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1.
Transfusion ; 63 Suppl 3: S67-S76, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36971031

RESUMEN

BACKGROUND: Data demonstrate the benefit of blood product administration near point-of-injury (POI). Fresh whole blood transfusion from a pre-screened donor provides a source of blood at the POI when resources are constrained. We captured transfusion skills data for medics performing autologous blood transfusion training. METHODS: We conducted a prospective, observational study of medics with varying levels of experience. Inexperienced medics were those with minimal or no reported experience learning the autologous transfusion procedures, versus reported experience among special operations medics. When available, medics were debriefed after the procedure for qualitative feedback. We followed them for up to 7 days for adverse events. RESULTS: The median number of attempts for inexperienced and experienced medics was 1 versus 1 (interquartile range 1-1 for both, p = .260). The inexperienced medics had a slower median time to needle venipuncture access for the donation of 7.3 versus 1.5 min, needle removal after clamping time of 0.3 versus 0.2 min, time to bag preparation of 1.9 versus 1.0 min, time to IV access for reinfusion of 6.0 versus 3.0 min, time to transfusion completion of 17.3 versus 11.0 min, and time to IV removal of 0.9 versus 0.3 min (all p < .05). We noted one administrative safety event in which an allogeneic transfusion occurred. No major adverse events occurred. Qualitative data saturated around the need for quarterly training. CONCLUSIONS: Inexperienced medics have longer procedure times when training autologous whole blood transfusion skills. This data will help establish training measures of performance for skills optimization when learning this procedure.


Asunto(s)
Transfusión de Sangre Autóloga , Personal Militar , Humanos , Estudios Prospectivos , Transfusión Sanguínea , Donantes de Tejidos
2.
Prehosp Emerg Care ; 27(7): 934-940, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36037100

RESUMEN

BACKGROUND: The MARCH (Massive hemorrhage, Airway, Respirations, Circulation, and Hypothermia/Head injuries) algorithm taught to military medics includes interventions to prevent hypothermia. As possible sequelae from major trauma, hypothermia is associated with coagulopathy and lower survival. This paper sought to define hypothermia within our combat trauma population using an outcomes-based method, and determine clinical variables associated with hypothermia. METHODS: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry focused on casualties who received prehospital care. A receiver operating curve was constructed and Youden's index was used to define hypothermia within the predetermined population based on mortality risk. A multivariable regression model was used to identify associations. RESULTS: There were 23,243 encounters that met the inclusion criteria for this study with patients having received prehospital care and documentation of at least one emergency department temperature. An optimal threshold of 36.2° C was found to predict mortality; 3,159 casualties had temperatures below this threshold (14%). Survival to discharge was lower among casualties with hypothermia (91% versus 98%). Hypothermic casualties were less likely to undergo blanket application (38% versus 40%). However, they had higher proportions with Hypothermia Prevention and Management Kit application (11% versus 7%) and radiant warming (2% versus 1%). On multivariable regression modeling, none of the hypothermia interventions were associated with a decreased likelihood of hypothermia. Non-hypothermia interventions associated with hypothermia included prehospital intubation (OR 1.57, 95% CI 1.45-1.69) and blood product administration. CONCLUSIONS: Hypothermia, including a single recorded low temperature in the patient care record, was associated with worse outcomes in this combat trauma population. Prehospital intubation was most strongly associated with developing hypothermia. Prehospital warming interventions were not associated with a reduction in hypothermia risk. Our dataset suggests that current methods for prehospital warming are inadequate.


Asunto(s)
Traumatismos Craneocerebrales , Servicios Médicos de Urgencia , Hipotermia , Heridas y Lesiones , Humanos , Hipotermia/prevención & control , Servicios Médicos de Urgencia/métodos , Servicio de Urgencia en Hospital , Hemorragia , Sistema de Registros , Heridas y Lesiones/terapia
3.
Transfusion ; 61 Suppl 1: S286-S293, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34269456

RESUMEN

BACKGROUND: Hemorrhage is the leading cause of death in trauma patients with most fatalities occurring before reaching a higher level of care-this applies to both the civilian setting and the military combat setting. Hemostatic resuscitation with increased emphasis on blood transfusion while limiting use of crystalloids has become routine in trauma care. However, the prehospital setting-especially in combat-presents unique challenges with regard to storage, transport, and administration. We sought to evaluate available technology on the market for storage and administration technology that is relevant to the prehospital setting. STUDY DESIGN AND METHODS: We conducted a market review of available technology through subject-matter expert inquiry, reviews of published literature, reviews of Federal Drug Administration databases, internal military publications, and searches of Google. RESULTS: We reviewed and described a total of 103 blood transporters, 22 infusers, and 6 warmers. CONCLUSIONS: The risk of on-scene fatality in trauma patients and recent developments in trauma care demonstrate the need for prehospital transfusion. These transfusions have been logistically prohibited in many operations. We have reviewed the current commercially available equipment and recommended pursuit of equipment that improves accessibility to field transfusion. Current technology has limited applicability for the prehospital setting and is further limited for the military setting.


Asunto(s)
Almacenamiento de Sangre , Transfusión Sanguínea , Transportes , Animales , Almacenamiento de Sangre/métodos , Transfusión Sanguínea/instrumentación , Transfusión Sanguínea/métodos , Hospitales , Humanos , Transportes/instrumentación
4.
Br J Dermatol ; 179(3): 582-589, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29774538

RESUMEN

BACKGROUND: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. OBJECTIVES: To provide unified guidelines for the treatment of IH with propranolol. METHODS: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting. RESULTS: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. CONCLUSIONS: These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.


Asunto(s)
Coartación Aórtica/tratamiento farmacológico , Dermatología/normas , Anomalías del Ojo/tratamiento farmacológico , Hemangioma/tratamiento farmacológico , Síndromes Neurocutáneos/tratamiento farmacológico , Pediatría/normas , Propranolol/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Administración Oral , Toma de Decisiones Clínicas , Consenso , Técnica Delphi , Humanos , Lactante , Sociedades Médicas/normas , Resultado del Tratamiento , Reino Unido
5.
Plant Dis ; 97(9): 1207-1211, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30722461

RESUMEN

Storms containing hail are a common occurrence in Wisconsin, with a few or many cranberry (Vaccinium macrocarpon) growers being affected every year. Growers usually apply fungicides immediately following hail events to prevent fruit rot, despite a lack of research to support this practice. We conducted field trials in 2010 and 2011 to address the question of whether applying fungicides to injured fruit reduces fruit rot incidence (% rotten fruit). Hail damage was simulated by forcibly projecting pea gravel into cranberry beds using a mist-blower sprayer modified for this purpose, and the fungicides azoxystrobin or copper hydroxide were applied to fruit immediately after applying gravel. Fruit rot incidence and yield were evaluated within 2 weeks prior to commercial harvest in late September and early October. Fruit rot incidence was greater (P ≤ 0.05) and yield was lower (P < 0.05) in plots treated with gravel than in the nontreated control plots in six of seven trials. Fungicides did not reduce fruit rot incidence (P ≥ 0.05) in gravel-treated plots compared to the nontreated control in six of seven trials. However, in a trial conducted on relatively immature berries, fruit rot incidence in gravel-treated plots treated with azoxystrobin was less (P = 0.0103) than fruit rot incidence in gravel-treated plots receiving no fungicide treatment. In that same trial, fruit rot incidence was not reduced (P = 0.1243) in gravel-treated plots treated with copper hydroxide compared to gravel-treated plots that were not treated with fungicide. Results suggest that under most circumstances, if cranberries are damaged by hail, it is unlikely that an application of fungicide will reduce the amount of fruit rot at the time of harvest.

6.
J Biomed Mater Res A ; 111(6): 863-878, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36951220

RESUMEN

During cataract surgery, diseased lenses in the eye are surgically removed and replaced with polymeric artificial intraocular lenses (IOLs). Patients can experience a complication called posterior capsular opacification (PCO) that is corrected through the removal of part of the posterior capsule using a neodymium: yttrium-aluminum-garnet (Nd-YAG) laser to restore the optical path. These interventions have increased costs and can damage the retina and the IOL. PCO develops when lens epithelial cells (LECs) proliferate, migrate, and undergo epithelial-to-mesenchymal transition. Neutrophils involved in the immune response triggered during implantation impact LEC behavior and produce damaging neutrophil extracellular traps (NETs). In this research, poly(2-hydroxyethyl methacrylate) (PHEMA) -based disks were synthesized with varying amounts of comonomer (HEMA with 0, 2, and 12 mol% MMA) and functionalized with carboxyl and amine groups, yielding nine different hydrogels. Material and chemical properties of the disks were characterized, and neutrophil-like HL60 cells and B3 LECs were incubated with the disks. HL60 cell behavior was more strongly influenced by chemical functionalization than by mechanical properties with increases in adherence and NET accumulation. Conversely, the behavior and viability of B3 LECs were more strongly influenced by mechanical properties with increases in cell adhesion and α-SMA expression with increasing compressive moduli. Interestingly, B3 LECs had decreased viability and increased α-SMA expression when cultured on PHEMA2 disks pretreated with isolated NETs. Critical to the understanding of PCO and its prevention are both surface chemistry and mechanics as well as the inflammatory response.


Asunto(s)
Catarata , Cápsula del Cristalino , Lentes Intraoculares , Humanos , Neutrófilos/metabolismo , Catarata/etiología , Catarata/metabolismo , Catarata/prevención & control , Cápsula del Cristalino/metabolismo , Cápsula del Cristalino/cirugía , Lentes Intraoculares/efectos adversos , Células Epiteliales/metabolismo
7.
Nat Commun ; 14(1): 8371, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38102132

RESUMEN

Quantum networks have the potential to transform secure communication via quantum key distribution and enable novel concepts in distributed quantum computing and sensing. Coherent quantum light generation at telecom wavelengths is fundamental for fibre-based network implementations, but Fourier-limited emission and subnatural linewidth photons have so far only been reported from systems operating in the visible to near-infrared wavelength range. Here, we use InAs/InP quantum dots to demonstrate photons with coherence times much longer than the Fourier limit at telecom wavelength via elastic scattering of excitation laser photons. Further, we show that even the inelastically scattered photons have coherence times within the error bars of the Fourier limit. Finally, we make direct use of the minimal attenuation in fibre for these photons by measuring two-photon interference after 25 km of fibre, demonstrating finite interference visibility for photons emitted about 100,000 excitation cycles apart.

8.
Mil Med ; 188(11-12): e3382-e3385, 2023 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-36583415

RESUMEN

INTRODUCTION: Uncontrolled hemorrhage remains the leading cause of preventable death in the prehospital, combat setting. Treatment guidelines emphasize immediate hemorrhage control and early resuscitation with whole blood or blood products. Current methods for the delivery of blood products are often insufficient to provide trauma resuscitation. The novel LifeFlow device is a hand-powered device that can rapidly infuse fluids, including blood products. However, successful use of this device in the hands of the intended end user has not been demonstrated. MATERIALS AND METHODS: We conducted a pilot study to assess how quickly and effectively medics could set up the LifeFlow device and infuse mock blood products into a casualty. They were provided with a brief block of instruction (<10 min) and the opportunity to handle the device. The time to set up the device and proportion of successful completion were recorded. Participants were surveyed regarding the use of the device including post-study interview. RESULTS: Forty medics, who were recruited and eligible to participate, completed the study procedures. All medics were able to successfully set up the device and perform the infusion. We had two instances of fluid leakage owing to malfunctions with the simulation arm, not the LifeFlow device. The mean time to device setup was 112 s (95% confidence interval [CI], 101-124). The mean time for infusion of 500 mL of fluid was 94 s (95% CI, 83-105). The mean time for all procedures was 197 s (95% CI, 178-213). On product feedback, they generally found it easier to use, easy to manipulate, possessing a useful grip, easily set up, and requiring minimal training. CONCLUSIONS: The medics were able to reliably assemble and use the LifeFlow rapid infusion device. However, there were concerns about the packaging and the single indication for the device.


Asunto(s)
Hemorragia , Resucitación , Humanos , Proyectos Piloto , Resucitación/métodos , Hemorragia/terapia
9.
J Spec Oper Med ; 22(3): 57-61, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-35877978

RESUMEN

BACKGROUND: Military helicopter mishaps frequently lead to multiple casualty events with complex injury patterns. Data specific to this mechanism of injury in the deployed setting are limited. We describe injury patterns associated with helicopter crashes. MATERIALS AND METHODS: This is a secondary analysis of a Department of Defense Trauma Registry (DODTR) dataset from 2007 to 2020 seeking to describe prehospital care within all theaters in the registry. We searched within the dataset for casualties injured by helicopter crash. A serious injury was defined by an abbreviated injury scale of =3 by body region. RESULTS: We identified 120 casualties injured by helicopter crash within the dataset. Most were Army (64%), the median age was 30 (interquartile range [IQR] 26-35), and most were male (98%), enlisted service members made up the largest cohort (47%), with most injuries occurring during Operation Enduring Freedom (69%). Only 2 were classified as battle injuries. The median injury severity score was 9 (IQR 4-22). Serious injuries by body region are the following: thorax (27%), head/neck (17%), extremities (17%), abdomen (11%), facial (3%), and skin/superficial (1%). The most common prehospital interventions focused on hypothermia prevention/management (62%) and cervical spine stabilization (32%). Most patients survived to hospital discharge (98%). CONCLUSIONS: Serious injuries to the thorax were most common. Survival was high, although better data capture systems are needed to study deaths that occur prehospital that do not reach military treatment facilities with surgical care to optimize planning and outcomes. The high proportion of nonbattle injuries highlights the risks associated with helicopters in general.


Asunto(s)
Personal Militar , Heridas y Lesiones , Accidentes de Tránsito , Adulto , Campaña Afgana 2001- , Aeronaves , Femenino , Humanos , Guerra de Irak 2003-2011 , Masculino , Sistema de Registros , Estudios Retrospectivos , Heridas y Lesiones/epidemiología , Heridas y Lesiones/terapia
10.
J Spec Oper Med ; 21(4): 26-29, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34969123

RESUMEN

BACKGROUND: Video laryngoscopy (VL) is shown to improve first-pass success rates and decrease complications in intubations, especially in novice proceduralists. However, the currently fielded VL devices are cost-prohibitive for dispersion across the battlespace. The novel i-view VL is a low-cost, disposable VL device that may serve as a potential solution. We sought to perform end-user performance testing and solicit feedback. METHODS: We prospectively enrolled Special Operations flight medics with the 160th Special Operations Aviation Regiment at Hunter Army Airfield, Savannah, Georgia. We asked them to perform an intubation using a synthetic cadaver model while in a mobile helicopter simulation setting. We surveyed their feedback afterward. RESULTS: The median age of participants was 30 and all were male. Of those, 60% reported previous combat deployments, with a median of 20 months of deployment time. Of the 10, 90% were successful with intubation, with 60% on first-pass success with an average of 83 seconds time to intubation. Most had a grade 1 view. Most agreed or strongly agreed that it was easy to use (70%), with half (50%) reporting they would use it in the deployed setting. Several made comments about the screen not being bright enough and would prefer one with a rotating display. CONCLUSIONS: We found a high proportion of success for intubation in the mobile simulator and a high satisfaction rate for this device by Special Operations Forces medics.


Asunto(s)
Laringoscopios , Aeronaves , Estudios de Factibilidad , Humanos , Intubación Intratraqueal , Laringoscopía , Masculino , Estudios Prospectivos
11.
Med J (Ft Sam Houst Tex) ; (PB 8-21-07/08/09): 90-96, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34449867

RESUMEN

INTRODUCTION: Airway obstruction is the second leading cause of potentially preventable death on the battlefield during the recent conflicts. Previous studies have noted challenges with enrolling medics using quantitative methods, with specific challenges related to limited prior experience with the devices presented. This limited the ability to truly assess the efficacy of a particular device. We sought to implement a qualitative methods design for supraglottic airway (SGA) device testing. METHODS: We performed prospective, qualitative-designed studies in serial to discover emerging themes on interview. We obtained consent and demographic information from all participants. Medics were presented 2-3 airway devices in the same session with formal training by a physician with airway expertise to include practice application and troubleshooting. Semi-structured interviews were used after the training to obtain end-user feedback with a focus on emerging themes. RESULTS: Of the 77 medics surveyed and interviewed, the median age was 24, and 86% were male. During the interview sessions, we noted five emerging themes: (1) insertion, which pertains to the ease or complexity of using the devise; (2) material, which pertains to the tactile features of the device; (3) versatility, which pertains to the conditions in which the device can be used as well as with which other devices it can be used; (4) portability, which refers to how and where the device is stored and carried; and (5) training, which refers to the ease and frequency of initial and ongoing training to sustain medics' technical capability when using the device. CONCLUSIONS: In our preliminary analysis after enrolling 77 medics, we noted 5 emerging themes focused on insertion material, versatility, portability, and training methodology. Our results will inform the future enrollment sessions with a goal of narrowing the market options from themes to ideal device or devices or modifications needed for the operational environment.


Asunto(s)
Obstrucción de las Vías Aéreas , Personal Militar , Adulto , Obstrucción de las Vías Aéreas/terapia , Diseño de Equipo , Humanos , Masculino , Estudios Prospectivos , Adulto Joven
12.
Biochem Pharmacol ; 173: 113754, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31837311

RESUMEN

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p < 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p > 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5-15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.


Asunto(s)
Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Pinus/química , Corteza de la Planta/química , Extractos Vegetales/farmacología , Polifenoles/farmacología , Adolescente , Adulto , Catequina/análisis , Catequina/sangre , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Voluntarios Sanos , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Nitratos/sangre , Óxido Nítrico/metabolismo , Nitritos/sangre , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Polifenoles/administración & dosificación , Polifenoles/aislamiento & purificación , Adulto Joven
13.
Science ; 291(5512): 2376-8, 2001 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-11269319

RESUMEN

The dynamic glycosylation of serine or threonine residues on nuclear and cytosolic proteins by O-linked beta-N-acetylglucosamine (O-GlcNAc) is abundant in all multicellular eukaryotes. On several proteins, O-GlcNAc and O-phosphate alternatively occupy the same or adjacent sites, leading to the hypothesis that one function of this saccharide is to transiently block phosphorylation. The diversity of proteins modified by O-GlcNAc implies its importance in many basic cellular and disease processes. Here we systematically examine the current data implicating O-GlcNAc as a regulatory modification important to signal transduction cascades.


Asunto(s)
Acetilglucosamina/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Proteínas/metabolismo , Transducción de Señal , Animales , Glucosa/metabolismo , Glicoproteínas/metabolismo , Glicosilación , Humanos , N-Acetilglucosaminiltransferasas/metabolismo , Proteínas Nucleares/metabolismo , Fosforilación
14.
Mil Med ; 184(11-12): e622-e625, 2019 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-31004142

RESUMEN

INTRODUCTION: The Accreditation Council for Graduate Medical Education stipulates that residents should participate in scholarly activity. As of 2019 that verbiage will be changed to, "Residents must participate in scholarship." However, scholarly activity is not clearly defined. We set out to define our graduation research requirement in a measurable way and structure a research curriculum that better prepared residents to conduct scholarly activity. MATERIALS AND METHODS: This study compares resident scholarly output in several categories before and after the initiation of a revised research curriculum and graduation requirement. Scholarly activity was measured by comparing the production of Pubmed Indexed (PMID) publications, online publications, and conference presentations of two Emergency Medicine Residency classes. The intervention class was represented by the class of 2018 which exposed 16 residents to the new curriculum and graduation requirement for the full three years of their residency. The comparison class was represented by the class of 2015 which exposed 16 residents to the old curriculum and old graduation requirement. The old graduation requirement and curriculum were undefined. The new requirement involved two options, participate in original research starting from the process of question formulation and carried through manuscript drafting or publishing at first author PMID of any kind. The new curriculum involved monthly journal clubs, two annual deep dives, and an 8-day Intern Research Course modeled after the Emergency Medicine Basic Research Skills workshop sponsored by the American College of Emergency Physicians. In addition to the new curriculum, several new leadership positions were created at both the staff and resident level that solely focused on the promotion of scholarly activity. In addition to creating a culture within the department that encouraged scholarship, these overlapping leadership positions also helped create continuity in a program that could easily be hampered by frequent staff turnover due to new military assignments and military deployments. RESULTS: Resident scholarly activity in the form of PMIDs increased from 4 to 22. The production of online publications was 0 and 12, respectively. There were 2 and 11 conference presentations, respectively. CONCLUSION: Resident scholarly activity increased following the institution of a new research curriculum and graduation requirement.


Asunto(s)
Medicina de Emergencia/tendencias , Internado y Residencia/tendencias , Personal Militar/estadística & datos numéricos , Investigación/educación , Educación de Postgrado en Medicina/métodos , Educación de Postgrado en Medicina/tendencias , Medicina de Emergencia/educación , Medicina de Emergencia/métodos , Humanos , Internado y Residencia/métodos , Personal Militar/psicología , Estados Unidos
15.
J Clin Invest ; 93(5): 2230-5, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8182155

RESUMEN

Prostacyclin (PGI2) is a key mediator of pulmonary vasomotor tone during late gestation and in the newborn, and its production in whole lung increases during that period. We investigated the developmental regulation of PGI2 synthesis in ovine intrapulmonary artery (PA) segments from 110 to 115 d (F1) and 125 to 135 d gestation fetal lambs (F2, term = 144 d) and 1- and 4-wk-old newborn lambs (NB1 and NB2). Basal PGI2 rose fourfold from F1 to F2, fourfold from F2 to NB1, and twofold from NB1 to NB2. In all age groups 66-72% of PGI2 was derived from the endothelium. Similar fold increases in PGI2 were observed with maturation in intact and endothelium-denuded segments. In intact PA from F2, NB1, and NB2, basal PGI2 synthesis and synthesis maximally stimulated by bradykinin, A23187, or arachidonic acid rose with development in a comparable manner. In contrast, PGI2 synthesis stimulated by exogenous PGH2, the product of cyclooxygenase, was similar at all ages. Immunoblot analyses of PA from F2, NB1, and NB2 revealed that there is a sixfold maturational increase in cyclooxygenase-1 protein; the cyclooxygenase-2 isoform was not detectable. Cyclooxygenase-1 mRNA abundance in whole lung also rose with development. Thus, PGI2 synthesis in ovine PA endothelium and vascular smooth muscle increases markedly during late fetal and early newborn life; the increase is due to a rise in cyclooxygenase activity related to enhanced expression of cyclooxygenase-1. We conclude that there is developmental regulation of PA cyclooxygenase-1 gene expression, and that this may be critical to successful cardiopulmonary transition and function in the newborn.


Asunto(s)
Epoprostenol/biosíntesis , Regulación Enzimológica de la Expresión Génica , Pulmón/enzimología , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Arteria Pulmonar/enzimología , Envejecimiento/metabolismo , Animales , Animales Recién Nacidos , Ácido Araquidónico/farmacología , Bradiquinina/farmacología , Calcimicina/farmacología , Embrión de Mamíferos/metabolismo , Endotelio Vascular/metabolismo , Técnicas In Vitro , Pulmón/irrigación sanguínea , Pulmón/crecimiento & desarrollo , Arterias Mesentéricas/enzimología , Músculo Liso Vascular/metabolismo , Prostaglandinas/biosíntesis , Arteria Pulmonar/crecimiento & desarrollo , Ovinos
16.
J Clin Invest ; 88(6): 2077-82, 1991 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1752965

RESUMEN

In patients with congestive heart failure (CHF), the poor relationship between systemic exercise performance and cardiac function, together with morphologic and metabolic abnormalities in skeletal muscle, raises the possibility that skeletal muscle function may be impaired and limit systemic exercise performance. We assessed strength and endurance of the knee extensors during static and dynamic exercise in 16 patients with Class I-IV CHF and eight age-matched sedentary controls and related these measurements to systemic exercise performance. To assess skeletal muscle function independent of peripheral blood flow, endurance was repeated under ischemic conditions. Strength was not significantly different in the two groups. Dynamic endurance, quantified as the decline in peak torque during 15 successive isokinetic knee extensions, was significantly reduced in the patients compared to controls during aerobic (peak torque 65 vs. 86% of initial for exercise at 90 deg/s and 60 vs. 85% for exercise at 180 deg/s; P less than 0.002 for both), and during ischemic exercise (56 vs. 76% of initial torque; P less than 0.01). Static endurance, defined as the time required for force during a sustained maximal voluntary contraction to decline to 60% of maximal, was reduced in the patients compared to controls (40 +/- 14 vs. 77 +/- 29 s; P less than 0.02). There were highly significant relationships between systemic exercise performance and skeletal muscle endurance at 90 and 180 deg/s in the patients with CHF (r = 0.90 and 0.66, respectively). These findings indicate that skeletal muscle endurance is impaired in patients with CHF, that this abnormality is in part independent of limb blood flow, and that these changes may be important determinants of systemic exercise performance.


Asunto(s)
Ejercicio Físico , Insuficiencia Cardíaca/fisiopatología , Músculos/fisiopatología , Adulto , Anciano , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Músculos/irrigación sanguínea , Consumo de Oxígeno
17.
J Clin Invest ; 94(6): 2231-6, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7527428

RESUMEN

Nitric oxide (NO) is an important mediator of physiologic and inflammatory processes in the lung. To better understand the role of NO in the airway, we examined constitutive NO synthase (NOS) gene expression and function in NCI-H441 human bronchiolar epithelial cells, which are believed to be of Clara cell lineage. NOS activity was detected by [3H]arginine to [3H]citrulline conversion (1,070 +/- 260 fmol/mg protein per minute); enzyme activity was inhibited 91% by EGTA, consistent with the expression of a calcium-dependent NOS isoform. Immunoblot analyses with antisera directed against neuronal, inducible, or endothelial NOS revealed expression solely of endothelial NOS protein. Immunocytochemistry for endothelial NOS revealed staining predominantly in the cell periphery, consistent with the association of this isoform with the cellular membrane. To definitively identify the NOS isoform expressed in H441 cells, NOS cDNA was obtained by degenerate PCR. Sequencing of the H441 NOS cDNA revealed 100% identity with human endothelial NOS at the amino acid level. Furthermore, the H441 NOS cDNA hybridized to a single 4.7-kb mRNA species in poly(A)+ RNA isolated from H441 cells, from rat, sheep, and pig lung, and from ovine endothelial cells, coinciding with the predicted size of 4.7 kb for endothelial NOS mRNA. Guanylyl cyclase activity in H441 cells, assessed by measuring cGMP accumulation, rose 6.6- and 5.4-fold with calcium-mediated activation of NOS by thapsigargin and A23187, respectively. These findings indicate that endothelial NOS is expressed in select bronchiolar epithelial cells, where it may have autocrine effects through activation of guanylyl cyclase. Based on these observations and the previous identification of endothelial NOS in a kidney epithelial cell line, it is postulated that endothelial NOS may be expressed in unique subsets of epithelial cells in a variety of organs, serving to modulate ion flux and/or secretory function.


Asunto(s)
Aminoácido Oxidorreductasas/biosíntesis , Bronquios/enzimología , Isoenzimas/biosíntesis , Aminoácido Oxidorreductasas/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bronquios/patología , Clonación Molecular , Endotelio Vascular/enzimología , Epitelio/enzimología , Epitelio/patología , Guanilato Ciclasa/análisis , Humanos , Immunoblotting , Inmunohistoquímica , Isoenzimas/genética , Datos de Secuencia Molecular , Óxido Nítrico Sintasa , Reacción en Cadena de la Polimerasa , Ratas , Ovinos , Especificidad de la Especie , Células Tumorales Cultivadas
18.
Eur J Pharm Biopharm ; 65(3): 329-35, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17156984

RESUMEN

Alginate has potential as a matrix for controlled delivery of protein-based drugs that require site-specific long-term delivery. In the current work albumin, lysozyme and chymotrypsin were encapsulated into alginate microspheres using a novel method that involved soaking the microspheres in a protein-containing NaCl solution. This was followed by recrosslinking with calcium chloride. High pI proteins also appeared to physically crosslink the sodium alginate which resulted in more sustained release. Release was affected by the nature of the releasate solution. In TRIS buffered saline, the high pI proteins chymotrypsin and lysozyme showed sustained release lasting over 150 h. Release into 0.15% NaCl led to relatively constant release of lysozyme and chymotrypsin over more than 2000 h; reduction of the releasate volume lengthened the lysozyme release to greater than 8 months. Released lysozyme was shown to remain active for at least 16 days, in some cases with activity greater than 100% of the active control. This encapsulation technique can therefore be used to rapidly load alginate microspheres with proteins, with high isoelectric point proteins showing particular promise. Furthermore, the interactions between the high pI proteins and the alginate gel could potentially be exploited to generate new protein delivery systems.


Asunto(s)
Alginatos/química , Portadores de Fármacos , Enzimas/química , Microesferas , Tecnología Farmacéutica/métodos , Tampones (Química) , Cloruro de Calcio/química , Química Farmacéutica , Quimotripsina/química , Reactivos de Enlaces Cruzados/química , Preparaciones de Acción Retardada , Composición de Medicamentos/métodos , Estabilidad de Enzimas , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Punto Isoeléctrico , Muramidasa/química , Albúmina Sérica Bovina/química , Cloruro de Sodio/química , Solubilidad , Factores de Tiempo
19.
West J Emerg Med ; 18(6): 1061-1067, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29085538

RESUMEN

INTRODUCTION: Our goal was to determine if heated gel for emergency department (ED) bedside ultrasonography improves patient satisfaction compared to room-temperature gel. METHODS: We randomized a convenience sample of ED patients determined by their treating physician to require a bedside ultrasound (US) study to either heated gel (102.0° F) or room-temperature gel (82.3° F). Investigators performed all US examinations. We informed all subjects that the study entailed investigation into various measures to improve patient satisfaction with ED US examinations but did not inform them of our specific focus on gel temperature. Investigators wore heat-resistant gloves while performing the examinations to blind themselves to the gel temperature. After completion of the US, subjects completed a survey including the primary outcome measure of patient satisfaction as measured on a 100-mm visual analogue scale (VAS). A secondary outcome was patient perceptions of sonographer professionalism measured by an ordinal scale (1-5). RESULTS: We enrolled 124 subjects; 120 completed all outcome measures. Of these, 59 underwent randomization to US studies with room-temperature gel and 61 underwent randomization to heated US gel. Patient 100-mm VAS satisfaction scores were 83.9 among patients undergoing studies with room-temperature gel versus 87.6 among subjects undergoing studies with heated gel (effect size 3.7, 95% confidence interval -1.3-8.6). There were similarly no differences between the two arms with regard to patient perceptions of sonographer professionalism. CONCLUSION: The use of heated ultrasound gel appears to have no material impact on the satisfaction of ED patients undergoing bedside ultrasound studies.


Asunto(s)
Geles/administración & dosificación , Satisfacción del Paciente , Ultrasonografía/métodos , Administración Tópica , Adulto , Servicio de Urgencia en Hospital , Femenino , Calor , Humanos , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Encuestas y Cuestionarios
20.
Clin Oncol (R Coll Radiol) ; 28(9): e121-5, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27184941

RESUMEN

The major role of the Oncology Registrars' Forum (ORF) of the Royal College of Radiologists is to voice the opinions of the clinical oncology trainee body and work towards improving all aspects of clinical oncology training in the UK. In order to provide data to support these efforts, the ORF undertakes a biennial survey of all trainees. As with the previous surveys, this year's ORF survey produced data that highlight areas of good training as well as new and ongoing areas of concern. This summary highlights the key survey results and provides recommendations for improving the delivery of clinical oncology training in the UK.


Asunto(s)
Oncología Médica/educación , Actitud del Personal de Salud , Personal de Salud , Humanos , Encuestas y Cuestionarios , Reino Unido
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