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Biomedical subjects

T Nicolai

Publications and source records attributed to T Nicolai.

At least 19 recordsLinked to original sources
PubMed2006

The physiological basis of respiratory support.

The complex interplay between the characteristics of the respiratory system, its changes as a result of respiratory disease and the effects of mechanical ventilation makes it important to analyse the physiology of the respiratory system in any given clinical situation. Key variables to be considered are the elastic recoil, resistance and time constant of the respiratory system, as well as the characteristics of the respiratory pump. The effects of respiratory support on the intrathoracic organs and lung perfusion must be taken into account. Respiratory support modes can then be tailored to provide maximum benefit and a minimum of negative effects. When the relatively few basic principles that underlie the mechanical behaviour of the respiratory system in most circumstances are kept in mind, the challenge of optimal support seems solvable for most children with respiratory insufficiency.

Airway Resistance↗
PubMed2006

Flocculation and percolation in reversible cluster-cluster aggregation.

Off-lattice dynamic Monte-Carlo simulations were done of reversible cluster-cluster aggregation for spheres that form rigid bonds at contact. The equilibrium properties were found to be determined by the life time of encounters between two particles (te). te is a function not only of the probability to form or break a bond, but also of the elementary step size of the Brownian motion of the particles. In the flocculation regime the fractal dimension of the clusters is df=2.0 and the size distribution has a power law decay with exponent tau=1.5. At larger values of te transient gels are formed. Close to the percolation threshold the clusters have a fractal dimension df=2.7 and the power law exponent of the size distribution is tau=2.1. The transition between flocculation and percolation occurs at a characteristic weight average aggregation number that decreases with increasing volume fraction.

Journal Article↗
PubMed2005

Influence of the Brownian step size in off-lattice Monte Carlo simulations of irreversible particle aggregation.

The influence of the Brownian step size in off-lattice Monte Carlo simulations of the aggregation and gelation of spheres is studied. It is found that the kinetics are strongly influenced if the step size is larger than the mean smallest distance between the sphere surfaces. The structure of the clusters and the gels is influenced, but only over length scales smaller than the step size. Using large step sizes leads to a narrower size distribution of the clusters. Implications of the present results are discussed for simulations reported in the literature in which the Brownian step size was chosen equal to the sphere diameter.

Journal Article↗
PubMed2005

Depletion from a hard wall induced by aggregation and gelation.

Diffusion-limited cluster aggregation and gelation of hard spheres is simulated using off-lattice Monte Carlo simulations. A comparison is made of the wall-particle correlation function with the particle-particle correlation function over a range of volume fractions, both for the initial system of randomly distributed spheres and for the final gel state. For randomly distributed spheres the correlation functions are compared with theoretical results using the Ornstein-Zernike equation and the Percus-Yevick closure. At high volume fractions (phi > 40%) gelation has little influence on the correlation function, but for phi < 10% it is a universal function of the distance normalized by correlation length (xi) of the bulk. The width of the depletion layer is about 0.5xi. The concentration increases as a power law from the wall up to r approximately = xi, where it reaches a weak maximum before decreasing to the bulk value.

Journal Article↗
PubMed2005

[Management of septic shock and acquired respiratory distress syndrome in pediatric cancer patients].

Septic shock occurs in 6 % of paediatric cancer patients with neutropenia and fever. The mortality of the septic shock is 40 % in BMT patients and 5 % in others. One third of paediatric ARDS cases affect immunocompromised individuals with a total mortality of 45 % and 80 % after BMT. Septic shock is caused by gram-negative bacteria in more than 75 %. ARDS is due to pneumonia in more than 50 %, sepsis in about 25 %. This article provides the recommendations of the Infectious Diseases Working Party of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Hematology/Oncology (GPOH) for treatment of septic shock and ARDS. Therapy of septic shock includes early antibiotic therapy and volume expansion (> or = 40 ml/kg initially). Refractory shock requires vasopressors (noradrenaline), followed by a judicious circulatory management. Hydrocortisone is indicated in patients with high probability of adrenal insufficiency. Mainstay of ARDS therapy is ventilation with sufficient end-expiratory pressure (PEEP) to prevent loss of functional residual capacity and with limited tidal volumes (< or = 6 ml/kg) and limited inspiratory pressure (< 35 cm H(2)O) respectively, to minimize ventilator induced lung injury. Volume therapy consists of maintenance of sufficient preload to counteract the impaired venous return, induced by positive pressure ventilation. Diuretics and eventually veno-venous haemofiltration are used to reduce free lung water. Surfactant application may be considered in severe cases. Steroids are indicated in pneumocystis carinii pneumonia and in engraftment pneumonitis.

Adolescent↗
PubMed2005

Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis.

BACKGROUND: Auto-antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF) may be central to the pathogenesis of adult sporadic pulmonary alveolar proteinosis (PAP). The role of anti-GM-CSF auto-antibodies in paediatric forms of PAP is as yet unclear. METHODS: Anti-GM-CSF auto-antibodies were determined with the help of an antigen capture assay using serum and/or bronchoalveolar lavage (BAL) fluid from 27 patients with PAP (nine adults, 15 children, three neonates) and from 185 children with different diseases as disease controls (various pulmonary conditions and patients with malignancies). RESULTS: Anti-GM-CSF auto-antibodies were detected in the serum of five of seven adult PAP patients. They were not found in the serum of any of the children or neonates with PAP nor in any of the disease control patients. Raised anti-GM-CSF titres were found in BAL fluid from three of four adult patients with PAP. Anti-GM-CSF auto-antibodies were detected in BAL fluid of only one of the 15 children (age at diagnosis 11 years, age at BAL 24 years) and in none of the neonates with PAP, nor in any of the disease control patients. CONCLUSIONS: The presence of anti-GM-CSF auto-antibodies seems to define an autoimmune disease underlying most of the adult sporadic type of PAP, but age at diagnosis may cause an overlap with children in some rare instances. In most of the children and all of the neonates the anti-GM-CSF titres were not significantly increased, indicating that alternative explanations are needed for the pathogenesis of the disease in these patients.

Adult↗
PubMed2004

Airway inflammation in children with tracheostomy.

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.

Bronchoalveolar Lavage↗
PubMed2004

Alpha1 antitrypsin and the prevalence and severity of asthma.

In a random sample of children (aged 9-11 years; n = 5629), who were studied according to the ISAAC phase II protocol, heterozygosity of the alpha1 antitrypsin (alpha1-AT) Pi genotypes MS or MZ, or low alpha1-AT plasma levels, were not associated with an increased risk of developing asthma. Asthmatics with low levels of alpha1-AT were particularly prone to develop airway hyperresponsiveness and reduced lung function.

Asthma↗
PubMed2004

Monte Carlo simulation of particle aggregation and gelation: I. Growth, structure and size distribution of the clusters.

Lattice and off-lattice Monte Carlo simulations of diffusion-limited cluster aggregation and gelation were done over a broad range of concentrations. The large-scale structure and the size distribution of the clusters are characterized by a crossover at a characteristic size (m(c)). For m < m(c), they are the same as obtained in a dilute DLCA process and for m >> m(c) they are the same as obtained in a static percolation process. m(c) is determined by the overlap of the clusters and decreases with increasing particle concentration. The growth rate of large clusters is a universal function of time reduced by the gel time. The large-scale structural and temporal properties are the same for lattice and off-lattice simulations. The average degree of connectivity per particle in the gels formed in off-lattice simulations is independent of the concentration, but its distribution depends on the concentration.

Cluster Analysis↗
PubMed2004

Monte Carlo simulation of particle aggregation and gelation: II. Pair correlation function and structure factor.

Diffusion-limited cluster aggregation and gelation are studied using lattice and off-lattice Monte Carlo simulations. The pair correlation function g(r) and the structure factor S(q) of the particle gels were investigated as a function of the volume fraction (05-49%) and time. At volume fractions below 5%, the gel structure is fractal on small length scales with d(f) = 1.8. g(r) shows a weak minimum at the correlation length (xi), before reaching the average concentration at large length scales. The cut-off function of g(r) varies during the aggregation process, but at a given t/t(g), where t(g) is the gel time, it is a universal function of r/xi. At high volume fractions, the structure is dominated by excluded-volume interactions, while at low volume fractions, it is determined by the connectivity.

Cluster Analysis↗
PubMed2003

Lymphangioma colli--a new classification contributing to prognosis.

The aim of the study was to introduce a classification of lymphangioma colli, which allows us to predict the expected morbidity and prognosis with surgical treatment. We defined 4 types, dependent on the volume of the lymphangioma as assessed by prenatal ultrasound or clinically: type I included tumors which had no or only a minimal effect on the contour of the neck; type II lymphangiomas were smaller than a line drawn at the lateral border of the head; type III tumors exceeded this line; in type IV the lymphangioma extended beyond the midline of the body. We report on the pre- and postoperative findings in 36 cases operated on between 1988 and 2000, mean follow-up was 4.2 years. 25 % of the cases were classified as type I, 36 % as type II, 22 % as type III, and 17 % as type IV. Cesarean section was carried out for 79 % of type III and IV lymphangiomas following prenatal diagnosis (71 %) and for 14 % of type I and II. MRT was indicated in 38 % of type II compared to 86 % in type III and IV lymphangiomas. Endoscopy was necessary in 25 % of type III and in 66 % of type IV lymphangiomas. In 2 cases (type I and IV), imaging revealed an intrathoracic portion. In 64 % of type I and II cases, resection was complete compared to 21 % in infants with more extended tumors. In all type IV cases, at least one further operation was required, likewise in 25 % of type III lymphangiomas. Postoperative effusion and infection occurred significantly more often in group IV than in groups I to III. 5 nerval lesions remained in children with operated type IV lymphangioma and 2 in type III cases. A visible lack of facial symmetry was evident at the follow-up examination in 83 % of type IV cases and moderate asymmetry was found in 19 % of all type I and II cases. Tracheostomy and gastrostomy were required only in type IV. The introduced classification of lymphangioma colli enables predictive statements to be made concerning the morbidity and prognosis with surgical therapy. The prognosis in type I is excellent; in type II, a cosmetically significant facial asymmetry remains in only 15 %. In type III lymphangiomas postoperative complications occurred in 38 % of cases, the necessity for reoperation with definitive lesions occurred in only 25 %. Morbidity gets significantly higher and the prognosis is worse if the lymphangioma exceeds the midline of the body.

Decompression, Surgical↗
PubMed2003

3d Monte Carlo simulation of site-bond continuum percolation of spheres.

We present off-lattice Monte Carlo simulations of site-bond percolation of semi-penetrable spheres or, equivalently, of hard spheres with a finite bond range. We will show that the crucial parameter is the effective volume fraction (phie), i.e. the volume that is occupied or within the bond range of at least one particle. For the equivalent system of semi-penetrable spheres 1-phie is the porosity. The bond percolation threshold (pb) can be described in terms of phie by a simple analytical expression: log(phie)/log(phiec) + log(pb)/log(pbc)=1, with pbc=0.12 independent of the bond range and phiec a constant that decreases with increasing bond range.

Journal Article↗
PubMed2003

Urban traffic and pollutant exposure related to respiratory outcomes and atopy in a large sample of children.

Conflicting results have been reported for the relationship between traffic exposure and inception of atopy. The effect of traffic on the prevalence of asthma and atopy at school age was investigated in a representative population. Random samples of schoolchildren (n=7,509, response rate 83.7%) were studied using the International Study of Asthma and Allergies in Childhood phase-II protocol with skin-prick tests, measurements of specific immunoglobulin E and lung function. Traffic exposure was assessed via traffic counts and by an emission model which predicted soot, benzene and nitrogen dioxide (NO2). Traffic counts were associated with current asthma, wheeze and cough. In children with tobacco-smoke exposure, traffic volume was additionally associated with a positive skin-prick test. Cough was associated with soot, benzene and NO2, current asthma with soot and benzene, and current wheeze with benzene and NO2. No pollutant was associated with allergic sensitisation. High vehicle traffic was associated with asthma, cough and wheeze, and in children additionally exposed to environmental tobacco smoke, with allergic sensitisation. However, effects of socioeconomic factors associated with living close to busy roads cannot be ruled out.

Asthma↗
PubMed2002

Pollution, environmental factors and childhood respiratory allergic disease.

Epidemiologic studies have shown that hay fever and asthma in children have increased over the last 50 years. Experimental data have suggested that exposure to environmental substances such as diesel exhaust particles can induce production of allergen specific IgE antibodies, while exposure to other substances such as endotoxins may rather induce non-allergic immune responses and suppress IgE production. The end of the East-West division of Europe provided the opportunity to assess the effect of different environmental conditions on the development of allergies. Differences in exposure to possible risk factors and their effect on allergic sensitisation in early life, a period considered critical for the development of persistent IgE reactions, are particularly important to analyse. Cars, NO(2) and NO exposure were more prevalent in Western Europe, while pollution by heavy industry and coal heating were present in Eastern cities. The results of population based comparisons have produced little evidence of air pollution causing new cases of allergy in children, and it seems rather unlikely than an excess in external toxic exposure is responsible for the world wide increase in pediatric atopy. However, some studies analysing local traffic exposure (in particular truck traffic) have found an increased allergy prevalence at least in subgroups of children. While a link between the inception of new allergies and air pollutants has to date not been convincingly shown, the increased respiratory morbidity associated with such exposure in children with established asthma as well as healthy children does result in considerable health costs.

Air Pollutants↗
PubMed2002

Allogeneic bone marrow transplantation for active Epstein-Barr virus-related lymphoproliferative disease and hemophagocytic lymphohistiocytosis in an infant with severe combined immunodeficiency syndrome.

A 5-month-old male presented with fever, hepatosplenomegaly, leukocytosis with atypical lymphoblasts, anemia and thrombocytopenia. Severe combined imunodeficiency syndrome (T-, B+, NK+), B lymphoproliferative disease and hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus (EBV) were diagnosed. As his clinical situation deteriorated rapidly, BMT was performed with unmanipulated marrow stem cells from his EBV-positive HLA-identical sister after conditioning with dexamethasone (1.75 mg/kg/day), cyclophosphamide (114 mg/kg) and etoposide (10 mg/kg), with no immunosuppression given post transplant. Engraftment occurred on day 6 with explosive proliferation of donor CD8(+) T cells. The patient died 3 days later from acute respiratory distress syndrome. Autopsy revealed full donor engraftment and no signs of hemophagocytic lymphohistiocytosis or B lymphoproliferative disease. Thus, transplanted T cells can expand very rapidly within days after BMT and clear EBV lymphoproliferative disease and hemophagocytic lymphohistiocytosis.

Acute Disease↗