Weaning from Mechanical Ventilation

For most patients who require mechanical ventilation weaning and extubation is simple. In these patients a variety of strategies can be successful. In addition, sim ple criteria may predict when the patient is ready for extubation. For the small group of patients who require prolonged mechanical ventilation, however, contro versy exists about how best to remove ventilator sup port by weaning, and available data are sparse. Much of the controversy has centered on T-piece weaning ver sus intermittent mandatory ventilation. To date no con trolled study has demonstrated the superiority of either intermittent mandatory ventilation or T-piece weaning in difficult-to-wean patients. In the evolution of this con troversy, concern has developed over the potential for increased inspiratory work and expiratory resistance that may be associated with certain intermittent manda tory ventilation systems. The possibility that significant inspiratory work may occur during assist-control venti lation has also been demonstrated. Respiratory muscle weakness and fatigue is likely important in failure to wean. Other possible causes are failure of the cardiovas cular system and impaired ability of the lung to carry out gas exchange. In this article we first examine criteria and techniques for weaning short-term ventilator pa tients. We then examine criteria to begin the weaning process in prolonged ventilation patients, potential causes of failure to wean, and techniques that can be used to remove ventilator support from patients who are difficult to wean. Much literature has been devoted to techniques and criteria for weaning and extubation of patients from mechanical ventilation. For most patients who require ventilatory support, weaning and extuba tion can be easily accomplished by a variety of tech niques [1-4]. At one referral center 77.2% of all surviving patients were weaned from the ventilator within 72 hours of the onset of mechanical ventila tion, and 91% were weaned within 7 days [1]. Less than 10% of ventilated patients potentially posed problems in weaning from mechanical ventilation. Similarly, at a community hospital, few surviving patients required prolonged ventilatory support [2]. In easy-to-wean patients, Sahn and Lakshminarayan [5] described simple criteria that are predictive of successful discontinuation of ventilator support. For the small group of patients who require pro longed mechanical ventilation, however, minimal data are available. In these patients criteria to deter mine weaning ability or which measurements to follow are not clearly defined. Furthermore, no controlled trials are available to compare the differ ent weaning techniques proposed. In this article we first address routine weaning of the patient who has not required prolonged ventilator support. We then examine the difficult-to-wean patient and dis cuss criteria to begin the weaning process, poten tial causes of failure to wean, and available weaning techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68923/2/10.1177_088506668800300207.pd

Dust detection by the wave instrument on STEREO: nanoparticles picked up by the solar wind?

The STEREO/WAVES instrument has detected a very large number of intense voltage pulses. We suggest that these events are produced by impact ionisation of nanoparticles striking the spacecraft at a velocity of the order of magnitude of the solar wind speed. Nanoparticles, which are half-way between micron-sized dust and atomic ions, have such a large charge-to-mass ratio that the electric field induced by the solar wind magnetic field accelerates them very efficiently. Since the voltage produced by dust impacts increases very fast with speed, such nanoparticles produce signals as high as do much larger grains of smaller speeds. The flux of 10-nm radius grains inferred in this way is compatible with the interplanetary dust flux model. The present results may represent the first detection of fast nanoparticles in interplanetary space near Earth orbit.Comment: In press in Solar Physics, 13 pages, 5 figure

Nanodust detection near 1 AU from spectral analysis of Cassini/RPWS radio data

Nanodust grains of a few nanometer in size are produced near the Sun by collisional break-up of larger grains and picked-up by the magnetized solar wind. They have so far been detected at 1 AU by only the two STEREO spacecraft. Here we analyze the spectra measured by the radio and plasma wave instrument onboard Cassini during the cruise phase close to Earth orbit; they exhibit bursty signatures similar to those observed by the same instrument in association to nanodust stream impacts on Cassini near Jupiter. The observed wave level and spectral shape reveal impacts of nanoparticles at about 300 km/s, with an average flux compatible with that observed by the radio and plasma wave instrument onboard STEREO and with the interplanetary flux models

Biological effects of particles from the paris subway system

Particulate matter (PM) from atmospheric pollution can easily deposit in the lungs and induce recruitment of inflammatory cells, a source of inflammatory cytokines, oxidants, and matrix metalloproteases (MMPs), which are important players in lung structural homeostasis. In many large cities, the subway system is a potent source of PM emission, but little is known about the biological effects of PM from this source. We performed a comprehensive study to evaluate the biological effects of PM sampled at two sites (RER and Metro) in the Paris subway system. Murine macrophages (RAW 264.7) and C57Bl/6 mice, respectively, were exposed to 0.01-10 microg/cm2 and 5-100 microg/mouse subway PM or reference materials [carbon black (CB), titanium dioxide (TiO2), or diesel exhaust particles (DEPs)]. We analyzed cell viability, production of cellular and lung proinflammatory cytokines [tumor necrosis factor alpha (TNFalpha), macrophage inflammatory protein (MIP-2), KC (the murin analog of interleukin-8), and granulocyte macrophage-colony stimulating factor (GM-CSF)], and mRNA or protein expression of MMP-2, -9, and -12 and heme oxygenase-1 (HO-1). Deferoxamine and polymixin B were used to evaluate the roles of iron and endotoxin, respectively. Noncytotoxic concentrations of subway PM (but not CB, TiO2, or DEPs) induced a time- and dose-dependent increase in TNFalpha and MIP-2 production by RAW 264.7 cells, in a manner involving, at least in part, PM iron content (34% inhibition of TNF production 8 h after stimulation of RAW 264.7 cells with 10 microg/cm2 RER particles pretreated with deferoxamine). Similar increased cytokine production was transiently observed in vivo in mice and was accompanied by an increased neutrophil cellularity of bronchoalveolar lavage (84.83+/-0.98% of polymorphonuclear neutrophils for RER-treated mice after 24 h vs 7.33+/-0.99% for vehicle-treated animals). Subway PM induced an increased expression of MMP-12 and HO-1 both in vitro and in vivo. PM from the Paris subway system has transient biological effects. Further studies are needed to better understand the pathophysiological implications of these findings

Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants

<p>Abstract</p> <p>Background</p> <p>Angiotensin converting enzyme (ACE) gene contains a polymorphism, consisting of either the presence (I) or absence (D) of a 287 base pair fragment. Deletion (D) is associated with increased circulating ACE (cACE) activity. It has been suggested that the D-allele of ACE genotype is associated with power-oriented performance and that cACE activity is correlated with muscle strength. Respiratory muscle function may be similarly influenced. Respiratory muscle strength in infants can be assessed specifically by measurement of the maximum inspiratory pressure during crying (Pi_max). Pressure-time index of the respiratory muscles (PTImus) is a non-invasive method, which assesses the load to capacity ratio of the respiratory muscles.</p> <p>The objective of this study was to determine whether increased cACE activity in infants could be related to greater respiratory muscle strength and to investigate the potential association of cACE with PTImus measurements as well as the association of ACE genotypes with cACE activity and respiratory muscle strength in this population.</p> <p>Methods</p> <p>Serum ACE activity was assayed by using a UV-kinetic method. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pi_mean/Pi_max) × (Ti/Ttot), where Pi_meanwas the mean inspiratory pressure estimated from airway pressure, generated 100 milliseconds after an occlusion (P_0.1), Pi_maxwas the maximum inspiratory pressure and Ti/Ttot was the ratio of the inspiratory time to the total respiratory cycle time. Pi_maxwas the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort.</p> <p>Results</p> <p>A hundred and ten infants were studied. Infants with D/D genotype had significantly higher serum ACE activity than infants with I/I or I/D genotypes. cACE activity was significantly related to Pi_maxand inversely related to PTImus. No association between ACE genotypes and Pdi_maxmeasurements was found.</p> <p>Conclusions</p> <p>These results suggest that a relation in cACE activity and respiratory muscle function may exist in infants. In addition, an association between ACE genotypes and cACE activity, but not respiratory muscle strength, was demonstrated.</p

GluD1, linked to schizophrenia, controls the burst firing of dopamine neurons

Human mutations of the GRID1 gene encoding the orphan delta1 glutamate receptor-channel (GluD1) are associated with schizophrenia but the explicit role of GluD1 in brain circuits is unknown. Based on the known function of its paralog GluD2 in cerebellum, we searched for a role of GluD1 in slow glutamatergic transmission mediated by metabotropic receptor mGlu1 in midbrain dopamine neurons, whose dysfunction is a hallmark of schizophrenia. We found that an mGlu1 agonist elicits a slow depolarizing current in HEK cells co-expressing mGlu1 and GluD1, but not in cells expressing mGlu1 or GluD1 alone. This current is abolished by additional co-expression of a dominant-negative GluD1 dead pore mutant. We then characterized mGlu1-dependent currents in dopamine neurons from midbrain slices. Both the agonist-evoked and the slow postsynaptic currents are abolished by expression of the dominant-negative GluD1 mutant, pointing to the involvement of native GluD1 channels in these currents. Likewise, both mGlu1-dependent currents are suppressed in GRID1 knockout mice, which reportedly display endophenotypes relevant for schizophrenia. It is known that mGlu1 activation triggers the transition from tonic to burst firing of dopamine neurons, which signals salient stimuli and encodes reward prediction. In vivo recordings of dopamine neurons showed that their spontaneous burst firing is abolished in GRID1 knockout mice or upon targeted expression of the dominant-negative GluD1 mutant in wild-type mice. Our results de-orphanize GluD1, unravel its key role in slow glutamatergic transmission and provide insights into how GRID1 gene alterations can lead to dopaminergic dysfunctions in schizophrenia

Allergic rhinitis: evidence for impact on asthma

BACKGROUND: This paper reviews the current evidence indicating that comorbid allergic rhinitis may have clinically relevant effects on asthma. DISCUSSION: Allergic rhinitis is very common in patients with asthma, with a reported prevalence of up to 100% in those with allergic asthma. While the temporal relation of allergic rhinitis and asthma diagnoses can be variable, the diagnosis of allergic rhinitis often precedes that of asthma. Rhinitis is an independent risk factor for the subsequent development of asthma in both atopic and nonatopic individuals. Controlled studies have provided conflicting results regarding the benefits for asthma symptoms of treating comorbid allergic rhinitis with intranasal corticosteroids. Effects of other treatments for comorbid allergic rhinitis, including antihistamines, allergen immunotherapy, systemic anti-IgE therapy, and antileukotriene agents, have been examined in a limited number of studies; anti-IgE therapy and antileukotriene agents such as the leukotriene receptor antagonists have benefits for treating both allergic rhinitis and asthma. Results of observational studies indicate that treating comorbid allergic rhinitis results in a lowered risk of asthma-related hospitalizations and emergency visits. Results of several retrospective database studies in the United States and in Europe indicate that, for patients with asthma, the presence of comorbid allergic rhinitis is associated with higher total annual medical costs, greater prescribing frequency of asthma-related medications, as well as increased likelihood of asthma-related hospital admissions and emergency visits. There is therefore evidence suggesting that comorbid allergic rhinitis is a marker for more difficult to control asthma and worsened asthma outcomes. CONCLUSION: These findings highlight the potential for improving asthma outcomes by following a combined therapeutic approach to comorbid allergic rhinitis and asthma rather than targeting each condition separately

Nitration of the Egg-Allergen Ovalbumin Enhances Protein Allergenicity but Reduces the Risk for Oral Sensitization in a Murine Model of Food Allergy

Nitration of proteins on tyrosine residues, which can occur due to polluted air under "summer smog" conditions, has been shown to increase the allergic potential of allergens. Since nitration of tyrosine residues is also observed during inflammatory responses, this modification could directly influence protein immunogenicity and might therefore contribute to food allergy induction. In the current study we have analyzed the impact of protein nitration on sensitization via the oral route.BALB/c mice were immunized intragastrically by feeding untreated ovalbumin (OVA), sham-nitrated ovalbumin (snOVA) or nitrated ovalbumin (nOVA) with or without concomitant acid-suppression. To analyze the impact of the sensitization route, the allergens were also injected intraperitoneally. Animals being fed OVA or snOVA under acid-suppressive medication developed significantly elevated levels of IgE, and increased titers of specific IgG1 and IgG2a antibodies. Interestingly, oral immunizations of nOVA under anti-acid treatment did not result in IgG and IgE formation. In contrast, intraperitoneal immunization induced high levels of OVA specific IgE, which were significantly increased in the group that received nOVA by injection. Furthermore, nOVA triggered significantly enhanced mediator release from RBL cells passively sensitized with sera from allergic mice. Gastric digestion experiments demonstrated protein nitration to interfere with protein stability as nOVA was easily degraded, whereas OVA and snOVA remained stable up to 120 min. Additionally, HPLC-chip-MS/MS analysis showed that one tyrosine residue (Y(107)) being very efficiently nitrated is part of an ovalbumin epitope recognized exclusively after oral sensitization.These data indicated that despite the enhanced triggering capacity in existing allergy, nitration of OVA may be associated with a reduced de novo sensitizing capability via the oral route due to enhanced protein digestibility and/or changes in antibody epitopes