RESUMEN
We have generated isolated attosecond pulses and performed attosecond streaking measurements using a two-colour synthesized laser field consisting of a strong near-infrared few-cycle pulse and a weaker multi-cycle pulse centred at 400 nm. An actively stabilized interferometer was used to coherently combine the two pulses. Using attosecond streaking we characterised the electric fields of the two pulses and accurately retrieved the spectrum of the multi-cycle pulse. We demonstrated a two-fold increase in the flux of isolated attosecond pulses produced and show that their duration was minimally affected by the presence of the weaker field due to spectral filtering by a multilayer mirror.
RESUMEN
For 2 × 2 tables, Egon Pearson's N - 1 chi-squared statistic is theoretically more sound than Karl Pearson's chi-squared statistic, and provides more accurate p values. Moreover, Egon Pearson's N - 1 chi-squared statistic is equal to the Mantel-Haenszel chi-squared statistic for a single 2 × 2 table, and as such, is often available in statistical software packages like SPSS, SAS, Stata, or R, which facilitates compliance with Ian Campbell's recommendations.
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Bioestadística/métodos , Distribución de Chi-Cuadrado , Humanos , Modelos Estadísticos , Programas InformáticosRESUMEN
OBJECTIVES: Psychotic symptoms associated with Alzheimer Disease (AD) contribute to excess functional dependence. Longitudinal studies have generally examined the association between rates of functional decline and the occurrence of psychotic symptoms from either a single evaluation or from multiple evaluations rather than through changes in frequency and severity of symptoms. Although the presence or absence of psychotic symptoms at initial or follow-up examinations may be associated with changes in functional status, the nature of the relationship between changes in these domains cannot be inferred. We examine the association between changes in the frequency of psychotic symptoms and changes in dependence in activities of daily living (ADL) over a period ranging from 1 to 74 months (median = 17.7). METHOD: Data from a cohort of 234 individuals referred to a memory clinic were analyzed using multilevel linear regression. Information on ADL, behavioral and psychological symptoms, depression, and cognition was collected. RESULTS: An increase in the frequency of psychotic symptoms had a unique influence on the deterioration of basic ADL, after controlling for demographic variables, changes in cognition, depression, and other behavioral and psychological symptoms (B = -.017, p = .003). However, changes in psychotic symptoms did not significantly contribute to declines in the ability to perform instrumental ADL (B = -.008, p = .439). CONCLUSION: Changes in psychotic symptoms may influence basic but not instrumental ADL over time. These findings may have ramifications for studies and treatment plans for individuals with AD who demonstrate psychotic symptoms.
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Actividades Cotidianas/psicología , Enfermedad de Alzheimer/psicología , Depresión/etiología , Trastornos Psicóticos/etiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Estudios de Cohortes , Análisis Factorial , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Escalas de Valoración PsiquiátricaRESUMEN
Most human papillomavirus (HPV) infections in young women become undetectable by standard assays after a few months. It is possible that many HPV infections do not actually clear, but persist at very low levels for years, becoming detected again later in life. The purpose of this study is to describe HPV 16 clearance, reappearance, and low-level persistence in a cohort of adolescent women. Adolescent women (N = 66), not vaccinated against HPV, were recruited from 1998 to 2008 into a longitudinal study. Self-collected vaginal samples were obtained quarterly and tested for HPV by Linear Array HPV Genotyping Test (LA-HPV). To explore low-level persistence, a type-specific nested PCR for HPV 16 (TSN-PCR-16) was developed. Women with HPV 16 detected by LA-HPV had their negative swabs retested with TSN-PCR-16. Forty-two participants with HPV 16, followed for a mean of 6.3 years, were analyzed. Using LA-HPV, the median duration of HPV 16 detection was 428 days (SD 852.5 days). TSN-PCR-16 detected HPV 16 during periods of LA-HPV non-detection in samples from many women. Using a combination of LA-HPV and TSN-PCR-16 results, the median duration of HPV 16 detection was 1,022.5 days (SD 943.7 days). The durations of detection differed significantly between the two methods (P = 0.0042) with a mean difference of 434.5 days. In adolescent females, duration of HPV 16 detection was significantly longer when TSN-PCR-16 was combined with LA-HPV. Some apparently cleared HPV 16 could be shown to persist at low levels using nested PCR.
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ADN Viral/aislamiento & purificación , Papillomavirus Humano 16/aislamiento & purificación , Infecciones por Papillomavirus/virología , Adolescente , Niño , ADN Viral/genética , Femenino , Papillomavirus Humano 16/genética , Humanos , Estudios Longitudinales , Reacción en Cadena de la Polimerasa/métodos , Vagina/virologíaRESUMEN
Cells respond to viral infection or double-stranded RNA with the transcriptional induction of a subset of alpha/beta interferon-stimulated genes by a pathway distinct from the interferon signal pathway. The transcriptional induction is mediated through a DNA sequence containing the alpha/beta interferon-stimulated response element (ISRE). We previously identified a novel transcription factor, designated double-stranded RNA-activated factor 1 (DRAF1), that recognizes this response element. The DNA-binding specificity of DRAF1 correlates with transcriptional induction, thereby distinguishing it as a positive regulator of alpha/beta interferon-stimulated genes. Two of the components of DRAF1 have now been identified as interferon regulatory factor 3 (IRF-3) and the transcriptional coactivator CREB-binding protein (CBP)/p300. We demonstrate that IRF-3 preexists in the cytoplasm of uninfected cells and translocates to the nucleus following viral infection. Translocation of IRF-3 is accompanied by an increase in serine and threonine phosphorylation. Coimmunoprecipitation analyses of endogenous proteins demonstrate an association of IRF-3 with the transcriptional coactivators CBP and p300 only subsequent to infection. In addition, antibodies to the IRF-3, CBP, and p300 molecules react with DRAF1 bound to the ISRE target site of induced genes. The cellular response that leads to DRAF1 activation and specific gene expression may serve to increase host survival during viral infection.
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Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , ARN Bicatenario , Transactivadores , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Alquilación , Animales , Proteína de Unión a CREB , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas de Unión al ADN/genética , Proteína p300 Asociada a E1A , Células HeLa , Humanos , Factor 3 Regulador del Interferón , Ratones , Virus de la Enfermedad de Newcastle/fisiología , Fosforilación , Proteínas Tirosina Fosfatasas/metabolismo , Conejos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Serina/metabolismo , Factores de Transcripción/genética , Células Tumorales Cultivadas , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismoRESUMEN
Viral double-stranded RNA (dsRNA) generated during the course of infection leads to the activation of a latent transcription factor, dsRNA-activated factor 1 (DRAF1). DRAF1 binds to a DNA target containing the type I interferon-stimulated response element and induces transcription of responsive genes. DRAF1 is a multimeric transcription factor containing the interferon regulatory factor 3 (IRF-3) protein and one of the histone acetyl transferases, CREB binding protein (CBP) or p300 (CBP/p300). In uninfected cells, the IRF-3 component of DRAF1 resides in the cytoplasm. The cytoplasmic localization of IRF-3 is dependent on a nuclear export signal, and we demonstrate IRF-3 recognition by the chromosome region maintenance 1 (CRM1) (also known as exportin 1) shuttling receptor. Following infection and specific phosphorylation, IRF-3 accumulates in the nucleus where it associates with CBP and p300. We identify a nuclear localization signal (NLS) in IRF-3 that is critical for nuclear accumulation. Mutation of the NLS abrogates nuclear localization even following infection. The NLS appears to be active constitutively, but it is recognized by only a subset of importin-alpha shuttling receptors. Evidence is presented to support a model in which IRF-3 normally shuttles between the nucleus and the cytoplasm but cytoplasmic localization is dominant prior to infection. Following infection, phosphorylated IRF-3 can bind to the CBP/p300 proteins resident in the nucleus. We provide the evidence of a role for CBP/p300 binding in the nuclear sequestration of a transcription factor that normally resides in the cytoplasm.
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Proteínas de Unión al ADN/metabolismo , Factores de Transcripción/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas de Unión al ADN/genética , Humanos , Factor 3 Regulador del Interferón , Señales de Localización Nuclear , Proteínas Nucleares/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Transactivadores/metabolismo , Factores de Transcripción/genética , Células Tumorales CultivadasRESUMEN
Interferon establishes an antiviral state in numerous cell types through the induction of a set of immediate-early response genes. Activation of these genes is mediated by phosphorylation of latent transcription factors of the STAT family. We found that infection of primary foreskin fibroblasts with human cytomegalovirus (HCMV) causes selective transcriptional activation of the alpha/beta-interferon-responsive ISG54 gene. However, no activation or nuclear translocation of STAT proteins was detected. Activation of ISG54 occurs independent of protein synthesis but is prevented by protein tyrosine kinase inhibitors. Further analysis revealed that HCMV infection induced the DNA binding of a novel complex, tentatively called cytomegalovirus-induced interferon-stimulated response element binding factor (CIF). CIF is composed, at least in part, of the recently identified interferon regulatory factor 3 (IRF3), but it does not contain the STAT1 and STAT2 proteins that participate in the formation of interferon-stimulated gene factor 3. IRF3, which has previously been shown to possess no intrinsic transcriptional activation potential, interacts with the transcriptional coactivator CREB binding protein, but not with p300, to form CIF. Activating interferon-stimulated genes without the need for prior synthesis of interferons might provide the host cell with a potential shortcut in the activation of its antiviral defense.
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Citomegalovirus/fisiología , Proteínas de Unión al ADN/metabolismo , Regulación Viral de la Expresión Génica , Interferón beta/farmacología , Proteínas Represoras , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , 2-Aminopurina/farmacología , Proteínas Reguladoras de la Apoptosis , Línea Celular , Cicloheximida/farmacología , Proteínas de Unión al ADN/fisiología , Inhibidores Enzimáticos/farmacología , Genisteína/farmacología , Humanos , Factor 1 Regulador del Interferón , Factor 2 Regulador del Interferón , Factor 3 Regulador del Interferón , Interferón-alfa/farmacología , Fosfoproteínas/metabolismo , Proteína Quinasa C/antagonistas & inhibidores , Inhibidores de la Síntesis de la Proteína/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas de Unión al ARN , Secuencias Reguladoras de Ácidos Nucleicos , Factor de Transcripción STAT1 , Factor de Transcripción STAT2 , Estaurosporina/farmacología , Transactivadores/fisiología , Activación Transcripcional , eIF-2 Quinasa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Postmenopausal osteoporosis results in an increased susceptibility to low-trauma fractures due to reduced bone volume and microarchitectural deterioration. Risedronate, a third generation bisphosphonate, has been shown in multiple clinical trials to reduce fracture risk and improve bone mineral density in postmenopausal women with osteoporosis. First and second generation bisphosphonates are known to have gastrointestinal side-effects and risedronate may be better tolerated. OBJECTIVES: To systematically review the efficacy of risedronate on bone density, and fracture reduction in postmenopausal women. SEARCH STRATEGY: The Cochrane Controlled Trials Registry Medline, and Current Contents were searched from 1990 - 2001. The electronic search was supplemented by handsearching four osteoporosis journals and their conference proceedings, as well as contacting content experts and industry sources for unpublished data. SELECTION CRITERIA: We included eight trials that randomised women to risedronate or an alternative (placebo or calcium and /or vitamin D) and measured bone mineral density for at least one year. DATA COLLECTION AND ANALYSIS: For each trial three independent reviewers assessed the methodological quality and abstracted data. Data was extracted for outcomes of fracture, bone mineral density and adverse events. The more conservative random effects model was used to pool data. The quality of trials was assessed according to the Jadad five-point scale. MAIN RESULTS: Both vertebral and non-vertebral fractures were statistically and clinically reduced with risedronate. Eleven out of one hundred women who received risedronate had a vertebral fracture compared to 17 out of one hundred of those who received calcium and vitamin D (pooled relative risk for vertebral fractures of 0.64 (95% CI 0.52 - 0.77). Three percent of participants who received risedronate had a non-vertebral fracture compared to 4.6% of those who received calcium and vitamin D (pooled relative risk for nonvertebral fractures of 0.73 (95% CI 0.61 - 0.87). The weighted mean difference for the percent change from baseline for bone mineral density with 5 mg daily for lumbar spine, femoral neck and trochanter was 4.54% (95%CI 4.12 - 4.97), p<0.01; 2.75% (95% CI 2.32 - 3.17), p<0.01; and 4.38% (95% CI 3.51 - 5.25), p<0.01 respectively. AUTHORS' CONCLUSIONS: There is good evidence for the efficacy of risedronate in the reduction of both vertebral and non-vertebral fractures. In addition, there is evidence from randomized trials that risedronate is able to achieve this without increasing risk for overall withdrawals due to adverse effects.
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Densidad Ósea/efectos de los fármacos , Ácido Etidrónico/análogos & derivados , Ácido Etidrónico/uso terapéutico , Fracturas Óseas/prevención & control , Osteoporosis Posmenopáusica/tratamiento farmacológico , Ácido Etidrónico/efectos adversos , Femenino , Humanos , Osteoporosis Posmenopáusica/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Fracturas de la Columna Vertebral/prevención & controlRESUMEN
Distress tolerance, the degree to which one is able to cope with and endure negative emotional states, has been broadly applied to understand and treat a variety of health (including behavioral) problems, but little is known about its role in oral health care and specifically dental care-related fear and anxiety, making it a novel construct in the oral health care literature. This cross-sectional study examined distress tolerance as a possible predictor of dental fear and anxiety among a sample of adults with and without diagnoses of dental phobia, investigated possible differences in levels of distress tolerance between adults with and without dental phobia, and determined possible associations between distress tolerance and fear of pain, anxiety sensitivity, and depression. Using 52 volunteers (n = 31, dental phobia group; n = 21, healthy comparison group), this investigation used self-report measures of distress tolerance, fear of pain, anxiety sensitivity, dental fear, and depression. The Anxiety Disorders Interview Schedule, a semi-structured interview, was used to assess for dental phobia and other psychological disorders. Distress tolerance significantly predicted dental fear and anxiety, even after controlling for age, sex, fear of pain, anxiety sensitivity, and depression. In addition, the dental phobia group had lower distress tolerance than the healthy comparison group. Distress tolerance was significantly associated with fear of pain, anxiety sensitivity, and depression. Findings indicate that low distress tolerance plays a unique and distinct role as a possible mechanism in the genesis of dental care-related fear and anxiety and phobia and may exacerbate the experience of other states, including fear of pain and anxiety sensitivity. Knowledge Transfer Statement: Results indicate that patients who have a lower ability to tolerate emotional and physical distress may have higher levels of dental care-related fear and anxiety and even dental phobia, as well as associated sequelae (e.g., avoidance of dental care). Treatment of highly fearful dental patients may helpfully include a focus on increasing distress tolerance.
RESUMEN
Dental patients generally recall more pain than they originally report, with ratings of pain related to state anxiety and dental fear, but the role of depression in recall of dental pain remains uncertain. This study examined the relative contributions of different variables in explaining dental pain recalled after tooth extraction. Patients presenting for tooth extraction, prior to extraction, rated their current dental pain and state anxiety, prediction of pain and state anxiety during extraction, depression, and dental fear. Immediately postprocedure and then 1 mo later, patients rated their pain and state anxiety during extraction. Hierarchical linear regression equations were used to explain variance in recalled pain and state anxiety. In addition, patients were divided into high and low dental fear and depression groups and compared on ratings of pain and state anxiety across time. In a final sample of 157 patients, the most important predictors of recalled pain were pain reported during extraction (ß = .53) and recalled state anxiety (ß = .52). Dental fear and depression had a significant interaction: only when patients reported less depression did those patients who reported more dental fear also report more pain than patients who reported less dental fear (P < 0.05, ω(2) = .07). Patients who reported more depression entered the dental operatory reporting more pain, but all patients generally reported less pain during extraction than they predicted or recalled. Memory of state anxiety and pain reported during tooth extraction, not depression or state anxiety at the time of extraction, were critical factors in memory of the pain associated with the procedure. At higher levels of depression, patients higher and lower in dental fear did not differ in report of pain. Future studies are needed to further clarify interactions of depression and dental fear over time.
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Ansiedad al Tratamiento Odontológico/psicología , Depresión/psicología , Dolor Facial/psicología , Miedo/psicología , Recuerdo Mental , Dolor Postoperatorio/psicología , Extracción Dental , Adulto , Femenino , Humanos , Masculino , Dimensión del DolorRESUMEN
The thyroid hormone receptor alpha (TR alpha) exhibits a dual role as an activator or repressor of gene transcription in response to thyroid hormone (T(3)). Our studies show that TR alpha, formerly thought to reside solely in the nucleus tightly bound to DNA, actually shuttles rapidly between the nucleus and cytoplasm. The finding that TR alpha shuttles reveals an additional checkpoint in receptor control of gene expression. Using Xenopus oocyte microinjection assays, we show that there are two coexisting mechanisms for nuclear entry of TR alpha. First, nuclear import of TR alpha (molecular mass 46 kDa) was not sensitive to general inhibitors of signal-mediated transport, indicating that TR alpha can enter the oocyte nucleus by passive diffusion. Second, when TR alpha was tagged with glutathione-S:-transferase, import of the fusion protein (molecular mass 73 kDa) was completely blocked by these inhibitors, demonstrating that an alternative, signal-mediated import pathway exists for TR alpha. Nuclear retention of TR alpha in oocytes is enhanced in the presence of T(3), suggesting that more intranuclear binding sites are available for the ligand-bound receptor. Using mammalian cells, we show that shuttling of green fluorescent protein (GFP)-tagged and untagged TR alpha is inhibited in both chilled and energy-depleted cells, suggesting that there is an energy-requiring step in the nuclear retention/export process. Nuclear export of TR alpha is not blocked by leptomycin B, a specific inhibitor of the export receptor CRM1, indicating that TR alpha does not require the CRM1 pathway to exit the nucleus. Dominant negative mutants of TR with defects in DNA binding and transactivation accumulate in the cytoplasm at steady state, illustrating that even single amino acid changes in functional domains may alter the subcellular distribution of TR. In contrast to TR alpha, nuclear export of its oncogenic homolog v-ErbA is sensitive to leptomycin B, suggesting that the oncoprotein follows a CRM1-mediated export pathway. Acquisition of altered nuclear export capabilities may contribute to the oncogenic properties of v-ErbA.
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Núcleo Celular/metabolismo , Citoplasma/metabolismo , Carioferinas , Receptores Citoplasmáticos y Nucleares , Receptores de Hormona Tiroidea/metabolismo , Animales , Apirasa/farmacología , Proteínas Portadoras/efectos de los fármacos , Proteínas Portadoras/metabolismo , Células Cultivadas , Ácidos Grasos Insaturados/farmacología , Femenino , Genes Dominantes , Proteínas Fluorescentes Verdes , Humanos , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Mamíferos , Ratones , Mutación , Proteínas Nucleares/metabolismo , Proteínas Oncogénicas v-erbA/metabolismo , Oocitos/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Receptores de Hormona Tiroidea/genética , Proteínas Ribosómicas/metabolismo , Temperatura , Xenopus , Proteína Exportina 1RESUMEN
Sustained smooth muscle contraction has been proposed to be regulated by either 1) sustained increases in intracellular Ca2+ concentration [(Ca2+]i)-dependent myosin phosphorylation or 2) diacylglycerol-dependent protein kinase C activation. We measured diacylglycerol mass with the diacylglycerol kinase assay and myoplasmic [Ca2+] with aequorin in swine carotid medial smooth muscle. Sustained and significant increases in [Ca2+], myosin light chain phosphorylation, and isometric stress were observed with histamine or endothelin stimulation. Neither stimuli, however, induced significant increases in diacylglycerol mass. Relaxation of histamine-stimulated tissues was induced by removal of histamine or removal of extracellular CaCl2 in the continued presence of histamine. The rate of decline of both [Ca2+] and force was similar in both protocols, suggesting that removal of Ca2+ (without removing the stimulus) was equivalent to removal of the stimulus. These data suggest that [Ca2+]i is the primary regulator of sustained swine arterial smooth muscle contraction, whereas diacylglycerol has, at most, only a minor role.
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Calcio/fisiología , Diglicéridos/fisiología , Glicéridos/fisiología , Músculo Liso Vascular/fisiología , Vasoconstricción/fisiología , Alcaloides/farmacología , Animales , Arterias/fisiología , Calcio/metabolismo , Diglicéridos/metabolismo , Endotelinas , Histamina/farmacología , Miosinas/metabolismo , Concentración Osmolar , Péptidos/farmacología , Forbol 12,13-Dibutirato/farmacología , Fosforilación , Proteína Quinasa C/antagonistas & inhibidores , Sistemas de Mensajero Secundario/fisiología , Estaurosporina , Porcinos , Factores de TiempoRESUMEN
Volunteers consumed a mixed-fat diet for 6 d (Pre-exp) and then either a canola-oil-based diet (CAN) containing linolenic acid (18:3n-3) or a sunflower-oil-based diet (SUN) rich in linoleic acid (18:2n-6) for 18 d, followed by the alternative diet in a crossover design. Platelet phospholipids were analyzed for changes in fatty acid composition. Eicosapentaenoic acid (EPA) (20:5n-3) was significantly higher in alkenylacyl ethanolamine phosphoglyceride (PPE) and in total phosphatidylcholine (PC) after CAN compared with SUN and Pre-exp. The 22:5n-3 was increased in PPE after CAN above concentrations found after both SUN and Pre-exp. Lower concentrations of 20:4n-6 and 22:4n-6 were observed with CAN in PC and lower concentrations of 22:4n-6 in PPE. These results indicate that the consumption of canola oil moderately increases EPA concentrations and alters the concentrations of other n-6 and n-3 fatty acids in human platelet phospholipids.
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Plaquetas/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Ácido Eicosapentaenoico/sangre , Ácidos Grasos Monoinsaturados/farmacología , Fosfatidiletanolaminas/sangre , Adulto , Humanos , Ácido Linoleico , Ácidos Linoleicos/farmacología , Ácidos Linolénicos/farmacología , Masculino , Fosfatidilcolinas/sangre , Fosfolípidos/sangre , Aceites de Plantas/farmacología , Ensayos Clínicos Controlados Aleatorios como Asunto , Aceite de Brassica napus , Aceite de GirasolRESUMEN
This study was undertaken to examine the effects that consumption of eggs from hens fed diets containing flaxseed would have on plasma and platelet lipids of male volunteers. Feeding diets containing 0%, 10%, and 20% ground flaxseed to Leghorn pullets provided a marked progressive increase in n-3 fatty acid content as alpha-linolenic acid (alpha-LNA) (28, 261, and 527 mg/egg) and docosahexaenoic acid (DHA) (51, 81, and 87 mg/egg) but no alteration in the cholesterol concentration of the egg yolk. Twenty-eight male volunteers, divided into three groups, were fed four eggs per day for 2 wk according to a cyclic Latin-square design. No statistically significant changes were observed in total cholesterol, high-density-lipoprotein cholesterol, or plasma triglyceride concentrations. Significant increases in total n-3 fatty acids and in DHA content (which rose from 1.5 to 2.0% by wt or 33% overall), and a significant decrease in ratio of n-6 to n-3 fatty acids were found in platelet phospholipids of subjects consuming eggs from flaxseed-fed hens. Health and Welfare Canada in 1990 set recommended intakes for dietary n-3 fatty acids and for the ratio of n-6 to n-3 fatty acids, which are not being met currently by the overall population. Eggs modified by the inclusion of flaxseed in the laying hens' diet could provide an important nutritional source of n-3 fatty acid.
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Pollos/metabolismo , Ácidos Docosahexaenoicos/análisis , Yema de Huevo/química , Lípidos/sangre , Ácido alfa-Linolénico/análisis , Adulto , Alimentación Animal/análisis , Animales , Plaquetas/química , Pollos/fisiología , Colesterol/análisis , Estudios Cruzados , Grasas de la Dieta/análisis , Grasas de la Dieta/farmacología , Método Doble Ciego , Ácidos Grasos/análisis , Ácidos Grasos/metabolismo , Ácidos Grasos/farmacología , Humanos , Masculino , Fosfolípidos/sangre , Plantas Comestibles , Semillas , Factores de TiempoRESUMEN
24 hypertensive patients were randomised into 2 groups to compare the antihypertensive effects of enalapril and captopril over a 10-week period. In the hydrochlorothiazide run-in period, blood pressure was reduced from 171 +/- 4/109 +/- 1mm Hg to 160 +/- 4/103 +/- 1mm Hg (p less than 0.05). Angiotensin-converting enzyme (ACE) inhibition decreased blood pressure to 132 +/- 3/87 +/- 2mm Hg. Captopril decreased diastolic blood pressure significantly more after 3 hours than enalapril (-24 versus -17mm Hg, p less than 0.05). After 10 weeks of therapy, this antihypertensive response was maintained at 134 +/- 3/83 +/- 1mm Hg. There was no difference between the captopril and enalapril treated groups. Acute and chronic responses of plasma renin activity, plasma aldosterone and ACE were determined. There was an acute positive correlation between the rise in plasma renin activity and the fall in blood pressures with captopril but not with enalapril. With chronic treatment there was no difference in the ability of either of the 2 drugs to reduce blood pressure, inhibit ACE, reduce aldosterone or stimulate plasma renin activity.
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Antihipertensivos/uso terapéutico , Captopril/uso terapéutico , Enalapril/uso terapéutico , Hormonas/sangre , Hipertensión/tratamiento farmacológico , Adulto , Inhibidores de la Enzima Convertidora de Angiotensina , Antihipertensivos/farmacología , Presión Sanguínea/efectos de los fármacos , Captopril/farmacología , Enalapril/farmacología , Femenino , Humanos , Hidroclorotiazida/uso terapéutico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Distribución AleatoriaRESUMEN
STUDY OBJECTIVE: To determine whether spinal muscular atrophy (SMA) type 1 can be managed without tracheostomy and to compare extubation outcomes using a respiratory muscle aid protocol vs conventional management. DESIGN: A retrospective cohort study. METHODS: Eleven SMA type 1 children were studied during episodes of respiratory failure. Nine children required multiple intubations. Along with standard treatments, these children received manually and mechanically assisted coughing to reverse airway mucus-associated decreases in oxyhemoglobin saturation. Extubation was not attempted until, most importantly, there was no oxygen requirement to maintain oxyhemoglobin saturation greater than 94%. After extubation, all patients received nasal ventilation with positive end-expiratory pressure. Successful extubation was defined by no need to reintubate during the current hospitalization. RESULTS: Two children have survived for 37 and 66 months and have never been intubated despite requiring 24-h nasal ventilation since 5 and 7 months of age, respectively. One other child underwent tracheostomy for persistent left lung collapse and inadequate home care, another for need for frequent readmission and intubation, and one child was lost to follow-up 3 months after successful extubation. The other six children have been managed at home for 15 to 59 (mean 30.4) months using nocturnal nasal ventilation after an episode of respiratory failure. The nine children were successfully extubated by our protocol 23 of 28 times. The same children managed conventionally were successfully extubated 2 of 20 times when not using this protocol (p < 0.001 by the two-tailed Fisher's Exact t Test). CONCLUSION: Although intercurrent chest colds may necessitate periods of hospitalization and intubation, tracheostomy can be avoided throughout early childhood for some children with SMA type 1.
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Intubación Intratraqueal , Respiración con Presión Positiva/métodos , Insuficiencia Respiratoria/terapia , Atrofias Musculares Espinales de la Infancia/terapia , Preescolar , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Lactante , Masculino , Recurrencia , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/mortalidad , Estudios Retrospectivos , Atrofias Musculares Espinales de la Infancia/complicaciones , Atrofias Musculares Espinales de la Infancia/mortalidad , Tasa de Supervivencia , Resultado del Tratamiento , Desconexión del Ventilador/métodosRESUMEN
OBJECTIVE: Almost every country in the developed world has a domiciliary oxygen program. Whether recipients meet program criteria has not been rigorously studied. DESIGN: Cross-sectional survey. PARTICIPANTS: Two hundred thirty-seven patients receiving domiciliary oxygen in the Ontario Ministry of Health Home Oxygen Program (HOP). METHODS: A respiratory therapist visited the patients' homes and administered questionnaires, obtained resting arterial blood gas measurements, and conducted a standardized home exercise test while monitoring oxygen saturation using an oximeter. MEASURES OF OUTCOME: We evaluated the extent to which patients met HOP criteria that are based on the inclusion criteria of randomized trials showing the life-prolonging effects of domiciliary oxygen. We also assessed the extent to which the patients' oxygen prescription was consistent with the results of rest and exercise testing. RESULTS: Ninety-six of 237 participants (40.5%; 95% confidence interval, 34.3 to 46.8) did not meet criteria for home oxygen. Patients aged < or = 70 years were more likely to meet criteria (71 of 105 patients; 67.9%) than those > 70 years old (70 of 132 patients; 53.0%). The proportion of patients meeting criteria was similar whether the referring physician was a specialist (71 of 112 patients; 62.5%) or a primary-care physician (69 of 123 patients; 56. 1%). A very important health benefit from oxygen was identified among 82% of those who met criteria and 88% of those who did not. Patients received higher flow rates than our criteria suggested were appropriate. Agreement between the independently assessed oxygen prescription at rest and the patients' report of oxygen use was extremely poor (chance-corrected agreement [kappa], 0.17), as was agreement concerning optimal exercise flow rates (kappa, 0.26). CONCLUSIONS: Current procedures for administration and reimbursement of home oxygen result in a large proportion of recipients not meeting criteria, as well as the prescription of excessive oxygen flow rates. These results are likely to apply to many jurisdictions and suggest a large potential for more efficient resource allocation.
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Servicios de Atención a Domicilio Provisto por Hospital , Terapia por Inhalación de Oxígeno , Factores de Edad , Anciano , Dióxido de Carbono/sangre , Intervalos de Confianza , Estudios Transversales , Prueba de Esfuerzo , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Modelos Logísticos , Enfermedades Pulmonares Obstructivas/fisiopatología , Enfermedades Pulmonares Obstructivas/terapia , Masculino , Ontario , Oxígeno/administración & dosificación , Oxígeno/sangre , Consumo de Oxígeno/fisiología , Selección de Paciente , Esfuerzo Físico/fisiología , Derivación y Consulta , Terapia Respiratoria , Descanso/fisiología , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Trunk position at 45 degrees from the horizontal is associated with a decreased risk of gastroesophageal aspiration. The objectives of this study were to determine the accuracy of trunk flexion estimates compared to a reference standard measurement, and to determine agreement about trunk flexion among ICU clinicians. DESIGN: Prospective observational study. SETTING: Two university-affiliated medical-surgical ICUs. PATIENTS AND PARTICIPANTS: Thirty-three mechanically ventilated ICU patients, seven residents, two fellows, three intensivists, and twenty-eight bedside nurses. INTERVENTIONS: Prospectively, concurrently, and independently during rounds, one bedside nurse, one resident, one fellow, and one intensivist clinically estimated the trunk flexion of mechanically ventilated patients. To record the reference standard, a trained investigator measured trunk position in the vertical plane using a goniometer. MEASUREMENTS AND RESULTS: We made 438 clinical assessments on 33 patients aged 57.2+/-19.4 (SD) years with an APACHE II score of 27.3+/-9.4. Mean trunk flexion estimates were: nurses 24.3+/-12.3 degrees from the horizontal, residents 20.2+/-13.7, fellows 20.3+/-10.8, and intensivists 21.1+/-13.1 compared to the reference standard measurement 16.2+/-9.0 degrees. The accuracy of trunk flexion estimates was fair to moderate [intraclass correlation for reference standard versus nurses (ICC 0.42), residents (ICC 0.52), fellows (ICC 0.36), and intensivists (ICC 0.55)]. The agreement among different groups of clinicians was moderate. CONCLUSIONS: In mechanically ventilated patients, we found that clinical estimates of trunk position were moderately good, agreement amongst caregivers was moderately good, but that all clinicians tended to overestimate the angle of semirecumbency.
Asunto(s)
Cuidados Críticos/métodos , Cuerpo Médico de Hospitales , Personal de Enfermería en Hospital , Neumonía por Aspiración/prevención & control , Postura , Respiración Artificial/métodos , APACHE , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios Prospectivos , Estándares de ReferenciaRESUMEN
OBJECTIVES: To determine how prostatic infarcts affect serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) levels. METHODS: Two hundred eighteen clinically benign, whole prostates were obtained at autopsy, completely sectioned, and examined histologically. PSA and PAP levels were determined from premortem serum. RESULTS: Six of the 218 (2.8%) prostates had infarcts. The infarcts were usually multiple and usually located in the central and/or middle concentric zones of the middle third of the prostate without a preference for a particular lobe. Serum PSA by immunoradiometric assay were elevated in all 6 cases. Serum PAP by both enzymatic assay (ACA), and immunoradiometric assay were available for 5 cases and were elevated by both methods in 2 cases, approached elevated levels by both methods in 1 case, and were normal by both methods in 2 cases. The PSA and PAP levels appeared to be affected more by the age than by the size of the infarct. CONCLUSIONS: Prostatic infarcts elevate PSA levels more frequently than PAP levels, and prostatic infarcts may be responsible for some unexplained elevations of serum PSA and PAP levels.