RESUMEN
Weevils are an unusually species-rich group of phytophagous insects for which there is increasing evidence of frequent involvement in brood-site pollination. This study examines phylogenetic patterns in the emergence of brood-site pollination mutualism among one of the most speciose beetle groups, the flower weevils (subfamily Curculioninae). We analysed a novel phylogenomic dataset consisting of 214 nuclear loci for 202 weevil species, with a sampling that mainly includes flower weevils as well as representatives of all major lineages of true weevils (Curculionidae). Our phylogenomic analyses establish a uniquely comprehensive phylogenetic framework for Curculioninae and provide new insights into the relationships among lineages of true weevils. Based on this phylogeny, statistical reconstruction of ancestral character states revealed at least 10 independent origins of brood-site pollination in higher weevils through transitions from ancestral associations with reproductive structures in the larval stage. Broadly, our results illuminate the unexpected frequency with which true weevils-typically specialized phytophages and hence antagonists of plants-have evolved mutualistic interactions of ecological significance that are key to both weevil and plant evolutionary fitness and thus a component of their deeply intertwined macroevolutionary success.
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Gorgojos , Animales , Gorgojos/genética , Polinización , Filogenia , Simbiosis , Plantas , FloresRESUMEN
BACKGROUND: The CORONIS trial reported differences in short-term maternal morbidity when comparing five pairs of alternative surgical techniques for caesarean section. Here we report outcomes at 3 years follow-up. METHODS: The CORONIS trial was a pragmatic international 2â×â2â×â2â×â2×â2 non-regular fractional, factorial, unmasked, randomised controlled trial done at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. In this follow-up study, we compared outcomes at 3 years following blunt versus sharp abdominal entry, exteriorisation of the uterus for repair versus intra-abdominal repair, single versus double layer closure of the uterus, closure versus non-closure of the peritoneum, and chromic catgut versus polyglactin-910 for uterine repair. Outcomes included pelvic pain; deep dyspareunia; hysterectomy and outcomes of subsequent pregnancies. Outcomes were assessed masked to the original trial allocation. This trial is registered with the Current Controlled Trials registry, number ISRCTN31089967. FINDINGS: Between Sept 1, 2011, and Sept 30, 2014, 13,153 (84%) women were followed-up for a mean duration of 3·8 years (SD 0·86). For blunt versus sharp abdominal entry there was no evidence of a difference in risk of abdominal hernias (adjusted RR 0·66; 95% CI 0·39-1·11). We also recorded no evidence of a difference in risk of death or serious morbidity of the children born at the time of trial entry (0·99, 0·83-1·17). For exteriorisation of the uterus versus intra-abdominal repair there was no evidence of a difference in risk of infertility (0·91, 0·71-1·18) or of ectopic pregnancy (0·50, 0·15-1·66). For single versus double layer closure of the uterus there was no evidence of a difference in maternal death (0·78, 0·46-1·32) or a composite of pregnancy complications (1·20, 0·75-1·90). For closure versus non-closure of the peritoneum there was no evidence of a difference in any outcomes relating to symptoms associated with pelvic adhesions such as infertility (0·80, 0·61-1·06). For chromic catgut versus polyglactin-910 sutures there was no evidence of a difference in the main comparisons for adverse pregnancy outcomes in a subsequent pregnancy, such as uterine rupture (3·05, 0·32-29·29). Overall, severe adverse outcomes were uncommon in these settings. INTERPRETATION: Although our study was not powered to detect modest differences in rare but serious events, there was no evidence to favour one technique over another. Other considerations will probably affect clinical practice, such as the time and cost saving of different approaches. FUNDING: UK Medical Research Council and the Department for International Development.
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Cesárea/métodos , Peritoneo/cirugía , Complicaciones Posoperatorias/epidemiología , Hemorragia Posparto/epidemiología , Útero/cirugía , Técnicas de Cierre de Heridas , Adulto , Catgut , Disección/métodos , Dispareunia/epidemiología , Femenino , Humanos , Histerectomía/estadística & datos numéricos , Dolor Pélvico/epidemiología , Poliglactina 910 , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: Variations exist in the surgical techniques used for caesarean section and many have not been rigorously assessed in randomised controlled trials. We aimed to assess whether any surgical techniques were associated with improved outcomes for women and babies. METHODS: CORONIS was a pragmatic international 2×2×2×2×2 non-regular fractional, factorial, unmasked, randomised controlled trial that examined five elements of the caesarean section technique in intervention pairs. CORONIS was undertaken at 19 sites in Argentina, Chile, Ghana, India, Kenya, Pakistan, and Sudan. Each site was assigned to three of the five intervention pairs: blunt versus sharp abdominal entry; exteriorisation of the uterus for repair versus intra-abdominal repair; single-layer versus double-layer closure of the uterus; closure versus non-closure of the peritoneum (pelvic and parietal); and chromic catgut versus polyglactin-910 for uterine repair. Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision. Women were randomly assigned by a secure web-based number allocation system to one intervention from each of the three assigned pairs. All investigators, surgeons, and participants were unmasked to treatment allocation. The primary outcome was the composite of death, maternal infectious morbidity, further operative procedures, or blood transfusion (>1 unit) up to the 6-week follow-up visit. Women were analysed in the groups into which they were allocated. The CORONIS Trial is registered with Current Controlled Trials: ISRCTN31089967. FINDINGS: Between May 20, 2007, and Dec 31, 2010, 15â935 women were recruited. There were no statistically significant differences within any of the intervention pairs for the primary outcome: blunt versus sharp entry risk ratio 1·03 (95% CI 0·91-1·17), exterior versus intra-abdominal repair 0·96 (0·84-1·08), single-layer versus double-layer closure 0·96 (0·85-1·08), closure versus non-closure 1·06 (0·94-1·20), and chromic catgut versus polyglactin-910 0·90 (0·78-1·04). 144 serious adverse events were reported, of which 26 were possibly related to the intervention. Most of the reported serious adverse events were known complications of surgery or complications of the reasons for the caesarean section. INTERPRETATION: These findings suggest that any of these surgical techniques is acceptable. However, longer-term follow-up is needed to assess whether the absence of evidence of short-term effects will translate into an absence of long-term effects. FUNDING: UK Medical Research Council and WHO.
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Cesárea/métodos , Complicaciones del Embarazo/cirugía , Práctica Profesional/estadística & datos numéricos , Adulto , Argentina , Cesárea/estadística & datos numéricos , Cesárea Repetida/métodos , Cesárea Repetida/estadística & datos numéricos , Chile , Femenino , Ghana , Humanos , India , Kenia , Pakistán , Embarazo , Resultado del Embarazo , Sudán , Técnicas de Cierre de Heridas/estadística & datos numéricosRESUMEN
BACKGROUND: Providing primary care for people with frailty can be challenging due to an increased risk of adverse outcomes and use of potentially inappropriate medications which may exacerbate characteristics of frailty. eConsult is a service where primary care providers can receive timely specialist advice for their patients through a secure web-based application. We aimed to develop a classification system to characterize medication-focused eConsult questions for older adults with frailty and assess its usability. METHODS: A classification system was developed and refined over three cycles of improvement through a cross-sectional study of 35 cases categorized as medication-focused from cases submitted in 2019 for patients aged 65 or older with frailty through the Champlain BASE eConsult service (Ontario, Canada). The final classification system was then applied to each case. RESULTS: The classification system contains 5 sections: (1) case descriptives; (2) intent and type of question; (3) medication recommendations and additional information in the response; (4) medication classification; and (5) potentially inappropriate medications. Among the 35 medication-focused cases, the most common specialties consulted were endocrinology (9 cases, 26%) and cardiology (5 cases, 14%). Medication histories were available for 29 cases (83%). Many patients were prescribed potentially inappropriate medications based on explicit tools (AGS Beers Criteria®, STOPPFall, Anticholinergic Cognitive Burden Scale, ThinkCascades) yet few consults inquired about these medications. CONCLUSION: A classification system to describe medication-related eConsult cases for patients experiencing frailty was developed and applied to 35 eConsult cases. It can be applied to more cases to identify professional development opportunities and enhancements for eConsult services.
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Fragilidad , Humanos , Anciano , Estudios Transversales , Fragilidad/diagnóstico , Atención Primaria de Salud , Derivación y Consulta , OntarioRESUMEN
Major histocompatibility complex (MHC) class I-linked microsatellite data and parental assignment data for a group of wild brown trout (Salmo trutta L.) provide evidence of closer spatial aggregation among fry sharing greater numbers of MHC class I alleles under natural conditions. This result confirms predictions from laboratory experiments demonstrating a hierarchical preference for association of fry sharing MHC alleles. Full-siblings emerge from the same nest (redd), and a passive kin association pattern arising from limited dispersal from the nest (redd effect) would predict that all such pairs would have a similar distribution. However, this study demonstrates a strong, significant trend for reduced distance between pairs of full-sibling fry sharing more MHC class I alleles reflecting their closer aggregation (no alleles shared, 311.5 ± (s.e.)21.03 m; one allele shared, 222.2 ± 14.49 m; two alleles shared, 124.9 ± 23.88 m; P<0.0001). A significant trend for closer aggregation among fry sharing more MHC class I alleles was also observed in fry pairs, which were known to have different mothers and were otherwise unrelated (ML-r = 0) (no alleles: 457.6 ± 3.58 m; one allele (422.4 ± 3.86 m); two alleles (381.7 ± 10.72 m); P<0.0001). These pairs are expected to have emerged from different redds and a passive association would then be unlikely. These data suggest that sharing MHC class I alleles has a role in maintaining kin association among full-siblings after emergence. This study demonstrates a pattern consistent with MHC-mediated kin association in the wild for the first time.
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Demografía , Genes MHC Clase I/genética , Conducta Espacial/fisiología , Trucha/genética , Animales , Electroforesis en Gel de Poliacrilamida , Frecuencia de los Genes , Genética de Población , Repeticiones de Microsatélite/genética , Dinámica Poblacional , Estadísticas no Paramétricas , Trucha/fisiologíaRESUMEN
Evidence is reported for balancing selection acting on variation at major histocompatibility complex (MHC) in wild populations of brown trout Salmo trutta. First, variation at an MHC class I (satr-uba)-linked microsatellite locus (mhc1) is retained in small S. trutta populations isolated above waterfalls although variation is lost at neutral microsatellite markers. Second, populations across several catchments are less differentiated at mhc1 than at neutral markers, as predicted by theory. The population structure of these fish was also elucidated.
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Genes MHC Clase I/genética , Variación Genética , Selección Genética , Trucha/genética , Animales , Genética de Población , Repeticiones de Microsatélite/genéticaRESUMEN
Mefloquine, an antimalarial medication with efficacy against JC virus, was used to treat progressive multifocal leukoencephalopathy. A 54-year-old woman with sarcoidosis presented with a progressive cerebellar syndrome. MRI showed lesions affecting the right cerebellum that progressed over time to the brainstem. JC virus was found in the cerebrospinal fluid (CSF), and brain biopsy confirmed the diagnosis of progressive multifocal leukoencephalopathy. Mefloquine 1000 mg/week was initiated 6 months after symptom onset. Clinical progression stopped immediately, and JC virus became undetectable in the CSF. No clinical or imaging evidence of disease progression has occurred over 20 months of follow-up. This is the first report of successful treatment of progressive multifocal leukoencephalopathy with mefloquine.
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Leucoencefalopatía Multifocal Progresiva/tratamiento farmacológico , Mefloquina/uso terapéutico , Líquido Cefalorraquídeo/virología , Femenino , Humanos , Virus JC/efectos de los fármacos , Leucoencefalopatía Multifocal Progresiva/virología , Imagen por Resonancia Magnética/métodos , Persona de Mediana EdadRESUMEN
The objective of this study was to measure how primary care family physicians perceived their own and pharmacists' contributions to medication processes as pharmacists become integrated into primary care group family practices. The 22- item Family Medicine Medication Use Processes Matrix was mailed to physicians in seven sites at the 3rd, 12th and 19th month of pharmacist integration. Paired sample t-tests for the third month results were conducted to compare perceptions between pharmacist and physician contributions. One way repeated measure ANOVA test was conducted to determine significant changes over time. Physicians initially perceived their own contributions to be significantly higher than pharmacists in three subscales: Diagnosis & Prescribing, Monitoring and Administration/Documentation and their own contributions to be significantly lower than the pharmacists in the Education subscale. Over time, physicians perceived increases in the pharmacists' contribution to the Diagnosis & Prescribing, Monitoring and Medication Review subscales and decreases in their own contribution to the Diagnosis & Prescribing and Education subscales. Changes in family physicians' perceptions of pharmacists' contribution demonstrate an initial underestimate of pharmacists' role in primary care family practice and a gradual recognition of expertise and competence. This may have led to increased comfort in sharing aspects of contribution to medication use processes.
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Actitud del Personal de Salud , Comunicación Interdisciplinaria , Farmacéuticos/organización & administración , Médicos/organización & administración , Prejuicio , Atención Primaria de Salud/organización & administración , Percepción Social , Adulto , Análisis de Varianza , Recolección de Datos , Escolaridad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Encuestas y CuestionariosRESUMEN
BACKGROUND: Elders living with polypharmacy may be taking medications that do not benefit them. Polypharmacy can be associated with elevated risks of poor health, reduced quality of life, high care costs, and persistently complex care needs. While many medications could be problematic, this project targets medications that should be deprescribed for most elders and for which guidelines and evidence-based deprescribing tools are available. These are termed potentially inappropriate prescriptions (PIPs) and are as follows: proton pump inhibitors, benzodiazepines, antipsychotics, and sulfonylureas. Implementation strategies for deprescribing PIPs in complex older patient populations are needed. METHODS: This will be a pragmatic cluster randomized controlled trial in community-based primary care practices across Canada. Eligible practices provide comprehensive primary care and have at least one physician that consents to participate. Community-dwelling patients aged 65 years and older with ten or more unique medication prescriptions in the past year will be included. The objective is to assess whether the intervention reduces targeted PIPs for these patients compared with usual care. The intervention, Structured Process Informed by Data, Evidence and Research (SPIDER), is a collaboration between quality improvement (QI) and research programs. Primary care teams will form interprofessional Learning Collaboratives and work with QI coaches to review electronic medical record data provided by their regional Practice Based Research Networks (PBRNs), identify areas of improvement, and develop and implement changes. The study will be tested for feasibility in three PBRNs (Toronto, Montreal, and Edmonton) using prospective single-arm mixed methods. Findings will then guide a pragmatic cluster randomized controlled trial in five PBRNs (Calgary, Winnipeg, Ottawa, Montreal, and Halifax). Seven practices per PBRN will be recruited for each arm. The analysis will be by intention to treat. Ten percent of patients who have at least one PIP at baseline will be randomly selected to participate in the assessment of patient experience and self-reported outcomes. Qualitative methods will be used to explore patient and physician experience and evaluate SPIDER's processes. CONCLUSION: We are testing SPIDER in a primary care population with complex care needs. This could provide a widely applicable model for care improvement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03689049 ; registered September 28, 2018.
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Polifarmacia , Atención Primaria de Salud/normas , Mejoramiento de la Calidad , Anciano , Anciano de 80 o más Años , Canadá , Humanos , Prescripción Inadecuada , Masculino , Calidad de Vida , Proyectos de InvestigaciónRESUMEN
This paper reviews results obtained using statistical state dynamics (SSD) that demonstrate the benefits of adopting this perspective for understanding turbulence in wall-bounded shear flows. The SSD approach used in this work employs a second-order closure that retains only the interaction between the streamwise mean flow and the streamwise mean perturbation covariance. This closure restricts nonlinearity in the SSD to that explicitly retained in the streamwise constant mean flow together with nonlinear interactions between the mean flow and the perturbation covariance. This dynamical restriction, in which explicit perturbation-perturbation nonlinearity is removed from the perturbation equation, results in a simplified dynamics referred to as the restricted nonlinear (RNL) dynamics. RNL systems, in which a finite ensemble of realizations of the perturbation equation share the same mean flow, provide tractable approximations to the SSD, which is equivalent to an infinite ensemble RNL system. This infinite ensemble system, referred to as the stochastic structural stability theory system, introduces new analysis tools for studying turbulence. RNL systems provide computationally efficient means to approximate the SSD and produce self-sustaining turbulence exhibiting qualitative features similar to those observed in direct numerical simulations despite greatly simplified dynamics. The results presented show that RNL turbulence can be supported by as few as a single streamwise varying component interacting with the streamwise constant mean flow and that judicious selection of this truncated support or 'band-limiting' can be used to improve quantitative accuracy of RNL turbulence. These results suggest that the SSD approach provides new analytical and computational tools that allow new insights into wall turbulence.This article is part of the themed issue 'Toward the development of high-fidelity models of wall turbulence at large Reynolds number'.
RESUMEN
OBJECTIVES: This study examined the effects of concurrent diuretic therapy on the hemodynamic responses to short-term and sustained therapy with transdermal nitroglycerin. BACKGROUND: Sodium retention and plasma volume expansion occur during therapy with nitroglycerin and may play a role in the loss of nitroglycerin effects during sustained therapy. METHODS: Twenty-two normal male volunteers were treated for 1 week with either hydrochlorothiazide and amiloride (50 + 5 mg) (n = 11) or placebo (n = 11) in a randomized, double-blind fashion. All 22 subjects then received continuous transdermal nitroglycerin (19 +/- 1 mg/24 h) for 5 to 7 days. RESULTS: On the first and last day of transdermal nitroglycerin therapy, standing heart rate, systolic blood pressure and hematocrit values were assessed at 8, 9 and 10 AM and 12 noon. Heart rate and blood pressure responses to sublingual nitroglycerin (0.6 mg) were also evaluated before and after sustained transdermal nitroglycerin therapy. A significant loss of the hemodynamic effects of transdermal and sublingual nitroglycerin occurred during sustained therapy in both the diuretic and placebo therapy groups. In both groups, transdermal nitroglycerin therapy was associated with a significant decrease in hematocrit that persisted for the entire treatment period. CONCLUSIONS: These results suggest that diuretic therapy does not prevent plasma volume expansion or the loss of hemodynamic effects during sustained transdermal nitroglycerin therapy. The persistent decrease in hematocrit suggests that plasma volume expansion plays a role in the attenuation of nitrate effects. It also provides evidence of continued vascular activity of nitroglycerin despite loss of systemic hemodynamic effects.
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Amilorida/farmacología , Hidroclorotiazida/farmacología , Nitroglicerina/farmacología , Volumen Plasmático/efectos de los fármacos , Administración Cutánea , Adulto , Presión Sanguínea/efectos de los fármacos , Método Doble Ciego , Interacciones Farmacológicas/fisiología , Quimioterapia Combinada , Tolerancia a Medicamentos/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Hematócrito , Humanos , Masculino , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéuticoRESUMEN
Beetles in the weevil subfamilies Scolytinae and Platypodinae are unusual in that they burrow as adults inside trees for feeding and oviposition. Some of these beetles are known as ambrosia beetles for their obligate mutualisms with asexual fungi--known as ambrosia fungi--that are derived from plant pathogens in the ascomycete group known as the ophiostomatoid fungi. Other beetles in these subfamilies are known as bark beetles and are associated with free-living, pathogenic ophiostomatoid fungi that facilitate beetle attack of phloem of trees with resin defenses. Using DNA sequences from six genes, including both copies of the nuclear gene encoding enolase, we performed a molecular phylogenetic study of bark and ambrosia beetles across these two subfamilies to establish the rate and direction of changes in life histories and their consequences for diversification. The ambrosia beetle habits have evolved repeatedly and are unreversed. The subfamily Platypodinae is derived from within the Scolytinae, near the tribe Scolytini. Comparison of the molecular branch lengths of ambrosia beetles and ambrosia fungi reveals a strong correlation, which a fungal molecular clock suggests spans 60 to 21 million years. Bark beetles have shifted from ancestral association with conifers to angiosperms and back again several times. Each shift to angiosperms is associated with elevated diversity, whereas the reverse shifts to conifers are associated with lowered diversity. The unusual habit of adult burrowing likely facilitated the diversification of these beetle-fungus associations, enabling them to use the biomass-rich resource that trees represent and set the stage for at least one origin of eusociality.
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Evolución Biológica , Escarabajos/clasificación , Escarabajos/genética , Cycadopsida/parasitología , Variación Genética , Magnoliopsida/parasitología , Filogenia , Agricultura , Animales , Ascomicetos/fisiología , Escarabajos/microbiología , Escarabajos/fisiología , Diploidia , Conducta Alimentaria , Haploidia , Proteínas de Insectos/genética , Oviposición , Fosfopiruvato Hidratasa/genética , Reacción en Cadena de la Polimerasa , Especificidad de la Especie , Árboles/microbiología , Árboles/parasitologíaRESUMEN
The abuse of ipecac syrup for three years resulted in painless, nonfatigable, chiefly proximal weakness in a 27-year-old woman. Electromyography (EMG) and a muscle biopsy revealed features of a myopathy similar to those previously reported in experimental emetine myopathy. Clinical weakness and EMG abnormalities improved after discontinuation of ipecac administration. A direct toxic action of ipecac (acting through its active alkaloid, emetine hydrochloride) on muscle fibers seemed to be responsible for the weakness in this patient.
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Ipeca/efectos adversos , Enfermedades Musculares/inducido químicamente , Adulto , Femenino , Humanos , Enfermedades Musculares/patología , Trastornos Relacionados con Sustancias/diagnósticoRESUMEN
Several shifts from ancestral conifer feeding to angiosperm feeding have been implicated in the unparalleled diversification of beetle species. The single largest angiosperm-feeding beetle clade occurs in the weevils, and comprises the family Curculionidae and relatives. Most authorities confidently place the bark beetles (Scolytidae) within this radiation of angiosperm feeders. However, some clues indicate that the association between conifers and some scolytids, particularly in the tribe Tomicini, is a very ancient one. For instance, several fragments of Gondwanaland (South America, New Caledonia, Australia and New Guinea) harbour endemic Tomicini specialized on members of the formerly widespread and abundant conifer family Araucariaceae. As a first step towards resolving this seeming paradox, we present a phylogenetic analysis of the beetle family Scolytidae with particularly intensive sampling of conifer-feeding Tomicini and allies. We sequenced and analysed elongation factor 1alpha and nuclear rDNAs 18S and 28S for 45 taxa, using members of the weevil family Cossoninae as an out-group. Our results indicate that conifer feeding is the ancestral host association of scolytids, and that the most basal lineages of scolytids feed on Aramucaria. If scolytids are indeed nested within a great angiosperm-feeding clade, as many authorities have held, then a reversion to conifer feeding in ancestral scolytids appears to have occurred in the Mesozoic, when Araucaria still formed a major component of the woody flora.
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Escarabajos/genética , Cycadopsida/parasitología , Animales , Secuencia de Bases , Cartilla de ADN/genética , Evolución Molecular , Magnoliopsida/parasitología , Factor 1 de Elongación Peptídica/genética , Filogenia , ARN Ribosómico 18S/genética , ARN Ribosómico 28S/genética , Especificidad de la EspecieRESUMEN
Eighteen patients with chronic, stable angina were studied in a double-blind, placebo-controlled, 3-way, crossover study in which they received 4 weeks of treatment with a once-daily dose of bepridil, 300 mg, a once-daily dose of long-acting propranolol, 160 mg, and placebo. Heart rate at rest during bepridil treatment was less than that during placebo (p less than 0.01), whereas propranolol reduced heart rate compared with placebo (p less than 0.001) and bepridil (p less than 0.01). Systolic blood pressure at rest did not change during the 3 treatment phases. Exercise time to onset of angina and to development of moderate angina were reproducible over the 24-hour period during each treatment phase. Treadmill walking time to onset of angina and to development of moderate angina was significantly prolonged during bepridil (p less than 0.01) and during propranolol treatment (p less than 0.05). Heart rate at peak exercise was similar during bepridil and during placebo, but was markedly reduced with propranolol treatment (p less than 0.001). Systolic blood pressure during exercise was similar during placebo and bepridil, but was substantially lower during propranolol treatment (p less than 0.01).
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Angina de Pecho/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Propranolol/uso terapéutico , Pirrolidinas/uso terapéutico , Anciano , Angina de Pecho/fisiopatología , Bepridil , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Método Doble Ciego , Electrocardiografía , Prueba de Esfuerzo , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Twenty patients with chronic, stable, exercise-induced angina pectoris were studied after receiving lingual sprays that delivered 0.2, 0.4 and 0.8 mg of nitroglycerin (GTN). The hemodynamic effects and changes in exercise time to the onset of angina and to the development of moderate angina were compared with those of placebo spray and 0.4 mg of sublingual GTN. A dose-response relation was apparent with the 3 doses of active spray for heart rate at rest but not for standing systolic blood pressure. Sublingual GTN produced effects similar to those with 0.4 and 0.8 mg of GTN spray, but exceeded the response to 0.2 mg of GTN spray. Treadmill walking time to the onset of angina and to the development of moderate angina was prolonged with each dose of GTN spray and showed a dose-response relation with significantly greater effects with increasing doses of GTN spray. This study indicates that GTN lingual spray is effective in the prophylaxis of angina and should be effective in the therapy of exercise-induced or spontaneous episodes of angina pectoris. The dose of 0.4 or 0.8 mg would appear to be most effective and similar to 0.4 mg of sublingual GTN.
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Angina de Pecho/tratamiento farmacológico , Nitroglicerina/administración & dosificación , Aerosoles , Anciano , Angina de Pecho/fisiopatología , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Evaluación de Medicamentos , Electrocardiografía , Prueba de Esfuerzo , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Nitroglicerina/uso terapéutico , Distribución Aleatoria , LenguaRESUMEN
Sixteen patients with chronic stable angina pectoris were studied to compare the hemodynamic and antianginal effects of buccal nitroglycerin (GTN) in a dose of 3 mg administered 3 times daily and oral isosorbide dinitrate (ISDN) in a dose of 30 mg administered 4 times daily. Compared with placebo, both oral ISDN and buccal GTN treatment induced a decrease in systolic blood pressure at rest over a 5-hour period during acute but not during sustained therapy. Neither buccal GTN nor oral ISDN modified the changes in systolic blood pressure during exercise. Both treatment programs were associated with a higher exercise heart rate during acute therapy. During sustained treatment with buccal GTN, the heart rate during exercise remained greater than that during placebo throughout the 5-hour test period, but during treatment with oral ISDN, only the exercise heart rate at 1 hour was greater than that seen with placebo. Treadmill walking time to the onset of angina and to the development of moderate angina increased significantly during acute therapy with both buccal GTN and oral ISDN. The clinical efficacy of buccal GTN was maintained after 2 weeks of 3-times-daily therapy. In contrast, during 4-times-daily therapy with oral ISDN, treadmill walking time was prolonged for only 1 hour after drug administration. This investigation indicates that tolerance develops during 4-times-daily therapy with oral ISDN, but 3 times daily therapy with buccal GTN is not associated with diminished antianginal effects.
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Angina de Pecho/tratamiento farmacológico , Isosorbida/uso terapéutico , Nitroglicerina/uso terapéutico , Sorbitol/análogos & derivados , Anciano , Quimioterapia Combinada , Tolerancia a Medicamentos , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Isosorbida/administración & dosificación , Masculino , Persona de Mediana Edad , Nitroglicerina/administración & dosificación , Esfuerzo Físico , DescansoRESUMEN
The mechanisms of hypertension in coarctation remain to be clearly defined. In other hypertensive states, abnormal plasma renin activity (PRA) has been unmasked by the depletion of extracellular volume and the use of angiotensin antagonists. In a group of patients with coarctation, preoperative and postoperative evaluations of the renin-angiotensin system have been performed. Before operation, a group of patients with coarctation and a group of normal control subjects both underwent salt restriction followed by diuresis. A standard angiotensin antagonist (saralasin) test was performed on the patients with coarctation, and they demonstrated excessive renin-angiotensin activity compared to the control subjects. Following operation, paradoxical hypertension developed in all of the patients. Repeat saralasin test in these patients again revealed excessive angiotensin activity in the same patients as preoperatively. It appears that the renin-angiotensin system plays a more active role in coarctation than previously believed.
Asunto(s)
Angiotensina II/sangre , Coartación Aórtica/sangre , Hipertensión/sangre , Renina/sangre , Adolescente , Coartación Aórtica/complicaciones , Coartación Aórtica/cirugía , Niño , Preescolar , Furosemida/farmacología , Humanos , Hipertensión/etiología , SaralasinaRESUMEN
HYPOTHESIS: Surgical intervention in palliative care is common; however, the indications, risks, and outcomes are not well described. DESIGN: Retrospective review of surgical cases during a 1-year period with a minimum 1-year survival update. SETTING: A National Cancer Institute-designated comprehensive cancer center. PATIENTS: Patients with a cancer diagnosis undergoing operative procedures. MAIN OUTCOME MEASURES: Number of palliative surgeries and analysis of length of stay, morbidity, and mortality. RESULTS: Palliative surgeries comprised 240 (12.5%) of 1915 surgical procedures. There were 170 major and 70 minor procedures. Neurosurgical (46.0%), orthopedic (31.3%), and thoracic (21.5%) surgical procedures were frequently palliative. The most common primary diagnoses were lung, colorectal, breast, and prostate cancers. Length of hospital stay was 12.4 days (range, 0-99 days), with 21.3% of procedures performed on an outpatient basis. The 30-day mortality was 12.2%, with 5 patients dying within 5 days of their procedure. The overall mortality was 23.3% (56/240). Mortality for surgical procedures classified as major was 21.9% (44/170) and 10.0% (7/70) for those classified as minor (Fisher exact test, P<.01). CONCLUSIONS: Significant numbers of palliative procedures are performed at our cancer center. Overall morbidity and mortality were high; however, a significant number of patients had short hospital stays and low morbidity. Palliative surgery should remain an important part of end-of-life care. Patients and their families must be aware of the high risks and understand the clear objectives of these procedures.