RESUMEN
BACKGROUND: Natural allergen sources contain a variety of allergens, against which allergic subjects have developed individual sensitization profiles. Ideal allergen products for skin prick testing (SPT) and allergen immunotherapy (AIT) should contain the complete set of allergens of the respective allergen sources to cover all sensitization profiles. However, commercially available allergen products were shown to vary regarding their allergen composition. METHODS: The qualitative allergen composition of different SPT and AIT products produced from pollen of grasses, birch, mugwort and from house dust mites was assessed by a consistent high-resolution liquid chromatography-coupled tandem mass spectrometry method (LC-MS/MS). RESULTS: All major, mid-tier and most minor allergens were detected in each of the investigated three batches of SPT and AIT products, demonstrating the completeness of the allergen composition and a high degree of batch-to-batch consistency. CONCLUSION: This is the first study using a single consistent high-resolution LC-MS/MS method to provide solid data on the qualitative allergen composition of SPT and AIT products manufactured from various common allergen sources. The applied method showed high reliability in qualitative batch-to-batch consistency testing and can be performed fast and with high throughput. High-resolution LC-MS/MS is applicable for process development and quality control to ensure market availability of allergen products corresponding to the composition of the respective natural allergen sources.
RESUMEN
AIM: The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. METHODS: All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. RESULTS: 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. CONCLUSION: In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.
Asunto(s)
Recien Nacido Extremadamente Prematuro , Trastornos del Neurodesarrollo , Humanos , Masculino , Femenino , Austria/epidemiología , Recién Nacido , Preescolar , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/etiología , Estudios Prospectivos , Desarrollo Infantil , Sistema de Registros , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/etiología , Edad Gestacional , LactanteRESUMEN
BACKGROUND: In respiratory distress syndrome, many neonatology centers worldwide perform minimal invasive surfactant application in premature infants, using small-diameter catheters for endotracheal intubation and surfactant administration. METHODS: In this single-center, open-label, randomized-controlled trial, preterm infants requiring surfactant administration after birth, using a standardized minimal invasive protocol, were randomized to two different modes of endotracheal catheterization: Flexible charrière-4 feeding tube inserted using Magill forceps (group 1) and semi-rigid catheter (group 2). Primary outcome was duration of laryngoscopy. Secondary outcomes were complication rate (intraventricular hemorrhage, soft-tissue damage in first week of life) and vital parameters during laryngoscopy. Between 2019 and 2020, 31 infants were included in the study. Prior to in-vivo testing, laryngoscopy durations were studied on a neonatal airway mannequin in students, nurses and doctors. RESULTS: Mean gestational age and birth weight were 27 + 6/7 weeks and 1009 g; and 28 + 0/7 weeks and 1127 g for group 1 and 2, respectively. Length of laryngoscopy was similar in both groups (61.1 s and 64.9 s) overall (p.77) and adjusted for weight (p.70) or gestational age (p.95). Laryngoscopy failed seven times in group 1 (43.8%) and four times (26.7%) in group 2 (p.46). Longer laryngoscopy was associated with lower oxygen saturation with lowest levels occurring after failed laryngoscopy attempts. Secondary outcomes were similar in both groups. In vitro data on 40 students, 40 nurses and 12 neonatologists showed significant faster laryngoscopy in students and nurses group 2 (p < .0001) unlike in neonatologists (p.13). CONCLUSION: This study showed no difference in laryngoscopy duration in endotracheal catheterization when comparing semi-rigid and flexible catheters for minimal invasive surfactant application in preterm infants. In accordance with preliminary data and in contrast to published in-vitro trials, experienced neonatologists were able to perform endotracheal catheterization using both semi-rigid and flexible catheters at similar rates and ease, in vitro and in vivo. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05024435 Registered 27 August 2021-Retrospectively registered.
Asunto(s)
Surfactantes Pulmonares , Síndrome de Dificultad Respiratoria del Recién Nacido , Lactante , Recién Nacido , Humanos , Recien Nacido Prematuro , Proyectos Piloto , Tensoactivos/uso terapéutico , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Catéteres , Lipoproteínas , Presión de las Vías Aéreas Positiva ContínuaRESUMEN
BACKGROUND: It is shown that meeting the increased nutritional demand of preterm infants from birth is not only important for survival but essentially contributes to the infants` overall development and long-term health. While there are established guidelines for weaning term infants, evidence regarding preterm infants is scarce and less precise. The aim of this study was to identify the current practices on introducing solids to preterm infants amongst caregivers in Salzburg and determine potential reasons for early weaning. METHODS: Altogether 68 infants born between 24 0/7 and 36 6/7 weeks were recruited and detailed structured interviews with the caregivers were conducted at 17 weeks corrected age. Weight, height and head circumference were collected. RESULTS: 52% of the study group received solids before the recommended 17 weeks corrected age. For this group the mean age being 13.77 ± 1.11 weeks corrected age. Premature introduction of solids significantly correlates with exclusively and early formula-feeding. 34% were weaned due to recommendation by their paediatrician. 23% of the preterm infants even received solids before 12 weeks corrected age, putting them at risks for developing obesity, celiac disease and diabetes. CONCLUSIONS: This study shows the necessity for clear guidelines regarding the introduction of complementary feeding in preterm infants as well as the importance of their implementation. Caregivers should receive information on this topic early enough and they should fully understand the difference between chronological and corrected age.
Asunto(s)
Lactancia Materna , Recien Nacido Prematuro , Conducta Alimentaria , Femenino , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Embarazo , DesteteRESUMEN
BackgroundPostnatally, the immature left ventricle (LV) is subjected to high systemic afterload. Hypothesizing that LV pumping would change during transition-adaptation, we analyzed the LV in preterm infants (GA≤32+6), clinically stable or with a hemodynamically significant patent ductus arteriosus (hPDA) by applying a pump model.MethodsPumping was characterized by EA (effective arterial elastance, reflecting afterload), EES (end-systolic LV elastance, reflecting contractility), EA/EES coupling ratios, descriptive EA:EES relations, and EA/EES graphs. Data calculated from echocardiography and blood pressure were analyzed by diagnosis (S group: clinically stable, no hPDA, n=122; hPDA group, n=53) and by periods (early transition: days of life 1-3; late transition: 4-7; and adaptation: 8-30).ResultsS group: LV pumping was characterized by an increased EA/EES coupling ratio of 0.65 secondary to low EES in early transition, a tandem rise of both EA and EES in late transition, and an EA/EES coupling ratio of 0.45 secondary to high EES in adaptation; hPDA group: time-trend analyses showed significantly lower EA (P<0.0001) and EES (P=0.006). Therefore, LV pumping was characterized by a lower EA/EES coupling ratio (P=0.088) throughout transition-adaptation.ConclusionsIn stable infants, facing high afterload, the immature LV, enhanced by the physiological PDA, increases its contractility. In hPDA, facing low afterload, the overloaded immature LV exhibits a consistently lower contractility.
Asunto(s)
Conducto Arterioso Permeable/fisiopatología , Ventrículos Cardíacos/fisiopatología , Adaptación Fisiológica , Arterias , Presión Sanguínea , Ecocardiografía , Hemodinámica , Humanos , Recién Nacido , Recien Nacido Prematuro , Modelos Cardiovasculares , Estudios Prospectivos , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Using near-infrared spectroscopy (NIRS) mixed tissue saturation can be calculated by measuring the oxygen saturation of oxygenated and deoxygenated erythrocytes in the tissue. Quality of the calculated value is not only dependent on the exposure of the measured values in the calculation, but also on external factors such as artifacts. Main object of this study was to determine whether and how the measurement quality of different devices varies in their long-term use in premature infants. PATIENTS AND METHODS: In 54 measurements, each lasting 2 hours, 4 NIRS devices were attached in pairs on the forehead of 9 cardio-respiratory stable, spontaneous breathing premature infants. Pooled meta-analysis was used to compare the correlation between regional tissue saturation to the pulse oximetry saturation per device. RESULTS: The pooled random effect of all Pearson's correlation coefficients was 0.490 (CI95: 0.403-0.568) with the NIRO 200, 0.575 (CI95: 0.463-0.668) with the INVOS 5100c, 0.712 (CI95: 0.640-0.772) with the Fore-Sight and 0.638 (CI95: 0.554-0.709) with the SenSmart X- 100. CONCLUSION: In this trial, a significant correlation between the tissue saturation and pulsoxymetry saturation was observed. The tremendous variation range among the measurements showed, however, that the measurement quality can be severely affected by unrecognized artifacts, after excluding other possible causes. None of the devices had reliable artifact detection for long-term measurements in very small premature infants. Key words: Near-Infrared-Spectroscopy, premature infants, Benchmark Test, Long-term measurements.
Asunto(s)
Benchmarking , Encéfalo/metabolismo , Recien Nacido Prematuro , Oxígeno/metabolismo , Espectroscopía Infrarroja Corta/instrumentación , Humanos , Lactante , Recién Nacido , OximetríaRESUMEN
OBJECTIVE: Mechanically ventilated neonates have been observed to receive substantially different ventilation after switching ventilator models, despite identical ventilator settings. This study aims at establishing the range of output variability among 10 neonatal ventilators under various breathing conditions. DESIGN: Relative benchmarking test of 10 neonatal ventilators on an active neonatal lung model. SETTING: Neonatal ICU. SUBJECTS: Ten current neonatal ventilators. INTERVENTIONS: Ventilators were set identically to flow-triggered, synchronized, volume-targeted, pressure-controlled, continuous mandatory ventilation and connected to a neonatal lung model. The latter was configured to simulate three patients (500, 1,500, and 3,500 g) in three breathing modes each (passive breathing, constant active breathing, and variable active breathing). MEASUREMENTS AND MAIN RESULTS: Averaged across all weight conditions, the included ventilators delivered between 86% and 110% of the target tidal volume in the passive mode, between 88% and 126% during constant active breathing, and between 86% and 120% under variable active breathing. The largest relative deviation occurred during the 500 g constant active condition, where the highest output machine produced 147% of the tidal volume of the lowest output machine. CONCLUSIONS: All machines deviate significantly in volume output and ventilation regulation. These differences depend on ventilation type, respiratory force, and patient behavior, preventing the creation of a simple conversion table between ventilator models. Universal neonatal tidal volume targets for mechanical ventilation cannot be transferred from one ventilator to another without considering necessary adjustments.
Asunto(s)
Benchmarking , Cuidado Intensivo Neonatal/normas , Pulmón/fisiología , Respiración Artificial/instrumentación , Ventiladores Mecánicos/normas , Humanos , Recién Nacido , Modelos Anatómicos , Respiración Artificial/normas , Respiración Artificial/estadística & datos numéricos , Volumen de Ventilación Pulmonar , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & control , Ventiladores Mecánicos/estadística & datos numéricosRESUMEN
AIM: Measuring cerebral oxygenation using near-infrared spectroscopy (NIRS) has taken on an increasingly important role in the field of neonatology. Several companies have already developed commercial devices, and more publications are reporting absolute boundary values or percentiles for neonates. We compared four commercially used devices to discover whether they provided consistent results in the same patients. METHODS: We recruited nine preterm infants and tested them for 2 h, using sensors from two different devices. The measurements were carried out six times on each child, so that all four devices were compared with each other. A total of 54 measurements were conducted. The following devices were compared: the NIRO 200 (Hamamatsu Photonics K.K), the INVOS 5100c (Somanetics), the Fore-Sight (CAS Med.) and the SenSmart X-100 (NONIN). RESULTS: The cerebral tissue oxygenation data yielded by the individual devices differed significantly from each other, ranging from a minimum difference of 2.93% to a maximum difference of 12.66%. CONCLUSION: The commercially available NIRS devices showed highly significant differences in local cerebral tissue oxygenation levels, to the extent that the industry cannot agree on uniform and reproducible standards. Therefore, NIRS should only be used for trend measurements in preterm infants.
Asunto(s)
Encéfalo/metabolismo , Oxígeno/metabolismo , Espectroscopía Infrarroja Corta/instrumentación , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , MasculinoRESUMEN
BACKGROUND: Dead space is the part of the airway where no gas exchange takes place. Any increase in dead space volume has a proportional effect on the required tidal volume and thus on the risk of ventilation-induced lung injury. Inserts that increase dead space are therefore not used in small preterm infants. This includes end-tidal CO2 measurement. OBJECTIVE: The aim of this study was to investigate the effect of the end-tidal CO2 measurement adapter on ventilation. METHODS: In an experimental setup, an end-tidal CO2 measurement adapter, three different pneumotachographs (PNT-A, PNT-B, PNT-Neo), and a closed suction adapter were combined in varying set-ups. The time required for CO2 elimination by a CO2-flooded preterm infant test lung was measured. RESULTS: PNT-A prolonged CO2 elimination time by 0.9 s (+3.3%), Neo-PNT by 3.2 s (+11.6%) and PNT-B by 9.0 s (+32.7%). The end-tidal CO2 measurement adapter prolonged the elimination time by an additional second without the pneumotachograph (+3.6%) and in combination with PNT-A (+3.1%) and PNT-Neo (+3.1%). In conjunction with PNT-B, the end-tidal CO2 measurement adapter reduced the elimination time by 0.3 seconds (-1%). The use of a closed suction adaptor increased the CO2 elimination time by a further second with PNT-Neo (+3.1%) and by an additional two seconds with no flow sensor (+6.9%), with PNT-A (+6.4%) and with PNT-B (+5.5%). CONCLUSION: The flow sensor had the greatest influence on ventilatory effort, while end-tidal CO2 measurement had only a moderate effect. The increased ventilatory effort levied by the CO2 measurement was dependent on the flow sensor selected. The use of closed suctioning more negatively impacted ventilatory effort than did end-tidal CO2 measurement.
Asunto(s)
Dióxido de Carbono , Recien Nacido Prematuro , Lactante , Recién Nacido , Humanos , Espacio Muerto Respiratorio , Pulmón , Volumen de Ventilación Pulmonar , Respiración ArtificialRESUMEN
In general, premature babies are discharged home when they reach full self-feeding. We established a discharge management protocol which allows for discharging late preterm babies with a feeding tube if necessary. This retrospective study included 108 preterm infants (34+ weeks) born in 2019 and 2020. The preterm infants discharged with a feeding tube (n = 32) were born at 35.23 weeks' gestation (±0.884), with a birth weight of 2423 g (±375.1), and were discharged at 7.22 days (±3.63) and had a weight of 3466 g (±591.3) at the first outpatient visit around the expected birth date. The preterm infants discharged without a feeding tube were born at 35.97 weeks' gestation (±0.702) with a birth weight of 2589 g (±424.84), discharged home at 6.82 days (±7.11) and a weight of 3784 g (±621.8) at the first outpatient visit. The gestational week and birth weight were statistically significantly different between the groups, with a p-value of <0.001 for each, and the length of hospital stay (p = 0.762) and weight at follow-up (p = 0.064) did not significantly differ. No infant required tube-feeding at the time of the first outpatient visit, i.e., the time of expected birth. Therefore, with well-thought-out management, it is possible and safe to discharge preterm infants home with a feeding tube.
RESUMEN
INTRODUCTION: Preterm infants close to viability commonly require mechanical ventilation (MV) for respiratory distress syndrome. Despite commonly used lung-sparing ventilation techniques, rapid lung expansion during MV induces lung injury, a risk factor for bronchopulmonary dysplasia. This study investigates whether ventilation with optimized lung expansion is feasible and whether it can further minimize lung injury. Therefore, optimized lung expansion ventilation (OLEV) was compared to conventional volume targeted ventilation. METHODS: Twenty preterm lambs were surgically delivered after 132 days of gestation. Nine animals were randomized to receive OLEV for 24 h, and seven received standard MV. Four unventilated animals served as controls (NV). Lungs were sampled for histological analysis at the end of the experimental period. RESULTS: Ventilation with OLEV was feasible, resulting in a significantly higher mean ventilation pressure (0.7-1.3 mbar). Temporary differences in oxygenation between OLEV and MV did not reach clinically relevant levels. Ventilation in general tended to result in higher lung injury scores compared to NV, without differences between OLEV and MV. While pro-inflammatory tumor necrosis factor-α messenger RNA (mRNA) levels increased in both ventilation groups compared to NV, only animals in the MV group showed a higher number of CD45-positive cells in the lung. In contrast, mean (standard deviations) surfactant protein-B mRNA levels were significantly lower in OLEV, 0.63 (0.38) compared to NV 1.03 (0.32) (p = .023, one-way analysis of variance). CONCLUSION: In conclusion, a small reduction in pulmonary inflammation after 24 h of support with OLEV suggests potential to reduce preterm lung injury.
Asunto(s)
Animales Recién Nacidos , Pulmón , Respiración Artificial , Lesión Pulmonar Inducida por Ventilación Mecánica , Animales , Ovinos , Lesión Pulmonar Inducida por Ventilación Mecánica/prevención & control , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Pulmón/fisiopatología , Modelos Animales de Enfermedad , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , FemeninoRESUMEN
OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.
Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Pulmón , Ultrasonografía , Humanos , Recién Nacido , Europa (Continente) , Ultrasonografía/métodos , Pulmón/diagnóstico por imagen , Encuestas y Cuestionarios , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico por imagen , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Pautas de la Práctica en Medicina/estadística & datos numéricosRESUMEN
AIM: A role of caspase-2 in chemotherapy-induced apoptosis has been suggested. Our study aimed to evaluate the prognostic and predictive importance of caspase-2 isoforms in breast cancer patients. MATERIALS & METHODS: Caspase-2L and -2S transcript levels were determined in paired tumor and non-malignant control tissues from 64 patients after neoadjuvant chemotherapy and 100 pretreatment patients (general set) by real-time PCR with absolute quantification. RESULTS: Low but statistically significant upregulation of caspase-2L in tumor versus control tissues was observed in both sets. Significant associations of the levels of caspase-2L, -2S or S/L ratio with clinical prognostic factors were observed. However, none of these associations were confirmed in both sets. Levels of caspase-2 isoforms or the S/L ratio did not significantly associate with progression-free survival in the general set or with chemotherapy response in the neoadjuvant set. CONCLUSION: Our results suggest that the role of caspase-2 isoforms in the progression of breast cancer may considerably differ between pre- and post-chemotherapy patients.
Asunto(s)
Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Caspasa 2/metabolismo , Cisteína Endopeptidasas/metabolismo , ARN Mensajero/metabolismo , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/mortalidad , Caspasa 2/genética , Quimioterapia Adyuvante , Cisteína Endopeptidasas/genética , Femenino , Frecuencia de los Genes , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Estimación de Kaplan-Meier , Persona de Mediana Edad , Terapia Neoadyuvante , ARN Mensajero/genética , Análisis de Secuencia de ADN , Regulación hacia ArribaRESUMEN
Because of its simplicity, pulse oximetry plays a ubiquitous role in neonatology. Its measurements are based on the absorption of light by hemoglobin. Ambient light can affect these values, therefore algorithms are designed to compensate for constant ambient light. Modern light-emitting diodes often flicker at a very high frequency. Such flickering ambient light can lead to significant measurement errors in saturation. To present a novel way in which light-emitting diodes influence the function of pulse oximeters and to demonstrate mathematically that a stroboscopic effect may well be responsible for this disturbance. Using publicly available data, a mathematical model of a pulse oximeter with a calibration curve and a proprietary measurement algorithm was created. This was used to simulate saturation measurements in flickering ambient light. To do this, photopletysmograms for red and infrared light at 98% oxygen saturation were mathematically superimposed on the light emission from an examination lamp used in the intensive care unit. From these results, presumable saturation measurements from a pulse oximeter were extrapolated. The light-emitting diodes in the examination lamp flicker at 207 Hz. The pulsating light from the light-emitting diodes causes superimposition of the photoplethysmogram due to the stroboscopic effect. With increasing brightness, the saturation dropped to 85% and the pulse rate to 108 bpm. The pulsed light of light-emitting diodes can distort pulse oximetry measurements. The stroboscopic effect leads to low saturation values, which can lead to the risk of blindness in premature infants due to excessive oxygenation.
Asunto(s)
Oximetría , Oxígeno , Recién Nacido , Lactante , Humanos , Oximetría/métodos , Recien Nacido Prematuro , Hemoglobinas , AlgoritmosRESUMEN
BACKGROUND: Phl p 5 is a major allergen of Timothy grass (Phleum pratense). A recombinant native Phl p 5 has already been used in clinical trials of allergen-specific immunotherapy as a component of a cocktail of allergens. Recombinant hypoallergenic allergens should further improve the treatment by reducing the risk of anaphylactic reactions at an increased therapeutic dosage. Native Phl p 5 is formed by α-helical regions separated by regions containing prolines. In order to generate hypoallergenic mutants, we studied the effect of proline mutations in single and multiple regions. METHODS: All mutants were analyzed by IgE inhibition assays and size exclusion chromatography with on-line mass determination. Selected mutants were additionally analyzed by field-flow fractionation, dynamic light scattering, circular dichroism spectroscopy, basophil activation and T-cell proliferation assays. RESULTS: Variants lacking prolines in a single region were obtained as soluble monomers. Six of eight molecules showed a slightly reduced IgE-binding capacity. Mutants carrying proline deletions in multiple regions formed monomers, dimers or insoluble aggregates. The mutant MPV.7 with five proline deletions and a substitution of proline 211 to leucine is monomeric, shows a strongly diminished IgE binding and maintains T-cell reactivity. The hydrodynamic radius and the content of the α-helical structure of MPV.7 are well comparable with the wild-type allergen. CONCLUSIONS: The hypoallergenic Phl p 5 variant MPV.7 combines multiple proline deletions with a substitution of proline 211 to leucine and meets basic demands for a pharmaceutical application. MPV.7 is a promising candidate for grass pollen immunotherapy with a cocktail of recombinant hypoallergens.
Asunto(s)
Alérgenos/genética , Alérgenos/inmunología , Proteínas de Plantas/genética , Proteínas de Plantas/inmunología , Polen/genética , Polen/inmunología , Adulto , Anciano , Sustitución de Aminoácidos , Basófilos/inmunología , Desensibilización Inmunológica/métodos , Femenino , Humanos , Inmunoglobulina E/metabolismo , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Proteínas Mutantes/química , Proteínas Mutantes/genética , Proteínas Mutantes/inmunología , Phleum/genética , Phleum/inmunología , Proteínas de Plantas/química , Prolina/genética , Multimerización de Proteína , Estructura Secundaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica Estacional/terapia , Eliminación de Secuencia , Solubilidad , Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: Invasive mechanical ventilation poses a strong risk factor for the development of chronic lung disease in preterm infants. A reduction of the dead space as part of the total breathing volume would reduce the ventilation effort and thereby lower the risk of ventilator-induced lung injuries. In this experimental study, we compared the efficacy of mechanical dead space washout via uncontrolled and controlled leakage flow in their ability to eliminate CO2 during conventional ventilation in preterm infants. METHODS: Three frequently used neonatal ventilators, operating under standard conventional ventilating parameters, were individually connected to a test lung. To maintain a constant physiological end-expiratory pCO2 level during ventilation, the test lung was continuously flooded with CO2 . A side port in the area of the connector between the endotracheal tube and the flow sensor allowed breathing gas to escape passively or in a second experimental setup, regulated by a pump. Measurements of end-expiratory pCO2 were taken in both experiments and compared to end-expiratory pCO2 levels of ventilation without active dead space leakage. RESULTS: Following dead space washout, a significant reduction of end-expiratory pCO2 was attained. Under conditions of uncontrolled leakage, the mean decrease was 14.1% while controlled leakage saw a mean reduction of 16.1%. CONCLUSION: Washout of dead space by way of leakage flow is an effective method to reduce end-expiratory pCO2 . Both controlled and uncontrolled leakage provide comparable results, but precise regulation of leakage allows for a more stable ventilation by preventing uncontrolled loss of tidal volume during inspiration.
Asunto(s)
Recien Nacido Prematuro , Espacio Muerto Respiratorio , Dióxido de Carbono/fisiología , Humanos , Lactante , Recién Nacido , Pulmón , Respiración Artificial/métodos , Espacio Muerto Respiratorio/fisiología , Volumen de Ventilación PulmonarRESUMEN
OBJECTIVE: In continuous positive airway pressure (CPAP) devices, pressure can be generated by two different mechanisms: either via an expiratory valve or by one or more jets. Valved CPAP devices are referred to as constant-flow devices, and jet devices are called variable-flow devices. Constant-flow CPAP devices are said to reduce the imposed work of breathing due to lower breath-dependent pressure fluctuations. The present study investigates the performance of various constant- and variable-flow CPAP devices in relation to breath-dependent pressure fluctuations. DESIGN: Experimental study comparing the pressure fluctuations incurred by seven neonatal CPAP devices attached to an active neonatal lung model. METHODOLOGY: Spontaneous breathing was simulated using a tidal volume of 6 ml at pressure levels of 5, 7, and 9 mbar. The main outcomes were respiratory pressure fluctuations, tidal volume, and end-expiratory pressure. RESULTS: All CPAP devices tested showed respiratory pressure fluctuations, varying from 0.631 to 3.466 mbar. The generated tidal volume correlated significantly with the pressure fluctuations (r = -0.947; p = 0.001) and varied between 5.550 and 6.316 ml. CPAP devices with jets showed no advantage over CPAP devices with expiratory valves. End-expiratory pressure in the nose deviated from the set pressure between -1.305 and 0.644 mbar and varied depending on whether the pressure was measured in the device or in the tube extending to the nose. CONCLUSION: During standard spontaneous breathing, breath-dependent pressure fluctuations in constant- and variable-flow devices are comparable. Pressure measurements taken in the tubing system can lead to a considerable deviation of the applied pressure.
Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Ventiladores Mecánicos , Humanos , Recién Nacido , Nariz , Respiración , Volumen de Ventilación PulmonarRESUMEN
Objective: Very low birthweight (VLBW) infants have an increased risk of mortality and frequently suffer from complications, which affects parental occupational balance. Occupational balance is the satisfaction with one's meaningful activities, which include everyday activities that people need to, want to, and are expected to do. In contrast to work-life balance, the construct of occupational balance addresses different activities equally and it applies to all persons, regardless of whether they are working or not. Parental occupational balance might be related to parents' and VLBW infants' health. Therefore, the objective of this study was to investigate associations between parental occupational balance, subjective health, and clinical characteristics of VLBW infants. Methods: A cross-sectional multicenter study was conducted in six Austrian neonatal intensive care units. Occupational balance and subjective health of parents of VLBW infants were assessed with six self-reported questionnaires. The following clinical characteristics of VLBW infants were extracted from medical records: gestational age, birthweight, Apgar scores, Clinical Risk for Babies II Score, and complications of prematurity. Spearman's rank coefficients were calculated. Results: In total, 270 parents, 168 (62%) female and their VLBW infants, 120 (44%) female, were included in this study. Parents' mean age was 33.7 (±6.0) years, mean gestational age of VLBW infants was 27 + 3 (±2) weeks. Associations between parental occupational balance, subjective health, and clinical characteristics of VLBW infants were identified (r s = 0.13 - 0.56; p ≤ 0.05), such as the correlation between occupational areas (r s = 0.22, p ≤ 0.01), occupational characteristics (r s = 0.17, p = 0.01), and occupational resilience (r s = 0.18, p ≤ 0.01) with bronchopulmonary dysplasia of VLBW infants. Conclusion: Occupational balance is associated with parents' and VLBW infants' health. Interventions to strengthen parental occupational balance might increase parental health and thereby also improve health and developmental outcomes of their VLBW infants.
RESUMEN
Continuous positive airway pressure (CPAP) systems for preterm infants work with conventional ventilators or use a jet ventilation system. It is assumed that the most important advantage of jet-CPAP systems is a lower expiratory resistance (R(E) ). We investigated the R(E) of seven different CPAP systems. We studied two primary-care CPAP systems, three jet-CPAP generators, and two conventional CPAP devices. All devices were adjusted at 6 mbar and connected with a test lung simulating a standardized expiration volume. Maximum pressure increase during expiration was measured and maximum R(E) was calculated. In primary-care CPAP devices, the maximum R(E) of the Benveniste valve was 9.7 mbar/L/s (SD 1.2) while that of the Neopuff was 102.8 mbar/L/s (SD 7.9) (P < 0.01). In jet-CPAP devices, the R(E) of the Infant Flow was 6.8 mbar/L/s (SD 1.7), the one of the Medijet REF 1000 was 43.5 mbar/L/s (SD 1.5), and that of the Medijet REF 1010 was 36.7 mbar/L/s (SD 0.3) (P < 0.01). In conventional CPAP systems, the R(E) of the Baby Flow was 29.7 mbar/L/s (SD 1.1) and that of the Bubble CPAP was 37.1 mbar/L/s (SD 4.3) (P < 0.01). All CPAP devices created an R(E). Jet-CPAP devices did not produce lower R(E) than conventional CPAP devices.