RESUMEN
Studies of genetic variation can clarify the role of geography and spatio-temporal variation of climate in shaping demography, particularly in temperate zone tree species with large latitudinal ranges. Here, we examined genetic variation in narrowleaf cottonwood, Populus angustifolia, a dominant riparian tree. Using multi-locus surveys of polymorphism in 363 individuals across the species' 1800 km latitudinal range, we found that, first, P. angustifolia has stronger neutral genetic structure than many forest trees (simple sequence repeat (SSR) FST=0.21), with major genetic groups corresponding to large apparent geographical barriers to gene flow. Second, using SSRs and putatively neutral sequenced loci, coalescent simulations indicated that populations diverged before the last glacial maximum (LGM), suggesting the presence of population structure before the LGM. Third, the LGM and subsequent warming appear to have had different influences on each of these distinct populations, with effective population size reduction in the southern extent of the range but major expansion in the north. These results are consistent with the hypothesis that climate and geographic barriers have jointly affected the demographic history of P. angustifolia, and point the importance of both factors as being instrumental in shaping genetic variation and structure in widespread forest trees.
Asunto(s)
Variación Genética , Genética de Población , Populus/genética , Flujo Génico , Geografía , Repeticiones de Microsatélite , Datos de Secuencia Molecular , Polimorfismo de Nucleótido Simple , Dinámica Poblacional , Sudoeste de Estados UnidosRESUMEN
BACKGROUND: Simulation training has become a core component in the training of ENT surgeons. It provides the opportunity for the repetitive practice of a surgical technique. Simulators are broadly categorised into low- and high-fidelity simulators. A method using a home microprocessor to enhance a low-fidelity surgical simulator is introduced. METHOD: The Yorick tonsil tie trainer was enhanced using an Arduino microcontroller attached to the simulated inferior pole of the tonsil. The Arduino was coded to give a visual stimulus when linear motion exceeded parameters. The prototype simulator was tested to gain information on whether the enhancement could identify differences between novice and expert users. CONCLUSION: An enhanced low-fidelity tonsil trainer was produced using a low-cost, simple home microprocessing board. The enhanced simulator gives objective feedback allowing for self-directed learning. Further research is required to evaluate the benefits of these enhancements above non-enhanced simulation training.
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Otorrinolaringólogos/educación , Tonsila Palatina/cirugía , Entrenamiento Simulado/métodos , Refuerzo Biomédico/métodos , Competencia Clínica/normas , Simulación por Computador , Retroalimentación , Humanos , Entrenamiento Simulado/economía , Entrenamiento Simulado/estadística & datos numéricos , Cirujanos/educaciónRESUMEN
Vertebrate hairy genes are expressed in patterns thought to be readouts of a "segmentation clock" in the presomitic mesoderm. Here we use transgenic Xenopus embryos to show that two types of regulatory elements are required to reconstitute the segmental pattern of Xenopus hairy2. The first is a promoter element containing two binding sites for Xenopus Su(H), a transcriptional activator of Notch target genes. The second is a short sequence in the hairy2 3' untranslated region (UTR), which most likely functions posttranscriptionally to modulate hairy2 RNA levels. 3' UTRs of other hairy-related, segmentally expressed genes can substitute for that of hairy2. Our results demonstrate a novel mechanism regulating the segmental patterns of Notch target genes and suggest that vertebrate segmentation requires the intersection of two regulatory pathways.
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Somitos/fisiología , Proteínas de Xenopus/genética , Xenopus/genética , Regiones no Traducidas 3'/genética , Animales , Animales Modificados Genéticamente , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Embrión no Mamífero/embriología , Regulación del Desarrollo de la Expresión Génica , Proteínas de la Membrana/genética , Datos de Secuencia Molecular , Regiones Promotoras Genéticas/genética , ARN/genética , Receptores Notch , Vertebrados , Proteínas de Xenopus/metabolismoRESUMEN
New World screwworm populations in North and Central America have been the targets of virtually continuous eradication attempts by sterile insect technique (SIT) since the 1950s. Nevertheless, in some areas, such as Jamaica, SIT control programmes have failed. Reasons for the failure of SIT-based control programmes in some locations are unknown, but it has been hypothesized that failure may be related to mating incompatibility between sterile and wild fly populations or to the existence of sexually incompatible cryptic species. This paper outlines the development of a suite of four new microsatellite loci which can be used to study intra-specific relationships between populations of Cochliomyia hominivorax from the Caribbean and South America, which represent those populations involved in, or earmarked for, forthcoming SIT control. Cross-amplification with the secondary screwworm, Cochliomyia macellaria, was also successful with three of the new loci. We present results which suggest that populations from Trinidad and Jamaica form distinct groupings of flies and that C. hominivorax from Trinidad appears particularly distinct.
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Dípteros/genética , Dípteros/patogenicidad , Repeticiones de Microsatélite/genética , Infección por Gusano Barrenador/prevención & control , Animales , Mapeo Cromosómico , Cartilla de ADN , Ecosistema , Filogenia , Infección por Gusano Barrenador/epidemiología , Infección por Gusano Barrenador/transmisión , América del Sur/epidemiología , Sudeste de Estados Unidos/epidemiología , Clima TropicalRESUMEN
Based on the reports of activity of interferons against metastatic melanomas, we conducted a phase II study of recombinant interferon alfa-2a (Roferon-A, Hoffmann-La Roche, Nutley, NJ) in 66 patients with disseminated melanoma. All patients had excellent Eastern Cooperative Oncology Group (ECOG) performance status (0 to 1), and no evidence of brain metastases. Thirty patients had previously received chemotherapy and the remainder were untreated. The first 35 patients were treated on a daily schedule starting with a Roferon-A dose of 3 X 10(6) U/d and escalating to a maximum of 36 X 10(6) U/d over a period of 12 days. Because of excessive toxicity, the second group of 31 patients were treated on a fixed dose of 18 X 10(6) U/d [corrected] three times weekly (TIW). Among the 62 evaluable patients, five achieved an objective response for a response rate of 8% (95% confidence limits, 3% to 18%). Four patients had minor regressions and eight patients had stability of disease. The responses were evenly distributed between the two dose schedules. The major toxicity of interferon consisted of a constitutional syndrome of anorexia, fever, weight loss, and fatigue, which required a dose reduction in 75% of the patients on the daily schedule. Our data revealed a modest level of activity, which was not influenced by prior treatment or by the dose or schedule of interferon. Because of substantial toxicity with the daily schedule, we recommend a dose of 18 X 10(6) U/d [corrected] if interferon is used in the treatment of patients with melanoma.
Asunto(s)
Interferón Tipo I/uso terapéutico , Melanoma/secundario , Adolescente , Adulto , Anciano , Anorexia/inducido químicamente , Enfermedades de la Médula Ósea/inducido químicamente , Esquema de Medicación , Fatiga/inducido químicamente , Fiebre/inducido químicamente , Humanos , Interferón Tipo I/administración & dosificación , Interferón Tipo I/efectos adversos , Melanoma/terapia , Persona de Mediana Edad , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéuticoRESUMEN
In a series of studies, recombinant interferon-alpha 2a (rIFN alpha 2a, Roferon-A) was administered alone (273 men) or combined with vinblastine (91 men) to patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Patients were treated with daily doses of rIFN alpha 2a ranging from 3 to 54 million international units (I.U.) administered intramuscularly. A dose of 36 million I.U. daily for approximately 10 weeks followed by a three times weekly maintenance schedule with the same dose resulted in the best overall therapeutic benefit. An escalating-dose regimen of 3, 9, and 18 million I.U. daily, each for 3 days, followed by 36 million I.U. daily, produced equivalent therapeutic benefit with amelioration of acute toxicity in some patients. Response was more likely in patients without a history of opportunistic infection or B symptoms (fever, night sweats, or weight loss). Response rate increased with increasing baseline CD4 lymphocyte count and was 45.5% in patients with a CD4 count of greater than 400/mm3. Responding patients with a CD4 count of greater than 200/mm3 had a distinct survival advantage over patients who had similar CD4 counts but whose tumors did not regress with therapy. The addition of vinblastine increased toxicity and did not improve the response rate or prolong survival. Side effects included fatigue, fever, chills, myalgias, headaches, anorexia, nausea, diarrhea, and dizziness. Mild abnormalities in hematologic and liver function tests occurred in some patients. Most adverse effects diminished or resolved with continued therapy. We conclude that rIFN alpha 2a offers important therapeutic benefit in a select group of patients with AIDS-related KS.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Interferón-alfa/uso terapéutico , Sarcoma de Kaposi/terapia , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Recuento de Leucocitos , Masculino , Infecciones Oportunistas/complicaciones , Proteínas Recombinantes , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/mortalidad , Tasa de Supervivencia , Linfocitos T Colaboradores-Inductores/patología , Vinblastina/administración & dosificación , Vinblastina/uso terapéuticoRESUMEN
Hypothyroidism is associated with cardiovascular dysfunction. It is increasingly apparent that stiffening of central arteries may lead to increased afterload and cardiac dysfunction. We noninvasively studied the peripheral and central pressure waveforms in 12 untreated hypothyroid patients as well as in 12 age-, sex-, and body mass index-matched controls using the technique of pulse wave analysis from recordings at the radial artery. Indexes of arterial stiffness, augmentation index (AI) and augmentation of central arterial pressure (AG), were derived as well as time of travel of the reflected wave (TR), a direct estimate of aortic pulse wave velocity. At baseline, there were no significant differences between the 2 groups in brachial and aortic blood pressures. Hypothyroid patients had significantly higher AI than controls (mean +/- SEM[SCAP], 32.0 +/- 3.4% vs. 17.0 +/- 2.4%; P < 0.0005) even when corrected for heart rate (AI(C); 28.0 +/- 3.2% vs. 17.0 +/- 2.4%; P < 0.006) and AG (13.0 +/- 2.2 vs. 7.0 +/- 2.1 mm Hg; P < 0.03) together with a lower TR (132.0 +/- 4.1 vs. 142.0 +/- 1.5 msec; P < 0.03). After 6 months of therapy with T(4), all patients were euthyroid. AI(C) had decreased in the patient group (23.0 +/- 3.2% vs. 28.0 +/- 3.2%; P < 0.01) as had AG (9.0 +/- 1.5 vs. 13.0 +/- 2.2 mm Hg; P < 0.008), but TR was significantly higher (142.0 +/- 3.0 vs. 132.0 +/- 4.1 msec; P < 0.008). AI correlated with age in all groups (hypothyroid group: r = 0.937; P < 0.0005; control group: r = 0.804; P < 0.0005), but correlated with TSH level only among controls (r = 0.591; P < 0.05). This study confirms that hypothyroidism is associated with increased cardiovascular risk, as evidenced by increased augmentation of central aortic pressures and central arterial stiffness. Furthermore, these abnormalities are reversed after adequate T(4) replacement.
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Arterias/fisiopatología , Hipotiroidismo/complicaciones , Hipotiroidismo/fisiopatología , Adulto , Anciano , Envejecimiento , Aorta/fisiopatología , Fenómenos Biomecánicos , Presión Sanguínea , Índice de Masa Corporal , Arteria Braquial/fisiopatología , Femenino , Frecuencia Cardíaca , Humanos , Hipotiroidismo/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Análisis de Regresión , Tiroxina/uso terapéuticoRESUMEN
Sex hormones appear to play a pivotal role in determining cardiovascular risk. Androgen deprivation therapy for males with prostate cancer results in a hypogonadal state that may have important, but as yet undetermined, effects on the vasculature. We studied the effects of androgen deprivation therapy on large artery stiffness in 22 prostate cancer patients (mean age, 67 +/- 8 yr) over a 6-month period. Arterial stiffness was assessed using pulse-wave analysis, a technique that measures peripheral arterial pressure waveforms and generates corresponding central aortic waveforms. This allows determination of the augmentation of central pressure resulting from wave reflection and the augmentation index, a measure of large artery stiffness. Body compositional changes were assessed using bioelectrical impedance analysis. Fasting lipids, glucose, insulin, testosterone, and estradiol were measured. After a 3-month treatment period, the augmentation index increased from 24 +/- 6% (mean +/- SD) at baseline to 29 +/- 9% (P = 0.003) despite no change in peripheral blood pressure. Timing of wave reflection was reduced from 137 +/- 7 to 129 +/- 10 msec (P = 0.003). Fat mass increased from 20.2 +/- 9.4 to 21.9 +/- 9.6 kg (P = 0.008), whereas lean body mass decreased from 63.2 +/- 6.8 to 61.5 +/- 6.0 kg (P = 0.016). There were no changes in lipids or glucose during treatment. Median serum insulin rose from 11.8 (range, 5.6-49.1) to 15.1 (range, 7.3-83.2) mU/liter at 1 month (P = 0.021) and to 19.3 (range, 0-85.0 mU/liter by 3 months (P = 0.020). There was a correlation between the changes in fat mass and insulin concentration over the 3-month period (r = 0.56; P = 0.013). In a subgroup of patients whose treatment was discontinued after 3 months, the augmentation index decreased from 31 +/- 7% at 3 months to 29 +/- 5% by 6 months, in contrast to patients receiving continuing treatment in whom the augmentation index remained elevated at 6 months compared with baseline (P = 0.043). These data indicate that induced hypogonadism in males with prostate cancer results in a rise in the augmentation of central arterial pressure, suggesting large artery stiffening. Adverse body compositional changes associated with rising insulin concentrations suggest reduced insulin sensitivity. These adverse hemodynamic and metabolic effects may increase cardiovascular risk in this patient group.
Asunto(s)
Arterias/patología , Composición Corporal/fisiología , Hipogonadismo/metabolismo , Hipogonadismo/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Tejido Adiposo/patología , Anciano , Arterias/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hemodinámica/fisiología , Humanos , Hipogonadismo/etiología , Insulina/sangre , Resistencia a la Insulina/fisiología , Lipoproteínas/metabolismo , Masculino , Manometría , Persona de Mediana Edad , Antígeno Prostático Específico/inmunología , Antígeno Prostático Específico/metabolismoRESUMEN
Although GH deficiency may underlie the increased cardiovascular risk in adult hypopituitarism, other coexisting hormonal deficiencies and/or unphysiological hormone replacement may contribute. L-Deamino-8-D-arginine (DDAVP), when administered parenterally, potentiates hemostasis by increasing plasma procoagulant factors. We investigated whether chronic intranasal DDAVP therapy influences clotting factors (plasma fibrinogen, factor VIII, and von Willebrand factor antigen) and endothelial function (flow-mediated dilation of the brachial artery) in 30 GH-treated hypopituitary subjects, including both DDAVP-treated subjects (group A) (mean age, 46 +/- 11 yr) and vasopressin-sufficient subjects (group B) (mean age, 47 +/- 16 yr). Fifteen healthy controls (group C) (mean age, 48 +/- 12 yr) were also studied. All hypopituitary patients were receiving stable GH replacement (median duration, 19 months). Comparing the three groups, concentrations of fibrinogen (mean +/- SD) (A, 3.3 +/- 1.0 g/liter vs. B, 3.5 +/- 0.9 vs. C, 2.6 +/- 0.8, P < 0.05), factor VIII (A, 130% +/- 30% vs. B, 128% +/- 30% vs. C, 104% +/- 35%, P < 0.05) and von Willebrand factor antigen (A, 124% +/- 35% vs. B, 134% +/- 45% vs. C, 93% +/- 36%, P < 0.05) were higher in hypopituitary subjects, compared with controls. However, there were no differences in clotting factors between groups A and B. Flow-mediated dilation did not differ significantly between the two hypopituitary groups (A, 5.9% +/- 2.0% vs. B, 4.7% +/- 1.6%) and was similar to that in the control group (C, 5.7% +/- 2.1%). In conclusion, although endothelium-dependent vasodilation is intact in GH-treated hypopituitary adults, elevated concentrations of hemostatic markers suggest the persistence of a prothrombotic tendency and endothelial dysfunction. Intranasal DDAVP does not appear to influence this proatherogenic profile in hypopituitary adults with vasopressin deficiency.
Asunto(s)
Factores de Coagulación Sanguínea/análisis , Desamino Arginina Vasopresina/uso terapéutico , Endotelio Vascular/fisiopatología , Hormona de Crecimiento Humana/uso terapéutico , Hipopituitarismo/tratamiento farmacológico , Hipopituitarismo/fisiopatología , Administración Intranasal , Adulto , Arteriosclerosis/etiología , Arteria Braquial/fisiopatología , Enfermedades Cardiovasculares/etiología , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Factor VIII/análisis , Fibrinógeno/análisis , Humanos , Hipopituitarismo/complicaciones , Factor I del Crecimiento Similar a la Insulina/análisis , Persona de Mediana Edad , Triglicéridos/sangre , Vasodilatación , Factor de von Willebrand/análisisRESUMEN
Acromegaly is associated with increased cardiovascular risk. Although conventional risk factors such as glucose intolerance, hypertension, and dyslipidemia probably contribute, there may also be direct effects of GH/IGF-I excess on the vasculature. To study the effects of GH excess on the vasculature, we have assessed arterial stiffness in acromegalic subjects with and without active disease and have investigated the effects of Sandostatin LAR (OCT-LAR) on vascular function. Sixteen normotensive subjects with acromegaly (10 males and 6 females) and 8 healthy controls were studied. Of the acromegalic subjects, eight had active disease (group A), and eight were cured (GH < 2.5 mU/liter; group B). The three groups were age, sex, and blood pressure matched. Group A subjects were restudied after 3 and 6 months of OCT-LAR therapy. Arterial stiffness was assessed by analyzing central arterial pressure waveforms derived from measured radial artery waveforms. This allowed determination of the augmentation of central pressure and the augmentation index. Lipids, glucose, and IGF-I were also measured. Comparing the three groups (ANOVA; mean +/- SD), the augmentation index was higher in group A (28 +/- 12 vs. 12 +/- 13%; P < 0.01) but not in group B (22 +/- 7 vs. 12 +/- 13%; P = 0.60), compared with controls. IGF-I was higher in group A (50.3 +/- 21.2 nmol/liter; P < 0.01), compared with group B (22.5 +/- 8.9 nmol/liter) and controls (19.5 +/- 5.3 nmol/liter). On regression analysis, IGF-I concentration was identified as a strong independent predictor of the augmentation index (beta = 0.50; P = 0.007). There were no significant differences in aortic systolic pressure, aortic diastolic pressure, lipids, or glucose. Compared with baseline, OCT-LAR treatment resulted in a lowering of augmentation index at 3 months (20 +/- 15 vs. 28 +/- 12%; P < 0.05), but at 6 months (24 +/- 16%; P = 0.21) there was no significant change. IGF-I was reduced from 50.3 +/- 21.2 nmol/liter at baseline to 31.4 +/- 13.2 nmol/liter at 3 months (P < 0.05) and 26.6 +/- 15.8 nmol/liter at 6 months (P < 0.05). In conclusion, acromegaly is associated with changes in the central arterial pressure waveform, suggesting large artery stiffening. This may have important implications for cardiac morphology and performance in acromegaly as well as increasing the susceptibility to atheromatous disease. Large artery stiffness is reduced in cured acromegaly and partially reversed after pharmacological treatment of active disease.
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Acromegalia/tratamiento farmacológico , Acromegalia/fisiopatología , Aorta/efectos de los fármacos , Arterias/efectos de los fármacos , Arterias/fisiopatología , Presión Sanguínea/efectos de los fármacos , Hormonas/administración & dosificación , Octreótido/administración & dosificación , Anciano , Aorta/fisiopatología , Estudios de Casos y Controles , Preparaciones de Acción Retardada , Elasticidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: Controversy persists with regard to the atherogenic risk associated with adult growth hormone deficiency (GHD). Endothelial dysfunction and enhanced oxidative stress are early features of atherogenesis. Therefore, we have studied the effect of three months of low dose GH replacement therapy (0.03IU/kg/day) on these parameters in GHD adults. SUBJECTS AND METHODS: Eight hypopituitary GHD adults (4 male, 4 female), who were receiving conventional hormone replacement therapy, were studied before and after 3 months of GH replacement (0.03IU/kg/day). All observations obtained were compared with similar measurements made in 8 matched control subjects. All study subjects were non-smokers, normotensive and gave no personal or family history of premature vascular disease. Endothelial function was assessed using a specialised vessel wall tracking system to measure endothelium-dependent, flow-mediated, brachial artery dilatation (FMD). Measurements were repeated following glyceryl-trinitrate (GTN) (endothelium-independent dilatation). Oxidative stress was assessed by directly measuring lipid-derived free radicals in venous blood by electron paramagnetic resonance spectroscopy. Fasting lipids, insulin, plasma glucose and IGF-I were also measured at baseline and following GH replacement. RESULTS: FMD, expressed as a percentage change from resting base-line diameter, was significantly impaired in the pre-treatment GHD patients compared with controls (3.1+/-2.1% vs 6.1+/-0.9%, P<0. 001; means+/-s.d.) indicating endothelial dysfunction. Significant increase in FMD was noted following GH therapy (3.1+/-2.1% vs 6. 5+/-1.9%, P<0.001). Free radicals (arbitrary units) were elevated in the pre-treatment GHD patients compared with controls (0.36+/-0.09 vs 0.11+/-0.12, P<0.05) and fell significantly following GH therapy (0.23+/-0.03 vs 0.36+/-0.09, P<0.05), although they remained elevated compared with controls. Fasting insulin was significantly higher (25.9+/-18.8 vs 13.9+/-6.7mu/l, P<0.05) and IGF-I concentrations lower (10.8+/-4.7 vs 20.2+/-6.3nmol/l, P<0.05) in the pre-treatment GHD subjects. After treatment there were no changes in insulin concentration, although IGF-I levels were normalised (10. 8+/-2.3 vs 23.6+/-11.4nmol/l, P<0.05). CONCLUSIONS: Endothelial dysfunction and enhanced oxidative stress are features of adult GHD. This study suggests plausible mechanisms underlying any proatherogenic tendency in adult GHD and demonstrates improvement of these factors following GH replacement.
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Endotelio Vascular/metabolismo , Hormona del Crecimiento/sangre , Hormona del Crecimiento/deficiencia , Hipopituitarismo/sangre , Hipopituitarismo/tratamiento farmacológico , Estrés Oxidativo , Adulto , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Estudios de Casos y Controles , Endotelio Vascular/fisiopatología , Femenino , Radicales Libres/sangre , Hormona del Crecimiento/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
The increased risk for Alzheimer's Disease (AD) associated with traumatic brain injury (TBI) suggests that environmental insults may influence the development of this age-related dementia. Recently, we have shown that the levels of the beta-amyloid peptide (A beta 1-42) increase in the cerebrospinal fluid (CSF) of patients after severe brain injury and remain elevated for some time after the initial event. The relationships of elevated A beta with markers of blood-brain barrier (BBB) disruption, inflammation, and nerve cell or axonal injury were evaluated in CSF samples taken daily from TBI patients. This analysis reveals that the rise in A beta 1-42 is best correlated with possible markers of neuronal or axonal injury, the cytoskeletal protein tau, neuron-specific enolase (NSE), and apolipoprotein E (ApoE). Similar or better correlations were observed between A beta 1-40 and the three aforementioned markers. These results imply that the degree of brain injury may play a decisive role in determining the levels of A beta 1-42 and A beta 1-40 in the CSF of TBI patients. Inflammation and alterations in BBB may play lesser, but nonetheless significant, roles in determining the A beta level in CSF after brain injury.
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Proteínas de Fase Aguda/líquido cefalorraquídeo , Péptidos beta-Amiloides/líquido cefalorraquídeo , Lesiones Encefálicas/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Enfermedad de Alzheimer/epidemiología , Precursor de Proteína beta-Amiloide/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Barrera Hematoencefálica , Lesiones Encefálicas/complicaciones , Estudios de Cohortes , Humanos , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Fosfopiruvato Hidratasa/líquido cefalorraquídeo , Factores de Riesgo , Factor de Crecimiento Transformador beta/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeoRESUMEN
AIMS: The number of patients with cardiac implantable electronic devices (permanent pacemakers and implantable cardioverter defibrillators) undergoing radiotherapy treatment is increasing. The aims of this audit were to establish current UK practice regarding the management of patients with implanted cardiac devices undergoing radiotherapy and to compare this practice with current 'gold standard' evidence-based guidelines. MATERIALS AND METHODS: All UK radiotherapy departments were contacted and asked to provide their current cardiac implantable electronic device policy or to indicate if there was no current policy. A proforma was created to analyse these policies and to compare with current best practice. RESULTS: In total, 47/67 (70%) radiotherapy departments responded and 45 departmental policies were submitted; 31/45 (69%) policies defined the radiotherapy tolerance dose to permanent pacemakers and 14/45 (31%) defined the monitoring procedure for patients in line with current best practice. Only 5/45 (11%) policies defined the radiotherapy tolerance dose to implantable cardioverter defibrillators and 12/45 (27%) defined the monitoring procedure in line with current best practice. CONCLUSION: Most UK cardiac device policies do not reflect current best evidence. Policies are based on research carried out in 1994 by the American Association of Physicists in Medicine. This evidence does not account for advances in cardiac implantable electronic device technology. Further research is urgently needed to establish the effect of radiotherapy on these devices.
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Desfibriladores Implantables/estadística & datos numéricos , Marcapaso Artificial/estadística & datos numéricos , Recolección de Datos , Humanos , Auditoría Médica , Radioterapia/efectos adversos , Radioterapia/instrumentación , Reino UnidoRESUMEN
INTRODUCTION: Since the late 1990s, a number of factors have reduced the threshold for parathyroidectomy in patients with primary hyperparathyroidism. This study examined whether this has translated into increased numbers of parathyroid operations over the last decade. METHODS: A retrospective analysis was performed of the Patient Episode Database for Wales and English Hospital Episode Statistics annual data from 2000 to 2010 for parathyroidectomy admissions per 100,000 population. Statistical analysis was by linear regression. RESULTS: Between 2000 and 2010 there were 24,247 parathyroid operations in England and Wales (0.005% of the population), with 3 times as many women treated as men. Overall, incidence of parathyroidectomy rose from 3.3/100,000 population in 2000 to 5.8/100,000 in 2010 (p<0.0001). In England, it increased from 3.3/100,000 population to 5.8/100,000 and in Wales, it increased from 2.4/100,000 population to 4.6/100,000. Despite similar population demographics, the difference in the rate of change between England and Wales was significant (p<0.05). Uptake also varied according to age; in those aged 0-14 years, incidence of parathyroidectomy remained static whereas in all other age groups, uptake of parathyroidectomy increased significantly from 2000 to 2010. Most notably, surgical intervention in those aged 60-74 and >75 years nearly doubled over the decade (p<0.0001). CONCLUSIONS: The incidence of parathyroidectomy in adults has increased significantly in the last decade in England and Wales. This likely reflects changes in population demography, available guidelines, lower threshold for referral, changing surgical approach and the realisation that surgical morbidity is now infrequent.
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Paratiroidectomía/estadística & datos numéricos , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Preescolar , Inglaterra/epidemiología , Femenino , Humanos , Hiperparatiroidismo/epidemiología , Hiperparatiroidismo/cirugía , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Paratiroidectomía/tendencias , Estudios Retrospectivos , Distribución por Sexo , Gales/epidemiología , Adulto JovenRESUMEN
Temperature has strong effects on metabolic processes of individuals and demographics of populations, but effects on ecological communities are not well known. Many economically and ecologically important pest species have obligate associations with other organisms; therefore, effects of temperature on these species might be mediated by strong interactions. The southern pine beetle (Dendroctonus frontalis Zimmermann) harbors a rich community of phoretic mites and fungi that are linked by many strong direct and indirect interactions, providing multiple pathways for temperature to affect the system. We tested the effects of temperature on this community by manipulating communities within naturally infested sections of pine trees. Direct effects of temperature on component species were conspicuous and sometimes predictable based on single-species physiology, but there were also strong indirect effects of temperature via alteration of species interactions that could not have been predicted based on autecological temperature responses. Climatic variation, including directional warming, will likely influence ecological systems through direct physiological effects as well as indirect effects through species interactions.
Asunto(s)
Consorcios Microbianos , Ácaros/fisiología , Simbiosis , Temperatura , Gorgojos/parasitología , Animales , Femenino , Masculino , Pinus/parasitología , Densidad de Población , Crecimiento Demográfico , Reproducción , Gorgojos/microbiologíaRESUMEN
IMPORTANCE OF THE FIELD: Postprandial hyperglycaemia is becoming topical, with studies suggesting a link to cardiovascular disease. Recently, a number of new therapies for the treatment of type 2 diabetes have become available. AREAS COVERED IN THIS REVIEW: This review looks at the evidence for the potential role of insulin analogue mix 50 to reduce postprandial hyperglycaemia and cardiovascular disease. SEARCH STRATEGY: Medline and Embase databases were searched using the MeSH terms to identify relevant studies from 1980 to 2009. Both original articles and reviews were extracted. Published reference lists were also examined. MeSH terms used for literature searching: human insulins, insulin analogues, insulin analogue mix 50, glycaemia, postprandial glucose, fasting glucose, type 2 diabetes, type 1 diabetes, cardiovascular disease. WHAT THE READER WILL GAIN: The reader is presented with evidence discussing the importance of postprandial hyperglycaemia and studies comparing different insulin regimes and in particular insulin analogue mix 50 and its potential to reduce postprandial glucose surges and reduce cardiovascular disease. TAKE-HOME MESSAGE: Insulin analogue mix 50 is a viable therapeutic option in a sub-group of patients with type 2 diabetes.
Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/epidemiología , Insulina/uso terapéutico , Factores de Riesgo , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hiperglucemia/sangre , Insulina/análogos & derivados , Insulina/química , Periodo Posprandial/fisiologíaRESUMEN
AIMS: To determine the impact of self-monitoring blood glucose (SMBG) strip use in patients with type 2 diabetes in the UK. METHODS: The study period was April 1, 2004 to July 31, 2005. Data from primary care was extracted from The Health Improvement Network database. Patients identified with diabetes and matching the inclusion criteria were defined as new users of SMBG, prevalent users, or non-users. Patients were also defined as treated with insulin, with oral agents (OA), or not pharmacologically treated. Change in glycosylated hemoglobin (HbA(1c)) at baseline and after 12 months was compared. RESULTS: 2559 patients met the inclusion criteria. For new users, HbA(1c) fell by 0.59% (P=0.399) for those treated with insulin, 1.52% (P<0.001) for those treated with OA, and 0.51% (P<0.001) for no treatment. In prevalent users, changes were 0.31% (P<0.001), 0.34% (P<0.001), and 0.09% (P=0.456), respectively. In non-users, changes were 0.28% (P=0.618), 0.42% (P<0.001), and an increase of 0.05% (P=0.043), respectively. A significant decrease in mean HbA(1c) was associated with increasing strip use in OA patients newly initiated on strips. CONCLUSION: This observational study showed a significant decrease in HbA(1c) for new users of SMBG treated either non-pharmacologically or with OA, and for prevalent users treated with insulin or OA. Reduced HbA(1c) with increasing strip use was observed but was only significant for OA-treated new users. This suggests that SMBG use has a role in the treatment of non-insulin treated patients with type 2 diabetes.