RESUMEN
BACKGROUND: Conceptually, allergic responses may involve cross-reactivity by antibodies or T-cells. While IgE cross-reactivity among grass-pollen allergens has been observed, cross-reactivity at the allergen-specific T-cell level has been less documented. Identification of the patterns of cross-reactivity may improve our understanding, allowing optimization of better immunotherapy strategies. OBJECTIVES: We use Phleum pratense as model for the studying of cross-reactivity at the allergen-specific CD4(+) T cell level among DR04:01 restricted Pooideae grass-pollen T-cell epitopes. METHODS: After in vitro culture of blood mono-nucleated cells from grass-pollen-allergic subjects with specific Pooideae antigenic epitopes, dual tetramer staining with APC-labelled DR04:01/Phleum pratense tetramers and PE-labelled DR04:01/Pooideae grass homolog tetramers was assessed to identify cross-reactivity among allergen-specific DR04:01-restricted T-cells in six subjects. Direct ex vivo staining enabled the comparison of frequency and phenotype of different Pooideae grass-pollen reactive T-cells. Intracellular cytokine staining (ICS) assays were also used to examine phenotypes of these T-cells. RESULTS: T-cells with various degrees of cross-reactive profiles could be detected. Poa p 1 97-116 , Lol p 1 221-240 , Lol p 5a 199-218 , and Poa p 5a 199-218 were identified as minimally cross-reactive T-cell epitopes that do not show cross-reactivity to Phl p 1 and Phl p 5a epitopes. Ex vivo tetramer staining assays demonstrated T-cells that recognized these minimally cross-reactive T-cell epitopes are present in Grass-pollen-allergic subjects. CONCLUSIONS: Our results suggest that not all Pooideae grass epitopes with sequence homology are cross-reactive. Non-cross-reactive T-cells with comparable frequency, phenotype and functionality to Phl p-specific T-cells suggest that a multiple allergen system should be considered for immunotherapy instead of a mono-allergen system.
Asunto(s)
Alérgenos/inmunología , Linfocitos T CD4-Positivos/inmunología , Reacciones Cruzadas/inmunología , Desensibilización Inmunológica , Poaceae/inmunología , Subgrupos de Linfocitos T/inmunología , Alelos , Secuencia de Aminoácidos , Antígenos de Plantas/química , Antígenos de Plantas/inmunología , Basófilos/inmunología , Basófilos/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Epítopos de Linfocito T/química , Epítopos de Linfocito T/inmunología , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Inmunoglobulina E/inmunología , Activación de Linfocitos/inmunología , Péptidos/química , Péptidos/inmunología , Polen/inmunología , Especificidad del Receptor de Antígeno de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
Hypoglossal (XII) motoneurons (MNs) contribute to diverse behaviors. Their innervation of the genioglossus muscle, a tongue protruder, plays a critical role in maintaining upper airway patency during breathing. Indeed, reduced activity in these motoneurons is implicated in sleep related disorders of breathing such as obstructive sleep apnea (OSA). The excitability of these MNs is modulated by multiple neurotransmitter systems. The focus of this review is on the modulation of XII MN excitability by norepinephrine (NE), which increases MN excitability through a variety of mechanisms. The level of noradrenergic drive, however, is very dynamic, varying on developmental, sleep-wake and even millisecond timescales relevant to transitions between behaviours. Here we review and provide new data on the maturation of the noradrenergic modulatory system, focusing on those elements specifically relevant to XII MN excitability including the: i) ontogeny of the noradrenergic cell group that provides the majority of the noradrenergic innervation to the XII nucleus, the Locus subcoeruleus (LsC); ii) time course over which the XII nucleus is innervated by noradrenergic nerve fibres, and; iii) ontogeny of XII MN sensitivity to NE. In the context of state-dependent changes in noradrenergic cell activity, we review mechanisms of NE action most relevant to its role in the muscle atonia of REM sleep. We conclude with a discussion of the hypothesis that the dynamics of MN modulation by NE extend to the spatial domain and recent data suggesting that noradrenergic modulation of the dendritic tree is not uniform but compartmentalized. Implications for information processing are discussed.
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Nervio Hipogloso/citología , Bulbo Raquídeo/citología , Bulbo Raquídeo/crecimiento & desarrollo , Neuronas Motoras/fisiología , Norepinefrina/metabolismo , Músculos Respiratorios/inervación , Potenciales de Acción/efectos de los fármacos , Adrenérgicos/farmacología , Factores de Edad , Animales , Femenino , Ácido Glutámico/farmacología , Humanos , Nervio Hipogloso/fisiología , Masculino , Vías Nerviosas/fisiología , Norepinefrina/farmacología , Ratas , Sueño REM/fisiología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
BACKGROUND: Knowledge of airflow in animal noses is sparse. Such knowledge could be important for selection of animal models used in environmental studies. From the phylogenetic and ontogenetic point of view, a comparison between the animal and human nose is interesting. METHOD: Nose models of 5 even-toed ungulate species (he-goat, sheep, cow, roebuck, wild boar) and two humans (new born infant and adult) were examined. Anatomical and physiological features of the nasal cavities of all species were compared. All models were rinsed with water and the flow was visualized for observation. Geometric and rhinoresistometric measurements were then performed. RESULTS AND CONCLUSIONS: Even-toed ungulates have two turbinates directly in the main part of the nasal airflow (respiratory turbinates) and a different number of turbinates in a so-called dead space of the nasal airflow above the nasopharyngeal duct (ethmoidal turbinates). The latter correspond with the upper and middle turbinate in analogy to the human nose. Respiratory turbinates of even-toed ungulates insert immediately behind the external nasal ostium. Thus, the whole nasal cavity acts as a functional area with the exception of a small area acting as dead space only detectable in ruminants, possibly indicating a small evolutionary progress from suinae to bovidae. The shape of the animal nasal cavity is stretched and flat. The airflow runs nearly completely turbulent through the nose. The nasal cavity in the adult human is relatively short and high. The area between the external nasal ostium and the head of the inferior turbinate is called inflow area. It distributes the airflow over the whole nasal cross section and generates a turbulent flow. So the airflow is prepared to contact the mucosa in the functional area (turbinate area). The morphology of the inflow area is approximately formed by the shape of the external nose. The nasal cavity of a newborn child is also stretched and flat and more similar to the nasal shape of the investigated animals. The inflow area in the newborn nose is not yet developed and corresponds with the growing external newborn nose. One can hypothesize that the inflow area in human noses is a morphological adaptation in the changed length-height-ratio of the nasal cavity.
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Nariz/anatomía & histología , Nariz/fisiología , Animales , Artiodáctilos , Humanos , Recién Nacido , Persona de Mediana Edad , Cavidad Nasal/anatomía & histología , Cavidad Nasal/fisiología , Respiración , Rinometría Acústica , Cornetes Nasales/anatomía & histologíaRESUMEN
We present a curve-fitting approach that permits quantitative comparisons of fatigue profiles obtained with different stimulation protocols in isolated slow-twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of mice. Profiles from our usual stimulation protocol (125 Hz for 500 ms, evoked once every second for 100-300 s) could be fitted by single-term functions (sigmoids or exponentials) but not by a double exponential. A clearly superior fit, as confirmed by the Akaiki Information Criterion, was achieved using a double-sigmoid function. Fitting accuracy was exceptional; mean square errors were typically <1% and r(2) > 0.9995. The first sigmoid (early fatigue) involved approximately 10% decline of isometric force to an intermediate plateau in both muscle types; the second sigmoid (late fatigue) involved a reduction of force to a final plateau, the decline being 83% of initial force in EDL and 63% of initial force in soleus. The maximal slope of each sigmoid was seven- to eightfold greater in EDL than in soleus. The general applicability of the model was tested by fitting profiles with a severe force loss arising from repeated tetanic stimulation evoked at different frequencies or rest periods, or with excitation via nerve terminals in soleus. Late fatigue, which was absent at 30 Hz, occurred earlier and to a greater extent at 125 than 50 Hz. The model captured small changes in rate of late fatigue for nerve terminal versus sarcolemmal stimulation. We conclude that a double-sigmoid expression is a useful and accurate model to characterize fatigue in isolated muscle preparations.
Asunto(s)
Modelos Biológicos , Fatiga Muscular/fisiología , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Músculo Esquelético/fisiología , Animales , Estimulación Eléctrica , Femenino , Ratones , Modelos AnimalesRESUMEN
BACKGROUND: The nasal septal deviation is a common cause of nasal obstruction. On the other hand, many septal deviations are asymptomatic. It seems a physiological adaptation occurs on both sides. Septal deviation leads to internal nasal asymmetry, which in turn causes compensatory change in turbinate morphology (e.g. turbinate hypertrophy respectively hypotrophy). This mechanism is investigated with the help of fluid dynamic experiments and functional rhinologic diagnostics. METHODS: Functional models of the nose (modified Mink's boxes) were used and assessment was made by acoustic rhinometry and rhinoresistometry, followed by flow dynamic investigations. Septal deviations of varying position, together with turbinates of differing grades of hypertrophy, were simulated and assessed. RESULTS AND CONCLUSIONS: We observed in models of septal deviation an increase in flow resistance on the ipsilateral side as a result of friction of flow particles in the narrowing. Furthermore, on the opposite side of the deviation, the enlargement of the stream channel did not generally lead to a reduction in flow resistance, but rather to a 'dead space', where only a slow-circling eddy was observed. This eddy causes an increase in turbulence. In vivo turbinate hypertrophy occurs to fill this dead space, thereby reducing turbulent flow without a significant increase in resistance. In cases of moderate septal deviation, compensatory mechanisms of the turbinates can lead to a normalization of nasal airflow and surgical therapy would not be indicated. Deviations in the anterior part of the septum seem to be more symptomatic, because the mechanism is missing and due to the physiological narrowing of the nasal isthmus. To differ between physiologic and pathologic deviation, functional diagnostics are needed.
Asunto(s)
Tabique Nasal/anomalías , Nariz/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/etiología , Cornetes Nasales/patología , Simulación por Computador , Humanos , Hipertrofia , Modelos Biológicos , Tabique Nasal/patología , Tabique Nasal/cirugía , Nariz/patología , Nariz/fisiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Rinomanometría , Rinometría Acústica , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The inspiratory medial movement of the nasal wing at high flow velocities is a protective physiologic mechanism. If this collapse of the nasal wing occurs at lower flow velocities, it may result in nasal obstruction. "Nasal wing collapse" is generally a clinical diagnosis. However, in the pressure-flow relationship of rhinomanometry, the medial movement of the nasal wing can be documented in the inspiratory arm of the graph. The diagnostic impact of this hysteresis was investigated. METHODS: The pressure-flow curves of three box models and three nasal models with a moveable valve (analogous to the nasal wing) in the entrance area as well as three volunteers with unstable nasal wings were investigated. We recorded synchronously the pressure-flow relationship and by endoscopy the movement of the valve in the box models and the nasal wing in the volunteers on video. For evaluation, we used the frame by frame analysis of the tape. RESULTS AND CONCLUSIONS: The medial movement of the nasal wing causes a hysteresis in the inspiratory arm of the pressure-flow curve. At this point, the graph runs on or between two border curves, termed the "no collapse curve" (for the maximally opened valve or a stable nasal wing) and the "collapse curve" (for the subtotally closed valve or a collapsed nasal wing), respectively. Analogous to the nasal wing motion, the descending course of hysteresis runs in two phases, and the ascending course runs in three phases. The medial movement of the nasal wing is expressed by a deviation of the graph from the "no collapse curve." The flow, at which the graph leaves this curve, depends on the elasticity module of the nasal wing. The extent of nasal wing collapse is reflected by the approximation of the pressure-flow curve to the "collapse curve" of the graph. The hysteresis appears because of a late opening of the collapsed nasal wing.
Asunto(s)
Inhalación/fisiología , Obstrucción Nasal/diagnóstico , Nariz/fisiopatología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Obstrucción Nasal/etiología , Presión , RinomanometríaRESUMEN
OBJECTIVE: Little information exists from formerly iodine-deficient areas regarding gender-specific risk factors for goiter and their synergisms. The aim of the present study was to investigate such gender-specific risk factors and their interactions in a large population-based sample. METHODS AND RESULTS: The Study of Health in Pomerania (SHIP) comprised 4310 randomly selected participants, aged 20 - 79 years. SHIP was performed in a previously iodine-deficient region. Data from 3915 participants with no known thyroid disorders were analyzed. Goiter was determined by thyroid ultrasound. Sociodemographic characteristics, smoking and alcohol drinking habits, marital status, education level, urine thiocyanate concentrations, and specifically in women, parity and previous or current use of oral contraceptives and hormone replacement therapy, were considered as candidate risk factors for multivariable statistical tests. Only two variables, an advanced age and current smoking, were independently associated with an increased risk for goiter in both genders. Analyses further revealed specific risk factor profiles for goiter which were different among men, pre- and postmenopausal women. CONCLUSION: We conclude that besides previous iodine deficiency, other risk factors for goiter exist which differ between gender. Among the avoidable risk factors, current smoking was strongly associated with the risk of goiter in men and women. These findings should influence activities which are intended to prevent thyroid disease.
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Bocio Endémico , Yodo/deficiencia , Adulto , Factores de Edad , Anciano , Anticonceptivos Orales/efectos adversos , Femenino , Bocio Endémico/epidemiología , Bocio Endémico/etiología , Bocio Endémico/prevención & control , Terapia de Reemplazo de Hormonas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversosRESUMEN
Any radiation exposition for medical purposes should be kept as low as is reasonably achievable. Mean patient radiation exposure of diagnostic cardiac catheterisation is high (16-106 Gy x cm2) and for this reason the International Commission on Radiological Protection (ICRP) recommends credentialing radiation protection training programmes. Twenty cardiologists each documented various dose parameters of 10 cardiac catheterisations, before and after a 90-minute mini-course of the ELICIT study group ("Encourage to Less Irradiating Cardiologic Interventional Techniques"), and could achieve a reduction of the mean dose-area product by 15.9+/-9.0 Gy x cm2, equivalent to 47%. The presented radiation-reducing planning of invasive cardiac catheterisation for this reason is the first one validated in clinical routine and consists of 6 standard runs--one for the left ventricle, 3 and 2 for the left (LCA) and right coronary artery (RCA), respectively--depending on anatomy and findings supplemented by 1...4 special projections. The caudal posteroanterior (PA) view documents the left coronary main stem, proximal and distal left anterior descending artery (LAD), and proximal and mid circumflex segments. The cranial PA view however is suitable for the left coronary orifice, circumflex periphery, LAD, all diagonal bifurcations, and collateral pathways towards the RCA. LCA standard angiography is completed by lateral 90 degrees/0 degrees left anterior oblique (LAO) angulation. The 60 degrees/0 degrees LAO angulation visualises the right posterolateral artery (RPL) and the RCA to its bifurcation. The more proximal one finds the bifurcation, the more the second standard cranial PA view for RCA should vary towards the cranial right anterior oblique (RAO) and finally 30 degrees/0 degrees RAO view. The efficiency of these less-irradiating angulations are improved by radiation-reducing techniques as follows: restriction to essential radiographic frames and runs, consistent collimation to the region of interest--particularly during coronary intubation--, adequate instead of best possible image quality, short skin-to-image-intensifier distance, inspiration during radiography, preference for projections that rotate out the spine, optimisation of fluoroscopy time, well-experienced and well-rested interventionists.
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Cateterismo Cardíaco/métodos , Angiografía Coronaria/métodos , Traumatismos por Radiación/prevención & control , Protección Radiológica/métodos , Carga Corporal (Radioterapia) , Angiografía Coronaria/efectos adversos , Humanos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Dosis de Radiación , Traumatismos por Radiación/etiologíaAsunto(s)
Aneurisma de la Aorta/diagnóstico , Disección Aórtica/diagnóstico , Aortografía , Cateterismo Cardíaco/efectos adversos , Enfermedad Iatrogénica , Disección Aórtica/etiología , Disección Aórtica/cirugía , Aneurisma de la Aorta/etiología , Aneurisma de la Aorta/cirugía , Enfermedad Crónica , Angiografía Coronaria/efectos adversos , Puente de Arteria Coronaria , Electrocardiografía , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada EspiralRESUMEN
BACKGROUND: Abnormalities of the external shape of the nose are often felt as cosmetically disturbing. In many cases an additional hampering of the respiratory function of the nose is seen and causes pathological nasal airflow patterns. For the functional outcome of aesthetic-surgery of the nose, knowledge of nasal flow is essential. In the medical literature there are some discrepancies between the relationship of nasal shape and nasal flow. We investigated typical airflow patterns in different abnormalities of the external nose. METHODS: We performed fluid dynamic experiments on exact, anatomical nasal models and functional nasal models (so-called modified Mink boxes). We investigated the inspiratory flow pattern in nose-models with typical variations of the shape of the external nose. RESULTS AND CONCLUSIONS: There were typical airflow patterns for every external nasal abnormalities. The normal nose shows a disturbance of the streamlines over the entire nasal cavum. Under physiological flow velocities we find laminar and turbulent flow. The pathological variations of the nasal shape show mostly different airflow patterns and characteristics. The main reason for that is a deformed or anatomically false configurated inflow area (vestibulum, isthmus and anterior cavum). During rhinoplasty the reconstruction of the nasal inflow area has to be taken into account.
Asunto(s)
Deformidades Adquiridas Nasales/fisiopatología , Nariz/anomalías , Nariz/fisiología , Ventilación Pulmonar/fisiología , Humanos , Modelos Anatómicos , Deformidades Adquiridas Nasales/cirugía , Rinoplastia , Cornetes Nasales/anatomía & histología , Cornetes Nasales/fisiologíaRESUMEN
PURPOSE: To analyze the effects of an optimized fluoroscopy time on patient radiation exposure in the course of coronary angiography (CA) and percutaneous coronary interventions (PTCA), in comparison to those with consistent collimation to the region of interest (ROI). Furthermore, to analyze efforts concerning reduction of radiographic frames as well as concerning adequate instead of best possible image quality. MATERIAL AND METHODS: For 3,115 elective CAs and 1,713 PTCA performed by one interventionist since 1997, we documented the radiographic dose-area products (DAP (R)) and fluoroscopic dose-area products (DAP (F)), the number of radiographic frames and the fluoroscopy times during selected 2-month intervals. Under conditions of constant image intensifier entrance dose, levels of DAP (R)/frame and DAP (F)/s represent valid parameters for consistent collimation. RESULTS: In 1997, the mean baseline values of DAP for elective CA and PTCA amounted to 37.1 and 31.6 Gy x cm (2), respectively. A reduction of mean fluoroscopy times from 264 to 126 seconds for CA and from 630 to 449 seconds for PCI, both resulted in an overall DAP-reduction of merely 20 %. Optimization of mean radiographic frames from 543 to 98 for CA and from 245 to 142 for PTCA enabled reductions of 53 and 13 %, respectively. By restriction to adequate instead of best-possible image quality for coronary angiography in clinical routine, we achieved an optimized radiographic DAP/frame of 30.3 to 13.3 mGy x cm (2), which enabled a 45 % reduction of overall DAP. Most efficient however was a consistent collimation to the ROI, which resulted in a remarkable radiation reduction by 46 % for CA and by 65 % for PTCA. CONCLUSIONS: Radiation-reducing educational efforts in the clinical routine of invasive cardiology should -- against widely held opinion -- focus less exclusively toward a reduction of fluoroscopy time but more efficiently toward consistent collimation to the region of interest, reduction of radiographic frames and restriction to an adequate instead of best-possible image quality.
Asunto(s)
Angioplastia Coronaria con Balón , Angiografía Coronaria/efectos adversos , Fluoroscopía/efectos adversos , Dosis de Radiación , Protección Radiológica/métodos , Angiografía Coronaria/instrumentación , Angiografía Coronaria/métodos , Humanos , Seguridad , Factores de Tiempo , Pantallas Intensificadoras de Rayos XRESUMEN
Multiple brainstem sites are proposed to contribute to central respiratory chemosensitivity, however, the underlying molecular mechanisms remain unknown. P2X2 subunit-containing ATP receptors, which mediate pH-sensitive currents, appear to contribute to central chemosensitivity in vivo [J. Physiol. 523 (2000) 441]. However, recent data from P2X2 knockout mice [J. Neurosci. 23 (2003) 11315] indicate that they are not essential. To further explore the role of P2 receptors in central chemosensitivity, we examined the effects of P2 receptor agonists/antagonists on respiratory-related activity and CO2-sensitivity of rhythmically-active in vitro preparations from neonatal rat. Our main findings: (i) that putative chemosensitive regions of the ventrolateral medulla are immunoreactive for the P2X2 subunit; (ii) that ATP potentiates respiratory frequency in a dose-dependent, and PPADS-sensitive (P2 receptor antagonist), manner; and (iii) that the increase in burst frequency produced by increasing CO2 is unaffected by PPADS, indicate that ATP is a potent modulator of respiratory activity, but that P2 receptors do not contribute to central chemosensitivity in vitro.
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Dióxido de Carbono/metabolismo , Células Quimiorreceptoras/fisiología , Bulbo Raquídeo/fisiología , Fosfato de Piridoxal/análogos & derivados , Receptores Purinérgicos P2/fisiología , Respiración , Potenciales de Acción/efectos de los fármacos , Adenosina Trifosfato/farmacología , Animales , Animales Recién Nacidos , Dióxido de Carbono/farmacología , Células Quimiorreceptoras/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Electrofisiología/métodos , Inmunohistoquímica/métodos , Técnicas In Vitro , Bulbo Raquídeo/citología , Bulbo Raquídeo/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Fosfato de Piridoxal/farmacología , Ratas , Ratas Wistar , Respiración/efectos de los fármacosRESUMEN
1. The effects of substance P (SP), acting at NK1 receptors, on the excitability and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated using rhythmically active medullary-slice preparations from neonatal mice (postnatal day 0-3). 2. Local application of the NK1 agonist [SAR(9),Met (O(2))(11)]-SP (SP(NK1)) produced a dose-dependent, spantide- (a non-specific NK receptor antagonist) and GR82334-(an NK1 antagonist) sensitive increase in inspiratory burst amplitude recorded from XII nerves. 3. Under current clamp, SP(NK1) significantly depolarized XII MNs, potentiated repetitive firing responses to injected currents and produced a leftward shift in the firing frequency-current relationships without affecting slope. 4. Under voltage clamp, SP(NK1) evoked an inward current and increased input resistance, but had no effect on inspiratory synaptic currents. SP(NK1) currents persisted in the presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and reversed near the expected E(K). 5. Effects of the alpha(1)-noradrenergic receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually identical to those of SP(NK1). Moreover, SP(NK1) currents were completely occluded by PE, suggesting that common intracellular pathways mediate the actions of NK1 and alpha(1)-noradrenergic receptors. In spite of the similar actions of SP(NK1) and PE on XII MN responses to somally injected current, alpha(1)-noradrenergic receptor activation potentiated inspiratory synaptic currents and was more than twice as effective in potentiating XII nerve inspiratory burst amplitude. 6. GR82334 reduced XII nerve inspiratory burst amplitude and generated a small outward current in XII MNs. These observations, together with the first immunohistochemical evidence in the newborn for SP immunopositive terminals in the vicinity of SP(NK1)-sensitive inspiratory XII MNs, support the endogenous modulation of XII MN excitability by SP. 7. In contrast to phrenic MNs (Ptak et al. 2000), blocking NMDA receptors with AP5 had no effect on the modulation of XII nerve activity by SP(NK1). 8. In conclusion, SP(NK1) modulates XII motoneuron responses to inspiratory drive primarily through inhibition of a resting, postsynaptic K+ leak conductance. The results establish the functional significance of SP in controlling upper airway tone during early postnatal life and indicate differential modulation of motoneurons controlling airway and pump muscles by SP.
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Nervio Hipogloso/citología , Nervio Hipogloso/fisiología , Neuronas Motoras/fisiología , Fisalemina/análogos & derivados , Receptores de Neuroquinina-1/fisiología , Animales , Animales Recién Nacidos , Nervio Hipogloso/química , Inmunohistoquímica , Técnicas In Vitro , Ratones , Ratones Endogámicos , Técnicas de Placa-Clamp , Fenilefrina/farmacología , Fisalemina/farmacología , Potasio/farmacología , Centro Respiratorio/fisiología , Mecánica Respiratoria/fisiología , Sustancia P/análisis , Sustancia P/farmacología , Simpatomiméticos/farmacología , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología , Tetrodotoxina/farmacologíaRESUMEN
PURPOSE: To examine the dosimetric benefit of self-gated radiotherapy at deep-inspiration breath hold (DIBH) in the treatment of patients with non-small-cell lung cancer (NSCLC). The relative contributions of tumor immobilization at breath hold (BH) and increased lung volume at deep inspiration (DI) in sparing high-dose lung irradiation (> or = 20 Gy) were examined. METHODS AND MATERIALS: Ten consecutive patients undergoing radiotherapy for Stage I-IIIB NSCLC who met the screening criteria were entered on this study. Patients were instructed to BH at DI without the use of external monitors or breath-holding devices (self-gating). Computed tomography (CT) scans of the thorax were performed during free breathing (FB) and DIBH. Fluoroscopy screened for reproducible tumor position throughout DIBH, and determined the maximum superior-inferior (SI) tumor motion during both FB and DIBH. Margins used to define the planning target volume (PTV) from the clinical target volume included 1 cm for setup error and organ motion, plus an additional SI margin for tumor motion, as determined from fluoroscopy. Three conformal treatment plans were then generated for each patient, one from the FB scan with FB PTV margins, a second from the DIBH scan with FB PTV margins, and a third from the DIBH scan with DIBH PTV margins. The percent of total lung volume receiving > or = 20 Gy (using a prescription dose of 70.9 Gy to isocenter) was determined for each plan. RESULTS: Self-gating at DIBH was possible for 8 of the 10 patients; 2 patients were excluded, because they were not able to perform a reproducible DIBH. For these 8 patients, the median BH time was 23 (range, 19-52) s. The mean percent of total lung volume receiving > or = 20 Gy under FB conditions (FB scan with FB PTV margins) was 12.8%. With increased lung volume alone (DIBH scan with FB PTV margins), this was reduced to 11.0%, tending toward a significant decrease in lung irradiation over FB (p = 0.086). With both increased lung volume and tumor immobilization (DIBH scan with DIBH PTV margins), the mean percent lung volume receiving > or = 20 Gy was further reduced to 8.8%, a significant decrease in lung irradiation compared to FB (p = 0.011). Furthermore, at DIBH, the additional benefit provided by tumor immobilization (i.e., using DIBH instead of FB PTV margins) was also significant (p = 0.006). The relative contributions of tumor immobilization and increased lung volume toward reducing the percent total lung volume receiving > or = 20 Gy were patient specific; however, all 8 of the patients analyzed showed a dosimetric benefit with this DIBH technique. CONCLUSION: Compared to FB conditions, at DIBH the mean reduction in percent lung volume receiving > or = 20 Gy was 14.3% with the increase in lung volume alone, 22.1% with tumor immobilization alone, and 32.5% with the combined effect. The dosimetric benefit seen at DIBH was patient specific, and due to both the increased lung volume seen at DI and the PTV margin reduction seen with tumor immobilization.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Inmovilización , Neoplasias Pulmonares/radioterapia , Radioterapia Conformacional/métodos , Respiración , Anciano , Algoritmos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Fenómenos Físicos , Física , RadiografíaRESUMEN
BACKGROUND: The NASA/American Cancer Society (ACS) flow cytometer can simultaneously analyze the electronic nuclear volume (ENV) and DNA content of cells. This study describes the schematics, resolution, reproducibility, and sensitivity of biological standards analyzed on this unit. METHODS: Calibrated beads and biological standards (lymphocytes, trout erythrocytes [TRBC], calf thymocytes, and tumor cells) were analyzed for ENV versus DNA content. Parallel data (forward scatter versus DNA) from a conventional flow cytometer were obtained. RESULTS: ENV linearity studies yielded an R value of 0.999. TRBC had a coefficient of variation (CV) of 1.18 +/- 0.13. DNA indexes as low as 1.02 were detectable. DNA content of lymphocytes from 42 females was 1.9% greater than that for 60 males, with a noninstrumental variability in total DNA content of 0.5%. The ENV/DNA ratio was constant in 15 normal human tissue samples, but differed in the four animal species tested. The ENV/DNA ratio for a hypodiploid breast carcinoma was 2.3 times greater than that for normal breast tissue. CONCLUSIONS: The high-resolution ENV versus DNA analyses are highly reliable, sensitive, and can be used for the detection of near-diploid tumor cells that are difficult to identify with conventional cytometers. ENV/DNA ratio may be a useful parameter for detection of aneuploid populations.
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American Cancer Society , Núcleo Celular/patología , ADN/análisis , Citometría de Flujo/métodos , Neoplasias/patología , United States National Aeronautics and Space Administration , Animales , Calibración , Eritrocitos/citología , Eritrocitos/metabolismo , Femenino , Citometría de Flujo/instrumentación , Citometría de Flujo/normas , Humanos , Leucocitos/citología , Leucocitos/metabolismo , Masculino , Neoplasias/genética , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Timo/citología , Timo/metabolismo , Células Tumorales Cultivadas , Estados UnidosAsunto(s)
Homosexualidad Femenina , Literatura , Sexualidad , Conducta Social , Derechos de la Mujer , Inglaterra/etnología , Femenino , Identidad de Género , Historia del Siglo XVIII , Homosexualidad Femenina/etnología , Homosexualidad Femenina/historia , Homosexualidad Femenina/psicología , Humanos , Literatura/historia , Conducta Sexual/etnología , Conducta Sexual/historia , Conducta Sexual/fisiología , Conducta Sexual/psicología , Sexualidad/etnología , Sexualidad/historia , Sexualidad/fisiología , Sexualidad/psicología , Cambio Social/historia , Condiciones Sociales/economía , Condiciones Sociales/historia , Condiciones Sociales/legislación & jurisprudencia , Mujeres/educación , Mujeres/historia , Mujeres/psicología , Salud de la Mujer/economía , Salud de la Mujer/etnología , Salud de la Mujer/historia , Salud de la Mujer/legislación & jurisprudencia , Derechos de la Mujer/economía , Derechos de la Mujer/educación , Derechos de la Mujer/historia , Derechos de la Mujer/legislación & jurisprudenciaRESUMEN
We examined developmental changes in breathing pattern and the ventilatory response to hypoxia (7.4% O(2)) in unanesthetized Swiss CD-1 mice ranging in age from postnatal day 0 to 42 (P(0)-P(42)) using head-out plethysmography. The breathing pattern of P(0) mice was unstable. Apneas were frequent at P(0) (occupying 29 +/- 6% of total time) but rare by P(3) (5 +/- 2% of total time). Tidal volume increased in proportion to body mass ( approximately 10-13 ml/kg), but increases in respiratory frequency (f) (55 +/- 7, 130 +/- 13, and 207 +/- 20 cycles/min for P(0), P(3), and P(42), respectively) were responsible for developmental increases in minute ventilation (690 +/- 90, 1,530 +/- 250, and 2,170 +/- 430 ml. min(-1). kg(-1) for P(0), P(3), and P(42), respectively). Between P(0) and P(3), increases in f were mediated by reductions in apnea and inspiratory and expiratory times; beyond P(3), increases were due to reductions in expiratory time. Mice of all ages showed a biphasic hypoxic ventilatory response, which differed in two respects from the response typical of most mammals. First, the initial hyperpnea, which was greatest in mature animals, decreased developmentally from a maximum, relative to control, of 2.58 +/- 0.29 in P(0) mice to 1. 32 +/- 0.09 in P(42) mice. Second, whereas ventilation typically falls to or below control in most neonatal mammals, ventilation remained elevated relative to control throughout the hypoxic exposure in P(0) (1.73 +/- 0.31), P(3) (1.64 +/- 0.29), and P(9) (1. 34 +/- 0.17) mice but not in P(19) or P(42) mice.
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Envejecimiento/fisiología , Animales Recién Nacidos/fisiología , Hipoxia/fisiopatología , Respiración , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Apnea/fisiopatología , Ratones , Ventilación Pulmonar/fisiologíaRESUMEN
1. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output. This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper is to review our recent data on synaptic factors important in the dynamic control of MN excitability over time scales ranging from weeks to milliseconds. 2. Developmental changes in modulation of MN excitability are well established. Noradrenergic potentiation of hypoglossal (XII) MN inspiratory activity in rhythmically active medullary slice preparations from rodents increases during the first two postnatal weeks. This is due to increasing alpha 1- and beta-adrenoceptor excitatory mechanisms and to a decreasing inhibitory mechanism mediated by alpha 2-adrenoceptors. Over a similar period, ATP potentiation of XII inspiratory activity does not change. 3. Motoneuron excitability may also change on a faster time scale, such as between different behaviours or different phases of a behaviour. Examination of this has been confounded by the fact that excitatory synaptic drives underlying behaviour can obscure smaller concurrent changes in excitability. Using the rhythmically active neonatal rat brain-stem-spinal cord preparation, we blocked excitatory inspiratory drive to phrenic MN (PMN) to reveal a reduction in PMN excitability specific to the inspiratory phase that: (i) arises from an inhibitory GABAergic input; (ii) is not mediated by recurrent pathways; and (iii) is proportional to and synchronous with the excitatory inspiratory input. We propose that the proportionality of the concurrent inhibitory and excitatory drives provides a means for phase-specific modulation of PMN gain. 4. Modulation across such diverse time scales emphasizes the active role that synaptic factors play in controlling MN excitability and shaping behaviour.