Noninvasive continuous positive airway pressure in elderly cardiogenic pulmonary edema patients

Objective To compare the physiological effects and the clinical efficacy of continuous positive airway pressure (CPAP) vs standard medical treatment in elderly patients (75 years) with acute hypoxemic respiratory failure related to cardiogenic pulmonary edema.Design A prospective, randomized, concealed, and unblinded study of 89 consecutive patients who were admitted to the emergency departments of one general, and three teaching, hospitals.Intervention Patients were randomly assigned to receive standard medical treatment alone (n=46) or standard medical treatment plus CPAP (n=43).Measurements Improvement in PaO₂/FIO₂ ratio, complications, length of hospital stay, early 48-h and overall mortality, compared between the CPAP and standard treatment groups.Results Study groups were comparable with regard to baseline physiological and clinical characteristics (age, sex ratio, autonomy, medical history, cause of pulmonary edema). Within 1 h, noninvasive continuous positive airway pressure led to decreased respiratory rate (respiratory rate, 27±7 vs 35±6 breaths/min; p=0.009), and improved oxygenation (PaO₂/F_IO₂, 306±104 vs 157±71; p=0.004) compared with baseline, whereas no differences were observed within the standard treatment group. Severe complications occurred in 17 patients in the standard treatment group, vs 4 patients in the noninvasive continuous positive airway pressure group (p=0.002). Early 48-h mortality was 7% in the noninvasive continuous positive airway pressure group, compared with 24% in the standard treatment group (p=0.017); however, no sustained benefits were observed during the overall hospital stay.Conclusion Noninvasive continuous positive airway pressure promotes early clinical improvement in elderly patients attending emergency departments for a severe pulmonary edema, but only reduces early 48-h mortality.     

Anatomic M-mode, a pertinent tool for the daily practice of transthoracic echocardiography.

OBJECTIVES: We sought to compare anatomic M-mode (AMM), a new echocardiographic postprocessing option, and conventional M-mode (CMM) using fundamental imaging and tissue harmonic imaging. METHODS: Transthoracic echocardiography was performed in 15 selected patients to analyze the reproducibility of AMM and in 47 patients to assess its clinical value versus CMM. Acquisitions were performed successively: CMM fundamental imaging; CMM tissue harmonic imaging; tissue harmonic imaging cineloops for AMM; and fundamental imaging cineloops for AMM. Quantitative analysis was performed offline. The angle alpha between the CMM line and the septal endocardial interface was calculated and the expected percentage of error in measuring left ventricular diameter was derived. RESULTS: AMM analysis was reproducible. Optimal AMM full echocardiographic definition was obtainable in 77% of the population, whereas CMM was optimal for 49% because of scan line misalignment, causing a measurement overestimation exceeding 5%. CONCLUSION: The ability with AMM to reduce the alpha angle to 0 degrees and, thus, avoid overestimation of left ventricular dimensions might improve follow-up in several pathologic conditions.     

Early prenatal exposure to MPTP does not affect nigrostrial neurons in macaque monkey

The discovery of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), a toxin that induces parkinsonism in both human and primate, has prompted the search for environmental toxins potentially responsible for idiopathic Parkinson's disease (PD). The present study reports the ultimate effects of MPTP intoxication of a female macaque monkey, which unraveled to be pregnant after parkinsonism had developed, upon its fetus. Detailed examination of the offpsring nigrostriatal pathway showed that tyrosine hydroxylase immunoreactivity in caudate‐putamen nuclei and substantia nigra compacta (SNc) was not different from an age‐matched control. Biochemical analysis of the tissue content of dopaminergic markers further suggested modification of metabolism in the MPTP‐exposed monkey. These data suggest that early prenatal intoxication does not destroy nigrostriatal neurons, most likely because dopamine neurons had not developed yet when exposed to MPTP. Synapse 70:52–56, 2016. © 2015 Wiley Periodicals, Inc.     

Double-dissociation of the catecholaminergic modulation of synaptic transmission in the oval bed nucleus of the stria terminalis

The bed nucleus of the stria terminalis (BST) is a cluster of nuclei within the extended amygdala, a forebrain macrostructure with extensive projection to motor nuclei of the hindbrain. The subnuclei of the BST coordinate autonomic, neuroendocrine, and somato-motor functions and receive robust neuromodulatory monoaminergic afferents, including 5-HT-, noradrenaline (NA)-, and dopamine (DA)-containing terminals. In contrast to 5-HT and NA, little is known about how DA modulates neuronal activity or synaptic transmission in the BST. DA-containing afferents to the BST originate in the ventral tegmental area, the periaqueducal gray, and the retrorubral field. They form a fairly diffuse input to the dorsolateral BST with dense terminal fields in the oval (ovBST) and juxtacapsular (jxBST) nuclei. The efferent-afferent connectivity of the BST suggests that it may play a key role in motivated behaviors, consistent with recent evidence that the dorsolateral BST is a target for drugs of abuse. This study describes the effects of DA on synaptic transmission in the ovBST. Whole cell voltage clamp recordings were performed on ovBST neurons in brain slices from adult rats in the presence or absence of exogenous DA and receptor-targeted agonists and antagonists. The results showed that DA selectively and exclusively reduced inhibitory synaptic transmission in the ovBST in a dose-dependent and D2-like dopamine receptor-dependent manner. DA also modulated excitatory synaptic transmission in a dose-dependent dependent manner. However, this effect was mediated by α2-noradrenergic receptors. Thus these data reveal a double dissociation in catecholaminergic regulation of excitatory and inhibitory synaptic transmission in the ovBST and may shed light on the mechanisms involved in neuropathological behaviors such as stress-induced relapse to consumption of drugs of abuse.     

Altered D(1) dopamine receptor trafficking in parkinsonian and dyskinetic non-human primates

Dyskinesias represent a debilitating complication of levodopa therapy for Parkinson's disease (PD). While we recently demonstrated that levodopa-induced dyskinesia results from increased dopamine D(1) receptor-mediated transmission, we also questioned the possible role of subcellular localization of D(1) and D(2) receptors in mediating these effects as we previously showed that D(1) receptors undergo differential trafficking in striatal neurons of non-dyskinetic PD patients. Taking advantage of a monkey brain bank, we here report changes affecting the cellular and subcellular distribution of D(1) and D(2) dopamine receptors within the striatum of three experimental groups: normal, parkinsonian and dyskinetic L-dopa-treated parkinsonian animals. Our studies at both light and electron microscopy levels show a recruitment of D(1) receptor at the plasma membrane of striatal neurons in the parkinsonian animals and a strong increase of D(1) expression both at the membrane and in cytoplasm of dyskinetic animals, whereas D(2) receptor distribution is only modestly affected in all conditions. Our results rule out the hypothesis of a pathological overinternalization of dopamine receptors in levodopa-induced dyskinesia but raise the possibility for involvement of D(1) receptors in the priming phenomenon through massive and sudden internalization in response to the first ever administration of L-dopa and for an altered homologous desensitization mechanism in dyskinesia leading to an increased availability of D(1) receptors at membrane. Further experiments including parkinsonian monkeys chronically treated with L-dopa that show no dyskinesia and parkinsonian monkeys treated only once with L-dopa are now necessary to confirm our hypothesis.