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BACKGROUND: Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability. AIM: To describe presentations to the emergency department in Europe related to the recreational use of benzodiazepines and Z-drugs and compare regional differences in these presentations with legal drug sales of benzodiazepines and Z-drugs within each country. METHODS: Emergency department presentations with recreational misuse of benzodiazepines and Z-drugs were obtained from the Euro-DEN dataset for the period from October 2013 to September 2015; data extracted included demographics, clinical features, reported coused drugs, and outcome data. Sales figures obtained by QuintilesIMS™ (Atlanta, Georgia) were used to compare regional differences in the proportion of benzodiazepines and Z-drugs in the emergency department presentations and legal drug sales across Europe. RESULTS: Over the 2 years, there were 2119 presentations to the Euro-DEN project associated with recreational use of benzodiazepines and/or Z-drugs (19.3% of all Euro-DEN presentations). Presentations with 25 different benzodiazepines and Z-drugs were registered in all countries, most (1809/2340 registered benzodiazepines and Z-drugs, 77.3%) of which were prescription drugs. In 24.9%, the benzodiazepine was not specified. Where the benzodiazepine/Z-drug was known, the most frequently used benzodiazepines and Z-drugs were respectively clonazepam (29.5% of presentations), diazepam (19.9%), alprazolam (11.7%), and zopiclone (9.4%). The proportions of types of benzodiazepines/Z-drugs related to ED-presentations varied between countries. There was a moderate (Spain, UK, Switzerland) to high (France, Ireland, Norway) positive correlation between ED presentations and sales data (Spearman Row's correlation 0.66-0.80, p < 0.005), with higher correlation in countries with higher ED presentation rates. CONCLUSION: Presentations to the emergency department associated with the non-medical use of benzodiazepines and/or Z-drugs are common, with variation in the benzodiazepines and/or Z-drugs between countries. There was a moderate to high correlation with sales data, with higher correlation in countries with higher ED presentation rates. However, this is not the only explanation for the variation in non-medical use and in the harm associated with the non-medical use of benzodiazepines/Z-drugs.
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Benzodiazepinas/efectos adversos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hipnóticos y Sedantes/efectos adversos , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Adulto , Compuestos de Azabiciclo/administración & dosificación , Compuestos de Azabiciclo/efectos adversos , Benzodiazepinas/administración & dosificación , Europa (Continente) , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Estudios Retrospectivos , Estadísticas no Paramétricas , Adulto Joven , Zolpidem/administración & dosificación , Zolpidem/efectos adversosRESUMEN
Benzodiazepines and Z-drugs are commonly prescribed for insomnia and anxiety syndromes and there is increasing concern regarding their misuse. Using an internet-based questionnaire we found that of 1500 respondents 7.7% (n = 116) had misused one or more of these medications. Almost 15% of those misusing at least one of these drugs did so once weekly or more often. The main reasons reported for their use were to help sleep (66.4%), to cope with stress (37.1%) and/or to get high (31.0%). A total of 31% obtained the medications from multiple sources; healthcare professionals (55.2%) and friends/family (39.7%) most commonly. Our study can be used to inform prevention measures for their misuse.
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Acetamidas/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Benzodiazepinas/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Piperazinas/uso terapéutico , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Piridinas/uso terapéutico , Pirimidinas/uso terapéutico , Acetamidas/administración & dosificación , Adolescente , Adulto , Ansiedad/tratamiento farmacológico , Compuestos de Azabiciclo/administración & dosificación , Benzodiazepinas/administración & dosificación , Femenino , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piridinas/administración & dosificación , Pirimidinas/administración & dosificación , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Encuestas y Cuestionarios , Adulto Joven , ZolpidemRESUMEN
Architects and engineers are beginning to consider a new dimension of indoor air: the structure and composition of airborne microbial communities. A first step in this emerging field is to understand the forces that shape the diversity of bioaerosols across space and time within the built environment. In an effort to elucidate the relative influences of three likely drivers of indoor bioaerosol diversity - variation in outdoor bioaerosols, ventilation strategy, and occupancy load - we conducted an intensive temporal study of indoor airborne bacterial communities in a high-traffic university building with a hybrid HVAC (mechanically and naturally ventilated) system. Indoor air communities closely tracked outdoor air communities, but human-associated bacterial genera were more than twice as abundant in indoor air compared with outdoor air. Ventilation had a demonstrated effect on indoor airborne bacterial community composition; changes in outdoor air communities were detected inside following a time lag associated with differing ventilation strategies relevant to modern building design. Our results indicate that both occupancy patterns and ventilation strategies are important for understanding airborne microbial community dynamics in the built environment.
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Microbiología del Aire , Contaminación del Aire Interior/prevención & control , Bacterias/aislamiento & purificación , Monitoreo del Ambiente/métodos , Filogenia , Aire Acondicionado , Bacterias/genética , ADN Bacteriano/química , ADN Bacteriano/genética , Humanos , Oregon , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/química , ARN Ribosómico 16S/genética , Factores de Tiempo , Universidades , VentilaciónRESUMEN
We present a theoretical framework to describe stochastic, size-structured community assembly, and use this framework to make community-level ecological predictions. Our model can be thought of as adding biological realism to Neutral Biodiversity Theory by incorporating size variation and growth dynamics, and allowing demographic rates to depend on the sizes of individuals. We find that the species abundance distribution (SAD) is insensitive to the details of the size structure in our model, demonstrating that the SAD is a poor indicator of size-dependent processes. We also derive the species biomass distribution (SBD) and find that the form of the SBD depends on the underlying size structure. This leads to a prescription for testing multiple, intertwined ecological predictions of the model, and provides evidence that alternatives to the traditional SAD are more closely tied to certain ecological processes. Finally, we describe how our framework may be extended to make predictions for more general types of community structure.
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Fenómenos Ecológicos y Ambientales , Biodiversidad , Biomasa , Procesos EstocásticosRESUMEN
INTRODUCTION: Our objective was to describe the characteristics of liquid laundry detergent packet (LDP) exposures and to develop referral and treatment recommendations. METHODS: This retrospective cohort study investigated LDP exposures reported to the National Poison Data System from January 1, 2013 through June 30, 2014. Three medical toxicologists reviewed the most significant exposures (n = 450). RESULTS: Of 17,857 reported LDP exposures, 13,307 involved only an LDP (no other substance) and were followed to a known medical outcome. The median age was 2 years (range 12 days to 100 years). Approximately 10% of exposures reported a major or moderate effect. The most common symptom was vomiting (51.7%; n = 6875), but stridor or aspiration pneumonia and respiratory depression secondary to central nervous system effects also occurred. Two pediatric and two adult deaths occurred, but no causal mechanism leading to death could be identified in any of the deaths. CONCLUSIONS: LDPs occasionally produce a toxidrome of vomiting, stridor, hypoxia, and sedation with metabolic acidosis and respiratory failure. These symptoms and the availability of LDPs highlight the need for referral and treatment recommendations and efforts to minimize unintentional exposures. Review of data from US poison centers may provide referral and treatment recommendations that improve patient outcomes.
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Detergentes/toxicidad , Productos Domésticos/toxicidad , Vómitos/inducido químicamente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Enfermedades Pulmonares , Masculino , Persona de Mediana Edad , Centros de Control de Intoxicaciones/estadística & datos numéricos , Estudios Retrospectivos , Suicidio , Adulto JovenRESUMEN
The tropopause can be detected and its altitude determined routinely with the use of meter-wavelength, very-high-frequency radar. At meter wavelengths and at vertical incidence, the tropopause is revealed by partial specular reflection from stable atmospheric layers. The echoes received at vertical incidence as a result of partial specular reflection are greatly enhanced over echoes received at oblique incidence arising from turbulent scatter. Very-high-frequency radars utilizing partial specular reflection promise a major advance in the remote sensing of the atmosphere.
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Microscopic inclusions of aqueous fluids trapped in interstices in quartz and other crystals provide novel systems for the deliberate study of liquids under tension. Liquids under tension should differ in interesting ways from those at ambient pressure or compressed liquids because attractive, rather than repulsive, forces should dominate their behavior. Static tensions in excess of 100 megapascals (~1000 atmospheres) have been obtained reproducibly. Video-recorded observations of the final liquid rupture process, coupled with extrapolations of data at positive pressure, suggest that the homogeneous vapor nucleation point was reached in two of the cases studied. Raman spectra of the fluids at -80 megapascals show that an isothermal volume stretch of -5 percent by volume has only a weak effect on the spectral features and is similar to the effect of isobaric heating.
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The IMAGE spacecraft uses photon and neutral atom imaging and radio sounding techniques to provide global images of Earth's inner magnetosphere and upper atmosphere. Auroral imaging at ultraviolet wavelengths shows that the proton aurora is displaced equatorward with respect to the electron aurora and that discrete auroral forms at higher latitudes are caused almost completely by electrons. Energetic neutral atom imaging of ions injected into the inner magnetosphere during magnetospheric disturbances shows a strong energy-dependent drift that leads to the formation of the ring current by ions in the several tens of kiloelectron volts energy range. Ultraviolet imaging of the plasmasphere has revealed two unexpected features-a premidnight trough region and a dayside shoulder region-and has confirmed the 30-year-old theory of the formation of a plasma tail extending from the duskside plasmasphere toward the magnetopause.
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CONTEXT: Prior works demonstrates an increased risk of death when opioid analgesics and benzodiazepines are used concomitantly to gain a high. Using poison center data, we described trends in abuse or misuse of benzodiazepines and opioid analgesics. We quantified mortality risk associated with abuse or misuse of benzodiazepines, opioid analgesics and the combination of opioid analgesics and benzodiazepines. METHODS: This was a retrospective chart review of data from the National Poison Data System which collects information from 55 poison centers located across the United States. We identified reported cases of "intentional abuse or misuse" of benzodiazepine and/or opioid analgesic exposures. Poisson regression was used to compare the number of cases from each year between 2001 and 2014 to the year 2000. Logistic regression was used to determine whether cases exposed to both benzodiazepines and opioids had greater odds of death relative to cases exposed to opioid analgesics alone. RESULTS: From 2000 to 2014, there were 125,485 benzodiazepine exposures and 84,627 opioid exposures among "intentional abuse or misuse" cases. Of the benzodiazepine exposures, 17.3% (n = 21,660) also involved an opioid. In 2010, exposures involving both opioids and benzodiazepines were 4.26-fold (95% CI: 3.87-4.70; p < .001) higher than in 2000. The risk of death was 1.55 (95% CI: 1.01-2.37; p = .04) times greater among those who used both an opioid and a benzodiazepine compared to opioids alone. This association held after adjusting for gender and age. CONCLUSION: Intentional abuse or misuse of benzodiazepines and opioids in combination increased significantly from 2000 to 2014. Benzodiazepine abuse or misuse far exceeded cases of opioid abuse or misuse. Death was greater with co-abuse or misuse of benzodiazepines and opioids. Population-level campaigns to inform the public about the risk of death with co-abuse or misuse of benzodiazepines and opioids are urgently needed to address this overdose epidemic.
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Analgésicos Opioides/efectos adversos , Benzodiazepinas/efectos adversos , Centros de Control de Intoxicaciones/estadística & datos numéricos , Centros de Control de Intoxicaciones/tendencias , Mal Uso de Medicamentos de Venta con Receta/mortalidad , Mal Uso de Medicamentos de Venta con Receta/tendencias , Adulto , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: Hepatic failure has been associated with reported therapeutic use of acetaminophen by alcoholic patients. The highest risk period for alcoholic patients is immediately after discontinuation of alcohol intake. This period exhibits the largest increase in CYP2E1 induction and lowest glutathione levels. Our hypothesis was that common liver tests would be unaffected by administration of the maximum recommended daily dosage of acetaminophen for 3 consecutive days to newly-abstinent alcoholic subjects. METHODS: Adult alcoholic subjects entering two alcohol detoxification centers were enrolled in a prospective double-blind, randomized, placebo-controlled trial. Subjects were randomized to acetaminophen, 4 g/day, or placebo for 3 consecutive days. The study had 95% probability of detecting a 15 IU/L difference in serum ALT. RESULTS: A total of 443 subjects were enrolled: 308 (258 completed) received acetaminophen and 135 subjects (114 completed) received placebo. Study groups did not differ in demographics, alcohol consumption, nutritional status or baseline laboratory assessments. The peak mean ALT activity was 57 +/- 45 IU/L and 55 +/- 48 IU/L in the acetaminophen and placebo groups, respectively. Subgroup analyses for subjects presenting with an elevated ALT, subjects fulfilling a diagnosis of alcoholic hepatitis and subjects attaining a peak ALT greater than 200 IU/L showed no statistical difference between the acetaminophen and control groups. The one participant developing an increased international normalized ratio was in the placebo group. CONCLUSION: Alcoholic patients treated with the maximum recommended daily dose of acetaminophen for 3 consecutive days did not develop increases in serum transaminase or other measures of liver injury. Treatment of pain or fever for 3 days with acetaminophen appears safe in newly-abstinent alcoholic patients, such as those presenting for acute medical care.
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Acetaminofén/efectos adversos , Alcoholismo/complicaciones , Analgésicos no Narcóticos/efectos adversos , Hepatopatías Alcohólicas/etiología , Acetaminofén/administración & dosificación , Acetaminofén/uso terapéutico , Adolescente , Adulto , Alanina Transaminasa/sangre , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Femenino , Fiebre/complicaciones , Fiebre/tratamiento farmacológico , Glutatión/sangre , Humanos , Relación Normalizada Internacional , Hepatopatías Alcohólicas/sangre , Masculino , Persona de Mediana Edad , Dolor/complicaciones , Dolor/tratamiento farmacológico , Medición de Riesgo , TemplanzaRESUMEN
BACKGROUND: Previous studies have suggested that therapeutic doses of paracetamol (acetaminophen) are safe in alcoholic patients when administered for up to 3 days. However, 14 days of therapeutic doses of paracetamol has been associated with an increase in serum transaminases. AIM: To determine the effect of 10 days of the maximal therapeutic dose of paracetamol on serum alanine aminotransferase (ALT) activity in subjects who consume 1 to 3 alcoholic beverages per day. METHODS: This was a randomized, double blind, placebo-controlled trial. Subjects took 4 g of paracetamol (or placebo) daily for 10 days. Serum aspartate aminotransferase (AST), ALT, bilirubin and INR were measured at baseline, day 4 and day 11. Symptoms potentially related to liver injury were also recorded. RESULTS: Paracetamol and placebo groups had no change from baseline values at day 4, but the paracetamol group had an increase in mean ALT at day 11 of 8.7 IU/L. No subject developed symptoms of liver injury or met predefined criteria for hepatotoxicity or liver failure. CONCLUSION: Therapeutic dosing of paracetamol administered for 10 days appears to elevate serum ALT in moderate drinkers, but does not produce clinically evident liver injury.
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Acetaminofén/administración & dosificación , Alanina Transaminasa/metabolismo , Analgésicos no Narcóticos/administración & dosificación , Hepatopatías Alcohólicas/enzimología , Acetaminofén/efectos adversos , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Hepatopatías Alcohólicas/tratamiento farmacológico , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
MiAMP1 is a recently discovered 76 amino acid residue, highly basic protein from the nut kernel of Macadamia integrifolia which possesses no sequence homology to any known protein and inhibits the growth of several microbial plant pathogens in vitro while having no effect on mammalian or plant cells. It is considered to be a potentially useful tool for the genetic engineering of disease resistance in transgenic crop plants and for the design of new fungicides. The three-dimensional structure of MiAMP1 was determined through homonuclear and heteronuclear ((15)N) 2D NMR spectroscopy and subsequent simulated annealing calculations with the ultimate aim of understanding the structure-activity relationships of the protein. MiAMP1 is made up of eight beta-strands which are arranged in two Greek key motifs. These Greek key motifs associate to form a Greek key beta-barrel. This structure is unique amongst plant antimicrobial proteins and forms a new class which we term the beta-barrelins. Interestingly, the structure of MiAMP1 bears remarkable similarity to a yeast killer toxin from Williopsis mrakii. This toxin acts by inhibiting beta-glucan synthesis and thereby cell wall construction in sensitive strains of yeast. The structural similarity of MiAMP1 and WmKT, which originate from plant and fungal phyla respectively, may reflect a similar mode of action.
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Antiinfecciosos/química , Magnoliopsida/química , Proteínas de Plantas/química , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Antiinfecciosos/clasificación , Cisteína/química , Cisteína/metabolismo , Disulfuros , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Factores Asesinos de Levadura , Modelos Moleculares , Datos de Secuencia Molecular , Micotoxinas/química , Micotoxinas/metabolismo , Resonancia Magnética Nuclear Biomolecular , Proteínas de Plantas/clasificación , Estructura Secundaria de Proteína , Alineación de Secuencia , Relación Estructura-Actividad , Temperatura , TermodinámicaRESUMEN
In sheep, the ACTH secretory response to CRH in vivo or in vitro changes as a function of development, with peak responses occurring several weeks before term (145 days of gestation). CRH-stimulated ACTH secretion is mediated via the G protein-coupled CRH type I (CRH R1) receptor. We used a quantitative ribonuclease protection assay and Western immunoblotting to determine messenger RNA (mRNA) and protein levels of the CRH R1 receptor in immature and mature fetuses and adults. In addition, we precociously elevated fetal plasma cortisol levels to determine whether the fetal CRH R1 receptor is sensitive to increases in plasma cortisol. CRH R1 receptor mRNA levels decreased markedly throughout gestation and into the transition to adult life (immature fetus, 1.24+/-0.17; mature fetus, 0.75+/-0.13; adult, 0.18+/-0.093 pg/microg total anterior pituitary RNA). Also, continuous cortisol infusion in immature fetuses significantly decreased CRH R1 mRNA levels by 41%. Similar decreases were noted in protein levels. Thus, the decreased ACTH response to CRH stimulation during late gestation may be related to decreased CRH R1 receptor expression. In addition, plasma cortisol levels may influence corticotroph responsiveness to CRH by decreasing CRH R1 receptor expression.
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Hidrocortisona/administración & dosificación , Hipófisis/embriología , ARN Mensajero/metabolismo , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Hormona Adrenocorticotrópica/sangre , Animales , Dióxido de Carbono/sangre , Expresión Génica/efectos de los fármacos , Hidrocortisona/sangre , Hidrocortisona/farmacología , Concentración de Iones de Hidrógeno , Oxígeno/sangre , Hipófisis/metabolismo , OvinosRESUMEN
A gene family in Plasmodium yoelii YM encodes p235, a group of high molecular mass erythrocyte-binding rhoptry proteins. Sequence analysis of 6 cDNA clones from the 3' end of expressed p235 genes divided them into two groups corresponding to genes on chromosomes 1, and 5 and 6, respectively. Twelve partial p235 protein sequences, derived from cDNA sequences from the region with greatest protein sequence similarity to Plasmodium vivax RBP2, fell into three groups, together with one chimeric sequence. A comparison of these cDNA sequences with genomic DNA sequences from the same region suggested that only a subset of the gene repertoire is expressed. Three genomic DNA clones, derived from the 5' end of p235 genes designated E1, E2, and E5 and located on chromosome 5/6, were also obtained and aligned with sequences from the known E8 and E3 genes. In the region of overlap there was only approximately 27% protein sequence identity, indicating that the sequences in this p235 N-terminal region are more diverse than at the C-terminal end. This sequence variation in the expressed genes did not result in antigenically different rhoptry proteins as detected with a panel of p235-specific mAbs. Only one schizont out of 500 examined with mAb 25.86 appeared to be an antigenic variant, with all of the developing merozoites in this schizont being mAb 25.86 negative. No other antigenic variants were detected with the other antibodies, and therefore it is likely that these antibodies recognise conserved epitopes.
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Variación Genética/genética , Plasmodium yoelii/genética , Plasmodium yoelii/inmunología , Polimorfismo Genético/genética , Proteínas Protozoarias/genética , Proteínas Protozoarias/inmunología , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antiprotozoarios/inmunología , Especificidad de Anticuerpos , Antígenos de Protozoos/química , Antígenos de Protozoos/genética , Antígenos de Protozoos/inmunología , Secuencia de Bases , Clonación Molecular , Exones/genética , Técnica del Anticuerpo Fluorescente , Datos de Secuencia Molecular , Peso Molecular , Mutación/genética , Plasmodium yoelii/química , Proteínas Protozoarias/químicaRESUMEN
BACKGROUND: Most respiratory tract infections (RTIs) in children have a viral cause, they resolve on their own, and antibiotics need not be prescribed. OBJECTIVE: We sought to provide evidence that judicious antibiotic use can be accomplished in private pediatric practice without observing an increase in return office visits or in the rate of bacterial infections that may follow. STUDY DESIGN: This was a prospective 12-month study from July 1, 1996 through June 30, 1997. On the same 1 day each week, a representative convenience sample of acute respiratory tract illness patients was enrolled, and laboratory studies performed as appropriate, including viral cultures on all. Children were then followed for 30 days to ascertain the outcomes of not prescribing antibiotics except when specific bacterial infections were present at the initial visit. RESULTS: Three hundred eighty-three children were enrolled; 293 (77%) did not receive antibiotics at the enrollment visit. Ninety children (23%) received antibiotics based on a diagnosis of acute otitis media (n = 53), acute streptococcal tonsillopharyngitis (n = 18), or other presumed or documented bacterial infections (n = 19). An unscheduled return visit related to the initial visit occurred for 86 (29%) of the 293 children not receiving antibiotics initially and in 40 (44%) of 90 children receiving antibiotics initially. Eighty-seven children (23%) had positive viral culture results. The most frequently isolated viruses were adenovirus, enterovirus, parainfluenzae virus, and influenza virus. CONCLUSION: Children with RTIs without a concomitant presumed or proven bacterial infection do not require antibiotics. In this busy office practice, >75% of the children presenting with an RTI did not have a presumed or proven bacterial infection. These children did not have a higher rate of return office visits or an increase in bacterial infections. This reinforces the judicious use of antibiotics in managing children with RTIs.outcomes, antibiotic, respiratory infections.
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Antibacterianos/uso terapéutico , Pautas de la Práctica en Medicina , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Pruebas de Aglutinación , Niño , Preescolar , Humanos , Lactante , Masculino , New York , Práctica Privada , Estudios Prospectivos , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virologíaRESUMEN
This is the first study in children from the United States that evaluates the immunogenicity of and adverse reactions to the Connaught/Biken two-component acellular pertussis vaccine compared with whole-cell pertussis vaccine when given as a primary immunization series at 2, 4, and 6 months of age. Three hundred eighty infants were studied; 285 received acellular diphtheria-tetanus toxoids-pertussis (DTP (ADTP)) and 95 received whole-cell DTP (WDTP). Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to lymphocytosis-promoting factor (enzyme-linked immunosorbent assay IgG geometric mean titer (GMT) = 131 vs 9 and Chinese hamster ovary cell assay GMT = 273 vs 16) and to filamentous hemagglutinin (IgG GMT = 73 vs 10) (all P less than .0001). Agglutinin responses were higher in WDTP compared with ADTP recipients (GMT = 50 vs 37; P = .02). Local reactions were fewer for all three doses following ADTP vaccination. Fever, irritability, drowsiness, anorexia, vomiting, and unusual crying all occurred less frequently in ADTP compared with WDTP recipients for one or more of the three doses. We conclude that this two-component ADTP vaccine when given as a primary series produces greater immunogenicity and fewer adverse effects than the currently licensed WDTP vaccine.
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Vacuna contra Difteria, Tétanos y Tos Ferina , Vacuna contra la Tos Ferina , Vacunación/efectos adversos , Formación de Anticuerpos/inmunología , Difteria/prevención & control , Ensayo de Inmunoadsorción Enzimática , Humanos , Lactante , Vacuna contra la Tos Ferina/efectos adversos , Tétanos/prevención & control , Estados Unidos/epidemiología , Tos Ferina/prevención & controlRESUMEN
The objective of this study was to evaluate reactogenicity and immunogenicity of the recently US-licensed Connaught/BIKEN (C/B) acellular DTP (ADTP) vaccine as a booster for children aged 15 to 20 months after they had received either the C/B ADTP or the US-licensed Connaught whole-cell DTP (WDTP) vaccine as infants. After infants had received either three doses of C/B ADTP (n = 109) or three doses of WDTP vaccine (n = 30) at 2, 4, and 6 months of age according to a 3:1, randomized, prospective design, they all received booster doses at 15 to 20 months of age with C/B ADTP. Fever > 101 degrees F (38.3 degrees C), irritability, injection site redness > or = 1 inch, injection site swelling, and injection site pain, among other reactions, were monitored for 14 days after vaccination. IgG antibody to pertussis toxin (PT) and filamentous hemagglutinin were analyzed by enzyme-linked immunosorbent assay and neutralizing antibody to PT was measured by Chinese hamster ovary (CHO) cell assay. No significant differences were observed between the WDTP- and ADTP-primed infants following their ADTP booster for any of the monitored reactions within 72 hours of vaccine administration or in the 4 to 14 days after vaccination. Prior to the ADTP booster, antibody levels were higher in children who had received ADTP compared with those who had received WDTP vaccine as infants for PT antibody as measured by enzyme-linked immunosorbent assay and CHO cell assay. Higher levels of IgG antibody following the ADTP booster were observed to filamentous hemagglutinin and to PT in ADTP-primed compared with WDTP-primed children.(ABSTRACT TRUNCATED AT 250 WORDS)
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Anticuerpos Antibacterianos/análisis , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Hipersensibilidad/etiología , Tos Ferina/inmunología , Anticuerpos Antibacterianos/biosíntesis , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/uso terapéutico , Humanos , Lactante , Tos Ferina/prevención & controlRESUMEN
Treatment with rimantadine of influenza in children and the potential development of resistance in clinical isolates associated with therapy have not been previously studied. We compared rimantadine to acetaminophen therapy in a controlled, double-blind study of 91 children with influenza-like illness. Of 69 children with proven influenza A/H3N2 infection, 37 received rimantadine and 32 received acetaminophen for five days. Children receiving rimantadine showed significantly greater reduction in fever and improvement in daily scores for symptoms and severity of illness during the first three days. Viral shedding also diminished significantly during the first two days but subsequently increased such that by days 6 and 7 the proportion of children shedding virus, as well as the quantity of virus shed, was significantly greater in the rimantadine group. During the seven-day study, of the 22 children in the rimantadine group with serial isolates tested, ten (45.5%) had resistant isolates compared with two (12.5%) of those with serial isolates in the acetaminophen group (P less than .03). Thus, of the total 37 children in the rimantadine group, 27% were found to have resistant isolated compared with 6% in the total group receiving acetaminophen (P less than .04). Furthermore, the mean inhibitory concentration of rimantadine increased with time in the rimantadine group (r = .4, P = .002) but not in the acetaminophen group. Rimantadine therapy, thus, appears to be significantly more effective than acetaminophen in ameliorating the clinical signs and symptoms of influenza in children. Treatment with rimantadine was also associated with increased viral shedding after the medication was discontinued and with the development of resistance in the clinical isolates, the significance of which is unknown.
Asunto(s)
Adamantano/análogos & derivados , Gripe Humana/tratamiento farmacológico , Rimantadina/uso terapéutico , Acetaminofén/uso terapéutico , Adolescente , Niño , Preescolar , Ensayos Clínicos como Asunto , Método Doble Ciego , Femenino , Humanos , Lactante , Masculino , Distribución AleatoriaRESUMEN
Sulfur dioxide (SO2) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO2, in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [3H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials after a 4-hr incubation period. The net nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [3H]-anti-BPDE-derived products bound to protein; however, binding to nuclear DNA increased by more than 200% with 10 mM sulfite. Analysis of the supernatants from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c-su lfonate (BPT-10-sulfonate). [3H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/metabolismo , Sistema Respiratorio/efectos de los fármacos , Sulfitos/farmacología , 7,8-Dihidro-7,8-dihidroxibenzo(a)pireno 9,10-óxido/farmacocinética , Animales , Núcleo Celular/metabolismo , Células Cultivadas , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Ratones , Ratones Endogámicos BALB C , Ensayo de Unión Radioligante , Sistema Respiratorio/metabolismo , Fracciones Subcelulares/metabolismoRESUMEN
Ninety-six healthy infants ages 2 to 5 months received rhesus rotavirus vaccine serotype 3 (RRV) as a single dose of 10(3), 10(4) or 10(5) plaque-forming units (pfu) in this double-blinded, placebo-controlled study. Half of the infants in each dose group were also randomized to receive either 30 ml of infant formula as buffer before vaccination or were vaccinated on an empty stomach. The incidence of fever, increased stool frequency and decreased activity level was consistently higher among infants who received RRV than those who received placebo. There was no consistent increase in incidence of symptoms as the dose of RRV was increased. Possible vaccine-related side effects were increased in older vaccinees and in those with higher pre-vaccination antibody titers. The seroconversion rate and pre to postvaccination antibody rise, evaluated by enzyme-linked immunosorbent assay and by plaque reduction neutralization, correlated well. The 10(5) and 10(4) pfu RRV dose produced significantly higher rates of seroconversion and higher antibody rises than did placebo (P less than 0.001 for 10(5) and P = 0.005 for 10(4]. The 10(3) pfu dose was no more immunogenic than placebo. In the 10(4) pfu dose group 73% of infants receiving formula as a "buffer" seroconverted compared with 36% of those not receiving formula; 63% of infants partially breast-fed or formula-fed seroconverted compared with 17% of those exclusively breast-fed. These differences in seroconversion rate were largely overcome by increasing the RRV dose to 10(5) pfu. Stool (copro IgA) antibody responses were examined; of six infants showing a copro IgA response only one had seroconverted based on enzyme-linked immunosorbent assay or plaque reduction neutralization. RRV was recovered by tissue culture more frequently from the stool in those infants who received RRV 10(5) and 10(4) pfu than among those receiving 10(3) pfu or placebo (P less than 0.001).