Performance characteristics of 10 home mechanical ventilators in pressure-support mode: a comparative bench study

OBJECTIVE: Inspiratory pressure (Pi) support delivered by a bilevel device has become the technique of choice for noninvasive home ventilation. Considerable progress has been made in the performance and functionality of these devices. The present bench study was designed to compare the various characteristics of 10 recently developed bilevel Pi devices under different conditions of respiratory mechanics. DESIGN: Bench model study. SETTING: Research laboratory, university hospital. MEASUREMENTS: Ventilators were connected to a lung model, the mechanics of which were set to normal, restrictive, and obstructive, that was driven by an ICU ventilator to mimic patient effort. Pressure support levels of 10 and 15 cm H(2)O, and maximum were tested, with "patient" inspiratory efforts of 5, 10, 15, 20, and 25 cm H(2)O. Tests were conducted in the absence and presence of leaks in the system. Trigger delay, trigger-associated inspiratory workload, pressurization capabilities, and cycling were analyzed. RESULTS: All devices had very short trigger delays and triggering workload. Pressurization capability varied widely among the machines, with some bilevel devices lagging behind when faced with a high inspiratory demand. Cycling was usually not synchronous with patient inspiratory time when the default settings were used, but was considerably improved by modifying cycling settings, when that option was available. CONCLUSIONS: A better knowledge of the technical performance of bilevel devices (ie, pressurization capabilities and cycling profile) may prove to be useful in choosing the machine that is best suited for a patient's respiratory mechanics and inspiratory demand. Clinical algorithms to help set cycling criteria for improving patient-ventilator synchrony and patient comfort should now be developed.     

Is there a close relationship between changes in amplitudes of distortion product otoacoustic emissions and hair cell damage after exposure to realistic industrial noise in guinea pigs?

In long-term experiments in awake guinea pigs (n=12), distortion product otoacoustic emissions (DPOAEs) at various frequencies were measured repeatedly over 6–8 months. About 9 weeks after the first measurement, the animals were exposed to industrial noise (car industry, maximal intensity about 110 dB SPL) for 2 h. The amplitudes of DPOAE were measured prior to noise exposure and 10 min, 70 min, 1 day and 2 days after the noise exposure and then once every week. Three to four months after noise exposure, the animals were killed, and the cochleae were prepared for scanning electron microscopy. The row of inner hair cells (IHCs) was complete in all animals, while the rows of outer hair cells (OHCs) showed a considerable hair cell loss in some of the animals without a correlation to the change in amplitudes of DPOAE. However, a closer relationship between the decline of amplitudes of DPOAE and the number of missing and changed OHCs (fused stereocilia bundles, missing tip links) could be established. The number of lost OHC does not reflect the decline in DPOAE in all cases. This discrepancy must be considered when the degree of hearing loss needs to be established from changed DPOAE.     

Characterization of two novel mutations of the antithrombin gene observed in Japanese thrombophilic patients

We investigated the molecular basis of reduced functional levels of antithrombin (AT) in two individuals suffering from thromboembolic events. In each case direct sequencing of amplified DNA revealed 13,260-13,262 del in one patient and 2511C>A in the other patient, predicting a heterozygous E381del and P16H, respectively. Both patients had no 20210A allele and factor V Leiden mutation. To understand the molecular mechanism responsible for antithrombin deficiency, stable expression experiments were performed using HEK293 cells transfected with the expression vector containing the wild-type or the mutated recombinant cDNA. In these experiments, the media levels of the two mutated antithrombins were the same as that of wild type, but the specific activity of the E381del mutant decreased significantly compared with that of wild type. These results showed that the E381del mutation was responsible for type II deficiency, whereas the other mutation, P16H, did not produce any definite abnormality which could contribute to antithrombin deficiency.     

Repeated contact with subtoxic soman leads to synaptic vulnerability in hippocampus

Soman, an anticholinesterase and dangerous nerve agent, produces convulsions, memory impairment, and cell loss in the brain, especially in the hippocampus. Soman-induced accumulation of acetylcholine initiates mechanisms responsible for the development of incapacitating seizures. The prolonged epileptiform nature of these seizures causes the release of another excitatory neurotransmitter, glutamate, which has been linked to the toxic action of the nerve agent. Here, we tested whether subtoxic soman exposures influence the brain's sensitivity to glutamate-based excitotoxicity. Over a 1-week period, hippocampal slice cultures were exposed daily to a transient level of soman that produced no evidence of synaptic deterioration. After the subtoxic soman treatments, however, the tissue became vulnerable to a brief episode of glutamate receptor overstimulation that normally resulted in little or no excitotoxic damage. In those slice cultures treated with subtoxic soman, a decline in synaptic markers as well as an increase in spectrin breakdown occurred 24 hr after the mild excitotoxic event. Exposure to high soman concentrations alone produced similar synaptic degeneration, but without evident cell death, suggesting that synaptic decline is an early neurotoxicological response to the nerve agent. Interestingly, enhanced excitotoxic sensitivity caused the brain tissue to become susceptible to disparate insults initiated before or after the soman contact. These findings indicate that seemingly innocuous soman exposures leave the hippocampus sensitive to the types of insults implicated in traumatic brain injury and stroke. They also warn that asymptomatic contact with soman may lead to progressive synaptopathogenesis and that early indicators of soman exposure are critical to prevent potential brain injury.     

Pressure support versus assisted controlled noninvasive ventilation in neuromuscular disease

Introduction: Noninvasive ventilation (NIV) is being increasingly used in patients with chronic neuromuscular disorders, but the optimal ventilation mode remains unknown. We compared physiological short-term effects of assist/controlled ventilation (ACV) and two pressure-limited modes (pressure-support ventilation [PSV] and assist pressure-controlled ventilation [ACPV]) in patients with neuromuscular disease who needed NIV. Methods: Tidal volume was 10 to 12 mL/kg. The ACPV mode used the same respiratory cycle timing as the volume-limited mode. The level of inspiratory support was set to achieve the same tidal volume during the other ventilatory modes. Results: Thirteen patients with neuromuscular disease who met international criteria for NIV were included. The three ventilatory modes increased alveolar ventilation and decreased respiratory effort indices. However, no difference in breathing or respiratory effort was found among the three modes, with the exception that inspiratory peak flow and percentage of triggered cycles were higher during PSV than volume-limited ventilation. Interestingly, no relationship was observed between subjective patient preference and inspiratory effort indices or percentage of triggered cycles. Conclusion: In chronic, stable patients with neuromuscular disease, both noninvasive ACV, ACPV, and PSV had similar effects on alveolar ventilation and respiratory muscle unloading, despite some differences in the pattern of breathing and percentage of triggered cycles.     

Immunocytochemical investigation of neurovascular relationships in human tooth pulp

This study sought to explore the anatomical relationships between peptidergic nerves and blood vessels within human primary and permanent teeth. Extracted primary and permanent molars (n = 120) were split longitudinally, placed in Zamboni's fixative and the coronal pulps were processed for indirect immunofluorescence. Ten-micrometre-thick serial frozen pulp sections were triple-labelled using combinations of the following antisera: (1) protein gene-product 9.5 (PGP 9.5), a general neuronal marker; (2) one of the neuropeptides, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP) or neuropeptide Y (NPY); and (iii) the lectin Ulex europeus, a label for vascular endothelium. The mid-coronal pulp region was examined, using fluorescence microscopy, to determine the proportion of blood vessels showing a positive innervation (recorded when PGP 9.5-labelled nerves appeared to intersect the vessel wall). In addition, the percentage of these vascular-related nerves expressing each of the above neuropeptides was recorded. Overall, 20% of pulpal blood vessels appeared to have a positive innervation. In the main these were thick-walled arterioles. Capillaries, venules and lymphatics were mostly devoid of an associated innervation. Ninety-two per cent of vascular-related nerves expressed CGRP, 87% expressed SP, 15% expressed VIP and 80% expressed NPY. There were no significant differences in overall innervation or peptide-related innervation between primary and permanent teeth (P < 0.05, ANOVA), indicating that pulpal blood flow is likely to be subject to similar neurological control mechanisms in both dentitions.     

Identification of the degradation product of ezlopitant,a non-peptidic substance P antagonist receptor,by hydrogen deuterium exchange,electrospray ionization tandem mass spectrometry (ESI/MS/MS) and nuclear magnetic resonance (NMR) spectroscopy

The degradation product of ezlopitant was isolated from low specific activity material and identified by solution phase hydrogen/deuterium (H/D) exchange and electrospray ionization tandem mass spectrometry (ESI/MS/MS) to be an isopropyl peroxide analog of ezlopitant. The structure of the degradant was further confirmed by nuclear magnetic resonance (NMR) spectroscopy utilizing complete ¹H and ¹³C assignments. Studies were also performed to identify the factors responsible for the oxidative degradation of ezlopitant, which included salt form, storage conditions and salt formation solvent. Of all the variable studies over a 3 weeks period, only a change in the salt form prevented this oxidative degradation.     

Anxiolytic properties of botanical extracts in the chick social separation-stress procedure

RATIONALE: The recent growth in sales of natural products labeled as dietary supplements in the United States has renewed scientific interest in the study of the therapeutic effects of multi-component botanical products. OBJECTIVES: This study sought to determine whether botanical extracts derived from the Rutaceae family, Acori graminei, the Magnoliaceae family, Alchemilla vulgaris and Primula veris, which had previously been identified in bioassays as having potential anxiolytic activity, were active in the chick social separation-stress procedure. METHODS: Eight-day-old chicks received IP injections of test articles 30 min before being tested in the presence of two social companions or in isolation for a 3-min observation period. Dependent measures were: a) latency to adopt a ventral recumbent posture to index sedation, b) number of vocalizations to index separation-distress and c) a composite pain score (comprised of footlift frequency and footlift duration in response to 50 microl of 0.10% formalin injected into the plantar surface of the foot) to index stress-induced analgesia. RESULTS: Proprietal extracts NPS00033 from the Rutaceae plant family and NPS00039 (Relora) from the Magnoliaceae plant family screened positive in this chick model without causing sedation. CONCLUSIONS: These results suggest that botanical extracts Relora and NPS00033 may be useful in modulating anxiety states.