Search PubMed⌕ Search

Biomedical subjects

D P White

Publications and source records attributed to D P White.

At least 19 recordsLinked to original sources
PubMed2000

The influence of a transmucosal cholinergic agonist on pharyngeal muscle activity.

STUDY OBJECTIVE: To assess the effect of high local oral nicotine administration on the upper airway (UA) of normal males during wakefulness. DESIGN: Nonrandomized study. SETTING: Brigham & Women's Hospital General Clinical Research Center. PARTICIPANTS: Two groups of 13 and 12 normal male subjects were evaluated. INTERVENTIONS: A "Fast acting" or "Intermediate acting" 2 mg transmucosal nicotine patch was attached to an upper molar tooth of study participants during wakefulness. MEASUREMENTS: All data were collected prior to, and at several time points after, patch placement. Data measured included serum nicotine levels, genioglossal EMG, and pharyngeal resistance during basal breathing as well as the UA muscle response and UA collapsibility during negative UA pressure pulses. RESULTS: None of the variables measured showed a statistically significant change with either nicotine patch despite a significant rise (p<0.05) in nicotine serum levels post patch placement in both groups. In several subjects, muscle activity and responsiveness to negative pressure increased after application of both patches and returned to near baseline levels at the last time point measured, a response consistent with the time course of nicotine release in both patches. CONCLUSIONS: Oral nicotine administration failed to consistently increase GG muscle activation which may be a problem of local bioavailability of nicotine in the muscle.

Adult↗
PubMed2000

Reduced genioglossal activity with upper airway anesthesia in awake patients with OSA.

We examined whether topical upper airway anesthesia leads to a reduction in genioglossal (GG) electromyogram (EMG) in patients with obstructive sleep apnea (OSA). Airway mechanics were also evaluated. In 13 patients with OSA, we monitored GG EMG during tidal breathing and during the application of pulses of negative airway pressure (-10 to -12 cmH(2)O). Airflow resistance and airway collapsibility were determined. All measurements were performed with and without topical anesthesia (lidocaine). Anesthesia led to a significant fall in the peak GG EMG response to negative pressure from 36.1 +/- 4.7 to 24.8 +/- 5.3% (SE) of maximum (P < 0.01). This was associated with a fall in phasic and tonic EMG during tidal breathing (phasic from 24.4 +/- 4.1 to 16.4 +/- 3.4% of maximum and tonic from 10.9 +/- 1.6 to 8.0 +/- 1.3% of maximum, P < 0.01). A significant rise in pharyngeal airflow resistance was also observed. Our results demonstrate that topical receptor mechanisms in the nasopharynx importantly influence dilator muscle activity and are likely important in driving the augmented dilator muscle activity seen in the apnea patient.

Airway Resistance↗
PubMed2000

Local mechanisms drive genioglossus activation in obstructive sleep apnea.

Individuals with obstructive sleep apnea (OSA) require increased pharyngeal muscle dilator activation during wakefulness to maintain upper airway patency. Negative pressure is one potential stimulus for this neuromuscular compensation. Individuals with OSA who have previously undergone tracheostomy provide an opportunity to study upper airway physiology in both the presence and absence of upper airway respiratory stimuli. If negative pressure (or another local airway stimulus) were important in driving pharyngeal dilator muscle activation, one would predict that during nasal breathing, the pharynx of a tracheostomized patient would be exposed to negative pressure, and that high levels of muscle activation would therefore be measured. Conversely, during breathing by the patient through the tracheal stoma, one would expect low levels of muscle activation in the absence of local stimuli. We measured a number of respiratory variables, including genioglossus activation under both nasal and tracheal stomal breathing conditions, in five patients. In all five patients there was a significant and substantial decrease in both peak phasic (100 +/- 0 to 53.4 +/- 9.2 arbitrary units [mean +/- SEM], p < 0.01) and tonic genioglossus activation (36.3 +/- 5.3 to 20.7 +/- 3.9 arbitrary units, p < 0.05) during stomal breathing as compared with nasal breathing. We conclude that local upper airway respiratory stimuli, possibly negative pressure, are important in mediating the increased pharyngeal dilator muscle activation seen in sleep apnea patients during wakefulness.

Airway Resistance↗
PubMed2000

Influence of chemoreceptor stimuli on genioglossal response to negative pressure in humans.

Genioglossal muscle (GG) activity is modulated by both chemoreceptive and mechanoreceptive reflexes that help stabilize airway patency. We assessed the effects of blood gas changes, within the range encountered during mild obstructive apnea-arousal cycles, on GG activity and the GG reflex to upper airway negative pressure. Eighteen healthy adults were studied while awake under 5 conditions: (1) baseline (PET(CO(2)) = 40 mm Hg, Sa(O(2)) = 99%); (2) hypercapnia (PET(CO(2)) = 45 mm Hg); (3) hypocapnia (PET(CO(2)) = 35 mm Hg, induced via hyperventilation with an iron lung ventilator); (4) hypoxia (Sa(O(2)) = 87%); and (5) hypercapnia plus hypoxia (PET(CO(2)) = 45 mm Hg, Sa(O(2)) = 87%). Measurements included airflow, choanal and epiglottic pressures (Pchoa and Pepi), upper airway resistance, phasic and tonic GG EMG, and the GG reflex to negative pressure (Pchoa = -12.5 cm H(2)O). Ventilation increased from a baseline of 10.7 up to 22.7 L. min(-1) under conditions of altered blood gases. Peak inspiratory phasic GG EMG increased from 6. 5 to 11.1% of maximal contraction but there were no significant changes in either tonic GG EMG (range, 4.3 to 5.8% of maximum) or magnitude of the GG reflex (range, 4.1 to 5.5% of maximum). Among conditions there was a high correlation between upper airway pressures and peak phasic GG EMG (Pchoa, r = 0.97, p < 0.01; Pepi, r = 0.87; p = 0.06). We conclude that in this range of blood gases: (1) the GG reflex to negative pressure is unchanged; (2) slow airway pressure changes throughout inspiration, generated either actively or passively, influence GG EMG activity; and (3) mechanoreceptive control of GG EMG can fully explain all changes in GG activity, suggesting that chemoreceptive inputs to GG are minimal, or are not simply summated with mechanoreceptor inputs.

Adult↗
PubMed1999

Effect of wake-sleep transitions and rapid eye movement sleep on pharyngeal muscle response to negative pressure in humans.

1. Genioglossus (GG) activation in response to upper airway negative pressure may be an important mechanism in the maintenance of airway patency. This reflex occurs during wakefulness but is diminished during stable non-rapid eye movement (NREM) sleep. Since obstructive events occur more commonly at wake-sleep transitions and during rapid eye movement (REM) sleep than during stable NREM sleep, we assessed the GG reflex during these two vulnerable states. 2. Seventeen healthy adults were studied throughout one evening and overnight. Electroencephalograms (EEGs), electro-oculograms (EOGs), submental electromyogram (EMG), GG EMG (intramuscular electrodes), and choanal plus epiglottic pressures were recorded. The GG reflex response to pulses of -8 cmH2O choanal pressure applied via nose mask during early inspiration was quantified repeatedly during relaxed wakefulness, within five breaths of wake-sleep transition (EEG alpha-theta transition) and during REM sleep. Only trials without EEG arousal were analysed, resulting in data from 14 subjects during sleep onset and 10 subjects during REM sleep (overall, 174-491 trials per state). 3. During wakefulness there was brisk GG reflex activation in response to negative pressure (amplitude: +78.5 +/- 28.3 % baseline (mean +/- s.e.m.); latency to maximal response: 177 +/- 16 ms). 4. At sleep onset, although there was marked variability among individuals, there was no significant reduction in the magnitude of the GG reflex for the group as a whole (amplitude: +33.2 +/- 8.2 % baseline; latency: 159 +/- 15 ms). 5. In contrast, during REM sleep there was a reduction of GG reflex (amplitude: -12.6 +/- 8.3 % baseline (P = 0.017 vs. awake); latency: 160 +/- 10 ms (n.s. vs. awake)) and greater airway collapsibility during the applied pressures (P = 0.043 vs. awake). 6. We conclude that there was no systematic reduction in the GG reflex to negative pressure at sleep onset. Nonetheless, it remains possible that sleep-deprived normal subjects and patients with sleep apnoea could react differently. 7. The apparent inhibition of the GG reflex during REM sleep may help explain why the upper airway is vulnerable to collapse during this state.

Adult↗
PubMed1999

Indications for positive airway pressure treatment of adult obstructive sleep apnea patients: a consensus statement.

We developed a short-length document that clearly delineates a prudent approach to and criteria for reimbursement of positive airway pressure (PAP) costs for the treatment of obstructive sleep apnea (OSA). Treatment modalities for OSA with PAP include continuous positive airway pressure, bilevel or variable PAP, and autotitrating PAP. This guidance on the appropriate criteria for PAP use in OSA is based on widely acknowledged peer-reviewed studies and widely accepted clinical practice. These criteria reflect current opinion on the appropriate clinical management of OSA in lieu of data pending from the Sleep Heart Health Study and upcoming outcome studies. This document is not intended to provide a complete review and analysis of the OSA clinical literature. The key to the success of this document is to foster consensus within and outside the clinical sleep community by providing a common sense and easily understood approach to the treatment of OSA with PAP.

Adult↗
PubMed1998

Evaluation of the Healthdyne NightWatch system to titrate CPAP in the home.

Although a number of devices have been developed to monitor sleep and breathing in the home, there are few publications on methodologies by which CPAP can be titrated in the home setting. This study was conducted to determine the outcome of CPAP titration in the home using the Healthdyne NightWatch (NW) system. This home sleep-evaluation system was used to diagnose sleep apnea in 30 patients using a previously described methodology. These patients subsequently underwent CPAP titration in the home using the NW system, with modem technology allowing the transfer of data from the home to the laboratory. This group was compared with 30 patients who were diagnosed with sleep apnea using standard in-lab polysomnography and had CPAP titrated on a full night in the laboratory. Both groups were subsequently placed on CPAP at the appropriate pressure for 6-8 weeks, after which a full in-lab study was completed to assess CPAP efficacy at the prescribed pressure. Compliance was also determined using a pressure-activated monitor. No differences in any variable assessed could be found between the two groups. Mean compliance was 4.6 + 0.5 (SEM) and 4.3 + 0.5 hours of CPAP use per night for the home and in-lab groups respectively. Mean AHIs on the follow-up study were 7.4 + 1.2 and 7.6 + 1.6 events per hour for the home versus in-lab groups. Sleep stage distribution was also quite comparable between groups. As a result, this study suggests that sleep apnea can be diagnosed and CPAP titrated in the home with a similar outcome, at least at 6 to 8 weeks, to standard in-laboratory testing.

Adult↗
PubMed1998

Evaluation of a computerized polysomnographic system.

Computerized polysomnographic systems have came into common use in sleep laboratories around the world. Despite potential advantages over standard paper polysomnography, these computerized systems have been minimally evaluated as to accuracy, analysis time, or cost effectiveness when compared to paper. We evaluated the Healthdyne ALICE 3 system for comparability to paper polysomnography in sleep quantification and technician analysis time. Fifty patients were recorded simultaneously both on paper and on the ALICE 3 system and analyzed blindly with summary data from these records being quantified and compared. Five additional patients were studied for epoch-by-epoch analysis. Score-rescore assessments were accomplished for both groups. The results indicate that when allowed to autoscore, this computerized system produced substantial errors in sleep staging (REM sleep time 56.4 + 4.9 minutes vs 73.2 + 8.4 minutes for paper versus computer). This was the case for respiratory (AHI of 26.5 + 4.3 vs 15.3 + 2.6 for paper vs computer) and arousal assessment as well. However, with editing, similar results to those obtained with paper were achieved (REM sleep time -56.4 + 4.9 vs 59.0 + 4.6; AHI -26.5 + 4.3 vs 26.1 + 4.7 for paper and computer respectively), with differences rarely exceeding score-rescore discrepancies. Analysis time was substantially reduced by use of the computer (172.6 + 9.9 vs 79.7 + 4.8 minutes for paper vs computer). Epoch-by-epoch analysis revealed a trend to score toward wakefulness or lighter sleep on computer compared to paper although the differences were small. Respiratory, arousal and PLM scoring were quite similar. In conclusion, this study suggests that the ALICE 3 system with editing can produce results similar to those obtained with paper.

Computers↗
PubMed1998

A look toward the future.

There will be many changes in the sleep field in the next 5 to 10 years. These will include increments in our knowledge of the basic neurobiologic mechanisms driving sleep and the impact of sleep loss on general health. The technology used in the sleep laboratory will likely change as well, leading to a larger range of available tests and new ways to conduct standard ones. Finally, as the knowledge base in sleep increases, the expertise required to practice sleep medicine will rise, leading to a better-trained, more focused practitioner.

Forecasting↗
PubMed1998

Upper airway muscle activity in normal women: influence of hormonal status.

Obstructive sleep apnea is a disorder with a strong male predominance. One possible explanation could be an effect of female hormones on pharyngeal dilator muscle activity. Therefore, we determined the level of awake genioglossus electromyogram (EMGgg) and upper airway resistance in 12 pre- and 12 postmenopausal women under basal conditions and during the application of an inspiratory resistive load (25 cmH2O . l-1 . s). In addition, a subgroup of eight postmenopausal women were studied a second time after 2 wk of combined estrogen and progesterone replacement in standard doses. Peak phasic and tonic genioglossus activity, expressed as a percentage of maximum, were highest in the luteal phase of the menstrual cycle (phasic 23.9 +/- 3.8%, tonic 10.2 +/- 1.0%), followed by the follicular phase (phasic 15.5 +/- 2.2%, tonic 7.3 +/- 0.8%), and were lowest in the postmenopausal group (phasic 11.3 +/- 1.6%, tonic of 5.0 +/- 0.6), whereas upper airway resistance did not differ. There was a weak but significant positive correlation between progesterone levels and both peak phasic (P < 0.05) and tonic (P < 0.01) EMGgg. Finally, there was a significant increase in EMGgg in the postmenopausal group restudied after hormone therapy. In conclusion, female hormones (possibly progesterone) have a substantial impact on upper airway dilator muscle activity.

Adult↗
PubMed1997

Ventilatory responses to sustained eucapnic hypoxia in healthy males during wakefulness and NREM sleep.

The effects of sustained eucapnic hypoxia (SEH, 20 minutes SaO2, approximately 80%) on ventilation and supraglottic airflow resistance (Rua) plus genioglossal (gg) and diaphragmatic (di) electromyograms (EMGs) were compared during wakefulness and nonrapid eye movement (NREM) sleep in six healthy normal male subjects. Early augmentation of ventilation was followed by decline or roll-off in both states. The augmentation of ventilation was less in sleep than wakefulness (e.g., after 5 minutes hypoxia, 140% and 167% of baseline, respectively, p < 0.05). This appeared to be due to three factors: 1) sleep-related increases in Rua [the ventilatory responses to SEH (sleep vs. awake) were inversely related to changes in Rua (sleep vs. awake) (p < 0.05)], 2. reduced central neural drive (inspiratory phasic EMG di after 5 minutes SEH, 111% and 121% of baseline, p < 0.05), and 3) failure to increase respiratory frequency during SEH sleep. There was also a nonsignificant trend to a biphasic response in EMG gg and a small increase in Rua during SEH.

Adult↗
PubMed1996

Serotonergic effects on hypoglossal neural activity and reflex responses.

We determined the effects of serotonin (5HT; 6 concentrations ranging from 0.005 to 500 microM) pressure microinjection into the hypoglossal (XII) motor nucleus (100-500 nl; pH = 7.2-7.4) on XII whole nerve activity and reflex response to upper airway negative pressure in 15 decerebrated, vagotomized, paralyzed and artificially ventilated cats. Increasing 5HT concentration resulted in a concentration dependent increase in ipsilateral tonic XII activity, with no change in phasic XII activity. Threshold concentrations ranged from 0.005 to 0.5 microM, with the maximal response reached at 5 microM. Increasing 5HT concentration also increased the duration of the XII response. This ranged from 50 s with 0.5 microM, to over 10 min with 500 microM 5HT. However, 5HT did not significantly change the XII whole nerve reflex response to upper airway negative pressure (-20 cm H2O) at any 5HT concentration (n = 5). All 5HT effects were reversed by microinjection of 1.0 mM methysergide. We conclude that XII responses to 5HT are elicited at low concentrations of 5HT, which have a relatively short duration of effect, but that 5HT at the XII motor nucleus has no effect on the XII reflex response to upper airway negative pressure.

Animals↗
PubMed1996

Complex home monitoring.

As the demand for sleep evaluations rises, one response has been to conduct such studies in the home. In this brief review, complex home sleep monitoring systems (those recording at least four channels of physiologic data) on which there is peer-reviewed data are assessed. Four currently available systems met these criteria and are discussed. Each such system has clear strengths and weaknesses. These overall data suggest that home monitoring systems are becoming increasingly complex and more successful in monitoring, the desired variables. This trend is likely to continue.

Electroencephalography↗
PubMed1996

Effects of sustained and repetitive isocapnic hypoxia on ventilation and genioglossal and diaphragmatic EMGs.

We compared the effects of sustained isocapnic hypoxia (SIH; 20 min) and repetitive isocapnic hypoxia (RIH; 10 2-min episodes) on ventilation (VI), genioglossal (EMGgg) and diaphragmatic electromyographic (EMGdi) activities, and supraglottic airway resistance in 11 normal supine male subjects (36.6 +/- 2.2 yr) during wakefulness. Seven of the subjects had control measurements on a separate day. Desaturation was similar (arterial O2 saturation 80-84%) in the SIH and RIH protocols. SIH and RIH caused a biphasic ventilatory response: early augmentation of VI (169.5 +/- 6.9 and 168.9 +/- 4.3% of baseline, respectively; not significant) followed by a significant roll-off (VI after 20 min of cumulative hypoxia 153 +/- 4.0 and 150.8 +/- 10.2% respectively; not significant). Moving-time-average EMGdi signals (peak inspiratory and phasic) demonstrated a similar biphasic response in the two protocols. Mean EMGgg responses, however, differed. During SIH, peak inspiratory EMGgg increased early and remained elevated. Phasic and tonic EMGgg signals showed a similar trend. During RIH, early augmentation of peak inspiratory and phasic EMGgg signals was followed by a marked roll-off in activity such that by the 10th hypoxic episode neither value increased above baseline. In the 2-min periods between hypoxic episodes, there was a progressive suppression of peak inspiratory and phasic EMGgg values below baseline. Supraglottic airway resistance did not change significantly during either SIH or RIH. VI and phasic EMGs did not change during control experiments. We conclude that in awake normal male subjects SIH and RIH cause similar biphasic responses in VI and EMGdi activity. Phasic EMGgg activity responses differ between SIH and RIH: EMGgg remains augmented during SIH, whereas during RIH early augmentation is followed by marked suppression.

Adult↗
PubMed1996

Influence of sleep onset on upper-airway muscle activity in apnea patients versus normal controls.

Current evidence suggests that patients with obstructive sleep apnea (OSA) may have augmented pharyngeal dilator muscle activity during wakefulness, to compensate for deficient anatomy. However, the isolated effect of sleep on the activity of these muscles (comparing OSA patients with controls) has not been studied. We therefore determined waking levels of genioglossus (GG) and tensor palatini (TP) muscle activity (% of maximum electromyographic [EMG] activity) in 10 OSA patients and eight controls, and then assessed the impact of the first two breaths of sleep (theta electroencephalographic [EEG] activity) following a period of stable wakefulness. Apnea patients demonstrated greater genioglossal (27.4 +/- 4.0 versus 10.7 +/- 2.1%) and tensor palatini (31.9 +/- 6.5 versus 10.6 +/- 1.9%) EMG activity than did controls during wakefulness. This augmented muscle activity in apnea patients could be reduced to near control levels during wakefulness with the application of continuous positive airway pressure (CPAP) to the upper airway. At sleep onset, control subjects demonstrated small but consistent decrements in the activity of both the TP and GG muscles. On the other hand, apnea patients demonstrated large, significantly greater decrements in TP EMG at sleep onset than did the control subjects. The effect of sleep on GG EMG in apnea patients was inconsistent, with most (n = 7) demonstrating large (significantly larger than controls) decrements in genioglossal activity. However, three OSA patients demonstrated small increments in GG EMG at sleep onset despite falling TP EMG and obstructive apnea or hypopnea. We conclude that sleep onset is associated with significantly larger decrements in TP muscle EMG activity in OSA patients than in controls, which may represent a loss of neuromuscular compensation that is present during wakefulness. However, our results for the GG muscle were more variable, and did not always support this hypothesis.

Adult↗
PubMed1995

Assessment of accuracy and analysis time of a novel device to monitor sleep and breathing in the home.

Obstructive sleep apnea is increasingly recognized as a common and debilitating disorder. As a result, a variety of diagnostic technologies have evolved to potentially decrease cost and improve access and ease of assessment. In this study we compared the Healthdyne NightWatch (NW) System (a home sleep diagnostic methodology) to standard polysomnography (PSG) in two sleep centers. Two separate studies were completed. NW was compared to a simultaneously obtained PSG in 30 patients (IN-LAB study). Seventy additional patients were studied in both the home with NW and in the laboratory with PSG (HOME-LAB study). The NW system records eye movement, leg movement, SaO2, nasal-oral airflow, chest and abdominal wall motion, body position and heart rate on a solid state recorder, which permits sleep staging based on body and eye movement and standard respiratory assessment. For the PSG, standard paper recording techniques were used. The IN-LAB study revealed a correlation between NW and PSG for total sleep time of r = 0.72, with NW tending to score some awake time as nonrapid eye movement sleep. The correlation for apnea-hypopnea index (AHI) was r = 0.94 between systems, with a sensitivity of 100% and specificity of 63.6% at an AHI threshold of 10. The HOME-LAB study demonstrated understandably poor correlations between NW and PSG for most measures of sleep, which is likely a product of night-to-night variability in sleep, home versus laboratory effects and the differences in sleep staging methodology. However, the correlation for AHI was r = 0.92, with a sensitivity of 90.7% and a specificity of 70.4% at an AHI threshold of 10. Using a new methodology to assess agreement between diagnostic systems, we observed 78.6% diagnostic agreement between NW and PSG in the HOME-LAB study, with NW underestimating AHI 4.3% of the time and overestimating it in 17.1% of cases. This may relate to night-to-night variability in AHI or greater NW computer sensitivity to subtle hypopneas. We conclude that NW provides an accurate determination of AHI in both the home and laboratory, using limited instrumentation. The analysis time for NW is also reduced compared to PSG, and patients generally prefer the NW evaluation.

Equipment Design↗