D-4F, an apoA-1 mimetic, decreases airway hyperresponsiveness, inflammation, and oxidative stress in a murine model of asthma.

Asthma is characterized by oxidative stress and inflammation of the airways. Although proinflammatory lipids are involved in asthma, therapies targeting them remain lacking. Ac-DWFKAFYDKVAEKFKEAFNH(2) (4F) is an apolipoprotein (apo)A-I mimetic that has been shown to preferentially bind oxidized lipids and improve HDL function. The objective of the present study was to determine the effects of 4F on oxidative stress, inflammation, and airway resistance in an established murine model of asthma. We show here that ovalbumin (OVA)-sensitization increased airway hyperresponsiveness, eosinophil recruitment, and collagen deposition in lungs of C57BL/6J mice by a mechanism that could be reduced by 4F. OVA sensitization induced marked increases in transforming growth factor (TGF)ß-1, fibroblast specific protein (FSP)-1, anti-T15 autoantibody staining, and modest increases in 4-hydroxynonenal (4-HNE) Michael's adducts in lungs of OVA-sensitized mice. 4F decreased TGFß-1, FSP-1, anti-T15 autoantibody, and 4-HNE adducts in the lungs of the OVA-sensitized mice. Eosinophil peroxidase (EPO) activity in bronchial alveolar lavage fluid (BALF), peripheral eosinophil counts, total IgE, and proinflammatory HDL (p-HDL) were all increased in OVA-sensitized mice. 4F decreased BALF EPO activity, eosinophil counts, total IgE, and p-HDL in these mice. These data indicate that 4F reduces pulmonary inflammation and airway resistance in an experimental murine model of asthma by decreasing oxidative stress.

On the pathway of an animal model for restless legs syndrome...

Restless legs syndrome (RLS) is a chronic sleep motor disorder that affects up to 10% of the general population. Except for periodic leg movements (PLM), which can be found in the great majority of RLS patients, no objective hematochimic or neurophysiological markers are available to prove the diagnosis, which is based on clinical standard criteria. Nowadays, the aetiopathogenesis of the syndrome is unknown. In a consistent sample of patients affected by the idiopathic form, the disease is inherited as an autosomal dominant trait related to an unidentified locus, while each symptomatic form is probably linked to a specific cause. Although of possible different origins, both the primary and secondary forms may share the same pathogenetic mechanism, which, even if unclear, could be characterised by a neurological dysfunction of the dopaminergic system. Several issues, including strong efficacy of dopamine-agonist treatments, support this theory, which is currently considered the main pathogenetic hypothesis. Most of the past studies tried to clarify the RLS mechanism using the neurophysiological, biochemical and neuroimaging techniques applied to the field of human research. Now the time has come to accept the challenge in creating an animal model of RLS, which may emerge as a decisive step in understanding RLS pathogenesis, and to develop and test new therapies. Even though there have been a few significant efforts, a valid animal model of RLS still does not exist. In past pioneering studies, the authors attempted to induce restless motor behaviour in animals by different strategies: antidopaminergic pharmacological interventions, spinal or cerebral lesions of specific regions involved in the motor control and in dopamine regulation, and selective deletion of genes coding for dopamine receptors. Rodents (mice and rats) were always chosen by the authors as the animals for their experiments. The current tendency in achieving an RLS model is generally represented by simulation of a symptomatic condition of RLS or by a direct interference of the dopaminergic system. In this regard, the pharmacological method had the intention to reproduce the neuroleptic-induced acathisia, the spinal lesional model was based on the hypothesis of myelopathic- related PLM, and the hypothalamic lesion tested the motor consequence of A11 dopaminergic neurons. Preliminary studies are underway to replicate the pregnancy-related form of RLS by using a hormonal intervention, and the iron-deficiency secondary form by using specific iron-free diets. Today, modern technologies are available to easily replicate in animals most of the symptomatic RLS conditions. In addition, more than a few well validated animal models of different diseases known to be related to RLS or PLM, for instance, Parkinson's disease, rheumatoid arthritis and renal failure, could also be exploited in addressing this topic. The real obstacle in achieving an RLS model is the absence of a certain diagnostic marker to recognise if the animal that underwent the different experimental procedures has developed the RLS condition or not. Concerning this issue, possible specific endpoints are represented by the increase in locomotor activity, which are ascertainable by different techniques, such as openfield or run-wheel activity, or by sleep fragmentation, in which the circadian shift can be verified by applying polysomnography on the animal. PLM are probably the only specific and reliable markers available to recognise and quantify experimentally induced RLS. Despite a few authors who reported the presence of limb-phasic, pseudoperiodic activity during sleep in old or in lesioned rats, the existence of spontaneous or provoked PLM in animals is still debated. Eventually, the PLM features in an animal could be markedly different compared to human ones. To recognise and characterise PLM in animals, three more essential steps are required: a method to record directly, as in humans, the activity of the tibialis anterior (TA) muscles, a consistent amount of normative control data on the TA activity in healthy animals, and reliable analysis to distinguish the generic phasic muscular activity to a possible unambiguous PLM pattern. This review includes a summary and a critical discussion of the previous tentative RLS models, proposals for other possible animal models, and firstly the preliminary normative data on TA activity during sleep in normal rodents.

Patterns of intercostal muscle activity in humans.

Coordination of activity of inspiratory intercostal muscles in conscious human subjects was studied by means of an array of electromyograph (EMG) electrodes. Bipolar fine wire electrodes were placed in the second and fourth parasternal intercostal muscles and in two or three external intercostal muscles in the midaxillary line from the fourth to eighth intercostal spaces. Subjects breathed quietly or rebreathed from a bag containing 8% CO2 in O2 in both supine and upright postures. Respiration was monitored by means of flow, volume, and separate rib cage and abdominal volumes. Onset of EMG activity in each breath was found near the beginning of inspiration in the uppermost intercostal spaces but progressively later in inspiration in lower spaces, indicating that activity spreads downward across the rib cage through inspiration. At higher ventilation stimulated by CO2, activity spread further and faster downward. In voluntary deep breathing, external intercostal muscles tended to be recruited earlier in inspiration than in CO2-stimulated breathing. The change from supine to sitting resulted in small and inconsistent changes. There was no lung volume or rib cage volume threshold for appearance of EMG activity in any of the spaces.

Effect of sleep and sighing on upper airway resistance in mongrel dogs.

We investigated the effect of sleep and sighing on supratracheal resistance in unrestrained mongrel dogs breathing through the nose by comparing within-breath changes in upper airway pressure-flow relationship in control, sigh, and five postsigh breaths recorded during wakefulness and during non-rapid-eye-movement and rapid-eye-movement sleep. A sigh breath was characterized by a high tidal volume and was typically followed by an apnea of a variable duration. Sleep had little or no effect on supratracheal resistance, measured at peak flow rates, during quiet breathing (awake 7.3 +/- 0.4, non-rapid eye movement 8.3 +/- 0.4, and rapid eye movement 6.8 +/- 0.4 cmH2O.l-1.s). The resistance was identical in the early part of inspiration in control and sigh breaths but increased during the augmented phase of sigh breaths. Resistance at peak inspiratory flow was higher in sigh breaths than in control breaths in all sleep states. The flow-pressure profile of postsigh breaths was identical to that of control breaths in all sleep states. We conclude that upper airway resistance is essentially unaffected by sleep state in the mongrel dog and that sighing increases upper airway resistance regardless of sleep state.

Reciprocal activation of hypopharyngeal muscles and their effect on upper airway area.

We examined in awake goats, 1) with intact upper airways (UAW), the effect of altering chemical drive on pharyngeal constrictors [thyropharyngeus (TP) and hypopharyngeus (HP)] and a dilator [stylopharyngeus (SP)], and 2) with an isolated UAW, the effect of activation of these muscles on supraglottic UAW (UAW(SG)) area. During eupnea in nine goats with intact UAW, the TP and HP were active during expiration, whereas the SP exhibited tonic expiratory and phasic inspiratory activity. After mechanically induced apneas (MIA), TP activity increased (263%, P < 0.02), HP activity exhibited a small, varied response, and SP activity greatly decreased (10%, P < 0.02). During resumption of respiratory effort, all goats exhibited absent/reduced airflow, and when diaphragm activity was 95% of control, TP activity remained elevated (135%) and SP activity was reduced (56%, P < 0.02). During hypercapnia, 1) TP activity decreased (P < 0.02), 2) HP response varied, and 3) SP activity increased (P < 0.02). After MIA in six goats with isolated UAW, TP activity increased 198% (P < 0.02) and UAW(SG) area (endoscopically determined) decreased (to 15% of control, P < 0.02). During recovery from MIA, a correlation was found between UAW(SG) area and the ratio of SP to TP activity. We conclude that the reciprocal activation of mechanically opposing dilator and constrictor muscles in the hypopharynx is correlated to changes in the UAW(SG) area, and an imbalance in activity of these opposing muscles can lead to UAW(SG) narrowing.

Interaction of cross-sectional area, driving pressure, and airflow of passive velopharynx.

Previous studies have shown that, when the pharyngeal muscles are relaxed, the velopharynx is a highly compliant segment of the pharynx. Thus, under these circumstances, cross-sectional area of the velopharynx (AVP), driving pressure across the velopharynx (DeltaP), and inspiratory airflow (VI) will be mutually interdependent variables. The purpose of the present investigation was to describe the interrelation among these three variables during inspiration. We studied 15 sleeping patients with obstructive sleep apnea/hypopnea when the pharyngeal muscles were rendered hypotonic by applying continuous positive airway pressure to the nasal airway. AVP, determined by endoscopic imaging, was significantly greater at onset of VI limitation than at minimum oropharyngeal pressure (P < 0. 01). Snoring was never observed during VI limitation. In a subgroup of six patients, values for DeltaP, VI, and AVP were obtained at 0. 1-s intervals at various levels of mask pressure. For these six patients, the mathematical expression VI = 0.657(AVP/Amax) . DeltaP0. 332, where Amax is maximal AVP, described the relationship among the three variables (R2 = 0.962) for flow-limited and non-flow-limited inspirations. The impedance of the passive velopharynx, defined as DeltaP0.33/V, was inversely related to AVP and increased dramatically when AVP was <0.3 cm2. In summary, we observed a progressive decrease in AVP during flow-limited inspiration in patients with obstructive sleep apnea. This constriction of the velopharynx contributes to an increase in velopharyngeal impedance that, in turn, counterbalances the increase in DeltaP during flow limitation.

Negative pressure effects on mechanically opposing pharyngeal muscles in awake and sleeping goats.

Our aim was to investigate the effects of the negative pressure reflex on mechanically opposing pharyngeal muscles during wakefulness, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. In four goats with isolated upper airways, we measured tracheal airflow and electrical activity of the thyropharyngeus (TP; constricting), the stylopharyngeus (SP; dilating), and the diaphragm (Dia). In the wakefulness state in response to negative pressure tests, TP decreased (65%), SP increased (198%), and tidal volume (VT) (66%) and rate of rise of Dia (Dia(slope), 69%) decreased (P < 0.02). Similarly, during SWS, the negative pressure response of TP (31%), VT (61%), and Dia(slope) (60%) decreased, whereas SP (113%) increased, relative to SWS control (P < 0.02). In REM sleep, the negative pressure response by TP and SP were small, whereas both VT (38%) and Dia(slope) (24%) were greatly decreased (P < 0.02) compared with REM control. Inspiratory duration remained unchanged in response to negative pressure tests in all states. These data provide evidence that mechanically opposing inspiratory and expiratory pharyngeal muscles are reciprocally controlled and their response to negative pressure are state dependent.

Small reduction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex area induces abnormal breathing periods in awake goats.

In awake rats, >80% bilateral reduction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-Bötzinger complex (pre-BötzC) resulted in hypoventilation and an "ataxic" breathing pattern (Gray PA, Rekling JC, Bocchiaro CM, Feldman JL, Science 286: 1566-1568, 1999). Accordingly, the present study was designed to gain further insight into the role of the pre-BötzC area NK1R-expressing neurons in the control of breathing during physiological conditions. Microtubules were chronically implanted bilaterally into the medulla of adult goats. After recovery from surgery, the neurotoxin saporin conjugated to substance P, specific for NK1R-expressing neurons, was bilaterally injected (50 pM in 10 microl) into the pre-BötzC area during the awake state (n = 8). In unoperated goats, 34 +/- 0.01% of the pre-BötzC area neurons are immunoreactive for the NK1R, but, in goats after bilateral injection of SP-SAP into the pre-BötzC area, NK1R immunoreactivity was reduced to 22.5 +/- 2.5% (29% decrease, P < 0.01). Ten to fourteen days after the injection, the frequency of abnormal breathing periods was sixfold greater than before injection (107.8 +/- 21.8/h, P < 0.001). Fifty-six percent of these periods were breaths of varying duration and volume with an altered respiratory muscle activation pattern, whereas the remaining were rapid, complete breaths with coordinated inspiratory-expiratory cycles. The rate of occurrence and characteristics of abnormal breathing periods were not altered during a CO2 inhalation-induced hyperpnea. Pathological breathing patterns were eliminated during non-rapid eye movement sleep in seven of eight goats, but they frequently occurred on arousal from non-rapid eye movement sleep. We conclude that a moderate reduction in pre-BötzC NK1R-expressing neurons results in state-dependent transient changes in respiratory rhythm and/or eupneic respiratory muscle activation patterns.

Large lesions in the pre-Bötzinger complex area eliminate eupneic respiratory rhythm in awake goats.

In awake goats, 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-Bötzinger complex (pre-BötzC) area with saporin conjugated to substance P results in transient disruptions of the normal pattern of eupneic respiratory muscle activation (Wenninger JM, Pan LG, Klum L, Leekley T, Bastastic J, Hodges MR, Feroah T, Davis S, and Forster HV. J Appl Physiol 97: 1620-1628, 2004). Therefore, the purpose of these studies was to determine whether large or total lesioning in the pre-BötzC area of goats would eliminate phasic diaphragm activity and the eupneic breathing pattern. In awake goats that already had 29% bilateral destruction of neurokinin-1 receptor-expressing neurons in the pre-BötzC area, bilateral ibotenic acid (10 microl, 50 mM) injection into the pre-BötzC area resulted in a tachypneic hyperpnea that reached a maximum (132 +/- 10.1 breaths/min) approximately 30-90 min after bilateral injection. Thereafter, breathing frequency declined, central apneas resulted in arterial hypoxemia (arterial Po2 approximately 40 Torr) and hypercapnia (arterial Pco2 approximately 60 Torr), and, 11 +/- 3 min after the peak tachypnea, respiratory failure was followed by cardiac arrest in three airway-intact goats. However, after the peak tachypnea in four tracheostomized goats, mechanical ventilation was initiated to maintain arterial blood gases at control levels, during which there was no phasic diaphragm or abdominal muscle activity. When briefly removed from the ventilator (approximately 90 s), these goats became hypoxemic and hypercapnic. During this time, minimal, passive inspiratory flow resulted from phasic abdominal muscle activity. We estimate that 70% of the neurons within the pre-BötzC area were lesioned in these goats. We conclude that, in the awake state, the pre-BötzC is critical for generating a diaphragm, eupneic respiratory rhythm, and that, in the absence of the pre-BötzC, spontaneous breathing reflects the activity of an expiratory rhythm generator.

Static mechanics of the velopharynx of patients with obstructive sleep apnea.

The static mechanics of the hypotonic pharynx were endoscopically evaluated in nine sleeping patients with obstructive sleep apnea, having a primary narrowing only at the velopharynx. The velopharynx closed completely at a mean pressure of 0.18 +/- 1.21 cmH2O, and the mean half-dilation pressure was 1.93 cmH2O above closing pressure. The dependence of area on pressure was distinctly curvilinear, being steep near closing pressure and asymptotically approaching maximum area (mean = 1.32 cm2). The data for each patient were satisfactorily fitted by an exponential function (mean R2 = 0.98), and a single exponential relationship usefully represented the dependence of relative area on pressure above closing pressure for the population (R2 = 0.85). During the test inspiration, flow limitation was consistently observed when mask pressure exceeded closing pressure by 0.5-3.0 cmH2O. In summary, the static mechanics of the hypotonic velopharynx of patients with obstructive sleep apnea can be described by an exponential pressure-area relationship, with a closing pressure near atmospheric pressure and a high compliance in the range of airway pressure 0-3 cmH2O above closing pressure.

Multiple rostral medullary nuclei can influence breathing in awake goats.

The purpose of this study was to determine the effect on breathing of neuronal dysfunction in the retrotrapezoid (RTN), facial (FN), gigantocellularis reticularis (RGN), or vestibular (VN) nuclei of adult awake goats. Microtubules were chronically implanted to induce neuronal dysfunction by microinjection of an excitatory amino acid (EAA) receptor antagonist or a neurotoxin. The EAA receptor antagonist had minimal effect on eupneic breathing, but 8--10 days after injection of the neurotoxin, 7 of 10 goats hypoventilated (arterial PCO(2) increased 3.2 +/- 0.7 Torr). Overall there were no significant (P > 0.10) effects of the EAA receptor antagonist on CO(2) sensitivity. However, for all nuclei, > or =66% of the antagonist injections altered CO(2) sensitivity by more than the normal 12.7 +/- 1.6% day-to-day variation. These changes were not uniform, inasmuch as the antagonist increased (RTN, n = 2; FN, n = 7; RGN, n = 6; VN, n = 1) or decreased (RTN, n = 2; RGN, n = 3; VN, n = 2) CO(2) sensitivity. Ten days after injection of the neurotoxin into the FN (n = 3) or RGN (n = 5), CO(2) sensitivity was also reduced. Neuronal dysfunction also did not have a uniform effect on the exercise arterial PCO(2) response, and there was no correlation between effects on CO(2) sensitivity and the exercise hyperpnea. We conclude that there is a heterogeneous population of neurons in these rostral medullary nuclei (or adjacent tissue) that can affect breathing in the awake state, possibly through chemoreception or chemoreceptor-related mechanisms.

Breathing of awake goats during prolonged dysfunction of caudal M ventrolateral medullary neurons.

Cooling the caudal M ventrolateral medullary (VLM) surface for 30 s results in a sustained apnea in anesthetized goats but only a 30% decrease in breathing in awake goats. The purpose of the present study was to determine, in the awake state, the effect of prolonged (minutes, hours) caudal M neuronal dysfunction on eupneic breathing and CO2 sensitivity. Dysfunction was created by ejecting excitatory amino acid receptor antagonists or a neurotoxin on the VLM surface through guide tubes chronically implanted bilaterally on a 10- to 12-mm2 portion of the caudal M VLM surface of 12 goats. Unilateral and bilateral ejections (1 microliter) of selective antagonists for N-methyl-D-aspartic acid or non-N-methyl-D-aspartic acid receptors had no significant effect on eupneic breathing or CO2 sensitivity. Unilateral ejection of a nonselective excitatory amino acid receptor antagonist generally had no effect on eupneic breathing or CO2 sensitivity. However, bilateral ejection of this antagonist resulted in a significant 2-Torr hypoventilation during eupnea and a significant reduction in CO2 sensitivity to 60 +/- 9% of control. Unilateral ejection of the neurotoxin kainic acid initially stimulated breathing; however, breathing then returned to near control with no incidence of apnea. After the kainic acid ejection, CO2 sensitivity was reduced significantly to 60 +/- 7% of control. We conclude that in the awake state a prolonged dysfunction of caudal M VLM neurons results in compensation by other mechanisms (e.g., carotid chemoreceptors, wakefulness) to maintain near-normal eupneic breathing, but compensation is more limited for maintaining CO2 sensitivity.

Effects on breathing in awake and sleeping goats of focal acidosis in the medullary raphe.

Our aim was to determine the effects of focal acidification in the raphe obscurus (RO) and raphe pallidus (RP) on ventilation and other physiological variables in both the awake and sleep states in adult goats. Through chronically implanted microtubules, 1) a focal acidosis was created by microdialysis of mock cerebrospinal fluid (mCSF), equilibrated with various levels of CO2, and 2) medullary extracellular fluid (ECF) pH was measured by using a custom-made pH electrode. Focal acidosis in the RO or RP, by dialyzing either 25 or 80% CO2 (mCSF pH approximately 6.8 or 6.3), increased (P < 0.05) inspiratory flow by 8 and 12%, respectively, while the animals were awake during the day, but not at night while they were awake or in non-rapid eye movement sleep. While the animals were awake during the day, there were also increases in heart rate and blood pressure (P < 0.05) but no significant change in metabolic rate or arterial Pco2. Dialysis with mCSF equilibrated with 25 or 80% CO2 reduced ECF pH by the same amount (25%) or three times more (80%) than when inspired CO2 was increased to 7%. During CO2 inhalation, the reduction in ECF pH was only 50% of the reduction in arterial pH. Finally, dialysis in vivo only decreased ECF pH by 19.1% of the change during dialysis in an in vitro system. We conclude that 1) the physiological responses to focal acidosis in the RO and RP are consistent with the existence of chemoreceptors in these nuclei, and 2) local pH buffering mechanisms act to minimize changes in brain pH during systemic induced acidosis and microdialysis focal acidosis and that these mechanisms could be as or more important to pH regulation than the small changes in inspiratory flow during a focal acidosis.

Do neurotoxic lesions in rostral medullary nuclei induce/accentuate hypoventilation during NREM sleep?

Experimentally induced neuronal dysfunction in respiratory regions of the rostral medulla decrease breathing more in anesthetized mammals than in awake mammals. Sleep is similar to anesthesia in that excitatory inputs to respiratory neurons are reduced compared to the awake state; thus, we hypothesized that neurotoxic lesions in rostral medullary nuclei would, relative to wakefulness (WK), induce and/or accentuate hypoventilation during non-rapid eye movement (NREM) sleep. To test the hypothesis, goats were studied between 21:00 h and 03:00 h: (1) before and 30 days after chronically implanting microtubules bilaterally into the rostral medulla and, (2) 9-15 h and 2-17 days after unilateral injections of 100 nl to 1 microl, 50 mM ibotenic acid into the vestibular, gigantocellularis reticularis, or facial nuclei, or the retrotrapezoid nucleus/parapyramidal region. Arterial blood was repeatedly sampled in all studies during WK, and NREM and rapid eye movement (REM) sleep states. There was no significant (P>0.10) change in Pa(CO(2)) between WK and NREM sleep (and REM sleep when sufficient data were obtained) before or after implantation of microtubules and in studies after creating the neurotoxic lesions. Breathing frequency also did not significantly (P>0.10) differ between states in any of the studies. The data thus did not support the hypothesis. We speculate that in goats efficient compensatory mechanisms maintain Pa(CO(2)) homeostasis during normal sleep and the same and/or other mechanisms maintain homeostasis when excitatory drive is further reduced by lesions in rostral medullary nuclei.

Ventilatory responses in awake guinea pigs exposed to acid aerosols.

This study reports experiments designed to evaluate the dose and temporal effects of an atmospheric pollutant, sulfuric acid (H2SO4) aerosol, on the dynamic components of the respiratory cycle. Ventilation was measured in a whole-body barometric plethysmograph in unanesthetized, unrestrained animals following a 4-h exposure to H2SO4 aerosol at 14.1, 20.1, or 43.3 mg/m3. Lung injury was assessed by histopathology and bronchoalveolar lavage (BAL). Aerosol exposure with H2SO4 caused marked alterations in both the magnitude and composition of the ventilatory response, which were both dose and time dependent. At the highest concentration tested, there was a significant increase in tidal volume (deltaVt) and a decrease in breathing frequency (f) immediately after exposure. Analysis of BAL fluid at this time showed increased inflammatory cells and protein in the acid exposed animals, and histology showed hyaline membranes and acute inflammatory cells in the proximal acinar region. By 24 h postexposure, f significantly increased whereas deltaVt decreased. This pattern of breathing was interspersed with short periods of apnea. The onset of rapid, shallow breathing was associated with histological evidence of diffuse pulmonary edema. By contrast, the immediate postexposure period at the lowest concentration of H2SO4 aerosol was characterized by a significant increase in f and little or no effect on deltaVt. These effects diminished with time, and at 24 h postexposure ventilatory parameters were indistinguishable from baseline values. An apparent crossover between the effects associated with the high and low exposure concentrations was seen at the intermediate exposure concentration; however, closer inspection of these findings on an animal-by-animal basis revealed two populations of animals with respiratory characteristics of either the high-exposure or low-exposure groups. The data suggest that the guinea pig exhibits complex interactions between dose and time to response that are consistent with the activation of neural reflexes. The indirect plethysmographic method provides a simple means to assess these responses in a model system that avoids the use of anesthetics, surgery, and restraint.

Posterior cephalometric radiographic analysis in obstructive sleep apnea.

Our objective was to evaluate the relationship between posterior facial cephalometric measures and obstructive sleep apnea syndrome (OSAS). We used a consecutive sample of 60 patients with OSAS who underwent upright lateral cephalograms, uvulopalatopharyngoplasty (UPPP), and preoperative and postoperative polysomnography. Successful responders to UPPP were arbitrarily defined as having a respiratory disturbance index reduced to fewer than 20 events per hour. Standard cephalometric measurements were used. Posterior facial height measures were constructed, based on a plane perpendicular to the Frankfort horizontal placed at hyoidale. The total and lower airway lengths were shorter and posterior mandibular height was longer in UPPP responders compared to nonresponders (p < or = .05). There was no difference between the two groups by standard cephalometric measurements. Responders and nonresponders to UPPP have significant differences in posterior airway measures that are not reflected in standard cephalometric measures. Airway length likely is a critical factor in OSAS and surgical response.

Relationship of the head impulse test and head-shake nystagmus in reference to caloric testing.

OBJECTIVE: The objective of this study was to determine the usefulness of the head impulse test (HIT) and head-shake nystagmus (HSN), two easily performed office maneuvers, in the evaluation of the dizzy patient with reference to caloric irrigation results. OBJECTIVE AND SETTING: This was a prospective double-blind trial conducted at an outpatient academic tertiary referral center. PATIENTS: The study population was composed of 105 patients (35 male, 70 female) who presented for evaluation of dizziness and ranged in age from 13 to 87 years (mean 52.1). INTERVENTION: The intervention was HIT and HSN evaluation followed by bithermal binaural air caloric irrigations. MAIN OUTCOME MEASURES: The main outcome measures were sensitivity, specificity, and predictive values of HIT and HSN evaluation (individually and in combination) in relation to caloric results. RESULTS: Sensitivity of the tests was equally low (35%), whereas specificity was high (HIT 95%, HSN 92%). The positive predictive value for the two tests in combination (80%) was greater than for each individually (HIT 64%, HSN 50%). Negative predictive values remained stable when considering each test individually (HIT 86%, HSN 86%) or in combination (88%). CONCLUSIONS: The low sensitivity renders both tests inadequate as a screening tool for peripheral vestibular disease based on caloric results. However, when HIT and HSN results are both abnormal, there is a high likelihood of a significant caloric deficit.

A method to evaluate upper airway mechanics following intervention in snorers.

PURPOSE: To describe a method that measures multisegment upper airway changes following intervention for snoring and obstructive apnea that controls for physiological fluctuations during sleep. PATIENTS AND METHODS: Retropalatal, retroglossal, and retrohyoid airway segments were evaluated before and after application of an oral appliance (OA) in four snoring subjects. Twelve airway segments were evaluated. Physiological fluctuations during sleep were controlled with variably applied nasal continuous positive pressure (CPAP), benzodiazepam-induced sleep, and obtaining measures at zero flow on the first test breath. Airway area was measured endoscopically. RESULTS: The methodology identified that following intervention with an OA, maximum retroglossal airway size increased 23.3% +/- 7.5% (P < .05) and retrohyoid size decreased -63.5% +/- 16.0% (P < .05). No changes in retropalatal area (-2.5% +/- 3.0%) or closing pressure were observed. The level of primary obstruction shifted inferiorly in one patient. Airway measures prior to intervention showed small alterations of applied pressure (1 cm H2O) changed retropalatal and retroglossal area an average of 10% +/- 0.9%/cm H2O. CONCLUSION: The mechanical effects of limited airway intervention can be measured with a hypotonic, pressure-controlled methodology. At small airway areas, the airway is highly collapsible and airway size fluctuates. Small changes in applied or physiological forces may alter the airway as significantly as the effects of the intervention being evaluated. The hypotonic upper airway method provides a method to control airway collapse and evaluate interventions, such as OA or surgery, for snoring and obstructive sleep apnea syndrome.