Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of central 5-HT2C receptors as a strategy for appetite suppression and weight control is supported by animal pharmacology and human clinical studies. Considerable evidence comes from the weight-loss effects of fenfluramine, a non-selective 5-HT2C agonist. Advances in molecular pharmacology have led to an understanding of the effects of 5-HT2C receptor activation on food intake and satiety, in addition to providing insight into the causes of cardiac valvular insufficiency and pulmonary hypertension associated with the use of fenfluramine. However, clinically validated animal models of drug-induced disease and knowledge of the molecular mechanisms of these safety issues is lacking. For this reason, the development of selective 5-HT2C agonists for the treatment of obesity has remained a challenge.
 ...
PMID:The potential use of selective 5-HT2C agonists in treating obesity. 1650 63

Alpha(2A)-adrenergic receptors (alpha(2A)AR) regulate multiple central nervous system, cardiovascular, and metabolic processes including neurotransmitter release, platelet aggregation, blood pressure, insulin secretion, and lipolysis. Complex diseases associated with alpha(2A)AR dysfunction display familial clustering, phenotypic heterogeneity, and interindividual variability in response to therapy targeted to alpha(2A)ARs, suggesting common, functional polymorphisms. In a multiethnic discovery cohort we identified 16 single-nucleotide polymorphisms (SNPs) in the alpha(2A)AR gene organized into 17 haplotypes of two major phylogenetic clades. In contrast to other adrenergic genes, variability of the alpha(2A)AR was primarily due to SNPs in the promoter, 5' UTR and 3' UTR, as opposed to the coding block. Marked ethnic variability in the frequency of SNPs and haplotypes was observed: one haplotype represented 70% of Caucasians, whereas Africans and Asians had a wide distribution of less common haplotypes, with the highest haplotype frequencies being 16% and 35%, respectively. Despite the compact nature of this intronless gene, local linkage disequilibrium between a number of SNPs was low and ethnic-dependent. Whole-gene transfections into BE(2)-C human neuronal cells using vectors containing the entire approximately 5.3-kb gene without exogenous promoters were used to ascertain the effects of haplotypes on alpha(2A)AR expression. Substantial differences (P < 0.001) in transcript and cell-surface protein expression, by as much as approximately 5-fold, was observed between haplotypes, including those with common frequencies. Thus, signaling by this virtually ubiquitous receptor is under major genetic influence, which may be the basis for highly divergent phenotypes in complex diseases such as systemic and pulmonary hypertension, heart failure, diabetes, and obesity.
 ...
PMID:Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A-adrenergic gene diversify receptor expression. 1656 12

The clinical spectrum of obstructive sleep apnea-(OSA-)related cardiovascular disease (CVD) comprises systemic arterial hypertension (prevalence: 40-60%), pulmonary hypertension (20-30%), coronary artery disease (20-30%), congestive heart failure (5-10%), and stroke (5-10%). During sleep, heart rhythm disorders such as atrioventricular blocks, sinus arrests and atrial fibrillation can be induced by OSA. OSA-related CVD mainly affects those patients with an apnea-hypopnea index > 30/h and, if left untreated, is linked to increased mortality. Epidemiologic data have clearly shown that cardiovascular risk is increased in OSA independent of confounding factors such as obesity and concomitant metabolic disease. In recent years, the pathophysiology of OSA-related CVD has been further elucidated showing that apart from the well-known sympathetic activation, increased oxidative stress and pro-inflammatory changes seem to play major roles. Furthermore, studies using high resolution ultrasonography have demonstrated endothelial dysfunction and enhanced atherosclerosis in these patients. Finally, animal models of OSA have delineated that daytime arterial hypertension is the consequence of the OSA-associated chronic intermittent hypoxia. Therapy of OSA by continuous positive airway pressure (CPAP) ventilation exerts cardioprotective effects. It has been shown to rectify the vascular micromilieu, restore endothelium-dependent vasodilation, lower 24-h blood pressure, eliminate nocturnal heart rhythm disorders, and improve left ventricular function. Furthermore, long-term CPAP therapy leads to a reduction in important clinical endpoints such as the rates of myocardial infarction and stroke.
 ...
PMID:[Obstructive sleep apnea-related cardiovascular disease]. 1660 89

The major respiratory complications of obesity include a heightened demand for ventilation, elevated work of breathing, respiratory muscle inefficiency and diminished respiratory compliance. The decreased functional residual capacity and expiratory reserve volume, with a high closing volume to functional residual capacity ratio of obesity, are associated with the closure of peripheral lung units, ventilation to perfusion ratio abnormalities and hypoxemia, especially in the supine position. Conventional respiratory function tests are only mildly affected by obesity except in extreme cases. The major circulatory complications are increased total and pulmonary blood volume, high cardiac output and elevated left ventricular end-diastolic pressure. Patients with obesity commonly develop hypoventilation and sleep apnea syndromes with attenuated hypoxic and hypercapnic ventilatory responsiveness. The final result is hypoxemia, pulmonary hypertension and progressively worsening disability. Obese patients have increased dyspnea and decreased exercise capacity, which are vital to quality of life. Decreased muscle, increased joint pain and skin friction are important determinants of decreased exercise capacity, in addition to the cardiopulmonary effects of obesity. The effects of obesity on mortality in heart failure and chronic obstructive pulmonary disease have not been definitively resolved. Whether obesity contributes to asthma and airway hyper-responsiveness is uncertain. Weight reduction and physical activity are effective means of reversing the respiratory complications of obesity.
 ...
PMID:Altered respiratory physiology in obesity. 1677 65

The first polysomnographic recordings with concomitant monitoring of cardiocirculatory parameters demonstrated that obstructive apneas arising during sleep are accompanied by a marked increase in pulmonary and systemic arterial pressure and severe alveolar hypoventilation. Apneas also may give rise to cardiac arrhythmias, namely potentially life-threatening bradyarrhythmias. The long-term repercussions of these nocturnal cardiocirculatory changes on subsequent cardiovascular diseases and the patient's life expectancy are more controversial. There is little doubt that patients with obstructive sleep apnea syndrome (OSAS) have systemic arterial hypertension, ischemic heart disease, transient ischemic attacks, or stroke more often than control populations and have a shorter life expectancy. However, these clinical manifestations may be at least partly due to myriad other risk factors almost always present in OSAS patients (in particular obesity, diabetes, alcoholism, and cigarette smoking). Few multivariate epidemiological surveys have addressed all these confounding factors. The effectiveness of continuous positive airway pressure treatment in reducing the incidence of cardiovascular comorbidity in OSAS patients is not disputed, even though controlled epidemiological surveys on large populations are scant. This overview of cardiovascular disorders and OSAS examines the latest literature findings aimed at establishing the true impact of nocturnal apneas on cardiocirculatory disease (systemic arterial hypertension, ischemic heart disease, stroke, pulmonary hypertension and right heart failure and mortality).
 ...
PMID:Cardiovascular disorders and obstructive sleep apnea syndrome. 1683 27

We report results of a case-control study in which we evaluated 41 risk factors potentially associated with the development of postsurgical mediastinitis. There were 163 case patients and 326 control patients. Independent risk factors kept in the final multivariate logistic regression model were obesity (defined as a body mass index of greater than 30), diabetes mellitus, chronic obstructive pulmonary disease, preoperative stay longer than 1 week, pulmonary hypertension, perioperative myocardial infarction, and reoperation.
 ...
PMID:Case-control study of risk factors for mediastinitis after cardiovascular surgery. 1715 41

Patients with obesity hypoventilation syndrome (OHS) have a lower quality of life, more healthcare expenses, a greater risk of pulmonary hypertension, and a higher mortality compared to eucapnic patients with obstructive sleep apnea (OSA). Despite significant morbidity and mortality associated with OHS, it is often unrecognized and treatment is frequently delayed. The objective of this observational study was to determine the prevalence of OHS in patients with OSA seen at the sleep disorders clinic of a large public urban hospital serving predominantly minority population and to identify clinical--not mechanistic--predictors that should prompt clinicians to measure arterial blood gases. In the first stage, we randomly selected 180 patients referred to our sleep disorders clinic between 2000 and 2004 for suspicion of OSA. From this retrospective random sample we calculated the prevalence of OHS in patients with OSA and identified independent clinical predictors using logistic regression. In the second stage, we prospectively validated these predictors in a sample of 410 consecutive patients referred to the sleep disorders clinic for suspicion of OSA between 2005 and 2006. The prevalence of OHS in patients with OSA was 30% in the retrospective random sample and 20% in the prospective sample. Three variables independently predicted OHS in both samples: serum bicarbonate level (p < 0.001), apnea-hypopnea index (p = 0.006), and lowest oxygen saturation during sleep (p < 0.001). Due to the serious morbidity associated with OHS, we selected a highly sensitive threshold of serum bicarbonate level. A threshold of 27 mEq/l had a sensitivity of 92% and a specificity of 50%. Only 3% of patients with a serum bicarbonate level <27 mEq/l had hypercapnia compared to 50% with a serum bicarbonate > or =27 mEq/l. In conclusion, OHS is common in severe OSA. A normal serum bicarbonate level excludes hypercapnia and an elevated serum bicarbonate level should prompt clinicians to measure arterial blood gases.
 ...
PMID:Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea. 1765 82

Obstructive sleep apnea (OSA) affects approximately 5% of women and 15% of men in the middle-aged adults, and associated with adverse health outcomes. Cardiovascular disturbances are the most serious complications of OSA. These complications include heart failure, left/right ventricular dysfunction, acute myocardial infarction, arrhythmias, stroke, systemic and pulmonary hypertension. All these cardiovascular complications increase morbidity and mortality of OSA. Several epidemiologic studies have demonstrated that sleep related breathing disorders are an independent risk factor for hypertension, probably resulting from a combination of intermittent hypoxia and hypercapnia, arousals, increased sympathetic activity, and altered baroreflex control during sleep. Arterial hypertension, obesity, diabetes mellitus and coronary artery disease (CAD) which are independent predictors of left ventricular dysfunction, often have co-existence with OSA. Especially severe OSA patients having diastolic dysfunction might have an increased risk of heart failure, since diastolic dysfunction might be combined with systolic dysfunction. Early recognition and appropriate therapy of ventricular dysfunction is advisable to prevent further progression to heart failure and death. Patients with acute myocardial infarction, especially if they had apneas and hypoxemia without evident heart failure should be evaluated for sleep disorders. So, patients with CAD should be evaluated for OSA and vice versa. Early recognition and treatment of OSA may improve cardiovascular functions. Continuous positive airway pressure (CPAP) applied by nasal mask, is still the gold standard method for treatment of the disease and prevention of complications.
 ...
PMID:Cardiovascular diseases in obstructive sleep apnea. 1720 27

Mechanical ventilation has become an important treatment option in chronic ventilatory failure. There are different diseases which lead to ventilatory failure and to home mechanical ventilation (HMV). A primary loss of in- and expiratory muscle strength is the reason for respiratory deterioration in neuromuscular disease. In most of these diseases ventilatory failure develops because of the progressive character of muscular damage. Initially, ventilatory failure can be found during night-time. In the case of hypercapnia at daytime, life expectancy is strongly reduced, especially in amyotrophic lateral sclerosis and Duchenne muscular dystrophy. HMV leads to a prolongation of life and to an increase in quality of life, if bulbar involvement is not severe. Impressive clinical improvements under HMV have been found in restrictive disorders of the rib cage like kyphoscoliosis or posttuberculosis sequelae, with an increase of quality of life, walking distance and a decrease in pulmonary hypertension. Only few data are published about long-term results of HMV in Obesity Hypoventilation. In terms of retrospective analyses of clinical data HMV seems to improve survival in this population. Some patients only need CPAP treatment, but most patients have to be treated with ventilatory support. The application of HMV in patients with chronic ventilatory failure due to chronic obstructive pulmonary disease (COPD) is growing, but there are controversial results in randomised clinical trials. Analysis of these data suggest better results of HMV in patients with severe hypercapnia, with the application of higher effective ventilatory pressure and a ventilator mode with a significant reduction in the work of breathing. Under such conditions HMV leads to a reduction of hypercapnia, an improvement in sleep quality, walking distance and quality of life, but until now there is no evidence in reduction of mortality in COPD.
 ...
PMID:[Mechanical ventilation in chronic ventilatory insufficiency]. 1762 Feb 31

Obesity independently increases the risk of pulmonary embolism (PE). We compare a superobese population (body mass index [BMI] > 55 kg/m(2)) undergoing open gastric bypasses (OGBs) with a similarly matched group of laparoscopic gastric bypasses (LGB) to see if the incidence of PE differs. We included all patients undergoing OGB (n = 193, average BMI = 51 kg/m(2)) at our institution by a single surgeon between July 1999 and April 2001. Thirty-one patients were superobese (BMI > 55 kg/m(2)). LGB was started at our institution in April 2001. Since that time 213 patients (average BMI = 52 kg/m(2)) have undergone the procedure. One hundred and nine patients were superobese. Pre- and postoperative prophylaxis included sequential compression stockings and subcutaneous heparin. Postoperatively, patients who developed signs of hypoxia, tachypnea, or tachycardia underwent a chest X-ray and spiral computed tomography. In addition, all patients who expired in the 30-day postoperative period underwent postmortem examination. Data were analyzed using the chi-squared test. In the OGB group, four patients (2.1%) developed PE. All occurred in superobese patients with a BMI > 55 kg/m(2). Three were fatal PEs and one was nonfatal. None of these patients had a prior history of deep vein thrombosis, PE, venous stasis disease, or pulmonary hypertension. In the LGB group, one patient (0.9%) had a nonfatal PE. This patient had a history of deep vein thrombosis. The incidence of PE was statistically higher in the superobese OGB group (P < 0.01). Despite the theoretical hindrance to venous return and vena caval compression observed with pneumoperitoneum, fewer PEs occurred in the laparoscopic group. Our data, however, suggest that patients with a BMI > 55 kg/m(2) might be at an increased risk for PE independent of operative approach.
 ...
PMID:The incidence of pulmonary embolism in open versus laparoscopic gastric bypass. 1782 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>