Surfactant status and respiratory outcome in premature infants receiving late surfactant treatment.

BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p < 0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r = 0.50, p < 0.00001) and inversely related to total protein (r = 0.39, p < 0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant. CONCLUSIONS:We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant

The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure

<p>Abstract</p> <p>Background</p> <p>Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO₂) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling <it>in vitro</it>. In addition, TiO₂effects on surfactant ultrastructure were visualized.</p> <p>Methods</p> <p>A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 μg/ml) of TiO₂NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope.</p> <p>Results</p> <p>TiO₂NSP, but not MSP, induced a surfactant dysfunction. For TiO₂NSP, adsorption surface tension (γ_ads) increased in a dose-dependent manner from 28.2 ± 2.3 mN/m to 33.2 ± 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (γ_min) slightly increased from 4.8 ± 0.5 mN/m up to 8.4 ± 1.3 mN/m (p < 0.01) at high TiO₂NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both γ_ads(63.6 ± 0.4 mN/m) and γ_min(21.1 ± 0.4 mN/m). Interestingly, TiO₂NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae.</p> <p>Conclusion</p> <p>TiO₂nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.</p

Clinical effect of continuous corrective force delivery in the non-operative treatment of idiopathic scoliosis: a prospective cohort study of the triac-brace

A prospective cohort study of skeletally immature idiopathic scoliotic patients treated with the TriaC brace. To determine if the TriaC brace is effective in preventing curve progression in immature adolescent idiopathic scoliotic patients with a very high risk of curve progression based on reported natural history data. The aim of the newly introduced TriaC brace is to reverse the pathologic transverse force pattern by externally applied and continuously present orthotic forces. In the frontal plane the force system used in the TriaC brace is similar to the force system of the conventional braces. However, in the sagittal plane the force system acts only on the thoracic region. In addition, the brace allows upper trunk flexibility without affecting the corrective forces during body motion. In a preliminary study it is demonstrated that the brace prevents further progression of both the Cobb angle and axial rotation in idiopathic scoliosis. Skeletally immature patients with idiopathic scoliosis with curves between 20 and 40° were studied prospectively. Skeletally immature was defined as a Risser sign 0 or 1 for both boys and girls, or pre-menarche or less than 1-year post-menarche for girls. Curves of less than 30° had to have documented progression before entry. The mean age of the patients at the start of treatment was 11.3 ± 3.1 years. All measurements were collected by a single observer, and all patients were followed up to skeletal maturity. Treatment was complete for all participants when they had reached Risser sign 4 and did not show any further growth at length measurements. This was at a mean age of 15.6 ± 1.1 years, with a mean follow-up of 1.6 years post bracing. In our study a successful outcome was obtained in 76% of patients treated with the TriaC brace. Comparing our data to literature data on natural history of a similar cohort shows that the TriaC brace significantly alters the predicted natural history. The current study demonstrates that treatment with the TriaC brace reduces the scoliosis, and that the achieved correction is maintained in some degree after skeletal maturity is reached and bracing is discontinued. It also prevents further progression of the Cobb angle in idiopathic scoliosis. The new brace does not differ from the conventional braces as far as maintaining the deformity is concerned

Effect of low tidal volume ventilation on lung function and inflammation in mice

<p>Abstract</p> <p>Background</p> <p>A large number of studies have investigated the effects of high tidal volume ventilation in mouse models. In contrast data on very short term effects of low tidal volume ventilation are sparse. Therefore we investigated the functional and structural effects of low tidal volume ventilation in mice.</p> <p>Methods</p> <p>38 Male C57/Bl6 mice were ventilated with different tidal volumes (Vt 5, 7, and 10 ml/kg) without or with application of PEEP (2 cm H₂O). Four spontaneously breathing animals served as controls. Oxygen saturation and pulse rate were monitored. Lung function was measured every 5 min for at least 30 min. Afterwards lungs were removed and histological sections were stained for measurement of infiltration with polymorphonuclear leukocytes (PMN). Moreover, mRNA expression of macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)α in the lungs was quantified using real time PCR.</p> <p>Results</p> <p>Oxygen saturation did not change significantly over time of ventilation in all groups (P > 0.05). Pulse rate dropped in all groups without PEEP during mechanical ventilation. In contrast, in the groups with PEEP pulse rate increased over time. These effects were not statistically significant (P > 0.05). Tissue damping (G) and tissue elastance (H) were significantly increased in all groups after 30 min of ventilation (P < 0.05). Only the group with a Vt of 10 ml/kg and PEEP did not show a significant increase in H (P > 0.05). Mechanical ventilation significantly increased infiltration of the lungs with PMN (P < 0.05). Expression of MIP-2 was significantly induced by mechanical ventilation in all groups (P < 0.05). MIP-2 mRNA expression was lowest in the group with a Vt of 10 ml/kg + PEEP.</p> <p>Conclusions</p> <p>Our data show that very short term mechanical ventilation with lower tidal volumes than 10 ml/kg did not reduce inflammation additionally. Formation of atelectasis and inadequate oxygenation with very low tidal volumes may be important factors. Application of PEEP attenuated inflammation.</p

Improved lung preservation relates to an increase in tubular myelin-associated surfactant protein A

BACKGROUND: Declining levels of surfactant protein A (SP-A) after lung transplantation are suggested to indicate progression of ischemia/reperfusion (IR) injury. We hypothesized that the previously described preservation-dependent improvement of alveolar surfactant integrity after IR was associated with alterations in intraalveolar SP-A levels. METHODS: Using immuno electron microscopy and design-based stereology, amount and distribution of SP-A, and of intracellular surfactant phospholipids (lamellar bodies) as well as infiltration by polymorphonuclear leukocytes (PMNs) and alveolar macrophages were evaluated in rat lungs after IR and preservation with EuroCollins or Celsior. RESULTS: After IR, labelling of tubular myelin for intraalveolar SP-A was significantly increased. In lungs preserved with EuroCollins, the total amount of intracellular surfactant phospholipid was reduced, and infiltration by PMNs and alveolar macrophages was significantly increased. With Celsior no changes in infiltration or intracellular surfactant phospholipid amount occurred. Here, an increase in the number of lamellar bodies per cell was associated with a shift towards smaller lamellar bodies. This accounts for preservation-dependent changes in the balance between surfactant phospholipid secretion and synthesis as well as in inflammatory cell infiltration. CONCLUSION: We suggest that enhanced release of surfactant phospholipids and SP-A represents an early protective response that compensates in part for the inactivation of intraalveolar surfactant in the early phase of IR injury. This beneficial effect can be supported by adequate lung preservation, as e.g. with Celsior, maintaining surfactant integrity and reducing inflammation, either directly (via antioxidants) or indirectly (via improved surfactant integrity)

Ischemia of the lung causes extensive long-term pulmonary injury: an experimental study

Background: Lung ischemia-reperfusion injury (LIRI) is suggested to be a major risk factor for development of primary acute graft failure (PAGF) following lung transplantation, although other factors have been found to interplay with LIRI. The question whether LIRI exclusively results in PAGF seems difficult to answer, which is partly due to the lack of a long-term experimental LIRI model, in which PAGF changes can be studied. In addition, the long-term effects of LIRI are unclear and a detailed description of the immunological changes over time after LIRI is missing. Therefore our purpose was to establish a long-term experimental model of LIRI, and to study the impact of LIRI on the development of PAGF, using a broad spectrum of LIRI parameters including leukocyte kinetics.Methods: Male Sprague-Dawley rats (n = 135) were subjected to 120 minutes of left lung warm ischemia or were sham-operated. A third group served as healthy controls. Animals were sacrificed 1, 3, 7, 30 or 90 days after surgery. Blood gas values, lung compliance, surfactant conversion, capillary permeability, and the presence of MMP-2 and MMP-9 in broncho-alveolar-lavage flui

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

Why do we treat adolescent idiopathic scoliosis? What we want to obtain and to avoid for our patients. SOSORT 2005 Consensus paper

BACKGROUND: Medicine is a scientific art: once science is not clear, choices are made according to individual and collective beliefs that should be better understood. This is particularly true in a field like adolescent idiopathic scoliosis, where currently does not exist definitive scientific evidence on the efficacy either of conservative or of surgical treatments. AIM OF THE STUDY: To verify the philosophical choices on the final outcome of a group of people believing and engaged in a conservative treatment of idiopathic scoliosis. METHODS: We performed a multifaceted study that included a bibliometric analysis, a questionnaire, and a careful Consensus reaching procedure between experts in the conservative treatment of scoliosis (SOSORT members). RESULTS: The Consensus reaching procedure has shown to be useful: answers changed in a statistically significant way, and 9 new outcome criteria were included. The most important final outcomes were considered Aesthetics (100%), Quality of life and Disability (more than 90%), while more than 80% of preferences went to Back Pain, Psychological well-being, Progression in adulthood, Breathing function, Scoliosis Cobb degrees (radiographic lateral flexion), Needs of further treatments in adulthood. DISCUSSION: In the literature prevail outcome criteria driven by the contingent treatment needs or the possibility to have measurement systems (even if it seems that usual clinical and radiographic methods are given much more importance than more complex Disability or Quality of Life instruments). SOSORT members give importance to a wide range of outcome criteria, in which clinical and radiographic issues have the lowest importance. CONCLUSION: We treat our patients for what they need for their future (Breathing function, Needs of further treatments in adulthood, Progression in adulthood), and their present too (Aesthetics, Disability, Quality of life). Technical matters, such as rib hump or radiographic lateral alignment and rotation, but not lateral flexion, are secondary outcomes and only instrumental to previously reported primary outcomes. We advocate a multidimensional, comprehensive evaluation of scoliosis patients, to gather all necessary data for a complete therapeutic approach, that goes beyond x-rays to reach the person and the family