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Introduction Pulmonary alveolar proteinosis (PAP) is defined by increased accumulation of surfactant in the alveolar space. PAP has been reported to be associated with a large number of clinical conditions and diseases. Whole lung lavages can be helpful to stabilize the clinical course of PAP until the underlying condition is identified, which may enable more specific treatment. Recently, heterozygous OAS1 gain-of-function variants were described as cause in a patient with infantile-onset PAP combined with hypogammaglobulinemia. Case presentation At age 4 months, a female infant born to term was diagnosed with hypogammaglobulinemia and treated with monthly immunoglobulin injections. At age 15 months, the girl needed supplemental oxygen at night, and at age 18 months, also during the day. At age 2 years, pulmonary alveolar proteinosis of unknown etiology was diagnosed by computed tomography scan and open lung biopsy. Subsequently, monthly whole lung lavages (WLLs) were started, which stabilized the clinical course for over 2 years until a disease-causing OAS1 variant was diagnosed and the patient was successfully treated by hematopoietic stem cell transplantation. Conclusion Here, we describe the successful management of a female patient with severe PAP caused by a heterozygous OAS1 gain-of-function variant until a definitive diagnosis was made and cured by hematopoietic stem cell transplantation. This article is protected by copyright. All rights reserved.

Background Long segment laryngotracheoesophageal clefts (LTECs) are very rare large‐airway malformations. Over the last 40 years mortality rates declined substantially due to improved intensive care and surgical procedures. Nevertheless, long‐term morbidity, comorbidity, and clinical outcomes have rarely been assessed systematically. Methods In this retrospective case series, the clinical presentation, comorbidities, treatment, and clinical outcomes of all children with long‐segment LTEC that were seen at our department in the last 15 years were collected and analyzed systematically. Results Nine children were diagnosed with long segment LTEC (four children with LTEC type III and five patients with LTEC type IV). All children had additional tracheobronchial, gastrointestinal, or cardiac malformations. Tracheostomy for long‐time ventilation and jejunostomy for adequate nutrition was necessary in all cases. During follow‐up one child died from multiorgan failure due to sepsis at the age of 43 days. The clinical course of the other eight children (median follow‐up time 5.2 years) was stable. Relapses of the cleft, recurrent aspirations, and respiratory tract infections led to repeated hospital admissions. Conclusions Long‐segment LTECs are consistently associated with additional malformations, which substantially influence long‐term morbidity. For optimal management, a multidisciplinary approach is essential.

MPI-CDG (formally called CDG 1b), caused by phosphomannose isomerase (MPI) deficiency, leads to hypoglycaemia, protein losing enteropathy, hepatopathy, and thrombotic events, whereas neurologic development remains unaffected. Dietary supplementation of mannose can reverse clinical symptoms by entering the N-glycosylation pathway downstream of MPI. When oral intake of mannose in patients with MPI-CDG is not possible, e.g. due to surgery, mannose has to be given intravenously. We report a patient with MPI-CDG on intravenous mannose therapy that showed severe depression of consciousness and seizures without apparent cause. EEG and cranial MRI findings were compatible with metabolic coma whereas extended laboratory examinations including repeated blood glucose measurements were normal. Importantly, an intravenous bolus of glucose immediately led to clinical recovery and EEG improvement. Mannose did not interfere with glucose measurement in our assay. We suggest that in patients with MPI-CDG, intravenous mannose infusion can lead to intracellular ATP deprivation due to several mechanisms: (1) in MPI deficiency, mannose 6-P cannot be isomerised to fructose 6-P and therefore is unavailable for glycolysis; (2) animal data has shown that accumulating intracellular mannose 6-P inhibits glycolysis; and (3) elevated intracellular mannose 6-P may induce an ATP wasting cycle of dephosphorylation and rephosphorylation ("honey bee effect"). The mannose-induced metabolic inhibition may be overcome by high-dose glucose treatment. We caution that, in patients with MPI-CDG, life-threatening central nervous system disturbances may occur with intravenous mannose treatment. These may be due to intracellular energy failure. Clinical symptoms of energy deficiency should be treated early and aggressively with intravenous glucose regardless of blood glucose levels.

Summary Background: Pulmonary alveolar proteinosis (PAP) is a rare alveolar filling syndrome where the mainstay of treatment is therapeutic whole-lung lavage (WLL). WLL techniques used in adults have to be modified for children because of their small-diameter airways. Aim: To describe a technique for WLL adapted for small children. Methods: We describe a WLL technique that combines safe single-lung ventilation with the use of an age-appropriate endotracheal tube and selective occlusion of the other main bronchus with a balloon catheter through which the lavage is performed. Effectiveness measured by change in oxygen requirements and adverse effects was noted. Results: We performed 64 WLL procedures in four children (age 13 months to 7 years; body weight 4.7–14 kg). Two children had idiopathic and two had secondary PAP. At referral, all children had dyspnoea at rest and required continuous oxygen supplementation. Two patients showed significantly decreased oxygen demands and radiological improvement after WLL. Two patients showed no significant response. The only adverse effect observed was transient hypoxemia. Complications comprised fluid leak at the balloon (4), balloon rupture (1), and pneumothorax (1). Conclusions: This technique for WLL combining single-lung ventilation with an endotracheal tube and lung exclusion for lavage with a balloon catheter can be safely and effectively performed in small children with PAP.

12 páginas, 3 figuras, 3 tablas.-- et al., [1]: The stress gradient hypothesis suggests a shift from predominant competition to facilitation along gradients of increasing environmental severity. This shift is proposed to cause parallel changes from prevailing spatial segregation to aggregation among the species within a community. [2]: We used 904 1-m2 plots, each subdivided into 100 10 × 10 cm, or 25 20 × 20 cm cells, respectively, from 67 European mountain summits grouped into 18 regional altitudinal transects, to test this hypothesized correlation between fine-scale spatial patterns and environmental severity. [3]: The data were analysed by first calculating standardized differences between observed and simulated random co-occurrence patterns for each plot. These standardized effect sizes were correlated to indicators of environmental severity by means of linear mixed models. In a factorial design, separate analyses were made for four different indicators of environmental severity (the mean temperature of the coldest month, the temperature sum of the growing season, the altitude above tree line, and the percentage cover of vascular plants in the whole plot), four different species groups (all species, graminoids, herbs, and all growth forms considered as pseudospecies) and at the 10 × 10 cm and 20 × 20 cm grain sizes. [4]: The hypothesized trends were generally weak and could only be detected by using the mean temperature of the coldest month or the percentage cover of vascular plants as the indicator of environmental severity. The spatial arrangement of the full species set proved more responsive to changes in severity than that of herbs or graminoids. The expected trends were more pronounced at a grain size of 10 × 10 cm than at 20 × 20 cm. [5. Synthesis]: In European alpine plant communities the relationships between small-scale co-occurrence patterns of vascular plants and environmental severity are weak and variable. This variation indicates that shifts in net interactions with environmental severity may differ among indicators of severity, growth forms and scales. Recognition of such variation may help to resolve some of the current debate surrounding the stress gradient hypothesis., The data used in this study were collected within the project GLORIA-Europe in the 5th RTD Framework Programme of the European Union (2001–03; No. EVK2-CT-2000–00056) with the support of Switzerland (OFES 00.0184–1). The analysis was supported by the Austrian Federal Ministry of Agriculture, Forestry, Environment and Water Management and through the project ALARM (‘Assessing large-scale risks for biodiversity with tested methods’; No. GOCE-CT- 2003–506675) of the 6th RTD Framework Programme of the EU.

High mountain ecosystems are defined by low temperatures and are therefore considered to react sensitively to climate warming. Responding to observed changes in plant species richness on high peaks of the European Alps, an extensive setup of 1 m � 1 m permanent plots was established at the alpine-nival ecotone (between 2900 and 3450 m) on Mount Schrankogel, a GLORIA master site in the central Tyrolean Alps, Austria, in 1994. Recording was repeated in a representative selection of 362 quadrats in 2004. Ten years after the first recording, we observed an average change in vascular plant species richness from 11.4 to 12.7 species per plot, an increase of 11.8% (or of at least 10.6% at a 95% confidence level). The increase in species richness involved 23 species (about 43% of all taxa found at the ecotone), comprising both alpine and nival species and was pronouncedly higher in plots with subnival/nival vegetation than in plots with alpine grassland vegetation. Only three species showed a decrease in plot occupancy: one was an annual species, one was rare, and one a common nival plant that decreased in one part of the area but increased in the uppermost part. Species cover changed in relation to altitudinal preferences of species, showing significant declines of all subnival to nival plants, whereas alpine pioneer species increased in cover. Recent climate warming in the Alps, which has been twice as high as the global average, is considered to be the primary driver of the observed differential changes in species cover. Our results indicate an ongoing range contraction of subnival to nival species at their rear (i.e. lower) edge and a concurrent expansion of alpine pioneer species at their leading edge. Although this was expected from predictive distribution models and different temperature-related habitat preferences of alpine and nival species, we provide first evidence on – most likely – warming-induced species declines in the high European Alps. The projected acceleration of climate warming raises concerns that this phenomenon could become the major threat to biodiversity in high mountains.

We hypothesised that long-term tracheostomy in infants and children may perpetuate chronic airway inflammation and airway remodeling due to easier access to the lungs for microorganisms. Pulmonary surfactant represents an important part of the initial host defense, and in particular, the surfactant proteins (SP) A and D may directly interact with invading microorganisms and also modulate the activity of local immune cells. The goals of this study were to determine the presence and intensity of a peripheral airway inflammation and of potential deficiency states of surfactant proteins in nonsymptomatic children with tracheostomy. Bronchoalveolar lavage (BAL) cell pattern, bacteria and viruses recovered, and concentrations of SP-A, SP-B, SP-C, and SP-D were assessed in 46 children (4.3 years (1.6–6)) median (range) carrying a tracheostomy for 2.4 years (1.3–4.9), and were compared to 16 children with no lung disease. Children with tracheostomy had an increased total number of cells, increased neutrophils, and more frequently bacteria, but no viruses were recovered. SP-D concentration was reduced by 50% on average (P = 0.0002). SP-A, SP-B, and SP-C were not different between the two groups. SP-D was inversely correlated to neutrophils, and high numbers of bacteria were associated with lower SP-D concentrations. We suggest that bacteria and low SP-D support neutrophilic inflammation in the lower respiratory tract of nonsymptomatic with children with tracheostomy. Pediatr Pulmonol. 2004; 37:356–361. © 2004 Wiely-Liss, Inc.

Induced by global warming, mountain Nival species will lose area and become restricted to specific topographical situations. Alpine and subnival plant species are migrating upwards. Species inhabiting the nival zone of today are threatened by competitors grassland species are predicted to expand their area, mainly along stable surface situations. Whether the which move from the alpine zone towards the summits. The manner in which species move depends on their migration will take place as a filling or a moving process is specific to the particular species. Overall, biodiversity abilities to cope with microtopographical situations. We present a spatially explicit predictive model which is apparently not threatened on the decadal scale. In special cases, however, genetic losses are likely both draws scenarios of future species distribution patterns at a typical high mountain of the European Alps. The on a local and on a regional scale. altitudinal temperature gradient is examined. Based on the lapse rate and on definitions of topographical niches Key words. Climate change, mountain vegetation, altitudinal gradient, predictive model, digital elevation of species, a +1∞C- and a +2∞C-warming scenario are modelled using a fine-scaled digital elevation model. model, European Alps.