Occurrence and correlates of sleep disordered breathing in the Australian town of Busselton: a preliminary analysis.
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Adult↗
Biomedical subjects
J Hedner
Publications and source records attributed to J Hedner.
Snoring and sleep apnoea in men: association with central obesity and hypertension.
The objective of this study was to examine the relationship between sleep apnoea, measures of obesity and blood pressure. The study was cross-sectional in design, involving 1464 consecutive men undergoing sleep studies at two non-hospital sleep laboratories. Detailed sleep studies, body mass index (BMI), neck, hip and waist circumferences and morning and evening blood pressures were measured in each patient. Twenty-eight per cent of patients were obese (BMI > 30 kg/m2) and 47% were overweight (BMI 26-30 kg/m2). Body fat distribution in these patients was typically central with a mean waist-hip ratio (WHR) for the entire group of 0.99 with over 80% of patients having a WHR more than 0.94. Increasing severity of sleep apnoea measured either by respiratory disturbance index (RDI) or minimum oxygen saturation in sleep (MOS) was associated with increasing central obesity and morning but not evening blood pressure. Normal weight patients (BMI < 25 kg/m2) with sleep apnoea were characterized by increased waist and hip circumferences and increased morning diastolic blood pressure compared to patients without sleep apnoea. The best explanatory variables for sleep apnoea were waist (r2 = 0.156, P < 0.001) and age (r2 = 0.013, P = 0.003) only. Morning but not evening blood pressure was related to sleep apnoea independently of obesity and age. We concluded that patients with sleep apnoea are centrally obese. Waist circumference is a better predictor for sleep apnoea than neck circumference or BMI suggesting that the link between obesity and sleep apnoea cannot be explained solely by neck fat deposition.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Localization of the central antinociceptive effects of diclofenac in the rat.
The ethacrynic acid-induced writhing response (WR) in the rat was studied after microinjections of diclofenac 0.1 ng-1 microgram/0.5 microliter (0.32 pmol to 3.2 nmol) into several brain regions involved in control of nociceptive behavior. The WR was inhibited after injections into the periaqueductal grey matter (PAG), ventromedial thalamus (VM), medial preoptic area (MPA) and the nucleus raphe magnus (NRM). Morphine 50 ng/0.5 microliter (0.16 nmol) was used as a positive control and vehicle injections were performed as negative reference. After diclofenac, there was a dose-dependent reduction of the WR with a threshold dose of approximately 1-10 ng in all brain areas studied except the nucleus reticularis paragigantocellularis interna (NRPGi). Naloxone 50 ng/0.5 microliter (0.15 nmol) administered into the same site 30 min after diclofenac injection, antagonized the diclofenac-induced inhibition of the WR almost completely in PAG and VM. Previous results demonstrate a central, naloxone-reversible component in the analgetic action of diclofenac. A qualitatively similar, centrally induced inhibition of the WR may be elicited after injections into PAG, VM and NRM. Thus, in addition to its peripheral mechanism of action, the non-steroidal anti-inflammatory drug, diclofenac, has a central mechanism of action which directly or indirectly involves a central opioid component.
Animals↗
The effects of nasal dilation on snoring and obstructive sleep apnea.
The effects of nasal valve dilation on snoring and obstructed breathing were studied in 11 patients with habitual snoring and/or obstructive sleep apnea. The anterior part of the nose, the valve region, was dilated by means of a plastic device. Ten patients underwent polysomnographic investigation including pulse oximetry and measurement of snoring noise with and without the nasal dilator in a randomized manner. Snoring, nocturnal arousals, and daytime hypersomnolence were rated by the patient and partner on a questionnaire before and after a 10-day treatment period with the dilator. The nasal airflow, as assessed by rhinomanometry when awake in the sitting position, increased by 18% (range, 5.5% to 45%) when the nasal dilator was used. The frequency and severity of obstructed breathing decreased significantly with the nasal dilator. The apnea index with and without the nasal dilator was 6.4 (range, 1.3 to 15) and 18 (range, 1.8 to 60), respectively. The mean decrease of the apnea index was 47%. The overnight minimum arterial oxygen saturation (with and without the nasal dilator was 84% (range, 76% to 88%) and 78% (range, 68% to 89%), respectively. There was a substantial decrease in snoring noise (number of epochs with Leq values, equal energy level, above 55 or 60 dB) with the dilator in all patients who presented with snoring noise above these levels during the control night. No subjective effects on arousal frequency or daytime hypersomnolence were reported. Four of 11 patients were positive to continue using the nasal dilator.
Adult↗
Yohimbine pharmacokinetics and interaction with the sympathetic nervous system in normal volunteers.
The pharmacokinetics of yohimbine and its effects on sympathoadrenal function were studied in 13 young, healthy, male volunteers after an IV bolus dose of 0.25 or 0.5 mg.kg-1. Pharmacokinetic analysis showed that distribution was rapid, with a half life between 0.4 and 18 min, and the elimination half life ranged between 0.25 and 2.5 h. The volume of distribution (Vss) was 74 l, (range 26 to 127 l). Only 0.5 to 1% of unchanged yohimbine was found in the urine, indicating that the major part of the drug was eliminated by hepatic clearance. Total plasma clearance was 117 l.h-1, which exceeds the hepatic plasma flow. This means that yohimbine is a high extraction drug with considerable extra-hepatic metabolism. Fractional urine sampling revealed that 0.5-1% of unchanged yohimbine was excreted in urine in a biphasic manner. The data also suggested the existence of a slower elimination phase, with a half life of 13 h. The venous plasma concentration of noradrenaline (NA) increased 3-fold within 15 min after the yohimbine injection while plasma adrenaline (A) and neuropeptide Y-like immunoreactivity (NPY-LI) remained unchanged. The plasma concentration-effect relationship of the changes in circulating NA followed counter-clockwise hysteresis. The results show that the hyperadrenergic state elicited by therapeutic doses of the alpha 2-adrenergic autoreceptor antagonist, yohimbine, is due to an interaction with NA but not to release of A or NPY in man.
Adult↗
Hemodynamic effects of the use of oral snuff.
The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.
Adult↗
Treatment of postoperative pain with diclofenac in uvulopalatopharyngoplasty.
Diclofenac sodium suppositories 150-200 mg day-1 were compared with placebo in a double-blind study during the first 3 days after uvulopalatopharyngoplasty in 40 patients with habitual snoring or obstructive sleep apnoea syndrome. Consumption of rescue analgesics (paracetamol suppositories) and pain assessed by a visual analogue scale were significantly less in the diclofenac group. Bleeding time (modified Ivy's test) and reported side effects did not differ between the two groups.
Acetaminophen↗
Secondary polycythaemia associated with nocturnal apnoea--a relationship not mediated by erythropoietin?
A polysomnographic study was undertaken in nine patients with unexplained polycythaemia and nine age- and sex-matched controls. Circulating plasma levels of immunoreactive erythropoietin (IrEPO) were analysed before and after sleep. Seven out of nine polycythaemia patients were found to have sleep-disordered breathing and fulfilled the criteria for the sleep apnoea syndrome. Erythrocyte volume fraction was by definition higher among polycythaemia patients, and showed a weak positive correlation with minimum oxygen saturation during sleep (P less than 0.05). However, plasma IrEPO did not differ between the two groups or between morning and evening samples within the respective groups. In a separate study, IrEPO was repeatedly analysed during sleep in a group of six patients with severe obstructive sleep apnoea and six matched controls. No correlation with severity of sleep-disordered breathing was found. None of these patients had polycythaemia, and there was no obvious diurnal variation in IrEPO levels. A nocturnal sleep study may be warranted in patients with unexplained polycythaemia. Obstructive sleep apnoea does not appear to be related to increased IrEPO levels, although polycythaemia has been reported as a relatively common finding in this disease.
Circadian Rhythm↗
Substance P, thyrotropin-releasing hormone, and monoamine metabolites in cerebrospinal fluid in sleep apnea patients.
The cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH), substance P (SP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were measured in 15 consecutive patients with the sleep apnea syndrome (SAS) and in healthy control subjects. Second measurements were performed 6 months after surgical treatment in 10 of the patients. The mean (+/- SD) concentration of TRH-like immunoreactive material (TRH-LIM) (pg/ml) did not differ significantly between patients with SAS (8.1 +/- 2.8) and control subjects (7.5 +/- 2.2). However, postoperatively, this concentration was increased in the six clinically cured patients with SAS, from 6.9 +/- 2.7 to 9.4 +/- 1.6 (p less than 0.03). Substance P-like immunoreactive material (SP-LIM) was higher in untreated patients with SAS than in control subjects: 19.2 +/- 6.7 versus 14.4 +/- 4.2 fmol/ml (p less than 0.02), and the level remained high after operation in the group treated surgically. The HVA, 5-HIAA, and MHPG concentrations were similar in patients with SAS and control subjects, and no consistent changes were found postoperatively. The CSF deviations in TRH-LIM and SP-LIM concentrations in the patients may reflect a primary central nervous system defect or they may be secondary to intermittent nocturnal hypoxia, progressive hypercapnia, and/or sleep fragmentation. In this sense, both these systems may be markers of SAS-SP as a "trait" marker and TRH as an indicator of the current state.
Adult↗
Obstructive sleep apnea in patients with pharyngeal tumours.
Six consecutive patients with pharyngeal tumours were investigated regarding disordered breathing during sleep. In addition to pulse oximetry, the investigations involved oral and nasal airflow as well as thoracic respiratory movements in four of the patients in whom the oxygen desaturation index (ODI, number of desaturations per hour of estimated sleep) was on average 24 (range 10-58). An almost total predominance of obstructive apnea was found in evaluated cases. In the 2 cases in whom only pulse oximetry was performed, numerous desaturations were found throughout the night (ODI 19 and 88, respectively). The overnight minimum oxygen saturation before treatment varied but was below 80% in 5 of the 6 patients (range less than 50-89%). On reinvestigation (n = 5) 3-4 months after treatment (radical surgery or, in one case, nasal continuous positive airway pressure (CPAP)), desaturations were totally or almost totally abolished in all patients. It is concluded that the obstructive sleep apnea syndrome may be a common finding in patients with tumours in the pharyngeal region. Radical surgery and/or nasal CPAP may result in complete disappearance of the disordered breathing during sleep in these patients.
Adult↗
Radioimmunoassay of endothelin in human plasma.
A specific and sensitive radioimmunoassay (RIA) for determination of endothelin-1 (ET-1) in human plasma has been developed. Antibodies were raised in rabbits using synthetic ET-1 conjugated to thyroglobulin as immunogen. The antibodies obtained were used at a final dilution of 1:300,000 yielding maximum binding of 61.7 +/- 3.0% (mean +/- 1 SD, n = 20) of 125I-ET-1. The ID50 (inhibitory dose 50%) was 4.5 +/- 0.6 fmol/100 microliters (mean +/- 1 SD, n = 20). The sensitivity of the RIA was 0.33 fmol/100 microliters standard solution. No cross reactivity was observed with endothelin-3, big-endothelin-1, atrial natriuretic factor, angiotensin I or angiotensin II. The cross-reactivity with endothelin-2 was 100%. Endothelin was extracted from acidified plasma with Sep-pak C18 cartridges and recovery of ET-1 added to normal plasma was 70.9 +/- 10.3% (mean +/- 1 SD, n = 12). The concentration of ET-1 in plasma from normal subjects was 1.5 +/- 0.4 pmol/l (mean +/- 1 SD, n = 11) ranging from 1.0 to 2.2 pmol/1. Extracts of normal human plasma subjected to high performance liquid chromatography on a reverse phase C18 column showed one peak of immunoreactivity co-eluting with the standard for ET-1. From these data it is concluded that the immunoreactive material measured in normal plasma with the present RIA is identical to ET-1.
Animals↗
[The CPAP therapy in sleep apnea is a simple treatment tolerated by many].
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Evaluation Studies as Topic↗
Antagonistic effects of somatostatin and substance P on respiratory regulation in the rat ventrolateral medulla oblongata.
Substance P (SP) in the dose range 0.75-1.5 nmol exerts a potent stimulatory effect on ventilation after microinjection into the rat ventrolateral medulla oblongata (VLM; n. reticularis lateralis, n. paragigantocellularis lateralis). A significant but less pronounced effect is also seen in the dorsal medulla (DM; n. tractus solitarius). Somatostatin (0.6-1.8 nmol) inhibited ventilation and induced apnoea after microinjection into the VLM but not the DM. Serial microinjections of the two peptides showed a reciprocal antagonistic action in the VLM but not in the DM. The apnoea-inducing effect of SOM was blunted by SP while SOM reduced the ventilatory stimulation induced by SP. Extracellular single unit recordings were performed following the microiontophoretic application of SP and/or SOM to respiratory-related and non-respiratory-related neurons in the VLM and DM. Although a heterogeneous population of neurons were recorded from, the majority of respiratory-related units in the VLM responded with excitation to SP and inhibitory to SOM. A direct interaction between the peptides was seen in some respiratory-related units. The neurons not responding to either of the peptides were usually non-respiratory. Dorsal to the VLM, the type of response to the two peptides was less likely to be antagonistic and a wider distribution of response types were recorded. The results indicate a direct physiological antagonism between SP and SOM regarding their effects on respiratory regulation elicited in the VLM.
Animals↗
Antinociceptive and ventilatory effects of the morphine metabolites: morphine-6-glucuronide and morphine-3-glucuronide.
Morphine and its major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were given intracerebroventricularly (i.c.v.) to rats. The antinociceptive effects were assessed in the tail-flick and hot-plate tests as well as the writhing test. Ventilatory effects were studied in halothane-anaesthetized rats. Based on calculated ED50 values, morphine-6-glucuronide was approximately 200 times more potent that morphine itself in the tail-flick and hot-plate tests. In the writhing test the difference in ED50 was approximately 9-fold. Morphine and morphine-6-glucuronide administered i.c.v. induced dose-related decreases in minute ventilation in the dose range 2.7 x 10(-9)-1.3 x 10(-7) mol. The dose-response curve for minute ventilation was steeper for morphine-6-glucuronide than for morphine. Morphine-6-glucuronide was approximately 10 times more potent than morphine in depressing minute ventilation. Morphine-6-glucuronide reduced both tidal volume and respiratory frequency, while morphine reduced only the tidal volume. Morphine-3-glucuronide, in contrast, increased both tidal volume and respiratory frequency, causing an increase in minute ventilation. Apnoea was elicited after the highest doses of morphine-6-glucuronide but not of morphine. The potency difference for depression of minute ventilation between morphine-6-glucuronide and morphine corresponded well to the difference in the writhing test but not to the potency difference in the tail-flick or hot-plate tests. The ventilatory depression induced by morphine and morphine-6-glucuronide was readily reversed by naloxone, while the hyperventilation caused by morphine-3-glucuronide was slightly potentiated by the opioid antagonist. Naloxone pretreatment completely blocked the ventilatory depression induced by morphine-6-glucuronide. These results show that the potent ventilatory depression induced by morphine-6-glucuronide is related to its antinociceptive effects in rats. Furthermore, the fact that morphine-3-glucuronide stimulated ventilation and that morphine had a more shallow ventilatory dose-response curve compared to morphine-6-glucuronide may indicate that morphine-3-glucuronide is a functional antagonist of the depressive effects of morphine and morphine-6-glucuronide on ventilation.
Analgesics↗
Resting and volume-stimulated circulating atrial natriuretic peptide in young normotensive men with positive family histories of hypertension.
Normotensive young men (36 +/- 5 years old) with positive family histories of hypertension (n = 11) and age-matched controls (n = 21) with negative family histories of hypertension were examined. The control group was divided into one group matched for body mass index with those subjects with positive family histories (n = 10) and one group with normal body mass index (n = 11). Blood pressure, central venous pressure (CVP), plasma atrial natriuretic peptide (ANP) and serum aldosterone were examined at a baseline and during an acute volume load with 1000 ml saline solution. Subjects with positive family histories and controls matched for body mass index had a higher blood pressure at baseline than controls with normal body mass index. CVP and serum aldosterone did not differ between the three groups, while sodium intake and plasma concentrations of ANP were significantly higher in subjects with positive family histories. During volume loading, CVP increased significantly more in subjects with positive family histories as compared with the two control groups. A blunted response to ANP was observed during volume loading in subjects with positive family histories, while subjects in the two control groups demonstrated comparable and significant increases in circulating ANP. Serum aldosterone, however, decreased during volume loading in all three groups, with no difference between the groups. We conclude that normotensive subjects with positive family histories are characterized by increased basal concentrations of ANP and exhibit a blunted response to an acute volume load.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Central, naloxone-reversible antinociception by diclofenac in the rat.
The antinociceptive effect of subcutaneously (s.c.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administered diclofenac was studied in a series of experiments employing the tail-flick (0.01-10.0 mg/kg body weight i.p., 1-50 micrograms i.c.v., 1-10 micrograms i.t.) and hot-plate (0.01-50 mg/kg body weight i.p., 1-50 micrograms i.c.v., 1-10 micrograms i.t.) models representing somatosensory stimuli and the writhing test (0.001 mg-10 mg s.c., 0.1-200 micrograms i.c.v., 0.1-100 micrograms i.t.) and colorectal distension (1-200 micrograms i.c.v.) models representing noxious visceral stimuli. Diclofenac did not exert any antinociceptive effects in the tail-flick or hot-plate models. In the writhing test, diclofenac dose-dependently inhibited the number of writhings after s.c. administration (0.001-10.0 mg/kg body weight) with an ED50 of 1 mg/kg. A similar dose-dependent action of diclofenac was seen after i.c.v. (0.1-200 micrograms) and i.t. (0.1-100 micrograms) administration with an ED50 of 3 micrograms in both cases. The antinociceptive effect of diclofenac administered s.c., i.c.v. or i.t. was almost completely reversed by pretreatment with naloxone, (1 mg/kg body weight s.c.). In the colorectal distension model, the i.c.v. administration of diclofenac (1-200 micrograms), which attenuated the cardiovascular response to colorectal distension, was reversed by naloxone. The pressor and tachycardia response to a 20 s, 80 mmHg colorectal distension was inhibited by diclofenac 100 micrograms i.c.v. (16.1 +/- 1.7 mmHg or 58% and 39.4 +/- 0.4 bpm or 70% versus control, respectively). It is concluded that diclofenac exerts a central, naloxone-reversible antinociceptive action in experimental animals after noxious visceral stimuli but not after somatosensory stimuli.
Analgesics↗
Comparative bioavailability of a cisapride suppository and tablet formulation in healthy volunteers.
The comparative bioavailability of cisapride as a 30 mg suppository and three 5 mg oral tablets was investigated in 12 non-smoking, healthy male volunteers. The two formulations were administered on two separate occasions following an overnight fast, according to a randomized cross-over design. The plasma concentration of cisapride was measured over 48 h after drug administration. The 30 mg suppository exhibited a mean time to the peak plasma concentration of 3.8 h, while the tablets showed a significantly earlier peak time of 1.5 h. The maximum plasma concentration of cisapride after the 30 mg suppository (50.3 ng.ml-1) was significantly lower than after the tablets (74.3 ng.ml-1). The AUCs following the two treatments did not differ significantly from each other. The comparative bioavailability of the 30 mg cisapride suppository in relation to the three 5 mg oral tablets was 85%, with a 95%-confidence interval of 67% to 102% (not adjusted for dose). Normalizing the mean AUC by dose, the relative bioavailability of the suppository was 43% of that of the tablet. The elimination half-life of cisapride was not significantly different following the administration of the two formulations (9.3 h for the suppository and 9.8 h for the tablet).
Adult↗
Acute and long-term changes in plasma levels of atrial natriuretic factor in patients with renal replacement therapy.
In 14 patients on hemodialysis who received kidney grafts from living related donors, plasma levels of immunoreactive atrial natriuretic factor (Ir-ANF) were determined in a sequence covering the last hemodialysis treatment, the day of transplantation, and a follow-up period of 6-12 months. The geometric mean value before dialysis was 196 pg/ml, the range 32-634. Weight loss during dialysis was 1.5 +/- 1.1 kg (mean +/- SD), but only a nonsignificant reduction in Ir-ANF levels occurred. On the day of transplantation, plasma Ir-ANF levels increased from 143 pg/ml before to 391 post-transplantation (P = 0.02, n = 12), probably in response to deliberate volume expansion. Post-transplant Ir-ANF levels correlated significantly to diuresis during the first 24 h, which ranged from 3.7 to 17.81 (mean 6.6; r = 0.65, P = 0.02). On day 2, mean 24 h diuresis decreased to 3.3 +/- 1.41. Most patients had reached their true dry weight by day 5, but Ir-ANF levels remained high, the geometric mean being 180 pg/ml. During further follow-up and preserved graft function (GFR range 34-88 ml/min per 1.73 m2 body surface area), Ir-ANF levels declined to a geometric mean of 63 pg/ml by 2-6 months and to 36 at 12 months post-transplant. We conclude that plasma Ir-ANF levels are chronically elevated in patients with chronic renal failure but may be further stimulated by acute overhydration. Transplanted kidneys initially respond to the increased levels but adapt within a day. Even with good graft function, normalization of plasma Ir-ANF requires several weeks or months.
Adolescent↗