Sympathetic activity is reduced by nCPAP in hypertensive obstructive sleep apnoea patients.

There is increasing evidence that nasal continuous positive airway pressure (nCPAP) lowers blood pressure in obstructive sleep apnoea (OSA) patients, not only during sleep but also in the daytime. However, both the mechanisms of blood pressure reduction and the considerable differences in the magnitude of the effect in the studies presented to date are not fully understood. Therefore, the authors prospectively studied the effect of nCPAP on noradrenaline plasma levels (NApl), blood pressure and heart rate (HR) in 10 normotensive and eight hypertensive OSA patients before and after 41.6 +/- 16.9 days of nCPAP therapy. Polysomnography and invasive blood pressure were continuously monitored over 24 h in the supine position before and with nCPAP. NApl were analysed every 15 min. In hypertensives, nCPAP reduced NApl by 36 +/- 25%, lowered mean arterial blood pressure substantially (night-time: -8.89 +/- 14.09 mmHg; daytime: -7.94 +/- 10.47 mmHg) and decreased HR by 6.6 +/- 5.4 beats x min(-1), whereas in normotensives there were only minor changes. The decrease in heart rate was associated with a decrease in mean arterial blood pressure and noradrenaline plasma levels, suggesting a causal effect of nasal continuous positive airway pressure therapy. This nasal continuous positive airway pressure effect occurs mainly in hypertensive obstructive sleep apnoea patients, whereas the effect is small in normotensives. This may explain, at least in part, some of the discrepant results in previous treatment studies.

Familial ACTH-independent Cushing's syndrome with bilateral macronodular adrenal hyperplasia clinically affecting only female family members.

Primary adrenal hyperplasia, which may occur as a familial disorder, is a rare cause of ACTH-independent Cushing's syndrome. In most of these cases the underlying pathology is primary adrenocortical micronodular dysplasia. Very few cases of familial Cushing's syndrome due to primary macronodular adrenal hyperplasia have been described. We report a family with seven affected family members. The pedigree indicates an autosomal dominantly inherited disorder. Interestingly only female family members developed the clinically apparent syndrome. The only available obligatory male gene carrier failed to adequately suppress his plasma cortisol level on overnight dexamethasone suppression test. His adrenal glands showed nodular enlargement on abdominal computed tomographic imaging. Screening of the MEN 1 gene and genetic analysis of the hot spot regions of the GNAS 1 (codons 201 and 227) and GNAI 2 (codons 179 and 205) genes did not show any mutations in the constitutional DNA or the adrenal tissue DNA of the index patient. In conclusion, this family is the largest kindred reported in the literature with ACTH-independent Cushing's syndrome due to autosomal dominant inherited macronodular adrenocortical hyperplasia. Four currently alive and affected family members in two generations and further careful observation of the yet unaffected members of the third available generation might offer the opportunity to identify the still unknown gene defect in the future.

Obstructive sleep apnoea in acromegaly: the role of craniofacial changes.

Obstructive sleep apnoea (OSA) is due to craniofacial changes and acromegaly. The question addressed by this study was whether growth hormone (GH) induced craniofacial changes might explain persisting OSA despite endocrine inactivity in acromegaly. Nineteen patients treated for acromegaly were examined cephalometrically for craniofacial changes and polysomnographically for OSA. Twelve patients proved to have OSA with an apnoea/hypopnoea index >15; seven patients showed no evidence of OSA at all. With respect to the endocrinological parameters, there were no differences between the two groups that would explain the presence or absence of OSA. Neither group differed with respect to sex, age, or body mass index. Craniofacial changes were predominantly found in the mandible. The group with OSA proved to have increased vertical, dolichofacial growth compared to those without OSA. Consecutively, in the OSA group the posterior airway space was narrowed, and the hyoid was displaced more caudally. Thus, it seems that craniofacial structures of patients with acromegaly and persisting obstructive sleep apnoea are different from those without obstructive sleep apnoea. Surgical corrections of pertaining acromegaly-induced craniofacial changes should be performed with an awareness of the individual craniofacial condition so as not to enhance obstructive sleep apnoea.

Atrial natriuretic peptide levels and pulmonary artery pressure awake, at exercise and asleep in obstructive sleep apnoea syndrome.

Elevated nocturnal plasma atrial natriuretic peptide (ANP) levels were found in patients with obstructive sleep apnoea (OSA). The purpose of our study was to examine the secretion of ANP during the night and to measure changes in oxygen saturation, pulmonary artery pressure and intrathoracic pressure swings in patients with OSA. Moreover, we analysed the secretion of ANP and the pulmonary artery pressure in different behavioural states, e.g. awake, at exercise and asleep. Consecutive apnoeas in non-rapid eye movement (NREM) sleep at the beginning, middle and end of the sleep study were analysed in six patients with obstructive sleep apnoea. In addition, we measured the plasma levels of ANP. The apnoea duration was significantly longer (P< 0.05) at the middle of the sleep study than at the beginning or end. Correspondingly, the end-apnoeic oxygen saturation and end-apnoeic oesophageal pressure were both significantly lower (P< 0.05) in the middle of the sleep study than at the beginning or end. No significant differences were found in the end-apnoeic systolic transmural pulmonary artery pressure (P(PATM)) and the levels of ANP. Evaluation of the ANP levels during different behavioural states revealed that the asleep levels were slightly, but not significantly, higher than the awake levels (0.235+/-0.088 vs. 0.207+/-0.057 nmol/L). However, the highest levels were found during exercise (0.334+/-0.170 nmol/L) with a significant difference compared with the awake and asleep levels. These data suggest that volume effects may be a potent factor in liberating ANP during exercise, but the role of OSA in ANP secretion when asleep is questionable.

High levels of circulating adrenomedullin in severe illness: correlation with C-reactive protein and evidence against the adrenal medulla as site of origin.

Adrenomedullin (AM) is a novel vasorelaxing peptide which was originally isolated from the extracts of human pheochromocytoma. It is produced by a number of organs among which the adrenal gland exhibits by far the highest concentrations. The peptide circulates in blood and its plasma levels have been reported to be increased in several diseases such as renal failure and sepsis. In the present study plasma concentrations of AM were measured in various forms of severe illness and compared to clinical and biochemical parameters in order to gain an insight into the factors controlling the plasma levels of this peptide. The highest concentrations of AM were found in patients with sepsis (344.4 +/- 60.4 pg/ml, n = 16) who exhibited up to 12-fold higher levels than a group of healthy subjects (74.1 +/- 4.1 pg/ml, n = 20). Markedly elevated levels were also measured in hemorrhagic (250.1 +/- 37.9 pg/ml, n = 9) and cardiogenic (216.2 +/- 29.4 pg/ml, n = 7) shock as well as in patients with cancer of the gastrointestinal tract (155.6 +/- 32.5 pg/ml, n = 11) or the lungs (146.5 +/- 19.1 pg/ml, n = 22). Plasma AM levels were positively correlated with serum creatinine concentrations in shock (r = 0.06, p < 0.001) and with C-reactive protein levels in patients with cancer (r = 0.64, p < 0.001) or sepsis (r = 0.63, p < 0.01). In order to examine the potential role of the adrenal gland as a site of AM release, hypoglycemia was induced in a group of healthy volunteers by graded infusion of insulin. Despite a more than 20-fold increase in plasma adrenalin indicating maximal stimulation of the adrenal medulla, no significant alterations of the plasma AM levels were observed. The study demonstrates that not only sepsis but also various forms of cancer and shock are associated with high levels of circulating AM. The correlation with C-reactive protein levels suggests a role of cytokines in mediating the elevations in plasma AM observed in sepsis and cancer. Reduced clearance of the peptide by the kidneys may be one of the mechanisms involved in the accumulation of AM in shock. The adrenal gland appears not to be a major source for circulating AM.

Impact of profile haemodialysis on intra-/extracellular fluid shifts and the release of vasoactive hormones in elderly patients on regular dialysis treatment.

In 15 patients with end-stage renal failure and proven coronary heart disease, profile haemodialysis with decreasing ultrafiltration rate and hyperionic, decreasing dialysate solute concentration was compared with conventional, extracorporeal bicarbonate haemodialysis (Na+D = 138 mmol/l). Body fluid distribution and the release of vasoactive hormones (plasma renin activity, aldosterone, norepinephrine, epinephrine, and atrial natriuretic peptide) were investigated. Haemodialysis with constant ultrafiltration rate and constant dialysate composition (A) was followed by two dialysis profiles: decreasing ultrafiltration rate (B) and additional hyperionic, decreasing dialysate sodium concentration (C). In all 15 patients, the dialysis procedures (A) - (C) were used for 2 weeks each with six sessions, the last being taken for investigation. Body fluid distribution was calculated. In patients with serum sodium above 136 mmol/l, the conventional dialysis (A) as well as the Uf profile (B) showed a net fluid shift from extracellular volume (ECV) to intracellular volume (ICV). Using the profile with hyperionic, decreasing Na+D (C), the reverse fluid shift with decreasing ICV was achieved not only in those with serum Na+ <136 mmol/l, but also in those with serum Na+ > or = 136 mmol/l. The release of vasoactive hormones decreased already at profile haemodialysis (B) compared with (A) and was further reduced in (C). These results would suggest, profile dialyses B and C to have less impact on the cardiovascular system in elderly patients assuming higher patient comfort compared with the standard dialysis procedure. A higher benefit was obtained in C compared with B, presumably due to the additional prevention of the ICV shift and plasma volume depletion in patients with initial serum sodium > or = 136 mmol/l using transiently hyperionic Na+D. These results show that in elderly patients, hyperionic profile haemodialysis (Na+D > Na+S) had less impact on cardiovascular regulation than conventional bicarbonate dialysis.

[Reactive thymus dysplasia following therapy for ACTH-producing tumors]. / Reaktive Thymushyperplasie infolge der Therapie ACTH-produzierender Tumoren.

UNLABELLED: Surgical or conservative treatment of ACTH-producing tumors results in acute drop of the previously excessively high cortisol levels. The following associated pathophysiological changes also occur in the organism's recovery from stress, such as trauma, operation or chemotherapy of tumors. Both cases result in a regeneration of the immune system, which might even be exalted. The corresponding radiographic feature is the "rebound" enlargement of the thymus occurring about six months after remission of hypercortisolism. Histological examination reveals benign thymus hyperplasia. Especially in cases of still unknown primary tumor the appearance of this anterior mediastinal mass can lead to misdiagnosis. We present the cases of two patients with diffuse thymic hyperplasia following surgical and medical correction of hypercortisolism. One patient suffered from classic Cushing's disease responding to transsphenoidal resection of an ACTH-secreting pituitary microadenoma. Six months later CT of the chest incidentally demonstrated an anterior mediastinal mass known as thymic hyperplasia. The second patient presented with an ectopic, still unkown source of ACTH-production. Six months after medical correction of hypercortisolism CT of the thorax showed an enlargement of the anterior mediastinum. Thymectomy was performed in order to exclude thymus carcinoid. Histological examination revealed benign thymus hyperplasia with negative immunostaining. CONCLUSION: Radiologists and clinicians should be familiar with the pathophysiological changes resulting from precipitously dropping cortisol levels in order to prevent diagnostic errors and unnecessary operations.

Radiommunological measurement of leptin in plasma of obese and diabetic human subjects.

Studies in mice have identified the ob gene product, leptin, as a signaling factor regulating body weight homeostasis and energy balance. Defective production of the encoded protein may be one of the causes for the development of obesity. Using a high affinity antibody, that in immunohistochemical studies specifically stained human adipocytes, a radioimmunoassay was established and leptin immunoreactivity was quantified in plasma of lean and obese human subjects. Chromatographic analysis suggested that the immunoreactive material in plasma is identical to that found in extracts from human fat and represent a protein with a molecular size of approximately 16 kD. Fasting levels were measured in plasma of 75 lean and obese human subjects (body mass index (BMI) 17.7 - 87.3). The mean concentration of leptin in plasma of lean subjects (BMI < or = 28) was 69.3 +/- 36.9 fmol/ml plasma (mean +/- SD, n=27). The highest concentration measured in obese was 533.3 fmol/ml plasma. The levels showed a strong positive correlation with BMI (r=0.77, p<0.001). A subgroup of diabetic patients did not significantly differ in their leptin plasma levels from non-diabetic subjects with similar BMI.

Successful treatment of osteoporosis in systemic mastocytosis with interferon alpha-2b.

Osteoporosis is frequently seen in systemic mastocytosis. Although diphosphonate therapy has been shown to be transiently effective, therapy options for this form of osteopenia are very limited. We have treated three patients with systemic mastocytosis and osteopenia successfully with interferon alpha-2b. Two patients had urticaria pigmentosa and two severe back pain due to vertebral compression fractures. All patients received a daily interferon dose of 3 x 5 mio units/week s.c. for a period of 6 months. Therapy was well tolerated, and back pain resolved in both patients. A marked decrease of mast cell numbers in the bone marrow and a significant increase of bone mineralization and bone density was observed in all patients. Our data suggest that alpha interferon may be a new treatment option for osteopenia in systemic mastocytosis.

[Plasma endothelin concentration during cold provocation in primary Raynaud's syndrome]. / Plasma-Endothelinkonzentration unter Kälteprovokation bei primärem Raynaud-Syndrom.

Plasma endothelin concentration was measured separately in each hand before and after unilateral whole-hand cooling in 23 patients (5 men, 18 women; mean age 35.2 [19-52] years) thought to have primary Raynaud's syndrome (Raynaud's disease). The diagnosis was confirmed, after excluding other causes, by strain-gauge plethysmography demonstrating cold-induced vasospasm in 8, disproved in 15. In the Raynaud patients (but not in the others) the plasma concentration of endothelin on the cooled side increased from 5.13 +/- 0.18 to 6.34 +/- 0.35 pg/ml (P < 0.05). On the non-cooled side there occurred a brief rise in endothelin concentration from 5.10 +/- 0.18 to 6.23 +/- 0.35 pg/ml (P < 0.05), although there had been no evidence of vasospasm. There had been no difference between the two sides in endothelin concentration before the cold provocation. The results suggest that cold provocation in primary Raynaud's syndrome causes an increase in endothelin liberation and that this plays a role in the pathogenesis of the vasospasms. Apparently not only local but also reflex mechanisms contribute to this.

Regulation of blood volume-implications for cardiovascular pathophysiology in sleep apnoea.

Volume homeostasis plays an important role in the regulation of the cardiovascular system and maintenance of haemodynamics. The heart-kidney axis represents the central part of the volume regulating system: the heart senses changes in the volume status and influences renal function via neural and humoral pathways in order to compensate for disturbances in volume homeostasis and prevent under- or overfilling of the heart. An undisturbed circadian rhythmicity of volume homeostasis, renal function and secretory pattern of volume regulating hormones may be of physiological importance. Disturbances in volume regulation are involved in the pathogenesis of cardiovascular diseases, e.g. arterial hypertension and heart failure. Nocturia in sleep apnoea (suggesting heart failure) may be explained by changes in volume-regulating hormones indicating hypervolaemia of the central part of the cardiovascular system ('central hypervolaemia') caused by exaggerated venous return during repetitive Müller manoeuvres. Treatment of sleep apnoea abolishes nocturia and restores normal circadian rhythm of volume homeostasis and secretion of volume-regulating hormones. Chronic cardiac volume overload during sleep may be implicated in the pathogenesis of cardiovascular sequelae in sleep apnoea: cardiac hypertrophy and heart failure. Central hypervolaemia during sleep can cause long-term disturbances in blood pressure control by different mechanisms and may be in part responsible for the development of daytime hypertension in sleep apnoea. In summary, volume homeostasis is controlled by a complex interaction of heart and kidney. Disturbances may reflect cardiovascular diseases or may even be the cause. In sleep apnoea disturbances in volume regulation may be important for the development of cardiovascular sequelae.

[Oral contraceptive-induced pancreatitis in the hyperchylomicronemia syndrome]. / Durch orale Kontrazeptiva induzierte Pankreatitis bei Hyperchylomikronämie-Syndrom.

A now 24-year-old woman was found at the age of 2 years to have an hyperchylomicronaemia syndrome due to lipoprotein lipase deficiency: the triglyceride level was then 6000 mg/dl. But in subsequent years it had been reduced to between 550 and 2600 mg/dl by dieting. There were no xanthomas or abdominal symptoms during those years. When aged 20 years she was put on oral contraceptives (one-phase preparation: 0.03 mg ethinylestradiol and 0.075 gestodene). Six months later she had the first attack of severe necrotizing pancreatitis; three more attacks followed in the subsequent 6 months. All four attacks occurred during the drug-free period of the menstrual cycle. The relationship with contraceptive intake was not established until the fourth attack. The last acute pancreatitis (lipase 3283 U/l amylase 595 U/l, triglyceride 2400 mg/dl, WBC count 13,899/microliters; ultrasonography revealed fluid swelling and necrotic areas, especially around the splenic hilus) regressed within 5 days and has not recurred for 3 years after the patient stopped taking oral contraceptives. On a diet the triglyceride level has been around 880 mg/dl.

Influence of somatostatin to biochemical parameters in patients with primary hyperparathyroidism.

Somatostatin (SRIF) is effective in the nonoperative management of a variety endocrine tumors. A potential role of SRIF for treatment of patients with primary hyperparathyroidism (pHPT) has been suggested. In a controlled, prospective, triple-blinded, randomized clinical trial, the somatostatin analogue octreotide (SMS 201-995, Sandostatin) was evaluated in 40 patients with well documented pHPT. Amongst other biochemical parameters, serum calcium and-phosphate and levels of parathyroid hormone, calcitonin, and osteocalcin as well as octreotide were assessed before and for 4 hours after a single iv. application of 200 micrograms ocreotide or placebo. SRIF-receptor autoradiography was performed in parathyroid tissue samples. Baseline values revealed a constellation of biochemical parameters typically found in pHPT. Following 200 micrograms octreotide, no significant changes in any of the biochemical parameters investigated for were observed. Multivariate analysis was performed to identify patient subpopulations in which any given combination of laboratory parameters changed in response to either drug or placebo. However, no 'responders' to octreotide were identified. 45% of patients receiving octreotide, reported side effects. Parathyroid tissue samples were negative for SRIF-receptor expression. It is concluded that a single dose iv. application of octreotide does not result in appreciable changes of biochemical parameters relevant in pHPT and carries a high rate of side effects. Furthermore, absence of SRIF-receptors in parathyroid tissue from patients with pHPT, together with lack of octreotide effects, suggests that somatostatin-analogues may not be effective in the non-operative therapy of pHPT.

Parathyroid function following ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy.

A randomized controlled trial was performed to compare two techniques of bilateral subtotal thyroidectomy for non-toxic nodular goitre with regard to postoperative parathyroid function. The 50 patients in group 1 underwent ligation of the trunks of the inferior thyroid arteries. In group 2 (50 patients) the branches of these arteries were suture-ligated at the thyroid capsule. Total calcium, ionized calcium and parathyroid hormone levels were determined before operation, and 6, 24 and 72 h after surgery. Ninety-one patients were seen at follow-up 5-10 months after operation. Ten patients in group 1 and 12 in group 2 required calcium and/or vitamin D supplementation for symptomatic hypocalcaemia in the immediate postoperative period. At follow-up only one patient in each group had mild hypoparathyroidism. No statistically significant differences were found between groups regarding total calcium, ionized calcium and parathyroid hormone levels. Truncal ligation of the inferior thyroid arteries during bilateral subtotal thyroidectomy does not cause hypoparathyroidism or hypocalcaemia.

[Iodine-induced hyperthyroidism in metastatic thyroid carcinoma]. / Jodinduzierte Hyperthyreose bei metastasiertem Schilddrüsenkarzinom.

A 75-year-old man with nodular goitre (for the preceding 2 years treated with 75 micrograms/dl L-thyroxine) complained of pain over the left hip: on auscultation an arterial flow murmur was audible over the hip. The radiograph demonstrated extensive osteolysis in the flat part of the ilium. Search for the primary tumour, including two pelvic angiographs, was unsuccessful. Examination of a biopsy from the right ilium revealed a metastasis from a highly differentiated follicular thyroid carcinoma, which could not be demonstrated scintigraphically because of a reduced 99mTc-pertechnetate and 123I-iodine uptake, the result of the L-thyroxine administration. A thyrotoxic crisis occurred 2 days after the second angiography (free thyroxine 3.17 ng/dl, triiodothyronine 219 ng/dl, thyroglobulin > 250 ng/ml). Treatment with thiamazole (40 mg/d) and perchlorate (1 g/d) reduced the concentration of peripheral thyroid hormone, but the patient's general condition improved only slowly. As a result, radioiodine treatment could not be started until 9 months later. He died a further 9 months later from septicaemia originating from the metastasis.

[Adrenomyeloneuropathy. A frequent cause of Addison's disease]. / Adrenomyeloneuropathie. Eine häufige Ursache des Morbus Addison.

Adrenomyeloneuropathy (AMN) is a "milder form" of adrenoleukodystrophy with a X-linked inheritance. Abnormal catabolism of the very long-chain fatty acids (VLCFA) results in Addison's disease and spastic paraparesis. The VLCFA concentration was measured in 23 of 26 patients with Addison's disease (mean age 48.5 [20-75] years) being treated at the University Hospital Marburg during May, 1991. The concentration was elevated in four of the 12 men with the disease, while it was within normal limits in the 11 women. Only two patients had paraparesis-like neurological deficits. This finding suggests that AMN is not as rare as has been supposed. It is recommended that the concentration of VLCFA be measured in all patients with Addison's disease, because an increase could have important consequences.

Lipoprotein (a), low-density, intermediate-density lipoprotein, and blood pressure in a young male population.

Both hypercholesterolemia and hypertension are risk factors for atherosclerotic vascular disease, and elevated cholesterol levels occur more frequently than expected in patients with hypertension. Elevated levels of intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL) were shown to be atherogenic, and LDL, comprising the major cholesterol-carrying fraction in human plasma, are structurally related to lipoprotein (a)[Lp(a)], a further risk factor for atherosclerosis. In the present study we investigated 200 male employees (mean age 26 +/- 7 years) to determine whether the relationship of IDL and Lp(a) to systemic blood pressure is similar to the reported correlations between total and LDL cholesterol and systemic blood pressure. To this end blood pressure was measured several times in each individual, and lipids, lipoprotein-cholesterol, apolipoprotein B (apo B), and Lp(a) were determined in fasting serum. IDL cholesterol and apo B, the main protein component of IDL and LDL correlated with blood pressure. However, levels of Lp(a) correlated neither with systolic or diastolic blood pressure nor with lipoprotein cholesterol, body weight, or age. Although IDL and Lp(a) are considered lipoprotein risk factors for atherosclerosis, levels of Lp(a), unlike IDL, are not related to blood pressure, body weight, or age. Our data suggest different metabolic and pathophysiological mechanisms of the risk factors, IDL, LDL, and Lp(a).

[Osteoporotic vertebral fractures in systemic mastocytosis without skin involvement]. / Osteoporotische Wirbelkörperfrakturen bei systemischer Mastozytose ohne Hautbeteiligung.

Radiological investigation of the vertebral column in two patients with low-back pain (53-year-old woman and a 52-year-old man) revealed unusually marked osteoporosis and sintering fractures of the 3rd, and 1st and 4th lumbar vertebrae, respectively. Biochemical tests failed to provide any evidence about metabolic or endocrinological abnormality. Iliac crest biopsy showed mastocytosis. There were no skin changes in either patient. Additional examinations excluded involvement of any internal organs. Despite treatment with calcium, sodium fluoride, vitamin D3 and calcitonin in the woman, and aspirin and chromoglycinic acid in the man the osteoporosis has slowly progressed during the last 7 and 5 years, but the disease has remained limited to the skeletal system. In a case of unusually marked osteoporosis, mastocytosis should be included in the differential diagnosis even in the absence of urticaria pigmentosa.

Reduction of nocturnal diuresis and natriuresis during treatment of obstructive sleep apnea (OSA) with nasal continuous positive air pressure (nCPAP) correlates to cGMP excretion.

In ten patients with severe obstructive sleep apnea (OSA) profound changes in renal function could be demonstrated at night during nCPAP therapy. Natriuresis and diuresis decreased by about 50% while creatinine excretion rate and urinary osmolality did not change. We found parallel changes in the excretion of ANP's second messenger cyclic guanosine monophosphate (cGMP) in a dose-response-related manner to natriuresis respectively diuresis. These data are in agreement with recently demonstrated decrease of nocturnal plasma levels of atrial natriuretic peptide (ANP) during nCPAP therapy in apneic patients. This may be an indicator for an increased cardiac volume load during obstructive apnea. The decrease of diuresis, natriuresis and cGMP excretion demonstrate the beneficial effects of nCPAP treatment on the cardiovascular system. Therefore measurements of cGMP excretion may be a useful parameter to assess the cardiovascular function of apneic patients before and during treatment.