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1.
Physiol Meas ; 40(2): 025008, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30736016

RESUMO

OBJECTIVE: Obstructive sleep-disordered breathing (SDB) events, unlike central events, are associated with increased respiratory effort. Esophageal pressure (P es) monitoring is the gold standard for measuring respiratory effort, but it is typically poorly tolerated because of its invasive nature. The objective was to investigate whether machine learning can be applied to routinely collected non-invasive, polysomnography (PSG) measures to accurately model peak negative P es. APPROACH: One thousand one hundred and nineteen patients from the Stanford Sleep Clinic with PSGs containing P es served as the sample. The selected non-invasive PSG signals included nasal pressure, oral airflow, thoracoabdominal effort, and snoring. A long short-term memory neural network was implemented to achieve a context-based mapping between the non-invasive features and the P es values. A hold-out dataset served as a prospective validation of the algorithm without needing to undertake a costly new study with the impractically invasive P es. MAIN RESULTS: The median difference between the measured and predicted P es was 0.61 cmH2O with an interquartile range (IQR) of 2.99 cmH2O and 5th and 95th percentiles of -5.85 cmH2O and 5.47 cmH2O, respectively. The model performed well when compared to actual esophageal pressure signal (ρ median = 0.581, p  = 0.01; IQR = 0.298; ρ 5% = 0.106; ρ 95% = 0.843). SIGNIFICANCE: A significant difference in predicted P es was shown between normal breathing and all obstructive SDB events; whereas, central apneas did not significantly differ from normal breathing. The developed system may be used as a tool for quantifying respiratory effort from the existing clinical practice of PSG without the need for P es, improving characterization of SDB events as obstructive or not.

2.
Immunol Res ; 62(2): 253, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25948476
3.
Immunol Res ; 58(2-3): 315-39, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24825774

RESUMO

Although narcolepsy was first described in the late nineteenth century in Germany and France, much of the research on this disorder has been conducted at Stanford University, starting with Drs. William C. Dement and Christian Guilleminault in the 1970s. The prevalence of narcolepsy was established, and a canine model discovered. Following the finding in Japan that almost all patients with narcolepsy carry a specific HLA subtype, HLA-DR2, Hugh Mac Devitt, F. Carl Grumet, and Larry Steinman initiated immunological studies, but results were generally negative. Using the narcoleptic canines, Dr. Nishino and I established that stimulants increased wakefulness by stimulating dopaminergic transmission while antidepressants suppress cataplexy via adrenergic reuptake inhibition. A linkage study was initiated with Dr. Grumet in 1988, and after 10 years of work, the canine narcolepsy gene was cloned by in 1999 and identified as the hypocretin (orexin) receptor 2. In 1992, studying African Americans, we also found that DQ0602 rather than DR2 was a better marker for narcolepsy across all ethnic groups. In 2000, Dr. Nishino and I, in collaboration with Dr. Lammers in the Netherlands, found that hypocretin 1 levels in the cerebrospinal fluid (CSF) were undetectable in most cases, establishing hypocretin deficiency as the cause of narcolepsy. Pursuing this research, our and Dr. Siegel's group, examining postmortem brains, found that the decreased CSF hypocretin 1 was secondary to the loss the 70,000 neurons producing hypocretin in the hypothalamus. This finding revived the autoimmune hypothesis but attempts at demonstrating immune targeting of hypocretin cells failed until 2013. At this date, Dr. Elisabeth Mellins and I discovered that narcolepsy is characterized by the presence of autoreactive CD4(+) T cells to hypocretin fragments when presented by DQ0602. Following reports that narcolepsy cases were triggered by vaccinations and infections against influenza A 2009 pH1N1, a new pandemic strain that erupted in 2009, our groups also established that a small epitope of pH1N1 resembles hypocretin and is likely involved in molecular mimicry. Although much remains to be done, these achievements, establishing hypocretin deficiency as the cause of narcolepsy, demonstrating its autoimmune basis, and showing molecular mimicry between hypocretin and sequences derived from a pandemic strain of influenza, are likely to remain classics in human immunology.


Assuntos
Narcolepsia , Pesquisa , Faculdades de Medicina , Universidades , Alelos , Animais , California , Modelos Animais de Doenças , Cães , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos de Histocompatibilidade/genética , Antígenos de Histocompatibilidade/imunologia , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Tolerância Imunológica , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Mimetismo Molecular , Narcolepsia/epidemiologia , Narcolepsia/etiologia , Narcolepsia/fisiopatologia , Neuropeptídeos/imunologia , Orexinas , Prevalência , Receptores de Antígenos de Linfócitos T/metabolismo , Pesquisa/história , Pesquisa/tendências , Infecções Respiratórias/complicações , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Sono REM
4.
Neurotherapeutics ; 9(4): 739-52, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23065655

RESUMO

Narcolepsy and other syndromes associated with excessive daytime sleepiness can be challenging to treat. New classifications now distinguish narcolepsy/hypocretin deficiency (also called type 1 narcolepsy), a lifelong disorder with well-established diagnostic procedures and etiology, from other syndromes with hypersomnolence of unknown causes. Klein-Levin Syndrome, a periodic hypersomnia associated with cognitive and behavioral abnormalities, is also considered a separate entity with separate therapeutic protocols. Non hypocretin-related hypersomnia syndromes are diagnoses of exclusion. These diagnoses are only made after eliminating sleep deprivation, sleep apnea, disturbed nocturnal sleep, and psychiatric comorbidities as the primary cause of daytime sleepiness. The treatment of narcolepsy/hypocretin deficiency is well-codified, and involves pharmacotherapies using sodium oxybate, stimulants, and/or antidepressants, plus behavioral modifications. These therapies are almost always needed, and the risk-to-benefit ratio is clear, notably in children. Detailed knowledge of the pharmacological profile of each compound is needed to optimize use. Treatment for other syndromes with hypersomnolence is more challenging and less codified. Preferably, therapy should be conservative (such as modafinil, atomoxetine, behavioral modifications), but it may have to be more aggressive (high-dose stimulants, sodium oxybate, etc.) on a case-by-case, empirical trial basis. As cause and evolution are unknown in these conditions, it is important to challenge diagnosis and therapy over time, keeping in mind the possibility of tolerance and the development of stimulant addiction. Kleine-Levin Syndrome is usually best left untreated, although lithium can be considered in severe cases with frequent episodes. Guidelines are provided based on the literature and personal experience of the author.


Assuntos
Distúrbios do Sono por Sonolência Excessiva/tratamento farmacológico , Narcolepsia/tratamento farmacológico , Antidepressivos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Humanos , Guias de Prática Clínica como Assunto , Síndrome
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