Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0037315 (sleep apnea)
 8,000 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The obstructive sleep apnoea syndrome (OSA) is a disorder characterised by repetitive closure and re-opening of the upper airway during sleep. Upper airway luminal patency is influenced by a number of factors including: intraluminal air pressure, upper airway dilator muscle activity, surrounding extraluminal tissue pressure, and also surface forces which can potentially act within the liquid layer lining the upper airway. The aim of the present study was to examine the role of upper airway mucosal lining liquid (UAL) surface tension (gamma) in the control of upper airway patency. Upper airway opening (PO) and closing pressures (PC) were measured in 25 adult male, supine, tracheostomised, mechanically ventilated, anaesthetised (sodium pentabarbitone), New Zealand White rabbits before (control) and after instillation of 0.5 ml of either 0.9 % saline (n = 9) or an exogenous surfactant (n = 16; Exosurf Neonatal) into the pharyngeal airway. The gamma of UAL (0.2 microl) was quantified using the 'pull-off' force technique in which gamma is measured as the force required to separate two curved silica discs bridged by the liquid sample. The gamma of UAL decreased after instillation of surfactant from 54.1 +/- 1.7 mN m-1 (control; mean +/- S.E.M.) to 49.2 +/- 2.1 mN m-1 (surfactant; P < 0.04). Compared with control, PO increased significantly (P < 0.04; paired t test, n = 9) from 6.2 +/- 0.9 to 9.6 +/- 1.2 cmH2O with saline, and decreased significantly (P < 0.05, n = 16) from 6.6 +/- 0.4 to 5.5 +/- 0.6 cmH2O with surfactant instillation. Findings tended to be similar for PC. Change in both PO and PC showed a strong positive correlation with the change in gamma of UAL (both r > 0.70, P < 0.001). In conclusion, the patency of the upper airway in rabbits is partially influenced by the gamma of UAL. These findings suggest a role for UAL surface properties in the pathophysiology of OSA.
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PMID:Decreased surface tension of upper airway mucosal lining liquid increases upper airway patency in anaesthetised rabbits. 1256 67

Two cases of sleep apnea syndrome caused by primary hypothyroidism are reported. The first patient was a 66-year-old man who complained of sleep apnea; his apnea-hypopnea index (AHI) was 50.8, as assessed by all-night monitoring. Hypothyroidism was subsequently suspected when he showed delayed recovery from general anesthesia following surgery involving uvulopalatopharyngoplasty. Hypothyroidism was diagnosed on the basis of blood tests His snoring and apnea improved after 2 months of levothyroxine sodium administration and the AHI fell from 50.8 to 13.0. The second patient was a 73-year-old man with an AHI of 41.3, as assessed by all-night monitoring. Hypothyroidism was diagnosed on the basis of blood tests and was suspected because of his slow speech. He was similarly treated with levothyroxine sodium. The AHI did not decrease after 4 months of treatment. His desaturation rate (rate of O2 saturation < 90%) improved however, from 56.6% to 31.9%, and the symptoms of hypothyroidism also improved markedly. In both patients, elevated creatine phosphokinase, a dull facial expression, peripheral edema and slow speech were recognized, and these symptoms were suggestive of hypothyroidism. The type of sleep apnea was mainly obstructive in both patients.
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PMID:Two cases of sleep apnea syndrome caused by primary hypothyroidism. 1273 45

At present, three methods are practiced to intensify hemodialysis (HD): 3 times weekly, 8-hour HD, short daily HD and slow daily nocturnal HD. Three times weekly 8-hour dialysis increase both the dialysis dose and time. The longest experiences are in Tassin. Five-year survival in Tassin was better in all age groups compared with the major registries - Japan, EDTA and US Medicare and more obvious for older age groups. The data of Tassin show that increasing the dialysis time provides better blood pressure control, need for no or less antihypertensive drugs, less intradialytic complications, better middle molecule and phosphate clearance, better nutritional status, less requirement for erythropoietin and increased survival. These data of Tassin could be mainly confirmed in our dialysis center. The main difference to Tassin was that in our center most of the patients still need few antihypertensive drugs. The reasons for the difference are that in Tassin the patients are on very low sodium diet (<5 g/day) and in Tassin extracellular volume (ECV) is reduced as far as possible independent of residual renal function. The concept of our center was to preserve residual renal function and accept slightly higher ECV and few antihypertensive drugs. Another concept to intensify HD is short daily HD (6 times/week for 90-180 min). This form of dialysis is offered as in-center and home HD with and without dialysis partner. All studies demonstrated significant improvement of nutritional status, quality of life, control of blood pressure, phosphate and anemia. Survival of AV fistula even with daily double punctures was excellent. The most extensive form of dialysis is slow daily nocturnal dialysis (6 times/week for 8-10 h). This form of dialysis provides excellent urea, phosphate clearance and fourfold increase of beta(2)-microglobulin clearance. Patients discontinue phosphate binders and several patients need phosphate addition to dialysis. Blood pressure control is excellent, all patients are off antihypertensive drugs. Improvement of nutrition, anemia, blood pressure and quality of life is even more pronounced compared to short daily HD or 3 times weekly 8-hour HD. Nocturnal dialysis was able to improve sleep apnea. Nocturnal dialysis is offered only as home HD with and without dialysis partner. Any patient who could be trained for home HD was eligible. Presence of co-morbidities was not a contraindication.
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PMID:Treatment options to intensify hemodialysis. 1277 32

Obesity is a progressive disease of unwanted fat accumulation which has multiple, organ-specific pathological consequences. The manifestations of obesity occur within virtually every subspecialty of medicine or surgery and they interact importantly to accelerate the ageing process in many organs. Many of the hazards of obesity have multiple causes (e.g., diabetes, heart disease, stroke, colonic and breast cancer, urinary incontinence, tiredness, back pain, breathlessness). All of these conditions become more prevalent with age and are also more prevalent among overweight persons, particularly those with a central fat distribution marked by a high waist circumference. Hypertension may be caused or aggravated by weight gain. It is mediated by the physical demands of an expanded circulating volume and increased metabolic rate by metabolic mechanisms related to central fat distribution and the "metabolic syndrome", and to increased sodium consumption by overweight people (because they need more food to maintain a higher metabolic rate). Since body mass index (BMI) and waist circumference increase significantly with age there is an escalation of the burden of ill health from obesity with age. The best simple indicator of disease risk with obesity is the waist circumference since this identifies people who have a high body fat content and also those who have an increased intraabdominal accumulation of fat. The quantitative burden of ill health from overweight and obesity varies within different specialties, but up to 80% of type 2 diabetes or polycystic ovarian syndrome can be attributed to obesity. Obesity is the cause of sleep apnea syndrome in around 50% of cases and heart disease in perhaps 10-20% of cases. In Scotland 80% of people with existing cardiovascular disease are overweight compared with 57% of the general population. The financial burden to health services from overweight and obesity has been incompletely assessed, although it is estimated that around 4% of total health care budgets are attributable to people having BMI > 25 kg/m(2). This is similar to the entire cost of diabetes, epilepsy or major cancers. Obesity is therefore an extremely expensive disease based on these conservative estimates from limited evaluations. More general assessments show how obesity increases the amount of time taken off work, the number of drugs prescribed and the expenditure from social services support. Thus, obesity represents a huge burden not only on the individual patient physically, psychologically, socially and financially but also on families and careers and is a huge drain on health care resources. Overweight affects well over half of all adults worldwide, progressing to BMI > 30 kg/m(2) in around 20% outside subsistence rural communities. Its rapidly increasing prevalence now described as an epidemic demands major preventive measures, as well as better medical treatment for individuals affected.
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PMID:Obesity: burdens of illness and strategies for prevention or management. 1284 36

Although nocturnal voiding is frequently attributed to urologic disorders, nocturia and enuresis are also important symptoms of sleep-disordered breathing. However, polyuria can be elicited by obstructive sleep apnea as well as bedrest, microgravity and other experimental conditions where the blood volume is shifted centrally to the upper body. The nocturnal polyuria of sleep apnea is an evoked response to conditions of negative intrathoracic pressure due to inspiratory effort posed against a closed airway. The mechanism for this natriuretic response is the release of atrial natriuretic peptide due to cardiac distension caused by the negative pressure environment. This cardiac hormone increases sodium and water excretion and also inhibits other hormone systems that regulate fluid volume, vasopressin and the rennin-angiotensin-aldosterone complex. Treatment of sleep apnea and airway compromise has been shown to reverse nocturnal polyuria and thereby reduce or eliminate nocturia and enuresis. Thus, careful evaluation of nocturia and enuresis for evidence of nocturnal polyuria can increase the diagnostic certainty of referring primary care providers and sleep specialists. In addition, the resolution of these bothersome symptoms after treatment can contribute to patient satisfaction as well as reinforce treatment compliance.
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PMID:Sleep disordered breathing and nocturnal polyuria: nocturia and enuresis. 1457 73

Patients with OSAS (obstructive sleep apnoea syndrome) demonstrate renal signs such as proteinuria, glomerular hypertrophy and focal glomerular sclerosis. We performed a clinical study to investigate the glomerular function in OSAS patients and the short-term effect of CPAP (continuous positive airway pressure) on it. OSAS patients underwent a sodium thiosulphate and p-aminohippurate double clearance test, polysomnography and ambulatory blood pressure monitoring before and a week after the induction of CPAP. Twenty-seven consecutive patients (24 males) with moderate-to-severe OSAS admitted to our hospital for the induction of CPAP, and 32 healthy donors for renal transplantation as controls participated in the study. Before treatment, the glomerular filtration rate, estimated by the sodium thiosulphate clearance test, was within normal range, and the renal plasma flow was significantly lower than normal in the OSAS patients, thus the FF (filtration fraction) value was much higher than normal. FF before CPAP was not significantly correlated with age, body mass index or blood pressure; however, indices of increased hypoxaemia correlated with increased FF values. Polysomnographic variables after CPAP showed significant improvements in all patients, and only the nocturnal blood pressures were slightly lower than before CPAP. In 21 patients who underwent the clearance test after CPAP, FF significantly decreased from 0.26 +/- 0.04 to 0.23 +/- 0.03 (P < 0.001). OSAS patients were generally in a glomerular-hyperfiltrating condition that appeared to cause the renal findings associated with OSAS. CPAP might prevent nephropathy by ameliorating the glomerular hyperfiltration in OSAS patients.
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PMID:Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome. 1519 64

Megalin is an endocytic receptor on the apical membranes of proximal tubule cells (PTC) in the kidney, and is involved in the reabsorption and metabolism of various proteins that have been filtered by glomeruli. Patients with diabetes, especially type 2 diabetes, or metabolic syndrome are likely to have elevated serum levels of advanced glycation end products, liver-type fatty acid binding protein, angiotensin II, insulin and leptin, and renal metabolism of these proteins is potentially overloaded. Some of these proteins are themselves nephrotoxic, while others are carriers of nephrotoxic molecules. Megalin is involved in the proximal tubular uptake of these proteins. We hypothesize that megalin-mediated metabolic overload in PTC leads to compensatory cellular hypertrophy and sustained Na+ reabsorption, causing systemic hypertension and glomerular hyperfiltration via tubuloglomerular feedback, and named this as 'protein metabolic overload hypothesis'. Impaired metabolism of bioactive proteins such as angiotensin II and insulin in PTC may enhance hypertrophy of PTC and/or Na+ reabsorption. Sleep apnoea syndrome, a frequent complication of diabetes and metabolic syndrome, may cause renal hypoxia and result in relative overload of protein metabolism in the kidneys. The development of strategies to identify patients with diabetes or metabolic syndrome who are at high risk for renal metabolic overload would allow intensive treatment of these patients in an effort to prevent the development of nephropathy. Further studies on the intracellular molecular signalling associated with megalin-mediated metabolic pathways may lead to the development of novel strategies for the treatment of nephropathies related to diabetes and metabolic syndrome.
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PMID:Role of megalin, a proximal tubular endocytic receptor, in the pathogenesis of diabetic and metabolic syndrome-related nephropathies: protein metabolic overload hypothesis. 1617 84

The association between hypertension and chronic renal disease is well known. The pathogenesis of hypertension in patients with chronic kidney disease (CKD) is complex and multifactorial, which may explain why it is resistant to treatment. The traditional paradigm is that hypertension in CKD is due either to an excess of intravascular volume (volume dependent) or to excessive activation of the renin-angiotensin system in relation to the state of sodium/volume balance (renin-dependent hypertension). This review focuses on the importance of less established mechanisms, such as increased activity of the sympathetic nervous system, increased endothelin production, decreased availability of endothelium-derived vasodilators and structural changes of the arteries, renal ischemia, and sleep apnea.
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PMID:Hypertension in renal parenchymal disease: why is it so resistant to treatment? 1652 45

Aldosterone concentrations are inappropriately high in many patients with hypertension, as well as in an increasing number of individuals with metabolic syndrome and sleep apnoea. A growing body of evidence suggests that aldosterone and/or activation of the MR (mineralocorticoid receptor) contributes to cardiovascular remodelling and renal injury in these conditions. In addition to causing sodium retention and increased blood pressure, MR activation induces oxidative stress, endothelial dysfunction, inflammation and subsequent fibrosis. The MR may be activated by aldosterone and cortisol or via transactivation by the AT(1) (angiotenin II type 1) receptor through a mechanism involving the EGFR (epidermal growth factor receptor) and MAPK (mitogen-activated protein kinase) pathway. In addition, aldosterone can generate rapid non-genomic effects in the heart and vasculature. MR antagonism reduces mortality in patients with CHF (congestive heart failure) and following myocardial infarction. MR antagonism improves endothelial function in patients with CHF, reduces circulating biomarkers of cardiac fibrosis in CHF or following myocardial infarction, reduces blood pressure in resistant hypertension and decreases albuminuria in hypertensive and diabetic patients. In contrast, whereas adrenalectomy improves glucose homoeostasis in hyperaldosteronism, MR antagonism may worsen glucose homoeostasis and impairs endothelial function in diabetes, suggesting a possible detrimental effect of aldosterone via non-genomic pathways.
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PMID:Aldosterone and end-organ damage. 1768 82

Theory predicts respiratory instabilities at elevated system loop gain (G), determined by such factors as ventilatory CO(2) sensitivity, set-point PCO(2), and metabolic rate. In anesthetized rabbits, the effects on G of carbonic anhydrase (CA) inhibitors and of different sodium/proton exchanger type 3 (NHE3) inhibitors were studied. Acetazolamide significantly reduced G by 42.0 +/- 9.3% and methazolamide by 35.0 +/- 9.5% (each n = 7, P<0.01). Irrespective of the substance, NHE3 inhibition reduced G by 33.0 +/- 7.8% (n = 10, P<0.01) at 35.5 +/- 1.6 mmHg PaCO(2) (mean +/-SE), but not at lower arterial CO(2) levels (n=5). Since high baseline PCO(2) coincides with elevated brainstem NHE3 mRNA expression, this may also account for a higher risk of sleep apnea (or even occurrence of sudden infant death). Therefore, NHE3 inhibitors may gain similar therapeutic importance in the treatment of irregular breathing as CA inhibitors. Generally, effective treatment should aim at a low system loop gain, by reducing respiratory chemosensitivity, improving blood gases and preventing low metabolic rates.
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PMID:Pharmacological impact on loop gain properties to prevent irregular breathing. 1844 86


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