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Biomedical subjects

N J Douglas

Publications and source records attributed to N J Douglas.

At least 19 recordsLinked to original sources
PubMed1997

Inhaled salmeterol or oral theophylline in nocturnal asthma?

Nocturnal cough and wheeze are common in asthma and often treated with beta2 agonists or theophyllines. As nocturnal asthma and these therapies may affect sleep and cognition, we compared 50 microg salmeterol inhaled every 12 h with individually dose-titrated sustained-release oral theophylline on sleep quality and cognitive performance in 15 patients with stable nocturnal asthma (overnight peak expiratory flow rate [PEFR] fall > or = 15%, > or = 1 asthmatic awakening/week) using a double-blind, double-dummy, crossover design with 14-d therapy limbs. Cognitive testing and polysomnography were performed on Nights 13 and 14. Trough plasma theophylline concentration after Night 14 on theophylline was median 11.1 (interquartile range 8.3, 15.2) microg/ml. Overnight PEFR falls were similar [salmeterol 2.3 (0, 10.6), theophylline 3.5 (-0.3, 9.6)%, p = 0.4] but on salmeterol there were more nights without awakenings [median difference 1 (0, 2), p < 0.01], fewer nocturnal arousals [difference -3 (-7, 2) h(-1), p < 0.05] and improved quality of life (p = 0.05). Sleep architecture did not otherwise differ. Visual vigilance improved on salmetrol (p < 0.05), but otherwise daytime cognition was unaffected. There was no patient preference for either therapy. Hence in patients with nocturnal asthma, we demonstrate no major clinical advantage, but a small benefit in sleep quality, quality of life, and daytime cognitive function with salmeterol.

Administration, Inhalation↗
PubMed1996

Ambulatory blood pressure on and off continuous positive airway pressure therapy for the sleep apnea/hypopnea syndrome: effects in "non-dippers".

Ambulatory blood pressure (BP) monitoring was performed in 13 patients with the sleep apnea/ hypopnea syndrome (SAHS) during a randomized, placebo controlled crossover trial of the effects of continuous positive airway pressure (CPAP) therapy. BP was monitored at half-hourly intervals for a 24-hour period both on CPAP and on an oral placebo, each given for a minimum of 3 weeks. Objective effective CPAP use averaged 4.3 hours per night. Weight and anti-hypertensive medications remained stable over the study period. Systolic, diastolic and mean arterial BP for 24-hour, daytime and nighttime periods were not significantly different on placebo compared to CPAP. Those patients with no significant overnight fall in BP on placebo ("non-dippers") showed a significant improvement in daytime mean arterial BP on CPAP (98 +/- 4 mm Hg) compared to placebo (102 +/- 4 mm Hg; p = 0.01). These findings, in a well-controlled trial, suggest that BP is not reduced by CPAP in a heterogeneous group of SAHS patients, but it may be selectively improved in those patients most at risk for cardiovascular morbidity and mortality.

Adult↗
PubMed1996

DNA sequence variation as a clue to the phylogenesis of orthopoxviruses.

We have sequenced DNA equivalent to the E5R ORF of Copenhagen vaccinia virus from an additional strain of vaccinia and from cowpox (three strains), camelpox (two strains), taterapox and ectromelia viruses. None of these showed the disruptions previously reported in the equivalent region of monkeypox virus. We also constructed a viable recombinant of vaccinia virus strain Dairen in which the E5R sequence was disrupted by a 436 bp deletion and substitution of the E. coli gpt gene. Quantitative analysis of the sequences, including available sequences from monkeypox, variola and vaccinia viruses revealed four main groupings, namely cowpox, ectromelia, monkeypox and a cluster which includes variola, camelpox, taterapox and vaccinia viruses. It was noted that, at over 75 % of the positions which differentiated species. all species but one had a common nucleotide. Although the analysis covers one single gene only, the results accord with what is known of the biology of the viruses.

Base Sequence↗
PubMed1996

Effect of chronic continuous positive airway pressure (CPAP) therapy on upper airway size in patients with sleep apnoea/hypopnoea syndrome.

BACKGROUND: There is evidence to suggest that chronic continuous positive airway pressure (CPAP) therapy may produce reversible changes in upper airway morphology and function in patients with sleep apnoea/hypopnoea. This study was designed to examine the effect of chronic CPAP therapy on upper airway calibre. METHODS: Twenty four men with the sleep apnoea/hypopnoea syndrome (mean (SE) apnoea/hypopnoea index 37 (5)) underwent lateral cephalometry with measurement of posterior airway space performed before and at least three months after initiation of CPAP therapy. RESULTS: There was no weight change between the two assessments and mean CPAP use was 4.8 (0.4) hours per night. Posterior airway space (PAS) was measured in erect and supine postures. PAS supine increased with CPAP therapy from a mean (SE) of 11.8 (0.8) mm to 13.4 (0.8) mm, but PAS erect did not. Correlation of the change in PAS (dPAS) before and after CPAP therapy showed an increase with increasing CPAP compliance measured as machine run time both for dPAS supine (r = 0.68) and dPAS erect (r = 0.47). CONCLUSIONS: Patients with the sleep apnoea/hypopnoea syndrome regularly using CPAP for more than four hours per night all showed an increase in dPAS supine. The use of chronic CPAP increases PAS supine probably by a reduction in upper airway oedema, and the change in size is dependent on CPAP use.

Cephalometry↗
PubMed1996

The effect of sleep fragmentation on daytime function.

Patients with the sleep apnea/hypopnea syndrome suffer from impaired daytime function. This has been attributed to both sleep fragmentation and hypoxemia. To help understand which is casual, we studied the effects of sleep fragmentation alone on daytime function. Sixteen normal subjects were studied on two pairs of two nights. The first night of each pair was for acclimatization, and on the second the subject either slept undisturbed or had sleep fragmented with sound pulses every 2 min. Sound volume and duration was titrated to cause a return to theta or alpha rhythm on the EEG for at least 3 s. Study nights were followed by daytime testing of psychometric function and mood and by a multiple sleep latency test (MSLT) and a maintenance of wakefulness test (MWT). Total sleep time did not differ between study nights (400 +/- 20 SD min undisturbed, 396 +/- 24 min fragmented; p = 0.6). Fragmentation decreased sleep latency on both the MSLT (11 +/- 3, 7 +/- 2 min; p = 0.001) and the MWT (34 +/- 8, 24 +/- 10 min; p<0.001). Energetic arousal (22 +/- 4, 19 +/- 4; p = 0.005) and hedonic tone (29 +/- 4, 27 +/- 4; p = 0.05) decreased after fragmentation. Fragmentation impaired daytime function adjudged by the Trailmaking B (p = 0.05) and PASAT 4-s tests (p<0.03). One night of sleep fragmentation makes normal subjects sleepier during the day, impairs their subjective assessment of mood, and decreases mental flexibility and sustained attention.

Arousal↗
PubMed1996

Uvulopalatopharyngoplasty may compromise nasal CPAP therapy in sleep apnea syndrome.

Uvulopalatopharyngoplasty (U3P) has been advocated for treatment of snoring and sleep apnea/hypopnea syndrome (SAHS), but often it does not effect a cure, so that other therapy (CPAP) is often required. We hypothesized that patients with U3P will have increased mouth air leak during CPAP because of loss of the soft palatal seal. This may result in decreased tolerance and compliance if CPAP therapy is required after U3P. We have therefore compared CPAP tolerance in 13 awake normal male subjects, 13 male patients with SAHS and 13 male patients treated with U3P, all naive to CPAP and matched for age and body mass index. All normal subjects and patients with SAHS were able to tolerate pressures of at least 20 cm H2O without mouth air leak or appreciable discomfort. In contrast male U3P patients started to leak air via the mouth at a mean CPAP pressure of 6.8 (SD, 2.4) cm H2O and were able to tolerate a mean maximal pressure of only 14.5 (SD, 2.6) cm H2O, which was significantly less than that in the other two groups (p < 0.001). We also examined nasal CPAP compliance (machine run time) in eight patients with SAHS who had previous U3P compared with 16 patients with SAHS without U3P. Both groups were matched for age, body mass index, and apnea/hypopnea index. Patients with U3P had significantly lower compliance (mean, 3.5 h/night) compared with patients without U3P (mean, 5.7 h/night), p = 0.01. We conclude that U3P may compromise nasal CPAP therapy by increasing mouth air leak and reducing the maximal level of pressure that can be tolerated.

Humans↗
PubMed1996

Palatopharyngeus has respiratory activity and responds to negative pressure in sleep apnoeics.

The intrinsic tongue muscle, genioglossus, and soft palatal muscles, tensor palatini, levator palatini and palatoglossus, are known to exhibit phasic respiratory activity and to respond reflexly to negative pressure in man, which may be important in the maintenance of upper airway patency. We hypothesized that the palatopharyngeus muscle should also have respiratory activity and increased activity in response to negative upper airway pressure. We have, therefore, examined the palatopharyngeus and the antagonist muscle, levator palatini, in eight awake sleep apnoea patients, using bipolar electromyography during nose- or mouth-breathing in different postures, and with or without application of negative pressure. Overall, palatopharyngeus and levator palatini demonstrated phasic respiratory activity. Palatopharyngeus demonstrated increased activity in the supine compared to erect posture. Analysis by route of respiration showed palatopharyngeus to be more active in the supine posture when nose-breathing compared to mouth-breathing. Graded negative pressure application caused significant increases in palatopharyngeus and levator palatini activity when applied via the mouth. Nasal negative pressure application caused a nonsignificant trend to increasing palatopharyngeus activity with increasing negative pressure compared to a significant increase for levator palatini. We conclude that palatopharyngeus and levator palatini demonstrate respiratory activity and reflex activation in response to negative pressure. Palatopharyngeus may, therefore, have a role as an upper airway dilator. The differential response of palatopharyngeus to oral and nasal negative pressure application may be important in the pathogenesis of sleep apnoea.

Adult↗
PubMed1996

Self-reported use of CPAP and benefits of CPAP therapy: a patient survey.

The benefits of continuous positive airway pressure (CPAP) therapy in patients with the sleep apnea/hypopnea syndrome (SAHS) are poorly documented and patients use CPAP less than physicians recommend. To establish patients' perceptions of benefit from CPAP and to identify determinants of CPAP use, 204 CPAP users completed a questionnaire relating to use of CPAP therapy, sleepiness, and road traffic incident rate before and after CPAP, perceived change in daytime function and nocturnal symptoms with treatment, and problems with CPAP. Variables from these domains of interest were examined, reduced through principal components analysis and correlated to assess associations between these and polysomnographic measures of illness severity. Self-reported CPAP use averaged 5.8 +/- SD 2 h a night. Subjective sleepiness rated by the Epworth sleepiness scale and road traffic incident rate were significantly reduced by CPAP (p<0.0001). A broad range of function and symptom items were highly significantly improved with CPAP (p<0.0001), corroborating the cost to community and industry from SAHS and the preventive value of CPAP. Road traffic incident rate before treatment was correlated with pre-CPAP sleepiness and SAHS severity. Subjective CPAP use correlated with sleepiness before treatment but not with SAHS severity. CPAP mask problems and side effects were not associated with reduced CPAP use, but "nuisance" complaints of awakenings, noise, and sore eyes from CPAP correlated negatively with reported use. Greater reported CPAP use was associated with better resolution of sleepiness and greater improvement in daytime function and nocturnal symptoms.

Accidents, Traffic↗
PubMed1995

Family studies in patients with the sleep apnea-hypopnea syndrome.

OBJECTIVE: To determine whether familial factors affect development of the sleep apnea-hypopnea syndrome and upper airway caliber. DESIGN: A case-control study. SETTING: Tertiary, referral clinical sleep laboratory. PARTICIPANTS: 51 first-degree relatives of patients with the sleep apnea-hypopnea syndrome and 51 controls matched for age, sex, height, and weight who were drawn at random from a family practice register. To avoid studying the familial nature of obesity, only relatives of index patients with body mass indices less than 30.0 kg/m2 were recruited. MEASUREMENTS: Assessment of sleep-related symptoms; breathing, sleep, and oxygenation patterns on overnight polysomnograms; upper airway dimensions by acoustic reflection; and facial structure by lateral cephalometry. RESULTS: More relatives of patients with the sleep apnea-hypopnea syndrome reported snoring (24 relatives compared with 7 controls; P < 0.001) and daytime sleepiness (28 relatives compared with 16 controls; P = 0.01). Relatives had more apneas and hypopneas per hour (median of 13/h [95% CI, 3 to 82/h] for relatives compared with median of 4/h [CI, 0 to 53/h] for controls; P < 0.001), more arousals from sleep (30/h [CI, 11 to 87/h] for relatives compared with 17/h [CI, 4 to 59/h] for controls; P < 0.001), poorer sleep quality, and more oxygen desaturations. Relatives also had narrower upper airways with retroposed maxillae and mandibles and longer soft palates with wider uvulae. CONCLUSION: The sleep apnea-hypopnea syndrome has a strong familial component. The familial tendency may be caused by differences in facial structure.

Adult↗
PubMed1995

Effect of breathing, pressure and posture on palatoglossal and genioglossal tone.

1. Patency of the upper airway is critical to respiration. Although about half of patients with the sleep apnoea/hypopnoea syndrome obstruct their upper airway at the retropalatal level, the respiratory actions of the palatal muscles have been little studied. We have therefore tested the hypothesis that the nasopharyngeal dilator muscle palatoglossus is activated during inspiration and by negative pressure. 2. Using intramuscular wire electrodes inserted perorally, we have compared the response of palatoglossus and genioglossus to breathing, posture change and airway negative pressure in 10 normal awake subjects before and after topical anaesthesia. The results are expressed as a percentage of maximal electromyogram. Data were analysed by repeated-measures analysis of variance. 3. Inspiratory activity was exhibited by both genioglossus [inspiratory, 10% +/- 2% (SEM); expiratory, 6% +/- 1%, P = 0.001] and palatoglossus (inspiratory, 16% +/- 5%, expiratory, 10% +/- 3%, P = 0.016), but only genioglossus exhibited increased activity on lying (supine 10% +/- 2%, erect 6% +/- 1% maximum, P = 0.01). 4. One hundred milliseconds after negative pressure application, activity increased in both genioglossus (7% +/- 2% and 13% +/- 3% respectively, P = 0.02) and palatoglossus (8% +/- 2% and 23% +/- 6% respectively, P < 0.001). After lignocaine surface anaesthesia to the nose and pharynx both genioglossus and palatoglossus still increased their activity in response to negative upper airway pressure, the extent of the increase being decreased for palatoglossus (P = 0.02) but not for genioglossus. 5. Thus, palatoglossus has respiratory activity and is activated by negative upper airway pressure.

Adult↗
PubMed1995

Frequency of EEG arousals from nocturnal sleep in normal subjects.

Brief arousals are clinically important and increasingly scored during polysomnography. However, the frequency of arousals during routine polysomnography in the normal population is unknown. We performed overnight polysomnography in the 55 of 59 control subjects from a family practice list who were approached and agreed to undergo polysomnography. Awakenings were scored according to the criteria of Rechtschaffen and Kales and briefer arousals according to three different criteria, including the American Sleep Disorders Association (ASDA) definition. There was a mean of 4 [95% confidence interval (CI), 1-15) Rechtschaffen and Kales awakenings per hour, whereas the ASDA definition gave 21 (95% CI, 7-56) per hour slept. Arousal frequencies increased significantly (p < 0.001) with age in our subjects, who ranged from the late teens to early 70s. The high upper limit of the frequency of brief arousals was not altered by exclusion of patients who snored or had witnessed apneas or daytime sleepiness. It is important that those scoring arousals on routine polysomnography recognize that high arousal frequencies occur in the normal population on 1-night polysomnography.

Adult↗
PubMed1995

Does sleep enhance the effect of subanesthetic isoflurane on hypoxic ventilation?

After surgery, patients may receive little audiovisual stimulation and may sleep. Lack of audiovisual stimulation enhances the suppression of the hypoxic ventilatory response (HVR) by 0.1 minimum alveolar anesthetic concentration (MAC) isoflurane. Sleep also reduces the HVR and may thus increase the risk of hypoxia in patients at this time. We therefore measured the ventilatory response in volunteers to a sustained step hypoxic stimulus (mean arterial oxygen saturation [SaO2] 80% [SEM 0.3] for 20 min) in the presence of 0.1 MAC isoflurane, with subjects in the awake and asleep states. The behavioral states were studied in random order in nine male subjects. The combination of isoflurane and sleep significantly reduced (P < 0.05) normoxic ventilation (6.71 [0.39] vs 8.24 [0.29] L/min) and increased end-tidal PCO2 (PETCO2) (43.1 [0.5] vs 40.4 [0.8] mm Hg) compared with the awake state. However, ventilation was similar in the asleep and awake states during early (15.10 [1.35] vs 15.50 [1.61] L/min) and late (10.45 [0.97] vs 11.03 [0.99] L/min) hypoxia in the presence of isoflurane. Thus sleep did not reduce ventilation during hypoxia in the presence of isoflurane sedation. The increase in PETCO2 during sleep may have offset suppression of the HVR.

Adult↗
PubMed1995

Comparison of polysomnography with ResCare Autoset in the diagnosis of the sleep apnoea/hypopnoea syndrome.

BACKGROUND: Increasing referral numbers make the development of simplified accurate methods of diagnosing the sleep apnoea/hypopnoea syndrome highly desirable. The accuracy of one such system--the ResCare Autoset--has been examined. METHODS: Thirty one consecutive patients assessed by polysomnography had simultaneous monitoring of their respiratory pattern using the Autoset system. The Autoset detects episodes of flattening of the flow/time profile using nasal cannulae. RESULTS: There was a good correlation (r = 0.85) between the number of apnoeas+hypopnoeas/hour in bed recorded using polysomnography and the Autoset system. The median difference in such events was 3.1 (95% confidence interval 8.4 to -1.6)/hour in bed. In two patients the Autoset scored 70 apnoeas+hypopnoeas/hour in bed compared with 34 apnoeas+hypopnoeas with 35 arousals/hour in bed by polysomnography; however, this did not alter the diagnostic category of either patient. Autoset gave a sensitivity of 100%, specificity of 92%, positive predictive value of 92%, and negative predictive value of 100%, which was better than oximetry alone. A sleep study using the Autoset system costs 14 pounds compared with 126 pounds for polysomnography. CONCLUSIONS: The Autoset is clinically useful for diagnosing the sleep apnoea/hypopnoea syndrome.

Costs and Cost Analysis↗
PubMed1995

Self assessment of daytime sleepiness: patient versus partner.

BACKGROUND: Patients with the sleep apnoea/hypopnoea syndrome (SAHS) and their spouses often differ in their assessment of the patient's sleepiness. A study was therefore undertaken to investigate whether either the patient's or partner's rating on the Epworth sleepiness scale (ESS) was better related to illness severity. METHODS: Nocturnal variables (apnoeas+hypopnoeas/hour (AHI) and arousals/hour) and patient and partner ESS scores were compared in 103 new patients attending the sleep clinic. RESULTS: Mean patient and partner ESS scores were not different. In the whole population neither patient nor partner ESS variables correlated with AHI or arousal frequency. In the patients with SAHS (AHI > or = 15), partner ESS correlated weakly with AHI, but patient ESS did not. CONCLUSIONS: This study suggests that neither patient nor partner ESS ratings are strong predictors of SAHS severity.

Disorders of Excessive Somnolence↗
PubMed1995

Effect of posture, route of respiration, and negative pressure on palatal muscle activity in humans.

Sleep apnea is worse in the supine posture and is associated with retropalatal airway narrowing or occlusion. We have, therefore, examined the effects of posture, negative pressure, and route of respiration on palatal muscle activity in 13 nonsnoring awake male subjects by using electromyography. Electromyographic activity of the levator palatini and palatoglossus was expressed as a percentage of maximum activity. Both the levator palatini (P = 0.002) and palatoglossus (P = 0.002) exhibited phasic inspiratory activity. Overall, posture did not affect the levator palatini (F = 1.58; P = 0.23) or palatoglossus (F = 0.98; P = 0.34) activity, but analysis by route of respiration showed the palatoglossus to be more active when the subjects were nose breathing supine (F = 6.64; P = 0.02). Levator palatini activity was lower when nose breathing was compared with mouth breathing in both the erect and supine postures (F = 6.67; P < 0.02). Nose breathing with the mouth held open caused an increase in palatoglossal activity (P = 0.04). Negative-pressure application (0 to -12.5 cmH2O) caused significant increases in levator palatini (P < 0.001) and palatoglossus (P < 0.001) activity, 100 ms after pressure stimulus, irrespective of route. However, the palatoglossus required significantly greater negative pressures to cause activation when applied via the nose compared with the mouth (P < 0.05). These observations indicate that the levator palatini and palatglossus have respiratory activity and are reflexly activated by negative pressure.

Adult↗
PubMed1995

The effect of posture on airway caliber with the sleep-apnea/hypopnea syndrome.

Snoring and sleep apnea are more common in the supine than seated position. We therefore studied the effect of posture on upper-airway caliber in normal subjects, snorers, and subjects with the sleep-apnea/hypopnea syndrome (SAHS). We measured upper-airway cross-sectional area by acoustic reflection in 110 SAHS patients (apnea/hypopnea index [AHI] > 15), 70 snorers without SAHS (AHI < 15), and 40 male controls matched for body-mass index (BMI) to the 40 SAHS patients. SAHS patients in the seated position had smaller upper-airway areas at the orophyngeal junction (OPJ) than either the snorers (p < 0.01) or the normal subjects (p < 0.02), but there were no differences between groups in airway cross-sectional areas in the supine or lateral recumbent positions. SAHS patients had significantly smaller decreases in OPJ area from the seated to either the supine (p < 0.001) or lateral recumbent (p < 0.001) positions than did the snorers. SAHS patients also had smaller (p < 0.05) decreases in OPJ area upon lying down than did the BMI-matched normal subjects. These data are compatible with SAHS patients defending their upper airway more upon lying down than do snorers or normal subjects.

Acoustics↗