Non-invasive ventilation in patients with hematologic malignancy: a new prospective.

Immunosuppressed patients are usually considered together without distinction. However, patients with hematologic malignancy should be included in a different subcategory. The outcome of this population has improved over the years. However, mortality rate continues to be high, especially when respiratory complications are present and mechanical ventilation is required. Non-invasive ventilation (NIV) demonstrated its efficacy on the process of respiratory failure improving clinical outcomes in patients of different diagnoses. Recommendations of guidelines to use NIV in immunosuppressed patients have been quite prudent. However, NIV has been recently applied in hematologic malignancy patients during an early or/and late respiratory failure, showing a favorable impact improving the outcome. At an early stage, one study showed CPAP to reduce respiratory complications and to improve the outcome of mortality rate from 75% in the control group to 15% in the treatment group, when compared to oxygen therapy. In other two randomized control trials, NIV in comparison to invasive mechanical ventilation demonstrated to reduce mortality rate from 100% to 53-61%. As most of the non-randomized control trials applied NIV in a general population of immunosuppressed patients, results are very difficult to analyze. So far, the treatment starting, and duration time are still not clearly defined. Novel clinical trials should be performed to elucidate the appropriate application of NIV in this population.

Are guidelines for non-invasive ventilation during weaning still valid?

Noninvasive ventilation (NIV) has gained increasing acceptance over the years to reduce endotracheal intubation, pneumonia and to prevent or treat respiratory failure in patients with different diagnoses. The international consensus conference, and the British society guidelines on NIV ventilation have analyzed its use during the weaning phase concluding that there were still conflicting results of its use. However, recent clinical trials have shown clear clinical benefits on the use of NIV in several patient populations during the weaning period. Acute respiratory failure (ARF) during the weaning process is the main object of recently published studies. The latest published randomized trials on the application of NIV for acute respiratory failure following extubation failed to demonstrate any favorable outcome. Even so, the use of NIV during the process of weaning in patients experiencing multiple weaning failure or as a preventive therapy in patients at higher risk of respiratory deterioration showed improved clinical outcomes only in chronic obstructive pulmonary disease and in particular in hypercapnic patients. Reduced invasive mechanical ventilation, tracheostomy and lower mortality rate at 90 days were the major advantages.

Simulation of ozone depletion using ambient irradiance supplemented with UV lamps.

In studies of the biological effects of UV radiation, ozone depletion can be mimicked by performing the study under ambient conditions and adding radiation with UV-B lamps. We evaluated this methodology at three different locations along a latitudinal gradient: Rimouski (Canada), Ubatuba (Brazil) and Ushuaia (Argentina). Experiments of the effect of potential ozone depletion on marine ecosystems were carried out in large outdoor enclosures (mesocosms). In all locations we simulated irradiances corresponding to 60% ozone depletion, which may produce a 130-1900% increase in 305 nm irradiance at noon, depending on site and season. Supplementation with a fixed percentage of ambient irradiance provides a better simulation of irradiance increase due to ozone depletion than supplementation with a fixed irradiance value, particularly near sunrise and sunset or under cloudy skies. Calculations performed for Ushuaia showed that, on very cloudy days, supplementation by the square-wave method may produce unrealistic irradiances. Differences between the spectra of the calculated supplementing irradiance and the lamp for a given site and date will be a function of the time of day and may become more or less pronounced according to the biological weighting function of the effect under study.

Rhythmicity of the cGMP-related signal transduction pathway in the mammalian circadian system.

Entrainment of mammalian circadian rhythms requires the activation of specific signal transduction pathways in the suprachiasmatic nuclei (SCN). Pharmacological inhibition of kinases such as cGMP-dependent kinase (PKG) or Ca2+/calmodulin-dependent kinase, but not cAMP-dependent kinase, blocks the circadian responses to light in vivo. Here we show a diurnal and circadian rhythm of cGMP levels and PKG activity in the hamster SCN, with maximal values during the day or subjective day. This rhythm depends on phosphodiesterase but not on guanylyl cyclase activity. Five-minute light pulses increased cGMP levels at the end of the subjective night [circadian time 18 (CT18)], but not at CT13.5. Western blot analysis indicated that the PKG II isoform is the one present in the SCN. Inhibition of PKG or guanylyl cyclase in vivo significantly attenuated light-induced phase shifts at CT18 (after 5-min light pulses) but did not affect c-Fos expression in the SCN. These results suggest that cGMP and PKG are related to SCN responses to light and undergo diurnal and circadian changes.

Cyclic AMP and protein kinase A rhythmicity in the mammalian suprachiasmatic nuclei.

The levels of cyclic AMP and protein kinase A, as well as the activity of this enzyme, were measured in the hamster suprachiasmatic nuclei at different time points throughout the daily or circadian cycle. Significant diurnal variations for levels of AMPc and the catalytic subunit of protein kinase A and the activity of this enzyme were found. All of these parameters tended to increase throughout the nocturnal phase, reaching higher values at the end of the night and the beginning of the day and minimal values around the time of lights off. This rhythmicity appears to be under exogenous control, since constant darkness abolished fluctuations throughout the circadian cycle. In vitro incubation in the presence of melatonin during the day significantly decreased cyclic AMP levels and basal protein kinase A activity in the SCN, while neither neuropeptide Y nor light pulses affected these parameters. These results suggest a significant diurnal regulation of the cyclic AMP-dependent system in the hamster circadian clock.

The relationship between gas delivery patterns and the lower inflection point of the pressure-volume curve during partial liquid ventilation.

STUDY QUESTION: To determine whether a positive end-expiratory pressure (PEEP) level equivalent to the lower inflection point (LIP) could be identified by evaluation of the airway pressure, flow (f1. gif" BORDER="0">), and volume vs time waveforms during partial liquid ventilation (PLV). DESIGN: Prospective application of PEEP during PLV in a healthy animal model. SETTING: University hospital animal laboratory. PARTICIPANTS: Five healthy sheep weighing 30 kg each. INTERVENTIONS: The sequential application of 0 to 20 cm H(2)O PEEP in 2.5-cm H(2)O steps during PLV with both pressure and volume ventilation. MEASUREMENTS: Analysis of the pressure, volume, and f1. gif" BORDER="0"> waveforms as PEEP is sequentially increased. RESULTS: At 0 cm H(2)O PEEP, VT was markedly reduced compared with PEEP VT at > or = 7.5 cm H(2)O (p < 0.05) in pressure control ventilation (PCV), and peak inspiratory pressure minus PEEP was markedly increased compared with PEEP at > or = 5.0 cm H(2)O (p < 0.05) in volume control ventilation. At 10 cm H(2)O PEEP, all waveforms began to stabilize, and no significant differences in any variable assessed were measured at > 12.5 cm H(2)O PEEP. CONCLUSIONS: The application of PEEP during PLV markedly alters airway waveforms. Low PEEP decreases VT in PCV and increases airway pressure in VCV. The PEEP level equal to the LIP during PLV can be grossly estimated from airway waveforms. PEEP at > or = 10 cm H(2)O is needed to normalize gas delivery to functional residual capacity in the uninjured lung that is partially filled with perfluorocarbon.

Photic control of nitric oxide synthase activity in the hamster suprachiasmatic nuclei.

Circadian rhythms are controlled by an endogenous clock, which in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN). A role for nitric oxide in circadian responses to light has been indicated. To test the role of nitric oxide synthase (NOS) in the SCN and in circadian responses to light, we examined NOS specific activity at different time points and photic conditions. NOS activity was determined by the conversion of 3H-arginine to 3H-citrulline. NOS enzymatic activity in the SCN was significantly higher during the dark phase than during the day, without any changes in the levels of the NOS protein. However, this difference disappeared when animals were placed under constant darkness, and NOS activity was similar at CT 8 and CT 18 (with CT 12 defined as the onset of the subjective night). When 5-min light pulses were administered at these time points (when light would induce no phase shift or a phase advance, respectively), NOS activity was significantly increased almost equally. A spectrophotometric assay was used to determine NO content in the SCN, showing relatively high constitutive levels enhanced by 100 microM glutamate. These results suggest that NOS activity is not controlled by the circadian clock, although it might mediate some of the effects of light on biological rhythms.