RYOUJI WAKAMATSU, SHINTARO YANO, TAKUJI NARUSE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Sulfite, a well known air pollutant, is toxic for humans, especially those with sulfite hypersensitivity. Sulfite is also generated endogenously, during normal metabolism of sulfur-containing amino acids. Mammalian tissues contain the enzyme sulfite oxidase, which detoxifies both endogenous and exogenous sulfite by oxidation to sulfate. Deficiency of sulfite oxidase in humans is fatal, demonstrating its physiologic importance. Nevertheless, information about serum and tissue levels of sulfite in normal and pathologic conditions is limited. Using a sensitive HPLC assay, it is shown here that sera from patients with chronic renal failure (CRF) contain significantly higher amounts of sulfite than those from healthy subjects. Mean ± SD of serum sulfite in healthy subjects ( n = 20) was 1.55 ± 0.54 μM, whereas those in patients under maintenance hemodialysis (HD patients; n = 44) and CRF patients before introducing dialysis therapy (pre-HD patients; n = 33) were 3.23 ± 1.02 μM ( P &lt; 0.01) and 3.80 ± 3.32 μM ( P &lt; 0.01), respectively. Among pre-HD patients, serum sulfite was positively correlated with serum creatinine ( r = 0.714, P &lt; 0.0001), and negatively with serum albumin ( r = -0.407, P = 0.0188), hematocrit ( r = -0.524, P = 0.0017), and total cholesterol ( r = -0.375, P = 0.0318). There was no significant association between sulfite and patient age, gender, or leukocyte counts. Multiple regression analysis revealed serum creatinine as the sole independent predictor of serum sulfite levels. Each HD treatment was associated with approximately 27% reduction in serum sulfite levels, suggesting the presence of a dialyzable form in serum. Thus, these results indicate that reduced glomerular filtration is a factor that determines serum sulfite levels. Chronic elevation in serum sulfite levels might contribute to tissue or organ dysfunction in patients with CRF.
Clinical relactions following rubella vaccination. A prospective analysis of joint, muscular, and neuritic symptoms
Authors: M. G. Grand
Journal: JAMA (1972)

A prospective study of rubella vaccine-associated joint, muscular, and neuritic reactions was conducted in Louisiana and North Carolina. Children, ages 1 to 12 years, received one of three currently licensed rubella vaccines. Vaccinates were then surveyed by mail during a 60-day postvaccination period, and reactors were interviewed. Cendehill and DE-5 vaccinates had similar incidence rates of reaction. Reactions to both vaccines were mild, transient, and comparable as to sites of involvement. Both vaccine groups had similar frequencies of arthritis and paresthesia. DK-12 vaccine produced a higher reaction rate, longer-duration symptoms, and a higher rate of arthritis and paresthesia than DE-5 vaccine. Cendehill and DE-5 rubella vaccines have an acceptably low rate of reactions for use in public programs. Factors other than vaccine strain may have a role in determining vaccine-associated reaction rates.
Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis
Authors: Tanaz A Kermani, Kenneth J Warrington, Cynthia S Crowson, Steven R Ytterberg, Gene G Hunder, Sherine E Gabriel, Eric L Matteson
Journal: Annals of the Rheumatic Diseases (2012)

Objectives To evaluate incidence-trends and timing of large-vessel (LV) manifestations in patients with giant cell arteritis (GCA), and to examine the influence of LV manifestations on survival. Methods A population-based incident cohort of patients diagnosed with GCA between 1950 and 2004 was used. LV involvement was defined as large-artery stenosis or aortic aneurysm/dissection that developed in the 1 year before GCA diagnosis or at any time thereafter. Patients were followed up until death or 31 December 2009. Results The study included 204 patients, 80% women, mean age at diagnosis of GCA 76.0 years (±8.2 years). Median length of follow-up was 8.8 years. The cumulative incidence of any LV manifestation at 10 years was 24.9% for patients diagnosed with GCA between 1980 and 2004 compared with 8.3% for patients diagnosed with GCA between 1950 and 1979. The incidence of any LV event was high within the first year of GCA diagnosis. The incidence of aortic aneurysm/dissection increased 5 years after GCA diagnosis. Compared with the general population, survival was decreased in patients with an aortic aneurysm/dissection (standardized mortality ratio (SMR) 2.63; 95% CI 1.78 to 3.73) but not in patients with large-artery stenosis (SMR 1.44; 95% CI 0.87 to 2.25). Patients with GCA and aortic manifestations had a higher than expected number of deaths from cardiovascular and pulmonary causes than the general population. Among patients with GCA, aortic manifestations were associated with increased mortality (HR=3.4; 95% CI 2.2 to 5.4). Conclusions Vigilance and screening for aortic aneurysms should be considered in all patients 5 years after the incidence of GCA. Aortic aneurysm/dissection is associated with increased mortality in GCA.
SPONTANEOUS INTERSTITIAL MYOCARDITIS IN RABBITS
Authors: C. Philip Miller
Journal: The Journal of Experimental Medicine (1924)

The hearts of thirty-four apparently healthy adult rabbits were carefully studied microscopically. Twenty, or 60 per cent, contained lesions consisting of lymphocytes and endothelial leucocytes invarying proportions, to which were sometimes added polymorphonuclear eosinophils, plasma cells, and fibroblasts in small numbers. The lesions occurred most frequently between the muscle fibers of the papillary muscles and ventricular walls, and occasionally beneath the endocardium and epicardium. No microorganisms or cell inclusion bodies were found in the lesions.
Management and interventions for asthma: Collaboration in action
Authors: Monica Lakhanpaul, Deborah Bird, Lorraine Culley, Nicky Hudson, Noelle Robertson, Melanie McFeeters, Narynder Johal, Logan Manikam, Jonathon Grigg, Mark Johnson
Journal: European Respiratory Journal (2013)

Marginalised communities have greater healthcare needs but receive inferior care: redressing this inequity is central to many governments’ health policies. Patient and public involvement in health research is widely promoted yet for minority ethnic communities (MECs) there is a gap between rhetoric and reality: MECs, viewed as hard to reach, are underrepresented in research.    Methods  : Management and Interventions for Asthma (MIA), a participatory study based on the Socio-Ecological Model of Health, enabled collaboration between South Asian (SA) children and families (the largest UK MEC) and health professionals to produce an asthma intervention programme tailored to the needs of SA children. MIA used innovative recruitment strategies (n=294); a qualitative exploration of knowledge and perceptions of asthma; collaborative prioritisation and refinement workshops; and an iterative, structured approach to develop programme components.    Results:   Thematic analysis identified 11 problem areas within asthma management. These were prioritised by participants and a multifaceted programme  Act on Asthma  developed, addressing problems identified by study participants utilising existing evidence and theory.    Conclusions:   MECs can be successfully engaged in collaborative intervention development. The overlapping, multifaceted nature of the results demonstrates the need to take user perspectives seriously in service design although balancing diverse adult, child and professional opinions is challenging.    Funding/Disclaimer:   Funded by the NIHR Health Services & Delivery Research programme (09/2001/19).Views and opinions are those of the authors and do not necessarily reflect those of the HS&DR programme, NIHR, NHS or Department of Health.
Responses to Bacteria, Virus, and Malaria Distinguish the Etiology of Pediatric Clinical Pneumonia
Authors: Clarissa Valim, Rushdy Ahmad, Miguel Lanaspa, Yan Tan, Sozinho Acácio, Michael A. Gillette, Katherine D. Almendinger, Danny A. Milner, Lola Madrid, Karell Pellé, Jaroslaw Harezlak, Jacob Silterra, Pedro L. Alonso, Steven A. Carr, Jill P. Mesirov, Dyann F. Wirth, Roger C. Wiegand, Quique Bassat
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Plasma-detectable biomarkers that rapidly and accurately diagnose bacterial infections in children with suspected pneumonia could reduce the morbidity of respiratory disease and decrease the unnecessary use of antibiotic therapy.Using 56 markers measured in a multiplexed immunoassay, we sought to identify proteins and protein combinations that could discriminate bacterial from viral or malarial diagnoses.We selected 80 patients with clinically diagnosed pneumonia (as defined by the World Health Organization) who also met criteria for bacterial, viral, or malarial infection based on clinical, radiographic, and laboratory results. Ten healthy community control subjects were enrolled to assess marker reliability. Patients were subdivided into two sets: one for identifying potential markers and another for validating them.Three proteins (haptoglobin, tumor necrosis factor receptor 2 or IL-10, and tissue inhibitor of metalloproteinases 1) were identified that, when combined through a classification tree signature, accurately classified patients into bacterial, malarial, and viral etiologies and misclassified only one patient with bacterial pneumonia from the validation set. The overall sensitivity and specificity of this signature for the bacterial diagnosis were 96 and 86%, respectively. Alternative combinations of markers with comparable accuracy were selected by support vector machine and regression models and included haptoglobin, IL-10, and creatine kinase-MB.Combinations of plasma proteins accurately identified children with a respiratory syndrome who were likely to have bacterial infections and who would benefit from antibiotic therapy. When used in conjunction with malaria diagnostic tests, they may improve diagnostic specificity and simplify treatment decisions for clinicians.
Shared Epigenetic Mechanisms in Human and Mouse Gliomas Inactivate Expression of the Growth Suppressor<i>SLC5A8</i>
Authors: Chibo Hong, Alika Maunakea, Peter Jun, Andrew W. Bollen, J. Graeme Hodgson, David D. Goldenberg, William A. Weiss, Joseph F. Costello
Journal: Cancer Research (2005)

Tumors arise in part from the deleterious effects of genetic and epigenetic mechanisms on gene expression. In several mouse models of human tumors, the tumorigenic phenotype is reversible, suggesting that epigenetic mechanisms also contribute significantly to tumorigenesis in mice. It is not known whether these are the same epigenetic mechanisms in human and mouse tumors or whether they affect homologous genes. Using an integrated approach for genome-wide methylation and copy number analyses, we identified SLC5A8 on chromosome 12q23.1 that was affected frequently by aberrant methylation in human astrocytomas and oligodendrogliomas. SLC5A8 encodes a sodium monocarboxylate cotransporter that was highly expressed in normal brain but was significant down-regulated in primary gliomas. Bisulfite sequencing analysis showed that the CpG island was unmethylated in normal brain but frequently localized methylated in brain tumors, consistent with the tumor-specific loss of gene expression. In glioma cell lines, SLC5A8 expression was also suppressed but could be reactivated with a methylation inhibitor. Expression of exogenous SLC5A8 in LN229 and LN443 glioma cells inhibited colony formation, suggesting that it may function as a growth suppressor in normal brain cells. Remarkably, 9 of 10 murine oligodendroglial tumors (from p53+/- or ink4a/arf+/- animals transgenic for S100beta-v-erbB) showed a similar tumor-specific down-regulation of mSLC5A8, the highly conserved mouse homologue. Taken together, these data suggest that SLC5A8 functions as a growth suppressor gene in vitro and that it is silenced frequently by epigenetic mechanisms in primary gliomas. The shared epigenetic inactivation of mSLC5A8 in mouse gliomas indicates an additional degree of commonality in the origin and/or pathway to tumorigenesis between primary human tumors and these mouse models of gliomas.