THE BRONCHOPULMONARY SYSTEM DAMAGE UNDER THE INFLUENCE OF IONIZING RADIATION EXPOSURE AND RADIONUCLIDES INHALATION IN THE CONDITIONS OF THE CHORNOBYL CATASTROPHE (SUMMARIZING OF 35 YEARS RESEARCH EXPERIENCE). / URAZhENNIa BRONKhOLEGENEVOÏ SYSTEMY VNASLIDOK VPLYVU IONIZUIuChOGO OPROMINENNIa TA INGALIaTsIINOGO NADKhODZhENNIa RADIONUKLIDIV V UMOVAKh ChORNOBYL'S'KOÏ KATASTROFY (UZAGAL'NENNIa DOSVIDU 35 ROKIV DOSLIDZhEN').

The review is devoted to the summarizing of 35 years of research of ionizing radiation exposure and radionuclidesinhalation influence on the bronchopulmonary system of clean-up workers of the Chornobyl NPP accident. Radiationand hygienic preconditions for the formation of chronic respiratory pathology are considered, taking into accountthe dosimetric data of irradiation of the bronchopulmonary system.The main clinical symptoms, features of disorders of pulmonary ventilation capacity and endoscopic forms of lesionsof the bronchopulmonary system of participants in the liquidation of the accident were determined.On the basis of pathomorphological, microbiological and immunological researches the pathomorphosis of chronicnonspecific lung diseases in the conditions of the Chernobyl catastrophe is proved.It is proved that under combined influence of external irradiation and inhalation of a fragmentary mixture ofradionuclides in the condition of the Chernobyl catastrophe, the bronchopulmonary system has become one of themain «targets¼-tissues, of realization of stochastic and nonstochastic effects.

Airway abnormalities in very early treated infantile-onset Pompe disease: A large-scale survey by flexible bronchoscopy.

Early enzyme replacement therapy (ERT) improve long-term outcomes in patients with infantile-onset Pompe disease (IOPD). Our cohort of patients with IOPD at Taipei Veterans General Hospital (TVGH) joined Taiwan Pompe newborn screening program from 2008, testing more than one million newborns until 2018. By 2010, we had established rapid diagnostic strategies. Now, the average age of ERT initiation starts at an average age of <10 days-old, the earliest group in the world. However, they still presented some airway problems. We present a retrospective study focused on airway abnormalities in these patients along 8 years of observation. Fifteen patients with IOPD, who received very early treatment at a mean age of 8.94 ± 3.75 days, underwent flexible bronchoscopy (FB) for dynamic assessment of the whole airway. Long-term clinical outcomes and relevant symptoms of the upper airway were assessed. All patients in the study had varying degrees of severity of upper airway abnormalities and speech disorders. The three oldest children (Age 94, 93, and 88 months, respectively) had poor movement of the vocal cords with reduced abduction and adduction and had silent aspiration of saliva through the glottis during respiration. This is the largest cohort study presented to date about airway abnormalities in very early treated patients with IOPD patients by FB. Despite very early treatment, we observed upper airway abnormalities in these IOPD patients. In IOPD, upper airway abnormalities seem inevitable over time. We suggest early and continuous monitoring for all IOPD patients, even with early and regular treatment.

Inflammatory mediators and lung abnormalities in HIV: A systematic review.

HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.

Fetal lung transcriptome patterns in an ex vivo compression model of diaphragmatic hernia.

BACKGROUND: The purpose of this study was to employ a novel ex vivo lung model of congenital diaphragmatic hernia (CDH) to determine how a mechanical compression affects early pulmonary development. METHODS: Day-15 whole fetal rat lungs (n = 6-12/group) from nitrofen-exposed and normal (vehicle only) dams were explanted and cultured ex vivo in compression microdevices (0.2 or 0.4 kPa) for 16 h to mimic physiologic compression forces that occur in CDH in vivo. Lungs were evaluated with significance set at P < 0.05. RESULTS: Nitrofen-exposed lungs were hypoplastic and expressed lower levels of surfactant protein C at baseline. Although compression alone did not alter the α-smooth muscle actin (ACTA2) expression in normal lungs, nitrofen-exposed lungs had significantly increased ACTA2 transcripts (0.2 kPa: 2.04 ± 0.15; 0.4 kPa: 2.22 ± 0.11; both P < 0.001). Nitrofen-exposed lungs also showed further reductions in surfactant protein C expression at 0.2 and 0.4 kPa (0.53 ± 0.04, P < 0.01; 0.69 ± 0.23, P < 0.001; respectively). Whereas normal lungs exposed to 0.2 and 0.4 kPa showed significant increases in periostin (POSTN), a mechanical stress-response molecule (1.79 ± 0.10 and 2.12 ± 0.39, respectively; both P < 0.001), nitrofen-exposed lungs had a significant decrease in POSTN expression (0.4 kPa: 0.67 ± 0.15, P < 0.001), which was confirmed by immunohistochemistry. CONCLUSIONS: Collectively, these pilot data in a model of CDH lung hypoplasia suggest a primary aberration in response to mechanical stress within the nitrofen lung, characterized by an upregulation of ACTA2 and a downregulation in SPFTC and POSTN. This ex vivo compression system may serve as a novel research platform to better understand the mechanobiology and complex regulation of matricellular dynamics during CDH fetal lung development.

Pathophysiology, evaluation, and management of sleep disorders in the mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) represent a heterogeneous group of lysosomal storage disorders, each one associated with a deficiency in one of the enzymes involved in glycosaminoglycan degradation. Sleep disorders are a frequent manifestation of all types of MPS. Underlying causes are diverse and comprised of both respiratory and central nervous system (CNS) abnormalities. Sleep disordered breathing such as obstructive sleep apnea and nocturnal hypoventilation can arise in patients with upper airway obstruction and/or with alterations in respiratory mechanics, causing restrictive pulmonary disease. MPS patients with CNS disease can also develop sleep disturbances unrelated to ventilatory impairments, often associated with severe behavioral problems or night-time epileptic seizures. The present review discusses the pathophysiology, evaluation, and management of sleep disorders in MPS based on information from a meeting on the brain in MPS, attended by an international group of experts (April 28-30, 2016, Stockholm, Sweden), and additional literature searches.

[Ventilation function disorder of flail arm syndrome].

OBJECTIVE: To study the features of ventilation function in patients with flail arm syndrome (FAS). METHODS: The clinical data of 351 patients with sporadic amyotrophic lateral sclerosis (ALS) from 2009 to 2013 were retrospectively reviewed. Among them, 329 were classical ALS and 22 were FAS. The differences of forced vital capacity (FVC) between FAS and classical ALS were analyzed. RESULTS: The percent predicted FVC (FVC% pred) values were (88.0 ± 9.5)% in FAS and (84.3 ± 16.8)% in classical ALS including 4 and 128 patients with abnormal FVC% pred (< 80%) in FAS and classical ALS, respectively. The FVC% pred levels were significantly higher in FAS subjects [(88.0 ± 9.5)%] than in classical ALS subjects of bulb [(80.0 ± 14.8)%] or those of upper limb [(80.8 ± 16.0)%] onset with duration over 12 months (All P < 0.05). The proportion of subjects with FVC% pred < 80% was statistically lower in FAS [18.2% (4/22)] than in both classical ALS of upper limb onset [42.8% (80/187); P = 0.037] and classical ALS with duration over one year [48.5% (48/99); P = 0.009]. CONCLUSIONS: Impaired ventilation function occurs less and later in FAS than that in classical ALS of upper limb onset with duration over one year, suggesting later and less requirement for non-invasive positive pressure ventilation treatment for FAS patients. Differentiation of FAS subjects from ALS helps assess prognosis and make treatment plan for these patients.

[Respiratory manifestations of Marfan's syndrome]. / Manifestations respiratoires du syndrome de Marfan.

Marfan's syndrome is a rare genetic disorder caused by a mutation of the gene FBN1, coding for the protein fibrillin-1. Cardiovascular, musculoskeletal and ophthalmic manifestations are the most commonly observed, but minor diagnostic criteria also include pulmonary manifestations. Pneumothorax, frequently relapsing, affects 5 to 11% of patients. Rib cage abnormalities (pectus excavatum or pectus carinatum) and apical blebs may contribute to their occurrence. Treatment does not require any specific procedure but there is an increased risk of recurrence. Pectus excavatum affects up to 60% of the patients, without any functional impairment in most cases. Surgery may be required (using the Nuss procedure) in case of cardiovascular or psychological symptoms. Marfan's syndrome is frequently associated with obstructive sleep apnoea, which may itself contribute to aortic dilatation. Some studies suggest a potential role of craniofacial abnormalities in the pathogenesis of sleep apnea in these patients. Pulmonologists should consider Marfan's syndrome when treating patients for recurrent spontaneous pneumothorax or rib cage abnormalities, since early detection of cardiac abnormalities improves the prognosis significantly.

Otolaryngologic manifestations of skeletal dysplasias in children.

This article reviews some of the otolaryngologic manifestations of skeletal dysplasias. Achondroplasia is discussed most comprehensively. Skeletal dysplasias are bone and cartilage disorders that disrupt the development of the long bones, craniofacial skeleton, and vertebral column, with the most notable characteristic being short stature. Children with skeletal dysplasias have various medical problems. These children often develop head and neck manifestations of their disorders. Hearing loss, middle ear disease, and respiratory difficulties are seen in these children. Otolaryngologists must be knowledgeable about these disorders to diagnose, treat, and appropriately refer children with skeletal dysplasias.

[Congenital lung malformations: natural history and pathophysiological mechanisms]. / Malformations pulmonaires congénitales: histoire naturelle et hypothèses pathogéniques.

INTRODUCTION: Congenital lung lesions comprise a broad spectrum of various malformations including congenital cystic adenomatoid malformation (CCAM), bronchopulmonary sequestration (BPS), congenital lobar emphysema, bronchial atresia and bronchogenic cyst. This review aims at the description of their natural history, and of the underlying pathophysiological mechanisms. STATE OF THE ART: Congenital lung lesions are frequently diagnosed antenatally and many remain asymptomatic after birth. In the absence of antenatal identification, they are usually revealed by the occurrence of infection. In some cases, spontaneous resolution of the malformation can occur. Different pathogenic hypotheses are discussed for the origin of these abnormalities, and common processes appear likely to all of these malformations. Factors involved in the process of branching seem to play a particularly important role. PERSPECTIVES: Prospective follow-up of operated and unoperated children would complete our knowledge about the natural history of these lesions. The contribution of experimental models has led to advances in the understanding of pathogenic mechanisms. Further studies are needed to identify the factors initiating the malformative process.

Congenital pulmonary malformations in pediatric patients: review and update on etiology, classification, and imaging findings.

Congenital pulmonary malformations represent a heterogeneous group of developmental disorders affecting the lung parenchyma, the arterial supply to the lung, and the lung's venous drainage. In both asymptomatic and symptomatic pediatric patients with congenital pulmonary malformations, the diagnosis of such malformations usually requires imaging evaluation, particularly in cases of surgical lesions for preoperative assessment. The goal of this article is to review the current imaging techniques for evaluating congenital pulmonary malformations and their characteristic imaging findings, which can allow differentiation among various congenital pulmonary malformations in pediatric patients.

Morphologic changes and methodological issues in the rabbit experimental model for diaphragmatic hernia.

Fetal lung development may be impaired by some congenital anomalies or in utero events. Animal models are used to understand the pathophysiology of these diseases and explore therapeutic strategies. Our group has an interest in the prenatal management of congenital diaphragmatic hernia (CDH). Isolated CDH remains associated with a 30% mortality because of lung hypoplasia and pulmonary hypertension. On day 23 of gestation (pseudoglandular stage) CDH was created in both ovarian-end fetuses (n= 28) in 14 time-mated pregnant white rabbits (hybrid of Dendermonde and New-Zealand White). At term (day 30) all survived operated fetuses and size-matched controls were harvested. Fetuses/lungs were assigned randomly to formalin fixation either under pressure of 25 cm H2O (CDH25 n=5; CTR25 n=5) or without (0 cm H2O (CDH0 n=7; CTR0 n=7). Fetuses and lungs were first weighed, and then the lungs were processed for morphometry. Pulmonary development was evaluated by lung-to-body weight ratio (LBWR) and airway and vascular morphometry. Surgical induction of CDH does reduce the LBWR to hypoplastic levels. The contralateral lung weight is 81% of what is expected, whereas the ipsilateral lung is only 46% of the normal. This was accompagnied by a loss of conducting airway generations, precisely, terminal bronchioles (TB), which were surrounded by less alveoli. The ipsilateral CDH lung demonstrated a thickened media in the peripheral arteries as well. As a result, in the severely hypoplastic ipsilateral lung, an airway fixation pressure of 25 H2O has no significant effect on the morphometric indices. The contralateral lung has a normal amount of alveoli around a single TB, which also behave like alveoli of the normal lung, i.e. expand under pressure fixation. The present study on severely hypoplastic lungs that never respirated, shows that in contrast to normal lungs, the morphometric indices are not significantly influenced by a difference in fixation pressure. Increasing fixation pressure seems to expand the lung only when sufficient alveolated parenchyma is present.

Era uma vez Ondina: relato de caso / Once upon a time Ondina...case report

Objetivo: relatar o caso de uma criança recém-nascida (RN) com comprometimento do sistema nervoso autônomo caracterizado por insensibilidade em detectar aumento de CO2 e diminuição de O2, denominado de Maldição de Ondina ou Síndrome da Hipoventilação Central Congênita ou Hipoventilação Alveolar Primária, com ênfase ao acompanhamento fonoaudiológico. Discussão: o diagnóstico de Maldição de Ondina deve ser aventado quando da presença de episódios de apneias em RN, sem que se consiga elucidar a causa e que seja afastada a possibilidade de crise epiléptica, distúrbio pulmonar e/ou cardíaco, lesão de tronco ou de outra região encefálica. A evolução respiratória desta criança foi de dependência do respirador por 24 horas até o final do terceiro mês de vida. Progressivamente, foi possível deixá-la com cateter nasal com fluxo contínuo de oxigênio enquanto se mantinha acordada, e respirador em modo controlado nos períodos de sono. O tratamento específico, com instalação de marca-passo diafragmático, é a única terapia existente até o momento.

Purpose: To report the case of a newborn (NB) with an autonomic nervous system disorder characterized by insensitivity to detect increased CO2 and decreased O2, referred to as Ondine's curse, Primary Hypoventilation Syndrome, or Congenital Central Alveolar Hypoventilation, with emphasis on speech therapy. Discussion: The diagnosis of Ondine's curse should be considered upon presence of episodes of apnea in newborns, with no clear indication of the cause and with no indications of seizures, severe pulmonary or cardiac injury of the brainstem or another cerebral region. The respiratory development characteristic of this child was being ventilator dependent for 24 hours a day until the end of the third month of life. Gradually, it was possible to leave the device with a continuous nasal oxygen flow while awake, and breathing with a ventilator under control during her periods of sleep. Specific treatment with installation of diaphragmatic pacemaker, is the only treatment available to date.

Objetivo: relatar el caso de un recién nacido (RN) con comprometimiento del sistema nervioso autónomo caracterizado por falta de sensibilidad para detectar el aumento de la emisión de CO2 y la disminución de O2, conocido como La Maldición de Ondina, o Síndrome de Hipoventilación Central Congénita o Hipoventilación Alveolar Primaria, con énfasis al acompañamiento fonoaudiológico. Discusión: El diagnóstico de la Maldición de Ondine debe ser considerado en la presencia de episodios de apnea en recién nacidos, sin que se pueda aclarar la causa y que sea rechazada la posibilidad de crisis epiléptica, trastorno pulmonar y/o cardiaco severo, lesión de tronco o otra región encefálica. El desarrollo respiratorio de este niño fue de dependencia del respirador por 24 horas hasta el final del tercer mes de vida. Progresivamente fue posible dejarla con un flujo nasal continuo de oxígeno mientras se mantenía despierta, y con respirador en forma controlada durante los períodos de sueño. El tratamiento específico con la instalación de un marcapasos diafragmático, es el único tratamiento disponible hasta la fecha.

Ultrasonographic assessment of laryngohyoid position as a predictor of dorsal displacement of the soft palate in horses.

Dorsal displacement of the soft palate is an important cause of poor performance in racehorses, yet its etiology is not fully understood. Diagnosis requires treadmill videoendoscopy, which is not widely available. The relationship of the larynx, the hyoid apparatus, and the remainder of the skull may be important in predisposing horses to dorsal displacement of the soft palate. We hypothesized that this relationship could be accurately assessed in unsedated horses through ultrasonographic examination. Fifty-six racehorses presented for evaluation of poor performance were subjected to treadmill videoendoscopy and resting ultrasonography. Using ultrasound-assisted percutaneous measures of laryngo-hyoid position, the relationship between selected anatomic structures and the occurrence of dorsal displacement of the soft palate was evaluated. A significant relationship was found between the depth of the basihyoid bone at rest and the occurrence of dorsal displacement of the soft palate at exercise (P = 0.03). Other measures of laryngohyoid position were not found to be associated with dorsal displacement of the soft palate. Thus, there is an association between the occurrence of dorsal displacement of the soft palate at exercise and the resting position of the basihyoid bone, whereby on average a more ventral location of the basihyoid bone is present in horses with dorsal displacement of the soft palate. The pathophysiologic implications of this finding are not fully understood but, based on our findings, ultrasound examination is of value in assisting in the diagnosis of dorsal displacement of the soft palate.

Significance of pulmonary artery size and blood flow as a predictor of outcome in congenital diaphragmatic hernia.

AIM: To determine if pulmonary artery size and blood flow have prognostic value in congenital diaphragmatic hernia (CDH). METHODS: Twenty-eight consecutive left-sided CDH patients treated according to a standard protocol with high frequency oscillatory ventilation (HFOV) + nitric oxide (NO) had right and left pulmonary artery (RPA, LPA) diameters, LPA/RPA diameter (L/R) ratios, and PA blood flows examined by echocardiography (EC) on days 0, 2, and 5 after birth and compared prospectively. RESULTS: Twenty-two patients (78.6%) survived. Of these, 15 required NO (NO-s), and seven did not (non-NO-s). All six patients that died required NO (NO-d). RPA in the NO-d group was significantly smaller than in the NO-s or non-NO-s groups on day 0 (2.90 +/- 0.41 vs. 3.40 +/- 0.49 or 4.01 +/- 0.43; P < 0.01, respectively). LPA in the NO-d group was significantly smaller than in the non-NO-s on day 0 (2.13 +/- 0.45 vs. 3.39 +/- 0.34; P < 0.01). L/R ratios in NO subjects were significantly smaller (NO-s 0.74 +/- 0.11; NO-d 0.73 +/- 0.11) than in non-NO-s subjects (0.84 +/- 0.03) on day 0 (P < 0.01). PA diameters and L/R ratios did not change significantly from day 0 to day 5 in all three groups. There was LPA flow on day 0 in all non-NO-s subjects, but none in all NO subjects. In the NO-s group, LPA flow was confirmed in 87% (13/15) on day 2 and in 100% on day 5, however, there was no LPA flow from day 0 to day 5 in any of the NO-d group. CONCLUSION: Our data indicate that PA diameters on day 0 and LPA flow are strongly prognostic in left-sided CDH and L/R ratio would appear to be a simple highly reliable indicator of the necessity for NO therapy.

Neuroanatomical basis of Sandifer's syndrome: a new vagal reflex?

Sandifer's syndrome is a gastrointestinal disorder with neurological features. It is characterized by reflex torticollis following deglutition in patients with gastroesophageal reflux and/or hiatal hernia. The authors believe that neurological manifestations of the syndrome are the consequence of vagal reflex with the reflex center in nucleus tractus solitarii (NTS). Three models for the neuroanatomical basis of the hypothetic reflex arc are presented. In the first one the hypothetic reflex arc is based on the classic hypothesis of two components nervus accessorius (n.XI) - radix cranialis (RC) and radix spinalis (RS) The nervous impulses are transmitted by nervus vagus (n.X) general visceral afferent (GVA) fibers to NTS situated in medulla oblongata, then by interneuronal connections on nucleus ambiguus (NA) and nucleus dorsalis nervi vagi (NDX). Special visceral efferent fibers (SVE) impulses from NA are in part transferred to n.XI ramus externus (RE) (carrying the majority of general somatic efferent (GSE) fibers) via hypothetic anastomoses in the region of foramen jugulare. This leads to contraction of trapezius and sternocleidomastoideus muscles, and the occurrence of intermittent torticollis. In the second suggested neuroanatomical model the hypothetic reflex arc is organized in the absence of n.XI RC, the efferent part of the reflex arc continues as NA, which is motor nucleus of nervus glossopharyngeus (n.IX) and n.X in this case while distal roots of n.XI that appear at the level of the olivary nucleus lower edge represent n.X roots. In the third presented model the hypothetic reflex arc includes no jugular transfer and could be realized via interneuronal connections directly from NTS to the spinal motoneurons within nucleus radicis spinalis nervi accessorii (NRS n.XI) or from NA to NRS n.XI. The afferent segment of the postulated reflex arc in all three models is mediated via n.X. We conclude that Sandifer's syndrome is a clinical manifestation of another vagal reflex that could be termed a "vagocervical" or "esophagocervical" reflex, based on the neuroanatomical hypotheses elaborated in this paper.

Respiratory systems abnormalities and clinical milestones for patients with amyotrophic lateral sclerosis with emphasis upon survival.

Respiratory system complications and abnormalities are common in patients with amyotrophic lateral sclerosis (ALS) and respiratory failure remains the most common cause of death. Extensive epidemiological longitudinal data have documented the extent, magnitude, and clinical course of these abnormalities, but few studies have provided objective information that can have prognostic significance for individual patients. In this study, the reported data represent results from a retrospective review of the medical records of 153 patients with ALS cared for at a single institution (The Penn State Milton S. Hershey Medical Center) over a 50-month period. Medical information in relation to respiratory system abnormalities and complications including pulmonary function measurements was extracted for data analyses. The intent of this review of longitudinal data from a relatively large cohort of patients with ALS was to identify clinically relevant easily-identifiable objective information and clinical milestones that could have potential prognostic significance when applied to individual patients. Demographic data including gender, survival outcome, respiratory symptoms, age of disease onset, and age at death were similar to previously published epidemiological studies: mean age at ALS disease onset was 58.9+/-12.7 years, and mean age at death was 66.7+/-10.8 years. For 151 patients with available data, the incidence of study defined respiratory complications included infectious pneumonia 13 (9%), venothromboembolism 9 (6%), and tracheostomy and mechanical ventilation 6 (4%). For 139 patients with serial measurements of forced vital capacity (FVC), median values for calculated rate of decline in FVC was 97 ml/30 days (2.4% predicted/30 days); 25% of patients had FVC rates of decline less than 52 ml/30 days (1.4% predicted/30 days) and 25% had rates of decline greater than 170 ml/30 days (4.4% predicted/30 days). Stratifying patients into two distinct clinical subgroups based upon rates of decline in FVC less than or greater than the median value of 97 ml/30 days identified an apparent two-fold increase in survival duration for ALS patients with slower rates of pulmonary physiology deterioration when referenced to either date of dyspnea onset or time from bi-level positive airway pressure (BiPAP) initiation (2.0+/-1.4 vs. 1.0+/-0.8 years; 1.9+/-1.5 vs. 1.0+/-0.9 years, respectively). We concluded that the correlation between clinically defined milestones, most importantly onset of dyspnea, and the calculated rate of decline in FVC represent obtainable and objective measurements that predict the natural course of respiratory muscle dysfunction in patients with ALS and provide important prognostic information in relation to individual patient survival duration.

A rudimentary epiglottis associated with Pierre Robin sequence.

Epiglottis anomaly associated with Pierre Robin sequence (PRS) is a rare occurrence. To the knowledge of the authors, this is the first reported case of epiglottic anomaly associated with PRS. Doctors should remain aware of this atypical presentation in a PRS patient, and the presented case highlights the clinical challenges that must be met to ensure effective treatment of the defect in terms of compromised respiration, swallowing and feeding.

Association between pulmonary hypoplasia and hypoplasia of arcuate nucleus in stillbirth.

OBJECTIVE: To investigate lung development and to correlate pulmonary hypoplasia with hypoplasia of the arcuate nucleus in stillbirths. STUDY DESIGN: We examined 26 stillbirths which occurred after 25 complete gestational weeks. The brainstem and the lung were the particular focus of this study. The brainstem was examined according to the protocol routinely followed in our Institute. As regards the lung examination, the development stage was evaluated on the basis of the correlation between lung and body weight (LW/BW), and according to microscopic parameters, that is, the presence of cartilaginous bronchi up to the distal level and the radial alveolar count (RAC). The normal reference values for the last 3 months of gestation correspond to >0.022 for LW/BW and from 2.2 to 4.4 for RAC. RESULTS: In 17 cases (65%) pulmonary hypoplasia was observed, characterized by a LW/BW value below 0.022 and RAC below 2.2. In nine cases (35%), microscopic examination of brainstem serial sections showed varying degrees of hypoplasia of the arcuate nucleus (ARCn). In eight cases (31%) the pulmonary hypoplasia was associated with hypoplasia/agenesis of the ARCn. CONCLUSIONS: This study demonstrated that in about a third of stillbirths there is a congenital hypodevelopment of both lung and arcuate nucleus. In these cases the ARCn hypoplasia would exert a negative effect on respiratory movements in utero and therefore on lung development. When the pulmonary hypoplasia is not accompanied by hypodevelopment of this nucleus the explanation could be a failure to block the inhibitory action of the Kölliker-Fuse nucleus.

Serotonin 1A receptor agonists reverse respiratory abnormalities in spinal cord-injured rats.

Contusion spinal cord injury (SCI) at T8 produces respiratory abnormalities in conscious rats breathing room air and challenged with CO2. In seeking ways to improve respiration after SCI, we tested drugs that stimulate serotonin 1A (5-HT1A) receptors, based on our previous findings that these agents can counteract respiratory depression produced by morphine overdose. Respiratory function was measured with a head-out plethysmograph system in conscious rats. T8 SCI rats (n = 5) showed decreased tidal volume (Vt; 0.90 +/- 0.02-0.66 +/- 0.03 ml; p < 0.05) and increased respiratory rate (f;91 +/- 3.7-132 +/- 5.7 breaths/min; p < 0.05) with room air ventilation at 24 hr after injury. They also exhibited a diminished response to the respiratory stimulating effect of 7% CO2; minute ventilation increased to 250 +/- 17 ml/min before, but only to 162 +/- 15 ml/min at 24 hr after SCI (p < 0.05). Respiratory deficits during room air ventilation were also observed at 7 d after injury (n = 3). Treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH-DPAT; 250 microg/kg, i.p.) at 24 hr (n = 5) or 7 d (n = 3) after injury normalized Vt, f, and the respiratory response to 7% CO2. Identical results were obtained with another 5-HT1A receptor agonist, buspirone (1.5 mg/kg, i.p.; n = 3). In contrast, intraperitoneal saline vehicle administration (n = 5) showed no beneficial effects on SCI-impaired respiration. Finally, pretreatment with a specific antagonist of 5-HT1A receptors, 4-iodo-N-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl-benzamide (3 mg/kg, i.p.; n = 3) given 20 min before 8-OH-DPAT, prevented 8-OH-DPAT from restoring respiration to normal. Our results demonstrate that drugs that stimulate 5-HT1A receptors counteract respiratory abnormalities in conscious rats after SCI.