Laryngeal sensitivity in the neonatal period: from bench to bedside

Laryngeal sensitivity in the newborn has been a subject of great interest for both researchers and clinicians for a number of years. From a clinical standpoint, laryngeal sensitivity is essential for both preventing foreign substances from entering into the lower airway and for finely tuning upper airway resistance. However, heightened reflexes originating from the laryngeal receptors in newborns and infants, due to neural immaturity, can lead to potentially dangerous cardiorespiratory events. The latter have been linked to apneas of prematurity, apparent life-threatening events, and sudden infant death syndrome (SIDS). From a physiological standpoint, many mechanisms pertaining to reflexes originating from laryngeal receptors are yet to be fully understood. This short review is an attempt to summarize current knowledge on laryngeal sensitivity and its potential consequences upon control of breathing abnormalities encountered within the first weeks of life.     

Effect of posture on respiratory function and drive in preterm infants prior to discharge

Our objective was to determine the effect of posture on respiratory function and drive in prematurely born infants immediately prior to discharge. Twenty infants (6 oxygen-dependent), median gestational age 29 weeks (range, 25-32), were studied at a median postconceptional age (PCA) of 36 weeks (range, 33-39). On 2 successive days, infants were studied both supine and prone; each posture was maintained for 3 hr. The order on each day in which postures were studied was randomized between infants. At the end of each 3-hr period, tidal volume (Vt), inspiratory (Ti) and expiratory (Te) time, respiratory rate, and minute ventilation were measured. In addition, respiratory drive was assessed by measuring the pressure generated in the first 100 msec of an imposed airway occlusion (P(0.1)), and respiratory muscle strength was assessed by recording the maximum inspiratory pressure (Pimax) generated against an occlusion which was maintained for at least five breaths. Overall, tidal volume was higher (P < 0.05), but respiratory rate (P < 0.05), P(0.1) (P < 0.05), and Pimax (P < 0.05) were lower in the prone compared to the supine position. There were no significant differences in Ti or Te between the two postures. In oxygen-dependent infants only, minute volume was higher in the prone position (P < 0.05). In conclusion, posture-related differences in respiratory function are present in prematurely born infants studied prior to neonatal unit discharge.     

Assessment of tidal volume over time in preterm infants using respiratory inductance plethysmography

Non-invasive techniques for monitoring ventilation in infants are widely used in short-term laboratory studies but have not been evaluated in routine clinical settings. To determine whether respiratory inductance plethysmography (RIP) can provide reproducible measurements of tidal volume (V_T) in premature infants over an extended period of time, we monitored respiration in eight healthy preterm infants over 4.9 ± 1.0 hours (mean ± SD). The algebraic sum (Sum) of rib cage (RC) and abdominal (AB) motion signals (obtained by RIP) was calculated and presented over the entire recording period as percent of an initial 5 minute calibration period. V_T was simultaneously measured with a nasal mask pneumotachometer with infants in prone and supine positions during active and quiet sleep. Infants were studied in the morning (am ) and again in the afternoon (pm ). Between these studies they were returned to the nursery wearing the RIP in a continuous record mode. For all patients there was a significant linear relationship between V_T (in mL measured by pneumotachometer) and Sum (in % of calibration value, RIP). Neither the slope of the relationship (0.074 ± 0.03 in am vs. 0.071 ± 0.02 in pm ), nor its variability as measured by standard error of the estimate (SEE) (2.3 ± 0.5 in am vs. 2.5 ± 0.8 in pm ) changed significantly from am to pm . The relationship between V_T and Sum, as well as the variability of that relationship, was not altered by position, asynchrony of RC and AB, respiratory rate, or percent RC contribution to Sum. We conclude that RIP produces consistent measurements of respiratory effort over 5 hours in healthy preterm infants without need for recalibration and is not affected by routine care. Pediatr. Pulmonol. 1997; 23:429–433. © 1997 Wiley-Liss, Inc.     

Biochemical,clinical, and morphologic studies on lungs of infants with bronchopulmonary dysplasia

We correlated clinical, biochemical, and morphologic findings in the lungs of 48 infants dying of either bronchopulmonary dysplasia (BPD) or hyaline membrane disease (HMD) to obtain a better idea of the disease process. The infants ranged from 24 weeks of gestation to 1½ postnatal years. The lungs of BPD and HMD infants had higher contents of DNA, alkali-soluble protein, hydroxyproline, and desmosine, as well as increased concentrations of DNA, hydroxyproline, and desmosine when compared with the lungs of 72 control infants. BPD was classified histologically into 4 groups: Group I was a phase of acute lung injury; Group II the proliferative phase; Group III the phase of early repair; and Group IV the phase of late repair. We saw a significant increase in hydroxyproline concentration in Groups II and III. The ratio of type VIII collagen decreased in BPD Groups II to IV. Desmosine was significantly higher only in Group III than in controls. When the pathological classification was related to biochemical and clinical features of BPD, the classification showed dependence on the number of days the infant survived postnatally and not on the gestational age of the infant. The number of days on assisted ventilation was a slightly better predictor of the disease classification than days on > 60% oxygen. A statistical model correctly predicted the pathologic classification 83% of the time. Pediatr Pulmonol. 1996; 22:215–229. © 1996 Wiley-Liss, Inc.     

The effect of nasal occlusion on the initiation of oral breathing in preterm infants

The ability to switch from nasal to oral breathing in response to nasal obstruction is crucial for survival, and has been suggested to be an important mechanism in preventing sudden infant death syndrome (SIDS). To know whether the ability to switch from nasal to oral breathing is uniformly present during the early neonatal period, we examined the effects of slow and fast nasal occlusions on the establishment of oral breathing in preterm infants. Slow occlusions were used to mimic more closely occlusions occurring spontaneously. We studied 17 healthy preterm infants [birth weight, 1830 ± 27 g (mean ± SE); study weight, 1800 ± 109 g; gestational age, 32 ± 1 weeks; postnatal age, 12 ± 2 days]. We used a nosepiece with a nasal occluder and a flow-through system to measure ventilation. A CO₂, sampling catheter at the mouth was used to detect oral breathing. Of 58 occlusions, 29 were slow [resistance increasing slowly from 0 to infinite (occlusion)], and 29 were fast (infinite elastance applied in <1 sec). Oral breathing was always established following slow and fast occlusions. In 44% of the slow occlusions, oral breathing started before complete occlusion. Arousal was observed in 12/58 (17%) of all occlusions, occurring primarily after initiation of oral breathing. Oxygen saturation and respiratory rate decreased significantly following occlusions, from 96 i 0.6 to 87 ± 1.2% and 49 ± 2.8 to 38 ± 2 breaths/min, respectively. These findings suggest (1) preterm infants usually establish oral breathing in response to nasal airway occlusion; (2) this switch to oral breathing is preceded by a decrease in O₂ saturation and in respiratory frequency; and (3) arousal does not always precede the switch to oral breathing as is traditionally accepted. Pediatr Pulmonol. 1994;18:374–378. ©1994 Wiley-Liss, Inc.     

A comparison of pneumogram recordings in infants in the hospital and at home

It is not known how environment affects the ventilatory pattern of infants during sleep. Pneumogram recordings of ventilatory pattern and electrocardiograms are performed both in the hospital and at home. However, it is not known if the data obtained in these two settings are comparable. Therefore, 12-hour overnight PNGs were recorded in the hospital and at home within 10 days on 64 infants in three diagnostic categories: apnea of infancy, apnea of prematurity, and siblings of victims of sudden infant death syndrome. Pneumograms were quantitated for total sleep time (TST in minutes), longest apnea (in seconds), periodic breathing, and the total duration of apneas lasting 6 seconds or longer. TST was longer at home for the total group (p less than 0.001) and for the apnea of infancy group (p less than 0.005). No other differences were found between hospital and home recordings for any parameter. There was no difference in the number of abnormal pneumograms recorded in the hospital and at home. Therefore, hospital and home pneumogram recordings are equally sensitive and accurate.     

Diagnostic accuracy of the 12-lead electrocardiogram in the first 48 hours of life for newborns of a parent with congenital long QT syndrome

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A Novel Missense Mutation Causing a G487R Substitution in the S2–S3 Loop of Human ether‐à‐go‐go‐Related Gene Channel

hERG(G487R) Channel . Introduction: Mutations of human ether‐à‐go‐go‐related gene (hERG), which encodes a cardiac K⁺ channel responsible for the acceleration of the repolarizing phase of an action potential and the prevention of premature action potential regeneration, often cause severe arrhythmic disorders. We found a novel missense mutation of hERG that results in a G487R substitution in the S2–S3 loop of the channel subunit [hERG(G487R)] from a family and determined whether this mutant gene could induce an abnormality in channel function. Methods and Results: We made whole‐cell voltage‐clamp recordings from HEK‐293T cells transfected with wild‐type hERG [hERG(WT)], hERG(G487R), or both. We measured hERG channel‐mediated current as the “tail” of a depolarization‐elicited current. The current density of the tail current and its voltage‐ and time‐dependences were not different among all the cell groups. The time‐courses of deactivation, inactivation, and recovery from inactivation and their voltage‐dependences were not different among all the cell groups. Furthermore, we performed immunocytochemical analysis using an anti‐hERG subunit antibody. The ratio of the immunoreactivity of the plasma membrane to that of the cytoplasm was not different between cells transfected with hERG(WT), hERG(G487R), or both. Conclusion: hERG(G487R) can produce functional channels with normal gating kinetics and cell‐surface expression efficiency with or without the aid of hERG(WT). Therefore, neither the heterozygous nor homozygous inheritance of hERG(G487R) is thought to cause severe cardiac disorders. hERG(G487R) would be a candidate for a rare variant or polymorphism of hERG with an amino acid substitution in the unusual region of the channel subunit. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1246–1253, November 2012)     

氧化应激所致C2C12肌源细胞核仁损伤的分子机制

目的探讨氧化应激诱导细胞核仁损伤的分子机制.方法向传代培养的C2C12肌源细胞中加入0.5mmol/L过氧化氢以模拟氧化应激.结果甲苯胺兰染色发现正常C2C12细胞可见一个位于中央的,浓染致密的核仁颗粒.过氧化氢处理后3h,可见明显的核仁分离,处理6h最为明显.细胞总蛋白质合成能力分析发现过氧化氢处理后6h细胞总蛋白质合成能力显著下降(与正常对照比P＜O.05),并持续至24h.免疫印迹检测核仁素(又称C23)发现,过氧化氢处理1h后可见-80kDa条带,而其110kDa主带明显减弱,过氧化氢处理6h和12h最为明显.用脂质体将核仁素反义核酸导入细胞后24h,免疫印迹发现核仁素表达明显被抑制,同时也可观察到细胞总蛋白合成能力下降及明显的核仁分离.结论氧化应激通过诱导核仁蛋白质核仁素的裂解并使其110kDa全长分子的量减少,而导致C2Cl2细胞核仁损伤.     

维生素C和维生素E对急性糖负荷致原发性高血压血管内皮功能损害的保护作用

为探讨急性糖负荷对高血压病患者内皮依赖性血管舒张功能的影响及急性期维生素C和维生素E对血管内皮功能的保护作用。选取 39例高血压病患者和 2 1例正常血压的对照者随机各分为 3组 (共 6组 ) ,禁食 12h后分别口服 75g葡萄糖 (糖负荷组 )、口服 75g葡萄糖同时服维生素C(维生素C组 )和口服 75g葡萄糖同时服维生素C和维生素E(维生素C和E组 )。在服糖前及服糖后 1、2、3h采用高分辨率血管外彩超检测相同时间点的肱动脉血流介导的内皮依赖性血管舒张功能 ,并分别测定血清抗氧化产物。在三组受试者中 ,高血压病组的基础内皮功能均较正常组下降 ,但未达到统计学意义 ;急性糖负荷明显损伤血管内皮功能 (9.4 8%± 3.33%比 13.0 9%±6 .78% ,P <0 .0 5 ) ,且高血压病患者较正常对照者更为显著 (9.4 8%± 3.33%比 14 .2 0 %± 6 .4 8% ,P <0 .0 5 )。抗氧化维生素对糖负荷所致的血管内皮功能的损害呈剂量依赖性的保护作用。由此可见 ,急性高血糖能造成血管内皮功能的损害 ,这种损害在原发性高血压患者中尤为明显 ,并能由高浓度的维生素C和维生素E逆转。     

Dynamics of the Enteric Virome in a Swine Herd Affected by Non-PCV2/PRRSV Postweaning Wasting Syndrome

A commercial pig farm with no history of porcine circovirus 2 (PCV2) or porcine reproductive and respiratory syndrome virus (PRRSV) repeatedly reported a significant reduction in body weight gain and wasting symptoms in approximately 20–30% of the pigs in the period between three and six weeks after weaning. As standard clinical interventions failed to tackle symptomatology, viral metagenomics were used to describe and monitor the enteric virome at birth, 3 weeks, 4 weeks, 6 weeks, and 9 weeks of age. The latter four sampling points were 7 days, 3 weeks, and 6 weeks post weaning, respectively. Fourteen distinct enteric viruses were identified within the herd, which all have previously been linked to enteric diseases. Here we show that wasting is associated with alterations in the enteric virome of the pigs, characterized by: (1) the presence of enterovirus G at 3 weeks of age, followed by a higher prevalence of the virus in wasting pigs at 6 weeks after weaning; (2) rotaviruses at 3 weeks of age; and (3) porcine sapovirus one week after weaning. However, the data do not provide a causal link between specific viral infections and the postweaning clinical problems on the farm. Together, our results offer evidence that disturbances in the enteric virome at the preweaning stage and early after weaning have a determining role in the development of intestinal barrier dysfunctions and nutrient uptake in the postweaning growth phase. Moreover, we show that the enteric viral load sharply increases in the week after weaning in both healthy and wasting pigs. This study is also the first to report the dynamics and co-infection of porcine rotavirus species and porcine astrovirus genetic lineages during the first 9 weeks of the life of domestic pigs.     

Evolution of Functional Exercise Capacity in Lung Transplant Patients With and Without Bronchiolitis Obliterans Syndrome: A Longitudinal Case–Control Study

Introduction

Bronchiolitis Obliterans Syndrome (BOS) is a debilitating disease with limited treatment options that threatens both the quality of life and long-term survival of lung transplant (LTx) recipients. This retrospective longitudinal case–control study was performed to compare the long-term functional evolution of LTx recipients with and without BOS.

Adipose tissue is influenced by hypoxia of obstructive sleep apnea syndrome independent of obesity

AimsObstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular risk and diabetes independent of obesity. We investigated whether adipose tissue dysfunction is exacerbated due to increased tissue hypoxia.MethodsAdipose tissue (AT) oxygenation was measured with a Clarke-type electrode (p_ATO₂) in 16 men with OSAS before and after 4 months of continuous positive airway pressure therapy (CPAP) and in BMI-matched controls. Oxygenation was simultaneously monitored in arterial blood by pulse oximetry (SaO₂); mixed blood in AT microcirculation by reflectance spectroscopy (S_ATO₂) along with blood flow. Markers of hypoxia, adipo- and angiogenesis, inflammation and fibrosis were analysed in AT and serum.ResultsOSAS subjects were more insulin resistant. Despite lower arterial SaO₂ (95.4 ± 1.3% vs. 97.1 ± 1.6%, P = 0.013) in subjects with OSAS, there was no difference in the oxygen content of AT microcirculation (61.6 ± 18.4 vs. 72.2 ± 7.0%, P = 0.07) or p_ATO₂ (49.2 ± 7.5 vs. 50.4 ± 14.7 mmHg, P = 0.83) between groups. Resting AT blood flow was higher in OSAS compared to controls (108.5 ± 22.7 vs. 78.9 ± 24.9 au, P < 0.005) and strongly associated with inflammation markers IL-6 and MCP-1. AT of OSAS subjects showed increased inflammation (TNFA P = 0.049) and fibrosis (COL3A1 P = 0.02), a trend of higher HIF1A expression (P = 0.06) and reduced adipogenesis (PPARG P = 0.006). After CPAP, only expression of the lipid deposition marker LPL increased (30%, P = 0.047).ConclusionsAdipose tissue of awake OSAS subjects appears no more hypoxic than adipose tissue of BMI-matched controls despite daytime hypoxaemia. Increased adipose tissue blood flow may be explained by an increased inflammatory response. We observe features of adipose dysfunction in subjects with OSAS, which attribute to increased cardiometabolic risk associated with this condition.