Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study.

BACKGROUND: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth. METHODS: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling. RESULTS: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes. CONCLUSION: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.

Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development.

The generation and homeostasis of bone tissue throughout development and maturity is controlled by the carefully balanced processes of bone formation and resorption. Disruption of this balance can give rise to a broad range of skeletal pathologies. Lethal osteosclerotic bone dysplasia (or, Raine syndrome) is an autosomal recessive disorder characterized by generalized osteosclerosis with periosteal bone formation and a distinctive facial phenotype. Affected individuals survive only days or weeks. We have identified and defined a chromosome 7 uniparental isodisomy and a 7p telomeric microdeletion in an affected subject. The extent of the deleted region at the 7p telomere was established by genotyping microsatellite markers across the telomeric region. The region is delimited by marker D7S2563 and contains five transcriptional units. Sequence analysis of FAM20C, located within the deleted region, in six additional affected subjects revealed four homozygous mutations and two compound heterozygotes. The identified mutations include four nonsynonymous base changes, all affecting evolutionarily conserved residues, and four splice-site changes that are predicted to have a detrimental effect on splicing. FAM20C is a member of the FAM20 family of secreted proteins, and its mouse orthologue (DMP4) has demonstrated calcium-binding properties; we also show by in situ hybridization its expression profile in mineralizing tissues during development. This study defines the causative role of FAM20C in this lethal osteosclerotic disorder and its crucial role in normal bone development.

[Corrective osteotomy of the humerus using perivascular axillary anesthesia according to Weber in a patient suffering from McCune-Albright syndrome]. / Oberarmkorrekturosteotomie bei einem Patienten mit McCune-Albright-Syndrom unter perivaskulärer axillärer Plexusanästhesie nach Weber.

We report on a 20-year-old patient with McCune-Albright syndrome suffering from global respiratory insufficiency who required continuous mask ventilation and where intubation had to be avoided. Perivascular axillary anesthesia according to Weber was performed for a double corrective osteotomy of the humerus. During plexus anesthesia the patient was positioned on the non-anesthesized side in a 15 degrees Trendelenburg position. An extension of analgesia was observed up to the complete upper arm region. Using the modified positioning an extension of brachial plexus anesthesia is possible.

Functional residual capacity measurements in healthy infants: ultrasonic flow meter versus a mass spectrometer.

Accurate, reproducible and portable bedside monitoring of lung volume could potentially facilitate the early recognition of both under and overinflation of the lungs in ventilated and nonventilated subjects. This study asked whether a prototype portable ultrasonic flow meter provided valid and reliable measurements of functional residual capacity (FRCUS) when compared to those obtained using a mass spectrometer (FRCMS) in nonventilated healthy infants. Paired, randomised measurements of FRCMS and FRCUS were obtained using the sulphur hexafluoride (SF6) multiple-breath washout technique in 23 healthy infants with a median (range) postnatal age of 34.6 (1.3-92.6) weeks and weight of 8.3 (3.9-11.7) kg. FRCUS was on average 5.7%, (95% CI: 1.0-10.4%) less than FRCMS equating to a difference of approximately 1 mL x kg(-1). The 95% limits of agreement (LA) between the two techniques were relatively wide (95% LA: -17.5% to 29%), although in keeping with previously reported within-patient variability for lung volume measurements. There was no significant difference between the within subject coefficient of variation for FRCMS (3.7%) and FRCUS (5.2%). The ultrasonic flow meter used in this study provides repeatable measurements of functional residual capacity in spontaneously breathing healthy infants that approximate those obtained during mass spectrometry.

Effect of raised lung volume technique on subsequent measures of V'maxFRC in infants.

Partial and "full" forced expiratory maneuvers are both used to assess airway function in infants. Despite the increasing use of the raised volume technique, there is little information regarding the influence of lung inflations as are necessary for the raised volume technique on other measurements of lung function in infants. The aim of this study was to assess whether application of the raised volume technique influences subsequent tidal measurements of maximal expired flow at functional residual capacity (V'maxFRC). Paired measurements of V'maxFRC were obtained in 29 healthy infants (aged 6-65 weeks) before and after raised volume maneuvers, wherein a lung inflation pressure of 3 kPa was used. When compared with measurements prior to raising lung volume, there was a highly significant (P < 0.001) decrease in V'maxFRC by 40 ml.sec(-1) when measurements were repeated (95% CI, -59, -20 ml.sec(-1)), equivalent to a reduction of 20% or -0.6 SD scores in flows. There was no significant change in selected tidal breathing parameters, 95% CI of differences between the two sets of measurements being -1.5, 1.2 bpm for respiratory rate; -0.5, 0.2 ml.kg(-1) for weight corrected tidal volume, and -0.04, 0.01 for tidal breathing ratio (tPTEF:tE). In conclusion, although the mechanism remains unclear, raised volume maneuvers may influence subsequent measures of lung function in infants. Further research is needed to clarify the potential mechanisms. In the meantime, the potential impact of the order of lung function tests within any given study protocol should be considered carefully.

[Pulmonary aspergillosis as initial manifestation of septic granulomatosis (chronic granulomatous disease, CGD) in a premature monozygotic female twin and FDG-PET diagnosis of spread of the disease]. / Pulmonale Aspergillose als Erstmanifestation einer septischen Granulomatose (chronic granulomatous disease, CGD) bei eineiigen weiblichen Zwillingsfrühgeborenen und Ausbreitungsdiagnostik mittels FDG-PET.

PURPOSE: To present the unusual case of chronic granulomatous disease (CGD) manifestating as pulmonal aspergillosis in female enzygotic twins during the neonatal period. To demonstrate and to discuss the complex diagnosis and the diagnostic value of FDG-PET in monitoring the spread and activity of the disease. PATIENTS: Plain chest x-ray and CT of the lung showed multiple, mostly round lesions in one of the former preterm twins at the age of 8 weeks. The girl with known ASD II was then suffering from dyspnoea and recurrent pulmonary infections. Because of the imaging findings invasive pulmonary aspergillosis due to an underlying immunodeficiency was suspected. RESULTS: Aspergillosis was confirmed histologically and microbiologically by specimens taken from an open lung biopsy. Because of coexisting granulocytic dysfunction the diagnosis of CGD was made. This diagnosis was equally confirmed by noninvasive methods in the asymptomatic sister. FDG-PET did not show any evidence of extra-pulmonary spread of disease. CONCLUSION: CGD can present as isolated pulmonal aspergillosis even in the neonatal period when an immunodeficiency is discussed. In enzygotic twins screening of the asymptomatic twin is mandatory. FDG-PET is a useful tool in screening for spread of the disease and in evaluating disease activity.

Airway compression following thymus hyperplasia in an infant with Pierre Robin sequence and congenital diaphragmatic hernia.

A female infant with respiratory embarrassment due to external compression of the tracheobronchial tree by the thymus is presented. After successful intrauterine drainage of pleural effusions, she was born with a diaphragmatic hernia and Pierre Robin sequence, which required long-term mechanical ventilation and several surgical interventions, including tracheostomy, until she breathed spontaneously. At age 7 months, she was rehospitalized in respiratory failure because of pneumonia. At this time, thymus hyperplasia was first diagnosed, which had caused tracheobronchomalacia and displacement of the tracheobronchial tree. Weaning from the ventilator was unsuccessful for 8 weeks. She underwent thymectomy, following which impairment of breathing resolved immediately. Different manifestations of thymus enlargement and their relation to impaired breathing are discussed.

Cervical encephalocele in a newborn--Chiari III malformation. Case report and review of the literature.

Chiari malformations are brain stem anomalies with or without spinal canal involvement. The combination of brain stem and cerebellar anomaly with a cervical cele is named Chiari III malformation. Patients with this extremely rare defect frequently present with severe neurological defects and can have a poor prognosis. Following a report on a newborn child with a Chiari III malformation that took a fatal but typical course the literature is reviewed.

Twenty-four hour intraesophageal pH monitoring in children and adolescents with scleroderma and mixed connective tissue disease.

OBJECTIVE: To investigate esophageal dysmotility and gastroesophageal reflux, which are important, but often occult features of gastrointestinal (GI) involvement in children and adolescents with mixed connective tissue disease (MCTD) and scleroderma. METHODS: We carried out intraesophageal 24 h pH monitoring of 14 patients with scleroderma and MCTD. RESULTS: We observed an elevated reflux index in 64% of the patients. An increased number of reflux events was found in 85%. Reflux events > 5 min were noted in 50% of the patients, which is indicative of possible development of esophagitis. Only 3 patients presented clinical symptoms. Four of 5 patients with localized scleroderma revealed a pathological reflux index. We found no relationship between gastroesophageal reflux, age of patients, duration of disease, and Raynaud's phenomenon. CONCLUSION: GI involvement in children with scleroderma or MCTD is more frequent than clinical symptoms indicate. An active diagnostic investigation for GI dysmotility and gastroesophageal reflux is necessary to detect these complications.

A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants.

UNLABELLED: This study was carried out to assess the feasibility of late cord clamping of 45 s in preterm infants delivered mainly by caesarean section and the effects on postpartal adaptation and anaemia of prematurity. Prior to delivery, 40 infants of < 33 gestational weeks were randomised to either 20 s or 45 s of late cord clamping. After the first shoulder was delivered, oxytocin was given intravenously to the mother in order to enhance placento-fetal transfusion while the infant was held below the level of the placenta. The 20 infants in group 1 (20 s) had a mean birth weight of 1070 g and a mean gestational age of 29 + 4/7 weeks versus 1190 g and 30 weeks in group 2 (45 s). On day 42 of life there were ten infants without transfusions in group 2 versus three in group 1 (P < 0.05). Out of the 20 infants in group 1, 19 and 15/19 in group 2 were delivered by caesarean section. There were no significant differences in Apgar scores, temperature on admission, heart rate, blood pressure and requirements for artificial ventilation. CONCLUSION: Delayed cord clamping of 45 s is feasible and safe in preterm infants below 33 weeks of gestation. It is possible to perform the procedure at caesarean section deliveries and it should be performed whenever possible. It reduces the need for packed red cell transfusions during the first 6 weeks of life.

Successful perioperative management of congenital cystic adenomatoid malformation of the lung by high frequency oscillatory ventilation--report of two cases.

BACKGROUND: Comparable to congenital diaphragmatic hernia, patients with congenital cystic adenomatoid malformation of the lung (CCAM) may develop life-threatening mediastinal shift and persistent pulmonary hypertension. In patients with diaphragmatic hernia, high frequency oscillatory ventilation (HFOV) has been shown to allow perioperative stabilisation. PATIENTS: One term and one premature newborn of 30 gestational weeks with CCAM. Both patients developed massive mediastinal shift and intermittend pulmonary hypertension. METHOD: Retrospective chart review. RESULTS: In both patients perioperative stabilisation could be achieved by institution of HFOV. This allowed safe operation in the almost immobile surgical site and controlled transient episodes of pulmonary hypertension. The resection of the malformed lobe was performed under continued HFOV on the neonatal intensive care unit. Hereby, transport stress and additional hyperinflation by hand ventilation could be avoided. CONCLUSION: Comparable with the situation when repairing a congenital diaphragmatic hernia, perioperative HFOV may be advantageous in managing severe CCAM.

[Manifestations and prognosis of congenital diaphragmatic hernia]. / Erscheinungsformen und Prognose kongenitaler Zwerchfelldefekte.

We conducted a retrospective examination of the data of 36 patients with congenital diaphragm defects detected at an early stage or even before birth. The course of pregnancy, pregnancy risks, prenatal findings, mode of delivery, clinical parameters, prenatal, perinatal and postnatal procedures, findings at surgery and surgical therapy were analyzed with respect to the patients' outcome. The following factors were seen to influence the prognosis: associated anomalies, prenatal diagnosis, maturity for age, weight, Apgar score, the size of the defect and the extent of the pulmonary hypoplasia (and--linked to this--the patient's cardiorespiratory condition prior to surgery), and possibly sex. The mortality of patients surviving until surgery became possible was 28%. Our standard procedure in case of diaphragm defects known before birth is primary intubation before the child's first spontaneous breath. We also consider the practice of delaying surgery until stabilization has been achieved and especially in the incubator on the ward the course of action with the fewest complications at present from the patient's point of view.