Respiratory modulation of the pharyngeal airway in lean and obese mice

Obesity is an important risk factor for pharyngeal airway collapse in obstructive sleep apnea (OSA). To examine the effect of obesity on pharyngeal airway size on inspiration and expiration, respiratory-gated MRI of the pharynx was compared in New Zealand obese (NZO) and New Zealand white (NZW) mice (weights: 50.4g vs. 34.7g, p<0.0001). Results: (1) pharyngeal airway cross-sectional area was greater during inspiration than expiration in NZO mice, but in NZW mice airway area was greater in expiration than inspiration; (2) inspiratory-to-expiratory changes in both mouse strains were largest in the caudal pharynx; and (3) during expiration, airway size tended to be larger, though non-significantly, in NZW than NZO mice. The respiratory pattern differences are likely attributable to obesity that is the main difference between NZO and NZW mice. The data support an hypothesis that pharyngeal airway patency in obesity is dependent on inspiratory dilation and may be vulnerable to loss of neuromuscular pharyngeal activation.     

Tensile radial stress in the spinal cord related to arachnoiditis or tethering: a numerical model

Spinal arachnoiditis comprises fibrous scarring of the subarachnoid space, following spinal trauma or inflammation, and is often associated with syringomyelia. We hypothesised that cord-to-dura attachments could cause transient tensile cord radial stress, as pressure waves propagate. This was tested in a fluid-structure interaction model, simulating three types of cord tethering, with 'arachnoiditis' confined to a short mid-section of the cord. The annular system was excited abdominally with a short transient, and the resulting Young and Lamb waves and reflections were analysed. Radial mid-section tethering was less significant than axial tethering, which gave rise to tensile radial stress locally when the cord was not fixed cranially. Simulated as inextensible string connections to the dura, arachnoiditis caused both localised tensile radial stress and localised low pressure in the cord as the transient passed. The extent of these effects was sensitive to the relative stiffness of the dura and cord. Tensile radial stress may create a syrinx in previously normal cord tissue, and transiently lowered pressure may draw in interstitial fluid, causing the syrinx to enlarge if fluid exit is inhibited. The suggested mechanism could also explain the juxtaposition of syrinxes to regions of arachnoiditis.     

阻塞性睡眠呼吸暂停低通气综合征生物力学研究进展

阻塞性睡眠呼吸暂停低通气综合征（obstructive sleep apnea hypopnea syndrome, OSAHS）是一种在睡眠时反复出现咽部塌陷导致呼吸暂停的疾病,其发病机制涉及多个方面。根据人体上气道系统解剖结构与生理学特点,从生物力学角度研究可能诱发睡眠呼吸暂停的各种因素,讨论近年来研究睡眠呼吸暂停的生物力学模型,分析可能导致OSAHS疾病的力学机制,并对OSAHS生物力学今后的研究进行展望。建立上气道生物力学模型是研究OSAHS发病机制的有效方法之一,对OSAHS术前评估和术后预测具有重要的临床意义。     

Surgical modifications of the upper airway for obstructive sleep apnea in adults: a systematic review and meta-analysis

A substantial portion of patients with obstructive sleep apnea (OSA) seek alternatives to positive airway pressure (PAP), the usual first-line treatment for the disorder. One option is upper airway surgery. As an adjunct to the American Academy of Sleep Medicine (AASM) Standards of Practice paper, we conducted a systematic review and meta-analysis of literature reporting outcomes following various upper airway surgeries for the treatment of OSA in adults, including maxillomandibular advancement (MMA), pharyngeal surgeries such as uvulopharyngopalatoplasty (UPPP), laser assisted uvulopalatoplasty (LAUP), and radiofrequency ablation (RFA), as well as multi-level and multi-phased procedures. We found that the published literature is comprised primarily of case series, with few controlled trials and varying approaches to pre-operative evaluation and post-operative follow-up. We include surgical morbidity and adverse events where reported but these were not systematically analyzed. Utilizing the ratio of means method, we used the change in the apnea-hypopnea index (AHI) as the primary measure of efficacy. Substantial and consistent reductions in the AHI were observed following MMA; adverse events were uncommonly reported. Outcomes following pharyngeal surgeries were less consistent; adverse events were reported more commonly. Papers describing positive outcomes associated with newer pharyngeal techniques and multi-level procedures performed in small samples of patients appear promising. Further research is needed to better clarify patient selection, as well as efficacy and safety of upper airway surgery in those with OSA.     

Normal and Hydrocephalic Brain Dynamics: The Role of Reduced Cerebrospinal Fluid Reabsorption in Ventricular Enlargement

CINE phase-contrast MRI (CINE-MRI) was used to measure cerebrospinal fluid (CSF) velocities and flow rates in the brain of six normal subjects and five patients with communicating hydrocephalus. Mathematical brain models were created using the MRI images of normal subjects and hydrocephalic patients. In our model, the effect of pulsatile vascular expansion is responsible for pulsatile CSF flow between the cranial and the spinal subarachnoidal spaces. Simulation results include intracranial pressure gradients, solid stresses and strains, and fluid velocities throughout the cranio-spinal system. Computed velocities agree closely with our in vivo CINE-MRI CSF flow measurements. In addition to normal intracranial dynamics, our model captures the transition to acute communicating hydrocephalus. By increasing the value for reabsorption resistance in the subarachnoid villi, our model predicts that the poroelastic parenchyma matrix will be drained and the ventricles enlarge despite small transmantle pressure gradients during the transitional phase. The poroelastic simulation thus provides a plausible explanation on how reabsorption changes could be responsible for enlargement of the ventricles without large transmantle pressure gradients.     

脑动脉Willis环局部低温的体外模型研究

目的 评价脑动脉低温时Willis环结构对脑组织温度的影响。 方法 基于患者脑血管CT图像构建脑Willis环体外模型,并通过灌流实验经右侧颈内动脉以30 mL/min的速度注入20 ℃冷水至中脑动脉,15 min后停止注入,通过27根和1根空间排布的热电偶观察中脑动脉周围区域以及流体的降温及复温特性,并通过注入染色溶液对冷水影响区域进行可视化。 结果 由右侧颈内动脉进行低温诱导时,冷水溶液主要影响右侧区域,也有少部分通过前脑交通动脉进入前脑动脉;离冷流体所经过的血管越近的区域在较快获得低温的同时,也会有较快的复温速率;由于受多个分叉血管的影响,垂直于中脑动脉流动方向对称区域的温度分布呈非对称性。结论 本文首次运用物理模型对脑动脉低温进行验证,为研究血管结构对脑动脉低温的影响以及设计个性化低温治疗方案提供依据。     

Daytime Sleepiness and Driving Performance in Patients with Obstructive Sleep Apnea: Comparison of the MSLT,the MWT,and a Simulated Driving Task

Study Objectives:

To test the reliability of a driving-simulation test for the objective measurement of daytime alertness compared with the Multiple Sleep Latency Test (MSLT) and with the Maintenance of Wakefulness Test (MWT), and to test the ability to drive safely, in comparison with on-road history, in the clinical setting of untreated severe obstructive sleep apnea.

Design:

N/A.

Setting:

Sleep laboratory.

Patients or Participants:

Twenty-four patients with severe obstructive sleep apnea and reported daytime sleepiness varying in severity (as measured by the Epworth Sleepiness Scale).

Interventions:

N/A.

Measurements and Results:

Patients underwent MSLT and MWT coupled with 4 sessions of driving-simulation test on 2 different days randomly distributed 1 week apart. Simulated-driving performance (in terms of lane-position variability and crash occurrence) was correlated with sleep latency on the MSLT and more significantly on the MWT, showing a predictive validity toward the detection of sleepy versus alert patients with obstructive sleep apnea. In addition, patients reporting excessive daytime sleepiness or a history of car crashes showed poorer performances on the driving simulator.

Conclusions:

A simulated driving test is a suitable tool for objective measurement of daytime alertness in patients with obstructive sleep apnea. Further studies are needed to clarify the association between simulated-driving performance and on-road crash risk of patients with sleep disordered breathing.

Citation:

Pizza F; Contardi S; Mondini S; Trentin L; Cirignotta F. Daytime sleepiness and driving performance in patients with obstructive sleep apnea: comparison of the MSLT, the MWT, and a simulated driving task. SLEEP 2009;32(3):382-391.     

Mimicking the humoral immune response in vitro results in antigen-specific isotype switching supported by specific autologous T helper cells: generation of human HIV-1-neutralizing IgG monoclonal antibodies from naive donors

Molecular and cellular requirements for antigen-specific isotype switch of human B cells have been investigated by mimicking signaling occurring in germinal centers. Peripheral blood mononuclear cells from healthy seronegative blood donors were first primary immunized in vitro, using a synthetic immunogen containing both a T and B cell epitope, which generated specific IgM-secreting B cells. We used the apex of the V3 loop of gp120 as B cell epitope linked to a promiscuous T helper epitope from tetanus toxin. In parallel, CD4⁺ T helper cell clones specific for the T epitope of the immunogen were established. In a secondary in vitro stimulation period, we co-cultured the antigen-specific T and B cells on CD32-transfected fibroblasts, together with an anti-CD40 monoclonal antibody. This resulted in isotype switching and human antigen-specific, IgG-secreting B cells were detected. This response was strictly dependent upon the presence of autologous T helper cells and the immunogen. Antigen-specific human B cells derived from this primary and secondary in vitro immunization were subsequently subjected to electrofield-induced somatic cell hybridization and hybridomas secreting human anti-V3 IgG monoclonal antibodies were isolated. One human antibody was further characterized and shown to be specific for the immunizing antigen with an affinity constant of 24 nM. This antibody also effectively neutralized different isolates of HIV-1, achieving a 50% neutralization at 0.46 μg/ml.