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1.
J R Army Med Corps ; 164(1): 19-24, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28835512

RESUMEN

AIM: To describe the mechanisms, burden of injury, inpatient management and rehabilitation requirements of wounded military personnel at the UK Role 4 (R4) facility within the first 12 months following cessation of combat operations in Afghanistan. METHODS: All aeromedical evacuations were recorded prospectively between October 2014 and October 2015. Demographic, logistical and clinical data were derived manually from referring medical unit and patient movement requests in addition to host nation and R4 medical records. RESULTS: Ninety-five patients were repatriated to R4 following traumatic injury: 98.9% (n=94) were male, and median age was 27 years (IQR 25-36 years). The most common mechanisms of injury (MOIs) were sports 26.3% (n=25), falls <2 m 11.6% (n=11) and road traffic collisions 9.8% (n=9). The most common anatomical regions of injury were isolated lower limb 24.1% (n=22), isolated hand 20.0% (n=19) and polytrauma 14.7% (n=14). Median Injury Severity Score was 4 (IQR 4-9), mean 8 (range 1-41). Eleven patients (11.6%) were discharged to rehabilitation units, of whom 7 (63.6%) required neurorehabilitation. CONCLUSION: Although service personnel sustain civilian-type injuries, the specific rehabilitation goals and shift in the acute rehabilitation requirements for military personnel must be considered in the absence of enduring combat operations. It is notable that permanent medical downgrading secondary to trauma still occurs outside of warfare. The colocation of civilian major trauma services and R4 has ensured a mutually beneficial partnership that contributes to institutional memory and improves the coordination of patient pathways. The importance of relevant resource allocation, training, support and logistical considerations remain, even during the current scale of military activity overseas.


Asunto(s)
Personal Militar/estadística & datos numéricos , Heridas y Lesiones/epidemiología , Accidentes por Caídas/estadística & datos numéricos , Accidentes de Tránsito/estadística & datos numéricos , Adulto , Traumatismos en Atletas/epidemiología , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación/estadística & datos numéricos , Masculino , Estudios Prospectivos , Reino Unido/epidemiología , Heridas y Lesiones/rehabilitación , Heridas y Lesiones/cirugía
2.
Injury ; 48(3): 738-744, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28187907

RESUMEN

Injuries to the hand during military combat operations, particularly from improvised explosive devices (IEDs) have a significant impact on form, function, mental health and future employment but remain underreported amidst the life and limb-threatening emergencies that garner more attention. An understanding the patterns of hand injuries encountered from IEDs is crucial to optimizing reconstruction and rehabilitation. The aim of this study was to re-evaluate hand injury sustained from IED in order to understand the clinical burden for reconstruction and direct the focus for future hand protection. We identified 484 hand injuries in 380 patients sustained as a result of IEDs among military personnel service in Afghanistan between 2006 and 2013. 53% of all surviving military personnel injured by IEDs sustain injuries to the hand. Analysis of the 103 patients who sustained injury to the metacarpal, phalanges or digital amputation revealed that the middle and ring fingers are most commonly injured. Amputation to the ring finger is strongly associated with injury to the adjacent fingers and amputations to the middle, ring and little fingers concurrently is a commonly observed pattern. The proximal phalanges of the middle and ring fingers had a strong correlation for fracture together. These findings disprove the conventional belief in an ulnar focus of injury and support the quest for a development of combat hand protection that addresses the injury pattern seen.


Asunto(s)
Amputación Traumática/cirugía , Traumatismos por Explosión/cirugía , Fracturas Óseas/cirugía , Traumatismos de la Mano/cirugía , Personal Militar , Procedimientos de Cirugía Plástica/métodos , Campaña Afgana 2001- , Amputación Traumática/epidemiología , Amputación Traumática/psicología , Traumatismos por Explosión/epidemiología , Traumatismos por Explosión/fisiopatología , Traumatismos por Explosión/psicología , Sustancias Explosivas , Falanges de los Dedos de la Mano/lesiones , Fracturas Óseas/epidemiología , Fracturas Óseas/fisiopatología , Fracturas Óseas/psicología , Traumatismos de la Mano/epidemiología , Traumatismos de la Mano/fisiopatología , Traumatismos de la Mano/psicología , Humanos , Puntaje de Gravedad del Traumatismo , Acontecimientos que Cambian la Vida , Huesos del Metacarpo/lesiones , Medicina Militar , Reino Unido/epidemiología
3.
J R Army Med Corps ; 157(2): 170-5, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21805768

RESUMEN

A joint meeting of the Limb Trauma and Wounds Working Groups resulted in the establishment of 29 consensus recommendations for the conduct of initial extremity war wound debridement. Pre-operative, operative and post-operative phases of debridement were considered along with wound irrigation and dressings. Wounds where a different surgical approach is required, such as superficial soft tissue wounds at one end of the spectrum and complex wounds sustained in close proximity to explosions at the other, were also discussed. The recommendations represent the consensus opinion of orthopaedic, vascular and plastic surgeons, as well as nursing officers, from across the Defence Medical Services and are intended to provide useful guidance to the deploying surgeon, regardless of their own personal experience.


Asunto(s)
Desbridamiento/normas , Medicina Militar/normas , Heridas y Lesiones/cirugía , Tejido Adiposo/lesiones , Tejido Adiposo/cirugía , Vendajes , Vasos Sanguíneos/lesiones , Huesos/lesiones , Huesos/cirugía , Procedimientos Quirúrgicos Dermatologicos , Fascia/lesiones , Fasciotomía , Humanos , Enfermedad Iatrogénica/prevención & control , Ligadura , Músculo Esquelético/lesiones , Músculo Esquelético/cirugía , Traumatismos de los Nervios Periféricos , Nervios Periféricos/cirugía , Cuidados Posoperatorios/normas , Cuidados Preoperatorios/normas , Piel/lesiones , Traumatismos de los Tendones/cirugía , Irrigación Terapéutica , Guerra
4.
J Obstet Gynaecol ; 31(5): 417-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21627426

RESUMEN

Polycystic ovary syndrome (PCOS) is associated with endothelial dysfunction, which may be caused by elevated levels of asymmetric dimethylarginine (ADMA). ADMA reduces nitric oxide production in diabetes mellitus, hypertension and renal failure. Symmetric dimethylarginine (SDMA) is a stereoisomer produced alongside ADMA, and has recently been described as a risk factor for cardiovascular events. In this cross-sectional study based in a teaching hospital, 16 women with PCOS were recruited alongside 15 healthy controls, and fasting venous blood samples were obtained. Renal function was measured, and ADMA and SDMA were analysed using a high-performance liquid chromatography method. After controlling for BMI, mean ADMA and SDMA levels in women with PCOS were higher than in controls (p = 0.036 and p = 0.030, respectively). Renal function was not different between the two groups (p = 0.152). Women with PCOS have raised levels of SDMA, a molecule implicated in endothelial dysfunction and long-term cardiovascular risk.


Asunto(s)
Arginina/análogos & derivados , Síndrome del Ovario Poliquístico/sangre , Adulto , Andrógenos/sangre , Antropometría , Arginina/sangre , Estudios de Casos y Controles , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Insulina/sangre , Riñón/fisiopatología , Proyectos Piloto , Síndrome del Ovario Poliquístico/fisiopatología , Adulto Joven
5.
Injury ; 42(5): 436-40, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-20362982

RESUMEN

BACKGROUND: Topical negative pressure (TNP) has been used as a method of wound management for some years. Use of TNP is accepted best practice at Role 4. There are advocates of using TNP after initial wound surgery at Role 3 or 2E. The evidence to support forward use of TNP is not comprehensive, especially when considering this narrow cohort of patients and injury pattern. It is the aim of this review to evaluate the current evidence for the use of TNP in all wounds, and to find what evidence there is that may be applicable to military wounds. METHODS: A literature search of Cinahl, Embase, Medline, ProQuest and the Cochrane Library was conducted; references were cross-referenced. All Randomised Controlled Trials (RCTs) were included in all languages over a comprehensive time period. An interim review was conducted by the Wound Management Working Group of the Academic Department of Military Surgery and Trauma. A further literature review was conducted to find all papers relating to the use of TNP on military wounds. RESULTS: 17 reports were reviewed relating to 14 studies including 662 patients. Of these 131 were reported to have had traumatic injuries. Significant results were reported with respect to time to wound healing, patient comfort and reduction in wound volumes. Bacterial load was not affected, in the 3 trials which commented on this, but in 1 there was a significant reduction in wound infections in the TNP group. Several of the trials were small, methodology was not consistent therefore no meta-analysis was possible. 2 papers were found describing case series of military patients being treated with TNP. CONCLUSIONS: There is very little published evidence in the form of RCTs to support the use of TNP in the acute traumatic military setting. This review supports the requirement for further investigation to evaluate whether this method of wound management has a place forward of Role 4.


Asunto(s)
Medicina Militar/métodos , Terapia de Presión Negativa para Heridas/métodos , Heridas y Lesiones/terapia , Práctica Clínica Basada en la Evidencia , Humanos , Guías de Práctica Clínica como Asunto , Cicatrización de Heridas , Heridas y Lesiones/clasificación
6.
J Obstet Gynaecol ; 30(5): 444-6, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20604643

RESUMEN

The aetiology of polycystic ovary syndrome (PCOS) is poorly understood, but an intrauterine hyperandrogenic environment has been implicated. This study was designed to assess whether the female offspring of mothers with PCOS are exposed to raised levels of testosterone (T) in utero. In this case-control study, three groups of pregnant women were recruited from the labour ward: PCOS women with a female baby (n = 10, PCOS girls); control women with a female baby (n = 20, control girls) and control women with a male baby (n = 10, control boys). Maternal and umbilical vein (UV) blood was assayed for T levels. UV T in PCOS girls was significantly raised, compared with control girls (p < 0.012). The difference in UV T between PCOS girls and control boys was not significant (p < 0.254). This is the first demonstration of a hyperandrogenic in utero environment in PCOS pregnancies; UV T in female infants is raised to male levels.


Asunto(s)
Hiperandrogenismo/sangre , Hiperandrogenismo/complicaciones , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/etiología , Efectos Tardíos de la Exposición Prenatal , Testosterona/sangre , Adulto , Andrógenos/sangre , Estudios de Casos y Controles , Femenino , Sangre Fetal , Humanos , Masculino , Embarazo , Venas Umbilicales
9.
Burns ; 32(3): 372-4, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16527419

RESUMEN

Approximately 6400 children per year are admitted to UK hospitals for treatment of burns [National Burn Care Review Committee Report (NBCRC). Standards and Strategy for Burn Care: a review of burn care in the British Isles. 2001.]. This paper investigates the financial costs involved in the management of uncomplicated, minor paediatric scalds. Three cases (2-4% TBSA scalds) were studied to quantify consumables used, services required during management and costs obtained from appropriate Purchasing Departments and Directorate Accountants. Management in all cases involved a general anaesthetic for cleaning of wounds, application of BioBrane (Bertek Pharmaceuticals) and dressings, observation on Children's Ward and discharge following wound review at 48 h. The calculated mean average cost per case was pound1850. In the period 01/12/2002-30/11/2003, 144 children were admitted to Frenchay hospital, Bristol, for treatment of a minor burn or scald (less than 10%TBSA). This caseload is therefore estimated to currently cost pound266,400 per year. These findings may facilitate improved planning for future resource allocation and could also contribute evidence towards the cost effectiveness of prevention strategies.


Asunto(s)
Bebidas , Quemaduras/economía , Quemaduras/terapia , Preescolar , Materiales Biocompatibles Revestidos/economía , Materiales Biocompatibles Revestidos/uso terapéutico , Análisis Costo-Beneficio , Desbridamiento/economía , Desbridamiento/métodos , Hospitalización/economía , Humanos , Lactante , Tiempo de Internación/economía , Masculino , Reino Unido
11.
Travel Med Infect Dis ; 3(4): 239-48, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17292042

RESUMEN

For the practitioner working in the wilderness environment, burns represent a significant challenge. There may be a requirement for non-specialists to provide care with fewer resources than would be available in a specialist unit in the UK. In the wilderness setting, delay prior to reaching specialist care is likely to be an ever present factor. Secondary complications of the burn wound, such as respiratory problems or sepsis may therefore supervene. The paper examines certain aspects of treatment relevant to the wilderness environment, including airway injury, fluid resuscitation and local treatment of the burn wound. Escharotomy and aspects of electrical and chemical injury are also considered.

12.
Surgeon ; 1(2): 96-8, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15573628

RESUMEN

BACKGROUND: Correction of prominent ears (otoplasty) is routinely done as an elective cosmetic procedure. The operation is typically performed under general anaesthesia, which is favoured in the paediatric population, being considered more 'humane' than local anaesthesia. AIM: Our aims were to demonstrate the feasibility of paediatric otoplasty as a day case procedure and to examine the relative efficacy of general versus local anaesthesia, paying particular attention to post-operative morbidity. METHODS: Data were gathered retrospectively from case notes, day case surgery pro-formas and dressing clinic notes to compare post-operative morbidity in the two groups. Specific parameters assessed included vomiting, post-operative bleeding, wound dehiscence, necessity of overnight stay and need for revision surgery. RESULTS: Eighty-five children, underwent a day case otoplasty procedure (age range 4-17 years; mean 7.3). Forty-four received a general anaesthetic, whilst forty-one received percutaneous infiltration of local anaesthetic. Local anaesthetic was well tolerated by the children. No procedure was abandoned due to pain. No disadvantage was demonstrable in either group by performing the operation as a day case procedure. Post-operative vomiting was shown to be a significantly greater problem in the children receiving general anaesthesia (p<0.0001). CONCLUSION: Otoplasty as a day case procedure appears acceptable whether general or local anaesthesia is used. In addition, percutaneous infiltration of local anaesthetic, results in a marked reduction in post-operative vomiting without compromising surgical outcome.


Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Anestesia General , Anestesia Local , Oído/cirugía , Procedimientos de Cirugía Plástica/métodos , Adolescente , Niño , Preescolar , Humanos , Complicaciones Posoperatorias , Procedimientos de Cirugía Plástica/efectos adversos , Estudios Retrospectivos
13.
J R Army Med Corps ; 147(2): 198-205, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11464415

RESUMEN

The initial management of burns, in common with all trauma, follows the ABCDE approach. The outline management plan detailed above assumes the availability of certain medical supplies but even simple measures are invaluable in burn care if they are all that are available. The most basic supplies required to resuscitate a casualty are oral salt and water in appropriate volumes. Similarly it should be possible in field conditions to monitor vital signs and urine output, dress the burns with clingfilm or plastic bags and wrap the casualty in absorbent materials.


Asunto(s)
Quemaduras/terapia , Servicios Médicos de Urgencia/métodos , Tratamiento de Urgencia/métodos , Medicina Militar/métodos , Enfermedad Aguda , Vendajes , Volumen Sanguíneo , Peso Corporal , Quemaduras/complicaciones , Quemaduras/diagnóstico , Quemaduras/epidemiología , Quemaduras/metabolismo , Quemaduras/fisiopatología , Protocolos Clínicos , Fluidoterapia/métodos , Humanos , Monitoreo Fisiológico/métodos , Cuidados de la Piel/métodos , Reino Unido/epidemiología
14.
Biophys J ; 80(3): 1538-46, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11222314

RESUMEN

High concentrations of free Zn2+ ions are found in certain glutamatergic synaptic vesicles in the mammalian brain. These terminals can be visualized histochemically with quinoline sulfonamide compounds that form fluorescent complexes with Zn2+. The present study was undertaken to examine the interaction of the water-soluble quinoline sulfonamide probe, Zinquin (2-methyl-8-(toluene-p-sulfonamido)-6-quinolyloxyacetic acid) with the complex heterogeneous cellular environment. Experiments on rat hippocampal and neocortical slices gave indications that Zinquin in its free acid form was able to diffuse across the plasma and synaptic vesicle membranes. Further experiments were undertaken on unilamellar liposomes to study the interaction of Zinquin and its metal complexes in membranes. These experiments confirmed that Zinquin is able to diffuse across lipid bilayers. Steady-state and time-resolved fluorimetric studies showed that Zinquin in aqueous solution mainly forms a 1:2 (metal:ligand) complex with small amounts of a 1:1 complex. Formation of the 1:1 complex was favored by the presence of lipid, suggesting that it partitions into membranes. Evidence is presented that Zinquin can act as a Zn(2+)-ionophore, exchanging Zn2+ for two protons. The presence of a pH gradient across vesicles traps the Zn(2+)-probe complex within the vesicles. Zinquin is useful as a qualitative probe for detecting the presence of vesicular Zn2+; however, its tendency to partition into membranes and to serve as an ionophore should be borne in mind.


Asunto(s)
Encéfalo/fisiología , Quinolonas , Vesículas Sinápticas/fisiología , Compuestos de Tosilo , Zinc/análisis , Animales , Encéfalo/citología , Membrana Celular/fisiología , Difusión , Colorantes Fluorescentes , Hipocampo/citología , Hipocampo/fisiología , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Cinética , Liposomas , Microscopía Fluorescente , Neocórtex/citología , Neocórtex/fisiología , Fosfatidilcolinas , Quinolonas/farmacocinética , Ratas , Ratas Long-Evans , Espectrometría de Fluorescencia , Vesículas Sinápticas/ultraestructura , Compuestos de Tosilo/farmacocinética , Zinc/metabolismo
15.
Curr Protoc Neurosci ; Chapter 6: Unit 6.5, 2001 May.
Artículo en Inglés | MEDLINE | ID: mdl-18428515

RESUMEN

The acute dissociation procedure provides a simple means of isolating neurons from the mature mammalian central nervous system. The method was primarily devised to isolate neurons for patch-clamp electrophysiology. It may also prove useful for single-cell PCR, immunocytochemistry, sorting of fluorescently labeled cells, or long-term tissue culture of mature neurons. Dissociation is brought about by a combination of proteolysis and an ionic environment that encourages breakdown of the tissue. The method allows the isolation of neurons free of glial ensheathments in as little as 45 min after the sacrifice of the animal. Neurons so isolated lose fine dendritic branches, although the structure proximal to the cell body is often maintained, allowing identification of the morphological type of the neuron. The preparation has the following advantages: (1) the neurons are fully differentiated; (2) the cells are electronically compact, which improves the fidelity of the voltage clamp; (3) the cells are removed from the influence of surrounding cells; and (4) neurons can be isolated from small, circumscribed loci within the adult central nervous system.


Asunto(s)
Separación Celular/métodos , Sistema Nervioso Central/citología , Neuronas/citología , Factores de Edad , Animales , Separación Celular/instrumentación , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/fisiología , Electrofisiología/instrumentación , Electrofisiología/métodos , Neuronas/efectos de los fármacos , Neuronas/fisiología , Péptido Hidrolasas/farmacología , Ratas
16.
Trends Neurosci ; 23(3): 131-7, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10675918

RESUMEN

The probabilistic gating of voltage-dependent ion channels is a source of electrical 'channel noise' in neurons. This noise has long been implicated in limiting the reliability (repeatability) of neuronal responses to repeated presentations of identical stimuli. More recently, it has been shown to increase the range of spiking behaviors exhibited in some neural populations. Channel numbers are tied to metabolic efficiency and the stability of resting potential, and channel noise might be exploited by future cochlear implants in order to improve the temporal representation of sound.


Asunto(s)
Activación del Canal Iónico/fisiología , Neuronas/fisiología , Potenciales de Acción/fisiología , Animales , Axones/fisiología , Implantes Cocleares , Estimulación Eléctrica , Humanos , Canales Iónicos/fisiología , Modelos Neurológicos , Neuronas/citología , Reproducibilidad de los Resultados , Procesos Estocásticos , Transmisión Sináptica/fisiología
18.
Neuron ; 24(4): 809-17, 1999 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-10624945

RESUMEN

The fluorescent probe FM1-43 has been used extensively for imaging vesicle recycling; however, high nonspecific adsorption resulting in elevated background levels has precluded its use in certain tissues, notably brain slices. We have found that a sulfobutylated derivative of beta-cyclodextrin (ADVASEP-7) has a higher affinity for FM1-43 than the plasma membrane. ADVASEP-7 was used as a carrier to remove FM1-43 nonspecifically bound to the outer leaflet of the plasma membrane or extracellular molecules, significantly reducing background staining. This has enabled us to visualize synaptic vesicle recycling in the nematode C. elegans, intact lamprey spinal cord, and rat brain slices.


Asunto(s)
Encéfalo/fisiología , Caenorhabditis elegans/fisiología , Colorantes Fluorescentes , Lampreas/fisiología , Compuestos de Piridinio , Compuestos de Amonio Cuaternario , Sinapsis/fisiología , Animales , Axones/fisiología , Encéfalo/anatomía & histología , Encéfalo/citología , Tronco Encefálico/anatomía & histología , Tronco Encefálico/fisiología , Ciclodextrinas/farmacología , Portadores de Fármacos , Procesamiento de Imagen Asistido por Computador , Técnicas In Vitro , Liposomas , Masculino , Ratas , Ratas Long-Evans , Ratas Wistar , Médula Espinal/anatomía & histología , Médula Espinal/fisiología , Sinapsis/ultraestructura
19.
J Neurophysiol ; 80(3): 1167-79, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9744930

RESUMEN

Whole cell voltage-clamp techniques were employed to characterize the sodium (Na) conductances in acutely dissociated, mature guinea-pig cerebellar Purkinje cells. Three phenomenological components were noted: two inactivating and a persistent component (I(P)(Na). All exhibited similar sensitivities to tetrodotoxin (TTX; IC50 approximately 3 nM). The inactivating Na current demonstrates two components with different rates of inactivation. The persistent component activates at a more negative membrane potential than the inactivating components and shows little inactivation during a 5-s pulse. The amplitude of the persistent Na conductance had a higher Q10 than the inactivating Na conductance (2.7 vs. 1.3). (I(P)(Na) rapidly activates (approximately 1 ms) and deactivates (< 0.2 ms) and like the fast component appears to be exclusively Na permeable. (I(P)(Na) is not a "window" current because its range of activation exceeds the small overlap between the steady-state activation and inactivation characteristics of the inactivating current. Anomalous tail currents were observed during voltage pulses above -40 mV after a prepulse above -30 mV. The tails rose to a maximum inward current with a time constant of 1.5 ms and decayed to a persistent inward current with a time constant of 20 ms. The tails probably arose as a result of recovery from inactivation through the open state. The noise characteristics of (I(P)(Na) were anomalous in that the measured variance was lower at threshold voltages than would be predicted by a binomial model. The form of the variance could be partially accounted for by postulating that the maximum probability of activation of the persistent current was less than unity. The noise characteristics of (I(P)(Na) are such as to minimize noise near spike activation threshold and sharpen the threshold.


Asunto(s)
Activación del Canal Iónico/fisiología , Células de Purkinje/química , Células de Purkinje/fisiología , Canales de Sodio/fisiología , Sodio/metabolismo , Animales , Artefactos , Dendritas , Potenciales Postsinápticos Excitadores/fisiología , Cobayas , Cinética , Potenciales de la Membrana/efectos de los fármacos , Potenciales de la Membrana/fisiología , Técnicas de Placa-Clamp , Células de Purkinje/ultraestructura , Procesos Estocásticos , Tetrodotoxina/farmacología
20.
J Neurophysiol ; 80(1): 262-9, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9658048

RESUMEN

Neurons of the superficial medial entorhinal cortex (MEC), which deliver neocortical input to the hippocampus, exhibit intrinsic, subthreshold oscillations with slow dynamics. These intrinsic oscillations, driven by a persistent Na+ current and a slow outward current, may help to generate the theta rhythm, a slow rhythm that plays an important role in spatial and declarative learning. Here we show that the number of persistent Na+ channels underlying subthreshold oscillations is relatively small (<10(4)) and use a physiologically based stochastic model to argue that the random behavior of these channels may contribute crucially to cellular-level responses. In acutely isolated MEC neurons under voltage clamp, the mean and variance of the persistent Na+ current were used to estimate the single channel conductance and voltage-dependent probability of opening. A hybrid stochastic-deterministic model was built by using voltage-clamp descriptions of the persistent and fast-inactivating Na+ conductances, along with the fast and slow K+ conductances. All voltage-dependent conductances were represented with nonlinear ordinary differential equations, with the exception of the persistent Na+ conductance, which was represented as a population of stochastic ion channels. The model predicts that the probabilistic nature of Na+ channels increases the cell's repertoire of qualitative behaviors; although deterministic models at a particular point in parameter space can generate either subthreshold oscillations or phase-locked spikes (but rarely both), models with an appropriate level of channel noise can replicate physiological behavior by generating both patterns of electrical activity for a single set of parameters. Channel noise may contribute to higher order interspike interval statistics seen in vitro with DC current stimulation. Models with channel noise show evidence of spike clustering seen in brain slice experiments, although the effect is apparently not as prominent as seen in experimental results. Channel noise may contribute to cellular responses in vivo as well; the stochastic system has enhanced sensitivity to small periodic stimuli in a form of stochastic resonance that is novel (in that the relevant noise source is intrinsic and voltage-dependent) and potentially physiologically relevant. Although based on a simple model that does not include all known membrane mechanisms of MEC stellate cells, these results nevertheless imply that the stochastic nature of small collections of molecules may have important effects at the cellular and network levels.


Asunto(s)
Corteza Entorrinal/fisiología , Neuronas/fisiología , Canales de Potasio/fisiología , Canales de Sodio/fisiología , Animales , Estimulación Eléctrica , Técnicas In Vitro , Activación del Canal Iónico , Masculino , Modelos Neurológicos , Neuronas/efectos de los fármacos , Probabilidad , Ratas , Canales de Sodio/efectos de los fármacos , Procesos Estocásticos , Tetrodotoxina/farmacología
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