Increased glucocorticoid activity in men with cardiovascular risk factors

The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5beta-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance.     

Enuresis and obstructive sleep apnea in adults

Adult enuresis is an unusual symptom of obstructive sleep apnea (OSA). Although it is described as a classic symptom of childhood OSA, enuresis is encountered infrequently in adult sleep medicine. Five adults with enuresis associated with sleep apnea presented to our Sleep Disorders Center. In all five cases, the onset of enuresis was associated with the progression of sleep apnea symptoms. In each case, the enuresis resolved with treatment with nasal continuous positive airway pressure. Current medical literature on the postulated mechanisms of nocturia and enuresis in sleep apnea is reviewed. Based on the experience of the authors and review of the medical literature, one may conclude that severe OSA may lead to new-onset enuresis in adults and that effective treatment of OSA is associated with resolution of enuresis.     

Cephalometric assessment in obstructive sleep apnea

It is reported that some specific craniofacial characteristics are associated with obstructive sleep apnea syndrome (OSAS). To test this finding, the present study developed and assessed the feasibility of a craniofacial index score (CIS) in differentiating patients with OSAS from habitual snorers. Anthropometric measurements and lateral head radiographs were obtained on 24 male and 4 female patients with OSAS who had physician-diagnosed OSAS (respiratory disturbance index (RDI) >20), and 25 male and 5 female habitual snorers (RDI <20). Thirteen cephalometric and four anthropometric measure- ments were used in a discriminant model to construct the CIS. The model was able to correctly classify 82.1% of the OSAS group and 86.7% of the snoring group. In addition, variables that were related to the soft tissues, hyoid bone to mandibular plane, Body Mass Index, and soft palate length had the highest predictive value. These findings indicate that a CIS constructed from cephalometric and anthropometric measurements can be used to identify subjects with and without OSAS.     

Pulmonary hypertension in patients with obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with an increased cardiovascular morbidity, including pulmonary hypertension. Little is known about factors influencing the degree of pulmonary hypertension and left ventricular dysfunction in patients with OSAS, especially in the absence of concomitant lung disease. METHODS: Right heart catheterization, arterial blood gas analysis, and pulmonary function tests were performed in 92 consecutive patients (81 men and 11 women; mean +/- SD age, 53.1 +/- 11.0 years) with polysomnographically verified OSAS, in whom clinically significant lung disease was excluded. RESULTS: Eighteen patients (20%) had mild pulmonary hypertension; 8 (44%) of them also had increased pulmonary capillary wedge pressures (Ppew). Left ventricular dysfunction was associated with arterial hypertension. Only Ppcw (r = 0.51; P < .001) and the percentage of time during sleep spent with an oxygen saturation below 90% (as an indicator of the severity of OSAS) (r = 0.34; P = .003) were significantly and independently associated with pulmonary artery pressure. CONCLUSIONS: Obstructive sleep apnea syndrome can cause mild pulmonary hypertension, even in the absence of pulmonary disease. In these patients, pulmonary hypertension is of the postcapillary type, or-in patients with normal left ventricular function-strongly related to the severity of OSAS. Our findings indicate that OSAS may constitute an important, and independent, risk factor for pulmonary hypertension.     

Incidence of parasomnias in children with obstructive sleep apnea

The incidence of parent-reported parasomnias in children with obstructive sleep apnea (OSA) is increased in comparison with a normative age-matched sample of children but is not higher than that for a similar clinical sample of children with a diagnosed behavioral sleep disorder.     

Sex-specific sleep anamnesis in obstructive sleep apnea syndrome?

Although the prevalence of obstructive sleep apnea syndrome (OSAS) is about 4% in men and 2% in women, women are underrepresented in clinical routine. The aim of this study was to determine whether differences in clinical features of OSAS may in part explain the bias observed. 224 men and 24 women with polysomnographically confirmed OSAS filled in a symptom-focussed multiple-choice questionnaire. Polysomnographical results were comparable in both groups. With regard to snoring, daytime sleepiness and tendency of falling asleep there were no differences between both groups. Women more frequently complained about difficulties of initiating and maintaining sleep and about apneas. Further investigations have to concentrate on the pathomechanisms of OSAS in women which may in part explain the gender differences in sleep apnea associated symptoms.     

Surgical options for obstructive sleep apnea

The pathology associated with obstructive sleep apnea is cumulative and progressive. When patients fail to improve with continuous nasal airway pressure or other, less-invasive treatments, surgery should be considered. The initial approach to the surgical patient is identification of all areas of potential obstruction. There are often several sites of obstruction, which can occur anywhere in the upper respiratory tract. One or more procedures may be needed to address these areas. The objective of surgery is to relieve these obstructing sites without interfering with the normal functionality of the upper airway.     

Preparing a child with obstructive sleep apnea for transplantation

All of the expected outcomes have been met for A.W. Intense collaboration among the pulmonary, nutrition, transplant, nephrology teams, and A.W.'s parents have accomplished what at first seemed to be quite difficult. After months of hard work and close monitoring of A.W., he was now at the 90th percentile on the growth curve. The diligence of the dietician and A.W.'s parents provided the intended outcome. A.W. had achieved a manageable weight and could be safely transplanted. The transplant team has decided to quickly taper prednisone until A.W. is completely off of this immunosuppressive after transplantation. A.W. is more cooperative with the nasal cannula at night and it is felt he will cooperate with the CPAP mask during the post-operative period in the hospital. He would need continued evaluation of his obstructive sleep apnea due to the potential of increased weight with immunosuppression medicines. All of A.W.'s blood culture results have been negative and his left tympanic membrane has not drained nor is there evidence of infection. A.W. is finally ready for transplantation. A date was set and A.W. and his living related donor were ready to proceed.     

Treatment of otherwise normal children with obstructive sleep apnea

There are many therapeutic approaches to children with OSA. Treatment should be considered only when the severity of the syndrome has been established by objective testing including overnight polysomnography. Anatomic abnormalities, including adenotonsillar hypertrophy, must be defined. Once the severity and underlying cause of OSA have been established, the most appropriate approach can be devised for the individual. Mild cases may simply be observed. Moderate or severe patients whose nasopharynx is obstructed by lymphoid hyperplasia may be treated with adenotonsillectomy. If surgery is declined or contraindicated, nasal CPAP is effective. CPAP is also useful as a temporary measure while weight loss is being effected.     

Chemical control of breathing in patients with obstructive sleep apnea

The authors have studied chemical control of breathing in 37 normocapnic patients with OSA. These patients had increased apnea-hypopnea index (AHI = 51 +/- 22), obesity (BMI = 32.4 +/- 5.6 kg/m2) and normal lung function tests. Control group consisted of 20 healthy subjects with normal weight (BMI = 23.1 +/- 2.4 kg/m2). Respiratory responses (ventilatory and P0.1) to hypercapnic and hypoxic stimulation during rebreathing tests were measured with computerized methods. The obtained results in OSA patients were compared with the data of the control group. The results exceeding mean values of the control group above 1.64 SD were recognized as hyperreactive responses. The majority e.g. 26 patients (OSA-N) had normal respiratory responses during hypercapnic stimulation. delta V/delta PCO2 = 16.8 +/- 4.5 L/min/kPa, P0.1/delta PCO2 = 3.5 +/- 2.4 cm H2O/kPa/. In remaining 11 patients (OSA-H) respiratory responses were significantly increased delta V/delta PCO2 = 39.1 +/- 18.8 L/min/kPa, P0.1/delta PCO2 = 8.6 +/- 3.9 cm H20/kPa). During isocapnic hypoxic stimulation majority e.g. 25 patients (OSA-H) had significantly increased respiratory responses delta V/delta SaO2 = 3.28 +/- 1.63 L/min/%, delta P0.1/delta SaO2 = 0.54 +/- 0.43 cm H2O/%/. In remaining 12 patients (OSA-N) respiratory responses were within normal limits delta V/SaO2 = 1.2 +/- 0.28 L/min/%, delta P0.1/ delta SaO2 = 0.21 +/- 0.07 cm H2O/%/. The above results indicated, that majority OSA patients (67.5%) had increased ventilatory and P0.1 responses to hypoxic stimulation. Among them also 11 patients had increased respiratory responses to hypercapnia. It seems, that increased respiratory responses to hypoxic stimulus in OSA patients are symptoms of protective reaction to hypoxaemia occurring during repetitive sleep apnoea and reveals increased neuro-muscular output.     

Functional palatoraphy and modified genioplasty in obstructive sleep apnea

10 patients with obstructive sleep apnea syndrome (OSAS) have been treated with the new surgical procedure functional palatoraphy and modified genioplasty. 5 months after surgery 7 patients with an apnea hypopnea index under 10 were cured. Three therapy refractory patients were all overweight with a body mass index of more than 29 kg/m2. Excessively overweight patients should therefore not be operated. Following the selection criteria we introduced an effective new treatment method for OSAS.     

Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction

BACKGROUND AND PURPOSE: Adrenomedullin is a recently discovered vasoactive peptide that is structurally related to calcitonin gene-related peptide (CGRP). Adrenomedullin is produced by vascular endothelium and smooth muscle and is present in the brain. The goals of this study were to determine (1) whether adrenomedullin produces dilatation of cerebral arterioles and whether this effect is mediated by activation of CGRP receptors and (2) whether vasodilatation to adrenomedullin was mediated by K+ channels. METHODS: Diameter of cerebral arterioles (mean +/- SE baseline, 46 +/- 1 microns) was measured using a closed cranial window in anesthetized rats. RESULTS: Application of rat adrenomedullin (10(-7) and 10(-6) mol/L) increased vessel diameter by 16 +/- 3% and 45 +/- 8% (n = 5), respectively. Vasodilator responses to repeated application of adrenomedullin were reproducible. Pretreatment of cerebral arterioles with the specific CGRP1 receptor antagonist CGRP-(8-37) (5 x 10(-7) mol/L) selectively inhibited the vasodilator responses to adrenomedullin without inhibiting responses to ADP (10(-5) to 10(-3) mol/L). Responses to adrenomedullin (10(-7) and 10(-6) mol/L) were 14 +/- 1% and 40 +/- 3% before and 2 +/- 2% and 6 +/- 1% after CGRP-(8-37), respectively (P < .01). Glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K+ channels, reduced the responses to adrenomedullin without attenuating responses to ADP. Responses to adrenomedullin were 19 +/- 4% and 35 +/- 6% before and 6 +/- 3% and 19 +/- 5% after glibenclamide, respectively (P < .05). Iberiotoxin (10(-7) mol/L), an inhibitor of calcium-dependent K+ channels, also significantly attenuated responses to adrenomedullin and did not inhibit vasodilatation to papaverine. Responses to adrenomedullin were 16 +/- 2% and 55 +/- 8% before and 12 +/- 4% and 26 +/- 3% after iberiotoxin, respectively (P < .01 for 10(-6) mol/L adrenomedullin). CONCLUSIONS: Adrenomedullin produces substantial dilatation of cerebral arterioles in vivo, and the response is mediated in large part by activation of CGRP1 receptors. Cerebral vasodilatation to adrenomedullin appears to be dependent on activation of K+ channels.     

Anamnestic and polygraphic parameters in obstructive sleep apnea syndrome patients with reduced nasal respiration during the day in comparison with obstructive sleep apnea patients with normal nasal respiration

Nasal obstruction is a predictive factor for snoring and may contribute to the development of an obstructive sleep apnea syndrome (OSAS). The aim of this study was to further evaluate the impact of nasal obstruction in OSAS. Therefore, we investigated 2 groups of OSAS-patients, matched pairs concerning gender, age, and BMI: OSAS-patients with nasal obstruction (N, n = 28), total nasal airflow < 500 ccm/s (referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s), and 28 OSAS-patients without nasal obstruction (control-group K, total nasal airflow > 700 ccm/s [referred to 150 pa pressure of difference or unilateral nasal resistance > 1 pa/ccm/s]). We performed anterior rhinomanometry, lung-function testing, cardio-respiratory polygraphy, and patients answered a standardized questionnaire. We found the following significant differences: 1) N complained more often (n = 17) about dyspnea at night than K (n = 7, p < 0.05, Chi2-test). 2) N had a higher apnea index (20.4 +/- 19.0/h) than K (9.6 +/- 10.0/h, p < 0.05, Student's t-test). There were, however, no significant differences concerning lung function, number of nocturnal hypopneas, nocturnal SaO2 and heart rate. Our results underline the importance of nasal ventilation in the pathogenesis of OSAS. At least in moderate cases of OSAS a therapy of nasal obstruction might be of success in order to abolish nCPAP-therapy or might reduce nasal problems during nCPAP-therapy and thus ameliorate patient's therapy compliance.     

Surgical maxillofacial treatment of obstructive sleep apnea

Obstructive sleep apnea is the most common sleep-related breathing disorder, with a surprisingly high prevalence. The treatment of choice is nasal continuous positive airway pressure (CPAP) ventilation during sleep, which has to be applied throughout the patient's whole life. Because of various underlying pathomechanisms in patients with certain craniofacial disorders--narrow posterior airway space and maxillary-mandibular deficiency--surgical therapy by craniofacial osteotomies seems possible. A series of 38 consecutive patients were treated by 10-mm maxillomandibular advancement by retromolar sagittal split osteotomy and Le Fort I osteotomy, respectively. Obstructive sleep apnea syndrome was improved considerably in all patients; there was no significant difference compared to the results under nasal CPAP. In 37 of 38 patients, the postoperative apnea-hypopnea index was reduced clearly to under 10 per hour, oxygen saturation rose, and sleep quality improved. This was achieved by maxillomandibular advancement of 10 mm without secondary refinements in all but 2 patients. In one patient, the apnea-hypopnea index could only be reduced to 20 per hour, probably because of insufficient maxillary advancement. These results indicate that successful surgical treatment is possible in a high percentage of selected patients with certain craniofacial characteristics. In addition to cardiorespiratory polysomnography, there should be routine cephalometric evaluation of all patients. Maxillomandibular advancement should be offered as an alternative therapy to all patients with maxillary and/or mandibular deficiency or dolichofacial type in combination with narrow posterior airway space.     

Neurostimulation for obstructive sleep apnea: investigations

Neurostimulation of the upper airway muscles (accessory muscles of respiration) was accomplished in anesthetized dogs and sleeping humans by electrical stimulation of the hypoglossal nerves. Such stimulations relieved partial airway obstructions in dogs. They also aborted (shortened) obstructive sleep apnea events in humans who suffer with obstructive sleep apnea syndrome. In one subject, stimulations delivered in advance of apneic events (by automatic cycling) prevented apneas. Neurostimulation for obstructive sleep apnea may be an important concept for future research and development.     

Cardiac arrhythmias in sleep apnea. Increased cardiovascular risk caused by nocturnal arrhythmia?

In sleep-disordered breathing (SDB), the greatest clinical relevance attaches to obstructive sleep apnea on account of its high prevalence and its concomitance with diseases of the cardiovascular system. The high mortality rate of untreated patients is believed to be due to the consequences of these latter diseases. Thus, for example, in addition to systemic arterial hypertension, elevated rates of such disorders as pulmonary hypertension, right heart insufficiency, coronary heart disease, myocardial infarction and stroke are also found. Up until quite recently bradycardic and tachycardic arrhythmias occurring during sleep have been held responsible of the increased mortality rate of these patients. Till the mid-eighties the prevalence of bradycardic arrhythmias was reported to be more than 30%. However, the importance of cardiac arrhythmias has been overestimated, as is supported in particular by current studies on large non-selected samples showing a much lower prevalence of apnea-related arrhythmias. In the differential diagnosis, however, consideration must be given to SDB in patients with nocturnal arrhythmias and heart rate variations.