Unpredictable results of laser assisted uvulopalatoplasty in the treatment of obstructive sleep apnoea.

BACKGROUND: Laser assisted uvulopalatoplasty (LAUP) is increasingly offered for the treatment of obstructive sleep apnoea (OSA), although there is a lack of objective data to support its indications and efficacy. A study was undertaken to determine the treatment response to LAUP. METHODS: Overnight polysomnography was performed before and at least three months after surgery in 44 consecutive patients with symptomatic mild to moderate OSA (apnoea + hypopnoea index (AHI) >10/h). Pharyngeal dimensions were measured by videoendoscopy (n = 11) and disease-specific quality of life, sleepiness and snoring frequency (n = 16) before and after surgery were determined in subgroups of patients. LAUP was performed under local anaesthesia as a one stage resection of the uvula and soft palate by one of two experienced otolaryngologists. RESULTS: Twelve patients (27%) had a good response (AHI 50% of pre-LAUP value); and 13 (30%) patients were worse (AHI >100% of pre-LAUP value). The velopharyngeal cross sectional area and anteroposterior diameter increased following LAUP (p<0.05). Quality of life indices improved significantly in all domains and sleepiness decreased. The snoring index did not decrease significantly. No preoperative anthropometric or videoendoscopic measures were predictive of a good response to LAUP. Patients who were worse after LAUP had milder baseline apnoea severity than those in the other response groups. CONCLUSIONS: The treatment response to LAUP is variable and unpredictable, and only a few patients achieve a satisfactory response. There appears to be no relationship between subjective and objective measures of treatment efficacy.

Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx.

BACKGROUND: The mechanisms of action of oral appliance therapy in obstructive sleep apnoea are poorly understood. Videoendoscopy of the upper airway was used during wakefulness to examine whether the changes in pharyngeal dimensions produced by a mandibular advancement oral appliance are related to the improvement in the severity of obstructive sleep apnoea. METHODS: Fifteen patients with mild to moderate obstructive sleep apnoea (median (range) apnoea index (AI) 4(0-38)/h, apnoea-hypopnoea index (AHI) 28(9-45)/h) underwent overnight polysomnography and imaging of the upper airway before and after insertion of the oral appliance. Images were obtained in the hypopharynx, oropharynx, and velopharynx at end tidal expiration during quiet nasal breathing in the supine position. The cross sectional area and diameters of the upper airway were measured using image processing software with an intraluminal catheter as a linear calibration. RESULTS: AI decreased to a median (range) value of 0 (0-6)/h (p<0.01) and AHI to 8 (1-28)/h (p<0.001) following insertion of the oral appliance. The median (95% confidence interval) cross sectional area of the upper airway increased by 18% (3 to 35) (p<0.02) in the hypopharynx and by 25% (11 to 69) (p<0.005) in the velopharynx, but not significantly in the oropharynx. Although in general the shape of the pharynx did not change following insertion of the oral appliance, the lateral diameter of the velopharynx increased to a greater extent than the anteroposterior diameter. Following insertion of the oral appliance the reduction in AHI was related to the increase in cross sectional area of the velopharynx (p = 0.01). CONCLUSIONS: A mandibular advancement oral appliance increases the cross sectional area of the upper airway during wakefulness, particularly in the velopharynx. Assuming this effect on upper airway calibre is not eliminated by sleep, mandibular advancement oral appliances may reduce the severity of obstructive sleep apnoea by maintaining patency of the velopharynx, particularly in its lateral dimension.

Mandibular posture during sleep in patients with obstructive sleep apnoea.

Vertical mandibular posture is thought to be related to narrowing of the upper airway, because mouth opening is associated with an inferior-posterior movement of the mandible and the tongue which influences pharyngeal airway patency. To test whether the mandibular posture is related to the occurrence and/or termination of obstructive sleep apnoea (OSA), the vertical mandibular position was recorded intraorally using a magnet sensor during a standard sleep study in seven patients with OSA. Measurements were recorded during sleep both in the supine and lateral recumbent positions. The percentage of total sleep time spent with mandibular opening greater than 5 mm was significantly larger (p<0.001) in patients with OSA (69.3+/-23.3%) compared with our previous results obtained from healthy adults without OSA (11.1+/-11.6%). The stage of sleep affected the vertical mandibular posture during sleep in the supine position, but not in the lateral recumbent position in patients with OSA. In non-rapid eye-movement sleep, mandibular opening increased progressively during apnoeic episodes and decreased at the termination of apnoeic episodes. In contrast, no significant change in mandibular posture occurred in apnoeic episodes during rapid eye-movement sleep. It was concluded that the vertical mandibular posture is more open during sleep in patients with OSA than in healthy adults and that mandibular opening increases progressively during apnoeic episodes and decreases at the termination of those episodes.

Mandibular posture during sleep in healthy adults.

To test whether the mandible opens more during deep sleep and whether the mandibular position is affected by body position during sleep, the vertical mandibular position was recorded intraorally using a magnet sensor at the same time as a standard sleep study in seven normal healthy male adults. Measurements were recorded during the period before sleep onset (WAKE) and during sleep. Two-way ANOVA showed that vertical mandibular position was significantly affected by sleep stage but not by body position (supine vs lateral recumbent). The proportion of time during which the mandible was in a near-closed position (0-2.5 mm) significantly and progressively decreased, and significantly more time was spent at wider gaps (2.5-5 mm) as non-rapid-eye-movement (NREM) sleep deepened. In REM sleep, the proportion of time during which the mandible was at wider gaps was significantly greater than in WAKE and stage 1 (but not later stages) of NREM sleep. It was concluded that mandibular posture during sleep in healthy adults is significantly influenced by sleep stage but not by body position. Mandibular opening progressively increases with the depth of NREM sleep stage, and the mandible is more open in REM sleep than in light NREM sleep.

Effect of mandibular and tongue protrusion on upper airway size during wakefulness.

Oral appliances for the treatment of obstructive sleep apnea (OSA) produce either mandibular or tongue protrusion, and are thought to enlarge the upper airway (UA). We used videoendoscopy to measure UA cross-sectional area (CSA) and shape in the hypopharynx, oropharynx, and velopharynx during various stages of active mandibular and tongue protrusion during wakefulness in 10 patients with OSA and nine control subjects. Measurements were made in the supine position at end-tidal expiration, and were normalized to the CSA in the normal bite position. Airway shape was expressed as the anteroposterior/lateral (AP/L) diameter ratio. There were no differences between OSA patients and controls in the effects of mandibular and tongue protrusion on UA caliber. Both mandibular and tongue protrusion increased CSA in the hypopharynx and oropharynx (p < 0.001), whereas only tongue protrusion increased CSA in the velopharynx (p < 0.001). Tongue protrusion caused a greater increase in oropharyngeal and velopharyngeal CSA than did mandibular protrusion (p < 0.05). Mandibular protrusion caused a greater increase in CSA in the hypopharynx than in the oropharynx or velopharynx (p < 0.05). Obese patients had a larger relative increase in oropharyngeal CSA with mandibular and tongue protrusion than did subjects of normal weight. Tongue protrusion increased the AP/L diameter ratio in the oropharynx and velopharynx (p < 0.001), and mandibular protrusion did so to a lesser extent in the oropharynx (p < 0.01), resulting in a more circular airway shape. We conclude that mandibular and tongue protrusion increase the CSA and alter the shape of the UA during wakefulness.

A short-term controlled trial of an adjustable oral appliance for the treatment of mild to moderate obstructive sleep apnoea.

BACKGROUND: Although oral appliances are effective in some patients with obstructive sleep apnoea (OSA), they are not universally effective. A novel anterior mandibular positioner (AMP) has been developed with an adjustable hinge that allows progressive advancement of the mandible. The objective of this prospective crossover study was to compare efficacy, side effects, patient compliance, and preference between AMP and nasal continuous positive airway pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS: Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7 (3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in and a two week wash-out period and two treatment periods (AMP and nCPAP) each of four months. Efficacy, side effects, compliance, and preference were evaluated by a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early in the study and three refused to cross over so treatment results are presented on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p < 0.01). Eleven of the 20 patients (55%) who used the AMP were treatment successes (reduction of AHI to < 10/hour and relief of symptoms), one (5%) was a compliance failure (unable or unwilling to use the treatment), and eight (40%) were treatment failures (failure to reduce AHI to < 10/hour and/or failure to relieve symptoms). Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six (30%) were compliance failures, and there were no treatment failures. There was greater patient satisfaction with the AMP (p < 0.01) than with nCPAP but no difference in reported side effects or compliance. CONCLUSIONS: AMP is an effective treatment in some patients with mild to moderate OSA and is associated with greater patient satisfaction than nCPAP.

Mechanical properties of the velopharynx in obese patients with obstructive sleep apnea.

Epidemiologic data indicate that the relationship between obesity and obstructive sleep apnea (OSA) is largely explained by variation in neck size. Fat deposits in the neck may predispose to upper airway (UA) occlusion during sleep by altering the mechanical properties of the UA, particularly at the level of the velopharynx (VP). To determine whether effective compliance (CEFF) of the VP is related to obesity in the neck, we have performed anthropometrics, polysomnography, and dynamic UA videoendoscopy in 18 patients with OSA and eight nonapneic control subjects. Following topical anesthesia (cocaine 4%) to one nasal passage, subjects were examined with a thin fiberscope (outer diameter [OD] 3.8 mm) while awake, supine, breathing exclusively through the nose, during a maximal vital capacity (VC) maneuver against an unoccluded airway. UA cross-sectional area (CSA), anteroposterior (AP) and lateral (L) diameters were measured from stored images. CEFF was expressed as the ratio of CSAVP in expiration (E) to inspiration (I) during the maximal VC maneuver (expiratory CSAMAX/inspiratory CSAMIN), and airway shape as AP/L diameter. The OSA patients were divided into two groups based on median neck circumference (NC). CEFF of the VP was greater in OSA patients compared with control subjects (CEFF 2.0 +/- 0.8 versus 1.1 +/- 0.5; p < 0.001). CEFF was greater in the large NC group compared with both the small NC group (p < 0.05) and control subjects (p < 0.01), but the difference between the small NC group and control subjects was not significant. CEFF was related to NC (r = 0.63; p = 0.001; n = 26), body mass index (r = 0.54; p < 0.01, n = 26), and apnea-hypopnea index (r = 0.43; p < 0.05; n = 23). The change in CSAVP during the maximal VC maneuver was mainly due to inspiratory narrowing. Obese patients with large necks have a more collapsible velopharynx during wakefulness, which may predispose to upper airway obstruction during sleep.

Energy expenditure in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are often obese and, in common with obese patients generally, find it difficult to lose weight. Obstructive sleep apnea may be associated with changes in total daily energy expenditure that could contribute to obesity and complicate its management. To determine whether resting metabolic rate and the thermogenic effect of food are reduced in OSA, we have compared postabsorptive resting energy expenditure (REE) and dietary thermogenesis (DT) in 14 patients with moderate to severe symptomatic OSA and 14 control subjects matched for obesity. Anthropometrics, body composition analysis using bioelectrical impedance and indirect calorimetry using a metabolic cart and canopy system were performed in all subjects. Dietary thermogenesis after a liquid meal equivalent to 35% of REE was measured in 13 patients and 8 control subjects. Measurements were repeated after chronic (mean +/- SD 12 +/- 5 weeks) nasal continuous positive airway pressure (CPAP) therapy in 10 patients with OSA. Energy expenditure was expressed in terms of metabolic body size. The patients with OSA were heavier and had larger necks and a larger lean body mass (LBM) than controls, but the two groups were well matched for body mass index (BMI) and percent body fat. REE was greater in OSA patients than controls, but when corrected for LBM there was no difference between the two groups (27 +/- 3 vs. 28 +/- 4 kcal/kg). DT was similar in patients and controls (17 +/- 6 vs. 15 +/- 10%). REE/LBM was quite consistent among patients with OSA, regardless of body weight. REE and DT did not change following chronic nasal CPAP therapy. (ABSTRACT TRUNCATED AT 250 WORDS)

Growth of Dictyostelium discoideum in the presence of antibiotics.

Cultures of the amoeboid slime mold, Dictyostelium discoideum, were grown in the presence of various antibiotics and antimetabolites. Results indicate that many antibiotics may be used in amoeba cultures to help minimize contamination (for example: polymyxin B, kanamycin, tetracycline, neomycin, oxacillin, ampicillin, cephalothin, and erythromycin). A few potent antibiotics were found to be unsuitable (colistin, nystatin, amphotericin B, actinomycin, and cycloheximide); the mechanisms of the inhibitions observed were not investigated further.

Inhibition of aggregation and differentiation of Dictyostelium discoideum by antibodies against adenosine 3':5'-cyclic monophosphate diesterase.

A specific antibody directed against adenosine 3':5'-cyclic monophosphate diesterase (c-AMP diesterase; EC 3.1.4.c), which is secreted by the amoeboid slime mold, Dictyostelium discoideum, was prepared in rabbits. Purified gammaglobulin fractions that contain the antibodies inhibited the activity of cAMP diesterase preparations in vitro and interfered with aggregation and development in vivo. While cells that were treated with antibody were unable to aggregate because of the inability to destroy cAMP, they aggregated normally when washed free of antibody.

The acrasin activity of 3',5'-cyclic nucleotides.

3',5'-Cyclic nucleotides are acrasins for the cellular slime mold, Dictyostelium discoideum; they have chemotactic activity on the myxamoebae at very low concentrations. However, not all cyclic nucleotides can evoke the adhesiveness necessary for aggregate formation. 2',3'-Cyclic nucleotides and dibutyrylcyclic adenosine monophosphate are not acrasins, though they enhance the rate of differentiation and morphogenesis. The addition of 3',5'-cyclic nucleotides to agar test plates stimulates the rate of morphogenesis. While the stimulatory effect of cyclic nucleotides is concentration-dependent, it is fairly uniform between pH 5 and 7, with an optimum at pH 6. The acrasins may be metabolized by extracellular phosphodiesterase to 5'-nucelotides which may then stimulate differentiation and morphogenesis.

Direct quantitative gas chromatographic separation of C2-C6 fatty acids, methanol, and ethyl alcohol in aqueous microbial fermentation media.

A method is described for the direct quantitative gas chromatographic separation of C(2)-C(6) lower fatty acid homologues, methanol, and ethyl alcohol in aqueous microbial fermentation media. A hydrogen flame detector and a single-phase solid column packing, comprising beads of a polyaromatic resin (polystyrene cross-linked with divinyl benzene), were employed. Direct injections of 1 to 10 muliters of aqueous culture supernatant fluids were made. Quantitative recoveries of C(2)-C(6) acids added to culture supernatant fluids were obtained.