RESUMO
PURPOSE: It is well established that, together with a multitude of other adverse effects on health, severe obstructive sleep apnoea causes reduced cerebral perfusion and, in turn, reduced cerebral function. Less clear is the impact of moderate obstructive sleep apnoea (OSA). Our aim was to determine if cerebral blood flow is impaired in people diagnosed with moderate OSA. METHODS: Twenty-four patients diagnosed with moderate OSA (15 ≤ apnoea-hypopnea index (AHI) < 30) were recruited (aged 32-72, median 59 years, 10 female). Seven controls (aged 42-73 years, median 62 years, 4 female) with an AHI < 5 were also recruited. The OSA status of all participants was confirmed at baseline by unattended polysomnography and they had an MRI arterial-spin-labelling scan of cerebral perfusion. RESULTS: Neither global perfusion nor voxel-wise perfusion differed significantly between the moderate-OSA and control groups. We also compared the average perfusion across three regional clusters, which had been found in a previous study to have significant perfusion differences with moderate-severe OSA versus control, and found no significant difference in perfusion between the two groups. The perfusions were also very close, with means of 50.2 and 51.8 mL/100 g/min for the moderate-OSAs and controls, respectively, with a negligible effect size (Cohen's d = 0.10). CONCLUSION: We conclude that cerebral perfusion is not impaired in people with moderate OSA and that cerebral flow regulatory mechanisms can cope with the adverse effects which occur in moderate OSA. This is an important factor in clinical decisions for prescription of continuous positive airway pressure therapy (CPAP).
Assuntos
Circulação Cerebrovascular , Polissonografia , Apneia Obstrutiva do Sono , Vigília , Humanos , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Circulação Cerebrovascular/fisiologia , Vigília/fisiologia , Imageamento por Ressonância Magnética , Valores de Referência , Encéfalo/fisiopatologia , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND AND OBJECTIVE: Oxygen is used in many clinical scenarios, however the variable performance of nasal cannulae makes determining the precise fraction of inspired oxygen (FiO2 ) difficult. We developed a novel method for measurement of the tracheal FiO2 using a catheter placed via bronchoscopy. We investigate the effects of oxygen delivery, respiratory rate, mouth position and estimated minute ventilation (VE ) on the FiO2 delivered by nasal cannulae. METHODS: The catheter was placed in 20 subjects. Tracheal gas concentrations were analysed during six 5-min treatments controlling for oxygen delivery rate, respiratory rate and mouth position. Ventilation was monitored with respiratory inductive plethysmography (RIP). The FiO2 delivered by nasal cannulae was compared between treatments, and we investigated the relationships among the FiO2 , alveolar partial pressure of oxygen (PA O2 ) and VE . RESULTS: The FiO2 increased by 0.038/L/min of oxygen. Respiratory rate had a significant effect on the FiO2 . A normal respiratory rate of 15 breaths/min and oxygen supplementation via nasal cannula at 2 L/min resulted in an FiO2 of 0.296; however, FiO2 decreased by 0.012 at 20 breaths/min and 0.004 at 10 breaths/min. The mean FiO2 decreased by 0.024 with the mouth open. The FiO2 and PA O2 were observed to decrease with increasing VE . CONCLUSIONS: Continuous measurement of the FiO2 using a transtracheal catheter provides detailed insight into inspiratory changes of the FiO2 delivered by nasal cannulae. Our study confirms that respiratory rate, VE and mouth position significantly influence the inspired oxygen concentration. These parameters should be accounted for when prescribing oxygen.
Assuntos
Broncoscopia/métodos , Intubação Intratraqueal/métodos , Oxigenoterapia , Oxigênio , Catéteres , Protocolos Clínicos , Monitoramento de Medicamentos/métodos , Humanos , Inalação/fisiologia , Oxigênio/administração & dosagem , Oxigênio/análise , Oxigenoterapia/instrumentação , Oxigenoterapia/métodos , Pletismografia/métodos , Testes de Função Respiratória/métodos , Taxa Respiratória/fisiologiaRESUMO
BACKGROUND: Healthy individuals are known to have significantly reduced oxygen saturations at rest when acutely exposed to moderate altitudes, such as during commercial flight. There is a paucity of data on the response of healthy individuals to exercise at these altitudes. The aim of this study was to establish the normal response to exercise during acute, moderate altitude exposure with regard to oxygen saturations. Secondary aims were to establish if this response can be predicted from pulmonary function measurements at sea level. METHODS: At sea level, 20 subjects performed pulmonary function tests, including submaximal steady state exercise, followed by replication of submaximal steady state exercise during acute altitude exposure at 6844 ft (2086 m). RESULTS: Mean resting oxygen saturation at 6844 ft (2086 m) was 96%, a significant reduction from the sea level value of 99%. Mean nadir oxygen saturation during steady state exercise at moderate altitude was 89%. There was a weak negative correlation between aerobic capacity and end exercise oxygen saturation at altitude. Modified BORG dyspnea scores were unchanged at rest at 6844 ft (2086 m) and higher post-exercise at 6844 ft (2086 m) when compared to sea level, although absolute values were low. DISCUSSION: Healthy individuals desaturate at rest and upon exercise during acute altitude exposure at 6844 ft (2086 m). A quarter of participants experienced SpO2 < or = 85% upon exercise at altitude, although this had no correlation with dyspnea scores or baseline pulmonary function measurements. The weak negative correlation between aerobic capacity and end exercise oxygen saturation is unexplained and merits further research.
Assuntos
Altitude , Exercício Físico/fisiologia , Hipóxia/fisiopatologia , Adulto , Medicina Aeroespacial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Consumo de Oxigênio , Testes de Função RespiratóriaRESUMO
BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the current policies of Australian and New Zealand airlines on the use of in-flight CPAP by passengers with OSA. METHODS: A survey was conducted of 53 commercial airlines servicing international routes. Information was obtained from airline call centres and websites. The policies, approval schemes and costs associated with in-flight use of CPAP were documented for individual airlines. RESULTS: Of the 53 airlines contacted, 28 (53%) were able to support passengers requiring in-flight CPAP. All these airlines required passengers to bring their own machines, and allowed the use of battery-operated machines. Six airlines (21%) allowed passengers to plug their machines into the aircraft power supply. The majority of airlines (19, 68%) did not charge passengers for the use of CPAP, while 9 (32%) were unsure of their charging policies. Many airlines only permitted certain models of CPAP machine or battery types. CONCLUSIONS: Many airlines are unaware of CPAP. Those who are, have relatively consistent policies concerning the use of in-flight CPAP.
Assuntos
Aeronaves , Pressão Positiva Contínua nas Vias Aéreas/estatística & dados numéricos , Política Pública/tendências , Apneia Obstrutiva do Sono/terapia , Austrália , Pressão Positiva Contínua nas Vias Aéreas/economia , Coleta de Dados , Humanos , Nova Zelândia , ViagemRESUMO
AIM: Obtain an overview of the current sleep habits and sleep hygiene practices in a group of intermediate-aged students, and establish whether these students achieve adequate sleep according to the New Zealand education and health guidelines. METHODS: A standardised sleep health questionnaire and seven-day sleep diary were completed by 163 participants (aged 11-13; 62% female) from a cross-section of five Christchurch schools. RESULTS: In this group, 71% of students reported 9-11 hours of sleep per night (averaged over seven days). Total sleep time was independent of gender and the day of the week. Bedtimes and wake-times were earlier from Monday-Thursday compared to the weekend (p<0.0001). Fifty-nine percent of students used a device in the hour before bed. Pre-bedtime device users were more likely to achieve less sleep than non-device users (p<0.001). The majority of students (66%) did not choose their bedtime. CONCLUSIONS: In this group of students, the majority achieved a sleep duration within the advised Ministry of Education and Sleep Health Foundation guidelines, despite non-recommended sleep hygiene practices in the pre-bed routine. Parental guidance, with respect to bed times and reduction in device usage before sleep are two factors that could be employed to improve sleep in this group.
Assuntos
Sono/fisiologia , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Nova Zelândia , Instituições Acadêmicas , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the current Australian/New Zealand airline policy on supplemental in-flight oxygen for passengers with lung disease. METHODS: Fifty-four commercial airlines servicing international routes were surveyed. Information was gathered from airline call centres and web sites. The survey documented individual airline policy on in-flight oxygen delivery, approval schemes, equipment and cost. RESULTS: Of the 54 airlines contacted, 43 (81%) were able to support passengers requiring in-flight oxygen. The majority (88%) of airlines provided a cylinder for passengers to use. Airline policy for calculating the cost of in-flight oxygen differed considerably between carriers. Six (14%) airlines supplied oxygen to passengers free of charge; however, three of these airlines charged for an extra seat. Fifteen airlines (35%) charged on the basis of oxygen supplied, that is, per cylinder. Fourteen airlines (33%) had a flat rate charge per sector. CONCLUSIONS: This study confirmed that most airlines can accommodate passengers requiring supplemental oxygen. However, the findings highlight inconsistencies in airline policies and substantial cost differences for supplemental in-flight oxygen. We advocate an industry standardization of policy and cost of in-flight oxygen.
Assuntos
Aeronaves , Política Organizacional , Oxigenoterapia , Política Pública , Viagem , Austrália , Auditoria Clínica , Humanos , Nova Zelândia , Oxigenoterapia/economia , Oxigenoterapia/instrumentaçãoRESUMO
BACKGROUND AND OBJECTIVE: Air travel guidelines recommend using baseline arterial oxygen levels and the hypoxic challenge test (HCT) to predict in-flight hypoxaemia and the requirement for in-flight oxygen in patients with lung disease. The purpose of the present study was to (i) quantify the hypoxaemic response to air travel and (ii) identify baseline correlate(s) to predict this response in passengers with non-obstructed lung disease. METHODS: Fourteen passengers (seven women) with chronic non-obstructed lung disease volunteered for this study. The study involved three phases: (i) respiratory function testing; (ii) in-flight measures (SpO(2), cabin pressure and dyspnoea); and (iii) a HCT. The in-flight hypoxaemic response was compared with the baseline arterial oxygen level, respiratory function and the HCT. RESULTS: All subjects flew without oxygen and no adverse events were recorded in-flight. Mean cabin pressure was 593 +/- 16 mm Hg. Pre-flight SpO(2) was 95 +/- 3% and significantly decreased to 85 +/- 9% in-flight, with further significant falls in subjects who walked during the flight (nadir SpO(2) 78 +/- 11%). The pre-flight SpO(2) showed the strongest correlation with in-flight SpO(2) (r = 0.91, P < 0.001). The HCT SpO(2) was moderately correlated to the in-flight SpO(2) (r = 0.58, P < 0.05). Spirometry, D(L,CO) and TLC measurements did not correlate with in-flight SpO(2). CONCLUSION: Significant in-flight desaturation can be expected in passengers with non-obstructive lung disease. Respiratory function did not predict in-flight desaturation. We found a good relationship between pre-flight SpO(2) and in-flight SpO(2) which supports the role of pre-flight oximetry for predicting in-flight hypoxaemia in passengers with non-obstructed lung disease.
Assuntos
Aeronaves , Hipóxia/etiologia , Pneumopatias/sangue , Pneumopatias/fisiopatologia , Guias de Prática Clínica como Assunto , Viagem , Adulto , Idoso , Pressão do Ar , Testes de Provocação Brônquica , Feminino , Humanos , Hipóxia/diagnóstico , Pneumopatias/complicações , Masculino , Pessoa de Meia-Idade , Oximetria , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
INTRODUCTION: Exposure to altitude invariably involves some form of physical activity. There are limited data available to help predict the response to activity at altitude in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the response to acute altitude exposure at rest and during exercise in patients with COPD. METHODS: Sea level measures of cardio-pulmonary function were compared to the resting and exercise hypoxemic response at the summit of the Mt. Hutt ski field (2086 m), New Zealand, in 18 patients with COPD. RESULTS: Ascent from sea level to altitude caused significant hypoxemia at rest (PaO2: 75 +/- 9 vs. 51 +/- 6 mmHg), and during a walk test (41 +/- 7 mmHg). At altitude, the walk test distance was reduced by 52%. Sea level PaO2 and SaO2 correlated with resting PaO2 (r = 0.69) and SaO2 (r = 0.79) at altitude. Diffusion capacity corrected for alveolar volume (K(CO)) correlated with resting SaO2 (r = 0.74) and exercise PaO2 (r = 0.75) at altitude. Aerobic capacity correlated with the walk test distance at altitude (r = 0.70). Spirometry, lung volumes, and ventilatory reserve did not correlate with the hypoxemic response to altitude. DISCUSSION: Baseline arterial oxygen levels and K(CO) are key measures in predicting the hypoxemic response to acute altitude exposure in patients with COPD. The impairment in gas exchange associated with COPD is a significant mechanism causing altitude-related hypoxemia in this group.
Assuntos
Altitude , Exercício Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Teste de Esforço , Feminino , Frequência Cardíaca , Humanos , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Testes de Função RespiratóriaRESUMO
INTRODUCTION: Altitude exposure will cause moderate to severe hypoxemia in patients with chronic obstructive pulmonary disease (COPD). Supplemental oxygen can be used to attenuate this hypoxemia; however, individual response is variable and difficult to predict. The aim of this study was to assess the efficacy of oxygen supplementation in patients with COPD at a barometric pressure similar to that of a commercial aircraft cabin. METHODS: Following sea-level (40 m) arterial blood gases measurements, 18 patients with COPD were driven to altitude (2086 m), where blood gases were repeated at rest and while on 2 L x min(-1) of supplementary oxygen (altitude O2). RESULTS: Ascent from sea level to altitude caused significant hypoxemia (75 +/- 9 vs. 51 +/- 6 mmHg), which was partially reversed by supplemental oxygen (64 +/- 9 mmHg). Oxygen supplementation did not significantly alter PaCO2 levels (vs. altitude PaCO2). There was a significant relationship between the sea-level CaO2 versus the altitude O2 CaO2 (r = 0.89, P < 0.001). There was a significant relationship (r = 0.81, P < 0.001) between altitude-induced desaturation and resaturation with the administration of oxygen. There was a significant negative correlation (r = -0.74, P < 0.001) between baseline K(CO) and the improvement in CaO2 with the administration of oxygen. CONCLUSION: Low-flow supplemental oxygen during acute altitude exposure will partially reverse altitude-induced hypoxemia in patients with COPD. Patients with diffusion impairments are likely to experience the greatest altitude desaturation, but will gain the most benefit from supplemental oxygen. Supplemental oxygen, delivered at 2 L x min(-1), should maintain clinically acceptable oxygenation during commercial air travel in patients with COPD.
Assuntos
Altitude , Hipóxia/terapia , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Medicina Aeroespacial , Idoso , Gasometria , Dióxido de Carbono/sangue , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hipóxia/fisiopatologia , Masculino , Oxigênio/sangue , Testes de Função RespiratóriaRESUMO
BACKGROUND: Limited data are available comparing air travel with the hypoxia inhalation test (HIT) in passengers with COPD. The aim of this study was to assess the predictive capability of the HIT to in-flight hypoxemia in passengers with COPD. METHODS: Thirteen passengers (seven female passengers) with COPD (mean [+/- SD], FEV(1)/FVC ratio, 44 +/- 17%) volunteered for this study. Respiratory function tests were performed preflight. Pulse oximetry, cabin pressure, and dyspnea were recorded in flight. The HIT and a 6-min walk test were performed postflight. The in-flight oxygenation response was compared to the HIT results and respiratory function parameters. RESULTS: All subjects flew without the use of oxygen, and no adverse events were recorded in-flight (mean cabin altitude, 2,165 m; altitude range, 1,892 to 2,365 m). Air travel caused significant desaturation (mean preflight oxygen saturation, 95 +/- 1%; mean in-flight oxygen saturation, 86 +/- 4%), which was worsened by activity (nadir pulse oximetric saturation [Spo(2)], 78 +/- 6%). The HIT caused mean desaturation that was comparable to that of air travel (84 +/- 4%). The mean in-flight partial pressure of inspired oxygen (Pio(2)) was higher than the HIT Pio(2) (113 +/- 3 mm Hg vs 107 +/- 1 mm Hg, respectively; p < 0.001). The HIT Spo(2) showed the strongest correlation with in-flight Spo(2) (r = 0.84; p < 0.001). CONCLUSION: Significant in-flight desaturation can be expected in passengers with COPD. The HIT results compared favorably with the air travel data, with differences explainable by Pio(2) and physical activity. The HIT is the best widely available laboratory test to predict in-flight hypoxemia.
Assuntos
Aeronaves , Altitude , Hipóxia/sangue , Hipóxia/diagnóstico , Oximetria/métodos , Oxigênio/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Feminino , Guias como Assunto , Humanos , Hipóxia/etiologia , Inalação/fisiologia , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/complicações , Testes de Função Respiratória , Fatores de RiscoRESUMO
Assessing the requirements for in-flight oxygen in passengers with pulmonary limitations can be a challenging task for clinicians. Aeromedical guidelines are available to help identify passengers that may require oxygen in flight. However, little is known about the actual in-flight response to passengers on oxygen. We measured the oxygen response (pulse oximetry) of a 67-yr-old female patient with chronic respiratory failure during a trans-Tasman flight (duration 170 min). This patient was assessed at the respiratory clinic before her journey and resting PaO2 (57 mmHg) indicated the requirement for in-flight oxygen. Bottled oxygen delivered at 2 L x min(-1) via nasal cannula was prescribed for her journey. Preflight SpO2 without supplemental oxygen was 92%. Mean in-flight SpO2 was well maintained at 93% while on oxygen at rest. There were four significant hypoxic events, which included light physical activity while on oxygen (three events; SpO2 to 84%) and a visit to the lavatory (off oxygen; SpO2 to 70%). Dyspnea and dizziness were reported during the lavatory visit. This case illustrates the importance of a preflight medical screening for passengers considered at risk during air travel and provides insight into the response of oxygen supplementation during flight.
Assuntos
Medicina Aeroespacial , Hipóxia/sangue , Oxigenoterapia , Insuficiência Respiratória/terapia , Idoso , Doença Crônica , Tontura/fisiopatologia , Dispneia/fisiopatologia , Feminino , Humanos , Hipóxia/fisiopatologia , Atividade Motora/fisiologia , Oximetria , Insuficiência Respiratória/sangue , Insuficiência Respiratória/fisiopatologiaRESUMO
Prior to 2007, increasing demand for sleep services, plus inability to adequately triage severity, led to long delays in sleep assessment and accessing continuous positive airway pressure. We established a community sleep assessment service carried out by trained general practices using a standardised tool and overnight oximetry. All cases were discussed at a multi-disciplinary meeting, with four outcomes: severe obstructive sleep apnoea treated with continuous positive airway pressure; investigation with more complex studies; sleep physician appointment; no or non-severe sleep disorder for general practitioner management. Assessment numbers increased steadily (~400 in 2007 vs. 1400 in 2015). Median time from referral to assessment and multi-disciplinary meeting was 28 and 48 days, respectively. After the first multi-disciplinary meeting, 23% of cases were assessed as having severe obstructive sleep apnoea. More complex studies (mostly flow based) were required in 49% of patients, identifying severe obstructive sleep apnoea in a further 13%. Thirty-seven percent of patients had obstructive sleep apnoea severe enough to qualify for funded treatment. Forty-eight percent of patients received a definitive answer from the first multi-disciplinary meeting. Median time from referral to continuous positive airway pressure for 'at risk' patients with severe obstructive sleep apnoea, e.g., commercial drivers, was 49 days, while patients with severe obstructive sleep apnoea but not 'at risk' waited 261 days for continuous positive airway pressure. Ten percent of patients required polysomnography, and 4% saw a sleep specialist. In conclusion, establishment of a community sleep assessment service and sleep multi-disciplinary meeting led to significantly more assessments, with short waiting times for treatment, especially in high-risk patients with severe obstructive sleep apnoea. Most patients can be assessed without more complex studies or face-to-face review by a sleep specialist. SLEEP DISORDERS: MORE ASSESSMENTS, SHORTER WAITS WITH COMMUNITY SLEEP SERVICE: A community-based service for common sleep disorders can provide rapid and easily accessed sleep assessment and treatment. A team led by Michael Hlavac and Michael Epton from Christchurch Hospital describe the creation of a sleep assessment service within the Canterbury district of New Zealand, in which initial assessments are conducted throughout the community by general practice teams under guidance and advice from sleep specialists at the region's largest hospital. Before the service, there were around 300 sleep assessments per year in all of Canterbury, a region with a population of around 510,000. Now, that number has more than tripled, with shorter waiting times for treatment, especially for people with severe sleep apnoea. The authors conclude that most patients can be assessed for a suspected sleep disorder without needing to visit a hospital's sleep unit.
Assuntos
Atenção à Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Desenvolvimento de Programas , Apneia Obstrutiva do Sono/diagnóstico , Pressão Positiva Contínua nas Vias Aéreas , Diagnóstico Tardio/prevenção & controle , Humanos , Nova Zelândia , Oximetria/métodos , Polissonografia , Encaminhamento e Consulta , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/terapia , Apneia Obstrutiva do Sono/terapia , Medicina do Sono , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/terapiaRESUMO
INTRODUCTION: There is little data available to determine the normal response to normobaric hypoxia inhalation testing (NHIT) and air travel. Quantifying a healthy response may assist in the evaluation of passengers considered at risk for air travel. The aims of this study were: (1) to quantify the degree of desaturation in healthy subjects during a NHIT and air travel; and (2) assess the validity of the NHIT when compared with actual in-flight responses. METHODS: There were 15 healthy adults (age 23-57; 10 women) who volunteered for this study. Preflight tests included lung function, arterial blood gas, pulse oximetry (SpO2), and NHIT (inspired oxygen 15%). SpO2 and cabin pressure were measured continuously on each subject during a commercial air flight (mean cabin altitude 2178 m; range 1719-2426 m). In-flight oxygenation was compared with the preflight NHIT. RESULTS: Lung function testing results were normal. There was significant desaturation (SpO2) during the NHIT (pre: 98 +/- 2%; post: 92 +/- 2%) and at cruising altitude (pre: 97 +/- 1%; cruise: 92 +/- 2%). There was no difference between the final NHIT SpO2 and the mean in-flight SpO2. There was a significant difference between the lowest in-flight SpO2 (88 +/- 2%) vs. the lowest NHIT SpO2, (90 +/- 2%). DISCUSSION: Oxygen saturation decreases significantly during air travel in normal individuals. In this group of healthy passengers the NHIT approximates some, but not all, aspects of in-flight oxygenation. These results can be used to describe a normal response to the NHIT and air-travel.
Assuntos
Medicina Aeroespacial , Hipóxia/sangue , Oxigênio/sangue , Adulto , Altitude , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oximetria , Testes de Função Respiratória , ViagemRESUMO
Ca(2+)-dependent mechanisms are important in regulating synaptic transmission. The results herein indicate that whole-cell perfusion of inositol 1,4,5-trisphosphate receptor (IP(3)R) agonists greatly enhanced excitatory postsynaptic current (EPSC) amplitudes in postsynaptic hippocampal CA1 neurons. IP(3)R agonist-mediated increases in synaptic transmission changed during development and paralleled age-dependent increases in hippocampal type-1 IP(3)Rs. IP(3)R agonist-mediated increases in EPSC amplitudes were inhibited by postsynaptic perfusion of inhibitors of Ca(2+)/calmodulin, PKC and Ca(2+)/calmodulin-dependent protein kinase II. Postsynaptic perfusion of inhibitors of smooth endoplasmic reticulum (SER) Ca(2+)-ATPases, which deplete intracellular Ca(2+) stores, also enhanced EPSC amplitudes. Postsynaptic perfusion of the IP(3)R agonist adenophostin (AdA) during subthreshold stimulation appeared to convert silent to active synapses; synaptic transmission at these active synapses was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Postsynaptic IP(3)R-mediated Ca(2+) release also produced a significant increase in spontaneous EPSC frequency. These results indicate that Ca(2+) release from intracellular stores play a key role in regulating the function of postsynaptic AMPARs.
Assuntos
Adenosina/análogos & derivados , Canais de Cálcio/fisiologia , Cálcio/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hipocampo/citologia , Inositol 1,4,5-Trifosfato/análogos & derivados , Neurônios/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Transmissão Sináptica/fisiologia , 2-Amino-5-fosfonovalerato/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Adenosina/farmacologia , Fatores Etários , Animais , Animais Recém-Nascidos , Bicuculina/farmacologia , Western Blotting/métodos , Agonistas dos Canais de Cálcio/farmacologia , Interações Medicamentosas , Estimulação Elétrica/métodos , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Antagonistas GABAérgicos/farmacologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Técnicas In Vitro , Indóis/farmacologia , Inositol 1,4,5-Trifosfato/farmacologia , Receptores de Inositol 1,4,5-Trifosfato , Neurônios/efeitos dos fármacos , Neurônios/efeitos da radiação , Técnicas de Patch-Clamp/métodos , Picrotoxina/farmacologia , Ratos , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Transmissão Sináptica/efeitos dos fármacos , Tapsigargina/farmacologia , Fatores de TempoRESUMO
STUDY OBJECTIVES: To investigate gray matter volume and concentration and cerebral perfusion in people with untreated obstructive sleep apnea (OSA) while awake. DESIGN: Voxel-based morphometry to quantify gray matter concentration and volume. Arterial spin labeling perfusion imaging to quantify cerebral perfusion. SETTING: Lying supine in a 3-T magnetic resonance imaging scanner in the early afternoon. PARTICIPANTS: 19 people with OSA (6 females, 13 males; mean age 56.7 y, range 41-70; mean AHI 18.5, range 5.2-52.8) and 19 controls (13 females, 6 males; mean age: 50.0 y, range 41-81). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There were no differences in regional gray matter concentration or volume between participants with OSA and controls. Neither was there any difference in regional perfusion between controls and people with mild OSA (n = 11). However, compared to controls, participants with moderate-severe OSA (n = 8) had decreased perfusion (while awake) in three clusters. The largest cluster incorporated, bilaterally, the paracingulate gyrus, anterior cingulate gyrus, and subcallosal cortex, and the left putamen and left frontal orbital cortex. The second cluster was right-lateralized, incorporating the posterior temporal fusiform cortex, parahippocampal gyrus, and hippocampus. The third cluster was located in the right thalamus. CONCLUSIONS: There is decreased regional perfusion during wakefulness in participants with moderate-severe obstructive sleep apnea, and these are in brain regions which have shown decreased regional gray matter volume in previous studies in people with severe OSA. Thus, we hypothesize that cerebral perfusion changes are evident before (and possibly underlie) future structural changes.
Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Apneia Obstrutiva do Sono/patologia , Apneia Obstrutiva do Sono/fisiopatologia , Vigília , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/anatomia & histologia , Encéfalo/patologia , Mapeamento Encefálico , Feminino , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/diagnóstico , Vigília/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: In the low pressure environment of commercial aircraft, hypoxaemia may be common and accentuated in patients with lung or heart disease. Regulations specify a cabin pressure not lower than 750 hPa but it is not known whether this standard is met. This knowledge is important in determining the hazards of commercial flight for patients and the validity of current flight simulation tests. METHODS: Using a wrist-watch recording altimeter, cabin pressure was recorded at 60 s intervals on 45 flights in Boeing 747-400 aircraft with three airlines. A log was kept of aircraft altitude using the in-flight display. Change in cabin pressure during flight, relationship between aircraft altitude and cabin pressure and proportion of flight time with cabin pressure approaching the minimum specified by regulation were determined. RESULTS: Flight duration averaged 10 h. Average cabin pressure during flight was 846 hPa. There was a linear fall in cabin pressure as the aircraft cruising altitude increased. At 10,300 m (34,000 ft) cabin pressure was 843 hPa and changed 8 hPa for every 300 m (1000 ft) change in aircraft altitude (r(2) = 0.993; P < 0.001). Lowest cabin pressure was 792 hPa at 12 200 m (40,000 ft) but during only 2% of flight time was cabin pressure less than 800 hPa. CONCLUSIONS: Cabin pressure is determined only by the engineering of the aircraft and its altitude and in the present study was always higher than required by regulation. Current fitness-to-fly evaluations simulate cabin conditions that passengers will not experience on these aircraft. There may be increased risks to patients should new or older aircraft operate nearer to the present minimum standard.
Assuntos
Aviação , Desenho de Equipamento , Humanos , PressãoRESUMO
SUMMARY: Tracker is a web-based email alert system for monitoring protein database searches using HMMER and Blast-P, nucleotide searches using Blast-N and literature searches of the PubMed database. Users submit searches via a web-based interface. Searches are saved and run against updated databases to alert users about new information. If there are new results from the saved searches, users will be notified by email and will then be able to access results and link to additional information on the NCBI website. Tracker supports Boolean AND/OR operations on HMMER and BLASTP result sets to allow users to broaden or narrow protein searches. AVAILABILITY: The server is located at http://jay.bioinformatics.ku.edu/tracker/index.html. A distribution package including detailed installation procedure is freely available from http://jay.bioinformatics.ku.edu/download/tracker/.
Assuntos
Sistemas de Gerenciamento de Base de Dados , Bases de Dados Genéticas , Correio Eletrônico , Armazenamento e Recuperação da Informação/métodos , Processamento de Linguagem Natural , PubMed , Análise de Sequência/métodos , Documentação/métodos , Internet , Alinhamento de Sequência/métodos , Interface Usuário-Computador , Vocabulário ControladoRESUMO
We show that activation of postsynaptic inositol 1,4,5-tris-phosphate receptors (IP(3)Rs) with the IP(3)R agonist adenophostin A (AdA) produces large increases in AMPA receptor (AMPAR) excitatory postsynaptic current (EPSC) amplitudes at hippocampal CA1 synapses. Co-perfusion of the Ca(2+) chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid strongly inhibited AdA-enhanced increases in EPSC amplitudes. We examined the role of AMPAR insertion/anchoring in basal synaptic transmission. Perfusion of an inhibitor of synaptotagmin-soluble n-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor SNARE-mediated exocytosis depressed basal EPSC amplitudes, whereas a peptide that inhibits GluR2/3 interactions with postsynaptic density-95 (PDZ) domain proteins glutamate receptor interacting protein (GRIP)/protein interacting with C-kinase-1 (PICK1) enhanced basal synaptic transmission. These results suggest that constitutive trafficking and anchoring of AMPARs help maintain basal synaptic transmission. The regulation of postsynaptic AMPAR trafficking involves synaptotagmin-SNARE-mediated vesicle exocytosis and interactions between AMPARs and the PDZ domains in GRIP/PICK1. We show that inhibitors of synaptotagmin-SNARE-mediated exocytosis, or interactions between AMPARs and GRIP/PICK1, attenuated AdA-enhanced increases in EPSC amplitudes. These results suggest that IP(3)R-mediated Ca(2+) release can enhance AMPAR EPSC amplitudes through mechanisms that involve AMPAR-PDZ interactions and/or synaptotagmin-SNARE-mediated receptor trafficking.