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We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.
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Antivirales/química , Tratamiento Farmacológico de COVID-19 , SARS-CoV-2/efectos de los fármacos , Proteínas no Estructurales Virales/química , Inteligencia Artificial , Sitios de Unión , Simulación por Computador , Bases de Datos de Compuestos Químicos , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Humanos , Simulación del Acoplamiento Molecular , Conformación Proteica , Glicoproteína de la Espiga del Coronavirus/química , Relación Estructura-ActividadRESUMEN
We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses.
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The continuing threat of antimicrobial resistance presents a considerable challenge to researchers to develop novel strategies ensuring that bacterial infections remain treatable. Many plant extracts have been shown to have antibacterial properties and could potentially be combined with other antibacterial agents to create more effective formulations. In this study, the antibacterial activity of three plant extracts and virulent bacteriophages have been assessed as individual components and in combination. When assessed with a modified suspension test, these plant extracts also exhibit antiviral activity at bacterial inhibitory concentrations. Hence, to investigate any potential additive effects between the extracts and virulent phages, the extracts were tested at subantiviral concentrations. Phages alone and in combination with plant extracts significantly reduced (P < 0·05) the bacterial concentration compared to untreated and extract treated controls up to 6 h (2-3log10 ), but this reduction did not extend to 24 h. In most cases, the phage and extract combinations did not significantly reduce bacterial content compared to phages alone. Additionally, there was little impact on the ability of the phages to reproduce within their bacterial hosts. To our knowledge, this study represents the first of its kind, in which antimicrobial plant extracts have been combined with virulent phages and has highlighted the necessity for plant extracts to be functionally characterized prior to the design of combinatorial therapies. Significance and Impact of Study This preliminary study provides insights into the potential combination of bacteriophages and antimicrobial plant bulk extracts to target bacterial pathogens. It is to our knowledge the first time in which virulent bacteriophages have been combined with antimicrobial plant extracts.
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Antibacterianos/farmacología , Agentes de Control Biológico/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/efectos de los fármacos , Myoviridae/crecimiento & desarrollo , Extractos Vegetales/farmacología , Siphoviridae/crecimiento & desarrollo , Bignoniaceae/química , Farmacorresistencia Bacteriana Múltiple , Escherichia coli/virología , Medicina Tradicional de Asia Oriental , Pruebas de Sensibilidad Microbiana , Prueba de Estudio Conceptual , Stephania/química , Zingiberaceae/químicaRESUMEN
Since their discovery in 1915, bacteriophages have been routinely used within Eastern Europe to treat a variety of bacterial infections. Although initially ignored by the West due to the success of antibiotics, increasing levels and diversity of antibiotic resistance is driving a renaissance for bacteriophage-derived therapy, which is in part due to the highly specific nature of bacteriophages as well as their relative abundance. This review focuses on the bacteriophages and derived lysins of relevant Gram-positive spore formers within the Bacillus cereus group and Clostridium genus that could have applications within the medical, food and environmental sectors.
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Bacteriófagos/fisiología , Terapia Biológica , Endopeptidasas/farmacología , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/virología , Infecciones por Bacterias Grampositivas/terapia , Esporas Bacterianas/efectos de los fármacos , Animales , Bacteriófagos/química , Endopeptidasas/metabolismo , Bacterias Grampositivas/crecimiento & desarrollo , Bacterias Grampositivas/fisiología , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Esporas Bacterianas/crecimiento & desarrolloRESUMEN
Percutaneous thrombectomy is being widely used as a sole therapy or as an adjunct to other therapies for the management of thrombotic occlusions in arteries, veins and grafts. Various techniques used can be broadly classified under percutaneous aspiration thrombectomy, pull-back thrombectomy and trapping, recirculation mechanical thrombectomy, direct contact/non-recirculation thrombectomy and direct or indirect ultrasound thrombectomy. In the following article, we will provide a review of these techniques describing the commonly utilized devices and their characteristics.
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Procedimientos Endovasculares/métodos , Trombectomía/métodos , Tromboembolia/cirugía , Humanos , Trombectomía/instrumentación , Ultrasonografía IntervencionalRESUMEN
UNLABELLED: The aim of this study was to determine the stability and purity of a phage cocktail to be delivered by nebulization. A cocktail of three phages active against Pseudomonas aeruginosa isolates from cystic fibrosis patients was developed for a potential nebulized formulation. The individual phages were examined for their retention of activity over time, while the phage cocktail was analysed for bacterial contaminant and endotoxin level according to regulatory requirements for nebulized products. The phage cocktail was nebulized using a Porta-neb nebulizer connected to an Anderson cascade impactor. The three phages retained activity over a period of 180 days storage at room temperature and at 4°C. Nebulized phages were recovered in the lower stages of the cascade impactor indicative of potential delivery deep into the lungs. The phage cocktail met bacterial limits but the endotoxin levels measured with the Limulus amoebocyte lysate (LAL) test remained considerably in excess of acceptable levels even following purification. These findings suggest that nebulization of phage is a viable delivery option; although, there is a need for appropriate depyrogenation strategies to remove bacterial endotoxins from phage-based preparations to meet regulatory requirements. SIGNIFICANCE AND IMPACT OF THE STUDY: With increasing reports of bacterial resistance to antibiotics and the lack of new antibiotics being produced, bacteriophage therapy is becoming an attractive alternative. There has been no published report on the quality assurance of bacteriophage product to date. This is the first study on the quality assurance of a Pseudomonas aeruginosa phage cocktail following pharmacopoeial requirements. The presence of bacterial endotoxin was found to be the key stumbling block for meeting regulatory criteria.
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Fagos Pseudomonas , Pseudomonas aeruginosa/virología , Fibrosis Quística/microbiología , Endotoxinas/análisis , Humanos , Nebulizadores y Vaporizadores , Fagos Pseudomonas/aislamiento & purificación , Fagos Pseudomonas/fisiologíaRESUMEN
INTRODUCTION: Pseudomonas aeruginosa is an opportunistic pathogen and is the main cause of respiratory infection in cystic fibrosis patients. Most strains prevalent within the UK are resistant to two or more antibiotics leading to the search for new therapeutic strategies including the use of bacteriophages. METHODS AND RESULTS: The infectivity of four bacteriophages was increased using an enhancement protocol based on the use of pomegranate rind extract. Their efficacy against 14 Ps. aeruginosa strains was measured using a qualitative streak test and a novel quantitative assay based on the Bioscreen C microbial growth analyzer. Streak test analysis illustrated an increase in the lytic activity of enhanced bacteriophages, whereas Bioscreen analysis showed that both enhanced and unenhanced bacteriophages failed to meet acceptable levels of activity in c. 50% of strains tested. CONCLUSIONS: The quantitative Bioscreen C analyzer showed comparable but not identical results in phage activity and identified significant bacterial re-growth by 20 h postinfection. SIGNIFICANCE AND IMPACT OF THE STUDY: With the resurgence of interest in bacteriophage therapy against infectious bacterial diseases, a rapid high throughput quantitative method for screening phage activity and bacterial resistance is required. The use of the Bioscreen C analyzer meets these criteria and was shown to be more stringent than the traditional streak test.
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Bacteriófagos/fisiología , Fibrosis Quística/microbiología , Técnicas Microbiológicas/métodos , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/virología , Humanos , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/aislamiento & purificación , Reproducibilidad de los ResultadosRESUMEN
This study of adolescent farmworkers describes employer compliance with pesticide safety training, a requirement of the EPA-mandated Worker Protection Standard (WPS), and identifies variables associated with having received training within the prior five years. Data are from "A Study of Work Injuries in Farmworker Children, " a three-year cohort study of high school students living along the Texas-Mexico border in Starr County. Data were collected using a web-based, self-administered, confidential survey. Of 324 students who participated in field work between January 1 and September 30, 2003, 68 (21.0%) reported ever receiving pesticide safety training. Overall, the 61 (18.8%) students who reported training within the prior five years also reported that their most recent instruction covered at least three key WPS areas (i.e., entry into a recently treated field, pesticide-related injuries/illnesses, and emergency care for pesticide exposure). Based on a multiple logistic regression, students who were male (OR = 1.97), worked only outside of Texas (OR = 2.73), worked only for commercial growers/owners (OR = 4.35), worked only for contractors (OR = 3.18), worked corn crops (OR = 2.93), and worked potato crops (OR = 3.11) were more likely to report receipt of training within the prior five years. Results suggest that increased enforcement may be needed, especially in Texas, and special educational efforts may be needed to reach female farmworker youth.
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Enfermedades de los Trabajadores Agrícolas/prevención & control , Educación en Salud/normas , Capacitación en Servicio/normas , Exposición Profesional/prevención & control , Plaguicidas/toxicidad , Prevención de Accidentes , Adolescente , Servicios de Salud del Adolescente , Niño , Estudios Transversales , Femenino , Adhesión a Directriz , Educación en Salud/organización & administración , Humanos , Masculino , Servicios de Salud del Trabajador , TexasRESUMEN
Adjunctive balloon dilatation strategy has been shown to improve optimal stent deployment. As improvements in current stent designs evolve, less adjunctive balloon dilatation may be needed. However, few data currently exist to support this practice. We evaluated 88 native coronary lesions treated with single stent implantation (Nir, Tristar or S670). Serial intravascular ultrasound was performed after successful stent deployment and again after adjunctive balloon dilatation. To investigate further the precise expansion characteristics of the stents, serial volumetric intravascular ultrasound analyses were performed in 40 patients with automated pullback. After adjunctive balloon dilatation, minimal stent area increased significantly, from 6.4 +/- 2.1 to 7.4 +/- 2.2 mm(2) (p <0.001). Volumetric analysis showed a corresponding increase in stent volume index (6.6 +/- 1.8 to 7.5 +/- 2.0 mm(3)/mm, p <0.001). In the analysis of cross sections at 0.5-mm axial intervals, the percentage of cross sections, where stent area was > or =80% of the average reference lumen area, increased from 51% to 78% (p <0.001). Similarly, the percentage of cross sections, where stent area was > or =90% of the average reference lumen area, increased from 29% to 56% (p <0.001) with postdilatation. Postdeployment high- pressure balloon dilatation improved minimal stent area and volumetric expansion throughout the stented segment.
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Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Stents , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: Limited information is available on the effects of 8 French (Fr) transradial procedures on radial patency. In addition, the effects of radial procedures and radial occlusion on hand function are unknown. METHODS: Two groups were recruited: twenty-four patients who had undergone 26 transradial 8 Fr interventions and 16 patients who had undergone 16 transradial 6 Fr procedures. At 1 year, radial patency, hand strength and hand endurance were measured. RESULTS: No major adverse cardiac events or vascular complications were noted in either group. Late radial occlusion was noted in 2/18 (11%) 8 Fr patients and 3/16 (19%) 6 Fr patients (p = ns). There were no differences in the 8 Fr group between the catheterized and uncatheterized radial arteries for diameter (3.2 +/- 1.1 mm versus 3.3 +/- 0.7 mm, respectively; p = NS) or volumetric flow (55 +/- 51 ml/minute versus 57 +/- 45 ml/minute, respectively; p = NS). No differences in hand strength or hand endurance were seen between the catheterized and uncatheterized arms in the 8 Fr group, between the 8 Fr and 6 Fr groups, or between occluded and non-occluded patients. CONCLUSION: Transradial use of 8 Fr guiding catheters appears to be feasible and safe in highly selected patients, albeit associated with a low incidence of silent radial occlusion. Additionally, neither the use of 8 Fr sheaths nor the presence of radial artery occlusion appear to adversely affect hand strength or endurance.
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Cateterismo Cardíaco/instrumentación , Mano/irrigación sanguínea , Isquemia/etiología , Revascularización Miocárdica/instrumentación , Arteria Radial , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/etiología , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Radial/lesiones , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: Previous data suggest that oral antigen induces interferon (IFN)-gamma production in intestinal T cells. However, oral tolerance is associated with decreased production of IFN-gamma by T cells after antigen sensitization. The aim of this study was to examine the role of IFN-gamma in oral tolerance. METHODS: Oral tolerance was examined in BALB/c mice after the adoptive transfer of T cells from chicken ovalbumin (OVA(323-339))-specific, DO11.10 x RAG-1(-/-) T-cell receptor transgenic mice. RESULTS: OVA feeding induced systemic tolerance of delayed-type hypersensitivity (DTH) and antibody responses. OVA feeding up-regulated IFN-gamma production by transgenic T cells in Peyer's patch and mesenteric lymph node but not splenic tissues. Treatment of OVA-fed mice with neutralizing monoclonal antibody to IFN-gamma prevented tolerance of DTH responses. Analysis of transgenic T-cell numbers in DTH sites by immunohistochemical staining suggested that induction of IFN-gamma by oral antigen decreased accumulation of transgenic T cells in cutaneous sites of antigen injection. IFN-gamma-deficient or wild-type DO11.10 and BALB/c mice were used to show that IFN-gamma production by donor transgenic T cells was critical for oral tolerance. CONCLUSIONS: These data suggest that the induction of IFN-gamma by oral antigen contributes to systemic tolerance by decreasing migration of T cells to peripheral sites of inflammation.
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Tolerancia Inmunológica/fisiología , Inflamación/fisiopatología , Interferón gamma/fisiología , Boca/inmunología , Linfocitos T/fisiología , Administración Oral , Traslado Adoptivo , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Movimiento Celular/fisiología , Pollos , Genes RAG-1/genética , Hipersensibilidad Tardía/inmunología , Hipersensibilidad Tardía/patología , Tolerancia Inmunológica/efectos de los fármacos , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Recuento de Leucocitos , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos/genética , Ovalbúmina/farmacología , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
BACKGROUND: Renal artery stenosis is a common disorder and is an established cause of hypertension and renal insufficiency. Although treatment with renal artery stents has been shown to improve blood pressure and renal function for some patients, the patient population most likely to benefit is unknown. The current study was designed to determine which factors are predictive of improved blood pressure and renal function when patients with renal artery stenosis are treated with renal artery angioplasty and stent placement. METHODS: In a prospective evaluation 127 consecutively enrolled patients with renal artery stenosis in 171 vessels were treated with angioplasty and intravascular stents. Blood pressure and serum creatinine concentration were measured before stent placement and during the follow-up period. RESULTS: The mean length of the follow-up period was 15 +/- 14 months. Mean systolic blood pressure improved among patients with hypertension (from 177 +/- 26 mm Hg before stent placement to 151 +/- 24 mm Hg 6 months after stent placement (P <.001). The greatest improvement occurred among those with the highest baseline systolic blood pressure. This beneficial effect on blood pressure was sustained for 3 years. Sex, age, diastolic blood pressure, number of vessels into which stents were placed, serum creatinine concentration, presence of bilateral disease, race, and severity of stenosis were not predictive of improved blood pressure. Mean creatinine concentration was not significantly changed for the group as a whole. A significant decrease in serum creatinine concentration occurred among 43% of patients with baseline renal insufficiency. None of the examined variables was predictive of improvement. CONCLUSIONS: Renal artery angioplasty and stent placement produced a significantly greater reduction in systolic blood pressure among patients with the highest baseline systolic blood pressure. Other examined variables were not predictive of a significant improvement in blood pressure. No examined variable was predictive of improved renal function. We concluded that management of renal artery stenosis with renal artery angioplasty and stent placement is most likely to result in significant improvement in systolic blood pressure among patients with the highest baseline systolic blood pressure.
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Angioplastia de Balón/instrumentación , Obstrucción de la Arteria Renal/terapia , Stents , Anciano , Angiografía , Presión Sanguínea , Creatinina/sangre , Femenino , Humanos , Hipertensión Renal/etiología , Hipertensión Renal/fisiopatología , Pruebas de Función Renal , Masculino , Pronóstico , Estudios Prospectivos , Obstrucción de la Arteria Renal/sangre , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/diagnóstico por imagenRESUMEN
Intestinal lamina propria (LP) CD4+ T cells are memory-like effector cells that proliferate at relatively low levels and require high levels of TCR signaling and costimulation for full activation in vitro. To study LP CD4+ T cell functional potential we used DO11.10 TCR transgenic (Tg) mice specific for the class II MHC-restricted OVA323-339 peptide and nontransgenic BALB/c mice. Activation of LP Tg+ T cells with Ag using mucosal explants induced high levels of IL-2, IL-4, and IFN-gamma. Culturing isolated LP cells with IL-12 enhanced IFN-gamma production and down-regulated IL-4 and IL-2, whereas addition of IL-4 maintained IL-4 production without inhibiting IFN-gamma production. Systemic administration of relatively high dose (HD; 100 nM) OVA323-339 peptide induced similar levels of bromodeoxyuridine (BrdU) incorporation by LP and splenic Tg+ T cells in vivo, whereas low dose (LD; 4.5 nM) peptide injections induced 4-fold greater levels of BrdU incorporation for LP compared with splenic Tg+ T cells. Coadministration of CTLA-4Ig reduced BrdU incorporation for splenic cells by 70% with HD and LD stimulation, but had little effect on LP responses to HD stimulation. Results of in vivo studies were confirmed in nontransgenic BALB/c mice using HD (200 microg) and LD (10 microg) anti-CD3 mAb+/- CTLA-4Ig. These results suggest that LP T cells are differentiated effector cells that respond at high levels when activated with relatively low levels of Ag- and B7-mediated costimulation in vivo. The reduced activation threshold of LP T cells may facilitate responses to low levels of Ag derived from mucosal pathogens.
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Linfocitos T CD4-Positivos/inmunología , Citocinas/biosíntesis , Intestinos/inmunología , Activación de Linfocitos , Receptor Cross-Talk , Animales , Antígeno B7-1/inmunología , Complejo CD3/inmunología , Complejo CD3/metabolismo , Linfocitos T CD4-Positivos/citología , Diferenciación Celular , Técnicas In Vitro , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Interleucina-4/farmacología , Intestinos/citología , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Ovalbúmina/inmunología , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T/genética , Bazo/citología , Bazo/inmunología , Células Th2/citología , Células Th2/inmunologíaRESUMEN
BACKGROUND: Transradial access is a recently developed alternative for diagnostic cardiac catheterization. Its effects on quality of life after the procedure, patient preference, and cost are unknown. METHODS AND RESULTS: We performed a randomized single-center trial in which 99 patients underwent transfemoral and 101 underwent transradial diagnostic cardiac catheterization. Quality of life was measured with the SF-36 and visual analog scales at baseline, 1 day, and 1 week. Patients were examined at 1 day and at 1 week after for complications. Costs were measured prospectively. One patient in the femoral group and 2 in the radial group crossed over to the alternative access site. There were no major access site complications. One patient in the transfemoral group had a minor stroke. Transradial catheterization significantly reduced median length of stay (3.6 vs 10.4 hours, P <.0001). Over the first day after the procedure, measures of bodily pain, back pain, and walking ability favored the transradial group (P <.05 for all comparisons). Over the week after the procedure, changes in role limitations caused by physical health, bodily pain, and back pain favored the transradial group (P <.05 for all comparisons). There was a strong patient preference for transradial catheterization as well (P <. 0001). Transradial catheterization led to significant reductions in bed, pharmacy, and total hospital costs ($2010 vs $2299, P <.0001). CONCLUSIONS: Among patients undergoing diagnostic cardiac catheterization, transradial access leads to improved quality of life after the procedure, is strongly preferred by patients, and reduces hospital costs.
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Cateterismo Cardíaco/economía , Cateterismo Cardíaco/métodos , Enfermedad Coronaria/diagnóstico por imagen , Costos de Hospital/estadística & datos numéricos , Calidad de Vida , Cateterismo Cardíaco/normas , Femenino , Arteria Femoral , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Arteria Radial , RadiografíaRESUMEN
Increased pulmonary resistance may reduce survival and treatment options in patients with congestive heart failure. Nitric oxide (NO) is a determinant of normal pulmonary resistance vessel tone. We tested the hypothesis that loss of NO function contributes to increased pulmonary vascular resistance index (PVRI) in congestive heart failure. Pulmonary arterial resistance vessel function was studied in 25 conscious adults. Three groups were studied: 8 controls, 9 patients with congestive heart failure and normal PVRI, and 8 patients with congestive heart failure and raised PVRI. Segmental arterial flow was determined with a Doppler wire and quantitative angiography. NG-monomethyl-L-arginine (L-NMMA) was used to inhibit NO, whereas phenylephrine was used as an endothelium-independent control. The response to inhibition of NO with L-NMMA was less in patients with congestive heart failure and elevated PVRI than in patients with congestive heart failure and normal PVRI (p <0.05). The difference in response between the congestive heart failure groups was specific to NO-dependent regulation because the response to the endothelium-independent constrictor phenylephrine was not different (p = 0.92). There was no difference in response to L-NMMA between controls and patients with congestive heart failure and normal PVRI. The response to L-NMMA correlated to PVRI. In adults with congestive heart failure, NO appears to play an important role in maintaining normal pulmonary resistance.
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Insuficiencia Cardíaca/fisiopatología , Óxido Nítrico/fisiología , Circulación Pulmonar/fisiología , Resistencia Vascular/fisiología , Adolescente , Adulto , Anciano , Femenino , Humanos , Infusiones Intraarteriales , Flujometría por Láser-Doppler , Masculino , Persona de Mediana Edad , Fenilefrina , omega-N-MetilargininaRESUMEN
Severe aortoiliac peripheral vascular disease (PVD) is considered a contraindication for the placement of an intraaortic balloon pump (IABP) because of a high risk of limb ischemia. Recent advances in percutaneous transluminal angioplasty (PTA) and stenting have altered the treatment of iliac stenoses such that the results of PTA with stenting compare favorably with surgery. We reviewed our experience with placement of IABP between July 1994 and February 1996. Of 64 patients receiving IABP, 17 had known or suspected peripheral vascular disease. Severe iliac or distal aortic stenoses were present in 9. These 9 patients underwent PTA with or without stenting prior to 10 IABP insertions. Limb ischemia occurred in 10% of PVD patients treated with percutaneous revascularization, compared to 11% in patients without PVD. No patient had a serious vascular complication or required vascular surgery. We conclude that percutaneous revascularization in patients with severe aortoiliac PVD, for whom this IABP insertion had previously been considered contraindicated, results in a low rate of limb ischemia.
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Angioplastia de Balón , Enfermedades de la Aorta/terapia , Arteria Ilíaca , Contrapulsador Intraaórtico , Anciano , Algoritmos , Constricción Patológica , Contraindicaciones , Femenino , Humanos , Arteria Ilíaca/patología , Isquemia/etiología , Pierna/irrigación sanguínea , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/terapia , Estudios Retrospectivos , StentsRESUMEN
The event-related brain potential (ERP) has been investigated extensively inan effort to understand the neurophysiological bases of intelligence. Measures derived from the ERP have been used as indices of intelligence, particularly the string measure of the complexity of the ERP. However, the string measure has been criticised for being non-specific and for being dependent on ERP amplitude. These criticisms were tested by investigating relationships between ERP string measure, ERP amplitude measures, and the ERP power spectrum. It was found that the string measure was non-specific in that it indexes both low and high frequency event-related activity; the string measure is also dependent on ERP amplitude. The string measure is therefore not a valid measure of the ERP. It was concluded that the string measure should be abandoned; human intelligence cannot map in a simple way onto gross measures of scalp-recorded electrocortical activity.
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Potenciales Evocados/fisiología , Inteligencia/fisiología , Adulto , Electroencefalografía , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: A system is presented for sequentially computing the risk of progression of retinopathy of prematurity (ROP) for infants born weighing not more than 1250 gm. A personal computer program is used to monitor infants' risk of threshold ROP from first appearance of ROP, and the progression in severity is tracked with multiple logistic risk models developed from data in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity. METHODS: After entry of the infant's birth weight, gestational age, ethnicity, birth in the current hospital or elsewhere, single or multiple birth, and maturity zone of retinal vessels, risk of progression to threshold severity is calculated. New estimates of risk are computed at onset of ROP and prethreshold ROP (any zone I ROP, zone II stage 2+ or 3) according to the extent of retinal vascularization when ROP first appears, how rapidly ROP progresses, and how severe it is. When threshold ROP (8 total or 5 contiguous clock hours of stage 3+ in zone I or II) is reached,the system provides separate estimates of risk that the eye will have an unfavorable 3-month outcome if treated or not. RESULTS: Estimates of risk of progression to threshold disease among the 4099 patients in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history study varied from less than 1% to more than 70%. For eyes with threshold disease, the risk of an unfavorable outcome at 3 months without treatment varied from less than 10% to more than 90%. CONCLUSION: This method of tracking identifies infants at high risk for severe ROP and poor structural outcome. It provides information about prognosis with a specificity heretofore impossible.